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Background: Transcription factor 21 (TCF21, epicardin, capsuling, pod-1) is expressed in the epicardium and is involved in the regulation of cell fate and differentiation via epithelial-mesenchymal transformation during development of the heart. In addition, TCF21 can suppress the differentiation of epicardial cells into vascular smooth muscle cells and promote cardiac fibroblast development. This study aimed to explore whether TCF21 gene (12190287G/C) variants affect coronary artery disease risk. Methods: We enrolled 381 patients who had stable angina, 138 with ST elevation myocardial infarction (STEMI), and 276 healthy subjects. Genotyping of rs12190287 of the TCF21 gene was performed. Results: Higher frequencies of the CC genotype were found in the patients with stable angina/STEMI than in the healthy controls. After adjusting for diabetes mellitus, hypertension, age, sex, smoking, body mass index and hyperlipidemia, the patients with the CC genotype of the TCF21 gene were associated with 2.49- and 9.19-fold increased risks of stable angina and STEMI, respectively, compared to the patients with the GG genotype. Furthermore, TCF21 CC genotypes showed positive correlations with both stable angina and STEMI, whereas TCF21 GG genotypes exhibited a negative correlation with STEMI. Moreover, the stable angina and STEMI patients with the CC genotype had significantly elevated high-sensitivity C-reactive protein levels than those with the GG genotype. In addition, significant associations were found between type 2 diabetes mellitus, hypertension, and hyperlipidemia with TCF21 gene polymorphisms (p for trend < 0.05). Conclusion: TCF21 gene polymorphisms may increase susceptibility to stable angina and STEMI.
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Angina Estável , Diabetes Mellitus Tipo 2 , Hiperlipidemias , Hipertensão , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Angina Estável/genética , Infarto do Miocárdio com Supradesnível do Segmento ST/genética , China , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genéticaRESUMO
Objective: Breast cancer is the second most common malignancy globally and a leading cause of cancer death in women. Analysis of factors related to disease-free survival (DFS) has improved understanding of the disease and characteristics related to recurrence. The aim of this study was to investigate the predictors of DFS in patients with breast cancer to enable the identification of patients at high risk who may benefit from prevention interventions. Methods: We retrospectively analyzed 559 women with breast cancer who underwent treatment between 2004 and 2022. The study endpoint was DFS. Recurrence was defined as local recurrence, regional recurrence, distant metastases, contralateral breast cancer, other second primary cancer, and death. Baseline tumor-related characteristics, treatment-related characteristics, sociodemographic and biochemical data were analyzed using Cox proportional hazards analysis. Results: The median DFS was 45 months (range, 2 to 225 months). Breast cancer recurred in 86 patients (15.4%), of whom 10 had local recurrence, 10 had regional recurrence, 17 had contralateral breast cancer, 29 had distant metastases, 10 had second primary cancer, and 10 patients died. Multivariate forward stepwise Cox regression analysis showed that AJCC stage III, Ki67 ≥14%, albumin, platelet, and red cell distribution width-standard deviation (RDW-SD) were predictors of worse DFS. In addition, the effects of albumin, platelet, and RDW-SD on disease recurrence were confirmed by structural equation model (SEM) analysis. Conclusion: In addition to the traditional predictors of worse DFS such as AJCC stage III and Ki67 ≥14%, lower pretreatment circulating albumin, higher pretreatment circulating platelet count and RDW-SD could significantly predict worse DFS in this study, and SEM delineated possible causal pathways and inter-relationships of albumin, platelet, and RDW-SD contributing to the disease recurrence among Chinese women with breast cancer.
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BACKGROUND: Inflammation has been associated with vascular access (VA) dysfunction. The adipocytokine leptin can directly induce pro-inflammatory T helper 1 immune responses and the pathogenesis of chronic inflammation. We explored the association between plasma leptin and VA dysfunction in patients on maintenance hemodialysis (HEMO). METHODS: A total of 344 consecutive patients who received anastomosis for VA at a single HEMO center between June 1, 2010 and December 31, 2021 were screened. Of these patients, 267 met the inclusion criteria and were included. ELISA was used to measure circulating levels of leptin. RESULTS: The VA dysfunction group had a higher leptin level than the patent VA group. A higher concentration of leptin was independently and significantly associated with an elevated risk of VA dysfunction. Multiple logistic regression analysis showed that leptin, female sex, and hypertension were independently associated with VA dysfunction, even after adjusting for known biomarkers. We then evaluated the ability of leptin, female sex, and hypertension to predict the risk of VA dysfunction, and the area under the curve (AUC) for leptin was 0.626 (p = 0.0001). When leptin, female sex, and hypertension were added to this multivariate model, the AUC increased to 0.679 (p = 0.001) for leptin and hypertension, and 0.690 for leptin, hypertension, and female sex (p = 0.004). In addition, plasma leptin levels were associated with sex, body mass index, and hemoglobin. CONCLUSIONS: In addition to the association between leptin and VA dysfunction, hypertension and female sex independently predicted VA dysfunction in patients with HEMO.
