RESUMO
Perfluorooctanyl sulfonate (PFOS), a cardiac toxicity compound, has been widely detected in the environment and in organisms. However, the toxic mechanism is not clear. Our previous study indicated that prenatal PFOS exposure led to swollen mitochondrial with vacuolar structure and loss of cristae in offsping's heart. The purpose of this study was to investigate the effect of PFOS on the apoptosis in developing heart and mitochondria-mediated apoptosis pathway. Pregnant Sprague-Dawley (SD) rats were exposed to PFOS at doses of 0.1, 0.6, and 2.0 mg/kg-d and 0.05% Tween 80 as control by gavage from gestation day 2 (GD 2) to GD 21. Apoptosis, as well as expression of apoptosis related genes associated with mitochondrial-mediated apoptosis pathway, including p53, bcl-2, bax, cytochrome c, caspase-9, and caspase-3 were analyzed in heart tissues from weaned (postnatal day 21, PND 21) offspring. The results showed that prenatal PFOS exposure resulted in apoptosis in the offspring's heart. The mRNA and protein expression levels of p53, bax, cytochrome c, caspase-9, and caspase-3 in the offspring's heart were enhanced in various PFOS-treated groups, meanwhile, the bcl-2 expression levels were decreased. Our results indicated that prenatal PFOS exposure induced the apoptosis of weaned offspring rat heart tissue via mitochondria-mediated apoptotic pathway.
Assuntos
Ácidos Alcanossulfônicos/toxicidade , Apoptose/efeitos dos fármacos , Fluorocarbonos/toxicidade , Coração/efeitos dos fármacos , Mitocôndrias/metabolismo , Animais , Caspase 3/genética , Caspase 3/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Citocromos c/genética , Citocromos c/metabolismo , Feminino , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Desmame , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
OBJECTIVE: To establish a detection method based on gas chromatography-mass spectrometry (GC-MS) for concentrations of volatile nitrosamine compounds in urine, and apply it to the test of real samples. METHODS: Target compounds dichloromethane in urine samples was extracted with dichloromethane through liquid-liquid extraction, then the dichloromethane extract was filtrated, evaporated with nitrogen at 40°C to dryness, and the volume was set with 0.2 ml dichloromethane. Analysis of nine volatile nitroso-compounds were performed with GC-MS under selected ion monitoring mode, external reference method was used for quantification, and the detection limit, repeatability and sensitivity were evaluated. In addition, nine volatile nitroso-compounds of 92 urine samples in a town of Anhui province were measured. RESULTS: A good linear range of 2 - 200 ng/ml (with correlation coefficient 0.9985 - 0.9999) were obtained for the above mentioned nine kinds of analyte, and the lowest examination concentration was 0.05 - 0.50 ng/ml. The addition standard recoveries were 68%-102% with the RSD of 0.4% - 5.5% (n = 3). The detection limits were 0.001 - 0.013 ng/ml urine. The detection rate of N-nitrosodimethylamine (NDMA), N-nitrosomethylethylamine (NMEA), N-nitrosodiethylamine (NDEA), N-nitrosodi-n-propylamine (NDPA), N-nitrosopyrrolidine (NPYR), N-nitrosomorpholine (NMOR), N-nitrosopiperidine (NPIP), N-nitrosodi-n-butylamine (NDBA) and N-nitrosodiphenylamine (NDPhA) were 71% (65), 74% (68), 65% (60), 80% (73), 92% (85), 78% (72), 76% (70), 87% (80), 98% (90), respectively, with the results (0.27 ± 0.12), (0.75 ± 0.29), (0.06 ± 0.02), (0.16 ± 0.07), (23.66 ± 5.18), (1.01 ± 0.35), (0.38 ± 0.11), (2.47 ± 0.52) and (15.13 ± 3.48) nmol/g creatinine. CONCLUSIONS: A gas chromatography-mass spectrometry detect method was developed for low level volatile nitrosamines in urine samples.
Assuntos
Cromatografia Gasosa-Espectrometria de Massas , Nitrosaminas/urina , Urinálise/métodos , Humanos , Compostos Orgânicos Voláteis/urinaRESUMO
It has been suggested that lead (Pb) exposure in early life may increase amyloid precursor protein (APP) expression and promote the pathogenesis of Alzheimer's disease in old age. The current study examined whether the DNA methylation patterns of APP gene in rat pheochromocytoma (PC12) cells changed after Pb acetate exposure. Undifferentiated PC12 cells were exposed to three doses of Pb acetate (50, 250, and 500 nM) and one control for 2 days or 1 week. The methylation patterns of APP promoter and global DNA methylation were analyzed. The DNA methyltransferase 1 (DNMT1) expression and the level of amyloid ß peptide (Aß) were also investigated. The results showed that the exposure of the three concentrations of Pb acetate could make the APP promoter hypomethylated. The global DNA methylation level and the expression of DNMT1 were changed in the 500 nM group after 2 days exposure and in the 250 and 500 nM group after 7 days exposure. Thus, Pb may exert neurotoxic effects through mechanisms that alter the global and promoter methylation patterns of APP gene. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.
