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1.
Artigo em Inglês | MEDLINE | ID: mdl-34617212

RESUMO

Prenatal air pollution, protein C (PROC) gene abnormal methylation, and genetic mutation can cause a series of neonatal diseases, but the complex relationship between them remains unclear. Here, we recruited 552 mothers and their own babies during January 2010-January 2012 in Zhengzhou to explore such association. The air pollutant data was obtained from the Environmental Monitoring Stations. The rs1799809 genotype and the methylation levels at the promoter region of PROC in genomic DNA samples were detected respectively by TaqMan probe and quantitative methylation specific PCR using real-time PCR system. The results show that the levels of neonatal PROC methylation were negatively associated with concentrations of NO2 during the entire pregnancy, particularly during the third trimester. Of particular significance, only in newborns carrying rs1799809 AA genotype, negatively significant associations between PROC methylation levels and exposure concentrations of air pollutants were observed. Further, we observed a significant interactive effect between neonatal rs1799809 genotype and SO2 exposure during the entire pregnancy on neonatal PROC methylation levels. Prenatal exposure to ambient air pollutants specifically was associated with the neonatal PROC promoter methylation level of newborns carrying the rs1799809 AA genotype. Taken together, these findings suggest that neonatal PROC methylation levels are associated with prenatal exposure to ambient air pollutants, and this association can be modified by rs1799809 genotype.

2.
Ecotoxicol Environ Saf ; 225: 112796, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34555722

RESUMO

To identify the role of the Hippo signaling pathway in the extracellular matrix degradation of chondrocytes induced by fluoride exposure. Environmental response genes (ERGs) of bone injury induced by fluoride exposure were obtained from the Comparative Toxicogenomics Database, and annotated by STRING for KEGG pathway enrichment analysis. The CCK-8 kit was used to measure the proliferation of ATDC5 cells. The malondialdehyde (MDA), total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-PX) levels in ATDC5 cells were measured using oxidative stress detection kit. Western blot analysis was used to measure the p-MST1/2, p-LATS1/2, and p-YAP/YAP1 expression levels in the Hippo pathway and the COL2A1, ACAN and MMP13 expression levels in the cartilage matrix. Localizations of YAP1 and COL2A1 proteins in chondrocytes were performed using cell immunofluorescence. Continuous data from the multiple groups were compared using one-way analysis of variance, and then the differences between groups were tested with Dunnett's t-test, with the test level α = 0.05. The 145 ERGs of bone injury induced by fluoride exposure were identified, and KEGG enrichment analysis revealed Hippo signaling pathways significantly related to bone injury. A CCK-8 assay revealed that the viability of the ATDC5 cells was significantly decreased with increased fluorine concentration. The MDA content in 20 mg/L sodium fluoride (NaF) exposure group was significantly higher than that in the control group, the T-SOD, T-AOC and GSH-PX activities in 15 and 20 mg/L NaF exposure groups were significantly lower than those in the control group (P < 0.05). Western blot results showed the protein levels of p-MST1/2, p-LATS1/2 and p-YAP1 in 15 and 20 mg/L NaF exposure groups were significantly lower than those in the control group, while the YAP1 protein level in 20 mg/L NaF group was significantly higher than that in the control group. The COL2A1 and ACAN proteins in 20 mg/L NaF group were significantly decreased, while the MMP13 protein level in 15 and 20 mg/L NaF groups were significantly increased (P < 0.05). It was observed that the expression of YAP1 protein expression level in the cytoplasm decreased with the increased fluoride exposure, whereas that the expression level of YAP1 protein in the nucleus increased. Fluoride inhibited the proliferation of ATDC5 cells, induced oxidative stress, inhibited the activity of the Hippo pathway, and eventually led to cartilage matrix degradation.


Assuntos
Condrócitos , Fluoretos , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Linhagem Celular Tumoral , Condrócitos/metabolismo , Matriz Extracelular , Glutationa Peroxidase/metabolismo , Camundongos , Transdução de Sinais
3.
Chemosphere ; 286(Pt 2): 131833, 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34426128

