Conclusions:
Linear CC were obtained with a correlation coefficient (R2 > 0.99) with acceptable results of accuracy and precision.
Ultraviolet visible and HPLC method development
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.
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.
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.
Linear CC were obtained with a correlation coefficient (R2 > 0.99) with acceptable results of accuracy and precision.
Ultraviolet visible and HPLC method development
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.
MPDA nanoparticles were synthesized and functionalized with camptothecin (CPT) payload and manganese dioxide (MnO2) coating to construct MPDA-CPT-MnO2 nanocomposites.
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.
The developed MPDA-CPT-MnO2 nanocomposites can kill tumor cells through collaborative chemo/photothermal/chemodynamic therapy (CDT).
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.
[Names] => Qiushi Chen ... Xuechen Li [Doi] => 10.37349/eds.2023.00004 [Published] => February 28, 2023 [Viewed] => 1576 [Downloaded] => 64 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2023.00004 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 124 [TitleAbbr] => Explor Drug Sci. [Pages] => 2023;1:31–54 [Recommend] => 0 [Keywords] => Sialyl Lewis X, biological function, synthesis, mass spectrometry, glycoproteins [DetailTitle] => Bioactive Peptides discovery and development [DetailUrl] => https://www.explorationpub.com/Journals/eds/Special_Issues/124 [Id] => 10084 [ris] => https://www.explorationpub.com/uploads/Article/A10084/48673389c441a0f91fcb5b5b5b49628a.ris [bib] => https://www.explorationpub.com/uploads/Article/A10084/4802dc0e3cd98c061b1dcdbd96f74891.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Chen Q, Liu H, Li X. Essential functions, syntheses and detection of sialyl Lewis X on glycoproteins. Explor Drug Sci. 2023;1:31–54. https://doi.org/10.37349/eds.2023.00004 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-02-27 02:14:45 [Bib_Time] => 2023-02-27 02:14:45 [KeysWordContens] => Essential functions, syntheses and detection of sialyl Lewis X on glycoproteins, Sialyl Lewis X, biological function, synthesis, mass spectrometry, glycoproteins, 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. ,Qiushi Chen ... Xuechen Li [PublishedText] => Published [IsEdit] => 0 [AccountId] => 22 [Zh] => 1 ) [4] => Array ( [ArticleId] => 507 [Create_Time] => 2023-03-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202304/20230410083130.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A10085/10085.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A10085/10085.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A10085/10085_cover.png [JournalsId] => 11 [Title] => Utilizing the Ethereum blockchain for retrieving and archiving augmented reality surgical navigation data [Abstract] => 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 o [AbstractComplete] =>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.
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.
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.
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.
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).
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.
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.
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.
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.
[Names] => Phillip Mitchell Johansen ... Brandon Lucke-Wold [Doi] => 10.37349/eds.2023.00009 [Published] => April 28, 2023 [Viewed] => 1133 [Downloaded] => 35 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2023.00009 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 0 [TitleAbbr] => Explor Drug Sci. [Pages] => 2023;1:107–125 [Recommend] => 0 [Keywords] => Low-intensity focused ultrasound, high-intensity focused ultrasound, magnetic resonance guided focused ultrasound, magnetic resonance-guided therapy, glioblastoma [DetailTitle] => [DetailUrl] => [Id] => 10089 [ris] => https://www.explorationpub.com/uploads/Article/A10089/c1561c283989109d4f1d435505127405.ris [bib] => https://www.explorationpub.com/uploads/Article/A10089/98c402f391355a3b83616350ffbf8af2.bib [ens] => [Cited] => 3 [Cited_Time] => 2024-04-28 [CitethisArticle] => Johansen PM, Hansen PY, Mohamed AA, Girshfeld SJ, Feldmann M, Lucke-Wold B. Focused ultrasound for treatment of peripheral brain tumors. Explor Drug Sci. 2023;1:107–25. https://doi.org/10.37349/eds.2023.00009 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-04-27 06:30:20 [Bib_Time] => 2023-04-27 06:30:20 [KeysWordContens] => Focused ultrasound for treatment of peripheral brain tumors, Low-intensity focused ultrasound, high-intensity focused ultrasound, magnetic resonance guided focused ultrasound, magnetic resonance-guided therapy, glioblastoma, 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. ,Phillip Mitchell Johansen ... Brandon Lucke-Wold [PublishedText] => Published [IsEdit] => 0 [AccountId] => 24 [Zh] => 1 ) [8] => Array ( [ArticleId] => 576 [Create_Time] => 2023-04-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202306/20230615013006.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A10088/10088.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A10088/10088.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A10088/10088_cover.png [JournalsId] => 11 [Title] => Nano theranostics involved in bladder cancer treatment [Abstract] => 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 inte [AbstractComplete] =>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.
[Names] => Kunpeng Liu ... Qingsong Yu [Doi] => 10.37349/eds.2023.00008 [Published] => April 28, 2023 [Viewed] => 965 [Downloaded] => 35 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2023.00008 [Inline] => 1 [Type] => 1 [Issue] => 2 [Topic] => 107 [TitleAbbr] => Explor Drug Sci. [Pages] => 2023;1:81–106 [Recommend] => 0 [Keywords] => Bladder cancer, theranostics, nanoparticles, diagnosis, therapy [DetailTitle] => Emerging Nanomedicine Technologies for Enhanced Cancer Theranostics [DetailUrl] => https://www.explorationpub.com/Journals/eds/Special_Issues/107 [Id] => 10088 [ris] => https://www.explorationpub.com/uploads/Article/A10088/0b5b75fa2187b9993e6143ff90606130.ris [bib] => https://www.explorationpub.com/uploads/Article/A10088/bc003d8389d32a51a100af0b97e7c0bb.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Liu K, Mo Q, Ding Z, Lai S, Ren J, Yu Q. Nano theranostics involved in bladder cancer treatment. Explor Drug Sci. 2023;1:81–106. https://doi.org/10.37349/eds.2023.00008 [Jindex] => 0 [CName] => JianRen,QingsongYu, [CEmail] => dr_rj@163.com,yuqs@mail.buct.edu.cn, [Ris_Time] => 2023-04-27 00:44:51 [Bib_Time] => 2023-04-27 00:44:51 [KeysWordContens] => Nano theranostics involved in bladder cancer treatment, Bladder cancer, theranostics, nanoparticles, diagnosis, therapy, 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. ,Kunpeng Liu ... Qingsong Yu [PublishedText] => Published [IsEdit] => 0 [AccountId] => 55 [Zh] => 1 ) [9] => Array ( [ArticleId] => 587 [Create_Time] => 2023-04-30 [zipUrl] => https://www.explorationpub.com/uploads/zip/202305/20230509095347.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100810/100810.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100810/100810.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100810/100810_cover.png [JournalsId] => 11 [Title] => Heterogeneous graph convolutional neural network for protein-ligand scoring [Abstract] => 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 [AbstractComplete] =>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.
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.
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.
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.
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.
