Publications by authors named "Changchun Hou"

36 Publications

Health risks of PM-bound polycyclic aromatic hydrocarbon (PAH) and heavy metals (PPAH&HM) during the replacement of central heating with urban natural gas in Tianjin, China.

Environ Geochem Health 2021 Jul 21. Epub 2021 Jul 21.

Department of Environment and Health, Tianjin Centers for Disease Control and Prevention, No.6 Huayue Rd, Tianjin, China.

To investigate the health effects of fine particulate matter (≤ 2.5 μm in aerodynamic diameter; PM)-bound heavy metals and polycyclic aromatic hydrocarbons (PAHs) before and after the implementation of the Urban Natural Gas Heating Project (UNGHP), the lifetime cancer risks, hazard quotients (HQs) of heavy metals and PAHs were calculated. Seven kinds of heavy metals (Al, As, Cd, Cr, Mn, Ni and Se) and 12 kinds of PAHs including acenaphthylene (ANY), acenaphthene (ANA), fluoranthene (FLT), pyrene (PYR), chrysene (CHR), benz[a]anthracene (BaA), benzo[b]fluoranthene (BbF), benzo[k]fluoranthene (BkF), benzo[a]pyrene (BaP), dibenz[a,h]anthracene (DBA), benzo[ghi]perylene (BPE) and indeno[1,2,3-cd]pyrene (IPY) were analyzed and used for the health risk assessments. It was found that HQ of Mn fell from 1.09 in the coal-burning period to 0.72 in the gas-burning period in the suburban area. And lifetime cancer risks of PAHs fell from 35.7 × 10 in the coal-burning period to 17.22 × 10 in the gas-burning period in the urban area. It could be concluded that, during the gas-burning period, downward trends were observed for the lifetime cancer risks and HQs of most kinds of heavy metals and PAHs in all regions of Tianjin compared to those during the coal-burning period. The UNGHP was effective, and we should also take other measures to control the pollution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10653-021-01040-8DOI Listing
July 2021

Fluoride exposure and children's intelligence: Gene-environment interaction based on SNP-set, gene and pathway analysis, using a case-control design based on a cross-sectional study.

Environ Int 2021 Oct 4;155:106681. Epub 2021 Jun 4.

Department of Epidemiology and Biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. Electronic address:

Background: Excessive fluoride exposure has been associated with intelligence loss, but little is known about gene-fluoride interactions on intelligence at SNP-set, gene and pathway level.

Objectives: Here we conducted a population-based study in Chinese school-aged children to estimate the associations of fluoride from internal and external exposures with intelligence as well as to explore the gene-fluoride interactions on intelligence at SNP-set, gene and neurodevelopmental pathway level.

Methods: A total of 952 resident children aged 7 to 13 were included in the current study. The fluoride contents in drinking water, urine, hair and nail were measured using the ion-selective electrode method. LASSO Binomial regression was conducted to screen the intelligence-related SNP-set. The gene-fluoride interactions at gene and pathway levels were detected by the Adaptive Rank Truncated Product method.

Results: The probability of high intelligence was inversely correlated with fluoride contents in water, urine, hair and nail (all P < 0.001). The SNP-set based on rs3788319, rs1879417, rs57377675, rs11556505 and rs7187776 was related to high intelligence (P = 0.001) alone and by interaction with water, urinary and hair fluoride (P = 0.030, 0.040, 0.010), separately. In gene level, CLU and TOMM40 interacted with hair fluoride (both P = 0.017) on intelligence. In pathway level, Alzheimer disease pathway, metabolic pathway, signal transduction pathway, sphingolipid signaling pathway and PI3K-AKT signaling pathway interacted with fluoride on intelligence in men.

Conclusions: Our study suggests that fluoride is inversely associated with intelligence. Moreover, the interactions of fluoride with mitochondrial function-related SNP-set, genes and pathways may also be involved in high intelligence loss.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envint.2021.106681DOI Listing
October 2021

Moderating Role of TSHR and PTPN22 Gene Polymorphisms in Effects of Excessive Fluoride on Thyroid: a School-Based Cross-Sectional Study.

Biol Trace Elem Res 2021 May 28. Epub 2021 May 28.

Dazhangzhuang Community Health Service Center, 31 Yongkang Road, Beichen District, Tianjin, 300400, People's Republic of China.

We aimed to investigate the relationship between the effects excessive of fluoride on thyroid health in children and the moderating role of thyroid stimulating hormone receptor (TSHR) or protein tyrosine phosphatase nonreceptor-22 (PTPN22) gene polymorphisms. Four hundred thirteen children (141 with dental fluorosis and 198 boys) were enrolled from both historical endemic and non-endemic areas of fluorosis in Tianjin, China. The fluoride exposure levels, thyroid health indicators, and TSHR (rs2268458) and PTPN22 (rs3765598) polymorphisms were examined. Multiple logistic models were applied to evaluate the relationship between dental fluorosis and thyroid abnormalities. Children over 9 year old with dental fluorosis have lower FT and TGAb levels and thyroid volume and higher TPOAb levels (all P < 0.05). In overall participants, children with dental fluorosis were more likely to have thyroid antibody single positive issues (adjusted P = 0.039) and less likely to have a goiter according to age or body surface area (age or BSA) (adjusted P = 0.003); In the TSHR (rs2268458) SNP = CC/CT or PTPN22 (rs3765598) SNP = CC subgroup, dental fluorosis may cause thyroid antibody single positive (adjusted P = 0.036; adjusted P = 0.002); in the TSHR (rs2268458) SNP = TT or PTPN22 (rs3765598) SNP = CC subgroup, dental fluorosis may protect children from goiter (age or BSA) (adjusted P = 0.018; adjusted P = 0.013). Excessive fluoride may induce thyroid antibody single positive and reduce goiter in children. Heterogeneity exists in the relationship between excessive fluoride and thyroid antibody single positive or goiter issues across children carrying different TSHR (rs2268458) or PTPN22 (rs3765598) genotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12011-021-02753-8DOI Listing
May 2021

Prognostic Significance of B-Type Natriuretic Peptide in Patients With Left Ventricular Thrombus.

Front Cardiovasc Med 2021 29;8:667908. Epub 2021 Apr 29.

Department of Cardiology, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China.

