Objective To investigate the relationship between with or without non?alcoholic fatty liver disease(NAFLD) and diabetic retinopathy(DR) in type 2 diabetes mellitus(T2DM)?Methods Clinical and laboratorial data of 517 cases T2DM hospitalized patients were collected,and the patients were divided into two groups according to if the NAFLD was complicated or not?Group A was T2DM with NAFLD and group B was T2DM without NAFLD?The general information and the laboratorial checking results were Compared, then various index were used as the independent variable, DR was used as the dependent variable for Logistic regression analysis?Results (1)In the 517 cases of T2DM patients,the incorporative rate of the NAFLD was 65?7%(349/517)?(2)Compared with group B,the levels of body mass index(BMI),insulin resistance index (HOMA?IR),glutamyltransferase(GGT),alanine aminotransferase(ALT),aspartate aminotransferase(AST), triglyceride(TG),total cholesterol(TC),low?density lipoprotein cholesterol(LDL?C) and uric acid(UA) for group A were significantly increased, while the high?density lipoprotein cholesterol ( HDL?C ) level was significantly decreased?All the differences were statistically significant( P<0?05)?( 3) Logistic analysis showed that the duration of the extension,hypertension,the increasing level of NAFLD,LDL?C were the risk factors of DR?Even though excluded the influence of duration,high blood pressure and LDL?C level,NAFLD was still the risk factor for T2DM complicated by the DR( OR=2?176,95% CI ( 1?354,3?199) )?Conclusion NAFLD and DR are closely related, so early diagnosis and intervention of NAFLD may prevent the occurrence and development of DR.

Objective To explore the expressions of endoplasmic reticulum stress (ERs) related factors including inositol requiring enzyme-1α(IRE1αα),p-IRE1 α,c-jun N-terminal Kinase(JNK),and p-JNK in rats with non-alcoholic fatty liver disease,and to investigate the effect of intervention with glucagon-like peptide 1 (GLP-1) analogue.Methods Forty male Sprague-Dawley rats were divided into normal chow group(n =15) and high-fat diet group(n=25).After 12 weeks,5 rats of each group were used to assess the establishment of rat models with non-alcoholic fatty liver disease.Then the high-fat diet group rats were divided into high-fat diet group (HF,n =10) and GLP-1 group(HG,n=10) and treated with normal saline and GLP-1 analogue for4 weeks respectively.Body weight and biochemical markers in rats were measured.The expressions of IRE1α,p-IRE1α,JNK,and p-JNK were measured by Western blot.Results Compared with the NC group,the levels of body weight,plasma triglyceride (TG),total cholesterol (TC),low density lipoprotein-cholesterol (LDL-C),alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in HF group were significantly higher (all P ＜ 0.01),high density lipoprotein-cholesterol(HDL-C) was decreased(P＜0.01),and p-IRE1 α/IRE1 α and p-JNK/JNK were increased(P＜0.05 and P＜0.01).After GLP-1 treatment,body weight,plasma TG,TC,LDL-C,AST,ALT in HF group were significantly lowered(P＜0.05 or P＜0.01),HDL-C was increased(P＜0.01),p-IRE1 α/IRE1 α and p-JNK/JNK were decreased (P＜0.05 and P＜0.01).Conclusion GLP-1 analogue may improve hepatic steatosis via regulating ERs related IRE1 α-JNK signaling pathway.

Animals ; Cell Hypoxia ; Cells, Cultured ; Chemokine CXCL12 ; genetics ; metabolism ; Endothelial Cells ; cytology ; metabolism ; Female ; Gene Expression Regulation ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Immunohistochemistry ; Male ; Pulmonary Artery ; cytology ; RNA Interference ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Swine

