Background. Diabetes mellitus (DM) can induce cardiomyocyte injury and lead to diabetic cardiomyopathy (DCM) which presently has no specific treatments and consequently increase risk of mortality. Objective. To characterize the therapeutic effect of 6‐gingerol (6‐G) on DCM and identify its potential mechanism. Methods. In vivo streptozotocin‐ (STZ‐) induced DM model was established by using a high‐fat diet and STZ, followed by low‐dose (25 mg/kg) and high‐dose (75 mg/kg) 6‐G intervention. For an in vitro DCM model, H9c2 rat cardiomyoblast cells were stimulated with high glucose (glucose = 33 mM) and palmitic acid (100 μM) and then treated with 6‐G (100 μM). Histological and echocardiographic analyses were used to assess the effect of 6‐G on cardiac structure and function in DCM. Western blotting, ELISA, and real‐time qPCR were used to assess the expression of ferroptosis, inflammation, and the Nrf2/HO‐1 pathway‐related proteins and RNAs. Protein expression of collagen I and collagen III was assessed by immunohistochemistry, and kits were used to assay SOD, MDA, and iron levels. Results. The results showed that 6‐G decreased cardiac injury in both mouse and cell models of DCM. The cardiomyocyte hypertrophy and interstitial fibrosis were attenuated by 6‐G treatment in vivo and resulted in an improved heart function. 6‐G inhibited the expression of ferroptosis‐related protein FACL4 and the content of iron and enhanced the expression of anti‐ferroptosis‐related protein GPX4. In addition, 6‐G also diminished the secretion of inflammatory cytokines, including IL‐1β, IL‐6, and TNF‐α. 6‐G treatment activated the Nrf2/HO‐1 pathway, enhanced antioxidative stress capacity proved by increased activity of SOD, and decreased MDA production. Compared with in vivo, 6‐G treatment of H9c2 cells treated with high glucose and palmitic acid could produce a similar effect. Conclusion. These findings suggest that 6‐G could protect against DCM by the mechanism of ferroptosis inhibition and inflammation reduction via enhancing the Nrf2/HO‐1 pathway.

There are sex differences in many inflammatory and immune diseases, and the differences tend to diminish after menopause. The underlying reasons are unclear, but sex hormone levels are likely to be an important factor. Blood leukocyte count and composition provide an indicator of the inflammatory and immune status of an individual. We performed a cross-sectional analysis of blood leukocyte data from 46,879 individuals (26,212 men and 20,667 women, aged 18 to 93 years) who underwent a routine health checkup. In women aged around 50 years, neutrophil percentage (NE%) dropped whilst lymphocyte percentage (LY%) rose. Accordingly, women before age 50 had significantly higher NE%, lower LY%, and higher neutrophil-to-lymphocyte ratio (NLR) than women of 51–70 years of age (p = 1.35×10⁻⁸², p = 5.32×10⁻¹⁰⁰, and p = 1.25×10⁻²⁶, respectively). In age groups of 51 years, it was the reverse (p = 1.92×10⁻¹⁵, p = 1.43×10⁻⁸⁴, and p = 1.51×10⁻⁴⁸, respectively). These results show that blood leukocyte composition differs between women before and after menopausal age, with distinct sexual dimorphism.