There is sparse information on the prognostic value of B-type natriuretic peptide (BNP) for the outcomes in patients with left ventricular thrombus (LVT). Patients diagnosed with LVT by transthoracic echocardiography between November 2009 to July 2020 at our institution were included. The endpoints were all-cause mortality and systemic embolism. Ninety-two subjects were finally included in the study. The mean age of the cohort was 56.73 ± 14.12, and 80.4% of the patients were male. The median BNP (1st quartile-3rd quartile) was 437.5 (112.74-1317.5). The total all-cause mortality rate was 30.44% (28/92), and the 1-year, 2-year, and 3-year cumulative survival rates were 85.4, 75.5, and 66.5%, respectively. Systemic embolism was identified in 10 subjects. COX multivariate analysis showed that Log BNP (HR, 4.16; 95%CI, 1.81-9.56; = 0.001) and BMI (HR, 0.86; 95%CI, 0.73-0.99; = 0.048) were significantly associated with all-cause mortality. In addition, patients with BNP levels in the upper median (≥ 437.5 pg/ml) had significantly higher all-cause mortality rate compared to those with lower median BNP (<437.5 pg/ml; = 0.004). The area under the receiver operating characteristic curve for BNP and all-cause mortality was 0.71. In the linear trend test, BNP quartiles were significantly related to all-cause mortality in all models, and the -values for trend in models 1, 2, and 3 were 0.005, 0.006, and 0.048, respectively. BNP level is a prognostic factor for all-cause mortality in LVT patients, and elevated BNP is indicative of a higher risk of LVT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2021.667908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116499PMC
April 2021

Fluoride exposure, dopamine relative gene polymorphism and intelligence: A cross-sectional study in China.

Ecotoxicol Environ Saf 2021 Feb 24;209:111826. Epub 2020 Dec 24.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing 100191, PR China. Electronic address:

Background: Excessive fluoride exposure is related to adverse health outcomes, but whether dopamine (DA) relative genes are involved in the health effect of low-moderate fluoride exposure on children's intelligence remain unclear.

Objectives: We conducted a cross-sectional study to explore the role of DA relative genes in the health effect of low-moderate fluoride exposure in drinking water.

Methods: We recruited 567 resident children, aged 6-11 years old, randomly from endemic and non-endemic fluorosis areas in Tianjin, China. Spot urine samples were tested for urinary fluoride concentration, combined Raven`s test was used for intelligence quotient test. Fasting venous blood were collected to analyze ANKK1 Taq1A (rs1800497), COMT Val158Met (rs4680), DAT1 40 bp VNTR and MAOA uVNTR. Multivariable linear regression models were used to assess associations between fluoride exposure and IQ scores. We applied multiplicative and additive models to appraise single gene-environment interaction. Generalized multifactor dimensionality reduction (GMDR) was used to evaluate high-dimensional interactions of gene-gene and gene-environment.

Results: In adjusted model, fluoride exposure was inversely associated with IQ scores (β = -5.957, 95% CI: -9.712, -2.202). The mean IQ scores of children with high-activity MAOA genotype was significantly lower than IQ scores of those with low-activity (P = 0.006) or female heterozygote (P = 0.016) genotype. We detected effect modification by four DA relative genes (ANKK1, COMT, DAT1 and MAOA) on the association between UF and IQ scores. We also found a high-dimensional gene-environment interaction among UF, ANKK1, COMT and MAOA on the effect of IQ (testing balanced accuracy = 0.5302, CV consistency: 10/10, P = 0.0107).

Conclusions: Our study suggests DA relative genes may modify the association between fluoride and intelligence, and a potential interaction among fluoride exposure and DA relative genes on IQ.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2020.111826DOI Listing
February 2021

Prognostic Value of Preoperative Hemoglobin Levels for Long-Term Outcomes of Acute Type B Aortic Dissection Post-thoracic Endovascular Aortic Repair.

Front Cardiovasc Med 2020 5;7:588761. Epub 2020 Nov 5.

Department of Cardiology, Institute of Cardiovascular Diseases of People's Liberation Army, Chongqing, China.

There is scant information available about the prognostic value of preoperative hemoglobin (Hb) levels on the long-term outcomes of acute type B aortic dissection (ABAD) following thoracic endovascular aortic repair (TEVAR). A retrospective analysis of consecutive patients from 2010 to 2018 regarding the relationship between Hb level and long-term outcomes was conducted. The primary endpoint was all-cause mortality. Major adverse cardiovascular events (MACEs) included all-cause death, recurrent ruptures, and secondary procedures. In total, 391 subjects treated by TEVAR were enrolled, with a mean age of 57.1 ± 12.0 years; 79.5% of them were male. Cox multivariate analysis showed that the preoperative Hb level was independently associated with all-cause death [adjusted hazard ratio (HR) 0.797 (per 1 g/dl), 95% confidence interval (CI) 0.693-0.918, = 0.002] and MACEs (adjusted HR 0.795, 95% CI 0.672-0.871, = 0.000). The area under the receiver operating characteristic curve of Hb for all-cause death and MACEs were 0.617 (95% CI 0.548-0.687, = 0.008) and 0.617 (95% CI 0.551-0.684, = 0.005), respectively. In the linear trend test, Hb concentration was significantly related to all-cause mortality ( for trend = 0.001) and MACEs ( for trend = 0.000). Moreover, in Kaplan-Meier analysis, lower Hb levels (< 12 g/dl) were significantly different from higher Hb (≥12 g/dl) levels for both all-cause death (log-rank = 0.001) and MACEs (log-rank = 0.001). Similar results were found when assessing the prognostic value of red blood cell count and anemia. Preoperative Hb may serve as a prognostic marker for long-range adverse outcomes for ABAD patients post-TEVAR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2020.588761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693721PMC
November 2020

How the constituents of fine particulate matter and ozone affect the lung function of children in Tianjin, China.

Environ Geochem Health 2020 Oct 23;42(10):3303-3316. Epub 2020 Apr 23.

Department of Environment and Health, Tianjin Centers for Disease Control and Prevention, No. 6 Huayue Rd., Tianjin, China.

As the pollution of fine particulate matter (≤ 2.5 μg/m in aerodynamic diameter; PM) and ozone (O) is becoming more and more serious in developing countries, we, hereby, investigated the effects of PM, constituents of PM and O on the lung function of children in Tianjin, China. The lung functions of 198 pupils from nine primary schools in Tianjin were examined (repeated five times) during the months of October to December in 2016, 2017 and 2018, respectively. And the mixed-effect models were used to evaluate the effects of air pollutants. A 10 μg/m increase in PM and O-8h might lead to reductions of forced vital capacity (FVC) in 1.03% (- 1.87 to - 0.19%) and 21.09% (- 25.54 to - 16.58%), respectively, while a 10 ng/m increment in ANY might account for the 166.44% (- 221.32 to - 112.31%) decreases in FVC. PM and O-8h might be more harmful to the lung functions of female students and participants with PS exposure at home. And the main sources of pollution resulting in the decrease in pulmonary function might be traffic pollution and coal combustion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10653-020-00574-7DOI Listing
October 2020

Health benefits on cardiocerebrovascular disease of reducing exposure to ambient fine particulate matter in Tianjin, China.

Environ Sci Pollut Res Int 2020 Apr 4;27(12):13261-13275. Epub 2020 Feb 4.

Department of Environment and Health, Tianjin Centers for Disease Control and Prevention, No. 6 Huayue Rd., Tianjin, China.

