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OBJECTIVE: Bayesian network (BN) models were developed to explore the specific relationships between influencing factors and type 2 diabetes mellitus (T2DM), coronary heart disease (CAD), and their comorbidities. The aim was to predict disease occurrence and diagnose etiology using these models, thereby informing the development of effective prevention and control strategies for T2DM, CAD, and their comorbidities. METHOD: Employing a case-control design, the study compared individuals with T2DM, CAD, and their comorbidities (case group) with healthy counterparts (control group). Univariate and multivariate Logistic regression analyses were conducted to identify disease-influencing factors. The BN structure was learned using the Tabu search algorithm, with parameter estimation achieved through maximum likelihood estimation. The predictive performance of the BN model was assessed using the confusion matrix, and Netica software was utilized for visual prediction and diagnosis. RESULT: The study involved 3,824 participants, including 1,175 controls, 1,163 T2DM cases, 982 CAD cases, and 504 comorbidity cases. The BN model unveiled factors directly and indirectly impacting T2DM, such as age, region, education level, and family history (FH). Variables like exercise, LDL-C, TC, fruit, and sweet food intake exhibited direct effects, while smoking, alcohol consumption, occupation, heart rate, HDL-C, meat, and staple food intake had indirect effects. Similarly, for CAD, factors with direct and indirect effects included age, smoking, SBP, exercise, meat, and fruit intake, while sleeping time and heart rate showed direct effects. Regarding T2DM and CAD comorbidities, age, FBG, SBP, fruit, and sweet intake demonstrated both direct and indirect effects, whereas exercise and HDL-C exhibited direct effects, and region, education level, DBP, and TC showed indirect effects. CONCLUSION: The BN model constructed using the Tabu search algorithm showcased robust predictive performance, reliability, and applicability in forecasting disease probabilities for T2DM, CAD, and their comorbidities. These findings offer valuable insights for enhancing prevention and control strategies and exploring the application of BN in predicting and diagnosing chronic diseases.
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Teorema de Bayes, Comorbidade, Doença das Coronárias, Diabetes Mellitus Tipo 2, Humanos, Diabetes Mellitus Tipo 2/epidemiologia, Pessoa de Meia-Idade, Feminino, Masculino, Doença das Coronárias/epidemiologia, Estudos de Casos e Controles, Idoso, Adulto, Fatores de RiscoRESUMO
Vitamin C is an important micronutrient for human. Association between vitamin C and trouble sleeping was less studied. Therefore, the purpose of this study was to investigate the possible link between vitamin C in serum and trouble sleeping. The cross-sectional data was derived from the National Health and Nutrition Examination Survey (NHANES, 2017-2018). Trouble sleeping was measured by asking participants: "Have you ever told doctor had trouble sleeping". Responses to this question was "yes" or "no". vitamin C in serum was obtained by measuring the serum samples. We used multivariable binary logistic regressions to examine the possible link between vitamin C in serum and trouble sleeping, and then a subgroup analysis was performed. Moreover, the non-linear relationship between vitamin C in serum and trouble sleeping was further detected using a restricted cubic spline (RCS) model. A total of 3227 participants were included in the study. After adjusting all potential confounders, the results of multivariable logistic regression showed the significant negative association between vitamin C in serum and trouble sleeping(OR = 0.816; 95% CI:0.669 ~ 0.995). The significant inverse association was also found in female(OR = 0.713; 95% CI:0.546 ~ 0.931), age ≤ 65 years(OR = 0.773; 95% CI:0.600 ~ 0.996), and in participants with high cholesterol level(OR = 0.738; 95% CI:0.548 ~ 0.994). In addition, the RCS model demonstrated the significant non-linear relationship between vitamin C in serum and trouble sleeping (P value of nonlinear = 0.010). Our study demonstrates the significant negative association between vitamin C in serum and trouble sleeping.
