Comparative Safety of JAK Inhibitors vs TNF Antagonists in Immune-Mediated Inflammatory Diseases: A Systematic Review and Meta-Analysis.

Importance: Janus kinase (JAK) inhibitors are highly effective medications for several immune-mediated inflammatory diseases (IMIDs). However, safety concerns have led to regulatory restrictions.

Objective: To compare the risk of adverse events with JAK inhibitors vs tumor necrosis factor (TNF) antagonists in patients with IMIDs in head-to-head comparative effectiveness studies.

Mechanistic insights into DNA binding by BD1 of the TAF1 tandem bromodomain module.

Transcription initiation factor TFIID subunit 1 (TAF1) is a pivotal component of the TFIID complex, critical for RNA polymerase II-mediated transcription initiation. However, the molecular basis by which TAF1 recognizes and associates with chromatin remains incompletely understood. Here, we report that the tandem bromodomain module of TAF1 engages nucleosomal DNA through a distinct positively charged surface patch on the first bromodomain (BD1).

Distinct codon usage signatures reflecting evolutionary and pathogenic adaptation in the Acinetobacter baumannii complex.

Purpose: This study investigates codon usage and amino acid usage bias in the genus Acinetobacter to uncover the evolutionary forces shaping these patterns and their implications for pathogenicity and biotechnology.

Methods: Codon usage patterns were examined in representative genomes of the genus Acinetobacter using standard codon bias indices, including GC content, relative synonymous codon usage (RSCU), effective number of codons (ENC), and codon adaptation index (CAI). Neutrality and parity plots were employed to evaluate the relative influence of mutational pressure and natural selection on codon preferences.

Environmental antibiotic stress and high-risk resistance genes in bacterial communities of the Gomti and Ganga Rivers, India.

Background: The river ecosystems provide habitats and source of water for a number of species including humans. The uncontrolled accumulation of pollutants in the aquatic environment enhances the development of antibiotic-resistant bacteria and genes.

Methods: Water samples were collected seasonally from different sites of Gomti and Ganga River.

Unveiling molecular signatures for precision drug design: machine learning insights from trypanothione reductase, PKC-θ, and CB1.

Traditional drug discovery methods like high-throughput screening and molecular docking are slow and costly. This study introduces a machine learning framework to predict bioactivity (pIC₅₀) and identify key molecular properties and structural features for targeting Trypanothione reductase (TR), Protein kinase C theta (PKC-θ), and Cannabinoid receptor 1 (CB1) using data from the ChEMBL database. Molecular fingerprints, generated via PaDEL-Descriptor and RDKit, encoded structural features as binary vectors.

Characterization of the pesticidal crystal toxin protein Cry11Aa from Bacillus thuringiensis serovar israelensis VCRC B646 for mosquito larvae control.

Effective mosquito control is essential for reducing the transmission of vector-borne diseases. This study focuses on the comprehensive characterization of mosquitocidal toxins produced by Bacillus thuringiensis serovar israelensis (Bti) VCRC B646 and the associated insecticidal genes. The bacterium was cultured, and the spore-crystal complex was purified to identify the mosquitocidal proteins.

Global challenges in diabetes research and care: which way forward? An appraisal from the EASD Global Council.

This review article, developed by the EASD Global Council, addresses the growing global challenges in diabetes research and care, highlighting the rising prevalence of diabetes, the increasing complexity of its management and the need for a coordinated international response. With regard to research, disparities in funding and infrastructure between high-income countries and low- and middle-income countries (LMICs) are discussed. The under-representation of LMIC populations in clinical trials, challenges in conducting large-scale research projects, and the ethical and legal complexities of artificial intelligence integration are also considered as specific issues.

Expression of long non-coding RNAs MALAT1, MEG3, and XIST in gestational diabetes mellitus: a cross-sectional study.

Background And Aims: Gestational diabetes mellitus (GDM) is defined as glucose intolerance first identified during pregnancy that does not meet the criteria for overt diabetes. Its pathophysiology shares key features with type 2 diabetes mellitus (T2D), including insulin resistance and inflammation. Emerging evidence suggests that long non-coding RNAs (lncRNAs) are implicated in T2D.

Evaluation of clozapine forgiveness under imperfect adherence scenarios: a population pharmacokinetic simulation study.

Clozapine, the only drug approved by the FDA for treatment-resistant schizophrenia, operates within a narrow therapeutic range (0.35-0.60 mg/mL) and requires titration from 12.

In silico design, synthesis of a novel chalcone derivative and its in vitro and in vivo anticancer activity against colon cancer-induced mouse model.

This study aimed to synthesize and evaluate the anticancer activity of novel chalcone derivative against colon cancer by in vitro cytotoxicity against HCT-116 (Research Resource Identifiers:CVCL_D4JB) cell line and in vivo using EAC (Research Resource Identifiers: CVCL_1306) and DLA (Research Resource Identifiers: CVCL_VR37) cells inoculated Swiss albino mice. The present study aimed to synthesize the new chalcone derivatives and conduct its anti-colon cancer activity both in vitro and in vivo. The designed compounds were subjected to in silico studies like binding pocket analysis, molecular docking, and ADME studies.

Adjuvant potential of metformin with standard anti-seizure medications in persons with active epilepsy: a randomised controlled trial.

