👤 Samarpan Majumder

Cardiometabolic risks affect cognition during aging, yet genetic basis for both remain understudied in Indians. This study constructs an ancestry-matched Indian haplotype reference panel for genotype imputation of 5111 rural Indians. Single-locus, gene-based, conditional genome-wide association analyses are performed on 20 cognitive and 10 cardiometabolic traits, with subsequent follow-up of identified associations through multimodal functional annotation. Furthermore, causal interrelationships between cardiometabolic and cognitive phenotypes by Mendelian randomization are investigated. One novel memory-associated and 17 novel cardiometabolic phenotypes-associated (high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], triglycerides [TG], total cholesterol [TC], TG:HDL, and visceral adiposity index [VAI]) genome-wide significant loci, and multiple genes are identified. AMIGO1 (delayed-recall) and ZPR1-APOA5 (metabolic syndrome) exhibit distinct haplotype structure compared to other populations. Causal roles of cardiometabolic traits on various cognitive domains are identified via genetic instruments in APOC3-APOA4-APOA5-ZPR1-BUD13 among others. These findings illustrate the impact of cardiometabolic factors on cognition in a rural socioeconomically disadvantaged population, advancing efforts to address health disparities. Our newly constructed ancestry-matched haplotype reference panel gives better genotype imputation accuracy for the Indian population. One and 17 novel genome-wide significant single-loci were identified to be associated with cognitive and cardiometabolic traits, respectively. Several subgenome-wide hits for all phenotypes were identified. Collapsing protein truncating variants (PTVs), there were two genes identified to be associated with cardiometabolic traits at a genome-wide level of significance, correcting for multiple phenotypes tested. Haplotypic differences were identified compared to 1000 Genomes superpopulations for genes influencing delayed recall and metabolic syndrome. Adverse causal roles of cardiometabolic traits on cognition were uncovered via genetic instruments in APOC3-APOA4-APOA5-ZPR1-BUD13, among others, through Mendelian randomization. Show less

Triple-negative breast cancer (TNBC) is an aggressive, heterogeneous subtype of breast cancer. miRNAs play an essential role in TNBC pathogenesis and prognosis. Obesity is linked with an increased risk for several cancers, including breast cancer. Obesity is also related to the dysregulation of miRNA expression in adipose tissues. However, there is limited knowledge about race- and obesity-specific differential miRNA expression in TNBC. We performed miRNA sequencing of 48 samples (24 tumor and 24 adjacent non-tumor tissues) and RNA sequencing of 24 tumors samples from Black (AA) and White (EA) TNBC patients with or without obesity. We identified 55 miRNAs exclusively associated with tumors in obese EA patients and 33 miRNAs in obese AA patients, each capable of distinguishing tumor tissues from obese from lean individuals within their respective racial groups. In EA, we detected 41 significant miRNA-mRNA correlations. Notably, miR-181b-5p and miR-877-5p acted as negative regulators of tumor-suppressor genes (e.g., Show less

Surface water pollution caused by the discharge of effluents from industrial estates has become a major concern for Dhaka (Bangladesh). This study aims to have a concise look at the severe river water pollution, mainly from effluents discharged from the tannery village. Effluent samples were collected from five ejected points, including the central effluent treatment plant (CETP), twenty adjacent river water, and two pond water nearby Hemayetpur, Savar. Thirty-one parameters have been observed at these sampling points for three seasons, from April 2021 to January 2022. The results obtained from water quality indices, i.e., water quality index (WQI), entropy water quality index (EWQI), and irrigation water quality index (IWQI), show that most studied surface water samples ranked "unsuitable" for consumption, irrigation, and anthropogenic purposes. The highest health risk was observed downstream of Hemayetpur city at the Savar CETP discharge site, indicating higher levels of heavy metal in the river water following the tannery village. Carcinogenic and non-carcinogenic human health risks could be triggered mainly by water consumption as concentrations of arsenic (As), chromium (Cr), nickel (Ni), and lead (Pb) exceeded the upper benchmark of 1 × 10 Show less

Our previous work depicted that benzo(a)pyrene (BaP)-induced lung cancer associated pulmonary redox imbalance and inflammation were effectively regulated by the combinatorial treatment of IL-27 and IL-28B. So in continuation of that finding the present study was designed to reveal the inflammation regulating signaling network modulated by IL-27 and IL-28B treatment related to BaP-induced lung cancer. Male Swiss albino mice were treated with BaP to induce lung tumor. Then they received individual as well as combinatorial treatment of IL-27 and IL-28B. At the end of the experimental schedule, the expression of NF-κB signaling proteins, the formation of NLRP3 inflammasome complex and IL-18; IL-17A expression in the lung were observed using Western blot and RT-PCR. The tissue and serum levels of some proinflammatory cytokines were also studied using ELISA. Mast cell density was also studied using toluidine blue staining procedure. Treatment with IL-27 or IL-28B alone was successful to regulate the expression of NF-κB signaling proteins and NLRP3 complex in some cases but best attenuation was observed in animals who received both IL-27 and IL-28B in combination. In combination, it was successful in down-regulating the expression of p-ERK1/2 and in reducing the accumulation of mast cells in the lung tissue associated with BaP-induced lung carcinogenesis. The impaired PPARγ expression was also reinstated upon combination treatment. Altogether, the treatment in combination with IL-27 and IL-28B is an effective regimen to attenuate the ROS/NF-κB/NLRP3 axis associated with BaP-induced lung carcinogenesis. Show less

The major cause behind lung cancer development is exposure to various polycyclic aromatic hydrocarbons like benzo(a)pyrene (BaP) present in tobacco smoke, motor vehicle, and industrial exhaust. BaP is reported to induce the expression of various pro-inflammatory cytokines and matrix remodeling proteins. It is also responsible for dysfunction and exhaustion of the killing capacity of CD8+ T lymphocytes, one of the important components of the immune system which can kill tumor cells. We tried to evaluate the synergistic role of IL-27 and IL-28B in modulation of BaP-induced lung carcinogenesis associated with various hallmarks like pulmonary redox imbalance, angiogenesis, inflammation and cell proliferation in lung tissue. BaP was treated to Swiss albino mice to develop lung tumor. After the confirmation of lung tumor development Swiss albino mice were treated with IL-27 and IL-28B alone or in combination intraperitoneally. Histological analysis, immunohistochemistry, biochemical assay, western blot analysis, cell cytotoxicity assay, real-time PCR assay etc. were performed to evaluate the modulatory role of IL-27 and IL-28B. We observed that IL-27 and IL-28B were able to suppress the expression of lung cancer-associated NFkB, COX-2, and iNOS. The expression of TNF-α, PCNA and some matrix remodeling enzymes were also modulated upon IL-27 and IL-28B treatment. Although the population of lung residing CD8+ T cells in tumor bearing lung tissue were unresponsive but the activity of systemic CD8+ cells was increased. Results hinted that IL-27 along with IL-28B were able to ameliorate various hallmarks ranging from angiogenesis to inflammation associated with the BaP-induced lung carcinogenesis. From this study, we propose that IL-27 and IL28B can be used as immunotherapeutic agent to regulate lung cancer. Show less

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10 Show less