[Names] => Maria G. Ciulla ... Kamal Kumar [Doi] => 10.37349/eds.2023.00011 [Published] => June 27, 2023 [Viewed] => 2164 [Downloaded] => 152 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2023.00011 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 100 [TitleAbbr] => Explor Drug Sci. [Pages] => 2023;1:140–171 [Recommend] => 0 [Keywords] => Short peptides, peptide drugs, peptide stability, pharmaceutical properties [DetailTitle] => Exploring Potential Drugs from Natural Products [DetailUrl] => https://www.explorationpub.com/Journals/eds/Special_Issues/100 [Id] => 100811 [ris] => https://www.explorationpub.com/uploads/Article/A100811/616af2b898cd5d86a1650a74edc8d8ed.ris [bib] => https://www.explorationpub.com/uploads/Article/A100811/240e30a1dc13238bbc5007f349f40743.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-28 [CitethisArticle] => Ciulla MG, Civera M, Sattin S, Kumar K. Nature-inspired and medicinally relevant short peptides. Explor Drug Sci. 2023;1:140–71. https://doi.org/10.37349/eds.2023.00011 [Jindex] => 0 [CName] => Maria G.Ciulla,KamalKumar, [CEmail] => maria.ciulla@unimi.it,kamal.kumar@aicuris.com, [Ris_Time] => 2023-07-19 05:08:57 [Bib_Time] => 2023-07-19 05:08:57 [KeysWordContens] => Nature-inspired and medicinally relevant short peptides, Short peptides, peptide drugs, peptide stability, pharmaceutical properties, 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. ,Maria G. Ciulla ... Kamal Kumar [PublishedText] => Published [IsEdit] => 0 [AccountId] => 56 [Zh] => 1 ) [11] => Array ( [ArticleId] => 612 [Create_Time] => 2023-06-30 [zipUrl] => https://www.explorationpub.com/uploads/zip/202306/20230629062544.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100812/100812.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100812/100812.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100812/10086_cover.png [JournalsId] => 11 [Title] => Identification of an inter-cysteine loop potentially involved in the activity of Opisthorchis viverrini-granulin-1 [Abstract] => 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 [AbstractComplete] =>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.
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.
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.
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.
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.
[Names] => Miguel García-Castro ... Juan Manuel López-Romero [Doi] => 10.37349/eds.2023.00013 [Published] => June 30, 2023 [Viewed] => 1204 [Downloaded] => 63 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2023.00013 [Inline] => 1 [Type] => 1 [Issue] => 3 [Topic] => 100 [TitleAbbr] => Explor Drug Sci. [Pages] => 2023;1:180–209 [Recommend] => 0 [Keywords] => Antibiotics, approved drugs, antibacterial agents, multi-drug resistance, organic synthesis [DetailTitle] => Exploring Potential Drugs from Natural Products [DetailUrl] => https://www.explorationpub.com/Journals/eds/Special_Issues/100 [Id] => 100813 [ris] => https://www.explorationpub.com/uploads/Article/A100813/65e20c3ccaf54b22719c58e3adabf8ee.ris [bib] => https://www.explorationpub.com/uploads/Article/A100813/836f1285a97a78268cfe85c157c68a29.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => García-Castro M, Sarabia F, Díaz-Morilla A, López Romero JM. Approved antibacterial drugs in the last 10 years: from the bench to the clinic. Explor Drug Sci. 2023;1:180–209. https://doi.org/10.37349/eds.2023.00013 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-06-30 18:56:51 [Bib_Time] => 2023-06-30 18:56:51 [KeysWordContens] => Approved antibacterial drugs in the last 10 years: from the bench to the clinic, Antibiotics, approved drugs, antibacterial agents, multi-drug resistance, organic synthesis, 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. ,Miguel García-Castro ... Juan Manuel López-Romero [PublishedText] => Published [IsEdit] => 0 [AccountId] => 21 [Zh] => 1 ) [13] => Array ( [ArticleId] => 645 [Create_Time] => 2023-07-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202306/20230630081027.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100814/100814.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100814/100814.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100814/100814_cover.png [JournalsId] => 11 [Title] => A dextrorotatory residues-incorporated bioactive dodecapeptide against enterohemorrhagic Escherichia coli [Abstract] => 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 [AbstractComplete] =>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.
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.
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%.
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.
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.
[Names] => Sohum Sheth ... Brandon Lucke-Wold [Doi] => 10.37349/eds.2023.00015 [Published] => August 28, 2023 [Viewed] => 1840 [Downloaded] => 66 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2023.00015 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 0 [TitleAbbr] => Explor Drug Sci. [Pages] => 2023;1:221–238 [Recommend] => 1 [Keywords] => Glucagon-like peptide 1, incretins, neuro-ophthalmology, neuroprotection [DetailTitle] => [DetailUrl] => [Id] => 100815 [ris] => https://www.explorationpub.com/uploads/Article/A100815/fc02d29ecf7d0cc39d4e39f09248a822.ris [bib] => https://www.explorationpub.com/uploads/Article/A100815/c2e507d1ab0a41f060f8b9f8242a6819.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Sheth S, Patel A, Foreman M, Mumtaz M, Reddy A, Sharaf R, et al. The protective role of GLP-1 in neuro-ophthalmology. Explor Drug Sci. 2023;1:221–38. https://doi.org/10.37349/eds.2023.00015 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-07-28 02:45:25 [Bib_Time] => 2023-07-28 02:45:25 [KeysWordContens] => The protective role of GLP-1 in neuro-ophthalmology, Glucagon-like peptide 1, incretins, neuro-ophthalmology, neuroprotection, 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. ,Sohum Sheth ... Brandon Lucke-Wold [PublishedText] => Published [IsEdit] => 0 [AccountId] => 56 [Zh] => 1 ) [15] => Array ( [ArticleId] => 664 [Create_Time] => 2023-08-25 [zipUrl] => https://www.explorationpub.com/uploads/zip/202308/20230831060326.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100816/100816.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100816/100816.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100816/100816_cover.png [JournalsId] => 11 [Title] => Iron depletion in “metabolic fatty liver syndromes”: a strong biological rationale with disappointing liver outcomes [Abstract] => Nonalcoholic fatty liver disease (NAFLD), its more rapidly progressive steatohepatitic variant [nonalcoholic steatohepatitis, (NASH)], and the recently defined metabolic dysfunction-associated fatty [AbstractComplete] =>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.
[Names] => Amedeo Lonardo [Doi] => 10.37349/eds.2023.00016 [Published] => August 28, 2023 [Viewed] => 455 [Downloaded] => 13 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2022.00016 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 167 [TitleAbbr] => Explor Drug Sci. [Pages] => 2023;1:239–252 [Recommend] => 0 [Keywords] => Dysmetabolic hyperferritinemia, dysmetabolic iron overload syndrome, ferroptosis, insulin resistance–associated hepatic iron overload, intestinal dysbiosis, iron depletion [DetailTitle] => Innovative Therapeutics in Hepato-Gastroenterology [DetailUrl] => https://www.explorationpub.com/Journals/eds/Special_Issues/167 [Id] => 100816 [ris] => https://www.explorationpub.com/uploads/Article/A100816/b00d2247ed00c67b4854afa4b15a1515.ris [bib] => https://www.explorationpub.com/uploads/Article/A100816/c8fa95299e0692d70de6d9af3a073f54.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Lonardo A. Iron depletion in “metabolic fatty liver syndromes”: a strong biological rationale with disappointing liver outcomes. Explor Drug Sci. 2023;1:239–52. https://doi.org/10.37349/eds.2023.00016 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-07-28 02:44:49 [Bib_Time] => 2023-07-28 02:44:49 [KeysWordContens] => Iron depletion in “metabolic fatty liver syndromes”: a strong biological rationale with disappointing liver outcomes, Dysmetabolic hyperferritinemia, dysmetabolic iron overload syndrome, ferroptosis, insulin resistance–associated hepatic iron overload, intestinal dysbiosis, iron depletion, 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. ,Amedeo Lonardo [PublishedText] => Published [IsEdit] => 0 [AccountId] => 56 [Zh] => 1 ) [16] => Array ( [ArticleId] => 668 [Create_Time] => 2023-08-25 [zipUrl] => https://www.explorationpub.com/uploads/zip/202308/20230831070734.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100817/100817.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100817/100817.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100817/100817_cover.png [JournalsId] => 11 [Title] => Natural compounds from medicinal plants against COVID-19 [Abstract] => 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 infecti [AbstractComplete] =>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.