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Hipertensão , Leptina , Humanos , Feminino , Diálise Renal/efeitos adversos , Biomarcadores , Hipertensão/complicações , Inflamação/complicações , Índice de Massa CorporalRESUMO
BACKGROUND: Mannose-binding lectin (MBL) has been associated with cardiovascular disease and its complications, the progression of diabetic nephropathy, and complement-mediated renal interstitial injury. However, the relationship between plasma MBL concentration with both heart failure and renal function is unclear. In this study, we examined associations of plasma MBL with both renal function and heart failure in patients with stable coronary artery disease (CAD). METHODS: We enrolled 348 consecutive stable CAD patients and used ELISA to evaluate plasma concentrations of MBL. Renal function was classified into KDIGO G1, G2 and G3a-G4 groups according to the eGFR of ≥ 90, 60-89 and 15-59, ml/min/1.73 m2, respectively. Patients with a left ventricular ejection fraction (LVEF) ≤ 40 % were classified to have heart failure. RESULTS: A significant positive association was found between MBL with diabetes mellitus, current smoker, blood urea nitrogen, creatinine, and brain natriuretic peptide, and a significant negative association was found between MBL with eGFR and LVEF. KDIGO stage G3a-G4 and heart failure increased along with tertiles of MBL (p for trend < 0.05). Multivariate analysis showed that compared to the patients with a low MBL concentration, the odds ratios of having KDIGO stage G3a-G4 were 1.89 (1.01-3.55) times and 2.37 (1.25-4.59) times higher for those with medium and high MBL concentrations. Furthermore, compared to the patients with a low MBL concentration, the OR of having heart failure were 1.97 (1.01-3.93) times higher for those with high MBL concentrations. Moreover, multivariate analysis showed an independent association between plasma MBL concentration with both KDIGO stage G3a-G4 and heart failure (LVEF < 40 %). In addition, the effect of MBL on both LVEF and eGFR was confirmed by structural equation model analysis. CONCLUSION: There are associations between circulating MBL concentration with both heart failure and renal function in stable CAD patients, suggesting that increased plasma MBL may contribute to the pathogenesis of both chronic kidney disease and heart failure.
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Doenças Cardiovasculares , Doença da Artéria Coronariana , Insuficiência Cardíaca , Humanos , Doença da Artéria Coronariana/complicações , Volume Sistólico , Função Ventricular Esquerda , Insuficiência Cardíaca/complicaçõesRESUMO
Background: Ficolin-3 (FCN3) is a well-known circulating pattern recognition molecule which plays a role in host immune responses to cancer via activation of the lectin complement pathway. Nevertheless, the clinical significance of FCN3 in patients with hepatocellular carcinoma (HCC) is unclear. Methods: Eighty-seven HCC patients who received hepatectomy at our hospital were included. Immunohistochemical staining was used to assess the FCN3 expression in both tumorous and non-tumorous tissues from the patients, who were classified into high and low expression groups. Differences in clinicopathological characteristics between the two groups were then analyzed. Results: Survival was significantly associated with FCN3 immunohistochemical score (p for trend = 0.048). Kaplan-Meier analysis revealed a higher overall survival rate in the patients with a high FCN3 expression than in those with a low FCN3 expression (p=0.031). A high FCN3 expression in tumor tissue was independently associated with better overall survival (p=0.042). However, multivariate analysis showed that FCN3 expression was not an independent risk factor for overall survival. Conclusion: Our findings suggest that FCN3 is significantly related to the prognosis of HCC. FCN3 may be a prognostic marker in patients with HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/metabolismo , Estimativa de Kaplan-Meier , Lectinas/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/metabolismo , Prognóstico , FicolinasRESUMO
Introduction: The prevalence of cardiovascular disease (CVD) and CVD-related deaths in patients with schizophrenia is high. An elevated risk of CVD has been associated with low heart rate variability (HRV). There is increasing evidence that fatty acid-binding protein (FABP)3 and FABP4 play roles in the development and progression of CVD. This study aimed to explore the association of circulating FABP3/FABP4 levels with HRV in patients with chronic schizophrenia. Methods: We included 265 consecutive patients with chronic schizophrenia who attended a disease management program. We used an enzyme-linked immunosorbent assay for the measurement of plasma concentrations of FABP3 and FABP4. Standard HRV was recorded at baseline following a standard protocol. Mean high- and low-frequency (HF/LF) HRV values were analyzed by tertile of FABP3 and FABP4 using one-way analysis of variance, and linear regression analysis was performed to assess trends. Results: A positive association between FABP3 and creatinine was found in multiple regression analysis. In addition, negative associations between levels of hematocrit, hemoglobin, HF HRV, and estimated glomerular filtration rate (eGFR) with FABP3 were also found. Moreover, positive associations between FABP4 with body mass index, diabetes mellitus, hypertension, systolic blood pressure, low-density lipoprotein-cholesterol, triglycerides, creatinine, and FABP3 were found. Furthermore, negative associations between levels of high-density lipoprotein-cholesterol, eGFR, and HF HRV with FABP4 were found. We also found a significant inverse association between FABP3 and HF HRV (p for trend = 0.008), and significant inverse associations between FABP4 with HF and LF HRV (p for trend = 0.007 and 0.017, respectively). Discussion: Together, this suggests that elevated levels of FABP3 and FABP4 may be linked to health problems related to CVD in patients with chronic schizophrenia.
