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2.
Plant Sci ; 312: 111024, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34620429

RESUMO

Fruit coloration is an appearance trait that directly affects the commercial value and market competitiveness of apples. The red color of apple fruit is mainly affected by anthocyanin accumulation, and the synthesis of anthocyanin is affected by various factors. The critical roles of hormones and environmental factors during apple anthocyanin biosynthesis are described. This review also elaborates the specific mechanisms of the responses of internal genes to stress and changes in anthocyanin when apples are exposed to different environmental stressors. This study provides direction for future research on apple anthocyanin and is a reference for anthocyanin studies in other species.


Assuntos
Adaptação Fisiológica/fisiologia , Antocianinas/biossíntese , Poluentes Ambientais/efeitos adversos , Malus/genética , Malus/metabolismo , Pigmentação/fisiologia , Reguladores de Crescimento de Plantas/metabolismo , Adaptação Fisiológica/genética , Antocianinas/genética , Vias Biossintéticas/genética , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Pigmentação/genética , Reguladores de Crescimento de Plantas/genética
3.
Int J Mol Sci ; 22(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34502168

RESUMO

Autism spectrum disorder (ASD) is an umbrella term that includes many different disorders that affect the development, communication, and behavior of an individual. Prevalence of ASD has risen exponentially in the past couple of decades. ASD has a complex etiology and traditionally recognized risk factors only account for a small percentage of incidence of the disorder. Recent studies have examined factors beyond the conventional risk factors (e.g., environmental pollution). There has been an increase in air pollution since the beginning of industrialization. Most environmental pollutants cause toxicities through activation of several cellular receptors, such as the aryl hydrocarbon receptor (AhR)/cytochrome P450 (CYPs) pathway. There is little research on the involvement of AhR in contributing to ASD. Although a few reviews have discussed and addressed the link between increased prevalence of ASD and exposure to environmental pollutants, the mechanism governing this effect, specifically the role of AhR in ASD development and the molecular mechanisms involved, have not been discussed or reviewed before. This article reviews the state of knowledge regarding the impact of the AhR/CYP pathway modulation upon exposure to environmental pollutants on ASD risk, incidence, and development. It also explores the molecular mechanisms involved, such as epigenesis and polymorphism. In addition, the review explores possible new AhR-mediated mechanisms of several drugs used for treatment of ASD, such as sulforaphane, resveratrol, haloperidol, and metformin.


Assuntos
Transtorno do Espectro Autista/etiologia , Transtorno do Espectro Autista/metabolismo , Suscetibilidade a Doenças , Poluentes Ambientais/efeitos adversos , Receptores de Hidrocarboneto Arílico/metabolismo , Poluição do Ar/efeitos adversos , Animais , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/psicologia , Biomarcadores , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Modelos Animais de Doenças , Exposição Ambiental/efeitos adversos , Poluição Ambiental/efeitos adversos , Epigênese Genética , Regulação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Receptores de Hidrocarboneto Arílico/agonistas , Receptores de Hidrocarboneto Arílico/genética , Transdução de Sinais
5.
PLoS One ; 16(9): e0257704, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34555072

