Int J Med Sci
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Colorectal cancer (CRC) is a prevalent malignancy with high morbidity and mortality rates globally. Advances in single-cell sequencing technology have enabled comprehensive analyses of tumor cells at single-cell resolution, providing valuable insights into the molecular mechanisms underlying CRC initiation and progression. In this study, we integrated single-cell sequencing data with the TCGA database to identify key molecular pathways involved in CRC pathogenesis. ⋯ Specifically, we observed aberrant expression of genes involved in sphingolipid biosynthesis and degradation, as well as altered levels of various sphingolipid metabolites in CRC cells. Furthermore, we identified several potential therapeutic targets, including SMPD1, GLTP, B3GALT4, and ST8SIA6, within the sphingolipid metabolism pathway that could be exploited for the development of novel CRC treatments. Overall, our findings provide novel insights into the molecular mechanisms underlying CRC and highlight the importance of targeting phospholipid metabolism, specifically sphingolipid metabolism, as a potential therapeutic strategy for CRC.
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Pancreatic ductal adenocarcinoma (PDAC) is a major global health challenge owing to late diagnosis and inherently metastatic nature. Although surgical intervention offers a potential remedy, only few patients are eligible, and drug resistance further complicates treatment. The therapeutic limitations have catalyzed a search for alternative treatments, particularly natural products. ⋯ Molecular docking analysis revealed that HMTA potentially could interact with tubulin, and in vitro assay confirmed it suppresses tubulin polymerization. HMTA significantly inhibited BxPC-3 xenograft tumor growth in mice. Overall, these findings suggested that HMTA is a promising candidate for PDAC therapy.
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Background: Myocardial injury is prone to occur during myocardial ischemia-reperfusion, which further causes adverse cardiac events. Cardiomyopeptide (CMP) has been found to protect the heart against ischemia-reperfusion injury. The present study will explore the molecular and signaling mechanisms associated with the therapeutic effects of CMP. ⋯ RNA-seq analysis results showed that PPARγ signaling pathway is a potential signaling pathway for CMP treatment of myocardial injury in rats. The experimental results showed that CMP can significantly up-regulate PPARγ expression in myocardial tissues, inhibit ischemia reperfusion-induced myocardial injury, and alleviate mitochondrial respiratory disorders. Conclusion: CMP can improve myocardial injury in rats by alleviating mitochondrial respiratory dysfunction and reducing myocardial tissue damage and inflammatory infiltration via the regulation of PPARγ signaling pathway.
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Aims: Investigate the role of the apelin/APLNR axis in metabolic dysfunction-associated steatotic liver disease (MASLD), focusing on the progression from metabolic dysfunction-associated simple steatotic liver (MASS) to metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis, with emphasis on liver B cells. Methods: Serum samples from MASLD patients and liver tissues from hepatocellular carcinoma patients were collected to measure apelin and APLNR protein expression. C57BL/6J mouse models of varying MASLD stages were developed using a high-fat diet and CCl4. ⋯ Sequencing and RT-PCR in Raji cells indicate that the apelin/APLNR axis promotes the expression of inflammatory cytokines and extracellular matrix molecules. Conclusion: The apelin/APLNR axis is crucial in MASLD progression. Targeting this axis may offer therapeutic potential to modulate B cell function and mitigate MASLD advancement.
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Introduction: Live microorganisms, named probiotics, can improve overall physical well-being, particularly the oral cavity's health. L. casei Shirota, a popular probiotic, can influence the immune response by increasing the number of macrophages and plasma cells that play a role in traumatic ulcer healing. Aims: To determine the expression of tumor necrosis factor-alpha (TNF-α) and the varied number of plasma cells and macrophages on a traumatic ulcer animal model treated with topical or systemic administration of a probiotic L. casei Shirota. ⋯ Results: The Mann-Whitney and Tukey HSD tests indicated significant differences (p < 0.05) in the results for the three groups. It was observed that topical administration provides more remarkable results than systemic administration for the expression of TNF-α, the number of plasma cells, and the number of macrophages. Conclusion: Topical administration of L. casei Shirota demonstrates better results than systemic administration for healing traumatic ulcers.