RESUMO
Previous epidemiologic research has shown that phthalate exposure in pregnant women is related to adverse birth outcomes in a sex-specific manner. However, the biological mechanism of phthalate exposure that causes these birth outcomes remains poorly defined. In this research, we investigated the association between phthalate exposure and placental oxidative stress in a large population-based cohort study, aiming to initially explore the relationship between phthalate exposure and gene expression in placental oxidative stress in a sex-specific manner. Quantitative PCR was performed to measure the expression of placental inflammatory mRNAs (HO-1, HIF1α, and GRP78) in 2469 placentae. The multiple linear regression models were used to investigate the associations between mRNA and urinary phthalate monoesters. Phthalate metabolites monomethyl phthalate (MMP) and mono-n-butyl phthalate (MBP) were positively correlated with higher HIF1α expression in placentae of male fetuses (p < .05). Mono-benzyl phthalate (MBzP) increased the expression of HO-1, HIF1α, and GRP78 in placentae of male fetuses, and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) up-regulated the expression of HIF1α and GRP78. Additionally, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) was negatively correlated with HO-1, HIF1α, and GRP78 in placentae of female fetuses. Maternal phthalate exposure was associated with oxidative stress variations in placental tissues. The associations were closer in the placentas of male fetuses than in that of female ones. The placenta oxidative stress is worth further investigation as a potential mediator of maternal exposure-induced disease risk in children.
Assuntos
Biomarcadores , Chaperona BiP do Retículo Endoplasmático , Exposição Materna , Estresse Oxidativo , Ácidos Ftálicos , Placenta , Humanos , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/urina , Feminino , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Masculino , Placenta/efeitos dos fármacos , Placenta/metabolismo , Biomarcadores/urina , Estudos Prospectivos , Adulto , Exposição Materna/efeitos adversos , Fatores Sexuais , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/genética , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética , Estudos de CoortesRESUMO
This cohort study sought to investigate the effects of phthalates exposure during pregnancy on offspring asthma and its association with placental stress and inflammatory factor mRNA expression levels. A total of 3474 pregnant women from the China Ma'anshan birth cohort participated in this study. Seven phthalate metabolites were detected in urine samples during pregnancy by solid phase extraction-high-performance liquid chromatography tandem mass spectrometry. Placenta stress and inflammation mRNA expression were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). Early pregnancy may be the critical period when phthalates exposure increases the risk of asthma in infants and young children, and there is a certain gender difference in the risk of asthma in infants and young children. Moreover, through the placenta stress and inflammatory factor associated with infant asthma found anti-inflammatory factor of interleukin-10 (IL-10) mRNA expression will reduce the risk of 36-month-old male infant asthma. The expression of interleukin-4(IL-4) and macrophage (M2) biomarker cluster of differentiation 206(CD206) mRNA reduced the risk of asthma in 18-month-old female infants. Placental stress and inflammatory response were analyzed using mediating effects. Tumor necrosis factor-α (TNFα) showed a complete mediating effect between mono-benzyl phthalate (MBzP) exposure in early pregnancy and asthma in 12-month-old males, and IL-10 also showed a complete mediating effect between mono-n-butyl phthalate (MBP) exposure in early and late pregnancy and asthma in 36-month-old males. In summary, exposure to phthalates during pregnancy may contribute to the development of asthma in infants, which may be associated with placental stress and inflammation.
Assuntos
Asma , Poluentes Ambientais , Ácidos Ftálicos , Criança , Humanos , Masculino , Feminino , Gravidez , Lactente , Pré-Escolar , Estudos de Coortes , Interleucina-10 , Placenta/metabolismo , Ácidos Ftálicos/toxicidade , Asma/induzido quimicamente , Asma/epidemiologia , Inflamação , RNA Mensageiro , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Poluentes Ambientais/análiseRESUMO
BACKGROUND: As an important alternative to bisphenol A (BPA), bisphenol AF (BPAF) is widely used and can be detected in multiple human biological samples. However, there are few studies on neurotoxicity of BPAF at present. In particular, no epidemiological studies have investigated BPAF in relation to depressive symptoms in adolescents. Here, our study aimed to evaluate the associations between serum BPAF concentrations and depressive symptoms in adolescents. METHODS: A nested case-control study within an ongoing longitudinal prospective adolescent cohort that was established in Huaibei, China was conducted. A total of 175 participants who had new-onset depressive symptoms (cases) and 175 participants without depressive symptoms (controls) were included. Serum BPAF concentrations was measured using ultra-high-performance liquid chromatography-tandem mass spectrometry. The associations between BPAF exposure and the risk of depressive symptoms in adolescents were assessed using conditional logistic regression. The dose-response relationship between BPAF level and depressive symptoms was estimated using restricted cubic spline analyses. RESULTS: In this study, the detection rate of serum BPAF was 100%, and the median (interquartile range, IQR) serum BPAF concentration was 5.24 (4.41-6.11) pg/mL in the case group and 4.86 (4.02-5.77) pg/mL in the control group (P = 0.009). Serum BPAF exposure was a risk factor for depressive symptoms (odds ratio (OR)= 1.132, 95% confidence interval (CI):1.013-1.264). After adjustment for all for confounders, compared with the low-exposure group, the high-exposure group had a 2.806-fold increased risk of depressive symptoms (OR=2.806, 95% CI: 1.188-6.626). Stratified analysis by sex revealed that males were more vulnerable to BPAF exposure than females. After adjustment for all confounders, compared with the low-exposure group, the relative risk of depressive symptoms in the high-exposure group was 3.858 (95% CI: 1.118-12.535) for males, however, no significant association between BPAF exposure and depressive symptoms was found in females. In addition, there was a marked linear association between BPAF exposure and the risk of depressive symptoms in the total population and in males. CONCLUSIONS: The adolescents in this study were widely exposed to low levels of BPAF. A significant positive association was found between serum BPAF levels and the risk of depressive symptoms. The association was significantly modified by sex, and males were more vulnerable to BPAF exposure than females.
