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1.
Front Genet ; 12: 711155, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899825

RESUMO

As a marker for glomerular filtration, plasma cystatin C level is used to evaluate kidney function. To decipher genetic factors that control the plasma cystatin C level, we performed genome-wide association and pathway association studies using United Kingdom Biobank data. One hundred fifteen loci yielded p values less than 1 × 10-100, three genes (clusters) showed the most significant associations, including the CST8-CST9 cluster on chromosome 20, the SH2B3-ATXN2 gene region on chromosome 12, and the SHROOM3-CCDC158 gene region on chromosome 4. In pathway association studies, forty significant pathways had FDR (false discovery rate) and or FWER (family-wise error rate) ≤ 0.001: spermatogenesis, leukocyte trans-endothelial migration, cell adhesion, glycoprotein, membrane lipid, steroid metabolic process, and insulin signaling pathways were among the most significant pathways that associated with the plasma cystatin C levels. We also performed Genome-wide association studies for eGFR, top associated genes were largely overlapped with those for cystatin C.

2.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(6): 699-704, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34821109

RESUMO

Objective: To establish a stable, rapid and improved method for isolation and culture of primary cardiomyocytes from neonatal rats. Methods: Ventricular tissues from neonatal SD rats were digested with 0.12% collagenase Ⅱ, and then subjected to Percoll density gradient centrifugation. The original cardiomyocytes were cultured in modified DMEM/F12 containing 5% horse serum and 5-bromodeoxyuracil(5-BrdU) in vitro for further purification, and medium was changed to normal high glucose DMEM with 10% FBS the next day. The difference between the improved method and traditional differential attachment one used for isolation and culture of primary cardiomyocytes was compared. Results: Cardiacmyocytes obtained through the improved method grew well. 24 hours after plating, most cells adhered to the dishes, with shapes looked triangular, fusiform or irregular, and some of them showed spontaneously contract at a frequency varying from 10~30 times/min. After 48 h culture, the cardiomyocytes became longer and stretched out pseudopodia. Some cells showed synchronous beats with the frequency close to 50~80 times/min. 72 hours later, cardiomyocytes were interwoven into a network in chrysanthemum patterns, and spontaneous beats tended to be more synchronous, with a frequency of 80-100 times/min. After 96 h, cells gathered into clusters as islands, with synchronous beat at a frequency of around 100~120 times/min. All cardiomyocytes were in good condition within one week. Yields((1.17±0.15)×106 vs (1.21±0.22)×106,P>0.05)and survival rate of primary cardiomyocytes obtained by the improved method was comparable to that gained using traditional differential attachment way (93.3%±1.4% vs 92.2%±0.7%, P>0.05), but the purity of primary cardiomyocytes obtained through the improved method was much higher (94.7%±2.1% vs 89.5%±1.3%, P<0.05), while with less time consuming ((3.1±0.4)h vs (4.3±0.3)h, P<0.01). Conclusion: This improved method is an ideal and simple method for the isolation and culture of primary cardiomyocytes with shorter time-consuming, high purity, intact structure and function, and with great repeatability and stability.


Assuntos
Ventrículos do Coração , Miócitos Cardíacos , Animais , Animais Recém-Nascidos , Células Cultivadas , Ratos , Ratos Sprague-Dawley
4.
PLoS Med ; 18(11): e1003830, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34784347

