Abstract:Nortrachelogenin is a dibenzylbutyrolactone lignan associated with redox-sensitive signaling. We examined its effects on receptor activator of nuclear factor kappa-B ligand (RANKL)-induced nuclear factor kappa-B (NF-κB) activation in osteoclast precursors. Nortrachelogenin attenuated IκB phosphorylation and degradation and reduced p65 phosphorylation. Consistently, it markedly decreased the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts. These findings identify nortrachelogenin as a lignan scaffold that suppresses nuclear factor kappa-B signaling and osteoclastogenesis in vitro.
Abstract Antiviral drugs are pivotal in the prevention and management of infections caused by viruses, ranging from common cold viruses to life-threatening pathogens like human immunodeficiency virus, hepatitis viruses, Ebola virus, etc. Furthermore, antiviral therapy is increasingly being integrated into the management of chronic viral infections to restrain their replication, avert disease progression, and minimize the risk of complications. The availability of newer generations of antiviral drugs, particularly direct-acting antivirals, and combination therapies have significantly improved treatment outcomes, offering better cure speed, shorter treatment time, and reduced side effects as compared to older-generation antivirals. This comprehensive review provides an in-depth analysis of the diverse classes of antiviral drugs, their mechanisms of action, clinical applications, challenges, and future directions. With a focus on recent advancements and emerging trends, the current landscape of antiviral drug development and its implications for global public health are also discussed.
Background:Heart failure is a significant global health burden. This study aims to identify heart failure-associated genes through transcriptome-wide association studies combined with genome-wide association studies. Methods:A transcriptome-wide association study was conducted using Functional Summary-based Imputation, integrating heart failure genome-wide association study summary data (47,309 cases and 930,014 controls) with Genotype-Tissues Expression Project V8 expression quantitative trait loci data from 49 tissues. Gene-level analysis was performed using Multi-marker Analysis of Genomic Annotation, followed by mendelian randomization and Bayesian colocalization. The functional implications of candidate genes were explored using GeneMANIA, and the druggability of the top gene, USP36, was evaluated via molecular docking simulations. Results:Functional Summary-based Imputation and Multi-marker Analysis of Genomic Annotation analyses identified 26 candidate genes. Further investigation highlighted USP36 as significant, particularly in left ventricular tissue, where it confers protection against heart failure. GeneMANIA showed that USP36 interacts with genes involved in oxidative stress-induced apoptosis, suggesting its role in heart failure pathogenesis. Molecular docking simulations confirmed USP36's binding affinity with heart failure therapeutics, supporting its potential as a therapeutic target. Conclusions:USP36 is a novel heart failure susceptibility gene and a promising therapeutic target. Its involvement in oxidative stress-related pathways offers new insights into heart failure risk and warrants further investigation for disease development and treatment.
Diabetes mellitus (DM) is a chronic metabolic disorder that continues to pose a major healthcare challenge worldwide. Despite the availability of several therapeutic options, achieving sustained glycaemic control and preventing long-term complications remain difficult in many patients. Walnut (Juglans regia L.) has gained attention as a potential complementary approach because of its diverse bioactive constituents and reported metabolic benefits. This review discusses the mechanistic, preclinical, and clinical evidence supporting the role of J. regia in diabetes management. The available studies indicate that walnut contains several phytochemicals, including juglone, flavonoids, polyphenols, and polyunsaturated fatty acids, which may contribute to antioxidant, anti-inflammatory, and insulin-sensitizing activities. Experimental findings suggest that these constituents help improve glucose homeostasis, protect pancreatic β-cells, and regulate insulin-signalling pathways. Preclinical studies consistently demonstrate beneficial effects on glycaemic parameters and pancreatic function, while clinical investigations report modest improvements in fasting blood glucose, HbA1c, and lipid profiles with good tolerability. However, differences in extract preparation, dosage, study design, and duration limit direct comparison among studies and highlight the need for further standardization. Future research should focus on well-designed clinical trials, optimized dosing strategies, and the evaluation of walnut preparations as adjuncts to conventional antidiabetic therapy. Overall, the current evidence supports J. regia as a promising complementary candidate for diabetes management and provides a basis for its further clinical development.
Objective:This study aimed to explore the spectrum of adverse events associated with hydroxyprogesterone and provide a comprehensive understanding of the drug's safety profile based on the Food and Drug Administration's Adverse Event Reporting System database. Methods:Adverse events associated with hydroxyprogesterone were extracted from the Food and Drug Administration's Adverse Event Reporting System database, covering the period from the first quarter of 2004 to the second quarter of 2025. Disproportionality analysis methods were used to detect potential safety signals related to hydroxyprogesterone. We further analyzed the demographic characteristics of the population and the onset time of adverse events. Results:A total of 40,450 adverse event reports related to hydroxyprogesterone were included, corresponding to 197 significant preferred terms categorized into 21 system organ classes per Medical Dictionary for Regulatory Activities criteria. In addition to commonly observed adverse events, several clinically relevant adverse events not previously documented were identified, including fetal distress syndrome, abnormal fetal heart rate deceleration, neonatal jaundice, neonatal respiratory distress, and low birth weight infant. The median time to the onset of hydroxyprogesterone-induced adverse events was 20 days (interquartile range: 0-72 d), with 57.8% of adverse events occurring within the initial 30 days following hydroxyprogesterone administration. Conclusions:In this study, we identified both clinically observed adverse events and potential safety signals associated with hydroxyprogesterone. These results provide valuable evidence to support clinical monitoring, safety risk identification, and the development of subsequent safety investigations.
