JSS University

Abstract Development of polymeric nanofibers using the electrospinning technique has found potential candidature for tremendous applications including protective clothing, sensors, energy sectors, tissue engineering, wound healing, air filtration, liquid filtration and cosmetics. This is because of the potentiality of the electrospinning method in producing ultrathin fibers ranging from nano to micrometers. Numerous efforts have been made by researchers using electrospinning techniques to regulate the morphology of the developed fibers. Similarly, various polymers and polymer composites have been employed for the development of fibers using electrospinning techniques for different applications. In the current research work, the electrospun nanofibers were produced from a composite solution of polydimethylsiloxane-polyvinyl alcohol (PDMS-PVA) polymers and synthesized zinc silicate (ZnSiO 3 ) nanoparticles. Nanofibrous membranes were produced from the prepared polymer composite solution using electrospinning under high voltage. A morphological study conducted by scanning electron microscopy revealed uniform fibers with diameters ranging from 142 nm to 410 nm. Wettability studies of the electrospun nanofibrous membrane showed an increase in water contact angle from 43° for pristine PDMS-PVA to 92° for ZnSiO 3 loaded membranes thereby indicating enhanced hydrophobicity. Air filtration performance testing on the membranes demonstrated that the filtration efficiency was improved from 63° for P 0 to 92° for P 3 , while the quality factor increased from 0.034 Pa −1 to 0.368 Pa −1 . Among all the samples, the membrane P 3 demonstrated the best performance, whereas P 0 showed the lowest performance. Thus, it can be inferred that the incorporation of ZnSiO 3 greatly enhanced the air filtration capability of the composite membranes, thereby making the membranes a suitable candidate for air filtration applications and air quality management.

The human intestine is continuously exposed to a variety of aggressive agents, including food antigens, xenobiotics, numerous pathogenic microorganisms, metabolic products, and toxins. Consequently, it has developed a specialized system for protection against these adverse factors. This study aims to investigate the biochemical compounds synthesized by Paneth cells and their mechanisms of action to develop new therapeutic approaches for gastroenterological diseases. We conducted a systematic review, excluding a comprehensive meta-analysis, of the current scientific literature sourced from electronic libraries (CyberLeninka, e-Library.ru, and Cochrane Library), search engines (Google Scholar, Embase, and Global Health), and scientific databases (Elsevier, Medline, PubMed-NCBI, eMedicine, the National Library of Medicine (NLM), and ReleMed and Scopus). Following PRISMA guidelines, a total of 104 articles were initially selected based on defined inclusion and exclusion criteria. After careful evaluation, 63 articles were included in this study. Our findings indicate that Paneth cells play a crucial role in regulating small intestine homeostasis by secreting numerous biologically active molecules. A key feature of these cells is their ability to recognize soluble microbial products via pattern recognition receptors and respond by releasing a variety of antimicrobial peptides and enzymes. These secretions contribute to the formation of a biochemical barrier that prevents pathogen adhesion and translocation. Paneth cells are integral to immunological protection, maintaining protective inflammatory responses under both normal and pathological conditions. Additionally, they regulate the division, growth, and differentiation of intestinal stem cells, ensuring proper enterocyte localization. Paneth cells also aid digestive processes through enzyme secretion and are the only epithelial cells capable of eliminating activated autoreactive lymphocytes and abnormal enterocytes. Paneth cells are unique epithelial cells that, through the synthesis of numerous biologically active molecules, control the timely regeneration of the intestinal epithelium, maintain a healthy microbiota, and prevent infectious, autoimmune, and cancerous diseases. Understanding their role in these processes is crucial for developing new therapies for gastroenterological diseases.