RESUMO

Due to the poor living and healthcare conditions, preterm birth (PTB) in rural population is a pressing health issue. However, PTB studies in rural population are rare. To explore the effects of air pollutants on PTB in rural population, we collected 697,316 medical records during 2014-2016 based on the National Free Preconception Health Examination Project. Logistic regression models were used to estimate the association between air pollutants and PTB and the modifying effects of demographic characteristics. Relative contribution and principal component analysis-generalized linear model (PCA-GLM) analysis were used to explore the most significant air pollutant and gestational period. Our results demonstrated that PTB risk is positively associated with exposure to air pollutants including PM10, PM2.5, SO2, NO2, and CO, while negatively associated with O3 exposure (P < 0.05). In addition, we found that NO2 was the largest contributor to the risk of PTB caused by air pollutants (26.5%). The third trimester of pregnancy was the most sensitive exposure window. PCA-GLM analysis showed that the first component (a combination of PM, SO2, NO2, and CO) increased the risk of PTB. Moreover, we found that rural women who are younger, had higher educated, multi-parity, or smoke appeared to be more sensitive to the association between air pollutants exposure and PTB (P-interaction<0.05). Our findings suggested that increased air pollutants except O3 were associated with elevated PTB risk, especially among vulnerable mothers. Therefore, the effects of air pollutants exposure on PTB should be mitigated by restricting emission sources of NO2 and SO2 in rural population, especially during the third trimester.

4.
Ecotoxicol Environ Saf ; 223: 112612, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34371455

RESUMO

Excessive fluoride exposure and epigenetic change can induce numerous adverse health outcomes, but the role of epigenetics underneath the harmful health effects induced by fluoride exposure is unclear. In such gap, we evaluated the associations between fluoride exposure and genome-wide DNA methylation, and identified that novel candidate genes associated with fluoride exposure. A total of 931 school-age children (8-12 years) in Tongxu County of Henan Province (China) were recruited in 2017. Urinary fluoride (UF) concentrations were measured using the national standardized ion selective electrode method. Participants were divided into a high fluoride-exposure group (HFG) and control group (CG) according to the UF concentrations. Candidate differentially methylated regions (DMRs) were screened by Infinium-Methylation EPIC BeadChip of DNA samples collected from 16 participants (eight each from each group). Differentially methylated genes (DMGs) containing DMRs associated with skeletal and neuronal development influenced by fluoride exposure were confirmed using MethylTarget™ technology from 100 participants (fifty each from each group). DMGs were verified by quantitative methylation specific PCR from 815 participants. Serum levels of hormones were measured by auto biochemical analyzer. The mediation analysis of methylation in the effect of fluoride exposure on hormone levels was also performed. A total of 237 differentially methylated sites (DMSs) and 212 DMRs were found in different fluoride-exposure groups in the epigenome-wide phase. Methylation of the target sequences of neuronatin (NNAT), calcitonin-related polypeptide alpha (CALCA) and methylenetetrahydrofolate dehydrogenase 1 showed significant difference between the HFG and CG. Each 0.06% (95% CI: -0.11%, -0.01%) decreased in NNAT methylation status correlated with each increase of 1.0 mg/L in UF concentration in 815 school-age children using QMSP. Also, each 1.88% (95% CI: 0.04%, 3.72%) increase in CALCA methylation status correlated with each increase of 1.0 mg/L in UF concentration. The mediating effect of NNAT methylation was found in alterations of ACTH levels influenced by fluoride exposure, with a ß value of 11.7% (95% CI: 3.4%, 33.4%). In conclusion, long-term fluoride exposure affected the methylation pattern of genomic DNA. NNAT and CALCA as DMGs might be susceptible to fluoride exposure in school-age children.


Assuntos
Metilação de DNA , Fluoretos , Criança , Epigênese Genética , Epigenoma , Fluoretos/toxicidade , Humanos , Instituições Acadêmicas
5.
Ecotoxicol Environ Saf ; 222: 112511, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34273848

RESUMO

This study examined the neuroprotective properties of resveratrol (Res) and its target sirtuin1 (SIRT1) against lead (Pb)-mediated toxicity and discovered that both resveratrol treatment and SIRT1 overexpression restored blocked autophagic flux as well as reduced ß-amyloid (Aß) contents. Four-week-old male C57BL/6 mice were employed to consumed 0.2% Pb(Ac)2 solution or deionized water for 3 months followed by 12 months of Res (50 mg/kg BW) or vehicle gavage. In in vitro study, SH-SY5Y cells were pretreated with the SIRT1 activator SRT1720 (2 µM) or the inhibitor EX527 (2 µM) for 2 h, then 25 µM of Pb(Ac)2 was added and incubated for 48 h. Western blotting, RT-qPCR, enzyme-linked immunosorbent assay (ELISA), and Lyso-Tracker Red Staining were next used to estimate the potential alterations of the autophagic pathway as well as BACE1-mediated amyloid processing in response to Pb exposure, respectively. Our data revealed that Res treatment or SIRT1 activation resisted the induction of autophagy by Pb exposure through inhibition of LC3 and Beclin-1 expression and promoted the degradation of Aß and Tau phosphorylation. Besides, the SIRT1 activator (SRT1720) downregulated the expression of BACE1, the rate-limiting enzyme for Aß production, by inhibiting the activation of nuclear factor-κB (NF-κB) in Pb-treated SH-SY5Y cells, which resulted in reduced Aß production. Collectively, we verified the role of Res-SIRT1-autophagy as well as the SIRT1-NF-κB-BACE1 pathway in Pb-induced neuronal cell injury by in vivo or in vitro models. Our findings further elucidate the important role of SIRT1 and Res in counteracting Pb neurotoxicity, which may provide new interventions and targets for the subsequent treatment of neurodegenerative diseases.


