Prevalence of gastrointestinal parasites in free-range yaks (Bos grunniens) in Gansu Province, Northwest China.

BACKGROUND: Little information about the prevalence of gastrointestinal parasites in yaks (Bos grunniens) in northwest China is available. Therefore, the objective of the study was to quantify faecal egg counts of gastrointestinal parasites (helminths and coccidia) in free-range yaks from Gannan Tibetan Autonomous Prefecture, Gansu Province, Northwest China. RESULTS: Parasites were detected in 290 of 733 (39.56%) faecal samples. The results showed that Strongylidae, Trichuris spp. and Eimeria spp. were detected all year round, Strongyloides papillosus was detected in autumn and summer, and Nematodirus spp. was detected in both autumn and spring. In contrast, Fasciola spp. was only detected in spring. The prevalence rates of parasitic infections in different seasons were significantly different. CONCLUSIONS: To our knowledge, this is the first investigation of gastrointestinal parasites in yaks (Bos grunniens) in Gansu, China. The results demonstrated a high prevalence of gastrointestinal parasitic infections, specifically GN infections, in yaks in GTAP and these infections can cause economic losses to the local cattle industry.

[Expression of nesfatin-1/NUCB2 and ghrelin in gastric mucosa of rats with intrauterine growth retardation].

OBJECTIVE: To investigate the expression of nesfatin-1/NUCB2 and ghrelin in the gastric mucosa of rats with intrauterine growth retardation (IUGR) and its significance. METHODS: The IUGR animal model was established by feeding rats low-protein diets during their pregnancy. Newborn rats were divided into catch-up growth, non-catch-up growth and control groups. Protein and mRNA levels of nesfatin-1/NUCB2 and ghrelin in the gastric mucosa of rats were determined by RT-PCR and Western blot, respectively. RESULTS: Nesfatin-1/NUCB2 mRNA and protein were expressed in the gastric mucosa of rats immediately after birth, and their expression increased in an age-dependent manner in all three groups. Furthermore, the level of nesfatin-1/NUCB2 in the catch-up growth group was higher than that in the control group before weaning, whereas there was no significant difference in nesfatin-1/NUCB2 expression between the two groups after weaning. The level of nesfatin-1/NUCB2 in the non-catch-up growth group was lower than that in the catch-up growth group during the whole observation period. The level of ghrelin in the catch-up growth group was higher than that in the control group starting from day 12 after birth, whereas there was no significant difference in ghrelin expression between the two groups after weaning. The level of ghrelin in the non-catch-up growth group was lower compared with those in the catch-up growth and control groups from days 12 to 28 after birth. CONCLUSIONS: Nesfatin-1 and ghrelin are co-expressed in the gastric mucosa of rats with IUGR after birth and interact with each other to produce long-term nutritional regulation.

[Progress in research of the mechanisms related with the hepatic steatosis in the nonalcoholic fatty liver disease].

With the increased morbidity of Nonalcoholic fatty liver disease, the pathogenesis of which has become one of the focuses for researchers. Many details need to be clarified. The hepatic steatosis has been taken as the clinical pathological characters and the "golden standard of diagnosis" for the nonalcoholic fatty liver disease. More and more studies have shown that the hepatic steatosis (mainly as triglycerides) is the consequence of hepatic lipid metabolism disequilibrium. Generally, the related metabolism pathways including lipid input, lipid uptake, de novo lipogenesis, fatty acid oxidation, fatty acid reesterification, and lipid secretion etc. In this review, we focused on the progress of some key enzymes involved in these pathways in order to clarify the possible molecular mechanisms and the effective targets so that to broad our vision about the prevention and treatment of non-alcoholic fatty liver disease.

Similar changes in muscle lipid metabolism are induced by chronic high-fructose feeding and high-fat feeding in C57BL/J6 mice.

