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1.
Front Immunol ; 12: 759187, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675937

RESUMO

Background: The concurrence of anti-contactin 1 (CNTN1) antibody-associated chronic inflammatory demyelinating polyneuropathy (CIDP) and membranous nephropathy (MN) has previously been reported in the literature. CIDP with autoantibodies against paranodal proteins are defined as autoimmune nodopathies (AN) in the latest research. In view of the unclear relationship between CIDP and MN, we performed a case study and literature review to investigate the clinical characteristics of anti-CNTN antibody-associated AN with MN. Methods: We detected antibodies against NF155, NF186, CNTN1, CNTN2, CASPR1 and PLA2R in blood samples of a patient with clinically manifested MN and concomitant peripheral neuropathy via double immunofluorescence staining and conducted a quantitative measurement of anti-PLA2R IgG antibodies via enzyme-linked immunosorbent assay (ELISA). Case reports of anti-CNTN1 antibody-associated AN, anti-CNTN1 antibody-associated AN with MN, and CIDP with MN were retrieved through a literature search for a comparative analysis of clinical characteristics. The cases were grouped according to the chronological order of CIDP and MN onset for the comparison of clinical characteristics. Results: A 57-year-old man with anti-PLA2R positive MN was admitted to the hospital due to limb numbness, weakness, and proprioceptive sensory disorder. He was diagnosed with anti-CNTN1 antibody-associated AN and recovered well after immunotherapy. Our literature search returned 22 cases of CIDP with MN that occurred before, after, or concurrently with CIDP. Good responses were achieved with early single-agent or combination immunotherapy, but eight out of the 22 patients with CIDP and concomitant MN ultimately developed different motor sequelae. Five patients had anti-CNTN1 antibody-associated AN with MN. Among these patients, males accounted for the majority of cases (male:female=4:1), the mean age at onset was late (60.2 ± 15.7 years, range 43-78 years), and 40% had acute to subacute onset. Clinical manifestations included sensory-motor neuropathy, sensory ataxia caused by proprioceptive impairment, and elevated cerebrospinal fluid protein levels. Conclusion: The age at onset of CIDP with MN was earlier than that of anti-CNTN1 antibody-associated AN. MN may occur before, after or concurrently with CIDP. The early detection and isotyping of anti-CNTN1 and anti-PLA2R antibodies and the monitoring of isotype switching may be essential for suspected CIDP patients.

2.
Chemosphere ; 287(Pt 3): 132305, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34563770

RESUMO

BACKGROUND: Metal exposures are suspected to associate with the risk of hyperuricemia (HUA), but the current results are still conflicting. OBJECTIVE: To investigate the associations between multiple plasma metal exposures and HUA risk. METHODS: A cross-sectional study was conducted in 1406 Chinese Han adults who underwent routine physical examination in the Eighth Affiliated Hospital of Sun Yat-Sen University in Shenzhen. The plasma levels of 13 metals were measured by the inductively coupled plasma mass spectrometry (ICP-MS). Multivariable logistic, linear regression models, least absolute shrinkage and selection operator (LASSO) penalized regression analysis, and restricted cubic spline (RCS) models were applied to assess the associations. RESULTS: The median plasma uric acid concentration in HUA group (434 µmol/L) was significantly higher than that in non-HUA group (305 µmol/L). The multivariate-adjusted odds ratios (95% confidence intervals) of HUA were 1.62(1.08-2.43) for magnesium, 1.61(1.05-2.47) for copper, 1.62(1.06-2.49) for zinc, 1.87(1.26-2.81) for arsenic, 1.50(1.01-2.23) for selenium, and 1.70(1.16-2.49) for thallium based on the single-metal logistic regression models, comparing the highest versus the lowest quartile of metal levels. Further multi-metal logistic, linear regression models and the LASSO analysis all indicated positive associations of zinc, arsenic with HUA risk or uric acid levels. RCS model indicated an inverted V-shaped positive association between zinc levels and HUA risk (p for non-linearity = 0.048, p for overall association = 0.022), while arsenic levels showed a positive and linear dose-response relationship with HUA risk (p for non-linearity = 0.892, p for overall association<0.001). CONCLUSIONS: Higher plasma levels of zinc and arsenic might increase HUA risk and showed positive dose-response relationships. Further cohort studies in larger population are required to testify our findings.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34444520

RESUMO

Temperature change is an important meteorological indicator reflecting weather stability. This study aimed to examine the effects of ambient temperature change on non-accidental mortality using diurnal temperature change (DTR) and temperature change between neighboring days (TCN) from two perspectives, intra-day and inter-day temperature change, and further, to explore seasonal variations of mortality, identify the susceptible population and investigate the interaction between temperature change and apparent temperature (AT). We collected daily data on cause-specific mortality, air pollutants and meteorological indicators in Shenzhen, China, from 1 January 2013 to 29 December 2017. A Quasi-Poisson generalized linear regression combined with distributed lag non-linear models (DLNMs) were conducted to estimate the effects of season on temperature change-related mortality. In addition, a non-parametric bivariate response surface model was used to explore the interaction between temperature change and AT. The cumulative effect of DTR was a U-shaped curve for non-accidental mortality, whereas the curve for TCN was nearly monotonic. The overall relative risks (RRs) of non-accidental, cardiovascular and respiratory mortality were 1.407 (95% CI: 1.233-1.606), 1.470 (95% CI: 1.220-1.771) and 1.741 (95% CI: 1.157-2.620) from exposure to extreme large DTR (99th) in cold seasons. However, no statistically significant effects were observed in warm seasons. As for TCN, the effects were higher in cold seasons than warm seasons, with the largest RR of 1.611 (95% CI: 1.384-1.876). The elderly and females were more sensitive, and low apparent temperature had a higher effect on temperature change-related non-accidental mortality. Temperature change was positively correlated with an increased risk of non-accidental mortality in Shenzhen. Both female and elderly people are more vulnerable to the potential adverse effects, especially in cold seasons. Low AT may enhance the effects of temperature change.


