Curcumin activates autophagy and attenuates high glucose-induced apoptosis in HUVECs through the ROS/NF-κB signaling pathway.

Curcumin (CUR) is well known for its anti-inflammatory and antioxidant effects. However, the endothelial protective effect of CUR in diabetes and the underlying signaling pathway remains unclear. The goal of the current study was to provide evidence regarding the protective mechanism of CUR against the high glucose (HG)-induced damage to human umbilical vein endothelial cells (HUVECs). HG-induced HUVECs injury model was used to evaluate the protective effect and the underlying mechanism of CUR against endothelial injury. The cell viability was determined by the MTT method. The cell reactive oxygen species (ROS) were determined by using flow cytometry. The protein expression levels of Bcl-2, Bax, LC3-II/I, Beclin-1, p62, cleaved caspase-3, IκBα and NF-κB were measured by the western blotting. Results showed that CUR significantly decreased the cell apoptosis, the ROS generation and the inflammatory cytokine NF-κB activity in the HG-induced HUVECs versus the control, P<0.05. In addition, CUR significantly increased the expressions of LC3-II/I, Beclin-1, IκBα and Bax/Bcl-2 in the HG-induced HUVECs versus the control, P<0.05. Furthermore, the addition of autophagy inhibitor 3-MA impaired the autophagy, exacerbated the apoptotic death and increased the ROS and NF-κB levels in HUVECs under the high glucose condition, P<0.05. In brief, autophagy served a protective role in the HG-induced apoptosis in HUVECs and CUR alleviated apoptosis by promoting autophagy and inhibiting the ROS/NF-κB signaling pathway.

Levels of brain natriuretic peptide are associated with peripheral arterial disease in subjects with type-2 diabetes mellitus.

BACKGROUND: The effects of brain natriuretic peptide (BNP) on the risk of cardiovascular disease and atherosclerosis have been studied. However, little information is available regarding peripheral arterial disease (PAD), particularly among subjects with type-2 diabetes mellitus (T2DM). The aim of our study was to assess the potential relationship between BNP levels and PAD among T2DM patients. METHODS: The study cohort was 507 T2DM outpatients in which BNP levels were measured. Cross-sectional associations between BNP levels (in tertiles) and PAD were examined. RESULTS: Compared withT2DM patients without PAD, BNP levels were markedly higher in patients with PAD (p = 0.001). Correlation analyses showed that the BNP level was negatively correlated with the ankle-brachial index (r = -0.453, p = 0.033). At a cutoff value of 78.2 pg/ml, the BNP level showed a sensitivity of 71.9%, a specificity of 68.1%, and a positive predictive value of 84.3% for a diagnosis of PAD. The area under the receiver-operating characteristic curve increased significantly if BNP levels were incorporated into a predictive model of the potential risk factors for PAD (0.85 vs 0.81, p = 0.029). CONCLUSIONS: BNP is a potential and promising biomarker for PAD screening in T2DM patients.

Serum galectin-3: a risk factor for vascular complications in type 2 diabetes mellitus.

BACKGROUND: Plasma galectin-3, a mediator of fibrogenesis and inflammation, its potential to associate with type 2 diabetes (T2DM) is poorly investigated. Here, we explored its interaction with the serum galectin-3 and vascular complications. METHODS: We conducted a population-based cross-sectional survey in Zhejiang, China involving 165 men and 119 women (age range, 43 - 84 years), investigating the relationship between serum galectin-3 and vascular disease in patients with T2DM. RESULTS: Serum galectin-3 was higher in subjects with T2DM than that in control participants (27.4 vs. 17.6 ng/ml, P < 0.001). Compared with subjects with galectin-3 values in the lowest quartile, those with values in the highest quartile had an increased likelihood of vascular complications (4th quartile odds ratio (OR) 2.52, 95% confidence interval (CI), 1.25 - 4.07). Increased risk of micro- or macrovascular complications correlated with serum galectin-3 concentration (ORs 11.4 and 8.5, respectively). An increased number of vascular complications was associated with high serum galectin-3 levels (P < 0.05). Patients with serum galectin-3 levels > 25 ng/ml had an elevated risk of diabetes relative to patients with levels < 10 ng/ml (OR for any vascular complication 2.64, for heart failure 3.97, for nephropathy 4.09, for peripheral arterial disease (PAD) 4.18; all P < 0.05). Complication risk was higher in patients with neurogenic, stroke, or retinopathy complications, but this difference was not significant after risk factor adjustment. Serum galectin-3 levels correlated with diabetes duration, C-reactive protein (CRP) levels, and albuminuria. CONCLUSION: High galectin-3 values were associated with increased odds of developing heart failure, nephropathy, and peripheral arterial disease in patients with T2DM.