Assuntos
Fármacos Neuroprotetores , Sirtuína 1 , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/farmacologia , Animais , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/farmacologia , Autofagia , Chumbo/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/farmacologia , Resveratrol/farmacologia , Sirtuína 1/genética
6.
Dermatol Surg ; 47(3): e71-e74, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34328286

RESUMO

BACKGROUND: Multiple lasers have been used for the treatment of café au lait macules (CALMs) with various results. Objective tools to predict therapeutic efficacy of CALMs treatment is lacking. OBJECTIVE: To determine whether reflectance confocal microscopy (RCM) characteristics correlate with CALMs response to laser treatment. MATERIALS AND METHODS: All CAMLs underwent RCM examination of length and density of dermal papillae followed by 3 sessions of Q-switched alexandrite laser (QSAL). A visual analog scale was used to assess clinical treatment efficacy. RESULTS: Forty-three patients were included, 22 had CALMs with irregular borders and 21 with smooth borders. Café au lait macules with irregular border had shorter rete pegs and less papillae (p < .05) on RCM compared with smooth border CAMLs and responded better to QSAL treatment (2.32 vs 1.10). CONCLUSION: Reflectance confocal microscopy measurement of length and density of papillae were inversely correlated with treatment response. Reflectance confocal microscopy may be a useful tool to predict CALMs response to laser treatment.


Assuntos
Manchas Café com Leite/diagnóstico por imagem , Manchas Café com Leite/cirurgia , Lasers de Estado Sólido/uso terapêutico , Microscopia Confocal , Manchas Café com Leite/patologia , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
7.
Environ Int ; 155: 106681, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34098334

RESUMO

BACKGROUND: Excessive fluoride exposure has been associated with intelligence loss, but little is known about gene-fluoride interactions on intelligence at SNP-set, gene and pathway level. OBJECTIVES: Here we conducted a population-based study in Chinese school-aged children to estimate the associations of fluoride from internal and external exposures with intelligence as well as to explore the gene-fluoride interactions on intelligence at SNP-set, gene and neurodevelopmental pathway level. METHODS: A total of 952 resident children aged 7 to 13 were included in the current study. The fluoride contents in drinking water, urine, hair and nail were measured using the ion-selective electrode method. LASSO Binomial regression was conducted to screen the intelligence-related SNP-set. The gene-fluoride interactions at gene and pathway levels were detected by the Adaptive Rank Truncated Product method. RESULTS: The probability of high intelligence was inversely correlated with fluoride contents in water, urine, hair and nail (all P < 0.001). The SNP-set based on rs3788319, rs1879417, rs57377675, rs11556505 and rs7187776 was related to high intelligence (P = 0.001) alone and by interaction with water, urinary and hair fluoride (P = 0.030, 0.040, 0.010), separately. In gene level, CLU and TOMM40 interacted with hair fluoride (both P = 0.017) on intelligence. In pathway level, Alzheimer disease pathway, metabolic pathway, signal transduction pathway, sphingolipid signaling pathway and PI3K-AKT signaling pathway interacted with fluoride on intelligence in men. CONCLUSIONS: Our study suggests that fluoride is inversely associated with intelligence. Moreover, the interactions of fluoride with mitochondrial function-related SNP-set, genes and pathways may also be involved in high intelligence loss.


