| 1. |
- Deng, Min, et al.
(författare)
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Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis
- 2013
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 45:6, s. 697-
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, P-combined = 2.92 x 10(-8), odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, P-combined = 2.35 x 10(-9), OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.
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| 2. |
- Qi, Xiaoying, et al.
(författare)
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High Throughput, Absolute Determination of the Content of a Selected Protein at Tissue Levels Using Quantitative Dot Blot Analysis (QDB)
- 2018
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Ingår i: Journal of Visualized Experiments. - : MyJove Corporation. - 1940-087X. ; :138
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Tidskriftsartikel (refereegranskat)abstract
- Lacking a convenient, quantitative, high throughput immunoblot method for absolute determination of the content of a specific protein at cellular and tissue level significantly hampers the progress in proteomic research. Results derived from currently available immunoblot techniques are also relative, preventing any efforts to combine independent studies with a large-scale analysis of protein samples. In this study, we demonstrate the process of quantitative dot blot analysis (QDB) to achieve absolute quantification in a high throughput format. Using a commercially available protein standard, we are able to determine the absolute content of capping actin protein, gelsolin-like (CAPG) in protein samples prepared from three different mouse tissues (kidney, spleen, and prostate) together with a detailed explanation of the experimental details. We propose the QDB analysis as a convenient, quantitative, high throughput immunoblot method of absolute quantification of individual proteins at the cellular and tissue level. This method will substantially aid biomarker validation and pathway verification in various areas of biological and biomedical research.
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| 3. |
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| 4. |
- Li, Wenting, et al.
(författare)
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Effects of prenatal exposure to five parabens on neonatal thyroid function and birth weight : Evidence from SMBCS study
- 2020
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Ingår i: Environmental Research. - : Academic Press. - 0013-9351 .- 1096-0953. ; 188
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Parabens, suspected as endocrine-disrupting chemicals, are nearly ubiquitous in the human body and exposure to these chemicals during pregnancy may disrupt thyroid hormones homeostasis and even affect fetal growth, although the impacts are still unclear.OBJECTIVES: We aimed to estimate associations of maternal urinary paraben concentrations with cord serum thyroid hormones and birth weight.METHODS: A subset of 437 mother-newborn pairs were included from a prospective birth cohort with five parabens quantified in maternal urine and seven thyroid function indicators measured in cord serum samples. Multivariable linear regression models and elastic net regression (ENR) models were applied to explore associations between individual and mixtures of prenatal urinary paraben concentrations and thyroid hormones and birth weight, respectively.RESULTS: Maternal urinary ethyl-paraben (EtP) concentrations were associated with increased cord serum total triiodothyronine levels (TT3) [percent change: 1.51%; 95% confidence interval (CI): 0.20%, 2.74%; p=0.017]. Urinary propyl-paraben (PrP) levels predicted higher thyroid peroxidase antibodies (percent change: 4.19%, 95% CI: 0.20%, 8.44%; p=0.041). Maternal urinary EtP and butyl-paraben (BuP) concentrations were significantly positively associated with birth weight [regression coefficient, (β)=40.9g, 95% CI: 3.99, 76.6; p=0.030; β=62.1g, 95% CI: 8.70, 115; p=0.023, for EtP and BuP, respectively]. In sex-stratified analyses, positive relationship between EtP levels and birth weight was observed in boys. Urinary EtP concentrations predicted higher TT3 levels in cord serum samples, assessing parabens as a chemical mixture with ENR models.CONCLUSIONS: Prenatal exposure to parabens may affect thyroid hormone indicators with increased serum TT3 levels and associate with higher birth weight, especially in boys. The underlying biological mechanisms and effects of prenatal paraben exposures on disruption of thyroid function homeostasis and potential impacts of childhood growth and development needed to be further investigated.
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| 5. |
- Zhu, Yanping, et al.
