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Intake of arsenic (As) via drinking water has been a serious threat to global public health. Though there are numerous reports of As neurotoxicity, its pathogenesis mechanisms remain vague especially its chronic effects on metabolic network. Hippocampus is a renowned area in relation to learning and memory, whilst recently, cerebellum is argued to be involved with process of cognition. Therefore, the study aimed to explore metabolomics alternations in these two areas after chronic As exposure, with the purpose of further illustrating details of As neurotoxicity. Twelve 3-week-old male C57BL/6J mice were divided into two groups, receiving deionized drinking water (control group) or 50 mg/L of sodium arsenite (via drinking water) for 24 weeks. Learning and memory abilities were tested by Morris water maze (MWM) test. Pathological and morphological changes of hippocampus and cerebellum were captured via transmission electron microscopy (TEM). Metabolic alterations were analyzed by gas chromatography-mass spectrometry (GC-MS). MWM test confirmed impairments of learning and memory abilities of mice after chronic As exposure. Metabolomics identifications indicated that tyrosine increased and aspartic acid (Asp) decreased simultaneously in both hippocampus and cerebellum. Intermediates (succinic acid) and indirect involved components of tricarboxylic acid cycle (proline, cysteine, and alanine) were found declined in cerebellum, indicating disordered energy metabolism. Our findings suggest that these metabolite alterations are related to As-induced disorders of amino acids and energy metabolism, which might therefore, play an important part in mechanisms of As neurotoxicity.
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Arsênio/toxicidade , Cerebelo/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Redes e Vias Metabólicas/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Arsênio/metabolismo , Cerebelo/metabolismo , Cerebelo/ultraestrutura , Cromatografia Gasosa-Espectrometria de Massas , Hipocampo/metabolismo , Hipocampo/ultraestrutura , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Metabolômica/métodos , Camundongos , Camundongos Endogâmicos C57BL , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Ratos , Poluentes Químicos da Água/metabolismoRESUMO
OBJECTIVE: To investigate the effect of air pollution on respiratory health in school-aged children in the main urban area of Chongqing, China. METHODS: The main urban area of Chongqing was divided into polluted area and clean area according to the air pollution data shown on the Environmental Protection Agency Website of Chongqing between 2010 and 2015. A cluster sampling method was used to select 695 third- or fourth-grade children from 2 primary schools in the clean or polluted area as study subjects, with 313 children from the clean area and 382 children from the polluted area. Pulmonary function was examined for all children and a standard American epidemiological questionnaire (ATS-DLD-78-C) was used to investigate the prevalence of respiratory diseases and symptoms. RESULTS: Compared with the clean area, the polluted area had significantly higher concentrations of inhalable particles (PM10), fine particulate matter (PM2.5), and nitric oxide (NOX) (P<0.05). The multivariate logistic regression analysis was performed after adjustment for confounding factors, and the results showed that compared with those in the clean area, the children in the polluted area had significantly higher risks of cough (OR=1.644), cough during cold (OR=1.596), expectoration during cold (OR=2.196), persistent expectoration (OR=1.802), and wheezing (OR=2.415). The boys and girls in the clean area had significantly higher forced vital capacity and forced expiratory volume in one second than those in the polluted area (P<0.05). CONCLUSIONS: Air pollution in the main urban area of Chongqing is associated with the increased prevalence of respiratory symptoms in school-aged children and has certain effect on children's pulmonary function.
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Poluição do Ar/efeitos adversos , Doenças Respiratórias/etiologia , Criança , Feminino , Volume Expiratório Forçado , Humanos , Modelos Logísticos , Masculino , Capacidade VitalRESUMO
The objective of this study was to explore the effects of different amounts of biochar on the migration process and characteristics of NO3--N in loessial soil. In this study, six groups of mixed soil samples with biochar and loessial soil mass ratios of 0% (T0), 1% (T1), 2% (T2), 3% (T3), 4% (T4), and 5% (T5) were used as research objects. NO3--N was used as the tracer. Through the indoor soil column solute transport simulation tests, the effects of different biochar application amounts on the NO3--N transport process in loessial soil were simulated and studied. The results showed that the breakthrough curve of NO3--N in loessial soil shifted to the right with the increasing of biochar application, and the peak value gradually decreased. The initial penetration time, complete penetration time, and total penetration time increased with the increasing of biochar application amount. The total penetration time of NO3- in the T1, T2, T3, T4, and T5 treatments was 1.26, 2.31, 2.72, 3.22, and 3.57 times that of T0, respectively. The R2 was > 0.997 and RMSE was < 2.083 of the two-zone model (TRM). Compared with the convection-dispersion equation (CDE), the TRM model had higher fitting accuracy and could better simulate the NO3--N migration process in loessial soil after the application of different contents of biochar. The analysis of the fitting parameters of the TRM model showed that the average pore velocity, hydrodynamic dispersion coefficient, and water content ratio in the movable zone gradually decreased with the increasing of biochar application, whereas the dispersion and mass exchange coefficient showed an increasing trend. The results showed that biochar application could effectively enhance the ability of loessial soil to fix NO3--N, reduce the leakage of NO3--N to groundwater, and play an important role in maintaining soil fertility and preventing groundwater pollution.
