Repurposing FDA-approved drugs targeting FZD10 in nasopharyngeal carcinoma: insights from molecular dynamics simulations and experimental validation.

Wnt signaling is a critical pathway implicated in cancer development, with Frizzled proteins, particularly FZD10, playing key roles in tumorigenesis and recurrence. This study focuses on the potential of repurposed FDA-approved drugs targeting FZD10 as a therapeutic strategy for nasopharyngeal carcinoma (NPC). The tertiary structure of human FZD10 was constructed using homology modeling, validated by Ramachandran plot and ProQ analysis.

Microsatellites markers fostering the understanding of malaria parasite biology, epidemiology and population genetics.

Microsatellites, or simple sequence repeats (SSRs), are short tandemly repeated DNA sequences widely dispersed throughout the genome. Their high variability, co-dominant inheritance, and ease of detection make them valuable genetic markers, frequently used to study genetic diversity, population structure, and evolutionary processes. In the context of malaria research, particularly with Plasmodium falciparum (P.

Ligand docking in the sigma-1 receptor compared to the sigma-1 receptor-BiP complex and the effects of agonists and antagonists on C. elegans lifespans.

Model organisms are commonly used to study human diseases; we set out to understand the relevance of several model organisms with relation to the σ1R protein. The study explored the interactions of σ1R with various agonists, antagonists across different species. Ligand and protein-protein (σ1R-BiP) docking approaches were used to understand the significance of σ1R in modulating neuroprotective mechanisms and its potential role in Alzheimer's.

Discovery of novel fatty acid amide hydrolase (FAAH) inhibitors as anti-alzheimer agents via in-silico-based drug design, virtual screening, molecular docking, molecular dynamics simulation, DFT, and non-clinical studies.

Aim: To identify some novel fatty acid hydrolase (FAAH) inhibitors that may contribute to the treatment of Alzheimer's disease (AD).

Methods: In-silico pharmacophore modelling including ligand-based pharmacophore modelling, virtual screening, molecular docking, molecular dynamics modelling, density functional theory and in-silico pharmacokinetics and toxicological studies were employed for the retrieving of novel FAAH inhibitors. Further, these compounds were evaluated for FAAH inhibitory activity using an in vitro enzymatic assay, and later, an in vivo streptozotocin (STZ)-induced AD model was examined in mice.

Does Metabolic Manager Show Encouraging Outcomes in Alzheimer's?: Challenges and Opportunity for Protein Tyrosine Phosphatase 1b Inhibitors.

Protein tyrosine phosphatase 1b (PTP1b) is a member of the protein tyrosine phosphatase (PTP) enzyme group and encoded as PTP1N gene. Studies have evidenced an overexpression of the PTP1b enzyme in metabolic syndrome, anxiety, schizophrenia, neurodegeneration, and neuroinflammation. PTP1b inhibitor negatively regulates insulin and leptin pathways and has been explored as an antidiabetic agent in various clinical trials.

Nyctanthes arbor-tristis Improves Blood Pressure via Endothelial Pathway: In Silico, Ex Vivo, and In Vivo Evidence.

Systemic hypertension, a common metabolic disorder, poses significant health risks despite the availability of antihypertensive drugs. Nyctanthes arbor-tristis has garnered increasing attention for its perceived efficacy and safety, though its mechanisms of action and the bioactive compounds responsible for its antihypertensive effects remain elusive. Therefore, this study aims to elucidate the antihypertensive activity of N.

Transforming cancer detection and treatment with nanoflowers.

Nanoflowers, an innovative class of nanoparticles with a distinctive flower-like structure, have garnered significant interest for their straightforward synthesis, remarkable stability, and heightened efficiency. Nanoflowers demonstrate versatile applications, serving as highly sensitive biosensors for rapidly and accurately detecting conditions such as diabetes, Parkinson's, Alzheimer's, and foodborne infections. Nanoflowers, with their intricate structure, show significant potential for targeted drug delivery and site-specific action, while also exhibiting versatility in applications such as enzyme purification, water purification from dyes and heavy metals, and gas sensing through materials like nickel oxide.