Assuntos
Poluentes Atmosféricos , Idoso , Poluentes Atmosféricos/análise , China/epidemiologia , Temperatura Baixa , Feminino , Temperatura Alta , Humanos , Mortalidade , Estações do Ano , Temperatura
4.
Environ Pollut ; 277: 116630, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33667749

RESUMO

Bisphenol S (BPS), an industrial chemical that is a structural analogue of bisphenol A, has been widely reported to be involved in various biological processes. Epidemiological studies have demonstrated that exposure to BPS is associated with dysglycaemia-related health outcomes. The role of BPS in glucose metabolism, however, remains controversial. In this study, we aimed to investigate the effects of chronic exposure to environmentally relevant concentrations of BPS on glucose metabolism in different nutritionally conditioned mice. Our results revealed that 1-month exposure to a BPS dosage of 100 µg/kg bw slightly increased the insulin sensitivity of normal diet-fed mice, and that this effect was enhanced after 3-month exposure. It was also found that BPS exposure attenuated insulin resistance and reduced gluconeogenesis in high-fat diet-fed mice. Consequently, the concentrations of hepatic metabolites related to glucose metabolism were altered in both groups of mice. Moreover, thyroid hormone signalling was disrupted after BPS administration in both groups of mice. Taken together, our results demonstrated that chronic exposure to environmentally relevant concentrations of BPS exerted an unexpected hypoglycaemic effect in mice of different nutritional statuses, and that this was partly attributable to disrupted thyroid hormone signalling.


Assuntos
Resistência à Insulina , Animais , Compostos Benzidrílicos/toxicidade , Gluconeogênese , Hipoglicemiantes , Masculino , Camundongos , Fenóis , Sulfonas
5.
Occup Environ Med ; 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33509904

RESUMO

OBJECTIVE: Evidence on the relationship between ambient temperature and morbidity of different stroke subtypes in China is limited. This study aimed to assess the influence of ambient temperature on stroke risk in Shenzhen, China. METHODS: From 1 January 2003 to 31 December 2014, 114 552 stroke cases in Shenzhen were collected. A generalised additive model with quasi-Poisson regression combined with a distributed lag non-linear model was applied to evaluate the temperature effects on stroke subtypes. Furthermore, this study explored the variability of the effects across sex, age and education. RESULTS: The immediate heat effects on ischaemic stroke (IS) and the persistent effects of ambient temperature on intracerebral haemorrhage (ICH) were significant. Overall, the cold-related relative risks (RRs) of IS, ICH and subarachnoid haemorrhage (SAH) were 1.02 (0.97-1.07), 1.16 (1.04-1.30) and 1.12 (0.61-2.04), whereas the heat-related RRs were 1.00 (0.97-1.04), 0.80 (0.73-0.88) and 1.05 (0.63-1.78), respectively. For IS, a weakly beneficial cold effect was found among men while a detrimental heat effect among both men and women, the elderly and higher-educated population at lag0. However, regarding ICH, the temperature effects in men, the young and higher-educated population are stronger at lag0-4, lag0-7 as cold reveals threat and heat reveals protection. CONCLUSION: Responses of diverse stroke subtypes to ambient temperature varied. Effective measures should be taken to increase public awareness about the effects of ambient temperature on stroke attack and to educate the public about self-protection.

6.
J Atheroscler Thromb ; 28(4): 320-328, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32641646

RESUMO

AIM: We aimed to investigate the relationship of trimethylamine N-oxide (TMAO) concentrations with ischemic stroke in a large-scale case-control study conducted among the hospital-based general population. METHODS: We recruited 953 case-control sex- and age-matched pairs, and cases were confined to first acute ischemic stroke in this study. Fasting plasma TMAO was measured using high-performance liquid chromatography-tandem mass spectroscopy. Conditional logistic regression analysis was conducted to calculate odds ratios (OR) for the association of plasma TMAO with ischemic stroke. RESULTS: We found that plasma TMAO concentrations in patients with ischemic stroke were significantly higher than that in the control group (median: 2.85 µmol/L vs. 2.33 µmol/L, P<0.001). In multivariable conditional logistic regression models, higher plasma TMAO concentrations were associated with increased odds of ischemic stroke [fully adjusted OR for highest vs. lowest TMAO quartile: 1.81; 95% confidence interval (CI): 1.27, 2.59; P for trend <0.001]. The multivariable-adjusted OR for ischemic stroke per 1 µmol/L increment of plasma TMAO was 1.05 (95% CI: 1.02, 1.08). Additionally, the positive association also persisted in subgroups stratified by age, sex, body mass index, smoking status, alcohol habits, history of diabetes, and history of hypertension. CONCLUSIONS: This study suggested a positive association between plasma TMAO and ischemic stroke. Further studies are required to explore the role of plasma TMAO concentrations in predicting stroke risk.