[Names] => Anton Kolodnitsky ... Vladimir Poroikov [Doi] => 10.37349/eds.2023.00017 [Published] => August 28, 2023 [Viewed] => 874 [Downloaded] => 37 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2023.00017 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 100 [TitleAbbr] => Explor Drug Sci. [Pages] => 2023;1:253–275 [Recommend] => 0 [Keywords] => SARS-CoV-2, COVID-19, medicinal plants, natural products, in vitro studies, clinical trials [DetailTitle] => Exploring Potential Drugs from Natural Products [DetailUrl] => https://www.explorationpub.com/Journals/eds/Special_Issues/100 [Id] => 100817 [ris] => https://www.explorationpub.com/uploads/Article/A100817/d962e4a1d3b4af707beaa98162f539c8.ris [bib] => https://www.explorationpub.com/uploads/Article/A100817/bc067e8dac6925be0053f05297e28062.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Kolodnitsky A, Ionov N, Gravel I, Poroikov V. Natural compounds from medicinal plants against COVID-19. Explor Drug Sci. 2023;1:253–75. https://doi.org/10.37349/eds.2023.00017 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-08-03 07:40:33 [Bib_Time] => 2023-08-03 07:40:33 [KeysWordContens] => Natural compounds from medicinal plants against COVID-19, SARS-CoV-2, COVID-19, medicinal plants, natural products, in vitro studies, clinical trials, 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. ,Anton Kolodnitsky ... Vladimir Poroikov [PublishedText] => Published [IsEdit] => 0 [AccountId] => 56 [Zh] => 1 ) [17] => Array ( [ArticleId] => 721 [Create_Time] => 2023-08-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202309/20230901011652.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100818/100818.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100818/100818.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100818/eds-01-100818_cover.png [JournalsId] => 11 [Title] => In silico study about β-amyloid’s role in Alzheimer’s disease and glaucoma and prediction of its interactions with glaucoma related proteins [Abstract] => 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 reporte [AbstractComplete] =>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.
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.
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.
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.
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.
[Names] => Katrin Sak [Doi] => 10.37349/eds.2023.00019 [Published] => August 30, 2023 [Viewed] => 431 [Downloaded] => 15 [Subject] => Commentary [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2023.00019 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 156 [TitleAbbr] => Explor Drug Sci. [Pages] => 2023;1:287–291 [Recommend] => 0 [Keywords] => Plant polyphenols, flavonoids, health benefits, oral bioavailability, intestinal absorption [DetailTitle] => Preventive and Therapeutic Potential of Nutraceuticals in Non-communicable Diseases [DetailUrl] => https://www.explorationpub.com/Journals/eds/Special_Issues/156 [Id] => 100819 [ris] => https://www.explorationpub.com/uploads/Article/A100819/b21500ef8c67d136c0d52b7d4fdd96d9.ris [bib] => https://www.explorationpub.com/uploads/Article/A100819/611ac198361489f49cb9a145306814bf.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Sak K. Could flavonoid aglycones prevent the absorption of flavonoid glycosides by inhibiting sodium-dependent glucose transporter-1 in the small intestine? Explor Drug Sci. 2023;1:287–91. https://doi.org/10.37349/eds.2023.00019 [Jindex] => 0 [CName] => KatrinSak, [CEmail] => katrin.sak.001@mail.ee, [Ris_Time] => 2023-08-28 07:00:54 [Bib_Time] => 2023-08-28 07:00:54 [KeysWordContens] => Could flavonoid aglycones prevent the absorption of flavonoid glycosides by inhibiting sodium-dependent glucose transporter-1 in the small intestine?, Plant polyphenols, flavonoids, health benefits, oral bioavailability, intestinal absorption, 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. ,Katrin Sak [PublishedText] => Published [IsEdit] => 0 [AccountId] => 72 [Zh] => 1 ) [19] => Array ( [ArticleId] => 747 [Create_Time] => 2023-08-30 [zipUrl] => https://www.explorationpub.com/uploads/zip/202308/20230830030650.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100820/100820.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100820/100820.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100820/100820_cover.png [JournalsId] => 11 [Title] => Single or multiple treatments with lusutrombopag in subjects with thrombocytopenia and chronic liver disease needing an invasive procedure [Abstract] => 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 increas [AbstractComplete] =>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.
[Names] => Davide Scalabrini ... Pietro Andreone [Doi] => 10.37349/eds.2023.00020 [Published] => August 30, 2023 [Viewed] => 412 [Downloaded] => 17 [Subject] => Case Report [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2023.00020 [Inline] => 1 [Type] => 1 [Issue] => 4 [Topic] => 167 [TitleAbbr] => Explor Drug Sci. [Pages] => 2023;1:292–298 [Recommend] => 0 [Keywords] => Thrombocytopenia, cirrhosis, thrombopoietin receptor agonists, lusutrombopag [DetailTitle] => Innovative Therapeutics in Hepato-Gastroenterology [DetailUrl] => https://www.explorationpub.com/Journals/eds/Special_Issues/167 [Id] => 100820 [ris] => https://www.explorationpub.com/uploads/Article/A100820/5e407536486feb2f5ba33415df1aab9c.ris [bib] => https://www.explorationpub.com/uploads/Article/A100820/554a6bab84a98ff637f5bf666d9c6cf5.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Scalabrini D, Sciuto P, Felicani C, Rudilosso A, Andreone P. Single or multiple treatments with lusutrombopag in subjects with thrombocytopenia and chronic liver disease needing an invasive procedure. Explor Drug Sci. 2023;1:292–8. https://doi.org/10.37349/eds.2023.00020 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-08-29 03:58:16 [Bib_Time] => 2023-08-29 03:58:16 [KeysWordContens] => Single or multiple treatments with lusutrombopag in subjects with thrombocytopenia and chronic liver disease needing an invasive procedure, Thrombocytopenia, cirrhosis, thrombopoietin receptor agonists, lusutrombopag, 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. ,Davide Scalabrini ... Pietro Andreone [PublishedText] => Published [IsEdit] => 0 [AccountId] => 83 [Zh] => 1 ) [20] => Array ( [ArticleId] => 811 [Create_Time] => 2023-09-21 [zipUrl] => https://www.explorationpub.com/uploads/zip/202310/20231031061350.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100821/100821.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100821/100821.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100821/100821_cover.png [JournalsId] => 11 [Title] => Electrochemical properties of hydroxyapatite immobilization material for potential cytosensor fabrication [Abstract] => 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 material [AbstractComplete] =>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.
