Mechanism-Based Allosteric Inhibition of PTP1B by Prenylated Flavonoids from Glycyrrhiza echinata: In Vitro Experiments and in Silico Validation.

A phytochemical investigation of Glycyrrhiza echinata led to the isolation and structural characterization of twelve phenolic compounds. An in silico target fishing analysis identified protein tyrosine phosphatase 1B (PTP1B) as a potential biological target for these phytochemicals, prompting an in vitro evaluation of their PTP1B inhibitory activities. Gancaonin Q and licoflavone C exhibited notably low IC₅₀ values (1.

Coumarin-Based Allosteric Inhibition of PTP1B: A Potential Strategy for Metabolic Regulation.

Protein Tyrosine Phosphatase 1B (PTP1B) is a key metabolic regulator and a promising therapeutic target for type 2 diabetes and obesity. This study evaluated the inhibitory potential of four coumarins-Bergapten, Imperatorin, Xanthotoxol, and Isopimpinellin, isolated from Ammi majus-through in silico and in vitro approaches. Molecular docking and molecular dynamics (MD) simulations identified Bergapten and Imperatorin as the most stable binders, forming key π-π stacking interactions with Phe280 and Phe196.

Rosmarinus officinalis suppresses cancer cell viability and inflammatory mediators in RAW 264.7 cells: in vitro and in silico analysis.

Called widely as rosemary, Rosmarinus officinalis is a fragrant herb that has been used for centuries for its medicinal properties and wide range of bioactive components. In order to better understand the anti-inflammatory and anticancer effects of R. officinalis essential oil (ROEO), this study will examine it.

Phenolic-based allosteric inhibition of PTP1B: unlocking new therapeutic potential for metabolic disorders.

Protein tyrosine phosphatase 1B (PTP1B) plays a critical role in insulin signaling and is associated with various metabolic diseases, including type 2 diabetes. In this study, we investigated the inhibitory potential of five phenolic compounds isolated from Tamarix aphylla against PTP1B. Using molecular docking, molecular dynamics (MD) simulations, and ADMET analysis, we assessed the binding modes, stability, and pharmacokinetic properties of these compounds.

Towards precision epitopes based vaccine against by integrating vaccinomics, reverse vaccinology and biophysics approaches.

is a Gram-positive bacterium and recognized as an etiological agent of different nosocomial infections. has developed resistance to several antibiotics. No licensed vaccine is available to prevent infections.

A comprehensive systematic review of prognostic factors, survival outcomes, and the role of targeted therapies in endometrial cancer.

Study Background And Objectives: Endometrial cancer, ranking as the 6th most prevalent cancer affecting women globally, is characterized by high mortality rates, recurrence, and poor prognosis. The disease lacks comprehensive understanding and effective treatment options. This meta-analysis focuses on randomized controlled trials to investigate targeted therapies, survival outcomes, and prognostic factors in endometrial cancer.

Watercress-derived glucosinolates as potential allosteric PTP1B inhibitors: a dual in silico and in vitro study on insulin signaling modulation.

This study investigates the inhibitory potential of four glucosinolates-glucoerucin, glucoiberin, gluconasturtiin, and glucotropaeolin-isolated from watercress (Nasturtium officinale) against Protein Tyrosine Phosphatase 1B (PTP1B), a key regulator of insulin signaling. Molecular docking, molecular dynamics (MD) simulations, and MM/PBSA free energy calculations identified glucoerucin (-17.18 ± 3.

Mycosynthesis of zinc oxide nanoparticles using Mucor racemosus with their antimicrobial, antibiofilm, anticancer and antioxidant activities.

The unregulated administration of currently available antimicrobial agents resulted in overspreading of resistant microbial phenotypes. In this study, Mucor racemosus was used for biosynthesis of zinc oxide nanoparticles (ZnO NPs) through fungi-based ecofriendly approach. The biosynthesized of ZnO NPs was initially considered based on analytical practices including UV-vis spectroscopy and transmission electron microscopy (TEM).

Multi-Omics Analysis of the virulence factors and designing of next-generation multi-epitopes Vaccines against Rickettsia prowazekii: a computer-aided vaccine designing approach.

Rickettsia is a genus of bacteria that are obligate intracellular parasites and are responsible for the febrile diseases known collectively as Rickettsioses. The emergence of antibiotic resistance is an escalating concern and thus developing a vaccine against Rickettsia is of paramount importance due to the significant public health threat posed by these bacteria. Thus, we employed structural vaccinology guided by machine learning algorithms to explore the virulence landscape of Rickettsia prowazekii to design a multi-epitopes-based vaccine (MEVC) that is immunogenic and safe.

Multi-pronged approaches to the mechanism-based inactivation of aldose reductase by natural coumarins: molecular insights and experimental validation.

In this study, we measured the inhibitory potential of six coumarins against aldose reductase using both computational and experimental approaches. Molecular docking, molecular dynamics simulations, and MM/PBSA binding free energy calculations identified auraptene, marmesin, and isopimpinellin as the most promising inhibitors, with binding affinities of ΔG = -34.88, -29.

Immunoinformatic approach for designing a multi-epitope vaccine against non-typhoidal salmonellosis using starvation-stress response proteins from Oranienburg.

Non-typhoidal is responsible for gastrointestinal illnesses worldwide. Therefore, it is important to implement effective therapeutic interventions for preventing these diseases. Vaccines have proven highly efficacious in the treatment and prevention of several illnesses.