7.
Environ Pollut ; 264: 113975, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32559873

RESUMO

As a crucial factor in male reproduction, androgens may represent an intermediate biological mechanism linking metal exposure with effects on semen quality. This study aimed to investigate the association between metal exposure and semen quality, and to assess the mediating role of seminal androgens between metal exposure and semen quality. We investigated the presence of 10 metals in semen and assessed their effect on semen quality in 1136 men recruited from a hospital in Shenzhen, China. Of these, 464 subjects were randomly selected for 4 androgens detection in semen. Cross-sectional associations between single/multiple metals, androgen levels and semen quality were explored by multivariable linear regressions. Mediation analysis was performed to detect the role of seminal androgens on the association between metal exposure and semen quality. Seminal selenium and iron were positively associated with both sperm concentration and total sperm count. Negative associations were observed between both manganese and zinc and sperm concentration, molybdenum and total sperm count, copper and sperm motility. Furthermore, we found significant dose-dependent relationships between both iron and selenium levels and dihydrotestosterone (DHT), arsenic levels and testosterone, as well as zinc and dehydroepiandrosterone. Mediation analysis indicated that higher seminal iron and selenium were associated with an increasing sperm concentration after controlling for DHT, with 10.32% and 12.89% of these associations were mediated by DHT, respectively. A similar mediation effect of DHT was observed in the associations between iron and selenium levels and total sperm count (13.39% and 21.57% mediation, respectively). Our findings suggested that the presence of selenium and iron in semen was beneficial to sperm concentration and total count. Seminal manganese, zinc, molybdenum and copper may be associated with reduced semen quality. The associations between seminal selenium and iron and sperm concentration and total count were partially explained by the concomitant variation of seminal DHT.


Assuntos
Androgênios , Análise do Sêmen , China , Estudos Transversais , Humanos , Masculino , Metais , Sêmen , Contagem de Espermatozoides , Motilidade Espermática , Espermatozoides
8.
Lancet Infect Dis ; 20(8): 911-919, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32353347

RESUMO

BACKGROUND: Rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, prompted heightened surveillance in Shenzhen, China. The resulting data provide a rare opportunity to measure key metrics of disease course, transmission, and the impact of control measures. METHODS: From Jan 14 to Feb 12, 2020, the Shenzhen Center for Disease Control and Prevention identified 391 SARS-CoV-2 cases and 1286 close contacts. We compared cases identified through symptomatic surveillance and contact tracing, and estimated the time from symptom onset to confirmation, isolation, and admission to hospital. We estimated metrics of disease transmission and analysed factors influencing transmission risk. FINDINGS: Cases were older than the general population (mean age 45 years) and balanced between males (n=187) and females (n=204). 356 (91%) of 391 cases had mild or moderate clinical severity at initial assessment. As of Feb 22, 2020, three cases had died and 225 had recovered (median time to recovery 21 days; 95% CI 20-22). Cases were isolated on average 4·6 days (95% CI 4·1-5·0) after developing symptoms; contact tracing reduced this by 1·9 days (95% CI 1·1-2·7). Household contacts and those travelling with a case were at higher risk of infection (odds ratio 6·27 [95% CI 1·49-26·33] for household contacts and 7·06 [1·43-34·91] for those travelling with a case) than other close contacts. The household secondary attack rate was 11·2% (95% CI 9·1-13·8), and children were as likely to be infected as adults (infection rate 7·4% in children <10 years vs population average of 6·6%). The observed reproductive number (R) was 0·4 (95% CI 0·3-0·5), with a mean serial interval of 6·3 days (95% CI 5·2-7·6). INTERPRETATION: Our data on cases as well as their infected and uninfected close contacts provide key insights into the epidemiology of SARS-CoV-2. This analysis shows that isolation and contact tracing reduce the time during which cases are infectious in the community, thereby reducing the R. The overall impact of isolation and contact tracing, however, is uncertain and highly dependent on the number of asymptomatic cases. Moreover, children are at a similar risk of infection to the general population, although less likely to have severe symptoms; hence they should be considered in analyses of transmission and control. FUNDING: Emergency Response Program of Harbin Institute of Technology, Emergency Response Program of Peng Cheng Laboratory, US Centers for Disease Control and Prevention.