Curcumin improves expression of SCF/c-kit through attenuating oxidative stress and NF-κB activation in gastric tissues of diabetic gastroparesis rats.

BACKGROUND: Diabetes mellitus is associated with many kinds of complications. Recent studies have shown that oxidative stress and inflammatory reactions have critical roles in the pathogenesis of diabetic gastroparesis. Curcumin is known to have antioxidant and anti-inflammatory properties. In the present study, we investigated the effect of curcumin on diabetic gastric motility in a Sprague Dawley rat model of type 1 diabetes mellitus. METHODS: Male SD rats were divided into a control group, a control group receiving curcumin, a diabetic group, and a diabetic group receiving curcumin. Diabetes was induced by intraperitoneal injection of streptozotocin. Curcumin (150 mg/kg) was given intragastrically for 6 weeks, and blood glucose levels and body weights were measured. Stomachs were excised for analysis of gastric emptying rates, and levels of oxidative stress. NF-κB, I-κB, and stem cell factor (SCF)/c-kit protein levels were assessed by western blot analysis, while the apoptosis of interstitial cells of Cajal (ICCs) was assessed by TUNEL staining. RESULTS: Curcumin-treated diabetic rats showed significantly improved gastric emptying rates [(59.4 ± 7.5)%] compared with diabetic rats [(44.3 ± 5.7)%], as well as decreased levels of MDA [21.4 ± 1.8 (nmol/mg) vs 27.9 ± 2.1 (nmol/mg)], and increased SOD activity [126.2 ± 8.8 (units/mg) vs 107.9 ± 7.5 (units/mg)]. On the other hand, the gastric emptying level in the control group was not significantly different from that in the control group receiving curcumin treatment. In addition, curcumin-treated diabetic rats showed significantly increased levels of SCF/c-kit protein in stomach tissues, inhibited I-κB degradation and NF-κB activation, and reduced ICC apoptosis index [(26.2 ± 4.1)% vs (47.5 ± 6.2)%], compared with the diabetic group. CONCLUSION: Curcumin treatment improved gastric emptying by blocking the production of oxidative stress, abolishing NF-κB signal transduction and enhancing expression of SCF/c-kit in rats with diabetic gastroparesis.

[The relationship between sleep quality and glucose level, diabetic complications in elderly type 2 diabetes mellitus].

