Animals ; Humans ; Interleukin-1 ; physiology ; Mice ; Pulmonary Fibrosis ; physiopathology ; Rats ; Receptors, Interleukin-1 ; physiology

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

Angioedema ; chemically induced ; Drug Eruptions ; etiology ; Drugs, Chinese Herbal ; adverse effects ; Humans ; Urticaria ; chemically induced

Adult ; Factor XIII ; antagonists & inhibitors ; Factor XIII Deficiency ; complications ; etiology ; Female ; Humans ; Sjogren's Syndrome ; complications

Objective To explore the biological characteristics and karyotype of bone marrow-derived mesenchymal stem cells(MSCs)in patients with systemic lupus erythematosus(SLE)and hematopoietic sup- port of MSCs.Methods MSCs were isolated from bone marrow of 11 SLE patients and 6 healthy controls by density centrifugation and adhesive culture in vitro.The surface markers were detected by flow cytometry (FCM).The morphological changes of MSCs were observed in primary and passage cultures.The growth curves were assayed.The karyotype of MSCs was detected by blocking cellular mitosis with colchicines.The MSCs from SLE patients and healthy controls were infused to ICR mice after high-dose chemotherapy.The changes of peripheral blood counts of the mice were recorded.Results Approximately(6～9)?10~9 MSCs from SLE were obtained after 5 passages and their growth was slower than normal controls(P＜0.01).Both groups were positive for CD29,CD44 and CD105,and negative for CD14,CD34,CD45 and HLA-DR.MSCs from SLE had a normal karyotype.MSCs infusions of the two groups were accompanied by no adverse event and the recovery of white blood cell,hemoglobin and platelet count was quicker when compared with the controls(P＜0.05).Conclusion MSCs from SLE have demonstrated abnormalities in expansion in vitro.MSCs from SLE have a normal karyotype.Ex vivo MSCs infusion from SLE patients can support hematopoiesis as normal MSCs.

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.

The theoretical basis of the alcohol precipitation process control was provided, the alcohol precipitation was optimized and the relationship equation was got. The monod glycoside, loganin and paeoniflorin were used as the evaluation indexes to determine the impact factors of alcohol precipitation techniques of Liuwei Dihuang decoction by the Plackett-Burman experimental design and the levels of non-significant factors were identified. Then, Box-Behnken response surface methodology was used to research and discuss the critical process parameters influence the effect of alcohol precipitation and draw interaction between key process parameters and the correlation equation with index components. Through the establishment and solving the quadratic regression model of composite score, the optimum preparation conditions of alcohol precipitation techniques of liuwei were as follows: stirring speed was 580 r x min(-1), standing time was 17 hours, alcohol concentration was 34%, the density of Liuwei Dihuang decoction was 1.13. The response surface methodology for optimized alcohol precipitation techniques of Liuwei Dihuang decoction is. reasonable and feasible.
Chemical Precipitation ; Chemistry, Pharmaceutical ; methods ; Drugs, Chinese Herbal ; chemistry ; Ethanol ; chemistry

Objective To explore the clinical efficacy of laparoscopic inguinal hernia repair (LIHR) in elderly patients.Methods The retrospective cohort study was adopted.The clinical data of 3 203 patients with inguinal hernias (3 847 sides) who were adnitted to the Ruijin Hospital of Shanghai Jiaotong University School of Medicine between January 2001 and December 2013 were collected.Of 3 203 patients,979 (1 107 sides) with age ＜ 60 years and 2 224 (2 740 sides) with age ≥ 60 years were respectively allocated into the under 60 years group and 60 years or older group.The surgical procedures including transabdominal preperitoneal (TAPP) approach,total extraperitoneal (TEP) approach and intraperitoneal onlay mesh (IPOM) approach were selected and performed by doctors in the same team.There were light-weight and heavy-weight patches.Observation indicators included (1) overall operation situations,(2) surgical comparison between the 2 groups,(3)comparison of postoperative indicators between the 2 groups,(4) follow-up.Follow-up using telephone interview and outpatient examination was performed to detect the recovery time of non-restricted activity,recurrence of hernia and complications.Measurement data with normal distribution were represented as ~ ± s and comparison between groups was done by the t test.Comparisons of count data were analyzed using the chi-square test or Fisher exact probability.Ranked data were compared by the nonparametric rank sum test.Results (1) Overall operation situations:3 203 patients with inguinal hernias (3 847 sides) underwent LIHR,including 1 475 (1 677 sides) using TAPP approach,1 718 (2 154 sides) using TEP approach and 10 (16 sides) using IPOM approach (6 using TAPP and IOPM approaches in each side).The light-weight patch was used in 2 206 sides and heavy-weight patch was used in 1 641 sides.Operation time was (31 ± 12) minutes in all 3 203 patients,(27 ±9)minutes in 2 559 patients with unilateral hernia and (44 ± 12)minutes in 644 patients with bilateral hernia,respectively.Duration of postoperative hospital stay was (1.5 ± 1.2) days.(2) Surgical comparison between the 2 groups:TAPP approach,TEP approach,IPOM approach,light-weight patch and heavy-weight patch were performed to 567,538,2,751,356 sides in the under 60 years group and 1 110,1 616,14,1 455,1 285 sides in the 60 years or older group,respectively,with statistically significant differences in above indicators between the 2 groups (X2 =37.976,70.022,P ＜ 0.05).Operation time in unilateral hernia and bilateral hernia and total operation time were (27 ± 9)minutes,(42 ± 10)minutes,(29 ± 10)minutes in the under 60 years group and (27 ± 10)minutes,(44 ± 12)minutes,(3 1 ± 13)minutes in the 60 years or older group,respectively,with no statistically significant difference between the 2 groups (t =-0.106,-1.768,-4.445,P ＞ 0.05).(3) Comparison of postoperative indicators between the 2 groups:the pain score at postoperative day 1 and duration of postoperative hospital stay were 2.4 ± 1.1,(1.5 ± 1.1) days in the under 60 years group and 2.3 ± 1.0,(1.5 ± 1.3) days in the 60 years or older group,respectively,with no statistically significant difference between the 2 groups (t =1.419,-0.126,P ＞0.05).(4) Follow-up:all the patients were followed up for 23-60 months,with a median time of 43 months.Cases with non-restricted activity recovery at postoperative week 2 and 4 were 973,978 in the under 60 years group and 2 208,2 222 in the 60 years or older group,respectively,showing no statistically significant difference between the 2 groups (X2=0.113,P ＞0.05).The recurrence of hernia,severe complications,serum tumescence,paresthesia and enteroparalysis were detected in 1,0,49,5,1 sides in the under 60 years group and 11,3,132,16,2 sides in the 60 years or older group,respectively,with no statistically significant difference between the 2 groups (x2=1.556,0.269,0.254,P ＞ 0.05).The urinary retention in the under 60 years group and 60 years or older group was respectively detected in 6 and 44 sides,showing a statistically significant difference between 2 groups (x2=6.956,P ＜ 0.05).Conclusion LIHR is safe and effective in elderly patients,and it can achieve good clinical efficacy under selecting reasonable operation procedures and patches.