Assuntos
Fluoretos , Interação Gene-Ambiente , Estudos de Casos e Controles , Criança , Estudos Transversais , Fluoretos/toxicidade , Humanos , Inteligência/genética , Masculino , Fosfatidilinositol 3-Quinases
8.
Brain Res ; 1767: 147567, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34175265

RESUMO

Lead (Pb) exposure damages synaptic structural plasticity that results in cognitive impairment. Resveratrol, a natural polyphenolic compound, is one of the most potent agonists of silencing information regulator 1 (SIRT1) discovered to date. However, the effects of SIRT1 on synaptic functional plasticity in early life Pb exposure are not well studied. Herein, the purpose of this study is to investigate the expression of synaptic markers and SIRT1 in rats exposed to Pb and to evaluate the regulatory effect of resveratrol during this process. The Pb exposed male SD pups were treated with resveratrol (50 mg/kg/d) or EDTA (150 mg/kg/d) followed by hippocampal and blood sampling for analysis at postnatal day 21 (PND21). In the Morrris water maze test, resveratrol treatement protected the rats against Pb-induced impairment of learning and memory (P < 0.05). Resveratrol also enhanced the expression of brain-derived neurotrophic factor (BDNF, P < 0.001 vs 0.2% Pb group), and reversed the effects of Pb exposure on SIRT1(P < 0.001 vs 0.2% Pb group). The DG, CA1 and CA3 regions of the hippocampus showed a considerable increase in the expression of pre- and postsynaptic proteins (P < 0.001 vs 0.2% Pb group). In conclusion, our study demonstrated that resveratrol, through the activation of SIRT1, played a protective role against Pb-induced defects in synaptic plasticity, and suggested a new potential adjuvant treatment for Pb poisoning.

9.
Environ Res ; 201: 111545, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34171374

RESUMO

BACKGROUND: A number of studies have explored the association between ambient temperature and preterm birth (PTB), but rarely among adolescent mothers. OBJECTIVES: To estimate the effects of ambient temperature on the risk of PTB and gestational age of newborns delivered by adolescent mothers in rural areas of Henan province. METHODS: We obtained 5394 medical records of adolescent mothers with results of pre-pregnancy physical examination and pregnancy outcomes from the National Free Preconception Health Examination Project (NFPHEP) in Henan province. Meteorological information was obtained from the China Meteorological Data Sharing Service System. Individual exposure levels were evaluated with an inverse distance-weighted model. A multiple logistic regression model and multiple linear regression model were used to estimate the effects of ambient temperature on the risk of PTB and gestational age, respectively. Stratified and interaction analyses were also performed. RESULTS: Of newborns in this study, 3.45% (186/5394) were PTB. Mean, maximum and minimum temperature during the entire pregnancy, especially the last 1-4 weeks of pregnancy, were positively associated with the risk of PTB and negatively associated with gestational age (P < 0.05). Nevertheless, a masking effect was observed that gestational age was positively associated with ambient temperature during the first trimester of pregnancy, due to the strongly inverse correlation between ambient temperature during the early and late stages of pregnancy. Stratified analyses showed that increasing temperature during the last 1-4 weeks of pregnancy increased the risk of PTB and decreased gestational age in newborns born in the cold season (P < 0.05). Furthermore, interaction analyses showed that birth season modified the effects of temperature on the gestational age (Pinteraction < 0.10). CONCLUSIONS: Elevated ambient temperature can decrease gestational age and increase the risk of PTB in offspring of adolescent mothers in rural areas. The birth season may modify the effects of temperature on gestational age.


Assuntos
Nascimento Prematuro , Adolescente , China/epidemiologia , Feminino , Humanos , Recém-Nascido , Meteorologia , Mães , Gravidez , Nascimento Prematuro/epidemiologia , Temperatura
10.
Environ Toxicol ; 36(8): 1664-1673, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33978298

RESUMO

Lead (Pb) poses a potential environmental risk factor for cognitive dysfunction during early life and childhood. Resveratrol is considered a promising antioxidant with respect to the prevention of cognitive deficits and act as a potent SIRT1 agonist. Herein, this study aims to investigate the profile of neurogenesis markers following Pb exposure and to determine the regulatory role of resveratrol in this process. We confirmed firstly the protective effects of resveratrol against Pb-induced impairments of hippocampal neurogenesis in Male SD rats. Pb exposure early in life caused the altered expression of Ki-67, NeuN, caspase-3 and SIRT1 signaling, thereby resulting in spatial cognitive impairment of adolescent rats. As expected, resveratrol reduced cognitive damage and promoted neurogenesis in Pb-induced injury by regulation of SIRT1 pathway. Collectively, our study establishes the efficacy of resveratrol as a neuroprotective agent and provides a strong rationale for further studies on SIRT1-mediated mechanisms of neuroprotective functions.


