Rhizomes of Drynaria quercifolia have long been traditionally used to manage rheumatic pain. However, there is limited research supporting this traditional practice and insufficient evidence demonstrating the molecular mechanisms of action of plant-derived bioactives in rheumatoid arthritis (RA). The current study aims to identify the effective components in Drynaria quercifolia methanol rhizome extract (DME) and their probable pharmacological mechanisms in alleviating Rheumatoid Arthritis (RA) using network-pharmacology, molecular docking, molecular-dynamics simulations, and gene expression-based validation. Gas chromatography–mass spectrometry (GC-MS) based screening identified 41 volatile phytocomponents from DME having drug-like potentiality. Network pharmacology-based screening revealed 117 therapeutic targets for RA of which 11 have been identified as core targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that key target genes were mostly enriched in the inflammatory response associated with multiple signalling pathways. Molecular docking and molecular dynamics studies revealed that key target proteins like serine/threonine-protein kinase (AKT1), peroxisome proliferator-activated receptor alpha (PPARA), and peroxisome proliferator-activated receptor gamma (PPARG), exhibited strong binding affinity and stable interactions with multiple phytocomponents present in DME. For experimental verification FCA (Freund’s complete adjuvant)-induced chronic arthritis model employed for further molecular investigation. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) results validated that DME significantly (p ≤ 0.05) regulate the expression of key identified target genes AKT and PPARG in experimental RA model. Moreover, this study further confirmed that DME significantly (p ≤ 0.05) downregulated pro-inflammatory mediators like COX-2, IL-6 and TNF-α at gene and protein levels and also normalized (p ≤ 0.05) different oxidative stress parameters in both the low and high dose groups of DME-treated arthritic animals. In conclusion, the network-based in silico approach indicated that the phytocomponents present in DME probably act in a synergistic way to modulate key identified targets associated with RA, which was further validated by experimental studies. Therefore, DME could be a potential alternative in immunomodulatory therapies to combat RA and related chronic inflammatory conditions.

Cisplatin, a powerful chemotherapy medication, has long been a cornerstone in the fight against cancer due to chemotherapeutic failure. The mechanism of cisplatin resistance/failure is a multifaceted and complex issue that consists mainly of apoptosis inhibition through autophagy sensitization. Currently, researchers are exploring ways to regulate autophagy in order to tip the balance in favor of effective chemotherapy. Based on this notion, the current study primarily identifies the differentially expressed genes (DEGs) in cisplatin-treated autophagic ACHN cells through the Illumina Hi-seq platform. A protein–protein interaction network was constructed using the STRING database and KEGG. GO classifiers were implicated to identify genes and their participating biological pathways. ClueGO, David, and MCODE detected ontological enrichment and sub-networking. The network topology was further examined using 12 different algorithms to identify top-ranked hub genes through the Cytoscape plugin Cytohubba to identify potential targets, which established profound drug efficacy under an autophagic environment. Considerable upregulation of genes related to autophagy and apoptosis suggests that autophagy boosts cisplatin efficacy in malignant ACHN cells with minimal harm to normal HEK-293 growth. Furthermore, the determination of cellular viability and apoptosis by AnnexinV/FITC-PI assay corroborates with in silico data, indicating the reliability of the bioinformatics method followed by qRT-PCR. Altogether, our data provide a clear molecular insight into drug efficacy under starved conditions to improve chemotherapy and will likely prompt more clinical trials on this aspect.

Dengue cases are increasing every year in the sub-Himalayan part of West Bengal, where Aedes albopictus (Skuse 1894) has emerged as a predominant dengue vector. Dengue management heavily relies on the recurrent application of chemical insecticides such as temephos (larvicide) and deltamethrin (adulticide). However Ae. albopictus can quickly develop resistance which complicates their management. Thus, detailed population-specific studies on resistance status and mechanism of resistance are useful for designing an effective dengue management strategy. In this study, wild mosquitoes were collected and bioassays with temephos and deltamethrin, including synergist assays, were conducted to investigate the probable mechanism of resistance. Furthermore, carboxylesterase activity and level of monooxygenase were measured followed by real-time polymerase chain reaction analysis to assess expression patterns of CCE and CYP genes. Bioassays confirmed temephos and deltamethrin resistance in Ae. albopictus population is driven by metabolic detoxification. Biochemical assay recorded significantly elevated carboxylesterase activity and monooxygenase levels compared to a susceptible laboratory strain. This is further supported by the elevated relative expression of CCE and CYP genes with consistent expression of CYP6A8 and CCEae3a in these populations. A molecular docking study suggested that the conformation of the binding site for temephos and deltamethrin may enhance their potential metabolism. These findings align with the global trend of insecticide resistance development and highlight the urgent need for more sustainable and informed approaches to dengue vector management.

Kanchnar Guggulu (KG) is a potent Ayurvedic remedy for hormonal imbalances, PCOS, ulcers, cystic swelling, and tumors