The increasing emotional distress among emerging adults highlights the importance of examining trauma-related factors, particularly complex trauma. This study investigates post-traumatic stress disorder (PTSD), complex post-traumatic stress disorder (C-PTSD), and emotional distress, emphasizing the predictive role of disturbances in self-organization (DSO) as defined by the International Classification of Diseases (11th revision) (ICD-11). A cross-sectional study was conducted among 538 college-going emerging adults (aged 15-29 years). The study received ethical clearance from the institute and informed consent from the participants, who completed validated measures: the International Trauma Questionnaire and Depression, Anxiety, and Stress Scale-21. Quantitative data were analyzed using descriptive statistics, Mann-Whitney/Kruskal-Wallis tests, Pearson's correlation, and multiple linear regression. Thematic analysis was used to explore self-reported traumatic experiences. Prevalence rates were 15.2% for C-PTSD, 20.8% for PTSD, 53.9% for depression, 66.5% for anxiety, and 36.2% for stress. DSO showed the strongest associations with all three domains of emotional distress. Thematic analysis revealed multidimensional trauma themes, including career anxiety, relational issues, abuse, loss, and social exclusion. Gender and psychiatric history significantly moderated distress levels, while rural-urban background showed no difference. Among the variables, DSO demonstrated the strongest and most consistent associations with depression, anxiety, and stress, pointing to its close link with complex trauma responses. Results highlight the need for trauma-informed screening and interventions in Indian academic settings and support ICD-11's distinction between PTSD and C-PTSD. A tiered intervention model is recommended for early detection and tailored care.

Rare diseases, though individually infrequent, collectively affect over 300 million people worldwide. The development of orphan drugs to treat these conditions is hampered by regulatory inconsistencies, high costs, and limited clinical trial populations. To systematically review the current landscape of orphan drugs and rare diseases, focusing on definitions, therapeutic approaches, health economic evaluations, and stakeholder perspectives. A systematic review was conducted using 70 reference-screened articles, out of which 10 were selected based on relevance to rare diseases or orphan drug policy, economics, or clinical management. Study types included systematic and scoping reviews, observational studies, and health economic evaluations. Data extraction focused on definitions, healthcare roles, cost analyses, and clinical outcomes. Definitions of rare diseases varied globally, impacting drug approval processes. Economic evaluations revealed disparities in funding orphan drugs. Studies emphasized the growing role of pharmacists and stakeholders in therapeutic access. High-cost burdens, ethical considerations, and diagnostic advancements were recurring themes. Pediatric and syndromic rare conditions, like Duchenne muscular dystrophy and Turner syndrome, were notably covered. Effective rare disease care requires harmonized definitions, ethical pricing models, interdisciplinary healthcare roles, and evidence-based policies to ensure equitable access and sustainability.

Background: Chronic Obstructive Pulmonary Disease (COPD) remains a leading cause of morbidity and mortality worldwide, particularly in low- and middle-income countries (LMICs), where both tobacco and biomass smoke exposure are major risk factors. While spirometry is the diagnostic gold standard, reliable non-invasive biomarkers are needed for early detection and disease monitoring. The soluble receptor for advanced glycation end-products (sRAGE), a circulating decoy receptor with anti-inflammatory activity, has shown potential in this context. Methods: In this prospective, exposure-stratified, cross-sectional study, 150 adults were enrolled into four groups of 25 each—tobacco-smoke COPD, male tobacco-exposed controls, biomass-smoke COPD, and female biomass-exposed controls—along with 50 healthy controls (25 males, 25 females). Participants underwent clinical evaluation, spirometry, and serum sRAGE quantification (ELISA). Systemic inflammation was assessed using neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Correlation and receiver operating characteristic (ROC) analyses determined diagnostic performance. Results: Serum sRAGE levels were significantly lower in tobacco-induced (545 ng/mL) and biomass-induced COPD (540 ng/mL) versus controls (1207–1462 ng/mL; p < 0.001). sRAGE correlated positively with FEV1, FVC, and FEV1/FVC (r = 0.54–0.75, p < 0.001), and negatively with CAT, mMRC, and SGRQ-C. ROC analysis showed excellent discrimination (AUC = 0.990; 94% sensitivity; 96% specificity at 946 ng/mL cutoff). Conclusions: Serum sRAGE is a robust, non-invasive biomarker for COPD diagnosis and severity assessment across exposure phenotypes. Its integration into clinical practice may enhance early detection and risk stratification, particularly in LMICs.