Assuntos
Sirtuína 1 , Estilbenos , Animais , Hipocampo/metabolismo , Chumbo , Masculino , Neurogênese , Ratos , Ratos Sprague-Dawley , Resveratrol , Sirtuína 1/metabolismo
11.
Stroke Vasc Neurol ; 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33941642

RESUMO

BACKGROUND AND OBJECTIVE: Moyamoya disease (MMD) is an increasingly recognised cause of stroke, mainly described in East Asia. China is the largest nation in Asia, but few studies reported the epidemiology of MMD, especially at a national level. We aimed to estimate the incidence and prevalence of MMD in China. METHODS: We performed a population-based study using data from the national databases of Urban Basic Medical Insurance between 2013 and 2016, covering approximately 0.50 billion individuals. MMD cases were identified by diagnostic code (International Classification of Diseases, 10th Revision I67.5) or related diagnostic text. RESULTS: A total of 1987 MMD patients (mean age 44.45±14.30 years, female-to-male ratio 1.12) were identified, representing a national crude incidence of 0.59 (95% CI: 0.49 to 0.68) and a prevalence of 1.01 (95% CI: 0.81 to 1.21) per 100 000 person-years in 2016. Rates were higher in females than in males for the incidence (0.66 vs 0.52) and prevalence (1.05 vs 0.90). And the age-specific rates showed a bimodal distribution, with the highest peak in middle-aged group and the second peak in child group. CONCLUSIONS: Our results confirm that MMD is relatively common in East Asians, but the rates in China were lower than those in other East Asian countries such as Japan and Korea. The unique epidemiological features, including a relatively weak female predominance and a shift in the highest peak of incidence from children to adults, revealed new sight into MMD. Further research is expected to explore the potential pathogenesis of MMD.

12.
Fluids Barriers CNS ; 18(1): 21, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952281

RESUMO

BACKGROUND: Chronic cerebral hypoperfusion (CCH) is the leading cause of cerebral small vessel disease (CSVD). CCH is strongly associated with blood-brain barrier (BBB) dysfunction and white matter lesions (WMLs) in CSVD. However, the effects of CCH on BBB integrity and components and the cellular and molecular mechanisms underlying the effects of BBB dysfunction remain elusive. Whether maintaining BBB integrity can reverse CCH-induced brain damage has also not been explored. METHODS: In this study, we established a rat model of CSVD via permanent bilateral common carotid artery occlusion (2VO) to mimic the chronic hypoperfusive state of CSVD. The progression of BBB dysfunction and components of the BBB were assessed using immunostaining, Western blotting, transmission electron microscopy (TEM) and RNA sequencing. We also observed the protective role of imatinib, a tyrosine kinase inhibitor, on BBB integrity and neuroprotective function following CCH. The data were analyzed using one-way or two-way ANOVA. RESULTS: We noted transient yet severe breakdown of the BBB in the corpus callosum (CC) following CCH. The BBB was severely impaired as early as 1 day postoperation and most severely impaired 3 days postoperation. BBB breakdown preceded neuroinflammatory responses and the formation of WMLs. Moreover, pericyte loss was associated with BBB impairment, and the accumulation of serum protein was mediated by increased endothelial transcytosis in the CC. RNA sequencing also revealed increased transcytosis genes expression. BBB dysfunction led to brain damage through regulation of TGF-ß/Smad2 signaling. Furthermore, imatinib treatment ameliorated serum protein leakage, oligodendrocyte progenitor cell (OPC) activation, endothelial transcytosis, microglial activation, and aberrant TGF-ß/Smad2 signaling activation. CONCLUSIONS: Our results indicate that reduced pericyte coverage leads to increased BBB permeability via endothelial transcytosis. Imatinib executes a protective role on the BBB integrity via inhibition of endothelial transcytosis. Maintenance of BBB integrity ameliorates brain damage through regulation of TGF-ß/Smad2 signaling following CCH; therefore, reversal of BBB dysfunction may be a promising strategy for CSVD treatment.