Assuntos
Betacoronavirus/isolamento & purificação , Controle de Doenças Transmissíveis/métodos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Transmissão de Doença Infecciosa/prevenção & controle , Transmissão de Doença Infecciosa/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Número Básico de Reprodução , COVID-19 , Criança , Pré-Escolar , China/epidemiologia , Controle de Doenças Transmissíveis/organização & administração , Busca de Comunicante , Infecções por Coronavirus/prevenção & controle , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Estudos Retrospectivos , Medição de Risco , SARS-CoV-2 , Adulto Jovem
9.
J Clin Endocrinol Metab ; 105(4)2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32160304

RESUMO

CONTEXT AND OBJECTIVE: This case control study was designed to investigate the association between mutation of 10 single nucleotide polymorphism (SNP) loci (rs1132506, rs5780218, rs192636495, rs4889, rs184749, rs12985070, rs708910, rs932491, rs8074995, and rs2306877) in all 5 genes (KISS1, GPR54, PLCB1, PRKCA, and ITPR1) in the kisspeptin/GPR54 pathway and the risk of early puberty in Chinese Han girls. DESIGN AND PARTICIPANTS: A total of 314 pairs of early puberty girls on their first visit to hospital and age-matched controls (± 3 months) were recruited. The genotypes of each SNP were determined and the effect of loci variation on early puberty was investigated. RESULTS: rs5780218 was significantly associated with early puberty in additive, dominant, and recessive models of inheritance after adjusting for confounding factors (Pr < .05). After stratification, rs5780218 variation (odds ratio [OR], 1.650, 95% confidence interval [CI], 1.155-2.355 in additive models and OR, 2.116; 95% CI, 1.187-3.770 in recessive models) increased the risk of central precocious puberty (CPP); mutation in rs708910 (OR, 2.768; 95% CI, 1.305-5.872 in recessive model) had a positive association with the risk of CPP; and rs932491 variation was negatively associated with early and fast puberty (EFP) (OR, 0.309; 95% CI, 0.144-0.661 in additive models and OR, 0.317; 95% CI, 0.141-0.713 in dominant models). CONCLUSIONS: Our study suggests that mutation in rs5780218 and rs708910 increases the risk of CPP. rs932491 variation may have a protective effect on the risk of EFP. Further studies in larger populations or with people from different regions are needed to verify our findings.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores/análise , Kisspeptinas/genética , Polimorfismo de Nucleotídeo Único , Puberdade Precoce/epidemiologia , Receptores de Kisspeptina-1/genética , Estudos de Casos e Controles , Criança , Feminino , Seguimentos , Humanos , Prognóstico , Puberdade Precoce/genética
10.
Int Heart J ; 61(1): 153-159, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31956131

RESUMO

A previous study and a gene-annotation enrichment analysis for potential targets of the microRNA miR-202-3p both suggest that this microRNA might be implicated in cardiovascular and metabolic diseases. In the present study, the role of miR-202-3p in the pathogenesis of coronary heart disease (CHD) was explored. We conduct a case-control study to detect the expression levels of miR-202-3p in peripheral blood cells and found that miR-202-3p expression was significantly higher in CHD cases than in controls (P < 0.001). miR-202-3p levels were negatively correlated with platelet distribution width (r = -0.348, P = 0.002) and mean platelet volume (r = -0.29, P = 0.01). Further functional analyses suggested that stimulation with oxidized low-density lipoprotein (ox-LDL) induced miR-202-3p expression, and that this microRNA suppressed the formation of ox-LDL-induced macrophage foam cells derived from THP-1 cells in a feedback manner. In addition, miR-202-3p overexpression modulated the expression of several key genes involved in foam cell formation, including that of ABCG4, NCEH1I, and SCARB2. In summary, miR-202-3p was associated with CHD, exerting a protective role against CHD by feedback suppression of ox-LDL-induced macrophage foam cell formation.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Doença das Coronárias/genética , Células Espumosas/citologia , MicroRNAs/genética , Idoso , Estudos de Casos e Controles , Células Cultivadas , Feminino , Células Espumosas/metabolismo , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Lipoproteínas LDL/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Células THP-1 , Regulação para Cima
11.
Environ Health ; 19(1): 1, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898503

RESUMO

BACKGROUND: Stroke, especially ischemic stroke (IS), has been a severe public health problem around the world. However, the association between air pollution and ischemic stroke remains ambiguous. METHODS: A total of 63, 997 IS cases aged 18 years or above in Shenzhen were collected from 2008 to 2014. We used the time-stratified case-crossover design combining with distributed lag nonlinear model (DLNM) to estimate the association between air pollution and IS onset. Furthermore, this study explored the variability across gender and age groups. RESULTS: The cumulative exposure-response curves were J-shaped for SO2, NO2 and PM10, and V-shaped for O3, and crossed over the relative risk (RR) of one. The 99th, 50th (median) and 1st percentiles of concentration (µg/m3) respectively were 37.86, 10.06, 3.71 for SO2, 116.26, 41.29, 18.51 for NO2, 145.94, 48.29, 16.14 for PM10, and 111.57, 49.82, 16.00 for O3. Extreme high-SO2, high-NO2, high-PM10, high-O3, and low-O3 concentration increased the risk of IS, with the maximum RR values and 95% CIs: 1.50(1.22, 1.84) (99th vs median) at 0-12 lag days, 1.37(1.13, 1.67) (99th vs median) at 0-10 lag days, 1.26(1.04, 1.53) (99th vs median) at 0-12 lag days, 1.25(1.04, 1.49) (99th vs median) at 0-14 lag days, and 1.29(1.03, 1.61) (1st vs median) at 0-14 lag days, respectively. The statistically significant minimal RR value and 95% CI was 0.79(0.66,0.94) at 0-10 lag days for extreme low-PM10. The elderly aged over 65 years were susceptible to extreme pollution conditions. Difference from the vulnerability of males to extreme high-SO2, high-NO2 and low-O3, females were vulnerable to extreme high-PM10 and high-O3. Comparing with the elderly, adults aged 18-64 year were immune to extreme low-NO2 and low-PM10. However, no association between CO and IS onset was found. CONCLUSIONS: SO2, NO2, PM10 and O3 exerted non-linear and delayed influence on IS, and such influence varied with gender and age. These findings may have significant public health implications for the prevention of IS.