The aim of the present study was to investigate the effects of high fructose and high fat feeding on muscle lipid metabolism and to illustrate the mechanisms by which the two different dietary factors induce muscle lipid accumulation. C57BL/J6 mice were fed either a standard, high-fructose (HFru) or high-fat diet. After 16 weeks feeding, mice were killed and plasma triglyceride (TG) and free fatty acid (FFA) levels were detected. In addition, muscle TG and long chain acyl CoA (LCACoA) content was determined, glucose tolerance was evaluated and the protein content of fatty acid translocase CD36 (FATCD36) in muscle was measured. Mitochondrial oxidative function in the muscle was evaluated by estimating the activity of oxidative enzymes, namely cytochrome oxidase (COx), citrate synthase (CS) and ß-hydroxyacyl CoA dehydrogenase (ß-HAD), and the muscle protein content of carnitine palmitoyltransferase-1 (CPT-1), cyclo-oxygenase (COX)-1 and proliferator-activated receptor coactivator (PGC)-1α was determined. Finally, sterol regulatory element-binding protein-1c (SREBP-1c) gene expression and fatty acid synthase (FAS) protein content were determined in muscle tissues. After 16 weeks, plasma TG and FFA levels were significantly increased in both the HFru and HF groups. In addition, mice in both groups exhibited significant increases in muscle TG and LCACoA content. Compared with mice fed the standard diet (control group), those in the HFru and HF groups developed glucose intolerance and exhibited increased FATCD36 protein levels, enzyme activity related to fatty acid utilization in the mitochondria and protein expressions of CPT-1, COX-1 and PGC-1α in muscle tissue. Finally, mice in both the HFru and HF groups exhibited increase SREBP-1c expression and FAS protein content. In conclusion, high fructose and high fat feeding lead to similar changes in muscle lipid metabolism in C57BL/J6 mice. Lipid accumulation in the muscle may be associated with increased expression of proteins related to lipid transportation and synthesis.

Nesfatin-1 in newborns: relationship with endocrine and metabolic and anthropometric measures.

OBJECTIVE: To explore the relationship between nesfatin-1 and growth and development in newborns. METHODS: Blood samples for nesfatin-1, ghrelin, insulinlike growth factor-1 (IGF-1), insulin and glucose were obtained from preterm (n = 53) and term infants (n = 60), including appropriate for gestational age (AGA) (n = 32) and small for gestational age (SGA) infants (n = 28). The relationship between nesfatin-1 and other metabolic hormones or anthropometric parameters was evaluated. RESULTS: The concentrations of nesfatin-1, ghrelin and insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR) were higher in SGA than AGA infants (p = 0.0358, 0.0163, 0.0001 and 0.0051, respectively), but IGF-1 levels and homeostasis model assessment-insulin sensitivity index (HOMA-ISI) were lower (p = 0.033 and 0.0001, respectively). Nesfatin-1 levels in SGA infants were higher on postnatal day 0 (PNDO) than in AGA infants (p = 0.0358) and lower on PND7 (p = 0.0002) and PND28 (p = 0.0488). A negative correlation showed between nesfatin-1 and oral calorie intake (r = -0.446; p = 0.017) and HOMA-ISI (r = -0.398; p = 0.036), and a positive correlation between nesfatin-1 and HOMA-IR (r = 0.43; p = 0.023) in SGA infants. CONCLUSION: Nesfatin-1 is involved in the physiological regulation of intrauterine and postnatal growth and development in SGA infants.

[The relationship between oxidative stress and endothelial progenitor cells count in the first-degree relatives of diabetes mellitus].

OBJECTIVE: To study the relationship between oxidative stress and endothelial progenitor cells (EPCs) count in the first-degree relatives of diabetes mellitus (FDRs). METHODS: Three groups were evaluated with 40 type 2 diabetes mellitus (T2DM) patients, 38 FDRs and 30 healthy individuals as the control (NC). Fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), TG, TC and fasting plasma insulin concentrations were measured and homeostasis model assessment-insulin resistance (HOMA-IR) was calculated. Quantity of EPCs and flow-mediated dilation (FMD) were evaluated. Malonaldehyde (MDA), glutathion peroxidase (GSH-Px), erythrocuprein (SOD) and total anti-oxidative capacity (TAO-C) were measured. RESULTS: In T2DM group FPG [(7.86 ± 0.77) mmol/L] and HbA1c [(7.24 ± 0.20) %] were significantly higher than those in NC [FPG (4.90 ± 0.35) mmol/L, HbA1c (5.34 ± 0.37)%] and FDRs group [FPG (5.13 ± 0.95) mmol/L, HbA1c (5.36 ± 0.36)%] (all P values < 0.05). TC in T2DM group [(5.88 ± 0.76) mmol/L] was higher than in NC [(4.66 ± 0.90) mmol/L] and FDRs [(4.95 ± 0.76) mmol/L]. HOMA-IR was 0.48 ± 0.25 in NC, 0.81 ± 0.46 in FDRs and 1.47 ± 0.24 in T2DM group, P < 0.01. In T2DM group, the plasma levels of SOD [(69.30 ± 2.21) U/ml], TAO-C [(7.30 ± 0.29) U/ml] and GSH-Px [(856.5 ± 9.01) U/ml] were significantly lower than those in NC [SOD (75.33 ± 3.63) U/ml, TAO-C (8.17 ± 0.58) U/ml and GSH-Px (938.1 ± 19.35) U/ml] and FDRs group [SOD (74.91 ± 4.53) U/ml, TAO-C (8.24 ± 0.46) U/ml and GSH-Px (936.9 ± 15.78) U/ml] (all P values < 0.01). Serum level of MDA was (2.87 ± 0.63) µmol/L in NC, (3.28 ± 0.71) µmol/L in FDRs and (3.69 ± 0.39) µmol/L in T2DM group (P < 0.01). The quantity of EPCs and FMD% were 96.75 ± 8.11 and 8.36 ± 2.21 in NC, 83.34 ± 12.43 and 6.78 ± 0.98 in FDRs and 58.45 ± 7.58 and 2.86 ± 0.35 in T2DM group with statistical differences between different groups (all P values < 0.05). Pearson correlation analysis showed that lnHOMA-IR was positively correlated with MDA (r = 0.486, P < 0.05) and negatively correlated with SOD, TAO-C, GSH-Px (r = -0.426, -0.601, -0.524, all P values < 0.05) in FDRs group. CONCLUSIONS: Insulin resistance, oxidative stress, decreased quantity of EPCs and impairment of endovascular function have already occurred in the FDRs of T2DM with normal glucose tolerance and they are correlated with each other.

