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.

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 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.

Mean hemoglobin (Hb) concentration of about 3 500 subjects derived from 17 studies of Himalayan highlanders (Tibetans, Sherpas, and Ladakhis) was compared with lowlanders (Chinese Han, Indian Tamils) lived in the Himalayas, and European climbers during Everest expeditions as well as Andean natives. The results found that Hb concentration in Himalayan highlanders was systemically lower than those reported for Andean natives and lowland immigrants. These comparative data demonstrated that a healthy native population may successfully reside at high altitude without a significant elevation in Hb, and the lower Hb levels of Himalayan highlanders than those of migrated lowlanders and Andean natives are an example of favourable adaptation over the generations. In addition, excessive polycythemia has frequently been used as a marker of chronic mountain sickness (CMS). Altitude populations who have a higher Hb concentration also have a higher incidence of CMS. The low Hb in Himalayans suggested as showing adaptation over many generations in Tibetan stock. Recent work in Tibet, suggested that Tibetans there may have adapted to high altitude as a result of evolutionary pressure selecting for genes which give an advantage at altitude. All of the population genomic and statistical analysis indicated that EPAS1 and EGLN1 are mostly likely responsible for high altitude adaptation and closely related to low Hb concentration in Tibetans. These data supported the hypothesis that Himalayan highlanders have evolved a genetically different erythropoietic response to chronic hypoxia by virtue of their much longer exposure to high altitude.
Adaptation, Physiological ; Altitude ; Asian Continental Ancestry Group ; genetics ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; Evolution, Molecular ; Hemoglobins ; genetics ; Humans ; Hypoxia-Inducible Factor-Proline Dioxygenases ; genetics ; Tibet

Human tissue kallikrein-binding protein (Kallistatin, KAL), a secretory protein that participates in the regulation of multiple signaling pathways by binding to the extracellular receptor, however, at present has not been reported about the intracellular activity, and whether it has the similar biological activity with extracellular activity. Here we constructed no signal peptide KAL (NSK) into the adeno-associated virus vector to explore the intracellular activity of KAL. Both the endothelial cell and lung cancer cells could express KAL, but not secreted after rAAV2-NSK transfection. The proliferation and migration of human umbilical vein endothelial cells (HUVECs) were inhibited, but the apoptosis rate was not affected. The proliferation rates, mobility and tubule formation of all the three tested lung cancer cells, such as NCI-H446, NCI-H460 and A549, were inhibited to different extents. This cellular study not only confirmed the intracellular activity, but also suggested it may serve as a kind of "balance factor" in multi-targeted controlling, which may provide a new train of thoughts to explain the regulatory contradiction in PI3K-Akt signaling pathways by KAL.
Apoptosis ; Cell Proliferation ; Dependovirus ; Genetic Vectors ; Human Umbilical Vein Endothelial Cells ; metabolism ; Humans ; Lung Neoplasms ; metabolism ; Serpins ; metabolism ; Signal Transduction ; Transfection

The study is aimed to distinguish morphological characteristics of Dalbergiae Lignum collected from crude drug's markets and establish a identification methods and the quality standard for Dalbergiae Lignum. The macroscopic and microscopic features of Dalbergiae Lignum from crude drug's market were observed, analyzed and compared according to Hongmu specification issued by the People's Republic of China in 2000, and by the characteristics recorded in domestic monograph of Mucai Shibie (wood identification). The redwood of Dalbergiae Lignum cut into small pieces as medicinal material are dry heart wood of mahogany (trees from Dalbergia sp.), which characteristics of the small pieces as crude drug are different. There are differences in macroscopic and microscopic features about texture of wood and color, odor, taste, transverse section, radial section, tangential section. The results can provide basis for identification, application and improment of the quality standard of Dalbergiae Lignum as medicinal material.
China ; Dalbergia ; anatomy & histology ; chemistry ; classification ; Herbal Medicine ; economics ; Plants, Medicinal ; chemistry ; classification ; Quality Control ; Xylem ; anatomy & histology ; chemistry

OBJECTIVETo explore the therapeutic effect of acupuncture for hypertensive cerebral hemorrhage at the early stage.

METHODSFifty-four cases of small-amount cerebral hemorrhage were randomized into an acupuncture group and a conventional treatment group, 27 cases in each one. In the conventional treatment group, special care, oxygen therapy, nerve nutrition and symptomatic support were applied. In necessary, dehydrant and hypotensive drugs were prescribed for antihypertension, or surgery was given. In the acupuncture group, on the basis of the treatment as the control group, acupuncture was applied at Quchi (LI 11), Neiguan (PC 6), Zusanli (ST 36), Sanyinjiao (SP 6) and Taichong (LR 3). Acupuncture was given at the admission, 4 h, 6 h and 12 h after disease onset respectively. Blood pressure was monitored in the whole procedure. 6 h and 24 h after disease onset, the cranial CT was re-examined. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), hematoma volume and neurological deficit score were compared at different time points between the two groups.

RESULTS(1) Blood pressure: from the admission to 12 h after disease onset, SBP, DBP and MAP were increased apparently in the conventional treatment group and increased slightly in the acupuncture group. The differences in SBP [(164.3 +/- 21.6) mmHg vs (158.6 +/- 21.5) mmHg] and MAP [(113.4 +/- 4.9) mmHg vs (106.7 +/- 6.1) mmHg] were significant between the two groups (both P < 0.05). From 12 h to 24 h after disease onset, compared with the conventional treatment group, SBP and MAP were decreased apparently in the acupuncture group [(147.3 +/- 21.6) mmHg vs (158.4 +/- 23.5) mmHg, (97.2 +/- 5.3) mmHg vs (106.6 +/- 5.1) mmHg, both P < 0.05)]. (2) Hematoma volume: from the admission to 6 h after disease onset, the volume was increased by (4.15 +/- 0.73) mL in the convertional treatment group and (2.67 +/- 0.33) mL in the acupuncture group, indicating the significant difference in comparison (P < 0.05). From the admission to 24 h after disease onset, it was increased by (5.57 +/- 1.26) mL in the convertional treatment group and (3.14 +/- 1.18) mL in the acupuncture group, indicating the significant difference in comparison (P < 0.05). (3) Neurological deficit score: the score was increasing gradually in first 3 days after disease onset in the two groups. The score (38.39 +/- 6.84) in the acupuncture group on the first day was different significantly as compared with that (42.37 +/- 7.46) in the conventional treatment group (P < 0.05). On the 10th days, the score (24.68 +/- 5.42) in the acupuncture group was different significantly from that (29.74 +/- 7.36) in the convertional treatment group (P < 0.05).

CONCLUSIONThere is no peak of blood pressure rising, and the continuous hemorrhagic volume is less in 24 h and neurological deficit score is improved in the acupuncture group. Acupuncture brings the positive significance in the treatment of cerebral hemorrhage at the early stage.

Acupuncture Therapy ; Adult ; Aged ; Blood Pressure ; Cerebral Hemorrhage ; physiopathology ; therapy ; Female ; Hematoma ; physiopathology ; therapy ; Humans ; Male ; Middle Aged

Adolescent ; Anti-Bacterial Agents ; therapeutic use ; Anti-Ulcer Agents ; therapeutic use ; Female ; Humans ; Penicillin G Procaine ; therapeutic use ; Stomach Ulcer ; drug therapy ; microbiology ; pathology ; Syphilis ; drug therapy ; microbiology ; pathology ; Syphilis Serodiagnosis ; methods ; Treponema pallidum ; isolation & purification