Nicotinamide and Exendin-4 could promote transdifferentiation of rat BM-MSCs into insulin-producing cells in vitro, which expressed insulin, C-peptide and related genes.

Objective:To evaluate the short-term prognostic value of model for end-stage liver disease (MELD) combined with high density lipoprotein-cholesterol (HDL-C) in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF).Methods:From December 2015 to December 2018, 182 patients with HBV-ACLF who were treated in Henan Provincial People′s Hospital were included. Prognosis and clinical data including HDL-C, total bilirubin, international standardized ratio (INR), creatinine of patients within 24 hours after admission were collected and analyzed retrospectively.The values of MELD were calculated. The binary logistic regression analysis was used to analyze the independent risk factors affecting 90-day mortality in HBV-ACLF patients.The receiver operator characteristic curve (ROC) and MedCalc 15.2 software were used to assess the predictive value of MELD, HDL-C and MELD-HDL-C model for prognosis. Kaplan-Meier survival curve was performed to analyze the prognosis of patients in different groups.Results:Sixty patients were divided into the death group and 122 patients were divided into the survival group according to the prognosis during hospitalization and 90 days after discharge. The MELD score of patients in the survival group was 21(19, 24), which was significantly lower than that in the death group (29(25, 34)), and the HDL-C value of patients in the survival group was significantly higher than that in the death group (0.3 (0.1, 0.6) mmol/L vs 0.2(0.1, 0.5) mmol/L). The differences were both statistically significant ( Z=-6.290 and -4.087, respectively, both P<0.01). Multivariate logistic regression analysis showed that MELD score and HDL-C value were the independent risk factors for 90-day mortality in patients with HBV-ACLF(odds ratio ( OR)=1.432, 95% confidence interval ( CI)1.271-1.613; OR=0.584, 95% CI 0.487-0.700, respectively; both P<0.01). Areas under the ROC of MELD, HDL-C and MELD-HDL-C scoring models were 0.775, 0.782 and 0.878, respectively. MELD-HDL-C scoring model was superior to both MELD and HDL-C , and the differences were both statistically significant ( Z=3.944 and 3.104, respectively, both P<0.01). When the MELD-HDL-C Youden′s index was set at 0.72, the optimal threshold was 24.69. Patients with MELD-HDL-C score≥24.69 had lower survival rate than patients with MELD-HDL-C score<24.69, and the difference was statistically significant ( χ2=142.900, P<0.01). Conclusion:MELD, HDL-C and MELD-HDL-C scoring systems could predict the short-term prognosis in patients with HBV-ACLF, and the predictive value of MELD-HDL-C has the superiority.

Objective To evaluate the gray matter alterations in amyotrophic lateral sclerosis (ALS)by voxel-based morphometry (VBM),and further analyze the correlation between volume changes of gray matter and clinical characteristics.Methods Twenty-seven non-demented patients with ALS and 27 age and gender matched healthy controls were recruited.FSL-VBM was used to detect whole brain gray matter differences between the two groups.Seven prior ROIs were set to be analyzed,including bilateral precentral gyrus,postcentral gyrus,superior,medial,inferior,middle frontal gyrus,and insular cortex.The mean gray matter density of the ROIs was extracted in order to explore the correlation with several clinical measurements such as disease durations and disease severity scores,by using partial correlation analysis with age as covariates.Results Whole brain analysis showed significant gray matter loss in the left precentral gyrus,superior frontal gyrus and postcentral gyrus (numbers of voxel in clusters were 338,112,127,Z =4.83,4.09,6.42,P ＜0.05,FWE corrected).A prior seven ROIs analysis detected gray matter loss in the left precental gyrus,right precentral gyrus,left postcentral gyrus,superior frontal gyrus and left insular cortex (numbers of voxel in clusters were 1104,34,114,91,107,Z =5.87,3.71,4.26,6.29 and 3.51,P ＜0.05,FWE corrected).No statistical significant correlation between regional gray matter loss and clinical measurements were found.Conclusions Motor and extra-motor gray matter loss are present among patients with ALS,which demonstrates ALS as a multi-system disorder.In contrast to whole brain gray matter analysis,ROI analysis is more sensitive to detect extensive cortical changes.The heterogeneity of disease and sensitivity of method may contribute to the lack of correlation between gray matter volume decrease revealed by VBM and clinical characteristics.

Glycemic excursion was induced in SD rats by intraperitoneal injection of 50% glucose solution, and cells isolated from bone marrow of these rats showed cell clusters which expressed insulin, c-peptide, glucagon, somatostatin and islet amyloid polypeptide, and other genes related to islet-cells development and functions.

The intrauterine growth retardation (IUGR) model was established by maternal nutrition restriction during mid- to late-gestation. IUGR rats had both impaired pancreatic development and islet β-cell dysfunction. As the animals grew, the rats gradually showed impaired glucose tolerance and decreased insulin sensitivity.

Genechip was applied to explore gene expression profile of islets in rats at various stages of pregnancy. Compared with the normal control group, differential expressions of hundreds of genes were detected during pregnancy. Reg3α gene expression was markedly increased during pregnancy, which may be related to islet regeneration.

The potential effect of donor CD4+ CD25+ regulatory T ceLls on the suppression of rejection for allogenetic islet transplantation in vivo was investigated. CD4+ CD25+ regulatory T cells were generated by magnetic activated cell sorting and were ailogeneically transfered with islet transplantation in streptozotocin-induced diabetic BALB/cByJ mice. The results showed that allogeneic CD4+ CD25+ regulatory T cells prolong islet graft survival and normoglycemia in transplanted allogeneic diabetic mice.

