Relationship between phthalates exposures and metabolic dysfunction-associated fatty liver disease in United States adults.

As a new definition for the evidence of hepatic steatosis and metabolic dysfunctions, the relationship between phthalates (PAEs) and metabolic dysfunction-associated fatty liver disease (MAFLD) remains virtually unexplored. This study included 3,137 adults from the National Health and Nutrition Examination Survey spanning 2007-2018. The diagnosis of MAFLD depended on the US Fatty Liver Index (US FLI) and evidence of metabolic dysregulation. Eleven metabolites of PAEs were included in the study. Poisson regression, restricted cubic spline (RCS), and weighted quantile sum (WQS) regression were used to assess the associations between phthalate metabolites and MAFLD. After adjusting for potential confounders, Poisson regression analysis showed that mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-n-butyl phthalate, mono-(3-carboxypropyl) phthalate, mono-ethyl phthalate (MEP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate were generally significant positively associated with MAFLD (P<0.05). Furthermore, the WQS index constructed for the eleven phthalates was significantly related to MAFLD (OR:1.43; 95%CI: 1.20, 1.70), MEHHP (33.30%), MEP (20.84%), MECPP (15.43%), and mono-isobutyl phthalate (11.78%) contributing the most. This study suggests that exposure to phthalates, individually or in combination, may be associated with an increased risk of MAFLD.

Association of exposure to polycyclic aromatic hydrocarbons with thyroid hormones in adolescents and adults, and the influence of the iodine status.

Some studies of endocrine-disrupting polycyclic aromatic hydrocarbon (PAH) exposure and thyroid hormones (THs) are inconclusive. To assess the associations between PAHs and THs, and the influence of the iodine status on PAHs-THs, we employed 648 adolescents (12-19 years old) and 2691 adults from the National Health and Nutrition Examination Survey 2007-2008 and 2011-2012. PAH metabolites [1-hydroxynaphthalene (1-NAP), 2-NAP, 1-hydroxyphenanthrene (1-PHE), 2-PHE, 3-PHE, 2-hydroxyfluorene (2-FLU), 3-FLU, 9-FLU, and 1-hydroxypyrene (1-PYR)], THs [total and free thyroxine (TT4 and FT4), total and free triiodothyronine (TT3 and FT3), thyroid stimulating hormone (TSH), and thyroglobulin (Tg)], peripheral deiodinase activity (GD) and thyroid's secretory capacity (GT) were involved. Multiple linear regression and weighted quantile sum (WQS) regression models were used to assess PAH-TH associations and the interaction between PAHs and the iodine status. Stratification analyses were conducted based on sex, smoking and iodine status. For adolescents, in a multivariable-adjusted regression model (ß; 95% CI), 1-PHE (4.08%; 1.01%, and 7.25%), 2-PHE (3.98%; 0.70%, and 7.25%) and 9-FLU (3.77%; 1.10%, 7.47%) were positively correlated with TT3; 3-PHE and 1-PYR interacted with the iodine status (P-int < 0.05); 9-FLU was positively correlated with GD in both sexes. Combined exposure to PAHs was positively associated with Tg (0.137; 0.030, and 0.243), and negatively correlated with TSH (-0.087; -0.166, and -0.008). For adults, 2-NAP was positively correlated with FT3 (0.90%; 0.20%, and 1.61%), FT4 (1.82%; 0.70%, and 2.94%), TT3 (1.31%; 0.10%, and 2.63%), TT4 (2.12%; 0.90%, and 3.36%) and GT (2.22%; 1.01%, and 3.46%), but negatively correlated with TSH (-4.97%; -8.33%, and -1.49%); 1-NAP interacted with the iodine status (P-int < 0.05); 1-PHE was inversely correlated with TT3 in males; 2-PHE was positively correlated with TT3 in females. Combined exposure to PAHs was positively associated with FT3 (0.008; 0.001, and 0.014). Combined exposure to PAHs was positively associated with FT3, TT3 and GD, and negatively correlated with FT4, TT4 and GT in non-smoking adults; but positively associated with Tg (ß = 0.140; 95% CI: 0.042, 0.237) in smoking adults. Our results indicated that combined and individual PAH exposure might be related to THs, and the iodine status had an influence on PAH-TH associations. These associations were not identical between adolescents and adults, and there were sex and smoking status differences.

