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

Objective To observe the effects of velcade on inflammatory reaction and cell apoptosis after ischemia-reperfusion injury, and to explore the neuroprotective mechanism of velcade.Methods The 15 male Wistar rats were randomly divided into sham-operated group, physiological saline control group and velcade-treated group (n= 5, each). The model of temporary middle cerebral artery occlusion (MCAO) was applied and reperfused after 2 hours. Immediately after the reperfusion, all rats were performed intraperitoneal injection with velcade 0. 2 mg/kg in velcadetreated group, and with the same volume of physiological saline in control group. After 24 hours, the rats were decapitated in all groups. The apoptosis cells were found by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and the expressions of nuclear factor-κBp65 (NF-κBp65) and interleukinh-1β (IL-1β) were detected by immunohistochemistry. Results The immunologically positive cells of NF-κBp65, IL-1β and apoptosis cells were occasionally found in shamoperated group [(1.21 ± 0. 16)/400 power, (11.56 ± 0. 99)/400 power and (2. 88 ± 0. 27)/400 power], while a lot of immunologically positive cells of NF-κBp65, IL-1β and apoptosis cells were found in velcade-treated group and control group. The control with compared group, these cells were significantly more in the velcade-treated group [(56.28± 1.95)/400 power vs. (29. 76±2.53)/400 power, (47. 64±2.06)/400 power vs. (29.6±1. 61)/400 power and (51. 05±4. 23)/400 power vs.(33.44±2.06)/400 power, all P＜0. 05]. Conclusions The velcade could decrease the expressions of the NF-κBp65 and IL-1β and diminish the neuronal apoptosis. The neuroprotective mechanism of velcade may lie in decreasing apoptosis through inhibiting inflammation.

Objective\ By inhibiting approach of apoptosis of T cells to observe if it could reduce the attacks of tumor cells upon lymphocytes and its possible role in tumor treatment. Methods\ The expressions of Fas/FasL genes in ovarian carcinoma cells were detected by using flow cytometry and RT\|PCR method.The construction of pcDNA3\|antisense Fas,the constructed vector was transfected into Jurkat cells with lipofectin,the change in expression of Fas gene was determined by flow cytometry.By means of Annexin\|V and MTT the effect of apoptosis in transduced Jurkat cells was investigated,and also using MTT cytotoxic test to investigate how 3AO cells kill Jurkat cells. Results\ Fas/FasL were expressed in 6 ovarian carcinomal cells.The expression level of Fas protein in Jurkat cells transduced with the constructed vector was decreased.Apoptosis was reduced in antisense Fas\|transfected Jurkat cells after anti\|Fas treatment. Conclusion\ FasL expression in ovarian carcinoma may be one of the reasons for ovarian carcinoma to escape immunosurveillance and attacking lymphocytes.Blocking Fas expression in lymphocytes can partially inhibit Jurkat cells apoptosis induced by anti\|Fas and reducing the attacks of tumor cells upon lymphocyte.\;

OBJECTIVETo observe the clinical effect of electric stimulation of long-term retaining needle on analgesia after laparoscopic cholecystectomy (LC) and the impacts on the post-surgical flatus time.

METHODSUnder static absorptive composite general anesthesia, 90 cases of LC were randomized into three groups, 30 cases in each one. In the control group, the analgesia was not applied after LC. In the analgesia-pumper group, the patient controlled intravenous analgesia (PCIA) was used. In the needle-retaining group, the electric acupuncture stimulator was used. The needles were inserted transversely at Riyue (GB 24), Qichong (ST 30) and Yanglingquan (GB 34) and fixed with sterile sticker. Separately, in 8 h and 24 h after surgery, the electric acupuncture stimulation with disperse-dense wave, 2 Hz/100 Hz frequency was applied continuously for 30 min. Visual analogue scale (VAS), adverse reactions such as vomiting and nausea and the postoperative flatus time in 2, 4, 8, 12, 24 and 36 h after surgery were observed and recorded in the three groups.

RESULTSIn 2, 4, 8, 12 and 24 h after surgery, VAS scores in the needle-retaining group and the analgesia-pumper group were all lower than those in the control group (P < 0.05, P < 0.01). The analgesia effect at the above time points in the needle-retaining group was better than that in the analgesia-pumper group (all P < 0.05). There was not adverse reaction in the needle-retaining group. But there were 3 cases of somnolence, 6 cases of nausea and 3 cases of vomiting in the analgesia-pumper group, and 2 cases of nausea and 1 case of vomiting in the control group. The flatus time was quite earlier in the needle-retaining group as compared with the other two groups [(14.77 +/- 4.99) h vs (18.50 +/- 4.22) h, P < 0.01; (14.77 +/- 4.99) h vs (18.17 +/- 4.69) h, P < 0.05].