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Ácido Ascórbico, Inquéritos Nutricionais, Humanos, Ácido Ascórbico/sangue, Feminino, Masculino, Pessoa de Meia-Idade, Adulto, Estudos Transversais, Idoso, Transtornos do Sono-Vigília/sangue, Transtornos do Sono-Vigília/epidemiologia, Modelos LogísticosRESUMO
Objective: The purpose of this investigation was to evaluate the potential link between physical activity (PA) and the heightened susceptibility to diabetes mellitus (DM), by examining whether remnant cholesterol (RC) might act as a mediator in this correlation. Methods: The research utilized data from the National Health and Nutrition Examination Survey, spanning from 2005 to 2018. Various statistical analyses were conducted for continuous and categorical variables, including the t-test, ANOVA, and χ2 test. Logistic regression was employed to analyze the association between PA and DM across three distinct models. Mediation analysis was also conducted to assess the potential mediation effects of RC. Results: The study encompassed a total of 9,149 participants, and it was observed that individuals with DM exhibited lower levels of PA. Furthermore, PA levels were found to be associated with all participant characteristics except poverty income ratio, fasting blood glucose, and HOMA-IR (p < 0.05). After adjusting for covariates (Model 3), individuals with high PA levels demonstrated a decreased likelihood of developing DM compared to those in the low PA group (OR: 0.73, 95%CI: 0.54-0.99). A significant dose-response relationship was identified (p < 0.05). No interaction between PA and RC in relation to DM risk was detected, and RC was found to serve as a mediator in the connection between PA and DM. After considering covariates, the mediating effect of RC between PA and DM weakens. Discussion: Our findings suggest that higher levels of PA are linked to a reduced risk of DM in U.S. adults, with RC likely playing a mediating role.
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Diabetes Mellitus, Adulto, Humanos, Inquéritos Nutricionais, Diabetes Mellitus/diagnóstico, Colesterol, Exercício FísicoRESUMO
The dietary inflammatory index (DII) is a measure of the inflammatory potential of the diet and is closely associated with insulin resistance (IR) and stroke. And IR may play an important role in the development of stroke. Therefore, this study aimed to evaluate the relationship between DII and stroke risk while delving into the potential role of IR in this association. We analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018, performing weighted univariate analyses, logistic regression, and mediation analyses. At baseline, 3.89% of participants developed stroke, and we observed stroke patients exhibited higher DII scores. After adjusting for covariates, compared to participants in the first quartile of DII scores, those in the third quartile and fourth quartile had increased odds of experiencing a stroke (OR: 1.78, 95% CI: 1.18-2.68) and (OR: 1.70, 95% CI: 1.16-2.50), respectively. Moreover, a significant dose-response relationship was observed (P-trend < 0.05). However, there was no observed interaction between DII and homeostatic model assessment-IR (HOMA-IR) concerning stroke risk, and HOMA-IR did not mediate the association between DII and stroke. In summary, our study elucidated the significant association between DII and stroke risk, independent of IR. This insight suggests that an anti-inflammatory diet may serve as an effective strategy for stroke prevention.
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Resistência à Insulina, Acidente Vascular Cerebral, Humanos, Inquéritos Nutricionais, Inflamação/diagnóstico, Dieta/efeitos adversos, Acidente Vascular Cerebral/epidemiologia, Acidente Vascular Cerebral/etiologiaRESUMO
BACKGROUND: Patients with diabetic feet are prone to be infected due to the impaired immune system. However, the prognostic outcome of different microbial infections remains controversial. Identification and rapid screening of the pathogenic microorganisms that pose the greatest threat to the prognosis of patients with diabetic foot infections (DFIs) is critical. METHODS: Clinical data were statistically analyzed, which were obtained from 522 patients with DFIs, including pathogenic bacterial culture results and treatment outcomes at the last return visit. In addition, a loop-mediated isothermal amplification (LAMP) detection method was developed to identify the prevalent subtype of methicillin-resistant Staphylococcus aureus (MRSA) in DFIs patients. This study was approved by the Ethics Committee of Nanfang Hospital (NFEC-202012-K6) and registered on ClinicalTrials.gov (NCT04916457) on June 1, 2021. RESULTS: We found that the proportion of patients with infections of Staphylococcus aureus (S. aureus) and MRSA was 27.7% (145/522) and 33.7% (49/145), respectively. Additionally, the incidence of osteomyelitis was 46.9% (23/49) and amputation/disability was 40.8% (20/49) in patients with MRSA infection, which were significantly higher compared to patients with other types of bacterial infections such as methicillin-susceptible Staphylococcus aureus (MSSA). Notably, we demonstrated that the main prevalent subtype of MRSA in DFIs patients in our hospital was Staphylococcal chromosomal cassettes mec (SCCmec) type II. In addition, it only takes 1.5 h to complete the entire experimental procedure in this LAMP assay, providing high sensitivity (100%) and specificity (77.8%) in hospitalized patients with DFIs. CONCLUSIONS: We demonstrated there is a very high rate of MRSA isolation in patients with DFIs and revealed that patients infected with MRSA are at a higher risk of developing osteomyelitis, and amputation or disability. Importantly, we have developed a method for quickly screening newly admitted patients for MRSA.