RESUMO

BACKGROUND: Previous studies have revealed the involvement of coffee and tea in the development of stroke and dementia. However, little is known about the association between the combination of coffee and tea and the risk of stroke, dementia, and poststroke dementia. Therefore, we aimed to investigate the associations of coffee and tea separately and in combination with the risk of developing stroke and dementia. METHODS AND FINDINGS: This prospective cohort study included 365,682 participants (50 to 74 years old) from the UK Biobank. Participants joined the study from 2006 to 2010 and were followed up until 2020. We used Cox proportional hazards models to estimate the associations between coffee/tea consumption and incident stroke and dementia, adjusting for sex, age, ethnicity, qualification, income, body mass index (BMI), physical activity, alcohol status, smoking status, diet pattern, consumption of sugar-sweetened beverages, high-density lipoprotein (HDL), low-density lipoprotein (LDL), history of cancer, history of diabetes, history of cardiovascular arterial disease (CAD), and hypertension. Coffee and tea consumption was assessed at baseline. During a median follow-up of 11.4 years for new onset disease, 5,079 participants developed dementia, and 10,053 participants developed stroke. The associations of coffee and tea with stroke and dementia were nonlinear (P for nonlinear <0.01), and coffee intake of 2 to 3 cups/d or tea intake of 3 to 5 cups/d or their combination intake of 4 to 6 cups/d were linked with the lowest hazard ratio (HR) of incident stroke and dementia. Compared with those who did not drink tea and coffee, drinking 2 to 3 cups of coffee and 2 to 3 cups of tea per day was associated with a 32% (HR 0.68, 95% CI, 0.59 to 0.79; P < 0.001) lower risk of stroke and a 28% (HR, 0.72, 95% CI, 0.59 to 0.89; P = 0.002) lower risk of dementia. Moreover, the combination of coffee and tea consumption was associated with lower risk of ischemic stroke and vascular dementia. Additionally, the combination of tea and coffee was associated with a lower risk of poststroke dementia, with the lowest risk of incident poststroke dementia at a daily consumption level of 3 to 6 cups of coffee and tea (HR, 0.52, 95% CI, 0.32 to 0.83; P = 0.007). The main limitations were that coffee and tea intake was self-reported at baseline and may not reflect long-term consumption patterns, unmeasured confounders in observational studies may result in biased effect estimates, and UK Biobank participants are not representative of the whole United Kingdom population. CONCLUSIONS: We found that drinking coffee and tea separately or in combination were associated with lower risk of stroke and dementia. Intake of coffee alone or in combination with tea was associated with lower risk of poststroke dementia.

5.
Chem Commun (Camb) ; 57(84): 11092-11095, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34617533

RESUMO

Tandem reactions of the yttrium(iii) catalyzed ring-opening reaction of 2,2'-diester aziridines with 3-(2-isocyanoethyl)indoles and the subsequent Friedel-Crafts/Mannich/desulfonylation were reported. A series of polycyclic spiroindolines containing tetrahydro-ß-carbolines were obtained in moderate to excellent yields (56-92%) in one step under mild reaction conditions. A possible catalytic mechanism was also proposed.

6.
Nutr Neurosci ; : 1-10, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34424144

RESUMO

BACKGROUND: Prior evidence suggests that coffee might be related to dementia, however, little is known about coffee and dementia in individuals with elevated genetic susceptibility for dementia. Additionally, most previous studies have focused on total coffee instead of examining coffee types separately. METHODS: This study included 203,776 participants (60-73 years old) from the UK Biobank who were initially free of dementia. Polygenic risk scores for dementia were divided into quintile to stratify individuals into low (lowest quintile), intermediate (quintile 2-4), and high (highest quintile) genetic risk categories. Coffee intake was assessed at baseline and included total, instant, ground, and decaffeinated coffee. RESULTS: During a median follow-up of 11.4 years, 4405 cases of dementia occurred (1856 Alzheimer's disease [AD], 1105 vascular dementia). Compared to non-coffee drinking, heavy instant coffee drinking (> 6 cups/day) and moderate decaffeinated coffee drinking (1-3 cups/day) were associated with a higher risk of dementia (hazard ratio [HR] 1.19-1.34) and AD (HR 1.41-1.51), while moderate ground coffee drinking was associated with a lower risk of dementia (HR, 0.78; P = 0.001) and vascular dementia (HR, 0.58; P < 0.001). Among participants at high genetic risk, heavy coffee drinking was associated with a 95% (HR; 1.95, 95% CI, 1.21-3.16) higher risk of AD than non-coffee drinking. We found an interaction between coffee and genetic risk in relation to AD (P = 0.038). CONCLUSION: The association of dementia and coffee varied by coffee types. Heavy coffee consumption was associated with a higher risk of AD in individuals with high genetic risk for dementia.

7.
Biol Trace Elem Res ; 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34462843

RESUMO

Selenium (Se), an essential nutrient for humans, has been reported to possess cardioprotective effect. However, the protective effects of Se against doxorubicin (DOX)-induced cardiotoxicity and the underlying mechanism are rarely reported. In this study, we sought to explore whether Se protected against DOX-induced cardiotoxicity by inhibiting Nrf2-NLRP3 pathway. We found that Se treatment effectively alleviated DOX-induced myocardial dysfunctions, decreasing plasma markers associated with myocardial injury. Moreover, Se treatment significantly inhibited DOX-induced oxidative damages and pro-inflammatory cytokine expression in heart tissues. Furthermore, Se treatment markedly promoted the expression of Nrf2 and prevented the activation of NLRP3 inflammasome. Importantly, suppression of Nrf2 abolished the cardioprotective effects of Se and diminished the inhibition of Se on NLRP3 inflammasome. Collectively, our study demonstrated that Se might protect against DOX-induced cardiotoxicity via regulating Nrf2-NLRP3 pathway. Se supplementation may be a potential therapeutic strategy to protect against DOX-induced cardiac injury.