RESUMO

Breast cancer (BC) is becoming one of the most prevalent non-infectious disease in low and middle income countries. The steady rise of BC incidence may be related to the different risk factors. Among many, rampant presence of environmental pollutants might be one of the risk factors. Therefore, the aim of this study is to investigate exposure to organochlorine pesticides as a risk factor to breast cancer. A case-control study design was employed among breast cancer patients and non-breast cancer individuals (controls). Blood samples were collected from 100 study participants (50 cases and 50 controls) followed by serum separation, extraction and cleanup using standard analytical procdures. The findings revealed that ten organochlorine pesticides were detected in the serum of the study participants. From the detected organochlorine pesticides, heptachlor was observed at higher concentration for breast cancer patients (6.90±4.37 µg/L) and controls (9.15±3.84 µg/L). Mean serum level of p,p'-DDE, p,p'-DDT, heptachlor, gamma-chlordane, endosulfan, and dibutyl-chlorendate were significantly higher in the serum of breast cancer patients than the controls. From the studied pesticides, p,p'-DDT and gamma-chlordane are significant predictors for BC, while, others are equivocal. A unit increment of the concentration of p,p'-DDT (AOR; 2.03, 95% CI: 1.041-3.969) increased the odds of developing breast cancer by two, while for gamma-chlordane (AOR;3.12, 95% CI; 1.186-8.203) by three. Our study results suggesting that, organochlorines are a risk factors for breast cancer in Ethiopia. Decreasing exposure to such organochlorines might have a significant public health relevance in reducing non-communicable chronic illnesses. Besides, continues monitoring of persistent organic pollutants using body biomarkers is important for disease prevention and device mitigation measures.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/epidemiologia , Hidrocarbonetos Clorados/sangue , Praguicidas/sangue , Adulto , Neoplasias da Mama/sangue , Neoplasias da Mama/induzido quimicamente , Estudos de Casos e Controles , Clordano/efeitos adversos , Clordano/sangue , DDT/efeitos adversos , DDT/sangue , Diclorodifenil Dicloroetileno/efeitos adversos , Diclorodifenil Dicloroetileno/sangue , Poluentes Ambientais/efeitos adversos , Poluentes Ambientais/sangue , Etiópia/epidemiologia , Feminino , Heptacloro/efeitos adversos , Heptacloro/sangue , Humanos , Hidrocarbonetos Clorados/efeitos adversos , Pessoa de Meia-Idade , Praguicidas/efeitos adversos
6.
Int J Mol Sci ; 22(12)2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-34203038

RESUMO

Heavy metals are toxic environmental pollutants associated with severe ecological and human health risks. Among them is mercury (Hg), widespread in air, soil, and water, due to its peculiar geo-biochemical cycle. The clinical consequences of Hg exposure include neurotoxicity and nephrotoxicity. Furthermore, increased risk for cardiovascular diseases is also reported due to a direct effect on cardiovascular tissues, including endothelial cells, recently identified as important targets for the harmful action of heavy metals. In this review, we will discuss the rationale for the potential use of erythrocytes as a surrogate model to study Hg-related toxicity on the cardiovascular system. The toxic effects of Hg on erythrocytes have been amply investigated in the last few years. Among the observed alterations, phosphatidylserine exposure has been proposed as an underlying mechanism responsible for Hg-induced increased proatherogenic and prothrombotic activity of these cells. Furthermore, following Hg-exposure, a decrease in NOS activity has also been reported, with consequent lowering of NO bioavailability, thus impairing endothelial function. An additional mechanism that may induce a decrease in NO availability is the generation of an oxidative microenvironment. Finally, considering that chronic Hg exposure mainly occurs through contaminated foods, the protective effect of dietary components is also discussed.


Assuntos
Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/fisiopatologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Metais Pesados/toxicidade , Animais , Vasos Sanguíneos/metabolismo , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Suscetibilidade a Doenças , Endotélio/efeitos dos fármacos , Endotélio/metabolismo , Poluentes Ambientais/efeitos adversos , Humanos , Mercúrio/toxicidade , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
7.
Commun Biol ; 4(1): 912, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312468

RESUMO

Lead is a toxin known to harm many organs in the body, particularly the central nervous system, across an individual's lifespan. To date, no study has yet investigated the associations between body lead level and the microstructural properties of gray matter areas, and brain activity during attention-demanding tasks. Here, utilizing data of diffusion tensor imaging, functional magnetic resonance imaging and cognitive measures among 920 typically developing young adults, we show greater hair lead levels are weakly but significantly associated with (a) increased working memory-related activity in the right premotor and pre-supplemental motor areas, (b) lower fractional anisotropy (FA) in white matter areas near the internal capsule, (c) lower mean diffusivity (MD) in the dopaminergic system in the left hemisphere and other widespread contingent areas, and (d) greater MD in the white matter area adjacent to the right fusiform gyrus. Higher lead levels were also weakly but significantly associated with lower performance in tests of high-order cognitive functions, such as the psychometric intelligence test, greater impulsivity measures, and higher novelty seeking and extraversion. These findings reflect the weak effect of daily lead level on the excitability and microstructural properties of the brain, particularly in the dopaminergic system.


