Int J Med Sci
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Background: Solute Carrier Family 3 Member 2 (SLC3A2) is a member of the solute carrier family that plays pivotal roles in regulation of intracellular calcium levels and transports L-type amino acids. However, there are insufficient scientific researches on the prognostic and immunological roles of SLC3A2 in breast cancer (BC) and whether everolimus regulates novel SLC3A2 related molecular mechanism in the immuno-oncology context of the tumor microenvironment (TME), therefore, we see a necessity to conduct the current in silico and biological experimental study. Methods: Using diverse online databases, we investigated the role of SLC3A2 in therapy response, clinicopathological characteristics, tumor immune infiltration, genetic alteration, methylation and single cell sequencing in BC. ⋯ Finally, SLC3A2 was illustrated to be expressed in diverse BC cellular populations at single cell level, and negatively linked to angiogenesis, inflammation and quiescence, but positively correlated with other functional phenotypes. Noteworthily, everolimus (a targeted therapy drug for BC) related protein, FK506-binding protein 1A (FKBP1A) was found to bind with SLC3A2, and negatively regulated SLC3A2 expression during the processes of everolimus inducing ferroptosis of BC cells and promoting anti-proliferation of Th9 lymphocytes. Conclusions: Altogether, our study strongly implies that SLC3A2 is an immuno-oncogenic factor and FKBP1A/SLC3A2 axis would provide insights for a novel immunotherapy approach for the treatment of BC in the context of TME.
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The development and formation of mammalian blood vessels are closely related to the regulation of signal transduction pathways. Klotho/AMPK and YAP/TAZ signaling pathways are closely related to angiogenesis, but the internal relationship between them is not clear. In this study, we found that Klotho heterozygous deletion mice (Klotho+/- mice) had obvious thickening of the renal vascular wall, obvious enlargement of vascular volume, and significant proliferation and pricking of vascular endothelial cells. ⋯ Subsequently, continuous overexpression of exogenous Klotho protein in Klotho heterozygous deficient mice effectively reversed the abnormal renal vascular structure by weakening the expression of the YAP signal transduction pathway. Therefore, we confirmed that Klotho and AMPKα proteins were highly expressed in vascular endothelial cells of adult mouse tissues and organs; this resulted in a phosphorylation modification of YAP protein, closed the activity of the YAP/TAZ signal transduction pathway, and inhibited the growth and proliferation of vascular endothelial cells. When Klotho was absent, the phosphorylation modification of YAP protein by AMPKα was inhibited, resulting in the activation of the YAP/TAZ signal transduction pathway and finally inducing the excessive proliferation of vascular endothelial cells.
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As colorectal cancer (CRC) usually presents at an advanced stage, it responds poorly to traditional surgery and chemoradiotherapy. Reactive oxygen species (ROSs) are a critical factor in cancer progression. Quercetin, a bioflavonoid derived from onion peel extract, provides great anti-oxidant and anti-cancer potential. ⋯ The results reveal that the combination was most effective in decreasing cellular oxidants and increasing glutathione levels, while there was a significant decrease in cancer cell migration and invasion involved in the suppression of iNOS, ICAM-1, and MMP-2 proteins. Furthermore, bioinformatic analysis verified that iNOS, ICAM-1, and MMP-2 were highly expressed in CRC tissue and also associated with a poor prognosis. This study demonstrated that Quercetin has higher efficacy when used in combination with NAC, representing a potential combination agent for anti-cancer drug development.
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The anatomical positions of pelvic floor organs are maintained by ligaments and muscles. Stress urinary incontinence (SUI) occurs when the pelvic floor tissues are repeatedly stimulated by excessive mechanical tension that exceeds the bearing capacity of ligaments or muscles. Besides, cells respond mechanically to mechanical stimulation by reconstituting the Piezo1 and cytoskeletal system. ⋯ Based on these findings, Piezo1 connects the actin cytoskeleton to the apoptosis of hAVWFs cells, providing an idea for the clinical diagnosis and treatment of SUI. However, the disassembly of the actin cytoskeleton suppressed the protective effect of Piezo1 silencing on MS. Based on these findings, Piezo1 connects the actin cytoskeleton to apoptosis of hAVWFs, providing new insight for the clinical diagnosis and treatment of SUI.
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The coronavirus disease 2019 (COVID-19) has caused over six million deaths worldwide since its emergence in Wuhan China, factors associated with COVID-19 mortality, such as comorbidities, age, and observed symptomatology still remain a major subject of study. In the present work, a total of 16,345 SARS-CoV-2 positive cases from Durango Mexico diagnosed from May 2020 to December 2021 were analyzed to establish an association of COVID-19 mortality with clinical and demographic variables in a case-control study. Selected variables include patient age, smoking status, sex, presence of comorbidities such as hypertension, diabetes and obesity, as well as patient symptomatology such as fever, dyspnea, abdominal pain and diarrhea. ⋯ On the other hand, the symptom associated with the highest risk factor was dyspnea with an odds ratio of 18.369 (IC 95%, 14.42-23.39). Our data suggests an association between hypertension and old age with COVID-19 mortality. Other findings include the prevalence of dyspnea, polypnea and cyanosis as a major predictor for COVID-19 mortality, as well as lower mortality risks among health workers.