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.
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.
The unique current and impedance differences among the cells could serve as potential markers for rapid cell detection.
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.
[Names] => Diogo Alvarenga Silva ... Vagner Rodrigues Santos [Doi] => 10.37349/eds.2023.00022 [Published] => October 9, 2023 [Viewed] => 1022 [Downloaded] => 22 [Subject] => Case Report [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2023.00022 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 0 [TitleAbbr] => Explor Drug Sci. [Pages] => 2023;1:312–321 [Recommend] => 0 [Keywords] => Head and neck cancer, radiotherapy, oral mucositis, green propolis gel [DetailTitle] => [DetailUrl] => [Id] => 100822 [ris] => https://www.explorationpub.com/uploads/Article/A100822/8dcdde3d9bf7e86936c84ae5c57dab60.ris [bib] => https://www.explorationpub.com/uploads/Article/A100822/c1e6407dc674aaf537df5b375e1322fb.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Silva DA, Caldeira PC, de Sousa SF, Santos VR. Grade IV oral mucositis treatment with Brazilian green propolis mucoadherent gel. Explor Drug Sci. 2023;1:312–21. https://doi.org/10.37349/eds.2023.00022 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-10-31 03:36:03 [Bib_Time] => 2023-10-31 03:36:03 [KeysWordContens] => Grade IV oral mucositis treatment with Brazilian green propolis mucoadherent gel, Head and neck cancer, radiotherapy, oral mucositis, green propolis gel, 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. ,Diogo Alvarenga Silva ... Vagner Rodrigues Santos [PublishedText] => Published [IsEdit] => 0 [AccountId] => 86 [Zh] => 1 ) [22] => Array ( [ArticleId] => 831 [Create_Time] => 2023-10-10 [zipUrl] => https://www.explorationpub.com/uploads/zip/202310/20231031073957.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100823/100823.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100823/100823.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100823/100823_cover.png [JournalsId] => 11 [Title] => Late-stage diversification strategy for the synthesis of peptide acids and amides using hydrazides [Abstract] => 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 s [AbstractComplete] =>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.
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.
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.
The developed protocols allow hydrazides to be converted to acids or amides, enabling late-stage diversification of peptide C-terminal residues.
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.
[Names] => Atri Das ... Shantanabha Das [Doi] => 10.37349/eds.2023.00024 [Published] => October 24, 2023 [Viewed] => 989 [Downloaded] => 47 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2023.00024 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 100 [TitleAbbr] => Explor Drug Sci. [Pages] => 2023;1:336–376 [Recommend] => 0 [Keywords] => Coronavirus disease 2019, severe acute respiratory syndrome coronavirus 2, phytochemicals, inflammation, cytokine storm, antivirals, combination therapy [DetailTitle] => Exploring Potential Drugs from Natural Products [DetailUrl] => https://www.explorationpub.com/Journals/eds/Special_Issues/100 [Id] => 100824 [ris] => https://www.explorationpub.com/uploads/Article/A100824/be3df2b03b5b4dec814a68151cf0b641.ris [bib] => https://www.explorationpub.com/uploads/Article/A100824/cf20c4b701c310c87a4a3cc5f58b488a.bib [ens] => [Cited] => 2 [Cited_Time] => 2024-04-27 [CitethisArticle] => Das A, Khan S, Roy S, Das S. Phytochemicals for mitigating the COVID-19 crisis: evidence from pre-clinical and clinical studies. Explor Drug Sci. 2023;1:336–76. https://doi.org/10.37349/eds.2023.00024 [Jindex] => 0 [CName] => SyamalRoy,ShantanabhaDas, [CEmail] => drsyamalroy@yahoo.com,shantanabha2008@gmail.com, [Ris_Time] => 2023-11-01 05:40:47 [Bib_Time] => 2023-11-01 05:40:47 [KeysWordContens] => Phytochemicals for mitigating the COVID-19 crisis: evidence from pre-clinical and clinical studies, Coronavirus disease 2019, severe acute respiratory syndrome coronavirus 2, phytochemicals, inflammation, cytokine storm, antivirals, combination therapy, 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. ,Atri Das ... Shantanabha Das [PublishedText] => Published [IsEdit] => 0 [AccountId] => 86 [Zh] => 1 ) [24] => Array ( [ArticleId] => 872 [Create_Time] => 2023-10-27 [zipUrl] => https://www.explorationpub.com/uploads/zip/202310/20231030013847.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100825/100825.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100825/100825.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100825/100825_cover.png [JournalsId] => 11 [Title] => Therapeutic proteins immunogenicity: a peptide point of view [Abstract] => 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 r [AbstractComplete] =>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.
[Names] => Feliciana Real-Fernandez ... Paolo Rovero [Doi] => 10.37349/eds.2023.00025 [Published] => October 26, 2023 [Viewed] => 1029 [Downloaded] => 39 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2023.00025 [Inline] => 1 [Type] => 1 [Issue] => 5 [Topic] => 124 [TitleAbbr] => Explor Drug Sci. [Pages] => 2023;1:377–387 [Recommend] => 0 [Keywords] => Peptides, anti-drug antibodies, immune response, peptide epitopes, therapeutics [DetailTitle] => Bioactive Peptides discovery and development [DetailUrl] => https://www.explorationpub.com/Journals/eds/Special_Issues/124 [Id] => 100825 [ris] => https://www.explorationpub.com/uploads/Article/A100825/c88461e2e3288c274f9587a3b5448207.ris [bib] => https://www.explorationpub.com/uploads/Article/A100825/2d17ba2ebab55b4e5e544e20c99e54ce.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Real-Fernandez F, Errante F, Di Santo A, Papini AM, Rovero P. Therapeutic proteins immunogenicity: a peptide point of view. Explor Drug Sci. 2023;1:377–87. https://doi.org/10.37349/eds.2023.00025 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-10-30 01:38:47 [Bib_Time] => 2023-10-30 01:38:47 [KeysWordContens] => Therapeutic proteins immunogenicity: a peptide point of view, Peptides, anti-drug antibodies, immune response, peptide epitopes, therapeutics, 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. ,Feliciana Real-Fernandez ... Paolo Rovero [PublishedText] => Published [IsEdit] => 0 [AccountId] => 86 [Zh] => 1 ) [25] => Array ( [ArticleId] => 907 [Create_Time] => 2023-10-31 [zipUrl] => https://www.explorationpub.com/uploads/zip/202312/20231218074859.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100826/100826.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100826/100826.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100826/100826_cover.png [JournalsId] => 11 [Title] => Creation and interpretation of machine learning models for aqueous solubility prediction [Abstract] => 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 o [AbstractComplete] =>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.
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.
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.
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.
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.
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.
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.
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.
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).
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).
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.
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.
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.
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.
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.
These statistical results can provide theoretical guidance for structural optimization, design, and synthesis of more effective non-covalent proteasome inhibitors in the future.
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.