Assuntos
Encéfalo/fisiopatologia , Cognição/efeitos dos fármacos , Poluentes Ambientais/efeitos adversos , Chumbo/efeitos adversos , Adulto , Imagem de Tensor de Difusão , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Adulto Jovem
8.
Methods Mol Biol ; 2326: 3-18, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34097257

RESUMO

Crude oil disasters, such as the Deepwater Horizon accident, have caused severe environmental contamination and damage, affecting the health of marine and terrestrial organisms. Some previous studies have demonstrated cleanup efforts using chemical dispersant induced more potent toxicities than oil alone due to an increase in bioavailability of crude oil components, such as PAHs. However, there still lacks a systematic procedure that provides methods to determine genotypic and phenotypic changes following exposure to environmental toxicants or toxicant mixture, such as dispersed crude oil. Here, we describe methods for identifying a mechanism of dispersed crude oil-induced reproductive toxicity in the model organisms, Caenorhabditis elegans (C. elegans). Due to the genetic malleability of C. elegans, two mutant strains outlined in this chapter were used to identify a pathway responsible for inducing apoptosis: MD701 bcIs39 [lim-7p::ced-1::GFP + lin-15(+)], a mutant strain that allows visualization of apoptotic bodies via a green fluorescent protein fused to CED-1; and TJ1 (cep-1(gk138) I.), a p53/CEP-1 defective strain that is unable to activate apoptosis via the p53/CEP-1 pathway. In addition, qRT-PCR was utilized to demonstrate the aberrant expression of apoptosis (ced-13, ced-3, ced-4, ced-9, cep-1, dpl-1, efl-1, efl-2, egl-1, egl-38, lin-35, pax-2, and sir-2.1) and cytochrome P450 (cyp14a3, cyp35a1, cyp35a2, cyp35a5, and cyp35c1) protein-coding genes following exposure to dispersed crude oil. The procedure outlined here can be applicable to determine whether environmental contaminants, most of time contaminant mixture, cause reproductive toxicity by activation of the proapoptotic, p53/CEP-1 pathway.


Assuntos
Apoptose/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/efeitos adversos , Células Germinativas/efeitos dos fármacos , Petróleo/efeitos adversos , Animais , Caenorhabditis elegans/citologia , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Exposição Ambiental/análise , Poluentes Ambientais/análise , Poluentes Ambientais/toxicidade , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células Germinativas/citologia , Células Germinativas/metabolismo , Petróleo/análise , Petróleo/toxicidade
9.
Methods Mol Biol ; 2326: 217-224, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34097271

RESUMO

Nanoparticles are an extensive class of naturally occurred or man-made objects; it has been widely using in our daily life. As increasing usage, nanoparticles are also released into the environment and are becoming an emerged environmental pollution. In the past decade, impact of nanoparticles on plant growth and development has been becoming a major research topic in the environmental toxicology. In this chapter, we introduce a step-by-step protocol for investigating the effects of nanoparticles on plant growth and development as well as biomass production. Additionally, this protocol also tests the water content and the rate of root and up-ground part to better explain the impact of nanoparticles on plant growth. This protocol adopts plant tissue culture technology to culture plants which makes test easier and can be tested anytime during the year.


Assuntos
Biomassa , Poluentes Ambientais/efeitos adversos , Nanopartículas/efeitos adversos , Desenvolvimento Vegetal , Germinação/efeitos dos fármacos , Desenvolvimento Vegetal/efeitos dos fármacos , Sementes/efeitos dos fármacos , Sementes/crescimento & desenvolvimento , Técnicas de Cultura de Tecidos/métodos
10.
Methods Mol Biol ; 2326: 241-249, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34097273

RESUMO

The overproduction of reactive oxygen species during abiotic stress in plants causes oxidative stress that damage the cell normal functions. For reactive oxygen species (ROS) scavenging, plants developed a defense system with antioxidant enzymes. To measure the oxidative stress and antioxidant enzymes activity spectral enzymatic analysis was used, that is material-intensive, time-consuming, and inefficient. In the present study, the four more studied and main antioxidant enzymatic assays are miniaturized in a 96-well plate system and monitored the activity of enzymes by spectrophotometry. This method has obvious advantages over the standard cuvette analysis method because the miniaturization of the 96-well microplate system decreases the amount of reaction mixture and enzymes extract, thrifts working time, and consumable costs as well.


