Effect of Exposure to Paternal Smoking on Overweight and Obesity in Children: Findings from the Children Lifeway Cohort in Shenzhen, Southern China.

INTRODUCTION: Paternal smoking associated with childhood overweight and obesity has been a concern, but studies have not investigated smoking exposure and smoking details. We investigated the association of exposures from paternal smoking as well as smoking details on offspring overweight/obesity. METHODS: A total of 4,513 children (aged 7-8 years) in Shenzhen were enrolled. Four different exposures from paternal smoking as well as smoking quantity, duration of smoking, and age of starting smoking details were the exposure variables and demographic characteristics, and circumstances of birth, dietary intake, lifestyle, and nonpaternal-smoking exposure were covariates in the logistic regression analysis to determine the effect of paternal smoking on childhood overweight/obesity, estimating odds ratios (ORs), and 95% confidence intervals (CIs). RESULTS: Paternal smoking was positively associated with childhood overweight/obesity (p < 0.05). Moreover, only preconception exposure, and both pre- and postconception exposure were significantly associated with childhood overweight/obesity (OR 1.54 [95% CI: 1.14-2.08] and OR 1.73 [95% CI: 1.14-2.61], respectively), restricted to boys but not girls. Furthermore, for children with only preconception paternal-smoking exposure, the dose-response relation was positive between smoking quantity, duration of smoking, age at starting, and overweight/obesity for boy offspring (p trend <0.001). We did not find any significant association between only postnatal exposure to paternal smoking and childhood overweight/obesity (p > 0.05). CONCLUSIONS: Our findings suggest that paternal smoking is associated with boys' overweight/obesity, and this association may be due to the paternal-smoking exposure before conception rather than the postnatal exposure to paternal smoking. Reducing paternal-smoking exposure before conception might help reduce overweight/obesity in boys.

Higher intake of microbiota-accessible carbohydrates and improved cardiometabolic risk factors: a meta-analysis and umbrella review of dietary management in patients with type 2 diabetes.

BACKGROUND: Microbiota-accessible carbohydrates (MACs) are critical substrates for intestinal microbes; the subsequent production of SCFAs may have some potential benefits for patients with type 2 diabetes mellitus (T2DM). OBJECTIVES: We conducted a meta-analysis of randomized controlled trials (RCTs) to assess the effects of higher compared with lower MAC intakes on cardiovascular risk factors in T2DM patients and performed an umbrella review of RCTs to evaluate the evidence quality concerning existing dietary T2DM interventions. METHODS: Publications were identified by searching MEDLINE, EMBASE, and CINAHL. In the meta-analysis, random-effects models were used to calculate pooled estimates, and sensitivity analyses, meta-regression, subgroup analyses, and Egger's test were performed. For the umbrella review, we summarized pooled estimates, 95% CIs, heterogeneity, and publication bias. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) and modified NutriGrade were used to assess the quality of evidence in the meta-analysis and umbrella review, respectively. RESULTS: Forty-five RCTs with 1995 participants were included in the meta-analysis. High MAC intake significantly reduced glycated hemoglobin (HbA1c) (weighted mean difference [WMD] -0.436% [-0.556, -0.315]), fasting glucose (WMD -0.835 mmol/L [-1.048, -0.622]), total cholesterol (WMD -0.293 mmol/L [-0.397, -0.190]), triglycerides (WMD -0.118 mmol/L [-0.308, -0.058]), BMI (WMD -0.476 [-0.641, -0.312]), and systolic blood pressure (WMD -3.066 mmHg [-5.653, -0.478]), with a moderate-to-high quality of evidence, compared with low intake. Region, dose, and MAC type were key variables. The umbrella review of all dietary interventions for cardiovascular risk factors in patients with T2DM included 26 meta-analyses with 158 pooled estimates. The evidence quality of MACs, dietary fiber, high-protein diet, ω-3 (n-3), viscous fiber, vitamin D, and vitamin E intake was moderate to high. CONCLUSIONS: When compared with lower intake, increased MAC intake improved glycemic control, blood lipid, body weight, and inflammatory markers for people with T2DM. This trial was registered at PROSPERO (https://www.crd.york.ac.uk/PROSPERO/#recordDetails) as CRD42019120531.