Adults allostatic load is less with greater dietary quality: National Health and Nutrition Examination Survey (NHANES) 2015-2018.

BACKGROUND AND OBJECTIVES: Few studies have explored the relationship between overall diet quality and stress load. Therefore, we have evaluated the association between dietary quality and allostatic load (AL) in adults. METHODS AND STUDY DESIGN: The data were derived from the 2015-2018 National Health and Nutri-tion Examination Survey (NHANES). Dietary intake information was obtained by 24-hour dietary recall. The Healthy Eating Index (HEI) 2015 version was estimated as an indicator of dietary quality. The AL was in-dicative of the accumulated chronic stress load. The weighted logistic regression model was used to explore the relationship between dietary quality and the risk of high AL in adults. RESULTS: A total of 7557 eligible adults older than 18 years were enrolled in this study. After being fully adjusted, we found a significant asso-ciation between HEI score and the risk of high AL (ORQ2 =0.73, 95% CI: 0.62,0.86; ORQ3 =0.66, 95% CI: 0.55,0.79; ORQ4 =0.56, 95% CI: 0.47,0.67) in logistic regression model. Increased intake of total fruits and whole fruits or decreased intake of sodium, refined grains, saturated fats and added sugars were associated with the risk of high AL (ORtotal fruits =0.93, 95%CI: 0.89,0.96; ORwhole fruits =0.95, 95%CI: 0.91,0.98; ORwhole grains =0.97, 95%CI: 0.94,0.997; ORfatty acid =0.97, 95%CI: 0.95,0.99; ORsodium =0.95, 95%CI: 0.92,0.98; ORre-fined grains =0.97, 95%CI: 0.94,0.99; ORsaturated fats =0.96, 95%CI: 0.93,0.98; ORadded sugars =0.98, 95%CI: 0.96,0.99). CONCLUSIONS: We found that dietary quality was inversely associated with allostatic load. High di-etary quality presumptively less cumulative stress.

The Mediating Effect of Central Obesity on the Association between Dietary Quality, Dietary Inflammation Level and Low-Grade Inflammation-Related Serum Inflammatory Markers in Adults.

To date, few studies have explored the role of central obesity on the association between diet quality, measured by the health eating index (HEI), inflammatory eating index (DII), and low-grade inflammation-related serum inflammatory markers. In this paper, we use the data from the 2015-2018 National Health and Nutrition Examination Survey (NHANES) to explore this. Dietary intakes were measured during two 24-h dietary recall interviews and using USDA Food Pattern Equivalence Database (FPED) dietary data. Serum inflammatory markers were obtained from NHANES Laboratory Data. Generalized structural equation models (GSEMs) were used to explore the mediating relationship. Central obesity plays a significant mediating role in the association between HEI-2015 and high-sensitivity C-reactive protein (hs-CRP), mediating 26.87% of the associations between the two; it also mediates 15.24% of the associations between DII and hs-CRP. Central obesity plays a mediating role in 13.98% of the associations between HEI-2015 and white blood cells (WBC); it also mediates 10.83% of the associations between DII and WBC. Our study suggests that central obesity plays a mediating role in the association of dietary quality with low-grade inflammation-related serum inflammatory markers (hs-CRP and WBC).

The Chain-Mediating Effect of Obesity, Depressive Symptoms on the Association between Dietary Quality and Cardiovascular Disease Risk.

In order to explore the relationship between the Healthy Eating Index (HEI-2015) and cardiovascular disease (CVD), and the mediating role of obesity and depressive symptoms, we used the data from the 2011-2018 National Health and Nutrition Examination Survey (NHANES) for further study. A total of 12,644 participants were included in the study. The HEI was derived using NHANES personal food data and USDA Food Pattern Equivalence Database (FPED) dietary data. The risk of cardiovascular disease was determined using the Framingham Heart Study's multifactorial calculation tool. The weighted multiple logistic regression model was used to explore the association between the HEI-2015 and CVD, and the generalized structural equation was used to explore the mediating effects of obesity and depression, respectively and jointly. Higher HEI-2015 scores were associated with a lower risk of CVD compared to lower quartiles. Obesity, depressive symptoms, and their chain effects all played significant mediating roles in the association between the HEI-2015 and CVD, with proportional mediations of 9.03%, 2.23% and 0.25%, respectively. Our results suggest that higher dietary quality is associated with a lower risk of CVD, mediated by obesity, depressive symptoms, and the chain effect of obesity and depressive symptoms.