Objective To compare the effects of intermittent high blood glucose and consistent hilgh blood glucose on pancreatic islet β-cell function and β-cell apoptosis in GK rats.Methods Twenty-two male GK rats were randomly divided into 2 groups consisting of consistent hish blood glucose group(HG)and intermittent high blood glucose group(FG).Eleven male Wistar rats were used as normal glucose controls(NG).The fluctuating high blood glucose animal model was induced by intraperitoneal injection of insulin and glucose at different time for six weeks.Intraperitoneal injection glucose tolerance test and insulin release test were performed.The area under curve of glucose(AUCg).the area under carve of insulin(AUCi)/AUCg and the ratio of insulin increment to blood glucose increment 15 min after glucose load(Δ115'/ΔG15')were calculated routinely.Then the pancreatic slides were stained with insulin antibody.The apoptotic β cells in islets were detected and quantified by the TUNEL technique.Results(1)The fasting plasma glucose and 15,30,60,and 120 min plasma glucose levels after glucose loading in FG group were significantly higher than those in control group(all P<0.01),and AUCg was also markedly increased[(1 012.14±82.62 vs 813.60±56.70)ng·ml~(-1)·h~(-1)·10~4,P<0.01].Insulin levels of FG group at 15,30,60,and 120 rain after glucose loading were significantly lower than those in HG group[(0.554± 0.18 vs 0.95±0.28.0.43±0.17 vs 0.85±0.21,0.47±0.11 vs 0.76±0.16,0.58±0.13 vs 1.08±0.26)ng/ml,P<0.05],along with decreased AUCi/AUCg and Δ115'/ΔG15'[(9.56±2.53 vs 21.36±4.16)×10~(-7);(3.95±3.45 vs 27.02±8.62)×10~(-7),both P<0.05].(2)Image analysis of pancreatic islet immunocytoehemistry showed that the insulin staining positive area,area ratio and total density of insulin positive cells per islet were significantly lower in FG group than those in HG group(P<0.05).(3)The percentage of β-cell apoptosis in the FG group was statistically higher than that in the HG group[(24.17±7.25 vs 16.55±5.11)%,P<0.01].Conclusion Compared with the consistent high blood glucose,intermittent high glucose could lead to further impairment of β-cell function and increased β-cell apoptosis may partially contribute to this process.

This study sought to assess the effects of serum containing Guilu-Erxian (GLEX) on treating osteoporosis at the cellular level. First, Enzyme-digestion was used to obtain osteoblasts from newborn SD rats. Alkaline phosphatase staining was used to identify osteoblasts. The proliferation and the secretion of Insulin Like Growth Factor-1 (IGF-1) of osteoblasts were examined. Second, osteoclasts were generated by inducing bone marrow cells of SD male rat (6-9 weeks) with 1,25(OH)2D3. The osteoclasts were identified through tartrate-resistant acid phosphatase (TRAP) staining. Bone pits of osteoclasts were observed through Electron Scanning Microscope. At the same time, TRAP(+) cells with more than two nuclei and TRAP activity of osteoclasts were examined. Last, serum containing Guilu-Erxian was made through serum pharmacology. And we observed the effects of serum containing Guilu-Erxian on the function of osteoblasts and osteoclasts. We found that high doses of serum containing Guilu-Erxian had obvious effects on stimulating the multiplication and capability of secreting IGF-1 of osteoblasts cultured in vitro. Middle doses obviously inhibited the formation of osteoclasts and bone pits; TRAP activity of osteoclasts was also lowered clearly. This study indicated that Guilu-Erxian has positive effects on treating osteoporosis.
Acid Phosphatase ; metabolism ; Alkaline Phosphatase ; metabolism ; Animals ; Animals, Newborn ; Cell Proliferation ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Insulin-Like Growth Factor I ; metabolism ; Male ; Osteoblasts ; cytology ; metabolism ; Osteoclasts ; cytology ; metabolism ; Osteoporosis ; drug therapy ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Serum

Objective To compare the effects of rat proinsulin gene therapy via intraportal infusion and intramuscular injection blood glucose level in streptozotocin-induced diabetic rots. Methods (1) Recombinant eukaryotic cell expression plasmid of rat proinsulin gene pCMV/proiusulin was transferred into streptozotocin-induced diabetic rats by intraportal infusion and intramuscular injection to observe the effect of rat proiusulin gene therapy in diabetic rats. The treatment group by intraportal infusion (group A) and the group by intramuscular injection (group C) were given pCMV/proinsulin naked plasmid DNA 100 μg, while the control groups by intraportal infusion (group B) or by intramuscular injection (group D) were treated with similar amount of pCMV DNA. Normal group and diabetes mellitus group were also observed at the same time. (2) Blood glucose level was tested and serum insulin was determined by radioimmunoassay. RT-PCR and immunohistochemistry were used to detemine proinsulin mRNA and protein expressions in liver and skeletal muscle and protein. Results (1) The blood glucose levels in two treated groups were both decreased. In group A, levels of blood sugar decreased about 7 mmol/L and glycemie control was maintained for 3-4 weeks. Serum insulin levels step up significantly after pCMV/proinsulin gene therapy. The blood glucose level in group A was significantly lower than those of group B and DM group (P<0.05), while the serum insulin level was higher than those of two groups (P<0.05). In group C, blood glucose levels decreased about 4 mmol/L and glycemic control was maintained for 1-2 weeks. Meanwhile, the concentrations of insulin increased markedly after gene therapy. The blood glucose in group C was significantly lower than those of group D and DM group (P<0.05), while the serum insulin level was higher than those of two groups (P<0.05). (2) Proinsulin mRNA and protein expressions could be detected in either hepatic cell of group A or skeletal muscle cell of group C, not in group B and group D. Conclusion Proiusulin genetherapy via intraportal infusion or intramuscular injection lowers significantly blood glucose in diabetic rats, and thus offers a potential approach to treatment of diabetes.