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Carvão Vegetal , Solo , NitrogênioRESUMO
INTRODUCTION: Currently, the cause of psoriatic arthritis (PsA) is unknown, and the effectiveness of current drug treatments is unsatisfactory. In March 2019, the US Food and Drug Administration (FDA) approved risankizumab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, for the treatment of PsA in adults. This study aimed to conduct a meta-analysis of double-blind, randomized, placebo-controlled trials to evaluate the effectiveness and safety of risankizumab in moderate-to-severe PsA. METHODS: We conducted a thorough search of relevant databases from the establishment of the databases to October 1, 2023. We conducted a meta-analysis using Stata 12.0 and utilized I2 and Egger tests to assess heterogeneity and publication bias among the studies. Bias assessment was performed using the risk bias map and bias risk summary diagram generated by Revman5.4 software. The review protocols were registered on PROSPERO (CRD42023451894) and adhered to the preferred reporting item of system evaluation (PRISMA) guideline. RESULTS: Six randomized controlled trials (RCTs) involving 5038 patients with PsA treated with either risankizumab or placebo were included in the analysis. At 24 weeks, the risankizumab group demonstrated a significantly higher American College of Rheumatology-20 (ACR20) response rate compared to the placebo group (RR 1.760, 95% CI 1.568-1.977, P < 0.001). Additionally, the risankizumab group showed a significantly higher Minimal Disease Activity (MDA) response rate compared to the placebo group (RR 1.827, 95% CI 1.048-3.184, P < 0.05). The risankizumab group also exhibited improvement in Short Form 36 Questionnaire (SF-36) score (SMD 0.51, 95% CI 0.33-0.69, P < 0.001), with significantly lower Health Assessment Questionnaire Disability Index (HAQ-DI) score (SMD - 0.27, 95% CI - 0.37 to - 0.17, P < 0.001) and higher Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score (SMD 0.27, 95% CI 0.20-0.35, P < 0.001) compared to the placebo group. Moreover, the risankizumab group had a significantly lower Psoriasis Area and Severity Index (PASI) score (SMD - 6.12, 95% CI - 10.02 to 2.23, P < 0.001). A study by Mease et al. indicated that patients receiving risankizumab generally demonstrated numerical improvements in the Leeds Enthesitis Index (LEI), although the small sample size limits the evidence. Further research is necessary to provide evidence-based guidelines. There were no significant differences in the incidence of serious adverse events (SAE) and serious treatment-emergent adverse events (STEAE) between the risankizumab and placebo groups (RR 0.76, 95% CI 0.45-1.28, P = 0.31; RR 0.99, 95% CI 0.49-1.99, P = 0.97, respectively), and the overall incidence of adverse events (AE) was not comparable (RR 1.10, 95% CI 0.63-1.94, P = 0.73). CONCLUSION: Risankizumab showed superior efficacy across multiple outcome measures compared to placebo, with no significant increase in adverse events. Our findings endorse risankizumab as an excellent treatment option for PsA, offering valuable insights for clinicians and patients when choosing appropriate therapeutic interventions. TRIAL REGISTRATION: Retrospectively registered (CRD42023451894, 16 August 2023).