With the development of the industrialization level in China, high concentrations of fine particulate matter (≤ 2.5 μg/m in aerodynamic diameter (PM)) could have a great impact on the health of the population. Our study is to quantify the health benefits on cardiocerebrovascular disease of reducing exposure to PM in Tianjin, China. We obtained the data on cardiovascular disease (CVD), ischemic heart disease (IHD), and cerebrovascular disease (CD) mortalities to quantify the association between CVD, CD, and IHD mortalities and PM and calculate health and economic benefits when the annual average concentration of PM was reduced to National Ambient Air Quality Standard (NAAQS) and World Health Organization (WHO) guidelines by using our concentration response (C-R) functions. There were 435.22 (95% CI 253.86 to 616.57) all-cause, 130.22 (95% CI 66.34 to194.09) IHD, and 204.07 (95% CI 111.66 to 296.47) CD deaths attributed to PM and the economic benefits obtained by preventing all-cause, IHD, and CD mortalities were equivalent to be 2.79%, 0.83%, and 1.31% of Baodi's GDP in Tianjin in 2017, respectively. PM concentration was positive with all-cause, IHD, and CD mortalities in rural, suburban, and urban area of Tianjin, China. Meanwhile, the number of avoidable deaths and economic cost of reducing PM concentrations to NAAQS and WHO guidelines was highest in the rural area.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-020-07910-5DOI Listing
April 2020

High mobility group protein B1 (HMGB1) interacts with receptor for advanced glycation end products (RAGE) to promote airway smooth muscle cell proliferation through ERK and NF-B pathways.

Int J Clin Exp Pathol 2019 1;12(9):3268-3278. Epub 2019 Sep 1.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University Nanning 530021, China.

Background: High-mobility graoup box protein 1 (HMGB1) has been shown to mediate a wide range of pathologic responses by interacting with RAGE (receptor for advanced glycation endproducts) and TLRs (Toll-like receptors). Our previous study showed that HMGB1 has been involved in pathogenesis of airway remodeling in an allergen-induced chronic mice asthma model. Increased airway smooth muscle (ASM) mass is a vital feature of airway remodeling.

Objective: To evaluate the effect of HMGB1 on proliferation of ASMs and the underlying mechanisms.

Methods: Rat airway smooth muscle cells (RASMs) were obtained by primary explant techniques. We investigated the effect of HMGB1 on the proliferation of RASMs. To identify which receptors and signaling pathways be involved in proliferation of RASMs, we performed western blot and CCK-8 assay by specific receptor blockade and inhibition of MAPK (p38, JNK and ERK) and NF-B signaling pathways.

Results: HMGB1 stimulated RASMs proliferation in a dose- and time-dependent manner and also increased proliferating cell nuclear antigen (PCNA) and RAGE expression of RASMs. The inhibitor of RAGE, but not TLR2 and TLR4, reversed HMGB1-induced RASM proliferation and PCNA expression. Incubation of RASMs with HMGB1 caused a rapid increase in P65 and ERK phosphorylation. RASM proliferation and PCNA expression toward HMGB1 were significantly inhibited by the inhibitors of ERK and NF-B.

Conclusion: HMGB1 induces proliferation of RASMs through a RAGE-dependent activation of ERK and NF-B signaling pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949814PMC
September 2019

Differential DAMP release was observed in the sputum of COPD, asthma and asthma-COPD overlap (ACO) patients.

Sci Rep 2019 12 17;9(1):19241. Epub 2019 Dec 17.

Department of respiratory medicine, The first affiliated hospital of Guangxi Medical University Nanning, Nanning, 530021, China.

Asthma-COPD overlap (ACO) has been under intensive focus; however, the levels of damage-associated molecular patterns (DAMPs) that can activate the innate and adaptive immune responses of ACO are unknown. The present study aimed to examine the levels of some DAMPs in asthma, COPD, and ACO and to identify the associations between clinical characteristics and DAMPs in ACO. Sputum from subjects with asthma (n = 87) or COPD (n = 73) and ACO (n = 68) or from smokers (n = 62) and never-smokers (n = 62) was analyzed for high mobility group protein B1 (HMGB1), heat shock protein 70 (HSP70), LL-37, S100A8, and galectin-3 (Gal-3). The concentration of HMGB1, HSP70, LL-37, and S100A8 proteins in sputum from ACO patients was significantly elevated, whereas that of Gal-3 was reduced, compared to that of smokers and never-smokers. The levels of HMGB1 and Gal-3 proteins in ACO patients were elevated compared to those in asthma patients. The sputum from ACO patients showed an increase in the levels of LL-37 and S100A8 proteins compared to that of asthma patients, whereas the levels decreased compared to those of COPD patients. The concentrations of HMGB1, HSP70, LL-37, and S100A8 proteins in the sputum of 352 participants were negatively correlated, whereas the levels of Gal-3 were positively correlated, with FEV1, FEV1%pred, and FEV1/FVC. Sputum HMGB1 had a high AUC of the ROC curve while distinguishing ACO patients from asthma patients. Meanwhile, sputum LL-37 had a high AUC of the ROC curve in differentiating asthma and COPD. The release of sputum DAMPs in ACO may be involved in chronic airway inflammation in ACO; the sputum HMGB1 level might serve as a valuable biomarker for distinguishing ACO from asthma, and the sputum LL-37 level might be a biomarker for differentiating asthma and COPD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-55502-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917785PMC
December 2019

Stopping the supply of iodized salt alone is not enough to make iodine nutrition suitable for children in higher water iodine areas: A cross-sectional study in northern China.

Ecotoxicol Environ Saf 2020 Jan 11;188:109930. Epub 2019 Nov 11.

Tianjin Centers for Disease Control and Prevention, 6 Huayue Road, Hedong District, Tianjin, 300011, PR China. Electronic address:

Background: For the sake of children's health, iodized salt supply has been stopped in many areas with excessive iodine in the drinking water, but children's iodine nutrition status and thyroid function after terminating the iodized salt supply is unknown. Objective We assessed the iodine nutrition, thyroid function and influencing factors for thyroid abnormalities in children from areas with different concentrations of water iodine; the supply of iodized salt has been stopped in high water iodine areas. This study aimed to evaluate whether the strategy of stopping the supplies of iodized salt alone is enough to avoid thyroid dysfunction in all areas with excess water iodine while still meeting the iodine nutrition needs of children.

Methods: A cross-sectional study was conducted in children from four areas with different drinking water iodine concentrations in Tianjin, China. The drinking water samplings and spot urine samples were collected to estimate the external and internal iodine exposure levels. The thyroid volume was measured, and blood samples were collected to assess thyroid function. Logistic regression analysis was used to analyze risk factors for thyroid abnormalities. A dietary survey was conducted to determine the sources of iodine nutrition among the areas with different iodine concentrations in the drinking water.