Assuntos
Poluentes Ambientais/efeitos adversos , Ensaios Enzimáticos/métodos , Metais Pesados/efeitos adversos , Proteínas de Plantas/metabolismo , Plantas/enzimologia , Estresse Oxidativo/efeitos dos fármacos , Plantas/efeitos dos fármacos , Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo
11.
Environ Health ; 20(1): 66, 2021 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090432

RESUMO

BACKGROUND: Prenatal exposure to heavy metals is implicated in the etiology of birth defects. We investigated whether concentrations of cadmium (Cd) and lead (Pb) in umbilical cord tissue are associated with risk for neural tube defects (NTDs) and whether selected genetic variants of the fetus modify their associations. METHODS: This study included 166 cases of NTD fetuses/newborns and 166 newborns without congenital malformations. Umbilical cord tissue was collected at birth or elective pregnancy termination. Cd and Pb concentrations were assessed by inductively coupled plasma-mass spectrometry, and 20 single-nucleotide polymorphisms (SNPs) in 9 genes were genotyped. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the risk for NTDs in association with metal concentrations or genotype using logistic regression. Multiplicative-scale interactions between the metals and genotypes on NTD risk were assessed with logistic regression, and additive-scale interactions were estimated with a non-linear mixed effects model. RESULTS: Higher concentrations of Cd were observed in the NTD group than in the control group, but no difference was found for Pb. Concentrations of Cd above the median level showed a risk effect, while the association between Pb and NTD risk was not significant in univariate analyses. The association of Cd was attenuated after adjusting for periconceptional folic acid supplementation. Fetuses with the AG and GG genotypes of rs4880 in SOD2 (superoxide dismutase 2) tended to have a lower risk, but fetuses with the CT and TT genotypes of rs1801133 in MTHFR (5,10-methylenetetrahydrofolatereductase) have a higher risk for NTDs when compared to their respective wild-type. rs4880 and Cd exhibited a multiplicative-scale interaction on NTD risk: the association between higher Cd and the risk for NTDs was increased by over fourfold in fetuses carrying the G allele [OR 4.43 (1.30-15.07)] compared to fetuses with the wild-type genotype. rs1801133 and Cd exposure showed an additive interaction, with a significant relative excess risk of interaction [RERI 0.64 (0.02-1.25)]. CONCLUSIONS: Prenatal exposure to Cd may be a risk factor for NTDs, and the risk effect may be enhanced in fetuses who carry the G allele of rs4880 in SOD2 and T allele of rs1801133 in MTHFR.


Assuntos
Cádmio/efeitos adversos , Poluentes Ambientais/efeitos adversos , Exposição Materna/efeitos adversos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Defeitos do Tubo Neural/genética , Superóxido Dismutase/genética , Adulto , Cádmio/análise , Estudos de Casos e Controles , China/epidemiologia , Poluentes Ambientais/análise , Feminino , Feto , Genótipo , Humanos , Recém-Nascido , Chumbo/análise , Troca Materno-Fetal , Defeitos do Tubo Neural/epidemiologia , Polimorfismo de Nucleotídeo Único , Gravidez
13.
Environ Health ; 20(1): 65, 2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-34044832

RESUMO

BACKGROUND: Alzheimer's disease (AD) and other dementias currently represent the fifth most common cause of death in the world, according to the World Health Organization, with a projected future increase as the proportion of the elderly in the population is growing. Air pollution has emerged as a plausible risk factor for AD, but studies estimating dementia cases attributable to exposure to fine particulate matter (PM2.5) air pollution and resulting monetary estimates are lacking. METHODS: We used data on average population-weighted exposure to ambient PM2.5 for the entire population of Sweden above 30 years of age. To estimate the annual number of dementia cases attributable to air pollution in the Swedish population above 60 years of age, we used the latest concentration response functions (CRF) between PM2.5 exposure and dementia incidence, based on ten longitudinal cohort studies, for the population above 60 years of age. To estimate the monetary burden of attributable cases, we calculated total costs related to dementia, including direct and indirect lifetime costs and intangible costs by including quality-adjusted life years (QALYs) lost. Two different monetary valuations of QALYs in Sweden were used to estimate the monetary value of reduced quality-of-life from two different payer perspectives. RESULTS: The annual number of dementia cases attributable to PM2.5 exposure was estimated to be 820, which represents 5% of the annual dementia cases in Sweden. Direct and indirect lifetime average cost per dementia case was estimated to correspond € 213,000. A reduction of PM2.5 by 1 µg/m3 was estimated to yield 101 fewer cases of dementia incidences annually, resulting in an estimated monetary benefit ranging up to 0.01% of the Swedish GDP in 2019. CONCLUSION: This study estimated that 5% of annual dementia cases could be attributed to PM2.5 exposure, and that the resulting monetary burden is substantial. These findings suggest the need to consider airborne toxic pollutants associated with dementia incidence in public health policy decisions.


