Endoplasmic reticulum (ER) stress inhibitor salubrinal protects against ceramide-induced SH-SY5Y cell death.

In the present study, we examined the mechanisms of ceramide-induced cell death in SH-SY5Y human neuroblastoma cells. Our results demonstrate a significant endoplasmic reticulum (ER) stress response in SH-SY5Y cells after short-chain ceramide (C6) treatment. Administration of ceramide (C6) to SH-SY5Y human neuroblastoma cells caused apoptotic cell death, which was inhibited by ER stress inhibitor salubrinal. Further, ceramide-induced cell death reduced significantly in stable SH-SY5Y cells expressing C/EBP homologous protein (CHOP) shRNA. Salubrinal inhibited ceramide-induced inositol-requiring enzyme 1α (IRE1α)/apoptosis signal regulating kinase 1 (ASK1)/c-Jun N-terminal kinase (JNK) phosphorylation. Taken together, these data suggest that ceramide-induced SH-SY5Y cell death may be linked to the ER stress-regulated intrinsic pathway, and proposed the potential protective effects of salubrinal.

Association Between Waist Circumference and the Prevalence of (Pre) Hypertension Among 27,894 US Adults.

Aims: This study aimed to investigate the association between waist circumference and the prevalence of (pre) hypertension. Methods: Cross-sectional data from the 2007-2018 National Health and Nutrition Examination Survey were analyzed. The historical trend of abdominal obesity was assessed by the Cochran-Armitage trend test. After preprocessed by the multiple imputation strategy, we used generalized additive models to assess the association of waist circumference with systolic/diastolic blood pressure and performed correlation analysis by the Spearman correlation coefficient. Moreover, we used multivariable logistic regression (non-adjusted, minimally adjusted, and fully adjusted models), restricted cubic spline, and sensitivity analysis to investigate the association between waist circumference and (pre) hypertension. Results: A total of 27,894 participants were included in this study. In the fully adjusted model, waist circumference was positively associated with (pre) hypertension with odds ratios (95% confidence intervals) of 1.28 (1.18-1.40) in the young group and 1.23 (1.15-1.33) in the old group. Restricted cubic spline showed a higher prevalence of (pre) hypertension with the increase of waist circumference. In the subgroup analysis, waist circumference showed a robust trend across all BMI categories with odds ratios (95% confidence intervals) of 3.33 (1.29-8.85), 1.35 (1.17-1.57), 1.27 (1.13-1.41), and 1.09 (1.01-1.17) in underweight, normal weight, overweight, and obese individuals, respectively. Conclusion: This study highlighted waist circumference as a significant biomarker to evaluate the risk of (pre) hypertension. Our results supported the measure of waist circumference regardless of BMI when evaluating the cardiometabolic risk related to fat distribution.

Cardiotoxicity in cancer immune-checkpoint therapy: Mechanisms, clinical evidence, and management strategies.

Immune-checkpoint inhibitors (ICIs), a unique antibody-based therapeutic strategy, have revolutionized the treatment landscape of solid and hematological cancers. Despite the proven benefits of ICIs, the cardiotoxicity from unspecific immune activation (uncommon but potentially fatal) is a continuing concern. Accumulating preclinical research has demonstrated that ICIs initiate inflammation in the myocardium, while clinically significant cardiotoxicity were reported in few patients receiving ICI therapy, probably due to the low incidence and unspecific symptoms. The subtle signs and symptoms (e.g., chest pain, dizziness, and dyspnea) were likely attributed to cancer and/or non-cardiac events by previous studies, thus limiting the understanding of the incidence, outcomes, risk factors, and management of ICI-related cardiotoxicity. The heterogeneous clinical presentation and complex diagnostic procedure further make it challenging to accurately identify ICI-related cardiac events in clinical trials. Therefore, ICI-related cardiotoxicity, whose incidence is probably underestimated, has not been well recognized. In this article, we provide an overview of potential mechanisms underlying ICI-related cardiotoxicity and review accumulating clinical evidence of ICI-related cardiotoxicity, with a focus on myocarditis. Moreover, we discuss possible strategies to manage ICI-related cardiotoxicity and highlight the importance of developing cardio-oncology.