The urinary level of 2,4,5-trichlorophenol was positively associated with both all-cause and cause-specific mortalities in general adult residents of United States.

Chlorophenols are widespread environmental organic pollutants with harmful effects on human beings. Although relationships between chlorophenols and various dysfunctions/diseases have been reported, the contribution of chlorophenols exposure to mortalities is underdetermined. In this cohort study, we included 4 types of urinary chlorophenols, aiming to estimate associations of chlorophenols exposure with all-cause and cause-specific mortalities. Urinary chlorophenols were examined at baseline of National Health and Nutrition Examination Survey (NHANES) 2003-2010, and adjusted for the urinary creatinine level. Associations between chlorophenols and mortalities were estimated using COX regression analyses, results were shown as hazard ratio (HR) and 95% confidence interval (95% CI). By dividing participants into four subgroups based on quartiles of urinary levels of chlorophenols, associations between mortalities and categorical variables of chlorophenols were estimated. Furthermore, the quantile g-computation analysis was used to estimate the joint effects of 4 chlorophenols on mortalities. Among 5817 adults (2863 men), 1034 were deceased during the follow-up. After adjusted for confounders, 2,4,5-trichlorophenol (2,4,5-TCP) was found to be positively associated with both all-cause (HR = 1.46; 95% CI: 1.16, 1.84) and cardiovascular disease (CVD) mortalities (HR = 1.60; 95% CI: 1.00, 2.55). Compared to the subgroup of the lowest level of chlorophenols, participants in subgroups of higher 2,4,5-TCP levels showed higher risk of all-cause mortality (P-value for trend = 0.003). For CVD mortality, HRs in subgroups of higher levels of 2,4-dichlorophenol (2,4-DCP) and 2,4,6-trichlorophenol (2,4,6-TCP) were statistically significant (P-values for trend were 0.017 for 2,4-DCP and 0.049 for 2,4,6-TCP). The HRs (95% CI) of joint effects of 4 chlorophenols were 1.11 (1.01, 1.21) and 1.32 (1.10, 1.57) for all-cause and CVD-specific mortalities, and 2,4,5-TCP showed the highest weight in joint effects. All of these findings implied that among 4 urinary chlorophenols we included, 2,4,5-TCP might be a sensitive one in associations with mortalities among general populations.

Dietary intakes of methionine, threonine, lysine, arginine and histidine increased risk of type 2 diabetes in Chinese population: does the mediation effect of obesity exist?

BACKGROUND: Published studies have shown positive associations of branched chain and aromatic amino acids with type 2 diabetes mellitus (T2DM), and the findings remain consistent. However, the associations of other essential and semi-essential amino acids, i.e., methionine (Met), threonine (Thr), lysine (Lys), arginine (Arg) and histidine (His), with T2DM remain unknown. Obesity is an important independent risk factor for T2DM, and excessive amino acids can convert into glucose and lipids, which might underlie the associations of amino acids with obesity. Therefore, we aimed to estimate the associations between dietary intakes of these 5 amino acids and T2DM risk, as well as the mediation effects of obesity on these associations, in a Chinese population. METHODS: A total of 10,920 participants (57,293 person-years) were included, and dietary intakes of 5 amino acids were investigated using 24-h dietary recalls. Anthropometric obesity indices were measured at both baseline and the follow-up endpoints. Associations of amino acids with T2DM were estimated using COX regression models, hazard ratios (HRs) and 95% confidence intervals (95% CIs) were shown. The mediation effects of obesity indices were analyzed, and the proportion of the mediation effect was estimated. RESULTS: Higher intakes of the 5 amino acids were associated with increasing T2DM risk, while significant HRs were only shown in men after adjustments. No interaction by gender was found. Regression analyses using quintiles of amino acids intakes showed that T2DM risk was positively associated with amino acids intakes only when comparing participants with the highest intake levels of amino acids to those with the lowest intake levels. Adjusted correlation coefficients between amino acid intakes and obesity indices measured at follow-up endpoints were significantly positive. Mediation analyses showed that mediation effects of obesity indices existed on associations between amino acids intakes and T2DM risk, and the mediation effect of waist circumference remained strongest for each amino acid. CONCLUSIONS: We found positive associations of dietary intakes of Met, Thr, Lys, Arg and His with increasing T2DM risk in general Chinese residents, on which the mediation effect of obesity existed. These findings could be helpful for developing more constructive guidance in the primary prevention of T2DM based on dietary interventions.