Metformin improves high-fat diet-induced insulin resistance in mice by downregulating the expression of long noncoding RNA NONMMUT031874.2.

Metformin (MET) is the first-line therapeutic option for patients with type 2 diabetes that has garnered substantial attention over recent years. However, an insufficient number of studies have been performed to assess its effects on insulin resistance and the expression profile of long noncoding RNAs (lncRNAs). The present study divided mice into three groups: Control group, high-fat diet (HFD) group and HFD + MET group. A high-throughput sequencing analysis was conducted to detect lncRNA and mRNA expression levels, and differentially expressed lncRNAs were selected. Subsequently, the differentially expressed lncRNAs were validated both in vivo and in vitro (mouse liver AML12 cells treated with Palmitic acid) models of insulin resistance. After validating randomly selected lncRNAs via reverse transcription-quantitative PCR a novel lncRNA, NONMMUT031874.2, was identified, which was upregulated in the HFD group and reversed with MET treatment. To investigate the downstream mechanism of NONMMUT031874.2, lncRNA-microRNA (miR/miRNA)-mRNA co-expression network was constructed and NONCODE, miRBase and TargetScan databases were used, which indicated that NONMMUT031874.2 may regulate suppressor of cytokine signaling 3 by miR-7054-5p. For the in vitro part of the present study, AML12 cells were transfected with small interfering RNA to knock down NONMMUT031874.2 expression before being treated with palmitic acid (PA) and MET. The results showed that the expression of NONMMUT031874.2 was significantly increased whereas miR-7054-5p expression was significantly decreased by PA treatment. By contrast, after knocking down NONMMUT031874.2 expression or treatment with MET, the aforementioned in vitro observations were reversed. In addition, it was also found that NONMMUT031874.2 knockdown and treatment with MET exerted similar effects in alleviating insulin resistance and whilst decreasing glucose concentration in AML12 cells. These results suggest that MET treatment can ameliorate insulin resistance by downregulating NONMMUT031874.2 expression.

ß-catenin mediates the effect of GLP-1 receptor agonist on ameliorating hepatic steatosis induced by high fructose diet.

The hypoglycemic drug GLP-1 receptor agonist can ameliorate hepatic steatosis but the mechanism is not clear. Intake of high fructose leads to non-alcoholic fatty liver disease by stimulating lipid synthesis, and ß-catenin is the key molecule for realizing GLP-1 function in extrahepatic tissues; with the discovery of GLP-1 receptor in liver, we speculate that ß-catenin might mediate GLP-1 receptor agonist on ameliorating hepatic steatosis induced by high fructose. Wistar rats were fed with high fructose diet for 8 weeks and then treated with GLP-1 receptor agonist exenatide for 4 weeks; the changes of lipid synthesis pathway factors, the expression and nuclear translocation of ß-catenin, and the hepatic steatosis of the rats were observed. After the intervention of exenatide, the hepatic steatosis induced by high fructose was improved, the nuclear translocation and expression of ß-catenin were facilitated, and the mRNA and protein expression of the upstream regulator SREBP-1 and the downstream key enzymes ACC, FAS and SCD-1 of de novo lipogenesis were down-regulated. GLP-1 receptor agonist may ameliorate hepatic steatosis induced by high fructose by ß-catenin regulating de novo lipogenesis pathway. GLP-1 receptor agonist may be a potential new drug for the treatment of non-alcoholic fatty liver disease, and the ß-catenin may be an important target for the drug therapy.

