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 understand the schistosomiasis endemic situation of surveillance sites in order to offer the scientific evidence for schistosomiasis control in Yunnan Province.Methods According to the protocol of national surveillance of schistosomiasis,four national sites in Yunnan Province were surveyed and the results were analyzed.Results In the four surveillance sites in Yunnan Province,the average infection rate of schistosomiasis of residents was 1.92%,and the infection rates of cattle and water buffaloes were 3.65% and 6.59% respectively.The snail area was 99.44 hm2,and the average density of the snails was 0.37 snail/0.1 m2,and the snail infection rate was 0.08%.There was the feature of higher infection rate and lower infection intensity in residents in Yunnan.Conclusions The endemic situation of schistosomiasis falls obviously after the control.However,the domestic animals still play an important role in the transmission of schistosomiasis,and the snails are not well controlled in some sites.So the surveillance and control to cattle and the snail should be continuously strengthened.

Objective To investigate the value of detecting HEART score and HEARTS3 score in risk stratification and prognosis of acute coronary syndrome (ACS) in patients with non-ST segment elevation chest pain in emergency department (ED).Methods Clinical data of case-control retrospective study of 775 patients with non-ST segment elevation chest pain in ED were collected from July 2011 to March 2015.The patients were estimated and risk stratification was made with HEART score and HEARTS3 score.After follow-up visiting by telephone for 30 days,outcomes were found to be ACS and myocardial infarction (MI).And the patients were categorized with score into low,intermediate and high risk groups.The correlation between the ACS and risk score in three groups was analyzed.Comparison of capability of performance in predicting 30-day ACS between the HEART score and HEARTS3 risk score.Statistical analyses were performed using SPSS13.0.Enumeration variables were expressed as percentage.For comparison of predictive value of the two sets of scores,area under the receiver operating curve (auROC) was calculated and compared by Z test.Results There were 92 cases with 30-day ACS.The rate of ACS had a trend of increase with increase in HEART score and HEARTS3 score.The patients with higher scores of HEART and HEARTS3,higher incidence of ACS in 30 days.Especially,the high-risk patients with score≥7 of HEART score and≥8 of HEARTS3 score had higher rate of ACS.And there was significant difference in predicting high-risk patients between two sets of scoring (P ＜ 0.05).The HEARTS3 score outperformed the HEART score as determined by comparison of areas under the ROC curve for MI (0.952 vs 0.813;P =0.028),30-day ACS (0.913 vs.0.815;P =0.034).Conclusions HEART score and HEARTS3 score both can be used to evaluate and perform risk stratification for non-ST segment elevation chest pain patients in ED.But HEARTS3 score can more precisely stratify high-risk patients with chest pain for 30-day ACS.

Objective To develop a rapid and efficient single cell PCR method for the non-invasive prenatal hemophilia A genetic diagnosis.Methods Six STR markers (DXS15,DXS9901,G6PD, DXS1073,DXS1108 and F8Civsl3) closely linked to F Ⅷ gene were examined in 118 healthy individuals and 12 hemophilia A families by muhi-plex fluorescent PCR.Three markers with the higher heterozygote rate and diagnostic rate were chosen and combined with amelogenin gene to establish the four-plex nested fluorescent PCR on single lymphocyte level.Results The single lymphocyte amplification rates of Amelogenin,DXS15,FSCivsl3 and DXSI073 were 94.3%,91.4%,100% and 100% in the normal male,and 100% ,97.1% ,97.1% and 97.1% in the normal female's respectively.The female was heterozygous in DXS1073 and DXS15.However,no allele dropout was found in both markers.Neither the false negative nor the false positive amplification was observed.Conclusion The single cell four-plex nested fluorescent PCR method established in this study is convenient and efficient,and will be hopefully employed in the clinical non-invasive prenatal genetic diagnosis for hemophilia A.

Background and purpose:LMP1 was one of the protein encoded by EBV latent gene,which was found to be able to transform cell lines and alter the phenotype of cells due to its oncogenic potential.In human epithelial cells,LMP1 alters many functional properties that are involved in tumor progression and invasions.In this study we investigated the influence of LMP1 silence on AP-1 signal transduction pathway and its downstream factors involved with cell transformation,proliferation and apoptosis.Methods:The chemically synthetic siRNA targeting LMP1 was transfected into EBV positive gastric carcinoma epithelial cell line by lipofectamine 2000 at 50 nmol/L final concentration.The protein expression of c-Jun,JunB and CDK4 was tested by,Western blotting.The mRNA of c-Jun,surviving,CDK4 and MMP9 mRNA were tested by RT-PCR.The expression of survivin were tested by immunohistochemistry.Results:Compared with the cell control,CDK4 mRNA was up regulated(P

Objective To evaluate the efficacy of radiosynovectomy with 32P colloid in haemophilic synovitis of adolescents. MethodsRadiosynovectomy with 32P colloid was primary performed on 26 male haemophilic patients(26 joints),whose average age was 16 years(11 to 21 years).The average dose of 32P colloid was 2.1 mCi(1.0 to 3.0 mCi). Results After 6-month interval,haemarthrosis was reduced by no less than 30% in 23 patients,with a total efficacy of 88.5%.The mean frequency of haemarthrosis was reduced from 1.9 per month of presynovectomy to 0.3 per month of postsynovectomy(P