Assuntos
Compostos Benzidrílicos , Depressão , Adolescente , Compostos Benzidrílicos/química , Compostos Benzidrílicos/toxicidade , Estudos de Casos e Controles , China/epidemiologia , Depressão/induzido quimicamente , Depressão/epidemiologia , Feminino , Fluorocarbonos , Humanos , Masculino , Estudos ProspectivosRESUMO
We assess the safety and feasibility of the left hepatic vein preferential approach (LHVPA) based on left hepatic vein (LHV) anatomy for living donor laparoscopic left lateral sectionectomy (LLLS). Data from 50 donors who underwent LLLS in Huashan Hospital from October 2016 to November 2019 were analyzed retrospectively. On the basis of the classification of the LHV anatomy, the vein was defined as the direct import type, upper branch type, or indirect import type. A subgroup analysis was performed to compare the outcomes between the LHVPA and non-LHVPA groups. All 50 patients underwent pure LLLS. The mean operative duration was 157.5 ± 29.7 minutes. The intraoperative blood loss was 160.4 ± 97.5 mL. No complications more severe than grade 3 occurred. LHVPA was applied in 13 patients, whereas non-LHVPA was applied in 10 patients with the direct import type and upper branch type anatomy. The operative duration was shorter in the LHVPA group than the non-LHVPA group (142.7 ± 22.0 versus 173.0 ± 22.8 minutes; P = 0.01). Intraoperative blood loss was reduced in the LHVPA group compared with the non-LHVPA group (116.2 ± 45.6 versus 170.0 ± 63.3 mL; P = 0.02). The length of the LHV reserved extrahepatically in the LHVPA group was longer than in the non-LHVPA group (4.3 ± 0.2 versus 3.3 ± 0.3 mm; P = 0.01). Fewer reconstructions of the LHV in the direct import type anatomy were required for the LHVPA group than for the non-LHVPA group (0/8 versus 4/6). LHVPA based on the LHV anatomy is recommended in LLLS because it can further increase the safety and the efficiency of surgery for suitable donors.
Assuntos
Laparoscopia , Transplante de Fígado , Hepatectomia/efeitos adversos , Veias Hepáticas/diagnóstico por imagem , Veias Hepáticas/cirurgia , Humanos , Tempo de Internação , Transplante de Fígado/efeitos adversos , Doadores Vivos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Numerous studies had focused on the association between air pollution and health outcomes in recent years. However, little evidence is available on associations between air pollutants and premature rupture of membranes (PROM). Therefore, we performed time-series analysis to evaluate the association between PROM and air pollution. The daily average concentrations of PM2.5, SO2 and NO2 were 54.58 µg/m3, 13.06 µg/m3 and 46.09 µg/m3, respectively, and daily maximum 8-h average O3 concentration was 95.67 µg/m3. The strongest effects of SO2, NO2 and O3 were found in lag4, lag06 and lag09, and an increase of 10 µg/m3 in SO2, NO2 and O3 was corresponding to increase in incidence of PROM of 8.74% (95% CI 2.12-15.79%), 3.09% (95% CI 0.64-5.59%) and 1.68% (95% CI 0.28-3.09%), respectively. There were no significant effects of PM2.5 on PROM. Season-specific analyses found that the effects of PM2.5, SO2 and O3 on PROM were more obvious in cold season, but the statistically significant effect of NO2 was observed in warm season. We also found the modifying effects by maternal age on PROM, and we found that the effects of SO2 and NO2 on PROM were higher among younger mothers (< 35 years) than advanced age mothers (≥ 35 years); however, ≥ 35 years group were more vulnerable to O3 than < 35 years group. This study indicates that air pollution exposure is an important risk factor for PROM and we wish this study could provide evidence to local government to take rigid approaches to control emissions of air pollutants.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China/epidemiologia , Fatores de Risco , Estações do AnoRESUMO
Multidrug resistance is one of the reasons for low survival of advanced hepatocellular carcinoma (HCC). Our previous studies indicate that the hedgehog signalling is involved in hepatic carcinogenesis, metastasis and chemo-resistance. The present study aims to uncover molecular mechanisms underlying hepatoma chemo-resistance. TAP1 and GLI1/2 gene expression was assessed in both poorly differentiated hepatoma cells and HCC specimens. Potential GLI-binding site in the TAP1 promoter sequence was validated by molecular assays. Approximately 75% HCC specimens exhibited an elevated expression of hedgehog GLI1 transcription factor compared with adjacent liver tissue. Both GLI1/2 and TAP1 protein levels were significantly elevated in poorly differentiated hepatoma cells. Both Huh-7-trans and Huh-7-DN displayed more karyotypic abnormalities and differential gene expression profiles than their native Huh-7 cells. Sensitivity to Sorafenib, doxorubicin and cisplatin was remarkably improved after either GLI1 or TAP1 gene was inhibited by an RNAi approach or by a specific GLI1/2 inhibitor, GANT61. Further experiments confirmed that hedgehog transcription factor GLI1/2 binds to the TAP1 promoter, indicating that TAP1 is one of GLI1/2 target genes. In conclusion, TAP1 is under direct transcriptional control of the hedgehog signalling. Targeting hedgehog signalling confers a novel insight into alleviating drug resistance in the treatment of refractory HCC.