[Names] => Yifan Huang ... Xiangyang Shi [Doi] => 10.37349/eds.2023.00030 [Published] => December 27, 2023 [Viewed] => 429 [Downloaded] => 17 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2023.00030 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 107 [TitleAbbr] => Explor Drug Sci. [Pages] => 2023;1:454–467 [Recommend] => 0 [Keywords] => Electrospinning, short fibers, drug delivery, cancer treatments, cancer theranostics [DetailTitle] => Emerging Nanomedicine Technologies for Enhanced Cancer Theranostics [DetailUrl] => https://www.explorationpub.com/Journals/eds/Special_Issues/107 [Id] => 100830 [ris] => https://www.explorationpub.com/uploads/Article/A100830/5089be34fc286740b9ee2a28883158c7.ris [bib] => https://www.explorationpub.com/uploads/Article/A100830/aa4b775a26a351024e6e0e96c9c323fd.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Huang Y, Zhan M, Shen M, Zhang L, Shi X. Electrospun short fibers: a new platform for cancer nanomedicine applications. Explor Drug Sci. 2023;1:454–67. https://doi.org/10.37349/eds.2023.00030 [Jindex] => 0 [CName] => XiangyangShi, [CEmail] => xshi@dhu.edu.cn, [Ris_Time] => 2023-12-22 02:42:42 [Bib_Time] => 2023-12-22 02:42:42 [KeysWordContens] => Electrospun short fibers: a new platform for cancer nanomedicine applications, Electrospinning, short fibers, drug delivery, cancer treatments, cancer theranostics, 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. ,Yifan Huang ... Xiangyang Shi [PublishedText] => Published [IsEdit] => 0 [AccountId] => 56 [Zh] => 1 ) [30] => Array ( [ArticleId] => 1028 [Create_Time] => 2023-12-27 [zipUrl] => https://www.explorationpub.com/uploads/zip/202312/20231227060653.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100831/100831.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100831/100831.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100831/100831_cover.png [JournalsId] => 11 [Title] => Reactivation of latent hepatitis B infection during immunosuppressive therapy with guselkumab for plaque psoriasis: a case report [Abstract] => 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 duri [AbstractComplete] =>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.
[Names] => Elena Franchi ... Pietro Andreone [Doi] => 10.37349/eds.2023.00031 [Published] => December 27, 2023 [Viewed] => 393 [Downloaded] => 10 [Subject] => Case Report [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2023.00031 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 167 [TitleAbbr] => Explor Drug Sci. [Pages] => 2023;1:468–474 [Recommend] => 0 [Keywords] => Hepatitis B infection, reactivation, guselkumab, psoriasis [DetailTitle] => Innovative Therapeutics in Hepato-Gastroenterology [DetailUrl] => https://www.explorationpub.com/Journals/eds/Special_Issues/167 [Id] => 100831 [ris] => https://www.explorationpub.com/uploads/Article/A100831/7af9aae14a24605d3f8657b9a7fec8ec.ris [bib] => https://www.explorationpub.com/uploads/Article/A100831/4a2977e78df5712faca2f67fe26d041d.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Franchi E, Costanzo AAC, Cursaro C, Lonardo A, Lasagni C, Andreone P. Reactivation of latent hepatitis B infection during immunosuppressive therapy with guselkumab for plaque psoriasis: a case report. Explor Drug Sci. 2023;1:468–74. https://doi.org/10.37349/eds.2023.00031 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-12-22 03:08:17 [Bib_Time] => 2023-12-22 03:08:17 [KeysWordContens] => Reactivation of latent hepatitis B infection during immunosuppressive therapy with guselkumab for plaque psoriasis: a case report, Hepatitis B infection, reactivation, guselkumab, psoriasis, 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. ,Elena Franchi ... Pietro Andreone [PublishedText] => Published [IsEdit] => 0 [AccountId] => 56 [Zh] => 1 ) [31] => Array ( [ArticleId] => 1043 [Create_Time] => 2023-12-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202312/20231228062520.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100832/100832.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100832/100832.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100832/100832_cover.png [JournalsId] => 11 [Title] => Harnessing the power of seaweed: unveiling the potential of marine algae in drug discovery [Abstract] => 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 sea [AbstractComplete] =>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.
[Names] => Leonel Pereira, Ana Valado [Doi] => 10.37349/eds.2023.00032 [Published] => December 28, 2023 [Viewed] => 1434 [Downloaded] => 45 [Subject] => Review [Year] => 2023 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2023.00032 [Inline] => 1 [Type] => 1 [Issue] => 6 [Topic] => 0 [TitleAbbr] => Explor Drug Sci. [Pages] => 2023;1:475–496 [Recommend] => 0 [Keywords] => Marine algae, drug discovery, bioactive compounds, polysaccharides, polyphenols, terpenoids, pharmacological activities [DetailTitle] => [DetailUrl] => [Id] => 100832 [ris] => https://www.explorationpub.com/uploads/Article/A100832/0a92d0812182a69efdfc8809b17f7844.ris [bib] => https://www.explorationpub.com/uploads/Article/A100832/13b3b3fd2762e12ffe50afa1f2a75ba9.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-27 [CitethisArticle] => Pereira L, Valado A. Harnessing the power of seaweed: unveiling the potential of marine algae in drug discovery. Explor Drug Sci. 2023;1:475–96. https://doi.org/10.37349/eds.2023.00032 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2023-12-26 02:24:50 [Bib_Time] => 2023-12-26 02:24:50 [KeysWordContens] => Harnessing the power of seaweed: unveiling the potential of marine algae in drug discovery, Marine algae, drug discovery, bioactive compounds, polysaccharides, polyphenols, terpenoids, pharmacological activities, 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. ,Leonel Pereira, Ana Valado [PublishedText] => Published [IsEdit] => 0 [AccountId] => 72 [Zh] => 1 ) [32] => Array ( [ArticleId] => 1076 [Create_Time] => 2024-01-22 [zipUrl] => https://www.explorationpub.com/uploads/zip/202401/20240122063804.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100833/100833.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100833/100833.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100833/100833_cover.png [JournalsId] => 11 [Title] => Histological diagnosis of primary biliary cholangitis in one patient without cholestasis alterations: a case report that escaped guidelines [Abstract] => 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, [AbstractComplete] =>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.
[Names] => Matteo Biagi ... Pietro Andreone [Doi] => 10.37349/eds.2024.00033 [Published] => January 22, 2024 [Viewed] => 298 [Downloaded] => 12 [Subject] => Case Report [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2024.00033 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 167 [TitleAbbr] => Explor Drug Sci. [Pages] => 2024;2:1–5 [Recommend] => 0 [Keywords] => Primary biliary cholangitis, alkaline phosphatase, liver histology, guidelines [DetailTitle] => Innovative Therapeutics in Hepato-Gastroenterology [DetailUrl] => https://www.explorationpub.com/Journals/eds/Special_Issues/167 [Id] => 100833 [ris] => https://www.explorationpub.com/uploads/Article/A100833/43089c2d6922db31325ac2007fd2dcf8.ris [bib] => https://www.explorationpub.com/uploads/Article/A100833/5d23f378c2c042cdd57720c95dc9e953.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Biagi M, Bernasconi E, Cursaro C, Ronconi E, Zanni F, Sighinolfi P, et al. Histological diagnosis of primary biliary cholangitis in one patient without cholestasis alterations: a case report that escaped guidelines. Explor Drug Sci. 2024;2:1–5. https://doi.org/10.37349/eds.2024.00033 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-01-22 06:38:04 [Bib_Time] => 2024-01-22 06:38:04 [KeysWordContens] => Histological diagnosis of primary biliary cholangitis in one patient without cholestasis alterations: a case report that escaped guidelines, Primary biliary cholangitis, alkaline phosphatase, liver histology, guidelines, 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. ,Matteo Biagi ... Pietro Andreone [PublishedText] => Published [IsEdit] => 0 [AccountId] => 86 [Zh] => 1 ) [33] => Array ( [ArticleId] => 1083 [Create_Time] => 2024-02-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202402/20240226045705.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100834/100834.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100834/100834.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100834/100834_cover.png [JournalsId] => 11 [Title] => Revisiting 310-helices: biological relevance, mimetics and applications [Abstract] => 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 releva [AbstractComplete] =>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.