(författare)
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Identification of prothymosin alpha (PTMA) as a biomarker for esophageal squamous cell carcinoma (ESCC) by label-free quantitative proteomics and Quantitative Dot Blot (QDB)
- 2019
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Ingår i: Clinical Proteomics. - : BMC. - 1542-6416 .- 1559-0275. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Esophageal cancer (EC) is one of the malignant tumors with a poor prognosis. The early stage of EC is asymptomatic, so identification of cancer biomarkers is important for early detection and clinical practice.Methods: In this study, we compared the protein expression profiles in esophageal squamous cell carcinoma (ESCC) tissues and adjacent normal esophageal tissues from five patients through high-resolution label-free mass spectrometry. Through bioinformatics analysis, we found the differentially expressed proteins of ESCC. To perform the rapid identification of biomarkers, we adopted a high-throughput protein identification technique of Quantitative Dot Blot (QDB). Meanwhile, the QDB results were verified by classical immunohistochemistry.Results: In total 2297 proteins were identified, out of which 308 proteins were differentially expressed between ESCC tissues and normal tissues. By bioinformatics analysis, the four up-regulated proteins (PTMA, PAK2, PPP1CA, HMGB2) and the five down-regulated proteins (Caveolin, Integrin beta-1, Collagen alpha-2(VI), Leiomodin-1 and Vinculin) were selected and validated in ESCC by Western Blot. Furthermore, we performed the QDB and IHC analysis in 64 patients and 117 patients, respectively. The PTMA expression was up-regulated gradually along the progression of ESCC, and the PTMA expression ratio between tumor and adjacent normal tissue was significantly increased along with the progression. Therefore, we suggest that PTMA might be a potential candidate biomarker for ESCC.Conclusion: In this study, label-free quantitative proteomics combined with QDB revealed that PTMA expression was up-regulated in ESCC tissues, and PTMA might be a potential candidate for ESCC. Since Western Blot cannot achieve rapid and high-throughput screening of mass spectrometry results, the emergence of QDB meets this demand and provides an effective method for the identification of biomarkers.
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| 6. |
- Guo, Jianqiu, et al.
(författare)
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Anthropometric measures at age 3 years in associations with prenatal and postnatal exposures to chlorophenols
- 2019
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Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 228, s. 204-211
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chlorophenols (CPs), suspected as endocrine disrupting chemicals, exposure during early life may contribute to body size. However, limited human data with inconsistent findings have examined the developmental effects of CPs exposure.Objective: To explore associations between prenatal and postnatal CPs exposure and anthropometric parameters in children aged 3 years.Methods: A subset of 377 mother-child pairs with urinary five CP concentrations were enrolled from a prospective birth cohort. Generalized linear models were conducted to evaluate associations of CPs exposure with children's anthropometric measures.Results: Maternal urinary 2,4,6-trichlorophenol (2,4,6-TCP) concentrations were significantly negatively associated with weight z scores [regression coefficient (beta)=-0.51, 95% confidence interval (Cl): -0.96, -0.05; p = 0.01], weight for height z scores (beta = -0.54, 95% Cl:-1.02, -0.06; p= 0.01) and body mass index (BMI) z scores (beta = -0.53, 95% CI;-1.03, 0.03; p = 0.01) of children aged 3 years, after adjustment for potential confounders and postnatal CPs exposure. In the sex-stratified analyses, these inverse associations remained among boys, while in girls, positive associations of prenatal 2,4,6-TCP exposure with weight for height z scores and BMI z scores were observed. Postnatal exposure to 2,5-diclorophenol (2,5-DCP) was positively associated with weight z scores (beta = 0.26, 95% CI: 0.02, 0.50; p = 0.04), after controlling for possible confounders and maternal CPs exposure during pregnancy. Considering potential sex-specific effects, these associations were only observed in girls.Conclusions: Our findings indicate that prenatal 2,4,6-TCP exposure and postnatal 2,5-DCP exposure may have adverse and sex-specific effects on children's physical development.
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| 7. |
- Guo, Jianqiu, et al.