Objective To evaluate the role of early cleavage embryo in combination with embryo growth rate and morphology scoring in embryo selection in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. Methods Six hundred and ten IVF/ICSI cycles were randomly assigned to group A(269 cycles) and group B(341 cycles). In group A, transferred embryos were chosen according to embryo growth rate and morphology scoring by 72 h(D3) after fertilization, while early cleavage embryo was added to the selecting system in group B. The pregnancy rate and implantation rate were compared between two groups, and the clinic outcomes were compared between transfers with early cleavage embryos and without early cleavage embryos in group B. Results The pregnancy rate and implantation rate in group B were significantly higher than those in group A (P < 0.05). Transfers with early cleavage embryos also achieved much higher pregnancy rate and implantation rate in group B (P < 0.01). Conclusion Compared with embryo growth rate and morphology scoring, early cleavage embryo in combination with embryo growth rate and morphology scoring can improve the clinical outcomes in IVF/ICSI cycles.

Objective To explore the problems in the introducing of complementary food in infants and provide a guidance for cli nical practice.Methods The questionnaire survey was carried out by childhood health doctors in mothers or caregivers on fixed outpatient health care day. The data of survey was entered into computer and analyzed with SPSS 11.5 software.Results 1.Earlier (

Objective To find out the status of prevention and control of iodine deficiency disorders and evaluate the iodine nutritional status of Jinan residents,to explore appropriate iodine level in drinking water,and to provide a scientific basis for adjustment of intervention strategies.MethodsAccording to the Monitoring Program of the National Iodine Deficiency Disorders (Trial),qualified iodized salt consumption rate,drinking water iodine content and urinary iodine levels of women of childbearing age were determined in iodine deficiency areas from 2003 to 2010.Salt iodine was detected by direct titrimetry,urinary iodine by As-Ce catalytic spectrophotometric assay and iodine in drinking water by cerous sulfate catalytic spectrophotometric method.Results Intake rate of qualified iodized salt was up to 90％ and above from 2003 to 2010,median water iodine was 13.65 μg/L in the 10 counties(cities,districts),of which less than 100 μg/L accounted for 79.82％(4560/5713 ) and ＞ 150 μg/L accounted for 12.73％(727/5713).With the increase of water iodine(0 ～ ＜ 10,10 ～ ＜ 50,50 ～ ＜ 100,100 ～ ＜ 150,150 ～ ＜ 300 and ≥300 μg/L),urinary iodine levels of women of childbearing age increased successively(median 156.56,175.81,267.04,349.00,524.22,583.20 μg/L,respectively,x2 =121.20,P ＜ 0.05),while the ratio of urinary iodine ＜ 100 μg/L was significantly lower.The ratio of urinary iodine between 100 and 300 μg/L was decreased gradually,but the ratio of great than 300 μg/L was gradually increased.ConclusionsIodine deficiency areas in Jinan have reached the standard of elimination of iodine deficiency disorders.We should insist to carry out our measures to suit local conditions,classified guidances and scientific principals of iodine supplementation.

AIM: To isolate and characterize the anti-complementary polysaccharide from the root of Bupleurum chinense. METHODS: Bioactivity-guided fractionation and purification was used to obtain the anti-complementary polysaccharide from the hot-water extract of the root of Bupleurum chinense. The polysaccharide was characterized by various chemical and spectral analyses. The anti-complementary activities were evaluated by hemolytic assay in vitro. The action targets were identified in the system with individual complement-depleted sera. RESULTS: A homogeneous polysaccharide BC-PS2 was isolated as an anti-complementary agent. It was identified as a branched polysaccharide with an average molecular weight about 2 000 KDa, composed of Glc, Ara, Gal, and Man in the ratio 3.5 : 2.4 : 2.0 : 1.0, respectively, along with a trace of Rha and Xyl, and only 1.11% of protein. The main linkages of the residues of BC-PS2 include terminal, 1, 6-linked, 1, 3-linked and 1, 3, 6-linked Glcp, terminal and 1, 5-linked Araf, terminal, 1, 4-linked, 1, 6-linked and 1, 4, 6-linked Galp, terminal, and, 1, 4-linked and 1, 4, 6-linked Manp. The bioassay experiments revealed that BC-PS2 inhibited complement activation on both the classical and alternative pathways, with CH50 and AP50 of (0.222 ± 0.013) and (0.356 ± 0.032) mg·mL(-1), respectively. Preliminary mechanism studies indicated that BC-PS2 interacted with C1q, C2, and C9 components. CONCLUSION The results demonstrated that BC-PS2 is an anti-complementary polysaccharide, and should be important constituent of the root of Bupleurum chinense for its application in the treatment of diseases associated with the excessive activation of complement system.
Adult ; Bupleurum ; chemistry ; Carbohydrate Sequence ; Complement Activation ; drug effects ; Complement Inactivating Agents ; chemistry ; isolation & purification ; pharmacology ; Hemolysis ; drug effects ; Humans ; Male ; Molecular Weight ; Plant Extracts ; chemistry ; isolation & purification ; pharmacology ; Plant Roots ; chemistry ; Polysaccharides ; chemistry ; isolation & purification ; pharmacology