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Doenças Cardiovasculares , Esquizofrenia , Humanos , Frequência Cardíaca , Esquizofrenia/complicações , Creatinina , Proteínas de Ligação a Ácido Graxo , Colesterol , Proteína 3 Ligante de Ácido GraxoRESUMO
BACKGROUND: Liver-type fatty acid-binding protein (L-FABP) is widely expressed in hepatocytes and plays a role in lipid metabolism. It has been demonstrated to be overexpressed in different types of cancer; however, few studies have investigated the association between L-FABP and breast cancer. The aim of this study was to assess the association between plasma concentrations of L-FABP in breast cancer patients and the expression of L-FABP in breast cancer tissue. METHOD: A total of 196 patients with breast cancer and 57 age-matched control subjects were studied. Plasma L-FABP concentrations were measured using ELISA in both groups. The expression of L-FABP in breast cancer tissue was examined using immunohistochemistry. RESULT: The patients had higher plasma L-FABP levels than the controls (7.6 ng/mL (interquartile range 5.2-12.1) vs. 6.3 ng/mL (interquartile range 5.3-8.5), p = 0.008). Multiple logistic regression analysis showed an independent association between L-FABP and breast cancer, even after adjusting for known biomarkers. Moreover, the rates of pathologic stage T2+T3+T4, clinical stage III, positive HER-2 receptor status, and negative estrogen receptor status were significantly higher in the patients with an L-FABP level greater than the median. Furthermore, the L-FABP level gradually increased with the increasing stage. In addition, L-FABP was detected in the cytoplasm, nuclear, or both cytoplasm and nuclear of all breast cancer tissue examined, not in the normal tissue. CONCLUSIONS: Plasma L-FABP levels were significantly higher in the patients with breast cancer than in the controls. In addition, L-FABP was expressed in breast cancer tissue, which suggests that L-FABP may be involved in the pathogenesis of breast cancer.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/metabolismo , Proteínas de Ligação a Ácido Graxo , Biomarcadores , Fígado/metabolismoRESUMO
BACKGROUND: Intrinsic capacity (IC) is a novel concept focusing on normal and healthy aging. The effect of IC on the risk of chronic kidney disease (CKD) according to KDIGO category in older type 2 diabetes mellitus (T2DM) patients has rarely been studied. We investigated whether a decline in IC is associated with the risk of CKD according to KDIGO 2012 categories. METHODS: This is a cross-sectional study. The exposure variables (IC score and body mass index) and outcome variable (KDIGO categories of the risk of CKD) were collected at the same timepoint. A total of 2482 older subjects with T2DM managed through a disease care program were enrolled. The five domains of IC, namely locomotion, cognition, vitality, sensory, and psychological capacity were assessed. Based on these domains, the IC composite score was calculated. CKD risk was classified according to the KDIGO 2012 CKD definition. Univariate and multivariate analyses were used to assess the association between IC score and KDIGO categories of risk of CKD. RESULTS: The KDIGO CKD risk category increased in parallel with IC score (p for trend < 0.0001). In multivariate analysis, compared to those with an IC score 0, the odds ratio of having a KDIGO moderately increased to very high risk category of CKD was 1.76 (1.31-2.37) times higher for those with an IC score of 2-5. Furthermore, an increased IC score was associated with a higher prevalence of moderate and severe obesity. Moreover, there was a synergistic interaction between IC score and obesity on the KDIGO moderately increased to very high risk category of CKD (synergy index = 1.683; 95% CI 0.630-3.628), and the proportion of the KDIGO moderately increased to very high risk category of CKD caused by this interaction was 25.6% (attributable proportion of interaction = 0.256). CONCLUSIONS: Our findings indicate that IC score may be closely related to the KDIGO moderately increased to very high risk category of CKD. In addition, there may be a synergistic interaction between IC score and obesity, and this synergistic interaction may increase the KDIGO CKD risk stage.