Assuntos
Precursor de Proteína beta-Amiloide/genética , Metilação de DNA , Chumbo/toxicidade , Regiões Promotoras Genéticas , Doença de Alzheimer/genética , Animais , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Compostos Organometálicos/toxicidade , Células PC12 , RatosRESUMO
OBJECTIVE: Gestational diabetes mellitus (GDM) and gestational weight gain (GWG) are important risk factors that are known to affect offspring growth, but these outcomes are inconsistent and it remains unknown if both risk factors have a synergetic effect on early childhood growth. The present study aimed to conduct offspring body mass index-for-age Z-scores (BMIZ) trajectories and to evaluate the independent and interactive effect of the status of GDM and excessive GWG on the risks of overweight/obesity from birth to 24 months of age. METHODS: A total of 7949 mother-child pairs were enrolled in this study. The weight and length of children were measured at birth, 6, 12, and 24 months of age to calculate BMIZ. RESULTS: The status of GDM was positively associated with offspring BMIZ and risk of macrosomia at birth but was not associated with offspring BMIZ or the risks of overweight/obesity at 6, 12, and 24 months of age. In contrast, excessive GWG was positively linked to offspring BMIZ, the stable high BMIZ trajectory pattern, and risks of overweight/obesity in the first 24 months of age. These two risk factors also had a significant synergistic effect on macrosomia at birth, but the interactive effect was only significant in boys during the follow-up years in the sex-stratified analyses. CONCLUSION: The maternal GWG was a more pronounced predictor than GDM with relation to BMIZ and risk of overweight/obesity in early childhood. The interactive effect between these risk factors on offspring overweight/obesity may vary by sex.
Assuntos
Diabetes Gestacional , Ganho de Peso na Gestação , Peso ao Nascer , Pré-Escolar , Diabetes Gestacional/epidemiologia , Feminino , Macrossomia Fetal/epidemiologia , Macrossomia Fetal/etiologia , Humanos , Recém-Nascido , Masculino , Obesidade/complicações , Sobrepeso/etiologia , Gravidez , Aumento de PesoRESUMO
BACKGROUND: Exposure to air pollution has been linked with altered immune function in adults, but little is known about its effects on early life. This study aimed to investigate the effects of exposure to air pollution during prenatal and postnatal windows on cell-mediated immune function in preschoolers. METHODS: Pre-school aged children (2.9 ± 0.5 y old, n = 391) were recruited from a mother-child cohort study in Wuhan, China. We used a spatial-temporal land use regression (LUR) model to estimate exposures of particulate matter with aerodynamic diameters ≤2.5 µm (PM2.5) and ≤10 µm (PM10), and nitrogen dioxide (NO2) during the specific trimesters of pregnancy and the first two postnatal years. We measured peripheral blood T lymphocyte subsets and plasma cytokines as indicators of cellular immune function. We used multiple informant models to examine the associations of prenatal and postnatal exposures to air pollution with cell-mediated immune function. RESULTS: Prenatal exposures to PM2.5, PM10, and NO2 during early pregnancy were negatively associated with %CD3+ and %CD3+CD8+ cells, and during late pregnancy were positively associated with %CD3+ cells. Postnatal exposures to these air pollutants during 1-y or 2-y childhood were positively associated with IL-4, IL-5, IL-6, and TNF-α. We also observed that the associations of prenatal or postnatal air pollution exposures with cellular immune responses varied by child's sex. CONCLUSIONS: Our results suggest that exposure to air pollution during different critical windows of early life may differentially alter cellular immune responses, and these effects appear to be sex-specific.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Criança , Pré-Escolar , Estudos de Coortes , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Feminino , Humanos , Imunidade Celular , Masculino , Dióxido de Nitrogênio/análise , Dióxido de Nitrogênio/toxicidade , Material Particulado/análise , Material Particulado/toxicidade , GravidezRESUMO
Both animal and human studies have demonstrated that exposure to chemical pollutants during critical developmental period causes adverse consequences later in life. In uterus, perfluorooctanesulfonate (PFOS) exposure has been known to cause developmental neurotoxicity, such as increased motor activity, reduced habitation and impaired cognitive function. The possible mechanism of the impaired cognitive function induced by prenatal PFOS exposure was evaluated in this study. Pregnant Sprague Dawley (SD) rats were given 0.1, 0.6, and 2.0 mg kg(-1) birth weight (bw) d(-1) by gavage from gestation day (GD) 0 to GD20. Control received 0.5% Tween-20 vehicle (4 ml kg(-1) bw d(-1)). PFOS concentration in hippocampus of offspring was observed on postnatal day (PND) 0 and PND21. The ultrastructure of hippocampus and the gene expression of synaptic vesicle associated proteins in offspring hippocampus, which were important for the neurotransmitter release, were investigated. The transmission electron photomicrographs of the offspring hippocampus from PFOS-treated maternal groups showed the ultrastructure of synapses was negatively affected. The offspring from PFOS-treated maternal groups also differed significantly from controls with respect to the expression of synaptic vesicle associated proteins. The mRNA levels of synapsin1 (Syn1), synapsin2 (Syn2), and synaptophysin (Syp) were decreased in treated groups either on PND0 or on PND21. However, the mRNA level of synapsin3 (Syn3) decreased in 0.6- and 2.0-mg kg(-1) group on PND0, and showed no significant difference among control group and all treated groups on PND21. These results indicate that the impairment of cognitive function induced by PFOS may be attributed to the lower mRNA levels of synaptic vesicle associated proteins and the change of synaptic ultrastructure in hippocampus.
