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Two common features of dietary polyphenols have hampered our mechanistic understanding of their beneficial effects for decades: targeting multiple organs and extremely low bioavailability. We show here that resveratrol intervention (REV-I) in high-fat diet (HFD)-challenged male mice inhibits chylomicron secretion, associated with reduced expression of jejunal but not hepatic scavenger receptor class B type 1 (SR-B1). Intestinal mucosa-specific SR-B1-/- mice on HFD-challenge exhibit improved lipid homeostasis but show virtually no further response to REV-I. SR-B1 expression in Caco-2 cells cannot be repressed by pure resveratrol compound while fecal-microbiota transplantation from mice on REV-I suppresses jejunal SR-B1 in recipient mice. REV-I reduces fecal levels of bile acids and activity of fecal bile-salt hydrolase. In Caco-2 cells, chenodeoxycholic acid treatment stimulates both FXR and SR-B1. We conclude that gut microbiome is the primary target of REV-I, and REV-I improves lipid homeostasis at least partially via attenuating FXR-stimulated gut SR-B1 elevation. Resveratrol intervention improves lipid homeostasis, but how it can target multiple organs with very low bioavailability remains elusive. Here, the authors report that gut microbiota-bile acids are linked to the hypolipidemic effect of resveratrol via inhibiting the intestinal FXR/SR-B1 signalling pathway. [ABSTRACT FROM AUTHOR]

Brussels chicory, a typical vegetable in Mediterranean diets, has been recently reported to stabilize advanced atherosclerotic plaques in the brachiocephalic artery of apoE-deficient (Apoe−/−) mice. Herein, we investigated whether Brussels chicory can stabilize advanced plaques in the aorta via improving oxidative stress. Thirty week old Apoe−/− mice were fed the AIN-93G diet or supplemented with 0.5% freeze-dried Brussels chicory for twenty weeks. Aortic plaque size and stability, aortic relaxation, monocyte adhesion to aortic endothelium, free radicals, and enzymatic and non-enzymatic factors involved in free radical production and elimination in aorta and serum were measured. Brussels chicory consumption did not alter aortic plaque size, however, it stabilized aortic plaques, promoted aortic relaxation, and also inhibited monocyte adhesion to aortic endothelium. Moreover, this administration reduced oxidized LDL (ox-LDL) and 4-hydroxynonenal (4-HNE) content in aortic plaques, associated with inhibited aortic NADPH oxidase (NOX) and uncoupled endothelial nitric oxide synthase (eNOS)-mediated free radical production. However, Brussels chicory consumption did not appreciably alter aortic and serum superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, aortic glutathione (GSH), as well as serum non-enzymatic antioxidants, such as bilirubin, uric acid, and GSH. Collectively, improved oxidative stress might contribute to the atheroprotective effect of Brussels chicory, supporting the prospect of the antioxidant therapy in advanced atherosclerosis progression. [ABSTRACT FROM AUTHOR]

Objective To identify the risk factors of women with premature coronary artery disease (PCAD) in the Kashgar area, mainly Uyghur residents, providing evidence for effective prevention and treatment of PCAD in this region. Methods Two hundred and forty-four Uighur females in Kashgar area who were hospitalized for coronary angiography (CAG) were enrolled. According to the results of CAG and ages, they were divided into three groups : 69 cases in the control group, 104 cases in the PCAD group, and 71 cases in the late-onset coronary artery disease group. Clinical data were compared among three groups. Univariate and multivariable logistic regression analyses were used to identify the risk factors of PCAD. Results The mean age of onset in the PCAD group was (54.25 ± 6.97) years, and 42.3% of them were admitted due to AMI, accounting for 59.4% in patients with coronary heart disease. Compared with the control group, patients with PCAD had higher prevalence of hypertension and diabetes mellitus, and higher levels of CHOL, TG, APO-B, Hcy and GLU, whereas lower levels of ALB and HGB (all P < 0.05), while compared with the late-onset coronary artery disease group, PCAD group had a lower level of Cys-C, but higher levels of ALB and APO-B, and there was no significant difference in other indicators between two groups (all P > 0.05). Multivariate logistic regression analysis showed that diabetes mellitus [OR = 4.349, 95%CI (1.411, 13.402)], hypertension [OR = 3.121, 95%CI (1.467, 6.639)], APO-B/APO-A1 ratio [OR = 5.603, 95%CI (1.128, 27.838)], Hcy [OR =1.188, 95%CI (1.070, 1.318)] were the independent risk factors of PCAD. Conclusions The onset of coronary heart disease is relatively common in female patients aged < 65 years. Diabetes mellitus, hypertension, high APO-B/APO-A1 ratio and high Hcy level are the independent risk factors for women with PCAD in Kashgar area. Early screening and intervention are needed to prevent PCAD in Kashgar area. [ABSTRACT FROM AUTHOR]

