Residential greenness and dyslipidemia risk: Dose-response relations and mediation through BMI and air pollution.

BACKGROUND: Evidence on associations of residential greenness with dyslipidemia is limited, particularly regarding dose-response relations and mediation. OBJECTIVES: To investigate associations between greenness and dyslipidemia, non-linear dose-response relationships and mediators. METHODS: This cross-sectional study draws on the 2018 Fujian Behavior and Disease Surveillance (FBDS) cohort that used multi-stage stratified random sampling from the general population of Fujian Province, China. Participants with one or more abnormities in total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C) were classified as having dyslipidemia. Residential greenness was operationalized as 3-year average of the normalized difference vegetation index (NDVI500m) and enhanced vegetation index (EVI500m). A doubly robust approach was used for effect quantification. Dose-response relations were studied with natural cubic splines. Mediation via physical activity (PA), body mass index (BMI), PM2.5, PM10, SO2, and NO2 was also examined. RESULTS: Data from 43,183 participants were analyzed. Increases in NDVI500m and EVI500m residential greenness were associated with decreased dyslipidemia risk and improved blood lipids. Non-linear dose response relationships were discovered. Significant reduction of dyslipidemia risk was observed at levels of EVI500m > 0.48 and NDVI500m > 0.65. Joint mediation effects of PA, BMI, PM2.5, PM10, NO2, and SO2 on the associations of NDVI500m and EVI500m with dyslipidemia risk were 49.74% and 44.64%, respectively. CONCLUSIONS: Increased residential exposure to greenness was associated with decreased risk of dyslipidemia. A non-linear dose-response relationship between greenness and dyslipidemia suggests that specific thresholds of greenness need to be reached in order to achieve effects. BMI, PM2.5, and PM10 partially mediated the association.

Rural-urban disparities in the associations of residential greenness with diabetes and prediabetes among adults in southeastern China.

AIMS: Greenness offers health benefits to prevent diabetes in urban areas. However, urban-rural disparities in this association have not been explored, with the underlying pathways understudied as well. We aimed to investigate and compare the associations and potential pathways between residential greenness and the risks for diabetes and prediabetes in urban and rural areas. METHODS: Diabetes and prediabetes were diagnosed by fasting blood glucose (FBG). The participants' residential greenness exposure was estimated by the normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI). The association of residential greenness with the risks for diabetes and prediabetes was estimated by logistic regression and the generalized additive model. The potential mediation effects of air pollution, body mass index (BMI), and physical activity (PA) were examined by causal mediation analysis. RESULTS: Of the 50,593 included participants, and the prevalence of prediabetes and diabetes were 21.22 % and 5.63 %, respectively. Each 0.1-unit increase in EVI500m and NDVI500m for healthy people reduced the risk for prediabetes by 12 % and 8 %, respectively, and substantially reduced the risk for diabetes by 23 % and 19 %, respectively. For those with prediabetes, each 0.1-unit increase in EVI500m and NDVI500m reduced the diabetes risk by 14 % and 12 %, respectively. Compared to the risks for diabetes at the 25th percentile of EVI500m/NDVI500m, such risks significantly reduced when EVI500m (NDVI500m) increased over 0.43 (0.48) and 0.28 (0.39) in urban and rural areas, respectively. The residential greenness-prediabetes/diabetes associations were mediated by air pollution and PA in urban areas and by air pollution and BMI in rural areas. CONCLUSIONS: Exposure to residential greenness was associated with a lower risk for prediabetes and diabetes in urban areas and, more strongly, in rural areas, which were partly mediated by air pollution, PA, and BMI.

Chronic Obstructive Pulmonary Disease Prevalence and Associated Risk Factors in Adults Aged 40 Years and Older in Southeast China: A Cross-Sectional Study During 2019-2020.

