Tissue Expression of Growth Differentiation Factor 11 in Patients with Breast Cancer.

Protein growth differentiation factor 11 (GDF11) plays crucial roles in cellular processes, including differentiation and development; however, its clinical relevance in breast cancer patients is poorly understood. We enrolled 68 breast cancer patients who underwent surgery at our hospital and assessed the expression of GDF11 in tumorous, ductal carcinoma in situ (DCIS), and non-tumorous tissues using immunohistochemical staining, with interpretation based on histochemical scoring (H-score). Our results indicated higher GDF11 expressions in DCIS and normal tissues compared to tumorous tissues. In addition, the GDF11 H-score was lower in the patients with a tumor size ≥ 2 cm, pathologic T3 + T4 stages, AJCC III-IV stages, Ki67 ≥ 14% status, HER2-negative, and specific molecular tumor subtypes. Notably, the patients with triple-negative breast cancer exhibited a loss of GDF11 expression. Spearman correlation analysis revealed associations between GDF11 expression and various clinicopathological characteristics, including tumor size, stage, Ki67, and molecular subtypes. Furthermore, GDF11 expression was positively correlated with mean corpuscular hemoglobin concentration and negatively correlated with neutrophil count, as well as standard deviation and coefficient of variation of red cell distribution width. These findings suggest that a decreased GDF11 expression may play a role in breast cancer pathogenesis.

Transcription factor 21 rs12190287 polymorphism is related to stable angina and ST elevation myocardial infarction in a Chinese Population.

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.

Sleep disturbances, glycaemic control, stress, and coping among diabetic patients: A structural equation modelling approach.

BACKGROUND: Sleep disturbances are more prevalent in diabetic patients than in the general population and may consequently be comorbid with hyperglycaemia. OBJECTIVE: The two study aims were to (1) verify the factors associated with sleep disturbances and glycaemic control and (2) further understand the mediation effects of coping and social support in the relationship among stress, sleep disturbances, and glycaemic control. METHODS: A cross-sectional study design was used. Data were collected at two metabolic clinics in southern Taiwan. The study recruited 210 patients with type II diabetes mellitus who were aged 20 years or above. Demographic information and data on stress, coping, social support, sleep disturbances, and glycaemic control were collected. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality, and PSQI scores >5 were considered to indicate sleep disturbances. Structural equation modelling (SEM) approaches were employed to analyse the path association for sleep disturbances in diabetic patients. RESULTS: The mean age of the 210 participants was 61.43 (standard deviation, SD 11.41) years old, and 71.9 % reported sleep disturbances. The final path model had acceptable model fit indices. Stress perception was divided into stress perceived positively and negatively. Stress perceived positively was associated with coping (ß = 0.46, p < .01) and social support (ß = 0.31, p < .01), whereas stress perceived negatively was significantly associated with sleep disturbances (ß = 0.40, p < .001). CONCLUSIONS: The study shows that sleep quality is essential to glycaemic control, and stress perceived negatively might play a critical role to sleep quality.

Inter-relationships of risk factors and pathways associated with all-cause mortality in patients with chronic schizophrenia.

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.

Application of Grey Relational Analysis to Predict Dementia Tendency by Cognitive Function, Sleep Disturbances, and Health Conditions of Diabetic Patients.

Background: The number of elderly diabetic patients has been increasing recently, and these patients have a higher morbidity of dementia than those without diabetes. Diabetes is associated with an increased risk for the development of dementia in elderly individuals, which is a serious health problem. Objectives: The primary aim was to examine whether diabetes is a risk factor for dementia among elderly individuals. The secondary aim was to apply grey theory to integrate the results and how they relate to cognitive impairments in elderly diabetic patients and to predict which participants are at high risk of developing dementia. Methods: Two hundred and twenty patients aged 50 years or older who were diagnosed with diabetes mellitus were recruited. Information on demographics, disease characteristics, activities of daily living, Mini Mental State Examination, sleep quality, depressive symptoms, and health-related quality of life was collected via questionnaires. The grey relational analysis approach was applied to evaluate the relationship between the results and health outcomes. Results: A total of 13.6% of participants had cognitive disturbances, of whom 1.4% had severe cognitive dysfunction. However, with regard to sleep disorders, 56.4% had sleep disturbances of varying degrees from light to severe. Further investigation is needed to address this problem. A higher prevalence of sleep disturbances among diabetic patients translates to a higher degree of depressive symptoms and a worse physical and mental health-related quality of life. Furthermore, based on the grey relational analysis, the grey relation coefficient varies from 0.6217~0.7540. Among the subjects, Participant 101 had the highest value, suggesting a need for immediate medical care. In this study, we observed that 20% of the total participants, for whom the grey relation coefficient was 0.6730, needed further and immediate medical care.