Results: In the area with a drinking water iodine concentration ≥300 μg/L, the median urinary iodine concentration (UIC) in children was 476.30 (332.20-639.30) μg/L, which was higher than that in other groups (all P < 0.05), and the prevalence of thyroid nodules and the thyroid goiter rate were higher than those in the <100 μg/L, 100-150 μg/L and 150-300 μg/L areas (all P < 0.01). Binary logistic regression analysis indicated that the risk of thyroid abnormalities was significantly increased in the UIC 200-299 μg/L group (OR: 4.534; 95% CI: 1.565, 13.135; bootstrapped 95% CI: 1.689, 21.206, P = 0.004) and in the UIC ≥ 300 μg/L group (OR: 6.962; 95% CI: 2.490, 19.460; bootstrapped 95% CI: 2.838, 32.570, P = 0.001) compared to the 100-199 μg/L group. The iodine contribution rates from water in areas with water iodine concentrations ≥300 μg/L are up to 63.04%.

Conclusions: After termination of the iodized salt supply, the level of iodine nutrition of children in the area with drinking water iodine concentrations ≥300 μg/L is still excessive. The water source needs to be replaced in this area. In the area with a water iodine concentration of 150-300 μg/L, it is proposed that stopping the supply of iodized salt is sufficient to achieve the proper iodine nutrition status in children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2019.109930DOI Listing
January 2020

Spatial distribution of fluoride in drinking water and health risk assessment of children in typical fluorosis areas in north China.

Chemosphere 2020 Jan 7;239:124811. Epub 2019 Sep 7.

Institute of Environment and Health, Tianjin Centers for Disease Control and Prevention, Tianjin, 300011, China. Electronic address:

China has been suffering from endemic fluorosis for the past 30 years. This study investigated fluoride concentrations in 10 districts of Tianjin, China, to illustrate their spatial distribution characteristics and potential human health risks. The results showed fluoride concentration of 0.01-6.30 mg L with a mean value of 0.99 mg L, and 78.82% of water fluoride reaches the standard for drinking water (1.5 mg L). Higher fluoride levels were recorded in deep well pumps supply zones, and more potential changes in fluoride occurred was positively correlated with pH in groundwater. Mean value of fluoride in drinking water in 10 districts followed the order of WQ > BC > JZ > NH > BD > BH > JN > JH > DL > XQ. Estimations of non-carcinogenic risk for drinking water indicated that mean hazard quotient values of fluoride for combined pathways (i.e., oral ingestion and dermal absorption) were >1.0 for all age groups of WQ and BC. The results also showed that the estimated risk primarily came from the ingestion pathway. Risk levels for children varied obviously, generally in the order of 1-4y > 4-7y > 7-9y (years old). In the central tendency center and reasonable maximum exposure conditions, estimated risks were 1.25, 1.12, 0.771 and 3.66, 3.29, 2.27, respectively. The results supply material information for health authorities in fluorosis areas to put forward more efficient policies to control the endemic diseases. Attention should be paid to the formulation of health promotion strategies and measures to reduce fluoride intake in order to protect the health of residents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2019.124811DOI Listing
January 2020

Thyroid function, intelligence, and low-moderate fluoride exposure among Chinese school-age children.

Environ Int 2020 01 4;134:105229. Epub 2019 Nov 4.

Department of Occupational and Environmental Health, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. Electronic address:

Background: Thyroid hormones (THs) are critical for brain development. Whether low-moderate fluoride exposure affects thyroid function and what the impact is on children's intelligence remain elusive.

Objectives: We conducted a cross-sectional study to examine the associations between low-moderate fluoride exposure and thyroid function in relation to children's intelligence.

Methods: We recruited 571 resident children, aged 7-13 years, randomly from endemic and non-endemic fluorosis areas in Tianjin, China. We measured fluoride concentrations in drinking water and urine using the national standardized ion selective electrode method. Thyroid function was evaluated through the measurements of basal THs [(total triiodothyronine (TT), total thyronine (TT), free triiodothyronine (FT), free thyronine (FT)] and thyroid-stimulating hormone (TSH) levels in serum. Multivariable linear and logistical regression models were used to assess associations among fluoride exposure, thyroid function and IQ scores.

Results: In adjusted models, every 1 mg/L increment of water fluoride was associated with 0.13 uIU/mL increase in TSH. Every 1 mg/L increment of urinary fluoride was associated with 0.09 ug/dL decrease in TT, 0.009 ng/dL decrease in FT and 0.11 uIU/mL increase in TSH. Fluoride exposure was inversely related to IQ scores (B = -1.587; 95% CI: -2.607, -0.568 for water fluoride and B = -1.214; 95% CI: -1.987, -0.442 for urinary fluoride). Higher TT, FT were related to the increased odds of children having high normal intelligence (OR = 3.407, 95% CI: 1.044, 11.120 for TT; OR = 3.277, 95% CI: 1.621, 6.623 for FT). We detected a significant modification effect by TSH on the association between urinary fluoride and IQ scores, without mediation by THs.

Conclusions: Our study suggests low-moderate fluoride exposure is associated with alterations in childhood thyroid function that may modify the association between fluoride and intelligence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envint.2019.105229DOI Listing
January 2020

Low-to-moderate fluoride exposure in relation to overweight and obesity among school-age children in China.

Ecotoxicol Environ Saf 2019 Nov 26;183:109558. Epub 2019 Aug 26.

Department of Occupational and Environmental Health, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. Electronic address:

High fluoride exposure has been related to harmful health effects, but the impacts of low-to-moderate fluoride on child growth and obesity-related outcomes remain unclear. We performed a large-scale cross-sectional study to examine the association between low-to-moderate fluoride in drinking water and anthropometric measures among Chinese school-age children. We recruited 2430 resident children 7-13 years of age, randomly from low-to-moderate fluorosis areas of Baodi District in Tianjin, China. We analyzed the fluoride contents in drinking water and urine samples using the national standardized ion selective electrode method. Multivariable linear and logistic analyses were used to assess the relationships between fluoride exposure and age- and sex-standardized height, weight and body mass index (BMI) z-scores, and childhood overweight/obesity (BMI z-score > 1). In adjusted models, each log unit (roughly 10-fold) increase in urinary fluoride concentration was associated with a 0.136 unit increase in weight z-score (95% CI: 0.039, 0.233), a 0.186 unit increase in BMI z-score (95% CI: 0.058, 0.314), and a 1.304-fold increased odds of overweight/obesity (95% CI: 1.062, 1.602). These associations were stronger in girls than in boys (P = 0.016), and children of fathers with lower education levels were more vulnerable to fluoride (P = 0.056). Each log unit (roughly 10-fold) increase in water fluoride concentration was associated with a 0.129 unit increase in height z-score (95% CI: 0.005, 0.254), but not with other anthropometric measures. Our results suggest low-to-moderate fluoride exposure is associated with overweight and obesity in children. Gender and paternal education level may modify the relationship.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2019.109558DOI Listing
November 2019

miR-19 targets PTEN and mediates high mobility group protein B1(HMGB1)-induced proliferation and migration of human airway smooth muscle cells.

