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

This study was based on live yeast cell derivative (LYCD), which was produced by live yeast cell stressed with high temperature and H 2O 2. The results showed that pretreating of low dose(37℃and 0.2mmol/L H 2O 2) could increase the content of GSH and the activity of SOD and CAT. These pretreatment could induce the resistance to lethal concentration of H 2O 2. LYCD was produced by yeast treated with 37℃ and 0.2mmol/L H 2O 2. And it was found that the survival of yeast treated with lethal concentration of H 2O 2 obviously increased, while LYCD was added in yeast culture. It indicated that LYCD could have resistance to oxidative condition.

Objective To evaluate the changes of cerebrospinal fluid dynamics of Chiari malformation type I associated syringomyelia patients with phase-contrast MRI (PC-MRI).Methods Thirty cases diagnosed with Chiari malformation type Ⅰ associated with syringomyelia clinically underwent cisterna plasty treatment.Cerebrospinal fluid dynamics changes were measured before 24 h and 6 months after operation with PC-MRI.The stroke volume (SV),mean flow (MF),regurgitation fractions (RF) and the maximum peak flow velocity (Vmax) were analyzed.Results After operation,PC-MRI showed SV and MF increased,the bidirectional Vmax decreased,which had statistical difference compared with those of preoperation (all P＜0.05),and the C2-3 level was the most obvious.Conclusion PC-MRI can quantitative analysis of preoperative and postoperative changes of cerebrospinal fluid flow and peak velocity.

OBJECTIVE To analyze the isolation rate and four consecutive years′(2004-2007) antibiotic-resistance trend of extended-spectrum ?-lactamases(ESBLs) producing Escherichia coli in urinary tract infection and to provide evidence for anti-infection therapy.METHODS The anti-microbial susceptibility test results of E.coli cultured from the midstream urine of outpatients and inpatients of our hospital from 2004 to 2007 were collected.Whonet 5.4 statistical analysis software was used for analysis.RESULTS During four years,no apparent change has been shown about antibiotic resistant rate of ESBLs producing E.coli.The isolation rate of this kind of E.coli increased year by year from 31% to 44% and showed high resistance to third generation cephalosporins and quinolones antibiotics,but was 100% sensitive to imipenem.CONCLUSIONS With the ESBLs-producing E.coli increasing year by year,the antibiotic-resistance rate of E.coli isolated from urinary tract infection is apparently increased and thus screening of antibiotics sensitive to enzyme-producing bacterial is the key point when the empirical therapy especially when the third and fourth generation cephalosporins are ineffective.

Objective To comparison anterior cervical decompression and plating techniques for CSM between under microscope and traditional method retrospectively, investigate clinical result of surgery under microscope. Methods Sixty-seven patients with CSM underwent surgery of anterior cervical decompression and plating techniques were evaluated retrospectively from January 2008 to June 2010. Thirty-three patients underwent operation under microscope; thirty-four patients underwent traditional operation. The operating time, bleeding volume during operating and poster operating, walking time post-operation and complication were observed. Clinical outcomes were assessed by Japanese Orthopaedic Association (JOA), Image of before and after operation. Results Microsurgery operation time averaged of 100 minutes. Bleeding volume during the operation averaged of 60 ml, and after operation averaged of 40 ml. The JOA scores were improved from 8.43 pre-operatively to 14.70. Six months post operation, the average rage of JOA improvement were 83.2%. Traditional operation time averaged of 115 minutes. Bleeding volume during operation averaged of 100 ml, and after operation averaged of 50 ml. The JOA scores were improved from 7.45 pre-operatively to 11.84. Six months post operation, the average rage of JOA improvement were 82.1%. There were difference between two groups(P ＞ 0.05) in the JOA scores. No statistical difference (P ＜ 0.05) in bleeding volume and operating time. Conclusion The operation under microscope is restored significantly than the traditional method in bleeding volume, the surgical field, safety of operation, time of recovery and so on.