SPLIF-Enhanced Attention-Driven 3D CNNs for Precise and Reliable Protein-Ligand Interaction Modeling for METTL3.

Structure-based virtual screening (SBVS) is a cornerstone of modern drug discovery pipelines. However, conventional scoring functions often fail to capture the complexities of protein-ligand binding interactions. To address this limitation, we developed DeepMETTL3, a novel scoring function that integrates 3D convolutional neural networks (CNNs) with multihead attention mechanisms and high-dimensional Structural Protein-Ligand Interaction Fingerprints (SPLIF).

Histone modifications as molecular drivers of cardiac aging: Metabolic alterations, epigenetic mechanisms, and emerging therapeutic strategies.

Cardiac aging represents a complex pathophysiological process characterized by progressive metabolic recombination and functional dedifferentiation of cardiac cellular components. Despite advancements in cardiovascular medicine, a critical research gap persists in understanding the precise epigenetic mechanisms that drive age-related cardiac dysfunction. This comprehensive review elucidates the pivotal role of histone modifications-including methylation, acetylation, and phosphorylation-in orchestrating the molecular landscape of cardiac aging.

A Multidimensional Approach to Understanding Genetic Diversity, Risk Stratification, and Personalized Interventions in Pediatric Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) in children presents unique challenges distinct from adult manifestations, with potentially devastating consequences, including sudden cardiac death. This comprehensive review synthesizes current evidence on the pathophysiology, clinical presentation, and management of pediatric HCM, highlighting critical differences from adult populations. While affecting approximately 1 in 500 individuals, pediatric HCM demonstrates more significant etiological heterogeneity, with up to 35% of cases stemming from non-sarcomeric causes, including RASopathies, metabolic disorders, and syndromic conditions.

The Potential Mechanism and the Role of Antioxidants in Mitigating Oxidative Stress in Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent cause of dementia and a significant contributor to health issues and mortality among older individuals. This condition involves a progressive deterioration in cognitive function and the onset of dementia. Recent advancements suggest that the development of AD is more intricate than its underlying brain abnormalities alone.

Acorus calamus as a promising source of new antibacterial agent against Pseudomonas aeruginosa and Staphylococcus aureus: Deciphering volatile compounds and mode of action.

Acorus calamus is a medicinal plant known for its multifaceted health benefits, especially against inflammation and infectious ailments. In the current work, we attempt to investigate the volatile constituents of A. calamus essential oil (ACEO) and, for the first time, to elucidate its antibacterial mechanism.

Advancing COVID-19 Treatment: The Role of Non-covalent Inhibitors Unveiled by Integrated Machine Learning and Network Pharmacology.

Introduction: The COVID-19 pandemic has necessitated rapid advancements in therapeutic discovery. This study presents an integrated approach combining machine learning (ML) and network pharmacology to identify potential non-covalent inhibitors against pivotal proteins in COVID-19 pathogenesis, specifically B-cell lymphoma 2 (BCL2) and Epidermal Growth Factor Receptor (EGFR).

Methods: Employing a dataset of 13,107 compounds, ML algorithms such as k-Nearest Neighbors (kNN), Support Vector Machine (SVM), Random Forest (RF), and Naïve Bayes (NB) were utilized for screening and predicting active inhibitors based on molecular features.

Advancements in Structural Basis of Covalent Inhibitors Targeting SARS-CoV-2 Essential Proteins.

Covalent inhibitors play a pivotal role in the development of pharmaceutical therapies, as they form stable, irreversible bonds with target biomolecules, leading to prolonged therapeutic effects and enhanced efficacy. Since covalent inhibitors first appeared in the late 1800s, the field has become innovative rapidly, and covalent inhibitors now account for around 30% of all marketed therapeutics. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the pandemic of coronavirus disease 2019 (COVID-19).

Exploring dihydropyrimidone derivatives as modulators of carbohydrate catabolic enzyme to mitigate diabetes.

Diabetes is a prevalent and serious metabolic disorder affecting millions globally, and it poses extensive health risks due to elevated blood glucose levels. One promising approach for managing diabetes is the inhibition of α-glucosidase, an enzyme that plays a crucial role in carbohydrate metabolism. Targeting α-glucosidase can help delay glucose absorption, thus controlling postprandial blood sugar spikes.

Impact of Various Washing Protocols on the Mitigation of Contamination in Raw Salad Vegetables.

Vegetables are an essential component of a balanced diet. The consumption of ready-to-eat foods may lead to the risk of infections and illnesses due to microbial contamination. To mitigate the potential of microbial contamination risks, it is critical to promote safe handling practices among consumers.

Phytochemical characterization, antimicrobial properties and modeling perspectives of essential oil.

Medicinal plants are used widely in the treatment of various infectious diseases. One of these medical plants is Moroccan plants such as . In this study, the essential oil isolated from the leaves of (APEO) by the hydrodistillation method was analyzed using (GC/MS) analysis.

Purification of Potential Antimicrobial Metabolites from Endophytic Fusarium oxysporum Isolated from Myrtus communis.

The rise of microbial resistance and emerging infections pose significant health threats. Natural products from endophytic fungi offer a promising source of novel compounds with the potential as major drug leads. This research aims to screen Myrtus communis and Moringa oleifera for endophytic fungi and screen their metabolites for antibacterial and antifungal potential.