Association between perfluoroalkyl substances exposure and the prevalence of nonalcoholic fatty liver disease in the different sexes: a study from the National Health and Nutrition Examination Survey 2005-2018.

There is evidence that perfluoroalkyl substances (PFASs) have effects on liver toxicity, and the effects may exhibit sex differences. Our study aims to explore the association between exposure to four PFASs (perfluorooctanoic acid, PFOA; perfluorooctane sulfonate, PFOS; perfluorohexane sulfonate, PFHxS; and perfluorononanoate, PFNA) and the risk of nonalcoholic fatty liver disease (NAFLD) in adults ≥ 20 years old in the US population. The data were based on the National Health and Nutrition Examination Survey (NHANES) 2005-2018. We used Poisson regression to explore the association between the four PFASs and NAFLD. We included 3464 participants; of these, 1200 (34.64%) individuals were defined as having NAFLD, and the prevalence of NAFLD was 39.52% in men and 30.40% in women. After Poisson regression, among the premenopausal and postmenopausal and total women, PFOA had a significantly positive association with NAFLD (p < 0.05). After principal component analysis, the "composite PFAS" was associated with NAFLD in postmenopausal and total women, and the RRs (95% CIs) were 1.306 (1.075, 1.586) and 1.161 (1.007, 1.339), respectively. In adults, we found that PFASs were associated with NAFLD, and the associations varied by sex, particularly for PFOA and PFNA, which had a positive association with NAFLD in women.

Association of Body Mass Index and Abdominal Obesity with the Risk of Airflow Obstruction: National Health and Nutrition Examination Survey (NHANES) 2007-2012.

This study aimed to explore the relationship between body mass index (BMI) and abdominal obesity and the risk of airflow obstruction, based on the data from the 2007-2012 National Health and Nutrition Survey (NHANES). Logistic regression was applied to assess the relationships between BMI or abdominal obesity and the risk of airflow obstruction by the fixed ratio method and the lower limit of normal (LLN) method. We further used the restricted cubic splines with 3 knots located at the 5th, 50th, and 95th percentiles of the distribution to evaluate the dose-response relationship. A total of 12,865 individuals aged 20-80 years old were included. In the fixed ratio method, underweight was positively correlated with the risk of airflow obstruction, and overweight and obesity were negatively correlated with the risk of airflow obstruction. In the LLN method, the results were consistent with the fixed ratio method. Abdominal obesity was positively associated with the risk of airflow obstruction only in the fixed ratio method (OR: 1.41, 95% CI: 1.04-1.90). There was an additive interaction between underweight and smoking on airflow obstruction in both methods. Abdominal obesity and smoking had additive interactions in the LLN method. Dose-response analysis indicated that there was a non-linear trend between BMI and the risk of airflow obstruction (Pfor nonlinearity < 0.01). Our study suggested that underweight and abdominal obesity were associated with the increased risk of airflow obstruction, and overweight and general obesity were associated with the decreased risk of airflow obstruction.

The association between periodontitis and lung function: Results from the National Health and Nutrition Examination Survey 2009 to 2012.

BACKGROUND: We aimed to explore the association between periodontitis and lung function in the United States. METHODS: The data was based on the National Health and Nutrition Examination Survey (NHANES) 2009 to 2012. Periodontitis was defined following the CDC/AAP (Centers for Disease Control and Prevention/American Academy of periodontology) classification. Lung function measurements included forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio. Linear regression and binary logistic regression were used to explore the association between periodontitis and lung function measurements. Restricted cubic spline was used to assess the dose-response relationships between the mean attachment loss (AL), the mean probing depth (PD) and spirometry-defined airflow obstruction (FEV1/FVC <0.7). RESULTS: A total of 6313 adults aged 30 years or older were included. Compared to those with non-periodontitis, the multivariate-adjusted odds ratios (ORs) of airflow obstruction for moderate and severe periodontitis were 1.38 (95% CI: 1.01 to 1.75) and 1.47 (95% CI: 1.06 to 2.01), the ß coefficients of FEV1 for moderate and severe periodontitis were -130.16 (95% CI: -172.30 to -88.01) and -160.46 (95% CI: -249.94 to -70.97), the ß coefficients of FVC for moderate and severe periodontitis were -100.96 (95% CI: -155.08 to -46.85) and -89.89 (95% CI: -178.45 to -1.33), the ß coefficients of FEV1/FVC for moderate and severe periodontitis were -0.01 (95% CI: -0.02 to -0.01) and -0.02 (95% CI: -0.03 to -0.01). In stratified analyses, the multivariate-adjusted ORs of airflow obstruction for the moderate and severe periodontitis were 1.27 (95% CI: 0.84 to 1.93) and 2.31 (95% CI: 1.10 to 4.83) in former smokers, 1.84 (95% CI: 1.03 to 3.30) and 1.79 (95% CI: 1.02 to 3.16) in current smokers, with no significant association observed in never smokers. Mean clinical AL and mean PD were negatively associated with FEV1, FVC, and FEV1/FVC in never, former, and current smokers. Dose-response relationship analysis showed that the risk of airflow obstruction increased with increasing mean clinical AL and mean PD, and showed a non-linear dose-response relationship. CONCLUSION: Our study suggested that moderate and severe periodontitis might be associated with the decline of lung function in the United States of America.

