Microbial secondary metabolites are one of the major sources of anti-bacterial, anti-fungal, antitumor, anti-virus and immunosuppressive agents for clinical use. Present challenges in microbial pharmaceutical development are the discovery of novel secondary metabolites with significant biological activities, improving the fermentation titers of industrial microbial strains, and production of natural product drugs by re-establishing their biosynthetic pathways in suitable microbial hosts. Synthetic biology, which is developed from systematic biology and metabolic engineering, provides a significant driving force for microbial pharmaceutical development. The review describes the major applications of synthetic biology in novel microbial secondary metabolite discovery, improved production of known secondary metabolites and the production of some natural drugs in genetically modified or reconstructed model microorganisms.

Hyperuricemia mice model was established with uricase inhibitor (potassium oxonate) and uric acids in serum were observed. Polydatin (5, 10, 20 mg · kg(-1)) and benzbromarone (16.7 mg · kg(-1)) were given ig for 7 d in mice. Kidney tissues were used to detect gene contents ofurate anion transporter 1 (URAT1), organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) by real-time-PCR. The results showed that polydatin and benzbromarone can significantly reduce uric acid in blood of hyperuricemia mice (P < 0.05), compared with the model group. URAT1, OAT1 and OAT3 contents of the kidney in hyperuricemia mice changed significantly (P < 0.05), compared with the blank group. Polydatin can significantly inhibit the changing trends in these genes induced by potassium oxonate in a dose-dependent manner, the difference was significant (P < 0.05), compared with the model group. Those indicated that polysatin could reduce the level of the serum uric acid through promoting uric acid excretion.
Animals ; Disease Models, Animal ; Glucosides ; pharmacology ; Hyperuricemia ; drug therapy ; Kidney ; drug effects ; metabolism ; Mice ; Stilbenes ; pharmacology ; Uric Acid ; blood

Animals ; Animals, Newborn ; Disease Models, Animal ; Enterocolitis, Necrotizing ; chemically induced ; Female ; Male ; Platelet Activating Factor ; toxicity ; Rats ; Rats, Sprague-Dawley ; Sulfalene ; toxicity ; Tumor Necrosis Factor-alpha ; toxicity

Objective: To investigate the effect of insulin-like growth factor-Ⅰon osteocalcin secretion in periodontal ligament cells. Methods: Human periodontal ligament cells were cultured by tissue explant in vitro, and the concentration of osteocalcin were determined with radio-immunological method. Results: Under the condition of L-ascorbic acid and β-glycerophosphate in culture medium, human periodontal ligament cells secreted osteocalcin time-dependently and peaked at the third week; IGF-Ⅰ3.125 ng/ml，6.250 ng/ml, 12.500 ng/ml, 25.000 ng/ml could promote the secretion of osteocalcin dose dependently. Conclusion: IGF-Ⅰ can increase the secretion of osteocalcin in human periodontal ligament cells.

Objectives:To study the enzymatic changes and protective effects of ciliary neurotrophic factor (CNTF) on neurons in spinal cord injury (SCI).Methods:SD rats were subjected to incomplete SCI with modified Allen methods.Activities of acetylcholinesterase (AChE) and acid phosphatase (ACP) in spinal cord were quantitatively measured preoperatively,and 3,7,14 days after SCI.Results:AChE activity decreased gradually after injury.ACP activity increased 3 days after injury,and reached peak on the 7th day,then recovered gradually.The rats treated with CNTF showed relatively smooth change of the 2 kinds of enzymes.Conclusions:CNTF plays a role in protecting the spinal cord neurons against injury.

Objective To evaluate the safety,biocompatibility and efficacy of transcatheter closure of atrial septal defect(ASD)with no stainless-steel-screw occluder in canine model.Methods The device was constructed from superelastic Nitinol wires tightly woven into two flat disks and sewed with polyester fibers inside,with a pliable loop on the right-atrial-disk of the device,connecting to the delivery cable.ASD was created by transcatheter puncture and balloon dilatation and then closed by occluder under fluoroscopy in the catheterization laboratory.The location and the influence of the implanted device on function of tricuspid valve and mitral valve were evaluated by echocardiography.At 1,2,3 and 6 months after the operation,the animals were killed and autopsy was conducted.Results Eight dogs with puncture-produced ASD underwent ASD closing procedure successfully.The occluder showed no influence on the function of MV and AV demonstrated by echocardiogram.The two disks of the implanted device were covered with a smooth intact neogenesis layer in all dogs.Endocardial cells fully covered the surface of the two disk without inflammating reaction 3 months later. There was no evidence of corrosion on the surface of the nitinol wire removed from the dog after 6 months.Light microscopic examination of the liver,kidney,lung and spleen showed no evidence of embolization and inflammation.Conclusion Transcatheter ASD occlusion with new-type occluder is safe,feasible,effective and good biocompatibility with a good prospective clinical application.