Electrocardiogram (ECG) is an important tool for the detection of acute ST-segment elevation myocardial infarction (STEMI). However, machine learning (ML) for the diagnosis of STEMI complicated with arrhythmia and infarct-related arteries is still underdeveloped based on real-world data. Therefore, we aimed to develop an ML model using the Least Absolute Shrinkage and Selection Operator (LASSO) to automatically diagnose acute STEMI based on ECG features. A total of 318 patients with STEMI and 502 control subjects were enrolled from Jan 2017 to Jun 2019. Coronary angiography was performed. A total of 180 automatic ECG features of 12-lead ECG were input into the model. The LASSO regression model was trained and validated by the internal training dataset and tested by the internal and external testing datasets. A comparative test was performed between the LASSO regression model and different levels of doctors. To identify the STEMI and non-STEMI, the LASSO model retained 14 variables with AUCs of 0.94 and 0.93 in the internal and external testing datasets, respectively. The performance of LASSO regression was similar to that of experienced cardiologists (AUC: 0.92) but superior (p < 0.05) to internal medicine residents, medical interns, and emergency physicians. Furthermore, in terms of identifying left anterior descending (LAD) or non-LAD, LASSO regression achieved AUCs of 0.92 and 0.98 in the internal and external testing datasets, respectively. This LASSO regression model can achieve high accuracy in diagnosing STEMI and LAD vessel disease, thus providing an assisting diagnostic tool based on ECG, which may improve the early diagnosis of STEMI. [ABSTRACT FROM AUTHOR]

Aims: Available evidence is incomplete and inconsistent in the outcomes of heart failure (HF) patients with preserved ejection fraction (HFpEF), mildly reduced ejection fraction (HFmrEF), and reduced ejection fraction (HFrEF). There are also limited data on the proportions and long‐term prognosis among the three HF phenotypes in China. We aimed to characterize the 5 year prognosis in three HF phenotypes according to EF in a cohort of hospitalized HF patients undergoing coronary angiography in southern China. Methods and results: Hospitalized patients with HF were enrolled from the Cardiorenal ImprovemeNt registry (CIN; ClinicalTrials.gov NCT04407936) between January 2007 and December 2014. HF phenotypes were defined as HFpEF (EF ≥ 50%), HFmrEF (EF 41–49%), and HFrEF (EF ≤ 40%). Kaplan–Meier and Cox proportional hazards models were constructed to examine differences in 5 year outcomes in HF patients with different phenotypes. A total of 4880 HF patients [mean age: 61.8 ± 10.3, male: 3156 (64.7%)] were included: 2768 (57%) had HFpEF, 1015 (21%) had HFmrEF, and 1097 (22%) had HFrEF. Patients with HFrEF were older than those with HFpEF (62.5 ± 10.6 vs. 61.3 ± 10.1, P < 0.001) and more likely to be male (78.0% vs. 55.9%, P < 0.001). With 5 year follow‐up through the end of December 2019, 1624 (27.6%) patients died. Controlling confounding variables, declined EF category was independently associated with increased 5 year mortality {HFrEF 25.2% vs. HFpEF 13.4%, adjusted hazard ratio [aHR]: 1.85 [95% confidence interval (CI): 1.45 to 2.35]; HFmrEF 18.1% vs. HFpEF 13.4%, aHR: 1.40 [95% CI: 1.08 to 1.81]; HFrEF 25.2% vs. HFmrEF 18.1%, aHR: 1.32 [95% CI: 1.02 to 1.71]}. Conclusions: In this Chinese cohort, patients with HFrEF account for less than a fourth of HF patients. One‐sixth individuals with HF died in 5 years. HFrEF was associated with a nearly two‐fold increased risk of 5 year mortality than HFpEF. Further studies are needed to prospectively evaluate the efficacy of improving treatment on outcomes in all three HF phenotypes. [ABSTRACT FROM AUTHOR]

