Association of TyG index with prehypertension or hypertension: a retrospective study in Japanese normoglycemia subjects

AimThe objective of our study was to investigate the potential association between the triglyceride and glucose (TyG) index and the occurrence of prehypertension or hypertension in a cohort of normoglycemic Japanese subjects.MethodsThe NAGALA physical examination program was conducted in 1994 at Murakami Memorial Hospital in Gifu City, Japan. For our retrospective study, we selected 15,450 participants who had taken part in this program. Our aim was to explore the potential link between the TyG index, a surrogate marker for insulin resistance, and the presence of prehypertension (pre-HTN) or hypertension (HTN). Our analysis included adjustments for clinical demographic attributes and serum biomarkers. Logistic regression was employed to assess the relationship between the TyG index and the likelihood of pre-HTN or HTN.ResultsA total of 15,450 study subjects were included in our analysis. Notably, the prevalence of both pre-HTN and HTN displayed an ascending trend with increasing quartiles of the TyG index. In our comprehensive multivariable logistic regression analysis, when evaluating TyG as a continuous variable, the adjusted odds ratio (OR) for pre-HTN was OR 1.31 [95% CI 1.11-1.56], while for HTN, it was OR 1.76 [95% CI 1.24-2.5] within the fully adjusted model (model 3). When TyG was stratified into quartiles within model 3, the adjusted ORs for pre-HTN were OR 1.16 [95% CI 1.02-1.31], OR 1.22 [95% CI 1.06-1.41], and OR 1.31 [95% CI 1.08-1.59], respectively, using quartile 1 as the reference. The adjusted ORs for HTN in quartiles 2, 3, and 4 were OR 1.22 [95% CI 0.89-1.66], OR 1.4 [95% CI 1.02-1.91], and OR 1.48 [95% CI 1.02-2.15], respectively, within the same model and analysis, with quartile 1 as the reference. Subgroup analysis indicated that the TyG index exhibited a significant positive correlation with the risk of hypertension or prehypertension, except in the subgroup aged ≥65 years.ConclusionOur study highlights a robust correlation between the TyG index and the likelihood of pre-HTN or HTN in normoglycemic Japanese subjects. This underscores the potential clinical relevance of the TyG index in refining early hypertension management strategies. Nonetheless, the validation of these findings necessitates larger studies with extended follow-up periods

Luteolin Induces Apoptosis and Autophagy in Mouse Macrophage ANA-1 Cells via the Bcl-2 Pathway

Plants rich in luteolin have been used as Chinese traditional medicines for inflammatory diseases, hypertension, and cancer. However, little is known about the effect of luteolin on the apoptosis or autophagy of the macrophages. In this study, mouse macrophage ANA-1 cells were incubated with different concentrations of luteolin. The viability of the cells was determined by an MTT assay, apoptosis was determined by flow cytometric analysis, the level of cell autophagy was observed by confocal microscopy, and the expression levels of apoptotic or autophagic and antiapoptotic or antiautophagic proteins were detected by Western blot analysis. The results showed that luteolin decreased the viability of ANA-1 cells and induced apoptosis and autophagy. Luteolin induced apoptosis accompanied by downregulation of the expression of Bcl-2 and upregulation of the expression of caspase 3 and caspase 8. And luteolin increased FITC-LC3 punctate fluorescence accompanied by the increased expression levels of LC3-I, ATG7, and ATG12, while it suppressed the expression level of Beclin-1. Luteolin treatment resulted in obvious activation of the p38, JNK, and Akt signaling pathways, which is important in modulating apoptosis and autophagy. Thus, we concluded that luteolin induced the apoptosis and autophagy of ANA-1 cells most likely by regulating the p38, JNK, and Akt pathways, inhibiting the activity of Bcl-2 and Beclin-1 and upregulating caspase 3 and caspase 8 expression. These results provide novel insights into a therapeutic strategy to prevent and possibly treat macrophage-related diseases through luteolin-induced apoptosis and autophagy

Image_1_Association between red blood cell distribution width to albumin ratio and prognosis of patients with sepsis: A retrospective cohort study.JPEG

