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Ecotoxicol Environ Saf ; 210: 111854, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33422839


OBJECTIVE: To explore the prospective correlation between serum metals before 24 weeks' gestation and gestational diabetes mellitus (GDM) or glucose in the late second trimester among southern Chinese pregnant women. METHODS: A total of 8169 pregnant women were included in our retrospective cohort study. Logistic regression was used to investigate the relationships between metals (Manganese [Mn], copper [Cu], lead [Pb], calcium [Ca], zinc [Zn], magnesium [Mg]) and GDM. Quantile regression was performed to detect the shifts and associations with metals and three time-points glucose distribution of oral glucose tolerance test (OGTT) focused on the 10th, 50th, and 90th percentiles. Weighted quantile sum (WQS) regression was used to explore the relationship of metal mixtures and GDM as well as glucose. RESULTS: Maternal serum concentrations of metals were assessed at mean 16.55 ± 2.92 weeks' gestation. Women with under weight might have 25% decreased risk of GDM for every 50% increase in Cu concentration within the safe limits. A 50% increase in Mn and Zn levels was related to a 0.051 µmol/L (95% CI: 0.033-0.070) and 0.059 µmol/L (95% CI: 0.040-0.079) increase in mean fasting plasma glucose of OGTT (OGTT0), respectively. The magnitude of association with Mn was smaller at the upper tail of OGTT0 distribution, while the magnitude of correlation with Zn was greater at the upper tail. However, there was a 0.012 mmol/L (95% CI: -0.017 to -0.008), 0.028 mmol/L (95% CI: -0.049 to -0.007), and 0.036 mmol/L (95% CI: -0.057 to -0.016) decrease in mean OGTT0 levels for every 50% increase in Pb, Ca, and Mg, respectively. The negative association of Pb, Ca, and Mg was greater at the lower tail of OGTT0 distribution. No significant relationship was observed in Cu and mean OGTT0 level (-0.010 mmol/L, 95% CI: -0.021 to 0.001), however, it showed a protective effect at the upper tail (-0.034 mmol/L, 95% CI: -0.049 to -0.017). No obvious correlation was found between metals and postprandial glucose levels (OGTT1 and OGTT2 from OGTT). The WQS index was significantly related to OGTT0 (P < 0.001). The contribution of Mn (80.19%) to metal mixture index was the highest related to OGTT0, followed by Cu (19.81%). CONCLUSIONS: Higher Mn and Zn but lower Pb, Ca, and Mg concentrations within a certain range before 24 weeks' gestation might prospectively impair fasting plasma glucose during pregnancy; a greater focus is required on Mn. It could provide early markers of metal for predicting later glucose and suggest implement intervention for pregnant women.

Glicemia/análise , Diabetes Gestacional/sangue , Metais/sangue , Adulto , Monitoramento Biológico , Biomarcadores/sangue , China/epidemiologia , Diabetes Gestacional/epidemiologia , Feminino , Humanos , Gravidez
Mol Cell Biochem ; 392(1-2): 95-107, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24633962


MCPH1, initially identified as an hTERT repressor, has recently been implicated in mediating DNA damage response and maintaining chromosome integrity. This study is to investigate its potential role in the onset of cervical cancer. In the study, decreased expression of MCPH1 was observed in 19 of 31 cases (61.3%) at mRNA level and 44 of 63 cases (69.8%) at protein level of cervical tumor tissues compared with the paired nontumor tissues. Reduced MCPH1 protein expression was significantly associated with high-tumor grade (1 vs. 3 P = 0.013; 2 vs. 3 P = 0.047). In addition to inhibit SiHa cell migration and invasion, the overexpression of MCPH1 inhibited cervical cancer cells growth through inducing S phase arrest and mitochondrial apoptosis. Further analysis demonstrated cyclinA2/CDK2, CDC25C-cyclinB/CDC2, and p53/p21 pathways were involved in the MCPH1 overexpression-induced S phase arrest. Moreover, the overexpression of MCPH1 activated mitochondrial apoptosis through regulating several apoptosis-related proteins such as p53, Bcl-2, Bax, cytochrome c, caspase-3, and PARP-1. Our findings indicate that downregulated MCPH1 correlates with tumor progression in cervical cancer, and MCPH1 has an important role in regulating cell growth through regulating the cell cycle and apoptosis. Thus, it may be a crucial tumor suppressor gene and a novel candidate therapeutic target for cervical cancer.

Caspase 3/metabolismo , Proteínas de Ciclo Celular/fisiologia , Divisão Celular/fisiologia , Citocromos c/metabolismo , Proteínas do Tecido Nervoso/fisiologia , Neoplasias do Colo do Útero/patologia , Sequência de Bases , Linhagem Celular , Proteínas do Citoesqueleto , Primers do DNA , Feminino , Humanos , Proteínas do Tecido Nervoso/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais , Neoplasias do Colo do Útero/enzimologia , Neoplasias do Colo do Útero/metabolismo