Objective To retrospectively analyze bacterial time distribution of ICU?acquired infections in Shengjing Hospital of China Medical Uni?versity,so as to provide reference for the early antibiotic use for ICU?acquired infections. Methods A total of 1 330 cases in ICU from Jan. 2012 to Mar. 2013 were collected,the bacterial culture was positive in 254 cases. A total of 1 110 strains were collected from all the patients. Excluding 288 strains which were detected within 48 hours of patients′admission in ICU and 222 strains which were repeatedly detected in the same patients,600 strains were finally enrolled in the statistical analysis. Results The rate of ICU?acquired infections was 19.1%. Postoperative infections accounted for 74.3%,most of which occurred after neurosurgeries,and abdominal,orthopedic operations. Pulmonary infection ranked the first in ICU?acquired infections,accounting for 40.3%,followed by blood stream infection(25.3%),postoperative drainage infection(14.2%)and urinary tract infection (7.3%). The rate of pathogenic bacteria detection was the highest in the first week of patients′admission in ICU,and was getting lower as time went by. Strains detected in ICU mainly were Bauman Acinetobacter,Pseudomonas aeruginosa,Klebsiella pneumonia and Enterococcus faecium,most of strains resulting in infections were gram negative bacilli throughout the time. In addition,the infection rate of fungi was increased at 2 weeks of pa?tients′admission in ICU. Conclusion The treatment of ICU?acquired infections should be targeted at gram negative bacilli. The detection rate of op?portunistic pathogens gradually increased with prolonged stay in ICU,most of which are non?fermentative bacteria. Fungi infections are most likely to occur at 2 weeks of patients′admission in ICU.

Objective To investigate the role of Twist and vascular endothelial growth factor (VEGF)in the development of epithelial ovarian cancer and their relationship with clinical pathological features.Methods The expressions of Twist and VEGF were detected by immunohistochemical staining (SP)method in 80 cases of epithelial ovarian cancer and 10 paired cases of normal ovarian tissue.Results In the 80 cases of ovarian cancer tissues,the positive expression rate of Twist and VEGF in epithelial ovarian cancer was 85% and 86.25%,respectively,which were remarkably higher than those in normal ovarian tissues (P <0.01).The expressions of Twist and VEGF were closely associated with clinical stages,pathological grades and lymph node metastasis,but not correlated with age or pathological patterns (P >0.05).There was a significant correlation between the expressions of Twist and VEGF in epithelial ovarian cancer (r =0.646,P <0.01).Conclusion The high expressions of Twist and VEGF may play a potential role in the occurrence,development and invasion process of epithelial ovarian cancer.

Objective To study the risk factors for children with acute central nervous system(CNS)viral in-fection,so that pediatrician may identify children with poor prognosis at early stages of the disease,and provide them with a theoretical basis for clinical treatment. Methods The clinical data of a cohort patients of acute CNS viral infec-tion who were hospitalized at the First Affiliated Hospital of Fujian Medical University between January 2010 and June 2013 were retrospectively collected and analyzed. According to Glasgow outcome scale on discharge,children were di-vided into good prognosis group and poor prognosis group. Clinical data and outcomes were analyzed by using univariate analysis and binary Logistic regression multivariate analysis. Results Three hundred and one cases were enrolled,278 (92. 36% )patients were assigned to the good prognosis group,and 23(7. 64% )patients were assigned to the poor prognosis group. By univariate analysis,the patients in the poor prognosis group had longer duration of sickness before admission,longer time of fever,lower white blood cell count in cerebrospinal fluid,a relatively lower calcium level,con-scious disturbance at the early stage,multiple seizures,convulsive status epilepticus,meningeal irritation sign,muscle weakness,severe changes in electroencephalogram(EEG),and abnormal neuroimaging findings(computed tomography or magnetic resonance imaging,or both)had significant differences between the good prognosis group and the poor short - term outcome groups(all P < 0. 05). By binary Logistic regression multivariate analysis,factors indicating a poor prognosis during the early stage were conscious disturbance at the early stage(0R = 4. 885,95% CI:1. 523 - 15. 670, P = 0. 008),multiple seizures(0R = 6. 352,95% CI:1. 905 - 21. 178,P = 0. 003),severe changes in EEG( 0R =4. 269,95% CI:1. 708 - 10. 666,P = 0. 002),and abnormal neuroimaging findings( 0R = 9. 740,95% CI:2. 360 -40. 192,P = 0. 002). Conclusions Conscious disturbance at the early stage,multiple seizures,severe changes in EEG and abnormal neuroimaging findings are risk factors for acute viral infection of CNS in children.

Diving ; Humans ; Otitis Externa ; prevention & control