Gong L.,Sichuan Industrial Institute of Antibiotics |
Zeng W.,Sichuan Agricultural University |
Yang Z.,Sichuan Industrial Institute of Antibiotics |
Chen Z.,Key Laboratory of Animal Disease and Human Health of Sichuan Province |
And 5 more authors.
Pancreas | Year: 2013
OBJECTIVES: Type 2 diabetes mellitus (T2DM) is the most common form of diabetes. To determine the similarities of development of T2DM between rhesus monkey [Macaca mulatta lasiotis (M. m. lasiotis)] and human being, the clinical parameters were determined during a period of 2 years in 60 adult male rhesus monkeys (M. m. lasiotis). METHODS: Sixty male monkeys whose fasting plasma glucose (FPG) level less than or equal to 5 mmol/L (90 mg/dL) were enrolled in this study. Of these, 50 monkeys aged 7 to 20 years were fed with high-fat diet and 10 aged 4 to 10 years fed with standard diet as normal monkeys. Body weight, body mass index, FPG, fasting plasma insulin, and hemoglobin A1c levels were measured and calculated. The responses of insulin and glucose levels to intravenous glucose tolerance test were analyzed. RESULTS: Of 50 monkeys fed with high-fat diet, 8 developed overt T2DM, 26 experienced impaired glucose tolerance and impaired fasting glucose, and FPG of 16 monkeys was normal. All monkeys with impaired glucose tolerance experienced obesity, compensatory increase of fasting plasma insulin, significant decline of postprandial glucose clearance rate (KGluc5-20), and decreased insulin secretion. CONCLUSIONS: In conclusion, rhesus monkey (M. m. lasiotis) has many similarities with human beings in terms of clinical manifestations and risk factors at different diabetes stages. Copyright © 2013 by Lippincott Williams & Wilkins.
PubMed | University of Sichuan, Sichuan PriMed Shines Bio Technology Co., Yaan Peoples Hospital and Sichuan Industrial Institute of Antibiotics
Type: | Journal: BMC cardiovascular disorders | Year: 2015
Diastolic heart failure is a common and deadly complication of diabetes mellitus, with the development of diabetic cardiomyopathy as one of the key determinants of the diseases complex pathology. The cause of the association is unknown and has no approved therapy strategies as of yet. However significant advances in this area may come from studies on suitable animal models.A total of 25 male rhesus monkeys (12-16 years, 9-13kg) were enrolled. Fifteen of them were diagnosed as spontaneous type 2 diabetes mellitus (T2DM, FPG104mg/dl, HbA1c: 4.7-5.5%, diabetes duration: 1-4 years). The other 10 monkeys were non-diabetic (ND, FPG<90mg/dl). Echocardiography and cardiac magnetic resonance were used for evaluating the cardiac structure and function. One T2DM monkey with impaired diastolic function and another ND monkey were both sacrificed to gain the necessary pathology and protein expression studies displayed here.Six out of 15 T2DM rhesus monkeys were diagnosed with diastolic dysfunction (DD) by echocardiography. Additionally, no abnormalities were found in the group which we determined as the ND monkeys. The six DD monkeys all showed low e velocity and decreased e/a ratio, among which three of them showing decreased E/A ratio and the other 3 having elevated E/A ratio, this appears to be similar to the impaired relaxation pattern and pseudonormal pattern found in human patients respectively. The EF and FS of monkeys with pseudonormal pattern decreased significantly compared with ND subjects. A CMR study showed that LVID at end systole of 5 DD monkeys is significantly longer than that of 3 ND monkeys. Of great interest, myocardium lesions and mitochondria impairments and increased expression of AGEs and caspase-3 were found in a sacrificed DD subject.The changes in the imaging and physiological markers of spontaneous T2DM rhesus monkeys are similar to those key markers found in human type 2 diabetes and diastolic dysfunction. This monkey model could help the medical community and us to understand the pathology of this debilitating disease and serve as a beginning to explore important measures to prevent and treat diabetic cardiomyopathy.
He M.,Babraham Institute |
He Y.,Sichuan Industrial Institute of Antibiotics |
Luo Q.,University of Sichuan |
Wang M.,Sichuan Industrial Institute of Antibiotics
Process Biochemistry | Year: 2011
Proteomics and biotechnology studies require simple and rapid methods to convert the genetic information into proteins. Whereas heterologous protein expression in living cells is a time-consuming process, in vitro translation directs protein synthesis in hours from added linear PCR DNA without the need for E. coli cloning, thus providing an attractive alternative to cell-based methods for high throughput production of proteins. Moreover, the open nature of cell-free systems and availability of various prokaryotic and eukaryotic cellular lysates offers a flexible choice of conditions for synthesis of folded proteins or production of "difficult" proteins that are not possible by in vivo systems. Finally, cell-free extracts express protein populations in a single reaction, allowing for the development of powerful proteomic tools. This article will review the recent advances in cell-free protein expression and its applications in biotechnology, proteomics and fundamental biological research. © 2010 Elsevier Ltd.
