More and more extrapancreatic actions of incretin-based therapies have been demonstrated and recently case reports have linked glucagon-like peptide-1 (GLP-1) receptor agouist therapy with the improvements in psoriasis.Psoriasis is a common skin disorder characterized by chronic inflammation.Epideminological studies have showed that patients with psoriasis exhibit increased rates of cardiovascular disease,obesity,and type 2 diabetes,owing probably to the enhanced local and (or) systemic inflammation.The observations of anti-inflammatory actions of GLP-1,which exerts direct and indirect actions on immune function,together with the improved psoriasis,offer new insights into the investigation of non-classical anti-inflammatory actions of incretin-based therapeutics and provide a new direction for the research of the novel clinical application of GLP-1.

ADVANCE study is designed to explore the effects of intensive glucose control and routine blood pressure lowering measures on major macro-and micro-vascular complications in patients with type 2 diabetes.It reveals a series of risk factors of macrovascular disease,and analysis for risk factors will take effective actions to prevent or intervene macrovascular events.

Objective To study the protective effects of tBHQ on type 2 diabetic rats retina and its related mechanism.Methods Sixty SD rats were divided into normal control group (NC group),model group (diabetes mellitus,DM group) and tBHQ group.After feeding with high fat and high sugar diets for 4 weeks,the rats in model group were induced by intraperitoneal injection of STZ for the model of type 2 diabetes mellitus.1％ tBHQ were added into the high fat and high sugar feed 1 week later after successfully modeled in the tBHQ group.Fasting plasma glucose (FPG) and fasting serum insulin (FINs) were detected at 4 and 12 weeks after modeled.Immunohistochemical method and real-time fluorescent quantitative PCR (qRT-PCR) were respectively used to detect the distributions and relative expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2),heme oxygenase 1 (HO-1),B-cell lymPhoma 2 (Bcl-2) and vascular endothelial growth factor (VEGF) in retinas of the rats.Results FPG levels totally comparative differences were statistically significant between each group (F =78.531,P =0.000).The level of FPG in DM and tBHQ group were obviously higher than that in NC group,the 12 weeks was higher than 4 weeks in DM group,and the 12 weeks was lower than 4 weeks in tBHQ group (all P ＜ 0.05).Totally comparative differences in the level of FINs were statistically significant (F=22.480,P =0.000),NC group was lower than DM and tBHQ group,12 weeks was higher than 4 weeks (all P ＜ 0.05).Immunohistochemical detection showed that each factor in each group were expressed in the retina of rat,and the relative expressions of Nrf2,HO-1,Bcl-2 and VEGF protein in retina have totally statistically differences in different time points after modeled (all P ＜0.05).The expressions of each factor in DM group were more than those in the NC group.The Nrf2,HO-1 and Bcl-2 in tBHQ group were more than those in the DM group,but the VEGF was lower.At 12 weeks,the expressions of VEGF and Nrf2 in DM group were more than those at 4 weeks,but the HO-1 was lower;the Nrf2,HO-1 and Bcl-2 in tBHQ group were more than those at 4 weeks (all P ＜ 0.05).PCR tests revealed that the relative expressions of Nrf2,HO-1,Bcl-2 and VEGF mRNA in retina have totally statistically differences in different time points after modeled(all P ＜ 0.05).The expressions of each factor in DM group were more than those in the NC group.The Nrf2,HO-1 and Bcl-2 mRNA in tBHQ group were more than those in the DM group,but the VEGF mRNA was lower.At 12 weeks,VEGF mRNA in DM group and Nrf2,HO-1,Bcl-2 in tBHQ group were more than those at 4 weeks (all P ＜ 0.05).Conclusion tBHQ maybe have protection for islet function on diabetic rat,and can induce the expressions of Nrf2,HO-1,Bcl-2 in retina of diabetic rats and reduce the expression of VEGF,inhibit the oxidative stress of retinal tissue damage,reduce cell apoptosis and inhibit the proliferation of retinal blood vessels.tBHQ may protect the retina of diabetic rats through the Nrf2/HO-1/VEGF and Nrf2/Bcl-2 way.

VP1, a capsid protein of swine vesicular disease virus, was cloned from the SVDV HK/70 strain and inserted into retroviral vector pBABE puro, and expressed in PK15 cells by an retroviral expression system. The ability of the VP1 protein to induce an immune response was then evaluated in guinea pigs. Western blot and ELISA results indicated that the VP1 protein can be recognized by SVDV positive serum, Furthermore,anti-SVDV specific antibodies and lymphocyte proliferation were elicited and increased by VP1 protein after vaccination. These results encourage further work towards the development of a vaccine against SVDV infection.