Objective: To observe whether liraglutide protects HepG2 cells from lipotoxicity by affecting mitogen-activated protein kinase (MAPKs) pathway. Methods: HepG2 cells were induced with 400μmol/L palmitic acid, and cells were treated with a final concentration of 100 nmol/L liraglutide. In addition, JNK inhibitor (SP600125) and p38 MAPK inhibitor (SB203580) were added in advance, respectively. Apoptosis rate, malondialdehyde (MDA) content, and caspase3 activity were detected. Western blot was used to detect p38 mitogen-activated protein kinase (p38 MAPK), c-jun amino terminal kinase (JNK), cytochrome oxidase P450 2E1 (CYP2E1), glucose regulatory protein 78 (GRP78), activated caspase 3, B cell lymphoma associated Protein X (Bax), B cell lymphoma 2 (Bcl-2), and expression of C/EBP homologous protein (CHOP) protein. LSD or Dunnett’s T3 test were used to compare the mean of multiple samples. Results: Palmitic acid increased the phosphorylation of p38 MAPK and JNK in HepG2 cells (P< 0.05). Furthermore, it increased the expression of GRP78, CHOP, CYP2E1, MDA, Bax, caspase3 and apoptosis rate, but inhibited the expression of Bcl-2 (Pvalue < 0.05). SP600125 and SB203580 had inhibited oxidative stress and apoptosis induced by palmitic acid (including CYP2E1, MDA, Bax, Bcl-2, caspase3, CHOP) (P< 0.05). The phosphorylation level of p38 MAPK and JNK was reduced with liraglutide and the expression of apoptosis-related proteins (Bax, Bcl-2, caspase3, CHOP) (P< 0.05) was regulated. There was no significant difference in the effect of liraglutide on apoptotic proteins (Bax, Bcl-2, caspase-3, CHOP) (P> 0.05) after pretreatment with those two inhibitors. Conclusion Palmitic acid has strong lipotoxicity to HepG2 cells and induces apoptosis. Glucagon-like peptide-1 analogue, liraglutide may improve lipotoxicity of palmitic acid by mediating p38 MAPK and JNK pathways.

OBJECTIVETo investigate the effects of glucagon-like peptide-1 (GLP-1) on liver oxidative stress injury using a rat model of non-alcoholic fatty liver disease.

METHODSSixty male Sprague-Dawley rats were fed 12 weeks of either a diet of normal chow (NC), for use as controls (n =15) or high-fat chow (HF), for use as models (n =45).The NC rats were administered normal saline, while the HF rats were treated with either normal saline (NS), for use as untreated model controls (n =10), low-dose GLP-1 (LG, 50 mutg/kg; n =10), mid-dose GLP-1 (MG, 100 mutg/kg; n =10), or high-dose GLP-1 (HG, 200 mug/kg; n =10); all treatments lasted for 4 weeks.The rats' weight, levels of serum biochemical markers (triglycerides, total cholesterol, high-density lipoproteincholesterol, low-density lipoprotein-cholesterol, alanine arninotransferase, and aspartate aminotransferase), levels of superoxide dismutase (SOD) and malondialdehyde (MDA), and expression of CYP2E1 mRNA and protein in liver homogenates were measured.The F test, t-test, least significant difference test and Dunnett's T3 test were used for statistical analyses.

RESULTSCompared with the NC group, the rars in the NS group showed significantly lower SOD (165.81 ± 11.64 vs.192.89 ± 16.53 U/mg, P < 0.05), significantly higher MDA (7.30 ± 1.79 vs.3.10 ± 1.30 nmol/ mg, P < 0.05), and significantly higher expressions of CYP2E1 mRNA and protein (both P < 0.05).After GLP1 treatment, the rats in the LG, MG and HG groups showed increased levels of SOD (compared to the NS group; 171.44 ± 9.80 vs.177.66 ± 14.77 vs.186.17 ± 15.43 U/mg; only the HG group had P < 0.05), significantly decreased levels of MDA (compared to the NS group; 5.16 ± 1.45 vs.4.08 ± 1.22 vs.3.31 ± 1.14 nmol/mg; all P < 0.05], and decreased levels of CYP2E1 mRNA and protein expressions (CYP2E1 mRNA:only the HG group had P < 0.05; CYP2E1 protein: both the MG and HG groups had P < 0.05).

CONCLUSIONGLP-1 treatment can improve oxidative stress injury, suggesting its potential as a therapeutic agent for non-alcoholic fatty liver disease.

Animals ; Aspartate Aminotransferases ; Cytochrome P-450 CYP2E1 ; Glucagon-Like Peptide 1 ; metabolism ; Male ; Malondialdehyde ; Non-alcoholic Fatty Liver Disease ; metabolism ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; Triglycerides

Objective To investigate the relationship between sex hormone binding globulin (SHBG) in serum and diabetic retinopathy (DR) in patients with type 2 diabetic mellitus (T2DM).Methods A total of 160 hospitalized people with T2DM was enrolled into the study.The patients were divided into two groups with or without merged DR.Clinical and laboratorial data were collected, and the correlation was analyzed between sex hormone binding globulin and diabetic retinopathy.Results (1) Compared to the group without DR, patients in T2DM with DR had significant lower SHBG concentration, triglyceride (TG) and total cholesterol (TC) concentration were increased significantly (P ＜ 0.01).(2) The level of SHBG was associated with waist circumference, body weight, fasting blood glucose, and glycosylated hemoglobin (P ＜ 0.05).(3) While the level of SHBG was significantly increased from Quartile 1 to Quartile4, the prevalence of DR was also significantly decreased (A:70％, B:51.2％,C:40.5％, D:29.7％) (P ＜ 0.01).(4) Logistic regressing analysis shows that with the decrease of SHBG level, the increase of triglyceride levels, the risk of DR was significantly increased (SHBG:OR:0.616,95％ CI:0.447-0.850,P ＜ 0.01;TG:OR:1.323,95％ CI:1.025-1.707,P＜0.05).Conclusions With the decrease of SHBG, the prevalence of DR is significantly increased, lower SHBG may be one of the hazards of T2DM patients with DR.

