Breast cancer remains a leading cause of cancer-related morbidity and mortality among women globally. Breast cancer is the most diagnosed cancer in women. Metastasis is the primary cause of mortality for breast cancer patients. In Bihar, there are so many cases of Breast Cancer patients found but most of them collected near the Gangetic plane. Also, we compared the real data of Breast cancer patients from the data available on TCGA. We performed comparison of the trend of ER, PR, and HER-2 expression trend in both data. This research has highlighted the significant role of inflammatory cytokines in the tumor microenvironment, particularly tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), and Interleukin-1 beta (IL-1β). These cytokines are implicated in various stages of breast cancer development, including tumor initiation, progression, and metastasis. TNF-α helps to promote tumor growth through enhancing processes such as angiogenesis and inhibition of apoptosis. IL-6 and IL-1β contribute to cancer cell proliferation, survival, and resistance to therapy by activating key signaling pathways like the JAK/STAT pathway. This research reveals the roles of TNF-α, IL-6, and IL-1β in breast cancer, and sheds light on how they affect the tumor microenvironment and the course of the illness. These cytokines contribute to breast cancer progression and may help to produce targeted therapy and open up new options for individualized treatment plans

Gastrointestine (GI) depression is a severe complication identified in individuals after intentional or unintentional radiation exposure. Early detection of radiation-induced GI injury (RIGI) is important for medical management with supportive care, which can largely be achieved using organ specific biomarkers. Fatty Acid Binding Proteins (FABPs) are 14-15 kDa cytosolic proteins which are quickly released into circulation in the event of tissue injuries. The present investigation aims to unravel the potential of FABPs as candidate targets to predict RIGI. Utilizing data mining approach, FABP genes differentially expressed in 06 microarray datasets retrieved from Gene Expression Omnibus (GEO) database across distinct species were identified. The abundance of 10 genes encoding FABPs were checked in intestinal tissue of male and female C57Bl/6 mice by qRT-PCR analysis. FABP1 and FABP2 were identified as the abundant genes expressed in small intestine of both the sexes. In order to explore FABP1 and FABP2 as possible targets for radioprotection, we selected approved hydrophilic and lipophilic statins to perform molecular docking studies. The findings highlighted that FABP1 and FABP2, expressed in intestine, can act as potential biomarkers for RIGI as well as their drug targets can be explored as promising radiation countermeasure agents.

Calcitonin Gene Related Peptide (CGRP) is expressed in the cardiovascular system and showed vasodilatory effects. This study aimed to investigate the effects of exercise training and a CGRP antagonist (CGRPi) on the expression of genes involved in mitochondrial dynamics in the aorta. Forty-two male rats were divided into six groups (n=7): 1) Control; 2) Endurance Training (ET); 3) High-Intensity Interval Training (HIIT); 4) CGRP antagonist (CGRPi,10 mg/kg) administered via intraperitoneal injections; 5) CGRPi + ET (CGRPi-ET); and 6) CGRPi + HIIT (CGRPi-HIIT). Protein expression was analyzed using Western blotting, while gene expression was quantified via Real-Time PCR. Both ET and HIIT significantly upregulated eNOS protein and the gene expression of Pgc-1α, Bcl-2, Nrf-1, Sirt3, Parkin, and eNOS. The increase in Bcl-2 expression induced by ET was attenuated by CGRPi in the groups with the combination of CGRPi and ET (P = 0.02). Exercise training enhanced mitochondrial biogenesis by affecting the expression of Pgc-1α, Nrf-1 and Sirt3. While CGRP is known to mediate vasodilation, we indicated that CGRPi did not affect eNOS expression, suggesting that CGRP exerts vasodilatory effects through mechanisms other than eNOS in the aorta. Furthermore, CGRPi does not showed negative effects over genes associated with mitophagy and mitochondrial biogenesis.

Tuberculosis is a highly contagious airborne disease that remains one of the leading causes of mortality worldwide. In the era of an increasing rate of drug-resistant strains and other shortcomings of current anti-TB therapies, we promptly need new, effective treatments to combat tuberculosis. Antimicrobial peptides have emerged as promising candidates, offering a novel approach to tackling tuberculosis, particularly drug-resistant strains. Antimicrobial peptides have broad-spectrum antimicrobial activity and the ability to modulate host immune responses. Their unique mechanism of disrupting microbial membranes reduces the likelihood of resistance development. Additionally, antimicrobial peptides can enhance immune function by recruiting immune cells, promoting phagocytosis, and modulating innate and adaptive immune responses. These properties make antimicrobial peptides particularly effective in managing infections like tuberculosis while the generation of drug-resistant and excessive inflammation, a critical consideration in tuberculosis treatment.

In-silico epitope-based vaccine is the cornerstone of modern vaccine development and is illuminating by a growing number of experimental and computational methods. The reverse vaccinology approach uses computational screening of the whole proteome of a pathogen to identify the proteins with the attributes of potential vaccine targets. The selection of the right components [antigenic determinants, linkers, and intramolecular adjuvants] results in the development of a multi-epitope vaccine construct with maximum efficacy and minimum adverse effects. We provide insight into the recent advancement in epitope-based vaccines and the procedure to design the modern or next-generation vaccine. The synergy between the computational screening of vaccine candidates and experimental verification to assess the immunogenic potential improves decision-making and reduces the cost and time of the development of new therapeutics

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are common clinico-pathological conditions that affecting over 30% of adults worldwide. Insulin resistance and hepatic lipid accumulation constitute the metabolic foundation of MASLD/MASH. Although previous studies have shown limited efficacy of activation of single PPARs (PPARα or PPARγ), ongoing clinical trials suggest that dual and pan-PPAR agonists may have a broader and more potent therapeutic effect on MASH by simultaneously targeting different inter-related mechanisms in this multisystem disease. Therefore, we hypothesized that a combination of PPARγ agonist (to enhance insulin sensitivity) with lipid lowering therapy (similar to PPARα) could have similar or better effects compared to PPARα/γ dual agonists. In the current study, we have investigated a novel combination of pioglitazone (a PPAR γ/α agonist) and ezetimibe (a cholesterol absorption inhibitor) in two different MASH animal models. We expected that anti-cholesterol absorption property of ezetimibe can augment the poor PPAR-α agonist property of pioglitazone in terms of lipid sensitivity in regulating steatosis. We tested pioglitazone at 2-3-fold reduced clinical dose (15mg/day) in combination to ezetimibe, since there are safety concerns associated with higher doses (30mg and 45mg, daily). Our results revealed that combination of low dose pioglitazone, with ezetimibe hold the ability to regulate the steatosis, hepatocyte inflammation and ballooning, which resulted in superior effects in terms of NAS as well as fibrosis score compared to pioglitazone alone (30mg/kg). Moreover, in vitro studies in human liver microsomes and mouse hepatocytes did not show any drug-drug interaction between pioglitazone and ezetimibe. Overall, this study provides a potential possibility for the clinical treatment of MASH with combination of pioglitazone and ezetimibe.