Assuntos
Poluição do Ar/efeitos adversos , Isquemia Encefálica/epidemiologia , Exposição Ambiental/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Poluentes Atmosféricos , Isquemia Encefálica/induzido quimicamente , China/epidemiologia , Cidades , Estudos Cross-Over , Feminino , Humanos , Incidência , Isquemia/induzido quimicamente , Isquemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Dinâmica não Linear , Risco , Estações do Ano , Acidente Vascular Cerebral/induzido quimicamente , Fatores de Tempo , Adulto Jovem
12.
Gene ; 731: 144364, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-31935511

RESUMO

Apolipoprotein C2 (ApoC2) is an important member of the apolipoprotein C family and functions as a major activator of lipoprotein lipase (LPL). In cardiovascular and cerebrovascular systems, the lipolytic activity of the LPL-ApoC2 complex is critical for the metabolism of triglyceride-rich lipoproteins and contributes to the pathogenesis of ischemic stroke (IS). However, the regulation of ApoC2 in IS development remains unclear. In this study, we first explored potential ApoC2-targeting microRNAs (miRNAs) by bioinformatics tool and compared the miRNA expression profiles in the blood cells of 25 IS patients and 25 control subjects by miRNA microarray. miR-1275 was predicted to bind with the 3' untranslated region of ApoC2, and a significant reduction of blood miR-1275 levels was observed in IS patients. Dual-luciferase reporter assay and quantitative RT-PCR confirmed the regulation of ApoC2 by miR-1275 in THP-1 derived macrophages. miR-1275 also inhibited cellular uptake of ox-LDL and suppressed formation of macrophage foam cell. Furthermore, the whole blood miR-1275 levels were validated in 279 IS patients and 279 control subjects by TaqMan assay. miR-1275 levels were significantly lower in IS cases and logistic regression analysis showed that miR-1275 level was negatively associated with the occurrence of IS (adjusted OR, 0.76; 95% CI, 0.69-0.85; p < 0.001). Addition of miR-1275 to traditional risk factors showed an additive prediction value for IS. Our study shows that blood miR-1275 levels were negatively associated with the occurrence of IS, and miR-1275 might exert an athero-protective role against the development of IS by targeting ApoC2 and blocking the formation of macrophage foam cells.


Assuntos
Apolipoproteína C-II/genética , Células Espumosas/patologia , MicroRNAs/sangue , Acidente Vascular Cerebral/genética , Apolipoproteína C-II/metabolismo , Aterosclerose/sangue , Aterosclerose/genética , Aterosclerose/patologia , Isquemia Encefálica/sangue , Isquemia Encefálica/complicações , Isquemia Encefálica/genética , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Células Espumosas/metabolismo , Regulação da Expressão Gênica , Células HEK293 , Humanos , Macrófagos/patologia , Macrófagos/fisiologia , Masculino , MicroRNAs/fisiologia , Fatores de Risco , Acidente Vascular Cerebral/sangue , Células THP-1
13.
Chemosphere ; 244: 125498, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31812049

RESUMO

BACKGROUND: Heavy metal exposure induces oxidative stress, which is critical for adverse male reproductive health. OBJECTIVE: To explore the mediating effect of oxidative stress on the relationship of heavy metal exposure with semen quality. METHODS: Urinary levels of three oxidative stress markers, semen quality, and urinary arsenic, cadmium and lead were examined among 1020 men. Multivariate linear regression was applied to explore cross-sectional associations, and the role of oxidative stress as mediators was investigated. RESULTS: Quartiles of metals showed significant dose-dependent relationships with increasing levels of 8-hydroxy-2deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA). Significant or suggestive associations were also found between urinary 8-OHdG levels and the percentage of normal sperm morphology (ptrend < 0.001), between urinary 8-isoPGF2α levels and total motility (ptrend = 0.052), progressive motility (ptrend = 0.050) respectively. The mediation analysis showed that about 14.59%, 18.06%, 15.35% or 16.49% of the association between arsenic/cadmium exposure and the decreased total motility/progressive motility was mediated by 8-isoPGF2α, respectively. In addition, about 16.47% of the relationship between lead exposure and the decreased percentage of normal sperm morphology was mediated by 8-OHdG. CONCLUSIONS: Our findings suggest that higher urinary arsenic, cadmium and lead levels were associated with increased oxidative stress markers, which also related with altered semen quality. 8-isoPGF2α and 8-OHdG might be the possible mediators of the associations between urinary heavy metals and total motility, progressive motility or the proportion of normal sperm morphology.