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Background: The clinical dangers of asymptomatic hyperuricemia to human health have become increasingly prominent over the past 20 years. Previous studies have shown the potential benefits of acupuncture on uric acid levels in the body. However, definitive evidence is lacking. Our objective is to evaluate the efficacy and safety of acupuncture on serum uric acid (SUA) in individuals with asymptomatic hyperuricemia. Methods: This is a randomized, single-blind, sham-controlled trial. A total of 180 eligible patients with asymptomatic hyperuricemia will be recruited at three hospitals in China. Patients will be randomly assigned in a 1:1 ratio to receive 16 sessions of manual acupuncture or sham acupuncture for 8 weeks. Patients will be followed up for 12 weeks. The primary outcome will be the change in SUA levels at week 8 after randomization. Secondary outcomes will include dynamic changes in SUA levels, efficacy rates, proportion of gout flare, body weight, and acute medication intake. The MGH Acupuncture Sensation Scale and adverse events related to acupuncture will be measured after each treatment. A blinding assessment will be performed on patients who receive at least one session of acupuncture. Data analyses will be performed on a full analysis set and a per-protocol set. Ethics and dissemination: Ethics approval has been obtained from the Clinical Trial Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology (approval no. 2021-S135). Written informed consent will be obtained from enrolled patients. The findings will be disseminated in a peer-reviewed journal. Clinical trial registration: ClinicalTrials.gov identifier, NCT05406830.
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Terapia por Acupuntura , Gota , Hiperuricemia , Humanos , Ácido Úrico , Método Simples-Cego , Exacerbação dos Sintomas , Terapia por Acupuntura/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVES: This study aimed to identify which element of body composition measurements taken before 17th week gestation was the strongest risk factor for gestational diabetes mellitus (GDM) in Chinese pregnant women. DESIGN AND SETTING: A retrospective study was performed using data retrieved from the Electronic Medical Record database of Chongqing Health Center for Women and Children (China) from January 2014 to December 2015. PARTICIPANTS: A total of 22,223 women were included with singleton pregnancies and no preexisting diabetes who underwent bioelectrical impedance analysis (BIA) before 17 gestational weeks and 75-g OGTT at 24-28 gestational weeks. RESULTS: The prevalence of GDM from 2014 to 2015 was 27.13% (IADPSG). All indicators of BIA (total body water, fat mass, fat-free mass, percent body fat, muscle mass, visceral fat levels, proteins, bone minerals, basal metabolic rate, lean trunk mass), age, weight and body mass index (BMI) were risk factors that significantly increased the occurrence of GDM (p < .001 for all). Women older than 30 years or with a BMI more than 23, had a significantly higher GDM prevalence (34.89% and 34.77%). After adjusted covariates, visceral fat levels at the third quartile, the ORs of GDM were 1.142 (95% CI 1.032-1.263) in model I and 1.419 (95% CI 1.274-1.581) in model II used the first quartile as reference (p < .05 for both); bone minerals at the third quartile, the ORs of GDM were 1.124 (95% CI 1.020-1.238) in model I and 1.311 (95% CI 1.192-1.442) in model II (p < .05 for both). After adjusted for age, visceral fat levels and bone minerals, OR of GDM for percent body fat more than 28.77% at the third quartile was 1.334 (95% CI 1.201-1.482) in model II (p < .05 for both). CONCLUSIONS: Visceral fat levels, bone minerals and percent body fat were significantly associated with an increased risk of GDM, providing the reference ranges of visceral fat levels, bone minerals and percent body fat as predictive factors for Chinese women to estimate the risk of GDM by BIA during pregnancy.
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Diabetes Gestacional , Composição Corporal , Índice de Massa Corporal , Criança , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Impedância Elétrica , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Fatores de RiscoRESUMO
The activation of microglia is a hallmark of neuroinflammation and contributes to various neurodegenerative diseases. Chronic inorganic arsenic exposure is associated with impaired cognitive ability and increased risk of neurodegeneration. The present study aimed to investigate whether chronic inorganic arsenic-induced learning and memory impairment was associated with microglial activation, and how organic (DMAV 600 µM, MMAV 0.1 µM) and inorganic arsenic (NaAsO2 0.6 µM) affect the microglia. Male C57BL/6J mice were divided into two groups: a control group and a group exposed to arsenic in their drinking water (50 mg/L NaAsO2 for 24 weeks). The Morris water maze was performed to analyze neuro-behavior and transmission electron microscopy was used to assess alterations in cellular ultra-structures. Hematoxylin-eosin and Nissl staining were used to observe pathological changes in the cerebral cortex and hippocampus. Flow cytometry was used to reveal the polarization of the arsenic-treated microglia phenotype and GC-MS was used to assess metabolomic differences in the in vitro microglia BV-2 cell line model derived from mice. The results showed learning and memory impairments and activation of microglia in the cerebral cortex and dentate gyrus (DG) zone of the hippocampus, in mice chronically exposed to arsenic. Flow cytometry demonstrated that BV-2 cells were activated with the treatment of different arsenic species. The GC-MS data showed three important metabolites to be at different levels according to the different arsenic species used to treat the microglia. These included tyrosine, arachidonic acid, and citric acid. Metabolite pathway analysis showed that a metabolic pathways associated with tyrosine metabolism, the dopaminergic synapse, Parkinson's disease, and the citrate cycle were differentially affected when comparing exposure to organic arsenic and inorganic arsenic. Organic arsenic MMAV was predominantly pro-inflammatory, and inorganic arsenic exposure contributed to energy metabolism disruptions in BV-2 microglia. Our findings provide novel insight into understanding the neurotoxicity mechanisms of chronic arsenic exposure and reveal the changes of the metabolome in response to exposure to different arsenic species in the microglia.
