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

Calpain ; genetics ; Diabetes, Gestational ; genetics ; Female ; Genotype ; Haploidy ; Humans ; Polymorphism, Single Nucleotide ; Pregnancy

[Objective] To investigate the pathogen spectrum and characteristics of diarrheal disea-ses among children under five and to provide the basis for prevention and control measures . [ Methods] From February 2012 to January 2013, a total of 619 cases from 2 sentinel hospitals were collected for case survey .From them were collected stool specimens for detection of enteric pathogenic bacteria and virus nu-cleic acids. [Results] The virus detection rate was norovirus (11.95%), rotavirus(7.27%), enteric adenovirus(2.91%), saporovirus(1.45%) and astrovirus(0.97%).The bacteria detection rate was E. coli(5.65%), nontyphoidal salmonella (2.42%), campylobacter (0.81%), aeromonas hydrophila (0.65%),shigella(0.48%) and yersinia enterocolitica (0.32%).The virus detection rate was 27.70%from August to next March, which showed higher than that of other months (18.48%) (χ2 =7.18,P <0.05).The bacteria detection rate was 15.34%from April to October, showing higher than the rate of oth-er months(3.15%)(χ2 =31.22,P<0.05). [Conclusion] Norovirus is the main pathogen for viral diarrheal diseases in children under five and E .coli is the main pathogen of bacterial diarrheal diseases . All study results suggested that summer and autumn should be as the focus time in prevention and control of bacterial diarrhea , while those of viral diarrhea should cover the whole year .

OBJECTIVETo study the effect of fluridone concentration, stimulating period, temperature and salt on the seed germination of three species of Cistanche.

METHODThe seeds were cultured in Petri dish, and the germination percentage was counted.

RESULTThe highest germination percentage was observed in Cistanche tubulosa, C. deserticola, C. sala seeds pre-treated by 0.1 mg x L(-1) fluridone for 24-29 h. The optimal temperature for the seeds germination of three species of Cistanche was at 20-30 degrees C, and the seeds did not germinate at sub-or supraoptimal temperatures (5 and 35 degrees C). The salt tolerance of C. sala seeds was strong, and the critical value of NaCl concentration was 0.04 mol x L(-1). By contrast, C. tubulosa and C. deserticola seeds were more sensitive to the salt stress, the critical value of NaCl concentration was 0.02 mol x L(-1).

CONCLUSIONThe optimal germination condition and the method of testing germination percentage of three species of Cistanche seeds are as follow: the seeds are pre-treated by 0.1 mg x L(-1) fluridone for 24 h and then cultured at 20-30 degrees C in salt solution which concentration is lower than 0.02 mol x L(-1).

Cistanche ; classification ; growth & development ; Germination ; drug effects ; physiology ; Plants, Medicinal ; growth & development ; Pyridones ; pharmacology ; Seeds ; growth & development ; Sodium Chloride ; pharmacology ; Species Specificity ; Temperature

·Familial exudative vitreoretinopathy ( FEVR ) is a hereditary disease associated with abnormal angiogenesis in the pediatric period. The most prominent finding of the disease is avascularity in the peripheral retina. Whereas, the phenotypic features are variable. In some minor cases, missed diagnosis would happened due to asymptom, while, in severe FEVR, neovascularization, retinal exudation, retinal folds, macular heterotopy and retinal detachment may occur and give rise to extremely poor vision or even blindness. Mutations in the FZD4, LRP5, NDP, TSPAN12, ZNF408, and KIF11 genes have been reported to contribute to FEVR with X - linked recessive, autosomal dominant, and autosomal recessive inheritance manners. We have summarized aspects of pathogenesis, clinical features and classification, mutations genes as well as diagnosis and treatment of FEVR in this review.

Objective To evaluate the effect of mental intervention for patient with amputation because of peripheral artery disease, and provide basis for the mental intervention of amputation patients.Methods From 2008 to 2010, 14 patients of peripheral artery disease amputation were divided into control group and mental intervention group randomly. At different time point the scores of SDS was taken to evaluate the psychological status. Results At 2 weeks post-operation-time, the SDS scores of mental intervention group is (70.29±5.41), the number of control group is (81.43 ±12.05) (P＜0. 05). Conclusions The mental intervention on patients with amputation because of peripheral artery disease could improve their psychological conditions.

OBJECTIVETo investigate the effects of formaldehyde inhalation on the morphological damage, and Glu, GABA and NOS contents in olfactory bulb and hippocampus of rats.

METHODSTwenty SD rats were equally divided into two groups: rats in the control group inhaled fresh air, while the animals in experimental group were exposed to the air containing formaldehyde (12.5 mg/m(3), 4 h/d) for 7 days. Then rats were sacrificed and frozen sections of olfactory bulb and hippocampus were prepared. The morphological changes were examined and the Glu, GABA and NOS contents were detected using Nissl-staining, immunohistochemistry and Western blot, respectively.

RESULTCompared with the control group, there was a significant confusion and shrink of neuron morphology in experimental group, the number and staining intensity of Glu and NOS positive cells and protein contents were reduced. The protein expression of GABA was also decreased in the formaldehyde group.