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Introduction: Of all psychiatric disorders, schizophrenia is associated with the highest risk of all-cause mortality. This study aimed to investigate independent risk factors for all-cause mortality in patients with chronic schizophrenia. In addition, the possible causal inter-relationships among these independent risk factors and all-cause mortality were also explored. Methods: We conducted an analysis of 1,126 patients with chronic schizophrenia from our psychiatric department from April 2003 to August 2022, and retrospectively reviewed their medical records. The study endpoint was all-cause mortality. Baseline clinical characteristics including sociodemographic data, biochemical data, lifestyle factors, comorbidities and antipsychotic treatment were examined with Cox proportional hazards analysis. Results: The all-cause mortality rate was 3.9% (44 patients). Multivariate Cox regression analysis revealed that several factors were independently associated with all-cause mortality, including diabetes mellitus (DM), hypertension, heart failure, gastroesophageal reflux disease (GERD), peptic ulcer disease, ileus, underweight, fasting glucose, triglycerides, albumin, and hemoglobin. Structural equation modeling (SEM) analysis revealed that several factors had statistically significant direct effects on all-cause mortality. Heart failure, hypertension, underweight, age at onset, and ileus showed positive direct effects, while albumin and hemoglobin demonstrated negative direct effects. In addition, several factors had indirect effects on all-cause mortality. GERD indirectly affected all-cause mortality through ileus, and peptic ulcer disease had indirect effects through albumin and ileus. Ileus, underweight, DM, and hypertension also exhibited indirect effects through various pathways involving albumin, hemoglobin, and heart failure. Overall, the final model, which included these factors, explained 13% of the variability in all-cause mortality. Discussion: These results collectively suggest that the presence of DM, hypertension, heart failure, GERD, peptic ulcer disease, ileus, and underweight, along with lower levels of albumin or hemoglobin, were independently associated with all-cause mortality. The SEM analysis further revealed potential causal pathways and inter-relationships among these risk factors contributing to all-cause mortality in patients with chronic schizophrenia.
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OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) has been associated with an increased risks of corrected QT (QTc) prolongation and left ventricular hypertrophy (LVH), both of which are associated with the development of cardiovascular disease. Rotating night shift work and a higher risk of incident NAFLD have been reported in male steelworkers. This study aimed to investigate the association of the severity of NAFLD with a prolonged QTc interval and LVH in a large cohort of Chinese male steelworkers. METHODS: We examined baseline data of 2998 male steel workers aged 26 to 71 years at two plants. All workers at both plants received regular health assessments, including 12-lead ECG and echocardiography. Abdominal ultrasonography was performed to evaluate the severity of NAFLD. QTc prolongation was defined as follows: normal ≤ 430 ms, borderline 431-450 ms, and abnormal ≥ 451 ms. LVH was defined as a left ventricular mass index (LVMI) >131 g/m2. Associations of NAFLD with an abnormal QTc interval and LVH were examined using univariate and multivariate analyses. RESULTS: The QTc interval and the LVMI were significantly correlated with the NAFLD fibrosis score, and the severity of NAFLD was correlated with an abnormal QTc interval and LVH (p for trend < 0.05). Multivariate analysis showed that in comparison to the workers without NAFLD, the odds ratios of having an abnormal QTc interval and LVH were 2.54 (95% CI: 1.22-5.39, p = 0.013) times and 2.23 (95% CI: 1.02-5.01, p = 0.044) times higher in the workers with moderate/severe NAFLD. CONCLUSIONS: NAFLD may be closely associated with the risks of an abnormal QTc interval and LVH, suggesting that regular electrocardiogram and echocardiogram monitoring could be used to evaluate the risk of arrhythmia and LVH in male steelworkers with NAFLD.