Background—: Non-O type of ABO blood group has been associated with a predisposition to coronary heart disease. It is thought that this association is partly mediated by increased cholesterol levels in non–O-type individuals. In this study, we sought to estimate the mediation effect size. Methods and Results—: In a group of individuals (n=6476) undergoing coronary angiography, we detected associations of non-O type with significant coronary artery disease with >50% stenosis in ≥1 coronary arteries (odds ratio, 1.24; 95% confidence interval, 1.10–1.39; P =2.6×10 ⁻⁴ ) and with prevalent or incident myocardial infarction (odds ratio, 1.22; 95% confidence interval, 1.09–1.37; P =1.2×10 ⁻³ ). Subjects of non-O type had higher levels of total cholesterol, low-density lipoprotein cholesterol, and non–high-density lipoprotein cholesterol (mean [SEM] in mmol/L: 4.931[0.021], 3.041 [0.018], and 3.805 [0.020] in non-O type compared with 4.778 [0.026], 2.906 [0.021], and 3.669 [0.024] in O type; P =3.8×10 ⁻⁷ , P =1.5×10 ⁻⁷ , and P =3.1×10 ⁻⁷ , respectively). Mediation analyses indicated that 10% of the effect of non-O type on coronary artery disease susceptibility was mediated by increased low-density lipoprotein cholesterol level ( P =7.8×10 ⁻⁴ ) and that 11% of the effect of non-O type on myocardial infarction risk was mediated by raised low-density lipoprotein cholesterol level ( P =2.0×10 ⁻³ ). Conclusions—: In a model in which it is presumed that cholesterol is a mediator of the associations of ABO group with coronary artery disease and myocardial infarction, around 10% of the effect of non-O type on coronary artery disease and myocardial infarction susceptibility was mediated by its influence on low-density lipoprotein cholesterol level.

Cardiovascular-kidney-metabolic (CKM) syndrome has been recently proposed by American Heart Association recently. The triglyceride glucose (TyG) index and TyG-related indices combined with obesity indicators have proven to be associated with the incidence of cardiovascular diseases (CVD). However, there are few studies to explore whether these associations exist among people with CKM syndrome stages 0–3. A total of 7,364 participants from the China Health and Retirement Longitudinal Study were included. Cox hazard regression and restricted cubic spline regression were used to analyze the associations of these indices with CVD incidence. To compare predictive performance, time-dependent Harrell’s C-indices, net reclassification index and integrated discrimination improvement were conducted. The CVD incidence was 20.55% over nine years. The TyG single index and all the modified TyG indices were capable of predicting CVD incidence. RCS regression analyses showed that all indicators had linear relationships with CVD incidence and these linear relationships of TyG combined with waist circumference (TyG-WC) or waist-to-height ratio (TyG-WHtR) still existed in CKM stage 1, stage 2 and stage 3. TyG-WC (C-index: 0.621, p < 0.001) and TyG-WHtR (C-index: 0.621, p < 0.001) almost had the highest C-indices in predicting CVD incidence, compared to single TyG index (C-index: 0.611, p < 0.001) and TyG combined with body mass index (C-index: 0.616, p < 0.001). The TyG index and all the modified TyG indices were independent predictors of CVD incidence among people with CKM syndrome stages 0–3. It was found that modified indices had better predictive performance, especially TyG combined with waist circumference or waist-to-height ratio.

Atherosclerosis is a systemic, lipid-driven immune-inflammatory disease. We retrospectively reviewed institutional electronic medical records to seek chest pain patients who were suspicious of acute coronary syndrome (ACS) between January 2011 and December 2013. All the patients were identified by undergoing coronary angiography. On admission white blood cell and its subtypes were measured as part of the automated complete blood count and fasting venous blood samples were obtained and analyzed for lipids profiles used automated analysis. A total of 376 consecutive patients with ACS were investigated. In the same period, 378 patients admitted with chest pain suspicious of ACS were also included in this study for control. Blood glucose, serum creatinine, white blood cell, neutrophil and monocyte were insignificantly higher in the ACS group. ACS group had higher total cholesterol and lower high density lipid-cholesterol. However, triglyceride and low density lipid-cholesterol were similar between ACS and control groups. Atherogenic index of plasma (AIP) was significantly higher in ACS group compared to control group (p = 0.029). Similarly, ACS group had higher neutrophil–lymphocyte ratio (NLR) than those in control group. In the subgroups, the NLR were significantly higher in the STEMI group (p < 0.001). However, AIP were similar between the three subgroups (p = 0.748). Our data firstly investigated the lipid-driven inflammatory state in acute coronary syndrome through two easily feasible parameters. There suggest that there are higher AIP and NLR in the ACS patients. Moreover, ACS subgroups are all lipid-driven states, but inflammation levels are different in the entity ACS subgroups.