Association between milk and dairy product intake and the risk of dental caries in children and adolescents: NHANES 2011-2016.

BACKGROUND AND OBJECTIVES: To date, few studies have comprehensively explored the associations between milk and dairy product intake and dental caries. Therefore, this study aimed to simultaneously assess the associations between whole milk, low-fat milk, skim milk, yogurt, milk desserts, cheese, creams, and total fluid milk intake and the risk of dental caries in children and adolescents. METHODS AND STUDY DESIGN: Data were from the National Health and Nutrition Examination Survey (NHANES) 2011-2016. Two 24-hour dietary recall interviews measured dietary milk and dairy product intake. Primary teeth caries was diagnosed by the dfs (decayed or filled primary tooth surfaces) index, and permanent teeth caries was diagnosed by the DMFS (decayed, missing, or filled permanent tooth surfaces) index. We used logistic regression to explore the associations between milk and dairy product intake and the risk of dental caries. RESULTS: A total of 6885 individuals aged 2-17 years were included in this study. In the fully adjusted model, the odds ratios (95% confidence intervals) of dental caries were 0.66 (0.47-0.93) for intake ≥123 g/day of yogurt and 0.82 (0.69-0.98) for intake <22.6 g/day of cheese, as compared with non-consumers. CONCLUSIONS: Our study indicates that high yogurt and low cheese intake were associated with a decreased risk of dental caries among American children and adolescents. These findings may be applied to update and supplement the evidence that informs public health policies on milk and dairy products and the prevention of dental caries.

Association of folate, vitamin B-12 and vitamin B-6 intake with diabetes and prediabetes in adults aged 20 years and older.

BACKGROUND AND OBJECTIVES: This study aimed to assess the association of folate, vitamin B-12 and vitamin B-6 from diet and supplements with diabetes and prediabetes in U.S. adults. METHODS AND STUDY DESIGN: We used data from the National Health and Nutrition Examination Survey (NHANES) 2007-2016 to conduct this crosssectional study. Diabetes and prediabetes status were based on self-report, medication use, fasting plasma glucose levels (FPG), haemoglobin A1c (HbA1c) levels and the two hours plasma glucose (PG) value during a 75-g oral glucose tolerance test (OGTT). Logistic regression models and restricted cubic spline models were used to evaluate the associations between dietary folate, vitamin B-12, vitamin B-6 and diabetes. RESULTS: After adjustment for the potential confounders, compared with the lowest quartile, the ORs (odds ratios) with 95%CIs (confidence intervals) of diabetes for the highest quartile intakes of folate and vitamin B-6 were 0.65 (0.47-0.90) and 0.61 (0.42-0.89), the OR with 95% CI of diabetes for the third quartile of dietary vitamin B-12 was 0.76 (0.60-0.97). Further excluded participants with diabetes history, the ORs with 95% CI of newly diagnosed diabetes were 0.60 (0.39-0.94), 0.84 (0.58-1.23), and 0.65 (0.43-0.98) for the third quartile of dietary folate, vitamin B-12 and vitamin B-6, respectively. A linear inverse relationship was found between vitamin B12 and diabetes, and a nonlinear inverse relationship was found between dietary folate, dietary vitamin B6 and diabetes. CONCLUSIONS: Our study suggested that folate, vitamin B-12 and vitamin B-6 intake were inversely associated with the risk of diabetes in US adults.