BackgroundRed blood cell distribution width (RDW) to albumin ratio (RAR) is associated with poor prognosis in diabetic comorbidities and cancer. However, the association between RAR and prognosis in patients with sepsis remains unclear, which was investigated in this study.MethodsWe conducted a retrospective cohort study based on the Medical Information Mart for Intensive Care (MIMIC) IV version 2.0 database. The primary outcome of this study was 28-day mortality. Secondary outcomes included 90-day mortality, in-hospital mortality, length of hospital stay, and length of intensive care unit (ICU) stay. Multivariate regression analysis and subgroup analysis were performed to investigate the association between RAR and prognosis in patients with sepsis.ResultsA total of 14,639 participants were included in this study. The mean age of the participants was 65.2 ± 16.3 years and the mean RAR was 5.5 ± 1.9 % /g/dl. For 28-day mortality, after adjusting for covariates, HRs [95% confidence intervals (CIs)] for tertiles 2 (4.4–5.8) and 3 (RAR > 5.8) were 1.33 (1.20, 1.46) and 1.98 (1.79, 2.19), respectively. Similar results were observed for 90-day mortality and in-hospital mortality. According to Kaplan-Meier curve analysis, the higher RAR group had higher 28-day mortality and 90-day mortality.ConclusionOur study shows that RAR is significantly associated with poor clinical prognosis in sepsis. The higher the RAR, the higher the 28-day, 90-day, and in-hospital mortality.</p

Image_3_Association between red blood cell distribution width to albumin ratio and prognosis of patients with sepsis: A retrospective cohort study.JPEG

BackgroundRed blood cell distribution width (RDW) to albumin ratio (RAR) is associated with poor prognosis in diabetic comorbidities and cancer. However, the association between RAR and prognosis in patients with sepsis remains unclear, which was investigated in this study.MethodsWe conducted a retrospective cohort study based on the Medical Information Mart for Intensive Care (MIMIC) IV version 2.0 database. The primary outcome of this study was 28-day mortality. Secondary outcomes included 90-day mortality, in-hospital mortality, length of hospital stay, and length of intensive care unit (ICU) stay. Multivariate regression analysis and subgroup analysis were performed to investigate the association between RAR and prognosis in patients with sepsis.ResultsA total of 14,639 participants were included in this study. The mean age of the participants was 65.2 ± 16.3 years and the mean RAR was 5.5 ± 1.9 % /g/dl. For 28-day mortality, after adjusting for covariates, HRs [95% confidence intervals (CIs)] for tertiles 2 (4.4–5.8) and 3 (RAR > 5.8) were 1.33 (1.20, 1.46) and 1.98 (1.79, 2.19), respectively. Similar results were observed for 90-day mortality and in-hospital mortality. According to Kaplan-Meier curve analysis, the higher RAR group had higher 28-day mortality and 90-day mortality.ConclusionOur study shows that RAR is significantly associated with poor clinical prognosis in sepsis. The higher the RAR, the higher the 28-day, 90-day, and in-hospital mortality.</p

Image_2_Association between red blood cell distribution width to albumin ratio and prognosis of patients with sepsis: A retrospective cohort study.JPEG

BackgroundRed blood cell distribution width (RDW) to albumin ratio (RAR) is associated with poor prognosis in diabetic comorbidities and cancer. However, the association between RAR and prognosis in patients with sepsis remains unclear, which was investigated in this study.MethodsWe conducted a retrospective cohort study based on the Medical Information Mart for Intensive Care (MIMIC) IV version 2.0 database. The primary outcome of this study was 28-day mortality. Secondary outcomes included 90-day mortality, in-hospital mortality, length of hospital stay, and length of intensive care unit (ICU) stay. Multivariate regression analysis and subgroup analysis were performed to investigate the association between RAR and prognosis in patients with sepsis.ResultsA total of 14,639 participants were included in this study. The mean age of the participants was 65.2 ± 16.3 years and the mean RAR was 5.5 ± 1.9 % /g/dl. For 28-day mortality, after adjusting for covariates, HRs [95% confidence intervals (CIs)] for tertiles 2 (4.4–5.8) and 3 (RAR > 5.8) were 1.33 (1.20, 1.46) and 1.98 (1.79, 2.19), respectively. Similar results were observed for 90-day mortality and in-hospital mortality. According to Kaplan-Meier curve analysis, the higher RAR group had higher 28-day mortality and 90-day mortality.ConclusionOur study shows that RAR is significantly associated with poor clinical prognosis in sepsis. The higher the RAR, the higher the 28-day, 90-day, and in-hospital mortality.</p