Assuntos
Exposição Ambiental/análise , Poluentes Ambientais/toxicidade , Metais Pesados/toxicidade , Sêmen/efeitos dos fármacos , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Biomarcadores/urina , Cádmio , Estudos Transversais , Humanos , Chumbo/toxicidade , Masculino , Estresse Oxidativo , Reprodução , Análise do Sêmen
14.
Biomed Pharmacother ; 118: 109332, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545231

RESUMO

Atherosclerosis (AS), a severe disease characterized by an accumulation of lipids and fibers in the large arteries, is the most important contributor to ischemic stroke (IS). Although microRNAs (miRNAs) have been found in circulating blood, the role of miRNAs in the progression of AS remains unknown. In a previous study, we demonstrated that the spleen tyrosine kinase (Syk) gene plays a vital role in the process of IS. In the present study, we aimed to clarify whether the miRNAs targeting the Syk gene might slow the development of AS. Candidate miRNAs were screened in U937 and THP-1 cells via Bioinformatics analyses, RT-qPCR and dual-luciferase reporter assay. ApoE-/- mice were used as an AS animal model. RAAV transfection was performed to identify the roles of Syk gene and miRNAs in the development of AS in ApoE-/- mice. HE staining, Oil red O staining and immunohistochemistry were used to determine the mechanism of AS. RT-qPCR and western blotting were performed to determine the expressions of miRNAs and proteins, respectively. Over-expression of the Syk gene accelerated the development of AS. miR-377 effectively mediated the expression of the Syk gene in vitro and in vivo experiments. Further analysis indicated that over-expression of miR-377 partly alleviated the development of AS by down-regulating the expression of the Syk gene. This study identifies a novel role of miR-377 in AS via targeting Syk.


Assuntos
Apolipoproteínas E/deficiência , Aterosclerose/genética , MicroRNAs/metabolismo , Quinase Syk/genética , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Aorta/metabolismo , Aorta/patologia , Aterosclerose/sangue , Aterosclerose/patologia , Sequência de Bases , Linhagem Celular , Citocinas/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Lipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Estresse Oxidativo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Quinase Syk/metabolismo
15.
Stroke ; 50(7): 1661-1668, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31167624

RESUMO

Background and Purpose- Circulating metals synchronously reflect multiple metal exposures from both natural and anthropogenic sources, which may be linked with the risk of stroke. However, there is a lack of prospective studies investigating the associations of multiple metal exposures with incident stroke. Methods- We performed a nested case-control study within the ongoing Dongfeng-Tongji cohort launched in 2008. A total of 1304 incident stroke cases (1035 ischemic strokes and 269 hemorrhagic strokes) were prospectively identified by December 31, 2016, and matched to incident identity sampled controls according to age (within 1 year), sex, and blood sampling date (within 1 month). We determined the concentrations of 24 plasma metals and assessed the associations of plasma multiple metal concentrations with incident stroke using conditional logistic regression and elastic net model. Results- The average follow-up was 6.1 years. After adjusting for established risk confounders, copper, molybdenum, and titanium were significantly associated with higher risk of ischemic stroke (odds ratios according to per interquartile range increase, 1.29 [95% CI, 1.13-1.46], 1.19 [95% CI, 1.05-1.35], and 1.30 [95% CI, 1.07-1.59]), whereas rubidium and selenium were associated with lower risk of hemorrhagic stroke (odds ratios according to per interquartile range increase, 0.66 [95% CI, 0.50-0.87] and 0.68 [95% CI, 0.51-0.91]). The predictive plasma metal scores based on multiple metal exposures were significantly associated with higher risk of ischemic and hemorrhagic stroke (adjusted odds ratios according to per interquartile range increase, 1.37 [95% CI, 1.20-1.56] and 1.53 [95% CI, 1.16-2.01]). Conclusions- Plasma copper, molybdenum, and titanium were associated with higher risk of ischemic stroke, whereas plasma rubidium and selenium were associated with lower risk of hemorrhagic stroke. These findings may have important public health implications given the ever-increasing burden of stroke worldwide.


Assuntos
Metais/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Adulto , Fatores Etários , Idoso , Grupo com Ancestrais do Continente Asiático , Isquemia Encefálica/complicações , Isquemia Encefálica/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Incidência , Hemorragias Intracranianas/complicações , Hemorragias Intracranianas/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores Sexuais
16.
Environ Int ; 129: 136-144, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31128434

