Int J Med Sci
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RAC1, a member of the Rho family GTPases, has been implicated in various cancers, yet its pan-cancer landscape and role in the tumor immune microenvironment remain underexplored. This study presents a comprehensive analysis of RAC1 across 33 cancer types, revealing its high expression in a broad range of cancers and its association with poor prognosis. RAC1 expression correlates with genomic alterations, including CNVs, TMB, and MSI. ⋯ Functional enrichment analysis showed that high RAC1 expression is linked to lower enrichment in B cell activation and immune response pathways. Single-cell transcriptome analysis identified RAC1 expression primarily in epithelial cells, associated with tumor progression, and spatial transcriptome analysis showed a mutually exclusive co-localization between B cell infiltration regions and RAC1-expressing epithelial cells. Based on RAC1 expression and B cell interaction, a prognostic signature was established to predict prognosis at the pan-cancer level.
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Background: Blood pressure (BP) control can slow down the progression of chronic kidney disease (CKD) and protect against cardiovascular diseases, significantly improving patient survival. Herein, we analyzed the changes in BP control in adult CKD patients with hypertension in the United States from 1999-2000 to 2017-2018. Methods: National Health and Nutrition Examination Survey (NHANES) data from 1999-2000 to 2017-2018 were analyzed, including 5,510 adult CKD patients with BP above 140/90 mmHg or those under an antihypertensive regimen. ⋯ Although adult CKD patients with albumin-creatinine rate (ACR) 30-299 mg/g or ACR ≥300 mg/g were more likely to take antihypertensive medication than those with ACR <30 mg/g (PR: 2.76, 95% CI: 1.63-4.79 and PR: 4.59, 95% CI: 2.37-9.51), they were more likely to have uncontrolled BP than those with ACR <30 mg/g ((multivariable-adjusted prevalence ratio (PR): 2.25, 95% CI: 1.39-3.75 and PR: 3.14, 95% CI: 1.71-6.07). Adult CKD patients (eGFR ≥60 mL/min/1.73m2) being aware of their high BP diagnosis were less likely to take antihypertensive medication than those with eGFR 30-59 mL/min/1.73m2 (PR: 0.27, 95% CI: 0.09-0.65). Conclusions: These results show that BP control should be reinforced in adult CKD patients, particularly in those with ACR ≥300 mg/g, while patients with eGFR ≥60 mL/min/1.73m2 should enhance awareness of taking antihypertensive medication.
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Background: The progression and metastasis of colorectal cancer (CRC) remain major clinical challenges due to a lack of effective therapeutic targets. Our preliminary study identified the upregulation of the propionyl-CoA carboxylase alpha chain (PCCA) gene in CRC, prompting further investigation into its functional roles. Methods: Bioinformatics analysis, colorectal tumor tissues, and CRC cell lines were used to determine PCCA expression. ⋯ Moreover, PCCA knockdown suppressed CRC tumor growth and lung metastasis, accompanied by an increase in M1-macrophage polarization. Conclusion: Knockdown PCCA inhibits the progression and metastasis of CRC, which is associated with EMT reversion, ERK/GSK3β signaling inactivation, and M1-macrophage polarization. These findings suggest that PCCA is a potential target for controlling CRC.
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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.
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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.