To gain a better understanding of the genetic diversity and evolution of PRRSV in the Ningxia Hui Nationality Autonomous Region (Ningxia) of China, the nsp2 genes from a series of PRRSV strains collected from the region in 2007 were partially sequenced. These sequences were then analyzed along with the classical strain (ch-la) and two other epidemic strains SD (3) and SD2006. Comparison of the nucleotide sequence with ch-la indicated that nsp2 genes of seventeen Ningxia isolates (NX strain) have deletions of 87 nucleotides. Sequence analysis indicated that homology between the Ningxia strain and ch-la was 60.3%-79.9% in the nucleotide sequence, and homology between the NX strains and SD strains was 80.3%-98.8% in the nucleotide sequence. The nsp2 genes of the seventeen isolates had 74.9%-100% nucleotide sequence identities with each other. This study was undertaken to assess the regional variation of prevalent PRRSV and to establish a sequence database for PRRSV molecular epidemiological studies.

E2 is an envelope glycoprotein of Classical swine fever virus (CSFV) and contains sequential neutralizing epitopes to induce virus-neutralizing antibodies and mount protective immunity in the natural host. In this study, four antigen domains (ABCD) of the E2 gene was cloned from CSFV Shimen strain into the retroviral vector pBABE puro and expressed in eukaryotic cell (PK15) by an retroviral gene expression system, and the activity of recombinant E2 protein to induce immune responses was evaluated in rabbits. The results indicated that recombinant E2 protein can be recognized by fluorescence antibodies of CSFV and CSFV positive serum (Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China) using Western blot, indirect immunofluorescence antibody test (IFAT) and ELISA, Furthermore, anti-CSFV specific antibodies and lymphocyte proliferation were elicited and increased by recombinant protein after vaccination. In the challenge test, all of rabbits vaccinated with recombinant protein and Chinese vaccine strain (C-strain) were fully protected from a rabbit spleen virus challenge. These results indicated that a retroviral-based epitope-vaccine carrying the major antigen domains of E2 is able to induce high level of epitope-specific antibodies and exhibits similar protective capability with that induced by the C-strain, and encourages further work towards the development of a vaccine against CSFV infection.

Background Apoptosis is a primary clinical pathological mechanism of diabetic retinopathy (DR).Oxidative stress and high glucose can activate cell apoptosis pathway and thus leads to cellular damage.It is confirmed that tert-butyl hydroquinone (tBHQ) plays an antioxidation effect,however,whether it has a protective role on retinal cells in DR is still unelucidated.Objective This study was to investigate the effect of tBHQ on vascular endothelial growth factor (VEGF) and bcl-2 expressions in retina of type 2 diabetic rats and its possible mechanism via nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signal pathway.Methods Fifty clean healthy male SD rats were included in this experimental study.Ten rats were fed with normal diet as the normal control group,and other rats were fed with high fatty and high sugar food for 4 weeks.After 12 hours of fasting,streptozotoin (STZ) (30 mg/kg) was intraperitoneally injected to induce the type 2 diabetic models.The model rats were randomly divided into the diabetic control group and tBHQ group and 1％ tBHQ was added into the high fatty and sugar food 1 week after modeling in the tBHQ group.Fasting plasma glucose (FPG) level,blood total cholesterol (TC) level,blood triglyceride (TG) level,high density lipoprotein-cholesterol (HDL-C),low density lipoproteincholesterol (LDL-C) and fasting serum insulin (FINs) were detected 4 and 12 weeks after modeling,respectively,and radio immunoassay was used to detect the FIN levels of the rats.The relative expression of VEGF and bcl-2 in retinas of the rats were assayed by immunohistochemistry and fluorescence real-time quantitative PCR (qRT-PCR).The use of the animals complied with the Regulations for the Administration of Affairs Concerning Experimental Animals by State and Technology Commission.Results Type 2 diabetic models were successfully established in 35 rats with successful rate 92.1％.The FIN levels were significantly different among different groups and time points (Fgroup =22.480,P =0.000;Ftime =7.636,P =0.008).The FPG,TC,TG and LDL-C levels were significantly different among the groups (FPG:Fgroup =78.531,P =0.000;TC:Fgroup =28.049,P =0.000;TG:Fgroup =13.108,P =0.000;LDL-C:Fgroup =6.804,P＜0.05).Immunohistochemistry showed that VEGF and bcl-2 were mainly expressed in retinal ganglion cell layer,inner plexiform layer and outer plexiform layer.The expressions of VEGF and bcl-2 proteins were significantly different among different groups (VEGF:Fgroup =11.805,P =0.000;bcl-2:Fgroup =22.943,P =0.000);the expression level of bcl-2 protein was higher in 12 weeks after modeling than that in 4 weeks after modeling in the tBHQ group (P＜0.05).The expressions of VEGF and Bcl-2 mRNA in rat retinas were significantly different among different groups and time points (VEGF:Fgroup =79.220,P =0.000;Ftimo =6.090,P＜0.05;Bcl-2:Fgroup =105.000,P=0.000;Ftime =13.170,P=0.001).Four and eight weeks after modeling,the expressions of VEGF and Bcl-2 mRNA in the diabetic control group and tBHQ group were significantly higher than that in the normal control group,and the expressions of Bcl-2 mRNA in the tBHQ group were significantly higher than that in the model control group (all at P＜0.05);the expression of Bcl-2 mRNA was higher at 12 weeks after modeling than that at 4 weeks in the tBHQ group (P＜0.05).Conclusions tBHQ produces anti-oxidative-damage and anti-apoptosis effects on retinal cells by up-regulating VEGF expression and down-regulating bcl-2 expression in DR rats.In addition,tBHQ may have effects on lowering high blood sugar,regulating insulin and blood lipid levels.