8.
J Physiol Sci ; 71(1): 26, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34445952

RESUMO

Sweat is a noninvasive biological fluid on the surface of human skin and has attracted increasing attention as a diagnostic specimen for disease and biomarker detection. Sweat metabolite quantification is possible due to progress in sweat analysis techniques; nevertheless, the role of sweat monitoring in energy metabolism, physiological or pathological state assessment, health status assessment, and the development and outcome of metabolism-related diseases remains unclear. This review provides a comprehensive overview of the literature on human sweat lactate concentration. The first, second, and third sections of this review present an introduction of sweat lactate, methods for the collection and storage of sweat lactate samples, and methods of detection and analysis of sweat lactate, respectively. The fourth section elaborates upon the current state of clinical application of sweat lactate monitoring and its prospects for health surveillance. The last section focuses on the challenges and future directions of this novel technology for detecting lactate in sweat.

9.
J Med Virol ; 93(11): 6172-6179, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34061379

RESUMO

Hand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) is a contagious viral disease, and toll-like receptors (TLRs) play essential roles in resisting the pathogen. The aim of this study was to assess the potential relationship between several TLRs polymorphisms and the HFMD severity in a Chinese children population. A total of 328 Chinese children with HFMD were included in the present study. The polymorphisms of TLR3 (rs3775290, rs3775291, rs3775296, rs1879026, rs5743312, rs5743313, rs5743303, rs13126816, and rs3775292), TLR4 (rs4986790, rs4986791, rs2149356, rs11536889, and rs41426344), TLR7 (rs179009, rs179010, rs179016, rs3853839, rs2302267, rs1634323, and rs5741880), and TLR8 (rs3764880, rs2159377, rs2407992, rs5744080, rs3747414, rs3764879, and rs5744069) genes were selected. The study indicated that individuals with the GG genotype of TLR3 single-nucleotide polymorphism rs1879026 had a higher risk of developing severe cases (GG vs. GT: OR = 1.875; 95% CI, 1.183-2.971; p = .007). Meanwhile, TLR3 rs3775290 CC genotype and C allele were associated with lower disease severity in females (CC vs. CT: OR = 0.350; 95% CI, 0.163-0.751; p = .006; C vs. T: OR = 0.566; 95% CI, 0.332-0.965; p = .036). TLR3 rs3775291 CC genotype showed 2.537 folds higher risk of developing severe cases in females (CC vs. CT: OR = 2.537; 95% CI, 1.108-5.806; p = .026). Moreover, TLR3 rs1879026 GG genotype was found to be related to increased risk of severe cases in males (GG vs. GT: OR = 2.076; 95% CI, 1.144-3.768; p = .016). The current findings show that the genetic variants of TLR3 rs1879026, rs3775290, and rs3775291 are associated with the severity of EV-A71-associated HFMD in a Chinese children population.

10.
Front Cardiovasc Med ; 8: 644405, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33834045

RESUMO

Introduction: Hypertension (HT) and atrial fibrillation (AF) often coexist. However, the causality between these two conditions remains to be determined. Methods: We used individual participant data from the Atherosclerosis Risk in Communities (ARIC) prospective cohort with 9,474 participants. HT was ascertained at visit 1 (1987-1989), and incident AF was identified by ECGs conducted during study examinations at each visit, hospital discharge codes, and death certificates. We used the Kaplan-Meier estimate to compute the cumulative incidence of AF by the HT subgroup. Then we used Cox hazard regression model to assess the association between HT and incident AF. The causality between genetically determined HT and AF was analyzed by the two-sample Mendelian randomization (MR) based on publicly summarized genome-wide association studies (GWASs) data. Results: A total of 1,414 cases (14.9%) of AF were identified during the follow-up period (median 24.1 years). After adjusting for all covariates, the hazard ratio between the participants with HT and incident AF was 1.50 [95% confidence interval (CI) 1.29-1.73]. In the HT → AF MR analysis, we detected a causal correlation between HT and AF (OR: 1.90, 95% CI 1.18-3.04, P = 0.01) with no evidence of heterogeneity from single-nucleotide polymorphisms. Besides, the genetically determined SBP and DBP (10 mmHg) were consistently associated with a higher risk of AF. Conclusions: In the ARIC study, the incident AF increased by 50% in patients with HT. In the MR analysis, our results supported causal inference between HT and AF.