Assuntos
Demência , Exposição Ambiental , Poluentes Ambientais , Material Particulado , Idoso , Idoso de 80 Anos ou mais , Efeitos Psicossociais da Doença , Demência/economia , Demência/epidemiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Exposição Ambiental/economia , Poluentes Ambientais/efeitos adversos , Poluentes Ambientais/análise , Poluentes Ambientais/economia , Humanos , Incidência , Pessoa de Meia-Idade , Material Particulado/efeitos adversos , Material Particulado/análise , Material Particulado/economia , Qualidade de Vida , Suécia/epidemiologia
14.
Sci Rep ; 11(1): 9898, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33972598

RESUMO

Neurodevelopmental disorders are constantly increasing on a global scale. Some elements like heavy metals are known to be neurotoxic. In this cross-sectional study we assessed the neurobehavioral effect of the exposure to trace elements including lead, mercury, cadmium, manganese, arsenic and selenium and their interactions among 299 schoolchildren residing in the heavily polluted Taranto area in Italy. Whole blood, urine and hair were collected for metal analyses, while the Child Behavior Checklist and the Social Responsiveness Scale, administered to the main teacher and the mothers were considered to identify behavioral problems in children. Blood lead mainly influenced social problems, aggressive behavior, externalizing and total problems. Urinary arsenic showed an impact on anxiety and depression, somatic problems, attention problems and rule breaking behavior. A significant interaction between lead and arsenic was observed, with a synergistic effect of the two metals increasing the risk of attention problems, aggressive behavior, externalizing problems and total problems. Overall, we were able to test that higher blood lead, urinary arsenic concentrations and their interaction increase the risk of neurobehavioral problems. This is in line with the U.S. Environmental Protection Agency's priority list of hazardous substances where arsenic and lead are ranked as first and second respectively.


Assuntos
Transtornos do Comportamento Infantil/diagnóstico , Poluentes Ambientais/efeitos adversos , Metais Pesados/efeitos adversos , Síndromes Neurotóxicas/diagnóstico , Criança , Comportamento Infantil/efeitos dos fármacos , Transtornos do Comportamento Infantil/sangue , Transtornos do Comportamento Infantil/induzido quimicamente , Transtornos do Comportamento Infantil/urina , Estudos Transversais , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/análise , Poluição Ambiental/efeitos adversos , Humanos , Itália , Masculino , Metais Pesados/análise , Síndromes Neurotóxicas/sangue , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/urina
15.
Ann Allergy Asthma Immunol ; 127(3): 312-317, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33971362

RESUMO

OBJECTIVE: To present an update of birth cohort study designs and their contributions to allergic risk. DATA SOURCES: The PubMed database was used to search for relevant articles. STUDY SELECTIONS: Peer-reviewed prospective and retrospective studies involving the assessment of allergy using human birth cohorts between 2014 and 2021 were evaluated. RESULTS: Parental history of allergic diseases, especially in cases involving both parents, is associated with increased risk of allergy. Exposure to prenatal and postnatal smoking and limited diet diversity were associated with increased allergic burden. The impact of early-life infections and antibiotics on disease development may be associated with the onset of asthma, though this remains debated. Cohort studies also revealed that the mode of delivery and breastfeeding duration affect the odds ratio of asthma and eczema development. Household exposures, including pets, house dust mites, and scented aeroallergens may confer protective effects, whereas high air pollution exposure and low socioeconomic status may be risk enhancing. Exposure to antibiotics during early life may be associated with increased asthma risk, whereas viral infections may lead to disease protection, though the impact of the coronavirus disease 2019 pandemic on allergic risk is yet to be understood. CONCLUSION: Although evaluating the risk of allergic disease development is complex, clinicians can apply these insights on the multifactorial nature of atopy to better understand and potentially mitigate disease development.


