The metabolism study of radiolabeled drugs plays an important role in the development of new drugs. It provides information on drug absorption, metabolism, tissue distribution and excretion, and plays an irreplaceable role in the metabolite safety evaluation and mass balance of new drugs. The new guidance draft on clinical trials of radiolabeled drugs recently released by the US FDA puts forward higher standards and has been widely concerned by the industry. In recent years, in the research and development of new drugs in China, ¹⁴C labeled drugs have been used to carry out clinical metabolism studies, which has overcome key technical bottlenecks and accumulated experience. This paper summarizes the above research progress, analyzes the existing problems, and preliminarily looks forward to the future technological development and application.

Archives ; Humans ; Occupational Health

Humans ; Occupational Diseases ; epidemiology ; prevention & control ; Occupational Health Services

Objective To study the state of erythrocyte immune function in neonates with hyperbilirubinemia,and analyze the influence of various clinical status on erythrocyte immune function.Methods Fifty-two neonates with hyperbilirubinemia were enrolled and 104 healthy neonates as the control group.The adherence rate of complement 3b-receptor on the surface of red blood cell(RBC-C3bRR) and the immune complex adherence rate of red blood cell(RBC-ICR) were detected with erythrocyte saccha-romycete rosettet test.Results 1.The level of RBC-C3bRR in neonates with hyperbilirubinemia was lower than that in control group,and the level of RBC-ICR in neonates with hyperbilirubinemia was higher than that of control group(Pa0.05).3.Comparing the neonates with unconjugated bilirubin of different concentrations,there were significant difference in RBC-ICR(Pa0.05).4.There were positive correlation between RBC-ICR and bilirubin,unconjugated bilirubin in the neonates(Pa0.05).Conclusion Erythrocyte immune function in neonates with hyperbilirubinemia is obviously lower than that of control group and it is influenced by the concentratron of bilirubin and the time of phototherapy.

OBJECTIVETo explore the feasibility of inducing human umbilical cord mesenchymal stem cells (HuMSCs) to differentiate into Leydig cells through conditioned medium derived from Leydig cells.

METHODSHuMSCs and Leydig cells were obtained by tissue blocks culture attachment and enzymatic digestion respectively. HuMSCs were induced by conditioned medium of Leydig cells as an experiment group while those before induction were cultured as a control group. The expressions of LHR, 3β-HSD and StAR in the induced HuMSCs were determined by RT-PCR after 3, 7 and 10 days of culture; those of CYP11A1, CYP17A1 and 3β-HSD measured by immunofluorescence staining after 2 weeks; and that of 3β-HSD detected by Western blot after 4 weeks.

RESULTSThe experimental group showed positively expressed LHR, 3β-HSD and StAR at 3, 7 and 10 days, CYP11A1, CYP17A1 and 3β-HSD at 2 weeks, and 3β-HSD at 4 weeks, while the control group revealed negative expressions at all the time points.

CONCLUSIONInduced with conditioned culture medium derived from Leydig cells, HuMSCs are likely to differentiate into steroidogenic cells and eventually into Leydig cells.

Cell Differentiation ; Culture Media, Conditioned ; Humans ; Leydig Cells ; cytology ; Male ; Mesenchymal Stromal Cells ; cytology ; Umbilical Cord ; cytology

Adult ; Fracture Fixation, Internal ; Fractures, Ununited ; surgery ; Humans ; Male ; Scaphoid Bone ; injuries ; surgery

To express recombinant carboxypeptidase from Thermus aquaticus (Cpase Taq) in Pichia pastosis, the open reading frame coding thermostable Cpase Taq was optimized based on the preference of P. pastoris codon usage and synthesized in vitro. The novel gene was cloned into P. pastoris expression vector pHBM905A and the sequence coding 6xHis tag was fused with the ORF of Cpase Taq gene. The recombinant plasmid was named pHBM905A-Cpase Taq and transformed into P. pastoris GS 115. Transformants were induced with 1% methanol for 72 h until the enzyme yield reached 0.1 mg/ml. The enzyme was purified and its enzymatic properties were analyzed. The results showed that the specific enzyme activity reached maximum at 75 °C and pH 7.5, which was about 80 U/mg. It was the first report about the secretory expression of Cpase Taq in P. pastoris GS115. Because of its large-scale preparation, this enzyme may be applied in industrial hydrolysis of peptides into amino acids in the future.
Bacterial Proteins ; biosynthesis ; genetics ; Carboxypeptidases ; biosynthesis ; genetics ; Cloning, Molecular ; Codon ; Hydrolysis ; Open Reading Frames ; Pichia ; metabolism ; Recombinant Proteins ; biosynthesis ; genetics ; Thermus ; enzymology

Adult ; Brain Diseases ; chemically induced ; Ethylene Dichlorides ; poisoning ; Female ; Humans ; Male ; Middle Aged ; Occupational Diseases ; chemically induced

Anemia, Hemolytic ; etiology ; Child ; Female ; Humans ; Insecticides ; poisoning ; Trichlorfon ; poisoning

3T3-L1 adipocytes were cultured with various concentrations of high-density lipoprotein ( HDL, 0, 10, 50, and 100 μg/ml ) for 16 h and with lipopolysaccharide ( LPS, 100 ng/ml ) for another 6 h. Interleukin-8 in the medium was determined by ELISA, and PPAR-γ mRNA expression by reverse transacription polymerase chain reaction (RT-PCR). Interleukin-8 levels were increased in LPS-treated cells ( P＜0.05 ), but decreased in HDL-treated cells in the dose-dependent manner. PPARγ mRNA expressions were increased in HDL-treated groups than those treated only with LPS. These results suggested HDL may decrease interleukin-8 secretion via up-regulating PPARγ expression in adipocytes.