OBJECTIVE: To explore the relationship between sleep quality and glucose level, diabetic complications in elderly type 2 diabetes mellitus. METHODS: A total of 130 hospitalized elderly type 2 diabetes in our hospital were included in the study. Questionnaires and other related clinical data were collected within one week after admission. Patients were divided into two groups: poor-sleeper group and good-sleeper group according to Pittsburgh Sleep Quality Index (PSQI). RESULTS: Sixty percent (78/130) of these patients were poor sleepers. The following parameters differed in the two groups: the duration of diabetes [(7.9 ± 1.8) years vs (7.2 ± 1.5) years, t = 2.318], systolic blood pressure [(148 ± 30) mm Hg (1 mm Hg = 0.133 kPa) vs (138 ± 23) mm Hg, t = 2.037], fasting plasma glucose (FPG) [(10.7 ± 2.2) mmol/L vs (9.8 ± 1.9) mmol/L, t = 2.410], hemoglobin A1c (HbA1c) [(8.6 ± 2.2)% vs (7.8 ± 2.1)%, t = 2.068], high-sensitive C-reactive protein (hs-CRP) [(5.27 ± 2.34) mg/L vs (4.44 ± 1.76) mg/L, t = 2.179], ratio of diabetic complications (61% vs 32%, χ(2) = 4.257), percentage of depression (20% vs 8%, χ(2) = 3.722), score of life quality [(98 ± 19) scores vs (89 ± 13) scores, t = 2.980], and proportion of patients treated with insulin (32% vs 12%, χ(2) = 4.489). All the above parameters were significantly higher in poor-sleeper group than the good-sleeper group (all P value < 0.05). Multiple correlation analysis showed that the factors affecting sleep quality were FPG, HbA1c, duration of diabetes, diabetic complications, depression, life quality and insulin application (r = 0.213, 0.257, 0.223, 0.335, 0.422, 0.3451, 0.231, respectively; all P value < 0.05). By multivariate logistic regression analysis, the followings were found: FPG (ß = 1.29, P < 0.05) and PSQI (ß = 1.07, P < 0.05) were found to be correlated with HbA1c. With increasing of PSQI, FPG, HbA1c, diabetic complications and life quality were changed significantly (all P value < 0.05). The independent risk factors of diabetic complications were duration of diabetes (OR = 1.32, 95%CI 1.01 - 2.01), HbA1c (OR = 2.01, 95%CI 1.63 - 2.67), hs-CRP (OR = 1.12, 95%CI 1.08 - 1.21) and PSQI (OR = 1.71, 95%CI 1.58 - 2.02). CONCLUSIONS: Elderly type 2 diabetes mellitus are usually poor sleepers. Sleep quality probably affects blood glucose regulation, and is closely correlated with the occurrence of complications. In addition, poor sleep quality results in poor life quality.

[Relationship between plasma total homocysteine and mild cognitive impairment in senile patients with type 2 diabetes].

OBJECTIVE: To explore the relationship between fasting plasma level of total homocysteine (tHcy) and mild cognitive impairment in senile patients with type 2 diabetes mellitus. METHODS: A total of 88 senile type 2 diabetics with mild cognitive impairment treated at our hospital from July 2008 to November 2010 were recruited into the MCI group while 52 senile type 2 diabetics into the DNC group. And the control group was composed of 36 healthy elders. The parameters of tHcy, total glyceride (TG), total cholesterol (TC), low density lipoprotein-C (LDL-C), high density lipoprotein-C (HDL-C), creatinine (Cr), hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), 2 h plasma glucose (2 hPG), fasting insulin (FINS), homeostasis model of insulin resistance (HOMA-IR), folic acid (FA) and vitamin B(12) (VitB(12)) were detected. RESULTS: The patients had a higher level of tHcy in the MCI group than those in the NCM and control groups [(11.3 ± 1.8) vs (9.8 ± 1.5) and (8.1 ± 1.1) µmol/L; P < 0.01]. ROC curve showed that tHcy level had some value of predicting the occurrence of mild cognitive impairment in senile patients with type 2 diabetes mellitus (AUC 0.825, 95%CI 0.758-0.893, P < 0.01). Logistic regression analysis showed that tHcy, SBP, HbA1c, 2 h PG, FINS, LDL-C, HOMA-IR, FA and VitB(12) [OR value: 3.64, 1.68, 1.10, 1.05, 0.81, 1.42, 0.83, 0.74, 0.86 (P < 0.05 or 0.01)] were independent risk factors of mild cognitive impairment in senile diabetic patients. CONCLUSION: Such factors as tHcy, SBP, HbA1c, FPG, 2 hPG, FINS, LDL-C, HOMA-IR, FA and VitB(12) induce senile patients with type 2 diabetes mellitus to suffer mild cognitive impairment. But tHcy level may play an important role in senile diabetic patients with mild cognitive impairment.

Predictive value of serum cholinesterase for the prognosis of aged patients with systemic inflammatory response syndrome.

