Mechanisms and Therapeutic Strategies for NLRP3 Degradation via Post-Translational Modifications in Ubiquitin-proteasome and Autophagy Lysosomal Pathway

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер 289, С. 117476 - 117476

Опубликована: Март 4, 2025

Язык: Английский

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Editorial: Methods in predictive toxicology 2023

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Фев. 25, 2025

Advancements in omics technologies and computational methods offer deeper mechanistic insights into toxicological processes. Two studies this collection leverage these approaches to unravel the underlying mechanisms of drug-induced toxicity.The study "Potential podophyllotoxin-induced cardiotoxicity male rats: evidence chain (TEC) concept" employs an integrative framework combining transcriptomics targeted metabolomics explore cardiotoxic effects podophyllotoxin (PPT). By constructing a (TEC), researchers identify key pathways involved PPT-induced cardiac injury, including oxidative stress, apoptosis, inflammatory responses, disruptions energy metabolism. This comprehensive approach not only elucidates molecular PPT but also provides template for investigating other compounds with complex profiles.In "Quantum chemical calculations nitrosamine activation deactivation carcinogenicity risk assessment," authors use quantum calculation assess carcinogenic potential N-nitrosamines , class significant concern due their presence as impurities pharmaceuticals. calculating comparing profiles non-carcinogenic nitrosamines, they uncover distinct differences reactivity stability. predicts mutagenic risks associated N-nitrosamines, demonstrating power silico regulatory decision-making .Pharmacovigilance plays crucial role detecting analyzing adverse drug reactions postmarketing. exemplify how large-scale data analysis can provide invaluable safety.In "Osteonecrosis jaw patients clear cell renal carcinoma treated agents: case series pharmacovigilance analysis," investigate association between tyrosine kinase inhibitors (TKIs), immune checkpoint (ICIs), osteonecrosis (ONJ). Utilizing FDA Adverse Event Reporting System (FAERS), perform disproportionality analyses detect signals indicating higher ONJ specific agents like sunitinib lenvatinib. underscores importance continuous monitoring mining identifying rare serious events, contributing safer therapeutic strategies carcinoma. Similarly, article "Post-marketing safety evaluation lurbinectedin: based on FAERS database" focuses lurbinectedin, novel agent approved metastatic small-cell lung cancer. The employ multiple algorithms event reports known toxicities such hematological gastrointestinal symptoms. Notably, new signal-tumor lysis syndrome-highlighting dynamic nature post-approval. work demonstrates reveal emerging guide clinicians managing side effects.The featured Research Topic highlight evolving landscape predictive toxicology, where interdisciplinary are essential. integration more precise toxicity predictions contributes development drugs. Looking ahead, future research should expand methods, by incorporating artificial intelligence machine learning analyze datasets subtle patterns. Efforts standardize protocols promote sharing will accelerate progress foster collaboration. Additionally, adoption advancement highthroughput modeling promise reduce animal testing providing alternative toxicities. understanding basis toxic effects, design interventions develop models that both accurate tailored mechanisms, classes, or target contexts.This exemplifies innovative transforming toxicology. leveraging insights, contribute significantly uncovering safety. We thank all valuable contributions reviewers critical feedback. hope inspire further dialogue, ultimately advancing field toxicology enhancing its impact public health.

Язык: Английский

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Computational and experimental study of terpolymers: spectroscopic, thermal, thermochemical, molecular property, and in silico toxicity analysis

Drug and Chemical Toxicology, Год журнала: 2025, Номер unknown, С. 1 - 17

Опубликована: Фев. 28, 2025

In this study, a comprehensive analysis of the CMA2OEM-co-DVB-co-AMPS (2-(bis(cyanomethyl)amino)-2-oxoethyl methacrylate-co-divinylbenzene-co-2-acrylamido-2-methyl-1-propanesulfonic acid) and CMA2OEM-co-DVB-co-VIM methacrylate-co-divinylbenzene-co-vinylimidazole) terpolymers was conducted. The structural chemical properties were examined using Fourier transform infrared (FT-IR) spectroscopy, frontier molecular orbital analysis, electrostatic potential (MEP) maps, 1H, 13C NMR thermochemistry surface maps (TCSM), toxicity assessments, physical properties, electron localization function (ELF), total (ESP) analyses. silico analyses, quantitative structure–activity relationship (QSAR) model used for Toxicity Estimation Software Tool (TEST) ProTox 3.0, web-based virtual laboratory, oral prediction. estimates TEST showed that both exhibited low profiles. Oral prediction emphasizes may pose greater risk compared to CMA2OEM-co-DVB-co-AMPS. addition, experimental thermal characterization these also performed. These analyses have provided significant insights into applications functional terpolymers.