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Diabetes Mellitus, Pé Diabético, Staphylococcus aureus Resistente à Meticilina, Osteomielite, Infecções Estafilocócicas, Humanos, Staphylococcus aureus Resistente à Meticilina/genética, Staphylococcus aureus/genética, Antibacterianos/uso terapêutico, Prevalência, Infecções Estafilocócicas/diagnóstico, Infecções Estafilocócicas/epidemiologia, Infecções Estafilocócicas/tratamento farmacológico, Testes de Sensibilidade Microbiana, Diabetes Mellitus/tratamento farmacológicoRESUMO
OBJECTIVES: To compare the prediction effects of six models based on machine learning theories, which can provide a methodological reference for predicting the risk of type 2 diabetes mellitus (T2DM). SETTING AND PARTICIPANTS: This study was based on the monitoring data of chronic disease risk factors in Dongguan residents from 2016 to 2018. The multistage cluster random sampling method was adopted at each monitoring site, and 4157 people were finally selected. In the initial population, we excluded individuals with more than 20% missing data and eventually included 4106 subjects. DESIGN: K nearest neighbour algorithm and synthetic minority oversampling technique were used to process the data. Single factor analysis was used for preliminary selection of variables. The 10-fold cross-validation was used to optimise the parameters of some models. The accuracy, precision, recall and area under receiver operating characteristic curve (AUC) were used to evaluate the prediction effect of models, and Delong test was used to analyse the differences of AUC values of each model. RESULTS: After balancing data, the sample size increased to 8013, of which 4023 are patients with T2DM and 3990 in control group. The comparison results of the six models showed that back propagation neural network model has the best prediction effect with 93.7% accuracy, 94.6% accuracy, 92.8% recall and the AUC value of 0.977, followed by logistic model, support vector machine model, CART decision tree model and C4.5 decision tree model. Deep neural network has the worst prediction performance, with 84.5% accuracy, 86.1% precision, 82.9% recall and the AUC value of 0.845. CONCLUSIONS: In this study, six types of risk prediction models for T2DM were constructed, and the predictive effects of these models were compared based on various indicators. The results showed that back propagation neural network based on the selected data set had the best prediction effect.
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Diabetes Mellitus Tipo 2, Humanos, Estudos Transversais, Diabetes Mellitus Tipo 2/epidemiologia, Algoritmos, Análise por Conglomerados, Aprendizado de MáquinaRESUMO
Objective: We aimed to evaluate whether depression is associated with increased risk of dietary inflammatory index (DII) or energy-adjusted DII (E-DII) and whether the association is partly explained by insulin resistance (IR). Methods: Base on the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Univariate analyses of continuous and categorical variables were performed using t-test, ANOVA, and χ 2 test, respectively. Logistic regression was used to analyze the relationship between DII or E-DII and depression in three different models. Mediation analysis was used to assess the potential mediation effects of homeostatic model assessment-IR (HOMA-IR). Results: A total of 70,190 participants were included, and the DII score was higher in the depressed group. DII score was related to all participant characteristics except age (p < 0.05). After being included in covariates (Model 3), participants in the highest quartile of DII score have increased odds of depression (OR: 1.82, 95% CI: 1.28-2.58) compared with those in the first quartile of DII score. And, a significant dose-response relationship was found (p-trend <0.05). No interaction between DII and HOMA-IR was observed in terms of the risk of depression, and HOMA-IR did not find to play a mediating role in the association between DII and depression. Similar results were obtained for the association between E-DII and depression. Conclusion: Our results suggest that a higher pro-inflammatory diet increases the risk of depression in U.S. adults, while there was no evidence of a multiplicative effect of DII or E-DII and HOMA-IR on disease risk, nor of a mediating effect of HOMA-IR.
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Background: Inflammation and obesity have been widely recognized to play a key role in Diabetes mellitus (DM), and there exists a complex interplay between them. We aimed to clarify the relationship between inflammation and DM, as well as the mediating role of obesity in the relationship. Methods: Based on the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Univariate analyses of continuous and categorical variables were performed using t-test, linear regression, and χ2 test, respectively. Logistic regression was used to analyze the relationship between Systemic Immune-Inflammatory Index (SII) or natural logarithm (Ln)-SII and DM in three different models. Mediation analysis was used to determine whether four obesity indicators, including body mass index (BMI), waist circumference (WC), visceral adiposity index (VAI) and lipid accumulation product index (LAP), mediated the relationship between SII and DM. Results: A total of 9,301 participants were included, and the levels of SII and obesity indicators (BMI, WC, LAP, and VAI) were higher in individuals with DM (p < 0.001). In all three models, SII and Ln-SII demonstrated a positive correlation with the risk of DM and a significant dose-response relationship was found (p-trend <0.05). Furthermore, BMI and WC were associated with SII and the risk of DM in all three models (p < 0.001). Mediation analysis showed that BMI and WC mediated the relationship between SII with DM, as well as Ln-SII and DM, with respective mediation proportions of 9.34% and 12.14% for SII and 10.23% and 13.67% for Ln-SII (p < 0.001). Conclusion: Our findings suggest that increased SII levels were associated with a higher risk of DM, and BMI and WC played a critical mediating role in the relationship between SII and DM.