Assuntos
Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/genética , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Proteínas Nucleares/antagonistas & inibidores , Proteína GLI1 em Dedos de Zinco/antagonistas & inibidores , Proteína Gli2 com Dedos de Zinco/antagonistas & inibidores , Carcinogênese/efeitos dos fármacos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas Hedgehog/antagonistas & inibidores , Proteínas Hedgehog/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Proteínas Nucleares/genética , Regiões Promotoras Genéticas/genética , Piridinas/farmacologia , Pirimidinas/farmacologia , Transdução de Sinais , Proteína GLI1 em Dedos de Zinco/genética , Proteína Gli2 com Dedos de Zinco/genéticaRESUMO
BACKGROUND: Mitochondrial dynamics plays an important role in tumour progression. However, how these dynamics integrate tumour metabolism in hepatocellular carcinoma (HCC) metastasis is still unclear. METHODS: The mitochondrial fusion protein mitofusin-1 (MFN1) expression and its prognostic value are detected in HCC. The effects and underlying mechanisms of MFN1 on HCC metastasis and metabolic reprogramming are analysed both in vitro and in vivo. RESULTS: Mitochondrial dynamics, represented by constant fission and fusion, are found to be associated with HCC metastasis. High metastatic HCC displays excessive mitochondrial fission. Among genes involved in mitochondrial dynamics, MFN1 is identified as a leading downregulated candidate that is closely associated with HCC metastasis and poor prognosis. While promoting mitochondrial fusion, MFN1 inhibits cell proliferation, invasion and migration capacity both in vitro and in vivo. Mechanistically, disruption of mitochondrial dynamics by depletion of MFN1 triggers the epithelial-to-mesenchymal transition (EMT) of HCC. Moreover, MFN1 modulates HCC metastasis by metabolic shift from aerobic glycolysis to oxidative phosphorylation. Treatment with glycolytic inhibitor 2-Deoxy-D-glucose (2-DG) significantly suppresses the effects induced by depletion of MFN1. CONCLUSIONS: Our results reveal a critical involvement of mitochondrial dynamics in HCC metastasis via modulating glucose metabolic reprogramming. MFN1 may serve as a novel potential therapeutic target for HCC.
Assuntos
Carcinoma Hepatocelular/metabolismo , Desoxiglucose/farmacologia , GTP Fosfo-Hidrolases/genética , Glucose/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , GTP Fosfo-Hidrolases/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Mitocôndrias/genética , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/genética , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Metástase Neoplásica , Fosforilação Oxidativa/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
The aim of this study was to explore the impact of prenatal Al and Mg on placental oxidative stress and inflammatory mRNA expression. A total of 2519 pregnant women from the China Ma'anshan birth cohort participated in this study. Al and Mg levels were measured by inductively coupled plasma mass spectrometry (ICP-MS). Placental stress and inflammatory mRNA expression were assessed by RT-PCR. The median Al levels in the first and second trimesters of pregnancy and in cord blood were higher than the corresponding median Mg levels. Predictors of lower Al and Mg levels included Han ethnicity and high education according to a mixed linear model. Multiple linear regression analysis revealed that Al and Al/Mg levels had a positive association with inflammatory mRNA expression and placental oxidative stress in the second trimester of pregnancy. A negative association existed between Al and Al/Mg levels and inflammatory mRNA expression and placenta oxidative stress in the cord blood, with the exception of IL-1ß expression. In conclusion, prenatal Al and Mg status was associated with placental oxidative stress and inflammatory mRNA expression. More preclinical studies are needed to confirm the relevant mechanism.