11.
Cancer Manag Res ; 13: 1877-1886, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33654432

RESUMO

Background: Triple negative breast cancer (TNBC) poses a great threat to patient prognosis. LncRNA-miRNA is a molecular module formed by a long non-coding RNA (LncRNA) and a microRNA (miRNA) that mediates the metastatic potential of tumours such as TNBC, and luteolin (LU) is a natural compound with anti-TNBC activity. Objective: We aim to explore the regulatory mechanism of terminal differentiation-induced non-coding RNA (TINCR)-miR-761 molecular module in early TNBC, as well as its influence on anti-tumor activity of LU. Methods: The serum was collected from TNBC patients in early stage to detect the expression of TINCR and miR-761 using RT-PCR. Transwell method was applied for the determination of cell migration and invasion, Western blot for epithelial-mesenchymal transition (EMT), flow cytometry (FCM) for cell apoptosis, and dual luciferase reporter and RNA pull-down experiment for the verification of the targeted relationship between TINCR and miR-761. Results: Both TINCR and miR-761 were up-regulated in the serum of patients with early TNBC and the area under the curve (AUC) of the two for distinguishing TNBC from BC was not less than 0.850. In the cell function tests, down-regulation of TINCR or miR-761 notably suppressed the metastatic potentials (cell migration, invasion and EMT) of TNBC cells were remarkably inhibited, while up-regulation of TINCR or miR-761 notably promoted the metastatic potentials. We also confirmed that TINCR acts as the molecular sponge of miR-761, and has positive regulation on it. Besides, LU can significantly down-regulate TINCR and miR-761, and partially offset the anti-TNBC activity of LU when they were abnormally up-regulated, which was mainly reflected in the decrease of anti-proliferation and pro-apoptotic ability of LU against TNBC. Conclusion: There is an imbalance of TINCR-miR-761 molecular module in early TNBC, which may be a potential new therapeutic target of TNBC.

12.
World J Diabetes ; 12(3): 261-277, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33758646

RESUMO

BACKGROUND: The causality between education and type 2 diabetes (T2DM) remains unclear. AIM: To identify the causality between education and T2DM and the potential metabolic risk factors [coronary heart disease (CHD), total cholesterol, low-density lipoprotein, triglycerides (TG), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fasting insulin, fasting glucose, and glycated hemoglobin] from summarized genome-wide association study (GWAS) data used a network Mendelian randomization (MR). METHODS: Two-sample MR and network MR were performed to obtain the causality between education-T2DM, education-mediator, and mediator-T2DM. Summary statistics from the Social Science Genetic Association Consortium (discovery data) and Neale Lab consortium (replication data) were used for education and DIAGRAMplusMetabochip for T2DM. RESULTS: The odds ratio for T2DM was 0.392 (95%CI: 0.263-0.583) per standard deviation increase (3.6 years) in education by the inverse variance weighted method, without heterogeneity or horizontal pleiotropy. Education was genetically associated with CHD, TG, BMI, WC, and WHR in the discovery phase, yet only the results for CHD, BMI, and WC were replicated in the replication data. Moreover, BMI was genetically associated with T2DM. CONCLUSION: Short education was found to be associated with an increased T2DM risk. BMI might serve as a potential mediator between them.