CONCLUSIONFormaldehyde inhalation can cause a severe morphological damage of olfactory bulb and hippocampus in SD rats,which may further impair memory and learning ability through the reduction of Glu, GABA and NOS expression.

Animals ; Formaldehyde ; toxicity ; Glutamic Acid ; metabolism ; Hippocampus ; drug effects ; metabolism ; pathology ; Inhalation Exposure ; Learning ; drug effects ; Neurons ; drug effects ; metabolism ; pathology ; Nitric Oxide Synthase ; metabolism ; Olfactory Bulb ; drug effects ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; gamma-Aminobutyric Acid ; metabolism

BACKGROUNDAtrioventricular nodal reentrant tachycardia (AVNRT) is one of the most common paroxysmal supraventricular tachyarrhythmias. The aim of the study was to prospectively compare the characteristics of radiofrequency catheter ablation of AVNRT guided by a magnetic navigation system with the conventional procedure.

METHODSPatients with AVNRT diagnosed by electrophysiological tests were randomized into two groups. In the conventional technique group (CMT), a common 4-mm-tip quadrapolar temperature-controlled ablation catheter was used. In the magnetic navigation system guidance group (MNS), a magnetic 4-mm-tip quadrapolar temperature-controlled ablation catheter was used. The following parameters were collected and compared between the two groups: ablation procedure time, patient fluoroscopy time, operator fluoroscopy time, energy delivery numbers, maximal energy per deployment, success rate, complication rate and operative cost.

RESULTSForty patients were enrolled and randomized into CMT and MNS groups. The age, gender, tachycardia history and basic cardiovascular diseases of the two groups were comparable (P > 0.05). All procedures were conducted successfully without complications. No tachycardia recurred during the follow-up period of (9.3 ± 2.6) months. In the MNS group, the patient and operator fluoroscopy times ((11.5 ± 4.3) min, (4.2 ± 1.5) min), energy delivery numbers (3.2 ± 0.9), and maximal energy per deployment ((16.9 ± 3.4) W) were shorter or lower than those of the CMT group ((14.3 ± 6.2) min, (13.6 ± 3.5) min, 6.3 ± 2.1, (23.7 ± 1.3) W, respectively) (P < 0.05). But the operative cost for the MNS group was higher than that of the CMT group (P < 0.01).

CONCLUSIONMagnetic navigation system guided radiofrequency catheter ablation of AVNRT has the advantages of shorter fluoroscopy time and lower energy delivery numbers and maximal energy per deployment compared to the present conventional ablation technique.

Catheter Ablation ; methods ; Humans ; Tachycardia, Atrioventricular Nodal Reentry ; surgery ; Treatment Outcome

OBJECTIVETo explore the influence on AM fungi infection rate and medicine quality of Pinellia ternate in the condition of three soil impact factors.

METHODSet the orthogonal test of three factors and levels. Determinate the AM fungi infection rate in early stage of mature & stage of mature of P. ternata, and the water content, water soluble extract, butanedioic acid content and alkaloid content of P. ternata tuber that be harvested also had be determinated.

RESULT AND CONCLUSIONWith the P levels to 30 mg x kg(-1) and 90 mg x kg(-1), AM fungi infection was the best when mixed inoculated of EM. Microbial agent inoculated played a decisive role in P. ternata growth and physiological activity, secondary influenced factor was P concentration, and the water stress was the minimal impact. Mixed inoculated of AM fungi and EM treatment with the low P levels (30, 90 mg x kg(-1)) proved better effect on enhancing the water extract content, anedioic acid and alkaloid content, while decreasing the water contents of P. ternata tuber.

Alkaloids ; chemistry ; Drugs, Chinese Herbal ; chemistry ; standards ; Fungi ; Pinellia ; chemistry ; microbiology ; Plant Extracts ; chemistry ; standards ; Soil

OBJECTIVETo construct T vectors based on Xcm I recognition site and optimize the PCR fragments for its ligation.

METHODSWe firstly cloned the human histone H4 cDNA containing one Xcm I recognition site at both its 5' and 3' end into pCDNA 3.0 vector and then generated T vector with pCDNA 3.0 backbone by cutting the recombinant plasmid with Xcm I. To increase the ligation efficiency, the primers were firstly phosphorylated before DNA fragments amplification and then the PCR products were treated with Taq DNA polymerase and dATP after PCR amplification. Two DNA fragments with the length of 312 bp and 1 329 bp were ligated to it and the ligation mixture was transformed into E. coli DH5α competent cells and the positive rates of the transformants were evaluated by PCR and DNA agarose gel electrophoresis.

RESULTSOur results showed that the T vector produced by our method could ligate to the target DNA fragments with high efficiency. Besides, the phosphorylation state of the primers used for PCR amplification is also an important factor determining the cloning efficiency. What's more, as for longer DNA fragments, retreatment with Taq DNA polymerase and dATP after PCR amplification and purification could improve the ligation efficiency significantly.

CONCLUSIONOur protocol may overcome the dependence on blue/white screening to get positive clones and provide a potent way to generate T vectors and ligate them to the target PCR fragment.

Cloning, Molecular ; DNA, Complementary ; genetics ; Escherichia coli ; genetics ; Genetic Vectors ; Histones ; genetics ; Humans ; Polymerase Chain Reaction ; methods