Assuntos
Alumínio/sangue , Poluentes Ambientais/sangue , Inflamação/genética , Magnésio/sangue , Estresse Oxidativo , Adulto , China , Estudos de Coortes , Exposição Ambiental/análise , Poluentes Ambientais/análise , Feminino , Sangue Fetal/química , Sangue Fetal/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Inflamação/sangue , Estilo de Vida , Estresse Oxidativo/genética , Placenta/metabolismo , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , RNA Mensageiro/genética , Análise de RegressãoRESUMO
OBJECTIVE: In the tumour microenvironment, critical drivers of immune escape include the oncogenic activity of the tumour cell-intrinsic osteopontin (OPN), the expression of programmed death ligand 1 (PD-L1) and the expansion of tumour-associated macrophages (TAMs). We investigated the feasibility of targeting these pathways as a therapeutic option in hepatocellular carcinoma (HCC) mouse models. DESIGN: We analysed the number of tumour-infiltrating immune cells and the inflammatory immune profiles in chemically induced liver tumour isolated from wild-type and OPNknockout (KO) mice. In vitro cell cocultures were further conducted to investigate the crosstalk between TAMs and HCC cells mediated by OPN, colony stimulating factor-1 (CSF1) and CSF1 receptor (CSF1R). The in vivo efficacy of anti-PD-L1 and CSF1/CSF1R inhibition was evaluated in OPN overexpressing subcutaneous or orthotopic mouse model of HCC. RESULTS: The numbers of TAMs, as well as the expression levels of M2 macrophage markers and PD-L1 were significantly decreased, but the levels of cytokines produced by T-helper 1 (Th1) cells were upregulated in tumour tissues from OPN KO mice compared with that from the controls. In addition, we observed a positive association between the OPN and PD-L1 expression, and OPN expression and TAM infiltration in tumour tissues from patients with HCC. We further demonstrated that OPN facilitates chemotactic migration, and alternative activation of macrophages, and promotes the PD-L1 expression in HCC via activation of the CSF1-CSF1R pathway in macrophages. Combining anti-PD-L1 and CSF1R inhibition elicited potent antitumour activity and prolonged survival of OPNhigh tumour-bearing mice. Histological, flow cytometric and ELISA revealed increased CD8+ T cell infiltration, reduced TAMs and enhanced Th1/Th2 cytokine balance in multiple mouse models of HCC. CONCLUSIONS: OPN/CSF1/CSF1R axis plays a critical role in the immunosuppressive nature of the HCC microenvironment. Blocking CSF1/CSF1R prevents TAM trafficking and thereby enhances the efficacy of immune checkpoint inhibitors for the treatment of HCC.
Assuntos
Antígeno B7-H1/antagonistas & inibidores , Carcinoma Hepatocelular/imunologia , Neoplasias Hepáticas/imunologia , Fator Estimulador de Colônias de Macrófagos/imunologia , Macrófagos/imunologia , Aminopiridinas/farmacologia , Aminopiridinas/uso terapêutico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Quimiotaxia/imunologia , Citocinas/biossíntese , Deleção de Genes , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Linfócitos do Interstício Tumoral/imunologia , Fator Estimulador de Colônias de Macrófagos/antagonistas & inibidores , Masculino , Camundongos Knockout , Terapia de Alvo Molecular/métodos , Osteopontina/genética , Osteopontina/imunologia , Prognóstico , Pirróis/farmacologia , Pirróis/uso terapêutico , Células Tumorais Cultivadas , Evasão Tumoral/imunologia , Microambiente Tumoral/imunologiaRESUMO
This study enrolled 3266 pregnant women, to explore the relationship of prenatal phthalate exposure with the risk of preterm birth and gestational age. All participants filled questionnaires and provided with up to three urine samples during three trimesters. Seven phthalate metabolites in urines were measured. The incidences of very preterm, late preterm, early-term, late-term and postterm births were 0.58%, 3.52%, 24.22%, 10.53%, and 0.34%, respectively. Non-linear relationships were shown between phthalate metabolites and gestational age. Except for monomethyl phthalate (ORâ¯=â¯1.65, 95%CIâ¯=â¯1.17-2.34), the average concentrations of phthalate metabolites were associated with a slightly and insignificantly increased risk of overall preterm birth (<37+0 gestational weeks). Through a restricted cubic spline regression, phthalate metabolites were found to be related to the risk of overall preterm birth in a linear manner (p-value >0.05) or a non-linear manner (p-value <0.05). All curves indicated the overall preterm birth risk rose with the increase of phthalate metabolite concentrations. Finally, compared with full-term birth (39+0 to 40+6 gestational weeks), phthalate metabolites were associated with the elevated risks of very preterm, late preterm and postterm births, although some relationships were not statistically significant. In conclusion, these findings suggested non-linear associations between phthalate metabolites and gestational age. Exposure to some phthalate metabolites was associated with increased risks of overall preterm birth and postterm birth.
