Exosomes are small, bilayer lipid vesicles with diameters ranging from approximately 40-160 nm. These vesicles carry a diverse array of molecular cargo, including DNA, RNA, lipids, and proteins, which play a critical role in intercellular communication. Among the various cell types, mesenchymal stem cells (MSCs) are recognized as highly efficient producers of exosomes. MSC-derived exosomes (MSC-exo) have been demonstrated to play dual roles in cancer progression, either promoting or inhibiting tumor growth, depending on the specific context. This unique ability positions MSC-exo as a promising tool for cancer therapy. This review examines the multifaceted roles of MSC-exo in various types of digestive system tumors. It highlights the exosomes’ potential to modulate tumor microenvironments, influence immune responses, and deliver therapeutic molecules, thereby offering new avenues for targeted cancer treatment. In addition, the review explores the clinical application value of MSC-exo as anti-tumor agents, emphasizing the exosomes’ potential for drug delivery and personalized medicine. However, despite the exosomes’ therapeutic potential, several challenges must be addressed before MSC-exo can be widely adopted in clinical settings. These include issues related to large-scale production, standardization, safety, and regulatory approval. By addressing these challenges, MSC-exo could emerge as a transformative approach in cancer treatment, offering innovative solutions for precision medicine and improved patient outcomes. This review underscores the importance of continued research to fully realize the potential of MSC-exo in oncology.
Snakebite envenomation remains a severe global health burden, particularly in impoverished, rural, and tropical regions where healthcare resources are sparse. Despite over 125 years of progress in antivenom therapy, numerous obstacles persist related to efficacy, specificity, cost, and availability. Conventional antivenoms, although life-saving, are associated with significant drawbacks, including species specificity and adverse immunologic reactions. This review explores the historical milestones in antivenom development, discusses present therapeutic limitations, highlights novel innovations through biotechnological approaches, and presents a list of ongoing clinical trials that aim to revolutionize the field. It emphasizes the pressing need for improved therapeutics and the critical role of translational research in mitigating the global impact of snakebite envenomation.
Protein tyrosine kinases (PTKs) are key enzymes of cellular signaling, regulating key processes such as proliferation, differentiation, migration, metabolism, and apoptosis. Tyrosine kinases (TKs) modulate protein functions in normal and disease states by phosphorylation of tyrosine residues on target proteins. In this critical role, dysregulation of TKs is directly linked with disease progression, particularly in cancer, therefore making TKs an attractive target for therapeutic intervention. The PTK family is broadly classified into receptor TKs (RTKs) and non-receptor TKs (NRTKs), having variation at both structural and functional levels. RTKs are membrane-bound kinases that initiate intracellular signaling when they react with extracellular ligands, whereas NRTKs within the cytoplasm or nucleus convey intracellular signaling upon receptor activation. This paper aims to review the organization, mechanistic activity, and therapeutic potential of PTKs, with a particular focus on epidermal growth factor receptor and proto-oncogene tyrosine-protein kinase (Src) as representatives of RTK and NRTK, respectively. In addition, this review also focuses on addressing emerging strategies to enhance tyrosine kinase inhibitor efficacy and overcome acquired resistance in cancer therapy.
Biocompatibility is a critical factor in the application of nanomaterials in medical fields, as these materials must interact safely and effectively with biological systems to be viable for therapeutic and diagnostic use. This article investigates this feature, focusing on the interactions of nanomaterials with cells, tissues, and the immune system. Key properties such as surface chemistry, size, shape, and material composition are examined for their influence on the biological response. The article also explores the role of nanomaterials in medical applications, including drug delivery, diagnostic imaging, and tissue engineering, while discussing the challenges involved in enhancing their biocompatibility. A case study on the calcium oxide (CaO)-calcium phosphate (CaP) binary system is presented, showcasing its potential in bone tissue engineering, particularly its osteoinductive properties and ability to mimic the bone mineral content. The analysis underscores both its therapeutic potential and the biocompatibility concerns of CaO-CaP scaffolds. The article concludes by outlining strategies to optimize nanomaterial biocompatibility and future directions for their translation into medical applications.