Arsenic metabolism, N6AMT1 and AS3MT single nucleotide polymorphisms, and their interaction on gestational diabetes mellitus in Chinese pregnant women.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in N6AMT1 and AS3MT are associated with arsenic (As) metabolism, and efficient As methylation capacity has been associated with diabetes. However, little is known about the gene-As interaction on gestational diabetes mellitus (GDM). OBJECTIVE: This study aimed to explore the individual and combined effects of N6AMT1 and AS3MT SNPs with As metabolism on GDM. METHODS: A cross-sectional study was performed among 385 Chinese pregnant women (86 GDM and 299 Non-GDM). Four SNPs in N6AMT1 (rs1997605 and rs1003671) and AS3MT (rs1046778 and rs11191453) were genotyped. Urinary inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were determined, and the percentages of As species (iAs%, MMA%, and DMA%) were calculated to assess the efficiency of As metabolism. RESULTS: Pregnant women with N6AMT1 rs1997605 AA genotype had lower iAs% (B: 2.11; 95% CI: 4.08, -0.13) and MMA% (B: 0.21; 95% CI: 0.39, -0.04) than pregnant women with GG genotype. The AS3MT rs1046778 and rs11191453 C alleles were negatively associated with iAs% and MMA% but positively associated with DMA%. Higher urinary MMA% was significantly associated with a lower risk of GDM (OR: 0.54; 95% CI: 0.30, 0.97). The A allele in N6AMT1 rs1997605 (OR: 0.46; 95% CI: 0.26, 0.79) was associated with a decreased risk of GDM. The additive interactions between N6AMT1 rs1997605 GG genotypes and lower iAs% (AP: 0.50; 95% CI: 0.01, 0.99) or higher DMA% (AP: 0.52; 95% CI: 0.04, 0.99) were statistically significant. Similar additive interactions were also found between N6AMT1 rs1003671 GG genotypes and lower iAs% or higher DMA%. CONCLUSIONS: Genetic variants in N6AMT1 and efficient As metabolism (indicated by lower iAs% and higher DMA%) can interact to influence GDM occurrence synergistically in Chinese pregnant women.

Association between Excessive Dietary Branched-Chain Amino Acids Intake and Hypertension Risk in Chinese Population.

The dietary intake of branched-chain amino acids (BCAAs) has been reported to be associated with both elevated blood pressure (BP) and hypertension risk, while published findings were inconsistent, and the causality has never been well disclosed. We performed this prospective study aiming to find out the relationship between dietary BCAAs intake and hypertension risk in the Chinese population. A total of 8491 participants (40,285 person-years) were selected. The levels of dietary BCAAs intake were estimated using the 24-h Food Frequency Questionnaire. Associations of both BP values and hypertension risk with per standard deviation increase of BCAAs were estimated using linear and COX regression analysis, respectively. The hazard ratios and 95% confidence interval were given. Restricted cubic spline analysis (RCS) was used to estimate the nonlinearity. Both systolic and diastolic BP values at the end points of follow-up were positively associated with dietary BCAAs intake. Positive associations between BCAAs intake and hypertension risk were shown in both men and women. By performing a RCS analysis, the nonlinear relationship between BCAAs intake and hypertension was shown. As the intake levels of Ile, Leu, and Val, respectively, exceeded 2.49 g/day, 4.91 g/day, and 2.88 g/day in men (2.16 g/day, 3.84 g/day, and 2.56 g/day in women), the hypertension risk increased. Our findings could provide some concrete evidence in the primary prevention of hypertension based on dietary interventions.

Metabolic characteristics related to the hazardous effects of environmental arsenic on humans: A metabolomic review.

