RESUMEN
Surgical resection followed by radiotherapy (RT) is recommended for malignant meningioma but poor outcome is unavoidable. To improve the efficacy of RT in malignant meningioma, a targeted radiosensitizer could be added. Nicotinamide phosphoribosyltransferase (NAMPT), highly expressed in high-grade meningiomas may have a role in determining the radioresponse. Here, we evaluated the impact of NAMPT inhibition on radiosensitivity in malignant meningioma in vivo and in vitro. IOMM-Lee and TTMM705 cells were treated with NAMPT inhibition (FK866 or shRNA NAMPT) before irradiation. The subsequent clonogenic assay demonstrated significantly increased radiosensitivity. Combination treatment with FK866 and irradiation significantly increased the number of G2/M-phase cells, the percentage of apoptotic cells and the γ-H2A.X level compared to FK866 or RT alone. We examined the effect of NAMPT inhibition on NMI and p53 expression in IOMM-Lee and TTMM705 cells. NAMPT inhibition by FK866 and shRNA treatment increased NMI, p53, CDKN1A and BAX expression. Additionally, we assessed the efficacy of FK866/RT combination treatment in vivo. The combination treatment exhibited increased antitumor efficacy compared to either treatment alone. The Ki-67 level was significantly lower and the p53 and γ-H2A.X level was significantly higher in the combination treatment group than in any of the other three groups. In conclusion, these results indicate that FK866 improves radiosensitivity in malignant meningioma, an effect that may be attributed to the increase in p53 expression.
RESUMEN
BACKGROUND: The KCa3.1 channel (KCNN4) is extensively investigated as an oncogene in human cancers. The current study aimed to explore the clinicopathological significance of KCNN4 expression in patients with primary adult-type diffuse gliomas. METHODS: Demographic, RNA-seq, and follow-up data of 477 patients were retrospectively reviewed. Patients were divided into the experimental and validation groups (278 and 199). KCNN4-related genes were determined by Pearson correlation analysis, and enrichment analyses and tumor-infiltrating immune cell assessments were applied to explore the potential mechanisms of KCNN4 involving glioma progression. The Kaplan-Meier method and the Cox regression analysis were used to evaluate the prognostic value of KCNN4 expression. RESULTS: KCNN4 showed significantly higher expression level in glioblastoma, IDH-wildtype, followed by astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant and 1p/19q-codeleted (p < 0.001). Enrichment analyses and tumor-infiltrating immune cell assessments suggested that KCNN4 could involve glioma progression through extracellular regulation, affecting immune response, and modulating subcellular trafficking. At last, the Kaplan-Meier analysis showed that high KCNN4 expression was significantly correlated with poor progression-free and overall survival (p < 0.001 for both). While multivariate Cox regression analysis obtained an insignificant result. CONCLUSIONS: KCNN4 was identified to be overexpressed in glioma cells and its expression level is positively related to tumor malignancy. It potentially participates in glioma biology by affecting extracellular regulation, subcellular trafficking, and immune escape. Additionally, high KCNN4 expression was correlated with poor survival outcomes of patients. The results can shed new light on the mechanisms of glioma progression, and provide a potential therapeutic target for treating gliomas.
RESUMEN
BACKGROUND: According to previous studies of male infertility, we found that the association between sexual dysfunction and male infertility was reported rarely and controversially. AIM: We carried out this 1meta-analysis to evaluate the prevalence of sexual dysfunction and the International Index of Erectile Function (IIEF) score in infertile men. METHODS: A systematic search of the target literature was conducted using PubMed, EMBASE, and Cochrane Library. Data were analyzed using Review Manager 5.4 software. Standardized mean differences (SMD) with the corresponding 95% confidence intervals (95% CIs) were implemented in 6 controlled studies as a measure of effect size to assess the relationship between sexual dysfunction and male infertility and Odds Ratio (OR) were performed for the morbidity between infertility group and fertility group. OUTCOMES: Men in infertile group were found with higher prevalence of sexual dysfunction and lower IIEF values than in controls. RESULTS: A meta-analysis of morbidity was performed in 8 of 10 controlled studies. Meta-analysis of the 8 studies found remarkable higher prevalence of sexual dysfunction in men with infertility than in controls (OR = 2.66, 95% confidence interval = 1.69-4.19, P < .0001; I² = 67%, P for heterogeneity = 0.004). Another meta-analysis of evidence suggested that IIEF in infertile men was lower than controls (SMD = -0.47, 95% confidence interval = -0.63 to -0.31, P < .00001; I² = 64%, p for heterogeneity = 0.02). CLINICAL IMPLICATIONS: We recommend further research based on the relevant criteria of region, sample size, rigorous statistical analysis, and research design. STRENGTHS & LIMITATIONS: This systematic review is the first to evaluate the prevalence of sexual dysfunction and the score of sexual dysfunction in male infertility. Investigation on the topic is scarce, and only few studies used appropriate measures. CONCLUSIONS: Male infertility was associated with an increase in the prevalence of sexual dysfunction. The areas most affected by sexual function were erectile function, orgasm and sexual desire. Liu Y, Wang Y, Dong C, et al. Sexual Dysfunction in Infertile Men: A Systematic Review and Meta-Analysis. Sex Med 2022;10:100528.
RESUMEN
The Wnt and Notch signalling pathways are important for maintenance of intestinal epithelial barrier integrity by intestinal stem cells (ISCs). Dysfunction of these pathways is implicated in inflammatory bowel disease (IBD) and colon cancer. The objective of this review is to summarise advancements of drugs that regulate Wnt and Notch in the treatment of IBD and colon cancer. The compositions and biological effects of Wnt and Notch modulators in both ISCs and non-ISCs are discussed. The drugs, including phytochemicals, plant extracts, probiotics and synthetic compounds, have been found to regulate Wnt and Notch signalling pathways by targeting regulatory factors (including secreted frizzled-related proteins or pathway proteins such as ß-catenin and γ-secretase) to alleviate IBD and colon cancer. This review highlights the potential for targeting Wnt and Notch pathways to treat IBD and colon cancer.
