Discovering potential therapeutic targets in glioblastoma multiforme using a multi-omics approach.

Background: Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor associated with high fatality rates, poor prognosis, and limited treatment options. In this study, we utilized RNA-Seq gene count data from GBM patients, sourced from the Gene Expression Omnibus (GEO) database, to conduct an in-depth analysis of gene expression patterns.

Methods: Our investigation involved stratifying samples into two distinct sets, Group I and Group II, comparing normal, low-grade, and GBM tumor samples, respectively.

Biochemical Screening of Phytochemicals and Identification of Scopoletin as a Potential Inhibitor of SARS-CoV-2 M, Revealing Its Biophysical Impact on Structural Stability.

The main protease (M or 3CL or nsp5) of SARS-CoV-2 is crucial to the life cycle and pathogenesis of SARS-CoV-2, making it an attractive drug target to develop antivirals. This study employed the virtual screening of a few phytochemicals, and the resultant best compound, Scopoletin, was further investigated by a FRET-based enzymatic assay, revealing an experimental IC of 15.75 µM.

Effect of muscle relaxant drug chlorzoxazone on the conformational stability and activity of bovine serum albumin: a spectroscopic and computational study.

The commonly used muscle relaxant chlorzoxazone (CZZ) is basic in nature and binds to acidic alpha-1-glycoprotein, affecting the levels of albumins as well as lipoproteins in the body. This can impact the biological half-life of the drug and interfere with its therapeutic requirements. Herein, we have shown the impact of CZZ on the structure of bovine serum albumin (BSA), a transport protein, through various spectroscopic techniques like UV-vis absorption, steady state emission, synchronous fluorescence, and also circular dichroism (CD).

Epidemiological trends of chlamydia, gonorrhoea, trichomoniasis, genital herpes and syphilis in India from 1990 to 2019: analysis from the Global Burden of Disease study (GBD 2019).

Background Sexually transmitted infections (STIs) other than HIV are a major public health concern globally. The goal of this study is to analyse the trends of the five most common STIs; chlamydia, gonococcal infection, trichomoniasis, genital herpes and syphilis in India and its states from 1990 to 2019. Methods We extracted data pertaining to STIs from the Global Burden of Disease study, 2019 (GBD 2019), and analysed the burden of disease based on individual STI, for both sexes, across multiple age groups, and for each state and union territory of India.

Impact of Cancer-Associated PKM2 Mutations on Enzyme Activity and Allosteric Regulation: Structural and Functional Insights into Metabolic Reprogramming.

Mammalian pyruvate kinase M2 (PKM2) is a key regulator of glycolysis and is highly expressed in proliferative tissues including tumors. Mutations in PKM2 have been identified in various cancers, but their effects on enzyme activity and regulation are not fully understood. This study investigates the structural and functional effects of cancer-associated PKM2 mutations on enzyme kinetics, allosteric regulation, and oligomerization.

Telomeric RNA quadruplexes as targets for cancer prevention: The therapeutic potential of agonodepsides.

Background: Cancer remains an awful challenge, despite years of targeting proteins to control its relentless growth and spread. Fungal metabolites, a treasure of natural chemicals, offer a glimmer of hope. Telomeres, the cellular "caps," are a focal point in cancer research.

Seven Hub Genes Associated with Huntington's Disease and Diagnostic and Therapeutic Potentials Identified by Computational Biology.

Huntington's disease (HD) is characterized by progressive motor dysfunction and cognitive decline. Early diagnosis and new therapeutic targets are essential for effective interventions. We performed integrative analyses of mRNA profiles from three microarrays and one RNA-seq dataset from the Gene Expression Omnibus database.

Exploring the potential of direct-acting antivirals against Chikungunya virus through structure-based drug repositioning and molecular dynamic simulations.

The Chikungunya virus (CHIKV) represents a significant global health threat, particularly in tropical regions, and no FDA-approved antiviral treatments are currently available. This study investigates the potential of Direct-Acting Antivirals (DAAs) and protease inhibitors (PIs) that have been developed for the hepatitis C virus (HCV) in treating CHIKV. We analyzed the binding of eight HCV DAAs to the nsP2 protease of CHIKV, which is essential for viral replication.

In silico screening and molecular dynamics analysis of natural DHPS enzyme inhibitors targeting Acinetobacter baumannii.