Arsenic (As) is a toxic metalloid exist ubiquitously in environment. Epidemiological studies and laboratory animal studies have verified that As damages multiple organs or tissues in the body and is associated with a variety of diseases. Changes in metabolites usually indicate disturbances in metabolic pathways and specific metabolites are considered as biomarkers of diseases or drugs/toxins or environmental effects. Metabolomics is the quantitative measurement of the dynamic multi-parameter metabolic responses of biological systems due to pathophysiological or genetic changes. Current years, some metabolomic studies on the hazardous effect of environmental As on humans have been reported. In this paper, we first overviewed the metabolomics studies of environmental As exposure in humans since 2011, emphasizing on the data mining process of metabolic characteristics related to the hazardous effects of environmental As on humans. Then, the relationship between metabolic characteristics and the toxic mechanism of environmental As exposure in humans were discussed, and finally, the prospects of metabolomics studies on populations exposed to environmental As were put forward. Our paper may shed light on the study of mechanisms, prevention and individualized treatment of As poisoning.

A prospective cohort study on the association of lean body mass estimated by mid-upper arm muscle circumference with hypertension risk in Chinese residents.

The associations of lean body mass (LBM) with elevated blood pressure (BP) and hypertension were controversial, and the causalities have never been shown. Mid-upper arm muscle circumference (MAMC), an easily obtained anthropometric measurement, could provide an accurate estimate for LBM. Therefore, a prospective cohort study in general Chinese residents aiming to find out the relationship between LBM estimated using MAMC and hypertension risk was performed. Eight thousand one hundred eighty-five eligible participants were included in the baseline analysis, among whom 3442 were subsequently selected into cohort analysis. MAMC was calculated using mid-upper arm circumference (MUAC) and triceps skinfold thickness (TST). Associations of MAMC with BP values and hypertension prevalence were estimated by linear and logistic regression models. Associations with hypertension incidence were estimated by COX regression models, hazard ratio (HR) and 95% confidence interval (CI) were given. Nonlinear relationship between MAMC and hypertension risk was estimated using restricted cubic spline method. Standardized coefficients of MUAC and TST were compared to estimate their strengths of associations with hypertension. Baseline analysis showed that after adjusted for confounders, the increase of systolic BP per standard deviation (SD) of MAMC were 1.97 mmHg (95%CI: 1.46, 2.48) and 1.63 mmHg (95%CI: 1.10, 2.16) respectively in men and women, and the increases of diastolic BP per SD were 1.58 mmHg (95%CI: 1.23, 1.92) and 1.08 mmHg (95%CI: 0.74, 1.42). Additionally, the association of MAMC with the prevalence of hypertension were also found in both men and women (OR = 1.36, 95%CI: 1.26, 1.47 in men; OR = 1.33, 95%CI: 1.22, 1.44 in women). Cohort analysis showed that MAMC increased the risk of hypertension (HR = 1.10, 95%CI: 1.01, 1.19 for men; HR = 1.15, 95%CI: 1.06, 1.26 for women), and a trend of J-shaped relationship was found. Additionally, the stronger associations of MUAC with both BP values and hypertension than that of TST were found in both baseline and cohort analyses. Findings in our study implied that we cannot neglect the capacity of LBM in predicting hypertension risk, and LBM estimates should be recommended in general health surveys or examinations.

Joint effect of urinary arsenic species and serum one-carbon metabolism nutrients on gestational diabetes mellitus: A cross-sectional study of Chinese pregnant women.

BACKGROUND: Growing evidence indicates that arsenic (As) exposure can increase the risk of gestational diabetes mellitus (GDM). However, little is known about As species and GDM and the combined effect of As and one-carbon metabolism (OCM) on GDM. OBJECTIVES: We aimed to examine the associations between As species and GDM and evaluate the potential interactions of folate, vitamin B12, and homocysteine (Hcy) with As species on GDM prevalence. METHOD: We measured levels of arsenite (As3+), arsenate (As5+), dimethylarsinic acid (DMA), and arsenobetaine (AsB) species in urine and folate, vitamin B12, and Hcy in serum from 396 pregnant women in Tianjin, China. The diagnosis of GDM was based on an oral glucose tolerance test. Associations of As species in urine with GDM were evaluated using generalized linear models (GLMs) and Bayesian kernel machine regression (BKMR). Additive interactions of As and OCM with GDM were estimated by determining the relative excess risk due to interaction (RERI). RESULTS: Of the 396 pregnant women, 89 were diagnosed with GDM. Continuous increases in urinary inorganic As were associated with GDM in the GLMs, with adjusted odds ratios of 2.12 (95% CI: 0.96, 4.71) for As3+, and 0.27 (95% CI: 0.07, 0.98) for As5+. The BKMR in estimating the exposure-response functions showed that As3+ and AsB were positively associated with GDM. However, As5+ showed a negative relationship with GDM. Although the additive interactions between As exposure and OCM indicators were not significant, we found that pregnant women with higher urinary As3+ and total As accompanied by lower serum vitamin B12 were more likely to have higher odds of GDM (3.12, 95% CI: 1.32, 7.38 and 3.10, 95% CI: 1.30, 7.38, respectively). CONCLUSIONS: Our data suggest a positive relation between As3+ and GDM but a negative relation between As5+ and GDM. Potential additive interaction of As and OCM with GDM requires further investigation.

