https://www.explorationpub.com/Journals/eds Most Recent Articles : Exploration of Drug Science. en-us Tue, 26 May 2026 23:48:07 GMT https://www.explorationpub.com/Journals/eds/Article/10081 Not applicable. Editorial Fri, 08 Jul 2022 00:00:00 GMT FernandoAlbericio, Fri, 08 Jul 2022 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/10081 https://www.explorationpub.com/Journals/eds/Article/10082 Aim: The aim of this research work was to develop a validated reversed-phase (RP)-high-performance liquid chromatography (HPLC) method for simultaneous estimation of oxytetracycline (OXY) and polymixin B (PMB) in fixed-dose combination. Methods: The HPLC assay method was validated on X-Bridge C18 [250 mm × 4.6 mm intradermal (i.d.), 5 μm], mobile phase consisting of aotearoa co-incidence network (ACN):water containing 0.5% (v/v) orthophosphoric acid (pH 3.5) in the ratio of 80:20 respectively. The flow rate was set at 0.9 mL/min and the column was maintained at room temperature. The RP-HPLC method was validated in terms of the calibration curve (CC), linearity and range, limit of detection (LOD), and limit of quantitation (LOQ), precision, robustness, and accuracy. Results: The method was found to be linear with a concentration range of 5–25 μg/mL. Precision results showed the developed method was found to be precise with a relative standard deviation [RSD (%)] value < 2. Accuracy showed acceptable recovery of prepared concentrations as per International Conference on Harmonization (ICH) guidelines. Moreover, the developed method was found to be robust and rugged, as per specified ranges. The assay of these two drugs in marketed formulation, i.e., Terramycin® Ointment showed satisfactory recovery, as per ICH guidelines. The results proved that the method can be used for the routine-based estimation of OXY and PMB. Conclusions: Linear CC were obtained with a correlation coefficient (R2 > 0.99) with acceptable results of accuracy and precision. Graphical abstract.Ultraviolet visible and HPLC method development Original Article Sat, 25 Feb 2023 00:00:00 GMT TanuChaudhary, Balak DasKurmi, DilpreetSingh, Sat, 25 Feb 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/10082 https://www.explorationpub.com/Journals/eds/Article/10083 Aim: The development of a collaborative strategy with improved efficacy holds great promise in tumor treatment. This study aims to develop an effective collaborative strategy based on functionalized mesoporous polydopamine (MPDA) nanocomposites for killing tumor cells. Methods: MPDA nanoparticles were synthesized and functionalized with camptothecin (CPT) payload and manganese dioxide (MnO2) coating to construct MPDA-CPT-MnO2 nanocomposites. Results: When uptaken by tumor cells, the nanocomposites can degrade to produce O2, release CPT, and generate manganese (Mn2+) under the stimulation of hydrogen peroxide (H2O2) and acid. The released CPT and Mn2+ can act as chemotherapeutic drug and Fenton-like agent, respectively. Abundant reactive oxygen species (ROS) are generated in 4T1 tumor cells through an Mn2+-mediated Fenton-like reaction. After that, the generated Mn4+ can react with glutathione (GSH) through redox reaction to produce Mn2+ and deplete GSH, disrupting the reducing capacity and benefiting the production of ROS in tumor cells. Under laser irradiation, the nanocomposites can generate hyperthermia to promote the production of ROS. Conclusions: The developed MPDA-CPT-MnO2 nanocomposites can kill tumor cells through collaborative chemo/photothermal/chemodynamic therapy (CDT). Original Article Tue, 28 Feb 2023 00:00:00 GMT YiOuyang, YanChen, TingXu, YihaoSun, ShengZhao, ChunmeiChen, YixinTan, LiangHe, HuiLiu, Tue, 28 Feb 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/10083 https://www.explorationpub.com/Journals/eds/Article/10084 It is widely acknowledged that sialyl Lewis X (sLeX), the composition and linkage of which are N-acetylneuraminic acid (Neu5Ac) α2-3 galactose (Gal) β1-4 [fucose (Fuc) α1-3] N-acetylglucosamine, is usually attached to the cell surface. It presents as a terminal structure on either glycoproteins or glycolipids and has been demonstrated to be related to various biological processes, such as fertilization and selectin binding. Due to the vital role of sLeX, its synthesis as well as its determination approaches have attracted considerable attention from many researchers. In this review, the focus is sLeX on glycoproteins. The biological importance of sLeX in fertilization and development, immunity, cancers, and other aspects will be first introduced. Then the chemical and enzymatic synthesis of sLeX including the contributions from more than 15 international research groups will be described, followed by a brief view of the sLeX detection focusing on monosaccharides and linkages. This review is valuable for those readers who are interested in the chemistry and biology of sLeX. Review Tue, 28 Feb 2023 00:00:00 GMT QiushiChen, HanLiu, XuechenLi, Tue, 28 Feb 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/10084 https://www.explorationpub.com/Journals/eds/Article/10085 Aim: Conventional techniques to share and archive spinal imaging data raise issues with trust and security, with novel approaches being more greatly considered. Ethereum smart contracts present one such novel approach. Ethereum is an open-source platform that allows for the use of smart contracts. Smart contracts are packages of code that are self-executing and reside in the Ethereum state, defining conditions for programmed transactions. Though powerful, limited attempts have been made to showcase the clinical utility of such technologies, especially in the pre- and post-operative imaging arenas. Herein, we therefore aim to propose a proof-of-concept smart contract that stores intraoperative three-dimensional (3D) augmented reality surgical navigation (ARSN) data and was tested on a private, proof-of-authority network. To the author’s best knowledge, the present study represents a first-use case of the InterPlanetary File Storage protocol for storing and retrieving spine imaging smart contracts. Methods: The content identifier hashes were stored inside the smart contracts while the interplanetary file system (IPFS) was used to efficiently store the image files. Insertion was achieved with four storage mappings, one for each of the following: fictitious patient data, specific diagnosis, patient identity document (ID), and Gertzbein grade. Inserted patient observations were then queried with wildcards. Insertion and retrieval times for different record volumes were collected. Results: It took 276 milliseconds to insert 50 records and 713 milliseconds to insert 350 records. Inserting 50 records required 934 Megabyte (MB) of memory per insertion with patient data and imaging, while inserting 350 records required almost the same amount of memory per insertion. In a database of 350 records, the retrieval function needs about 1,026 MB to query a record with all three fields left blank, but only 970 MB to obtain the same observation from a database of 50 records. Conclusions: The concept presented in this study exemplifies the clinical utility of smart contracts and off-chain data storage for efficient retrieval/insertion of ARSN data. Systematic Review Wed, 01 Mar 2023 00:00:00 GMT SaiBatchu, Michael J.Diaz, LaurenLadehoff, KevinRoot, BrandonLucke-Wold, Wed, 01 Mar 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/10085 https://www.explorationpub.com/Journals/eds/Article/10086 Aim: In the present study, the natural products levistolide A (LA) and periplogenin (PPG) were studied for their growth inhibitory effects on the development of gastric cancer cells in vitro and, more critically, in vivo, alone or in combination with the therapeutic medication 5-fluorouracil (5-FU). Methods: Methyl thiazolyl tetrazolium (MTT), also known as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays were used for the cell viability study. Apoptosis was detected by western blot to detect the cleavage of caspase substrate poly (ADP-ribose) polymerase (PARP) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick-end labelling (TUNEL) assays. The nude mice bearing gastric cancer cells were used for the anti-cancer activity detection of LA and its combinational treatment effect with 5-FU. Results: The results in the present study shown that the two compounds were able to inhibit the viability of the cancer cells in a dose- and time-dependent manner by MTT method. They could trigger apoptosis when used alone, and more potently, in combination with 5-FU detected by TUNEL positivity and the cleavage of caspase substrate PARP. In nude mice bearing gastric cancer cells, injection (i.p.) of LA or PPG alone inhibited the growth of the cancer cells. The treatment using one of the compounds in combination with 5-FU inhibited the cancer cell growth at a higher level than the treatment by a compound alone. Conclusions: LA and PPG could inhibit the growth of the cancer cells, alone or in combination with 5-FU, in vitro and in vivo, suggesting that they are promising investigational drugs for therapeutic development. Original Article Thu, 30 Mar 2023 00:00:00 GMT Jia LiGuo, Hong MeiHu, Shao ChinLee, Ji ZhongZhao, Thu, 30 Mar 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/10086 https://www.explorationpub.com/Journals/eds/Article/10087 Not applicable. Editorial Sun, 16 Apr 2023 00:00:00 GMT Walter F. de AzevedoJr., Sun, 16 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/10087 https://www.explorationpub.com/Journals/eds/Article/10089 Malignant brain tumors are the leading cause of cancer-related death in children and remain a significant cause of morbidity and mortality throughout all demographics. Central nervous system (CNS) tumors are classically treated with surgical resection and radiotherapy in addition to adjuvant chemotherapy. However, the therapeutic efficacy of chemotherapeutic agents is limited due to the blood-brain barrier (BBB). Magnetic resonance guided focused ultrasound (MRgFUS) is a new and promising intervention for CNS tumors, which has shown success in preclinical trials. High-intensity focused ultrasound (HIFU) has the capacity to serve as a direct therapeutic agent in the form of thermoablation and mechanical destruction of the tumor. Low-intensity focused ultrasound (LIFU) has been shown to disrupt the BBB and enhance the uptake of therapeutic agents in the brain and CNS. The authors present a review of MRgFUS in the treatment of CNS tumors. This treatment method has shown promising results in preclinical trials including minimal adverse effects, increased infiltration of the therapeutic agents into the CNS, decreased tumor progression, and improved survival rates. Review Fri, 28 Apr 2023 00:00:00 GMT Phillip MitchellJohansen, Payton YerkeHansen, Ali A.Mohamed, Sarah J.Girshfeld, MarcFeldmann, BrandonLucke-Wold, Fri, 28 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/10089 https://www.explorationpub.com/Journals/eds/Article/10088 Bladder cancer (BC) is a complex disease with multiple clinical manifestations and treatment challenges, and current standard-of-care therapies remain limited and unfavorable. Theranostics, the integration of diagnostic and therapeutic technologies, has emerged as a promising strategy to address these challenges. The rapid development of nanomedicine has been a source of hope for the improvement of BC therapies and diagnostics by reducing side effects, enhancing tumor suppression, and overcoming drug resistance. Metal nanoparticles (NPs), inorganic NPs, polymer NPs, etc. have their respective advantages and show encouraging potential in the therapy of BC. In this review, we provide an overview on the state of the art in nanotechnology-based theranostics for BC, offering insights into the design and discovery of novel NPs for future BC management. Review Fri, 28 Apr 2023 00:00:00 GMT KunpengLiu, QixiMo, ZhenshanDing, ShicongLai, JianRen, QingsongYu, Fri, 28 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/10088 https://www.explorationpub.com/Journals/eds/Article/100810 Aim: Drug discovery is a long process, often taking decades of research endeavors. It is still an active area of research in both academic and industrial sectors with efforts on reducing time and cost. Computational simulations like molecular docking enable fast exploration of large databases of compounds and extract the most promising molecule candidates for further in vitro and in vivo tests. Structure-based molecular docking is a complex process mixing both surface exploration and energy estimation to find the minimal free energy of binding corresponding to the best interaction location. Methods: Hereafter, heterogeneous graph score (HGScore), a new scoring function is proposed and is developed in the context of a protein-small compound-complex. Each complex is represented by a heterogeneous graph allowing to separate edges according to their class (inter- or intra-molecular). Then a heterogeneous graph convolutional network (HGCN) is used allowing the discrimination of the information according to the edge crossed. In the end, the model produces the affinity score of the complex. Results: HGScore has been tested on the comparative assessment of scoring functions (CASF) 2013 and 2016 benchmarks for scoring, ranking, and docking powers. It has achieved good performances by outperforming classical methods and being among the best artificial intelligence (AI) methods. Conclusions: Thus, HGScore brings a new way to represent protein-ligand interactions. Using a representation that involves classical graph neural networks (GNNs) and splitting the learning process regarding the edge type makes the proposed model to be the best adapted for future transfer learning on other (protein-DNA, protein-sugar, protein-protein, etc.) biological complexes. Original Article Sun, 30 Apr 2023 00:00:00 GMT KevinCrampon, AlexisGiorkallos, XavierVigouroux, StephanieBaud, Luiz AngeloSteffenel, Sun, 30 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100810 https://www.explorationpub.com/Journals/eds/Article/100811 Peptides constitute an important component of Nature’s pharmacy and they play a significant role in several signaling pathways acting as natural biological messengers. While nature has mastered the cycle of creation, application, and destruction of large and short peptides to the benefit of the host organism, organic and medicinal chemists have in their capacity and small steps, made big developments in the field of peptide synthesis as well as in developing them as therapeutics. In comparison to their big counterparts, i.e. proteins, short peptides encompass several advantages, from the ease of synthesis to their physico-chemical properties. However, the real challenge for in vivo application of therapeutic peptides is to overcome their low plasma availability and their fast enzymatic degradation. This review briefly covers the relevant areas of medicinally important short peptides and the recent developments made to turn these peptides into therapeutics. Also presented in this article are important efforts and strategies used to overcome some of the inherent limitations of peptidic molecules and thereby facilitate their progression in the clinical phases towards approved drugs. Review Wed, 28 Jun 2023 00:00:00 GMT Maria G.Ciulla, MonicaCivera, SaraSattin, KamalKumar, Wed, 28 Jun 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100811 https://www.explorationpub.com/Journals/eds/Article/100812 Aim: Identification of small bioactive regions in proteins and peptides can be useful information in drug design studies. The current study has shown that an inter-cysteine loop of the N-terminal domain of Opisthorchis viverrini granulin-1 (Ov-GRN-1), a granulin protein from the flatworm liver fluke Opisthorchis viverrini which has potent wound healing properties, maintains the bioactivity of the full-length protein. Methods: Peptides corresponding to the three inter-cysteine loops of the N-terminal domain were produced using synthetic chemistry, and their structures and bioactivities were analyzed using nuclear magnetic resonance (NMR) spectroscopy and cell proliferation assays, respectively. Results: As expected for such small peptides, NMR analysis indicated that the peptides were poorly structured in solution. However, a seven-residue peptide corresponding to loop 2 (GRN-L2) promoted cell proliferation, in contrast to the other fragments. Conclusions: The results from the current study suggest that GRN-L2 might be responsible, in part, for the bioactivity of Ov-GRN-1, and might be a useful lead molecule for subsequent wound healing studies. Original Article Fri, 30 Jun 2023 00:00:00 GMT RozitaTakjoo, David T.Wilson, Paramjit S.Bansal, AlexLoukas, Michael J.Smout, Norelle L.Daly, Fri, 30 Jun 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100812 https://www.explorationpub.com/Journals/eds/Article/100813 Bacterial infections constitute one of the major cases of primary medical incidences worldwide. Historically, the fight against bacterial infections in humans has been an ongoing battle, due to the ability of bacteria to adapt and to survive. Indeed, bacteria have developed various mechanisms of resistance against several therapeutic agents. Consequently, the scientific community is always interested in search of new therapeutic agents, which are able to efficiently kill resistant-bacterial strains. This article covers the most recent antibacterial molecules approved by the Food and Drugs Administration (FDA) and European Medicines Agency (EMA) from 2012 to 2022 and intends to focus on synthetic derivatives to give a pedagogical view, with the goal of highlighting the importance of organic synthesis to obtain greater efficacy. A focus will be made on studies describing the structure and activity of the organic molecules and their interactions with their respective biological targets. Review Sat, 01 Jul 2023 00:00:00 GMT MiguelGarcía-Castro, FranciscoSarabia, AmeliaDíaz-Morilla, Juan ManuelLópez-Romero, Sat, 01 Jul 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100813 https://www.explorationpub.com/Journals/eds/Article/100814 Aim: This study aims to report an engineered peptide zp39 with favorable bioactivity against enterohemorrhagic Escherichia coli (E. coli, EHEC). Its antibacterial mechanisms and application in a real food system are assessed. Methods: Spatial conformation of synthetic peptide zp39 (GIIAGIIiKIKk-NH2, lowercase letters indicate dextrorotatory amino acids) was predicted by PEPstrMOD and its secondary structure was further determined by circular dichroism (CD) spectroscopy. Then, standard E. coli O157:H7 strain ATCC 43888 was used to evaluate the bioactivity of zp39. A double dilution method was applied to investigate its efficacy in normal broth medium, serum, and highly saline conditions. Its effects on cell membrane permeability and potential were measured by fluorescent assays. Thereafter, morphological changes of E. coli O157:H7 cells were monitored by electron microscopy technologies. Finally, the potential application of zp39 in controlling EHEC in food was tested with spinach juice and the Galleria mellonella larvae model was employed to assess the in vivo efficacy. Results: Peptide zp39 presented an amphiphilic helical structure. It effectively inhibited the growth of E. coli O157:H7 at a concentration of 4 μmol/L in a bactericidal mode. Mechanistic studies revealed that it affected membrane permeability and potential in a dose-dependent manner. Moreover, zp39 maintained satisfactory bioactivity against E. coli O157:H7 even in the presence of 70% serum or 1,000 μmol/L chloride salts. In spinach juice application, > 90% E. coli O157:H7 cells were killed within 2 h after exposure to 64 μmol/L zp39. In vivo study proved that treatment with 64 μmol/L zp39 could effectively boost the survival ratio of infected larvae by 50%. Conclusions: This study depicts a synthetic dodecapeptide that shows the potential application in controlling EHEC. This molecule may be developed into a highly effective antimicrobial agent applied to prevent food contamination and associated infections. Original Article Sat, 01 Jul 2023 00:00:00 GMT PingZeng, XuemeiYang, Kwok-YinWong, ShengChen, Kin-FaiChan, Sharon Shui YeeLeung, LanhuaYi, Sat, 01 Jul 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100814 https://www.explorationpub.com/Journals/eds/Article/100815 Despite recent advancements in the field of neuro-ophthalmology, the rising rates of neurological and ophthalmological conditions, mismatches between supply and demand of clinicians, and an aging population underscore the urgent need to explore new therapeutic approaches within the field. Glucagon-like peptide 1 receptor agonists (GLP-1RAs), traditionally used in the treatment of type 2 diabetes, are becoming increasingly appreciated for their diverse applications. Recently, GLP-1RAs have been approved for the treatment of obesity and recognized for their cardioprotective effects. Emerging evidence indicates some GLP-1RAs can cross the blood-brain barrier and may have neuroprotective effects. Therefore, this article aims to review the literature on the neurologic and neuro-ophthalmic role of glucagon-like peptide 1 (GLP-1). This article describes GLP-1 peptide characteristics and the mechanisms mediating its known role in increasing insulin, decreasing glucagon, delaying gastric emptying, and promoting satiety. This article identifies the sources and targets of GLP-1 in the brain and review the mechanisms which mediate its neuroprotective effects, as well as implications for Alzheimer’s disease (AD) and Parkinson’s disease (PD). Furthermore, the preclinical works which unravel the effects of GLP-1 in ocular dynamics and the preclinical literature regarding GLP-1RA use in the management of several neuro-ophthalmic conditions, including diabetic retinopathy (DR), glaucoma, and idiopathic intracranial hypertension (IIH) are discussed. Review Fri, 25 Aug 2023 00:00:00 GMT SohumSheth, AashayPatel, MarcoForeman, MohammedMumtaz, AkshayReddy, RamySharaf, SiddharthSheth, BrandonLucke-Wold, Fri, 25 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100815 https://www.explorationpub.com/Journals/eds/Article/100816 Nonalcoholic fatty liver disease (NAFLD), its more rapidly progressive steatohepatitic variant [nonalcoholic steatohepatitis, (NASH)], and the recently defined metabolic dysfunction-associated fatty liver disease (MAFLD) may be collectively alluded to as “metabolic fatty liver syndromes” (MFLS). MFLS is a common clinical complaint for which no licensed drug treatment is available and a public health issue posing a heaven burden on healthcare systems. Iron plays a key role in many of the key pathogenic steps concurring in the development and progression of MFLS, notably including genetics, intestinal dysbiosis, adipositis, insulin resistance, metaflammation, oxidative stress and ferroptosis, endoplasmic reticulum stress, and hepatic fibrosis. This notion raises the logical expectation that iron depletion, which can easily be implemented with venesection, might improve several aspects of MFLS. However, few published studies have globally failed to support these expectations. In conclusion, venesection in MFLS exhibits a strong biological rationale and possible metabolic benefits. However, confronted with failures in hepato-histological outcomes, data call for additional studies aimed to reconcile these inconsistencies. Review Fri, 25 Aug 2023 00:00:00 GMT AmedeoLonardo, Fri, 25 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100816 https://www.explorationpub.com/Journals/eds/Article/100817 The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), known to cause the coronavirus disease 2019 (COVID-19), was declared a pandemic in early 2020. During the past time, several infections control methods have been developed. Nevertheless, all of them have certain limitations: uncertainty in duration, limited efficacy of vaccines, and lack of effective drugs for COVID-19 treatment. So, the issue of creating drugs for symptomatic and etiotropic therapy is still relevant. This review summarizes the current knowledge of using natural compounds as anti-SARS-CoV-2 agents by analysing the results of in vitro studies and completed clinical trials (CTs). Also, this work highlighted the most active molecules and discussed the possibility of using some compounds in clinical practice. Review Fri, 25 Aug 2023 00:00:00 GMT AntonKolodnitsky, NikitaIonov, IrinaGravel, VladimirPoroikov, Fri, 25 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100817 https://www.explorationpub.com/Journals/eds/Article/100818 Aim: The significance of β-amyloid protein as a key player in neuro-degenerative disorders viz. Alzheimer’s disease (AD), Parkinson’s disease (PD) has been extensively researched and reported. Glaucoma being another prominent form of neuro-degeneration involving the loss of retinal ganglion cells (RGCs) and human trabecular meshwork (HTM) cells, is also found to be similar to AD in many aspects, but its relation with β-amyloid has not been studied too far up to understanding its causation and pathogenesis where β-amyloid is expected to play important role. This study is an attempt to evaluate the chances of β-amyloid’s role in pathogenesis of retinal neurodegenerative disorder called glaucoma, in silico. Methods: The study involved determination of feasibility of interaction between β-amyloid and well known glaucoma related proteins namely, myocilin and optineurin. The computational tool called Hex 8.0.0 has been used in this work. Results: The docking score for β-amyloid and myocilin was found to be –724.1 kJ mol–1 while that for β-amyloid and wild-type optineurin pair was found to be –296.9 kJ mol–1 and that for β-amyloid and mutated optineurin was –607.1 kJ mol–1. Conclusions: Interaction of β-amyloid with myocilin and optineurin in both forms (wild-type and mutated) is quite energetically favorable. The binding between β-amyloid and mutated optineurin is higher in comparison to that between β-amyloid and wild-type optineurin. Thus, functional significance of β-amyloid in glaucoma pathogenesis is fairly possible which should be studied and proved through in vitro and in vivo studies. Original Article Tue, 29 Aug 2023 00:00:00 GMT NancyMaurya, Tue, 29 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100818 https://www.explorationpub.com/Journals/eds/Article/100894 Aim: The objective of this study was to develop a minimal physiologically based pharmacokinetic (mPBPK) model to predict area under the curve (AUC) and maximum plasma concentration (Cmax) of drugs in subjects with varying degrees of hepatic impairment and compare this mPBPK model with the whole body PBPK model. Methods: Hepatic impairment classification system, which is based on Child-Pugh score was used. In this mPBPK model, 4 physiological parameters [portal and renal blood flow, glomerular filtration rate (GFR), and liver size] and 2 biochemical parameters (albumin and bilirubin) were used. Total number of drugs analyzed in this study was 52, and the predicted Cmax and AUC values were compared with dedicated clinical trials. Out of 52 drugs, the predictive performance of mPBPK was compared with the whole body PBPK model for 27 drugs, and the remaining 25 drugs were used to further test the robustness of the mPBPK model. Results: The results of the study indicated that the predictive performance of the mPBPK model was comparable with the whole body PBPK model, both in terms of Cmax and AUC. For 52 drugs, there were 120 data points for AUC (37, 47, and 36 for mild, moderate, and severe hepatic impairment, respectively), and from mPBPK model, 92%, 94%, and 89% data points were within 0.5–2-fold prediction error, respectively. Conclusions: Overall, the results of the study indicated that the proposed mPBPK model, in its predictive performance, is as robust and accurate as whole body PBPK model. Original Article Fri, 28 Feb 2025 00:00:00 GMT IftekharMahmood, Fri, 28 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100894 https://www.explorationpub.com/Journals/eds/Article/100819 Flavonoids present a large group of natural polyphenols with numerous important health benefits for preventing and treating a diverse variety of pathological conditions. However, the actual therapeutic use of these phytochemicals is impeded by their low oral bioavailability. In this commentary article, an interesting paradox is presented: while the ingested flavonoid glycosides can be absorbed by means of sodium-dependent glucose transporters (SGLTs; SGLT1) located in the brush border membrane facing the lumen of the small intestine, certain flavonoid aglycones are able to inhibit these shuttle proteins. It is expected that avoiding the co-intake of such SGLT1 inhibitors concomitantly with flavonoid-rich foods might provide a new option for enhancing the oral bioavailability of flavonoids, thereby preventing the transport of unabsorbed compounds to the large intestine and conversion into catabolites by the colonic microbiota. Altogether, the administration of flavonoids in appropriate combinations is highlighted for getting the maximal health benefits from consuming these bioactive compounds. Commentary Wed, 30 Aug 2023 00:00:00 GMT KatrinSak, Wed, 30 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100819 https://www.explorationpub.com/Journals/eds/Article/100820 Thrombocytopenia is one of the most frequent implications of liver cirrhosis. This condition, when present in the severe form [platelet count (PLT) less than 50 × 109/L] correlates, with an increased risk of bleeding during the main diagnostic-therapeutic procedures which cirrhotic patients usually undergone. In these cases, generally, an infusion of platelets is performed, albeit in recent years has been replaced by a cycle of second generation thrombopoietin receptor (TpoR) agonists. This article reports two different cases concerning respectively an 83-year-old female patient suffering from arterial hypertension, aneurysm of the sub-renal aorta, hepatitis C virus (HCV)-positive liver cirrhosis responsive to treatment with antiviral drugs, and a 2.0 cm diameter hepatocellular carcinoma (HCC) nodule localized in the hepatic segment III and a 53-year-old female patient with HCV-positive liver cirrhosis complicated by portal hypertension with splenomegaly, thrombocytopenia, and F3 esophageal varices at high risk of bleeding. Both of them, eligible for invasive procedures such as HCC transarterial chemoembolization (TACE) and for esophageal variceal band ligation, were prescribed prophylaxis with TpoR agonists due to their severe and persistent thrombocytopenia. These two cases show how a short course of lusutrombopag allows to safely perform one or more invasive procedures and how the administration of the drug can be repeated without losing efficacy. Furthermore, this drug shows an excellent safety profile and avoids the risks of platelet transfusion. In conclusion, second generation TpoR agonists can be considered the prophylactic treatment of choice to reduce the risk of bleeding in patients with liver cirrhosis and severe thrombocytopenia. Case Report Wed, 30 Aug 2023 00:00:00 GMT DavideScalabrini, PaoloSciuto, CristinaFelicani, AntoniaRudilosso, PietroAndreone, Wed, 30 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100820 https://www.explorationpub.com/Journals/eds/Article/100870 According to the International Union of Pure and Applied Chemistry (IUPAC), peptides are small proteins with a size between 2 and 50 amino acids residues. They are ubiquitous across the evolutionary scale, fulfilling a wide variety of functions, from immune system effectors in simple organisms to signaling or neuromodulating agents in high vertebrates. Following nature’s example, peptides have emerged as alternatives in various fields. One particularly relevant area is in drug discovery, offering alternatives to face the emergence of antibiotic-resistant microorganisms. Peptides are also prevalent in other sectors, such as the food industry, where they serve as food additives to enhance nutritional characteristics or aid in food preservation. Moreover, peptides are increasingly being utilized in cosmetics. Additionally, peptides serve as valuable tools in both basic and applied research, facilitating the exploration of specific activity mechanisms and the verification of particular activities, among various other applications. Despite certain limitations and disadvantages compared to other bioactive molecules, peptides remain a focal point of interest in research, as well as in applied and developmental fields, due to their versatility. In this report, we provide an overview of the extensive application landscape of synthetic peptides, presenting examples developed in-house across different areas which include a summary of the methodologies and results obtained. Review Wed, 16 Oct 2024 00:00:00 GMT ConstanzaCárdenas, PaulaSantana, ClaudioÁlvarez, LuisMercado, SergioMarshall, FernandoAlbericio, FannyGuzmán, Wed, 16 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100870 https://www.explorationpub.com/Journals/eds/Article/100821 Aim: The biorecognition unit of an electrochemical biosensor requires molecules that are immobilised to serve as a bridge between the recognition unit and the transducing surface. Unique materials that enhance immobilisation of biorecognition molecules and improve electrochemical signal transduction are important in overcoming challenges based on the sensitivity of biosensors. In this regard, the electrochemical properties (EPs) of hydroxyapatite (HAp) material for the direct immobilisation of cells was investigated. Methods: Snail shell HAp (SHAp) material was synthesised from Achatina achatina snail shells and phosphate-containing solutions. The SHAp material was characterised using X-ray diffractometry (XRD), Fourier transform infrared (FTIR) spectroscopy, and Raman spectroscopy to determine the structural configuration, after which it was blended with a conductive polymer [poly(3,4-ethylenedioxythiophene): poly-4-styrene sulfonate (PEDOT: PSS)] to improve the electrochemical responses. The SHAp/PEDOT: PSS blend was used to modify a screen-printed carbon electrode (SPCE) by drop-casting, followed by seeding of pheochromocytoma (PC 12) and human embryonic kidney (HEK)-293T cells on the modified SPCE to record the EP using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Red blood cells (RBCs) were used as a control. Results: The CV analysis showed lower peak currents for HEK 293T (50 µA) and PC 12 (120 µA) compared to the