PubMed | Sichuan Primed Bio Technology Group Co. and Sichuan Industrial Institute of Antibiotics
Type: Journal Article | Journal: Chinese journal of natural medicines | Year: 2015
The present study was designed to characterize the blood chemistry, hematology, and lymphocyte subsets in pregnant rhesus monkeys and provide baseline parameters for future studies of reproductive and developmental toxicity and developmental immunotoxicity. Harem-mating was used in 96 female and 16 male rhesus monkeys. Pregnancy was confirmed on gestation day (GD)18 by ultrasound. The blood samples of rhesus monkeys were collected at various times (20 days before pregnancy and GD20, 100 and 150). The analyses of blood chemistry, hematology, and lymphocyte subsets were performed. Compared with 20 days before pregnancy, Significant decreases (P < 0.05) were observed in HCT and RBC on GD20, GD150 and in HGB on GD150, Significant increases in NEUT and decreases in LYMPH on GD20 were observed. Significant decreases in ALB from GD20 to GD150 were observed, significant decreases in TP was observed on GD100. Significant increases in mean GLU were observed on GD20 and GD150 during pregnancy. Significant decreases (P < 0.05) in CD20(+) subsets on GD100, GD150 and CD4(+)/CD8(+)ratio on GD150 were observed, The significant changes of MCV, MCHC, RDW-SD, MCV, MONO, ALT, AST, GLB, ALP, TBIL, DBIL, IBIL, GGT, CR-S, URIC, TC, TG and CK were observed during the pregnant period, but no biologic change were observed, There were no significant changes in MCH, RDW-CV, MPV, BUN, CD3(+), CD4(+) and CD8(+) during pregnancy. These data provide a database for preclinical study in rhesus monkeys. Physiological anemia, hyperglycemia, and immune suppression may occur in pregnant rhesus monkey which is similar to that found in human, and it is essential to distinguish the physiological changes from the pharmacological effects in reproductive and developmental toxicity and developmental immunotoxicity studies of pharmaceuticals.
Chen F.,Chinese Academy of Sciences |
Chen F.,Sichuan Industrial Institute of Antibiotics |
Lin L.,Chinese Academy of Sciences |
Lin L.,Northeast Agricultural University |
And 7 more authors.
Applied Microbiology and Biotechnology | Year: 2011
To investigate the distribution of dTDP-glucose-4,6-dehydratase (dTGD) gene and diversity of the potential 6-deoxyhexose (6DOH) glycosylated compounds in marine microorganisms, a total of 91 marine sediment-derived bacteria, representing 48 operational taxonomic units and belonging to 25 genera, were screened by polymerase chain reaction. In total, 84% of the strains were dTGD gene positive, suggesting 6DOH biosynthetic pathway is widespread in these marine sediment-derived bacteria. BLASTp results of dTGD gene fragments indicate a high chemical diversity of the potential 6DOH glycosylated compounds. Close phylogenetic relationship occurred between dTGDs involved in the production of same or similar 6DOH glycosylated compounds, suggesting dTGD can be used to predict the structure of potential 6DOH glycosylated compounds produced by new strains. In two cases, where dTGD shared ≥85% amino acid identity and close phylogenetic relationship with their counterparts, 6DOH glycosylated compounds were accurately predicted. Our results demonstrate that phylogenetic analysis of dTGD gene is useful for structure prediction of glycosylated compounds from newly isolated strains and can therefore guide the chemical purification and structure identification process. The rapid identification of strains that possess dTGD gene provides a bioinformatics assessment of the greatest potential to produce glycosylated compounds despite the absence of fully biosynthetic pathways or genome sequences. © 2011 Springer-Verlag.
PubMed | University of Sichuan, Peoples Hospital of Jinghong and Sichuan Industrial Institute of Antibiotics
Type: Journal Article | Journal: Biomedical chromatography : BMC | Year: 2016
Nitrofibriate, a new compound of hypolipidemic, is modified based on fenofibrate. Both of them are used for prevention and treatment of cardiovascular diseases. In this study, an accurate and sensitive analytical method of reversed-phase high-performance liquid chromatography was developed to determine fenofibric acid, which is an active metabolite of both nitrofibriate and fenofibrate in rat plasma. This method was validated and successfully applied to pharmacokinetic study of nitrofibriate and fenofibrate after oral administration. The results suggested that the pharmacokinetic behavior of nitrofibriate followed a nonlinear process, while fenofibrate was linear, demonstrating that the two drugs were different in pharmacokinetic behaviors. Moreover, the effect of fenofibrate and nitrofibriate on releasing NO in rat serum was explored. This study showed that nitrofibriate, as a nitric oxide donor, could slowly release nitric oxide in vivo. This study provided a biopharmaceutical basis for further study of nitrofibriate.
