The integration of three-dimensional (3D) printing techniques into the domains of biomedical research and personalized medicine highlights the evolving paradigm shifts within contemporary healthcare. This technological advancement signifies potential breakthroughs in patient-specific therapeutic interventions and innovations. This systematic review offers a critical assessment of the existing literature, elucidating the present status, inherent challenges, and prospective avenues of 3D printing in augmenting biomedical applications and formulating tailored medical strategies. Based on an exhaustive literature analysis comprising empirical studies, case studies, and extensive reviews from the past decade, pivotal sectors including tissue engineering, prosthetic development, drug delivery systems, and customized medical apparatuses are delineated. The advent of 3D printing provides precision in the fabrication of patient-centric implants, bio-structures, and devices, thereby mitigating associated risks. Concurrently, it facilitates the ideation of individualized drug delivery paradigms to optimize therapeutic outcomes. Notwithstanding these advancements, issues concerning material biocompatibility, regulatory compliance, and the economic implications of avant-garde printing techniques persist. To fully harness the transformative potential of 3D printing in healthcare, collaborative endeavors amongst academicians, clinicians, industrial entities, and regulatory bodies are paramount. With continued research and innovation, 3D printing is poised to redefine the trajectories of biomedical science and patient-centric care. The paper aims to justify the research objective of whether to what extent the integration of 3D printing technology in biomedicine enhances patient-specific treatment and contributes to improved healthcare outcomes.

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Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and paranasal sinuses. Eosinophilic inflammation is described as a common endotype. The anti-interleukin-5 (IL-5) antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe CRSwNP when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, therapy monitoring and follow-up documentation are required, and therapy discontinuation has not been adequately established yet. In this paper, recommendations for monitoring the course and efficacy of therapy as well as for reviewing the duration and possible termination of therapy are provided. For this purpose, a literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching MEDLINE, PubMed, and the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including October 2022 were considered. Based on the international literature and previous experience, recommendations for follow-up, adherence to therapy intervals and possible therapy breaks, as well as termination of therapy when using mepolizumab for the indication CRSwNP in the German health care system are given by an expert panel on the basis of a documentation sheet.

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Patients with unresectable biliary tract carcinomas (BTCs) have a poor prognosis with a median overall survival of fewer than 12 months following systemic chemotherapy. In recent years, the identification of distinct molecular alterations with corresponding targeted therapies is modifying this therapeutic algorithm. The aim of this review is to present an overview of targeted therapy for BTCs, describing published available data and potential future challenges in ongoing trials. From clinicaltrials.gov online database all ongoing trials for BTCs (any stage) was examinated in July 2021, and data regarding study design, disease characteristics and type of treatments were registered. Oncogenic-driven therapy (targeted therapy) was investigated in 67 trials. According to research, 15 ongoing trials (22.4%) are investigating fibroblast growth factor (FGF) receptor (FGFR)-inhibitors in BTCs. Three (18.7%) are open-label randomized multicenter phase 3 trials, 8 (50%) are single-arm phase two trials, and 4 (25%) are phase one studies. Twelve (17.9%) clinical trials dealt with isocitrate dehydrogenase (IDH) 1/2 targeting therapy either in combination with cisplatin (Cis) and gemcitabine (Gem) as first-line treatment for BTCs or in monotherapy in patients with IDH1 mutant advanced malignancies, including cholangiocarcinoma (CCA). Nine (13.4%) clinical trials tested human epidermal growth factor receptor (HER) 2 targeting therapy. Four (44.4%) studies are phase I trials, two (22.2%) are phase I/II trials, and three (33.3%) phase II trials. Rare molecular alterations in BTCs, such as anaplastic lymphoma kinase (ALK), c-ros oncogene1 receptor tyrosine kinase (ROS1), and v-RAF murine sarcoma viral oncogene homologue B1 (BRAF), are also under investigation in a few trials. Forty-four clinical trials (17.2%) are investigating not oncogenic-driven multitarget therapy like multireceptor tyrosin kinase inhibitors and antiangiogenetic agents. In conclusion, this review shows that BTCs management is experiencing important innovations, especially in biomarker-based patient selection and in the new emerging therapeutic approach. Many ongoing trials could answer questions regarding the role of molecular inhibitors leading to new therapeutic frontiers for molecular subcategories of BTCs.