RBC (230 µA). Also, the EIS showed impedance values of 0.70 for HEK 293T, 0.62 for PC 12, and 0.52 mΩ for RBC. The findings indicate that SHAp/PEDOT: PSS enables the differentiation of cell proliferation signals through voltammetric and impedimetric measurements. Conclusions: The unique current and impedance differences among the cells could serve as potential markers for rapid cell detection. Original Article Thu, 21 Sep 2023 00:00:00 GMT DennisAdusei, Bernard O.Asimeng, Francis D.Krampa, Elvis K.Tiburu, Thu, 21 Sep 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100821 https://www.explorationpub.com/Journals/eds/Article/100822 Green propolis is collected by Apis mellifera from the flowers and buds of Baccharis dracunculifolia. It has several chemical compounds that confer anti-inflammatory, antimicrobial, healing, and antioxidant biological activities. To report a series of clinical cases in the treatment of oral mucositis (OM) in patients with cancer undergoing radiotherapy in the head and neck region. Rapid treatment of OM means restoring quality of life to patients and lowering the cost of cancer treatment for public health. There male patients with oral carcinoma undergoing radiotherapy treatment were followed between August 2018 and April 2019. The patients presented themselves to the clinics in the Faculty of Dentistry of Federal University of Minas Gerais with erythematous and ulcerated coalescing lesions with purulent fibrin pseudomembranes in the oral mucosa, classified as grade IV OM according to the World Health Organization. The patients complained about the inability to eat, drink, and speak, which caused the radiotherapy interruption. After completing the clinical forms, anamnesis, and proper oral hygiene of each patient, a mucoadherent gel containing 5% propolis was prescribed for daily use, with a 3 time-a-day application every 8 h. After 7 days of use, there was an 80% lesion reduction, with total remission after 15 days of its application. The rapid response with total remission of lesions seems to be related to the chemical composition of propolis. Clinical and cellphone monitoring of patients, weekly and daily, respectively, were essential for successful treatment. The patients were monitored for one year, being encouraged to make constant use of the gel to control hyposalivation caused by changes in the salivary glands during radiotherapy. Case Report Mon, 09 Oct 2023 00:00:00 GMT Diogo AlvarengaSilva, Patrícia CarlosCaldeira, Silvia Ferreirade Sousa, Vagner RodriguesSantos, Mon, 09 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100822 https://www.explorationpub.com/Journals/eds/Article/100823 Aim: Modification of the C-terminus of a peptide to improve its properties, particularly after constructing the peptide chain, has great promise in the development of peptide therapeutics. This study discusses the development of a late-stage diversification method for synthesizing peptide acids and amides from hydrazides which can serve as a common precursor. Methods: Peptide hydrazides were synthesized solely by using conventional solid-phase peptide synthesis (SPPS). Hydrazides were subjected to oxidation by potassium peroxymonosulfate (Oxone) to afford carboxylic acids. Azidation of hydrazides using sodium nitrite (NaNO2) under acidic conditions, followed by the addition of β-mercaptoethanol (BME), could also be used to generate carboxylic acids. For the preparation of peptide amides, azides that can be prepared from hydrazides were reacted with ammonium acetate (NH4OAc) or tris(2-carboxyethyl)phosphine (TCEP)∙hydrochloride (HCl) to develop the products through ammonolysis or a Staudinger reaction, which produces iminophosphorane from an azide and a phosphine. The antimicrobial activity of modelin-5 derivatives synthesized from the corresponding hydrazides was evaluated by the colony count of Escherichia coli (E. coli) after treatment with the peptides. Results: Oxone oxidation yielded the corresponding acids rapidly although oxidation-prone amino acids were incompatible. Azidation and subsequent treatment with BME afforded peptide acids an acceptable yield even in sequences containing amino acids that are prone to oxidation. Both methods for conversion of hydrazides to amides were found to afford the desired products in good yield and compatibility. The conditions that were developed were adapted to the synthesis of modelin-5 derivatives from the corresponding hydrazides, yielding late-stage production of the desired peptides. The amides of the resulting peptide showed more potent activity against E. coli than the acid form, and the most potent activity was observed from the hydrazide. Conclusions: The developed protocols allow hydrazides to be converted to acids or amides, enabling late-stage diversification of peptide C-terminal residues. Original Article Tue, 10 Oct 2023 00:00:00 GMT ShokoTanaka, MizukiKanno, YosukeTashiro, TetsuoNarumi, NobuyukiMase, KoheiSato, Tue, 10 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100823 https://www.explorationpub.com/Journals/eds/Article/100824 The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in December 2019 quickly escalated to pandemic levels and had a severe impact on public health. There are 761 million confirmed coronavirus disease 2019 (COVID-19) cases, with over 6.88 million deaths worldwide till March 2023. Severe cases of the disease caused critical respiratory failure followed by multiorgan involvement. Clinical escalation of COVID-19 has been correlated with markedly increased plasma inflammatory markers [e.g., C-reactive protein (CRP)] and pro-inflammatory cytokine levels [e.g., interleukin (IL)-6, tumor necrosis factor-α (TNF-α)]. Therapeutic options have mostly utilized corticosteroids, antivirals (e.g., remdesivir), and monoclonal antibody-based immunomodulation (e.g., tocilizumab). These existing treatments have adverse side effects, inadequate efficacy, and limitations in administering to patients with comorbidities and other underlying diseases. Monoclonal antibody-based therapies and some of the antivirals are very costly. Many phytochemicals have previously reported anti-inflammatory, antiviral, and antioxidant properties. Studying the effectiveness of such phytochemicals against COVID-19 and identifying new plant-derived molecules with antiviral properties have been a focus since the SARS-CoV-2 outbreak. This review article has documented in vitro, in vivo, and clinical studies encompassing 28 different phytochemicals belonging to various chemical groups (e.g., polyphenols, alkaloids, terpenes) that show anti-COVID-19 activity. These findings suggest that multiple phytochemicals can interfere with virus entry and replication inside the host cell. Many of them can protect from cytokine storm by acting on intracellular signalling pathways in addition to inhibiting virus multiplication. Phytochemicals may prove useful in alleviating post-COVID complications associated with kidney injury, and central nervous system complications, as well. Plant-derived compounds are usually cheaper and have fewer side effects. But, developing new formulations with better absorption and bioavailability remains a priority. This review informs the readers of the current status and indicates the ongoing research in this highly relevant field. Review Wed, 25 Oct 2023 00:00:00 GMT AtriDas, SwarnaliKhan, SyamalRoy, ShantanabhaDas, Wed, 25 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100824 https://www.explorationpub.com/Journals/eds/Article/100825 Protein therapeutics are extensively used in the treatment of autoimmune diseases, but a subset of patients appears to be refractory to these treatments, mainly due to the development of an immune response to the drug. A better understanding of the mechanism underlying the therapeutic drug’s failure becomes fundamental for the development of new and more effective treatments. Unfortunately, there are few cases where the exact mechanisms through which drugs bypass immunological tolerance and provoke immunogenicity have been studied. In this context, peptide epitope identification gained increasing importance in investigating the molecular mechanism of therapeutic drug’s immune responses. Despite peptide identification and use to monitor anti-drug antibody (ADA) profiles is a promising research field, their use is far away from a wide application both at the research and at the commercial level. Herein it is reported a compilation of studies in which peptides are directly involved in anti-drug immune responses, becoming the molecular key step for a better understanding of refractory reactions in therapeutic drugs. An overview on T-cell and B-cell peptide recognition is given, showing the growing potential and advantages of peptides when used in the field of refractoriness to drugs. This review includes studies describing antigenic peptides that enable enhanced ADA detection directly in patients’ sera, as well as the proof of concept that asses the use of peptides instead of proteins, to facilitate the identification of neutralizing ADA. Review Fri, 27 Oct 2023 00:00:00 GMT FelicianaReal-Fernandez, FoscaErrante, AndreaDi Santo, Anna MariaPapini, PaoloRovero, Fri, 27 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100825 https://www.explorationpub.com/Journals/eds/Article/100826 Aim: Solubility prediction is an essential factor in rational drug design and many models have been developed with machine learning (ML) methods to enhance the predictive ability. However, most of the ML models are hard to interpret which limits the insights they can give in the lead optimization process. Here, an approach to construct and interpret solubility models with a combination of physicochemical properties and ML algorithms is presented. Methods: The models were trained, optimized, and tested in a dataset containing 12,983 compounds from two public datasets and further evaluated in two external test sets. More importantly, the SHapley Additive exPlanations (SHAP) and heat map coloring approaches were used to explain the predictive models and assess their suitability to guide compound optimization. Results: Among the different ML methods, random forest (RF) models obtain the best performance in the different test sets. From the interpretability perspective, fragment-based coloring offers a more robust interpretation than atom-based coloring and that normalizing the values further improves it. Conclusions: Overall, for certain applications simple ML algorithms such as RF work well and can outperform more complex methods and that combining them with fragment-coloring can offer guidance for chemists to modify the structure with a desired property. This interpretation strategy is publicly available at https://github.com/Pharmacelera/predictive-model-coloring and could be further applied in other property predictions to improve the interpretability of ML models. Original Article Tue, 31 Oct 2023 00:00:00 GMT MinyiSu, EnricHerrero, Tue, 31 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100826 https://www.explorationpub.com/Journals/eds/Article/100827 Aim: Harzianoic acids A and B (Hz-A/B) are two rare cyclobutene-containing sesquiterpenes isolated from a marine strain of the sponge-associated fungus Trichoderma harzianum. They display anticancer and antiviral effects, reducing the entry of hepatitis C virus (HCV) into hepatocarcinoma cells. The large extracellular loop (LEL) of the tetraspanin protein CD81 represents a molecular target for both Hz-A and Hz-B. Methods: The interaction of Hz-A/B with CD81 has been modeled, using structures of the cholesterol-bound full-length protein and a truncated protein corresponding to the LEL portion. The models mimicked the closed and open conformations of the LEL. Results: The best ligand Hz-B can form stable complexes with the open LEL structure, whereas binding to the closed form is drastically reduced. Key H-bonds between the acid groups of Hz-B and the CD81-LEL domain stabilize the ligand-protein complex. A comparison of the interaction with the homologous tetraspanin CD9, which also presents a dynamic open/closed equilibrium, underlined the marked selectivity of Hz-A/B for CD81 over CD9. The cyclobutane-containing monoterpene grandisol, an insect pheromone, has been identified as a fragment that could be modulated to improve its modest interaction with CD81-LEL. Conclusions: The modeling docking analysis suggests that Hz-B is a robust CD81 binder, better interacting with the LEL portion of CD81 compared to CD9-LEL. The docking study paves the way to the design of small molecules targeting CD81. The study has implications for a better understanding of CD81 binding properties and the regulation of its activities. Original Article Wed, 01 Nov 2023 00:00:00 GMT GérardVergoten, ChristianBailly, Wed, 01 Nov 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100827 https://www.explorationpub.com/Journals/eds/Article/100828 Aim: This study discloses the synthesis and the antimicrobial and anticancer activities of four molecules of structural basis saccharin-thiadiazolyl (4), saccharin-pyridyl (6, 8), and tetrazole-thiadiazolyl (11). Methods: Antimicrobial properties of the molecules were evaluated by the well-diffusion method, against Gram-positive bacteria [Staphylococcus aureus American Type Culture Collection (ATCC) 25923, Staphylococcus epidermidis ATCC 12228, Mycobacterium smegmatis ATCC 607], Gram-negative bacteria (Pseudomonas aeruginosa ATCC 27853) and yeast (Saccharomyces cerevisiae ATCC 2601 and Candida albicans ATCC 10231) strains. The anticancer activity of the compounds was assessed through i) proliferation assays for HCT116, MCF-7, and A375 human cell lines [cells were treated with serial dilutions of compounds and the effect on cell propagation was evaluated by sulforhodamine B (SRB) assay]; ii) antiproliferative and cytotoxic assays for glioma-type cell lines A172 (glioblastoma), U87 (brain-likely glioblastoma), and H4 (neuroglioma; cells were treated with diverse concentrations and the cell viability was assessed using a modified Alamar blue® assay). Results: Compound 11 exhibited significant inhibitory activity against S. aureus and S. epidermidis, with the further molecules demonstrating some inhibitory potential against all the tested Gram-positive, Gram-negative, and yeast strains. Similarly, derivative 11 showed an interesting antiproliferative activity against human colon adenocarcinoma (HCT116), human breast adenocarcinoma (MCF-7), and melanoma (A375) cells, with 50% growth inhibition (GI50) values varying from 3.55 µmol/L to 11.5 µmol/L, in the same order of magnitude of those shown by etoposide. Treatment of brain-like glioblastoma cells (U87) with 11, at the concentration of 100 µg/mL, induced a decrease in cell viability by 50% after 48 h and 72 h. Besides, results attained for A172 cells have shown that compound 11 only induces a significant decrease in cell viability upon treatment at 100 µg/mL for 72 h. A divergent observation was recorded for H4 cells, where the treatment with derivative 11 had promoted a significant decrease in cell viability (< 40–60%), even at concentrations as low as 0.39 µg/mL, after 24 h. Conclusions: This investigation reveals the potential of distinct azole-based conjugates, in particular the tetrazole-thiadiazolyl (11) derivative, as scaffolds worth further investigations, in the frame of antimicrobial and antineoplastic chemotherapy. Original Article Fri, 24 Nov 2023 00:00:00 GMT Luís M. T.Frija, Bruno E. C.Guerreiro, Inês C. C.Costa, Vera M. S.Isca, LucíliaSaraiva, Beatriz G.Neves, MarianaMagalhães, CéliaCabral, Maria L. S.Cristiano, PatríciaRijo, Fri, 24 Nov 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100828 https://www.explorationpub.com/Journals/eds/Article/100829 Aim: The purpose of this paper is to use different structures and ligand-based drug design methods properly to provide theoretical guidance for the design of novel non-covalent proteasome inhibitors, and conduct theoretical analysis of the binding interaction mode between receptors and ligands. At the same time, the pharmacokinetic (PK) prediction, drug-likeness, and synthesis prediction were made for the screened novel drugs. Therefore, potentially attractive non-covalent proteasome inhibitors with low toxicity could be found as anticancer drugs. Methods: In this work, computer-aided drug design methods, including quantitative structure-activity relationship (QSAR), molecular docking, absorption, distribution, metabolism, excretion, and toxicology (ADMET) prediction, and drug-likeness prediction methods were performed. Results: In this study, the structure-activity relationship (SAR) of a series of non-covalent proteasome inhibitors were studied and the optimal comparative molecular field analysis (CoMFA; Q2 = 0.574, r2 = 0.999, r2pred = 0.755) and comparative molecular similarity indices analysis (CoMSIA)-SEHA (Q2 = 0.584, r2 = 0.989, r2pred = 0.921) models were obtained. According to the results of the QSAR model, some vital clues were found that would effectively enhance the biological activity of the compound. Based on these clues, 24 novel non-covalent proteasome inhibitors (D01–D24) were finally designed and screened. While the binding models between proteasome [protein data bank (PDB) code: 3MG6] and three representative compounds (15, 20, and D24) were also analyzed by using the molecular docking method. The results suggested that hydrogen bond and hydrophobic interaction played a key role in binding interaction between the receptor and ligand. In addition, the results of ADMET prediction indicated that the new designed compounds had reasonable PK parameters and drug-like properties. Conclusions: These statistical results can provide theoretical guidance for structural optimization, design, and synthesis of more effective non-covalent proteasome inhibitors in the future. Original Article Wed, 27 Dec 2023 00:00:00 GMT MiaoYuan, HanwenJi, FengxinSun, QiangChen, PingCheng, Wed, 27 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100829 https://www.explorationpub.com/Journals/eds/Article/100830 With the continuous development of nanomaterials, nanofibers prepared by electrospinning have gradually occupied people’s vision because of their unique advantages, such as crisscross network and extracellular matrix-mimicking structure, high drug loading efficiency, and sustained release kinetics. Traditionally, electrospun fibers are mainly used as filter materials, wound dressings, and tissue engineering scaffolds, while their wide applications are limited to cancer nanomedicine applications due to their dense network structure. In recent years, two-dimensional fiber membranes have been transformed into short fibers that can be reconstructed to form fibrous rings or microspheres for cancer theranostics. Herein, this paper provides an overview of the recent advances in the design of electrospun short fibers that retain the advantages of nanofibers with good dispersibility for different nanomedicine applications, including cancer cell capture, cancer treatments, and cancer theranostics. The rational preparation of electrospun short fibers that are available to boost the development of nanomedicine is also discussed. Review Wed, 27 Dec 2023 00:00:00 GMT YifanHuang, MengsiZhan, MingwuShen, LiliZhang, XiangyangShi, Wed, 27 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100830 https://www.explorationpub.com/Journals/eds/Article/100831 Reactivation of hepatitis B virus (HBV; RHBV) is a significant concern during immunosuppressive therapy, as it can lead to severe hepatitis and liver failure. The article reports a case of RHBV during treatment with guselkumab, an interleukin-23 inhibitor in a patient with inactive HBV infection and psoriasis. This report highlights the importance of screening for HBV prior to immunosuppressive therapy and initiating prophylactic therapy when necessary to prevent reactivation and its complications. Case Report Wed, 27 Dec 2023 00:00:00 GMT ElenaFranchi, Arianna A. C.Costanzo, CarmelaCursaro, AmedeoLonardo, ClaudiaLasagni, PietroAndreone, Wed, 27 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100831 https://www.explorationpub.com/Journals/eds/Article/100832 Seaweeds, also known as marine algae, have gained attention as a promising source of bioactive compounds with potential applications in drug discovery. This review explores the emerging field of seaweed-based drug discovery and highlights the diverse range of bioactive compounds found in seaweeds, including polysaccharides, phlorotannins, pigments, and peptides. These compounds exhibit various pharmacological activities such as antioxidant, anti-inflammatory, antimicrobial, antiviral, and anticancer effects. Seaweeds have demonstrated particular promise in the areas of cancer research, with certain species showing potent antitumor properties. Additionally, their anti-inflammatory, antimicrobial, and neuroprotective potential has captured scientific interest in the treatment of chronic diseases and neurodegenerative disorders. However, challenges related to compound identification, extraction methods, scalability of seaweed cultivation, and understanding the mechanisms of action still need to be addressed. As researchers employ advanced technologies and dive deeper into the chemical composition of seaweeds, the untapped potential of these marine organisms in drug discovery awaits further exploration and holds significant promise for future therapeutic advancements. Review Thu, 28 Dec 2023 00:00:00 GMT LeonelPereira, AnaValado, Thu, 28 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100832 https://www.explorationpub.com/Journals/eds/Article/100833 Primary biliary cholangitis (PBC) is an autoimmune cholangiopathy that affects mainly women and, if untreated, can evolve into biliary cirrhosis. Its prevalence varies worldwide, depending on race, and accounts for 22.27 cases/100,000 habitants in Europe. To establish the diagnosis of PBC according to the European Association for the Study of the Liver (EASL) guidelines, two criteria must be satisfied among alkaline phosphatase (ALP) alterations, autoantibody positivity, and histologic abnormalities. Early treatment is effective in prolonging survival. Current guidelines do not suggest hepatic biopsy in patients with autoantibody positivity without cholestasis alterations. However, many patients with these characteristics have been diagnosed with PBC disease only histologically, mainly patients with normal ALP and elevated gamma-glutamyl transferase (GGT), whose normalization has been used as a marker for the follow-up. In contrast, this is the case of a patient with autoantibody positivity and both ALP and GGT within the range, diagnosed for PBC by histology. The manuscript wants to propose the re-evaluation of the role of liver biopsy in PBC diagnosis and the need for a serological or histological biomarker in the follow-up of patients without cholestatic alterations. Case Report Mon, 22 Jan 2024 00:00:00 GMT MatteoBiagi, ElisaBernasconi, CarmelaCursaro, EnricoRonconi, FilippoZanni, PamelaSighinolfi, PietroAndreone, Mon, 22 Jan 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100833 https://www.explorationpub.com/Journals/eds/Article/100834 310-Helices represent the third most abundant secondary structure proteins. Although understandably overshadowed by α-helices for decades, the 310-helix structure is slowly regaining certain relevance in protein science. The key role of this secondary structure in biological processes has been highlighted in reports over the last decade. In addition, 310-helices are considered key intermediates in protein folding as well as a crucial structure for the antimicrobial activity of naturally occurring peptaibols. Thus, it is clear that 310-helices are relevant scaffolds to take into consideration in the field of biomimetics. In this context, this review covers the strategies developed to stabilize the 310-helix structure in peptide chains, from the incorporation of constrained amino acids to stapling methodologies. In the last section, the use of 310-helices as scaffolds of interest in the development of bioactive compounds, catalysts for enantioselective reactions, supramolecular receptors, and membrane-embedded signal transducers are discussed. The present work aims to highlight the relevance, sometimes underestimated, of 310-helices in chemical biology and protein science, providing the tools to develop functional biomimetics with a wide range of potential applications. Review Thu, 01 Feb 2024 00:00:00 GMT DiegoNúñez-Villanueva, Thu, 01 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100834 https://www.explorationpub.com/Journals/eds/Article/1008126 Nanotechnology is a relatively young field of science that has found wide application in medicine, especially in oncology. It focuses on studying molecules at the atomic, molecular, and supramolecular levels, enabling the development of innovative therapeutic solutions. Thanks to research in this field, it has become possible to introduce nanoparticles (NPs) into therapy, specially designed molecules that release the drug in a precisely defined place. This approach allows for maintaining the appropriate therapeutic concentration of the drug substance in the body for a longer period of time. The use of NPs in the treatment of cancer diseases helps to overcome the limitations of traditional chemotherapy, such as systemic, toxic effects of drugs, lack of specificity towards cancer cells, and limited bioavailability. NPs can be used not only as drug carriers, but also as contrast agents enabling imaging at the molecular level. More accurate visualization of diseased tissues is possible thanks to the small size of NPs, optical properties, and the ability to accumulate in the tumor area. Additionally, the use of specific ligands allows detection of pathological changes at the cellular level, allowing for earlier detection of changes, which in turn increases the probability of complete recovery of the patient. Review Tue, 19 Aug 2025 00:00:00 GMT DorotaBartusik-Aebisher, AleksandraKotlińska, KatarzynaKoszarska, DavidAebisher, Tue, 19 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008126 https://www.explorationpub.com/Journals/eds/Article/100835 Nucleic acid therapeutics are emerging as a promising class of medicines, offering unique therapeutic options for cancer at the gene level. However, the druggability of nucleic acid therapeutics is fundamentally restricted by their low stability, poor membrane permeability, and low bioavailability, necessitating the use of delivery vectors. Various delivery vectors have been developed for nucleic acid therapeutics. The fate of established nucleic acid delivery systems (NADS) in vivo substantially affects the delivery efficiency and therapeutic efficacy. The physicochemical properties of NADS (such as size, charge, shape, etc) are crucial for the interaction of NADS with various biological barriers in the body, thereby determining the fate of NADS in the body. Nanoparticle (NP) size is an important parameter defining the blood circulation, distribution, tumor accumulation, and cellular uptake of NADS. This mini-review briefly introduces the various biological barriers of NADS in cancer treatment and focuses on the influence of the particle size of delivery vectors on the in vivo fate of NADS and their therapeutic efficacy, which provides new insights into the rational design of NADS. Review Thu, 01 Feb 2024 00:00:00 GMT MengyunYe, JunniGong, WangChen, XiaoxuanLiu, DandanZhu, Thu, 01 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100835 https://www.explorationpub.com/Journals/eds/Article/100836 The environmental impact of drug manufacturing raises concerns about sustainability in healthcare. To address this, exploring alternative approaches to drug production is crucial. This review focuses on seaweed as a sustainable resource for greening drug manufacturing processes. Seaweed offers advantages such as renewability, abundance, and a positive environmental footprint. The review begins by providing an overview of sustainable drug manufacturing practices and the challenges faced in achieving sustainability. It then discusses seaweed as a sustainable resource, including cultivation techniques and environmental benefits. Seaweed has various applications in drug manufacturing, including extracting and purifying bioactive compounds with potential therapeutic properties. Seaweed’s role in developing green technologies, such as seaweed-based excipients, biodegradable packaging materials, and as a source of sustainable energy for drug manufacturing processes, is highlighted. The environmental and economic implications of incorporating seaweed-based solutions are discussed, emphasizing reduced carbon footprint and cost-effectiveness. Regulatory and industrial perspectives are addressed, examining challenges, and opportunities for implementing seaweed-based drug manufacturing. Collaboration between academia, industry, and regulatory bodies is crucial for successful integration. The review presents future directions and opportunities, including emerging trends and innovations in seaweed-based drug manufacturing, areas for further research, policy development, and industry engagement recommendations. Incorporating seaweed into drug production facilitates a reduction in environmental impact, promotes resource efficiency, and contributes to sustainable healthcare. This review showcases seaweed-based solutions as a means to foster a greener future for drug manufacturing, addressing environmental concerns, and promoting sustainability. Review Tue, 27 Feb 2024 00:00:00 GMT LeonelPereira, JoãoCotas, Tue, 27 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100836 https://www.explorationpub.com/Journals/eds/Article/100837 The influenza virus glycoprotein hemagglutinin (HA) participates in critical steps of the attachment of viral particles to the host cell membrane receptor and membrane fusion. Due to its crucial involvement in the initial phases of influenza A infections, HA emerges as a promising target in the search of novel drug-like candidates. Given its pivotal role in the early stages of influenza A infections, intense drug discovery efforts have been undertaken to target HA in the past decades. Drug discovery studies mainly rely on preventing the recognition of sialic acid units by the receptor binding site in the globular head (GH) domain, or the conformational rearrangement required for the fusion of viral and cell membranes. In this work, the aim is to summarize the progress made in HA-targeted development of small molecule fusion inhibitors. To this end, attention will primarily be focused on the analysis of the X-ray crystallographic structures of HA bound to fusion inhibitors. Furthermore, this study also aims to highlight the efforts made in exploiting the structural information in conjunction with molecular modeling techniques to discern the mechanism of action of the fusion inhibitors and to assist the design and interpretation of structure-activity relationships of novel lead compounds will be highlighted. The final section will be dedicated to elucidating novel and promising antiviral strategies proceeding from the transformation of known small molecule antivirals in proteolysis targeting chimera (PROTAC)-based targeted protein degradation. This knowledge will be valuable to assist the exploitation of classical and novel antiviral structure-based strategies, together with a deeper understanding of the mechanism of action and minimization of the impact of drug resistance. Review Thu, 29 Feb 2024 00:00:00 GMT Francisco JavierHermoso-Pinilla, AitorValdivia, María-JoséCamarasa, TizianaGinex, Francisco JavierLuque, Thu, 29 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100837 https://www.explorationpub.com/Journals/eds/Article/100838 The search for novel therapeutic agents to combat the crisis of antimicrobial resistance has spanned from terrestrial to unique, marine environments. Currently, most of the drugs available for usage are derived from microbial metabolites, especially those belonging to the bacterial group, actinobacteria. Actinobacteria are hotspot organisms that exist in all habitats with a myriad of unique biosynthetic metabolites. Seagrasses appear to be a key ecosystem within the coastal environment worth bioprospecting for novel natural products. Unfortunately, literature about the bioactive potential of their associated prokaryotes, including actinobacteria remains limited. In this context, this review focused on actinobacteria with antibiotic-producing capabilities derived from different parts of seagrass plants (i.e. roots, rhizomes, and leaves). To date, there were no purified molecules derived from seagrass-associated actinobacteria that were subjected to structure elucidation. From the underpinning of numerous biological profiles such as antibacterial, antifungal, and algicidal activities of seagrass-derived actinobacteria reported in this review during the period from 2012–2020, it provides a continual growth of knowledge accruing overtime, providing a foundation for future research. Mini Review Thu, 29 Feb 2024 00:00:00 GMT GalanaSiro, AtanasPipite, Thu, 29 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100838 https://www.explorationpub.com/Journals/eds/Article/100839 Pharmaceutical interventions play a vital role in managing various conditions, including weight-related issues such as obesity. In this context, lifestyle changes are often challenging to maintain, especially for individuals struggling with this condition. Obesity is strongly linked to serious health conditions like cardiovascular disease and insulin resistance, leading to a cascade of health risks. Importantly, the development of effective and safe weight loss medications has been challenging. Diabetes mellitus (DM), the incidence of which is also rising, is closely related to obesity. The annual rate of DM cases has increased significantly, mirroring trends in obesity. Pharmaceutical companies have made significant progress in developing drugs that address both diabetes and obesity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a promising class of medications with dual benefits in managing diabetes and aiding weight loss such as semaglutide, liraglutide, dulaglutide, exenatide, among others. However, despite their effectiveness, they can be expensive. The availability of various GLP-1RAs offers flexibility in diabetes management, but the surge in their prescription has led to a global shortage. Health authorities are working to address this issue, while