Current drug discovery technologies最新文献

Chromothripsis, a phenomenon of massive genomic rearrangements, introduces extensive mutations in critical genes, affecting cell survival and apoptosis. Among these genes, the BCL2 (B-cell lymphoma 2) gene, which plays a crucial antiapoptotic role in cancer cells, is often subjected to significant alterations. Here, we present a computational pipeline to model and analyze the structural and functional impacts of chromothripsis-induced Single-Nucleotide Polymorphisms (SNPs) within the BCL2 gene. This pipeline integrates mutation simulation, homology modeling, and protein inter-action analysis to evaluate the stability and apoptotic potential of BCL2 mutations. These results indicate that chromothripsis-induced mutations can destabilize the Bcl-2 protein, thereby disrupting its binding affinity with apoptotic regulators, such as Bax. These findings support the potential of ergodic anticancer therapy to exploit such mutations, facilitating the apoptosis of cancer cells. Our computational model offers a novel in silico approach for understanding mutation-driven alterations in cancer biology, aiding the development of therapeutic strategies targeting apoptotic pathways.

Diabetes mellitus (DM) is a prevalent metabolic disorder with a rapidly rising global inci-dence, presenting a significant burden to healthcare systems worldwide. Flavonoids, a class of natu-rally occurring polyphenolic compounds, are well-documented for their diverse pharmacological ac-tivities, particularly their anti-diabetic and anti-inflammatory effects. These secondary metabolites are commonly found in fruits, vegetables, and fungi and are classified into six main subclasses: fla-vanols, flavones, flavanones, isoflavones, anthocyanidins, and chalcones. The interplay between hy-perglycemia, inflammation, and vascular complications in diabetes is now well recognized. Flavo-noids with anti-diabetic properties may help mitigate inflammation by reducing hyperglycemia through various mechanisms. This review explores the antidiabetic potential and molecular mecha-nisms of citrus flavonoids, drawing on updated evidence from in vitro and in vivo studies. Flavonoids are shown to regulate biomarkers of glycemic control, lipid metabolism, renal function, hepatic en-zymes, and antioxidant defenses. They also modulate signaling pathways implicated in glucose up-take and insulin sensitivity, which are central to the development of diabetes and its complications. Furthermore, this review synthesizes current knowledge on the antidiabetic effects of dietary flavo-noids, emphasizing their molecular mechanisms in modulating key pathways such as glucose trans-porters, hepatic enzymes, tyrosine kinase inhibitors, AMP-activated protein kinase (AMPK), peroxi-some proliferator-activated receptors (PPARs), and nuclear factor kappa B (NF-κβ). Further research is essential to deepen our understanding of flavonoids' therapeutic mechanisms in managing diabetes.

Habitual inflammation is defined as the persistent activation of the body's susceptible sys-tem in response to harmful events. This ongoing inflammatory process can sometimes harm normal organs & tissues. Crucially, chronic inflammation has been linked to the emergence and advancement of a variety of disorders, including cardiovascular diseases, respiratory issues, metabolic illnesses, neurological disorders, and cancer. These diseases are classified as chronic-degenerative conditions due to the sustained and persistent nature of the underlying chronic inflammatory processes. Treating patient's inflammation creates new therapeutic opportunities for these related illnesses. In this review, we will study the role of inflammation during the onset of rheumatoid arthritis. Further-more, we will explore diseases associated with chronic inflammation. Rheumatoid Arthritis (RA) is a persistent autoimmune condition causing joint inflammation. It commonly affects joints of hands, wrists, fingers, elbows, shoulders, neck, back, hips, knees, ankles, and toes. We will discuss various herbal drug therapies that help in treating and providing relief from joint pain in rheumatoid arthritis. Herbal medicines are preferable since they are safer and have fewer adverse effects than the synthetic ones. However, they are not completely safe, and therefore, toxicity studies are being conducted. . Herbal medications' phytochemicals are generally beneficial in the treatment of infectious, autoim-mune, and seditious disorders; they are especially helpful in the management of arthritis. Arthritis is one of the leading causes of impairment in the quality of life for millions of people globally. The purpose of this review is to explore the role of inflammation in rheumatoid arthritis and its association with chronic inflammation. This article highlights the importance of herbal medicine as one of the treatment options for rheumatoid arthritis.

Microgravity, space radiation, and pharmaceutical degradation are all long-term chal-lenges for astronauts traveling through space. Radiation exposure is one of the greatest health risks to astronauts in space. Associated with these conditions are acute radiation syndromes, degenerative tissue effects, damage to the central nervous system (CNS), and carcinogenesis. Microgravity and the stress people experience as astronauts cause immunological dysregulation. This study explores strat-egies to counteract the problems of microgravity and its related health risks, including protection against space radiation, prevention of pharmaceutical degradation, and advancements in the emerging field of astropharmacy.

Background: Biofilm formation by microorganisms, specifically bacteria, threatens vari-ous fields, including biomedicine and the environment. The development of biofilms has associations with increased resistance to antimicrobial agents and immune responses; it poses a significant threat to human health. ESKAPE pathogens, a group of bacteria known for their multidrug resistance, are particularly adept at biofilm formation. This research explores strategies to combat biofilm-associated infections, with a focus on natural compounds as potential anti-biofilm agents.