Glucagon-like peptide-1 (GLP-1) is a crucial incretin hormone that regulates glucose homeostasis by enhancing insulin secretion, suppressing glucagon release, and delaying gastric emptying. While synthetic GLP-1 receptor agonists such as semaglutide have demonstrated efficacy in managing type 2 diabetes mellitus and obesity, their high cost, limited accessibility, and adverse effects have limited their applicability, necessitating the search for alternative therapeutic strategies. Peganum harmala (harmal), a traditional medicinal plant, has gained attention for its bioactive alkaloids, harmine, and harmaline, which have been shown to modulate key molecular pathways involved in GLP-1 secretion and insulin sensitization. These alkaloids enhance Akt phosphorylation (pS473-Akt), facilitating glucose transporter type 4 translocation and glucose uptake, while concurrently activating the nuclear factor erythroid 2-related factor 2 pathway, leading to increased antioxidant defenses and reduced oxidative stress in pancreatic β-cells and enteroendocrine L-cells. Furthermore, P. harmala alleviates insulin resistance by suppressing IRS-1 serine phosphorylation (pS307-IRS-1) and improving phosphoinositide 3-kinase/Akt signaling, thereby optimizing insulin receptor sensitivity and metabolic homeostasis. Despite these promising pharmacological properties, the poor solubility and rapid metabolism of harmine and harmaline pose challenges to their clinical application. Nanotechnology-based drug delivery systems, including liposomal encapsulation and polymeric nanoparticles, offer a potential solution to enhance bioavailability, prolong systemic circulation, and enable targeted delivery to GLP-1-secreting cells. This paper delves into the molecular mechanisms by which P. harmala stimulates GLP-1 secretion and improves insulin sensitivity, compares its effects with semaglutide, and highlights the potential role of nanotechnology in optimizing its therapeutic applications. By integrating traditional medicine with modern pharmaceutical advancements, P. harmala represents a promising, cost-effective, and sustainable approach to metabolic disorder management, warranting further investigation through pre-clinical and clinical studies.
Diorganotin (IV) complexes have attracted considerable attention due to their diverse structural features and promising biological properties. The investigation into diorganotin (IV) compounds as potential antimicrobial agents is an active and captivating area of research, particularly emphasizing the synthesis and characterization of diorganotin (IV) complexes with bioactive and sterically hindered ligands. In this study, novel diorganotin (IV) azomethine chelates were synthesized from sterically hindered 4-(2’-mercapto-phenyl-iminoaryl/alkyl)-2,4-dihydro-5-methyl-2-phenyl-3H-pyrazol-3-ones, characterized, and evaluated for their antimicrobial potential. These complexes were obtained by reacting dimethyltin dichloride with the corresponding disodium salts in benzene and characterized through infrared, 1H, 13C, and 119Sn nuclear magnetic resonance spectroscopy, along with molecular weight determination. Structural optimization and electronic property analyses were performed using density functional theory (DFT) at the B3LYP/LanL2DZ level. Conceptual DFT descriptors indicated subtle variations in reactivity, with Chelate-4 exhibiting the highest softness and the lowest energy gap, suggesting enhanced electron-accepting capability. Molecular docking studies were conducted on the ligand moieties (L-1 to L-4) against proteins from Gram-positive and Gram-negative bacteria using cephalosporin and sulfamethoxazole as reference drugs. Ligand L-4 displayed superior binding affinities across all targets, aligning with its DFT-predicted reactivity. Absorption, distribution, metabolism, and excretion analysis revealed that while L-1 and L-2 showed favorable drug-likeness and oral bioavailability, L-4 demonstrated higher lipophilicity and possible metabolic concerns despite its potent antibacterial potential.
Commelina diffusa, also known as the climbing dayflower or spreading dayflower, is an herbaceous plant from the Commelinaceae family, found throughout tropical regions, including Bangladesh. The crude methanol extract and different fractions of C. diffusa were evaluated for their antimicrobial, analgesic, and hypoglycemic activities. The whole plant was extracted with methanol by the cold extraction method. The concentrated extract was then partitioned into petroleum ether- and chloroform-soluble fractions. The antimicrobial test was performed using the disc diffusion method. The analgesic effects were evaluated through both writhing and tail-flick tests at doses of 100 and 200 mg/kg body weight. The oral glucose tolerance test (OGTT) was performed to observe the hypoglycemic effect. The chloroform and methanol soluble fractions showed potent antimicrobial activity against Gram-positive bacteria and fungi. Statistical evaluation of the tail-flick test confirmed that the chloroform soluble fraction (100 mg/kg body weight) of C. diffusa had a significant amount of central analgesic activity (p<0.001). The petroleum ether soluble fraction showed significant central analgesic activity only at higher doses (p <0.01; 200 mg/kg body weight). The acetic acid-induced writhing test also confirmed the peripheral analgesic activity of the samples. The maximum inhibition was noted for the chloroform soluble fraction (64.56%), followed by crude methanolic extract (56.96%) and petroleum ether soluble fraction (53.16%). However, all the extracts showed no significant hypoglycemic activity in the OGTT. This observation, derived from an acute model of non-diabetic animals, does not preclude the possibility of antidiabetic effects in disease-related conditions. Further investigation is warranted to explore the specific metabolites and their pharmacological activities in relevant disease models.