pharmaceutical companies are exploring new paths to improve the quality of these drugs. In this context, tirzepatide stands out as a medication targeting key hormones involved in obesity and DM. Another potential breakthrough, retatrutide, is also being developed for these two conditions, but it requires further research. In this paper, the authors address all the GLP-1RA options developed to date, covering their mechanisms of action, efficacy, and chemical structures, among other aspects. Review Wed, 03 Apr 2024 00:00:00 GMT Alexander C.Martins, Beatriz G.de la Torre, FernandoAlbericio, Wed, 03 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100839 https://www.explorationpub.com/Journals/eds/Article/100840 Five families of investigational products are in clinical investigation to slow or reverse normal aging processes [longevity candidates, mesenchymal stem cells, senolytics drugs, sirtuin activators, and nicotinamide adenine dinucleotide (NAD)+ precursors]. The longevity candidates, vitamin D and metformin, appear to significantly reduce all-cause mortality and prolong life expectancy. This should be confirmed by interventional studies. The mesenchymal stem cell family is the most advanced in clinical trial development [phase 2b randomized controlled trial (RCT)]. An allogeneic bone marrow stem cell preparation (Lomecel-B) reduced locomotor frailty in older people. The improvement in locomotion was modest. In the future, attempts could be made to improve potency through a precondition or genetic modification of naive bone marrow stem cells. Autologous adipose stem cell-assisted fat grafting increased graft survival, facial volume, and skin quality. The association of the senolytic drugs dasatinib and quercetin was well tolerated, with low brain penetration of dasatinib and undetectable levels of quercetin. The sirtuin-1 activator resveratrol (combined with physical exercise) improved physical function in older adults with physical limitations. The NAD+ precursor nicotinamide riboside improved physical exercise performance. In conclusion, Lomecel-B is the most advanced agent in clinical trial development for normal aging processes (phase 2b for locomotion frailty), followed by resveratrol and nicotinamide riboside. Perspective Thu, 11 Apr 2024 00:00:00 GMT Ricardo P.Garay, Thu, 11 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100840 https://www.explorationpub.com/Journals/eds/Article/100843 With the surge of antibiotic resistance in bacteria, the need for a larger arsenal of effective antibiotics and vaccines has drastically increased in the past decades. Antibiotics like vaccines can benefit from significant potentiation when used in combination with adjuvants. Antibiotic adjuvants can allow for gram-positive bacteria (GPB) specific treatments to be used against gram-negative bacteria (GNB) infections, with minimal antimicrobial resistance (AMR). In the case of vaccines, they allow for modulation and increase of the immune response. Lipopeptides are molecules of choice because of their ability to activate specific cell surface receptors, penetrate the outer membrane of GNB, safety and ease of synthesis. This review explores the recent developments in lipopeptide adjuvants for antibiotics and vaccines, providing a roadmap on how to develop adjuvants to efficiently combat AMR. After a brief overview of bacterial resistance, lipopeptide adjuvants for antibiotics and vaccines are discussed, providing insights into stability, sources, and delivery methods. Findings discussed in this review could be applied to the development of safer, more effective adjuvants, that could expand the use or repurpose current antibiotics or improve vaccination results in future clinical trials. Review Tue, 30 Apr 2024 00:00:00 GMT Chloé O.Sebilleau, Steven J.Sucheck, Tue, 30 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100843 https://www.explorationpub.com/Journals/eds/Article/100841 Protein-protein interactions (PPIs) impersonate a significant role in many biological processes and are potential therapeutic targets in numerous human diseases. Stapled peptides, as the most promising therapeutic candidate for interfering with PPIs, have a higher degree of α-helicity, improved binding affinity, more resistance to proteolytic digestion, longer serum half-life, and enhanced cell permeability, which exhibits higher pharmacological activity compared with small molecule drugs and biologics. This review outlined the continuous progress of stapled peptides mainly concerning the design principle, structural stability, bioactivity, cell permeability, and potential applications in therapeutics, which is aimed at providing a broad reference for the design and exploration of stapled peptides with enhanced biological and pharmacokinetic properties as the next-generation therapeutic peptide drugs targeting various diseases. Review Thu, 18 Apr 2024 00:00:00 GMT QianZhang, ZiyangWang, XiaohanMei, QuanChen, ChunqiuZhang, Thu, 18 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100841 https://www.explorationpub.com/Journals/eds/Article/1008130 Not applicable. Correction Wed, 24 Sep 2025 00:00:00 GMT Maria G.Gorobets, Anna V.Toroptseva, Madina I.Abdullina, Vadim S.Pokrovsky, Derenik S.Khachatryan, Anna V.Bychkova, Wed, 24 Sep 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008130 https://www.explorationpub.com/Journals/eds/Article/100842 Cyclophane-containing peptides comprise an important group of macrocyclic peptides with unique structural properties and pharmaceutical relevance. Darobactin A is a ribosomally synthesized and post-translationally modified peptide (RiPP) antibiotic, which features an unusual biscyclophane moiety formed via the class-defining ether crosslink in addition to a carbon-carbon (C-C) crosslink. Because darobactin-like peptides (daropeptides) are widespread in nature, further exploration of these emerging RiPP natural products featuring ether crosslinked cyclophane could facilitate the discovery and development of new bioactive peptides. This perspective provides updated insights into the biosynthesis and classification of daropeptides, highlighting the potential to manipulate daropeptide maturases to access novel bioactive peptide cyclophanes. Perspective Fri, 19 Apr 2024 00:00:00 GMT SuzeMa, SijiaGuo, WeiDing, QiZhang, Fri, 19 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100842 https://www.explorationpub.com/Journals/eds/Article/100844 Aim: Isoliquiritigenin (ISL) is a natural flavonoid found in many natural plants, which exhibits numerous pharmacological properties including anti-inflammatory, antioxidant, antitumor, and antiviral activities. However, the low bioavailability and stability of ISL limit its application in clinical practice. To overcome these limitations, ISL-zein phosphatidylcholine hybrid nanoparticles (ISL@ZLH NPs) have been developed to improve the bioavailability and stability of ISL. The present study aimed to evaluate the acute and subacute toxicity of ISL@ZLH NPs in Sprague-Dawley (SD) rats. Methods: The ISL@ZLH NPs were prepared by the solvent evaporation method. The acute toxicity was evaluated by administering a single dose of 110 mg/kg and 160 mg/kg of ISL@ZLH NPs extracted in distilled water via oral gavage in rats and mice, respectively. The subacute toxicity was evaluated by administering doses of 27.5 mg/(kg∙day), 55 mg/(kg∙day), and 110 mg/(kg∙day) of ISL@ZLH NPs for 30 days and 90 days. The biochemical, hematological, and histopathological parameters were analyzed in both studies. Results: In the acute toxicity study, no mortality or significant changes in the biochemical and hematological parameters were observed in both Kunming (KM) mice and SD rats. In the subacute toxicity study, no toxic reactions were observed in both species at all doses tested. Moreover, no significant changes in the biochemical, hematological and histopathological parameters were observed in both species. Conclusions: The results of this study suggest that ISL@ZLH NPs are safe and non-toxic in both KM mice and SD rats. The nanoparticles (NPs) did not induce any adverse effects on the biochemical, hematological, and histopathological parameters in both acute and subacute toxicity studies. These results indicate that ISL@ZLH NPs are safe for prolonged consumption. Further studies are needed to evaluate the long-term toxicity and efficacy of these NPs in vivo. Original Article Tue, 30 Apr 2024 00:00:00 GMT KeYang, KumarGanesan, FeiGao, ChunguangXie, JianpingChen, Tue, 30 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100844 https://www.explorationpub.com/Journals/eds/Article/100845 Aim: The purpose of this study is to conduct a comprehensive investigation into the modulatory effects of Stryphnodendron adstringens (Mart.; S. adstringens), a Brazilian wound-healing plant, on the expression of inflammatory cytokines. This will be achieved using an in vitro protocol with the commercial macrophage cell line RAW 264.7. Methods: The macrophage inflammatory response was induced by the natural antigen phytohemagglutinin (PHA), with and without supplementation of different concentrations of S. adstringens extract. The effects on cell proliferation rate and the concentration and production of transcripts of pro-inflammatory cytokines interleukin 1β (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ), as well as the anti-inflammatory cytokine IL-10, were assessed using spectrophotometric, immunoassay, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) techniques. Results: S. adstringens extract at all concentrations tested here reduced the cellular proliferation rate of activated macrophages. Extracts at concentrations of 0.49 mg/mL and 0.99 mg/mL decreased the protein and gene expression of pro-inflammatory cytokines, exhibiting the opposite effect concerning IL-10. Conclusions: The findings suggest that the wound-healing action of S. adstringens may encompass differential modulation of inflammation associated with tissue injury. Original Article Sat, 11 May 2024 00:00:00 GMT Ivana Beatrice Mânicada Cruz, Cibele FerreiraTeixeira, Neida LuizaPellenz, Moisés HenriqueMastella, Verônica FarinaAzzolin, Euler EstevesRibeiro, FernandaBarbisan, Sat, 11 May 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100845 https://www.explorationpub.com/Journals/eds/Article/100846 The potent pain-relieving properties of opioids come at a steep price. Their addictive nature and side effects raise critical concerns in managing pain after surgical spine procedures. Postoperatively, spinal surgeries often accompany acute intense pain, which presents a significant challenge in optimal recovery. This paper reviews the historical approach to pain management in spine surgeries and expands on the use of alternatives and novel agents with reduced addictive potential. Additionally showcasing individualized multimodal strategies for postoperative pain management beyond pharmacological approaches such as cognitive behavioral therapy (CBT), physical therapy, and transcutaneous electrical nerve stimulation (TENS). Given the global opioid addiction crisis, there is a growing need for a fundamental shift towards safer and effective alternatives. Transitioning beyond opioid-centric practices in spinal surgery can optimize pain relief while improving patient outcomes and minimizing risk. Mini Review Tue, 21 May 2024 00:00:00 GMT Ashley M.Carter, SamanthaYost, JessicaTobin, SimranPhuyal, BrandonLucke-Wold, Tue, 21 May 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100846 https://www.explorationpub.com/Journals/eds/Article/100847 Aim: New microtubule-targeting agents are needed to improve cancer treatment. The recent characterization of the anticancer alkaloid securinine as a tubulin-binding agent prompted us to explore the interaction of related monomeric and dimeric analogues with tubulin. The interaction between the α/β-tubulin dimer and alkaloids fluevirines A–F and flueggenines A–I, isolated from the bush Flueggea virosa (Roxb. ex Willd.) Royle, was investigated using molecular docking. Methods: Two molecular models were initially compared for the binding of securinine to α/β-tubulin. The pironetin-binding site model (5FNV) was selected for the subsequent docking analysis with all compounds. Empirical energies of interaction (ΔE) were measured and compared. Results: Fluevirine A has been identified as a potent tubulin binder. This dimeric alkaloid formed more stable complexes with tubulin than the monomeric counterparts, such as fluevirines B–D. The bis-indole derivative fluevirine E also provided more stable complexes than (nor)securinine. The study was extended to the dimeric alkaloids flueggenines A–I and three compounds were identified as potential tubulin binders: the polycyclic product flueggenine B, the norsecurinine-indole hybrid flueggenine E, and the norsecurinine dimer flueggenine I. This later compound proved to be well adapted to fit into the pironetin site of tubulin, extending its two norsecurinine units between the colchicine-binding area and the pironetin site, in close proximity to the pironetin-reactive cysteine-316 residue. Structure-binding relationships were delineated. Conclusions: The study identifies the dimeric alkaloids fluevirine A and flueggenine I as potential α-tubulin binding agents. For the first time, dimeric alkaloids including two C-C connected norsecurinine units are characterized as tubulin ligands. The study contributes to a better understanding of the mechanism of action of Flueggea alkaloids and should help the design of anticancer analogues targeting the pironetin site of α-tubulin. Original Article Tue, 21 May 2024 00:00:00 GMT GérardVergoten, ChristianBailly, Tue, 21 May 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100847 https://www.explorationpub.com/Journals/eds/Article/100848 In recent times, there has been a revolutionary surge in antioxidant research, with a focus on harnessing microalgae to enhance wellness and extend human longevity. Microalgae, a diverse group of unicellular photosynthetic organisms, have emerged as promising sources of natural antioxidants due to their ability to synthesize various bioactive compounds, including carotenoids, polyphenols, and tocopherols. These antioxidants play a pivotal role in scavenging free radicals and reducing oxidative stress, known contributors to aging and chronic diseases. This review provides an over-view of recent advancements in understanding microalgae’s antioxidant potential, covering their biochemical composition, extraction techniques, and purification methods. Moreover, it delves into compelling in vitro and in vivo studies showcasing microalgae-derived antioxidants’ protective effects against oxidative damage, inflammation, cardiovascular diseases, and neurodegenerative disorders. The sustainable cultivation of microalgae in controlled environments further supports the potential for large-scale production and commercialization of their antioxidant compounds. As microalgae continue to revolutionize antioxidant research, they hold immense promise in developing novel preventive and therapeutic strategies to promote human health and wellbeing. Review Fri, 31 May 2024 00:00:00 GMT LeonelPereira, JoãoCotas, AnaValado, Fri, 31 May 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100848 https://www.explorationpub.com/Journals/eds/Article/100849 Aim: This study was aimed at finding the binding site on the human E-cadherin for Ala-Asp-Thr Cyclic 5 (ADTC5), ADTC7, and ADTC9 peptides as blood-brain barrier modulator (BBBM) for determining their mechanism of action in modulating the blood-brain barrier (BBB). Methods: ADTC7 and ADTC9 were derivatives of ADTC5 where the Val6 residue in ADTC5 was replaced by Glu6 and Tyr6 residues, respectively. The binding properties of ADTC5, ADTC7, and ADTC9 to the extracellular-1 (EC1) domain of E-cadherin were evaluated using chemical shift perturbation (CSP) method in the two dimensional (2D) 1H-15N-heteronuclear single quantum coherence (HSQC) nuclear magnetic resonance (NMR) spectroscopy. Molecular docking experiments were used to determine the binding sites of these peptides to the EC1 domain of E-cadherin. Results: This study indicates that ADTC5 has the highest binding affinity to the EC1 domain of E-cadherin compared to ADTC7 and ADTC9, suggesting the importance of the Val6 residue as shown in our previous in vitro study. All three peptides have a similar binding site at the hydrophobic binding pocket where the domain swapping occurs. ADTC5 has a higher overlapping binding site with ADTC7 than that of ADTC9. Binding of ADTC5 on the EC1 domain influences the conformation of the EC1 C-terminal tail. Conclusions: These peptides bind the domain swapping region of the EC1 domain to inhibit the trans-cadherin interaction that creates intercellular junction modulation to increase the BBB paracellular porosity. Original Article Thu, 27 Jun 2024 00:00:00 GMT ElinazFarokhi, Ahmed L.Alaofi, Vivitri D.Prasasty, FiliaStephanie, Marlyn D.Laksitorini, KrzysztofKuczera, Teruna J.Siahaan, Thu, 27 Jun 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100849 https://www.explorationpub.com/Journals/eds/Article/100850 Traditional medicine systems worldwide utilize natural products (NPs), including plant-derived compounds, minerals, and organisms, harnessing their healing potential. NPs offer a rich source of potential drug candidates, driving innovation in drug discovery. Recent breakthroughs have reignited interest in harnessing the therapeutic benefits of natural compounds. Clinical applications of NP-based immunotherapies, such as curcumin and resveratrol in cancer treatment, highlight their diverse pharmacological properties. However, despite these advancements, challenges persist in the clinical implementation of NPs. Issues such as standardization, regulatory approval, and supply sustainability remain significant hurdles. Overcoming these limitations requires a concerted effort to address the complexities of NP drug development. Nevertheless, ongoing research efforts and interdisciplinary collaboration hold promise for advancing NP-based therapeutics, paving the way for the development of innovative treatments for various diseases. In the world of precision medicine, a new chapter unfolds as NPs join the therapeutic journey. The exploration of NPs as sources of bioactive compounds has revealed promising prospects for precision therapeutics in medicine. This article explores the therapeutic potential of NPs within the context of precision medicine. It examines the intricate pathways through which bioactive compounds derived from nature offer tailored therapeutic prospects, emphasizing their role in precision medicine interventions. Exploring the synergy between NPs and precision therapeutics at a molecular level, this article delineates the exciting prospect of customized treatments, signifying a transformative impact on modern medical care. The review article further highlights their potential in tailoring treatments based on individual genetic makeup and disease characteristics. Additionally, it discusses challenges and prospects, addressing issues of sourcing, standardization, scalability, and regulatory considerations to realize the full therapeutic potential of NPs. Review Thu, 27 Jun 2024 00:00:00 GMT Maya G.Pillai, HelenAntony, Thu, 27 Jun 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100850 https://www.explorationpub.com/Journals/eds/Article/100851 Premature aging can be partially explained by inefficient autophagy (the process of cellular self-digestion that recycles intracellular components) and premature senescence (cease of cellular division without cell death activation). Autophagy and senescence are among the basic biochemical pathways in plants and fungi suggesting that some of their metabolites have the potential to act as autophagy inducers (AI) and senescence inhibitors (SI) and to inhibit inflammation and human aging. Several compounds have already been identified: trehalose and resveratrol are natural compounds that act as AI; flavonoids found in fruit and vegetables (curcumin, quercetin, and fisetin) are among the first SI discovered so far. New AI/SI can be identified using various approaches like hypothesis-driven approach for screening receptor agonists using an in-silico library of thousands of natural compounds; cheminformatics studies of phytochemicals using docking and molecular dynamics simulation, structure similarities/mimicry in vitro, “blind” high throughput screening (HTS) of libraries of natural metabolites against relevant models, and more. This article aims to promote the use of plant and fungi novel resources to identify bioactive molecules relevant for healthy aging based on the knowledge that plants and fungi use autophagy and senescence mechanisms for their own survival and homeostasis. As autophagy and senescence are interconnected, how drugs targeting autophagy, senescence, or both could contribute to healthy aging in humans will be speculated. Perspective Tue, 02 Jul 2024 00:00:00 GMT RivkaOfir, Tue, 02 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100851 https://www.explorationpub.com/Journals/eds/Article/100852 Aim: Evaluate the selective cytotoxic effect of the palindromic sequence RWQWRWQWR and its analogues obtained by replacement of L-amino acids by D-amino acids or the functionalization by adding the RGD (integrin ligand motif) to the peptide. Methods: Peptides were obtained by SPPS, characterized by RP-HPLC and ESI-QTOF and its biological activity was evaluated using MTT assays. Evaluation of mechanism associated to the cytotoxic effect were carried out by flow cytometry, RT-qPCR, wound healing, transwell and zymography. Results: The peptides with replacements of D-amino acid showed a lesser cytotoxic effect against breast cancer cell lines, regardless it was one or several residues modified which suggested a possible specific interaction between the peptide and the cancer cell membrane besides its initial electrostatically contact. On the other hand, addition of the RGD sequence to the palindromic peptide in the N-terminal end resulted in a greater cytotoxic effect against cell lines derived from the three mainly diagnosed breast cancer molecular subtypes. An approximation on mechanisms associated to this effect was evaluated on MCF-7 cells, it shows that the peptide induced apoptosis by activating intrinsic and extrinsic pathway, which correlates with the possibility of a specific interaction, and induces mitochondrial depolarization with release of oxygen reactive species. Also, this peptide induces a reduction in migration and invasion associated with a diminish in metalloprotease 9 activity and a lesser release of IL-6, IL-10 and arginase cytokines. Conclusions: Our results suggest that this promising peptide can be considered for preclinical evaluation in the development of drugs to treat breast cancer and thus mitigate the impact of this disease. Original Article Fri, 19 Jul 2024 00:00:00 GMT AndreaBarragán-Cárdenas, DanielCastellar-Almonacid, YerlyVargas-Casanova, ClaudiaParra-Giraldo, AdrianaUmaña-Pérez, JoelLópez-Meza, ZulyRivera-Monroy, JavierGarcía-Castañeda, Fri, 19 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100852 https://www.explorationpub.com/Journals/eds/Article/100853 Aim: The lipophilicity of amino acids plays a crucial role in delineating their physicochemical properties, offering insights into solubility, binding affinity, and bioavailability, properties that are a cornerstone for the use of peptides as therapeutic agents. In this study, we employ the integral equation formalism polarizable continuum model/Miertus-Scrocco-Tomasi (IEFPCM/MST) implicit solvation model to compute the n-octanol/water partition coefficient, serving as a lipophilic descriptor for non-standard amino acids. This approach allows us to expand upon our prior scale developed for canonical amino acids. Methods: Using the IEFPCM/MST implicit solvation model, we extended our previous work on the hydrophobicity scale of amino acids. To this end, we employed two structural models, Model 1 and 2, differentiated solely by their C-terminal capping groups using an N- or O-methyl substituent, respectively. Results: Our findings revealed substantial similarities between the models, validating the lipophilicity values for the non-standard side chains. Differences were observed in fewer cases, indicating an effect of the capping group on the side chain hydrophobicity. This effect is expected as one model contains a hydrogen bond donor (Model 1) while the other one uses a hydrogen bond acceptor (Model 2). Conclusions: Overall, both models exhibit good correlations with the experimental values, with Model 1 showing lower statistical errors. In addition, our predictions were able to correctly predict the experimental hydrophobicity change due to the number of acetylated lysines in peptide pairs determined by HPLC, suggesting that our scale can be employed for proteomics studies that include post-translational modifications beyond acetylation. Original Article Tue, 30 Jul 2024 00:00:00 GMT AntonioViayna, PaulinaMatamoros, DavidBlázquez-Ruano, William J.Zamora, Tue, 30 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100853 https://www.explorationpub.com/Journals/eds/Article/100854 Traditional medicines and their active ingredients and some natural products and derived analogs have been used for treating multiple diseases including cancer. Among these compounds cytotoxic agents such as bleomycin, paclitaxel and vincristine block essential pathways and genes required for cancer cell growth and these agents have diverse clinical applications. Dietary phenolics including flavonoids and related compounds are associated with multiple health benefits however most individual dietary compounds and other natural products that show promising anticancer activity in preclinical studies exhibit minimal clinical effectiveness and this is particularly true for cancer. Many of the compounds perform poorly in clinical trials due to pharmacokinetic consideration and limited uptake (e.g., curcumin) and these are issues that can be addressed. The clinical effectiveness of flavonoids and many other natural product-derived anticancer compounds can also be enhanced by a more targeted approach. This would include identifying a significant response/gene or target in a specific cancer and then identifying the optimal compound. In this review, I have discussed a limited number of targets including non-oncogene addiction genes such as Sp transcription factors, reactive oxygen species (ROS) or the orphan nuclear receptor 4A (NR4A) sub-family. Thus, the most active compound for these responses could be used only for treating patients that are ROS-inducible or highly express targets such as Sp1 or NR4A sub-family members. A mechanism-based precision medicine approach should enhance the clinical efficacy of dietary and related natural products as anticancer agents and decrease toxic side effects for some combination therapies. Review Tue, 30 Jul 2024 00:00:00 GMT StephenSafe, Tue, 30 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100854 https://www.explorationpub.com/Journals/eds/Article/100855 Coronavirus disease-2019 (COVID-19) has emerged as an aggressive viral infection in the last few years. Initially reported in the Wuhan area of the People’s Republic of China, it soon emerged across the globe. Researchers confront a worrying situation to rapidly develop effective strategies to combat this novel infection and its long-term aftereffects. To date, there have been myriad reports ranging from the repurposing of the classical antimalarial drug hydroxychloroquine to several other antiviral and anti-bacterial agents like remdesivir, favipiravir, and most recently azithromycin, which has entered clinical use in many countries for combating COVID-19 infections. Several studies have highlighted the nexus between COVID-19-associated morbidity and diabetes in a wide-ranging class of subjects ranging from pediatric cases to adults and patients with other co-morbidities. Metformin is a mainstay in the treatment of type 2 diabetes (T2D). It is safe, inexpensive, and effective and does more than merely control blood sugar levels. Important metabolites that encourage blood clotting and inflammation are also suppressed by metformin. Pro-inflammatory molecules are linked to obesity and T2D. Both are major risk factors for aggravated COVID-19. These characteristics gave rise to a hypothesis that metformin may find use as an efficacious treatment for COVID-19 especially if it decreases the inflammatory molecules that fuel the COVID-19 virus-induced effects. In this review, we attempt to elucidate the role of classical anti-diabetic medicine metformin in the treatment of COVID-19 infections by highlighting the pharmacological role of this drug during elevated glucose levels and insulin resistance. We examine how COVID-19 has correlations to diabetic physiology and thereby the possibility of repurposing metformin for COVID-19 treatment. Review Wed, 31 Jul 2024 00:00:00 GMT Gaurav KumarChaubey, RahulDilawari, RadheshyamModanwal, SharmilaTalukdar, AsmitaDhiman, ManojRaje, Wed, 31 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100855 https://www.explorationpub.com/Journals/eds/Article/100856 Age-related pathologies, particularly cardiovascular disorders, pose a significant global health concern. The World Health Organization (WHO) predicts an increase in advanced mortality by 2030 unless critical interventions are implemented. Atherosclerosis remains the major cause of various cardiovascular diseases. Hence, this review focused on the interaction between known mechanisms of vascular aging, disease manifestation, and progression during atherosclerosis. In the review, we highlighted five altered vascular mechanisms in cardiovascular models: genomic instability, neurohormonal deregulation, epigenetics, protein regulation, and the gut microbiome. The articles were selected from various indexed scientific databases. It is important to note that the mechanisms are equally interrelated with other aging pathways, such as inflammation and senescence. In conclusion, atherosclerosis is multifaceted and cholesterol-lowering therapy has been widely used. However, more than one specific action line is required to eradicate or slow down its manifestation. Equally, establishing a balance between aging stressors resulting in vascular injuries and stress buffering mechanisms during aging is critical to the treatment of atherosclerosis. The promising therapeutic targets reviewed include the angiotensin (1–7)/MAS axis, the gut microbiome, histone deacetylases, DNA repair systems, noncoding RNAs, β3/dopamine adrenoceptors, senescence and inflammation checkpoints. Review Fri, 02 Aug 2024 00:00:00 GMT Silumbwe CeaserWankumbu, Xiao-ManJi, MingXu, Fri, 02 Aug 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100856 https://www.explorationpub.com/Journals/eds/Article/100857 Aim: In this study, antioxidant activities and antibacterial activities of acetone and chloroform extracts obtained from Rosa canina, Echinacea purpurea, Althaea officinalis and Glycyrrhiza glabra were explored. Methods: Disc diffusion method and minimum inhibition concentration (MIC) assays were used to reveal antibacterial activity of the extracts. Total phenolic content, total flavonoid content, total antioxidant capacity, DPPH and ABTS radical scavenging activity tests were performed to determine antioxidant activity of the extracts. Results: Acetone extracts of the studied plants showed higher activity than chloroform extracts. Both acetone and chloroform extracts of G. glabra produced higher inhibition zones compared to other plant extracts. The highest total phenol content was found in acetone extract of G. glabra while the lowest total phenol content was found in chloroform extract of R. canina. The highest and lowest total antioxidant capacity was determined as 247.28 ± 0.0557 µg ascorbic acid equivalent (AAE)/mL and 50.91 ± 0.0294 µg AAE/mL in chloroform extract of A. officinalis and acetone extract of A. officinalis, respectively. Conclusions: In the light of the obtained data, it was concluded that R. canina, E. purpurea, A. officinalis and G. glabra can be used as alternative natural antibacterial and antioxidant sources to synthetic antibacterial and antioxidant agents. Original Article Thu, 22 Aug 2024 00:00:00 GMT SinemAydin, Thu, 22 Aug 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100857 https://www.explorationpub.com/Journals/eds/Article/100858 The presence of high-quality water is essential not only for human survival but also for the well-being of plants and animals. This research aimed to examine studies investigating the occurrence of antibiotics, endocrine disruptors, and other pharmaceutical products in water, sediments, and organisms within aquatic ecosystems. These substances have been linked to numerous adverse health effects on both humans and aquatic life, including reproductive issues and neurotoxic effects. The pervasive utilization of antibiotics in medical and agricultural domains has precipitated their ascension as formidable environmental contaminants. Effluents discharged from pharmaceutical industries constitute significant contributors to aquatic ecosystems’ contamination with antibiotics. These pharmacological agents permeate diverse environmental niches, spanning groundwater, surface water, soils, and wastewater treatment facilities, exhibiting concentrations ranging from nanograms to grams per liter. Concurrently, the indiscriminate and excessive application of antibiotics worldwide has engendered escalating apprehensions pertaining to antimicrobial resistance—a formidable global health exigency. This review also delves into the impact of pharmaceutical pollutants on aquatic environments, particularly as endocrine-disrupting compounds. Analysis of surface water in River Taff and River Ely reveals a consistent discharge of approximately 6 kilograms of pharmaceuticals per day. The study examines particular pharmaceuticals, such as diethylstilbestrol (DES), chlorotriazines, chloroquine, and antineoplastic drugs, elucidating their varied effects on reproductive cycles. Pharmaceutical pollutants in aquatic ecosystems, originating from sources like wastewater, agriculture, and improper disposal, persist and adversely affect organisms through bioaccumulation and biomagnification. These contaminants pose significant ecological and health risks, necessitating effective mitigation strategies. Review Thu, 29 Aug 2024 00:00:00 GMT Jaya