Purpose: Chronic obstructive pulmonary disease (COPD) is one of many major public health problems in China, and its prevalence and associated risk factors in the southeast of China need to be determined to facilitate disease control and prevention. Methods: A multistage stratified cluster sampling method was used to select 5486 participants aged ≥ 40 years from nine COPD monitoring districts in Fujian Province during 2019-2020. Participants were interviewed using a laptop-based questionnaire and underwent pulmonary function tests. COPD was diagnosed according to the 2019 Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Results: Final analysis was conducted using data from 4999 participants with qualified post-bronchodilator results. The prevalence of COPD was 11.6% (95% confidence interval [CI]: 10.5-12.7). Risk factors for COPD in the logistic regression model were being male (odds ratio [OR] = 2.83, 95% CI: 2.01-3.98), > 70 years old (OR = 16.16, 95% CI: 8.14-32.08), having a low body mass index (BMI) (OR = 1.81, 95% CI: 1.13-2.89), parental history of respiratory disease (OR = 1.78, 95% CI: 1.50-2.10), being a current (OR = 2.82, 95% CI: 1.83-4.36) or former (OR = 2.47, 95% CI: 1.45-4.19) smoker, and indoor exposure to biomass (OR = 1.28, 95% CI: 1.05-1.58). Conclusion: The estimated prevalence of COPD in southeast China is high. COPD was strongly associated with sex, aging, a low BMI, parental history of respiratory diseases, smoking, and indoor exposure to biomass in adults aged ≥ 40 years. The government should urgently implement comprehensive measures to reduce the risk factors for COPD.

Synergy effects of Asperosaponin VI and bioactive factor BMP-2 on osteogenesis and anti-osteoclastogenesis.

Osteoporosis is a reduction in skeletal mass due to the decrease of osteogenic ability and the activation of the osteoclastic function. Inhibiting bone resorption and accelerating the new bone formation is a promising strategy to repair the bone defect of osteoporosis. In this study, we first systematically investigated the roles of Chinese medicine Asperosaponin VI (ASP VI) on osteogenic mineralization of BMSCs and osteoclastogenesis of BMMs, and then explored the synergistic effect of ASP VI and BS (BMP-2 immobilized in 2-N, 6-O-sulfated chitosan) on bone formation. The result showed that ASP VI with the concentration lower than 10-4 M contributed to the expression of osteogenic gene and inhibited osteoclastic genes RANKL of BMSCs. Simultaneously, ASP VI significantly reduced the differentiation of mononuclear osteoclasts in the process of osteoclast formation induced by M-CSF and RANKL. Furthermore, by stimulating the SMADs, TGF-ß1, VEGFA, and OPG/RANKL signaling pathways, ASBS (ASP VI and BS) substantially enhanced osteogenesis, greatly promoted angiogenesis, and suppressed osteoclastogenesis. The findings provide a new perspective on osteoporosis care and prevention.

Regulation of Inflammatory Response and Osteogenesis to Citrate-Based Biomaterials through Incorporation of Alkaline Fragments.

A proper pH microenvironment is crucial to mobilizing regeneration function of biomaterials. Neutralizing the acidity in bone defects with alkaline substances is a promising strategy to create favorable environments for cell proliferation and bone repair. In this study, to neutralize the acidity and reduce the inflammation caused by the rapid release of citric acid, a novel citrate-based biodegradable elastomeric poly(citric acid-1,8-octanediol-1,4-bis(2-hydroxyethyl)piperazine (BHEp)) (POPC) is synthesized with the introduction of the alkaline fragment BHEp, and then POPC/ß-tricalcium phosphate (ß-TCP) porous scaffolds are fabricated by 3D printing technique. The results reveal that the alkaline fragment BHEp effectively corrects the acid environment and improves the biocompatibility, cells affinity and promoted cell adhesion, and proliferation of POPC. Furthermore, the improved pH of POPC15/ß-TCP (PTCP15) enhances the adhesion and the proliferation of rabbit bone marrow mesenchymal stem cells, and the expression of osteogenesis-related genes. Moreover, PTCP15 scaffolds relieve inflammatory response and switch RAW 264.7 toward a prohealing extreme. The rat femoral defect model further demonstrates good biocompatibility and enhanced bone regeneration of PTCP15. In conclusion, the results offer a promising approach for biodegradable polymers to address the degradation acidity issue. Meanwhile, a positive regulation strategy is provided for biopolymer to enhance cell proliferation, osteogenic differentiation, and bone repair.

Associations and pathways between residential greenness and metabolic syndromes in Fujian Province.