Interactive effect of obesity and cognitive function decline on the risk of chronic kidney disease progression in patients with type 2 diabetes mellitus: a 9.1-year cohort study.

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.

Low plasma growth/differentiation factor 1 levels are associated with liver fibrosis in patients with stable angina.

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.

Fibroblast growth factor 21 is associated with widening QRS complex and prolonged corrected QT interval in patients with stable angina.

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.

The Lower Limit of Reference of Urinary Albumin/Creatinine Ratio and the Risk of Chronic Kidney Disease Progression in Patients With Type 2 Diabetes Mellitus.

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.

Association of plasma fatty acid-binding protein 3 with estimated glomerular filtration rate in patients with type 2 diabetes mellitus.

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.

Elevated plasma level of neutrophil gelatinase-associated lipocalin (NGAL) in patients with breast cancer.

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.

Elevated plasma fatty acid-binding protein 3 is related to prolonged corrected QT interval and reduced ejection fraction in patients with stable angina.

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.

Association between Triglyceride Glucose Index and Corrected QT Prolongation in Chinese Male Steelworkers.

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.

Associations among total p-cresylsulfate, indoxyl sulfate and hippuric acid levels with hemodialysis quality indicators in maintenance hemodialysis patients.

BACKGROUND: Total p-cresylsulfate (PCS), indoxyl sulfate (IS) and hippuric acid (HA) are harmful uremic toxins known to be elevated in patients with uremia. Serum total PCS, IS and HA levels have been associated with coronary atherosclerosis, left ventricular hypertrophy, metabolic acidosis, neurological symptoms, and accelerated renal damage associated with chronic kidney disease; however, no study has examined the effect of total PCS, IS and HA on hemodialysis (HD) quality indicators. The aim of this study was to examine associations among total PCS, IS and HA with HD quality indicators in patients undergoing HD treatment. METHODS: This study included 264 consecutive patients at a single HD center who assessed using previously demonstrated HD quality indicators including anemia, bone-mineral metabolism, dialysis dose, cardiovascular risk, and middle molecule removal area. Serum HA was measured using a capillary electrophoresis method. Serum total PCS and IS concentrations were measured using an Ultra Performance LC System. RESULTS: Multiple regression analysis showed that sex, potassium, systolic blood pressure (SBP), average BP, ß2-microglobulin, and creatinine were independently positively associated with IS level, and that age, total cholesterol, and estimated glomerular filtration rate (eGFR) was independently negatively associated with IS level. In addition, ß2-microglobulin was independently positively associated with total PCS. Moreover, potassium, diastolic blood pressure, average BP, ß2-microglobulin, dialysis vintage, and albumin were independently positively associated with HA level, and age, transferrin saturation, fasting glucose, and eGFR were independently negatively associated with HA level. When the patients were stratified by age and sex, serum IS and HA levels were still independently associated with some hemodialysis quality indicators. In addition, canonical correlation analysis also confirmed the relationship between uremic toxins (IS and HA) and HD quality indicators (potassium, ß2-microglobulin, average BP, creatinine, and eGFR). CONCLUSION: This study demonstrated that uremic toxins (IS and HA) and HD quality indicators (potassium, ß2-microglobulin, average BP, creatinine, and eGFR) constructs were correlated with each other, and that there were sex and age differences in these associations among maintenance HD patients.

Circulating hepassocin level in patients with stable angina is associated with fatty liver and renal function.

Background: Chronic kidney disease (CKD) is a major risk factor for coronary artery disease and it is often associated with hepatic steatosis. Hepassocin (also known as hepatocyte-derived fibrinogen related protein or fibrinogen-like 1) is a novel hepatokine that causes hepatic steatosis and induces insulin resistance. However, the role of hepassocin in renal function status remains unclear. Our objective was to investigate the association of plasma hepassocin level with fatty liver and renal function status in patients with stable angina. Methods: Plasma hepassocin levels were determined by enzyme-linked immunosorbent assays in 395 consecutive patients with stable angina. Renal function was defined as an estimated glomerular filtration rate (eGFR). Fatty liver was defined by ultrasonography and fibrosis-4 (FIB-4) index. Results: With increasing hepassocin tertiles, patients had higher prevalence of fatty live, an increased waist-to-hip ratio, and neutrophil count, monocyte count, and FIB-4 index, higher levels of uric acid, blood urine nitrogen and higher sensitivity C-reactive protein. They also had incrementally lower eGFR, serum hemoglobin and albumin levels. In multiple linear stepwise regression analysis, only eGFR was significantly independent negatively associated with plasma hepassocin levels. Conclusion: Our results indicate that circulating hepassocin in patients with stable angina is associated with fatty liver and renal function, which suggests that increased plasma hepassocin may be involved in the pathogenesis of fatty liver and CKD.