[The study of heart rate variability and endothelial function in the first degree relatives of type 2 diabetes with normal glucose tolerance.].

OBJECTIVE: To study the heart rate variability (HRV) and vascular endothelial function in the first degree relatives of type 2 diabetes with normal glucose tolerance (FDRs) and to compare with those of healthy controls. METHODS: HRV, endothelial-dependent vasodilation (EDV) and HOMA insulin resistance index (HOMA-IR) were measured in 37 controls (17 men and 20 women) and 60 FDRs (29 men and 31 women). RESULTS: HRV in FDRs [standard deviation of all normal-normal intervals (SDNN) (124.6 +/- 20.6) ms, standard deviation of average all normal-normal intervals (SDANN) (110.1 +/- 20.1) ms, rate mean square of the differences of successive RR intervals (rMSSD) (33.9 +/- 9.2) ms, low frequency (LF) (1128.5 +/- 314.7) ms(2)/Hz, high frequency (HF) (904.6 +/- 461.6) ms(2)/Hz] was lower than that of the controls [SDNN (140.5 +/- 20.5) ms, SDANN (129.5 +/- 20.3) ms, rMSSD (40.9 +/- 11.4) ms, LF (1678.3 +/- 276.2) ms(2)/Hz, HF(1112.6 +/- 513.7) ms(2)/Hz]. EDV was lower in FDRs than that in the controls [(5.10 +/- 0.14)% vs (12.50 +/- 3.30)%]. HOMA-IR in FDRs was higher than that in the controls (0.57 +/- 0.36 vs. 0.42 +/- 0.23, P < 0.05). CONCLUSIONS: There are increased HOMA-IR, decreased HRV and impaired endothelial function in the FDRs and insulin resistance is positively related with endothelial dysfunction and decreased HRV.

Polycystic Ovary Syndrome is Associated with Elevated Periostin Levels.

PURPOSE: Periostin is a secreted extracellular matrix protein that is strongly associated with triglyceride metabolism, chronic inflammation, and insulin resistance. Growing evidence suggests that there is a link between periostin and ovarian function. Our aim was to ascertain whether circulating periostin levels are altered in women with polycystic ovary syndrome (PCOS) and to further explore the relationship between periostin and glucose metabolism disorder in PCOS patients. METHODS: In total, 50 women with PCOS and 30 age-matched controls without PCOS were recruited for this cross-sectional study. Periostin levels were measured using ELISA as well. RESULTS: Circulating periostin levels were significantly elevated in PCOS women compared with controls [4206.75(222.00, 4815.25) vs. 430.75(142. 13, 730.86) ng/ml, P=0. 005]. Spearman's correlation analysis showed that serum periostin levels had a positive correlation with body mass index (BMI), uric acid, homeostasis model assessment of insulin resistance (HOMA-IR), high-sensitive C reactive protein (hs-CRP), and a negative correlation with insulin sensitivity index (ISI). Logistic regression models revealed that PCOS was correlated with waist to hip ratio (WHR), fasting blood glucose (FBG), and periostin levels. In addition, multivariate linear regression analyses showed that FBG, HOMA-IR, and the lipid accumulation index (LAP) were independent factors influencing serum periostin levels. CONCLUSION: PCOS is associated with elevated levels of periostin.

Efficacy and Safety of Dulaglutide Versus Insulin Glargine in Chinese T2DM Patients: A Subgroup Analysis of a Randomized Trial (AWARD-CHN2).