Over time, antimicrobial agents are losing their credibility in curbing infections due to the development of resistant pathogen strains. The resistant strains have proven to invade living beings and cause various diseases, leading to deaths at an alarming rate. Acinetobacter baumannii is one such pathogen, and to target it through enzyme inhibition, Dihydropteroate synthase enzyme's active site is virtually screened for antimicrobial agents against in-house libraries of natural molecules from medicinally important plants and Agaricus spp.

Identification of potential inhibitors of Fyn-Kinase from bioactive phytochemicals of for therapeutic targeting of neurodegenerative disease.

Fyn is classified as a member of the Src family of kinases (SFKs), a group of non-receptor tyrosine kinases. It is a critical component of many fundamental central nervous system (CNS) processes. Recently, a connection has been shown between Fyn malfunction and the pathogenic processes exhibited in neurodegenerative conditions, such as Alzheimer's disease (AD), which is a significant factor in worldwide mortality and disability.

A structural genomics approach to investigate Dystrophin mutations and their impact on the molecular pathways of Duchenne muscular dystrophy.

Background: Dystrophin is a key protein encoded by the gene, serves as a scaffold linking the cytoskeleton to the extracellular matrix that plays a critical role in muscle contraction, relaxation, and structural integrity. Mutations, particularly single-point amino acid substitutions, can lead to dysfunctional Dystrophin, causing muscular dystrophies, with Duchenne muscular dystrophy (DMD) being the most severe form.

Objective: This study aimed to evaluate the effects of 184 single-point amino acid substitutions on the structure and function of Dystrophin using computational approaches.

Therapeutic Targeting of Interleukin-2-Inducible T-Cell Kinase (ITK) for Cancer and Immunological Disorders: Potential Next-Generation ITK Inhibitors.

Interleukin-2-inducible T-cell kinase (ITK) is a critical tyrosine kinase enzyme that is involved in the activation and differentiation of T cells. ITK is mainly found in T cells, which plays an essential role in controlling T-cell receptor signaling and downstream pathways. ITK regulates the synthesis of cytokines, particularly interleukin-2 (IL-2), and the development of Th2 cells.

In Vitro and In Silico Assessment of Antileishmanial Potential of Novel Tri- and Penta-Valent Antimony Complexes With Phenolic Ligands.

Leishmaniasis, caused by protozoan parasites of the genus Leishmania, affects nearly 12 million people annually worldwide, and has limited, highly toxic therapeutic options. This study reports the synthesis, in vitro and in silico evaluations of four novel antimony complexes (3a-3d) as potent and safe antileishmanial agents. The complexes were synthesized using Sb-salts with different phenolic ligands and characterized by elemental analysis, FT-IR and NMR spectroscopic techniques.

Sustainable lipid production by oleaginous yeasts: Current outlook and challenges.

Yeast lipid has gained prominence as a sustainable energy source and so various oleaginous yeasts are being investigated to create efficient lipogenic platforms. This review aims to assess the various biotechnological strategies for enhanced production of yeast lipids via agro-waste processing and media engineering including multiomic analyses, genetic engineering, random mutagenesis, and laboratory adaptive evolution. The review also emphasizes the role of cutting-edge omics technologies in pinpointing differentially expressed genes and enriched networks crucial for designing advanced metabolic engineering strategies for prominent oleaginous yeast species.

Understanding of Alzheimer's disease pathophysiology for therapeutic implications of natural products as neuroprotective agents.

Alzheimer's disease (AD) is a leading cause of dementia, affecting more than 24.3 million people worldwide in 2024. Sporadic AD (SAD) is more common and occurs in the geriatric population, while familial AD (FAD) is rare and appears before the age of 65 years.

Identification and prioritization of novel therapeutic candidates against glutamate racemase from Klebsiella pneumoniae.

Background: Klebsiella pneumoniae, a gram-negative bacterium in the Enterobacteriaceae family, is non-motile, encapsulated, and a major cause of nosocomial infections, particularly in intensive care units. The bacterium possesses a thick polysaccharide capsule and fimbriae, which contribute to its virulence, resistance to phagocytosis, and attachment to host cells. The bacterium has developed serious resistance to most antibiotics currently in use.

4,6-Disubstituted pyrimidine-based microtubule affinity-regulating kinase 4 (MARK4) inhibitors: synthesis, characterization, activity and studies.

Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder that significantly impacts the cognitive function and memory of a person. Despite the significant research efforts, the ability to completely prevent or effectively treat AD and its related dementias remains limited. Protein kinases are integral to AD pathology and represent promising targets for therapeutic intervention.

Unraveling the catalase dynamics: Biophysical and computational insights into co-solutes driven stabilization under extreme pH conditions.

Catalase plays a vital role in eliminating toxic peroxides from the human body and the environment. The versatile applications of this enzyme extend across biotechnological industries and innovative bioremediation approaches. Nonetheless, ensuring enzyme stability is a challenging task.

Structure-guided identification of mitogen-activated protein kinase-1 inhibitors towards anticancer therapeutics.

Mitogen-activated protein kinase 1 (MAPK1) is a serine/threonine kinase that plays a crucial role in the MAP kinase signaling transduction pathway. This pathway plays a crucial role in various cellular processes, including cell proliferation, differentiation, adhesion, migration, and survival. Besides, many chemotherapeutic drugs targeting the MAPK pathway are used in clinical practice, and novel inhibitors of MAPK1 with improved specificity and efficacy are required.

Thymoquinone-loaded Nanosized Ethosomal-based Hydrogels: Their Preparation, Characterization, , and Antimicrobial Evaluation against .

Background: Thymoquinone (TQ) is found in the seeds of . It has immunomodulatory, antibacterial, anti-inflammatory, antioxidant, astringent, antifungal, and antihistaminic properties, making it a highly valuable compound of interest. However, the use of it as a therapeutic drug is highly challenging because of its poor solubility, low bioavailability, and short-term stability.

Apigenin-mediated MARK4 inhibition: a novel approach in advancing Alzheimer's disease therapeutics.

Apigenin, a dietary flavonoid with notable anti-cancer properties, has emerged as a promising candidate for the treatment of neurodegenerative disorders, particularly Alzheimer's disease (AD). While extensively studied for its ability to modulate key molecular pathways in cancers, apigenin also exerts neuroprotective effects by reducing neuroinflammation, protecting neurons from oxidative stress, and enhancing neuronal survival and synaptic plasticity. This dual functionality makes apigenin an intriguing therapeutic option for diseases like AD, where kinase dysregulation plays a central role.

Discovering potential ERK1 inhibitors from natural products for therapeutic targeting of Alzheimer's disease.

Background: Extracellular signal-regulated kinase 1 (ERK1) belongs to mitogen-activated protein kinases, which are essential for memory formation, cognitive function, and synaptic plasticity. During Alzheimer's disease (AD), ERK1 phosphorylates tau at 15 phosphorylation sites, leading to the formation of neurofibrillary tangles. The overactivation of ERK1 in microglia promotes the release of pro-inflammatory cytokines, which results in neuroinflammation.

Phytochemicals Withanolide N and Dryobalanolide as Potential Bioactive Leads for Developing Anticancer Drugs Targeting Tyrosine-Protein Kinase Mer.

There is a growing interest in harnessing natural compounds and bioactive phytochemicals to accelerate drug discovery and development, including in the treatment of human cancers. Receptor tyrosine kinases (RTKs) are critical regulators of many fundamental cellular processes and have been implicated in cancer pathogenesis as well as targets for anticancer drug development. The members of TAM, Tyro3, Axl, and MERTK subfamily RTKs, especially Mer, affect immune homeostasis in the tumor microenvironment.

Adsorption kinetics and solubilisation of ciprofloxacin in quaternary ammonium-based surface-active compounds: experimental and computational study.

The adsorption and aggregation of amphiphiles at different solvent interfaces are of great scientific and technological importance. In this study, interfacial tension measurements of surface-active compounds-ionic liquid 2-dodecyl-2,2dimethylethanolammonium bromide (12Cho.Br) and cationic surfactant cetyltrimethylammonium bromide (CTAB)-were conducted both in the absence and presence of ciprofloxacin (CIP).

Epigallocatechin-3-gallate therapeutic potential in human diseases: molecular mechanisms and clinical studies.

Green tea has garnered increasing attention across age groups due to its numerous health benefits, largely attributed to Epigallocatechin 3-gallate (EGCG), its key polyphenol. EGCG exhibits a wide spectrum of biological activities, including antioxidant, anti-inflammatory, antibacterial, anticancer, and neuroprotective properties, as well as benefits for cardiovascular and oral health. This review provides a comprehensive overview of recent findings on the therapeutic potential of EGCG in various human diseases.