Mesenchymal stem cells (MSCs) are potential sources of cells for tissue repair. However, little information is available about the time course of homing and differentiation of systemically delivered MSCs after acute myocardial ischemia (MI). In the present study, MSCs were isolated from male rat bone marrow and expanded in vitro. Female rats were divided randomly into three groups. Three hours after coronary ligation, the transplanted group received an infusion of MSCs through the tail vein; at the same time, a coronary-ligated control group was injected with culture medium, and a normal (unligated) group received MSCs. Homing of MSCs to the heart was assessed by expression of the Y chromosome sry gene using fluorescence in situ hybridization (FISH) at 3 days, 1, 4, and 8 weeks after transplantation. Immunofluorescent staining was used to examine markers for cardiomyocytes, endothelial cells, and smooth muscle cells. Hemodynamics in the hearts was also measured to assess cardiac function. At each time point, sry-positive cells were present in the cardiac tissue in transplanted group but not in the hearts of normal and control group animals. The number of sry-positive cells was significantly higher at 1 week compared to 3 days after transplantation. No significant difference was found in the number of sry-positive cells among those of 1, 4, and 8 weeks after transplantation. At 3 days and 1 week after transplantation, the sry-positive cells in the transplanted group lacked troponin, desmin, smooth muscle alpha-actin, and CD31. At the later time points, cardiomyocytes, smooth muscle cells, and endothelial cells bearing sry were identified in the transplanted group. The cardiac function in transplanted group showed higher improvement at 4 and 8 weeks compared to 1 week after transplantation. Our data suggest that intravenously delivered MSCs are capable of homing toward the ischemic myocardium, and the fastigium of homing appeared around 1 week after MI. The differentiation of MSCs to cardiomyocytes, smooth muscle cells, and endothelial cells shows to be time dependent and arises at 1 to 4 weeks after transplantation.
Background Brucellosis has extensive clinical spectrum, clinicians have insufficient understanding of the disease, and the misdiagnosis rate is still high. By collecting and analyzing the clinical characteristics of patients with brucellosis in Heilongjiang Province to provide guidance and reference for clinicians to make timely diagnosis and treatment. Methods The demographic and epidemiological characteristics, clinical features, complications, laboratory findings were retrospectively evaluated in 850 brucellosis patients admitted in the Department of Infectious Diseases of the First Affiliated Hospital of Harbin Medical University and the Second Hospital of Daqing from 2012 to 2017. Results Of the 850 patients, the most common clinical manifestations were fever (93.3%), joint pain (69.8%), sweating (45.2%), fatigue (38.6%), and splenomegaly (34.0%). Peripheral arthritis, spondylitis and epididymal-orchitis were the common complications. Of the 398 patients who were followed up and completed treatment, 22 (5.5%) had relapse. Conclusions Brucellosis is a multisystem disease with diverse clinical manifestations. In areas where brucellosis is endemic, the possibility of the disease should be considered in patients with unexplained fever and joints pain. In addition, the high rate of relapse is mainly due to the misdiagnosis of complications, so local CT or MRI examination is necessary for patients with joint pain and low back pain. Timely diagnosis, early detection of complications are essential to improve the prognosis and reduce relapse.
We have recently identified a missense mutation, G604S, in the human ether-a-go-go related gene (hERG) that results in a malignant phenotype in a full pedigree of a Chinese congenital long QT syndrome (LQTS) family. The present study characterized the pathophysiological consequences of the mutation at the cellular level. Mutant G604S-hERG channels were expressed in HEK293 cells using a lipofectamine method. hERG currents were recorded using the voltage clamp technique. The expression of hERG protein was detected by Western blotting, and the subcellular location of hERG channels in cell was analyzed by confocal microscopy. We found that the G604S mutation did not lead to any expression of detectable currents, which was consistent with Western blotting analysis that the G604S-hERG mutation only expressed a band at 135 kDa. When coexpressed with wild-type (WT)-hERG, G604S-hERG exhibited strong dominant-negative current suppression resulting in decreased current density and altered gating properties of the WT-hERG channel, as well as interference with the trafficking of WT-hERG channel protein. In addition, confocal microscopy demonstrated that G604S-hERG subunits could be inserted into the cell membrane when forming heteromultimeric channels with WT-hERG channel subunits. Our results suggest that G604S mutation causes a loss of function in hERG through a strong dominant-negative effect on WT-hERG channel function that caused by impaired trafficking of WT-hERG channels, and further accentuates this suppression by forming heteromultimeric functional channels with WT-hERG subunits.
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