Significant progress has been achieved in the realm of therapeutic interventions for multiple myeloma (MM), leading to transformative shifts in its clinical management. While conventional modalities such as surgery, radiotherapy, and chemotherapy have improved the clinical outcomes, the overarching challenge of effecting a comprehensive cure for patients afflicted with relapsed and refractory MM (RRMM) endures. Notably, adoptive cellular therapy, especially chimeric antigen receptor T-cell (CAR-T) therapy, has exhibited efficacy in patients with refractory or resistant B-cell malignancies and is now also being tested in patients with MM. Within this context, the B-cell maturation antigen (BCMA) has emerged as a promising candidate for CAR-T-cell antigen targeting in MM. Alternative targets include SLAMF7, CD38, CD19, the signaling lymphocyte activation molecule CS1, NKG2D, and CD138. Numerous clinical studies have demonstrated the clinical efficacy of these CAR-T-cell therapies, although longitudinal follow-up reveals some degree of antigenic escape. The widespread implementation of CAR-T-cell therapy is encumbered by several barriers, including antigenic evasion, uneven intratumoral infiltration in solid cancers, cytokine release syndrome, neurotoxicity, logistical implementation, and financial burden. This article provides an overview of CAR-T-cell therapy in MM and the utilization of BCMA as the target antigen, as well as an overview of other potential target moieties.

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is rising globally, including in India, yet community-based data remain scarce. We address this critical knowledge gap by assessing the prevalence, distribution, and characteristics of MASLD subgroups and fibrosis, leveraging the Phenome India cohort. In this prospective study, we recruited 10,267 adults across 37 laboratories of the Council of Scientific and Industrial Research (CSIR) from 27 Indian cities. All permanent staff members of the CSIR, including current employees, retirees, and their spouses who responded to the recruitment campaign and provided voluntary consent, were considered for participation in the Phenome India Cohort. Steatosis and fibrosis were assessed using Transient Elastography, along with associated clinical, biochemical, cytokine and anthropometric data. Overall, crude and age-adjusted prevalence rates were estimated in the study population and various subgroups. Of 10,267 individuals screened, 7764 were included, 3712 (47.8%) fulfilled MASLD criteria, corresponding to an age-adjusted prevalence of 38.9% (95% CI 37.2–40.6). Significant fibrosis, defined as liver stiffness measurement (LSM) ≥8.2 kPa (≥F2), was more frequent in MASLD (6.3% [234 of 3688]) than in cases without-MASLD (1.7% [69 of 4027]), corresponding to an age-adjusted prevalence of 4.1% in MASLD. Overall age-adjusted prevalence of significant fibrosis was 2.4%, which clustered in older adults (>60 years) and in those with diabetes or obesity class II, with evidence of possible regional variation. MASLD affected over one-third of participants. Site-specific disparities were observed, which suggest the need for large-scale longitudinal studies to elucidate region-specific risk factors and temporal trends. Community-based awareness and targeted public health interventions across diverse geographical and socio-cultural settings in India may help curb the rising burden. The work was funded by CSIR, India grant HCP47.

Cardiomyopathies affect over 3 million individuals globally, with conventional treatments exhibiting up to 60% resistance and 25% 30-day readmission rates. This review synthesizes the current evidence on the role of neuro-immune interactions in the pathogenesis of cardiomyopathy and evaluates emerging therapies targeting this axis. We systematically examined clinical trials and mechanistic and multi-omics data across cardiomyopathy phenotypes, focusing on autonomic-immune dysregulation. Sympathetic overactivation, present in approximately 85% of patients, correlates with elevated pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and contributes significantly to therapeutic non-response. Concurrent parasympathetic withdrawal impairs cholinergic anti-inflammatory pathways, as reflected by reduced heart rate variability and baroreflex sensitivity. At the molecular level, shared mechanisms include inflammasome activation, neuroimmune synaptic signaling, and neurogenic inflammation. Emerging therapies targeting this axis are promising. Vagus nerve stimulation, as demonstrated in the INOVATE-HF trial, improves functional outcomes, whereas IL-1β antagonists reduce cardiovascular events by 15–20% in the context of inflammatory diseases. Bioelectronic interventions, such as transcutaneous vagal nerve stimulation and baroreflex activation therapy, offer noninvasive dual-modulatory strategies that address both neural and immune pathways, positioning the neuroimmune axis as a central driver of cardiomyopathy, regardless of etiology. The integration of genetic and metabolomic profiling may enable precision therapies targeting neuroimmune circuits, thereby overcoming the limitations of hemodynamic-focused care. This mechanistic framework shifts the therapeutic paradigm from symptomatic relief to targeted modulation of pathogenic pathways, with implications for millions of patients with cardiomyopathy and broader inflammatory cardiovascular disorders.