VinnyEapen, SweetyThomas, ShelmiAntony, PaulGeorge, JayeshAntony, Thu, 29 Aug 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100858 https://www.explorationpub.com/Journals/eds/Article/100859 Leishmanial diseases, caused by various species of the protozoan parasite Leishmania, continue to pose a significant global health challenge. Medicinal drugs have been at the forefront of combating these diseases, offering hope for afflicted populations. This review article provides: (1) a comprehensive analysis of current knowledge and the evolving landscape of heterocyclic drug therapies for leishmanial diseases; (2) focusing on the mechanism of drug action; (3) therapeutic effects; (4) side effects; (5) potential future directions. The review begins by outlining the critical importance of heterocyclic drugs in treating leishmanial diseases. It highlights the diverse array of drugs used to combat Leishmania and elucidates the unique mechanisms underlying their efficacy. These mechanisms include disruption of cellular processes within the parasite, interference with DNA replication, and modulation of host immune responses. In addition, the article delves into the effects and side effects of drug therapy, providing an in-depth analysis of their impact on patients. It emphasizes the need for a fine balance between effective parasite clearance and minimizing adverse effects, stressing the importance of continuous research to refine drug regimens and reduce drug resistance. The review also explores various therapies for leishmanial diseases, from chemotherapy to immunotherapy, and discusses their advantages and limitations. Furthermore, it discusses ongoing research efforts aimed at developing novel drug formulations, such as liposomal and nano-carrier-based delivery systems, to enhance drug efficacy and reduce toxicity. This article crucially focuses on future perspectives in heterocyclic drug therapies for leishmanial diseases. It emphasizes the importance of interdisciplinary research and integrating emerging technologies, such as genomics and proteomics, to identify new drug targets and strategies for disease control. The potential for combination therapies and immunomodulators to improve treatment outcomes and combat drug resistance will also discussed. Review Fri, 06 Sep 2024 00:00:00 GMT TejaswiniMasne, DileepKumar, DeepaliBansode, Fri, 06 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100859 https://www.explorationpub.com/Journals/eds/Article/100860 Chemo-select modification of peptides, targeting a handful of the most reactive proteinogenic amino acids (AAs), is gradually utilized to address the medical needs of peptide drugs and biopharmaceuticals. Cysteine (Cys), one of the less abundant AAs in many biological proteins, plays a vital role in the catalysis, signal transduction, and redox regulation of gene expression. In natural AAs (α-AAs) residues, Cys exhibits high nucleophilicity and low redox-active potential, making it a primary target for site-selective conjugation. This review summarizes several representative Cys-peptide/protein conjugation strategies developed in recent years, including polar reactions, radical coupling reactions, and stapling techniques. Review Fri, 06 Sep 2024 00:00:00 GMT YanyanLiao, XuefengJiang, Fri, 06 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100860 https://www.explorationpub.com/Journals/eds/Article/100861 Aim: This study aimed to evaluate the utility of the combined use of contrast-enhanced ultrasound (CEUS) and intracavitary CEUS (IC-CEUS) with diluted SonoVue in the management of percutaneous treatment for pyogenic liver abscess (PLA). Methods: 36 patients (23 males, 13 females; mean age 64 ± 13.9 years) with 39 PLAs (mean size 7.6 ± 3.4 cm) were selected for percutaneous catheter drainage (PCD) and/or percutaneous needle aspiration (PNA). CEUS and IC-CEUS were employed during the interventional maneuver and follow-up during hospital stay in all cases. Results: 33 patients with 24 PLAs underwent PCD, 8 patients with 10 PLAs were treated with single or multiple PNA, and the combination of PCD and PNA was used in the remaining 5 cases. During the treatment planning phase, the combined use of CEUS and IC-CEUS affected therapeutic choices (e.g., drainage technique, additional therapeutic measures) in comparison with pre-operative imaging in 66.7% of patients. Throughout the follow-up period, CEUS and IC-CEUS facilitated monitoring of PLA evolution, providing crucial information, especially with IC-CEUS, on the optimal timing of catheter removal. No adverse events occurred after CEUS and IC-CEUS. Conclusions: The combination of CEUS and IC-CEUS proved to be a powerful and safe tool for tailoring US-guided percutaneous treatments to patients with PLA. Original Article Sat, 14 Sep 2024 00:00:00 GMT GiampieroFrancica, Sat, 14 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100861 https://www.explorationpub.com/Journals/eds/Article/100862 Glioblastoma (GBM) remains a formidable challenge in neuro-oncology due to its aggressive nature and propensity for therapeutic resistance. Anti-vascular endothelial growth factor (VEGF) therapies, although promising, often encounter resistance that limits their clinical efficacy. A multi-target and multi-drug approach has emerged as compelling strategies to address this resistance to enhance the treatment outcomes. This review examines the complex environment of anti-VEGF resistant GBM and analyses a multi-target therapeutic approach using natural products. Review Sat, 14 Sep 2024 00:00:00 GMT Sasikumar JalajakumariSoumya, Kesavan RathiArya, Chandran SheelaAbhinand, PadmanabhanSunitha, Ajitha PrabhakaranAthira, Achuthsankar SukumaranNair, Oommen V.Oommen, Perumana R.Sudhakaran, Sat, 14 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100862 https://www.explorationpub.com/Journals/eds/Article/100863 Cervical cancer (CaCx) is the fourth most prevalent cancer in women contributing to 341,831 annual deaths globally in 2020. Owing to its high mortality rate, the identification of novel inhibitors preventing CaCx progression is of utmost importance. Recent studies have emphasized the use of phytochemicals for cancer prevention due to their low toxicity. Psoralidin, a bioactive compound extracted from the seeds of the medicinal plant Psoralea corylifolia, showcases the potential for promoting health benefits. A range of studies showing anti-inflammatory, anti-oxidant, estrogenic, neuroprotective, anti-diabetic, anti-depressant, antimicrobial, and anti-tumor activities substantiate its promising biological effects. The anti-tumor potential of psoralidin has been well-documented. Its capacity to effectively target cancer stem cells (CSCs) in general adds to its therapeutic potential. Psoralidin carries out its anti-cancer activity by inducing oxidative stress, autophagy, and apoptosis. This unique characteristic suggests its potential to be used as an adjunct molecule in combination with existing treatment to enhance the efficacy of chemo/radiotherapy for treating CaCx. However, low bioavailability and intestinal efflux limit the use of psoralidin in clinical applications. Therefore, further investigation is needed in area of drug delivery and mechanism of action to fully harness the beneficial effects of psoralidin. The present study examines the current understanding of the molecular properties of this coumestan, as well as its various molecular targets with a particular emphasis on its anti-cancer activity. The study will help in designing effective and novel therapeutic interventions for targeting signaling pathways and other regulators involved in mediating CaCx progression, which will eventually help in effective management of CaCx. Review Tue, 24 Sep 2024 00:00:00 GMT TanyaTripathi, ApoorvaChaudhary, DivyaJanjua, UditJoshi, NikitaAggarwal, Chetkar ChandraKeshavam, Alok ChandraBharti, Tue, 24 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100863 https://www.explorationpub.com/Journals/eds/Article/100864 Aim: The aim of this research was to generate new peptide molecules with cytotoxic activity against cervical cancer that can become effective in mitigating the impact of the disease and preventing its progression. The design is based on the hybrid peptide formation strategy that allows new chemical entities to be obtained from the union of fragments of different bioactive peptides. Specifically, we worked by combining the RWQWRWQWR sequence derived from bovine lactoferricin with different functional peptides such as anticancer peptides, cervical cancer cell-targeting peptides, and cell-penetrating peptides. Methods: Hybrid peptides and precursors were synthesized by solid-phase peptide synthesis using the Fmoc/tBu strategy, purified via reverse phase (RP)-solid phase extraction, and characterized by RP-high performance liquid chromatography (RP-HPLC) chromatography and mass spectrometry. In vitro cytotoxicity of hybrid peptides in human cervical cancer cells lines HeLa and Ca Ski was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: All hybrid peptides were obtained with high purity and the experimental mass corresponds with the theoretical mass. Some hybrid peptides exhibited significant, fast, and selective cytotoxic activity against the cancerous cells evaluated, specifically those containing sequences of anticancer peptides and cell-penetrating peptides. The cytotoxic effect exerted by the monomeric and dimeric hybrid peptides depended on the concentration of the peptide, which allowed the determination of the IC50 values and the selectivity index (SI). Conclusions: We obtained hybrid peptides with the core sequence RWQWRWQWR that are active against HeLa and Ca Ski cell lines. The combination of the RWQWRWQWR sequence with short anticancer peptides and cell-penetrating peptides allowed the creation of hybrid peptides with improved cytotoxic potency against cervical cancer. Hybrid peptides constitute a novel, viable, and useful strategy for the design and identification of peptide drugs with anticancer activity. Original Article Fri, 27 Sep 2024 00:00:00 GMT NataliaArdila-Chantré, Claudia MarcelaParra-Giraldo, YerlyVargas-Casanova, Andrea CarolinaBarragán-Cardenas, RicardoFierro-Medina, Zuly JennyRivera-Monroy, Jhon ErickRivera-Monroy, Javier EduardoGarcía-Castañeda, Fri, 27 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100864 https://www.explorationpub.com/Journals/eds/Article/100865 Aim: Biofilms of pathogenic bacteria are phenotypically resistant to antibiotics and other antimicrobial agents, host immune systems, and adverse environmental conditions, and are responsible for most chronic infections. Antimicrobial photodynamic therapy (APDT) is based on using of photosensitizers (PS), which generate reactive oxygen species when exposed to visible or infrared light. Previously, we demonstrated the high efficacy of new polycationic bacteriochlorins as PS against biofilms of Gram-negative bacteria Pseudomonas aeruginosa in vitro. Now, we compared the toxicity of these PS to bacteria and human fibroblasts, under irradiation and in the dark. Another goal was to study the interaction of the PS with the biofilm matrix without irradiation. Methods: Photodynamic inactivation of eucaryotic cells was obtained with MTT test, and with plating of planktonic bacteria P. aeruginosa and biofilms after disrupting. The interaction of PS with the matrix was studied with electron microscopy, alcian blue staining, and quantitative evaluation of polysaccharides. Results: The absence of dark toxicity of polycationic bacteriochlorins BCl-6 and BCl-7 for human fibroblasts WI-38 at concentrations up to 200 µM and the selectivity of the studied PS to P. aeruginosa 32 bacteria, including these in biofilms, under irradiation, were found. After incubation of P. aeruginosa 32 biofilms with tetracationic BCl-6 and BCl-5 without irradiation, gross disturbances in the structure of the biofilm matrix were observed by SEM, as well as a significant reduction of Alcian blue staining and polysaccharides in the matrix. Conclusions: Polycationic bacteriochlorins BCl-6 and BCl-7 had no dark toxicity for human fibroblasts and were selective to P. aeruginosa 32 bacteria, including these in biofilms, under irradiation. The incubation of biofilms of Gram-negative bacteria with polycationic bacteriochlorin led to the destruction of the matrix without irradiation. Original Article Fri, 27 Sep 2024 00:00:00 GMT IrinaTiganova, YuliaZhizhimova, EteriTolordava, ElenaMakarova, NataliaShevlyagina, AlexanderBarmashov, MariaBaryshnikova, VladimirZhukhovitsky, YuliaRomanova, Fri, 27 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100865 https://www.explorationpub.com/Journals/eds/Article/100866 Envenomation caused by snakes, scorpions, and spiders represents a serious public health problem in Latin America. The antivenoms used for its treatment are produced by immunizing horses repeatedly with sublethal doses of animal venoms along with the adjuvant. However, venom availability is a bottleneck. Furthermore, toxin-neutralizing antibodies are only a few of the total produced with this classical method. Therefore, high doses of antivenom are required to achieve the neutralization power, which usually causes adverse reactions in the patient. With the aim of obtaining a higher proportion of toxin-neutralizing antibodies while reducing the dependency on venom availability, alternative immunization protocols have been explored using synthetic peptides with epitopes from clinically relevant toxins. The process to design an immunogenic peptide entitles: (a) choice of the medical relevant toxins in the venom; (b) identification of the epitopes in the selected toxins; (c) improvement of peptide immunogenicity; (d) immunogen synthesis; and e) in vitro and in vivo evaluation. The present article aims to review the advances in the design of immunogenic synthetic peptides for their application in antivenom production in Latin America during the 21st century. Epitopes have been identified from many clinically important toxins in Latin American snakes (snake venom metalloproteinases, snake venom serine proteases, crotamine, phospholipases A2, and three-finger toxins), scorpions (beta-mammal/insect toxin Ts1, alpha-mammal toxin Ts2, alpha-mammal toxin Ts3, toxin Ts4, and beta-mammal Tt1g neurotoxin), and spiders (dermonecrotic toxin and delta-ctenitoxin-Pn2a). Nevertheless, their application is still experimental, even though they are ideal for large-scale and low-cost antivenom production, factors that are necessary to meet national and regional demands. Review Mon, 30 Sep 2024 00:00:00 GMT Jésica A.Rodríguez, Gabriela R.Barredo-Vacchelli, Joaquin A.Eloy, Silvia A.Camperi, Mon, 30 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100866 https://www.explorationpub.com/Journals/eds/Article/100867 Migraine, a commonly occurring neurological disorder, disproportionately affects women during their reproductive years, and its symptoms are often intensified by hormonal fluctuations. This narrative review examines the impact of hormonal contraceptives, particularly combined oral contraceptives (COCs), on menstrual migraine (MM). This review assessed the impact of COCs on MM through a literature search in PubMed, Google Scholar, Web of Science, and Scopus using keywords like “menstrual migraine”, “hormone therapy”, and “COCs”. The selection criteria were peer-reviewed studies published between 2014 and 2024, written in English, and focused on MM treatment with COCs. Exclusion criteria were duplicates, editorials, irrelevant articles, and non-English studies. The literature reveals inconsistent results, with some studies reporting aggravation of migraine symptoms with COC use, whereas others indicate a decrease in the frequency and severity of attacks, especially with continuous use. Factors affecting these outcomes include patient age, menstrual cycle characteristics, and migraine type. It is crucial to choose contraceptives that suit individual patient profiles, considering the potential for increased migraine frequency or onset of migraine with aura in some women. Further studies are required to establish clear clinical guidelines. It is recommended to create personalized treatment plans that balance the effectiveness of migraine management with the overall health risks. Review Mon, 30 Sep 2024 00:00:00 GMT YethindraVityala, RuchikaGarg, SaminaAusvi, ManjulaShantaram, SrikanyaTippabathini, Lekhashree Hosur BrahmanandaReddy, YashJain, PavaniJaladi, Sai PraneethDuvvuri, Krishna ChaitanyaMeduri, Mon, 30 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100867 https://www.explorationpub.com/Journals/eds/Article/100868 Aim: The objective of this study was to evaluate the predictive performance of a proposed method to predict absolute bioavailability of medicines in children (infants to adolescents). Methods: From the literature, systemic and oral clearances as well as absolute bioavailability values for 15 medicines (28 observations across different age groups) from infants to adults were obtained. Systemic and oral clearances of these medicines in children were predicted using age-dependent exponent (ADE) allometric model using observed adult clearance values. Then using the predicted clearance values, absolute bioavailability was predicted in children. The predictive performance of the proposed method was evaluated by comparing the predicted absolute bioavailability of the studied medicines with the observed absolute bioavailability in children. Results: The results of the study indicated that the ADE model provided a good prediction of systemic and oral clearances in children from adult clearance values [89% and 82% observations within 0.5–1.5-fold prediction error following intravenous (IV) and oral administration, respectively]. The predicted absolute bioavailability by the proposed method was within 0.5–1.5-fold prediction error for 93% observations. Conclusions: This study indicated that it was possible to estimate absolute bioavailability of medicines in children with acceptable accuracy (within 0.5–1.5-fold prediction error) by the proposed method. The estimated absolute bioavailability in children could be useful in designing a first-in-children dose during pediatric drug development. Original Article Mon, 30 Sep 2024 00:00:00 GMT IftekharMahmood, Mon, 30 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100868 https://www.explorationpub.com/Journals/eds/Article/100869 Biochemist Svetlana Mojsov, both as a graduate student at The Rockefeller University under the mentorship of Bruce Merrifield during the 1970s, and as an independent investigator at the Massachusetts General Hospital (MGH) during the 1980s, devised effective and robust methods for the chemical synthesis of the peptide hormones glucagon and glucagon-like peptide (GLP-1), along with numerous analogues of these key biomolecules. Working separately from MGH’s powerhouse endocrine research laboratory, Mojsov developed a tool-kit of reliable assays that were indispensable to later in vitro and in vivo collaborative studies that established profound insulinotropic effects of this peptide family, findings that were subsequently harnessed clinically with blockbuster drugs directed at often-serious endocrine conditions such as type 2 diabetes and obesity. Significantly, Mojsov was the first to recognize the critical cleavage sites in preproglucagon that give rise to the biologically active species, a truncated form known as GLP-1 (7–37), and carried out the key experiments that proved her hypothesis. Despite being the first author on critical formative publications for the field, and being acknowledged, along with Joel Habener, as one of two co-inventors on the controlling United States patents, Mojsov’s foundational contributions were initially overlooked when GLP-1 biochemistry began to be the subject of major scientific prizes. Fortunately, Mojsov’s work has, within the past year, been better appreciated and deservedly lauded. Perspective Thu, 03 Oct 2024 00:00:00 GMT GeorgeBarany, Michael J.Barany, Thu, 03 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100869 https://www.explorationpub.com/Journals/eds/Article/100871 Aim: Develop technology to apply bicyclic peptides for discovering covalent inhibitors of proteases and use this technology to create bicyclic peptide—warhead conjugates for targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like (3CL) protease. Enhance the potency of the discovered bicyclic peptides for potential development into anti-SARS-CoV-2 drugs. Methods: Rational design was employed to discover the initial bicyclic peptide—warhead conjugates. Medicinal chemistry optimization was conducted to improve the potency of these peptides. Enzymatic assays and mass spectrometry characterization were performed to validate the covalent inhibition of the target protease. Results: The need for peptide display selection in discovering hit bicyclic peptides was overcome. Active bicyclic peptide—vinyl sulfone inhibitors with nanomolar potency were discovered. Optimization through medicinal chemistry strategies not only improved the potency of the peptides but also revealed residue preferences at individual positions of the bicyclic peptide inhibitors. The most potent bicyclic peptide can inhibit the target with a half-maximal inhibitory concentration (IC50) of 40.46 ± 6.35 nM. Mass spectrometry tests confirmed the covalent inhibition of the target protease by the developed peptides. Conclusions: Bicyclic peptide and vinyl sulfone conjugates are a form of covalent and potent inhibitors for targeting proteases. The rational design of bicyclic peptide ligands is feasible when structural and amino acid preference information is available. Structural information is also crucial for optimizing the potency of bicyclic peptide ligands. Original Article Thu, 17 Oct 2024 00:00:00 GMT QianWang, YanhuiWang, JianLi, HongLiu, ShiyuChen, Thu, 17 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100871 https://www.explorationpub.com/Journals/eds/Article/100872 The excessive use of antibiotics to treat bacterial infectious diseases in all living beings has caused a global epidemic of bacterial resistance to antibiotics, leading to the emergence of multidrug-resistant and pandrug-resistant strains. In 2019, the World Health Organization (WHO) reported that antimicrobial resistance causes at least 700,000 deaths per year worldwide. Therefore, in this global war against microorganisms, a therapeutic alternative is necessary to help us win this battle. A key in this race against the clock could be lactoferrin (Lf), a cationic glycoprotein of the mammalian innate immune system that is highly conserved among mammals. Lf is a multifunctional glycoprotein with immunomodulatory, anticarcinogenic, wound-healing, antioxidant, antimicrobial, and bone regeneration properties, in addition to improving the gut microbiota. Lf limits the growth of microorganisms through the sequestration of iron but can also interact directly with some components of the outer membrane of Gram-negative bacteria or bind to teichoic acids in Gram-positive bacteria, destabilizing the membrane and resulting in lysis. Moreover, cleavage of the Lf molecule could promote the production of lactoferricins (Lfcins) and lactoferrampin (Lfampin) from the N-terminal end, which are known to often have stronger antimicrobial effects than the native molecule, as well as analogous peptides, such as HLopt2, which have also shown enhanced antimicrobial activity. Bovine Lf (bLf) has been approved by the US Food and Drug Administration (FDA), and the European Food Safety Authority for its use as a dietary supplement in food products. Because of its effectiveness, accessibility, low cost, and nontoxicity, Lf could be a promising alternative for preventing or treating infections in animals and humans. Mini Review Tue, 22 Oct 2024 00:00:00 GMT LuceroRuiz-Mazón, GerardoRamírez-Rico, Mireyade la Garza, Tue, 22 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100872 https://www.explorationpub.com/Journals/eds/Article/100873 Phytochemicals, the bioactive compounds derived from plants, play a significant role in modulating pathways leading to cancer and inflammation, rendering themselves promising candidates for therapeutic interventions. This review explores the multifaceted potential of various phytochemicals in modulating key mechanisms involved in the development and progression of cancer and inflammation. The diverse array of phytochemicals discussed here encompasses polyphenols, flavonoids, alkaloids, terpenoids, and many others, each with distinct molecular targets and modes of action. This review is an attempt to elucidate and correlate the regulatory role of phytochemicals on cellular signaling pathways implicated in oncogenesis and inflammatory responses, highlighting the significance and potential of phytochemical-based therapies for cancer prevention and treatment, as well as for managing inflammatory conditions. By exploring the promising potential of phytochemical-based remedies for cancer prevention, treatment, and inflammatory conditions and emphasizing their diverse roles in modulating critical regulatory mechanisms, this review addresses the current research landscape, challenges, and future directions in utilizing phytochemicals as effective agents against cancer and inflammation. Review Wed, 30 Oct 2024 00:00:00 GMT Shifana C.Sadiq, Maria PellisseryJoy, Sreekumar U.Aiswarya, AbhishekAjmani, Chenicheri K.Keerthana, Tennyson P.Rayginia, NoahIsakov, Ruby JohnAnto, Wed, 30 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100873 https://www.explorationpub.com/Journals/eds/Article/100875 A very new and highly specialized category of radiotracers that is still growing is radiolabeled peptides. Radiolabeled peptides, or radiopeptides, are powerful elements for diagnostic imaging and radionuclide therapy. These laboratory-manufactured peptides have gained attention due to their unique properties. The tiny structure of these peptides compared to proteins and antibodies makes them favorable regarding their availability through simple synthesis from amino acids, easy uptake by receptors on cancer cells, and high specificity and affinity for high-quality and accurate radio imaging. This study highlighted the potential of technetium-99m-labeled peptides in advancing diagnostic capabilities in directed research in Latin America. Review Thu, 21 Nov 2024 00:00:00 GMT VaezehFathi Vavsari, SaeedBalalaie, Thu, 21 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100875 https://www.explorationpub.com/Journals/eds/Article/100876 In recent years, research efforts have increased to develop new therapeutics aimed at combating antibiotic-resistant bacterial infections. These efforts focus on inhibiting the virulence factors bacteria secrete to proliferate. This review aims to highlight the advances in these antivirulence therapies, with a particular emphasis on those utilizing peptides to inhibit toxin activity. Specifically, we will review the mechanism of action of a group of toxins known as Repeat in ToXins (RTX) and the progress made regarding the use of peptides to inhibit their action. Notably, we will discuss the use of peptides mimicking either cholesterol recognition/interaction amino acid consensus (CRAC) or CARC motifs, which are similar to CRAC motifs but have the opposite orientation, to reduce their interaction with cholesterol in target cells. We will present results corresponding to the inhibition of three characteristic toxins of this group: HlyA from Escherichia coli, LtxA from Aggregatibacter actinomycetemcomitans, and CyaA from Bordetella pertussis. While these advances are very recent, they are promising for the development of new therapies. The advantage of this type of therapy is that it reduces the selective pressure for the growth of resistant bacteria. Review Thu, 21 Nov 2024 00:00:00 GMT VanesaHerlax, Thu, 21 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100876 https://www.explorationpub.com/Journals/eds/Article/100877 Traumatic brain injury (TBI) is a complex disease that leads to significant mortality and disability worldwide each year. TBI disrupts the normal activity of kinases and molecular signaling pathways, but the effective therapeutic methods for patients remain limited. Nowadays, kinase inhibitors approved by the Food and Drug Administration (FDA) mainly for cancer treatment have shown potential effects in TBI. Preclinical studies suggest their potential in promoting recovery. There are fewer randomized clinical studies that evaluate efficacy. We search the kinase inhibitors approved by the FDA and traumatic brain injury as keywords on websites and analyze associated research. This review explores the therapeutic efficacy of kinase inhibitors, identifies limitations that must be addressed in future research to advance the application of FDA-approved kinase inhibitors, and emphasizes their promising potential. Review Mon, 02 Dec 2024 00:00:00 GMT DezhuGao, YuShi, ZhiliangWang, WeimingLiu, Mon, 02 Dec 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100877 https://www.explorationpub.com/Journals/eds/Article/100878 The FDA’s approval of resmetirom (Rezdiffra) marks a significant breakthrough in treating metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis, conditions linked to non-alcoholic fatty liver disease (NAFLD). MASH is a growing global health concern, and resmetirom offers a novel therapeutic option by targeting liver pathophysiology through thyroid hormone receptor-beta activation. This mechanism effectively reduces fibrosis markers, improves liver enzyme levels, and minimizes liver fat buildup. Clinical trials have shown that resmetirom has a favorable safety profile, with manageable side effects like diarrhea and nausea. Additionally, it may lower cardiovascular risks associated with MASH, enhancing patient outcomes and quality of life. As the first FDA-approved drug for MASH, resmetirom’s introduction fills a crucial treatment gap, providing new hope for millions of patients and representing a pivotal moment in hepatology. Short Communication Wed, 04 Dec 2024 00:00:00 GMT Muhammad MazharAzam, SameenMukhtar, MuhammadHaris, FatimaLaique, SuhainaAmir, MubashirMohiuddin, BibekGiri, Wed, 04 Dec 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100878 https://www.explorationpub.com/Journals/eds/Article/100879 Not applicable. Correction Wed, 04 Dec 2024 00:00:00 GMT LeonelPereira, JoãoCotas, AnaValado, Wed, 04 Dec 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100879 https://www.explorationpub.com/Journals/eds/Article/100881 Sirtuins are a family of NAD+-dependent class III histone deacetylases that regulate histones and other proteins. The mammalian sirtuins comprise seven members that have a role in energy metabolism, DNA repair, inflammation, cell survival, apoptosis, cellular senescence, oxidative stress, and mitochondrial production. Sirtuin modulation may have beneficial effects on aging and age-related diseases; thus, attracting a growing interest in discovering small molecules modifying their activity. A class of compounds both natural and chemically synthesized has emerged as sirtuin activators. This review discusses mammalian sirtuins in aging, the small molecules that activate sirtuins, modulation of sirtuin activity, and its impact in alleviating the effects of aging. Review Mon, 13 Jan 2025 00:00:00 GMT PujaSah, Anita K.Rai, DonkuparSyiem, Mon, 13 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100881 https://www.explorationpub.com/Journals/eds/Article/100882 Aim: To expand the understanding of the structure-activity relationship within a family of amino acid-derived β-lactam TRPM8 (transient receptor potential melastatin channel, subtype 8) antagonists, this work investigated both the configuration-dependence of potency and selectivity, and explored strategies for increasing total polar surface area (TPSA). Methods: Diastereoisomeric compounds derived from H-Phe-OtBu, and analogues incorporating differently substituted benzoyl groups, were synthesized by stereoselective solution pathways. Ca2+ microfluorometry assays were used for TRPM8 antagonist activity assessment, and then confirmed through electrophysiology (patch-clamp assay). The pharmacological activity in vivo was studied on a mice model of oxaliplatin-induced peripheral neuropathy. Results: For OtBu derivatives, a 3S,4S-configuration was preferred, while compounds with 2'R chiral centers show higher selectivity for TRPM8 versus transient receptor potential vanilloid, subtype 1 (TRPV1) than their 2'S-counterparts. N-terminal benzoyl derivatives, which increased TPSA values, resulted in equipotent compounds as previous prototypes, but also showed activity in other pain-related targets [TRPV1 and cannabinoid receptor, subtype 2 (CB2R)]. A selected N-benzoyl derivative displays antinociceptive activity in vivo. Conclusions: The potency and selectivity of these β-lactam TRPM8 antagonists developed from amino acid derivatives depend not only on the configuration but also on the substituents at the 4-carboxy and at the N-benzoyl groups. Dual and multitarget compounds were discovered within this family of TRPM8 antagonists. Original Article Tue, 14 Jan 2025 00:00:00 GMT CristinaMartín-Escura, Maria AngelesBonache, AliciaMedina-Peris, ThomasVoets, AntonioFerrer-Montiel, AsiaFernández-Carvajal, RosarioGonzález-Muñiz, Tue, 14 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100882 https://www.explorationpub.com/Journals/eds/Article/100883 The integration between the tumor-suppressive and oncogenic signaling pathways controls various cellular activities of cancer cells, including cell growth and apoptosis. While the activation of oncogenes fuels cancer progression and escape mechanisms, tumor suppressors regulate and counterbalance the negative effects of oncogenic signaling. Notably, phosphatase and tensin homolog (PTEN) constitute one of the important family members of tumor suppressor genes, which play critical roles in regulating the activities of tumor cells. Thus, an impaired, mutated, or loss of PTEN is associated with low survival or high tumor recurrence rates in cancer patients. Importantly, high tumor expression of a G-protein coupled platelet-activating factor-receptor (PAFR) is associated with increased tumor progression as well as decreased overall survival and poor prognosis in malignancies such as non-small cell lung cancer (NSCLC). Along similar lines, overactivation or mutations in epidermal growth factor receptor (EGFR) signaling are detected in various human malignancies and associated with poor prognosis. The goal of the current