Identification and validation of a new target is one of the most important steps for new antituberculosis (TB) drug discovery. Researches have shown that Mycobacterium tuberculosis (Mtb) encodes 20 CYP450 enzymes which play important roles in the synthesis and metabolism of lipid, cholesterol utilization, and the electron transport of respiratory chain in Mtb. With the critical roles within the organism as well as the protein structures of six Mtb CYP450 enzymes being clarified, some of them have been highlighted as potential anti-tuberculosis targets. In this paper, the phylogenetic analysis, the structural features, and the enzymatic functions of Mtb CYPs, as well as the mechanism of interactions with selective inhibitors such as azole antifungal agents for the CYPs have been reviewed and summarized. The druggability of the CYPs has also been analyzed for their further utility as targets in high throughput screening and rational design of more selective inhibitors.
Antitubercular Agents ; chemistry ; pharmacology ; Azoles ; chemistry ; pharmacology ; Cytochrome P-450 Enzyme Inhibitors ; chemistry ; pharmacology ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Drug Delivery Systems ; methods ; Drug Discovery ; Humans ; Mycobacterium tuberculosis ; drug effects ; enzymology ; genetics ; Phylogeny ; Tuberculosis ; drug therapy ; microbiology

With the development of medical education,the traditional cell biology teaching modes and methods need constant adjustment to adapt to the current teaching.In view of the present high-speed development of cell biology,we seriously picked some representative themes to carry out thematic teaching.Students were encouraged to read some references about the corresponding content and thought primarily before the class.After the lesson,the teacher guided students to discuss and find the answers to the questions they asked before.Participation in class discussion and homework completion accounted for 10％ of the final assessment results.The thematic teaching helped to optimize classical teaching contents and frontier progress.This teaching mode not only stimulated learning interest but also fully exercised learning ability.

Objective To investigate the possible pathogenesis of type 2 diabetes mellitus (T2DM) combined with Alzheimer's disease (AD). Methods Wistar rats were randomly divided into control, T2DM, AD and T2DM +AD groups. The blood glucose levels were assayed, and the behavior changes were tested by Morris water maze. The glycogen synthase kinase-3β (GSK-3β) and hyperphosphorylation of tau protein were detected by immunohistochemistry staining. Results Compared with the control rats, the learning and memory abilities were weakened significantly in the model rats (F=28. 65, P<0.001). The expression of GSK-3β was higher in T2DM + AD group (4319. 02±653. 24) than in AD group (304. 39 ± 175. 83), T2DM group (540.43 ± 558.49) and control group (315. 56 ± 91. 64, H=19. 335, all P<0. 01). The level of hyperphosphorylation of tau protein was significantly increased in T2DM + AD group (8583. 81 ± 2236. 11) and AD group (2799. 61±1070. 02) than in control group (252. 02 ± 58. 37) and T2DM group (287. 75 ± 192. 53, H=32. 950, P< 0.001). There was no significantly difference of hyperphosphorylation of tau between T2DM group and control group (H = 32. 950, P>0. 05). Conclusions The increasing of GSK-3β activity in T2DM may be caused by hyperphosphorylation of tau.

Objective To analyze the distribution and antimicrobial resistance of pathogens isolated from department of hematology during the past three years.Methods Pathogenic strains isolated from patients hospitalized in a hematology de-partment between January 2011 and December 2013 were collected,antimicrobial susceptibility testing was performed by Kirby-Bauer disk diffusion method or automatic system,antimicrobial susceptibility testing results were judged according to American Clinical and Laboratory Standards Institute 2011, data were analyzed by WHONET 5.6 software. Results A total of 462 clinical isolates were collected in 2011—2013,including 161 gram-positive cocci isolates,279 gram-negative bacilli,and 22 fungi.Of Staphylococcus spp ,detection rate of methicillin-resistant coagulase negative Staphylo-coccus(MRCNS)and methicillin-resistant Staphylococcus aureus (MRSA)was 81.37% and 62.50%respectively.The re-sistant rate of Staphylococcus spp .and Enterococcus spp .to linezolid was 1.69% and 3.57% respectively,resistant rate of Staphylococcus spp .to teicoplanin was 3.39%,vancomycin-resistant gram-positive coccus was not found.Enterobacte-riaceae strains Escherichia coli and Klebsiella pneumoniae were highly susceptible to carbapenems,the sensitivity rates were 97.56%—98.88%;while nonfermentative gram-negative bacilli Pseudomonas aeruginosa and Acinetobacter bauman-nii strains were obviously resistant to carbapenems,the resistance rates were 38.71%—64.00%.Conclusion Antimicrobial resistance of major pathogenic strains from hematology department is high,antimicrobial agents should be used according to pathogenic distribution characteristics and antimicrobial susceptibility testing results,healthcare-associated infection control should be strengthened to reduce antimicrobial resistant rate.