Glossogyne tenuifolia Attenuates Proliferation and Migration of Vascular Smooth Muscle Cells.

The proliferation and migration of vascular smooth muscle cells (VSMCs) are essential in the pathogenesis of various vascular diseases, such as atherosclerosis and restenosis. Among the mediators of VSMC during atherosclerosis development, platelet-derived growth factor (PDGF)-BB is a potent mitogen for VSMCs and greatly contributes to the intimal accumulation of VSMCs. Glossogyne tenuifolia (GT, Xiang-Ru) is a traditional antipyretic and hepatoprotective herb from Penghu Island, Taiwan. This study evaluated the inhibitory effect of GT ethanol extract (GTE) and GT water extract (GTW) on proliferative and migratory activities in PDGF-BB-induced VSMCs. The experimental results demonstrated that GTE significantly inhibited the PDGF-BB-stimulated VSMC proliferation and migration, as shown by MTT, wound healing, and Boyden chamber assays. GTE was found to have a much more potent inhibitory activity than GTW. Based on the Western blot analysis, GTE significantly blocked the PDGF-BB-induced phosphorylation of NF-κB and mitogen-activated protein kinase (MAPK) pathways, including extracellular signal-regulated kinase (ERK), p38, and JNK, in VSMCs. In addition, GTE retarded the PDGF-BB-mediated migration through the suppression of matrix metalloproteinase (MMP)-2 and MMP-9 expression in VSMCs. Three main ingredients of GT-chlorogenic acid, luteolin-7-glucoside, and luteolin-all showed significant anti-proliferative effects on PDGF-BB-induced VSMCs. As a whole, our findings indicated that GTE has the potential to be a therapeutic agent to prevent or treat restenosis or atherosclerosis.

Use and effectiveness of dapagliflozin in patients with type 2 diabetes mellitus: a multicenter retrospective study in Taiwan.

AIMS/INTRODUCTION: To investigate the clinical outcomes of patients with type 2 diabetes mellitus (T2DM) who initiated dapagliflozin in real-world practice in Taiwan. MATERIALS AND METHODS: In this multicenter retrospective study, adult patients with T2DM who initiated dapagliflozin after May 1st 2016 either as add-on or switch therapy were included. Changes in clinical and laboratory parameters were evaluated at 3 and 6 months. Baseline factors associated with dapagliflozin response in glycated hemoglobin (HbA1c) were analyzed by univariate and multivariate logistic regression. RESULTS: A total of 1,960 patients were eligible. At 6 months, significant changes were observed: HbA1c by -0.73% (95% confidence interval [CI] -0.80, -0.67), body weight was -1.61 kg (95% CI -1.79, -1.42), and systolic/diastolic blood pressure by -3.6/-1.4 mmHg. Add-on dapagliflozin showed significantly greater HbA1c reduction (-0.82%) than switched therapy (-0.66%) (p = 0.002). The proportion of patients achieving HbA1c <7% target increased from 6% at baseline to 19% at Month 6. Almost 80% of patients experienced at least 1% reduction in HbA1c, and 65% of patients showed both weight loss and reduction in HbA1c. Around 37% of patients had at least 3% weight loss. Multivariate logistic regression analysis indicated patients with higher baseline HbA1c and those who initiated dapagliflozin as add-on therapy were associated with a greater reduction in HbA1c. CONCLUSIONS: In this real-world study with the highest patient number of Chinese population to date, the use of dapagliflozin was associated with significant improvement in glycemic control, body weight, and blood pressure in patients with T2DM. Initiating dapagliflozin as add-on therapy showed better glycemic control than as switch therapy.

Antrodia cinnamomea Extraction Waste Supplementation Promotes Thermal Stress Tolerance and Tissue Regeneration Ability of Zebrafish.