Analysis of diagnostic biomarkers for malaria: Prospects on rapid diagnostic test (RDT) development.

Accurate malaria diagnosis remains a formidable challenge in remote regions of malaria-endemic areas globally. Existing diagnostic methods predominantly rely on microscopy and rapid diagnostic tests (RDTs). While RDTs offer advantages such as rapid results and reduced dependence on highly skilled technicians compared to microscopy, persistent challenges emphasize the critical need to identify novel diagnostic biomarkers to further enhance RDT based malaria diagnosis.

Green Synthetic and Pharmacological Developments in the Hybrid Quinazolinone Moiety: An Updated Review.

Bicyclic quinazolinone constitutes an important class of organic framework enveloping numerous biological properties which enthused organic and medicinal chemists to explore green synthetic strategies for the construction of quinazolinone hybrids with significantly improved pharmacodynamics and pharmacokinetic profiles. In this perspective, the present review summarizes the most recent green synthetic strategies, biological properties, structure-activity relationship, and molecular docking studies of the 4-quinazolinone-based scaffold. This review provides deeper insight into the hit-to-lead synthesis of quinazolinone derivatives in the development of clinically important therapeutic candidates.

Mutations in Plasmodium falciparum Kelch13 (PfK13) dysregulates PI3K/AKT signalling pathway in artemisinin resistance.

Background: PfK13 protein mutations are associated with the emergence of artemisinin resistance in Plasmodium falciparum. PfK13 protein is essential for mediating ubiquitination and controlling the PI3K/AKT pathway. Mutant PfK13 variations can interfere with substrate binding, especially with PfPI3K, which raises PfPI3K levels.

Role of Epigenetic Modulation in Neurodegenerative Diseases: Implications of Phytochemical Interventions.

Epigenetics defines changes in cell function without involving alterations in DNA sequence. Neuroepigenetics bridges neuroscience and epigenetics by regulating gene expression in the nervous system and its impact on brain function. With the increase in research in recent years, it was observed that alterations in the gene expression did not always originate from changes in the genetic sequence, which has led to understanding the role of epigenetics in neurodegenerative diseases (NDDs) including Alzheimer's disease (AD) and Parkinson's disease (PD).

Tissue regeneration properties of hydrogels derived from biological macromolecules: A review.

The successful tissue engineering depends on the development of biologically active scaffolds that possess optimal characteristics to effectively support cellular functions, maintain structural integrity and aid in tissue regeneration. Hydrogels have emerged as promising candidates in tissue regeneration due to their resemblance to the natural extracellular matrix and their ability to support cell survival and proliferation. The integration of hydrogel scaffold into the polymer has a variable impact on the pseudo extracellular environment, fostering cell growth/repair.

Tetrazole derivatives in the management of neurological disorders: Recent advances on synthesis and pharmacological aspects.

Neurological disorders are the leading cause of a large number of mortalities and morbidities. Nitrogen heterocyclic compounds have been pivotal in exhibiting wide array of therapeutic applications. Among them, tetrazole is a ubiquitous class of organic heterocyclic compounds that have attracted much attention because of its unique structural and chemical properties, and a wide range of pharmacological activities comprising anti-convulsant effect, antibiotic, anti-allergic, anti-hypertensive to name a few.

Network analysis-guided drug repurposing strategies targeting LPAR receptor in the interplay of COVID, Alzheimer's, and diabetes.

The COVID-19 pandemic caused by the SARS-CoV-2 virus has greatly affected global health. Emerging evidence suggests a complex interplay between Alzheimer's disease (AD), diabetes (DM), and COVID-19. Given COVID-19's involvement in the increased risk of other diseases, there is an urgent need to identify novel targets and drugs to combat these interconnected health challenges.