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Mitochondria are present in all mammalian cells except matured red blood cells. Mitochondria consist of several metabolic pathways for glucose, fatty acids, amino acids, and bioenergetic pathways for ATP synthesis, membrane potential, and reactive oxygen production. In the liver, hepatic mitochondria play a key role in hepatic steatosis because mitochondrial metabolism produces acetyl-CoA which is the building block for synthesis of lipids and cholesterol. Mitochondria inner membrane is impermeable of metabolites, reducing equivalents, and small molecules such as phosphate, and sulfate. Thus, mitochondrial shuttles and carriers function as the routes of influx and efflux of these metabolites and molecules across the inner membrane. The signal regulation of these shuttles and mitochondrial enzymes could play a key role in coordinating the mitochondrial metabolism to adapt the cytosolic part of metabolic pathways in liver metabolic stress. Intriguingly, the interaction of mitochondria protein SH3 domain-binding protein 5 (SAB/SH3BP5) and c-Jun N-terminal kinase (JNK) was found as a pivotal role in sustained activation of JNK and phosphorylated-JNK (P-JNK) mediated activation of lipogenic pathway in nutritional excess. Knockout or knockdown of SAB prevented or reversed the hepatic steatosis, inflammation, and fibrosis, and improved metabolic intolerance and energy expenditure. Moreover, blocking the SAB peptide prevents palmitic acid-induced P-JNK interaction with SAB and inhibition of mitochondrial bioenergetics, implying the P-JNK effect on mitochondrial metabolism. This review focuses on the flow of mitochondrial metabolites in metabolic stress conditions and the contribution of mitochondria and mitochondrial stress signals in hepatic steatosis.

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In spite of the immense advancement in the diagnostic and treatment modalities, cancer continues to be one of the leading causes of mortality across the globe, responsible for the death of around 10 million patients every year. The foremost challenges faced in the treatment of this disease are chemoresistance, adverse effects of the drugs, and the high cost of treatment. Though scientific studies over the past few decades have foreseen and are focusing on the cancer-preventive and therapeutic potential of natural products and their underlying mechanism of action, many more of these agents are not still explored. Piperlongumine (PL), or piplartine, is one such alkaloid isolated from Piper longum Linn., which is shown to be safe and has significant potential in the prevention and therapy of cancer. Numerous shreds of evidence have established the ability of this alkaloid and its analogs and nanoformulations in modulating various complex molecular pathways such as phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin, nuclear factor-kappa B, Janus kinases/signal transducer and activator of transcription 3, etc. and inhibit different hallmarks of cancer such as cell survival, proliferation, invasion, angiogenesis, epithelial-mesenchymal-transition, metastases, etc. In addition, PL was also shown to inhibit radioresistance and chemoresistance and sensitize the cancer cells to the standard chemotherapeutic agents. Therefore, this compound has high potential as a drug candidate for the prevention and treatment of different cancers. The current review briefly reiterates the anti-cancer properties of PL against different types of cancer, which permits further investigation by conducting clinical studies.

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Neurological disorders constitute a major global health burden with limited effective treatments. Despite advances in molecular neuroscience, critical gaps persist in understanding intercellular communication systems underlying central nervous system homeostasis and neurodegeneration. Extracellular vesicles (EVs), nanoscale to microscale membrane-bound vesicles secreted by virtually all cell types, have emerged as pivotal mediators of intercellular communication in neurological pathologies. This review examines molecular mechanisms governing EV biogenesis, cargo selection, and pathological functions in neurological disorders, emphasizing the emerging role of ubiquitin-like protein 3 (UBL3) as a novel regulator of EV-mediated protein sorting. Neural cell populations produce specialized EV subtypes containing distinct molecular cargo reflecting their physiological states. UBL3, a membrane-anchored post-translational modifier, operates through geranylgeranylation-dependent mechanisms to promote selective protein incorporation into small EVs (sEVs), with knockout studies demonstrating approximately 60% reduction in EV protein content. Proteomic analyses reveal UBL3 interacts with over 1,200 proteins, with ~30% classified as EV cargo proteins. Critically, UBL3-mediated sorting influences disease-associated protein trafficking, including α-synuclein in Parkinson’s disease and mutant huntingtin in Huntington’s disease, suggesting involvement in prion-like spreading mechanisms. EVs’ dual nature as pathological mediators and therapeutic vehicles represents a paradigm shift in neurological medicine. EVs offer advantages as natural drug delivery systems capable of crossing the blood-brain barrier, accessible biomarkers for noninvasive disease monitoring via liquid biopsies (achieving diagnostic accuracies exceeding 0.88 ROC-AUC), and engineered therapeutic platforms for delivering CRISPR-Cas9 systems and neuroprotective factors. However, clinical translation requires addressing challenges, including standardizing isolation protocols, elucidating cell-type-specific cargo sorting mechanisms, and defining optimal administration routes. Understanding UBL3-mediated cargo sorting mechanisms presents promising therapeutic opportunities by selectively modulating pathogenic protein trafficking. EVs, positioned at the intersection of pathogenesis and therapy, represent attractive targets for precision medicine approaches in neurological conditions, with UBL3 emerging as a novel molecular handle for manipulating EV composition and function.