BACKGROUND: Some studies found that cholinesterase (ChE) can be an independent risk factor for patients with multiple organ dysfunction syndrome. To assess aged patients with systemic inflammatory response syndrome (SIRS) early and predict their prognosis, the predictive value of ChE for the prognosis of aged patients with SIRS was analyzed. METHODS: From September 2009 to September 2010, all aged patients with SIRS in the ICU of the Second Affiliated Hospital of Zhejiang University School of Medicine were retrospectively analyzed if they met inclusion criteria: patients aged ≥ 65 years and met American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference criteria for SIRS. Serum ChE, albumin, D-dimer, lactic acid and C-reactive protein (CRP) were measured, and the Acute Physiology and Chronic Health Evaluation (APACHE) II and Glasgow Coma Scale (GCS) scores were evaluated within the first 24 hours in the ICU. Fisher's exact test was used for comparison of the primary disease between the deceased group and surviving group. For comparison of study variables between the two groups, the Student's t test or Mann-Whitney U test was used. Multivariate significance was tested with binary Logistic regression analysis. RESULTS: The clinical data of 124 aged patients with SIRS were collected and analyzed. Sixty-six patients (46 male, 20 female, mean age (78.70 ± 8.08) years) who died were included in the deceased group and 58 patients (34 male, 24 female, mean age (76.02 ± 6.57) years) who survived were included in the surviving group. There were no significant differences in age, gender, APACHE II score and GCS score between the deceased group and surviving group (all P > 0.05), but there were significant differences in lactic acid (P = 0.011), D-dimer (P = 0.011), albumin (P = 0.007), CRP (P = 0.008), and ChE (P < 0.0001). The correlation analysis showed that the APACHE II score and CRP were not correlated with ChE (both P < 0.05). D-dimer and albumin were correlated with ChE (Spearman's rho correlation coefficients were -0.206 and 0.324, the corresponding P values were 0.022 and < 0.0001). Multiple Logistic regression analysis showed that age, gender, lactic acid, D-dimer, albumin, CRP, APACHE II score, and GCS score were not independent risk factors for prognosis of aged patients with SIRS, but that ChE was (P < 0.0001). The receiver operating characteristic curve of ChE had an area under the curve of 0.797 (standard error = 0.04; P < 0.0001), and a ChE of 103.00 U/L was the cut-off value with sensitivity = 0.793, specificity = 0.742. CONCLUSION: Serum ChE might be a predictive marker for the prognosis of aged patients with SIRS, with low serum ChE levels indicating poor prognosis.

Neferine inhibits angiotensin II-stimulated proliferation in vascular smooth muscle cells through heme oxygenase-1.

AIM: To explore the effect of neferine on angiotensin II (Ang II)-induced vascular smooth muscle cell (VSMC) proliferation. METHODS: Human umbilical vein smooth muscle cells (HUVSMCs) were used. Cell proliferation was determined by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis. Heme oxygenase (HO)-1 protein expression was tested by Western blot analysis. Extracellular signal-regulated protein kinase 1/2 (ERK1/2) activation was determined by using immunoblotting. RESULTS: Pre-incubation of HUVSMCs with neferine (0.1, 0.5, 1.0, and 5.0 micromol/L) significantly inhibited Ang II-induced cell proliferation in a concentration-dependent manner and neferine 5.0 micromol/L increased HO-1 expression by 259% compared with control. The antiproliferative effect of neferine was significantly attenuated by coapplication of zinc protoporphyrin IX (ZnPP IX, an HO-1 inhibitor) with neferine. Ang II-enhanced ERK1/2 phosphorylation was markedly reversed by neferine. By inhibiting HO-1 activity with ZnPP IX, the inhibitive effect of neferine on ERK1/2 phosphorylation was significantly attenuated. Cobalt-protoporphyrin (CoPP), an HO-1 inducer, significantly decreased Ang II-induced ERK1/2 phosphorylation and inhibited Ang II-induced cell proliferation. The ERK1/2 pathway inhibitor PD98059 significantly blocked Ang II-enhanced ERK1/2 phosphorylation and inhibited cell proliferation. CONCLUSION: These findings suggest that neferine can inhibit Ang II-induced HUVSMC proliferation by upregulating HO-1, leading to the at least partial downregulation of ERK1/2 phosphorylation.