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

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

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 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.

An increasing number of monopartite begomoviruses are being identified that a satellite molecule (DNAbeta) is required to induce typical symptoms in host plants. DNAbeta encodes a single gene (termed betaC1) encoded in the complementary-sense. We have produced transgenic Nicotiana benthamiana and N. tabacum plants expressing the betaC1 gene of a DNAbeta associated with Tomato yellow leaf curl China virus (TYLCCNV), under the control of the Cauliflower mosaic virus 35S promoter. Transgenic plants expressing betaC1 showed severe developmental abnormalities in both species. Microscopic analysis of sections of both transgenic and non-transgenic N. tabacum leaves showed abnormal outgrowths of transgenic N. tabacum to be due to disorganized cell division (hyperplasia) of spongy and palisade parenchyma. Immuno-gold labeling of sections with a polyclonal antibody against the betaC1 protein showed that the betaC1 protein accumulated in the nuclei of cells. The possible biological function of the betaC1 protein was discussed.
Cell Division ; physiology ; Cell Nucleus ; genetics ; metabolism ; ultrastructure ; Cells, Cultured ; DNA, Viral ; genetics ; Geminiviridae ; genetics ; Plant Diseases ; genetics ; virology ; Plant Leaves ; cytology ; genetics ; growth & development ; metabolism ; Plants, Genetically Modified ; growth & development ; metabolism ; Recombinant Proteins ; metabolism ; Tobacco ; cytology ; growth & development ; metabolism ; ultrastructure ; Viral Proteins ; genetics ; metabolism

Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Fibula ; transplantation ; Humans ; Male ; Middle Aged ; Periosteum ; transplantation ; Radius ; surgery ; Transplantation, Autologous ; Ulna ; surgery

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

OBJECTIVETo explore methods of treating middle and distal tibia nonunion with the treatment of advanced bone graft combined with locking compression plate.

METHODSFrom January 2011 to December 2012, 12 patients with middle and distal tibia nonunion were treated with advanced bone graft combined with locking compression plate. Among patients, there were 8 males and 4 females aged from 20 to 69 with an average of 47 years old. The time from first injuries to bone nonunion was from 9 months to 5 years, avergaed 19 months. Four cases were treated with external fixation, 6 cases were treated with plate fixation, 2 cases of 12 patients occurred broken of plate and nail. Eleven patients were non-infective bone nonunion and 1 patient was infective bone nonunion. Preoperative X-ray and CT showed all patients had sequestration and formation of ossified bone with different degrees. Operative time, blood loss, wound healing were observed, fracture healing time was evaluated by postoperative X-ray. Johner-Wruhs scoring standards was used to evaluate ankle joint function after operation at 10 months.

RESULTSOperative time ranged from 90 to 185 min with an average of (125.00±20.15) min; blood loss ranged from 225 to 750 ml with an average of (415.00±120.00) ml. All patients were followed up from 10 months to 2.5 years with an average of 1.5 years. Postoperative X-ray showed bone union was formed around fracture after operation at 4 months in all patients, 3 cases obtained bone healing within 6 months after operation, 9 cases obtained from 8 to 12 months. No infection, injury of nerve and vessles, and broken of plate and nail were ocurred. According to Johner-Wruhs scoring at 10 months after operation, 10 cases obtained excellent results, 1 good and 1 moderate.

CONCLUSIONAdvanced bone graft combined with locking compression plate, which can build fracture multi-point supporting based on full compression of bone nonunion to get effective fixation, is an effective method in treating middle and distal tibia nonunion.

Adult ; Aged ; Bone Plates ; Bone Transplantation ; Female ; Fracture Healing ; Fractures, Ununited ; surgery ; Humans ; Male ; Middle Aged ; Tibial Fractures ; surgery