Interactions of arsenic metabolism with arsenic exposure and individual factors on diabetes occurrence: Baseline findings from Arsenic and Non-Communicable disease cohort (AsNCD) in China.

The interaction between arsenic metabolism and potential modifiers on the risk of diabetes is unclear. This research aimed to investigate arsenic metabolism and diabetes prevalence and to identify the interactive effects of arsenic metabolism with some risk factors on diabetes in a Chinese population. A baseline cross-sectional survey was performed in two areas with groundwater arsenic contamination in China. Arsenic levels in water and arsenic metabolites in urine were analyzed. The proportions of each arsenic metabolite (inorganic arsenic [iAs%], monomethylarsonic acid [MMA%], and dimethylarsinic acid [DMA%]) were computed to evaluate arsenic metabolism. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association between arsenic and diabetes. Interaction on the additive scale between arsenic methylation index and effect modifier was evaluated by calculating the relative excess risk due to interaction (RERI). Compared with participants in the lower tertile of MMA%, participants in the middle and upper tertiles of MMA% were less prone to diabetes (OR: 0.47 and 0.31, respectively). However, participants in the upper tertiles of urinary DMA% (OR: 3.18) were more likely to have diabetes than those participants in the lower tertiles. The stratified analyses revealed that a one-unit increase in DMA% was associated with higher odds of diabetes in females (OR: 1.06, 95% CI: 1.01, 1.11), older people (OR: 1.05, 95% CI: 1.00, 1.10), and subjects with body mass index (BMI) under 25 kg/m2 (OR: 1.07, 95% CI: 1.01, 1.14). The additive interactions between DMA% and female gender (RERI: 0.40, 95% CI: 0.01, 11.88), DMA% and age (RERI: 0.02, 95% CI: 0.01, 8.85), as well as DMA% and BMI (RERI: 0.49, 95% CI: 0.01, 9.62), were statistically significant. In conclusion, efficient arsenic metabolism is associated with higher odds of diabetes. Urinary DMA% and individual factors interact to synergistically influence diabetes occurrence in the Chinese population.

The association of wrist circumference with hypertension in northeastern Chinese residents in comparison with other anthropometric obesity indices.

BACKGROUND: Wrist circumference (WrC) is an easily obtained measure in estimating the body frame and regional fat distribution, and has increasingly used as an obesity index. The aim of our study is to estimate the association of WrC with elevated blood pressure (BP) among northeastern Chinese community-dwelling residents, and compare the strength of this association to other anthropometric obesity indices. METHODS: A total of 2,331 adult participants (761 male participants, and 1,570 female participants) were included. WrC and other five generally used obesity indices, including body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and neck circumference (NC) were measured. Hypertension was defined as systolic blood pressure (SBP)/diastolic blood pressure (DBP) ≥140/90 mmHg or anti-hypertensive medication use. Multivariable linear and logistic regression models were performed to identify associations of BP and hypertension with per standard deviation (SD) increase of obesity indices. Areas under receiver operative characteristic curves (AUC) were calculated to compare the predicting capacity of WrC and other obesity indices on hypertension. RESULTS: All of the six obesity indices were positively associated with both SBP and DBP after adjustment for age and gender (P-values of associations of SBP with obesity indices were 0.043 for WrC, and <0.001 for other five indices; P-values of associations of DBP with obesity indices were 0.011 for WrC, 0.031 for WHR, and <0.001 for other four indices), while the association between SBP and WrC showed no statistically significant after further adjusted for life-style and metabolic risk factors (P-value was 0.062). The increases of both SBP and DBP per SD increase of BMI were the largest. The positive associations of five obesity indices but WHR with hypertension were observed after adjustment for all risk factors (P-values were 0.024 for WrC, 0.064 for WHR and <0.001 for other four indices). However, the odd ratios (OR) of WrC was the smallest, while BMI was the largest. Consistently, the AUC of BMI was the largest and statistically larger than that observed for WrC (P-value <0.001). CONCLUSIONS: WrC was associated with hypertension among northeastern Chinese populations. However, the association was not stronger than the other generally used indices, particularly BMI.