Assuntos
Idade Gestacional , Exposição Materna/estatística & dados numéricos , Ácidos Ftálicos , Nascimento Prematuro/epidemiologia , Feminino , Humanos , Recém-Nascido , Gravidez , Trimestres da Gravidez , Estudos ProspectivosRESUMO
BACKGROUND/AIMS: Effective drug treatment for intrahepatic cholangiocarcinoma (ICC) is currently lacking. Therefore, there is an urgent need for new targets and new drugs that can prolong patient survival. Recently targeting the ubiquitin proteasome pathway has become an attractive anti-cancer strategy. In this study, we aimed to evaluate the therapeutic effect of and identify the potential mechanisms involved in targeting the proteasome subunit ADRM1 for ICC. METHODS: The expression of ADRM1 and its prognostic value in ICC was analyzed using GEO and TCGA datasets, tumor tissues, and tumor tissue arrays. The effects of RA190 on the proliferation and survival of both established ICC cell lines and primary ICC cells were examined in vitro. Annexin V/propidium iodide staining, western blotting and immunohistochemical staining were performed. The in vivo anti-tumor effect of RA190 on ICC was validated in subcutaneous xenograft and patient-derived xenograft (PDX) models. RESULTS: ADRM1 levels were significantly higher in ICC tissues than in normal bile duct tissues. ICC patients with high ADRM1 levels had worse overall survival (hazard ratio [HR] = 2.383, 95% confidence interval [CI] =1.357 to 4.188) and recurrence-free survival (HR = 1.710, 95% CI =1.045 to 2.796). ADRM1 knockdown significantly inhibited ICC growth in vitro and in vivo. The specific inhibitor RA190 targeting ADRM1 suppressed proliferation and reduced cell vitality of ICC cell lines and primary ICC cells significantly in vitro. Furthermore, RA190 significantly inhibited the proteasome by inactivating ADRM1, and the consequent accumulation of ADRM1 substrates decreased the activating levels of NF-κB to aggravate cell apoptosis. The therapeutic benefits of RA190 treatment were further demonstrated in both subcutaneous implantation and PDX models. CONCLUSIONS: Our findings indicate that up-regulated ADRM1 was involved in ICC progression and suggest the potential clinical application of ADRM1 inhibitors (e.g., RA190 and KDT-11) for ICC treatment.
Assuntos
Apoptose/efeitos dos fármacos , Compostos de Benzilideno/farmacologia , Neoplasias dos Ductos Biliares/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Glicoproteínas de Membrana/antagonistas & inibidores , NF-kappa B/metabolismo , Proteínas de Neoplasias , Idoso , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Linhagem Celular Tumoral , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismoRESUMO
OBJECTIVE: Hypertensive disorders of pregnancy (HDP) have been associated with adverse health outcomes for both mothers and children. Previous studies examining associations of maternal thyroid autoantibodies with HDP indicate conflicting results. The objective of this study was to examine associations of maternal thyroid autoantibody positivity in the first and the second trimesters with the risk of HDP. DESIGN, PARTICIPANTS AND MEASUREMENTS: In the Ma'anshan Birth Cohort study, a population-based prospective study in China, a total of 3474 pregnant women were enrolled between May 2013 and September 2014. Thyroid autoantibodies, including antithyroperoxidase autoantibody (TPOAb) and antithyroglobulin autoantibody (TgAb), as well as thyroid function tests, were measured in both the first and the second trimesters in 2893 pregnant women. Multivariate logistic regression analyses were conducted to calculate the odds ratio (OR) and 95% confidence interval (CI) for the associations between thyroid autoantibodies and HDP. RESULTS: Multivariate logistic regression analyses showed that TPOAb positivity in the first trimester was associated with a 1.80 (95% CI = 1.17-2.78) increased odds of HDP after adjustment for confounders, which was mainly due to an increased risk of gestational hypertension (OR = 1.93, 95% CI = 1.17-3.18). In addition, TgAb positivity in the first trimester was associated with a higher risk of HDP (OR = 1.78, 95% CI = 1.16-2.73) after adjustment for confounders, which was mainly due to an increased risk of gestational hypertension (OR = 1.89, 95% CI = 1.15-3.11). These associations were also seen among euthyroid women. Women with positive TPOAb in the second trimester seemed to have a higher risk of gestational hypertension (OR = 1.87, 95% CI = 1.02-3.43) after adjustment for confounders. However, among euthyroid women, TPOAb positivity in the second trimester was not associated with HDP. The TgAb status in the second trimester was not associated with HDP. CONCLUSIONS: Our results show that TPOAb positivity and TgAb positivity in the first trimester are associated with an increased risk of HDP. These data demonstrate that these associations are even seen among euthyroid women.