Ginsenoside Rb1 (Rb1) exerts many beneficial effects and protects against cardiovascular disease. To investigate whether Rb1 could attenuate age-related vascular impairment and identify the mechanism. Female C57BL/6J mice aged 2 and 18 months, randomly assigned to Young, Young + 20 mg/kg Rb1, Old + vehicle, Old + 10 mg/kg Rb1 and Old + 20 mg/kg Rb1 groups, were daily intraperitoneal injected with vehicle or Rb1 for 3 months. The thoracic aorta segments were used to inspect the endothelium-dependent vasorelaxation. Left thoracic aorta tissues were collected for histological or molecular expression analyses, including ageing-related proteins, markers relevant to calcification and fibrosis, and expression of Gas6/Axl. We found that in Old + vehicle group, the expression of senescence proteins and cellular adhesion molecules were significantly increased, with worse endothelium-dependent thoracic aorta relaxation (58.35% ± 2.50%) than in Young group (88.84% ± 1.20%). However, Rb1 treatment significantly decreased the expression levels of these proteins and preserved endothelium-dependent relaxation in aged mice. Moreover, Rb1 treatment also reduced calcium deposition, collagen deposition, and the protein expression levels of collagen I and collagen III in aged mice. Furthermore, we found that the downregulation of Gas6 protein expression by 41.72% and mRNA expression by 52.73% in aged mice compared with young mice was abrogated by Rb1 treatment. But there was no significant difference on Axl expression among the groups. Our study confirms that Rb1 could ameliorate vascular injury, suggesting that Rb1 might be a potential anti-ageing related vascular impairment agent. [ABSTRACT FROM AUTHOR]

T helper 17 (Th17) cells have been involved in the pathogenesis of many autoimmune and inflammatory diseases, like psoriasis, multiple sclerosis (MS), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). However, the role of Th17 cells in psoriasis has not been clarified completely. Th17-derived proinflammatory cytokines including IL-17A, IL-17F, IL-21, IL-22, and IL-26 have a critical role in the pathogenesis of these disorders. In this review, we introduced the signaling and transcriptional regulation of Th17 cells. And then, we demonstrate the immunopathology role of Th17 cells and functions of the related cytokines in the psoriasis to get a better understanding of the inflammatory mechanisms mediated by Th17 cells in this disease. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction and senescence are closely associated with cardiovascular diseases including atherosclerosis and hypertension. Ginsenoside Rb1 (Rb1), the major active constituent of ginseng, has been investigated intensively because of its anti-obesity and anti-inflammatory effects. In a previous study, hydrogen peroxide (H2O2) was applied to induce human umbilical vein endothelial cell (HUVEC) aging. It was demonstrated that Sirtuin-1 (SIRT1) was activated by Rb1 to protect HUVECs from H2O2-induced senescence. However, the mechanisms are not fully understood. The present study examined the role of AMP-activated protein kinase (AMPK), an energy sensor of cellular metabolism, in the signaling pathway of SIRT1 during H2O2-stimulated HUVEC aging. It was identified that Rb1 restored the H2O2-induced reduction of SIRT1 expression, which was consistent with our previous study, together with the activation of AMPK phosphorylation. Using compound C, an AMPK inhibitor, the role of AMPK in the protective effect of Rb1 against H2O2-induced HUVEC senescence was examined. It was identified that the induction of phosphorylated AMPK by Rb1 markedly increased endothelial nitric oxide synthase expression and nitric oxide production, and suppressed PAI-1 expression, which were abrogated in HUVECs pretreated with compound C. Further experiments demonstrated that nicotinamide, a SIRT1 inhibitor, downregulated the phosphorylation of AMPK and reduced the protective effects of Rb1 against H2O2-induced endothelial aging. Taken together, these results provide new insights into the possible molecular mechanisms by which Rb1 protects against H2O2-induced HUVEC senescence via the SIRT1/AMPK pathway. [ABSTRACT FROM AUTHOR]