Investigation of inflammation inducing substances in PM2.5 particles by an elimination method using thermal decomposition.

The substances associated with PM2.5-induced inflammatory response were investigated using an elimination method. PM2.5 were heated at temperatures of 120, 250, and 360°C. The results demonstrated microbial substances such as LPS and b-glucan, and chemicals including BaP, 1,2-NQ, and 9,10-PQ were reduced drastically in PM2.5 heated at 120°C. On the other hand, DBA, 7,12-BAQ, and BaP-1,6-Q were not noticeably reduced. Most of these substances had disappeared in PM2.5 heated at 250°C and 360°C. Metals (eg, Fe, Cu, Cr, Ni) in PM2.5 exhibited a slight thermo-dependent increase. RAW264.7 macrophages with or without NAC were exposed to unheated PM2.5, oxidative stress-related and unrelated inflammatory responses were induced. PM2.5-induced lung inflammation in mice is caused mainly by thermo-sensitive substances (LPS, b-glucan, BaP, 1,2-NQ, 9,10-PQ, etc.). Also, a slight involvement of thermo-resistant substances (DBA, 7,12-BAQ, BaP-1,6-Q, etc.) and transition metals was observed. The thermal decomposition method could assist to evaluate the PM2.5-induded lung inflammation.

Chronic arsenic exposure in drinking water interferes with the balances of T lymphocyte subpopulations as well as stimulates the functions of dendritic cells in vivo.

The immunomodulatory properties of arsenic are nowadays supposed be associated with pathological injuries of this toxicant and the details have not been clarified. Our objective was to explore inflammation, differentiation of diverse T cell subsets, as well as the phenotypic molecules and functions of dendritic cells (DCs) by chronic arsenic exposure in vivo. We exposed different concentrations of arsenic (0, 0.1, 1 and 10 mg/L) in drinking water for 6 and 12 months in C57BL/6 mice. We first confirmed that low levels of arsenic induced excess inflammation evidenced by accumulation of macrophages and lymphocytes in bronchoalveolar lavage fluid (BALF), secretion of pro-inflammatory cytokine IL-1ß in BALF and serum, as well as histological analysis. Flow cytometry analysis revealed that arsenic disturbed CD4/CD8 T-cell ratio in isolated pneumonocytes and splenocytes, as well as enhanced IFN-γ and reduced IL-4 in spleen. The mRNA expressions of transcription factors (T-bet, GATA3, ROR-γt) and cytokines (IFN-γ, IL-4, IL-10, IL-23, IL-22) showed the imbalanced Th1/Th2/Th17 differentiation in arsenic exposed lung and spleen. We further testified that arsenic enhanced the percentages of CD11c+ DCs, and promoted the expressions of antigen presentation molecule MHC II and cytokine IL-12, co-stimulatory molecules (CD86, CD80), and chemokine receptors (CCR7, CCR5) in vivo. Moreover, arsenic activated the expressions of immune-related MAPKs and NF-κB. Taken together, our study here demonstrated that chronic arsenic exposure could disrupt the immune homeostasis in vivo possibly by interfering with the differentiation of Th1/Th2/Th17 subsets as well as the function of DCs.

Role of iron and oxidative stress in the exacerbation of allergic inflammation in murine lungs caused by urban particulate matter <2.5 µm and desert dust.