Association of Body Mass Index with Risk of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

The association between body mass index (BMI) and chronic obstructive pulmonary disease (COPD) remains controversial. Therefore, a meta-analysis was conducted to further evaluate the relationship. A comprehensive literature search was performed in PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), and Wanfang databases to identify eligible articles until July 15, 2020. Random effect model (REM) was used to compute the pooled results with 95% confidence intervals (CIs). We conducted meta-regression and subgroup analysis to explore potential sources of heterogeneity. Publication bias was evaluated by funnel plots and Egger's test. Thirty articles with 1,578,449 participants were included in the meta-analysis. The pooled OR of COPD was 1.96 (95% CI: 1.78-2.17) for the underweight group, 0.80 (95% CI: 0.73-0.87) for overweight group, and 0.86 (95% CI: 0.73-1.02) for obesity group. After further excluding 5 studies of high between-study heterogeneity in sensitivity analysis, the pooled OR of COPD was 0.77 (95% CI: 0.68-0.86) for the obesity group. This meta-analysis indicated that BMI was associated with COPD. Specifically, underweight might increase the risk of COPD; overweight and obesity might reduce the risk of COPD.

Associations between PHACTR1 gene polymorphisms and pulse pressure in Chinese Han population.

A genome-wide association study (GWAS) in Chinese twins was performed to explore associations between genes and pulse pressure (PP) in 2012, and detected a suggestive association in the phosphatase and actin regulator 1 (PHACTR1) gene on chromosome 6p24.1 (rs1223397, P=1.04e-07). The purpose of the present study was to investigate associations of PHACTR1 gene polymorphisms with PP in a Chinese population. We recruited 347 subjects with PP ≥ 65 mmHg as cases and 359 subjects with 30 ≤ PP ≤ 45 mmHg as controls. Seven single nucleotide polymorphisms (SNPs) in the PHACTR1 gene were genotyped. Logistic regression was performed to explore associations between SNPs and PP in codominant, additive, dominant, recessive and overdominant models. The Pearson's χ2 test was applied to assess the relationships of haplotypes and PP. The A allele of rs9349379 had a positive effect on high PP. Multivariate logistic regression analysis showed that rs9349379 was significantly related to high PP in codominant [AA vs GG, 2.255 (1.132-4.492)], additive [GG vs GA vs AA, 1.368 (1.049-1.783)] and recessive [AA vs GA + GG, 2.062 (1.051-4.045)] models. The positive association between rs499818 and high PP was significant in codominant [AA vs GG, 3.483 (1.044-11.613)] and recessive [AA vs GG + GA, 3.716 (1.119-12.339)] models. No significant association of haplotypes with PP was detected. There was no significant interaction between six SNPs without strong linkage. In conclusion, the present study presents that rs9349379 and rs499818 in the PHACTR1 gene were significantly associated with PP in Chinese population. Future research should be conducted to confirm them.

Limonin ameliorates acetaminophen-induced hepatotoxicity by activating Nrf2 antioxidative pathway and inhibiting NF-κB inflammatory response via upregulating Sirt1.