CONCLUSIONThe electric stimulation of long-term retaining needle is safe and effective in analgesia after LC. It avoids the adverse reactions of analgesics and promotes postoperative flatus.

Acupuncture Analgesia ; instrumentation ; Adult ; Aged ; Cholecystectomy, Laparoscopic ; adverse effects ; Electroacupuncture ; instrumentation ; Female ; Humans ; Male ; Middle Aged ; Pain Management ; Pain, Postoperative ; etiology ; therapy

Objective To analyze the differential proteomics of ASMC stimulated by wild IL-13 and mutant IL-13 and to investigate the relations of protein profiles of ASMC to asthma and possible targets for the treatment of bronchial asthma.Methods The total proteins of ASMC stimulated by wild IL-13 and mutant IL-13 were separated by immobilized pH gradient(IPG)-based 2-DE and the differentially expressed protein spots were identified by matrix assisted laser desorption-time of flight mass spectrometry(MALDI-TOF-MS). Results The 2-DE detected approximately(840?21)spots on wild IL-13 samples and(892?17)spots on mutant IL-13 samples(n=3)and(685?19)spots matched.Six significantly differential proteins were subjected to MALDI-TOF-MS analysis and three of them were identified as stathmin 1,Ribosomal protein p~0 and NADH dehydrogenase.Conclusions ASMCs stimulated by wild IL-13 and mutant IL-13 present different proteomic profiles that may shed some light on the mechanism for the asthma causing effect of wild IL-13 and mutant IL-13.

Objective To study the detection rate of early esophageal carcinoma using magnifying endoscopy,and to evaluate the relationship between the imaging patterns of microvasculature change and his- tological diagnosis.Methods Two hundred and fourteen patients with esophageal mucosa roughness,ero- sion,plaque,abnormal color and indentation in conventional endoscopy and 16 healthy volunteers were en- rolled.The magnifying endoscopy images were graded as four patterns by intraepithelial papillary capillary loop(IPCL)changes after iodine dyeing.The biopsies underwent pathologic evaluation.The comparison be- tween the imaging patterns of endoscopy and histological diagnosiswas was evaluated.Results 80.4%(90/ 112)esophagitis was type 2,and 85.7%(12/14)early esophageal carcinoma was type 3 and type 4.The difference was significant between early esophageal carcinoma and normal mueosa(?~2=27.32,P

ObjectiveTo analyze the obvious and hidden preoperative and intraoperative blood loss during treatment of the intertrochanter fracture with proximal femoral nail anti-rotation (PFNA) so as to provide necessary data support for clinical perioperative treatment.MethodsThe clinical data of 216 patients with intertrochanteric fractured treated with PFNA between December 2005 and September 2010 were analyzed retrospectively.An analysis was done on preoperative and postoperative blood routine, perioperative and postoperative blood loss and transfusion, perioperative obvious and hidden blood loss and perioperative and postoperative blood transfusion.ResultsThe average blood loss was 48.9ml during operation, with no blood transfusion.Obvious hemochrome decrease (＜9 g/L) was found in 42 patients at 2-4 days after operation and the patients received blood transfusion for mean 300 ml.The mean obvious blood loss was 62.3 ml, while the mean hidden blood loss was 385 ml in all the patients.There was no obvious difference between males and females.ConclusionThe intertrochanter fracture is mostly seen in the elder patients.Compared with the minimal invasive operation, PFNA has more hidden blood loss, as indicates that much attention should be paid to the vital signs of the patients after surgery for prevention of the complications.

0.05).The serum PICP of tubercular meningitis children after 4 neeks glucocorticoid therapy (108.85?46.13) ?g/L was significantly lower than that in control group((154.38)?47.98) ?g/L and glucocorticoid- pretreatment (152.99?44.78) ?g/L (P

Objective To explore the dynamic changes of expressions of surfactant protein A,B(SP-A,B)and aquaporin5(AQP5)mRNA of specificity mark in alveolar epithelial cell(AEC)of premature rats with chronic lung disease(CLD)and those significances.Methods Eighty premature rats were randomly and equally divided into model group(hyperoxia group)and control group(room air group).CLD was induced by hyperoxia exposure.The gene expressions of SP-A,SP-B and AQP5 were assayed with reverse transcription polymerase chain reaction(RT-PCR)after 1,3,7,14 and 21 days.Results Compared with control group,in hyperoxia group,the levels of SP-A and SP-B mRNA increased from day 7(Pa

This paper is to build a finite element model of brain with a real brain shapeon which simulation studies of electrical impedance tomography EIT in the brain is based. A curve of a real brain shape is simulated with the curve-fitting methods and EIT in the brain is finished with finite-element methods and Equipotential Lines Back-Projection algorithm.The locationarea and amplitude of the change of the resistivity are reconstructed accurately. But the image quality has to be further improved.This paper provides a basis for clinical applications of EIT in brain.