Background: Gastric cancer is a leading cause of cancer-related mortality worldwide, with approximately one million new cases diagnosed annually. While Helicobacter pylori infection remains a primary etiological factor, mounting evidence implicates obesity and lipid metabolic dysregulation, particularly in hypercholesterolemia, as emerging drivers of gastric tumorigenesis. This study investigates the molecular intersections between gastric cancer, obesity, and hypercholesterolemia through a comprehensive multi-omics and systems biology approach. Methods: We conducted integrative transcriptomic analysis of gastric adenocarcinoma using The Cancer Genome Atlas (TCGA) RNA-sequencing dataset (n = 623, 8863 genes), matched with standardized clinical metadata (n = 413). Differential gene expression between survival groups was assessed using Welch’s t-test with Benjamini–Hochberg correction (FDR < 0.05, |log₂FC| ≥ 1). High-confidence gene sets for obesity (n = 128) and hypercholesterolemia (n = 97) were curated from the OMIM, STRING (confidence ≥ 0.7), and KEGG databases using hierarchical evidence-based prioritization. Overlapping gene signatures were identified, followed by pathway enrichment via Enrichr (KEGG 2021 Human) and protein–protein interaction (PPI) analysis using STRING v11.5 and Cytoscape v3.9.0. CD36’s prognostic value was evaluated via Kaplan–Meier and log-rank testing alongside clinicopathological correlations. Results: We identified 36 genes shared between obesity and gastric cancer, and 31 genes shared between hypercholesterolemia and gastric cancer. CD36 emerged as the only gene intersecting all three conditions, marking it as a unique molecular integrator. Enrichment analyses implicated dysregulated fatty acid uptake, adipocytokine signaling, cholesterol metabolism, and NF-κB-mediated inflammation as key pathways. Elevated CD36 expression was significantly correlated with higher tumor stage (p = 0.016), reduced overall survival (p = 0.001), and race-specific expression differences (p = 0.007). No sex-based differences in CD36 expression or survival were observed. Conclusions: CD36 is a central metabolic–oncogenic node linking obesity, hypercholesterolemia, and gastric cancer. It functions as both a mechanistic driver of tumor progression and a clinically actionable biomarker, particularly in metabolically comorbid patients. These findings provide a rationale for targeting CD36-driven pathways as part of a precision oncology strategy and highlight the need to incorporate metabolic profiling into gastric cancer risk assessment and treatment paradigms.

Diabetic atherosclerosis results from the interplay between metabolic dysfunction and immune dysregulation and remains the major cause of mortality in patients with diabetes mellitus (DM) worldwide. Emerging evidence indicates that impaired immune checkpoint signaling, particularly through the PD-1/PD-L1 and CTLA-4 pathways, contributes to the chronic vascular inflammation characteristic of diabetic cardiovascular disease. These checkpoints normally help maintain vascular homeostasis by limiting proatherogenic immune responses. In type 2 diabetes (T2D), which accounts for 90–95% of cases, chronic hyperglycemia downregulates checkpoint expression in both immune effector cells and the vascular endothelium. In type 1 diabetes (T1D), autoimmune-mediated checkpoint failure within the pancreatic islets extends to the vascular tissues, creating an early cardiovascular risk through overlapping but distinct mechanisms. The loss of checkpoint regulation amplifies Th1 and Th17 responses while impairing regulatory T cell function and accelerating plaque formation and destabilization. Observations from cancer patients receiving checkpoint inhibitors, who exhibit increased cardiovascular events, further highlight the importance of these pathways in vascular integrity. Restoring checkpoint signaling through targeted interventions, combined with biomarker-driven stratification and personalized immune profiling, may provide new strategies for preventing or slowing atherosclerotic progression in patients with diabetes.

Background: Metabolically–dysfunction–associated steatotic liver disease (MASLD) is rising globally, including in India, yet community-based data remain scarce. We addressed this critical knowledge gap by assessing the prevalence, distribution, and characteristics of MASLD subgroups and fibrosis, leveraging the Phenome India–CSIR Health Cohort Knowledgebase (PI-CHeCK) study. Methods: In this prospective, nationwide study, we recruited 10267 adults across 37 laboratories of the Council of Industrial Research (CSIR) from 27 Indian cities. Steatosis and fibrosis were assessed by Transient Elastography using Fibroscan, with associated clinical, biochemical, cytokine, anthropometric, and lifestyle data collected. Overall, crude and age-adjusted prevalence rates were estimated in the study population and various subgroups. Findings: Of the 10267 individuals screened, 7764 were eligible for analysis after exclusions. Among these, 3,712 (47.8%) fulfilled MASLD criteria, corresponding to an age-adjusted prevalence of 36.3%. Significant fibrosis (≥F2) was more frequent in MASLD (6.3% [234 of 3688]) than in cases of cryptogenic fibrosis without MASLD (1.7% [69 of 4027]), corresponding to an age-adjusted prevalence of 4.1% in MASLD. Overall age-adjusted prevalence of significant fibrosis was 2.3% in the entire cohort, which clustered in older adults (>60 years) and in those with diabetes or obesity II, with evidence of regional variation, peaking in Jorhat, Assam. Importantly, fibrosis in participants without MASLD emerged as a distinct subgroup with disproportionately elevated cytokine levels, exceeding those in MASLD with fibrosis, suggesting a cytokine-rich, high-risk phenotype. Conclusion: In this nationwide Indian cohort, MASLD affected over one-third of participants with a substantial burden of fibrosis. Notably, fibrosis without-MASLD emerged as a cytokine-rich, high-risk phenotype, underscoring an underrecognized dimension of liver disease with major public health implications.