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Arsênio/toxicidade , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Metaboloma/fisiologia , Metabolômica/métodos , Microglia/efeitos dos fármacos , Animais , Arsênio/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Masculino , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismoRESUMO
OBJECTIVE: Studies investigating the impact of chocolate consumption on cardiovascular disease (CVD) have reached inconsistent conclusions. As such, a quantitative assessment of the dose-response association between chocolate consumption and incident CVD has not been reported. We performed a systematic review and meta-analysis of studies assessing the risk of CVD with chocolate consumption. METHODS: PubMed and EMBASE databases were searched for articles published up to 6 June 2018. Restricted cubic splines were used to model the dose-response association. RESULTS: Fourteen publications (23 studies including 405 304 participants and 35 093 cases of CVD) were included in the meta-analysis. The summary of relative risk (RR) per 20 g/week increase in chocolate consumption was 0.982 (95% CI 0.972 to 0.992, I2=50.4%, n=18) for CVD (heart failure: 0.995 (0.981 to 1.010, I2=36.3%, n=5); total stroke: 0.956 (0.932 to 0.980, I2=25.5%, n=7); cerebral infarction: 0.952 (0.917 to 0.988, I2=0.0%, n=4); haemorrhagic stroke: 0.931 (0.871 to 0.994, I2=0.0%, n=4); myocardial infarction: 0.981 (0.964 to 0.997, I2=0.0%, n=3); coronary heart disease: 0.986 (0.973 to 0.999, n=1)). A non-linear dose-response (pnon-linearity=0.001) indicated that the most appropriate dose of chocolate consumption for reducing risk of CVD was 45 g/week (RR 0.890;95%CI 0.849 to 0.932). CONCLUSIONS: Chocolate consumption may be associated with reduced risk of CVD at <100 g/week consumption. Higher levels may negate the health benefits and induce adverse effects associated with high sugar consumption.
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Doenças Cardiovasculares/epidemiologia , Chocolate , Ingestão de Alimentos/fisiologia , Humanos , Medição de RiscoRESUMO
OBJECTIVE: To analyze the changes in endogenous small molecule metabolites after benzo[a]pyrene (B[a]P) exposure in rat cerebral cortex and explore the mechanism of B[a]P neurotoxicity. METHODS: Five-day-old SD rats were subjected to gavage administration of 2 mg/kg B[a]P for 7 consecutive weeks. After the exposure, the rats were assessed for spatial learning ability using Morris water maze test, ultrastructural changes of the cortical neurons under electron microscope, and metabolite profiles of the cortex using GC/MS. The differential metabolites between the exposed and control rats were identified with partial least squares discriminant analysis (PLS-DA) and the metabolic pathways related with the differential metabolites were analyzed using Cytoscape software. RESULTS: Compared with the control group, the rats exposed to B[a]P showed significantly increased escape latency (P<0.05) and decreased time spent in the target area (P<0.05). The exposed rats exhibited widened synaptic cleft, thickened endplate membrane and swollen cytoplasm compared with the control rats. Eighteen differential metabolites (VIP>1, P<0.05) in the cortex were identified between the two groups, and 9 pathways associated with B[a]P neurotoxicity were identified involving amino acid metabolism, tricarboxylic acid cycle and Vitamin B3 (niacin and nicotinamide) metabolism. CONCLUSION: B[a]P can cause disturbance in normal metabolisms and its neurotoxicity is possibly related with disorders in amino acid metabolism, tricarboxylic acid cycle and vitamin metabolism.