Assuntos
Ácidos Alcanossulfônicos/toxicidade , Poluentes Ambientais/toxicidade , Fluorocarbonos/toxicidade , Hipocampo/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Sinapsinas/efeitos dos fármacos , Sinaptofisina/efeitos dos fármacos , Animais , Feminino , Hipocampo/metabolismo , Hipocampo/ultraestrutura , Microscopia Eletrônica de Transmissão , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Sinapses/ultraestrutura , Sinapsinas/biossíntese , Sinaptofisina/biossínteseRESUMO
Perfluorooctane sulfonate (PFOS), a kind of widely distributed environmentally organic compound, has been found to cause developmental toxicity. Although microRNAs (miRNAs) play an important role in many metabolic tasks, whether and how they are involved in the process of PFOS-induced toxicity is largely unknown. To address this problem, PFOS-induced changes in miRNAs and target gene expression in zebrafish embryos, and the potential mechanism of PFOS-induced toxic action were studied in this research. Zebrafish embryos were exposed to 1 µg ml(-1) PFOS or DMSO control from 6 h post-fertilization (hpf) to 24 or 120 hpf. Subsequently, RNA was isolated from the embryo pool and the expression profiles of 219 known zebrafish miRNAs were analyzed using microarray. Finally, quantitative real-time polymerase chain reaction was used to validate several miRNAs expression of microarray data. The analysis revealed that PFOS exposure induced significant changes in miRNA expression profiles. A total of 39 and 81 miRNAs showed significantly altered expression patterns after PFOS exposure 24 and 120 hpf. Of the changed miRNAs, 20 were significantly up-regulated and 19 were significantly down-regulated (p < 0.01) at 24 hpf, whereas 41 were significantly up-regulated and 40 were significantly down-regulated (p < 0.01) at 120 hpf. These miRNAs were involved in development, apoptosis and cell signal pathway, cell cycle progression and proliferation, oncogenesis, adipose metabolism and hormone secretion, whereas there is still little functional information available for 32 miRNAs. Our results demonstrate that PFOS exposure alters the expression of a suite of miRNAs and may induce developmental toxicity.
Assuntos
Ácidos Alcanossulfônicos/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Fluorocarbonos/toxicidade , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , MicroRNAs/metabolismo , Peixe-Zebra/embriologia , Anormalidades Induzidas por Medicamentos/etiologia , Anormalidades Induzidas por Medicamentos/genética , Anormalidades Induzidas por Medicamentos/metabolismo , Animais , Embrião não Mamífero/anormalidades , Desenvolvimento Embrionário/genética , Longevidade/efeitos dos fármacos , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro , Fatores de Tempo , Peixe-Zebra/genética , Peixe-Zebra/fisiologiaRESUMO
Oxidative stress has been considered as one of the possible mechanisms leading to the neurotoxicity of lead. One of the effective ways to prevent cellular damage after lead exposure is using antioxidants. In this paper, a novel C(60) -methionine derivate (FMD), a fullerene molecule modified with methionine, was synthesized. The protective effect of FMD on lead-exposed human SH-SY5Y neuroblastoma cells was investigated. In this research, after incubating with 500 µm Pb acetate alone for 72 h, the cells had undergone a series of biological changes including viability loss, apoptotic death, the depletion of glutathione (GSH), the peroxidation of membrane lipid and DNA damage. Pretreatment with FMD before lead exposure could improve cell survival, increase the GSH level, reduce malondialdehyde content and attenuate DNA damage without obvious toxicity. In addition, the protective effects of FMD were proven to be greater than those of other two C(60) -amino acid derivates, ß-alanine C(60) derivate and cystine C(60) derivate, which have been confirmed in our previous work to be able to protect rat pheochromocytoma PC12 cells from hydrogen dioxide-induced oxidative injuries. These observations suggest that FMD may serve as a potential antioxidative and neuroprotective agent in the prevention of lead intoxication.
