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1.
Environ Res ; 200: 111459, 2021 09.
Article in English | MEDLINE | ID: mdl-34126051

ABSTRACT

BACKGROUND: Bisphenol A (BPA) and its alternatives, including BPF and BPS, exhibit endocrine disruption activities. However, the effects of bisphenols on fetal growth in twins remain unclear. OBJECTIVE: To explore the associations of prenatal BPA, BPF, and BPS exposure with birth outcome differences in twins. METHODS: We recruited 289 twin pregnant women who visited the hospital for prenatal examination during the first trimester from 2013 to 2016. Urinary bisphenol levels were determined during the first, second, and third trimesters. The associations of maternal exposure to bisphenols with birth outcome differences in twins were analyzed after stratification by different trimesters. We applied the multiple informant model to estimate trimester-specific associations between urinary bisphenol concentrations and birth outcome differences in twins. RESULTS: We found low reproducibility (ICC<0.40) for maternal urinary BPA and moderate reproducibility (0.40 < ICC<0.75) for BPF and BPS. Urinary BPA concentrations were positively associated with within-pair twin birth weight difference when comparing the third vs. the first tertile in each of the three trimesters (i.e., 133.06 g, 95% CI: 68.19, 197.94; 144.5 g, 95%CI: 81.82-207.18 g; and 135.04 g, 95%CI: 71.37-198.71 g for the 1st, 2nd, and 3rd trimester, respectively). The effect of urinary BPA concentration on increased birth length difference within-pair twins were also observed across different trimesters (All P for trends < 0.05). Urinary BPA levels were positively associated with the within-pair birth weight and birth length differences across pregnancy trimesters (All of Type 3 P for values < 0.05). CONCLUSION: Maternal BPA exposure appeared to influence birth wight and birth length differences in twins. Our results warrant further confirmation.


Subject(s)
Prenatal Exposure Delayed Effects , Benzhydryl Compounds/toxicity , Cohort Studies , Female , Humans , Maternal Exposure/adverse effects , Phenols , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/epidemiology , Reproducibility of Results
2.
Acta Pharmacol Sin ; 40(10): 1292-1302, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31015738

ABSTRACT

Microglia, the brain-resident macrophage, is known as the innate immune cell type in the central nervous system. Microglia is also the major cellular component of tumor mass of gliomas that plays a key role in glioma development. Mutations of isocitrate dehydrogenases 1 and 2 (IDH1/2) frequently occur in gliomas, which leads to accumulation of oncometabolic product 2-hydroxyglutarate (2HG). Moreover, IDH1/2 mutations were found to correlate with better prognosis in glioma patients. In the present study, we investigated the effects of the 2HG on microglial inflammatory activation. We showed that the conditioned media (CM) from GL261 glioma cells stimulated the activation of BV-2 microglia cells, evidenced by markedly increased expression of interleukin-6 (IL-6), IL-1ß, tumor necrosis factor-α (TNF-α), CCL2 (C-C motif chemokine ligand 2) and CXCL10 (C-X-C motif chemokine 10). CM-induced expression of proinflammatory genes was significantly suppressed by pretreatment with a synthetic cell-permeable 2HG (1 mM) or a nuclear factor-κB (NF-κB) inhibitor BAY11-7082 (10 µM). In lipopolysaccharide (LPS)- or TNF-α-stimulated BV-2 microglia cells and primary microglia, pretreatment with 2HG (0.25-1 mM) dose-dependently suppressed the expression of proinflammatory genes. We further demonstrated that 2HG significantly suppressed LPS-induced phosphorylation of IκB kinase α/ß (IKKα/ß), IκBα and p65, IκB degradation, and nuclear translocation of p65 subunit of NF-κB, as well as NF-κB transcriptional activity. Similarly, ectopic expression of mutant isocitrate dehydrogenase 1 (IDH1) (R132H) significantly decreased TNF-α-induced activation of NF-κB signaling pathway. Finally, we revealed that activation of adenosine 5'-monophosphate-activated protein kinase (AMPK) and subsequent inhibition of mammalian target of rapamycin (mTOR) signaling contributed to the inhibitory effect of 2HG on NF-κB signaling pathway in BV-2 cells. Taken together, these results, for the first time, show that oncometabolite 2HG inhibits microglial activation through affecting AMPK/mTOR/NF-κB signaling pathway and provide evidence that oncometabolite 2HG may regulate glioma development via modulating microglial activation in tumor microenvironment.