In this study, microcalorimetry was adopted to establish a novel method for detecting the hemagglutination process of Radix Isatidis (Banlangen in Chinese, BLG), and to evaluate the hemagglutination activity diversity of BLG from various habitats. The hemagglutination biothermokinetics curves of positive reagent (phytohemagglutinin, PHA) and 8 batches BLG from different regions of the hemagglutination with 20% rabbit erythrocyte were recorded by microcalorimetry, then biothermokinetics parameters were abstracted, the hemagglutination utility of samples were calculated and analyzed by principal component analysis (PCA) and cluster analysis (CA), meanwhile the results were authenticated by micro-plate agglutination. It showed that the hemagglutination was an exothermic reaction, the reaction rate constant (k: 0.039-73.6 min(-1)), maximum reaction power (Pmax: -1 140.2 - 988.2 microW) and reaction enthalpy (Hi: -529.9 - 717.9 microJ) had good linear correlation with BLG extraction concentration (0.2-1.0 g mL(-1), r > 0.97), and PCA showed Pmax (531-1 335 microW) and Ht (585.2-989.2 microJ) could represent the hemagglutination activity diversity of BLG samples, just confirming with the results of micro-plate agglutination (the agglutination dilution was 3-11 respectively). According to the hemagglutination utility, the BLG samples from Good Agriculture Practice (GAP) regions, main producing area and general regions could be clustered correctly; meanwhile, the biothermokinetics curves with perfect distinctive fingerprint and specificity could give out more information for the quality control and evaluation for BLG. In conclusion, the microcalorimetry method established for detecting the hemagglutination activity of BLG samples on rabbit erythrocyte is sensitive and reliable, and could be adopted as an effective technique in detection aggulatination precisely, quantitatively and consecutively; and provide a novel approach for examining and evaluating quality for Chinese herbal medicine with aggulatinative activity such as BLG.

OBJECTIVETo investigate the effect of component I from agkistrodon acutus venomon (AAVC-I) the migration of human umbilical vein endothelial cells (HUVECs), and to elucidate the possible anti-angiogenic mechanism of AAVC-I.

METHODSThe effect of AAVC-I on the migration of HUVECs which was cultivated in vitro and treated with AAVC-1 at four concentrations: 0, 20, 40, 80 microg/ml, was observed by methods of scratch wound-healing and Transwell assay. The expression level of mRNA and protein of P-selectin and intercellular cell adhension molecule-I (ICAM-1) were examined by RT-PCR and Western blot assay.

RESULTSCompared with the blank group, the migration ability of HUVECs in each AAVE-I treated group was reduced in a dose-dependent manner, and the expression level of the mRNA and protein of P-selectin and ICAM-1 were decreased.

CONCLUSIONAAVC-I inhibits the migration of endothelial cell, which is acted by down-regulation of the expression content of mRNA and protein of P-selectin and ICAM-1.

Cell Movement ; drug effects ; Cells, Cultured ; Crotalid Venoms ; pharmacology ; Down-Regulation ; Human Umbilical Vein Endothelial Cells ; drug effects ; Humans ; Intercellular Adhesion Molecule-1 ; metabolism ; P-Selectin ; metabolism ; RNA, Messenger