Objective To study the effects of ω-3 fatty acid on liver function in patients undergoing hepatectomy. Methods A PubMed, Embase and Cochrane Library database search was performed to retrieve all of the randomized controlled trial (RCT) evaluating the value of perioperative ω-3 fatty acid in patients undergoing hepatectomy until the end of September 2016. Data extraction and quality assessment of RCT were performed in accordance with PRISMA guidelines. The quality of evidence for each postoperative outcome was assessed using the GRAD Profiler system. A random-effects model was used to conduct a Meta-analysis with RevMan 5.3.5 software. Results Five documents were identified according to the inclusion criteria. Meta- analysis results showed that ω- 3 fatty acid significantly reduced the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) on the third day of the operation in patients undergoing hepatectomy: mean difference ( MD ) = -74.89 and-60.87, 95% CI-110.02?39.76 and-96.05?-25.68, P＜0.01; ω-3 fatty acid significantly increased the level of prealbumin (Pre-Alb) on the third day of the operation: MD＝9.61, 95% CI 4.22?15.00, P＜0.01; but ω-3 fatty acid did not improve the levels of total bilirubin (TBil) and albumin (Alb) on the third day of the operation: MD=-1.13 and 1.16, 95% CI-2.48?0.21 and-0.35?2.68, P＞0.05. Conclusions The ω-3 fatty acid is potentially beneficial in reducing the levels of ALT and AST, and increases the level of Pre-Alb on the third day of the operation in patients undergoing hepatectomy, but does not improve the levels of TBil and Alb.

Non-alcoholic fatty liver disease(NAFLD), the incidence of which grows rapidly, has become the main cause of abnormal liver enzymes in healthy individuals. By now, no clear consensus has been reached on the treatment due to the multi-factorial pathogenesis of NAFLD. It has been indicated by a lot of studies that there is a close association between the pathogenesis, treatment and prognosis of non-alcoholic fatty liver disease and type 2 diabetes. So some measures of type 2 diabetes, including lifestyle intervention, medication and bariatric surgery, have been gradually used for NAFLD patients. This article introduces and summarizes the above-mentioned treatment for nonalcoholic fatty liver disease.

Objective Rats were fed with high-fat diet and were successfully induced the models with non-alcoholic fatty liver disease,and to investigate the effects of liraglutide on the expression of ERp46.Methods Thirty male Sprague-Dawley rats were assigned to normal chow group(NC,n=10)and high-fat diet group(n=20),after 12 weeks,the high-fat diet group rats were divided into high-fat diet group(HF,n=10)and liraglutide group(100L,n=10) and treated with normal saline and liraglutide(100 μg/kg)for 4 weeks respectively. Liver tissues were measured by hematoxylin-eosin(HE),Oil Red O staining,hepatic triglyceride(TG),and hyperinsulinemic-euglycemic clamp test(HECT). Hepatocyte apoptosis rate were evaluated by TdT-mediated dUTP nick-end labeling(TUNEL),and the expressions of ERp46 mRNA and protein were measured.Results Compared with the NC group,the liver tissues in the HF group have steatosis,insulin resistance,and the percentage of apoptosis was significantly increased. ERp46 mRNA and protein expressions were decreased(P<0.05). Compared with the HF group,liraglutide treatment was sufficient to reduce steatosis,insulin resistance,apoptosis,and increase the ERp46 mRNA and protein(P<0.05). Furthermore,the expression of ERp46 protein in the liver was negatively correlated with hepatocyte apoptosis rate,and positive correlated with glucose infusion rate(GIR, P<0. 05). Conclusion Liraglutide may up-regulate the expression of ERp46 to improve IR and hepatocyte apoptosis in NAFLD rats.

Asthma is a common respiratory disease charaeterized by airway inflammation and airway hyperresponsiveness.Dopamine is an important neurotransmitter in human body.In reeent years it has been reported that dopamine reeeptor is expressed in immune eells, type I alveolar eells, airway epithelium and airway smooth muscle, and affects ovalbumin ( OVA )-indueed asthma in animals.This review introduees the role of dopamine in the occurrence and development of asthma from the aspeets of airway inflammation, pulmonary nerve regulation, airway epithelial and smooth muscle abnormalities.