RESUMO

BACKGROUND: Phytoestrogens (PEs) are naturally estrogen-like chemicals, and increasing evidences have indicated their endocrine disruption effects on male reproductivity, but the conclusions from previous epidemiological studies were controversial. OBJECTIVE: To examine the associations between nine phytoestrogens in semen and semen quality in a Chinese population. METHODS: In this cross-sectional study, a total of 1319 reproductive-aged men were recruited from Shenzhen, China. Semen phytoestrogens were measured by ultra-performance liquid chromatography and tandem mass spectrometry. Semen quality was assessed by sperm concentration, sperm count, progressive motility, total motility, volume, and the sperm motion parameters. Both multivariate linear regression and logistic regression models were conducted to evaluate the associations between semen phytoestrogens and semen quality with adjustment for confounders. RESULTS: In logistic regression models, we found significant associations between semen secoisolariciresinol (SEC) and lower sperm concentrations (odd ratios (OR): 2.38; 95% confidence interval, 95% CI: 1.47, 3.93), sperm counts (OR: 2.27; 95% CI: 1.34, 3.94), and total motility (OR: 1.55; 95% CI: 1.08, 2.24). Negative associations were also observed for semen genistein (GEN) with sperm counts (OR: 2.28; 95% CI: 1.29, 4.14; p for trend = 0.04) and sperm concentrations (OR: 1.98; 95% CI: 1.21, 3.03; p for trend = 0.07). Semen naringenin (NAR) were found to be positively associated with progressive motility (OR: 0.57; 95% CI: 0.38, 0.83) and total motility (OR: 0.57; 95% CI: 0.40, 0.81). Results from multivariate linear regression models were similar to those from logistic regression models for semen SEC, GEN, and NAR. CONCLUSIONS: We suggested that semen levels of phytoestrogens may be associated with semen quality in men. Further investigations are warranted to confirm the findings in prospective studies and to explore the underlying mechanism.


Assuntos
Fitoestrógenos/farmacologia , Sêmen/efeitos dos fármacos , Adulto , Butileno Glicóis/farmacologia , China , Estudos Transversais , Genisteína/farmacologia , Humanos , Lignanas/farmacologia , Masculino , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos
17.
Acta Diabetol ; 56(9): 1037-1044, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30989380

RESUMO

AIMS: Observational studies indicated that resting heart rate (RHR) was associated with diabetes mellitus (DM) risk; however, it remains unclear whether the association between RHR and DM is causal. We aimed to examine whether there was causal association of RHR with DM risk. METHODS: A prospective study including 16,201 middle-aged and older Chinese (7031 males and 9170 females) derived from the Dongfeng-Tongji cohort was performed. Cox proportional hazard regression models were conducted to estimate the associations between RHR and incident DM risk. In 7481 participants, 65 single nucleotide polymorphisms related to RHR were genotyped. A genetic risk score (GRS) of RHR was calculated based on the RHR-associated variants. The causal associations of RHR with DM risk were investigated by Mendelian randomization analysis. RESULTS: During a mean (SD) follow-up of 4.5 (0.5) years, 1110 diabetes were identified. Compared with the referential RHR group (≤ 60 beats per minute [bpm]), individuals with RHR > 80 bpm have a higher incident diabetes risk, with a hazard ratio of 1.40 (95% confidence interval [CI], 1.05-1.88). With per SD increase in the weighted genetic risk score, the resting heart rate increased by 0.71 bpm (95% CI 0.49-0.93). By using the GRS to estimate the unconfounded effect, we found that higher resting heart rate did not have a causal effect on diabetes risk (OR 1.00 [95% CI 0.95-1.05]). CONCLUSIONS: The present study supported a positive but not a causal association of RHR with incident diabetes risk. More studies are needed to verify our findings.


Assuntos
Diabetes Mellitus/epidemiologia , Diabetes Mellitus/genética , Diabetes Mellitus/fisiopatologia , Frequência Cardíaca/genética , Polimorfismo de Nucleotídeo Único , Descanso/fisiologia , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , China/epidemiologia , Estudos de Coortes , Feminino , Estudos de Associação Genética/métodos , Estudos de Associação Genética/estatística & dados numéricos , Predisposição Genética para Doença/epidemiologia , Genótipo , Humanos , Incidência , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
18.
Environ Int ; 125: 125-134, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30716572

RESUMO

BACKGROUND: Ischemic stroke (IS) is a major cause of morbidity and mortality globally. Environmental exposure to metals may be linked to the risk of IS, but the association remains uncertain in Chinese populations. OBJECTIVES: The present study aimed to examine the associations between the concentrations of 11 metals (aluminum, arsenic, cadmium, cobalt, copper, iron, manganese, molybdenum, selenium, thallium, and zinc) in plasma and the risk of IS in a Chinese population. METHODS: A total of 1277 pairs of newly diagnosed IS patients and controls matched on age (±3 years) and sex were recruited in our study. Plasma metal concentrations were measured using inductively coupled plasma mass spectrometry. Multivariable conditional logistic regression models were conducted to investigate the impacts of single and multiple metals, respectively. RESULTS: In the single-metal model, exposure to seven metals (aluminum, arsenic, cadmium, cobalt, iron, manganese and selenium) was individually associated with the risk of IS based on the trend test. Further stepwise regression analyses with the multiple-metal model revealed increasing trends in the risk of IS associated with aluminum, arsenic, and cadmium quartiles and decreasing trends with iron and selenium quartiles (p-trend < 0.01). Compared to the lowest quartiles, the odds ratios (95% confidence intervals) for the highest quartiles of these five metals were 4.23 (2.63, 6.79), 1.88 (1.25, 2.81), 5.02 (3.30, 7.63), 0.59 (0.40, 0.89), and 0.10 (0.06, 0.17), respectively. CONCLUSIONS: Our study suggested that higher plasma concentrations of aluminum, arsenic, and cadmium, and lower concentrations of iron and selenium may increase the risk of IS. Further prospective studies in larger populations are warranted to confirm our findings.