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Merozoite invasion of erythrocytes relies on molecular interactions between parasite and host proteins, making these proteins potential therapeutic targets. This review summarizes research on Plasmodium falciparum merozoite invasion conducted at the Instituto de Inmunología, San Juan de Dios Hospital, between 1990 and 2000. Erythrocyte-binding analyses of P. falciparum proteins merozoite surface protein 1 (MSP-1), MSP-2, acid basic repeat antigen (ABRA) (MSP-9), apical membrane antigen-1 (AMA-1), rhoptry-associated protein 1 (RAP-1), glycophorin-binding protein 130 (GBP-130), serine repeat antigen 5 (SERA-5), erythrocyte-binding antigen 140 (EBA-140), and EBA-175 identified 50 high-activity binding peptides (HABPs) with nanomolar-range dissociation constants. Most of these peptides inhibit merozoite invasion and belong to erythrocyte-binding regions of their respective proteins. Several HABPs overlap with epitopes recognized by inhibitory monoclonal antibodies (mAbs). MSP-1 HABP-5501 contains epitopes for mAbs 12.8, 12.10, MaliM03 fragment antigen binding (Fab), and 42D6 Fab, all of which block invasion. MSP-2 HABPs include epitopes targeted by opsonizing antibodies, while MSP-9 HABPs (2148–2153) interact with Band 3 during invasion. AMA-1 HABPs (4315, 4316, and 4325) contribute to the 1F9 epitope, a key target of immune recognition. RAP-1 HABP-26188 elicits inhibitory antibodies, including cross-reactive mAbs SP5.2 and SP8.18, the latter displaying parasite growth inhibition. GBP-130 HABP-2220 binds glycophorin and induces invasion-blocking antibodies. SERA-5 HABP-6725 contains sequences targeted by native SERA-5 antibodies, while HABPs 6727 and 6733 are recognized by antibodies from natural infection and vaccination. EBA-140 HABPs (26135, 26144, and 26147) are located in Region II (RII) and are recognized by mAbs with moderate to strong neutralizing activity. EBA-175 HABPs (1779, 1783, 1814, 1815, and 1818) are in recombinant fragments recognized by antibodies eluted from immune complexes. HABPs 1779 and 1783, located in RII, bind erythrocytes independently of sialic acid, inhibit rRII-EBA binding, and interact with α(2,3)-sialyllactose. HABP-1783 also contains the target site of mAb R217, which potently blocks EBA-175 binding to glycophorin A and inhibits invasion.

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Arginase-1 (Arg1) and the inducible nitric oxide synthase 2 (NOS2) compete for the common substrate L-arginine, semi-essential amino acid, and central intestinal metabolite. Both enzymes exhibit various, sometimes opposing effects on immune responses, tissue regeneration, or microbial growth and replication. In sub-mucosal tissues of patients suffering from inflammatory bowel disease (IBD), similar as in experimental colitis, the expression and activity of both enzymes, Arg1 and NOS2 are more prominent than in respective controls. Accordingly, the metabolism of L-arginine is altered in IBD patients. Thus, L-arginine represents a promising medical target for clinical intervention in these devastating diseases. Previous studies primarily focused on the host side of L-arginine metabolism. Initial reports using Arg1 inhibitors generated conflicting results in murine colitis models. Subsequently, only the generation of conditional Arg1 knockout mice allowed reliable functional analyses of Arg1 and the L-arginine metabolism in the immune system. Utilizing cell-specific conditional Arg1 knockouts, we have recently reported that Arg1, surprisingly, hampered the resolution of experimental colitis due to the restriction of the intraluminal availability of L-arginine. Reduced levels of L-arginine restrained the compositional diversity of the intestinal microbiota and subsequently the mutual metabolism between the microbiota and the host. Thus, the intraluminal microbiota represents a potential therapeutic target for L-arginine metabolism aside from host-dependent L-arginine consumption.

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Diabetic wound healing presents a unique and complex challenge due to the impaired cellular and molecular functions associated with diabetes. Chronic wounds in diabetic patients are characterized by prolonged inflammation, reduced angiogenesis, and impaired collagen deposition, which significantly hinder the healing process. This comprehensive review focuses on the innovative applications of designer cytokines in precision therapy for diabetic wound healing, emphasizing the remarkable advancements made in overcoming the limitations of natural cytokines, such as their short half-life, potential cytotoxicity, and lack of specificity. We begin by detailing the intricate biological characteristics of diabetic wounds and the essential role that cytokines play in orchestrating the healing process. The review critically examines the constraints of natural cytokines and traces the evolution of synthetic alternatives, with a particular emphasis on peptide-based and nucleic acid-based artificial cytokines. Advanced strategies for designing these artificial cytokines are discussed, including molecular modifications, functional enhancements, and specificity improvements to better target pathological conditions in diabetic wounds. Furthermore, we explore the utilization of synthetic biology techniques to engineer effective cytokine-based therapies. The promising therapeutic potential of rationally designed cytokines is highlighted, showcasing their ability to modulate the wound microenvironment, enhance tissue regeneration, and reduce chronic inflammation. This review not only provides valuable perspectives on the future research directions but also offers insights into the potential clinical applications of these innovative therapies, aiming to significantly improve the outcomes for patients suffering from diabetic wounds.

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