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Síndrome do QT Longo , Hepatopatia Gordurosa não Alcoólica , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/epidemiologia , Hipertrofia Ventricular Esquerda/etiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Eletrocardiografia , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/etiologia , China/epidemiologiaRESUMO
The progression of neurodegenerative diseases is associated with oxidative stress and inflammatory responses. Abelmoschus manihot L. flower (AMf) has been shown to possess excellent antioxidant and anti-inflammatory activities. This study investigated the protective effect of ethanolic extract (AME), water extract (AMW) and supercritical extract (AMS) of AMf on PC12 neuronal cells under hydrogen peroxide (H2O2) stimulation. This study also explored the molecular mechanism underlying the protective effect of AME, which was the best among the three extracts. The experimental results showed that even at a concentration of 500 µg/mL, neither AME nor AMW showed toxic effects on PC12 cells, while AMS caused about 10% cell death. AME has the most protective effect on apoptosis of PC12 cells stimulated with 0.5 mM H2O2. This is evident by the finding when PC12 cells were treated with 500 µg/mL AME; the viability was restored from 58.7% to 80.6% in the Treatment mode (p < 0.001) and from 59.1% to 98.1% in the Prevention mode (p < 0.001). Under the stimulation of H2O2, AME significantly up-regulated the expression of antioxidant enzymes, such as catalase, glutathione peroxidase and superoxide dismutase; promoted the production of the intracellular antioxidant; reduced glutathione; and reduced ROS generation in PC12 cells. When the acute inflammation was induced under the H2O2 stimulation, AME significantly down-regulated the pro-inflammatory cytokines and mediators (e.g., TNF-α, IL-1ß, IL-6, COX-2 and iNOS). AME pretreatment could also greatly promote the production of nucleotide excision repair (NER)-related proteins, which were down-regulated by H2O2. This finding indicates that AME could repair DNA damage caused by oxidative stress. Results from this study demonstrate that AME has the potential to delay the onset and progression of oxidative stress-induced neurodegenerative diseases.
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Background: Obesity and cognitive function decline are independent risk factors for chronic kidney disease (CKD). However, few studies have examined the combined effects of obesity status and cognitive function on change in CKD risk. We aimed to evaluate the association between obesity status, cognitive function and CKD risk change in patients with type 2 diabetes mellitus (T2DM). Methods: Data on 3399 T2DM patients were extracted from a diabetes disease management program between 2006 and 2018. Univariate and multivariate analyses were used to assess the association between obesity, cognitive decline, and CKD risk change. Three indexes, including the relative excess risk of interaction (RERI), attributable proportion of interaction (API), and synergy index (SI), were used to analyze interactions. CKD risk was classified according to the KDIGO 2012 CKD definition. Results: In multivariate analysis, the hazard ratio (HR, 95%Cis) for CKD risk progression was 1.34 (1.12-1.61) times higher in the moderate and severely obese patients compared with the normal weight patients, and 1.34 (1.06-1.67) times higher in the patients with a Mini-Mental State Examination (MMSE) score ≤18 compared to those with an MMSE score ≥24. There was a synergistic interaction between moderate and severe obesity and MMSE score ≤18 on CKD risk progression (SI=4.461; 95% CI: 1.998-9.962), and the proportion of CKD risk progression caused by this interaction was 52.7% (API=0.527; 95% CI: 0.295-0.759). However, normal weight and MMSE score ≥24 were not beneficial on CKD risk improvement in the patients with a moderate risk and very high-risk stage of CKD. Conclusion: There may be a synergistic interaction between obesity and cognitive function decline, and the synergistic interaction may increase the risk of CKD progression.
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Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Cognição , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Progressão da Doença , Taxa de Filtração Glomerular , Humanos , Obesidade/complicações , Obesidade/epidemiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Growth differentiation factor 1 (GDF1) is a member of the transforming growth factor-ß (TGF-ß) superfamily and a protective mediator against the development of post-infarction cardiac remodeling by negatively regulating MEK-ERK1/2 and Smad signaling pathways in the heart. The TGF-ß/SMAD pathway has been shown to play a key role in the development of hepatic fibrosis. In addition, fatty liver disease has been associated with reduced MEK/ERK1/2 signaling. However, no previous study has investigated the association between GDF1 and liver fibrosis. Therefore, the aim of this study was to investigate the association between plasma GDF1 and liver fibrosis in patients with stable angina. METHODS: We included 327 consecutive patients with stable angina. ELISA was used to measure circulating levels of GDF1, and the fibrosis-4 index was used to assess liver fibrosis. RESULTS: The advanced liver fibrosis group had lower median plasma GDF1 levels than those with minimal liver fibrosis. There was a significant negative association between GDF1 plasma level and fibrosis-4 index (r = -0.135, p = 0.019). A lower concentration of GDF1 was significantly and independently associated with an increased risk of liver fibrosis when concentration was analyzed as a continuous variable and by tertile. In addition, fibrosis-4 index, aspartate aminotransferase (AST)-to-platelet ratio index, and AST/alanine aminotransferase ratio were significantly associated with GDF1 concentration. CONCLUSIONS: Our results indicated an association between low plasma GDF1 and liver fibrosis in the enrolled patients. Further investigations into the role of plasma GDF1 in the pathogenesis of liver fibrosis are warranted.
