Int J Med Sci
-
Background: Evidence increasingly indicates that HPV infection plays a pivotal role in the initiation and progression of bladder cancer (BC). Yet, determining the predictive value of HPV-associated genes in BC remains challenging. Methods: We identified differentially expressed HPV-associated genes of BC patients from the TCGA and GEO databases. ⋯ Risk scores were correlated with tumor microenvironment (TME) scores, immune cell infiltration, and sensitivities to both chemotherapy and immunotherapy. Conclusion: We have formulated a risk-assessment model pinpointing 13 central HPV-associated genes in BC. These genes present potential as prognostic indicators and therapeutic targets, emphasizing the intertwined relationship between HPV-induced BC progression and the immune landscape.
-
While the gluten-free diet (GFD) is primarily used to treat celiac disease (CD), recent research suggests it may also offer benefits for autoimmune-related diseases (ARDs), though findings remain inconsistent. This study aimed to investigate the potential protective effect of a GFD against ARDs by Mendelian Randomization (MR) analysis. ⋯ These findings suggest that GFD may help reduce RA risk by modulating specific immune cell populations. However, further research is necessary to clarify the exact mechanisms underlying these associations.
-
Background: Doublecortin-like kinase 1 (DCLK1) has been revealed to be involved in modulating cancer stemness and tumor progression, but its role in prostate cancer (PCa) remains obscure. Castration-resistant and metastatic PCa exhibit aggressive behaviors, and current therapeutic approaches have shown limited beneficial effects on the overall survival rate of patients with advanced PCa. This study aimed to investigate the biological role and potential molecular mechanism of DCLK1 in the progression of PCa. ⋯ Consistent with the in vitro findings, the in vivo findings confirmed that DCLK1 promoted the tumorigenicity and stem cell-like traits of PCa cells via Hippo-YAP signaling. Conclusion: DCLK1 promotes stem cell-like characteristics by inducing LATS1-mediated YAP signaling activation, ultimately leading to PCa tumor growth and progression. Thus, our findings identify an attractive candidate for the development of cancer stem cell-targeted therapies to improve treatment outcomes in advanced PCa.
-
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.
-
Receptor-interacting protein 3 (Ripk3) plays a crucial part in acute lung injury (ALI) by regulating inflammation-induced endothelial damage in the lung tissue. The precise mechanisms through which Ripk3 contributes to the endothelial injury in ALI still remain uncertain. In the current research, we employed Ripk3-deficient (Ripk3-/-) mice to examine the role of Ripk3 in ALI progression, focusing on its effects on endothelial cells (ECs), mitochondrial damage and necroptosis. ⋯ Ripk3 upregulation suppressed the AMP-activated protein kinase (AMPK) pathway and activated Drp1-mediated mitochondrial fission, increasing mitochondrial permeability transition pore (mPTP) opening and PMVEC necroptosis. Conversely, Ripk3 deletion activated the AMPK/Drp1-mitochondrial fission pathway, preventing mPTP opening and PMVEC necroptosis in ALI. These findings demonstrated that Ripk3 promotes necroptosis through the AMPK/Drp1/mPTP opening pathway, identifying a potential therapeutic target for ALI treatment.