PLoS One 2019 27;14(6):e0219081. Epub 2019 Jun 27.

Department of Respiratory Medicine, the second affiliated hospital of Guangxi Medical University, Nanning, China.

Background: The abnormal proliferation and migration of airway smooth muscle (ASM) cells contributes to airway remodeling during asthma. MiR-19a has been demonstrated to promote cell proliferation and angiogenesis of several cancer types by regulating the PTEN/PI3K/AKT pathway. Our previous study has shown that High-mobility group box protein 1 (HMGB1) is involved in the pathogenesis of airway remodeling using a mouse model of chronic asthma. However, the effects of HMGB1 on proliferation and migration of ASM cells and its underlying mechanisms remain unknown.

Methods: Human ASM cells were obtained by primary explant techniques. MiR-19a expression was evaluated using qRT-PCR. Cell proliferation and migration were evaluated by the CCK-8 and the transwell migration assays, respectively. Transfection studies of ASM cells were performed to identify the underlying mechanisms.

Results: HMGB1 stimulated ASM cell proliferation and migration in a dose-dependent manner. The expression levels of miR-19a and the PTEN and AKT signaling proteins were also modulated by HMGB1. Functional studies indicated that overexpression of miR-19a enhanced the proliferation and migration of ASM cells, whereas inhibition of miR-19a decreased the proliferation and migration of ASM cells. Western blot analysis demonstrated that miR-19a negatively regulated PTEN expression and positively regulated p-AKT expression. MiR-19 only regulates the proliferation of HASM cells induced by HMGB1, but not PDGF, EGF, TGF-β1. Furthermore, we demonstrated that miR-19 contributed to the promoting effects of HMGB1 on ASM cells by targeting PTEN 3'-UTR.

Conclusion: Our results demonstrated that HMGB1 induced proliferation and migration of ASM cells via the miR-19a /PTEN/AKT axis and provided direct evidence on the role of HMGB1 in ASM cells proliferation in vitro. The present study further indicated that miR-19a may be explored as a potential novel therapeutic target to reverse proliferation and migration of ASM cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219081PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597099PMC
February 2020

Interactive effect between temperature and fine particulate matter on chronic disease hospital admissions in the urban area of Tianjin, China.

Int J Environ Health Res 2021 Jan 13;31(1):75-84. Epub 2019 Jun 13.

Department of Environment and Health, Tianjin Centers for Disease Control and Prevention , Tianjin, China.

This study focuses on effects of fine particulate matter (PM) on chronic disease under different levels of temperature. We obtained type 2 diabetes, cerebral stroke and coronary heart disease hospital admissions (HAs) from five hospitals in urban Tianjin as well as the concentrations of PM, nitrogen dioxide (NO) and sulphur dioxide (SO). We used distributed lag nonlinear models to explore nonlinear and lag effects of PM. In single-pollutant models, PM was positively associated with type 2 diabetes, cerebral stroke and coronary heart disease HAs, with strongest effects at lag1, lag0 and lag06, respectively. The corresponding relative risk rates (%) were 1.836%, 2.083% and 6.428%. In co-pollutant models, the correlation between PM and HAs on high-temperature days was generally stronger than that on low-temperature days. This study indicated that PM can increase HA rates for these chronic diseases, and effects of PM on high-temperature days were stronger than that on low-temperature days.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09603123.2019.1628928DOI Listing
January 2021

3-Methyladenine alleviates excessive iodine-induced cognitive impairment via suppression of autophagy in rat hippocampus.

Environ Toxicol 2019 Aug 9;34(8):912-920. Epub 2019 May 9.

Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, China.

Drinking water with high levels of iodine has been identified as the key contributor to iodine excess, but the mechanisms of neurotoxicity induced by excessive iodine remain elusive. The present study aimed to explore the role of autophagy in the neurotoxic effect induced by excessive iodine in vivo. The Morris water maze test results demonstrated that excessive iodine impaired the learning and memory capabilities of rats, which were associated with marked body weight and brain weight abnormalities. In addition, iodine treatment increased malondialdehyde accumulation, decreased superoxide dismutase activity and glutathione (GSH) level, and enhanced levels of autophagy markers in the hippocampus. Notably, inhibition of autophagy with 3-methyladenine (3-MA) could significantly alleviate excessive iodine-induced cognitive impairment. These data imply that autophagy is involved in the cognitive impairment elicited by excessive iodine as a pathway of cell death, and inhibition of autophagy via 3-MA may significantly alleviate the above damage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/tox.22762DOI Listing
August 2019

Elevated S100A4 in asthmatics and an allergen-induced mouse asthma model.

J Cell Biochem 2019 06 19;120(6):9667-9676. Epub 2018 Dec 19.

The Department of Respiratory Medicine, The Second Affiliated Hospital of Guangxi Medical University, China.

The elevated S100A4 level has been found in some inflammatory diseases. However, the expression and role of S100A4 in asthma is unknown. The expression of S100A4 in induced sputum and plasma from healthy control and asthmatics were assessed by ELISA. Then an allergen-induced asthma mouse model treatment with anti-S100A4 antibody was used to explore the role of S100A4 in the pathogenesis of asthma. The S100A4 levels in sputum not in plasma in asthmatics were significantly increased than those of healthy controls and were negatively correlated with some lung function parameters and were positively correlated with sputum eosinophilia and lymphocyte. The expression of S100A4 in the lung as well as in BALF were also significantly higher in the asthma mouse model and treatment with anti-S100A4 antibody exhibited reductions in inflammatory cell accumulation, inflammatory mediators, and airway hyper-responsiveness. We further showed that LY294002, a specific inhibitor of PI3K, markedly decreased S100A4 expression in lung and S100A4 secretion in BALF in asthmatic mice. In conclusion, these data demonstrated that S100A4 may be involved in the pathogenesis of airway inflammation in asthma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcb.28245DOI Listing
June 2019

Dopamine receptor D2 gene polymorphism, urine fluoride, and intelligence impairment of children in China: A school-based cross-sectional study.

Ecotoxicol Environ Saf 2018 Dec 8;165:270-277. Epub 2018 Sep 8.

Tianjin Centers for Disease Control and Prevention, 6 Huayue Road, Hedong District,Tianjin 300011, PR China; School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, PR China. Electronic address:

Objective: We aimed to study the association of urine fluoride with intelligence quotient (IQ) in children with a careful consideration of up to 30 potential confounding factors as well as possible heterogeneity of the relation between urine fluoride levels and IQ scores across children with different dopamine receptor-2 (DRD2) Taq 1A genotypes (CC, CT, and TT).