Assuntos
Isquemia Encefálica/induzido quimicamente , Metais/sangue , Metais/toxicidade , Acidente Vascular Cerebral/induzido quimicamente , Idoso , Grupo com Ancestrais do Continente Asiático , Isquemia Encefálica/sangue , Estudos de Casos e Controles , Exposição Ambiental , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Acidente Vascular Cerebral/sangue
19.
Am J Clin Nutr ; 109(2): 1-7, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30753322

RESUMO

Background: Epidemiologic studies on whole grains and risk of stroke have reported inconsistent results, with some suggesting a protective effect but others showing a null association. Objectives: The aim of this study was to examine whether plasma 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), a biomarker of whole-grain wheat and rye intake, is associated with risk of ischemic stroke. Methods: A hospital-based case-control study was conducted between March 2011 and May 2016. Cases (n = 990) with first ischemic stroke were matched to controls (n = 990) by sex and age. Concentrations of plasma DHPPA were determined by high-performance liquid chromatography-tandem mass spectrometry. We calculated ORs for the association of plasma DHPPA concentrations with ischemic stroke risk through the use of logistic regression. Results: Plasma DHPPA was inversely associated with ischemic stroke risk. After adjustment for potential confounding factors, the ORs for ischemic stroke across increasing quartiles of plasma DHPPA concentrations were 1 (referent), 0.76 (95% CI: 0.58, 0.99), 0.71 (95% CI: 0.54, 0.92), and 0.59 (95% CI: 0.45, 0.77), respectively (P-trend = 0.001). The inverse association was also observed in all subgroups of participants according to sex, age, body mass index, smoking status, alcohol consumption, history of hypertension, and history of diabetes. Conclusions: Our study showed that higher plasma DHPPA concentrations were associated with lower risk of ischemic stroke. This finding provides further evidence to support the health benefits of whole-grain consumption.


Assuntos
Dieta , Propionatos/sangue , Resorcinóis/sangue , Secale/química , Acidente Vascular Cerebral/sangue , Triticum/química , Grãos Integrais/química , Idoso , Biomarcadores/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/prevenção & controle , Estudos de Casos e Controles , Fibras na Dieta/administração & dosagem , Fibras na Dieta/uso terapêutico , Comportamento Alimentar , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fenilpropionatos/sangue , Acidente Vascular Cerebral/prevenção & controle
20.
Environ Int ; 122: 369-380, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30503314

RESUMO

BACKGROUND: All humans are now co-exposed to multiple toxic chemicals, among which metals and polycyclic aromatic hydrocarbons (PAHs) are of special concern as they are often present at high levels in various human environments. They can also induce similar early health damage, such as genetic damage, oxidative stress, and heart rate variability (HRV). Exposure to metals, PAHs, and their combined pollutants can alter microRNA (miRNA) expression patterns. OBJECTIVES: To explore the associations of metal-PAH co-exposure with miRNA expression, and of the associated miRNAs with early health damage. METHODS: We enrolled 360 healthy male coke oven workers and quantified their exposure levels of metals and PAHs by urinary metals, urinary monohydroxy-PAHs (OH-PAHs), and plasma benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts, respectively. We selected and measured ten miRNAs: let-7b-5p, miR-126-3p, miR-142-5p, miR-150-5p, miR-16-5p, miR-24-3p, miR-27a-3p, miR-28-5p, miR-320b, and miR-451a. For miRNAs influenced by the effect modification of metals or PAHs and/or metal-PAH interactions, we further evaluated their associations with biomarkers for genetic damage, oxidative stress, and HRV. RESULTS: After adjusting for PAHs and other metals, miRNA expression was found to be negatively associated with aluminum, antimony, lead, and titanium, and positively associated with molybdenum and tin (p < 0.05). Antimony showed modifying effects on the PAH-miRNA associations, while OH-PAHs and BPDE-Alb adducts modified the associations of metals with miRNAs (p for modifying effect < 0.05). Furthermore, miRNA expression was influenced by the antagonistic interactions between antimony and OH-PAHs, and by the synergistical interactions between metals and BPDE-Alb adducts (pinteraction < 0.05). Let-7b-5p, miR-126-3p, miR-16-5p, and miR-320b were additionally found to be associated with increased genetic damage in the present study [false discovery rate (FDR)-adjusted p < 0.05]. CONCLUSIONS: Associations of metal-PAH co-exposure with miRNA expression, and of associated miRNAs with early health damage, suggested potential mechanistic connections between the complex metal-PAH interactions and their deleterious effects that are worthy of further investigation.


Assuntos
Coque , Doença/etiologia , Poluentes Ambientais/toxicidade , Metais/toxicidade , Exposição Ocupacional , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Adulto , Biomarcadores , Dano ao DNA/efeitos dos fármacos , Poluentes Ambientais/urina , Humanos , Masculino , Metais/urina , MicroRNAs/análise , Pessoa de Meia-Idade , Estresse Oxidativo , Hidrocarbonetos Policíclicos Aromáticos/urina
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