Simultaneous exposure of lipopolysaccharide (LPS) and urban particulate matter <2.5 µm (PM2.5) or desert dust exacerbated murine asthma. In the present study, the role of iron (Fe) contained in particles and oxidative stress was investigated using Fe chelator deferoxamine (DFO) and oxidative stress scavenger N-acetylcysteine (NAC) in a murine asthma model exacerbated by LPS + PM2.5 or LPS + Asian sand dust (ASD). When BALB/c mice were intratracheally challenged with ovalbumin (OVA) + LPS and either urban PM2.5 or ASD, LPS + PM2.5 and LPS + ASD caused exacerbation of OVA-induced lung eosinophilia along with T-helper 2 cytokine and eosinophil-relevant chemokine production in bronchoalveolar lavage fluid as well as the production of OVA-specific IgE in serum. LPS + PM2.5 with NAC tended to reduce the lung eosinophilia compared to the LPS + PM2.5 host, whereas LPS + PM2.5 with DFO did not reduce them. LPS + ASD with NAC moderately reduced the lung eosinophilia compared to the LPS + ASD host. LPS + ASD with DFO drastically reduced the lung eosinophilia compared to the LPS + ASD host. The concentration of Fe in urban PM2.5 and ASD were almost the same. However, the concentrations of trace metals Pb, Cu, As, Ni, Cr, Mo, Sb, Co, Se and Cd were greater in PM2.5 than in ASD. These results suggested that Fe and oxidative stress are at least partly involved in lung eosinophilia exacerbation caused by LPS + ASD. However, trace metals (except Fe) might also be involved in lung eosinophilia exacerbated by LPS + PM2.5.

Co-exposure to lipopolysaccharide and desert dust causes exacerbation of ovalbumin-induced allergic lung inflammation in mice via TLR4/MyD88-dependent and -independent pathways.

BACKGROUND: Lipopolysaccharide (LPS) often presents in high concentrations in particulate matter (PM), few studies have reported the enhancing effects of both LPS and PM on airway inflammation in mice and the role of toll-like receptors (TLRs) in this process. Asian sand dust (ASD) is observed most frequently during the spring. This study aimed to clarify the role of TLRs in murine lung eosinophilia exacerbated by ASD and LPS. METHODS: The effects of LPS and ASD co-treatment on ovalbumin (OVA)-induced lung eosinophilia were investigated using wild-type (WT), TLR2-/-, TLR4-/-, and adaptor protein myeloid differentiation factor 88 (MyD88)-/- BALB/c mice. ASD was heated (H-ASD) to remove the toxic organic substances. WT, TLR2-/-, TLR4-/- and MyD88-/- BALB/c mice were intratracheally instilled with four different combinations of LPS, H-ASD and OVA treatment. Subsequently, the pathological changes in lungs, immune cell profiles in bronchoalveolar lavage fluid (BALF), inflammatory cytokines/chemokines levels in BALF and OVA-specific immunoglobulin (Ig) in serum were analyzed. RESULTS: In WT mice, H-ASD + LPS exacerbated OVA-induced lung eosinophilia. This combination of treatments increased the proportion of eosinophils and the levels of IL-5, IL-13, eotaxin in BALF, as well as the production of OVA-specific IgE and IgG1 in serum compared to OVA treatment alone. Although these effects were stronger in TLR2-/- mice than in TLR4-/- mice, the expression levels of IL-5, IL-13, eotaxin were somewhat increased in TLR4-/- mice treated with OVA + H-ASD + LPS. In MyD88-/- mice, this pro-inflammatory mediator-induced airway inflammation was considerably weak and the pathological changes in lungs were negligible. CONCLUSIONS: These results suggest that LPS and H-ASD activate OVA-induced Th2 response in mice, and exacerbate lung eosinophilia via TLR4/MyD88, TLR4/TRIF and other TLR4-independent pathways.

Gender Stratified Analyses of the Association of Skinfold Thickness with Hypertension: A Cross-Sectional Study in General Northeastern Chinese Residents.