BACKGROUND: Limonin, a bioactive compound from citrus plants, exerts antioxidant activities, however its therapeutic potential in acetaminophen (APAP)-induced hepatotoxicity remains unclear. PURPOSE: Our study aims to investigate the protective effect of limonin on APAP-induced hepatotoxicity and illuminate the underlying mechanisms. STUDY: design In vitro, we chose L-02 cells to establish in vitro APAP-induced liver injury model. L-02 cells were treated with APAP (7.5 mM) for 24 h after pre-incubation with limonin (10, 25, 50 µM) or NAC (250 µM) for 2 h. In vivo, we used C57BL/6 mice as an in vivo APAP-induced liver injury model. C57BL/6 mice with pre-treatment of limonin (40, 80 mg/kg) or NAC (150 mg/kg) for 1 h, were given with a single dose of APAP (300 mg/kg). METHODS: After pre-incubation with limonin (10, 25, 50 µM) for 2 h, L-02 cells were treated with APAP (7.5 mM) for 24 h.The experiments in vitro included MTT assay, Annexin V/PI staining, measurement of reactive oxygen species (ROS), quantitative real-time PCR analysis, Western blot analysis, immunofluorescence microscopy and analysis of LDH activity. Transfection of Nrf2 or Sirt1 siRNA was also conducted in vitro. In vivo, C57BL/6 mice with pre-treatment of limonin (40, 80 mg/kg) or NAC (150 mg/kg) for 1 h, were given with a single dose of APAP (300 mg/kg). Mice were sacrificed at 4, 12 h after APAP poisoning, and analysis of ALT and AST in serum, GSH level in liver tissues, liver histological observation and immunohistochemistry were performed. RESULTS: Limonin increased the cell viability and alleviated APAP-induced apoptosis in hepatocytes. Limonin also inhibited APAP-induced mitochondrial-mediated apoptosis by decreasing the ratio of Bax/Bcl-2, recovery of mitochondrial membrane potential (MMP), inhibiting ROS production and cleavage of caspase-3 in L-02 cells. Moreover, limonin induced activation of Nrf2 and increased protein expression and mRNA levels of its downstream targets, including HO-1, NQO1 and GCLC/GCLM. The inhibition of limonin on apoptosis and promotion on Nrf2 antioxidative pathway were lessened after the application of Nrf2 siRNA. In addition, limonin inhibited NF-κB transcriptional activation, NF-κB-regulated genes and protein expression of inflammatory related proteins iNOS and COX2. Furthermore, limonin increased the protein expression of Sirt1. Sirt1 siRNA transfection confirmed that limonin activated Nrf2 antioxidative pathway and inhibited NF-κB inflammatory response by upregulating Sirt1. Finally, we established APAP-induced liver injury in vivo and demonstrated that limonin alleviated APAP-induced hepatotoxicity by activating Nrf2 antioxidative signals and inhibiting NF-κB inflammatory response via upregulating Sirt1. CONCLUSION: In summary, this study documented that limonin mitigated APAP-induced hepatotoxicity by activating Nrf2 antioxidative pathway and inhibiting NF-κB inflammatory response via upregulating Sirt1, and demonstrated that limonin had therapeutic promise in APAP-induced liver injury.

The Relationship Between Serum Copper and Overweight/Obesity: a Meta-analysis.

The relationship between serum copper (Cu) level and overweight/obesity remains controversial. The purpose of this meta-analysis is to evaluate the relationship. A comprehensive literature search was performed in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases for relevant articles until March 20, 2019. The random-effect model (REM) was adopted to compute the combined standardized mean difference (SMD) with 95% confidence interval (CI). Publication bias was estimated using the visualization of funnel plots and Egger's test. In the end, twenty-one articles were included in the meta-analysis. Compared with controls, serum Cu level was higher in obese children (SMD (95% CI) 0.74 (0.16, 1.32)) and in obese adults (SMD (95% CI) 0.39 (0.02, 0.76)). There was no significant difference in serum Cu between overweight and control groups in children (SMD (95% CI) 1.52 (- 0.07, 3.12)) and in adults (SMD (95% CI) 0.16 (- 0.06, 0.38)). Moreover, subgroup analysis revealed a higher serum Cu level in obese children (SMD (95% CI) 0.90 (0.36, 1.45)) and obese adults (SMD (95% CI) 0.47 (0.05, 0.88)) compared with healthy weight controls. The SMD differs significantly between obese children diagnosed by weight-for-height and controls (SMD (95% CI) 1.56 (0.57, 2.55)), and there was a significant difference of serum Cu level between obese adults diagnosed by BMI (WHO) and controls (SMD (95% CI) 0.54 (0.08, 1.01)). This meta-analysis indicates that a higher serum Cu level might be associated with the risk of obesity in children and adults, and these findings need to be further confirmed.

Glaucocalyxin A reverses EMT and TGF-ß1-induced EMT by inhibiting TGF-ß1/Smad2/3 signaling pathway in osteosarcoma.