13.
Biol Trace Elem Res ; 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33844169

RESUMO

To evaluate the association between selenoprotein gene polymorphisms and Kashin-Beck disease (KBD) susceptibility through a systematic review and updated meta-analysis. PubMed, Google Scholar, Cochrane library, and Chinese National Knowledge Infrastructure (CNKI) were electronically searched using the terms "selenoprotein" and "Kashin-Beck disease" or "KBD" with a search time from the establishment of the database to January 2021. The Newcastle-Ottawa Scale (NOS) was used for methodological quality evaluation of the included studies. Stata 14.0 software was used to pooled odds ratio (OR) and 95% confidence interval. There were a total of eight included case-control studies covering 2025 KBD patients and 1962 controls. Meta-analysis results show that the pooled odds ratios (OR) and 95% confidence intervals (CI) for DIO2 (rs225014) were 0.69 (0.52, 0.91), 0.69 (0.50, 0.96), and 0.72 (0.52, 0.99) in the allele, heterozygote, and dominant models, respectively. The OR and 95%CI for SEPS1 (-105G>A) were 2.47 (1.85, 3.29), 9.36 (4.58, 19.12), 2.17 (1.53, 3.08), and 8.60 (4.25, 17.38) in the allele, homozygote, dominant, and recessive models, respectively. In addition, the OR and 95%CI for Sep15 (rs5859) were 2.05 (1.06, 3.96) in the allele model. These results illustrate that there was a significant association between DIO2 (rs225014), SEPS1 (-105G>A), Sep15 (rs5859), and KBD. For GPX1 (rs1050450, rs1800668, rs3811699), DIO2 (rs225014, rs1352815, rs1388382), TrxR2 (rs1139793, rs5746841), GPX4 (rs713041, rs4807542), and SEPP1 (rs7579, 25191g/a), there was no significant statistical difference between the KBD and control groups (P>0.05). We conclude that the DIO2 (rs225014), SEPS1 (-105G>A), and Sep15 (rs5859) gene polymorphism are associated with susceptibility to KBD.

14.
Mol Neurobiol ; 58(7): 3290-3307, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33675023

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by progressive memory decline and cognitive dysfunctions. Although the causes of AD have not yet been established, many mechanisms have been proposed. Axon-guidance molecules play the roles in the occurrence and development of AD by participating in different mechanisms. Therefore, what roles do axon-guidance molecules play in AD? This study aimed at elucidating how axon-guidance molecules Netrins, Slits, Semaphorins, and Ephrins regulate the levels of Aß, hyperphosphorylation of tau protein, Reelin, and other ways through different signaling pathways, in order to show the roles of axon-guidance molecules in the occurrence and development of AD. And it is hoped that this study can provide a theoretical basis and new perspectives in the search for new therapeutic targets for AD.

15.
Front Public Health ; 9: 578134, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33748055

RESUMO

Objective: This study is aimed to explore the potential association among the estrogen receptor alpha (ESRα) promoter methylation, lipid metabolism and the risk of type 2 diabetes mellitus (T2DM). Methods: A total of 1143 rural residents were recruited randomly from Henan Province, China. The circulating methylation levels in ESRα promoter region were determined by quantitative methylation-specific polymerase chain reaction. Serum high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC) and fasting plasma-glucose (FPG) were measured. Results: The ESRα promoter methylation levels were negatively associated with HDL-C levels whether gender stratification was performed (P < 0.05) and positively correlated with LDL-C in men (P < 0.05). Each unit standard deviation (SD) increment in TG was associated with a 43% increase (95% CI: 1.25, 1.64) in the risks of T2DM in all participants, a 36% increase (95% CI: 1.13, 1.64) in the risks of T2DM in men and a 49% increase (95% CI: 1.21, 1.83) in the risks of T2DM in women. Furthermore, each SD increment in HDL-C was associated with a reduction of 25% (OR = 0.75, 95% CI: 0.58, 0.97) in the risks of T2DM in men, and the risk of T2DM in men may be more susceptible to HDL-C than that in women (P for interaction < 0.05). Additionally, we found that the risk of T2DM in participants with lower methylation levels (≤4.07%) were more susceptible to HDL-C (P for interaction < 0.05). Conclusions: These findings suggested that lipid metabolism was associated with ESRα promoter methylation levels and the risk of T2DM. Besides, the levels of ESRα promoter methylation and gender can modify the association of HDL-C and T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , China/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Receptor alfa de Estrogênio/genética , Fazendeiros , Feminino , Humanos , Metabolismo dos Lipídeos/genética , Masculino , Metilação , Regiões Promotoras Genéticas
16.
Biol Trace Elem Res ; 199(10): 3658-3666, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33479887