The association of hypertension with skinfold thickness (ST) in adults is not clear. Our study was aimed at finding out the association of hypertension with ST in different gender and obesity categories. This is a cross-sectional study based on 2336 Chinese residents (767 men). Both subscapular skinfold thickness (SST) and tricep skinfold thickness (TST) were examined. We estimated the association of hypertension with per SD increase of SST and TST using multivariable logistic regression analyses in men and women. Six subgroups were stratified using cutoff points of body mass index (BMI) and ST: larger and smaller ST in normal weight (BMI < 24 kg/m²), overweight (24 kg/m² ≤ BMI < 28 kg/m²) and obesity (BMI ≥ 28 kg/m²), respectively. The association of hypertension with ST was only shown in women after adjustment for other risk factors. Among women of the normal weight subgroup, higher prevalence of hypertension was shown in those with larger ST. No difference of the prevalence of hypertension was found between women with larger ST in the normal weight subgroup and those with smaller ST in overweight or obesity subgroups. Our study suggested that even for people with normal weight, it was necessary to monitor the subcutaneous fat using ST for preventing hypertension at least in general Chinese women.

Effects of Nrf2 deficiency on arsenic metabolism in mice.

Inorganic arsenic (iAs) is a known toxicant and carcinogen. Worldwide arsenic exposure has become a threat to human health. The severity of arsenic toxicity is strongly correlated with the speed of arsenic metabolism (methylation) and clearance. Furthermore, oxidative stress is recognized as a major mechanism for arsenic-induced toxicity. Nuclear factor-E2-related factor 2 (Nrf2), a key regulator in cellular adaptive antioxidant response, is clearly involved in alleviation of arsenic-induced oxidative damage. Multiple studies demonstrate that Nrf2 deficiency mice are more vulnerable to arsenic-induced intoxication. However, what effect Nrf2 deficiency might have on arsenic metabolism in mice is still unknown. In the present study, we measured the key enzymes involved in arsenic metabolism in Nrf2-WT and Nrf2-KO mice. Our results showed that basal transcript levels of glutathione S-transferase omega 2 (Gsto2) were significantly higher and GST mu 1 (Gstm1) lower in Nrf2-KO mice compared to Nrf2-WT control. Arsenic speciation and methylation rate in liver and urine was then studied in mice treated with 5mg/kg sodium arsenite for 12h. Although there were some alterations in arsenic metabolism enzymes between Nrf2-WT and Nrf2-KO mice, the Nrf2 deficiency had no significant effect on arsenic methylation. These results suggest that the Nrf2-KO mice are more sensitive to arsenic than Nrf2-WT mainly because of differences in adaptive antioxidant detoxification capacity rather than arsenic methylation capacity.

Interactions of homocysteine and conventional predisposing factors on hypertension in Chinese adults.

This study aimed to investigate whether conventional predisposing factors modify the associations of homocysteine with blood pressure levels and hypertension. A total of 2615 adults were recruited from Liaoning province. An elevated homocysteine level was significantly associated with increased hypertension risk and blood pressure (all P<.05). Interaction analyses showed that homocysteine acted synergistically with age, overweight/obesity, dyslipidemia, and family history of hypertension to affect hypertension risk, and the relative excess risk due to interaction was 1.21 (95% confidence interval, 0.07-2.35), 0.72 (95% confidence interval, 0.07-1.36), 0.45 (95% confidence interval, 0.06-0.85), and 1.87 (95% confidence interval, 0.77-2.97), respectively. Increases in blood pressure were higher in patients who were overweight/obese or had a family history of hypertension than in their counterparts (all Pinteraction <.05). This study provides some strong evidence for interactions of homocysteine with conventional predisposing factors on hypertension.

Urban PM2.5 exacerbates allergic inflammation in the murine lung via a TLR2/TLR4/MyD88-signaling pathway.

Nevertheless its mechanism has not been well explained yet, PM2.5 is recognized to exacerbate asthma. In the present study, the roles of toll-like receptor (TLR) 2, TLR4 and MyD88, in exacerbation of allergen-induced lung eosinophilia caused by urban PM2.5 was investigated. TLR2-, TLR4-, MyD88-deficient and WT BALB/c mice were intratracheally challenged with PM2.5 +/- ovalbumin (OVA) four times at 2-week intervals. PM2.5 increased neutrophil numbers and KC in bronchoalveolar lavage fluid and caused slight peribronchiolar inflammation in WT mice. However, these changes were attenuated, but not completely suppressed in gene-deficient mice, especially in MyD88-/- mice. In WT mice, PM2.5 + OVA exacerbated OVA-related lung eosinophilia. This exacerbation includes increase of IL-5, IL-13, eotaxin and MCP-3; infiltration of eosinophils into the airway submucosa; proliferation of goblet cells in the airway epithelium; and the production of antigen-specific IgE and IgG1 in serum. All these effects were stronger in TLR2-/- mice than in TLR4-/- mice. In MyD88-/- mice, this pro-inflammatory mediator-inducing ability was considerably weak and lung pathology was negligible. These results suggest that urban PM2.5 may exacerbate allergic inflammation in the murine lung via a TLR2/TLR4/MyD88-signaling pathway. PM2.5-bound trace microbial elements, such as lipopolysaccharide may be a strong candidate for exacerbation of murine lung eosinophilia.