Methods: A school-based cross-sectional study design was applied. A total of 323 children (2014-2015, 7-12 years old) were enrolled from four schools in both historical endemic and non-endemic areas of fluorosis in Tianjin of China using a cluster sampling method. Urine fluoride levels and age-specific IQ scores in children were measured at the enrollment. Polymerase chain reaction-restriction fragment length polymorphism methods were used to genotype DRD2 Taq 1A polymorphism with genomic DNA isolated from whole blood collected at the enrollment. Multiple linear regression models were applied to evaluate the relationship between urine fluoride levels and IQ scores overall and within the DRD2 Taq 1A SNP = CC/CT and TT subgroups. Model robustness was tested through bootstrap, sensitivity analysis, and cross-validation techniques. A safety threshold of urine fluoride levels for IQ impairment was determined in the subgroup TT.

Results: In overall participants, the DRD2 Taq 1A polymorphism itself was not related to IQ scores in children who had a high level of urine fluoride. In the CC/CT subgroup, urine fluoride levels and IQ scores in children were unrelated (adjusted β (95% confidence interval (CI)) = - 1.59 (- 4.24, 1.05), p = 0.236). Among the participants carrying the TT genotype, there was a strong and robust negative linear relationship between log-urine fluoride and IQ scores in children (adjusted β (95% CI) = - 12.31 (- 18.69, - 5.94), p < 0.001). Urine fluoride levels had a stronger association with IQ in children carrying the TT genotype (adjusted β = - 12.31, bootstrapped standard error (SE) = 1.28), compared to that in overall participants (adjusted β = - 2.47, bootstrapped SE = 3.75) (Z = 2.483 and bootstrapped p = 0.007). The safety threshold of urine fluoride levels in the subgroup TT was 1.73 mg/L (95% CI = (1.51, 1.97) (mg/L)).

Conclusions: There is heterogeneity in the relation between urine fluoride and IQ across children carrying different DRD2 Taq 1A genotypes. Large-scale epidemiological studies are needed to confirm our findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2018.09.018DOI Listing
December 2018

Excessive apoptosis and disordered autophagy flux contribute to the neurotoxicity induced by high iodine in Sprague-Dawley rat.

Toxicol Lett 2018 Nov 29;297:24-33. Epub 2018 Aug 29.

Tianjin Centers for Disease Control and Prevention, 6 Huayue Road, Hedong District, Tianjin 300011, People's Republic of China; School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, People's Republic of China; Tianjin Municipal Inspection Bureau for Health and Family Planning, 94 Guizhou Road, Heping District, Tianjin 300070, People's Republic of China. Electronic address:

In recent years, the detrimental effects of high iodine on intelligence are gaining tons of attention, but the relationship between high iodine and neurotoxicity is controversial. This study aimed to explore whether high iodine intake may impair intelligence and the roles of apoptosis and autophagy in high iodine-induced neurotoxicity. The results showed that high iodine exposure reduced brain coefficient and intelligence of rats, and caused histopathological abnormalities in hippocampus. Moreover, high iodine increased hippocampal apoptosis, as confirmed by elevation of apoptotic proteins and TUNEL-positive incidence. Further study showed that high iodine impaired mitochondrial ultrastructure and caused elevation of Bax, cytochrome c and decline of Bcl2, indicating the participation of mitochondrial apoptotic pathway. Simultaneously, high iodine also increased the number of autophagosomes. Intriguingly, the expression of autophagosomes formation protein Atg7, Beclin1 and autophagic substrate p62 were elevated, suggesting that the accumulated autophagosomes is not only due to the enhancement of formation but also the decline of clearance. These, together with the numerous damaged organelles observed in hippocampal ultrastructure, reveal the crucial role of disordered autophagy flux in high iodine-elicited neurotoxicity. Collectively, these findings suggest that excessive apoptosis and disordered autophagy flux contribute to high iodine-elicited neurotoxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxlet.2018.08.020DOI Listing
November 2018

Oxidative stress-mediated autophagic cell death participates in the neurotoxic effect on SH-SY5Y cells induced by excessive iodide.

Environ Toxicol 2018 Jun 19. Epub 2018 Jun 19.

Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong Universityof Science and Technology, 13 Hangkong Road, Hubei, Wuhan, 430030, People's Republic of China.

Excessive iodide could induce intellectual damage in children, which has attracted broad attention. To investigate the neurotoxic effect of iodide and its mechanism, a human dopaminergic neuroblastoma cell line (SH-SY5Y) was treated with different concentrations of potassium iodide (KI). The results showed that excessive iodide could decrease cell viability, reduce glutathione (GSH) and superoxide dismutase (SOD), and increase the degree of autophagy (by changing the cellular ultrastructure and raising the autophagy-related mRNA and protein expression of LC3, Beclin1, and p62), which were correlated with the immunofluorescence labeling. Furthermore, treatment with the autophagy inhibitor 3-methyladenine (3MA), antioxidant N-acetylcysteine (NAC) and 30 mM KI for 24 h was conducted in the following research. 3MA significantly decreased autophagy-related mRNA and protein expression and improved cell viability, indicating that excess iodide induced autophagic cell death. In addition, oxidative stress regulated autophagy, reflected by the results that NAC decreased the mRNA and protein expression of LC3, Beclin1, and p62. In summary, autophagic cell death mediated by oxidative stress may participate in excessive iodide-induced SH-SY5Y cell death.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/tox.22571DOI Listing
June 2018

Threshold effects of moderately excessive fluoride exposure on children's health: A potential association between dental fluorosis and loss of excellent intelligence.

Environ Int 2018 09 2;118:116-124. Epub 2018 Jun 2.

Department of Occupational and Environmental Health, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. Electronic address:

Background: Excessive fluoride exposure is associated with adverse health outcomes, but little is known of the effects of moderately chronic fluoride exposure on children's health.

Objectives: We conducted a cross-sectional study to explore the health impact of moderately excessive fluoride in drinking water.

Methods: We recruited 2886 resident children, aged 7 to 13 years, randomly from endemic and non-endemic fluorosis areas in Tianjin, China. The fluoride levels in drinking water and urine were measured using the national standardized ion selective electrode method. We examined the dose-response effects of low-to-moderate fluoride exposure on dental fluorosis (DF) and intelligence quotient (IQ), and evaluated the potential relationships between DF grades and intelligence levels using piecewise linear regression and multiple logistic regression, respectively.

Results: The adjusted odds ratios (ORs) of DF were 2.24 (95% confidence interval [CI]: 2.02 to 2.48) for every 0.1 mg/L increment in the water fluoride concentration in the range of 0.80 to 1.50 mg/L, and 2.61 (95% CI: 2.32 to 2.93) for every 0.5 mg/L increment in the urinary fluoride level up to 1.80 mg/L. Every 0.5 mg/L increment in the water fluoride level was associated with a reduction of 4.29 in the IQ score (95% CI: -8.09 to -0.48) in the range of 3.40 to 3.90 mg/L, and a decreased probability of developing excellent intelligence (IQ ≥ 130, OR = 0.60, 95% CI: 0.47 to 0.77) in the range of 0.20-1.40 mg/L, respectively. Every 0.5 mg/L increment in the urinary fluoride level was related to a decrease of 2.67 in the IQ scores (95% CI: -4.67 to -0.68) between 1.60 mg/L to 2.50 mg/L. Excellent intelligence decreased by 51% in children with higher urinary fluoride, and by 30% with each degree increment of DF.