Repurposing FDA-approved drugs to target malaria through inhibition of dihydrofolate reductase in the folate biosynthesis pathway: A prospective approach.

Dihydrofolate reductase (DHFR) is a ubiquitous enzyme that regulates the biosynthesis of tetrahydrofolate among various species of Plasmodium parasite. It is a validated target of the antifolate drug pyrimethamine (Pyr) in Plasmodium falciparum (Pf), but its clinical efficacy has been hampered due to the emergence of drug resistance. This has made the attempt to screen Food & Drug Administration-approved drugs against wild- and mutant PfDHFR by employing an in-silico pipeline to identify potent candidates.

A computational strategy for systematic virtual screening of plasmodium falciparum heme detoxification protein inhibitors from the Drugbank database.

Antimalarial drug resistance poses one of the greatest threats to malaria treatment, resulting in increased morbidity and mortality. Heme Detoxification Protein (HDP) is among the essential hemoglobinases of P. falciparum (Pf), a vital molecular target for the treatment of malaria.

Genomic insights and advanced machine learning: characterizing autism spectrum disorder biomarkers and genetic interactions.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by altered brain connectivity and function. In this study, we employed advanced bioinformatics and explainable AI to analyze gene expression associated with ASD, using data from five GEO datasets. Among 351 neurotypical controls and 358 individuals with autism, we identified 3,339 Differentially Expressed Genes (DEGs) with an adjusted p-value (≤ 0.

Tinospora cordifolia ameliorates paclitaxel-induced neuropathic pain in albino rats.

Ethnopharmacological Relevance: Tinospora cordifolia (T. cordifolia) (Willd.) Miers, a member of the Menispermaceae, family documented in the ancient textbooks of the Ayurveda System of Medicine, has been used in the management of sciatica pain and diabetic neuropathy.

Mitochondrial transfer restores impaired liver functions by AMPK/ mTOR/PI3K-AKT pathways in metabolic syndrome.

Aim: We investigated the effect of mitochondria transfer in high fat diet and streptozotocin (HFD + STZ) induced metabolic syndrome (MeS) in rats. The effect of mitochondria transfer in MeS with co-existing hypertension, hyperlipidaemia, diabetes and fatty liver together, has not been reported.

Materials And Methods: Heathy mitochondria was transferred intravenously and the effect on several physiological parameters and biochemical parameters were examined in HFD + STZ rats.

Mechanism insights of curcumin and its analogues in cancer: An update.

Cancer is the world's second leading cause of mortality and one of the major public health problems. Cancer incidence and mortality rates remain high despite the great advancements in existing therapeutic, diagnostic, and preventive approaches. Therefore, a quest for less toxic and more efficient anti-cancer strategies is still at the forefront of the current research.

An insight into PI3k/Akt pathway and associated protein-protein interactions in metabolic syndrome: A recent update.

Akt, a known serine/threonine-protein kinase B has been revealed to be an imperative protein of the PI3K/Akt pathway. Akt is available in three isoforms, Akt1, Akt2, and Akt3. Ubiquitously expressed Akt1 & Akt2 are essential for cell survival and are believed to be involved in regulating glucose homeostasis.

Comparative impact of yoga and ayurveda practice in insomnia: A randomized controlled trial.

Background: Insomnia is connected with a lifted hazard for neurocognitive dysfunction and psychiatric disarranges. Clinical observations of psychosomatic patients indicate that their distorted somatopsychic functioning necessitates their practice of yoga-like therapy. Sleep and its modifications and management have also been explained well in ayurveda.

New insights on mode of action of vasorelaxant activity of simvastatin.

Simvastatin is a semisynthetic inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and is used extensively to treat atherosclerotic cardiovascular disease. Apart from the lipid-lowering effect, simvastatin has been documented to offer impressive vasorelaxant activity. However, the mechanism associated with this vasorelaxant activity has yet not been substantially explored.