Adipose tissue inflammation is closely associated with the development of obesity and insulin resistance. Free fatty acids (FFAs) are a major inducer of obesity-related insulin resistance. Previously, we reported that endoplasmic reticulum (ER) stress potentially mediated retinal inflammation in diabetic retinopathy. The unfolded protein response (UPR) protects cells against damage induced by oxidative stress. X-box binding protein 1 (XBP1) plays a major role in protecting cells by modulating the UPR. However, the link between ER stress and adipocyte inflammation has been poorly investigated. In the present study, we found that pretreatment of 3T3-L1 adipocytes with a low dose of ER stress inducer tunicamycin inhibited FFA-induced upregulated expression of inflammatory cytokines. In addition, FFAs induced phosphorylation of the p65 subunit of NF-κB was largely inhibited by pretreatment with tunicamycin in 3T3-L1 adipocytes. Knockdown of XBP1 by siRNA markedly mitigated the protective effects of preconditioning against inflammation. Conversely, overexpression of XBP1 alleviated FFA-induced phosphorylation of IκB-α, IKKα/β, and NF-κB, which was accompanied by decreased inflammatory cytokine expression. Collectively, these results imply a beneficial role of ER stress preconditioning in protecting against FFA-induced 3T3-L1 adipocyte inflammation, which is likely mediated through inhibition of the IKK/NF-κB pathway via XBP1. [ABSTRACT FROM AUTHOR]

Atherosclerosis is the major cause of cardiovascular diseases. Current evidences indicate that inflammation is involved in the pathogenesis of atherosclerosis. Human gingiva-derived mesenchymal stem cells (GMSC) have shown anti-inflammatory and immuno-modulatory effects on autoimmune and inflammatory diseases. However, the function of GMSC in controlling atherosclerosis is far from clear. The present study is aimed to elucidate the role of GMSC in atherosclerosis, examining the inhibition of GMSC on macrophage foam cell formation, and further determining whether GMSC could affect the polarization and activation of macrophages under different conditions. The results show that infusion of GMSC to AopE-/- mice significantly reduced the frequency of inflammatory monocytes/macrophages and decreased the plaque size and lipid deposition. Additionally, GMSC treatment markedly inhibited macrophage foam cell formation and reduced inflammatory macrophage activation, converting inflammatory macrophages to anti-inflammatory macrophages in vitro. Thus, our study has revealed a significant role of GMSC on modulating inflammatory monocytes/macrophages and alleviating atherosclerosis. [ABSTRACT FROM AUTHOR]