Assuntos
Hipertensão Induzida pela Gravidez/imunologia , Glândula Tireoide/imunologia , Adulto , Estudos de Coortes , Feminino , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Estudos Prospectivos , Adulto JovemRESUMO
Arsenic is an environmental toxicant. The association of gestational arsenic exposure with adverse pregnant outcomes remains controversial. This study was to investigate the association of serum As level with adverse pregnant outcomes in a large Chinese cohort population. Total 3194 mother-and-infant pairs were recruited from the China-Anhui Birth Cohort Study. Maternal serum arsenic (As) concentration was measured using hydride generation-atomic fluorescence spectrometry. Subjects were divided into L-As group and H-As group in accordance to the 75th percentile of serum As concentration. The associations of serum As level during gestation with adverse pregnant outcomes were analyzed. The incidence of small-for-gestational-age (SGA) newborns was elevated in H-As group compared to L-As group (9.9% vs 7.6%, Pâ¯=â¯.044). After controlling confounders and stratified analysis, the adjusted OR for SGA was significant only in girls with H-As but not in boys. Moreover, the incidence of preterm delivery (PTD) was elevated in H-As group compared to L-As group (7.0% vs 4.8%, Pâ¯=â¯.016). Further analysis found that the adjusted OR for moderate-to-late PTD was 1.47 (95%CI: 1.03, 2.09; Pâ¯=â¯.034) in H-As group as compared with L-As group. These results indicate that maternal serum As level during gestation is positively associated with adverse pregnant outcomes.
Assuntos
Arsênio/sangue , Exposição Materna/efeitos adversos , Resultado da Gravidez , Adulto , Povo Asiático , Peso ao Nascer , China/epidemiologia , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Trabalho de Parto Prematuro/induzido quimicamente , Trabalho de Parto Prematuro/epidemiologia , Gravidez , Fatores Sexuais , Espectrometria de Fluorescência , Adulto JovemRESUMO
OBJECTIVE: There is concern over the potential placental effects of prenatal phthalate exposure, and the potential adverse effects of prenatal phthalate exposure require further study; however, few data are available in humans. We investigated the associations between phthalate exposure in each trimester and both placental size and shape at birth. METHODS: We measured the urinary concentrations of phthalate metabolites among 2725 pregnant women in the Ma'anshan Birth Cohort. Before collecting urine samples from each of the three trimesters, the pregnant women were interviewed via questionnaires. Placental information was obtained from hospital records. We estimated the sex-specific associations between urinary phthalate concentrations in each trimester and both placental size and shape at birth using adjusted multiple regression. A linear mixed model was used for the repeated measures analysis with subject-specific random intercepts and slopes for gestational age at sample collection to test the effect of phthalate levels on placental size and shape and to estimate the effect sizes. RESULTS: Overall, placental breadth increased by 0.148cm (95% CI: 0.078, 0.218) with each 1 ln-concentration increase in MBP in the first trimester. The difference between placental length and breadth (length-breadth) decreased by 0.086cm (95% CI: -0.159, -0.012) and 0.149cm (95% CI: -0.221, -0.076) with each 1 ln-concentration increase in MMP and MBP, respectively, in the first trimester. In the second trimester, placental thickness increased by 0.017cm (95% CI: 0.006, 0.027), 0.020cm (95% CI: 0.004, 0.036), 0.028cm (95% CI: 0.007, 0.048), and 0.035cm (95% CI: 0.018, 0.053) with each 1 ln-concentration increase in MMP, MBP, MEOHP, and MEHHP, respectively. In the third trimester, placental thickness increased by 0.037cm (95% CI: 0.019, 0.056) and 0.019cm (95% CI: 0, 0.037) with each 1 ln-concentration increase in MBP and MEHP, respectively. Multiple linear regression for each offspring sex indicated that prenatal phthalate exposure increased placental thickness in both the first and second trimesters in males, whereas the corresponding relationship was close to null in females. Linear mixed models (LMMs) yielded similar results. CONCLUSION: Our results suggest the presence of associations between prenatal phthalate exposure and placental size and shape. Exposure to certain phthalates may cause the placenta to become thicker and more circular. Associations appeared stronger for the subsample representing male offspring than those for the subsample representing female offspring. Given the few studies on this topic, additional research is warranted.
Assuntos
Exposição Materna/efeitos adversos , Ácidos Ftálicos/efeitos adversos , Placenta/efeitos dos fármacos , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Masculino , Ácidos Ftálicos/urina , Placenta/patologia , Gravidez , Adulto JovemRESUMO
The Li1.20[Mn0.54Ni0.13Co0.13]0.80-xYbxO2 (x = 0, 0.01, 0.02, 0.03) cathode materials have been synthesized by using sol-gel method and characterized by means of XRD, SEM, ICP-OES analysis. The galvanostatic charge-discharge tests results showed the improved electrochemical properties were obtained through the Yb3+ doping modification. With the increase of Yb3+ doping content, the capacity retentions enhanced from 85.6% to 88.9% and then decrease to 86.5% after 100 cycles with x = 0.01, 0.02 and 0.03, respectively, while the un-doped sample delivered the capacity retention of 83.0%. Besides, the discharge capacity of Li1.20 [Mn0.54Ni0.13Co0.13]0.78Yb0.02O2 was about 23.1 mAh g-1 larger than that of un-doped sample at 5C high rate. The electrochemical impedance spectroscopy (EIS) and cyclic voltammetric results indicated that the Yb3+ doping modification could suppress the layered-spinel phase transformation during cycling and maintain a lower value of charge transfer impedance.