The antagonist of P2Y11 receptor NF157 ameliorates oxidized LDL-induced vascular endothelial inflammation.

Atherosclerosis is the chronic inflammatory disease, and inflammation-elicited endothelial activation is an early event in the development of atherosclerosis. The P2Y11 receptor is a purinergic receptor and a member of the P2 family of G coupled protein which has been shown to modulate vascular function. Progress in the study of purine receptors has been tremendous and these receptors have become pharmacological targets for various diseases. In this study, we show that the P2Y11R antagonist NF157 can mitigate oxidized LDL (ox-LDL)-induced endothelial inflammation. Our study demonstrates that P2Y11R is expressed to a fair degree in human aortic endothelial cells and is induced by treatment with ox-LDL. Blockage of P2Y11R by its selective antagonist NF157 ameliorates ox-LDL-induced adhesion of THP-1 monocytes to endothelial cells. NF157 inhibits ox-LDL-induced expression of adhesion molecules including E-selectin and VCAM-1. NF157 also suppresses ox-LDL-associated ROS production and induction of the NADPH oxidase subunit NOX-4. Moreover, NF157 has an inhibitory effect on the production of major cytokines including IL-6 and TNF-α. Mechanistically, we show that NF157 mitigates ox-LDL-induced phosphorylation of MAPK kinase p38 and NF-κB activation. Our findings indicate that blockage of P2Y11R signalling by its antagonist NF157 may protect endothelial cells from ox-LDL-induced endothelial inflammation. Therefore, NF157 may have therapeutic implications in the modulation of atherosclerosis-associated inflammation.

Neuroglobin protects cardiomyocytes against apoptosis and cardiac hypertrophy induced by isoproterenol in rats.

Neuroglobin (Ngb) is well known as a physiological role in oxygen homeostasis of neurons and perhaps a protective role against hypoxia and oxidative stress. In this study, we found that Ngb is expressed in rat heart tissues and it is related to isoproterenol induced cardiac hypertrophy. Moreover, overexpression or knock-down of Ngb influences the expression of hypertrophic markers ANP and BNP and the ratio of hypertrophic cells in rat H9c2 myoblasts when isoproterenol treatment. The Annexin V-FITC/PI Staining, Western blot and qPCR analysis showed that the involvement in p53-mediated apoptosis of cardiomyocytes of Ngb is might be the mechanism. This protein could prevent the cells against ROS and POS-induced apoptosis not only in nervous systems but also in cardiomyocytes. From the results, it is concluded that Ngb is a promising protectant in the cardiac hypertrophy, it may be a candidate target to cardiac hypertrophy for clinic treatment.

An early warning scoring system for the prevention of acute heart failure.

BACKGROUND: Early prediction and identification of the onset of acute heart failure (AHF) in high-risk patients are of great significance for preemptive treatment and a better prognosis. We sought to find a scoring system to predict the onset of AHF in patients in the acute heart failure unit (AHFU). METHODS: Data for 433 patients at of AHF in the AHFU were analyzed. We recorded sex, age, history of coronary artery disease, hypertension, diabetes, and primary percutaneous coronary intervention. We also reviewed temperature, pulse, SpO2, respiratory rate, urine volume, and emotional state every hour before the onset of AHF. All admission and follow-up data were retrieved from hospital charts. Factors were analyzed using a binary logistic regression model to create the SUPER (SpO2, urine volume, pulse, emotional state, and respiratory rate) scoring model. We divided the scoring system into four levels: low-, intermediate-, high-, and extremely high-risk. Patients fitting the four risk levels were followed up for 6 to 24 months. RESULTS: SpO2, hourly urine volume, pulse, emotional state and respiratory rates were associated with an independent increased risk for the onset of AHF. The SUPER score for the patients in the AHFU predicted the onset of AHF 3.90 ± 1.94 h (1-17 h) earlier. The areas under the ROC curve for the SUPER score and the modified early warning score were 0.811 and 0.662 (p<0.05), indicating that the SUPER score provided a better warning of the AHF. A low-, intermediate-, high-, and very high-risk SUPER predicted the likelihood of AHF at 17.3%, 61.3%, 84.4%, and 94.0%, respectively. The differences in mortality rates between the four levels were statistically significant (p<0.05). CONCLUSIONS: In patients at high risk of AHF, the SUPER scoring system could predict the onset of AHF 2 to 6h earlier. Preemptive treatment according to the SUPER score may prevent or delay AHF occurrence to improve quality of life and reduce mortality.