(författare)
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Associations of melamine and cyanuric acid exposure with markers of kidney function in adults : Results from NHANES 2003-2004
- 2020
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 141
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Tidskriftsartikel (refereegranskat)abstract
- Higher melamine exposure may increase the risk of kidney stone formation and kidney injury in infants, but little is known about the potential nephrotoxic effects of environmental low-dose melamine and its derivative exposure on kidney function of adults in the general population. Our objective was to assess associations between urinary concentrations of melamine and its derivative, cyanuric acid, and kidney function through analyzing the data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004. Information on 298 participants aged ≥20 years was utilized. Urinary melamine and cyanuric acid levels were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) were calculated to reflect kidney function. Covariate-adjusted creatinine standardization concentrations accounting for sex, race, age, race/ethically, and body mass index, was employed to control potential confounding of kidney function. Multivariable linear regression models were conducted to estimate associations of covariate-adjusted creatinine standardization urinary melamine and cyanuric acid concentrations with eGFR and UACR. Log-binomial regression models were performed to estimate risks of impaired kidney function and hypertension associated with urinary melamine and cyanuric acid levels. The geometric mean values of urinary melamine and cyanuric acid concentrations were 1.51 μg/L [95% confidence interval (CI): 1.21 μg/L, 1.89 μg/L] and 5.86 μg/L (95% CI: 5.34 μg/L, 6.44 μg/L), respectively. The median value of estimated daily intake (EDI) for melamine was 0.06 (ranging from undetectable to 1.11) μg/kg body weight/day calculated by urinary concentration and creatinine excretion accounting for sex and body weight. Adults in the fourth quartile of melamine and cyanuric acid exposure had 0.142 mL/min/1.73 m2 (95% CI: -0.271, -0.014) and 0.106 mL/min/1.73 m2 (95% CI: -0.020, 0.006) lower eGFR for melamine and cyanuric acid, respectively, compared to participants in the first quartile of exposure with adjustment for potential confounders. To our best knowledge, this is the first study to report associations between melamine and its derivative and kidney function of the U.S. adults from NHANES 2003-2004. The suggestive evidence revealed that individuals with high melamine exposure had lower eGFR than those with low melamine exposure, although no significant association between melamine and cyanuric acid exposure and markers of kidney function was observed. These findings should be interpreted with caution regarding the possible reverse causality.
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| 8. |
- Guo, Jianqiu, et al.
(författare)
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Associations of prenatal and childhood chlorpyrifos exposure with Neurodevelopment of 3-year-old children
- 2019
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Ingår i: Environmental Pollution. - : Elsevier. - 0269-7491 .- 1873-6424. ; 251, s. 538-546
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Tidskriftsartikel (refereegranskat)abstract
- Chlorpyrifos (CPF), an organophosphate insecticide, has been linked to adverse neurodevelopmental effects in animal studies. However, little is known about long-term neurotoxicity of early-life CPF exposure in humans. We aimed to evaluate the associations of both prenatal and early childhood CPF exposure with neurodevelopment of children. In this observational study based on Sheyang Mini Birth Cohort, pregnant women were recruited from an agricultural region between June 2009 and January 2010, and their children were followed up from birth to age three. Urinary 3,5,6-Trichloro-2-pyridinol (TCPy), a specific metabolite of CPF, was quantified using large-volume-injection gas chromatography tandem mass spectrometry. Developmental quotients (DQs) of children in motor, adaptive, language, and social areas were assessed by trained pediatricians. Data from 377 mother-child pairs were used in the current study. Associations between CPF exposure and neurodevelopmental indicators were estimated using generalized linear models with adjustment for potential confounders. The median concentrations of TCPy in maternal and children's urine were 5.39 mu g/L and 5.34 mu g/L, respectively. No statistically significant association was found between maternal urinary TCPy concentrations and children neurodevelopment. While for postnatal exposure, we found lower motor area DQ score 0.61 [95% confidence interval (CI): -1.13, -0.09; p = 0.02] and social area DQ score 0.55 (95% CI: -1.07, -0.03; p = 0.04) per one-unit increase in the In-transformed childhood urinary TCPy concentrations. Further stratification by sex indicated that the inverse associations were only observed in boys, but not in girls. Our findings suggest that adverse neurodevelopmental effects were associated with early childhood CPF exposure, but not prenatal exposure. Additional longitudinal studies are needed to replicate these results and to further understand the toxicological mechanisms of CPF.
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| 9. |
- Guo, Jianqiu, et al.