13.
Mech Ageing Dev ; 194: 111433, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33444631

RESUMO

Coronavirus disease 2019 (COVID-19) is a current pandemic, and studies reported that older people have higher rates of infection and more severe cases. Recently, studies have revealed the involvement of both genetic and exposure factors in the susceptibility of COVID-19. However, the correlation between them is still unclear. Thus, we aimed to investigate the correlation between genetic and exposure factors associated with COVID-19. We retrieved the information of 7362 participants with COVID-19 testing results from the UK Biobank. We identified genetic factors for COVID-19 by genome-wide association studies (GWAS) summary analysis. In this study, 21 single-nucleotide polymorphisms (SNPs) and 15 exposure factors [smoking, alcohol intake, daytime dozing, body mass index (BMI), triglyceride, High Density Lipoprotein (HDL), diabetes, chronic kidney disease, chronic liver disease, dementia, atmosphere NO2 concentration, socioeconomic status, education qualification, ethnicity, and income] were found to be potential risk factors of COVID-19. Then, a gene-exposure (G × E) association network was built based on the correlation among and between these genetic factors and exposure factors. rs140092351, a SNP on microRNA miR1202, not only had the most significant association with COVID-19, but also interacted with multiple exposure factors. Dementia, alcohol consumption, daytime dozing, BMI, HDL, and atmosphere NO2 concentration were among most significant G × E interactions with COVID-19 infection (P = 0.001).


Assuntos
COVID-19/epidemiologia , COVID-19/genética , Pandemias , Polimorfismo de Nucleotídeo Único , SARS-CoV-2 , Idoso , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Socioeconômicos , Reino Unido/epidemiologia
14.
Cancer Manag Res ; 13: 439-447, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33500658

RESUMO

Objective: To explore the regulatory role of miR497-5p-CCNE1 axis in triple-negative breast cancer (TNBC) cells and its predictive value for early diagnosis. Methods: Cancer tissue and adjacent tissue samples were collected from 86 patients with TNBC.RT-PCR was used to detect the expression of miR497-5p and CCNE1 (target gene) mRNA, determined by biological prediction in tissue and TNBC cells. ROC was used to analyze the diagnostic value of miR497-5p in TNBC. MTT, invasion, and flow cytometry were used to detect the proliferation, invasion, cycle, apoptosis rate, and expression of related proteins of TNBC cells with overexpression of miR497-5p or knockdown of CCNE1. Results: RT-qPCR results showed that miR497-5p levels were significantly downregulated in TNBC tissue and cells, while CCNE1 expression was significantly upregulated, and miR497-5p expression was negatively correlated with that of CCNE1 (P<0.001). ROC analysis showed that the AUC of miR497-5p for TNBC was >0.9, which had better diagnostic value. The cell tests revealed that miR497-5p played a role in tumor inhibition, including inhibiting proliferation and invasion of TNBC cells, blocking the cell cycle, and promoting apoptosis. Bioinformatic prediction and subsequent experiments revealed that CCNE1 was the direct target of miR497-5p. Furthermore, after knocking down the expression of CCNE1 in TNBC cells, the proliferation and invasion of TNBC cells were significantly inhibited, the cell cycle blocked, and the apoptosis rate significantly increased (P<0.001), and expression of the proapoptosis-related proteins Bax and caspase 3 (cleaved) were upregulated, while expression of the antiapoptosis-related protein BCL2 was downregulated (P<0.001). Conclusion: miR497-5p inhibited the proliferation and invasion of TNBC cells by targeting CCNE1, blocked the cell cycle and promoted the apoptosis of TNBC cells, and had better diagnostic value for TNBC. miR497-5p can be used as a new potential target for the treatment of TNBC.

15.
Int J Cardiol ; 324: 115-121, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33017630

RESUMO

INTRODUCTION: We aim to characterize the nature and magnitude of the prospective association between education and incident heart failure (HF) in the Atherosclerosis Risk in Communities (ARIC) Study and investigate any causal relevance to the association between them. METHODS: The final sample size was 12,315 in this study. Baseline characteristics between education levels were compared using 1-way ANOVA test, the Kruskal-Wallis test, or the χ2 test. We used the Kaplan-Meier estimate to compute the cumulative incident of HF by education levels and the difference in estimate was compared using the log-rank test. Cox hazard regression models were used to explore the association between education levels and incident HF. Two-sample Mendelian randomization (MR) based on publicly available summary-level data from genome-wide association studies (GWASs) was used to estimate the causal influence of the education and incident HF. RESULTS: During a median follow-up of 25.1years, 2453 cases (19.9%) of incident HF occurred. After multiple adjustments in the final model, participants in the intermediate and advanced education levels were still associated with 18% and 21% decreased rate of incident HF separately. In MR analysis, we detected a protective causal association between education and HF (P=0.005). CONCLUSIONS: Participants with higher education levels were associated with a decreased rate of incident HF. There was a causal association between education and HF.


