Cross-talk between disulfidptosis and immune check point genes defines the tumor microenvironment for the prediction of prognosis and immunotherapies in glioblastoma.

Disulfidptosis is a condition where dysregulated NAPDH levels and abnormal accumulation of cystine and other disulfides occur in cells with high SLC7A11 expression under glucose deficiency. This disrupts normal formation of disulfide bonds among cytoskeletal proteins, leading to histone skeleton collapse and triggering cellular apoptosis. However, the correlation between disulfidptosis and immune responses in relation to glioblastoma survival rates and immunotherapy sensitivity remains understudied. Therefore, we utilized The Cancer Genome Atlas and The Chinese Glioma Genome Atlas to identify disulfidptosis-related immune checkpoint genes and established an overall survival (OS) prediction model comprising six genes: CD276, TNFRSF 14, TNFSF14, TNFSF4, CD40, and TNFRSF18, which could also be used for predicting immunotherapy sensitivity. We identified a cohort of glioblastoma patients classified as high-risk, which exhibited an upregulation of angiogenesis, extracellular matrix remodeling, and epithelial-mesenchymal transition as well as an immunosuppressive tumor microenvironment (TME) enriched with tumor associated macrophages, tumor associated neutrophils, CD8 + T-cell exhaustion. Immunohistochemical staining of CD276 in 144 cases further validated its negative correlation with OS in glioma. Disulfidptosis has the potential to induce chronic inflammation and an immunosuppressive TME in glioblastoma.

PYCR2, induced by c-Myc, promotes the invasiveness and metastasis of breast cancer by activating AKT signalling pathway.

BACKGROUND: Pyrroline-5-carboxylate reductase 2 (PYCR2) expression is aberrantly upregulated in colon cancer. However, the functions and underlying mechanisms of PYCR2 in breast cancer remain elusive. The primary objective of the present study was to elucidate the function of PYCR2 in breast cancer and investigate whether PYCR2 may be transcriptionally regulated by c-Myc to activate the AKT signaling pathway. METHODS: Immunohistochemical analysis was performed to examine the expression of PYCR2 in breast cancer and adjacent non-cancerous tissues. Western blot and RT-qPCR were utilized to detect PYCR2 expression in breast cancer cells. Cellular functionalities were evaluated through Transwell assays in vitro and lung metastasis formation assays in vivo. Moreover, the impact of PYCR2 on the activation of AKT signaling was determined through western blot and immunohistochemistry analysis. The transcriptional regulation of PYCR2 expression by c-Myc was evaluated via both western blot analysis and luciferase gene reporter assay. RESULTS: PYCR2 overexpression was noted in breast cancer. Silencing PYCR2 expression attenuated the invasive and metastatic abilities of breast cancer cells. Furthermore, the activation of the AKT signaling pathway is indispensable for the promotion of invasion and metastasis mediated by PYCR2. Lastly, the binding of c-Myc to the promoter sequence of PYCR2 resulted in the upregulation of PYCR2 transcription. CONCLUSION: Taken together, these results indicate that PYCR2 is transcriptionally regulated by c-Myc and promotes invasion and metastasis in breast cancer through the activation of the AKT pathway.

Inverse association between isoflavones and prediabetes risk: evidence from NHANES 2007-2010 and 2017-2018.

Introduction: Prediabetes is a metabolic condition characterized by blood glucose levels that are higher than normal but do not meet the threshold for a diabetes diagnosis. Individuals with prediabetes are at an increased risk of developing type 2 diabetes and associated complications. However, limited epidemiological studies have investigated the association between flavonoids from plant-based diets and the risk of prediabetes, and the existing evidence from these studies is inconsistent. Methods: Therefore, we utilized data from 19,021 participants (mean age: 32.03 years) in the National Health and Nutrition Examination Survey (NHANES) conducted during 2007-2010 and 2017-2018 to investigate the potential association between dietary flavonoid intake and prediabetes risk by weighted logistic regression analysis. Furthermore, the data from 3,706 participants (mean age: 35.98 years) from NHANES 2007-2010 were used to assess the correlation between concentrations of isoflavones and their metabolites in urine and prediabetes risk by weighted logistic regression analysis. Results: Our findings revealed an inverse association between the intake of glycitein (OR: 0.88; 95% CI: 0.82-0.96; p = 0.003), genistein (OR: 0.98; 95% CI: 0.97-0.99; p = 0.004), daidzein (OR: 0.98; 95% CI: 0.96-0.99; p = 0.009), and total isoflavones (OR: 0.99; 95% CI: 0.98-1.00; p = 0.005) with the risk of prediabetes. Moreover, we observed an inverse association between the concentration of daidzein in urine (OR: 0.84; 95% CI: 0.73-0.96; p = 0.012) and the concentration of genistein in urine (OR:0.83; 95% CI: 0.75-0.93; p = 0.003) with the risk of prediabetes using weighted logistic regression. Conclusion: In conclusion, our findings suggest a potential protective effect of isoflavones against the development of prediabetes.

The associations between dietary flavonoid intake and the prevalence of diabetes mellitus: Data from the National Health and Nutrition Examination Survey 2007-2010 and 2017-2018.

Background: Diabetes mellitus (DM) is a prominent health concern worldwide, leading to the high incidence of disability and mortality and bringing in heavy healthcare and social burden. Plant-based diets are reported associated with a reduction of DM risk. Plant-based diets are rich in flavonoids, which possess properties such as scavenging free radicals and exerting both anti-inflammatory and antioxidant effects. Purpose: However, whether dietary flavonoids are associated with the prevalence of DM remains controversial. The potential reasons for contradictory epidemiological outcomes on the association between dietary flavonoids and DM prevalence have not been determined. Methods: To address these limitations, we employed data from 22,481 participants in the National Health and Nutrition Examination Survey to explore the association between the intake of flavonoids and DM prevalence by weighted Logistic regression and weighted restricted cubic splines. Results: We found that the prevalence of DM was inversely associated with the intake of total flavonoids in the second quartile [Odds Ratio (OR) 0.78 95% confidence interval (CI) (0.63, 0.97), p = 0.028], in the third quartile [0.76 (0.60, 0.97), p = 0.031], and in the fourth quartile [0.80 (0.65, 0.97), p = 0.027]. However, the p for trend was not significant [0.94 (0.88, 1.01), p = 0.096]. Moreover, the association between DM prevalence and the intake of total flavonoids was significantly influenced by race (p for interaction = 0.006). In Mexican Americans, there was a significant positive association between DM prevalence and total flavonoid intake within the third quartile [1.04 (1.02, 1.07), p = 0.003]. Total flavan-3-ol and subtotal catechin intake exhibited a non-linear U-shaped association with DM prevalence (p for non-linearity < 0.0001 and p for non-linearity < 0.0001, respectively). Compared to the first quartile of corresponding intakes, consumption within the third quartile of subtotal catechins [0.70 (0.55, 0.89), p = 0.005] and total flavan-3-ols [0.65 (0.50, 0.84), p = 0.002] was associated with a lower prevalence of DM. Conclusion: Taken together, our study may provide preliminary research evidence for personalized improvement of dietary habits to reduce the prevalence of diabetes.