INTRODUCTION: To evaluate efficacy and safety data of dulaglutide in Chinese patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with 1-2 oral antihyperglycemic medications (OAMs). METHODS: This is a subgroup analysis of a phase 3, open-label, randomized, parallel-arm, 52-week study in Chinese patients aged ≥ 18 years with T2DM who had inadequate glycemic control with OAMs (glycated hemoglobin [HbA1c] ≥ 7.0% and ≤ 11.0%). The primary endpoint was assessment of the noninferiority of dulaglutide 1.5 mg as measured by change in HbA1c, compared with insulin glargine (glargine), using a 0.4% noninferiority margin at week 26. RESULTS: A total of 607 patients from China were randomized 1:1:1 to once-weekly dulaglutide 1.5 or 0.75 mg or once-daily glargine. At week 26, the least squares mean (LSM) change from baseline in HbA1c was greater with dulaglutide 1.5 mg (- 1.67%) and dulaglutide 0.75 mg (- 1.31%) compared with glargine (- 1.11%). The LSM (95% confidence interval) for the difference of dulaglutide 1.5 mg and 0.75 mg vs glargine was - 0.56% (- 0.75 to - 0.37) and - 0.20% (- 0.39 to - 0.01), respectively. Both doses of dulaglutide were noninferior and superior to glargine at 26 weeks and 52 weeks (two-sided P value < 0.05). The mean body weight decreased (P < 0.001) and total hypoglycemia rates were lower (P < 0.05) in the dulaglutide groups compared with the glargine group. Gastrointestinal adverse events (AEs) were the most frequently reported AEs in dulaglutide groups. CONCLUSION: Both doses of dulaglutide are efficacious and tolerable in Chinese patients with T2DM who had inadequate glycemic control on OAMs. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01648582. FUNDING: Eli Lilly and Company.

MicroRNA-802 regulates hepatic insulin sensitivity and glucose metabolism.

The expression level of microRNA-802 (miR-802) is increased in livers of high-fat diet (HFD)-fed mice and obese human subjects; however, the function of miR-802 in the development of obesity-associated insulin resistance remains incompletely understood. Here we studied the potential role of miR-802 in regulating hepatic glucose metabolism and insulin sensitivity. Mice were fed either a standard chow diet or HFD for 12 weeks, and then the HFD mice were infected by injection with an adeno-associated virus expressing miR-802 or miR-802-SP. Six weeks after the injection, we measured blood glucose, plasma insulin, and insulin sensitivity in the mice. In addition, hepatic glucose levels and PI3K-Akt pathway gene expression were analyzed. Adeno-associated viral-mediated overexpression of miR-802 in the livers of HFD mice caused impaired glucose homeostasis and insulin sensitivity, thus giving rise to decreased protein level of pAkts473 and pPI3K, and increased protein levels of pPTEN, G6PC, and GluT2. In contrast, loss of miR-802 function in the liver of HFD mice led to increased pAkts473 and pPI3K, and decreased levels of pPTEN, G6PC, and GluT2, thereby improving glucose metabolism and insulin resistance. Our findings confirmed MiR-802 as a regulator of liver glucose metabolism and insulin signaling.

Role of X-Box Binding Protein-1 in Fructose-Induced De Novo Lipogenesis in HepG2 Cells.

BACKGROUND: A high consumption of fructose leads to hepatic steatosis. About 20-30% of triglycerides are synthesized via de novo lipogenesis. Some studies showed that endoplasmic reticulum stress (ERS) is involved in this process, while others showed that a lipotoxic environment directly influences ER homeostasis. Here, our aim was to investigate the causal relationship between ERS and fatty acid synthesis and the effect of X-box binding protein-1 (XBP-1), one marker of ERS, on hepatic lipid accumulation stimulated by high fructose. METHODS: HepG2 cells were incubated with different concentrations of fructose. Upstream regulators of de novo lipogenesis (i.e., carbohydrate response element-binding protein [ChREBP] and sterol regulatory element-binding protein 1c [SREBP-1c]) were measured by polymerase chain reaction and key lipogenic enzymes (acetyl-CoA carboxylase [ACC], fatty acid synthase [FAS], and stearoyl-CoA desaturase-1 [SCD-1]) by Western blotting. The same lipogenesis-associated factors were then evaluated after exposure of HepG2 cells to high fructose followed by the ERS inhibitor tauroursodeoxycholic acid (TUDCA) or the ERS inducer thapsigargin. Finally, the same lipogenesis-associated factors were evaluated in HepG2 cells after XBP-1 upregulation or downregulation through cell transfection. RESULTS: Exposure to high fructose increased triglyceride levels in a dose- and time-dependent manner and significantly increased mRNA levels of SREBP-1c and ChREBP and protein levels of FAS, ACC, and SCD-1, concomitant with XBP-1 conversion to an active spliced form. Lipogenesis-associated factors induced by high fructose were inhibited by TUDCA and induced by thapsigargin. Triglyceride level in XBP-1-deficient group decreased significantly compared with high-fructose group (4.41 ± 0.54 µmol/g vs. 6.52 ± 0.38 µmol/g, P < 0.001), as mRNA expressions of SREBP-1c (2.92 ± 0.46 vs. 5.08 ± 0.41, P < 0.01) and protein levels of FAS (0.53 ± 0.06 vs. 0.85 ± 0.05, P = 0.01), SCD-1 (0.65 ± 0.06 vs. 0.90 ± 0.04, P = 0.04), and ACC (0.38 ± 0.03 vs. 0.95 ± 0.06, P < 0.01) decreased. Conversely, levels of triglyceride (4.22 ± 0.54 µmol/g vs. 2.41 ± 0.35 µmol/g, P < 0.001), mRNA expression of SREBP-1c (2.70 ± 0.33 vs. 1.00 ± 0.00, P < 0.01), and protein expression of SCD-1 (0.93 ± 0.06 vs. 0.26 ± 0.05, P < 0.01), ACC (0.98 ± 0.09 vs. 0.43 ± 0.03, P < 0.01), and FAS (0.90 ± 0.33 vs. 0.71 ± 0.02, P = 0.04) in XBP-1s-upregulated group increased compared with the untransfected group. CONCLUSIONS: ERS is associated with de novo lipogenesis, and XBP-1 partially mediates high-fructose-induced lipid accumulation in HepG2 cells through augmentation of de novo lipogenesis.