Antrodia cinnamomea (AC) has been shown to have anti-inflammatory, anti-tumor, and immunomodulation activities. It is estimated that hundreds of metric tons of AC extraction waste (ACEW) are produced per year in Taiwan. This study aims to assess the feasibility of applying ACEW as feed supplement in the aquaculture industry. ACEW significantly inhibited the growth of microorganisms in the water tank, by around 39.4% reduction on the fifth day with feed supplemented of 10% ACEW. The feed conversion efficiency of zebrafish with 10% ACEW supplementation for 30 days was 1.22-fold compared to that of the control. ACEW dramatically improved the tolerances of zebrafish under the heat and cold stresses. When at water temperature extremes of 38 °C or 11 °C, compared to the 100% mortality rate in the control group, the 10% ACEW diet group still had 91.7% and 83.3% survival rates, respectively. In a caudal fin amputation test, the fin recovery of zebrafish was increased from 68.4% to 93% with 10% ACEW diet after 3-week regeneration. ACEW effectively down-regulated the gene expression of TNF-α, IL-1ß, IL-6, and IL-10, and up-regulated the gene expression of IL-4/13A. Additionally, the supplement of ACEW in the feed can maintain and prevent the fish's body weight from dropping too much under enteritis. Taken together, ACEW has beneficial potential in aquaculture.

FABP1 and FABP2 as markers of diabetic nephropathy.

Background: Diabetes mellitus is the leading cause of diabetic nephropathy and a major public health issue worldwide. Approximately 20-30% of patients with type 2 diabetes mellitus (T2DM) have renal impairment. Fatty acid-binding protein 1 (FABP1) is expressed in renal proximal tubule cells and released into urine in response to hypoxia caused by decreased peritubular capillary blood flow, and FABP2 is responsible for the transport of free fatty acids in the intestinal endothelium cells. There is increasing evidence that FABP1 and FABP 2 play a role in the development and progression of chronic kidney disease. The aim of this study was to investigate the relation of circulating FABP1 and FABP2 levels to nephropathy in patients with T2DM. Methods: For this study, 268 subjects with T2DM who were enrolled in a disease management program were stratified according to urinary microalbumin and serum creatinine measurements. The plasma FABP1 and FABP2 concentrations were examined by enzyme-linked immunosorbent assay. Demographic and potential metabolic confounding factors were analyzed with logistic regression to calculate the effects of FABP1 and FABP2 levels on diabetic nephropathy. Results: The FABP1 and FABP2 levels increased in parallel with the advancement of diabetic nephropathy. Increasing concentrations of FABP1 and FABP2 were independently and significantly associated with diabetic nephropathy. Multiple logistic regression analysis revealed FABP1 and FABP2 as an independent association factor for diabetic nephropathy, even after full adjustment of known biomarkers. Furthermore, receiver operating characteristic curve analysis showed that a FABP1 level of >33.8 ng/mL and a FABP2 level of >2.8 ng/mL were associated with diabetic nephropathy. Conclusion: Our results suggest that FABP1 and FABP2 may be novel biomarkers of diabetic nephropathy.

Common and Unique Factors and the Bidirectional Relationship Between Chronic Kidney Disease and Nonalcoholic Fatty Liver in Type 2 Diabetes Patients.

PURPOSE: This study aimed to investigate the common and unique risk factors and bidirectional relationship between chronic kidney disease (CKD) and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: This was a cross-sectional study of patients with T2DM enrolled in a disease management program at two specialized diabetes outpatient clinics. Common and unique risk factors for CKD and NAFLD were examined using structural equation models (SEMs). SEMs were also used to examine direct and indirect effects of NAFLD on CKD and those of CKD on NAFLD. RESULTS: A total of 1992 subjects with T2DM were enrolled in this study. In multivariate analysis, NAFLD was independently associated with the odds of CKD (adjusted odds ratio=1.59, 95% confidence interval=1.12-2.25, P=0.009). SEMs showed that age, triglyceride, uric acid (UA), albumin, and HbA1c levels had statistically significant direct effects on CKD, and the final model could explain 22% of the variability in CKD. Age, triglycerides, body mass index (BMI), UA, white blood cell (WBC) count, serum glutamic pyruvic transaminase (SGPT) level, and smoking status had statistically significant direct effects on NAFLD, and the final model could explain 43% of the variability in NAFLD. The common risk factors contributing to both CKD and NAFLD were age, triglycerides, and UA. The unique risk factors were albumin and HbA1c for CKD, and BMI, WBC, SGPT, and smoking for NAFLD. In addition, SEM analysis also confirmed the bidirectional causal relationship between NAFLD and CKD. CONCLUSION: Common and unique risk factors and a bidirectional relationship existed between CKD and NAFLD in our patients with T2DM.