Assuntos
Antioxidantes/farmacologia , Fulerenos/farmacologia , Metionina , Neuroblastoma/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Compostos Organometálicos/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Fulerenos/química , Glutationa/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Metionina/análogos & derivados , Metionina/química , Metionina/farmacologia , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Estresse Oxidativo/efeitos dos fármacosRESUMO
Perfluorooctane sulfonate (PFOS) is an environmental organic pollutant, the potential neurotoxicity of which is causing great concern in fish. In the present study, we examined the effects of PFOS on motor neurons, and investigated the potential toxicological mechanisms oxidative stress in zebrafish embryos. Six-hour post-fertilization (hpf) zebrafish embryos were exposed to 1.0 mg/L PFOS, then we examined the expression of alpha-tubulin, proliferating cell nuclear antigen (PCNA), cyclin-dependent kinase 5 (CDK5), and peroxiredoxin 2 (PRX2) after PFOS exposure until 120 hpf. The results showed that PFOS increased alpha-tubulin in the coccygeal spinal cord (CSC) at 96 hpf, whereas decreased alpha-tubulin in the brain and spinal cord at 120 hpf. PCNA expression was highly increased in CSC and abdomen compared with control at 96 and 120 hpf after PFOS exposure. In addition, PFOS exposure caused CDK5 expression to be highly increased in brain region following by down-regulation of PRX2 expression at 96 hpf. These results indicated that, at least in part, the effect on motor neurons induced by PFOS was mediated by dynamically interfering with the expression of alpha-tubulin and PCNA. Furthermore, PFOS-induced toxicity was associated with oxidative stress by deregulating CDK5 and PRX2.
Assuntos
Ácidos Alcanossulfônicos/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Fluorocarbonos/toxicidade , Neurônios Motores/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/embriologia , Animais , Proliferação de Células/efeitos dos fármacos , Quinase 5 Dependente de Ciclina/genética , Quinase 5 Dependente de Ciclina/metabolismo , Relação Dose-Resposta a Droga , Embrião não Mamífero/anormalidades , Expressão Gênica/efeitos dos fármacos , Crescimento e Desenvolvimento/efeitos dos fármacos , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Tubulina (Proteína)/metabolismo , Peixe-Zebra/anormalidades , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
Perfluorooctane sulfonate (PFOS) is an environmental persistent acid found at low levels in human, wildlife, and environmental media samples. To study the apoptosis effects of PFOS on microglia, murine N9 cell line was used as a model in current research. The results showed that PFOS could reduce the cell viability significantly, and the cellular apoptosis induced by PFOS was closely accompanied with dissipation of mitochondria membrane potential, upregulation messenger RNAs (mRNAs) of p53, Bax, caspase 9, and caspase 3, and decreased expression of Bcl-2 mRNA. These results suggested that PFOS could disturb homeostasis of N9 cells, impact mitochondria, and affect gene expression of apoptotic regulators, all of which resulted in a start-up of apoptosis.
Assuntos
Ácidos Alcanossulfônicos/toxicidade , Apoptose/efeitos dos fármacos , Fluorocarbonos/toxicidade , Microglia/citologia , Animais , Biomarcadores , Caspase 3/genética , Caspase 3/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citotoxinas/toxicidade , Regulação da Expressão Gênica , Homeostase , Camundongos , Microglia/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Membranas Mitocondriais/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
Pregnancy-induced hypertension (PIH), including gestational hypertension and preeclampsia, accounts for the majority of maternal and perinatal morbidity and mortality. Strontium (Sr) has been recently associated with preeclampsia in a small group of women; however, the role of Sr in PIH is not fully understood and warrants further investigation. In this study, we examined the association between urinary Sr levels and PIH, and assessed the effect of maternal age on the association. Urinary Sr concentrations were measured in 5423 pregnant women before delivery by inductively coupled plasma mass spectrometry (ICP-MS). Logistic regression analysis adjusting for potential confounders was applied to explore the association between Sr and PIH, and to evaluate the Sr-PIH relationship stratified by maternal age. Among the participants, 200 (3.83%) women were diagnosed with PIH. Compared with non-PIH women, women who developed PIH had lower urinary Sr concentrations (131.26 vs. 174.98 µg/L creatinine, P<0.01). With the natural log-transformed urinary creatinine-standardized Sr concentrations increasing, the risk of PIH decreased significantly [adjusted OR=0.60 (95%CI: 0.51, 0.72)]. Furthermore, the significant association of Sr with PIH was found among women under 35 years (P<0.01). Our finding suggested that Sr may play a potential protective role in the pathogenesis of PIH, especially among young pregnant women under 35 years old.