Assuntos
Aterosclerose , Insuficiência Cardíaca , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Aterosclerose/genética , Estudo de Associação Genômica Ampla , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/genética , Humanos , Incidência , Análise da Randomização Mendeliana , Estudos Prospectivos , Fatores de Risco
16.
Chemistry ; 27(11): 3766-3771, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33084132

RESUMO

The development of high-efficiency bifunctional electrocatalysts toward the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in alkaline surroundings is essential and challenging for the large-scale generation of clean hydrogen. Herein, a novel self-assembled two-dimensional (2 D) NiO/CeO2 heterostructure (HS) consisting of NiO and CeO2 nanocrystals is prepared through a facile two-step approach, and utilized as an enhanced bifunctional electrocatalyst for the HER and OER under alkaline conditions. It is concluded that this 2 D NiO/CeO2 HS, rich in oxygen vacancies, demonstrates attractive electrocatalytic properties for both the HER and OER in 1 m KOH, including low onset overpotential (η1 ), η10 and Tafel slope, excellent durability, as well as large active surface area. Therefore, the self-assembled 2 D NiO/CeO2 HS is believed to be an efficient bifunctional electrocatalyst toward the HER and OER.

17.
Rev Endocr Metab Disord ; 22(2): 461-469, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32926312

RESUMO

Both genetic and nongenetic factors have been found to be associated with type 2 diabetes, however, the correlation between them is still unclear. In the present study, we aimed to fully decipher the nongenetic and genetic factor association network for type 2 diabetes. We identified risk factors for type 2 diabetes by systematically searching for related meta-analyses and genome-wide association studies (GWAS) database. Among a total of 27,822 studies screened, 202 articles were eligible, from which 174 nongenetic factors and 210 genetic factors associated with type 2 diabetes were identified. Then, we obtained 584 associations between the nongenetic and genetic factors of type 2 diabetes, based on which a risk factor association network was conducted. The nongenetic factors could be classified into seven categories according to the Global Burden of Diseases (GBD). Of these seven categories of nongenetic factors, five were found to be correlated with genes associated with type 2 diabetes, including environmental risks, behavioral risks, metabolic risks, related disease of type 2 diabetes, and treatments. Specifically, air pollutants of environmental risks, alcohol using of behavioral risks, obesity of metabolic risks, rheumatoid arthritis of related disease risk, and simvastatin of treatment was correlated with the largest number of genes. In summary, the correlation between genetic factors and nongenetic factors identified in this study indicates that there is a common phenotype-genotype association in type 2 diabetes, with the combinations of genotypes ("genetic signature") clustering in phenotypes related to type 2 diabetes. Thus, we should take a systematic approach to explore the relationship of various factors for type 2 diabetes, as well as other noncommunicable diseases.

18.
J Transl Med ; 18(1): 409, 2020 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-33129322

RESUMO

BACKGROUND: Hypertension and high triglyceride are two of the most important risk factors for hyperuricemia. Epidemiological records show that hypertension and dyslipidemia often coexist and may significantly increase the risk of target organ damage. However, their combined effect on incident hyperuricemia is poorly understood. Thus, we aimed to investigate the separate and combined effect of hypertension and hypertriglyceridemia on the incidence of hyperuricemia. METHODS: A prospective cohort study of 6424 hyperuricemia-free participants aged 20 to 94 years between August 2009 and October 2017 was performed at Tianjin General Hospital of China. Participants were categorized into four groups by combining hypertension and hypertriglyceridemia status at baseline. The restricted cubic spline fitting Cox regression model was used to evaluate the relationship between blood pressure and triglyceride and hyperuricemia. Cox regression models were performed to calculate hazard ratios (HRs) and 95% confident intervals (CIs) to estimate baseline factors and their association with the incidence of hyperuricemia. A Kaplan-Meier survival analysis was performed to compare the incidence of hyperuricemia among subjects in each separate and combined hypertension and hypertriglyceridemia group. RESULTS: During the 8-year follow-up period, 1259 subjects developed hyperuricemia (20.6%). There existed positive relationships between blood pressure and triglyceride levels and hyperuricemia. This risk factor arising from a combination of the two (HR, 3.02; 95% CI 2.60-3.50) is greater than that from hypertension (HR, 1.48; 95% CI 1.28-1.71) or hypertriglyceridemia (HR, 1.84; 95% CI 1.55-2.18) separately. The Kaplan-Meier survival analysis indicated that combined effect of hypertension and hypertriglyceridemia may predict higher onset of hyperuricemia. CONCLUSION: The combined effect of hypertension and hypertriglyceridemia on the risk of hyperuricemia is much stronger than that by hypertension or hypertriglyceridemia separately. Hypertension combined with hypertriglyceridemia may be an independent and powerful predictor for hyperuricemia.