Conclusions: Our study suggests threshold and saturation effects of moderately excessive fluoride exposure on DF and intelligence loss in children, and a potential association between DF and the loss of excellent intelligence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envint.2018.05.042DOI Listing
September 2018

Erythromycin combined with corticosteroid reduced inflammation and modified trauma-induced tracheal stenosis in a rabbit model.

Ther Adv Respir Dis 2018 Jan-Dec;12:1753466618773707

Department of Respiratory Medicine, Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, China.

Background: Patients with endotracheal intubation or tracheostomy are subject to benign tracheal stenosis (TS), for which current therapies are unsatisfactory. We conducted a preliminary investigation of drugs and drug combinations for the prevention and treatment of TS in a rabbit model.

Methods: Fifty-four rabbits were apportioned into nine groups according to treatment: sham-operated control; untreated TS model; amikacin; budesonide; erythromycin; penicillin; amikacin + budesonide; erythromycin + budesonide; and penicillin + budesonide. TS was induced by abrasion during surgery. The drugs were applied for 7 days before and 10 days after the surgery. Rabbits were killed on the eleventh day. Tracheal specimens were processed for determining alterations in the thicknesses of tracheal epithelium and lamina propria via hematoxylin and eosin. The tracheal mRNA (assessed by real-time quantitative polymerase chain reaction) expressions of the following fibrotic-related factors were determined: transforming growth factor-β1 (TGF- β1), collagen type I (COL1A1), collagen type III (COL3A1), and interleukin-17 (IL-17). The protein levels of TGF-β1, COL1A1, and COL3A1 were determined through immunohistochemistry and integrated optical densities.

Results: Compared with all other groups, the untreated TS model had significantly thicker tracheal epithelium and lamina propria, and higher mRNA and protein levels of all targeted fibrotic factors. The mRNA and protein levels of the targeted fibrotic factors in all the drug-treated groups were lower than those of the untreated TS model, and differences were most significant in the erythromycin + budesonide group.

Conclusions: Erythromycin combined with budesonide may reduce inflammation and modify fibrosis progression in TS after tracheal injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1753466618773707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966843PMC
January 2019

Autophagy regulates high concentrations of iodide-induced apoptosis in SH-SY5Y cells.

Toxicol Lett 2018 Mar 11;284:129-135. Epub 2017 Dec 11.

School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, People's Republic of China; Tianjin Centers for Disease Control and Prevention, 6 Huayue Road, Hedong District, Tianjin 300011, People's Republic of China; Tianjin Municipal Inspection Bureau for Health And Family Planning, 94 Guizhou Road, Heping District, Tianjin 300070, People's Republic of China. Electronic address:

To date, there are many people residing in areas with high levels of iodide in water. Our previous epidemiological study showed that exposure to high iodine in drinking water significantly reduced the intelligence of children although the mechanisms remain unclear. To explore whether high concentrations of iodide may cause cytotoxic effect and the role of autophagy in the high iodide-induced apoptosis, human neuroblastoma cells (SH-SY5Y cells) were exposed to high concentrations of iodide. Morphological phenotypes, cell viability, Hoechst 33258 staining, the expression levels of apoptosis and autophagy-related proteins were detected. A possible effect of an inhibitor (3-methyladenine, 3-MA) or an inducer (rapamycin) of autophagy on high iodide-induced apoptosis also was examined. Results indicated that high iodide changed cellular morphology, decreased cell viability and increased the protein's expression level of apoptosis and autophagy. In addition, high iodide-induced apoptosis was enhanced by inhibition of autophagy and inhibited by activation of autophagy in SH-SY5Y cells. Collectively, high concentrations of iodide are toxic to SH-SY5Y cells, as well as induce apoptosis and autophagy. Furthermore, autophagy plays a regulatory role in high concentrations of iodide-induced apoptosis in SH-SY5Y cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxlet.2017.12.007DOI Listing
March 2018

Role of endoplasmic reticulum stress-induced apoptosis in rat thyroid toxicity caused by excess fluoride and/or iodide.

Environ Toxicol Pharmacol 2016 Sep 9;46:277-285. Epub 2016 Aug 9.

Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030 Hubei, PR China. Electronic address:

Excess fluoride and iodide coexist in drinking water in many regions, but few studies have investigated the single or interactive effects on thyroid in vivo. In our study, Wistar rats were exposed to excess fluoride and/or iodide through drinking water for 2 or 8 months. The structure and function of the thyroid, cells apoptosis and the expression of inositol-requiring enzyme 1 (IRE1) pathway-related factors were analyzed. Results demonstrated that excess fluoride and/or iodide could change thyroid follicular morphology and alter thyroid hormone levels in rats. After 8 months treatment, both single and co-exposure of the two microelements could raise the thyroid cells apoptosis. However, the expressions of IRE1-related factors were only increased in fluoride-alone and the combined groups. In conclusion, thyroid structure and thyroid function were both affected by excess fluoride and/or iodide. IRE1-induced apoptosis were involved in this cytotoxic process caused by fluoride or the combination of two microelements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.etap.2016.08.007DOI Listing
September 2016

Baicalein Inhibits Staphylococcus aureus Biofilm Formation and the Quorum Sensing System In Vitro.

PLoS One 2016 29;11(4):e0153468. Epub 2016 Apr 29.

The Institute of Respiratory Diseases, First Affiliated Hospital, Guangxi Medical University, Nanning, China.

Biofilm formed by Staphylococcus aureus significantly enhances antibiotic resistance by inhibiting the penetration of antibiotics, resulting in an increasingly serious situation. This study aimed to assess whether baicalein can prevent Staphylococcus aureus biofilm formation and whether it may have synergistic bactericidal effects with antibiotics in vitro. To do this, we used a clinically isolated strain of Staphylococcus aureus 17546 (t037) for biofilm formation. Virulence factors were detected following treatment with baicalein, and the molecular mechanism of its antibiofilm activity was studied. Plate counting, crystal violet staining, and fluorescence microscopy revealed that 32 μg/mL and 64 μg/mL baicalein clearly inhibited 3- and 7-day biofilm formation in vitro. Moreover, colony forming unit count, confocal laser scanning microscopy, and scanning electron microscopy showed that vancomycin (VCM) and baicalein generally enhanced destruction of biofilms, while VCM alone did not. Western blotting and real-time quantitative polymerase chain reaction analyses (RTQ-PCR) confirmed that baicalein treatment reduced staphylococcal enterotoxin A (SEA) and α-hemolysin (hla) levels. Most strikingly, real-time qualitative polymerase chain reaction data demonstrated that 32 μg/mL and 64 μg/mL baicalein downregulated the quorum-sensing system regulators agrA, RNAIII, and sarA, and gene expression of ica, but 16 μg/mL baicalein had no effect. In summary, baicalein inhibited Staphylococcus aureus biofilm formation, destroyed biofilms, increased the permeability of vancomycin, reduced the production of staphylococcal enterotoxin A and α-hemolysin, and inhibited the quorum sensing system. These results support baicalein as a novel drug candidate and an effective treatment strategy for Staphylococcus aureus biofilm-associated infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0153468PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851419PMC
February 2017

HMGB1 binding to receptor for advanced glycation end products enhances inflammatory responses of human bronchial epithelial cells by activating p38 MAPK and ERK1/2.