Assuntos
Asma/imunologia , Aleitamento Materno/métodos , Dieta/métodos , Eczema/imunologia , Hipersensibilidade/imunologia , Padrões de Herança/imunologia , Alérgenos/administração & dosagem , Animais , Antibacterianos/efeitos adversos , Asma/etiologia , Asma/genética , Asma/prevenção & controle , Estudos de Coortes , Eczema/etiologia , Eczema/genética , Eczema/prevenção & controle , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/efeitos adversos , Feminino , Humanos , Hipersensibilidade/etiologia , Hipersensibilidade/genética , Hipersensibilidade/prevenção & controle , Animais de Estimação/imunologia , Gravidez , Pyroglyphidae/química , Pyroglyphidae/imunologia , Fatores de Risco , Viroses/imunologia , Viroses/virologia
16.
Ecotoxicol Environ Saf ; 220: 112341, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34020281

RESUMO

Cadmium (Cd) is an important industrial and environmental pollutant, which is closely correlated with female infertility. Although Cd-induced developmental disorders of human ovarian follicles have been widely reported, the underlying mechanisms remain not fully elucidated. In this study, we explored the mechanism underlying Cd-triggered apoptosis in granulosa cells. Following the treatment with various levels of Cd (0, 0.625, 1.25, 2.5 and 5 µM), we found that Cd triggered the death of KGN cells (a human granulosa-like tumor cell line) in a dose- as well as time-dependent manner. The levels of expressions of Bax and Bak were significantly increased, whereas the expression levels of Mcl-1 and Bcl-2 were considerably decreased after being treated with high levels of Cd. We showed that Cd exposure remarkably triggered mitochondrial dysfunction, including increased intracellular ROS and free Ca2+ levels, and decreased ATP generation and mitochondrial membrane potential. Furthermore, we found that mitochondrial dysfunction, especially excessive ROS production and intracellular Ca2+ overload, serve a vital role in Cd-triggered apoptosis of KGN cells. After using inhibitors to block the corresponding signaling cascades, Cd-mediated apoptosis was markedly repressed by ASK1 and p38 inhibitors in contrast with the control group. This suggests the activation of downstream pathways triggered by mitochondrial dysfunction participates in granulosa cell death and may cause female reproductive toxicity after Cd exposure.


Assuntos
Apoptose , Cádmio/efeitos adversos , Poluentes Ambientais/efeitos adversos , Mitocôndrias/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Feminino , Células da Granulosa/metabolismo , Humanos , Fatores de Tempo
17.
Ecotoxicol Environ Saf ; 220: 112345, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34020283

RESUMO

Microplastics (MPs) and tributyltin (TBT) are both potential environmental pollutants that enter organisms through the food chain and affect bodily functions. However, the effects and mechanisms of MPs and TBT exposure (especially the co-exposure of both pollutants) on mammals remain unclear. In this study, Ф5µm MPs (5MP) was administered alone or in combination with TBT to investigate the health risk of oral exposure in mice. All three treatments induced inflammation in the liver, altered gut microbiota composition and disturbed fecal bile acids profiles. In addition to decreasing triglyceride (TG) and increasing aspartate aminotransferase (AST) and macrophage-expressed gene 1 (Mpeg1), 5MP induced hepatic cholestasis by stimulating the expression of the cholesterol hydroxylase enzymes CYP8B1 and CYP27A1, and inhibiting multidrug resistance-associated protein 2 and 3 (MRP2, MRP3), and bile-salt export pump (BSEP) to prevent bile acids for entering the blood and bile. Correspondingly, 5MP treatment decreased 7-ketolithocholic acid (7-ketoLCA) and taurocholic acid (TCA), which were positively correlated with decreased Bacteroides and Marvinbryantia and negatively correlated with increased Bifidobacterium. In addition, TBT increased interferon γ (IFNγ) and Mpeg1 levels to induce inflammation, accompanied by decreased 7-ketoLCA, tauro-alpha-muricholic acid (T-alpha-MCA) and alpha-muricholic acid (alpha-MCA) levels, which were negatively related to Coriobacteriaceae_UCG-002 and Bifidobacterium. Co-exposure to 5MP and TBT also decreased TG and induced bile acids accumulation in the liver due to inhibited BSEP, which might be attributed to the co-regulation of decreased T-alpha-MCA and Harryflintia. In conclusion, the administration of 5MP and TBT alone and in combination could cause gut microbiome dysbiosis and subsequently alter bile acids profiles, while the combined exposure of 5MP and TBT weakened the toxic effects of 5MP and TBT alone.