minireview was to highlight the significance of the mechanistic insights between the PTEN and PAFR as well as the PAFR and EGFR pathways in impacting cancer growth and/or efficacy of therapeutic agents in experimental model systems. Mini Review Wed, 15 Jan 2025 00:00:00 GMT AnitaThyagarajan, ZaidSirhan, Ravi P.Sahu, Wed, 15 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100883 https://www.explorationpub.com/Journals/eds/Article/100884 Microbial biotransformations are valuable tools from “green chemistry” and involve converting parental molecules into new daughter ones with unique physical, chemical, or pharmacological properties. These reactions are often carried out by cells grown under a planktonic phenotype. However, microbial cells grown under a phenotype of biofilm can improve biotransformation bioprocesses once they form more biomass per volume, are more resistant to extreme conditions (pH, temperature, and toxic substances), remain active for extended periods, are less prone to cell washouts, and reduce re-inoculation demands, leading to increased production rates due to their unique physiological features. In addition, experience has shown that biofilms may furnish a broader array of new daughter molecules. This review highlighted the benefits of using biofilms in microbial biotransformations to obtain a variety of bioactives. Mini Review Wed, 15 Jan 2025 00:00:00 GMT Nicoly Subtilde Oliveira, Romeu Cassiano Puccida Silva Ramos, Rafaela Caldasde Paula, Matheus Gonçalvesda Costa Pereira, Rosimeire TakakiRosa, Luiz FernandoBianchini, Edvaldo Antonio RibeiroRosa, Wed, 15 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100884 https://www.explorationpub.com/Journals/eds/Article/100886 Aim: The aim of this study was to examine the effectiveness and safety of lysozyme-based spray in the treatment of oral mucositis in patients undergoing head and neck radiotherapy. Methods: A prospective, open-label study was conducted on patients with ulcerative inflammation of the oral cavity and pharynx mucous membranes clinically assessed for oral mucositis according to the World Health Organization (WHO) Oral Toxicity Scale. Patients were randomly divided into a lysozyme group (using a spray containing lysozyme + cetylpyridinium + lidocaine) and a control group (using a compounded preparation containing gentamicin + dexamethasone + lidocaine). The efficacy and safety of therapy were evaluated on the baseline and three follow-up visits (7, 14, and 21 days after the baseline visit). Results: The total number of participants was 56, of which 26 were in lysozyme and 30 in the control group. The efficacy parameters were similar between the groups and there was no deterioration of symptoms during the follow-up period of 21 days. A significantly lower pain intensity when eating solid food was observed after 21 days in lysozyme compared to the control group. No adverse reactions were observed. Conclusions: This study showed the efficacy and safety of lysozyme-based spray for treating radiotherapy-induced oral mucositis. The availability of new treatment options based on lysozyme, a natural enzybiotic present in the saliva of healthy subjects, could bring added value to the treatment of oral mucositis and the prevention of its complications. However, a larger randomized, blinded study is needed to confirm our results [the study was registered at the Agency for Medicinal Products and Medical Devices of Bosnia and Herzegovina (https://klinicka.almbih.gov.ba/pages/klinicka-registar-javni) under the protocol number LCS-OM-01]. Original Article Thu, 23 Jan 2025 00:00:00 GMT ZdenkaGojković, JelenaRožić, NatašaGašpar, AzizŠukalo, MelihaMehić, AmnaTanović Avdić, UnaGlamočlija, Thu, 23 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100886 https://www.explorationpub.com/Journals/eds/Article/100887 Antibiotic resistance is a significant threat to public health and drug development, driven largely by the overuse and misuse of antibiotics in medical and agricultural settings. As bacteria adapt to evade current drugs, managing bacterial infections has become increasingly challenging, leading to prolonged illnesses, higher healthcare costs, and increased mortality. This review explores the critical role of antibiotics in fighting infections and the mechanisms that enable bacteria to resist them. Key antibiotics discussed include carvacrol, dalbavancin, quinolones, fluoroquinolones, and zoliflodacin, each with unique actions against bacterial pathogens. Bacteria have evolved complex resistance strategies, such as enzyme production to neutralize drugs, modifying drug targets, and using efflux pumps to remove antibiotics, significantly reducing drug efficacy. Additionally, the review examines the challenges in antibiotic development, including a declining discovery rate of novel drugs due to high costs and regulatory complexities. Innovative approaches, such as structure-based drug design, combination therapies, and new delivery systems, are highlighted for their potential to create compounds with enhanced action against resistant strains. This review provides valuable insights for researchers and developers aiming to combat antibiotic resistance and advance the development of robust antibacterial therapies for future health security. Review Sun, 26 Jan 2025 00:00:00 GMT Aiswarya M.Rajesh, Shraddha SubhashPawar, KruthiDoriya, RambabuDandela, Sun, 26 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100887 https://www.explorationpub.com/Journals/eds/Article/100885 Lutein, a natural dihydroxy carotenoid and a member of the non-vitamin A carotenoids family, is abundant in yellow-colored fruits and green leafy vegetables such as spinach and lettuce. As the second most common type of carotenoid found in human serum, lutein offers a plethora of medicinal benefits, including anti-cancer, anti-inflammatory, and anti-oxidative properties. It is well-absorbed and systemically localized to the liver, lung, and retina, where it can cross the blood-retina barrier and accumulate in the macular pigment. Due to its anti-oxidative and singlet oxygen quenching properties, lutein is reported to reduce the risk of age-related macular degeneration (AMD). Higher concentrations of fasting plasma carotenoids and enhanced skin yellowing after lutein consumption indicate its presence in various regions of the human body, including the skin, breast, brain, and cervix. Lutein has remarkable benefits for neurodegenerative diseases, cardiovascular health, liver protection, and bone disease prevention. In the central nervous system (CNS), lutein supports brain homeostasis through its antioxidant and anti-inflammatory properties, increasing interleukin-10 (IL-10) and reducing tumor necrosis factor-α (TNF-α). It reduces the risk of coronary artery disease and exerts anti-inflammatory effects on peripheral blood mononuclear cells (PBMCs). Lutein protects against alcohol-induced liver damage by modulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. Additionally, lutein promotes bone health by enhancing mineralized bone nodule development and inhibiting osteoclast production, reducing bone resorption, and suppressing soluble receptor activator of nuclear factor kappa B ligand (RANKL). These multifaceted benefits make lutein a valuable agent in disease prevention and health promotion. This review discusses the comprehensive profile of lutein as a phytochemical activity, including anti-inflammatory, antioxidant, anti-cancer, hepatoprotective, neurological, and cardioprotective effects. Additionally, it discusses lutein’s beneficial impact on macular degeneration and eye diseases, showcasing its potential as a natural, plant-based therapeutic agent. Review Sun, 26 Jan 2025 00:00:00 GMT ParadentavidaPrathyusha, GeethaViswanathan, Anjilikal TomyTomcy, Ponnamparambil P.Binitha, Smitha V.Bava, Edakkadath R.Sindhu, Sun, 26 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100885 https://www.explorationpub.com/Journals/eds/Article/100888 Over the last 60 years, only four new classes of antibiotics have been introduced, while the prevalence of antibiotic-resistant Gram-positive and Gram-negative bacteria has risen. This underscores the urgent need for new antibacterial therapeutics. This commentary leverages the recent exploration of γ-substituted-N-acylated-N-aminoethyl amino acid peptides (γ-AApeptides) to mimic the structures and function of natural antimicrobial peptides (AMPs), highlighting the promise and limitations for developing a new, effective treatment for antibiotic-resistant bacteria. Commentary Wed, 19 Feb 2025 00:00:00 GMT JaraisFontaine, JianfengCai, Wed, 19 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100888 https://www.explorationpub.com/Journals/eds/Article/100889 Aim: This research utilizes the ethanolic extract from seeds of Monodora myristica and its biosynthesized selenium nanoparticles (SeNPs) for the treatment of diabetic nephropathy (DN) in male Wistar rats. Methods: Biosynthesis of crystalline, quasi-spherical shape 5.0 ± 0.25 nm SeNPs was achieved using M. myristica seed extract as a reducing agent, followed by surface plasmon resonance measurement by ultraviolet-visible (UV-Vis) spectrophotometer, Fourier transformed infrared spectroscopy (FTIR), high-resolution transmission electron microscopy (HR-TEM), and selected area electron diffraction (SAED) for confirmation of nanoparticle biosynthesis. Male Wistar rats were induced with diabetes using a 3-weeks high-fat diet and a single intraperitoneal injection of streptozotocin (STZ). Experimental groups included normal control group, untreated diabetic controls and those treated with either metformin (a standard drug), ethanolic extract or biosynthesized SeNPs of M. myristica seed extract. Biochemical analyses assessed renal function via serum creatinine and urea levels. Histological evaluations of kidney tissues were performed to assess structural changes. Results: Treatment with M. myristica seed extract and its biosynthesized SeNPs significantly improved renal function, evidenced by reduced serum creatinine and urea levels. Histopathological studies showed preserved renal architecture and reduced inflammatory damage, particularly in the combination therapy group, indicating a synergistic effect. Conclusions: This study highlights the potential of M. myristica and its biosynthesized SeNPs in mitigating DN through nephroprotective mechanisms. These findings advocate for the exploration of nanotechnology combined with bioactive plant compounds as effective strategies for managing DN. Original Article Wed, 19 Feb 2025 00:00:00 GMT Babalola OlaYusuf, UsmanOkeme, Akeem OmolajaAkinfenwa, Ibrahim AdeolaMoronfolu, Zaynab AbiodunBisiriyu, Halimat YusufLukman, Olanrenwaju SuleimanOlakunle, Lateefat BelloAbdulfatah, Motunrayo AzeezatAiwinilomo, Rasheed BolajiIbrahim, Wed, 19 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100889 https://www.explorationpub.com/Journals/eds/Article/100874 Apoptosis is a crucial process to maintain the correct balance between healthy cells and committed-to-death cells in every tissue. The internal (or mitochondrial) and external (or death receptor) pathways are responsible for driving a series of molecular events that lead to apoptosis by releasing pro-apoptotic proteins, such as B-cell lymphoma-2 (BCL-2) homology 3 (BH3)-only proteins and second mitochondria-derived activator of caspases/diablo inhibitor of apoptosis protein-binding mitochondrial protein (SMAC/DIABLO), that in turn activate the caspase family of proteases. By counterbalancing the apoptogenic machinery, anti-apoptotic BCL-2 family members turn off pro-apoptotic signalling, favouring cell survival, a circumstance that is particularly pronounced in tumour cells in which apoptosis is deranged. Therefore, targeting the defective apoptotic process has become a viable therapeutic option for the treatment of several cancers and much effort is being made in the research and development of effective compounds. This review discussed and updated the most promising therapeutic strategies that target deranged apoptosis process in cancer by mimicking the pro-apoptotic effects of BH3-only and SMAC/DIABLO proteins. Review Mon, 11 Nov 2024 00:00:00 GMT AndreaVenerando, DeniseLovison, RossellaDe Marco, Mon, 11 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100874 https://www.explorationpub.com/Journals/eds/Article/100880 Throughout history, biopharmaceuticals have been essential in addressing health crises and enhancing human well-being. With advancements in genetic engineering, biotechnology, and bioinformatics, the development and approval rates of new biopharmaceuticals have surged, placing them at the forefront of the pharmaceutical field. Modern manufacturing processes and streamlined regulatory pathways have further expedited approval timelines, providing hope for previously untreatable conditions and significantly improving patients’ quality of life worldwide. However, despite these advancements, ambiguity persists regarding the definition of biopharmaceuticals due to the use of varied terms and a lack of standardized definitions. This article addresses this confusion by proposing a clear and comprehensive definition of biopharmaceuticals. Additionally, we present a reclassification of biopharmaceuticals into seven distinct verticals based on their functions. We assert that biopharmaceuticals not only offer superior therapeutic benefits for human health but also contribute to environmental sustainability, promoting a healthier planet. Thus, this article aims to clarify the scope of biopharmaceuticals and advocate for their broader adoption in the pursuit of global health and environmental integrity. Review Fri, 10 Jan 2025 00:00:00 GMT Abhay H.Pande, Yenisetti RajendraPrasad, J.Anakha, Fri, 10 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100880 https://www.explorationpub.com/Journals/eds/Article/100891 Aim: To identify peptides derived from bovine lactoferricin (LfcinB) as potential therapeutics for colon cancer treatment. We systematically modified dimeric peptides to enhance their selectivity against colon cancer cells and reduce toxicity. We examined the effects of specific changes, such as substituting L-arginine (Arg) with L-ornithine (Orn) and/or D-Arg, on cytotoxic activity in colon cancer cells, as well as activity in prostate and cervical cancer cell lines. Additionally, we assessed the type of cell death induced and the in vivo toxicity of the dimeric peptides. Methods: The peptides were synthesized by manual solid-phase peptide synthesis, purified by reverse phase-solid phase extraction (RP-SPE), and characterized by RP-high performance liquid chromatography (RP-HPLC), and mass spectrometry (MS). Their cytotoxic effect on cancer and non-cancerous cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The most promising dimeric peptide underwent scale-up synthesis to yield approximately 1 g. The type of induced cell death was analyzed through cytometry assays, while preliminarily toxicity studies were conducted in Galleria mellonella, zebrafish, and CD1 mice. Results: Our findings demonstrated that dimeric peptides containing L-Orn or D-Arg residues exhibited potent and selective cytotoxic effects against colon cancer cells (Caco-2 and HT-29), prostate cancer cells (DU-145), and cervical adenocarcinoma (HeLa). Notably, these modified peptides showed minimal toxicity in human erythrocytes, HEK 293 cells or fibroblasts, and Galleria mellonella larvae. Peptide 3: (R-Orn-WQWRFKKLG)2-K-Ahx, emerged as particularly promising, preserving its integrity and anticancer activity during scaled-up synthesis. Furthermore, peptide 3 induced behavioral changes and sedation in CD1 mice and showed significantly lower toxicity in zebrafish. Conclusions: The results suggested that specific modifications of Arg/Orn residues in dimeric peptides enhance their cytotoxicity against colon cancer cells and reduce in vivo toxicity. These modified peptides hold promise as safe and effective therapeutic candidates, potentially expanding the treatment options available for cancer. Original Article Wed, 26 Feb 2025 00:00:00 GMT Karen JohannaCárdenas-Martínez, Juan EstebanReyes-Calderon, Claudia MarcelaParra-Giraldo, YerlyVargas-Casanova, Andrea CarolinaBarragán-Cárdenas, RicardoFierro-Medina, Joel E.Lopez-Meza, Luis FernandoOspina-Giraldo, Zuly JennyRivera-Monroy, Javier EduardoGarcía-Castañeda, Wed, 26 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100891 https://www.explorationpub.com/Journals/eds/Article/100890 Ischemic stroke (IS) is a leading cause of death globally. IS occurs due to a blockage of cerebral arteries, leading to neuronal injury, tissue death, and brain infarcts. This induces lack of oxygenation to the brain which induces neuroinflammation, characterised by interactions involving molecules which can exacerbate brain damage but also aid recovery through processes like microglial phagocytosis. Post-stroke depression (PSD) affects 30–33% of stroke survivors, complicating recovery with various symptoms. The pathophysiology of PSD involves disruptions in the glutamatergic and monoaminergic systems, the gut-brain axis, and neuroinflammation. Agomelatine, an atypical antidepressant, can potentially treat both IS and PSD. It acts as a melatonin receptor agonist and a serotonin receptor antagonist, enhancing dopamine and norepinephrine availability in the prefrontal cortex. Agomelatine’s neuroprotective, anti-inflammatory, antioxidative, and antiapoptotic properties have been demonstrated in research, where it reduces reactive oxygen species (ROS) levels and activates the Nrf2 pathway, promoting antioxidative enzyme expression. Additionally, it prevents microglial activation by inhibiting the toll-like receptor 4 (TLR4)/nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) pathway, thus reducing inflammation. This review examines the pathophysiology of IS and PSD, highlighting agomelatine’s multifaceted therapeutic potential. Agomelatine’s distinct pharmacological profile and minimal side effects make it a compelling candidate for IS and PSD treatment, necessitating further exploration to optimise stroke management and improve patient outcomes. Review Tue, 25 Feb 2025 00:00:00 GMT AamnaArshad, Aqsa RafiqueShaikh, Syed HassanAli, Umais AhmedShaikh, Syeda KainatBibi, UmaymaNoor, KainatWajahat, FatimaLaique, MuhammadUmar, BibekGiri, Tue, 25 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100890 https://www.explorationpub.com/Journals/eds/Article/100892 Protein phosphorylation is a fundamental regulatory mechanism governing a broad spectrum of cellular processes. In the nervous system, it is critical for modulating neurotransmitter release, synaptic plasticity, neuronal excitability, and cell survival. Dysregulation of protein kinase activity is closely linked to the pathogenesis of various neurological and psychiatric disorders, positioning several kinases as promising therapeutic targets. Although protein kinase inhibitors (PKIs), a major class of compounds that modulate kinase activity, have shown considerable therapeutic success in oncology, their application in neurological diseases remains in the early stages of exploration. Of the 82 PKIs approved by the Food and Drug Administration (FDA), 37 are now in various preclinical and clinical trials for neurological conditions, primarily targeting signaling pathways mediated by key protein kinases implicated in these diseases. This review examines the roles of critical protein kinases and the therapeutic effects of their inhibitors in neurodegenerative, psychiatric, and selected neurological disorders, such as autism spectrum disorders (ASD) and epilepsy. We focus on Abelson kinase I (ABL1), calmodulin-dependent kinase II (CaMKII), casein kinase 1δ (CK1δ), c-Jun N-terminal kinase (JNK), cyclin-dependent kinase 5 (CDK5), dual-specificity tyrosine-phosphorylated and regulated kinase 1A (DYRK1A), leucine-rich repeat kinase 2 (LRRK2), extracellular signal-regulated kinase 1/2 (ERK1/2), glycogen synthase kinase 3β (GSK3β), mammalian target of rapamycin (mTOR), p38 mitogen-activated protein kinase, and protein kinase C (PKC) in neurodegenerative diseases. Additionally, we discuss CaMKII, CDK5, ERK1/2, PI3K/AKT/GSK3, protein kinase A (PKA), and PKC in psychiatric disorders, focusing on schizophrenia and mood disorders, and analyze GSK3β, ERK1/2, and mTOR in ASD and epilepsy. This review underscores the therapeutic potential of PKIs in neurological disorders while highlighting ongoing challenges and the need for further research to refine kinase-targeted therapies. Review Thu, 27 Feb 2025 00:00:00 GMT AngelaAsir R V, PolinaBuzaeva, IzhakMichaelevski, Thu, 27 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100892 https://www.explorationpub.com/Journals/eds/Article/100893 Bunium persicum Boiss. Fedtsch., a highly valued spice crop from the Apiaceae family, is renowned for its rich phytochemical profile, including compounds such as cuminaldehyde, α-terpinene-7-al, γ-terpinene-7-al, γ-terpinene, p-cymene, and β-pinene. These bioactive constituents contribute to its diverse therapeutic properties, including antioxidant, antimicrobial, anti-inflammatory, lipid and glucose-lowering, and anti-carcinogenic activities. Due to its limited growth in specific wild regions and over-exploitation, B. persicum faces significant conservation challenges, both in vitro and in situ. In India, its primary hotspots are in Jammu and Kashmir, Himachal Pradesh, and Uttarakhand. This review provides a comprehensive examination of B. persicum’s functional properties, with a focus on its traditional uses, phytochemistry, and pharmacological activities, highlighting the need for its conservation and sustainable use. Review Thu, 27 Feb 2025 00:00:00 GMT PrachiBhatt, SonalPant, ShaifaliBhardwaj, SamnaSneha, PriyanshuDobhal, MamtaBaunthiyal, Thu, 27 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100893 https://www.explorationpub.com/Journals/eds/Article/100895 Aim: This study evaluates the efficacy of amino-functionalized mesoporous silica nanoparticles (MSNs) in the controlled release of dexamethasone phosphate (DexaP), aiming to enhance therapeutic outcomes and minimize systemic toxicity. Methods: In this study, amino-functionalized MSNs were synthesized using a modified Stöber process and characterized their chemical and physical properties through various analytical techniques. The study focused on the adsorption and release kinetics of DexaP, employing multiple kinetic models to explore the interaction dynamics. Results: The amino-functionalized MSNs demonstrated effective DexaP loading and controlled release profiles. The kinetic analysis revealed a predominance of chemisorptive interactions, supporting sustained drug release. Enhanced biocompatibility was confirmed through cytotoxicity assays. Conclusions: Amino-functionalized MSNs offer a promising platform for the targeted and controlled delivery of anti-inflammatory drugs, with significant potential to improve patient adherence and reduce adverse effects. The findings advocate for further development of MSNs as a versatile tool in advanced drug delivery systems. Original Article Fri, 28 Feb 2025 00:00:00 GMT Juan ManuelGaldopórpora, María VictoriaOlivera, AngelinaIbar, Darío HernánFarriol, Martín FedericoDesimone, Cynthia Melisa MeliánQueirolo, HelenaPardo, María VictoriaTuttolomondo, Fri, 28 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100895 https://www.explorationpub.com/Journals/eds/Article/100896 Not applicable. Retraction Mon, 17 Mar 2025 00:00:00 GMT Juan ManuelGaldopórpora, María VictoriaOlivera, AngelinaIbar, Darío HernánFarriol, Martín FedericoDesimone, Cynthia Melisa MeliánQueirolo, HelenaPardo, María VictoriaTuttolomondo, Mon, 17 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100896 https://www.explorationpub.com/Journals/eds/Article/100897 Multiple drug-resistant Staphylococcus aureus bacterial pathogens are causative agents of serious infectious disease and are responsible for significant morbidity and mortality rates. Of particular concern in the public health domain are strains of methicillin-resistant S. aureus (MRSA), a member of the Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., Escherichia coli (ESKAPEE) group of bacterial pathogens, many of which are recalcitrant to effective chemotherapy in the clinical setting due to their resistance to multiple antimicrobial agents. An important mechanism that confers multi-drug resistance in MRSA involves the active efflux of structurally different antimicrobial agents by members of the major facilitator superfamily (MFS) of proteins. The multidrug efflux pumps of the MFS share similar amino acid sequences, protein structures, and a common evolutionary origin. As such, the multidrug efflux pumps of the MFS are thought to operate by a similar solute transport mechanism and, thus, represent suitable targets for modulating their transport activities. This review article addresses MRSA as a serious pathogen, the mechanisms of antimicrobial resistance, and the functional and structural roles of the multidrug efflux pumps of the MFS in conferring pathogenicity. Review Thu, 20 Mar 2025 00:00:00 GMT EbenezerAborah, MatthewAyitah, Kwesi FelixBoafo, AnelyOrtiz-Alegria, ManjushaLekshmi, Chandrashekar K.Dhanush, SanathKumar, Manuel F.Varela, Thu, 20 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100897 https://www.explorationpub.com/Journals/eds/Article/100898 4-Aminobenzoic acid (PABA, para-aminobenzoic acid) exhibits multifaceted therapeutic potential in neuropsychiatric disorders through its roles in neurotransmitter modulation, anti-inflammatory action, and antioxidant defense. Experimental and clinical evidence demonstrates that PABA enhances serotonin and dopamine synthesis by activating key enzymes (e.g., tryptophan hydroxylase and tyrosine hydroxylase), thereby stabilizing mood and improving cognitive function. Mechanistically, PABA suppresses neuroinflammation by inhibiting NF-κB signaling and cytokine production (e.g., IL-1β, TNF-α) while scavenging reactive oxygen species (ROS) to mitigate oxidative stress and protect neuronal integrity. Clinical studies indicate that PABA may synergize with traditional antidepressants by targeting serotonin reuptake transporters (SERT) and monoamine oxidase (MAO), offering improved outcomes in major depressive disorder. Despite promising results, further research is needed to optimize dosing regimens, validate long-term safety, and explore pharmacogenomic interactions. Crucially, experimental validation through cellular and animal models is required to substantiate PABA’s proposed mechanisms, particularly its regulation of NF-κB signaling and enzyme activity in neurotransmitter synthesis. This review underscores PABA’s potential as a neuroprotective agent and calls for integrated strategies to translate mechanistic insights into clinical applications for complex neurological conditions. Review Thu, 20 Mar 2025 00:00:00 GMT SiyuChen, YanSu, WeiyanWu, YutingChen, TiandongLin, YangyangLiu, Thu, 20 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100898 https://www.explorationpub.com/Journals/eds/Article/100899 Aim: To evaluate the efficacy of experimental propolis varnish containing 15% green propolis in reducing Streptococcus mutans (SM) from saliva and dental biofilms. Methods: Patients aged 8–11 years were recruited from a preventive program. After prophylaxis, propolis varnish was applied to collect saliva and biofilm samples at regular times (baseline/T0, 2nd day/T1, 3rd day/T2, 4th day/T3, 5th day/T4, 10th day/T5, 15th day/T6, and 30th day/T7). After each sampling, stimulated whole saliva was homogenized for 30 s, and tenfold serial dilutions in saline were plated on mitis-salivarius-bacitracin (MSB) agar and incubated at 37°C for 48 h. Colonies with typical morphology were counted, and the number of colony-forming units (CFU)/mL was compared via an independent sample t test. For quantitative real-time PCR (qPCR), the data were statistically analysed via one-way ANOVA with the Holm‒Sidak post hoc test. Results: There was a significant difference in salivary SM levels between T0/T1 (baseline/2nd day) and T1/T7 (2nd day/30th day), but no difference was observed from the 3rd day onwards. The qPCR results also revealed a decrease in the number of SMs in the biofilm in the first days after varnish application. Conclusions: A single application of green propolis varnish reduced SM in saliva and biofilms for three days. Whether these findings affect the incidence of caries needs to be confirmed through studies, which may improve the original formulation (International Clinical Trials Registry Platform registration code: NCT02052973). Original Article Fri, 21 Mar 2025 00:00:00 GMT Mariana PassosDe Luca, Pablo SilveiraSantos, Frederico MarianettiSoriani, Vagner RodriguesSantos, Fri, 21 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/100899 https://www.explorationpub.com/Journals/eds/Article/1008100 Proteins from the neurotrophin family perform trophic and regulatory functions in the nervous and other body systems. Understanding the mechanisms of neurotrophin action is crucial not only for the evolution of fundamental scientific knowledge but also for developing new treatment strategies targeting neurotrophin signaling regulation. At our center, dimeric dipeptide mimetics of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) have been obtained based on the structure of neurotrophins’ individual loops β-turns. These mimetics activated tyrosine kinase (Trk) receptors TrkA, TrkB, or TrkC specific to their respective neurotrophins, but exhibited varied activation patterns in the main post-receptor signaling cascades. Thus, some dipeptides activated all three main phosphoinositide 3-kinase (PI3K)/threonine-protein kinase (Akt), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and phospholipase C-gamma (PLC-γ) pathways, while others triggered only PI3K/Akt and PLC-γ or MAPK/ERK and PLC-γ. Herewith, dipeptides exhibited a specific set of effects (neuroprotective, differentiating, antidepressant-like, anxiolytic, memory-enhancing, analgesic, antidiabetic) within the spectrum of biological activities of their corresponding native neurotrophin. It was revealed that these effects are influenced by both the patterns of post-receptor signaling activation and the nature of progenitor neurotrophin, uncovering significant correlations. This article is dedicated to reviewing the data that has been collected. Review Fri, 21 Mar 2025 00:00:00 GMT TatianaGudasheva, PolinaPovarnina, VladimirDorofeev, Fri, 21 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008100 https://www.explorationpub.com/Journals/eds/Article/1008101 Folic acid (FA) residue is a well-known and widely spread targeting ligand, or biovector, used as a component in engineering artificial nanosized and submicron particles (NSPs) to target various cells and treat a variety of diseases that are associated with FA (or folate) receptors (FR) overexpression. A particular place in the list of these diseases is held by various cancer types, for which overexpression of FR on the cell surface is often accompanied by a more severe disease course, increased resistance to the conventional chemotherapy, and poorer prognosis. The incorporation of albumin into NSPs has been shown to enhance their biocompatibility, give high compatibility with drug molecules, prolong their circulation, reduce thrombogenic activity, and improve their colloidal stability. Nowadays albumin-based NSPs with FA residue as a targeting agent are used for chemotherapy, photothermal and photodynamic therapy, combined therapy, visualization, and theranostics (also known as theragnostics) for various types of cancer: breast, cervical, ovarian, prostate, nasopharyngeal, gastric, colorectal, liver cancer, and brain tumors. A limited number of studies have also focused on the use of NSPs in rheumatoid arthritis treatment. In this review, we discuss the ways of FA-albumin conjugation and conjugation of FA to albumin-modified NSPs systems. An application of nanosized and submicron delivery systems on the base of serum albumin and FA for therapy and diagnostics is discussed. Review Wed, 26 Mar 2025 00:00:00 GMT Maria G.Gorobets, Anna V.Toroptseva, Madina I.Abdullina, Vadim S.Pokrovsky, Derenik S.Khachatryan, Anna V.Bychkova, Wed, 26 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008101 https://www.explorationpub.com/Journals/eds/Article/1008102 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that causes a global epidemic named COVID-19. It still continues to plague humans with severe complications and unique sequelae, causing huge economic losses in the world. Pathophysiological studies showed that important life organs, such as the lungs, brain, kidneys, heart, liver, and immune system, and even reproductive ones are affected directly or indirectly in patients with COVID-19. Classically and newly discovered drugs, concerning antiviral replication, anti-inflammation, blockage of pathogenic processes, alleviation of symptoms, and especially distinctive multi-actions of Traditional Chinese Medicine, were screened out and tested, presenting promising therapeutic effects on the virus before or even though abundant effective vaccines come out. Moreover, other strategies are underway, including the use of plasma therapy, monoclonal neutralizing antibodies, vaccine trials, and emerging drugs with distinct interference mechanisms. This review features the novel progress on the latest-discovered antiviral drugs and the effective Traditional Chinese Medicine, and highlights the advantages and shortages of different therapeutic strategies and the predicted potential targets of the used Traditional Chinese Medicine components, which provides a valuable reference for clinical treatment continuously to combat COVID-19. Review Wed, 26 Mar 2025 00:00:00 GMT YongjiaXiong, YunLi, FeiyueXing, Wed, 26 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008102 https://www.explorationpub.com/Journals/eds/Article/1008103 Epstein-Barr virus (EBV), human papillomavirus (HPV), and hepatitis C virus (HCV) are significant human pathogens associated with various diseases, employing complex molecular mechanisms for cellular entry and immune evasion. Peptide-based research, using more than 700 synthetic peptides, has deciphered some of the molecular interactions between viral proteins and host cell receptors, offering promising diagnostics and therapeutic strategies. In EBV, binding peptides have been identified: 11382, 11389, and 11416 derived from gp350/220; 11435, 11436, and 11438 from