Effects of long-term high-saturated and unsaturated fatty acid diets on relaxation and contraction of renal arteries in insulin resistant rats.

The present study was designed to investigate the effects of high-saturated and high-unsaturated fatty acid diets on relaxation and contraction of the renal arteries in insulin resistance (IR) rats. Wistar rats were fed normal chow diet (control), high-saturated fatty acid diet or high-unsaturated fatty acid diet for 6 months (n=14 in each group). IR was evaluated by glucose infusion rate (GIR) of hyperinsulinemic euglycemic clamp. Blood pressure was measured via the tail-cuff method. Body weight (BW), plasma total triglyceride (TG), free fatty acid (FFA), insulin, fasting blood glucose (FBG) and nitric oxide metabolite (NO2(-)/NO3(-)) were compared among the three groups. The rats were sacrificed and the renal arterial rings were placed in the physiological tissue baths for measurement of vascular response to various agents. After the arterial rings were constricted with 3 mmol/L noradrenaline (NA), endothelium-dependent vasorelaxation to acetylcholine (ACh) and endothelium-independent vasorelaxation to sodium nitroprusside (NTP) were measured. Endothelium-dependent vasorelaxation to ACh was also observed in renal arterial rings incubated with L-arginine (L-Arg), N(omega)-nitro-L-arginine (L-NNA) and methylene blue (MB), respectively. Arterial contractility was evaluated from concentration-response curves to 10 nmol/L-100 micromol/L NA. Saturated or unsaturated fatty acids led to moderate rises in blood pressure (P<0.05). It was associated with higher levels of plasma lipids and lower whole body insulin sensitivity (P<0.01). There were no significant differences in BW, FBG, TG, insulin and FFA between saturated and unsaturated fatty acid-fed rats. A decrease in endothelium-dependent vasorelaxation of the renal arteries in saturated and unsaturated fatty acid-fed rats was observed (P<0.01), but there was no marked difference between the two high-fatty acid diet groups. Endothelium-dependent vasorelaxation was increased when the arteries were incubated with L-Arg and decreased when incubated with L-NNA and MB in both high-fatty acid diet groups (P<0.05, P<0.01). But no difference was found before and after incubation with L-Arg, L-NNA and MB in the control rats. In the mean time, endothelium-independent maximal vasorelaxation response of renal arteries to NTP and renal arterial contractile responses to cumulative dose of NA were assayed, and there was no difference among the three groups (P>0.05). Endothelium-dependent vasorelaxation was negatively correlated with systolic blood pressure and TG, and positively correlated with NO2(-)/NO3(-) and GIR. There was a significantly negative correlation between FFA and NO2(-)/NO3(-). The present study suggests that both high-saturated and unsaturated fatty acid diets result in hypertension associated with significantly decreased endothelium-dependent vasorelaxation, dyslipidemia and IR, and that decreased endothelium-dependent vasorelaxation induced by high fatty acid diets is associated with impaired L-Arg-NO-cGMP pathways.

[Vascular endothelial function and plasma free fatty acids in the high-risk population of type 2 diabetes].