[Names] => Diego Núñez-Villanueva [Doi] => 10.37349/eds.2024.00034 [Published] => February 01, 2024 [Viewed] => 570 [Downloaded] => 29 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2024.00034 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 250 [TitleAbbr] => Explor Drug Sci. [Pages] => 2024;2:6–37 [Recommend] => 0 [Keywords] => Peptide secondary structure, helical peptides, biomimetics, protein folding, 310-helices, peptidomimetics, foldamers, constrained amino acids [DetailTitle] => Mimicking Nature: Biomimetics as Tools for Diagnosis and Therapeutics [DetailUrl] => https://www.explorationpub.com/Journals/eds/Special_Issues/250 [Id] => 100834 [ris] => https://www.explorationpub.com/uploads/Article/A100834/ce0d842fe57bac71fc8a69341780e202.ris [bib] => https://www.explorationpub.com/uploads/Article/A100834/b9118a26b47191fc9db0e6f500a9a5ff.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Núñez-Villanueva D. Revisiting 310-helices: biological relevance, mimetics and applications. Explor Drug Sci. 2024;2:6–37. https://doi.org/10.37349/eds.2024.00034 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-02-01 05:07:55 [Bib_Time] => 2024-02-01 05:07:55 [KeysWordContens] => Revisiting 310-helices: biological relevance, mimetics and applications, Peptide secondary structure, helical peptides, biomimetics, protein folding, 310-helices, peptidomimetics, foldamers, constrained amino acids, 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. ,Diego Núñez-Villanueva [PublishedText] => Published [IsEdit] => 0 [AccountId] => 56 [Zh] => 1 ) [34] => Array ( [ArticleId] => 1094 [Create_Time] => 2024-02-01 [zipUrl] => https://www.explorationpub.com/uploads/zip/202402/20240229023154.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100835/100835.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100835/100835.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100835/100835_cover.png [JournalsId] => 11 [Title] => Effect of the size of nucleic acid delivery systems on their fate in cancer treatment [Abstract] => 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 [AbstractComplete] =>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.
[Names] => Mengyun Ye ... Dandan Zhu [Doi] => 10.37349/eds.2024.00035 [Published] => February 01, 2024 [Viewed] => 345 [Downloaded] => 15 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2024.00035 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 107 [TitleAbbr] => Explor Drug Sci. [Pages] => 2024;2:38–49 [Recommend] => 0 [Keywords] => Nucleic acid therapeutics, cancer treatment, delivery vectors, physicochemical properties, size [DetailTitle] => Emerging Nanomedicine Technologies for Enhanced Cancer Theranostics [DetailUrl] => https://www.explorationpub.com/Journals/eds/Special_Issues/107 [Id] => 100835 [ris] => https://www.explorationpub.com/uploads/Article/A100835/849bd9c775eb7e58d0639ccef7876d65.ris [bib] => https://www.explorationpub.com/uploads/Article/A100835/2f8d502959de26cf3b6b604833a88632.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Ye M, Gong J, Chen W, Liu X, Zhu D. Effect of the size of nucleic acid delivery systems on their fate in cancer treatment. Explor Drug Sci. 2024;2:38–49. https://doi.org/10.37349/eds.2024.00035 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-01-26 07:55:56 [Bib_Time] => 2024-01-26 07:55:56 [KeysWordContens] => Effect of the size of nucleic acid delivery systems on their fate in cancer treatment, Nucleic acid therapeutics, cancer treatment, delivery vectors, physicochemical properties, size, 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. ,Mengyun Ye ... Dandan Zhu [PublishedText] => Published [IsEdit] => 0 [AccountId] => 72 [Zh] => 1 ) [35] => Array ( [ArticleId] => 1149 [Create_Time] => 2024-02-27 [zipUrl] => https://www.explorationpub.com/uploads/zip/202402/20240227061101.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100836/100836.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100836/100836.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100836/100836_cover.png [JournalsId] => 11 [Title] => Seaweed: a sustainable solution for greening drug manufacturing in the pursuit of sustainable healthcare [Abstract] => 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 focuse [AbstractComplete] =>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.
[Names] => Leonel Pereira, João Cotas [Doi] => 10.37349/eds.2024.00036 [Published] => February 27, 2024 [Viewed] => 1101 [Downloaded] => 33 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2024.00036 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 168 [TitleAbbr] => Explor Drug Sci. [Pages] => 2024;2:50–84 [Recommend] => 0 [Keywords] => Macroalgae, drug manufacturing, sustainability, greening, sustainable healthcare, bioactive compounds, green technologies, regulatory perspectives [DetailTitle] => Greening Drug Manufacturing for a Sustainable Healthcare [DetailUrl] => https://www.explorationpub.com/Journals/eds/Special_Issues/168 [Id] => 100836 [ris] => https://www.explorationpub.com/uploads/Article/A100836/19fa894c9e7416006ed298139cf128bc.ris [bib] => https://www.explorationpub.com/uploads/Article/A100836/a188aa4218fd97a9102e445dfb375f95.bib [ens] => [Cited] => 1 [Cited_Time] => 2024-04-28 [CitethisArticle] => Pereira L, Cotas J. Seaweed: a sustainable solution for greening drug manufacturing in the pursuit of sustainable healthcare. Explor Drug Sci. 2024;2:50–84. https://doi.org/10.37349/eds.2024.00036 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-02-27 06:11:01 [Bib_Time] => 2024-02-27 06:11:01 [KeysWordContens] => Seaweed: a sustainable solution for greening drug manufacturing in the pursuit of sustainable healthcare, Macroalgae, drug manufacturing, sustainability, greening, sustainable healthcare, bioactive compounds, green technologies, regulatory perspectives, 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. ,Leonel Pereira, João Cotas [PublishedText] => Published [IsEdit] => 0 [AccountId] => 86 [Zh] => 1 ) [36] => Array ( [ArticleId] => 1150 [Create_Time] => 2024-02-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202402/20240229071844.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100837/100837.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100837/100837.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100837/100837_cover.png [JournalsId] => 11 [Title] => Influenza A virus hemagglutinin: from classical fusion inhibitors to proteolysis targeting chimera-based strategies in antiviral drug discovery [Abstract] => 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 inv [AbstractComplete] =>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.