Assuntos
Hipertensão Induzida pela Gravidez/urina , Pré-Eclâmpsia/urina , Estrôncio/urina , Adulto , Índice de Massa Corporal , Creatinina/sangue , Feminino , Idade Gestacional , Humanos , Hipertensão Induzida pela Gravidez/sangue , Hipertensão Induzida pela Gravidez/epidemiologia , Hipertensão Induzida pela Gravidez/patologia , Modelos Logísticos , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/patologia , Gravidez , Fatores de RiscoRESUMO
BACKGROUND: Wuhan was the first epicentre of COVID-19 in the world, accounting for 80% of cases in China during the first wave. We aimed to assess household transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and risk factors associated with infectivity and susceptibility to infection in Wuhan. METHODS: This retrospective cohort study included the households of all laboratory-confirmed or clinically confirmed COVID-19 cases and laboratory-confirmed asymptomatic SARS-CoV-2 infections identified by the Wuhan Center for Disease Control and Prevention between Dec 2, 2019, and April 18, 2020. We defined households as groups of family members and close relatives who did not necessarily live at the same address and considered households that shared common contacts as epidemiologically linked. We used a statistical transmission model to estimate household secondary attack rates and to quantify risk factors associated with infectivity and susceptibility to infection, accounting for individual-level exposure history. We assessed how intervention policies affected the household reproductive number, defined as the mean number of household contacts a case can infect. FINDINGS: 27â101 households with 29â578 primary cases and 57â581 household contacts were identified. The secondary attack rate estimated with the transmission model was 15·6% (95% CI 15·2-16·0), assuming a mean incubation period of 5 days and a maximum infectious period of 22 days. Individuals aged 60 years or older were at a higher risk of infection with SARS-CoV-2 than all other age groups. Infants aged 0-1 years were significantly more likely to be infected than children aged 2-5 years (odds ratio [OR] 2·20, 95% CI 1·40-3·44) and children aged 6-12 years (1·53, 1·01-2·34). Given the same exposure time, children and adolescents younger than 20 years of age were more likely to infect others than were adults aged 60 years or older (1·58, 1·28-1·95). Asymptomatic individuals were much less likely to infect others than were symptomatic cases (0·21, 0·14-0·31). Symptomatic cases were more likely to infect others before symptom onset than after (1·42, 1·30-1·55). After mass isolation of cases, quarantine of household contacts, and restriction of movement policies were implemented, household reproductive numbers declined by 52% among primary cases (from 0·25 [95% CI 0·24-0·26] to 0·12 [0·10-0·13]) and by 63% among secondary cases (from 0·17 [0·16-0·18] to 0·063 [0·057-0·070]). INTERPRETATION: Within households, children and adolescents were less susceptible to SARS-CoV-2 infection but were more infectious than older individuals. Presymptomatic cases were more infectious and individuals with asymptomatic infection less infectious than symptomatic cases. These findings have implications for devising interventions for blocking household transmission of SARS-CoV-2, such as timely vaccination of eligible children once resources become available. FUNDING: National Natural Science Foundation of China, Fundamental Research Funds for the Central Universities, US National Institutes of Health, and US National Science Foundation.
Assuntos
COVID-19/transmissão , SARS-CoV-2 , Adolescente , Adulto , Fatores Etários , Idoso , COVID-19/etiologia , Criança , Pré-Escolar , China/epidemiologia , Suscetibilidade a Doenças , Características da Família , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Experimental studies have demonstrated that cadmium exposure induces alterations on immune function, but epidemiological evidence is lacking. OBJECTIVE: To examine the associations between prenatal and postnatal cadmium exposure and cellular immune responses among pre-school children. METHODS: Pre-school aged children (nâ¯=â¯407) were followed from a prospective birth cohort study in Wuhan, China. Maternal urinary and children's plasma cadmium concentrations were measured as biomarkers of prenatal and postnatal cadmium exposure, respectively. Children's cellular immune responses were assessed by peripheral blood T lymphocyte subsets and plasma cytokines. Multivariable adjusted models were applied to estimate the associations of prenatal and postnatal cadmium exposure with T lymphocyte subsets and cytokines, and the effect modification by child gender were also examined. RESULTS: Maternal urinary cadmium was associated with reduced absolute counts of CD3+CD4+ cells (-12.45%; 95% CI: -23.74%, 0.40% for the highest vs. lowest quartile; p for trendâ¯=â¯0.045). Inverse associations of maternal urinary cadmium with %CD3+CD4+ cells and CD4+/CD8+ ratio were only observed among females (both p-interactionâ¯<â¯0.050); whereas an inverse association with absolute counts of CD3+CD8+ cells was only observed among males (p-interactionâ¯=â¯0.057). Positive associations of maternal urinary cadmium with %CD3+CD4+ cells, interleukin-4 (IL-4), and IL-6 were only observed among females, although there were no significant interactions. We observed no clear associations of children's plasma cadmium with T lymphocyte subsets and cytokines. CONCLUSION: Prenatal but not postnatal cadmium exposure was associated with sex-specific alterations on children's cellular immune responses.