Metastatic osteosarcoma usually has an unsatisfactory response to the current standard chemotherapy and causes poor prognosis. Currently, epithelial-mesenchymal transition (EMT) is reported as a critical event in osteosarcoma metastasis. Glaucocalyxin A, a bioactive ent-kauranoid diterpenoid, exerts anti-cancer effect on osteosarcoma by inducing apoptosis in previous study. However, the effect of Glaucocalyxin A on EMT and metastasis of osteosarcoma is unclear. In this study, we investigated the potential mechanisms of Glaucocalyxin A on EMT and metastasis of osteosarcoma. We found that Glaucocalyxin A inhibited migration and invasion of MG-63 and 143B cells. Moreover, Glaucocalyxin A increased the protein and mRNA levels of E-cadherin and decreased the protein and transcription expression of N-cadherin, Vimentin. Glaucocalyxin A also inhibited the protein and mRNA levels of EMT-associated transcription factor including Snail and Slug. Furthermore, Glaucocalyxin A inhibited transforming growth factor-ß1 (TGF-ß1)-induced migration, invasion and EMT of low-metastatic osteosarcoma U2OS cells. Glaucocalyxin A inhibited TGF-ß-induced phosphorylation of Smad 2/3 in osteosarcoma U2OS cells. Finally, we established transplanted metastatic models of highly metastatic osteosarcoma 143B cells. Glaucocalyxin A inhibited lung metastasis in vivo. Interestingly, Glaucocalyxin A increased the protein expression of E-cadherin and reduced the protein expression of N-cadherin and Vimentin. Glaucocalyxin A inhibited the protein expression of Snail and Slug in vivo. In summary, this study demonstrated that Glaucocalyxin A inhibited EMT and TGF-ß1-induced EMT by inhibiting TGF-ß1/Smad2/3 signaling pathway in osteosarcoma. Therefore, Glaucocalyxin A might be a promising candidate against the metastasis of human osteosarcoma.

Breastfeeding and risk of habitual snoring in children: A meta-analysis.

Research regarding the effects of breastfeeding on habitual snoring in children has yielded conflicting results. Therefore, a meta-analysis was carried out to evaluate the effect of breastfeeding on the risk of habitual snoring in children. Relevant studies published in English or Chinese were identified by a search of PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, China Biology Medical literature, and Wanfang databases up to October 2018. Random effects model was used to pool the findings, and results were expressed as odds ratios (OR) with 95% CIs. Eleven studies with 71,622 participants were included in the present meta-analysis. The pooled OR of habitual snoring for more versus less breastfeeding (duration) was 0.74 (95% CI [0.62, 0.90]), and the result remained significant in cohort studies (OR, 0.74; 95%CI [0.66, 0.84]). We found no evidence of publication bias. This meta-analysis of observational studies indicates that breastfeeding for a long time is associated with reduced risk of habitual snoring in children. The finding needs to be investigated in well-designed prospective studies.

The association between serum zinc level and overweight/obesity: a meta-analysis.

PURPOSE: The association between serum zinc level and overweight/obesity remains controversial. Hence, we performed a meta-analysis to summarize the relationships. METHODS: A systematic literature search was performed in PubMed, Web of Science and Embase for relevant English articles up to April 20, 2018. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated with the random-effect model. RESULTS: For children and adults, the results showed that serum zinc level was significantly lower in the cases compared to controls ([SMD (95% CI): - 1.13 (- 2.03, - 0.23), Z = 2.45, P for Z = 0.014; I2 = 97.1%, P for I2 < 0.001] and [SMD (95% CI): - 0.41 (- 0.68, - 0.15), Z = 3.03, P for Z = 0.002; I2 = 62.9%, P for I2 = 0.009], respectively). The difference of serum zinc level between overweight adults and controls was not statistically significant [SMD (95% CI): - 0.09 (- 0.27, 0.09), Z = 0.97, P for Z = 0.334; I2 = 0.0%, P for I2 = 0.411]. In subgroup analyses, a lower serum zinc level in obese children compared with non-obese controls was observed [SMD (95% CI): - 2.14 (- 3.20, - 1.09)], and the SMD differ significantly between obese adults and controls in the case-control studies [SMD (95% CI): - 0.49 (- 0.90, - 0.08)]. CONCLUSION: Our meta-analysis suggested that the serum zinc level was significantly lower in obese children and adults. More large observational studies are required to confirm these results in future research.

Oridonin prevents epithelial-mesenchymal transition and TGF-ß1-induced epithelial-mesenchymal transition by inhibiting TGF-ß1/Smad2/3 in osteosarcoma.