PubMed | University of Sichuan, Sichuan Industrial Institute of Antibiotics and China Pharmaceutical University
Type: Comparative Study | Journal: Chinese journal of natural medicines | Year: 2016
The present study investigated the chemical composition of ethylacetate extracts from an endophytic actinomycete Streptomyces sp. A0916 and its host Polygonum cuspidatum. A comparative analysis of the antimicrobial and antioxidant properties of the extracts was also conducted. 32 compounds of P. cuspidatum and 23 compounds of Streptomyces sp. A0916 were isolated and identified by GC/MS. Antimicrobial activities of the extracts were evaluated using eight microbial strains (3 Gram-positive bacteria, 3 Gram-negative bacteria, and 2 fungi). The Streptomyces sp. A0916 extracts showed a wide range of antimicrobial activities and presented greater antimicrobial effectiveness than the P. cuspidatum extracts. The minimum inhibitory concentration (MIC) of Streptomyces sp. A0916 extracts against the ampicillin-resistant strain Enterococcus faecium SIIA843 was 32 gmL(-1). Furthermore, the extracts had greater antimicrobial effect against Gram-positive bacteria than Gram-negative bacteria. Finally, the antioxidant activity of the Streptomyces sp. A0916 extracts was equal to that of the P. cuspidatum extracts. In conclusion, our results suggest that the endophytic actinomycetes of the medicinal plants are an important source of bioactive substances.
Qu F.,Sichuan Industrial Institute of Antibiotics
Wei sheng wu xue bao = Acta microbiologica Sinica | Year: 2012
The intracellular alpha-amino acid ester hydrolase (AEH) from Xanthomonas rubrillineans was purified and characterized. AEH was extracted by butyl acetate, and then purified to electrophoretic homogeneity by calcium phosphate gel precipitation, ammonium sulfate fraction precipitation, anion exchange with DEAE Sephadex A-50, cation exchange with CM cellulose 52, and Sephadex G 200 column chromatography. The subunit molecular mass of AEH was 70 kDa by SDS-PAGE. The optimal reaction pH for cefaclor synthesis was 6.8, and optimal temperature was 42 degrees C. The enzyme was stable between pH 5.0 and 8.0, and at 35 degrees C. The enzyme activity was enhanced by Mn2+ and Ca2+, however was strongly inhabited by Cu2+, Fe2+ and high concentration of acetone. The kinetic parameters that the enzyme hydrolyzed D-Phenylglycine methyl ester, D-Hydroxyphenylglycine methyl ester and cefaclor were determined, and the values of k(cat)/K(m) were 123.7 +/-3.7, 2.9 +/- 0.6 and 101.3 +/- 2.1 mmol(-1) x s(-1) x L respectively. The k(cat)/K(m) values indicated that the enzyme hydrolyzed D-Phenylglycine methyl ester more efficiently than other substrates. The mechanism of enzymatic reaction with bi-substrates by AEH is Ping-Pong kinetics, and the k(cat) value that the enzyme catalyzed the synthesis of cefaclor is 547.3 +/- 38.2 s(-1). The studies of AEH from Xanthomonas rubrillineans were rare, and our research may provide an important basis for industrial application of AEH for beta-lactam antibiotics synthesis.
Zhou P.-J.,Sichuan Industrial Institute of Antibiotics |
Deng S.-Q.,Sichuan Industrial Institute of Antibiotics |
Gong Q.-F.,Sichuan Industrial Institute of Antibiotics
Yaoxue Xuebao | Year: 2010
Targeted drug delivery can significantly increase the concentration of the drug in treatment site, and decrease the dosage of drugs, cost of treatment and the drug's adverse effects on the body. So targeted drug delivery is the hotspot of recent studies. This paper reviews the development of targeted drug delivery research in recent years, including three areas: passive targeting, active targeting, and physical and chemical targeting.
Pan J.,Sichuan Industrial Institute of Antibiotics |
Wang L.,Sichuan Industrial Institute of Antibiotics |
Li D.,Sichuan Industrial Institute of Antibiotics |
Ye L.,Sichuan Industrial Institute of Antibiotics
Shengwu Gongcheng Xuebao/Chinese Journal of Biotechnology | Year: 2013
To explore the enzymatic route of cefatrizine synthesis, α-amino acid ester hydrolase (AEH) gene was cloned from the whole genome of Xanthomonas rubrillineans, and expressed heterologously in Escherichia coli BL21 (DE3). The effects of temperature, pH and substrates' molar ratio upon the transformation yield of cefatrizine by purified recombinant AEH were investigated. The monomer of AEH was determined as 70 kDa by SDS-PAGE. The optimal pH and temperature reaction were (6.0±0.1) and 36°C for cefatrizine synthesis. The transformation yield was 64.3% under 36°C, pH (6.0±0.1), when the concentrations of two substrates were about 30 mmol/L (7-ATTC) and 120 mmol/L (HPGM·HCl), respectively, and the enzyme consumption was 22 U/mL. The results pave the way for optimization of the industrial enzymatic synthesis of cefatrizine. © 2013 Chin J Biotech, All rights reserved.