Assuntos
Efeitos Tardios da Exposição Pré-Natal , Cádmio , Pré-Escolar , China , Estudos de Coortes , Feminino , Humanos , Imunidade Celular , Masculino , Gravidez , Estudos ProspectivosRESUMO
Despite the global abundance of studies on children's lead (Pb) exposure, the magnitude of Pb exposure among children across China remains unclear, especially for rural areas. In 2000, Pb was removed from petrol, marking a change in the sources of Pb exposure in China. To better understand children's Pb exposure and inform potential approaches to exposure reduction, we conducted a national blood Pb survey of 31,373 children (0-84â¯months old) from May 2013 to March 2015, using a multi-stage and multi-strata sampling method. Blood lead levels (BLLs) were tested using graphite furnace atomic absorption spectrometry with a detection limit of 1⯵g/L. The results show that Chinese children had a contemporary geometric mean (GM) BLL of 26.7⯵g/L, with 8.6% of BLLs exceeding 50⯵g/L. Boys had higher BLLs (GM 27.2⯵g/L) compared to girls (GM: 25.9⯵g/L) (pâ¯<â¯0.001). Children at the age of 0-36â¯months had a lower PbB (GM 25.7⯵g/L) level compared with those aged 36-84â¯months (GM 27.9⯵g/L) (pâ¯<â¯0.001). When taking into account sociodemographic factors, a multivariate logistic regression analysis shows that the odds ratios (OR) of having a BLL of 27⯵g/dL (i.e., median BLL of this study) or higher were 1.88 (95% CI: 1.76, 2.02) and 1.35 (95% CI: 1.22, 1.49) for homes using coal and biomass fuels, respectively, compared to those using gas or electricity. Meanwhile, children in homes close to roads were more likely to have BLLs exceeding 27⯵g/dL (OR: 1.11, 95% CI: 1.03, 1.20). In China, rural children had higher BLLs compared to urban children. As a result of pediatric exposure to Pb, there were approximately 144 million and 36 million IQ points lost for rural children and urban children, respectively, revealing a disparity of Pb exposure between rural and urban areas in China. Cleaner domestic fuels and improved cooking/heating equipment will reduce contemporary Pb exposure in rural areas. In addition, the association between contemporary BLLs and distance away from roads further suggests that resuspension of legacy soil/dust Pb should not be neglected in future remediation programs and household interventions. As a large scale survey, this study provides evidence for revising the reference value of BLL, improving the guideline for clinical and public health management, and implementing interventions to prevent adverse health outcomes associated with low-level Pb exposure in children.
Assuntos
Intoxicação por Chumbo , Criança , Pré-Escolar , China , Estudos Transversais , Exposição Ambiental , Feminino , Humanos , Lactente , Recém-Nascido , Chumbo , MasculinoRESUMO
With the wide application of nanoscaled particles, the risk of human exposure to these particles has been markedly increased. However, knowledge about their safety falls far behind the utility of these nanoparticles. Here we have analyzed the activation of brain microglia and astrocytes, which are sensitive to changes of brain environment after peripheral exposure to nanoscaled aluminum oxide suspension. Sprague-Dawley rats (six rats per treatment) were intraperitoneally injected once every second day for 30 or 60 days with nanoscaled aluminum oxide (NSAO; 1 mg/kg or 50 mg/kg), non-nanoscaled aluminum oxide (nNSAO, 1 mg/kg), or vehicle (saline). After 60 days' exposure the numbers of ED1+, GFAP+, and nestin+ cells in cortex and hippocampus were significantly higher in NSAO-treated rats than nNSAO- or vehicle-treated rats; thus, compared with nNSAO, NSAO has potential effects on the innate immune system of rat brain. This should be considered when evaluating the toxicological effects of nanosized particles. FROM THE CLINICAL EDITOR: Sprague-Dawley rats were intraperitoneally injected with nanosized aluminum oxide, (NSAO); non-nanoscaled aluminum oxide, or vehicle (saline). The numbers of ED1+, GFAP+, and nestin+ cells in cortex and hippocampus were significantly higher in NSAO-treated rats than nNSAO- or vehicle-treated rats; thus, NSAO has potential effects on the innate immune system of rat brain.