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Angina Estável , Fator 1 de Diferenciação de Crescimento , Cirrose Hepática , Humanos , Fator 1 de Diferenciação de Crescimento/sangue , Fígado/metabolismo , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
BACKGROUND: Fibroblast growth factor 21 (FGF21) is produced by cardiac cells, may acts in an autocrine manner, and was suggested to has a cardioprotective role in atherosclerosis. Wide QRS complex and heart rate-corrected QT interval (QTc interval) prolongation are associated to dangerous ventricular arrhythmias and cardiovascular disease mortality. Yet, the role of FGF21 in cardiac arrhythmia has never been studied. The aim of the study was to investigate the relationship between plasma FGF21 and the QRS duration and QTc interval in patients with stable angina. METHODS: Three hundred twenty-one consecutive stable angina patients were investigated. Plasma FGF21 was measured through ELISA, and each subject underwent 12-lead electrocardiography. RESULTS: FGF21 plasma levels were positively associated with the QRS duration (ß = 0.190, P = 0.001) and QTc interval (ß = 0.277, P < 0.0001). With increasing FGF21 tertiles, the patients had higher frequencies of wide QRS complex and prolonged QTc interval. After adjusting for patients' anthropometric parameters, the corresponding odd ratios (ORs) for wide QRS complex of the medium and high of FGF21 versus the low of FGF21 were 1.39 (95% CI 0.51-3.90) and 4.41 (95% CI 1.84-11.59), respectively, and p for trend was 0.001. Furthermore, multiple logistic regression analysis also showed the corresponding odd ratios (ORs) for prolonged QTc interval of the medium and high of FGF21 versus the low of FGF21 were 1.02 (95% CI 0.53-1.78) and 1.93 (95% CI 1.04-3.60) respectively with the p for trend of 0.037. In addition, age- and sex-adjusted FGF21 levels were positively associated with fasting glucose, HbA1c, creatinine, and adiponectin, but negatively associated with albumin, and the estimated glomerular filtration rate. CONCLUSIONS: This study indicates that plasma FGF21 is associated with wide QRS complex and prolonged corrected QT interval in stable angina patients, further study is required to investigate the role of plasma FGF21 for the underlying pathogenesis.
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Angina Estável , Fatores de Crescimento de Fibroblastos , Síndrome do QT Longo , Humanos , Adiponectina , Albuminas , Arritmias Cardíacas , Creatinina , Eletrocardiografia , Eletrólitos , Fatores de Crescimento de Fibroblastos/metabolismo , Glucose , Hemoglobinas GlicadasRESUMO
A urine albumin/creatinine ratio (UACR) <30 mg/g is considered to be normal, while increased risk of incident hypertension and cardiovascular disease mortality in subjects with high normal UACR level had been observed. However, a mild elevated but normal UACR level was associated with the risk of initiating chronic kidney disease (CKD) is uncertain. We investigated whether higher normal UACR is associated with the risk of developing CKD. A total of 4821 subjects with type 2 diabetes mellitus (T2DM), an estimated glomerular filtration rate >60 ml/min/1.73 m2 and UACR <30 mg/g enrolled in a diabetes disease management program between 2006 and 2020 were studied. The optimal cutoff point for baseline UACR as a predictor for progression to CKD according to the 2012 KDIGO definition was calculated using receiving operating characteristic curve analysis. After a mean of 4.9 years follow-up, the CKD risk progression increased in parallel with the quartiles of baseline UACR <30 mg/g (p for trend <0.0001). UACR cutoff points of 8.44 mg/g overall, 10.59 mg/g in males and 8.15 mg/g in females were associated with the risk of CKD progression. In multivariate Cox regression analysis, the hazard ratios for the association between UACR (>8.44 mg/g, >10.9 mg/g, >8.15 mg/g in overall, male, and female patients, respectively) and the risk of CKD progression were significant. This study demonstrated that a cutoff UACR value of >10 mg/g could significantly predict the cumulative incidence and progression of CKD in patients with T2DM.