[Names] => Francisco Javier Hermoso-Pinilla ... Francisco Javier Luque [Doi] => 10.37349/eds.2024.00037 [Published] => February 29, 2024 [Viewed] => 396 [Downloaded] => 23 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2024.00037 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 0 [TitleAbbr] => Explor Drug Sci. [Pages] => 2024;2:85–116 [Recommend] => 0 [Keywords] => Influenza A virus, hemagglutinin, fusion inhibitors, drug design, targeted protein degradation, antiviral proteolysis targeting chimeras [DetailTitle] => [DetailUrl] => [Id] => 100837 [ris] => https://www.explorationpub.com/uploads/Article/A100837/2bd57cb1e56aa1a16e26993c32e318e6.ris [bib] => https://www.explorationpub.com/uploads/Article/A100837/41b4fd6d1615dfe92f2e6223a2fb81f0.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Hermoso-Pinilla FJ, Valdivia A, Camarasa MJ, Ginex T, Luque FJ. Influenza A virus hemagglutinin: from classical fusion inhibitors to proteolysis targeting chimera-based strategies in antiviral drug discovery. Explor Drug Sci. 2024;2:85–116. https://doi.org/10.37349/eds.2024.00037 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-02-29 07:18:44 [Bib_Time] => 2024-02-29 07:18:44 [KeysWordContens] => Influenza A virus hemagglutinin: from classical fusion inhibitors to proteolysis targeting chimera-based strategies in antiviral drug discovery, Influenza A virus, hemagglutinin, fusion inhibitors, drug design, targeted protein degradation, antiviral proteolysis targeting chimeras, 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. ,Francisco Javier Hermoso-Pinilla ... Francisco Javier Luque [PublishedText] => Published [IsEdit] => 0 [AccountId] => 83 [Zh] => 1 ) [37] => Array ( [ArticleId] => 1153 [Create_Time] => 2024-02-29 [zipUrl] => https://www.explorationpub.com/uploads/zip/202402/20240229080523.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100838/100838.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100838/100838.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100838/100838_cover.png [JournalsId] => 11 [Title] => Mini-review on the antimicrobial potential of actinobacteria associated with seagrasses [Abstract] => 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 [AbstractComplete] =>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.
[Names] => Galana Siro, Atanas Pipite [Doi] => 10.37349/eds.2024.00038 [Published] => February 29, 2024 [Viewed] => 362 [Downloaded] => 21 [Subject] => Mini Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2024.00038 [Inline] => 1 [Type] => 1 [Issue] => 1 [Topic] => 100 [TitleAbbr] => Explor Drug Sci. [Pages] => 2024;2:117–125 [Recommend] => 0 [Keywords] => Actinobacteria, seagrasses, biosynthetic metabolites, marine ecosystem, antimicrobial resistance [DetailTitle] => Exploring Potential Drugs from Natural Products [DetailUrl] => https://www.explorationpub.com/Journals/eds/Special_Issues/100 [Id] => 100838 [ris] => https://www.explorationpub.com/uploads/Article/A100838/4fc18046806331fa1ef661eadcaf7258.ris [bib] => https://www.explorationpub.com/uploads/Article/A100838/ac99b96453aac366698caf9493d73183.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Cite this article: Siro G, Pipite A. Mini-review on the antimicrobial potential of actinobacteria associated with seagrasses. Explor Drug Sci. 2024;2:117–25. https://doi.org/10.37349/eds.2024.00038 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-02-29 08:05:24 [Bib_Time] => 2024-02-29 08:05:24 [KeysWordContens] => Mini-review on the antimicrobial potential of actinobacteria associated with seagrasses, Actinobacteria, seagrasses, biosynthetic metabolites, marine ecosystem, antimicrobial resistance, 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. ,Galana Siro, Atanas Pipite [PublishedText] => Published [IsEdit] => 0 [AccountId] => 86 [Zh] => 1 ) [38] => Array ( [ArticleId] => 1201 [Create_Time] => 2024-04-03 [zipUrl] => https://www.explorationpub.com/uploads/zip/202404/20240408021405.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100839/100839.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100839/100839.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100839/100839_cover.png [JournalsId] => 11 [Title] => Glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide agonists for the treatment of obesity and diabetes mellitus [Abstract] => 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, [AbstractComplete] =>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.
[Names] => Alexander C. Martins ... Fernando Albericio [Doi] => 10.37349/eds.2024.00039 [Published] => April 03, 2024 [Viewed] => 273 [Downloaded] => 14 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2024.00039 [Inline] => 1 [Type] => 0 [Issue] => [Topic] => 0 [TitleAbbr] => Explor Drug Sci. [Pages] => 2024;2:126–143 [Recommend] => 0 [Keywords] => Glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, obesity, diabetes mellitus, tirzepatide, semaglutide, liraglutide, peptides [DetailTitle] => [DetailUrl] => [Id] => 100839 [ris] => https://www.explorationpub.com/uploads/Article/A100839/85721034007ac24af3695e38d6affb56.ris [bib] => https://www.explorationpub.com/uploads/Article/A100839/f9327c04c3c88a7e6fa7fcffbf7537c7.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Martins AC, de la Torre BG, Albericio F. Glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide agonists for the treatment of obesity and diabetes mellitus. Explor Drug Sci. 2024;2:126–43. https://doi.org/10.37349/eds.2024.00039 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-04-08 02:14:05 [Bib_Time] => 2024-04-08 02:14:05 [KeysWordContens] => Glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide agonists for the treatment of obesity and diabetes mellitus, Glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, obesity, diabetes mellitus, tirzepatide, semaglutide, liraglutide, peptides, 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. ,Alexander C. Martins ... Fernando Albericio [PublishedText] => Published [IsEdit] => 0 [AccountId] => 86 [Zh] => 1 ) [39] => Array ( [ArticleId] => 1211 [Create_Time] => 2024-04-11 [zipUrl] => https://www.explorationpub.com/uploads/zip/202404/20240410060718.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100840/100840.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100840/100840.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100840/100840_cover.png [JournalsId] => 11 [Title] => Clinical studies with drugs and biologics aimed at slowing or reversing normal aging processes—emerging results and future perspectives [Abstract] => 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, [AbstractComplete] =>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.
[Names] => Ricardo P. Garay [Doi] => 10.37349/eds.2024.00040 [Published] => April 10, 2024 [Viewed] => 103 [Downloaded] => 5 [Subject] => Perspective [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2024.00040 [Inline] => 1 [Type] => 0 [Issue] => [Topic] => 281 [TitleAbbr] => Explor Drug Sci. [Pages] => 2024;2:144–153 [Recommend] => 0 [Keywords] => Aging, clinical trials, frailty, longevity, rejuvenation, senolytics, stem cells, vitamin D [DetailTitle] => Recent Advances with Investigational Compounds and Strategies to Delay or Reverse Normal Aging Processes [DetailUrl] => https://www.explorationpub.com/Journals/eds/Special_Issues/281 [Id] => 100840 [ris] => https://www.explorationpub.com/uploads/Article/A100840/5f04583d77ed0db28bca14c72a1c16e1.ris [bib] => https://www.explorationpub.com/uploads/Article/A100840/bc1f29b28474312106ca7fdc4f7f3619.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Garay RP. Clinical studies with drugs and biologics aimed at slowing or reversing normal aging processes—emerging results and future perspectives. Explor Drug Sci. 2024;2:144–53. https://doi.org/10.37349/eds.2024.00040 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-04-03 07:22:26 [Bib_Time] => 2024-04-03 07:22:26 [KeysWordContens] => Clinical studies with drugs and biologics aimed at slowing or reversing normal aging processes—emerging results and future perspectives, Aging, clinical trials, frailty, longevity, rejuvenation, senolytics, stem cells, vitamin D, 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. ,Ricardo P. Garay [PublishedText] => Published [IsEdit] => 0 [AccountId] => 86 [Zh] => 1 ) [40] => Array ( [ArticleId] => 1264 [Create_Time] => 2024-04-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202404/20240428064023.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100843/100843.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100843/100843.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100843/100843_cover.png [JournalsId] => 11 [Title] => Lipopeptide adjuvants for antibiotics and vaccines: the future step in the fight against multidrug-resistant and extensively drug-resistant pathogens [Abstract] => 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 [AbstractComplete] =>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.