Subject(s)
AMP-Activated Protein Kinases/antagonists & inhibitors , Glutarates/pharmacology , Microglia/drug effects , NF-kappa B/antagonists & inhibitors , TOR Serine-Threonine Kinases/antagonists & inhibitors , AMP-Activated Protein Kinases/metabolism , Animals , Cells, Cultured , Dose-Response Relationship, Drug , HEK293 Cells , Humans , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Mice , Microglia/metabolism , NF-kappa B/metabolism , Structure-Activity Relationship , TOR Serine-Threonine Kinases/metabolism , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/metabolism
3.
Am J Hypertens ; 25(5): 576-82, 2012 May.
Article in English | MEDLINE | ID: mdl-22337208

ABSTRACT

BACKGROUND: There is little information regarding the obesity epidemical situation and risk factors of childhood hypertension (HTN) in China. The present study aimed to determine the prevalence of HTN/prehypertension (PHTN), as well as the associated risk factors, among adolescents in Changsha city, China. METHODS: A total of 88,974 adolescents from 49 middle schools in Changsha city between 12 and 17 years of age were examined during 2009. Body weight, height, and blood pressure (BP) were measured in all adolescents. HTN and PHTN were defined according to sex- and age-specific Chinese reference data. Overweight and obesity were also defined according to sex- and age-specific Chinese reference data. RESULTS: It was determined that the prevalence of PHTN and HTN were 7.2 and 3.1%, respectively. Furthermore, 14.6% of male adolescents were overweight and 7.0% were obese, whereas 8.6% of female adolescents were overweight and 2.9% were obese. The risk ratio (RR) of HTN were significantly higher in overweight (RR: 2.8, 95% confidence interval (CI): 2.6-3.2) and obese (RR: 8.7, 95% CI: 8.1-9.5) adolescents adjusted for age, sex, and height. CONCLUSIONS: Chinese reference data were used to evaluate BP and body mass index (BMI) of children and adolescents. Higher prevalence of HTN was associated with higher BMI percentiles. Being overweight or obese markedly increased the risk of both HTN and PHTN among adolescents between 12 and 17 years of age in Changsha city, China.


Subject(s)
Blood Pressure/physiology , Hypertension/epidemiology , Obesity/complications , Prehypertension/epidemiology , Schools , Adolescent , Body Mass Index , Child , China/epidemiology , Humans , Male , Obesity/physiopathology , Prevalence , Retrospective Studies , Risk Factors
4.
Zhonghua Liu Xing Bing Xue Za Zhi ; 32(10): 978-82, 2011 Oct.
Article in Chinese | MEDLINE | ID: mdl-22333078

ABSTRACT

OBJECTIVE: This study was to estimate the prevalence of elderly mistreatment (EM) in rural community and to examine the association between social support and the risk of the EM. METHODS: A cross-sectional descriptive study was performed in three rural communities (17 villages) in Macheng city of Hubei province. 2000 subjects aged 60 years or older were selected using cluster sampling. Questionnaire being developed would include general information, a scale to measure social support, and a modified vulnerability on abuse screening scale (VASS) to measure the EM. RESULTS: The prevalence rates of EM, physical abuse, emotional abuse, neglect and financial exploitation for rural elderly people in Macheng city were 36.2%, 4.9%, 27.3%, 15.8%, and 2.0% respectively. After adjusting for potential confounding factors, necessary practical support from family (OR = 1.28, 95%CI: 1.01 - 1.63) was the risk factor causing EM while having got practical support (OR = 0.76, 95%CI: 0.58 - 0.98) or moral support (OR = 0.63, 95%CI: 0.49 - 0.82) from family and moral support from friends (OR = 0.73, 95%CI: 0.59 - 0.90) when in need were the protective factors. The protective factors on physical abuse, emotional abuse, neglect and financial exploitation would include: getting practical support from family when in need (OR = 0.59, 95%CI: 0.35 - 0.99), getting moral support from family (OR = 0.67, 95%CI: 0.51 - 0.89) and friends (OR = 0.67, 95%CI: 0.54 - 0.84) and getting practical support from family when in need (OR = 0.63, 95%CI: 0.45 - 0.88), getting practical support from family (OR = 0.38, 95%CI: 0.14 - 0.98) and getting moral support from friends when in need (OR = 0.42, 95%CI: 0.20 - 0.87), respectively. CONCLUSION: High prevalence of EM was seen in the rural areas of Macheng city. Social support was an important protective factor for EM in this population.


Subject(s)
Elder Abuse/statistics & numerical data , Social Support , Aged , Aged, 80 and over , China , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Risk Factors , Rural Population , Surveys and Questionnaires
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