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Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Albuminas , Albuminúria/complicações , Albuminúria/epidemiologia , Creatinina , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Masculino , Insuficiência Renal Crônica/complicaçõesRESUMO
The flower of Abelmoschus manihot L. is mainly used for the treatment of chronic kidney diseases, and has been reported to have bioactivities such as antioxidant, anti-inflammatory, antiviral, and antidepressant activities. This study used wild-type adult zebrafish as an animal model to elucidate the potential bioactivity of A. manihot flower ethanol extract (AME) in enhancing their sexual and reproductive functions. Zebrafish were fed AME twice a day at doses of 0.2%, 1%, and 10% for 28 days, and were then given the normal feed for an additional 14 days. The hormone 17-ß estradiol was used as the positive control. Sexual behavioral parameters such as the number of times males chased female fish, the production of fertilized eggs, and the hatching rate of the fertilized eggs were recorded at days 0.33, 7, 14, 21, 28, and 42. The expression levels of sex-related genesincluding lhcgr, ar, cyp19a1a, and cyp19a1bwere also examined. The results showed that the chasing number, fertilized egg production, and hatching rate were all increased with the increase in the AME treatment dose and treatment time. After feeding with 1% and 10% AME for 28 days, the chasing number in the treated group as compared to the control group increased by 1.52 times and 1.64 times, respectively; the yield of fertilized eggs increased by 1.59 times and 2.31 times, respectively; and the hatching rate increased by 1.26 times and 1.69 times, respectively. All three parameters exhibited strong linear correlations with one another (p < 0.001). The expression of all four genes was also upregulated with increasing AME dose and treatment duration. When feeding with 0.2%, 1%, and 10% AME for 28 days, the four sex-related genes were upregulated at ranges of 1.79−2.08-fold, 2.74−3.73-fold, and 3.30−4.66-fold, respectively. Furthermore, the effect of AME was persistent, as the promotion effect continued after the treatment was stopped for at least two weeks. The present findings suggest that AME can enhance the endocrine system and may improve libido and reproductive performance in zebrafish.
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Abelmoschus , Animais , Feminino , Flores , Masculino , Extratos Vegetais/farmacologia , Excitação Sexual , Peixe-ZebraRESUMO
Background: Fatty acid-binding protein 3 (FABP3) located in renal mesangial and distal tubular cells, and had been shown to be a sensitive marker of renal injury, potentially be a mediator in pathogenesis of chronic kidney disease (CKD). Our previous study revealed that plasma FABP1 and FABP2 were independently associated with CKD, however, little is known about the relationship between plasma FABP3 level and CKD. The aim of this study was therefore to evaluate the plasma levels of FABP3 at different stages of estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 334 subjects with T2DM who enrolled in a disease management program were included in this study and stratified according to eGFR. Plasma FABP3 concentrations were measured by an enzyme-linked immunosorbent assay. Results: FABP3 levels increased in parallel with the eGFR level. Increasing concentrations of FABP3 were independently and significantly associated with eGFR stage G2-G4. Age- and sex-adjusted FABP3 levels were positively associated with uric acid, urinary albumin-to-creatinine ratio, FABP1, FABP2, and fatty liver index, but negatively associated with eGFR and hemoglobin. Conclusion: Our results indicate that circulating FABP3 in patients with T2DM is associated with eGFR, which suggests that increased plasma FABP3 may be involved in the pathogenesis of CKD.