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Diabetes Mellitus, Análise de Mediação, Humanos, Inquéritos Nutricionais, Obesidade/epidemiologia, Diabetes Mellitus/epidemiologia, InflamaçãoRESUMO
Background: This study explores the causal links between genetically predicted lifestyle factors, socioeconomic status, and coronary artery disease (CAD) risk in individuals with diabetes using a bidirectional Mendelian-randomization approach. Methods: This study explored the potential causal relationships of lifestyle factors and socioeconomic status with the risk of CAD in diabetes patients by a bidirectional, two-sample Mendelian-randomization (MR) analysis. Results: Genetically predicted smoking initiation (p = 0.005, 95% CI: 1.08-1.55) and insomnia (p = 0.001, 95% CI: 1.06-1.29) were associated with a higher risk of CAD in individuals with diabetes, whereas educational attainment (p = 0.0001, 95% CI: 0.47-0.78) was associated with a lower risk of CAD. The lifetime smoking index (p = 0.016, 95% CI: 1.12-3.03) was suggestively associated with a higher risk of CAD, while household income before taxes (p = 0.048, 95% CI: 0.41-1.00) was suggestively associated with a lower risk of CAD. In addition, we observed a suggestive negative association between the genetically predicted risk of CAD and the lifetime smoking index (p = 0.016, 95% CI: 0.98-0.99) and a significant causal relationship between the risk of CAD and household income before taxes (p = 0.006, 95% CI: 0.97-0.99). Conclusion: The results of this study provide evidence that smoking initiation, lifetime smoking index and insomnia are associated with an increased risk of CAD in individuals with diabetes, educational attainment and household income before taxes are associated with a reduced risk of CAD in individuals with diabetes, and the possible role of lifetime smoking index and household income before taxes on the risk of CAD in individuals with diabetes. It provides an opportunity for the prevention and management of CAD in individuals with diabetes.
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Doença da Artéria Coronariana, Diabetes Mellitus, Distúrbios do Início e da Manutenção do Sono, Humanos, Doença da Artéria Coronariana/epidemiologia, Doença da Artéria Coronariana/genética, Análise da Randomização Mendeliana, Diabetes Mellitus/epidemiologia, Classe Social, Estilo de VidaRESUMO
Accumulating evidence has highlighted that sirtuin-6 (SIRT6) plays an important role in hepatic gluconeogenesis and lipogenesis. We aim to investigate the underlying mechanisms and pharmacological interventions of SIRT6 on hepatic steatosis treatment. Herein, our results showed that atractylenolide I (ATL I) activated the deacetylase activity of SIRT6 to promote peroxisome proliferator-activated receptor alpha (PPARα) transcription and translation, while suppressing nuclear factor NF-kappa-B (NFκB)-induced NACHT, LRR, and PYD domains containing protein 3 (NLRP3) inflammasome formation. Together, these decreased the infiltration of F4/80 and CD11B positive macrophages, accompanied by decreased mRNA expression and serum levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL6), and interleukin-1 beta (IL1ß). Additionally, these changes decreased sterol regulatory element-binding protein-1c (SREBP-1c) expression, while restoring carnitine O-palmitoyltransferase 1a (Cpt1a) expression, to decrease the size of adipocytes and adipose deposition, which, in turn, reversed high-fat diet (HFD)-induced liver weight and body weight accumulation in C57 mice. SIRT6 knockout or hepatic SIRT6 knockout in C57 mice largely abolished the effect of ATL I on ameliorating hepatic steatosis. Taken together, our results suggest that ATL I acts as a promising compound that activates SIRT6/PPARα signaling and attenuates the NLRP3 inflammasome to ameliorate hepatic inflammation and steatosis.