Objective To observe the growth characteristic of bulge-originated cells from human hair follicles in vitro. Methods The bulges which were isolated from human hair follicles by dispase and microdissection were cultured. The morphological and biological characteristic of the cultured bulge cells were observed by light microscopy and immunocytochemistry (ICC). Results Proliferated cells could be observed in the second day after being inoculated. The number of these cells, with greater proliferation potential, reached the peak at the sixth day and maintain several days. In addition, the mitotic figures appeared and the cells behave the similar morphologic features, meanwhile the cells strongly expressed K19 and showed a descensive tendency in long-time growth.Conclusion The cultured bulge cells kept the primitive characteristic, which suggested that the putative follicle stem cells resided in the bulge area.;

Objective To study the expression of ?-catenin and cox-2 in the bulge cells of hair follicle and investigate the relationship of their expression on cell proliferation. Methods The hair follicle was prepared from the resected cheek skin of 20 Wistar rats aged 7 days. The bulge cells were resected from the intact hair follicle and cultured in vitro. Immunocytochemical technique (ICC) was applied to detect ?-catenin and cox-2 expression in bulge cells at culture day 3, 5, 8, 13. Results ?-catenin and cox-2 strongly expressed in bulge cells and the expression correlated with the culture days. ?-catenin appeared in both plasma and nucleus, while cox-2 only in nucleus. Conclusion ?-catenin and cox-2 were correlated with bulge cells proliferation, and cox-2 might be the target gene of ?-catenin signaling pathway in nucleus.

Astrocytoma ; blood supply ; pathology ; Capillaries ; pathology ; Central Nervous System Neoplasms ; blood supply ; pathology ; Diagnosis, Differential ; Ependymoma ; blood supply ; pathology ; Glioblastoma ; blood supply ; pathology ; Hemangioblastoma ; blood supply ; pathology ; Humans ; Hyperplasia ; Microvessels ; pathology ; Neoplasms, Neuroepithelial ; blood supply ; pathology ; Oligodendroglioma ; blood supply ; pathology ; Paraganglioma ; blood supply ; pathology

Objective To study the cause and treatment of chronic instability of the elbow.Methods Between August 1998 and August 2002,12 patients with chronic instability of the elbow were treated in our de- partment:They underwent complete medical check-ups and imaging examinations.Surgical exploration was done to determine the causes of their conditions.Their radial and(or)ulnar collateral ligaments were repaired respectively or simultaneously through the medial and lateral approaches for all the patients.All the patients were followed up for two to six years,with an average of three years.Results The follow-ups revealed no recurrent dislocation of elbow in this group.The stress valgus test and lateral pivot shift test(PST)were negative for all the patients.No elbow pain occurred.The mean flexion and extension of elbow ranged from 0 to 135?.The mean pronation was 85?and mean supination 80?.According the evaluation system of Chinese Medical Association,eight cases were rated as excellent and four as fine,with the excellent and fine rate of 100%.Conclusions Lesions of radial and(or) ulnar collateral ligaments are the major cause for chronic instability of the elbow.Surgical reconstruction of the collateral ligaments can obtain good effects in treatment of recurrent dislocation of the elbow.

Responses of mouse lymphocytes to the soybean paste fermented by Korean traditional fashion was examined to clarify its effects in cytokine production in vitro. A fraction of the soybean paste (KFSP-100) was prepared by precipitation with ammonium sulfate and by filtration through ultrafiltration membrane. KFSP-100 were added into cultures of fresh mouse splenic cells in vitro. KFSP-100 significantly enhanced the amount of IL-6 and TNF-a produced by macrophages and IL-6 and IFN-r produced by lymphocytes. Production of IL-12 by macrophages was not much affected by KFSP-100 treatments. The most noticeable finding was the fact that lymphocytes treated with KFSP-100 proliferated to an exceeding numbers (more than 10 times to the control) in 72 hours. The KFSP-100-induced proliferative response was specific to B cells since almost all of the KFSP-100-induced cells in the cultures of splenic cells were B cells. Furthermore, such a proliferative responses were equally observed only in cultures of purified B cells but not in cultures of T cells. In thermostability test, the biologically active components of the KFSP-100 is assumed to be either linear protein or glycoprotein. KFSP-100 did not induce agglutination of lymphocytes demonstrated by lectins in the same cells. These observations suggest that KFSP-100 may be a novel mitogen for B lymphocytes. The component (s) responsible for the B cell proliferation in KFSP-100 might be a factor gained by natural fermentation. None of the fractions of not fermented soybean paste prepared by the same methods demonstrate the same effect.
Agglutination ; Ammonium Sulfate ; Animals ; B-Lymphocytes ; Cell Proliferation ; Fermentation ; Filtration ; Glycoproteins ; Immunologic Factors* ; Interleukin-12 ; Interleukin-6 ; Lectins ; Lymphocytes ; Macrophages ; Membranes ; Mice ; Soybeans* ; T-Lymphocytes ; Ultrafiltration

Objective To investigate the effects and safety of sequential treatments with methotrexate and mifepristone for ectopic pregnancy with fetal cardiac activity.Methods 4 cases of ectopic pregnancy with fetal car- diac activity in our hospital were given by sequential therapy with methotrexate and mifepristone.Serum?-HCG,liv- er function and renal function,blood routine and gastrointestinal response were observed.Results 4 cases of ectopic pregnancy with fetal cardiac activity with 1～4 periods of sequential treatments were cured.Except light gastroin- testinal response,and one had slight rise of serum ALT level and AST level,no one had rnyelosuppression and heavy hepatic injury.Conclusion The sequential therapy with methotrexate and mifepristone is an effective and safe method for the treatment to ectopic pregnancy with fetal cardiac activity.