Osteosarcoma is the most common primary bone tumor with highly invasive characteristic and low long-term survival. Recently, epithelial-mesenchymal transition (EMT) is reported as a key event in cancer invasion and metastasis. Oridonin, a bioactive diterpenoid, has been proved to possess anti-cancer effects. However, the effect of oridonin on EMT and metastasis of osteosarcoma is unclear. In this study, we investigated the underlying mechanism of oridonin on EMT and metastasis of osteosarcoma. We found that oridonin inhibited migration and invasion of MG-63 and 143B cells. Moreover, oridonin increased the protein expression of E-cadherin and decreased that of N-cadherin and Vimentin. Oridonin upregulated the transcription of E-cadherin and downregulated N-cadherin and Vimentin. Oridonin inhibited the protein and mRNA levels of Snail and Slug. Furthermore, oridonin inhibited TGF-ß-induced phosphorylation of Smad 2/3, prevented Smad dimer translocation into the nucleus. Finally, we established metastatic models of osteosarcoma 143B cells, and found that oridonin inhibited lung metastasis in vivo. Oridonin increased the protein expression of E-cadherin and reduced N-cadherin and Vimentin. Oridonin inhibited the protein expression of Snail and Slug as well as Smad 2/3 activation. In conclusion, our study demonstrated that oridonin inhibited EMT and TGF-ß1-induced EMT by inhibiting TGF-ß1/Smad2/3 signaling pathway in osteosarcoma.

Glaucocalyxin A exerts anticancer effect on osteosarcoma by inhibiting GLI1 nuclear translocation via regulating PI3K/Akt pathway.

Osteosarcoma, the most common malignant bone tumor with recurring disease or lung metastases, has become one of the leading causes of death in humans. In the current study, we made an investigation on the anticancer effect of glaucocalyxin A, a bioactive ent-kauranoid diterpenoid isolated from Rabdosia japonica var., and unraveled the underlying mechanisms. Here, we found that Glaucocalyxin A inhibited the cell viability of numerous osteosarcoma cells. Our results showed that Glaucocalyxin A exerted the pro-apoptotic effect on human osteosarcoma cells, MG-63 and HOS cells. Glaucocalyxin A induced apoptosis by mitochondrial apoptotic pathway through several steps including increasing the Bax/Bcl-2 ratio, triggering the intracellular reactive oxygen species (ROS) generation, reducing mitochondrial membrane potential (MMP), and inducing cleavage of caspase-9 and caspase-3. We demonstrated that Glaucocalyxin A induced apoptosis via inhibiting Five-zinc finger Glis 1 (GLI1) activation by overexpression and knockdown of GLI1 in vitro. We also found that Glaucocalyxin A inhibited GLI1 activation via regulating phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathway. We further confirmed our findings by using PI3K activator and inhibitor to verify the inhibitory effect of Glaucocalyxin A on PI3K/Akt/GLI1 pathway. Moreover, our in vivo study revealed that glaucocalyxin A possessed a remarkable antitumor effect with no toxicity in the xenograft model inoculated with HOS tumor through the same mechanisms as in vitro. In conclusion, our results suggested that Glaucocalyxin A induced apoptosis in osteosarcoma by inhibiting nuclear translocation of GLI1 via regulating PI3K/Akt signaling pathway. Thus, Glaucocalyxin A might be a potential candidate for human osteosarcoma in the future.

Environmental tobacco smoke exposure and risk of habitual snoring in children: a meta-analysis.

BACKGROUND: The association between environmental tobacco smoke (ETS) exposure and habitual snoring (HS) risk in children remains controversial. Therefore, a meta-analysis was carried out to evaluate and compare the effect of ETS by different family members and prenatal smoke exposure on the risk of HS in children. METHODS: Relevant studies published in English were identified by a search of PubMed, Embase and Web of Science up to December 2017. Random effect model and fixed effect model were used to pool the findings. Restricted cubic splines were used to assess the dose-response relationship. RESULTS: A total of 24 studies with 87 829 participants were included in the present meta-analysis. When comparing ETS exposed with non-ETS exposed, the pooled OR of HS were 1.46 (95% CI, 1.29 to 1.65) for household smoking exposure, 1.45 (95% CI, 1.27 to 1.65) for paternal smoking exposure, 1.87 (95% CI, 1.56 to 2.23) for maternal smoking exposure and 1.95 (95% CI, 1.63 to 2.34) for prenatal tobacco smoke exposure. For dose-response analysis, evidence of a linear association was found between household smoking exposure and HS, and the risk of HS increased by 2.1% (OR=1.02, 95% CI, 1.00 to 1.04, p=0.022) for every 1 cigarette/day increment of smoking by people living with children. CONCLUSIONS: This meta-analysis of observational studies indicates that exposure to ETS, in particularly prenatal tobacco smoke exposure and maternal smoking, is associated with an increased risk of HS.