Imbalanced immune responses involving inflammatory molecules and immune-related pathways in the lung of acute and subchronic arsenic-exposed mice.

Inorganic arsenic has been claimed to increase the risk of pulmonary diseases through ingestion, as opposed to inhalation, which makes it a unique and intriguing environmental toxicant. However, the immunotoxic effects of lung, one of the targets of arsenic exposure, have not been extensively investigated in vivo. In the present study, we first confirmed that 2.5, 5 and 10mg/kg NaAsO2 orally for 24h dose-dependently triggered the infiltration of neutrophils, lymphocytes and macrophages in BALF. Not only the transcription activity, but also the secretion of proinflammatory cytokines IL-1ß, IL-6 and TNF-α were consistently raised in the lung and BALF of acute arsenic-exposed mice. Acute oral administration of NaAsO2 also raised pulmonary MPO activity and mRNA levels of chemokine Mip-2 and Mcp-1. Meanwhile, obvious histopathological damages with inflammatory cells infiltration and erythrocyte aggregation around the capillaries were verified in the lung of mice drank arsenic-rich water freely for 3 months. Furthermore, we affirmed notable disturbance of CD4+ T-cell differentiation in the lung of acute arsenic-exposed mice, as demonstrated by up-regulated mRNA levels of regulator Gata3 and cytokine Il-4 of Th2, enhanced Foxp3 and Il-10 of Treg, down-regulated T-bet and Ifn-γ of Th1, as well as lessened Ror-γt and Il-23 of Th17. However, impressive elevation of cytokine Ifn-γ and Il-23, as well as moderate enhancement of Il-4 and Il-10 were found in the lung by subchronic arsenic administration. Finally, our present study demonstrated that both a single and sustained arsenic exposure prominently increased the expression of immune-related p38, JNK, ERK1/2 and NF-κB proteins in the lung tissue. While disrupting the pulmonary redox homeostasis by increasing MDA levels, exhausting GSH and impaired enzyme activities of CAT and GSH-Px, antioxidant regulator NRF2 and its downstream targets HO-1 and GSTO1/2 were also up-regulated by both acute and subchronic arsenic treatment. Conclusively, our present study demonstrated both acute and subchronic oral administration of arsenic triggers multiple pulmonary immune responses involving inflammatory molecules and T-cell differentiation, which might be closely associated with the imbalanced redox status and activation of immune-related MAPKs, NF-κB and anti-inflammatory NRF2 pathways.

Neck circumference associated with arterial blood pressures and hypertension: A cross-sectional community-based study in northern Han Chinese.

Although several studies have investigated the associations of neck circumference (NC) with arterial blood pressures (BPs) and hypertension, no such studies have been conducted among Northern Chinese population. Between April and June 2015, a total of 2631 subjects aged ≥35 years old were recruited from Northeastern China. NC and arterial BPs were measured by trained personnel. Generalized linear and logistic regression analyses were applied to examine the associations of NC with arterial BPs and hypertension risk. The optimal cut-off points of NC for predicting hypertension were assessed by the receiver operating characteristic analysis. We found that NC was significantly associated with arterial BPs and hypertension risk in the Northeastern Chinese adults, even after adjusting for many covariates including body mass index, waist circumference or waist-to-hip ratio. The optimal cut-off values for NC to predict hypertension differed with sex, age, and body mass index. Our study suggests that NC may play an independent role in predicting hypertension beyond the classical anthropometric indices, and that it could be used as a valuable anthropometric measurement for routine assessment in primary care clinics and future epidemiological studies.

PM2.5-induced lung inflammation in mice: Differences of inflammatory response in macrophages and type II alveolar cells.

Particulate matter 2.5 (