Endothelial progenitor cells (EPCs) play a key role in tissue repair and regeneration. Previous studies have shown a positive correlation between the number of circulating EPCs and clinical outcomes of patients with traumatic brain injury (TBI). A recent study has further shown that intravenous infusion of human umbilical cord blood-derived endothelial colony-forming cells (ECFCs) improves outcomes of mice subjected to experimental TBI. This follow-up study was designed to determine whether intracerebroventricular (i.c.v.) infusion of ECFCs, which may reduce systemic effects of these cells, could repair the blood-brain barrier (BBB) and promote angiogenesis of mice with TBI. Adult nude mice were exposed to fluid percussion injury and transplanted i.c.v. with ECFCs on day 1 post-TBI. These ECFCs were detected at the TBI zone 3 days after transplantation by SP-DiIC18(3) and fluorescence in situ hybridization. Mice with ECFCs transplant had reduced Evans blue extravasation and brain water content, increased expression of ZO-1 and claudin-5, and showed a higher expression of angiopoietin 1. Consistent with the previous report, mice with ECFCs transplant had also increased microvascular density. Modified neurological severity score and Morris water maze test indicated significant improvements in motor ability, spatial acquisition and reference memory in mice receiving ECFCs, compared to those receiving saline. These data demonstrate the beneficial effects of ECFC transplant on BBB integrity and angiogenesis in mice with TBI.
Paracetamol may confer comparable treatment efficacy for the closure of PDA as ibuprofen, although paracetamol is associated with lower risk of adverse events.
Glioma is the most common malignant tumor of the central nervous system with poor survival. Temozolomide (TMZ) is the first-line chemotherapy drug for initial and recurrent glioma treatment with a relatively good efficacy, which exerts its antitumor effects mainly through cell death induced by DNA double-strand breaks in the G1 and S phases. However, endogenous or acquired resistance to TMZ limits glioma patients’ clinical outcome and is also an important cause of glioma replase. MicroRNA-195 (miR-195) plays an important role in the regulation of G1-phase/S-phase transition, DNA damage repair, and apoptosis of tumor cells. We found that miR-195 expression was significantly decreased in TMZ-resistant glioma cells induced with TMZ and correlated to the resistance index negatively. Also, the exogenous expression of miR-195 reversed TMZ resistance and induced the apoptosis of TMZ-resistant glioblastoma cells. Further bioinformatics analysis showed cyclin E1 (CCNE1) was a potential target gene of miR-195. Knockdown of CCNE1 partially reversed the effect of decreased miR-195 on TMZ resistance. The data from The Cancer Genome Atlas – Cancer Genome further suggested that hsa-miR-195 could negatively regulate the expression of CCNE1 in glioma. In conclusion, miR-195 reverses the resistance to TMZ by targeting CCNE1 in glioma cells and it could act as a potential target for treatment in glioma with TMZ resistance.
We isolated human epidermis-derived mesenchymal stem cell-like pluripotent cells (hEMSCPCs) and demonstrate efficient harvesting, maintenance in vitro for at least 30 passages, reprogramming into multiple phenotypes in vivo, and integration into adult host tissues after injection into the mouse blastocyst to create chimeras. Cell phenotype was examined by karyotyping, immunostaining, immunofluorescence, and flow cytometry. A nested PCR protocol using primers specific for human SRY genes was designed to detect hEMSCPC-derived cells in female chimeric mice. FISH was used to validate the results of nested PCR. Results indicated that hEMSCPCs were derived from epidermis but were distinct from epidermal cells; they resembled mesenchymal stem cells (MSCs) morphologically and expressed the main markers of MSCs. About half of all female offspring of mice implanted with embryos injected with hEMSCPCs at the blastocyst stage harbored the human Y chromosome and tissue-specific human protein, thereby demonstrating the transdifferentiation of hEMSCPCs.
The aim of this study was to investigate the expression levels of microRNA-208 (miR-208) and sex-determining region Y-box 6 (SOX6) in patients with progressive cardiac hypertrophy. A total of 50 patients with essential hypertension accompanied by left ventricular hypertrophy, and 30 healthy individuals were enrolled. Peripheral blood samples were collected in order to compare miR-208 expression levels between the cardiac hypertrophy patients and healthy individuals. In addition, an in vitro cellular model of cardiac hypertrophy was established to determine the association between miR-208 and SOX6 expression. Rat cardiomyocytes were treated with phenylephrine (PE) to induce cardiac hypertrophy. Some of the hypertrophic cardiomyocytes were subsequently transfected with antagomiR-208, an miR-208 antagonist, in order to determine the effects of silencing miR-208 expression. Differences between healthy and hypertrophic cardiomyocyte morphology were evaluated using immunofluorescence staining. The mRNA expression levels of the hypertrophy-associated genes β-myosin heavy chain, α-sarcomeric actin and atrial natriuretic peptide were determined using quantitative polymerase chain reaction (qPCR). The mRNA and protein expression levels of miR-208 and SOX6 in peripheral blood and cardiomyocytes were detected using qPCR and western blot analysis, respectively. The expression levels of miR-208 were significantly increased in the peripheral blood of patients with left ventricular hypertrophy (P<0.05). PE-stimulated cardiomyocytes were significantly increased in size compared with normal cardiomyocytes. In the PE-stimulated cardiomyocytes, miR-208 expression levels were significantly increased (P<0.05). However, SOX6 expression levels were significantly decreased compared with those in normal cardiomyocytes (P<0.05). Following transfection with antagomiR-208, SOX6 expression levels in the PE-stimulated cardiomyocytes significantly increased, while the total mRNA and protein expression levels of hypertrophy-associated genes significantly decreased (P<0.05). miR-208 expression levels are increased in the peripheral blood of patients with cardiac hypertrophy. Therefore, the results of this study suggest that the expression levels of miR-208 are associated with cardiac hypertrophy by the negative regulation of SOX6.
The most stable structures and electronic properties of TmSi (n = 3-10) clusters and their anions have been probed by using the ABCluster global search technique combined with the PBE, TPSSh, and B3LYP density functional methods. The results revealed that the most stable structures of neutral TmSi and their anions can be regarded as substituting a Si atom of the ground state structure of Si with a Tm atom. The reliable AEAs, VDEs and simulated PES of TmSi (n = 3-10) are presented. Calculations of HOMO-LUMO gap revealed that introducing Tm atom to Si cluster can improve photochemical reactivity of the cluster. The NPA analyses indicated that the 4f electron of Tm atom in TmSi (n = 3-10) and their anions do not participate in bonding. The total magnetic moments of TmSi are mainly provided by the 4f electrons of Tm atom. The dissociation energy of Tm atom from the most stable structure of TmSi and their anions has been calculated to examine relative stability.
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