Breast cancer is one of the leading causes of cancer-related mortality globally. Recent advances in targeted therapies have focused on selectively inhibiting signalling pathways that are vital for cancer cell survival and proliferation. Identifying novel small molecules with such inhibitory capabilities remains a critical step toward more effective treatments. A computational approach was utilized to design and identify small molecule inhibitors targeting key signalling pathways implicated in breast cancer progression. Virtual screening and molecular docking analyses were conducted to identify potential lead compounds. The selected compounds were further evaluated in vitro using MCF7 breast cancer cells to determine cytotoxicity (via IC50) and to assess apoptotic effects. ADMET profiling was performed to predict pharmacokinetic properties. Two lead compounds, C12 and C18, demonstrated strong binding affinities to serine-threonine protein kinase and MAP3K5, both of which are critical regulators of apoptosis. In vitro studies revealed significant cytotoxic effects, with IC50 values of 22.49 ± 1.01 µg/ml for C12 and 14.61 ± 0.01 µg/ml for C18. Microscopic and biochemical analyses showed hallmark features of apoptosis, including nuclear condensation, DNA fragmentation, and mitochondrial membrane potential loss. ADMET predictions indicated favourable pharmacokinetic profiles for both compounds. The identified compounds C12 and C18 exhibit potent cytotoxic and pro-apoptotic activity in breast cancer cells, highlighting their potential as promising novel therapeutic agents. However, further in vivo studies are essential to validate their efficacy and safety profiles.

IntroductionTriple-negative breast cancer (TNBC) is a challenging subtype of breast cancer to treat because it lacks the expression of progesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2). A significant majority of deaths related to cancer are caused by tumor metastasis and angiogenesis. Vascular endothelial growth factor receptor 2 (VEGFR2) plays a significant role in angiogenesis. Instead of developing new molecules, drug repurposing, also known as repositioning, seeks innovative uses for outdated drugs or those that fail due to ineffectiveness.MethodsIn this study, we performed high-throughput virtual screening of FDA approved drug library taken from Enamine bioactive collection targeting VEGFR proteins, and the top hit compounds analyzed by molecular dynamics simulations and MM-GBSA were considered for further in vitro analyses against human breast cancer cells, MDA-MB-231 and MDA-MB-468 cells followed by in ovo assay using the Chorioallantoic Membrane (CAM) model.ResultsThe results revealed that risperidone was effective against triple-negative breast cancer, with IC50 values ranging from 46.53 to 49.76 µM. The findings of our study demonstrated that risperidone, an antipsychotic drug, could successfully inhibit human breast cancer cells in silico, in vitro and in ovo.DiscussionWe could prove that a structure-based drug repurposing approach is an effective strategy to produce a promising antiangiogenic repurposed drug that could also inhibit VEGFR2 in breast cancer. Although risperidone showed modest potency, its clinical availability and repurposing potential support further evaluation in preclinical and clinical settings.

ABSTRACT The global cancer burden data 2022 estimated 2.3 M newly diagnosed breast cancer cases with over 6 M mortalities. Moreover, the cases are expected to increase by 10% by 2045, raising health concerns worldwide. Triple‐negative breast cancer is a highly aggressive subtype of BC with a shorter survival rate and a higher likelihood of recurrence. EGFR overexpression is seen in 15%–45% of BC. It is associated with nearly 50% of TNBC and inflammatory breast cancer incidences, associated with motility, survival, and differentiation through mutation. This study investigates pyrrolo[2,1‐f][1,2,4]triazine analogs as potential inhibitors of both wild‐type and mutant (T790M) EGFR, utilizing computational approaches to address resistance and enhance breast cancer therapeutics. A dataset of pyrrolo[2,1‐f][1,2,4]triazine analogs was used to develop pharmacophore models and a predictive 3D‐QSAR model. The designed library underwent ADME screening, molecular docking with mutant and wild‐type EGFR, MM‐GBSA calculations, DFT, MD simulations, and post‐MD studies using Schrödinger 2025–2 software. Compound SK31 showed favorable docking (wild‐type: −10.8 kcal/mol; mutant: −9.4 kcal/mol), strong MM‐GBSA binding energies, and stable interactions in MD. DFT confirmed favorable electronic behavior. Post‐MD analyses revealed low‐energy conformational stability and strong residue correlations. This study provides a framework for designing pyrrolo[2,1‐f][1,2,4]triazine‐based EGFR inhibitors and offers valuable insights into future breast cancer therapeutic development.