RESUMO

Excessive fluoride exposure has detrimental effects on the thyroid gland, which may be modified by iodine. However, the role of iodine in it remains unclear. This study aims to evaluate the role of iodine in thyroid abnormalities caused by fluoride exposure in school-age children. A total of 446 children aged 7-12 years were recruited from Tongxu County, Henan province, in 2017 (ZZUIRB 2017-018). We obtained demographic information through questionnaire surveys. The concentrations of urinary fluoride (UF) and urinary iodine (UI) were determined by the ion-selective electrode method and the catalytic spectrophotometric method, respectively. The radiation immunoassay was used to determine the serum concentrations of total triiodothyronine (TT3), total thyroxine (TT4), and thyroid-stimulating hormone (TSH). The B-mode ultrasound was performed to assess thyroid volumes (Tvols). The associations between fluoride exposure and thyroid-related indicators were tested by linear regression models. We found that Tvols increased by 0.22 (95% CI: 0.14, 0.31) cm3 with each standard deviation increment of UF. Moreover, Tvols in boys were more susceptible to fluoride exposure than those in girls, and the Tvols of children with high urinary iodine are less susceptible to fluoride exposure (P for interaction < 0.05). We also observed that TT3 levels were negatively related to UF concentrations at moderate urinary iodine levels (≤ 300 µg/l). Fluoride exposure can elevate the Tvols of school-age children, especially in boys, and high levels of iodine may alleviate this effect to some extent.


Assuntos
Iodo , Glândula Tireoide , Criança , China , Estudos Transversais , Feminino , Fluoretos , Humanos , Masculino , Rios , Instituições Acadêmicas , Tireotropina , Tiroxina
17.
Biomater Sci ; 9(3): 658-662, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33463639

RESUMO

A pH-responsive fluorinated chitosan-chlorin e6 (FC-Ce6) was employed here for the intracellular delivery of catalase to relieve the hypoxic micro-environment. Upon simple mixing, FC-Ce6 and catalase co-assemble to form stable nanoparticles, which show a greatly improved cross-membrane penetration capacity compared with catalase alone or nonfluorinated CS-Ce6/catalase nanoparticles. Under catalase catalysis, a high concentration of intracellular H2O2 can be transformed into O2. Upon irradiation, due to the continuous formation of cytotoxic singlet oxygen (1O2), our nanoparticles showed superior anti-cancer activity in contrast to free Ce6 and nonfluorinated CS-Ce6/catalase nanoparticles. Our study proposes an effective intracellular catalase delivery system to overcome hypoxia for enhanced PDT against oral cancer.


Assuntos
Quitosana , Neoplasias Bucais , Nanopartículas , Fotoquimioterapia , Porfirinas , Catalase , Linhagem Celular Tumoral , Humanos , Peróxido de Hidrogênio , Neoplasias Bucais/tratamento farmacológico , Fármacos Fotossensibilizantes , Microambiente Tumoral
18.
Environ Sci Pollut Res Int ; 28(8): 9407-9416, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33145731

RESUMO

Changes in the preconception ambient temperature (PAT) can affect the gametogenesis, disturbing the development of the embryo, but the health risks of PAT on the developing fetus are still unclear. Here, based on the National Free Preconception Health Examination Project in the rural areas of Henan Province, we evaluate the effects of PAT on preterm birth (PTB). Data of 1,231,715 records from self-reported interviews, preconception physical examination, early gestation follow-up, and postpartum follow-up were collected from 1 January 2013 to 31 December 2016. Generalized additive models were used to assess the cumulative and lag effects of PAT upon PTB. The significant cumulative effects of mean temperature within 2 weeks and 3 weeks on the risk of PTB, especially upon late PTB (34-36 weeks) (P < 0.05), were observed. Exposure to extreme heat (> 90th percentile) within 2 weeks (RR = 1.470) and 3 weeks (RR = 1.375) before conception could increase the risk of PTB. After stratifying PTB, exposure to extreme heat within 2 weeks before conception can increase the risks of early (< 34 weeks) and late PTB (P < 0.05). Besides, exposure to extreme cold (< 10th percentile) within 3 weeks or longer before conception can elevate the risk of PTB, especially late PTB. The significant lag effects of temperature changes on the risk of early PTB (lag-8 days or earlier) were observed. In conclusion, the risk of PTB was susceptible to PAT changes within 2 weeks or longer before conception. Our findings provide (i) guidance for rural couples to make pregnancy plans and (ii) scientific evidence for the government to formulate policies to prevent PTB.