The purpose of this study was to investigate the efficacy and safety of add-on metformin treatment in persons with active epilepsy (a-PWE). This is a single-centric, double-blind, placebo-controlled trial randomised a-PWE (1:1) to receive either metformin (extended-release 500 mg) or matching placebo for 6 months along with background antiseizure medications. Primary outcome was percentage change in seizure frequency/month, and secondary outcomes were 50% responder rate, serum mTOR expression, and serum total antioxidant capacity (TAC), body composition analysis, quality of life (QOL), and safety assessment.

Spirituality and Medicine in the USA, Europe, and the UK: A Systematic Review and Meta-analysis of Integrative Approaches to Patient Satisfaction, Quality of Life, and Health Outcomes.

Spiritual interventions, including meditation, prayer, mindfulness, and compassionate care, have gained increasing attention for their potential to enhance both psychological resilience and overall health. This systematic review and meta-analysis examined eight eligible studies conducted across the USA, Europe, and China to assess the impact of such interventions on key outcomes, namely anxiety reduction, quality of life, chronic disease symptom management, and patient satisfaction. Seven studies contributed quantitative data.

Targeting NLRP3 inflammasome with curcumin: mechanisms and therapeutic promise in chronic inflammation.

The NOD‑like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a key molecular complex that amplifies inflammatory cascades by maturing interleukin‑1 beta (IL-1β) and interleukin‑18 (IL-18) and inducing pyroptosis. It serves as a major driver and co-driver of numerous diseases associated with chronic inflammation. Dysregulated NLRP3 activation contributes to the progression of disorders such as rheumatoid arthritis, inflammatory bowel disease, neurodegenerative diseases and atherosclerosis.

Identification of known and novel genetic variants in sensorineural hearing loss: insights from whole exome sequencing in Indian families.

Background: Hearing loss (HL) is one of the most common congenital anomalies and is a complex etiologically diverse condition. Molecular genetic characterization of HL remains challenging owing to the high genetic heterogeneity. This study aimed to screen for potential disease-causing genetic variations in a cohort of Indian patients with congenital bilateral severe-to-profound sensorineural HL.

RNA sequencing of the lncRNA regulome modulated by Withania somnifera in human neuroblastoma SK-N-SH cells.

Background: The dysregulation of long-chain noncoding RNAs (lncRNAs) causes several complex human diseases including neurodegenerative disorders across the globe.

Methods And Results: This study aimed to investigate lncRNA expression profiles of Withania somnifera (WS)-treated human neuroblastoma SK-N-SH cells at different timepoints (3 & 9 h) and concentrations (50 & 100 µg/mL) using RNA sequencing. Differential gene expression analysis showed a total of 4772 differentially expressed lncRNAs, out of which 3971 were upregulated and 801 were downregulated compared to controls.

Molecular phylogeny of Psoroptes ovis isolated from ear canker in a domestic rabbit from South India.

Background: Ear canker in domestic rabbits is caused by infestations of non-burrowing parasitic mites, Psoroptes spp., but the specific species responsible for these infestations remains unclear. This study reports the clinical signs and performs the molecular characterization and phylogenetic analysis of Psoroptes ovis isolated from the ear canal of a domestic rabbit in South India.

Mechanistic insights and nanomedicine innovations of oligomeric proanthocyanidin in precision oncology: Ablating self-renewal capacity of metastatic cancer stem cells via multi-pathway modulation.

Oligomeric proanthocyanidins (OPCs), condensed tannins found plentiful in grape seeds and berries, have higher bioavailability and therapeutic benefits due to their low degree of polymerization. Recent evidence places OPCs as effective modulators of cancer stem cell (CSC) plasticity and tumor growth. Mechanistically, OPCs orchestrate multi-pathway inhibition by destabilizing Wnt/β-catenin, Notch, PI3K/Akt/mTOR, JAK/STAT3, and Hedgehog pathways, triggering β-catenin degradation, silencing stemness regulators (OCT4, NANOG, SOX2), and stimulating tumor-suppressive microRNAs (miR-200, miR-34a).

Safety and efficacy of tranexamic acid in pelvi-acetabular trauma surgery: a systematic review and meta-analysis of randomized controlled trials.

Background: Pelvic and acetabular fractures, often resulting from high-impact trauma, pose significant challenges due to extensive blood loss and complex surgical procedures. Tranexamic acid (TXA), widely used in elective orthopedic surgeries, offers a potential strategy for managing blood loss. However, its efficacy and safety in pelvic-acetabular trauma surgeries have shown inconsistent results in prior studies.

The evolution of targeted intra operative radiotherapy in early breast cancer.

Targeted intraoperative radiotherapy (IORT) delivers a single dose of radiation to a fresh tumour bed immediately after lumpectomy, commonly used to treat early breast cancer (EBC). It is delivered during the same sitting, with improved patient compliance and better sparing of adjacent healthy tissue, compared to conventional adjuvant radiotherapy to the whole breast. The recently published 12-year results (median follow up of 8.

Boron-Rich Metallaboranes from κ-N,E-Chelated Ru Complexes (E = S or Se): A Direct Route to Ruthenaboranes.

We have established a new route for boron-rich ruthenaborane clusters utilizing [BH·THF] and a ruthenium precursor featuring chelating ligands. Salt elimination reactions between [K(CHNE)], (E = S; Se) and [RuCl(PPh)], afforded -[Ru(κ--CHNE)(PPh)], -- (-: E = S and -: E = Se). Following the ligand exchange reaction with the 1,2-bis (diphenylphosphino)ethane (dppe) ligand yielded -[Ru(κ--CHNE)(dppe)] (-: E = S; -: E = Se).