ABSTRACT
Xeroderma pigmentosum (XP) is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patient-specific induced pluripotent stem cells (iPSCs) harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated. Mutation of XPA in either neural stem cells (NSCs) or neurons resulted in severe DNA damage repair defects, and these neural cells with mutant XPA were hyper-sensitive to DNA damage-induced apoptosis. Thus, XP-mutant neural cells represent valuable tools to clarify the molecular mechanisms of neurological abnormalities in the XP patients.
Subject(s)
Female , Humans , Male , DNA Damage , DNA Repair , DNA-Binding Proteins , Genetics , Metabolism , Induced Pluripotent Stem Cells , Metabolism , Pathology , Models, Biological , Mutation , Neural Stem Cells , Metabolism , Pathology , Xeroderma Pigmentosum , Genetics , Metabolism , PathologyABSTRACT
Objective To evaluated the application value of two kinds of mass spectrometer(MS)and Vitek MS system in the i-dentification of routinely isolated bacteria in clinic.Methods 149 strains of common bacteria(including 14 genera and 30 species)i-solated from blood,urine,cerebral spinal fluid,secretion and sputum samples in our hospital from March 2012 to January 2013 were collected and simultaneously identified by 2 kinds of matrix-assisted laser desorption ionization-time of flight mass spectrometer (MALD-TOF-MS).The identification results were compared with those identified by the conventional biochemical identification (Vitek2 compact).The strains with the inconsistent results identified by 3 kinds of method were confirmed by 16S rDNA gene se-quencing.Results Among 149 common bacteria,the correct identification rates of genus and species by the Bruker Biotyper MS were 98% and 96% respectively and which by the Vitek MS system were 97% and 95% respectively.There were no misidentified bacterial strains by these two kinds of MS.Conclusion No statistical difference in the identification results was observed between these two kinds of MS system(P >0.05).Both exhibit excellent identification level and are suitable for the routine laboratory iden-tification of clinical microorganism.
ABSTRACT
Objective Right ventricular outflow tract septum has become widely used us an electrode placement site. However, data concerning lead performances and complications for lead repositioning with this technique were scant. The purpose of this study was to observe long-term lead performances and complications of right ventricular outflow tract septal pacing and provide evidences for choosing an optimal electrode implantation site. Methods Thirty-six patients with septal active electrode implantation and 39 with apical passive electrode implantation were enrolled in this study. Pacing threshold, R-wave sensing, lead impedance, pacing QRS width and pacing-related compli-cations for two groups at implantation and follow-up were compared. Results There were higher pacing threshold and shorter pacing QRS width at implantation in the septal group compared with the apical group. There were no differences between the septal and the apical groups in pacing threshold, R-wave sensitivity, lead impedance and pace-related complication during a follow-up. Conclusions Right ventricular outflow tract septum could be used as a first choice for implantation site because it had long-term stable lead performances and no serious complications compared with the traditional apical site.
ABSTRACT
Objective Atrioventricular block (AVB) is a common and serious arrhythmia. At present, there is no perfect method of treatment for this kind of arrhythmia. The purpose of this study was to regenerate cardiac atrioventricular conduction by autologous transplantation of bone marrow mesenchymal stem cells (MSCs), and explore new methods for therapy of atrioventricular block. Methods Eleven Mongrel canines were randomized to MSCs transplantation (n=6) or control (n=5) group. The models of permanent and complete AVB in 11 canines were established by ablating His bundle with radiofrequency technique. At 4 weeks after AVB, bone marrow was aspirated from the iliac crest. MSCs were isolated and culture-expanded by means of gradient centrifugal and adherence to growth technique, and differentiated by 5-azacytidine in vitro. Differentiated MSCs (1ml, 1.5×107cells) labeled with BrdU were autotransplanted into His bundle area of canines by direct injection in the experimental group, and 1ml DMEM in the control group. At 1-12 weeks after operation,the effects of autologous MSCs transplantation on AVB models were evaluated by electrocardiogram, pathologic and immunohistochemical staining technique. Results Compared with the control group, there was a distinct improvement in atrioventricular conduction function in the experimental group. MSCs transplanted in His bundle were differentiated into analogous conduction system cells and endothelial cells in vivo, and established gap junction with host cardiomyocytes. Conclusions The committed-induced MSCs transplanted into His bundle area could differentiate into analogous conduction system cells and improve His conduction function in canine AVB models.
ABSTRACT
AIM: Although endovascular radiotherapy inhibits neointimal hyperplasia, the exact alterations induced by ?-particles irradiation remain to be elucidated. The objective of this study was to investigate the ability and the cellular mechanism of local ?-particles emission from 188 Re to inhibit vascular smooth muscle cells (SMCs).METHODS: The SMCs in vitro were irradiated by 188 Re with single doses of 2.6 Gy-25.8 Gy. The effects of ?-particles on SMCs, such as effective irradiate doses, the period of inhibition for SMCs proliferation, the changes of cell proliferation rate and DNA synthesis rate, cell cycle progression and related gene expression, were investigated by cell count,-TdR incorporation, cell cycle progression analysis, cell viability and immunocytochemistry, respectivecy.RESULTS: ?-particles irradiation with dose of 5.2 Gy could inhibit significantly SMCs proliferation. At dose of 20.6 Gy DNA synthesis inhibitory rate was 92%, SMCs proliferation rate was only 3%. Renoval of 188 Re did not abolish the inhibitory effects of ?-particles on SMCs proliferation. The expression of P53 was up regulation and PCNA was down regulation after irradiation. CONCLUSION: ?-particles from 188 Re was significantly effective and permanent in inhibiting SMCs proliferation, and inhibitory effect was in dose-dependet manner ED50 was 5 Gy, the best dose to inhibit SMCs proliferation was 20 Gy. ?-particles irradiation induced SMCs to occur G 0/G 1 arrest, damaged the ability of SMCs reproliferation and led to cell clonogenic death. P53 and PCNA had regulatiory effects on SMCs proliferation after ?-particles irradiation.