gp85 [glycoprotein H (gH)]; and 11521 from BNRF1/p140. Most of these peptide sequences are surface-exposed and are part of the contact regions with human cell receptors, making them promising candidates for strategies aimed at inhibiting EBV invasion of human cells. Peptide 11382 is the target of the neutralizing antibody 72A1; peptides 11382 and 11416 induce interleukin-6 production; peptide 11435 binds to integrin αvβ6, and peptide 11438 triggers a cytokine storm. In the HPV L1 protein, a major component of the viral capsid, peptides 18283 and 18294 have been identified as epithelial cell-binding peptides located on the virus surface. Parts of the sequences are recognized by anti-HPV neutralizing antibodies. These two peptides, along with peptide 18301, have been identified as potential biomarkers for HPV infection because they are recognized by antibodies elicited during natural HPV infection, making them suitable targets for serological detection. In the envelope proteins E1 and E2 from HCV, five hepatocyte- and CD81-positive cell-binding peptides have been identified. The sequences of these peptides contain linear B-cell epitopes recognized by neutralizing antibodies, and some of them have been used to develop serological tests for determining HCV infection. Peptide-based approaches can lead to innovative strategies for the prevention, diagnosis, and treatment of these viral diseases. Additionally, these peptides and their sequences can be used to modulate the immune response and generate tools for cancer theragnostic. Review Wed, 26 Mar 2025 00:00:00 GMT DanielaPerdomo-Joven, FannyGuzmán-Quimbayo, MauricioUrquiza-Martinez, Wed, 26 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008103 https://www.explorationpub.com/Journals/eds/Article/1008104 Aim: This study aimed to computationally identify and optimize 4-hydroxy isoleucine (4HILe) derivatives from fenugreek as multitarget antidiabetic agents against α-glucosidase, α-amylase, and aldose reductase [PDB (protein data bank) IDs: 5NN8, 4GQR, 4QX4]. Methods: A multi-step computational workflow was employed to identify and optimize 4HILe derivatives as antidiabetic agents. Molecular docking using the Schrödinger Suite screened 23 ligands against three enzyme targets to evaluate binding affinities and interactions. Molecular dynamic (MD) simulations conducted with GROMACS (Groningen machine chemical simulations) over 100 ns assessed conformational stability through RMSD (root mean square deviation) and RMSF (root mean square fluctuation) analysis. Binding free energy calculations [MM-GBSA (molecular mechanics-generalized Born surface area)] and free energy landscape (FEL) studies are performed to validate the thermodynamics of protein-ligand interactions. Additionally, generative AI modeling using LigDream generated 100 novel compounds derived from 4HILe, subsequently validated through docking studies to identify promising inhibitors. Results: The study identified 4HILe-4, 2R-3S-4R-4HILe, and 4HILe-Amide-2 as potent derivatives with superior binding affinities [ΔG (Gibbs free energy): −49.3 to −42.3 kcal/mol] compared to co-crystal ligands (−45.3 kcal/mol), as determined by docking and MM-GBSA calculations. MD revealed stable protein-ligand complexes, evidenced by low RMSD values (0.2–0.4 nm) and minimal residue fluctuations (RMSF), confirming their structural integrity. The generative AI approach using LigDream also generated 100 novel 4HILe derivatives, with top candidates exhibiting strong docking scores and key molecular interactions against α-glucosidase, α-amylase, and aldose reductase. Notably, compound 10 (−9.424 kcal/mol), compound 4 (−8.167 kcal/mol), and compound 28 (−13.760 kcal/mol) emerged as promising inhibitors for further investigation. Conclusions: The study highlights 4HILe derivatives as promising inhibitors for diabetes-associated enzymes, demonstrating robust binding and dynamic stability. Integrating molecular dynamics, free energy calculations, and AI-driven generative modeling provides a strong framework for accelerating antidiabetic drug discovery. These findings pave the way for experimental validation and the development of next-generation therapeutics targeting insulin resistance and hyperglycemia. Original Article Thu, 10 Apr 2025 00:00:00 GMT Lakshmi MounikaKelam, Manjinder SinghGill, M. ElizabethSobhia, Thu, 10 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008104 https://www.explorationpub.com/Journals/eds/Article/1008105 Metabolic syndrome is a complex, multifactorial disorder, with emerging research emphasizing the significant role of gut health in its prevention and management. Recent studies suggest that dietary strategies promoting a healthy gut microbiome, including the incorporation of fiber, fermented foods, and healthy fats, are crucial for regulating metabolism. Additionally, the use of postbiotics and supplements, such as probiotics, omega-3 fatty acids, and polyphenols, provides promising avenues for enhancing metabolic health. This holistic approach to managing metabolic syndrome not only supports gut health but also offers the potential for improving long-term health outcomes. This review examines the influence of the gut microbiome on metabolism, highlighting the increasing significance of dietary strategies and supplements in managing metabolic syndrome. Review Tue, 15 Apr 2025 00:00:00 GMT SunilChopra, VandanaDahiya, AnuSaini, Ramendra PatiPandey, Tue, 15 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008105 https://www.explorationpub.com/Journals/eds/Article/1008106 Cancer remains the second leading cause of death globally, posing an ongoing threat to public health. A hallmark of cancer cells is their capacity to invade adjacent tissues and evolve into malignant forms, often resulting in aggressive tumors resistant to conventional treatments. At the heart of this therapeutic challenge are cancer stem cells (CSCs), which possess distinctive capabilities for self-renewal, differentiation, and generation of diverse tumor cell populations. These CSCs have been identified across multiple tissue types, including lung, colon, breast, pancreas, and ovary. Research has demonstrated that CSC subpopulations contribute significantly to therapeutic resistance, tumor recurrence, and metastasis by regulating multiple signaling pathways, making them compelling targets for cancer therapy. Notably, emerging evidence suggests that natural products may offer protective benefits against cancer development while potentially targeting CSCs. This review synthesizes current knowledge of CSCs, examining their identifying markers, isolation techniques, study methods, and associated signaling pathways. Additionally, we explore various natural products that specifically target CSCs across different cancer types, presenting potential strategies to address the persistent challenges of drug resistance and cancer relapse. Review Fri, 18 Apr 2025 00:00:00 GMT Julia K.Opara, SierraSanchez, Sufi MaryThomas, ShrikantAnant, Fri, 18 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008106 https://www.explorationpub.com/Journals/eds/Article/1008107 Aim: The development of selective and potent antitumor agents remains a significant challenge. This study aimed to synthesize and evaluate biaryl hydroxy-1,2,3-triazoles and 9H-fluorene-1,2,3-triazole hybrids, inspired by previously identified bioactive 1,2,3-triazoles, for their cytotoxic potential against human cancer cell lines. Methods: A library of 13 biaryl hydroxy-1,2,3-triazoles and 11 fluorene-1,2,3-triazoles was synthesized using optimized Suzuki and telescopic one-pot reactions, with yields ranging from 16% to 97%. The cytotoxicity of these compounds was tested against HCT-116 (colorectal cancer), SNB-19 (astrocytoma), MDA-MB-231 (triple-negative breast cancer), and MOLM-13 (acute myeloid leukemia, FLT3-ITD mutant) cell lines. Results: Two fluorene-triazoles, 1-(2-bromophenyl)-4-(9H-fluoren-9-yl)-1H-1,2,3-triazole (LSO258) and 1-(4-bromophenyl)-4-(2-fluoro-9H-fluoren-9-yl)-1H-1,2,3-triazole (LSO272), both containing bromine substituents, exhibited selective cytotoxicity against MOLM-13, with half-maximal inhibitory concentration (IC50) values of 25.5 μM and 12.5 μM, respectively. Furthermore, LSO258 and LS0272 showed a selectivity index ≥ 2 towards the MOLM-13 cell line. Biaryl hydroxy-1,2,3-triazoles displayed broader activity, with [1,1’-biphenyl]-2-yl(1-(2,5-dibromophenyl)-1H-1,2,3-triazol-4-yl)methanol (LSO278), featuring two bromine groups, demonstrating potency across HCT-116, MDA-MB-231, and MOLM-13 (IC50: 23.4 μM, 34.3 μM, and 18.7 μM, respectively). However, structural rigidity did not consistently predict activity, as 1-(2,5-dibromophenyl)-4-(9H-fluoren-9-yl)-1H-1,2,3-triazole (LSO275), a rigid fluorene-triazole, was inactive. MOLM-13 was the most sensitive cell line, with compounds such as 4-(9H-fluoren-9-yl)-1-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazole (LSO259) and (1-(4-bromophenyl)-1H-1,2,3-triazol-4-yl)(4’-fluoro-[1,1’-biphenyl]-2-yl)methanol (LSO280), achieving maximum growth inhibition (MGI > 55%) despite not reaching IC50 values. Conclusions: The results highlight the critical role of bromine substitution on the aryl azide-derived ring in modulating cytotoxic activity. The study reinforces the potential of rigid fluorene-based scaffolds as promising leads for the development of targeted therapies against FLT3-mutant leukemia, aligning with previous reports on 1,2,3-triazole hybrids antiproliferative activity in leukemia models. Original Article Tue, 22 Apr 2025 00:00:00 GMT David ChafiZeitune, Marcelo Folhadella Martins FariaAzevedo, MarianeSenna Rangel, Robertde Sousa Bastos, Joséde Brito Vieira Neto, Claudiado Ó Pessoa, Camilla DjenneBuarque, Tue, 22 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008107 https://www.explorationpub.com/Journals/eds/Article/1008108 Aim: The PI3K (phosphoinositide 3-kinase)-alpha isoform is found upregulated in 30–40% of breast cancer. Currently, there are limited selective and specific drugs that target PI3K-alpha, and no natural therapeutic option is available. This study aims to develop natural hybrid antagonists of PI3K-alpha for breast cancer therapeutics. Methods: 25 pan-PI3K and PI3K-alpha targeting drugs were obtained from various sources, including the COCONUT (Collection of Open Natural Products) database. On the parent dataset, high throughput virtual screening (HTVS), standard precision (SP) docking, and extra precision (XP) docking were performed to produce Murcko scaffolds and heterogenous fragments. Murcko scaffolds are hybridized with fragments of natural compounds (Category 1) and drugs (Category 2), respectively. Hybrids are docked with HTVS, SP, and XP, followed by induced fit docking and ADME (absorption, distribution, metabolism, and excretion) prediction. MM/GBSA (molecular mechanics/generalized Born and surface area) was performed on the docked poses. Results: Highest docking scores of –13.354 kcal/mol and –12.670 kcal/mol were achieved by hybrids in Category 1 and Category 2, respectively. MM/GBSA free energy ranged from –51.14 kcal/mol to –72.66 kcal/mol. In terms of binding docking, pharmacological properties, and Lipinski’s rule of five, the natural hybrids outperformed the parent drugs. Conclusions: PI3K-alpha kinase proteins can be targeted with natural-drug hybrid antagonists for breast cancer treatment. Hybrid molecules, such as NH-01 and NH-06, show better binding with promising ADME properties. Thus, in vivo and in vitro testing is necessary to prove the value of such hybrids. Original Article Tue, 29 Apr 2025 00:00:00 GMT NavyaAggarwal, ShinjiniSen, BanashreeBondhopadhyay, Tue, 29 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008108 https://www.explorationpub.com/Journals/eds/Article/1008110 Microbial pathogens with antibiotic resistance have become challenging to manage in the last few decades. The situation is alarming and a threat to humankind. Despite emerging new drug candidates, there are numerous strategies for efficient antibiotic delivery for treating such infections; antibiotic-resistant bacteria are still not eradicated adequately from the infected hosts. Recently, antimicrobial peptides (AMPs) have emerged as saviors in overcoming antibiotic resistance against bacteria. AMPs are being produced naturally as well as synthetically. Irrespective of the source of production, AMPs have shown higher specificity and lower toxicity to the host. Such functions have been attributed to distinct structures, functions, and varied mechanisms of action. This review highlights sources, structural and physiological characteristics, action mechanisms, and biological potency towards clinical applications. Most recently, AMPs have also been explored in treating cancers and tumors. Despite the entry of a few AMPs into clinical trials, there are limitations associated with their usage, like shorter half-life, protease cleavage, and toxicity. There is an urgent need to produce AMPs with intensified activity, biocompatibility, and lesser toxicity. This review sheds light on these aspects and the future of AMPs for the betterment of the human race. Review Fri, 09 May 2025 00:00:00 GMT RahulDilawari, Gaurav KumarChaubey, NiteshPriyadarshi, MeghnaBarik, NehaParmar, Fri, 09 May 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008110 https://www.explorationpub.com/Journals/eds/Article/1008109 Aim: This paper investigates two possible treatment targets for neuroblastoma (NB) stage 4 (NBS4), c-Src kinase (Csk) and retinoic acid (RA) signalling pathways as potential candidates for a multi-target drug. Research has demonstrated that many cancer cells overexpress and/or hyperactivate c-Src, a tyrosine that is a member of the Src-family kinases. In the case of NBS4, there are indications that successful inhibition of c-Src could inhibit disease progression. Research into the altered signalling of RA, which preserves the differentiated state of adult neurons, neural stem cells, and NB cells (SH-SY5Y), is also investigated as a potential multi-target drug. Methods: Using computer-aided technology, including OpenEye Scientific suite, Molegro Virtual docking, Samson suite, and Discovery Studio Visualiser, the results revealed that the receptors for both targets, Csk and RA, share similar amino acid sequencing that ranges from 80–100%, offering the possibility of further testing for multi-target drug use. Work was done to explore possible synthesis routes for each of the four compounds using the retrosynthesis program Spaya. Predictive toxicology was done using the Toxicity Estimation Software Tool (T.E.S.T.). Results: Four compounds (inhibitors) targeting the Csk tyrosine kinase and RA pathways were identified as potential inhibitors. Conclusions: Currently, no effective therapeutic agents for NBS4 exist. Immunotherapy which has proven effective in treating various cancers, is currently used to treat NBS4 and has a 40% to 50% survival rate. This paper investigates two possible treatment targets for NBS4, Csk and RA signalling pathways as possible candidates for a multi-target drug. Four potential inhibitors have been identified. Original Article Fri, 09 May 2025 00:00:00 GMT AmgadGerges, UnaCanning, Fri, 09 May 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008109 https://www.explorationpub.com/Journals/eds/Article/1008112 Pentafuranosylnucleos(t)ides represent a class of natural compounds regulating diverse cell functions being preferably components of biopolymers and also participating as cyclic regulatory low-molecular ligands. Disaccharide nucleosides and related analogs are considered as therapeutically potent compounds for the treatment of cancer, viral diseases, and a variety of metabolic disorders by mimicking a structure of biochemically occurring molecules participating in nicotinamide adenine dinucleotide (NAD+) transformation. Several approaches have been developed on the way to the chemical synthesis of poly(adenosine diphosphate ribose) (PAR), a unique biopolymer taking part in DNA repair and associated functions, that would allow extensive studies of molecular mechanisms of a variety of diseases. The present review consists of the following main parts, the first one including structural characterization, biochemical roles, and chemical synthesis of disaccharide nucleosides from different sources and biopolymers on their basis, the second one describing therapeutic applications of disaccharide nucleosides and their analogs. General conclusion and perspectives are summarized in the last part. Review Fri, 30 May 2025 00:00:00 GMT DmitriiPlatov, AnnaKozlova, CyrilAlexeev, MikhailDrenichev, Fri, 30 May 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008112 https://www.explorationpub.com/Journals/eds/Article/1008111 Aim: This study aimed to elucidate the structural basis for the interaction of five natural anti-arthritic compounds, diacerein, rhein, glucosamines [glucosamine 3-sulfate (G3S), and glucosamine 6-sulfate (G6S)], and chondroitin disaccharide Δdi-4S (C4S) with cytochrome P450 2C9 (CYP2C9). Methods: The investigated compounds were docked individually to the defined binding site in CYP2C9 based on the published crystal structure (PDB code: 1R9O). Results: All investigated ligands bound deep in the active site pocket in close proximity to the heme. Except for chondroitin, all ligands are bonded to residues found in critical secondary structures that form the boundary of the active site cavity, including B-C loop, F helix, F-G loop, and I helix. A total of 12 amino acids were involved in the binding, and all were critical residues located in four out of six substrate recognition sites (SRSs) that have been identified as important substrate binding and catalysis regions in other CYP isoforms. The relatively more potent binding (lower CDOCKER interaction energy) observed for diacerein and rhein compared to glucosamines and C4S are likely due to two main factors: a higher number of bonds between the ligand molecule and CYP2C9 active site residues (14 versus 0–4), and direct interaction with the heme moiety. The binding residues identified in both diacerein and rhein were the residues that also bonded with sulfaphenazole, the specific and potent CYP2C9 inhibitor. Conclusions: Collectively, this study has provided insights into structural features of CYP2C9 critical for inhibition and formed a basis for further exploration of structural determinants for potency and specificity of therapeutic compounds as CYP2C9 inhibitors. Original Article Wed, 28 May 2025 00:00:00 GMT Boon HooiTan, NafeesAhemad, YanPan, Uma DeviPalanisamy, Chin EngOng, Wed, 28 May 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008111 https://www.explorationpub.com/Journals/eds/Article/1008113 Aim: The immunosuppressive drug brequinar (BQR) is a potent inhibitor of dihydroorotate dehydrogenase (DHODH) active against autoimmune diseases and viral infections. This oral drug is currently evaluated for the treatment of cancers, notably acute myeloid leukemia to limit the suppressive function of myeloid cells. A combination of BQR and an anti-PD-1 (programmed death-1) antibody has revealed potent antitumor and antimetastatic activities. BQR induced a marked down-regulation of PD-L1 (programmed death-ligand 1) gene expression and a large decrease of PD-L1 protein expression in implanted tumors in mice. Methods: The present study evaluated the capacity of BQR to interact directly with the PD-L1 protein dimer using molecular modeling. Results: Molecular docking experiments revealed a modest capacity of BQR to stabilize PD-L1 dimers. The PD-L1 binding capacities of four known BQR analogs were compared to establish structure-binding relationships. The protein binding was significantly enhanced when the acid function of BQR was replaced with a trifluoroethanol substituent. The interaction was further reinforced when BQR was coupled to a mitochondria-targeted triphenylphosphine (TPP) unit. Among three BQR-TPP hybrids, compound B2 with a short alkyl linker revealed a prominent capacity to interact with PD-L1, superior to that of the reference biphenyl ligand BMS-202. Conclusions: Two PD-L1 binders derived from BQR have been identified and the protein interaction modeled. Our study underlines the possibility of designing novel small molecule ligands targeted to the PD-L1 dimer interface based on the BQR scaffold. Original Article Mon, 09 Jun 2025 00:00:00 GMT GérardVergoten, ChristianBailly, Mon, 09 Jun 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008113 https://www.explorationpub.com/Journals/eds/Article/1008114 Merozoite invasion of erythrocytes relies on molecular interactions between parasite and host proteins, making these proteins potential therapeutic targets. This review summarizes research on Plasmodium falciparum merozoite invasion conducted at the Instituto de Inmunología, San Juan de Dios Hospital, between 1990 and 2000. Erythrocyte-binding analyses of P. falciparum proteins merozoite surface protein 1 (MSP-1), MSP-2, acid basic repeat antigen (ABRA) (MSP-9), apical membrane antigen-1 (AMA-1), rhoptry-associated protein 1 (RAP-1), glycophorin-binding protein 130 (GBP-130), serine repeat antigen 5 (SERA-5), erythrocyte-binding antigen 140 (EBA-140), and EBA-175 identified 50 high-activity binding peptides (HABPs) with nanomolar-range dissociation constants. Most of these peptides inhibit merozoite invasion and belong to erythrocyte-binding regions of their respective proteins. Several HABPs overlap with epitopes recognized by inhibitory monoclonal antibodies (mAbs). MSP-1 HABP-5501 contains epitopes for mAbs 12.8, 12.10, MaliM03 fragment antigen binding (Fab), and 42D6 Fab, all of which block invasion. MSP-2 HABPs include epitopes targeted by opsonizing antibodies, while MSP-9 HABPs (2148–2153) interact with Band 3 during invasion. AMA-1 HABPs (4315, 4316, and 4325) contribute to the 1F9 epitope, a key target of immune recognition. RAP-1 HABP-26188 elicits inhibitory antibodies, including cross-reactive mAbs SP5.2 and SP8.18, the latter displaying parasite growth inhibition. GBP-130 HABP-2220 binds glycophorin and induces invasion-blocking antibodies. SERA-5 HABP-6725 contains sequences targeted by native SERA-5 antibodies, while HABPs 6727 and 6733 are recognized by antibodies from natural infection and vaccination. EBA-140 HABPs (26135, 26144, and 26147) are located in Region II (RII) and are recognized by mAbs with moderate to strong neutralizing activity. EBA-175 HABPs (1779, 1783, 1814, 1815, and 1818) are in recombinant fragments recognized by antibodies eluted from immune complexes. HABPs 1779 and 1783, located in RII, bind erythrocytes independently of sialic acid, inhibit rRII-EBA binding, and interact with α(2,3)-sialyllactose. HABP-1783 also contains the target site of mAb R217, which potently blocks EBA-175 binding to glycophorin A and inhibits invasion. Review Thu, 26 Jun 2025 00:00:00 GMT MauricioUrquiza-Martinez, DanielaBenavides-Rubio, FannyGuzmán-Quimbayo, Thu, 26 Jun 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008114 https://www.explorationpub.com/Journals/eds/Article/1008115 Aim: The objective of this study was to develop a simple quantitative model (SQM) to predict maximum plasma concentration (Cmax) and the area under the curve (AUC) of renally excreted drugs (n = 16) in pregnant women from non-pregnant women. Methods: The SQM was developed using 6 physiological parameters and the fraction unbound protein in plasma (fup) as the product characteristic. The six physiological parameters used in this study were total body water, blood volume, cardiac output, glomerular filtration rate (GFR), volume of the fetoplacental unit and blood flow of the fetoplacental unit. A factor was derived based on the average values of the physiological parameters and fup for different gestational ages to predict Cmax and AUC values in pregnant women from non-pregnant women. The predicted values from SQM were then compared with the dedicated clinical studies as well as predicted values by a physiologically-based pharmacokinetic (PBPK) model. Results: Out of 17 Cmax data points, 15 (88.2%), 15 (88.2%), and 12 (70.6%) data points were within 0.5–2.0-fold, 0.5–1.5-fold and 0.7–1.30-fold prediction error, respectively, by SQM, whereas, 17 (100%), 15 (88.2%), and 13 (76.5%) data points were within 0.5–2.0-fold, 0.5–1.5-fold and 0.7–1.30 fold prediction error, respectively, by PBPK. Out of 36 AUC data points, 36 (100%), 34 (94.4%), and 30 (83.3%) data points were within 0.5–2.0-fold, 0.5–1.5-fold and 0.7–1.30-fold prediction error, respectively, by SQM, whereas, 35 (97.2%), 33 (91.7%), and 27 (75%) data points were within 0.5–2.0-fold, 0.5–1.5-fold and 0.7–1.30-fold prediction error, respectively, by PBPK. The results of the study indicated that the predictive power of both models was very good. Conclusions: The results of the study indicate that the SQM in its predictive performance is as robust and accurate as whole body PBPK. Original Article Tue, 01 Jul 2025 00:00:00 GMT IftekharMahmood, Tue, 01 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008115 https://www.explorationpub.com/Journals/eds/Article/1008116 Since our previous summary of the 74 FDA-approved kinase inhibitors in clinical and preclinical trials for non-cancerous neurological treatment, the US FDA has approved 13 additional kinase inhibitors since early 2022. This update incorporates new evidence for the now 87 FDA-approved kinase inhibitors in clinical and preclinical trials for the treatment of non-cancerous neurological disorders. By the end of October 2024, nearly all 87 FDA-approved kinase inhibitors have been tested in various animal models of non-cancerous neurological disorders, with twenty entered into clinical trials and six used for off-label treatments of neurological conditions in humans. Considering the challenges posed by intellectual property (IP), legal considerations, and limited blood-brain barrier (BBB) permeability, which may restrict some FDA-approved kinase inhibitors from effectively targeting the central nervous system (CNS), we further discuss the feasibility of designing novel proprietary analogs with enhanced BBB penetration to improve their therapeutic potential in neurological disorders. The new drugs typically retain full IP rights and remain costly; while repurposing kinase inhibitors may provide effective and affordable treatments for non-cancerous neurological disorders. Review Wed, 02 Jul 2025 00:00:00 GMT HassanAliashrafzadeh, DeweyLiu, SamanthaDe Alba, ImadAkbar, AustinLui, JordanVanleuven, RyanMartin, ZhangWang, Da ZhiLiu, Wed, 02 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008116 https://www.explorationpub.com/Journals/eds/Article/1008117 Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn’s disease, is becoming a major public health concern in Africa, particularly in cities, due to urbanization, dietary changes, and improved diagnostic tools. The present study discusses the benefits, disadvantages, and practical limitations of the pharmacological treatments for IBD patients that are currently accessible in Africa. Given the limits of conventional treatments, such as their potential for considerable side effects, high cost, and often limited accessibility, this review explores emerging new treatment approaches such as nanomedicine, personalized medicine, and the use of traditional African medicines. Highlighting the urgency for potential alternative treatments, this review explores new and developing therapeutic innovations to enhance IBD management and improve the quality of life for African patients. Review Thu, 10 Jul 2025 00:00:00 GMT Murtada A.Oshi, Thu, 10 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008117 https://www.explorationpub.com/Journals/eds/Article/1008118 The tropics are abundant in both animals and plants, but also in pathogenic agents. There, the world’s greatest burden of diseases and mortality is concentrated. Co-infections are the rule, making laboratory diagnosis complex. Simultaneous multidiagnostic methods are desirable; however, they are mostly expensive and inaccessible to the populations of the region. The aim of our research was to produce synthetic peptides of the most important pathogens that can be used in a simultaneous multidiagnostic technique. Thus, we designed a low-cost method to detect antibodies, the multiple antigen blot assay (MABA), using synthetic peptides as the main source of antigens from endemic tropical diseases. This method allows the simultaneous detection of antibodies against 26 different agents with only a few microliters of sera, plasma, or saliva. The development of this system is the result of a long process, and the pipeline of our approach from then to nowadays is presented. Specific epitopes with the greatest antigenic potential using immunoinformatic algorithms have been selected from worldwide and tropical pathogens and then assayed by a successive chain of immunological techniques [PEPSCAN®, enzyme-linked immunosorbent assay (ELISA), and MABA] to evaluate the sensitivity and specificity of those synthetic peptides for their usefulness in diagnosis. Years of work have been required for this complex process, with the recent incorporation of new immunoinformatic predictive tools, methodologies, and cost advantages. It can be concluded that synthetic peptides are a promising approach for diagnostic processes based either on the detection of antigens or antibodies. Review Fri, 18 Jul 2025 00:00:00 GMT OscarNoya, HenryBermúdez, DianaPachón, BelkisyoléAlarcón de Noya, DianaOrtiz-Princz, Flor HelenePujol, SandraLosada, Fri, 18 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008118 https://www.explorationpub.com/Journals/eds/Article/1008120 Aim: Depression is one of the most important mental diseases. Different pharmacological and non-pharmacological methods are used to treat depression. Traditional and complementary medicine also have a special role in the treatment of depression. Among the specific medicinal formulations mentioned in Traditional Persian Medicine (TPM), an important and widely used form is “Mufarrah” (exhilarating), which indirectly refers to the mood-stabilizing group. In this work, a related traditional formulation has been reformulated and standardized as a conventional tablet. Methods: A simple and famous example among this group is “Mufarrah-e-Bared-e-Saghir”, containing Rosa × damascena Herrm., Coriandrum sativum L., Melissa Officinalis L. Following tablet preparation of the mentioned remedy, total phenolic and flavonoid content was determined using the spectrophotometric method. Volatile constituent analysis and quantification of linalool as the main component were carried out via gas chromatography (GC) [GC/MS (mass spectrometry) and GC/FID (flame ionization detector)]. Results: According to the results, the main compound of the final product was linalool (54.6%). Linalool, total phenol, and total flavonoid amounts have been calculated, respectively, 2,379.65 ± 262.13 µg/mL of the extracted essential oil, 163.23 ± 0.61, and 41.41 ± 2.3 mg/g extract. Conclusions: Prepared tablets as a reformulated traditional medicine product with rich total phenols and flavonoids, as well as the presence of linalool as a considerable icon with antidepressant activities, can be introduced to the Persian medicinal plants market to control depression. Original Article Wed, 23 Jul 2025 00:00:00 GMT AliSahragard, AidaAlipour, Mohammad M.Zarshenas, Wed, 23 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008120 https://www.explorationpub.com/Journals/eds/Article/1008119 Nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal regulator of cellular redox balance and detoxification, critical for maintaining hepatocyte homeostasis. However, its dysregulation has emerged as a key driver in hepatocellular carcinoma (HCC), the most prevalent form of liver cancer. This review synthesizes recent advancements (2023–2025) to elucidate Nrf2’s context-dependent dual functions: tumor suppressive roles during early carcinogenesis through oxidative stress mitigation, versus oncogenic effects in advanced stages via promoting proliferation, survival, and treatment resistance. We systematically analyze molecular mechanisms of Nrf2 activation, including Kelch-like ECH-associated protein 1 (KEAP1)-dependent/independent pathways and epigenetic regulation, supported by clinical data linking Nrf2 expression to patient prognosis. Preclinical and translational research on Nrf2-targeted therapies is evaluated, with a focus on combinatorial strategies overcoming resistance. Despite challenges in developing selective modulators, integrating multi-omics biomarkers and context-specific interventions offers promise for precision medicine in HCC. Mini Review Tue, 22 Jul 2025 00:00:00 GMT HouhongWang, ShangBian, Tue, 22 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008119 https://www.explorationpub.com/Journals/eds/Article/1008121 Aim: The objective of this study is to ascertain the antimicrobial and anticancer properties of dry Morinda citrifolia L. (noni) pulp hydroalcoholic extracts. Methods: In this study, dry noni samples were immersed in hydro-alcoholic solvents, ethanol (EtOH) and methanol (MeOH). Using the intelligent-flash extractor (KBE-I5) and freeze-vacuum dryer, noni ethanol (NE) and noni methanol (NM) extracts were obtained for antimicrobial testing against bacterial and fungal strains via disc diffusion assay. Cell viability was assessed using the cell counting kit-8 (CCK-8) assay, acridine orange (AO) staining, and western blotting to evaluate anticancer effects on human cancer cells. Novel phytoconstituents were identified using dual-mode ultra-performance liquid chromatography quadrupole exactive orbitrap-tandem mass spectrometer (UPLC-Q-exactive orbitrap-MS/MS) analysis. Results: Extraction yielded 16.8% for NE and 25.8% for NM. NE minimum inhibitory concentrations (MICs) against Escherichia coli (EC), Saccharomyces cerevisiae (SC), Staphylococcus aureus (SA), and Streptococcus thermophilus (ST) being 177, 52, 388, and 283 mg/mL. NM MICs values were 105, 47, 312, and 135 mg/mL, respectively. Anticancer half inhibitory concentrations (IC50s) for NE against human colon adenocarcinoma cell (HT-29) and human bladder cancer cell lines (UMUC-3) were 758 and 899 µg/mL. For NM, IC50s were 1,231 (HT-29) and 1,173 (UMUC-3) µg/mL. Cell death indicators include organelle deformities, AO fluorescence, and autophagy protein expression. In dual ion-scan mode UPLC analysis, 17 distinct phytoconstituents were identified, including 2-Hydroxycinnamic acid, 4-Hydroxycinnamic acid, and riboflavin, known for