Assuntos
Hipertensão , Hipertrigliceridemia , Hiperuricemia , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Hipertrigliceridemia/complicações , Hipertrigliceridemia/epidemiologia , Hiperuricemia/complicações , Hiperuricemia/epidemiologia , Incidência , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
19.
Environ Pollut ; 267: 115382, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32866863

RESUMO

Bisphenol S (BPS) is an endocrine disruptor which is widely used in commercial plastic products. Previous studies have shown that exposure to BPS has toxic effects on various aspects of mammalian, but there are few reports about reproductive toxicity. In order to investigate the effects of maternal BPS exposure on the reproductive of F1 and F2 female mice, the pregnant mice were orally administered with different dosages of BPS only once every day from 12.5 to 15.5 days post-coitus (dpc). The results showed that maternal BPS exposure to 2 µg per kg of body weight per day (2 µg/kg) and 10 µg/kg accelerated the meiotic prophase I (MPI) of F1 female mice and the expression of the genes related to meiotic were increased. Further studies showed that maternal BPS exposure resulted in a significant increase in the percentage of oocytes enclosed in primordial follicles in the 3 days post-partum (3 dpp) ovaries of F1 female mice. And at the time of 21 days post-partum (21 dpp) in F1 female mice, the number of antral follicles were significantly lower compare to controls. In the study of five-week female mice of F1, we found that BPS disturbed the folliculogenesis, and the maturation rates and fertilization rates of oocytes were significantly decreased. Of note, maternal BPS exposure disrupted H3K4 and H3K9 tri-methylation levels in F1 ovaries. Maternal BPS exposure only affected the cyst breakdown in F2 female mice. Taken together, our results suggest that, maternal BPS exposure impaired the process of meiosis and oogenesis of F1 and F2 offspring, resulting in abnormal follicular development and serious damage to the reproduction.


Assuntos
Meiose , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Humanos , Exposição Materna , Camundongos , Fenóis/toxicidade , Gravidez , Reprodução , Sulfonas
20.
Vet Microbiol ; 246: 108740, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32605757

RESUMO

Alphaherpesviral ribonucleotide reductase (RNR) is composed of large (pUL39, RR1) and small (pUL40, RR2) subunits. This enzyme can catalyze conversion of ribonucleotide to deoxynucleotide diphosphates that are further phosphorylated into deoxynucleotide triphosphate (dNTPs). The dNTPs are substrates for de novo viral DNA synthesis in infected host cells. The enzymatic activity of RNR depends on association between RR1 and RR2. However, the molecular basis underlying alphaherpesviral RNR complex formation is still largely unknown. In the current study, we investigated the pseudorabies virus (PRV) RNR interaction domains in pUL39 and pUL40. The interaction of pUL39 and pUL40 was identified by co-immunoprecipitation (co-IP) and colocalization analyses. Furthermore, the interaction amino acid (aa) domains in pUL39 and pUL40 were mapped using a series of truncated proteins. Consequently, the 90-210 aa in pUL39 was identified to be responsible for the interaction with pUL40. In turn, the 66-152, 218-258 and 280-303 aa in pUL40 could interact with pUL39, respectively. Deletion of 90-210 aa in pUL39 completely abrogated the interaction with pUL40. Deletion of 66-152, 218-258 and 280-303 aa in pUL40 remarkably weakened the interaction with pUL39, whereas a weak interaction could still be observed. Amino acid sequence alignments showed that the interaction domains identified in PRV pUL39/pUL40 were relatively non-conserved among the selected RNR subunits in alphaherpesviruses HSV1, HSV2, HHV3(VZV), BHV1, EHV1 and DEV. However, they were relatively conserved among PRV, HSV1 and HSV2. Collectively, our findings provided some molecular targets for inhibition of pUL39-pUL40 interaction to antagonize viral replication in PRV infected hosts.


Assuntos
Herpesvirus Suídeo 1/enzimologia , Subunidades Proteicas/química , Ribonucleotídeo Redutases/química , Linhagem Celular , Células HEK293 , Humanos , Nucleotidases/metabolismo , Alinhamento de Sequência , Replicação Viral
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