(författare)
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Early life triclosan exposure and neurodevelopment of children at 3 years in a prospective birth cohort
- 2020
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Ingår i: International journal of hygiene and environmental health. - : Urban & Fischer. - 1438-4639 .- 1618-131X. ; 224
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Early life exposure to triclosan, an emerging endocrine disrupting chemical, may adversely impact childhood neurodevelopment, but limited epidemiologic studies have examined the associations.OBJECTIVE: We evaluated the associations between prenatal and postnatal triclosan exposure and child neurodevelopment at 3 years.METHODS: The study included 377 mother-child pairs who participated in Sheyang Mini Birth Cohort Study (SMBCS), a longitudinal birth cohort in China. Triclosan concentrations in maternal and 3-year-old child urine samples were quantified using gas chromatography-tandem mass spectrometry (GC-MS/MS). Gesell Developmental Schedules (GDS) were used to assess child neurodevelopment at 3 years of age. Multivariate linear regression models were applied to estimate associations of prenatal and postnatal urinary triclosan concentrations with children's developmental quotients (DQs).RESULTS: Detection frequencies of triclosan in maternal and childhood urine samples were 100% and 99.5%, respectively. The median values of prenatal and postnatal urinary triclosan levels were 0.65 and 0.44 μg/L, respectively. One ln-unit increase of maternal urinary triclosan concentration was associated with increase of DQ scores in motor area of children (regression coefficient, β = 0.28, 95% confidence interval, CI: 0.03, 0.54; p = 0.03). In sex-stratified analyses, maternal urinary triclosan levels were significantly related to increases in DQ scores in motor area among boys (β = 0.25, 95%CI: 0.01, 0.50; p = 0.04), while postnatal urinary triclosan concentrations were inversely associated with DQ scores in social area in boys (β = -0.37, 95%CI: -0.72, -0.03; p = 0.03).CONCLUSIONS: The findings suggested that prenatal triclosan exposure predicted increases in motor scores, while postnatal triclosan exposure was related to reductions in social scores of 3-year-old children. These associations were only observed in boys. The biological mechanisms linking triclosan exposure to neurodevelopment await further studies.
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| 10. |
- Guo, Jianqiu, et al.
(författare)
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Maternal and childhood urinary phenol concentrations, neonatal thyroid function, and behavioral problems at 10 years of age : The SMBCS study
- 2020
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 743
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Environmental phenols, bisphenol A (BPA), triclosan (TCS), and benzophenone-3 (BP-3), are known as emerging endocrine-disrupting chemicals; however, their impacts on thyroid hormones and children's neurobehaviors are still unclear.OBJECTIVES: We aimed to examine the associations of prenatal and childhood exposure to phenols with neonatal thyroid function and childhood behavioral problems aged 10 years.METHODS: A total of 386 mother-singleton pairs were included from Sheyang Mini Birth Cohort Study (SMBCS), a longitudinal birth cohort in China. We quantified urinary BPA, TCS and BP-3 concentrations in maternal and 10-year-old children's urine samples using gas chromatography tandem mass spectrometry and thyroid function parameters in cord serum samples. Caregivers completed the Strength and Difficulties Questionnaire (SDQ) for their children at 10 years of age. Multivariable linear regression models and logistic regression models were applied to estimate associations of urinary phenol concentrations with thyroid hormones and risks of children's behavioral problems, respectively.RESULTS: The median values of urinary BPA, TCS and BP-3 concentrations for pregnant women were 1.75 μg/L, 0.54 μg/L and 0.37 μg/L, while 1.29 μg/L, 6.64 μg/L and 1.39 μg/L for children, respectively. Maternal urinary BPA concentrations were in associations with 1.00% [95% confidence interval (CI): 0.20%, 1.92%] increases in cord serum FT4 concentrations and significantly associated with increased risks of total difficulties [odds ratio (OR): 1.45, 95% CI: 1.07, 1.97], while maternal urinary levels of BP-3 were significantly related to poorer prosocial behaviors (OR: 1.58, 95% CI: 1.04, 2.39) of children at 10 years of age. In sex-stratified analyses, maternal urinary BPA concentrations were related to increased total difficulty subscales only in boys.CONCLUSIONS: The findings indicated that higher prenatal urinary BPA concentrations were associated with increased risks of total difficulties, especially in boys and maternal urinary BP-3 concentrations were related to poorer prosocial behaviors at 10 years.
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