Int J Med Sci
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Purpose: Mounting evidence indicates that psychological stress adversely affects cancer progression including tumor growth and metastasis. The aim of this study was to investigate the role of chronic stress-induced microbiome perturbation in colorectal cancer (CRC) progression. Methods: Chronic restraint stress (CRS) was used to establish the chronic stress mouse model, behavioral tests were used for the CRS model evaluation. ⋯ Furthermore, the LC-MS data indicated that with only 2 exceptions of carpaine and DG (15:0/20:4(5Z,8Z,11Z,14Z)/0:0), the majority of these 24 metabolites were less abundant in CRS-exposed mice. Bioinformatics analysis and correlation analyses indicated that only Ruminoscoccaceae-UCG-014 was significantly associated with inflammation (IL-6), neurotransmission (5-HT), and microbial metabolism (PS). Conclusion: CRS exposure altered diversity, composition and metabolites of the gut microbiome, with Ruminococcaceae_UCG-014 perturbation consistently correlated to inflammatory responses, suggesting a particular role of this bacterial genus in CRC growth and metastasis.
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This study aims to elucidate the roles of Phosphoglycerate Mutase Family Member 5 (Pgam5) and Prohibitin 2 (Phb2) in the context of hyperglycemia-induced myocardial dysfunction, a critical aspect of diabetic cardiomyopathy. The research employed primary cardiomyocytes, which were then subjected to hyperglycemia treatment to mimic diabetic conditions. We used siRNA transfection to knock down Pgam5 and overexpressed Phb2 using adenovirus transfection to assess their individual and combined effects on cardiomyocyte health. ⋯ The study elucidates the critical roles of Pgam5 and Phb2 in regulating mitochondrial dynamics in the setting of hyperglycemia-induced myocardial dysfunction. By modulating mitochondrial fission and mitophagy, Pgam5 and Phb2 emerge as key players in preserving mitochondrial integrity and cardiomyocyte health under diabetic conditions. These findings contribute significantly to our understanding of the molecular mechanisms underlying diabetic cardiomyopathy and suggest potential therapeutic targets for mitigating myocardial dysfunction in diabetes.
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The T cell immunoglobulin and ITAM domain (TIGIT) is a recently discovered synergistic co-suppressor molecule that plays an important role in immune response and tumor immune escape in the context of cancer. Importantly, CD155 acts as a receptor for TIGIT, and CD155 signaling to immune cells is mediated through interactions with the co-stimulatory immune receptor CD226 (DNAM-1) and the inhibitory checkpoint receptors TIGIT and CD96. Aspirin (ASA) has been shown to reduce the growth and survival of colorectal cancer (CRC) cells, but the immunological mechanisms involved have not been sufficiently elucidated. ⋯ TIGIT is expressed at higher levels on infiltrating lymphocytes within CRC tumor tissue than adjacent. Further, aspirin could inhibit Jurkat cell proliferation and induce apoptosis via downregulation of TIGIT expression and the anti-apoptosis B cell lymphoma 2 (BCL2) protein and upregulation of BCL2-associated X protein (BAX) expression. The present study suggests that aspirin can inhibit specific aspects of T cell function by reducing interleukin-10 and transforming growth factor-β1 secretion via the TIGIT-BCL2-BAX signaling pathway, resulting in improved effector T cell function that inhibits tumor progression.
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Arbutin, predominantly derived from the bearberry plant, exhibits promising immunomodulatory properties. Given its ability to influence the programmed cell death-ligand 1/ programmed cell death-1 (PD-L1/PD-1) pathway, it is emerging as a potential alternative treatment for cancer. A reduced expression of PD-L1, as seen after arbutin treatment, can bolster immune responses critical step in effective tumor immunotherapy. ⋯ Arbutin can downregulate the expression of PD-L1 on the cell surface via the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. The findings suggest the protective role of arbutin and provide novel insights into immunotherapy, which involves inhibiting the AKT/mTOR signaling pathway. Arbutin might serve as a potential therapeutic agent alone or in combination with other treatments.
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Cardiac hypertrophy is the most prevalent compensatory heart disease that ultimately leads to spontaneous heart failure. Mounting evidence suggests that microRNAs (miRs) and endogenous hydrogen sulfide (H2S) play a crucial role in the regulation of cardiac hypertrophy. In this study, we aimed to investigate whether inhibition of miR-27a could protect against cardiac hypertrophy by modulating H2S signaling. ⋯ Interestingly, our findings demonstrated that glucagon-like peptide-1 (GLP-1) agonists could mitigate myocardial damage by down-regulating miR-27a and up-regulating CSE. In summary, our study suggests that inhibition of miR-27a holds therapeutic promise for the treatment of cardiac hypertrophy by increasing H2S levels. Furthermore, our findings unveil a novel mechanism of GLP-1 agonists involving the miR-27a/H2S pathway in the management of cardiac hypertrophy.