Assuntos
Calor Extremo , Nascimento Prematuro , China/epidemiologia , Feminino , Feto , Humanos , Recém-Nascido , Gravidez , Nascimento Prematuro/epidemiologia , Temperatura
19.
Environ Pollut ; 268(Pt A): 115773, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33065364

RESUMO

Polybrominated diphenyl ethers (PBDEs) are flame retardants and the congener 2, 2', 4, 4'-tetrabromodiphenyl ether (PBDE-47) is capable of inducing thyroid endocrine disruption and developmental toxicity. However, little is known about whether developmental PBDE-47 exposure-elicited alterations in semen quality is associated with thyroid hormones (THs) perturbation. In this research, we sought to explore the impacts of gestational and lactational PBDE-47 exposure on adult sperm quantity and motility, and its link with THs levels. For this purpose, female Sprague-Dawley rats were administered environmentally relevant PBDE-47 levels (0.1, 1.0, 10 mg/kg/day) by oral gavage from prepregnancy through lactation cessation to achieve early-life exposure of offspring and to mimic the actual exposure. Sperm quantity and motility together with serum THs levels from male offspring were determined on postnatal day 88. In utero and lactational exposure to PBDE-47 boosted the weight gain while reduced the relative testis weight in adult male offspring. These were accompanied with the reductions in sperm counts (total and living sperm counts), the percentage of progressive sperm motility, sperm velocities (curvilinear velocity, straight-line velocity and average path velocity), motion path (beat cross frequency, linearity and wobble) and linear motile sperm parameters (count, motility and concentration). Further studies identified that the levels of serum triiodothyronine (T3) were increased by PBDE-47 exposure and negatively associated with those differential semen parameters on quantity and motility. Collectively, our results indicate that exposure to low-level PBDE-47 during early-life development impairs semen quality in adult rats, which could be mediated partially by abnormal T3 levels.


Assuntos
Retardadores de Chama , Éteres Difenil Halogenados , Animais , Feminino , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/toxicidade , Humanos , Lactação , Masculino , Ratos , Ratos Sprague-Dawley , Análise do Sêmen , Motilidade Espermática , Espermatozoides , Hormônios Tireóideos
20.
BMC Public Health ; 20(1): 1657, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33148225

RESUMO

BACKGROUND: The intellectual loss induced by fluoride exposure has been extensively studied, but the association between fluoride exposure in different susceptibility windows and children's intelligence is rarely reported. Hence, we conducted a cross-sectional study to explore the association between fluoride exposure in prenatal and childhood periods and intelligence quotient (IQ). METHODS: We recruited 633 local children aged 7-13 years old randomly from four primary schools in Kaifeng, China in 2017. The children were divided into four groups, of which included: control group (CG, n = 228), only prenatal excessive fluoride exposure group (PFG, n = 107), only childhood excessive fluoride exposure group (CFG, n = 157), both prenatal and childhood excessive fluoride exposure group (BFG, n = 141). The concentrations of urinary fluoride (UF) and urinary creatinine (UCr) were determined by fluoride ion-selective electrode assay and a creatinine assay kit (picric acid method), respectively. The concentration of UCr-adjusted urinary fluoride (CUF) was calculated. IQ score was assessed using the second revision of the Combined Raven's Test-The Rural in China (CRT-RC2). Threshold and saturation effects analysis, multiple linear regression analysis and logistic regression analysis were conducted to analyze the association between fluoride exposure and IQ. RESULTS: The mean IQ score in PFG was respectively lower than those in CG, CFG and BFG (P < 0.05). The odds of developing excellent intelligence among children in PFG decreased by 51.1% compared with children in CG (OR = 0.489, 95% CI: 0.279, 0.858). For all the children, CUF concentration of ≥1.7 mg/L was negatively associated with IQ scores (ß = - 4.965, 95% CI: - 9.198, - 0.732, P = 0.022). In children without prenatal fluoride exposure, every 1.0 mg/L increment in the CUF concentration of ≥2.1 mg/L was related to a reduction of 11.4 points in children's IQ scores (95% CI: - 19.2, - 3.5, P = 0.005). CONCLUSIONS: Prenatal and childhood excessive fluoride exposures may impair the intelligence development of school children. Furthermore, children with prenatal fluoride exposure had lower IQ scores than children who were not prenatally exposed; therefore the reduction of IQ scores at higher levels of fluoride exposure in childhood does not become that evident.


Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Fluoretos/efeitos adversos , Inteligência/efeitos dos fármacos , Adolescente , Adulto , Criança , China , Estudos Transversais , Feminino , Fluoretos/urina , Humanos , Testes de Inteligência , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Instituições Acadêmicas , Adulto Jovem
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