Assuntos
Ácidos e Sais Biliares/metabolismo , Poluentes Ambientais/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Poliestirenos/efeitos adversos , Compostos de Trialquitina/efeitos adversos , Animais , Bactérias/metabolismo , Microbioma Gastrointestinal/fisiologia , Masculino , Metaboloma , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , Microplásticos/efeitos adversos , RNA Bacteriano/análise , RNA Ribossômico 16S/análise
18.
Environ Health ; 20(1): 63, 2021 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-34022907

RESUMO

Per- and polyfluoroalkyl substances (PFAS) have been found to be associated with gestational diabetes mellitus (GDM) development, a maternal health disorder in pregnancy with negative effects that can extend beyond pregnancy. Studies that report on this association are difficult to summarize due to weak associations and wide confidence intervals. One way to advance this field is to sharpen the biologic theory on a causal pathway behind this association, and to measure it directly by way of molecular biomarkers. The aim of this review is to summarize the literature that supports a novel pathway between PFAS exposure and GDM development. Epidemiological studies demonstrate a clear association of biomarkers of thyroid hormones and glucose metabolism with GDM development. We report biologic plausibility and epidemiologic evidence that PFAS dysregulation of maternal thyroid hormones and thyrotropin (TSH) may disrupt glucose homeostasis, increasing the risk of GDM. Overall, epidemiological studies demonstrate that PFAS were positively associated with TSH and negatively with triiodothyronine (T3) and thyroxine (T4). PFAS were generally positively associated with glucose and insulin levels in pregnancy. We propose dysregulation of thyroid function and glucose metabolism may be a critical and missing component in the accurate estimation of PFAS on the risk of GDM.


Assuntos
Diabetes Gestacional/epidemiologia , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/efeitos adversos , Fluorcarbonetos/efeitos adversos , Biomarcadores/metabolismo , Diabetes Gestacional/metabolismo , Feminino , Glucose/metabolismo , Humanos , Gravidez , Risco , Hormônios Tireóideos/metabolismo
19.
Aging (Albany NY) ; 13(9): 12710-12732, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33973531

RESUMO

Calcific aortic valve disease (CAVD) is associated with increased morbidity and mortality. We aimed to elucidate the 30-year epidemiology of CAVD globally. Global CAVD incidence, prevalence, and deaths increased 3.51-, 4.43-, and 1.38-fold from 1990 to 2019, respectively, without any decreasing trends, even after age standardization. In 2019, Slovenia had the highest age-standardized rate (ASR) of CAVD incidence (62.21/100,000 persons) and prevalence (1,080.06/100,000) whereas Cyprus had the highest ASR of deaths (8.20/100,000). Population aging was an important contributor to incidence. Compared with women, more men had CAVD and men had earlier peaks in disease prevalence. High systolic blood pressure, diet high in sodium, and lead exposure were the main risk factors for deaths owing to CAVD. The estimated annual percentage change, a measure to estimate the variation of ASR, was significantly associated with the ASR and sociodemographic index (SDI) in 2019 for incidence and prevalence across all 204 countries and territories (all p<0.0001). With increased lifespan and risk factors, the overall burden of CAVD is high and remains on the rise, with differences by sex, age, and SDI level. Our findings serve to sound the alarm for organizations, institutions, and resources whose primary purpose is to improve human health.


Assuntos
Estenose da Valva Aórtica/epidemiologia , Valva Aórtica/patologia , Calcinose/epidemiologia , Carga Global da Doença , Saúde Global/tendências , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Exposição Ambiental , Poluentes Ambientais/efeitos adversos , Feminino , Saúde Global/estatística & dados numéricos , Humanos , Incidência , Chumbo/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Prevalência , Anos de Vida Ajustados por Qualidade de Vida , Fatores de Risco , Fatores Sexuais , Fatores Socioeconômicos , Sódio na Dieta/efeitos adversos
20.
Environ Health Prev Med ; 26(1): 59, 2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34022817

RESUMO

BACKGROUND: The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco. METHODS: The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures. RESULTS: The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies. CONCLUSIONS: Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future.


Assuntos
Saúde da Criança , Poluentes Ambientais/efeitos adversos , Hipersensibilidade/epidemiologia , Transtornos do Neurodesenvolvimento/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/efeitos adversos , Biomarcadores/sangue , Criança , Pré-Escolar , Estudos de Coortes , Exposição Ambiental/efeitos adversos , Saúde Ambiental , Feminino , Sangue Fetal/química , Seguimentos , Crescimento/efeitos dos fármacos , Humanos , Hipersensibilidade/etiologia , Lactente , Japão/epidemiologia , Masculino , Transtornos do Neurodesenvolvimento/etiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Prevalência
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