RESUMO
BACKGROUND: Truly anatomic coracoclavicular ligament reconstruction (TACCR) according to the original insertions is a creative new method for the treatment of severe acromioclavicular separation. This research analyzed the clinical and radiologic results of TACCR in 25 patients with at least 2-year follow-up. METHODS: The study enrolled 25 patients with Rockwood type V acromioclavicular joint dislocations who underwent TACCR using 2 Endobutton (Smith & Nephew Inc., Andover, MA, USA) devices from May 2013 to October 2015. Patients were assessed with clinical and radiologic follow-up at 3, 6, 12, 18, and 24 months postoperatively. The clinical assessments consisted of the visual analog scale and the Constant score. The radiographic evaluations were performed by measurements of the coracoclavicular distance. RESULTS: The mean follow-up was 34 ± 6.8 months (range, 24-48 months). The visual analog scale and Constant scores revealed significant advancements from 5 ± 0.9 (range, 4-7) and 45 ± 5.6 (range, 30-54) scores preoperatively to 0 ± 0.5 (range, 0-2) and 95 ± 2.9 (range, 91-98) scores at 24 months postoperatively, respectively. The coracoclavicular distance significantly decreased from 23 ± 5.4 mm (range, 16-34 mm) preoperatively to 8 ± 0.9 mm (range, 7-10 mm) at the final follow-up. CONCLUSIONS: TACCR represents a safe, reliable and creative surgical technique that yields good to excellent clinical and radiologic outcomes in the treatment of severe acromioclavicular separation.
Assuntos
Articulação Acromioclavicular/cirurgia , Luxações Articulares/cirurgia , Ligamentos Articulares/cirurgia , Procedimentos de Cirurgia Plástica/instrumentação , Procedimentos de Cirurgia Plástica/métodos , Articulação Acromioclavicular/diagnóstico por imagem , Articulação Acromioclavicular/fisiopatologia , Adolescente , Adulto , Assistência ao Convalescente , Idoso , Feminino , Humanos , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Período Pós-Operatório , Radiologia , Escala Visual Analógica , Adulto JovemRESUMO
A recent study found that gestational serum Pb concentration is associated with an increased risk of preterm birth. The purpose of this study was to analyze whether gestational Pb exposure elevates risk of small-for-gestational-age (SGA) births in a Chinese population. In the present study, total 3125 mother-infant pairs were recruited from the China-Anhui Birth Cohort Study (C-ABCS). Pb concentration in maternal serum was detected by GFAAS. All subjects were classified into three groups according to the tertile division of serum Pb concentration: L-Pb (low-Pb, <1.18µg/dl), M-Pb (medium-Pb, 1.18-1.70µg/dl), and H-Pb (high-Pb, ≥1.71µg/dl). There was no difference on birth length, head circumference and chest circumference among different groups. The rate of SGA was 6.2% in subjects with L-Pb, 8.7% in subjects with M-Pb, and 10.1% in subjects with H-Pb, respectively. The adjusted OR of SGA was 1.45 (95%CI: 1.04, 2.02; P=0.03) in subjects with M-Pb and 1.69 (95%CI: 1.22, 2.34; P=0.002) in subjects with H-Pb. Interestingly, the rate of SGA infants was elevated only in subjects with H-Pb in the first trimester (adjusted OR: 2.13; 95%CI: 1.24, 3.38; P=0.007). Collectively, high serum Pb level in the first trimester is associated with an elevated risk of SGA infants.
Assuntos
Recém-Nascido Pequeno para a Idade Gestacional/sangue , Chumbo/sangue , Chumbo/toxicidade , Primeiro Trimestre da Gravidez , Povo Asiático , China , Estudos de Coortes , Feminino , Humanos , Lactente , Modelos Logísticos , Masculino , Exposição Materna/efeitos adversos , Análise Multivariada , Gravidez , Fatores de RiscoRESUMO
BACKGROUND: Evidence exists that maternal zinc status during pregnancy is linked to adverse pregnancy outcomes including abortion, fetal growth restriction, and neural tube defects. However, it remains unclear whether maternal serum zinc concentration (SZC) during pregnancy is associated with risk of preterm birth. OBJECTIVE: This study was designed to investigate the association between maternal SZC during pregnancy and risk of preterm birth. METHODS: For this substudy of the China-Anhui Birth Cohort Study, 3081 maternal-singleton pairs with detailed birth records and available serum samples were identified. The maternal SZC was determined with flame atomic absorption spectroscopy. A total of 169 preterm births were identified. In this study, the women were divided into tertiles on the basis of their SZC: low (<76.7 µg/dL), medium (76.7-99.6 µg/dL), and high (≥99.7 µg/dL). The ORs for preterm birth were estimated by using multiple logistic regression models. RESULTS: The median SZC was 87.3 µg/dL (range: 11.1-211 µg/dL). Incidences of preterm birth were 7.3% and 6.0% among subjects with low and medium SZCs, respectively, which were significantly higher than 3.1% among subjects with a high SZC [ORs (95% CIs) for low and medium SZCs: 2.45 (1.60, 3.74), P < 0.001, and 2.00 (1.29, 3.09), P < 0.01, respectively]. After adjustment for prepregnancy body mass index, maternal age, time of serum collection, gravidity, parity, and monthly income, adjusted ORs were 2.41 (95% CI: 1.57, 3.70; P < 0.001) and 1.97 (95% CI: 1.27, 3.05; P < 0.01) among subjects with low and medium maternal SZCs. CONCLUSIONS: Maternal serum zinc concentration during pregnancy is inversely associated with risk of preterm birth in the Chinese population, and the results are driven by maternal SZC in the first trimester.