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Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/diagnóstico , Proteína 3 Ligante de Ácido Graxo/sangue , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/diagnóstico , Biomarcadores/sangue , Estudos Transversais , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Background: Neutrophil gelatinaseassociated lipocalin (NGAL), also known as lipocalin 2, siderocalin, 24p3 or uterocalin, plays a key role in inflammation and in different types of cancer. In this study, we investigated whether plasma NGAL levels were altered in patients with breast cancer. The relationship between plasma NGAL levels and pretreatment hematologic profile was also explored. Methods: Plasma NGAL concentrations were measured using ELISA in breast cancer patients and control subjects. A total of 75 patients with breast cancer and 65 age- and body mass index-matched control subjects were studied. All of the study subjects were female. Results: Plasma NGAL level was found to be elevated in the patients with breast cancer compared to the control subjects (94.3 ng/mL (interquartile range 39.3-207.6) vs. 55.0 ng/mL (interquartile range 25.8-124.7), p = 0.007). Multiple logistic regression analysis revealed that NGAL was independently associated with breast cancer, even after adjusting for known biomarkers. Furthermore, NGAL level was elevated in the breast cancer patients who were negative progesterone receptor status, had a histologic grade ≥ 2, clinical stage III, and pathologic stage T2+T3+T4. In addition, NGAL level was significantly correlated with white blood cell (WBC) count, monocyte count, neutrophil count, and platelet count (all p < 0.01). Moreover, WBC count, neutrophil count, monocyte count, lymphocyte count, platelet count, and NGAL level gradually increased as the stage progressed. Conclusions: Increased plasma NGAL levels were associated with breast cancer independently of risk factors, and were correlated with inflammatory biomarkers. These results suggest that NGAL may act through inflammatory reactions to play an important role in the pathogenesis of breast cancer.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/diagnóstico , Lipocalina-2/sangue , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/sangue , Neoplasias da Mama/imunologia , Estudos de Casos e Controles , Feminino , Voluntários Saudáveis , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/imunologia , Lipocalina-2/metabolismo , Pessoa de Meia-Idade , Transdução de Sinais/imunologiaRESUMO
Objectives: Increased triglyceride glucose (TyG) index appears to be linked to carotid and coronary atherosclerosis and calcifications and possesses an elevated future risk of developing cardiovascular disease. Corrected QT (QTc) interval prolongation is associated with ventricular arrhythmias and sudden cardiac death, and a high prevalence of prolonged QTc interval was previously reported in blue-collar workers. The purpose of this study was to find the possible causal inter-relationship between TyG index and QTc interval in a large population of Chinese male steelworkers. Methods: A total of 3189 male workers from two steel plants were enrolled. They responded to a cross-sectional questionnaire on basic attributes and lifestyle, including sleep patterns. All workers in the two plants underwent periodic health checkups, including twelve-lead electrocardiography. Structural equation modeling (SEM) was used to assess the direct and indirect effects of TyG index on QTc interval. Results: With increasing TyG index tertile, the male steelworkers had an increased QTc interval. Applying multivariate analysis, TyG index was associated independently with the odds of QTc prolongation (adjusted odds ratio = 2.73, 95% confidence interval = 1.39-5.24, p = 0.004). SEM revealed that TyG index, hypertension, obesity, lifestyle, white blood cell (WBC) count, and liver function had statistically significant direct effects on QTc interval. Furthermore, TyG index also had an indirect effect on QTc interval through hypertension, obesity, WBC count, and liver function. Moreover, lifestyle had an indirect effect on QTc interval through TyG index. The final model explained 14% of the variability in QTc interval. Conclusions: An increased TyG index was associated with QTc interval prolongation in this study, and SEM delineated possible causal pathways and inter-relationships of the risk factors contributing to the occurrence of QTc prolongation among Chinese male steelworkers.
Assuntos
Glucose , Síndrome do QT Longo , China/epidemiologia , Estudos Transversais , Eletrocardiografia , Humanos , Masculino , Fatores de Risco , TriglicerídeosRESUMO
Background: Higher concentrations of plasma fatty acid-binding protein 3 (FABP3) play a role in the development of cardiovascular events, cerebrovascular deaths, and acute heart failure. However, little is known about the relationship between plasma FABP3 level and prolonged QT interval and reduced ejection fraction (EF). This study aimed to investigate the relationship between plasma FABP3 level and prolonged corrected QT (QTc) interval and reduced EF in patients with stable angina. Inflammatory cytokine and adipocytokine levels were also measured to investigate their associations with plasma FABP3. Methods: We evaluated 249 consecutive patients with stable angina. Circulating levels of FABP3 were measured by ELISA. In addition, 12-lead ECG and echocardiography recordings were obtained from each patient. Results: Multiple regression analysis showed that high-density lipoprotein cholesterol, high sensitivity C-reactive protein (hs-CRP), white blood cell (WBC) count, visfatin, adiponectin, FABP4, heart rate, QTc interval, left atrial diameter, left ventricular mass index, end-systolic volume, end-systolic volume index, fractional shortening, and EF were independently associated with FABP3 (all p<0.05). Patients with an abnormal QTc interval had a higher median plasma FABP3 level than those with a borderline and normal QTc interval. With increasing FABP3 tertiles, the patients had higher frequencies of abnormal QTc interval, left ventricular systolic dysfunction, and all-cause mortality, incrementally lower EF, higher WBC count, and higher levels of hs-CRP, visfatin, adiponectin, and FABP4. Conclusion: This study indicates that plasma FABP3 may act as a surrogate parameter of prolonged QTc interval and reduced EF in patients with stable angina, partially through the effects of inflammation or cardiomyocyte injury. Further studies are required to elucidate whether plasma FABP3 plays a role in the pathogenesis of QTc prolongation and reduced EF.