Assuntos
Óxido de Alumínio/administração & dosagem , Óxido de Alumínio/farmacologia , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Nanopartículas/administração & dosagem , Neuroglia/citologia , Neuroglia/efeitos dos fármacos , Animais , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Encéfalo/metabolismo , Imuno-Histoquímica , Nanopartículas/ultraestrutura , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
BACKGROUND: Bisphenol F (BPF) and bisphenol S (BPS) are increasingly used as alternatives to endocrine disrupting chemical bisphenol A (BPA). Evidence from in vitro and animal studies demonstrates that BPA, BPF and BPS induce oxidative stress, a proposed mechanism that is relevant to various adverse health effects. Evaluation in humans is hampered by the potentially high within-subject variability of urinary measurements. OBJECTIVE: To evaluate the variability and associations of levels of BPA, BPS, BPF and 3 oxidative stress markers [i.e., 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)] in urine collected on multiple occasions over 3â¯months. METHOD: A total of 529 spot urine samples, including 88 first morning voids (FMVs) and 24-h specimens, were gathered from 11 adult men on days 0, 1, 2, 3, 4, 30, 60 and 90 and analyzed for BPA, BPF, BPS, 8-OHdG, 8-isoPGF2α and HNE-MA. Intraclass correlation coefficients (ICCs) were estimated to characterize the reproducibility of urinary bisphenols and oxidative stress markers, and linear mixed models were applied to assess the associations between markers of exposure and response. RESULTS: BPA and BPF were detected in ≥85% of the spot samples, while BPS in 13% of the samples. High degrees of within-subject variability were found for BPA, BPF, 8-OHdG, 8-isoPGF2α and HNE-MA in spot samples, FMVs and 24-h specimens (creatinine-corrected ICCsâ¯≤â¯0.37). The sensitivities were low-to-moderate (0.30-0.63) when using single spot samples or FMVs to predict high (>27th, or 36th percentile) 3-month average urinary levels of BPA, BPF, 8-OHdG, 8-isoPGF2α and HNE-MA. Collecting repeated specimens at different time points improved the accuracy of classification for markers of exposure and response. Elevated urinary BPA and BPF were associated with significantly higher levels of oxidative stress markers. CONCLUSIONS: Repeated urinary specimens are required to characterize bisphenol exposure levels and the oxidative stress status of individuals. Exposure to BPA and BPF may partly contribute to the elevated urinary levels of oxidative stress makers in adult men.
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Compostos Benzidrílicos/urina , Estresse Oxidativo , Fenóis/urina , Sulfonas/urina , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Animais , Variação Biológica Individual , Biomarcadores/urina , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Humanos , Masculino , Reprodutibilidade dos TestesRESUMO
MicroRNAs are important posttranscriptional regulators of gene expression in animals and plants. A sensitive and specific detection method is urgently needed for intensive studies on differential expression and regulatory roles of microRNA. Here we present a simple and reliable method for the quantification of microRNA. The hybridization products of target microRNA with capture probe and gold nanoparticle probe are immobilized onto the surface of a streptavidin-coated microplate, and the signal is amplified by silver enhancement. Distribution of miR-122a/miR-128 in mouse brain and liver tissue was detected by this method, and synthetic miRNA122a was quantified. This method allowed a lower detect limit of 10 fM with a linear dynamic range from 10 pM to 10 fM and a high specificity to discriminate one single oligonucleotide mismatch of the target microRNA.
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Ouro/química , Nanopartículas Metálicas/química , MicroRNAs/análise , Animais , Encéfalo/metabolismo , Fígado/metabolismo , Camundongos , MicroRNAs/genética , Nanotecnologia/métodos , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJECTIVE: Venous compression might be the main cause of incomplete decompression and symptom recurrence after microvascular decompression (MVD) in patients with trigeminal neuralgia. Although it can be killed in most cases, cutting the vein sometimes has the potential risk arising from venous congestion. To maneuver the vein safely, we introduced a temporary occlusion test of the vein. METHODS: Among 407 consecutive MVD cases, 48 (11.8%) offending and 157 block veins were encountered. The vein was cut directly in 147 (71.7%). Owing to the potential risk following killing of the vein, 58 (28.3%) patients underwent venous occlusion test with neurophysiologic monitoring during the operation. The temporal occlusion should be ceased immediately as soon as any changes in brainstem auditory evoked potential (BAEP) or trigeminal evoked potential (TEP) wave figuration turn up; otherwise, it would last for 15 minutes. RESULTS: The occlusion test was negative in 53 (91.4%), while positive in five patients (8.6%). According to the results, we cut the vein in test-negative patients, which made the operation easy and offered a satisfactory decompression. Among the five positive cases, the vein was finally saved in two and cut in three cases. Yet, all the three patients developed a severe ipsilateral cerebellar edema and brainstem shift after the vein was sacrificed. Despite those patients were reoperated on immediately for posterior fossa decompression, they remained equilibrium disorder with numbness in ipsilateral face and mind hemiparesis in contralateral extremities post-operatively. The residual two patients had an incomplete pain relief. CONCLUSION: This venous occlusion test could help the surgeon in making a right decision before manipulation of the petrosal veins during MVD.