Objective To study the role of pancreatic renin-angiotensin system (RAS) on insulin secretion, proliferation, apoptosis, oxidative stress, and fibrosis of β-cells. Methods The effect of angiotensin Ⅱ on βTC3 cells was studied and the role and mechanism of AT1 R were analyzed with RNAi technology. The expression of AT1 R was measured by Western Blotting. The change of intracellular calcium was detected by microfluorimetry with Furo3-1oaded cells. Peroxide-sensitive fluorescent probe DCFH-DA was used to analyze intracellular ROS by flow cytometry. Real-time PCR was performed to evaluate mRNA levels related to proliferation and fibrosis in βTC3 cells. Apoptosis was detected by flow cytometry and Tunel method. Results Insulin secretion was significantly increased up to four fold and the level of intracellular calcium was sharply increased in response to high glucose in βTC3 cells. Angiotensin Ⅱ has no direct effect on insulin secretion in βTC3 cells and its role in secretion was associated with the role in proliferation. Oxidative stress in βTC3 cells caused by angiotensin Ⅱ may be partially mediated through AT1R, protein kinase C and NAD(P) H. With the decrease of AT1R expression by RNAi technology, apoptosis, and fibrosis of βTC3 cells induced by angiotensin Ⅱ might be ameliorated.Conclusions By means of AT1R, angiotensin Ⅱ plays an important role in insulin secretion, proliferation,apoptosis, oxidative stress and fibrosis in β-cells.

Betacellulin (BTC) is one of "islets regeneration factors" which received more and more attention these years. BTCe is the C-terminal 50-residue region of mature BTC protein and can bind with erbB-1?erbB-4 receptor. It has the same mitogenic activity on cells as the whole section. BTC and BTCe can improve the level of glucose-stimulated insulin secretion (GSIS) during islets culture in vitro though they had no effect on the acute insulin secretion. BTCe also effectively ameliorated the hyperglycemia of STZ-induced diabetic rats by a single plasmid injection into muscle of rats. It is supposed that BTCe promote the proliferation of PDX-1 positive cells or repair some signal transduction pathway. Perhaps the latter is more important.

Accumulated evidences suggest that reduction in blood pressure may reduce cardiovascular morbidity and mortality in diabetes patients. However, the optimal blood pressure level to which blood pressure should be reduced in diabetes patients have not reached an agreement and significant controversy has surrounded this topic in these years. After reviewing the data from observational studies and clinical trials, we compared the similarities and differences of recommendations about blood pressure target for people with diabetes and hypertension. Based on our study about the 10 years effects of different blood pressure levels on cardiovascular disease events among Chinese adults with different glucose metabolism, we analyzed the critical factors on conducting randomized controlled trials concerning optimal blood pressure level among patients with diabetes or prediabetes.