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The structure of a back propagation neural network was optimized by a particle swarm optimization (PSO) algorithm, and a back propagation neural network model based on a PSO algorithm was constructed. By comparison with a general back propagation neural network and logistic regression, the fitting performance and prediction performance of the PSO algorithm is discussed. Furthermore, based on the back propagation neural network optimized by the PSO algorithm, the risk factors related to hypertension were further explored through the mean influence value algorithm to construct a risk prediction model. In the evaluation of the fitting effect, the root mean square error and coefficient of determination of the back propagation neural network based on the PSO algorithm were 0.09 and 0.29, respectively. In the comparison of prediction performance, the accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of the back propagation neural network based on PSO algorithm were 85.38%, 43.90%, 96.66%, and 0.86, respectively. The results showed that the backpropagation neural network optimized by PSO had the best fitting effect and prediction performance. Meanwhile, the mean impact value algorithm could screen out the risk factors related to hypertension and build a disease prediction model, which can provide clues for exploring the pathogenesis of hypertension and preventing hypertension.
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Hipertensão, Humanos, Hipertensão/diagnóstico, Hipertensão/epidemiologia, Redes Neurais de Computação, Fatores de RiscoRESUMO
Objectives: Farnesoid X receptor (FXR) activation is involved in ameliorating inflammatory bowel disease (IBD), such as ulcerative colitis (UC), and inflammatory regulation may be involved in its mechanism. Ginsenoside Rc (Rc) is a major component of Panax ginseng, and it plays an excellent role in the anti-inflammatory processes. Our aim is to explore the alleviative effect of Rc on dextran sulfate sodium (DSS)-induced inflammation and deficiencies in barrier function based on FXR signaling. Materials and Methods: In vitro, we treated human intestinal epithelial cell lines (LS174T) with LPS to explore the anti-inflammatory effect of Rc supplementation. In vivo, a DSS-induced IBD mice model was established, and the changes in inflammatory and barrier function in colons after Rc treatment were measured using the disease activity index (DAI), hematoxylin and eosin (H&E) staining, immunofluorescence, ELISA, and qPCR. Molecular docking analysis, luciferase reporter gene assay, and qPCR were then used to analyze the binding targets of Rc. DSS-induced FXR-knockout (FXR-/-) mice were used for further validation. Results: Rc significantly recovered the abnormal levels of inflammation indexes (TNF-α, IL-6, IL-1ß, and NF-KB) induced by LPS in LS174T. DSS-induced C57BL/6 mice exhibited a significantly decreased body weight and elevated DAI, as well as a decrease in colon weight and length. Increased inflammatory markers (TNF-α, IL-6, IL-1ß, ICAM1, NF-KB, F4/80, and CD11b displayed an increased expression) and damaged barrier function (Claudin-1, occludin, and ZO-1 displayed a decreased expression) were observed in DSS-induced C57BL/6 mice. Nevertheless, supplementation with Rc mitigated the increased inflammatory and damaged barrier function associated with DSS. Further evaluation revealed an activation of FXR signaling in Rc-treated LS174T, with FXR, BSEP, and SHP found to be upregulated. Furthermore, molecular docking indicated that there is a clear interaction between Rc and FXR, while Rc activated transcriptional expression of FXR in luciferase reporter gene assay. However, these reversal abilities of Rc were not observed in DSS-induced FXR-/- mice. Conclusion: Our findings suggest that Rc may ameliorate inflammation and barrier function in the intestine, which in turn leads to the attenuation of DSS-induced UC, in which Rc may potentially activate FXR signaling to protect the intestines from DSS-induced injury.
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The aim of the present study is to explored the relationship between ADIPO signalling pathway and T2DM, to provide clues for further study of the pathogenesis of T2DM and to determine the possible drug targets. This study employed a case-control study design. Twenty-three single nucleotide polymorphisms (SNPs) of 13 genes in the selected ADIPO signalling pathway were genotyped by SNPscanTM kit. All statistical analysis was performed by SPSS 25.0, PLINK 1.07, R 2.14.2, Haploview 4.2, SNPstats, and other statistical software packages. In the association analysis based on a single SNPs, rs1044471 had statistical significance in the overdominant model without adjusting covariates. Rs1042531 had statistical significance in the overdominant model. Rs12718444 had statistical significance in the recessive model. There was a linkage disequilibrium between the loci within 9 genes, and the two loci in RXRA gene did not form blocks. Four kernel functions were used for SNPs set analysis based on ADIPO signalling pathway showed that there was no statistical significance whether covariates were added or not, P>0.05.According to our research results, it is found that some single nucleotide polymorphisms (ADIPOR2 rs1044471, PCK1 rs1042531, GLUT1 rs12718444) in the adiponectin signalling pathway may be associated with T2DM.