Purposes: We have previously reported that Ginsenoside Rb1 may effectively prevent HUVECs from senescence, however, the detailed mechanism has not demonstrated up to now. Recent studies have shown that sirtuin-1 (Sirt1) plays an important role in the development of endothelial senescence. The purpose of this study was to explore whether Sirt1 is involved in the action of Ginsenoside Rb1 regarding protection against H2O2-induced HUVEC Senescence. Methods and Results: Senescence induced by hydrogen peroxide (H2O2) in human umbilical vein endothelial cells (HUVECs) was examined by analyzing plasminogen activator inhibitor-1 (PAI-1) expression, cell morphology, and senescence-associated beta-galactosidase (SA-β-gal) activity. The results revealed that 42% of control-treated HUVECs were SA-β-gal positive after treatment by 60 µmol/L H2O2, however, this particular effect of H2O2 was decreased more than 2-fold (19%) in the HUVECs when pretreated with Rb1 (20 µmol/L) for 30 min. Additionally, Rb1 decreased eNOS acetylation, as well as promoted more NO production that was accompanied by an increase in Sirt1 expression. Furthermore, upon knocking down Sirt1, the effect of Rb1 on HUVEC senescence was blunted. Conclusions: The present study indicated that Ginsenoside Rb1 acts through stimulating Sirt1 in order to protect against endothelial senescence and dysfunction. As such, Sirt1 appears to be of particular importance in maintaining endothelial functions and delaying vascular aging. [ABSTRACT FROM AUTHOR]

Serum gamma-glutamyltransferase (GGT) has been reported to predict vascular risk. We enrolled 978 patients (507 men and 471 women) with established coronary artery disease (CAD). The GGT, brachial–ankle pulse wave velocity ([baPWV] to assess arterial stiffness), and conventional risk factors were evaluated. The means of baPWV tend to increase in both genders according to GGT tertiles. Body mass index, GGT, logarithmical (systolic blood pressure [LnSBP]), uric acid (UA), total bilirubin, Ln (cholinesterase), and Ln (total cholesterol) were correlated with baPWV in men in a multivariate model. However, only GGT, LnSBP, UA, and Ln (high-density lipoprotein cholesterol) were correlated with baPWV in women. The GGT was a significant determinant for increased baPWV both in men (β = 0.017; P < .001) and in women (β = 0.015; P < .001). In conclusion, GGT was independently associated with increased arterial stiffness both in men and in women with established CAD. [ABSTRACT FROM PUBLISHER]

Background: To investigate the effect of visit-to-visit fasting plasma glucose (FPG) variability on the left cardiac structure and function in patients with type 2 diabetes mellitus (T2DM). Methods: In this prospective cohort study, 455 T2DM patients were included and follow-up for a median of 4.7 years. FPG measured on every hospital visit was collected. FPG variability was calculated by its coefficient of variation (CV-FPG). Left cardiac structure and function were assessed using echocardiography at baseline and after follow-up. Multivariable linear regression analyses were used to estimate the effect of FPG variability on the annualized changes in left cardiac structure and function. Subgroup analysis stratified by mean HbA1c levels (< 7% and ≥ 7%) were also performed. Result: In multivariable regression analyses, CV-FPG was independently associated with the annualized changes in left ventricle (β = 0.137; P = 0.031), interventricular septum (β = 0.215; P = 0.001), left ventricular posterior wall thickness (β = 0.129; P = 0.048), left ventricular mass index (β = 0.227; P < 0.001), and left ventricular ejection fraction (β = − 0.132; P = 0.030). After additionally stratified by mean HbA1c levels, CV-FPG was still independently associated with the annualized changes in the above parameters in patients with HbA1c ≥ 7%, while not in patients with HbA1c < 7%. Conclusions: Visit-to-visit variability in FPG could be a novel risk factor for the long-term adverse changes in left cardiac structure and systolic function in patients with type 2 diabetes. Trial registration ClinicalTrials.gov (NCT02587741), October 27, 2015, retrospectively registered. [ABSTRACT FROM AUTHOR]

A response by Cansheng Zhu and colleagues to a letter to the editor about his article "Association of serum gamma-glutamyltransferase with arterial stiffness in established coronary artery disease" in the September 21, 2012 issue is presented.