Язык: Английский

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Computational analysis of antimicrobial peptides targeting key receptors in infection-related cardiovascular diseases: molecular docking and dynamics insights

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 14, 2025

Infection-related cardiovascular diseases (CVDs) pose a significant health challenge, driving the need for novel therapeutic strategies to target key receptors involved in inflammation and infection. Antimicrobial peptides (AMPs) show potential disrupt pathogenic processes offer promising approach CVD treatment. This study investigates binding of selected AMPs with critical implicated CVDs, aiming explore their potential. A comprehensive computational was employed assess AMP interactions CVD-related receptors, including ACE2, CRP, MMP9, NLRP3, TLR4. Molecular docking studies identified high affinities these targets, notably Tachystatin, Pleurocidin, Subtilisin A, which showed strong MMP9. Following docking, 100 ns molecular dynamics (MD) simulations confirmed stability AMP-receptor complexes, MM/PBSA calculations provided quantitative insights into energies, underscoring modulate receptor activity infection contexts. The highlights targeting infection-related pathways CVDs. These demonstrate properties models. Future research should focus on vitro vivo confirm efficacy safety, paving way clinical applications managing conditions.

Язык: Английский

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Modulatory Sedative Activity of Helicide on Diazepam in Thiopental Sodium Mediated Sleeping Mice: An In Vivo Approach With Molecular Docking

Revista Brasileira de Farmacognosia, Год журнала: 2025, Номер unknown

Опубликована: Март 18, 2025

Язык: Английский

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Exploring bioactive molecules released during inter- and intraspecific competition: A paradigm for novel antiparasitic drug discovery and design for human use

Current Research in Parasitology and Vector-Borne Diseases, Год журнала: 2025, Номер unknown, С. 100256 - 100256

Опубликована: Март 1, 2025

Many antiparasitic drugs have become obsolete and ineffective in treating parasitic diseases. This ineffectiveness arises from parasite drug resistance, high toxicity, low efficacy. Thus, the discovery of novel agents is urgently needed to control Various strategies are employed discovery, design, development. review highlights paradigm searching for bioactive molecules produced during inter- intraspecific competition among organisms, particularly between microbes parasites, as a strategy de novo discovery. Competitive interactions occur when individuals same or different species coexist overlapping niches compete space resources. These well recognized. Therefore, released these promising targets Compelling data indicate that remain potential source because their diversity. antimicrobial producers nature yet be isolated investigated. body evidence underscores success numerous therapeutic drugs, including penicillin, β-lactams, tetracyclines, which been successfully discovered developed infectious comprehensively covers concepts, with particular focus on agents. approach will pave way identifying alternative eradicate diseases continue threaten human health. Additionally, this discusses current mechanisms action, limitations, existing gaps. discussion emphasizes ongoing need explore drugs.

Язык: Английский

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Drug repurposing through Biophysical Insights: Focus on Indoleamine 2,3-Dioxygenase and Tryptophan 2,3-Dioxygenase Dual Inhibitors

Cell Biochemistry and Biophysics, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Язык: Английский

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Snake Venom Peptide Fractions from Bothrops jararaca and Daboia siamensis Exhibit Differential Neuroprotective Effects in Oxidative Stress-Induced Zebrafish Models

Pharmaceuticals, Год журнала: 2025, Номер 18(5), С. 678 - 678

Опубликована: Май 2, 2025

Introduction: Snake venoms are rich sources of bioactive peptides with therapeutic potential, particularly against neurodegenerative diseases linked to oxidative stress. While the peptide fraction (<10 kDa) from Bothrops jararaca venom has shown in vitro neuroprotection, analogous fractions related species remain unexplored vivo. Methods: This study comparatively evaluated neuroprotective effects two (pf) Daboia siamensis (pf-Ds) and B. (pf-Bj) H2O2-induced stress using (PC12 cells) vivo (zebrafish, Danio rerio) models. Results: In vitro, pf-Ds (1 µg mL−1) did not protect PC12 cells cytotoxicity, unlike previously reported pf-Bj. vivo, neither nor pf-Bj (1–20 induced significant developmental toxicity zebrafish larvae up 120 h post-fertilization (hpf). The both pf were experimental models: (I) Larvae at 96 hpf exposed either or (10 for 4 h, followed by co-exposure H2O2 (0.2 mmol L−1) an additional 10 induce (4–20 model); (II) Embryos treated continuously until hpf, after which they another 24 (96–120 model). a short-term treatment model, reversed deficits metabolism locomotor activity. However, prolonged significantly impairment, whereas confer protection. Conclusions: These findings demonstrate, first time, potential stress-induced behavioral zebrafish, contingent on regimen. differential between highlight species-specific composition underscore value evaluating venom-derived peptides.

Язык: Английский

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A clinical chemical atlas of xenobiotic toxicity for the Sprague–Dawley rat

Archives of Toxicology, Год журнала: 2025, Номер unknown

Опубликована: Май 6, 2025

Язык: Английский

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Fate-tox: fragment attention transformer for E(3)-equivariant multi-organ toxicity prediction

Journal of Cheminformatics, Год журнала: 2025, Номер 17(1)

Опубликована: Май 14, 2025

Язык: Английский

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