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Veias Cerebrais/cirurgia , Descompressão Cirúrgica/métodos , Microcirculação/cirurgia , Procedimentos Neurocirúrgicos/métodos , Neuralgia do Trigêmeo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Edema Encefálico/etiologia , Edema Encefálico/fisiopatologia , Edema Encefálico/prevenção & controle , Infarto Cerebral/etiologia , Infarto Cerebral/fisiopatologia , Infarto Cerebral/prevenção & controle , Veias Cerebrais/patologia , Veias Cerebrais/fisiopatologia , Fossa Craniana Média/anatomia & histologia , Fossa Craniana Média/cirurgia , Cavidades Cranianas/anatomia & histologia , Descompressão Cirúrgica/efeitos adversos , Feminino , Humanos , Masculino , Microcirculação/patologia , Microcirculação/fisiopatologia , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/prevenção & controle , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/fisiopatologia , Hemorragia Pós-Operatória/prevenção & controle , Estudos Retrospectivos , Aderências Teciduais/patologia , Aderências Teciduais/fisiopatologia , Aderências Teciduais/cirurgia , Resultado do Tratamento , Nervo Trigêmeo/irrigação sanguínea , Nervo Trigêmeo/fisiopatologia , Nervo Trigêmeo/cirurgia , Neuralgia do Trigêmeo/fisiopatologia , Insuficiência Venosa/etiologia , Insuficiência Venosa/fisiopatologia , Insuficiência Venosa/prevenção & controleRESUMO
OBJECTIVE: To study the effects of benzene and selenium on telomerase in mouse lymphocytes in vivo and evaluate telomerase activity as an early marker of benzene effects on lymphocytes. METHODS: Male Kunming mice were divided randomly into 8 groups, including negative control group, reagent control group, 100 mg/kg benzene group, 200 mg/kg benzene group, 400 mg/kg benzene group, 200 mg/kg benzene + 0.75 mg/kg selenium group, 200 mg/kg benzene + 1.50 mg/kg selenium group and 200 mg/kg benzene + 3.00 mg/kg selenium group, 5 mice in each group. The mice in different groups were treated with different methods, once daily for 5 days. After 48 hours of the final exposure, lymphocytes were separated and the telomerase activities were detected with TRAPELISA. RESULTS: Compared with negative and reagent control groups, the telomerase activity was increased after treatment with different dose of benzene and at the dose of 100 mg/kg benzene group it was significantly increased (P < 0.01). At the dose of 200 mg/kg benzene + 0.75 mg/kg selenium group, it was significantly increased (P < 0.01). Compared with the counterpart treated with 200 mg/kg benzene group, the expression of telomerase was increased at the different concentrations after treatment with benzene combined with selenium and it was significantly increased at the dose of 200 mg/kg benzene + 0.75 mg/kg selenium group (P < 0.05). CONCLUSION: Increased telomerase activity in lymphocytes stimulated by benzene at different concentrations indicates activation and proliferation of these lymphocytes of mice in vivo. Telomerase activity is probably a sensitive early marker of lymphocyte proliferation by benzene. Selenium can upregulate the telomerase activity.
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Benzeno/farmacologia , Linfócitos/enzimologia , Selênio/farmacologia , Telomerase/metabolismo , Animais , Células Cultivadas , Linfócitos/efeitos dos fármacos , Masculino , CamundongosRESUMO
Objective: To explore the effects of different dosages of 4-nonylphenol (4-NP) on the fatty acid synthesis and estrogen receptor α (ERα) expression in the livers of F1 and F2 rats. Method: Pregnant rats were randomly divided into four groups: control, NP-5 (5 µg per kg per day), NP-25 (25 µg per kg per day) and NP-125 (125 µg per kg per day). 4-NP was gavaged from gestation day (GD) 6 to postnatal day (PND) 21. Some female rats from the experimental groups were mated with male rats from the control group to obtain the F2 rats. F1 generation rats (23 weeks old) and F2 generation rats (13 weeks old) were killed to detect blood biochemistry and the expression of genes and proteins. Results: Compared with the control group, 4-NP (NP-5, NP-25 and NP-125) can increase the liver organ coefficient of the F1 male offspring (P < 0.05 or P < 0.01). The concentration of high density lipoprotein (HDL) in the F1 female NP-5 group was significantly higher than that of the control group (P < 0.01); other indicators had not changed, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC) and low density lipoprotein (LDL). As the dosage of 4-NP increased, more significant changes of blood biochemistry were found, especially in the NP-125 rats (P < 0.05 or P < 0.01). The changes of histopathology by liver biopsy were consistent with biochemical indices of blood (P < 0.05 or P < 0.01). Compared with the control group, the expression of genes involved in fatty acid synthesis increased significantly (P < 0.05 or P < 0.01), and the degrees of increase were proportional to the dose of 4-NP, as measured by lipoprotein lipase (Lpl), fatty acid synthetase (Fas), sterol regulatory element-binding protein 1 (Srebp-1) and peroxisome proliferator-activated receptor (Ppar)-γ. The expression of genes and proteins of ERα were changed significantly, as well (P < 0.05 or P < 0.01). The above changes in the liver tissues of F2 generation rats were consistent with the F1 generation rats. Conclusion: Perinatal exposure to 4-NP can affect the synthesis of fatty acid in the livers of F1 and F2 generation rats. The low expression of ERα may be one of the mechanisms by which 4-NP affected fatty acid synthesis in the livers of rats.