Background: Greenness exposure is beneficial to human health, but its potential mechanisms through which the risk for metabolic syndrome (MetS) could be reduced have been poorly studied. We aimed to estimate the greenness-MetS association in southeast China and investigate the independent and joint mediation effects of physical activity (PA), body mass index (BMI), and air pollutants on the association. Methods: A cross-sectional study was conducted among the 38,288 adults based on the Fujian Behavior and Disease Surveillance (FBDS), established in 2018. MetS was defined as the presence of three or more of the five components: abdominal obesity, elevated triglyceride, reduced high-density lipoprotein cholesterol (HDL-C), high blood pressure, and elevated fasting glucose. The residential greenness exposure was measured as the 3-year mean values of the normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) within the 250, 500, and 1,000 meters (m) buffer zones around the residential address of each participant. Logistic regression models were used to estimate the greenness-MetS association. The causal mediation analysis was used to estimate the independent and joint mediation effects of PA, BMI, particulate matter with an aerodynamic diameter of 2.5 µm (PM2.5), particulate matter with an aerodynamic diameter ≤ 10 µm (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2). Results: Each interquartile range (IQR) increase in greenness was associated with a decrease of 13% (OR = 0.87 [95%CI: 0.83, 0.92] for NDVI500m and OR = 0.87 [95%CI: 0.82, 0.91] for EVI500m) in MetS risk after adjusting for covariates. This association was stronger in those aged < 60 years (e.g., OR = 0.86 [95%CI: 0.81, 0.92] for NDVI500m), males (e.g., OR = 0.73 [95%CI: 0.67, 0.80] for NDVI500m), having an educational level of primary school or above (OR = 0.81 [95%CI: 0.74, 0.89] for NDVI500m), married/cohabitation (OR = 0.86 [95%CI: 0.81, 0.91] for NDVI500m), businessman (OR = 0.82 [95%CI: 0.68, 0.99] for NDVI500m), other laborers (OR = 0.77 [95%CI: 0.68, 0.88] for NDVI500m), and non-smokers (OR = 0.77 [95%CI: 0.70, 0.85] for NDVI500m). The joint effect of all six mediators mediated about 48.1% and 44.6% of the total effect of NDVI500m and EVI500m on the MetS risk, respectively. Among them, BMI showed the strongest independent mediation effect (25.0% for NDVI500m), followed by NO2 and PM10. Conclusion: Exposure to residential greenness was associated with a decreased risk for MetS. PA, BMI, and the four air pollutants jointly interpreted nearly half of the mediation effects on the greenness-MetS association.

Early and Late Effects of Cardiac Resynchronization Therapy in Adult Congenital Heart Disease.

Background There are limited data about cardiac resynchronization therapy (CRT) in adult congenital heart disease. We aimed to assess early and late outcomes of CRT among patients with adult congenital heart disease. Methods and Results We retrospectively studied 54 patients with adult congenital heart disease (median age, 46 years; range, 18-73 years; 74% men) who received CRT implantation (biventricular paced >90%) between 2004 and 2017. Clinical and echocardiographic data were analyzed at baseline and early (mean±SD: 1.8±0.8 years) and late (4.7±0.8 years) follow-up after CRT. Compared with baseline, CRT was associated with significant improvement at early follow-up in New York Heart Association functional class, QRS duration, and cardiothoracic ratio (P<0.05 for all); improvement in New York Heart Association class was sustained at late follow-up. Among patients with a systemic left ventricle (LV; n=39), there was significant increase in LV ejection fraction and reduction in LV end-systolic volume at early and late follow-up (P<0.05 for both). For patients with a systemic right ventricle (n=15), there was a significant early but not late reduction in systemic right ventricular basal and longitudinal diameters. Eleven patients died, and 2 had heart transplantation unrelated to systemic ventricular morphological characteristics. Thirty-five patients (65%) responded positively to CRT, but only baseline QRS duration was predictive of a positive response. Conclusions CRT results in sustained improvement in functional class, systemic LV size, and function. Patients with a systemic LV and prolonged QRS duration, independent of QRS morphological characteristics, were most likely to respond to CRT.

Matrine pre-treatment suppresses AGEs- induced HCSMCs fibrotic responses by regulating Poldip2/mTOR pathway.