treating cancer, metabolic dysfunctions, and COVID-19. The 14 constituents were discovered in noni fruit for the first time. Conclusions: Noni fruit extracts show antimicrobial/anticancer activity and therapeutic potential, establishing noni fruit as a promising food and medicinal source based on composition. Original Article Fri, 25 Jul 2025 00:00:00 GMT AsleeTailulu, HanyueCui, LirenWu, YuhuShen, PingShi, Fri, 25 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008121 https://www.explorationpub.com/Journals/eds/Article/1008122 Aim: This study evaluates the in vitro and in vivo antiplasmodial, hemolytic, and antioxidant activities of a combined extract of Ageratum conyzoides (A. conyzoides) and Bidens pilosa (B. pilosa), a traditionally used but scientifically unvalidated combination. Methods: Plant leaves were extracted via aqueous decoction and cold maceration, combining equal parts to mimic traditional preparation. In vitro antiplasmodial activity against the chloroquine-sensitive Plasmodium falciparum 3D7 (Pf3D7) strain was assessed using the SYBR Green I assay. Cytotoxicity was evaluated via hemolysis test, and antioxidant potential using DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS [2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)], and FRAP (ferric ion reducing antioxidant potential) assays. The most potent combination was tested for acute toxicity and curative antimalarial activity in a rodent model. Results: Extract yields ranged from 6.6% (cold maceration extract of B. pilosa) to 29.2% [aqueous decoction extract of combination (Cd)]. Extracts showed moderate to mild in vitro antiplasmodial activity [IC50 (median inhibitory concentration): 24.8–96.6 µg/mL], with the aqueous Cd showing potential synergism [CI (combination index) < 1]. No significant cytotoxicity was observed (< 10% hemolysis). Moderate to good antioxidant activity was found in DPPH [SC50 (median scavenging concentration): 134.65–307.55 µg/mL] and ABTS assays (SC50: 92.23–183.45 µg/mL), with Cd showing the highest activity. FRAP values were low. The Cd extract demonstrated no significant acute toxicity up to 5,000 mg/kg and significant in vivo antimalarial activity, achieving 65% parasite inhibition at 200 mg/kg/day. It also prolonged survival time, with a maximum survival of 28 days at 200 mg/kg/day. Conclusions: This preliminary investigation suggests that combined extracts of A. conyzoides and B. pilosa exhibit noteworthy in vitro and in vivo antiplasmodial activity against the tested strains. Further studies are warranted to validate these findings and develop optimized formulations as potential antimalarials. Original Article Tue, 29 Jul 2025 00:00:00 GMT Patrick ValereTsouh Fokou, Courthney AkwiMboh, Kenneth LifoterNavti, Marius Jaurès TsakemNangap, RaoulKemzeu, Canis Parfait DonbouDjiotie, Aubin YoubiKamche, Hubert NanaDjigang, Arnold TegenTah, Mariscal Brice TchatatTali, Lauve Rachel TchokouahaYamthe, VincentNgouana, Fabrice FekamBoyom, Tue, 29 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008122 https://www.explorationpub.com/Journals/eds/Article/1008123 Aim: The science of manipulating matter at almost atomic scales to create new structures and devices that function at nanoscale dimensions is known as nanotechnology, which is essential to many sciences, such as medicine and environment. This field of study has been reported to investigate better alternatives for the advancement of medicine; one such alternative is the use of plants, which contain substantial amounts of essential phytochemicals. This study aims to utilize such a plant species, Canna indica (C. indica) leaves, known as traditional medicinal plants or commonly grown plants, to synthesize silver nanoparticles (AgNPs) and evaluate their potential in green medicine. Methods: The synthesis was carried out using five varieties of leaf water extracts: Pink red, Yellow, Pink, Yellow red, and Red, under different conditions, to which scanning electron microscopy was performed. The antioxidant capacity was evaluated by total flavonoid content, total phenolic content, total antioxidant capacity, and 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay. The antibacterial activity of AgNPs and water extracts was evaluated against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Finally, the cytotoxicity of AgNP is evaluated using the brine shrimp lethality assay. Results: The optimum condition for AgNP synthesis was determined to be room temperature, and Pink_AgNPs were observed as spherical with a size of 27–48 nm in scanning electron microscopy. The antioxidant assays concluded that AgNPs show significantly higher antioxidant capacity and exhibit higher scavenging activity. This study’s findings showed the efficiency of AgNPs against both strains, and higher efficiency against S. aureus. It was observed that with 240 ppm of AgNPs, 100% viability is obtained. Conclusions: These novel findings emphasize the significance of C. indica AgNPs, their promise in the medical field, and their application in manufacturing green medicine for environmentally friendly healthcare. Original Article Wed, 06 Aug 2025 00:00:00 GMT MathivathaniKandiah, NaihaRizan, BeneliGunaratne, OmindaPerera, Wed, 06 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008123 https://www.explorationpub.com/Journals/eds/Article/1008124 Gene-based medicine is transforming modern healthcare by offering precise, personalized interventions that target the genetic causes of disease. Breakthroughs in gene editing technologies, including clustered regularly interspaced short palindromic repeat (CRISPR)-associated (Cas) nuclease technologies (CRISPR-Cas9), base editing, and prime editing, are enabling promising therapeutic applications for rare inherited disorders and complex conditions like cancer. Furthermore, improvements in both viral and non-viral delivery methods are expanding clinical possibilities and enhancing safety measures. Despite these advancements, challenges such as off-target effects, ethical considerations, production complexities, and high costs continue to hinder widespread adoption. This review explores current innovations in gene-based medicine, addresses remaining obstacles, and outlines future directions, emphasizing the transformative potential of genomic-driven therapies for patients worldwide. Review Mon, 11 Aug 2025 00:00:00 GMT RalfWeiskirchen, Mon, 11 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008124 https://www.explorationpub.com/Journals/eds/Article/1008125 Cholecystokinin (CCK) is the most prevalent neuropeptide in the brain, where it affects satiety, pain modulation, memory, and anxiety. Its effects are mediated by GPCRs known as the “alimentary (gastrointestinal)” CCK1r (CCK 1 receptor) and the brain-specific CCK2r (CCK 2 receptor). While stress causes CCK to be released and full CCK2r agonists are potent panicogenic agents, specific CCK2r antagonists are ineffective at lowering human anxiety. As a result, the therapeutic potential of CCK as a target in psychiatry has been questioned. By compiling relevant new and historical scientific data retrieved from Scopus and PubMed, the aim of this review was to suggest a new function of CCK neurotransmission, the regulation of neuronal homeostasis during stress. Four lines of evidence were discussed that support the hypothesis of a CCK-driven neuronal homoestasis: (1) Homeostatic plasticity including synaptic scaling and intrinsic excitability; (2) its interaction with retrograde endocannabinoid signaling; (3) neuroprotective role; and (4) dynamic neuromodulation of CCK release. CCK functions as a crucial and essential molecular switch of neural circuits and neuroplasticity through its remarkable cell-specific modulation of glutamate and GABA release via CCK2r. CCKergic neurons are downstream of the activation of cannabinoid type-1 (CB1) receptors in order to generate and stabilize rhythmic synchronous network activity in the hippocampus. CCK is also released to modulate other neurotransmitters like dopamine and opioids when neuronal firing is intense during the processing of anxiety/fear, memory, and pain. CCK likely functions to restore baseline neuronal function and protect neurons from harm under these conditions. Anxiety, depression, and schizophrenia could result from compensatory plastic changes of the CCKergic system that go awry during neuronal homeostasis. This review concludes by examining the benefits of putative compounds that exhibit a combination of CCK agonist and antagonist activity at multiple locations within the CCKergic system, as well as off-targets in managing mental conditions. Review Tue, 19 Aug 2025 00:00:00 GMT Santiago J.Ballaz, Tue, 19 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008125 https://www.explorationpub.com/Journals/eds/Article/1008127 Aim: Menopausal women are suffering from stress-related disorders, and in the previous studies, Khaya anthotheca (K. anthotheca) decoction exhibited estrogenic and anxiolytic properties. Taken together, the aim of this study was to evaluate the effects of K. anthotheca decoction on behavioral disorders and oxidative stress induced by repeated variable stress in ovariectomized Wistar rats. Methods: Forty-two female Wistar rats (10–12 weeks old; 145 ± 10 g) were used. They were ovariectomized (except those from the sham operated group). Fourteen days after ovariectomy, animals were randomly distributed into 7 groups (n = 6): sham operated and negative control groups receiving distilled water; two positive control groups receiving estradiol valerate and diazepam (1 mg/kg each), and three other groups receiving the tested doses of K. anthotheca extract (125, 250, and 500 mg/kg each). The treatment was applied every week. Anxiety, depression, and motor coordination were assessed throughout the experimental procedure. The anti-oxidative potential of the extract was evaluated in rat brain homogenate. Results: It was noted that K. anthotheca extract induced anxiolytic effects marked by an increase in the locomotory activity during open field, light/dark, and elevated plus maze tests. Besides, its anti-depressive effects were shown by a significant (p < 0.05) decrease in the immobilization time during the forced swimming test. By improving the suspension time during grid and wire grip tests, the distance covered, and the number of switch directions during the beam walking test, the extract increased motor coordination. The antioxidant potential of the extract was marked by a significant decrease (p < 0.01) in malondialdehyde level and an increase (p < 0.05) in reduced glutathione level. Conclusions: These results provide valuable insights into the potential therapeutic application of the K. anthotheca extract; however, more studies are needed to elucidate mechanisms of action. Original Article Wed, 03 Sep 2025 00:00:00 GMT Franklin GamoZemo, SefirinDjiogue, Yolande Sandrine NgadenaMengue, Charline FlorenceAwounfack, Rudig Nikanor TadahDjikem, Constant AnatolePieme, DieudonneNjamen, Wed, 03 Sep 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008127 https://www.explorationpub.com/Journals/eds/Article/1008128 Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more rapidly progressive variant steatohepatitis (MASH) are widespread chronic liver conditions linked to obesity and other common metabolic disorders. The emergence of tirzepatide, a dual incretin receptor agonist targeting both the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, presents major therapeutic potential for MASLD. This review article explores the mechanisms of action of tirzepatide, highlighting its ability to improve glycemic control, promote weight loss, and potentially ameliorate hepatic steatosis and fibrosis. Recent studies suggest that tirzepatide may offer significant benefits in managing MASLD/MASH by modulating metabolic pathways and enhancing liver health. However, further research is needed to fully understand its long-term impact on MASLD/MASH progression and outcomes across diverse patient populations. Review Fri, 05 Sep 2025 00:00:00 GMT AmedeoLonardo, RalfWeiskirchen, Fri, 05 Sep 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008128 https://www.explorationpub.com/Journals/eds/Article/1008129 Probiotics, originating at birth, play a crucial role in the development and maintenance of a healthy and disease-free environment within the gut of both humans and animals. These beneficial microorganisms from fermented, processed, and non-dairy foods provide numerous health benefits, such as stress reduction, disease prevention, immune stimulation, gut microbiota control, nutritional supplementation, diarrheal disease relief, vitamin production, weight management, and anticancer activities. With more health problems on the rise and the negative side effects of conventional medication and antibiotics prevailing, natural supplements such as probiotics are a relief. Probiotics, such as Lactobacillus, Bifidobacterium, and Saccharomyces, have been identified as safe and effective candidates for gut health applications. This review addresses the current understanding of the mechanism of action of probiotics, their functions in human health, and their therapeutic potential for various diseases. We emphasize the importance of prioritizing probiotic administration along with conventional medicinal drugs for their wide benefits and fewer side effects. Our findings aim to direct future studies on the modes of action of probiotics against emerging health challenges. Review Thu, 18 Sep 2025 00:00:00 GMT Seemi TasnimAlam, Abdullah Bin HossainRayhan, Miraz UddinAhmed, Md. TanvirKhan, Jannatul FerdausJame, Md. MarufIslam, Md. Azad RahmanRaj, Md. AftabUddin, Thu, 18 Sep 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008129 https://www.explorationpub.com/Journals/eds/Article/1008131 Cedarwood essential oil (CWO), obtained from Cedrus and related species, has a long history in traditional medicine but remains relatively underexplored in modern pharmacology. This review consolidates current evidence on its phytochemical composition and pharmacological activities. Literature was retrieved from PubMed, Web of Science, and Scopus up to July 2025, including in vitro, in vivo, and limited clinical studies. Findings suggest antimicrobial, anti-inflammatory, sedative, and dermatological properties, primarily attributed to sesquiterpenes such as cedrol and α-cedrene. However, most data derive from small-scale or preclinical studies, with limited standardization of dosage and formulations. Safety aspects and toxicological gaps are also highlighted as essential considerations for future clinical translation. We conclude that CWO shows therapeutic potential, but rigorous clinical trials, standardized protocols, and comprehensive toxicological evaluations are essential before its safe and effective integration into evidence-based practice. Review Thu, 16 Oct 2025 00:00:00 GMT SaraDiogo Gonçalves, Thu, 16 Oct 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008131 https://www.explorationpub.com/Journals/eds/Article/1008132 Metabolic dysfunction-associated steatohepatitis (MASH) is emerging as a leading cause of cirrhosis, hepatocellular carcinoma, and liver-related mortality worldwide. Among the most advanced pharmacologic candidates are resmetirom, a highly liver-selective thyroid hormone receptor-β (THR-β) agonist, and semaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) already approved for diabetes and obesity. Although both agents improve hepatic steatosis, their mechanisms of action, extra-hepatic benefits, and safety signatures diverge markedly. Resmetirom, which was approved by the Food and Drug Administration (FDA) in March 2024, acts hepatocentrically to accelerate β-oxidation, lower atherogenic lipoproteins, and deliver early signals necessary for fibrosis regression, all while largely avoiding systemic thyrotoxic effects. Semaglutide acts systemically by reducing caloric load through pronounced weight loss and glycemic control, producing the highest rates of histologic MASH resolution reported to date, albeit with less direct antifibrotic efficacy and characteristic gastrointestinal tolerability issues. This comparative perspective juxtaposes the two compounds with respect to molecular pharmacology, clinical efficacy, safety, and potential clinical positioning, and proposes that, because resmetirom primarily targets hepatic lipid disposal whereas semaglutide unloads systemic caloric pressure, their complementary actions could be harnessed sequentially or in combination to achieve broader, more durable disease modification across the heterogeneous spectrum of patients with MASH. Perspective Fri, 31 Oct 2025 00:00:00 GMT RalfWeiskirchen, Fri, 31 Oct 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008132 https://www.explorationpub.com/Journals/eds/Article/1008133 The escalating threat of antibiotic resistance and its advancing mechanisms for resistance development underscore the imperative need for alternative approaches to treat life-threatening infections. Consideration of bacteriophages, as well as antimicrobial peptides (AMPs) that can specifically target and eliminate particular bacteria, is gaining prominence for the improved treatment of infections. The effectiveness of bacteriophages and AMPs has been known for a long time, and their combined use is being investigated recently. Studies have shown that the use of phages or phage-derived enzymes (endolysins) in combination with AMPs has shown promising results in combating multidrug resistant bacteria. Bacteriophages lyse bacteria by hijacking the bacterial cell’s metabolic machinery, leading to the production of phage virus inside it and finally bursting the bacteria, while AMPs act by disrupting the bacterial cell membrane or affecting intracellular targets after penetration. In this review, we discuss previous studies on the combined use of both phages or phage-derived enzymes and AMPs, demonstrating their synergistic effects for combating multidrug resistant pathogens. Their mechanisms of action, and possible mechanisms of synergy and development of bacterial resistance to these, are discussed. Approaches, including genetic engineering, for improving their efficacy have been discussed. Safety and ethical issues regarding their use in human subjects are discussed. In summary, this review emphasizes the need for further research on the combined use of AMPs and bacteriophages to tap their potential effectiveness for treating antimicrobial-resistant infections. Review Wed, 12 Nov 2025 00:00:00 GMT SehrishNayab, KinzaIdrees, Muhammad AamirAslam, Wed, 12 Nov 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008133 https://www.explorationpub.com/Journals/eds/Article/1008134 Buarque et al. (Explor Drug Sci. 2025;3:1008107. DOI: 10.37349/eds.2025.1008107) reported the synthesis of 13 biaryl hydroxy-1,2,3-triazoles and 11 fluorene-1,2,3-triazole hybrids via optimized Suzuki and telescopic one-pot reactions. Cytotoxicity evaluations against colorectal cancer (HCT-116), astrocytoma (SNB-19), triple-negative breast cancer (MDA-MB-231), and acute myeloid leukemia, FLT3-ITD mutant (MOLM-13) cell lines revealed promising antitumor activity. 1-(2-bromophenyl)-4-(9H-filoren-9-yl)-1H-1,2,3-triazole (LSO258) and 1-(4-bromophenyl)-4-(2-fluoro-9H-fluron-9-yl)-1H-1,2,3-triazole (LSO272), both being fluorene-1,2,3-triazole hybrids with bromine substituents, could selectively inhibit the activity of MOLM-13 cells, while the biaryl hydroxy-1,2,3-triazoles compounds exhibited broader antitumor activity. It is worth noting that an inevitable phenomenon is observed: The above compounds have significant aromatic structural characteristics, and their large aromatic systems lead to increased molecular hydrophobicity, resulting in poor water solubility. This critical druggability limitation will directly restrict the development of formulations. To tackle this issue, this paper proposes micelles as the optimal solution. As a carrier structure formed by the self-assembly of amphiphilic surfactants, micelles possess a unique “hydrophobic core-hydrophilic shell” configuration. Their hydrophobic core layer can efficiently encapsulate triazole compounds containing aromatic structures. Compared to other nanomedicine formulations such as solid dispersions and nanoencapsulation technology, micelles demonstrate significant advantages in terms of stability, process simplicity, and biocompatibility. Letter to the Editor Thu, 20 Nov 2025 00:00:00 GMT ZhiqiLiu, MeihongZhang, ZhengweiHuang, Thu, 20 Nov 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008134 https://www.explorationpub.com/Journals/eds/Article/1008135 Antimicrobial peptides (AMPs) are a heterogeneous group of small, naturally occurring molecules that are an integral part of the innate immunity of nearly all life forms. Their amphiphilic nature, cationic character, and small size distinguish AMPs, which have a wide spectrum antimicrobial activity against bacteria, fungi, parasites, and viruses. Their specific ability to selectively destroy microbial membranes, without harming host cells, makes them promising contenders to treat the growing threat of antimicrobial resistance (AMR), which has undermined the effectiveness of traditional antibiotics. The action mechanisms of AMPs are multifaceted, involving both membrane-disruptive mechanisms, like barrel stave pore formation, toroidal pore induction, and carpet-like membrane degradation, and non-membrane targeting mechanisms, like inhibition of nucleic acid synthesis, protein translation, and cell wall biosynthesis. AMPs are structurally diverse, from α-helices and β-sheets to cyclic and unstructured peptides, and are distributed abundantly in nature, being derived from mammals, amphibians, insects, plants, and microorganisms. Apart from antimicrobial activity, AMPs have immunomodulatory and regenerative activities, enabling their use in many therapeutic and industrial applications. These are for the construction of new anti-infective agents, wound healing compounds, medical device coatings to inhibit biofilm growth, natural food preservatives, adjuvants for vaccines, and possible anti-cancer drugs. Although they hold great promise, stability, toxicity, and production scale issues continue to hinder translation to the clinic. This review highlights the structural variability, modes of action, and novel uses of AMPs, with a focus on their status as next-generation therapeutics against multidrug-resistant microbes and for promoting biomedical innovation. Review Tue, 09 Dec 2025 00:00:00 GMT RahulKumar, Tue, 09 Dec 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008135 https://www.explorationpub.com/Journals/eds/Article/1008137 Aim: One of the causes of Alzheimer’s disease (AD) is the structural change and aggregation of target proteins due to the binding of metal ions. In this study, we investigated where copper(II) ions bound to the protein egg white lysozyme crystals in a hydrophilic buffer solution after ions were synthesized from an amino acid Schiff base copper(II) complex with a hydrophobic azobenzene group. Methods: X-ray crystallographic studies of the complexes and egg white lysozyme were then studied. Molecular docking studies for the binding of copper(II) ion with egg white lysozyme were also carried out. Results: The results suggest that the hydrophobicity of the introduced complex affected how deeply the resultant copper(II) ion penetrated into the protein. It has been revealed that when metal complexes are soaked into protein crystals, the metal complexes act as carriers, and metal ions tend to dissociate and bind to appropriate functional groups on certain specific residues of the protein. His15 and Glu35 were the more common binding residues of the protein that bound to the metal ion. Conclusions: An anti-Irving-Williams behaviour was observed for the interaction of the copper(II) complex with the lysozyme. Docking studies revealed various potential binding sites of copper(II) ion with the lysozyme. Original Article Tue, 16 Dec 2025 00:00:00 GMT AyumuOdaka, Temitayo O.Aiyelabola, SeiyaAkimoto, DaisukeNakane, Patience DooshimaIorungwa, TakashiroAkitsu, Tue, 16 Dec 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008137 https://www.explorationpub.com/Journals/eds/Article/1008136 Aim: Diabetes mellitus is a serious public health problem, and the condition is managed using herbal medicine by many African traditional healers. This study aimed to provide scientific evidence on the effects of aqueous and ethanol extracts of Xymalos monospora (X. monospora) leaves on some biochemical parameters in diabetic rats. Methods: This experiment included 63 male Wistar rats. Diabetes was induced for 10 days by intraperitoneal injection of dexamethasone (16 mg/kg) in overnight fasted rats. The diabetic rats were treated with aqueous (100 and 200 mg/kg) and ethanol (100 and 200 mg/kg) extracts of X. monospora leaves and metformin (40 mg/kg) for 15 days. Fasting blood glucose, serum lipid profile, atherogenicity indices (Castelli’s Risk Index, Atherogenic Coefficient, Atherogenic Index of Plasma), tumor necrosis factor alpha, and hepatic glycogen were evaluated. Results: Treatment with the aqueous extracts at 100 and 200 mg/kg significantly reduced fasting blood glucose by 29.2% (p = 0.016) and 35.9% (p = 0.009), respectively. Also, the ethanol extracts at 100 and 200 mg/kg significantly reduced fasting blood glucose by 20.7% (p = 0.038) and 31.2% (p = 0.027), respectively. The aqueous extract (200 mg/kg) significantly reduced total cholesterol and triglyceride concentrations by 31.5% (p = 0.017) and 30.7% (p = 0.023), respectively. There was a significant reduction in atherogenicity indices (p < 0.05), and liver glycogen levels improved. The extracts reduced the levels of tumor necrosis factor alpha, but this was not significant (p > 0.05). However, histopathological studies were not carried out, and the above findings may not directly translate to clinical efficacy. Conclusions: These findings demonstrate that the oral administration of aqueous and ethanol extracts of X. monospora leaves has significant antidiabetic effects, including a decrease in fasting blood glucose, improvement of serum lipid profile, and increased glycogen storage. Original Article Tue, 16 Dec 2025 00:00:00 GMT Awah AdolfAnguh, Mache AndreGilles, Brice Ulrich SahaFoudjo, Lifoter KennethNavti, Tue, 16 Dec 2025 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008136 https://www.explorationpub.com/Journals/eds/Article/1008138 Aim: This study aimed to establish the in vitro efficacy of chlorhexidine (CHX)-silver nanoparticles (AgNP) based preparation, against Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) in planktonic cultures, biofilms, and on inert stainless-steel surfaces. Methods: The in vitro antimicrobial activity of the CHX-AgNP formulation (Dermosedan MRSA Nano AG®) was evaluated against reference and multidrug-resistant (MDR) strains of S. aureus and P. aeruginosa by determining the minimum inhibitory and bactericidal concentrations (MIC and MBC), as well as the minimum biofilm inhibitory and eradication concentrations (MBIC and MBEC). Also, the residual bactericidal activity on inert stainless-steel surfaces was evaluated. Results: MIC against methicillin-resistant S. aureus (MRSA) and MDR P. aeruginosa (MDR-PA) isolates ranged between 5/2.5–20/10 µg/mL, up to 8,000 times lower than the manufacturer’s recommended concentration, while MBC ranged from 500 to 2,000 times lower. MBIC matched the MBC, while higher concentrations were needed to eradicate preformed biofilms. On stainless-steel surfaces, high antimicrobial activity was observed for both pathogens. No bacterial survival was detected even after 6 hours at 4% CHX + 2% AgNP concentration. The CHX-AgNP combination demonstrated strong antimicrobial and antibiofilm activity against both S. aureus and P. aeruginosa. Conclusions: These results support the potential application of Dermosedan MRSA Nano AG® as a strategy for managing topical resistant infections and for environmental disinfection in both veterinary and clinical settings. Original Article Mon, 05 Jan 2026 00:00:00 GMT DanielBuldain, AndreaBuchamer, LihuelGortari Castillo, KarenJulca Lozano, FlorenciaAliverti, Juliadi Filippo, GustavoCastellano, GuillermoBroglia, AlanParis, LauraMarchetti, Mon, 05 Jan 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008138 https://www.explorationpub.com/Journals/eds/Article/1008154 Intranasal drug delivery exhibits therapeutic potential for the treatment of central nervous system (CNS) diseases, as it allows pharmaceuticals to bypass the blood-brain barrier (BBB) via the olfactory and trigeminal pathways. The primary advantage of this method lies in its non-invasiveness and low systemic toxicity. Nevertheless, this delivery method faces notable challenges, including limited nasal mucosal absorption and short residence time in the olfactory region. To address these limitations, intranasal nanomedicine has gained research attention. Nanomedicines can improve brain bioavailability by enhancing drug solubility, permeability, and stability. The following discussion summarizes recent advancements in nanotechnology-enabled nose-to-brain delivery systems, with the aim of synthesizing progress in the field and outlining future research directions. Perspective Tue, 10 Mar 2026 00:00:00 GMT RuiYang, ZhengweiHuang, XuejuanZhang, Tue, 10 Mar 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008154 https://www.explorationpub.com/Journals/eds/Article/1008144 Background: Antimicrobial resistance (AMR) among Gram-positive bacteria has emerged as a significant global health threat, with pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) exhibiting increasing resistance to conventional antibiotics. This systematic review evaluates new advances in nanomaterial-based antimicrobial agents as innovative solutions to combat AMR in Gram-positive bacteria. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, studies published between 2014 and 2024 were systematically screened and analysed from databases including PubMed, Scopus, Google Scholar, and HINARI. From an initial 1,405 articles, 131 experimental studies that met the inclusion criteria were systematically analysed to harness the advances in nanomaterial-based antimicrobial agents in combating AMR in Gram-positive bacteria. Results: The included studies demonstrated that various nanomaterials, including silver nanoparticles (AgNPs), gold nanoparticles (AuNPs), zinc oxide nanoparticles (ZnO NPs), copper and copper oxide nanoparticles (Cu/CuO NPs), as well as polymeric and hybrid systems, exhibited potent antibacterial and antibiofilm activities. Key mechanisms of action included bacterial membrane disruption, reactive oxygen species (ROS) generation, intracellular interference, and targeted drug delivery. Many nanomaterials showed enhanced efficacy and synergistic effects when combined with conventional antibiotics, effectively reducing bacterial load and inhibiting biofilm formation in resistant strains like MRSA. Discussion: Nanomaterials offer a multifaceted approach to overcome the evolving resistance mechanisms in Gram-positive pathogens, showing significant preclinical and clinical success. Despite these substantial preclinical results, challenges such as cytotoxicity, environmental impact, scalability, and the potential for resistance adaptation remain unaddressed. Furthermore, important translational barriers persist, most notably insufficient pharmacokinetic data and unclear regulatory pathways. Future efforts must focus on standardized manufacturing, comprehensive toxicity studies, and robust clinical trials to bridge the gap between laboratory innovation and practical therapeutic application. Systematic Review Thu, 29 Jan 2026 00:00:00 GMT Olalekan JohnOkesanya, Tolutope AdebimpeOso, Uthman OkikiolaAdebayo, Oluwatobi BabajideAyelaagbe, Khalifat BoluwatifeObadeyi, Moyosore EstherOgunmuyiwa-James, Abdulrahman KayodeYahaya, Clement NgeleChukwu, Kabiru OlalekanTajudeen, Olaoluwa JosephOso, Mohamed MustafAhmed, IfrahAli, Don EliseoLucero-Prisno III, Thu, 29 Jan 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008144 https://www.explorationpub.com/Journals/eds/Article/1008139 Background: The root cause of diabetes is dysregulated pathways, including those involving AMP-activated protein kinase (AMPK), GLUT-mediated glucose transport, and the PI3K/AKT pathway. There has been a notable increase in research on phytoconstituents as pathway-specific treatments for diabetes; however, the comprehensiveness of this evidence remains unclear. Methods: This systematic review followed PRISMA guidelines and was registered on PROSPERO (CRD420251073083). Databases searched included PubMed, Scopus, Google Scholar, and Europe PMC for experimental studies (in vivo, in vitro, and in silico) published between 2015 and 2024. The final search was conducted in April 2025, and 2025 publications available as “early access” before this date were included. Only English-language studies were included. Animal studies (in vivo) were assessed for risk of bias using the SYRCLE tool, while in vitro studies were evaluated using the ToxRTool, based on test substance characterization, test system description, study design, and data reporting. Narrative synthesis was employed due to the heterogeneity of the data. Results: Out of 3,222 articles, 177 articles met the inclusion criteria. Study types included in vitro (92; 52%), in vivo (66; 37.3%), in silico (15; 8.5%), and other experimental types (4; 2.3%). Phytoconstituents predominantly targeted PI3K/AKT (44.6%), GLUT transporters (19.8%), and AMPK (14.1%) pathways. Rodent models were most used (48.02%). Primary outcomes included improved insulin sensitivity, enhanced glucose homeostasis, and reduced oxidative stress and inflammation. The risk of bias analysis revealed 68.93% of the studies carried a moderate risk, 29.94% a low risk, and 1.13% a high risk. Discussion: Phytoconstituent activity was consistent with the activation of diabetes-relevant signaling pathways, particularly PI3K/AKT, GLUT transporters, and AMPK cascades. However, most evidence was correlative, with limited loss-of-function validation. Methodological irregularities, moderate risk of bias, and limited translational research reduce the strength and generalizability of these findings. Systematic Review Wed, 07 Jan 2026 00:00:00 GMT Chizurum PhilipIkegbuna, Elodie Sepde MbwanzuhTompene, Ebube FavourEdwin, Mmesoma RuthIkegbuna, Wed, 07 Jan 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008139 https://www.explorationpub.com/Journals/eds/Article/1008140 Aim: The prevalence of multidrug-resistant “superbugs”, particularly Acinetobacter baumannii and Klebsiella pneumoniae, is a menacing phenomenon in society, rendering last-resort antibiotics increasingly suboptimal and ineffective. Carbapenemase enzymes play a major role in this resistance by hydrolysing carbapenem antibiotics. This study aims to identify and characterize potential non-covalent carbapenemase inhibitors using multiscale computational approaches. Methods: A focused library of 245 compounds, comprising pharmacopeial derivatives and chemogenomic molecules, was screened using a hierarchical virtual screening workflow. Top-ranked hits were further evaluated by rescoring for thermodynamic affinity. The most promising candidate was subjected to a 100 ns molecular dynamics (MD) simulation to assess binding stability, followed by Well-Tempered Metadynamics (WTMetaD) to characterise the free energy landscape and binding behaviour. Pharmacokinetic and toxicity profiles were predicted using SwissADME and ProTox 3.0. Results: Three compounds, daunorubicin, doxorubicin, and EUB0000226b, emerged as potential carbapenemase inhibitors. EUB0000226b demonstrated the most favourable binding affinity and structural novelty. MD simulations showed protein stability, while ligand RMSD fluctuations (2.4–5.6 Å) suggested flexible binding. WTMetaD analysis revealed a solvent-separated metastable state that increased ligand residence time within the active site. ADME and toxicity predictions indicated acceptable drug-likeness, good gastrointestinal absorption, and a generally safe profile. Conclusions: Multiscale computational analysis identified EUB0000226b as a promising non-covalent carbapenemase inhibitor with favourable binding energetics, dynamic stability, and drug-like properties. These findings support its further experimental validation and potential development for combating carbapenem-resistant bacterial pathogens. Original Article Fri, 09 Jan 2026 00:00:00 GMT Ayuba OlanrewajuMustapha, Adefunke JelilatAdeniyi, Mazeedah EniolaAlaka, Sulyman OlalekanIbrahim, Yusuf OloruntoyinAyipo, Fri, 09 Jan 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008140 https://www.explorationpub.com/Journals/eds/Article/1008141 Immunotherapy has transformed oncology, yet has only been marginally effective in prostate cancer (PCa), which is a malignancy with a low mutational load and a highly immunosuppressive tumor microenvironment (TME). This critical review is a reflection on the changing position of the innovative immunotherapies in PCa that extends beyond the description stage to synthesize the synergies and constraints of immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) T-cell therapy, and next-generation modalities such as bispecific T-cell engagers (BiTEs). We assess the mechanistic reasoning of combination therapies, comprising androgen receptor signaling communicators, PARP communicators, and radioligand therapies, which seek to modulate the immunogenicity of the immune-cold PCa TME. Also, we combine new knowledge to novel resistance pathways, including the newly discovered thrombospondin-1-CD47 axis, in the process of T cell exhaustion through calcineurin-NFAT signaling. Although some preclinical data and initial clinical indicators in biomarker-selected subpopulations are promising, the vast majority of Phase III trials of ICIs in unselected populations with metastatic castration-resistant prostate cancer (mCRPC) have failed. This review reveals that the next generation of PCa immunotherapy would not be sequential monotherapies but rather rationally designed multimodal combinations guided by profound molecular and immune profiling to overcome inherent resistance mechanisms. Review Fri, 09 Jan 2026 00:00:00 GMT Daniel KofiNyame, VongaiBaye, Ibrahim JoelKamara, XiaohuiZhou, Fri, 09 Jan 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008141 https://www.explorationpub.com/Journals/eds/Article/1008142 Not applicable. Correction Fri, 09 Jan 2026 00:00:00 GMT AmgadGerges, UnaCanning, Fri, 09 Jan 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008142 https://www.explorationpub.com/Journals/eds/Article/1008143 Background: Vascular aging is a major driver of cardiovascular, metabolic, and degenerative diseases, characterized by oxidative stress, mitochondrial dysfunction, endothelial senescence, and impaired proteostasis. Emerging data show that anti-infective drugs can influence these aging pathways beyond antimicrobial activity. However, their capacity to accelerate or slow vascular ageing has not been clearly defined. This review summarizes current evidence on how anti-infective agents modulate vascular ageing mechanisms. Methods: A systematic review was conducted following PRISMA 2020 guidelines. Studies from 2000 to 2024 were searched in major indexed databases. Eligible studies included in vitro, animal, and human research evaluating the effects of anti-infective agents on endothelial function, vascular senescence markers (p16INK4a, p21, SA-β-gal), oxidative stress, mitochondrial activity, inflammation, or proteostasis, key determinants of vascular ageing. Studies lacking mechanistic aging endpoints were excluded. Extracted data included drug class, model type, study design, and age-related outcomes. Risk of bias was assessed using SYRCLE, RoB-2, ROBINS-I, and narrative appraisal for in vitro studies. Results: Ninety-eight studies were identified; after removing six duplicates, ninety-two met the criteria. Macrolides, tetracyclines, and selected antivirals exerted anti-ageing effects by suppressing senescence-associated secretory phenotype (SASP), preserving mitochondrial integrity, reducing oxidative stress, and enhancing autophagy. Aminoglycosides and fluoroquinolones accelerated vascular ageing by generating reactive oxygen species, inducing DNA damage, and disrupting proteostasis. Antiviral protease inhibitors worsened endothelial dysfunction and metabolic aging. Antifungals such as itraconazole and amphotericin B impaired mitochondrial activity and angiogenesis, contributing to ageing phenotypes. Antiparasitic drugs showed mixed aging outcomes: chloroquine promoted autophagy and longevity, whereas thiabendazole impaired vascular stability. Broad-spectrum antibiotics disrupted the gut-vascular axis, increasing trimethylamine N-oxide, a mediator of inflammatory vascular aging. Discussion: Anti-infective drugs display diverse, class-specific effects on vascular aging. Recognizing these age-related actions is essential for safer prescribing and for repurposing anti-infective agents to target pathological vascular aging mechanisms. Systematic Review Wed, 14 Jan 2026 00:00:00 GMT Ceaser WankumbuSilumbwe, JuliusMulumba, Satheesh KumarDharmarajan, AnushaChennuru, LukundoSiame, KebbyMazyamuna, Wed, 14 Jan 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008143 https://www.explorationpub.com/Journals/eds/Article/1008145 Aim: To design, synthesize, and test small molecules and fragment-based compounds with putative selective anti-mycobacterial activity. Methods: Standard chemosynthetic processes were used to synthesize 42 compounds. A cell-based phenotypic screen for inhibitors of mycobacterial growth was used to identify several fragments and small molecules as representatives of urea-, carbamothioate-, and α,β-unsaturated systems (Michael acceptors) chemotypes. Results: All 42 compounds exhibited selective toxicity for mycobacteria as demonstrated by their lack of activity against various Gram-positive and Gram-negative bacteria and acid-fast Corynebacterium glutamicum. A thiadiazole compound, similar to (3-((5-(methylthio)-1,3,4-thiadiazol-2-yl)thio)pyrazine-2-carbonitrile), which activates the human lecitin: cholesterol acyltransferase (LCAT), exhibits growth-inhibitory activity [0.6 μg/mL in bovine serum albumin (BSA)-free media] against drug-susceptible Mycobacterium tuberculosis (Mtb). From the urea class, a 1,2,4-triazole-containing urea demonstrated anti-Mtb activity (4.7 μg/mL in BSA-free media). Several carbamothioate-based fragments demonstrated activity against Mycobacterium marinum [with a best minimum inhibitory concentration (MIC) of 6.25 μg/mL in minimal BSA-free media]. Conclusions: This foundational study demonstrates the utility of these newly designed and synthesized low molecular-weight compounds and fragments as potential antimycobacterials. Original Article Mon, 02 Feb 2026 00:00:00 GMT Monika I.Konaklieva, KritiArora, Helena I. M.Boshoff, Balbina J.Plotkin, Mon, 02 Feb 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008145 https://www.explorationpub.com/Journals/eds/Article/1008147 Over the past several decades there has been a growing recognition of the role that covalent drug candidates have played in the drug development process. With this recognition, compounds that are capable of selectively and irreversibly inactivating their targets through covalent bond formation are now being specifically designed rather than being serendipitously identified. Until recently, vinyl sulfones comprised only a small fraction of the warheads under development as covalent drug candidates, but an increasing number of compounds containing this versatile functional group are now under development and consideration as drug candidates. Vinyl sulfones are generally more reactive than structurally-related acrylamides and vinyl sulfonamides, presenting a challenge for producing target-specific inactivators. The most progress in overcoming this challenge has been made in designing vinyl sulfones as selective inactivators of microbial and human cysteine proteases, incorporating these reactive warheads into peptide and peptide mimetic structures that utilize the substrate recognition motifs of these proteases. However, effective vinyl sulfones have also been produced against a growing range of phosphoryl-utilizing enzymes including kinases, phosphatases and metabolic enzymes. Here, target selection takes advantage of the capability of the sulfonyl group to act as a phosphoryl mimic. An example of this approach is presented for the targeting of a metabolic enzyme, fungal aspartate semialdehyde dehydrogenase, an essential microbial enzyme in amino acid metabolism. The studies conducted to date demonstrate the potential utility of designing vinyl sulfone drug candidates to achieve selectivity against challenging and new drug-resistant targets. Review Mon, 02 Feb 2026 00:00:00 GMT Ronald E.Viola, Mon, 02 Feb 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008147 https://www.explorationpub.com/Journals/eds/Article/1008148 Aim: To evaluate the real-world effectiveness of prophylactic metoclopramide in preventing opioid-induced nausea and vomiting (OINV) during the initial phase of strong opioid therapy in opioid-naïve patients with cancer-related pain. Methods: This retrospective, single-center observational cohort study included adult patients with pathologically confirmed malignancies who initiated strong opioid therapy between January 2023 and December 2024. Patients were categorized into a prophylactic metoclopramide group or a no-prophylaxis control group. Complete control (CC) of OINV during the first 7 days was defined as the absence of nausea, vomiting, and rescue antiemetic use. Univariate and multivariate logistic regression analyses were performed to identify factors associated with CC, adjusting for age, sex, body mass index, cancer subtype, cancer stage, comorbidity status, and morphine-equivalent daily dose (MEDD). Subgroup analyses were conducted based on age, sex, and cancer subtype. Results: A total of 244 patients were included, of whom 199 received prophylactic metoclopramide, and 45 received no prophylaxis. The prophylactic group achieved significantly higher CC rates than the control group (74.9% vs. 37.8%, p < 0.001). Multivariate logistic regression confirmed that prophylactic metoclopramide was independently associated with higher odds of achieving CC (adjusted OR = 0.20, 95% CI: 0.10–0.40; p < 0.001). Similar improvements were observed for nausea and vomiting control. Subgroup analyses demonstrated consistent benefits across age and sex groups, with particularly notable effects in patients with gastrointestinal cancers. Conclusions: Prophylactic metoclopramide significantly improves OINV control in opioid-naïve patients with cancer-related pain during the initiation of strong opioids. These findings support the rational use of early antiemetic prophylaxis in routine clinical practice. Prospective randomized trials are warranted to validate these real-world results and assess long-term safety. Original Article Mon, 02 Feb 2026 00:00:00 GMT XianglianMa, YinyinYe, LiSha, LongxiangZhao, DengfengRen, YongxinLi, ZhiboLiu, JiudaZhao, Mon, 02 Feb 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008148 https://www.explorationpub.com/Journals/eds/Article/1008146 Type 2 diabetes mellitus (T2DM) is a global health challenge often complicated by poor treatment adherence, suboptimal lifestyle habits, and progressive metabolic deterioration. Cognitive behavioral therapy (CBT) has been shown to improve adherence and psychological outcomes, yet its integration with structured lifestyle modification and pharmacotherapy in routine clinical care remains underexplored. A descriptive case series of five patients with uncontrolled T2DM (baseline HbA1c 11–14.5%) was conducted in a primary care setting in Palestine. The intervention combined CBT-inspired behavioral counseling (goal setting, problem-solving, cognitive restructuring) with a structured two-meal low-carbohydrate diet, exercise and sleep hygiene guidance, and pharmacotherapy optimization (withdrawal of insulin/sulfonylureas, initiation of metformin, DPP-4 inhibitors, and SGLT2 inhibitors as appropriate). Patients were followed for 3–6 months. All five patients achieved clinically meaningful improvements. Mean HbA1c decreased from 12.6% at baseline to 7.4% at follow-up. Weight loss ranged from 5–17 kg (mean ~10 kg). Additional benefits included reductions in blood pressure, improvements in renal function and lipid profiles, and resolution of quality-of-life issues such as fatigue and erectile dysfunction. Several patients discontinued insulin or sulfonylurea therapy while maintaining improved glycemic control. The integration of CBT-inspired counseling with structured lifestyle intervention and pharmacotherapy adjustments was associated with short-term improvements in uncontrolled T2DM, including outcomes approaching remission. Although the small sample size and uncontrolled design limit causal interpretation, the program is being done in a low-income, limited-resources area like Palestine. Patients do not have the privilege to attend and receive care from several healthcare professionals. Hence, conducting such practice in a primary care clinic and yielding such results and improvement in diabetes status is promising and provides hope to the patients with low income. Case Report Mon, 02 Feb 2026 00:00:00 GMT AhmedNouri, Bassam AbuMadi, Mon, 02 Feb 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008146 https://www.explorationpub.com/Journals/eds/Article/1008149 The s-triazine scaffold has emerged as a privileged heterocyclic nucleus/moiety in pharmaceutical discovery and development, owing to its presence in several natural products and clinically relevant therapeutic agents, including enasidenib, gedatolisib, bimiralisib, atrazine, indaziflam, and triaziflam. s-Triazine derivatives are not only economically accessible and synthetically versatile, but they also exhibit a broad spectrum of noteworthy biological activities, encompassing anticancer, anti-inflammatory, antiviral, antidiabetic, anticonvulsant, antitubercular, and antimicrobial properties. Their widespread utility is further supported by the ease of synthesis from inexpensive precursors such as amidines or the readily available 2,4,6-trichloro-1,3,5-triazine (cyanuric chloride), which enables sequential functionalization and the rapid generation of diverse analogues. The heightened reactivity and modularity of the s-triazine core have facilitated the development of structurally rich heterocyclic hybrids with enhanced potency and improved pharmacological profiles. These multitarget-directed systems offer exciting opportunities for addressing various forms of cancer. Considering the increasing pace of innovation in this field, a comprehensive overview of recent advancements in s-triazine-based hybrid molecules is both timely and necessary. This review highlights current progress, key design strategies, and emerging perspectives to inspire continued efforts toward the identification of promising s-triazine-based lead candidates for future drug development as anticancer agents. Review Wed, 11 Feb 2026 00:00:00 GMT AnamikaSharma, IhabShawish, AshishKumar, Beatriz G.de la Torre, FernandoAlbericio, AymanEl-Faham, Wed, 11 Feb 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008149 https://www.explorationpub.com/Journals/eds/Article/1008150 Aim: A seven amino acid cyclic peptide has been applied to human blood plasma treated with glucose metabolite methylglyoxal (MG) in “proof of concept” experiments to determine the peptide’s ability to counteract pathologies associated with hyperglycemia. Similar pathologies are evident during aging and in age-related disorders. In fact, elevated MG levels in the blood lead directly to diabetic complications and accelerated aging, including cognitive decline. These changes are attributed to oxidant stress and amyloidogenesis, the latter involving toxic accumulations of blood and tissue proteins. Methods: cSKE7 was redesigned from cell survival-promoting and anti-inflammatory fragments near the N-terminus of human/primate “orphan” protein DSEP/Dermcidin and incubated at low micromolar concentrations with the MG-stressed human plasma for 24 hours. The modified design of the new compound offers several practical advantages over predecessors including cyclic stability and a marked increase in aqueous solubility. Results: The peptide dispersed thioflavin-T-stained amyloid aggregates and reduced oxidant stress as measured by plasma levels of free thiols and of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity. Since these N-terminal fragments of DSEP/Dermcidin have been shown to bind and influence the activity of heat shock protein 70 (HSP70), HSP70 inhibitor pifithrin-μ was added to the plasma prior to peptide treatment. The inhibitor disrupted amyloid dispersion and both peptide-induced and, in some cases, normally occurring antioxidant effects, suggesting these reparative activities are HSP70 dependent. Conclusions: The results are discussed in terms of their potential use in new therapies for the complications of metabolic disease and disorders of aging that result from a deterioration of the quality control mechanisms of proteostasis. Original Article Wed, 25 Feb 2026 00:00:00 GMT Timothy J.Cunningham, Wed, 25 Feb 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008150 https://www.explorationpub.com/Journals/eds/Article/1008151 The significant medicinal constituents and pharmacological potential of several botanicals suggest promising therapeutic applications. Scorzonera undulata displayed a diverse phytochemical profile, with 25 volatile and 21 phenolic compounds identified, including quinic and chlorogenic acids, along with flavonoids such as kaempferol, apigenin, luteolin derivatives, quercitrin, and naringin—mostly concentrated in the aerial parts. These extracts exhibited notable antioxidant, antimicrobial, anti-inflammatory, and cytotoxic activities, especially methanolic extracts against MCF-7 breast cancer cells, indicating therapeutic relevance. Andrographis paniculata extracts, rich in andrographolide, showed clinical potential in alleviating mild COVID-19 symptoms. However, the compound’s nonlinear pharmacokinetics highlight the need for optimized delivery strategies. Morinda citrifolia fruit extracts demonstrated considerable in vitro antimicrobial effects and moderate cytotoxicity, supported by UPLC–Orbitrap MS identification of unique bioactives. These findings reinforce the need for further pharmacological and clinical validation. The antiviral efficacy of Houttuynia cordata against dengue virus type 2 was evident, with aqueous extracts showing strong virucidal action and inhibition of viral replication. Hyperoside was identified as the dominant active constituent, supported by a rich phytochemical profile including flavonoids, aristolactams, and triterpenoids. Genotoxicity assessments indicated a favorable safety profile, suggesting potential for phytotherapeutic development. Achillea millefolium (yarrow) contained essential oils enriched in camphor, 1,8-cineole, artemisia ketone, and azulene derivatives, alongside phenolic acids and flavonoids like chlorogenic acid, apigenin, luteolin, and quercetin. These contributed to its antioxidant, anti-inflammatory, antimicrobial, and hemostatic effects, validating traditional medicinal applications and warranting clinical standardization. Flavonoids such as luteolin and apigenin offered anticancer and cardiovascular benefits by inhibiting PD-L1 via STAT3 suppression and promoting autophagy to counter vascular calcification. Bryophyllum pinnatum demonstrated broad pharmacological activity attributed to bufadienolides, flavonoids, and phenolic acids, supporting its ethnomedicinal use while emphasizing the need for clinical safety validation. Review Thu, 26 Feb 2026 00:00:00 GMT Saurabh DilipBhandare, Sarika ShivajiMalode, Thu, 26 Feb 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008151 https://www.explorationpub.com/Journals/eds/Article/1008152 Ageing is a gradual, multifactorial process that leads to the deterioration of physical and mental health, increasing the risk of disease and eventually death. Indicators of ageing manifest at the molecular level, including genomic instability, telomere attrition, epigenetic alterations, mitochondrial dysfunction, loss of proteostasis, and dysregulation of key signalling pathways such as the mechanistic target of rapamycin (mTOR) and insulin signalling. These molecular hallmarks of ageing are interconnected, amplifying one another over time. The resulting cellular stress triggers apoptosis or drives cells into a pathological state known as cellular senescence, in which they secrete inflammatory, pro-ageing factors. Consequently, there is a progressive decline in tissue function and regenerative capacity, accompanied by atrophy and stem cell exhaustion under a chronically inflamed microenvironment. Although functional decline with age is irreversible, research indicates it can be delayed. In this review, we discuss the hallmarks of ageing, conventional pharmacological interventions with demonstrated anti-ageing effects in cellular and animal models, and emerging therapeutic strategies being explored as ageing becomes increasingly recognized as a major risk factor for disease development. Review Thu, 26 Feb 2026 00:00:00 GMT Magaa LakshmiDhinakaran, SohnnaksheeMurugesu, Dinesh KumarSrinivasan, Thu, 26 Feb 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008152 https://www.explorationpub.com/Journals/eds/Article/1008153 Not applicable. Correction Mon, 02 Mar 2026 00:00:00 GMT AnamikaSharma, IhabShawish, AshishKumar, Beatriz G.de la Torre, FernandoAlbericio, AymanEl-Faham, Mon, 02 Mar 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008153 https://www.explorationpub.com/Journals/eds/Article/1008155 Antibodies currently represent a leading segment of the biopharmaceutical market and are expected to maintain a significant presence in the therapeutic landscape. Development of therapeutic antibodies represents one of the most transformative advances in the modern medicine field, with hundreds of successful products on the market that have changed the lives of millions and the history of mankind by revolutionizing medical treatment. In its broadest context, antibody-based products consist of full-length antibodies, antibody fragments, polyvalent and polyspecific antibodies, and their conjugates (for targeted delivery of other therapeutic drugs/agents). High target specificity, tailored mechanisms of action, and broad applicability have made antibodies indispensable in a variety of diseases. With advancements in protein engineering as well as growing integration of computational biology, the field of antibody development continues to push boundaries and is expected to drive the next era of breakthroughs. This article charts the journey of therapeutic antibodies from their conceptual roots to their central role in current medicine, and offers a forward-looking perspective on what lies ahead in this dynamic field. Review Thu, 19 Mar 2026 00:00:00 GMT Abhay H.Pande, Sandeep, J.Anakha, Thu, 19 Mar 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008155 https://www.explorationpub.com/Journals/eds/Article/1008156 Aim: Bisoprolol fumarate (BF), commonly prescribed for cardiovascular conditions, is usually split to achieve specific doses. This study evaluated the effects of tablet splitting on the quality parameters of scored BF tablets from three different brands marketed in Saudi Arabia. Methods: The products were evaluated for weight variation, content uniformity, and dissolution for intact and split tablets. A UPLC-sensitive assay was used for drug quantification. Results: The results showed that all products lost less than 3% of its weight upon splitting, meeting the USP requirements. Content uniformity was between 85% and 115% for all products, complying with pharmacopoeial standards. Dissolution studies showed some variation between intact and split tablets. The f2 similarity factor was calculated to compare the dissolution profiles of BF from both forms. The f2 values showed a similar dissolution profile for the innovator product (f2 was 62.53), but dissimilar profiles for Generic-1 and -2 (f2 values were 48.90 and 34.43, respectively). Conclusions: These results should be taken into consideration by healthcare professionals to avoid sub-therapeutic or toxic effects resulting from tablet splitting. Original Article Wed, 01 Apr 2026 00:00:00 GMT Doaa HasanAlshora, Nadia MisbelAlamri, Mohamed AbbasIbrahim, Fars K.Alanazi, Wael A.Abdelhafez, Mohammed AAmin, Hamzah M.Maswadeh, Wed, 01 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008156 https://www.explorationpub.com/Journals/eds/Article/1008157 Aim: Chitosan (CHS)-based nanoparticulate systems have gained much interest due to their high drug loading capacity and the simplicity of their fabrication. The physical properties of two types of curcumin-loaded CHS nanoparticles (CHS-NPs) were determined and compared. A new in-vitro release method was developed based on mathematical modeling in which the drug is first released from the NP into the surrounding medium and subsequently diffuses through the membrane. Methods: Curcumin-loaded CHS-NPs were fabricated by ionotropic gelation using sodium tripolyphosphate (TPP) and sodium hexametaphosphate (SHMP) crosslinking, and characterized by NP tracking analysis, loading capacity, zeta potential, Fourier transform infrared spectroscopy (FTIR), and in-vitro release rates. Results: The data showed that compared to SHMP crosslinked CHS-NPs, TPP crosslinking demonstrated a decrease in entrapment efficiency at a relatively high concentration of the agent, probably by narrowing the space between the polymeric chains. As indicated by zeta potential measurements, TPP crosslinking at all levels was more uniformly distributed inside the NPs, whereas the higher molecular weight SHMP at a low concentration creates NPs mostly by binding onto the surface. It was found that the release rates of curcumin from CHS-NPs crosslinked by SHMP at higher concentrations were about twice as high as the release rates of curcumin from TPP-crosslinked CHS-NPs, accompanied by notable lag times. Conclusions: This significant increase in the release rates of curcumin from SHMP-crosslinked CHS-NPs is explained by the large spatial structure of this crosslinker compared to the small TPP molecules. This study advances the literature on drug diffusion by making it possible to accurately determine its release from nanoparticulate systems. Original Article Thu, 16 Apr 2026 00:00:00 GMT IlyaEydelman, DoronYariv, ShimonBen-Shabat, Amnon C.Sintov, Thu, 16 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008157 https://www.explorationpub.com/Journals/eds/Article/1008158 Aim: The iridium(III) [Ir(III)] complexes exhibit anticancer properties, and along with their photoluminescence properties, they can be employed as diagnostic agents. Hence, we have tried to evaluate both properties. For this, the complexes of Ir(III) with pyridyl-based heterocyclic ligands, viz., [(TPQ)3Ir] (1), [(TPQ)2Ir(4-EO2-pic)] (2), and [(ppy)2Ir(dfpmpy)] (3) were prepared and evaluated for their cytotoxicity and emissive properties. Methods: These complexes were authenticated by NMR (1H and 13C{1H}) spectroscopy and high-resolution mass spectrometry (HRMS). Their photophysical properties were evaluated by UV-Vis spectroscopy and photoluminescence studies. Among them, [(TPQ)3Ir] (1) and [(TPQ)2Ir(4-EO2-pic)] (2) complexes have exhibited red emission centred at ~600–625 nm range, which is appropriate for bio-imaging. The cellular internalization of [(TPQ)2Ir(4-EO2-pic)] (2) complex was investigated by confocal microscopy and flow cytometry at time intervals of 3 h and 6 h after its treatment with cancer cells. These Ir(III) complexes (1–3) were evaluated for their cytotoxicity against 4T1 mammary carcinoma cells by MTT assay. The moderately potent [(TPQ)2Ir(4-EO2-pic)] (2) complex was evaluated in vivo against 4T1 mammary carcinoma induced in BALB/c mice. Results: Among these Ir(III) complexes (1–3), the [(TPQ)2Ir(4-EO2-pic)] (2) complex has exhibited moderate cytotoxicity (IC50 ~60 µM) as observed from their evaluations against triple-negative breast cancer (TNBC), a 4T1 mammary carcinoma cell line in vitro by MTT assay. Hence, its in vivo anticancer potency was evaluated by its treatment against 4T1 mammary carcinoma induced in BALB/c mice. This study exhibited tumor-inhibitory activity. Conclusions: The [(TPQ)2Ir(4-EO2-pic)] (2) complex has exhibited a moderate tumor inhibitory property. The presented results have given us insights for designing and developing better Ir(III) complexes in our future endeavours. Original Article Tue, 28 Apr 2026 00:00:00 GMT Natesan SundarmurthyKarthikeyan, Shishu KantSuman, Prasad P.Phadnis, LalrinawmaZote, ChandanKumar, VasanthakumaranSudarsan, Tue, 28 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008158 https://www.explorationpub.com/Journals/eds/Article/1008159 Antimicrobial resistance (AMR) poses a growing global health threat, progressively undermining the clinical effectiveness of conventional antibiotic therapies. Despite their proven efficacy and standardized clinical frameworks, antibiotics exert strong selective pressures that accelerate resistance, disrupt host microbiota, and limit treatment options for chronic, biofilm-associated, and multidrug-resistant infections. Bacteriophage therapy has re-emerged as a potential adjunct or alternative approach, offering pathogen-specific antibacterial activity, preservation of commensal microbiota, and the capacity for co-evolution with bacterial hosts. This focused review critically compares antibiotics and bacteriophage therapy across mechanistic foundations, preclinical and clinical evidence, translational readiness, and real-world implementation challenges. While preclinical models consistently demonstrate robust antibacterial activity of bacteriophages, clinical evidence remains heterogeneous, with few randomized controlled studies available. Key system-level barriers, including regulatory inconsistency, manufacturing complexity, and lack of standardization, currently limit widespread clinical integration. Rather than positioning bacteriophages as replacements for antibiotics, this review emphasizes their potential role as complementary agents, particularly through bacteriophage-antibiotic synergy, to enhance treatment efficacy and mitigate resistance. Addressing methodological gaps, standardizing clinical trial designs, and developing integrated stewardship models will be critical to defining the future role of bacteriophage therapy in modern infectious disease management. Review Mon, 18 May 2026 00:00:00 GMT Rana Hussain AbdulRehman, Durr-E-Najaf, Afra WasamaIslam, Syed IftiqarAhmed, Kholoud Mohamed SaidAbdelaziz, Anoud SalimFodkar, Mubassir ShahAwan, Mafaza AhmarZia, Mon, 18 May 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008159 https://www.explorationpub.com/Journals/eds/Article/1008160 Aim: Two empirical methods were used to predict the absolute bioavailability (F) of medicines {XE “bioavailability”} in adults and children following oral administration in the absence of intravenous (IV) dosing. This study systematically evaluates the predictive performance of Equation 1 to predict F in adults and children. Methods: Equation 3 [F = Q/(Q + CLoral)] was used for the prediction of F in adults and children. In Equation 3, clearance is the observed oral clearance following oral administration of a medicine and Q is either liver blood or plasma flow rate. The predictive performance of Equation 3 was evaluated in adults and children for three categories of medicines; medicines which are mainly metabolized in the liver, medicines which are metabolized both in the liver and the gut, and medicines which are mainly renally excreted. From the literature, oral clearance and F values for adults and children were obtained. The predictive performance of these two methods (blood or plasma flow rate) was assessed by comparing the predicted F of the medicines used in this study with the observed F (obtained from clinical studies). Results: More than 90% predicted F values were within 0.5–2-fold prediction error in adults and children by both methods for all three categories of medicines. Plasma flow rate provided slightly better results than the blood flow rate. Conclusions: The proposed methods indicate that the estimation of F of medicines in adults and children is possible with reasonable accuracy (within 0.5–2-fold prediction error). The method is useful to estimate F, especially in children, because it is not ethical to administer medicines by both IV and oral routes to children just for the sake of estimating F. Original Article Thu, 21 May 2026 00:00:00 GMT IftekharMahmood, Thu, 21 May 2026 00:00:00 GMT https://www.explorationpub.com/Journals/eds/Article/1008160