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Benzo(a)pireno/efeitos adversos , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Metaboloma , Animais , Aprendizagem em Labirinto , Ratos , Ratos Sprague-DawleyRESUMO
Benzo[a]pyrene (B[a]P) is a common environmental pollutant that is neurotoxic to mammals, which can cause changes to hippocampal function and result in cognitive disorders. The mechanisms of B[a]P-induced impairments are complex .To date there have been no studies on the association of epigenetic, transcriptomic, and metabolomic changes with neurotoxicity after B[a]P exposure. In the present study, we investigated the global effect of B[a]P on DNA methylation patterns, noncoding RNAs (ncRNAs) expression, coding RNAs expression, and metabolites in the rat hippocampus. Male Sprague Dawley rats (SD rats) received daily gavage of B[a]P (2.0 mg/kg body weight [BW]) or corn oil for 7 weeks. Learning and memory ability was analyzed using the Morris water maze (MWM) test and change to cellular ultrastructure in the hippocampus was analyzed using electron microscope observation. Integrated analysis of epigenetics, transcriptomics, and metabolomics was conducted to investigate the effect of B[a]P exposure on the signaling and metabolic pathways. Our results suggest that B[a]P could lead to learning and memory deficits, likely as a result of epigenetic and transcriptomic changes that further affected the expression of CACNA1C, Tpo, etc. The changes in expression ultimately affecting LTP, tyrosine metabolism, and other important metabolic pathways.
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Benzo(a)pireno/toxicidade , Metilação de DNA/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Redes e Vias Metabólicas/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Relação Dose-Resposta a Droga , Epigenômica , Perfilação da Expressão Gênica , Hipocampo/metabolismo , Hipocampo/ultraestrutura , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Redes e Vias Metabólicas/genética , Metabolômica , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Ratos , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
OBJECTIVE: To explore the effect of exposure to vehicle exhaust in pregnant mice on the reproductive function and DNA methylation in male offspring mice. METHODS: Twenty pregnant mice were randomized into control group and vehicle exhaust exposure group (n=10) and exposed to routine laboratory condition and to vehicle exhaust for 10 consecutive days (8 h per day) in a tunnel with a heavy traffic, where the concentrations of TSP, PM10, PM2.5, SO2 and NOX and the decibel of noise were measured. The offspring mice were raised till reaching maturity, and the epididymides of the male mice were collected to test the weight coefficients, DNA methylation level, and mRNA levels of Aldh7a1 and Rpe. RESULTS: The body weight and the weight coefficients of the epididymides and testes differed significantly between the exposure group and the control group (P>0.05). The concentrations of TSP, PM2.5, PM10 and NOx and the decibel of noise were significantly higher in the traffic environment and the control environment (P<0.05). Reduced representation bisulphite sequencing (RRBS) and Gene ontology (GO) showed that 58 genes had significantly different methylation levels between the two groups, mostly relating to the process of spermatogenesis (P<0.05). Compared with the control group, Aldh7a1 and Rpe mRNA expressions in the testes were down-regulated significantly in the exposure group (P<0.05). CONCLUSION: Exposure of pregnant mice to vehicle exhaust causes damages of the reproductive function in the male offspring mice.
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Metilação de DNA , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Testículo/fisiopatologia , Emissões de Veículos/toxicidade , Animais , Feminino , Masculino , Camundongos , Gravidez , Espermatogênese/efeitos dos fármacos , Espermatogênese/genética , Testículo/efeitos dos fármacosRESUMO
OBJECTIVE: To observe the effect of chronic arsenic exposure on cerebral cortex and serum metabolics of mice and explore the mechanism of arsenic neurotoxicity. METHODS: Twelve 3-week-old male C57BL/6J mice were randomly assigned into exposure group and control group and exposed to sodium arsenite (50 mg/L) via drinking water and deionized water for 12 weeks, respectively. After the exposure, arsenic level in the cerebrum was determined by hydride generation-atomic fluorescence spectrometry. The metabolites in the cerebral cortex and serum were determined using gas chromatography-mass spectrometry (GC/MS) analysis. Principal component analysis (PCA) was used to analyze the difference of the metabolites between the exposure and the control groups. Online tools for analyzing metabolic pathways were used to identify the related metabolites pathways. RESULTS: Arsenic content in the brain of exposure group was significantly higher than that in the control group (P<0.05). The mice exposed to arsenic had a higher level of citric acid, phenylalanine, tyrosine, histidine and lysine in the cerebral cortex (P<0.05). Serum levels of serine, glycine, proline, aspartate and glutamate were significantly higher while α-ketoglutaric acid level was significantly lower in the exposure group than in the control group (P<0.05). PCA analysis showed a significant difference in cerebral cortex and serum metabolites between the two groups. CONCLUSION: Chronic arsenic exposure may affect the function of the central nervous system by interfering with amino acid metabolism and tricarboxylic acid cycle, which may be one of the mechanisms of arsenic neurotoxicity.