Mol Cell Biochem 2015 Jul 11;405(1-2):63-71. Epub 2015 Apr 11.

The Research Department of Respiration Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China,

The proinflammatory factor high mobility group box protein 1 (HMGB1) has been implicated as an important mediator of many chronic inflammatory diseases, including asthma. Human bronchial epithelial cells (HBECs) play a central role in the pathogenesis of asthma. However, the effects of HMGB1 on HBECs and the underlying mechanisms remain unknown. Here, we investigated receptor expression and proinflammatory cytokine production by primary cultures of HBECs stimulated by HMGB1. We then examined the effects of specific receptor blockade and inhibition of p38 MAPK, ERK1/2, or PI3-K on HMGB1-induced expression of proinflammatory cytokines. HMGB1 increased the expression and secretion of TNF-α, TSLP, MMP-9, and VEGF in a dose- and time-dependent manner. HMGB1 also induced elevated expression of RAGE protein. Secretion of TNF-α, VEGF, MMP-9, and TSLP was significantly decreased by RAGE blockade and p38 MAPK pathway inhibition, while a less pronounced effect was mediated by ERK1/2 inhibition. These observations suggest that HMGB1 binds RAGE and promotes activities of p38 MAPK and ERK1/2 pathways in HBECs. This then enhances the expression of TNF-α, VEGF, MMP-9, and TSLP, which are the important inflammatory factors in asthma. These results demonstrate that HMGB1 enhances the inflammatory responses of HBECs, which are involved in the modulation of inflammatory processes in asthma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11010-015-2396-0DOI Listing
July 2015

HMGB1 contributes to allergen-induced airway remodeling in a murine model of chronic asthma by modulating airway inflammation and activating lung fibroblasts.

Cell Mol Immunol 2015 Jul 25;12(4):409-23. Epub 2014 Aug 25.

The pro-inflammation factor high-mobility group box protein 1 (HMGB1) has been implicated in the pathogenesis of asthma. In this study, we used a murine model of chronic asthma to evaluate the effects of HMGB1 on airway remodeling. Female BALB/c mice were randomly divided into four groups: control, ovalbumin (OVA) asthmatic, OVA+isotype antibody and OVA+anti-HMGB1 antibody. Anti-HMGB1 antibody therapy was started on day 21 and was administered three times per week for 6 weeks before intranasal challenge with OVA. In this mouse model, HMGB1 expression is significantly elevated. The anti-HMGB1 antibody group exhibited decreased levels of immunoglobulin E (IgE) and inflammatory mediators and reduced inflammatory cell accumulation, airway hyperresponsiveness (AHR), mucus synthesis, smooth muscle thickness and lung collagen content compared with the OVA groups. Treatment with HMGB1 increased proliferation, migration, collagen secretion and α-smooth muscle actin (SMA) expression in MRC-5 cells. Treatment with the HMGB1/IL-1β complex significantly increased the expression and secretion of transforming growth factor (TGF-β1), matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF). Altogether, these results suggest that blocking HMGB1 activity may reverse airway remodeling by suppressing airway inflammation and modulating lung fibroblast phenotype and activation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/cmi.2014.60DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496537PMC
July 2015

The effects and underlying mechanism of excessive iodide on excessive fluoride-induced thyroid cytotoxicity.

Environ Toxicol Pharmacol 2014 Jul 27;38(1):332-40. Epub 2014 Jun 27.

Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Hubei, Wuhan 430030, PR China. Electronic address:

In many regions, excessive fluoride and excessive iodide coexist in groundwater, which may lead to biphasic hazards to human thyroid. To explore fluoride-induced thyroid cytotoxicity and the mechanism underlying the effects of excessive iodide on fluoride-induced cytotoxicity, a thyroid cell line (Nthy-ori 3-1) was exposed to excessive fluoride and/or excessive iodide. Cell viability, lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) formation, apoptosis, and the expression levels of inositol-requiring enzyme 1 (IRE1) pathway-related molecules were detected. Fluoride and/or iodide decreased cell viability and increased LDH leakage and apoptosis. ROS, the expression levels of glucose-regulated protein 78 (GRP78), IRE1, C/EBP homologous protein (CHOP), and spliced X-box-binding protein-1 (sXBP-1) were enhanced by fluoride or the combination of the two elements. Collectively, excessive fluoride and excessive iodide have detrimental influences on human thyroid cells. Furthermore, an antagonistic interaction between fluoride and excessive iodide exists, and cytotoxicity may be related to IRE1 pathway-induced apoptosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.etap.2014.06.008DOI Listing
July 2014

The role of the IRE1 pathway in excessive iodide- and/or fluoride-induced apoptosis in Nthy-ori 3-1 cells in vitro.

Toxicol Lett 2014 Jan 11;224(3):341-8. Epub 2013 Nov 11.

Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Hubei, Wuhan 430030, People's Republic of China. Electronic address:

Excessive iodide and fluoride coexist in the groundwater in many regions, causing a potential risk to the human thyroid. To investigate the mechanism of iodide- and fluoride-induced thyroid cytotoxicity, human thyroid follicular epithelial cells (Nthy-ori 3-1) were treated with different concentrations of potassium iodide (KI), with or without sodium fluoride (NaF). Cell morphology, viability, lactate dehydrogenase (LDH) leakage, apoptosis, and expression of inositol-requiring enzyme 1 (IRE1) pathway-related molecules were assessed. Results showed 50 mM of KI, 1 mM of NaF, and 50 mM of KI +1 mM of NaF changed cellular morphology, decreased viability, and increased LDH leakage and apoptosis. Elevated expression of binding protein (BiP), IRE1, and C/EBP homologous protein (CHOP) mRNA and protein, as well as spliced X-box-binding protein-1 (sXBP-1) mRNA, were observed in the 1 mM NaF and 50 mM KI +1 mM NaF groups. Collectively, excessive iodide and/or fluoride is cytotoxic to the human thyroid. Although these data do not manifest iodide could induce the IRE1 pathway, the cytotoxicity followed by exposure to fluoride alone or in combination with iodide may be related to IRE1 pathway-induced apoptosis. Furthermore, exposure to the combination of excessive iodide and fluoride may cause interactive effects on thyroid cytotoxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxlet.2013.11.001DOI Listing
January 2014