Objective To explore the relationships between erythropoietin( EPO), endothelin - 1 (ET - 1) and perinatal anoxia. Method ELISA was used to test cord blood EPO and ET-1 in 54 high risk neonates as subjects and 14 healthy neonates as controls.Results The cord blood EPO levels in amniotic fluids turbid Ⅲ degree group and group eclampsia/pre - eclampsia were higher than those in control group (t= 4.0842,3 680 allP

AIM: To investigate the role of nitric oxide synthase (NOS), soluble guanylyl cyclase (sGC) and protein kinase C (PKC) signaling in tumor necrosis factor-? (TNF-?)-induced cardioprotection against hypoxia/reoxygenation (H/R) injury. METHODS: Neonatal rat ventricular myocytes were pretreated with TNF-? or sodium nitroprusside (SNP) or L-arginine (L-Arg), respectively, for 12 h and then subjected to continuous hypoxia for 12 h, followed by reoxygenation for 6 h. The manganese superoxide dismutase (Mn-SOD) activity of the cells was measured after H/R. Myocyte injury was determined by the release of lactic dehydrogenase (LDH). RESULTS: TNF-? (10~5 (U/L)) significantly increased the Mn-SOD activity and decreased release of LDH from ventricular myocytes. The cardioprotection against H/R injury was induced by the pretreatment with SNP (5 ?mol/L) or L-Arg (5 mmol/L), which was blocked by ODQ (10 ?mol/L), the specific sGC inhibitor, and Chel (5 ?mol/L), the specific PKC inhibitor. Pretreatment with L-NAME (100 ?mol/L), ODQ, Chel, antoxidant 2-MPG (400 ?mol/L) or tyrosine kinase inhibitor genistein (50 ?mol/L) attenuated the increased Mn-SOD activity and reduced LDH level induced by TNF-?. CONCLUSION: The results suggest that NO may play a role in TNF-?-induced cardioprotection, which is mediated by sGC and PKC. [

Objective The hsa-miR-106b-25 gene cluster is involved in various biological processes of carcinoma .This study aims at a prediction and function analysis of the hsa-miR-106b-25 gene cluster, miR-106b, miR-93, and miR-25, so as to provide some evidence for further studies on the functions of the three miRNAs and the mechanisms of their interaction . Methods We obtained the sequences of miR-106b, miR-93, and miR-25 from the miRBase, predicted their target genes with TargetScan , PicTar, and miRanda, and used 3 or more experimentally verified target genes from the miRTarbase as the gene set for further bioinformatic analysis .We predic-ted the biological processes of the target genes by GeneOntology analysis and enriched KEGG ( Kyoto Encyclopedia of Genes and Genomes) by pathway analysis, produced protein-protein interaction ( PPI) networks with STRING . Results The target genes of the miR-106b-25 gene cluster were significantly enriched in such biological processes as the regulation of macromolecule metabolism , regulation of metabolic process , and cell cycle process , while the KEGG pathway mainly in glioma, melanoma, prostate cancer , and gallbladder carcino-ma.The proteins encoded by the targeted genes of showed complicated interactions , and those encoded by the KAT2B, PTEN, TP53, CDH1, MDM2, E2F1, RB1, and SMAD7 plaid a core role in the interac-tion network. Conc lusoi n MiRNAs of the miR-106b-25 gene cluster regulate the downstream target proteins involved in tumorigenesis by participating in the cell cycle and cancer signaling pathway .

10.3969/j.issn.1000-3606.2013.06.003

Objective: To observe the inhibitory effect of scopolamine(Spm) and chlopromazine (Clo) on withdrawal syndromes in morphine dependent rats. Methods: The intensity of withdrawal syndromes on the model of morphine dependent rats was recorded after single or muiltiple subcutaneous administration(sc) of Spm and Clo at different doses. Results: Withdrawal syndromes were markedly decreased when single Spm 1 mg/kg and Clo 0.5 mg/kg combined with morphine were injected (P<0.05). Spm+Clo(sc) had much stronger effects on inhibiting withdrawal syndromes after intraperitoneal (ip) naloxone in morphine dependent rats (P<0.01). Conclusion: Spm can act on Ach-receptor and relieve morphine withdrawal syndromes. Clo may have a synergistic action with Spm via α2-receptor in the locus coeruleus of the rat brain stem.