Assuntos
Povo Asiático , Nascimento Prematuro/sangue , Nascimento Prematuro/epidemiologia , Zinco/sangue , Adulto , Índice de Massa Corporal , China/epidemiologia , Feminino , Humanos , Incidência , Recém-Nascido , Modelos Logísticos , Estado Nutricional , Gravidez , Estudos Prospectivos , Fatores de Risco , Fatores Socioeconômicos , Adulto JovemRESUMO
Metallothioneins (MTs) are a family of low molecular weight, cysteine-rich, metal-binding proteins that are able to make cells to uptake heavy metals from the environment. Molecular and functional characterization of this gene family improves understanding of the mechanisms underlying heavy metal tolerance in higher organisms. In this study, a cDNA clone, encoding 74-a.a. metallothionein type 1 protein (ZjMT), was isolated from the cDNA library of Ziziphus jujuba. At the N- and C-terminals of the deduced amino acid sequence of ZjMT, six cysteine residues were arranged in a CXCXXXCXCXXXCXC and CXCXXXCXCXXCXC structure, respectively, indicating that ZjMT is a type 1 MT. Quantitative PCR analysis of plants subjected to cadmium stress showed enhanced expression of ZjMT gene in Z. jujuba within 24 h upon Cd exposure. Escherichia coli cells expressing ZjMT exhibited enhanced metal tolerance and higher accumulation of metal ions compared with control cells. The results indicate that ZjMT contributes to the detoxification of metal ions and provides marked tolerance against metal stresses. Therefore, ZjMT may be a potential candidate for tolerance enhancement in vulnerable plants to heavy metal stress and E. coli cells containing the ZjMT gene may be applied to adsorb heavy metals in polluted wastewater.
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Metalotioneína/metabolismo , Metais Pesados/metabolismo , Ziziphus/metabolismo , Sequência de Aminoácidos , Cádmio/metabolismo , Cádmio/toxicidade , Clonagem Molecular , DNA Complementar/genética , DNA Complementar/metabolismo , Eletroforese em Gel de Poliacrilamida , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Metalotioneína/química , Metalotioneína/genética , Metais Pesados/toxicidade , Dados de Sequência Molecular , Plasmídeos/genética , Plasmídeos/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/isolamento & purificação , Alinhamento de Sequência , Ziziphus/efeitos dos fármacosRESUMO
UNLABELLED: MicroRNA (miR)-26a can suppress tumor growth and metastasis of hepatocellular carcinoma (HCC). Since angiogenesis is important for tumor growth and metastasis, we investigated the possible roles of miR-26a in tumor angiogenesis. Down-regulation of miR-26a was found to correlate with an increased angiogenic potential of HCC. Through gain- and loss-of-function studies, miR-26a was demonstrated to significantly inhibit vascular endothelial growth factor A (VEGFA) expression in HCC cells and then suppress the promoting effects of HCC cells on in vitro proliferation, migration, and capillary tube formation of endothelial cells, as well as in vivo tumor angiogenesis of HCC. Hepatocyte growth factor (HGF) was identified as a target of miR-26a. HGF simulation antagonized the effects induced by miR-26a up-regulation. In contrast, silencing HGF induced similar effects to miR-26a. We further found that miR-26a exerted its antiangiogenesis function, at least in part, by inhibiting HGF-hepatocyte growth factor receptor (cMet) and its downstream signaling pathway, in turn, suppressing VEGFA production in HCC cells and impairing VEGFR2-signaling in endothelial cells. HCC patients who had high miR-26a, low HGF, low VEGFA, or low microvessel density (MVD) in tumor tissues had a better prognosis with longer overall survival (OS) and time to recurrence (TTR). In multivariate analysis, miR-26a, or in combination with HGF, was demonstrated to be an independent prognostic indicator for OS and TTR of HCC patients. CONCLUSION: miR-26a could suppress tumor angiogenesis of HCC through HGF-cMet signaling, and it is a new hopeful therapeutic target and prognostic marker for HCC.