Data_Sheet_1_Association between red blood cell distribution width to albumin ratio and prognosis of patients with sepsis: A retrospective cohort study.docx

BackgroundRed blood cell distribution width (RDW) to albumin ratio (RAR) is associated with poor prognosis in diabetic comorbidities and cancer. However, the association between RAR and prognosis in patients with sepsis remains unclear, which was investigated in this study.MethodsWe conducted a retrospective cohort study based on the Medical Information Mart for Intensive Care (MIMIC) IV version 2.0 database. The primary outcome of this study was 28-day mortality. Secondary outcomes included 90-day mortality, in-hospital mortality, length of hospital stay, and length of intensive care unit (ICU) stay. Multivariate regression analysis and subgroup analysis were performed to investigate the association between RAR and prognosis in patients with sepsis.ResultsA total of 14,639 participants were included in this study. The mean age of the participants was 65.2 ± 16.3 years and the mean RAR was 5.5 ± 1.9 % /g/dl. For 28-day mortality, after adjusting for covariates, HRs [95% confidence intervals (CIs)] for tertiles 2 (4.4–5.8) and 3 (RAR > 5.8) were 1.33 (1.20, 1.46) and 1.98 (1.79, 2.19), respectively. Similar results were observed for 90-day mortality and in-hospital mortality. According to Kaplan-Meier curve analysis, the higher RAR group had higher 28-day mortality and 90-day mortality.ConclusionOur study shows that RAR is significantly associated with poor clinical prognosis in sepsis. The higher the RAR, the higher the 28-day, 90-day, and in-hospital mortality.</p

Celastrol suppresses human pancreatic cancer via m6A-YTHDF3-mediated downregulation of Claspin and Bcl-2

Abstract Background Celastrol has been revealed to exhibit anticancer pharmacological activity, however, the molecular mechanisms of celastrol involved in pancreatic cancer remain to be further elucidated. The present study was to illustrate whether celastrol suppresses pancreatic cancer through modulating RNA m6A modification. Methods Effect of celastrol treatment on the malignant phenotypes of pancreatic cancer cells was evaluated by CCK-8 assay, EdU assay, colony formation assay, flow cytometry analysis and subcutaneous xenograft experiments. RNA sequencing (RNA-seq) analysis was carried out to analyze the genes differentially expressed in celastrol-treated pancreatic cancer cells. RT-qPCR, Western blotting and immunohistochemistry were employed to evaluate the expression of the indicated genes. RNA dot blot and quantification of total RNA m6A modification assays, MeRIP-qPCR assay, RIP-qPCR assay, RNA stability and protein stability assays were applied to evaluate the regulatory mechanism of celastrol treatment in pancreatic cancer cells. Results We demonstrated that celastrol suppressed cell proliferation and induced cell cycle arrest and apoptosis of pancreatic cancer cells in vitro, and decreased tumor growth in vivo. Specifically, Bcl-2, Claspin, METTL3 and YTHDF3 were identified as the potential targets of celastrol treatment in pancreatic cancer cells. Moreover, our results indicated that celastrol treatment downregulated METTL3 and decreased m6A levels of Claspin and Bcl-2 mRNA, leading to the degradation of Claspin and Bcl-2 mRNA in pancreatic cancer cells. Furthermore, we revealed that celastrol treatment downregulated Claspin and Bcl-2, at least in part, in an m6A-YTHDF3-mediated manner in pancreatic cancer cells. Conclusion Our study highlighted a novel mechanism underlying celastrol-induced cellular proliferation inhibition and apoptosis in pancreatic cancer cells via m6A-YTHDF3-mediated downregulation of Claspin and Bcl-2