Methods: The study investigates 23 natural compounds for their druglike properties in fighting against antibiotic-resistant biofilms. These compounds include flavonoids, terpenes, and alkaloids, and exhibit promising bioavailability and usage potential as ligands. Molecular docking analysis em-ploying AutoDock Vina was used to evaluate the binding affinities of these ligands to key biofilm-forming genes and membrane proteins in ESKAPE pathogens.

Results: Despite a few violations of a variety of established criteria, the overall safety and efficiency of oral drug reception are maintained, emphasizing their potential for further drug development. The results show specific ligands, such as Baicalin, Apigenin, Azadirachtin, Curcumin, Hyperforin, etc., demonstrating high binding energies against biofilm-associated proteins. This approach aligns with the pursuit of sustainable alternatives to combat biofilm-related infections.

Conclusion: Natural compounds like Baicalin, Apigenin, Azadirachtin, Curcumin, Hyperforin not only exhibit broad-spectrum coverage but also show reduced risks of resistance development com-pared to synthetic antibiotics. The integration of natural compounds into multifaceted strategies con-siders the complexities of the biofilm matrix, bacterial diversity, and pathogen characteristics, offer-ing a sustainable approach to address biofilm-associated infections.

Background: Type II diabetes mellitus is treated as one of the detrimental diseases and the drugs used for its treatment often lead to several side effects. Therefore, herbal medication of plant origin with lesser offshoot is a significant concern. Petroselinum crispum is a plant of pharma-ceutical interest. The present work aims to explore the potentiality assessment of flavonoids of Pe-troselinum crispum as an α-amylase inhibitor.

Methods: Compounds were extracted from the database and evaluated through drug likeliness prop-erties, ADMET and toxicity assessment. Molecular docking was done to identify the best ligand, and the dynamics simulation study was performed with the leading ligand-protein complex.

Results: Amongst the 15 bioactive compounds, apigenin appeared as the best ligand among all the studied compounds. Moreover, drug likeliness, physiochemical characteristics, and ADMET anal-yses revealed that apigenin does not deviate from Lipiniski's rule of five. Non-toxic apigenin showed a satisfactory docking score of -9.5 kcal/mol with human pancreatic α-amylase compared to the ref-erence molecule acarbose. Apigenin- α-amylase complex and apoprotein were subjected to 100ns molecular dynamics simulation to analyze the stability of the docked protein-ligand complex. The values of RMSD, RMSF, Rg, SASA and hydrogen bonding of the screened complexes showed high stability and less fluctuations of the apigenin- α-amylase complex.

Conclusion: This finding suggests apigenin as alternative therapeutics in treating diabetes mellitus by targeting the enzyme α-amylase which can be used for in vitro cross-validation studies. This study is the first documentation of the antidiabetic potentiality of the flavonoid compounds of Petroselinum crispum through in silico investigation.

Scopoletin, a naturally occurring coumarin derivative, has garnered significant attention for its diverse pharmacological properties, including potent anticancer activity. This review provides a comprehensive examination of scopoletin's anticancer effects across a wide range of tumor cell lines. The paper explores its modulation of apoptotic pathways, inhibition concentration (IC50) of cancer cell proliferation, and suppression of metastasis and angiogenesis. Additionally, the review discusses the role of scopoletin in regulating oxidative stress, inflammation, and cell cycle arrest in cancer cells. A detailed analysis of in vitro and in vivo studies highlights its efficacy, specificity, and potential for synergistic effects when used in combination with conventional chemotherapeutics. Hence, this comprehensive review aims to provide a foundation for future research and development of scopoletin as a promising anticancer agent.

The temperate, subtropical climates of Odisha state, India, provide significant benefits that can help it become a potent producer of many species of edible mushrooms. The importance of mush-rooms in diets has gained more attention in recent years due to their nutritional benefits. We aimed to update and discuss the current research information on nutritional components, including carbo-hydrates (β-glucans, trehalose, glucose), dietary fiber, proteins (ostreatin), amino acids (valine, glu-tamine, glutamic acid, aspartic acid, and arginine, lipids, vitamins (thiamine, riboflavin, pyridoxine, pantothenic acid, niacin, folic acid, nicotinic acid, and cobalamin), minerals (K, P, Na, Ca, Mg), flavor and taste contents of Odisha cultivated edible mushrooms. Additionally, their biological appli-cation in terms of antimicrobial action, antitumor, anti-inflammatory, anti-diabetic, cardioprotective properties, and antioxidant properties with mechanism of action are highlighted. Besides, we men-tioned the limitations and prospects of mushrooms.

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An imbalance between Reactive Oxygen Species (ROS) and antioxidants in the circulatory system leads to oxidative stress, which has been linked to several pathological conditions, including cancer, aging, and neurological and cardiovascular diseases. Antioxidants play a crucial role in re-ducing oxidative damage by neutralizing harmful free radicals and preventing cellular injury. The processes generating cellular oxidative stress and the curative effects of antioxidants, the origins and effects of reactive oxygen species (ROS), the role that oxidative stress plays in the pathogenesis of disease, and the several kinds of antioxidants-including enzymatic and non-enzymatic antioxidants are thoroughly explored in this review. We also emphasized the medicinal uses of antioxidants, both natural and synthetic, in the prevention and treatment of disorders associated with oxidative stress. Furthermore, we discussed the challenges and potential paths ahead for antioxidant research, such as developing new antioxidant molecules with higher efficacy and improving antioxidant delivery sys-tems. This study provides information regarding the complicated dynamics of oxidative stress and the potential benefits of antioxidants for preserving cellular homeostasis and advancing human health.