The fibrotic response of vascular smooth muscle cells (VSMCs) takes responsibilities in atherosclerosis. Advanced glycation end products (AGEs) induce and promote the fibrotic responses of VSMCs. Matrine shows potent anti-fibrotic and cardio-protective effects. This study was aimed to investigate the underlying mechanisms of matrine's inhibitory effects on AGEs-induced VSMCs fibrotic responses. Cultured human coronary smooth muscle cells (HCSMCs) were pre-treated with matrine and exposed to AGEs. Specific siRNA was used to silence polymerase delta interacting protein 2 (Poldip2) expression. Sircol collagen assay was used to assess collagen content. Protein expression and phosphorylation levels were determined by Western blotting. Matrine pre-treatment significantly reduced collagen content, increased smooth muscle myosin heavy chain 11 (MYH11) and Poldip2 expression, decreased expressions of collagen I, ß1-integrin, phsphoinositide-3-kinase (PI3K) and nuclear phosphorylated p70S6k, and reduced phosphorylation levels of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR) in HCSMCs exposed to AGEs in a concentration dependent manner. Specific siRNA effectively silenced Poldip2 expression and impaired matrine's effect on collagen content, expressions of MYH11, collagen I, ß1-integrin, PI3K, nuclear p-p70S6k and phosphorylation levels of Akt and mTOR in HCSMCs exposed to AGEs. Matrine suppresses AGEs- induced fibrotic responses in HCSMCs via regulating Poldip2/mTOR signaling pathway.

Allicin disrupts cardiac Cav1.2 channels via trafficking.

CONTEXT: Allicin is a potential antiarrhythmic agent. The antiarrhythmic properties of allicin rely on its blockade of various cardiac ion channels. The l-type calcium (Cav1.2) channel provides a pivotal substrate for cardiac electrophysiologic activities. The mechanism of allicin on Cav1.2 remains unclear. OBJECTIVE: This study evaluated the potential of allicin on the synthesis and trafficking of Cav1.2 channels. MATERIALS AND METHODS: Primary cardiomyocytes (CMs) from neonatal Sprague-Dawley (SD) rats were exposed to allicin (0, 0.0001, 0.001, 0.01, 0.1, 1, 10, 100 µg/mL) for 24 and 48 h. The CellTiter-Glo assay was performed to measure CM viability. Western blot with grayscale analysis and confocal laser scanning microscopy were used to evaluate the effects of allicin on the synthesis and trafficking of Cav1.2 channel proteins in primary CMs. RESULTS: There was no significant difference in apoptotic toxicity from the actual cell viability (p > 0.05) in any group (0, 0.0001, 0.001, 0.01, 0.1, 1, 10, 100 µg/mL allicin), except that viability in the 0.001 and 0.01 µg/mL groups at 24 h were significantly greater (137.37 and 135.96%) (p < 0.05). Western blot with grayscale analysis revealed no substantial inhibition by allicin of the synthesis of Cav1.2 proteins. Confocal laser scanning microscopy revealed trafficking dysfunction of Cav1.2 channels caused by allicin in primary CMs. CONCLUSION: This study is the first to demonstrate that allicin inhibits cardiac Cav1.2 channels by disrupting trafficking, possibly mediating its antiarrhythmic benefits. Therefore, allicin might serve as a new antiarrhythmic agent in the future.

Telmisartan Ameliorates Nephropathy in Metabolic Syndrome by Reducing Leptin Release From Perirenal Adipose Tissue.

Metabolic syndrome (MetS) is associated with nephropathy. Along with common risk factors such as hypertension and hyperglycemia, adipocytokines released from perirenal adipose tissue (PRAT) are implicated in the pathogenesis of MetS nephropathy. The study was designed to elucidate the adverse effects of PRAT-derived leptin on nephropathy and to determine whether the angiotensin II type 1 receptor antagonist telmisartan exerts a renoprotective effect by decreasing the PRAT-derived leptin level in the high-fat diet-induced MetS rat. In MetS rats, PRAT-derived leptin expression increased concomitant with dysfunction of adipogenesis, and the activities of the angiotensin II-angiotensin II type 1 receptor and the angiotensin-converting enzyme 2-angiotensin (1-7)-Mas receptor axes were imbalanced in PRAT. PRAT-derived leptin from MetS rats promoted proliferation of rat glomerular endothelial cells (GERs) by activating the p38 MAPK (mitogen-activated protein kinase) pathway, thereby contributing to the development of nephropathy. Long-term telmisartan treatment improved metabolic parameters and renal function, decreased the amount of PRAT, promoted adipogenesis, increased the expression of angiotensin-converting enzyme 2, restored balanced activities of the angiotensin II-AT1R and angiotensin-converting enzyme 2-angiotensin (1-7)-Mas axes, and exerted an indirect renoprotective effect on MetS rats by decreasing PRAT-derived leptin release. Our results demonstrate a novel link between nephropathy and PRAT in MetS and show that telmisartan confers an underlying protective effect on visceral adipose tissue and the kidney, suggesting that it has potential as a therapeutic agent for the treatment of MetS-associated nephropathy.