[Names] => Chloé O. Sebilleau, Steven J. Sucheck [Doi] => 10.37349/eds.2024.00043 [Published] => April 28, 2024 [Viewed] => 1 [Downloaded] => 1 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2024.00043 [Inline] => 0 [Type] => 0 [Issue] => [Topic] => 124 [TitleAbbr] => Explor Drug Sci. [Pages] => 2024;2:203–233 [Recommend] => 0 [Keywords] => Lipopeptide, adjuvant, vaccine, antibiotic [DetailTitle] => Bioactive Peptides discovery and development [DetailUrl] => https://www.explorationpub.com/Journals/eds/Special_Issues/124 [Id] => 100843 [ris] => https://www.explorationpub.com/uploads/Article/A100843/e7703fd461cb95d9dd78378cb42a5c51.ris [bib] => https://www.explorationpub.com/uploads/Article/A100843/efc9f75c165f730cf330c49dab31332d.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Sebilleau CO, Sucheck SJ. Lipopeptide adjuvants for antibiotics and vaccines: the future step in the fight against multidrug-resistant and extensively drug-resistant pathogens. Explor Drug Sci. 2024;2:203–33. https://doi.org/10.37349/eds.2024.00043 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-04-28 03:07:44 [Bib_Time] => 2024-04-28 03:07:44 [KeysWordContens] => Lipopeptide adjuvants for antibiotics and vaccines: the future step in the fight against multidrug-resistant and extensively drug-resistant pathogens, Lipopeptide, adjuvant, vaccine, antibiotic, 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. ,Chloé O. Sebilleau, Steven J. Sucheck [PublishedText] => Published [IsEdit] => 0 [AccountId] => 72 [Zh] => 0 ) [41] => Array ( [ArticleId] => 1231 [Create_Time] => 2024-04-18 [zipUrl] => https://www.explorationpub.com/uploads/zip/202404/20240426091507.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100841/100841.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100841/100841.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100841/100841_cover.png [JournalsId] => 11 [Title] => Stapled peptides: targeting protein-protein interactions in drug development [Abstract] => 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 promis [AbstractComplete] =>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.
[Names] => Qian Zhang ... Chunqiu Zhang [Doi] => 10.37349/eds.2024.00041 [Published] => April 18, 2024 [Viewed] => 118 [Downloaded] => 12 [Subject] => Review [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2024.00041 [Inline] => 1 [Type] => 0 [Issue] => [Topic] => 124 [TitleAbbr] => Explor Drug Sci. [Pages] => 2024;2:154–189 [Recommend] => 0 [Keywords] => Stapled peptides, protein-protein interactions, pharmacological [DetailTitle] => Bioactive Peptides discovery and development [DetailUrl] => https://www.explorationpub.com/Journals/eds/Special_Issues/124 [Id] => 100841 [ris] => https://www.explorationpub.com/uploads/Article/A100841/8893dbb545b41f48c0f92170b9d2b3e0.ris [bib] => https://www.explorationpub.com/uploads/Article/A100841/795cd3234f513c55fa09c4c291930f27.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Zhang Q, Wang Z, Mei X, Chen Q, Zhang C. Stapled peptides: targeting protein-protein interactions in drug development. Explor Drug Sci. 2024;2:154–89. https://doi.org/10.37349/eds.2024.00041 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-04-12 02:39:49 [Bib_Time] => 2024-04-12 02:39:49 [KeysWordContens] => Stapled peptides: targeting protein-protein interactions in drug development, Stapled peptides, protein-protein interactions, pharmacological, 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. ,Qian Zhang ... Chunqiu Zhang [PublishedText] => Published [IsEdit] => 0 [AccountId] => 56 [Zh] => 0 ) [42] => Array ( [ArticleId] => 1232 [Create_Time] => 2024-04-19 [zipUrl] => https://www.explorationpub.com/uploads/zip/202404/20240419012711.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100842/100842.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100842/100842.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100842/100842_cover.png [JournalsId] => 11 [Title] => Daropeptide natural products [Abstract] => 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- [AbstractComplete] =>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.
[Names] => Suze Ma ... Qi Zhang [Doi] => 10.37349/eds.2024.00042 [Published] => April 19, 2024 [Viewed] => 163 [Downloaded] => 13 [Subject] => Perspective [Year] => 2024 [CiteUrl] => https://api.crossref.org/works/10.37349/eds.2024.00042 [Inline] => 1 [Type] => 0 [Issue] => [Topic] => 124 [TitleAbbr] => Explor Drug Sci. [Pages] => 2024;2:190–202 [Recommend] => 0 [Keywords] => Biosynthesis, radical S-adenosylmethionine, antibiotic, cyclophane [DetailTitle] => Bioactive Peptides discovery and development [DetailUrl] => https://www.explorationpub.com/Journals/eds/Special_Issues/124 [Id] => 100842 [ris] => https://www.explorationpub.com/uploads/Article/A100842/09fb9ad770608b52da518aa4a3f9573c.ris [bib] => https://www.explorationpub.com/uploads/Article/A100842/42a1207f088dfb63ee6a25ac40d301ea.bib [ens] => [Cited] => 0 [Cited_Time] => [CitethisArticle] => Ma S, Guo S, Ding W, Zhang Q. Daropeptide natural products. Explor Drug Sci. 2024;2:190–202. https://doi.org/10.37349/eds.2024.00042 [Jindex] => 0 [CName] => [CEmail] => [Ris_Time] => 2024-04-12 02:46:17 [Bib_Time] => 2024-04-12 02:46:17 [KeysWordContens] => Daropeptide natural products, Biosynthesis, radical S-adenosylmethionine, antibiotic, cyclophane, 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. ,Suze Ma ... Qi Zhang [PublishedText] => Published [IsEdit] => 0 [AccountId] => 86 [Zh] => 0 ) [43] => Array ( [ArticleId] => 1266 [Create_Time] => 2024-04-28 [zipUrl] => https://www.explorationpub.com/uploads/zip/202404/20240428063304.zip [xmlUrl] => https://www.explorationpub.com/uploads/Article/A100844/100844.xml [pdfUrl] => https://www.explorationpub.com/uploads/Article/A100844/100844.pdf [coverUrl] => https://www.explorationpub.com/uploads/Article/A100844/100844_cover.png [JournalsId] => 11 [Title] => Subacute toxicity of isoliquiritigenin-zein phosphatidylcholine nanoparticles on biochemical, hematological, and histopathological parameters in Sprague-Dawley rats [Abstract] => Aim: Isoliquiritigenin (ISL) is a natural flavonoid found in many natural plants, which exhibits numerous pharmacological properties including anti-inflammatory, antioxidant, antitumor, and antiv [AbstractComplete] =>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.
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.
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.
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.