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Diabetes Mellitus Tipo 2, Predisposição Genética para Doença, Estudos de Casos e Controles, China, Diabetes Mellitus Tipo 2/genética, Humanos, Transdução de Sinais/genéticaRESUMO
OBJECTIVE: This study is aimed at analyzing the relationship between leptin (LEP) signaling pathway and type 2 diabetes mellitus (T2DM) and at providing support for molecular genetic research on the pathogenesis of T2DM in Chinese Han population. METHODS: A case-control study was designed, including 1092 cases with T2DM and 1092 healthy controls of Chinese Han origin recruited from ten hospitals in Guangdong Province, Southern China. Twenty-three single nucleotide polymorphisms (SNPs) of 15 genes in LEP signaling pathway were genotyped by SNPscan™ kit. The Pearson chi-square test, Cochran-Armitage trend test, MAX3, and logistic regression were applied to analyze the association between single nucleotide polymorphism (SNP) and T2DM; unconditional logistic regression was used to analyze haplotype in LD block; and SNP set analysis based on logistic kernel machine regression was used to analyze pathway. All statistical analysis was performed by SPSS25.0, R2.14, Haploview4.2, SNPStats, and other statistical software packages. RESULTS: In association analysis based on SNP, rs2167270 had statistical significance both in the adjusted and unadjusted covariate dominant model and in the unadjusted covariate overdominant model while it had no significant difference in the adjusted covariate overdominant model. Compared to GG genotype, rs2167270 of AG genotype had statistical significance in both the adjusted and unadjusted covariate codominant models. And rs16147 had statistical significance in robust test, stealth model and overdominant model, and adjusting and unadjusting covariate. This study found linkage disequilibrium existed between rs2167270 and rs4731426 of LEP, rs10889502 and rs17127107 of JAK1, rs2970847 and rs6821591 of PPARGC1A, rs249429 and rs3805486 of PRKAA1, rs1342382 and rs6588640 of PRKAA2, rs3766522 and rs6937 of PRKAB2, rs2970847 and rs6821591 of PRKAG2, and rs6436094 and rs645163 of PRKAG3. There was no positive finding with statistical significance from the unconditional logistic regression of the mentioned genes' haplotype of LD block. CONCLUSIONS: LEP signaling pathway association with T2DM remained to be confirmed in Chinese Han population, although rs2167270 and rs16147 were significantly associated with T2DM.
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Povo Asiático/genética, Diabetes Mellitus Tipo 2/genética, Etnicidade/genética, Estudos de Associação Genética, Leptina/metabolismo, Transdução de Sinais, Alelos, Estudos de Casos e Controles, China, Feminino, Predisposição Genética para Doença, Haplótipos/genética, Humanos, Leptina/genética, Desequilíbrio de Ligação/genética, Modelos Logísticos, Masculino, Pessoa de Meia-Idade, Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Background: The aim of this study was to investigate the association between single nucleotide polymorphism (SNP) rs9891119 of the signal transducer and activator of the transcription 3 (STAT3) gene and genetic susceptibility to type 2 diabetes in Chinese Han population from the Guangdong province. Objective: The aim of the present study was to explore the relationship between single nucleotide polymorphism rs9891119 of STAT3 gene and type 2 diabetes mellitus (T2DM), which provides a basis for molecular genetic research on the pathogenesis of T2DM in Chinese Han population. Methods: In our case-control study, the SNP rs9891119 was picked out from the STAT3 gene and the SNP genotyping was performed by using the SNPscan™ kit in 1092 patients with type 2 diabetes as cases and 1092 normal persons as controls. The distributions of genotype and allele frequencies in two groups were analyzed by SPSS 20.0 software. Results: Our results showed that the alleles of A and C of rs9891119 of the STAT3 gene were 54.3 and 45.7% in patients with type 2 diabetes, while 55.5% and 44.5% in the normal persons, which have no statistical significance (P > 0.05). There were also no significant differences in AA, AC, and CC genotype frequencies between type 2 diabetes patients and normal persons. There were no significant differences in codominant, dominant, recessive, and overdominant genetic models of SNP rs9891119 before and after adjusting the covariant factors (P > 0.05). Conclusions: Therefore, genetic susceptibility to type 2 diabetes may be not associated with SNP rs9891119 of the STAT3 gene in Chinese Han population from the Guangdong province.