OBJECTIVE: To study the vascular endothelial function and the level of plasma free fatty acids (FFA) in patients with type 2 diabetes mellitus (T2DM), their first degree relatives (FDRs) with normal glucose tolerance and subjects with impaired glucose tolerance (IGT) and to compare these with health control. METHODS: Endothelial-dependent vasodilation (EDV), plasma level of FFA, and insulin active index (IAI) were measured in 36 controls with normal glucose tolerance (16 men and 20 women), 57 FDRs (27 men and 30 women), 59 subjects with IGT (25 men and 34 women) and 35 patients with T2DM (15 men and 20 women). RESULTS: EDV was lower in FDRs, IGT and T2DM than that in the controls [FDRs (5.03+/-0.34)%, IGT (3.09+/-0.28)%, T2DM (2.62+/-0.29)%, controls (12.45+/-3.37)%]. The plasma level of FFA was higher in FDRs, IGT and T2DM than that in the controls [FDRs (0.52+/-0.08) mmol/L, IGT (0.52+/-0.12) mmol/L, T2DM (0.59+/-0.23) mmol/L, controls (0.46+/-0.18) mmol/L], IAI was lower in FDRs, IGT and T2DM than that in the controls (FDRs -4.20+/-0.38, IGT -4.41+/-0.72, T2DM -4.65+/-0.64, controls -3.79+/-0.57), P<0.05. CONCLUSIONS: There are decreased IAI, impaired endothelial function and increased plasma level of FFA in the FDRs with normal glucose tolerance, subjects with IGT and patients with T2DM.

Molecular characterization of Giardia duodenalis from white yaks in China.

Giardia duodenalis is one of the most common enteric parasites of humans and animals, including companion animals, livestock and wildlife. To date, the information about the prevalence and molecular characterization of G. duodenalis infection in white yaks was limited. In the present study, a total of 208 white yak fecal samples were collected from Tianzhu Tibetan Autonomous County (TTAC) between September 2013 and March 2014. Of the 208 white yak fecal samples, four samples (1.92%, all collected in March 2014) tested G. duodenalis-positive by PCR amplification of triosephosphate isomerase (tpi) gene. Sequence analysis confirmed the presence of G. duodenalis assemblage E. The present study revealed the presence and genotype of G. duodenalis in white yaks for the first time, and extended the host range of G. duodenalis. These results provided useful information for further genotyping or subtyping studies of G. duodenalis in white yaks.

Impact of activating transcription factor 4 signaling on lipogenesis in HepG2 cells.

Non-alcoholic fatty liver disease (NAFLD) is a rapidly growing health threat that has previously been associated with lipogenesis. The direct effect of endoplasmic reticulum stress (ERS) inhibition on the induction of lipogenesis has not been investigated in hepatocytes in vitro. The impact of activating transcription factor­4 (ATF4) on the lipogenic pathway and hepatic insulin transduction in liver cells also requires further investigation. In the present study, the triglyceride (TG) content of HepG2 cells stimulated with fructose was investigated using a commercially available enzymatic assay, and the expression levels of lipogenesis­associated factors were determined by western blotting and reverse transcription­quantitative polymerase chain reaction. Notably, the TG content of HepG2 cells was increased following incubation with fructose, which was accompanied by ERS. 4­Phenylbutyric acid, an inhibitor of ERS, lowered the TG content by reducing the mRNA expression levels of sterol regulatory element­binding protein 1 (SREBP­1c) and carbohydrate­responsive element­binding protein (ChREBP), and the protein expression levels of fatty acid synthase (FAS), acetyl­CoA carboxylase (ACC) and stearoyl­CoA desaturase­1 (SCD­1). Conversely, tunicamycin, which is an inducer of ERS, increased the TG content and stimulated the expression of the above lipogeneic markers. ATF4 deficiency relieved TG accumulation and decreased the mRNA expression levels of SREBP­1c and ChREBP, and protein expression levels of FAS, ACC and SCD­1 in fructose­treated HepG2 cells. Conversely, ATF4 overexpression increased the TG content by upregulating the mRNA expression levels of SREBP­1c and ChREBP and protein expression levels of FAS, ACC and SCD­1. Inhibition of ERS was shown to protect HepG2 cells against fructose­induced TG accumulation, whereas induction of ERS stimulated hepatic lipogenesis. As a downstream transcription factor of the unfolded protein response, a deficiency in ATF4 attenuates fructose­induced lipogenesis; while an overexpression of ATF4 can induce TG accumulation through stimulating hepatic lipogenesis. The results of the present study suggested that ATF4 may exert various physiological roles in lipid metabolism depending on the nutrient composition. In addition, these results suggested that ATF4 has a role in regulating lipogenesis and in the development of NAFLD; thus ATF4 may be considered a therapeutic target for NAFLD.