Effect of intermittent hypoxia on neuro-functional recovery post brain ischemia in mice.

Intermittent hypoxia was a simulation of a high-altitude environment. Neuro-inflammation post brain ischemia was considered as a vital impact which contributed to cognitive-functional deficit. The isoform of nitric oxide synthase (iNOS) was an inflammation factor secreted by microglias in neuro-inflammation. In this study, we established a high-altitude environment as the hypoxic condition. Twenty mice were selected and randomized into a hypoxia group (n = 10) or a normoxia group (n = 10) post three vessel occlusion-induced brain ischemia. An enhancement of cognitive-functional recovery was presented in the hypoxia group by survival neuron counting and revealed by the Morris water maze test. Meanwhile, a high level of hypoxia-inducable factor 1 (HIF-1) expression associated with a lower expression of iNOS was observed in the border between infarcts and normal tissue of the hippocampus in the hypoxia group. However, these phenomenons were blocked by HIF-1 inhibition. This suggested that the acceleration of cognitive-functional recovery induced by intermittent hypoxia may depend on HIF-1 activating. An imitation of the hypoxic condition with or without HIF-1 inhibition was operated on the BV-2 cell. A high level of HIF-1 expression associated with a lower-level expression of iNOS was performed in the hypoxic condition. These data suggested that intermittent hypoxia can accelerate cognitive function recovery through attenuating neuro-inflammation.

Efficacy and safety of sirolimus-eluting stents versus bare-metal stents in coronary artery disease patients with diabetes: a meta-analysis.

OBJECTIVE: To compare by meta-analysis the efficacy and safety of sirolimus-eluting and bare-metal stents in coronary artery disease (CAD) patients with diabetes. METHOD: PubMed, MEDLINE and EMBASE were searched from 1971 to 2012. Data on the efficacy and safety of sirolimus-eluting and bare-metal stents in patients with diabetes were collected. A meta-analysis was then performed on a total of 1 259 CAD patients with diabetes from six studies. The odds ratio (OR) was used for comparison. Subgroup analysis was performed according to the sample size, year of study, subjects' geographic area and study method. RESULTS: Compared with those in the bare-metal stent group (BMS), the subjects in the sirolimus-eluting stent (SES) group had a reduced risk for major cardiac events [OR 0.42, 95% confidence interval (CI): 024-0.74, p < 0.01] and target-lesion revascularisation (OR 0.26, 95% CI: 0.11 - 0.59, p < 0.01). There was no difference for myocardial infarction (OR 0.92, 95% CI: 0.61-1.40, p > 0.05) or mortality (OR 1.19, 95% CI: 0.74-1.92, p > 0.05). Subgroup analysis showed a significant difference for overall risk of major cardiac events between SES and BMS when the sample size was ≤ 90 (OR 0.28, 95% CI: 0.16-0.48, p < 0.01), when it was a randomised control trial (RCT) (OR 0.28, 95% CI: 0.19-0.42, p < 0.01), or when it was performed on European subjects (OR 0.45, 95% CI: 0.27-0.77, p < 0.01). The sensitivity was not different when one study was removed at a time. CONCLUSION: Our study confirmed that SES are safer and more effective than BMS in CAD patients with diabetes, as far as major cardiac events are concerned.