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Diabetes Mellitus Tipo 2, Predisposição Genética para Doença, Estudos de Casos e Controles, China, Diabetes Mellitus Tipo 2/genética, Predisposição Genética para Doença/genética, Humanos, Polimorfismo de Nucleotídeo Único/genética, Fator de Transcrição STAT3/genética, TransdutoresRESUMO
Alzheimer's disease (AD), a common irreversible neurodegenerative disease characterized by amyloid-ß plaques, neurofibrillary tangles, and changes in tau phosphorylation, is accompanied by memory loss and symptoms of cognitive dysfunction. Increases in disease incidence due to the ageing of the population have placed a great burden on society. To date, the mechanism of AD and the identities of adequate drugs for AD prevention and treatment have eluded the medical community. It has been confirmed that phytochemicals have certain neuroprotective effects against AD. For example, some progress has been made in research on the use of resveratrol, a natural polyphenolic phytochemical, for the prevention and treatment of AD in recent years. Elucidation of the pathogenesis of AD will create a solid foundation for drug treatment. In addition, research on resveratrol, including its mechanism of action, the roles of signalling pathways and its therapeutic targets, will provide new ideas for AD treatment, which is of great significance. In this review, we discuss the possible relationships between AD and the following factors: synapses, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs), silent information regulator 1 (SIRT1), and estrogens. We also discuss the findings of previous studies regarding these relationships in the context of AD treatment and further summarize research progress related to resveratrol treatment.
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Doença de Alzheimer/tratamento farmacológico, Antioxidantes/uso terapêutico, Pesquisa Biomédica/tendências, Resveratrol/uso terapêutico, Doença de Alzheimer/metabolismo, Animais, Antioxidantes/metabolismo, Humanos, Receptores de AMPA/metabolismo, Resveratrol/metabolismo, Sinapses/efeitos dos fármacos, Sinapses/metabolismoRESUMO
OBJECTIVE: This study aimed to investigate the effect of antioxidant vitamins, including vitamins E and C, on patients with diabetes and albuminuria by conducting a meta-analysis of randomized controlled trials. DESIGN: The PubMed, Embase, CENTRAL (the Cochrane Central Register of Controlled Trials at the Cochrane Library), Web of Science, OVID, and www.clinicaltrials.gov (latest search: December 10, 2018) databases were searched. This study was limited to randomized controlled trials. Patients with diabetes and albuminuria were included regardless of diabetic type, and patients must have received treatment with vitamins C or E. RESULTS: Ten studies, representing 445 participants, were identified for analysis. Antioxidant vitamins had significant effects on serum creatinine levels (mean difference = -0.11 mg/dL, 95% confidence interval -0.19 to -0.03, P = .007) and systolic pressure (mean difference = -6.02 mm Hg, 95% confidence interval -9.65 to -2.40, P = .001) with low heterogeneity. Antioxidant vitamins had no effect on albuminuria or proteinuria, diastolic blood pressure, glucose, or lipid metabolism. CONCLUSION: This meta-analysis indicated that antioxidant vitamins can benefit kidney function and systolic blood pressure in patients with diabetes and albuminuria. Further studies with larger sample sizes and longer follow-up are needed to completely understand the effect of antioxidant vitamins in these patients.
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Albuminúria/tratamento farmacológico, Antioxidantes/farmacologia, Diabetes Mellitus/tratamento farmacológico, Suplementos Nutricionais, Vitaminas/farmacologia, Humanos, Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: To investigate the relationship between genetic polymorphisms of RXRG rs1467664, rs3753898 and the genetic susceptibility of type 2 diabetes in the Chinese Han population from South China. METHODS: In our case-control study, single-nucleotide polymorphisms (SNPs) rs1467664 and rs3753898 were genotyped by SNPscanTM kit in 1092 patients with T2D as cases and 1092 normal persons as controls. The distributions of genotype and allele frequencies in two groups were analyzed by the SPSS 20.0 software. RESULTS: The distribution of genotypes and alleles of RXRG rs3753898 was statistically significant between the two groups, but there was no significant difference in the distribution of genotypes and alleles of the rs1467664. Before and after the adjustment of age, sex and BMI, rs3753898 in the two groups had statistical significance under the additive, dominant and recessive models (P<0.05), but no statistical differences were found under the overdominance and co-dominant genetic models (P>0.05). There was no significant difference in the genetic models of rs1467664 between the two groups (P>0.05). The haplotype, which consists of rs1467664 allele T and rs3753898 allele A was a high-risk factor for T2D, OR=1.27, 95% CI (1.09-1.47), Padj=0.002. CONCLUSION: Our results showed that the single nucleotide polymorphism of RXRG rs3753898 may be related to genetic susceptibility of type 2 diabetes. The haplotype consisting of the allele T of rs1467664 and the allele A of rs3753898 is a risk factor for type 2 diabetes, suggesting that the genetic variation of RXRG gene may be the genetic cause of diabetes mellitus in the Chinese Han population.