[A study on endothelial function and inflammation factors in the first degree relatives of type 2 diabetics with normal glucose tolerance].

OBJECTIVE: To study the vascular endothelial function and the level of inflammation factors in the first degree relatives (FDR) of type 2 diabetes (T2DM) patients with normal glucose tolerance and related factors. METHODS: Vascular endothelial function, plasma plasminogen activator inhibitor-1 (PAI-1), vascular cell adhesion molecule-1 (VCAM-1) and insulin active index (IAI) were measured in 57 FDR and 31 controls. RESULTS: As compared with the controls, there were less endothelium-dependent vasodilation [(12.45 +/- 3.37)% vs (5.03 +/- 0.34)%] and IAI [(-3.79 +/- 0.57) vs (-4.11 +/- 0.46)], higher PAI-1 [(30.46 +/- 12.28) microg/L vs (39.25 +/- 6.54) microg/L] and higher VCAM-1 [(637.31 +/- 107.32) microg/L vs (742.39 +/- 124.31) microg/L] in the FDR (P < 0.05). CONCLUSION: There were decreased IAI, damaged endothelial function and impaired fibrinolysis in the first degree relatives of T2DM patients with normal glucose tolerance.

[Effect of Astragalus injection on plasma levels of apoptosis-related factors in aged patients with chronic heart failure].

OBJECTIVE: To investigate the effect of Astragalus injection (AI) on plasma levels of apoptosis-related factors in aged patients with chronic heart failure (CHF). METHODS: Seventy-two CHF patients were randomly divided into the AI group (36 cases) treated with AI and the control group (36 cases) treated with conventional treatment. Plasma levels of soluble Fas (sFas), soluble Fas ligand (sFasL), tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assays (ELISA) with monoclonal anti-human antibodies. Besides, New York Heart Association (NYHA) grading was assessed according to improved symptoms and left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF) were assessed by echocardiogram after 4 weeks of treatment. RESULTS: After 4 weeks of treatment, NYHA grading was markedly improved in the two groups, but it was significantly better in AI group than that in the control group (P < 0.05). As compared with the control group, sFas, sFasL, TNF-alpha and IL-6 in the AI group were obviously lower, the difference between the two groups and between before and after treatment were significant (P < 0.05 or P < 0.01). Moreover, in AI group, LVESV and LVEDV decreased, LVEF increased, which was significantly different than that before treatment (P < 0.05), respectively. CONCLUSION: AI could lower plasma levels of apoptosis-related factors, and is one of the effective drugs in improving cardiac function in the aged patients with CHF.

Relationship between thioredoxin-interacting protein (TXNIP) and islet ß-cell dysfunction in patients with impaired glucose tolerance and hypertriglyceridemia.

AIMS: To study the relationship between thioredoxin-interacting protein (TXNIP) and pancreatic ß-cell function in patients with impaired glucose regulation and patients with both impaired glucose regulation and hypertriglyceridemia. METHODS: We analyzed a population of 90 patients with impaired glucose regulation (IGR), 87 patients with IGR and hypertriglyceridemia, and 90 subjects with normal glucose tolerance (NGT). The levels of plasma TXNIP, a regulator of cellular oxidative stress, were measured. The homeostasis model assessment for insulin resistance (HOMA-IR) was used to evaluate insulin resistance in all subjects. In addition, two factors (HOMA for ß-cell function [HOMA-ß]) and first-phase insulin response [FPIR]) were used to evaluate pancreatic ß-cell function. The correlations between the plasma levels of TXNIP, insulin resistance, and islet ß-cell dysfunction were analyzed using Pearson's correlation analysis. RESULTS: Compared with NGT, patients with IGR had significantly lower HOMA-ß and FPIR, and higher plasma levels of TXNIP. Compared with the IGR group, patients with both IGR and hypertriglyceridemia had significantly lower HOMA-ß and FPIR, and higher plasma levels of TXNIP. There was also a negative correlation between TXNIP and HOMA-ß or FPIR, and a positive correlation between TXNIP and HOMA-IR. CONCLUSIONS: These data showed that the level of TXNIP is increased in patients with IGR and patients with both IGR and hypertriglyceridemia, islet ß-cell dysfunction was related to the increased TXNIP in IGR patients.