Assuntos
Polimorfismo de Nucleotídeo Único/genética, Receptor X Retinoide gama/genética, Idoso, Alelos, Povo Asiático, Estudos de Casos e Controles, Diabetes Mellitus Tipo 2/genética, Feminino, Frequência do Gene/genética, Estudos de Associação Genética, Predisposição Genética para Doença/genética, Genótipo, Haplótipos/genética, Humanos, Desequilíbrio de Ligação/genética, Masculino, Pessoa de Meia-Idade, SoftwareRESUMO
Impaired wound healing is one of the major complications of diabetes, involving prolonged inflammation, delayed re-epithelialization, and consistent oxidative stress. The detailed mechanism remains unclear, and there is currently no effective treatment for diabetic wound healing. In this study, we aim to investigate the potential role and effect of nuclear factor erythroid-2-related factor-2 (Nrf2) activation on diabetic wound healing. In vitro experiments in rat macrophages showed that hyperglycemia treatment suppresses Nrf2 activation, resulting in oxidative stress with decreased expression of antioxidant genes, including NAD(P)H:quinone oxidoreductase 1 and heme oxygenase 1, together with increased secretion of proinflammatory cytokines, including interleukin 1ß (IL1ß), IL6, and monocyte chemoattractant protein-1. Both Nrf2 overexpression and Nrf2 activator dimethyl fumarate (DMF) treatment significantly ameliorated oxidative stress and inflammation. On the other hand, both Nrf2 knockdown or Nrf2 inhibitor ML385 mimicked the effect of diabetes. Further in vivo experiments in rats showed that DMF treatment significantly accelerated wound healing in streptozocin-induced diabetic rats with increased expression of antioxidant enzymes and decreased secretion of proinflammatory cytokines, while Nrf2 inhibitor ML385 mimicked the effect of diabetes. We conclude that Nrf2 activation accelerates impaired wound healing by ameliorating diabetes-mediated oxidative stress and inflammation. This provides a new clinical treatment strategy for diabetic wound healing using Nrf2 activator DMF.
RESUMO
OBJECTIVE: To observe the effects of resveratrol (Res) on the antioxidative function and estrogen level in an Alzheimer's disease (AD) mouse model. METHODS: First, we examined the effects of Res on an AD mice model. SAMP8 mice were selected as the model, and normal-aging SAMR1 mice were used as the control group. The model mice were randomly divided into three groups: a model group, high-dose Res group (40mg/kg, intraperitoneal (ip)), and low-dose Res group (20mg/kg, ip). After receiving medication for 15 days, the mice were subjected to the water maze test to assess their spatial discrimination. The spectrophotometric method was used to detect the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) as well as the malondialdehyde (MDA) content. Quantitative PCR (q-PCR) was used to detect SOD, GSH-Px, CAT, and heme oxygenase-1 (HO-1) mRNA level changes. Western blot analysis detected HO-1 and Nrf2 protein expression. Second, we researched the effect of Res on the estrogen level in the SAMP8 model mice. The model mice were randomly divided into four groups: a model group, estrogen replacement group (0.28 mg/kg, intramuscular (im), estradiol benzoate), high-dose Res group (5 mg/kg, im), and low-dose Res group (2.5 mg/kg, im). The mice were injected, once every three days, for 5 weeks. Q-PCR was used to detect brain tissue mRNA expression changes. Western blot analysis detected ERα, ERß, and ChAT protein expression. An enzyme-linked immunosorbent assay (ELISA) kit was used to detect the expression of E2 and amyloid ß protein (Aß) in brain tissue. RESULTS: Compared with the control treatment, Res could improve the spatial abilities of the mice to a certain extent and also increase the expression of SOD, GSH-Px, CAT, and HO-1 at the mRNA level (P<0.05). In addition, enhanced SOD, GSH-Px, and CAT activities and HO-1 protein levels and decreased MDA content (P<0.05) were detected in the brain tissue of the Res-treated mice. The cytoplasmic Nrf2 content in the Res-treated mice was also decreased while the nuclear Nrf2 content and the nuclear translation rate of Nrf2 were increased (P<0.05). Res could decrease the expression of ERß in the brain tissue at the mRNA and protein levels and the expression of Aß in the brain tissue at the protein level. Res could also increase the mRNA and protein expression of ERα and ChAT and the protein expression of estradiol in the brain tissue. CONCLUSION: Res can increase the antioxidant capacity of AD models through the Nrf2/HO-1 signaling pathway. In addition, Res can enhance estrogen levels in an AD model. These findings provide a new idea for the treatment of AD.
