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BACKGROUND@#Mesenchymal stem cell (MSC)-based cell transplantation is an effective means of treating chronic liver injury, fibrosis and end-stage liver disease. However, extensive studies have found that only a small number of transplanted cells migrate to the site of injury or lesion, and repair efficacy is very limited. @*METHODS@#Bone marrow-derived MSCs (BM-MSCs) were generated that overexpressed the erythropoietin (EPO) gene using a lentivirus. Cell Counting Kit-8 was used to detect the viability of BM-MSCs after overexpressing EPO. Cell migration and apoptosis were verified using Boyden chamber and flow cytometry, respectively. Finally, the anti-fibrosis efficacy of EPO-MSCs was evaluated in vivo using immunohistochemical analysis. @*RESULTS@#EPO overexpression promoted cell viability and migration of BM-MSCs without inducing apoptosis, and EPO-MSC treatment significantly alleviated liver fibrosis in a carbon tetrachloride (CCl4 ) induced mouse liver fibrosis model. @*CONCLUSION@#EPO-MSCs enhance anti-fibrotic efficacy, with higher cell viability and stronger migration ability compared with treatment with BM-MSCs only. These findings support improving the efficiency of MSCs transplantation as a potential therapeutic strategy for liver fibrosis.
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BACKGROUND@#Mesenchymal stem cell (MSC)-based cell transplantation is an effective means of treating chronic liver injury, fibrosis and end-stage liver disease. However, extensive studies have found that only a small number of transplanted cells migrate to the site of injury or lesion, and repair efficacy is very limited. @*METHODS@#Bone marrow-derived MSCs (BM-MSCs) were generated that overexpressed the erythropoietin (EPO) gene using a lentivirus. Cell Counting Kit-8 was used to detect the viability of BM-MSCs after overexpressing EPO. Cell migration and apoptosis were verified using Boyden chamber and flow cytometry, respectively. Finally, the anti-fibrosis efficacy of EPO-MSCs was evaluated in vivo using immunohistochemical analysis. @*RESULTS@#EPO overexpression promoted cell viability and migration of BM-MSCs without inducing apoptosis, and EPO-MSC treatment significantly alleviated liver fibrosis in a carbon tetrachloride (CCl4 ) induced mouse liver fibrosis model. @*CONCLUSION@#EPO-MSCs enhance anti-fibrotic efficacy, with higher cell viability and stronger migration ability compared with treatment with BM-MSCs only. These findings support improving the efficiency of MSCs transplantation as a potential therapeutic strategy for liver fibrosis.
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Aim To study the therapeutic effect of CpG-ODN, an agonist of Toll-like receptor 9 (TLR9), on hypoxic/ischemic encephapathy in neonatal rats and investigate the mechanisms.Methods Fifty healthy 7-day-old neonatal Wistar rats (in either gender, weighing 12~17g) were randomly divided into sham operation group, HIBD group, and CpG-ODN low group(0.35 mL·kg-1), CpG-ODN middle group(1.40 mL·kg-1), CpG-ODN high group(5.60 mL·kg-1).The neurological function was scored after 48h operation;ten rats of each group was executed respectively and brains tissue was taken;HE staining was used to observe the brain pathological changes.Western blot assay was used to detect the expressions of TLR9 and phosphor-p38 mitogen-activated protein kinases(p-p38 MAPK), and enzyme linked immunosorbent assay (ELISA) method was adopted to detect TNF-α expression.Results The CpG-ODN low, middle group were improved in impairment significantly compared with the HIBD group, and the brain pathological change was lessened, while the CpG-ODN high group was impaired significantly compared with the HIBD group (P<0.05), and brain pathological change was sharpened.Western blot showed the up-regulation in TLR9 and p-p38 MAPK and a significant increase of the expression of TNF-α in the brain tissue in CpG-ODN group with statistical difference in HIBD group and sham operation group(P<0.05).Conclusions The neuro-behavioral score and nervous system function can be improved and the hypoxic/ischemic brain damage can be reduced in neonatal rats in the CpG-ODN low, middle group.The protective mechanisms may be suitably via activating p38 MAPK signaling pathway to promote p38 MAPK phosphory1ation and up-regulation of the expression of TNF-α in the brain tissue of rats.
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Objective To investigate the association of single nucleotide polymorphisms (SNPs) in COX-2 with aspirin resistance in Chinese cerebral infarction patients. Methods A total of 150 Chinese cerebral infarction patients were recruited. Platelet aggregation response was measured by light transmission aggregometry method and four SNPs located in COX2 gene were genotyped by sequencing method. Results Sixty patients of the total were classified as aspirin non-responders. For clinical variables , concentrations of high homocysteine and the frequency of recurrence cerebral infarction were significantly higher in aspirin non-responders when compared with aspirin responders. Univariate analysis of SNPs showed that rs20417 , rs689465 and rs689466 were significantly associated with aspirin resistance. Multivariate analysis indicated that after adjusting other SNPs and clinical risk factors, rs20417 and rs689466 were still significantly associated with aspirin resistance. Conclusions Rs689466 is significantly associated with aspirin resistance in Chinese cerebral infarction patients even after the adjustment of rs20417. By combining rs689466 , rs20417 and other clinical risk factors , we may better classify the aspirin non-responders from aspirin responders.
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Objective To investigate the effect of phosphatidylinesitol-3 kinase/serine threonine kinase (PI3K/Akt) signaling pathway on expression of beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) in the hippocampus neurons of rat brain. Methods Forty SD rats were randomly divided into 4 groups: blank control group, sham-operated group, insulin group and wortmannin group. Insulin or the specific inhibitor of PI3K, wortmannin was injected into hippocampus neurons to activate or inhibit the signaling pathway in insulin group or wortmannin group, respectively. Immunoprecipitation and Western blot were used to analyze the proteins levels of PI3K/Akt and BACE1. Results In insulin treatment group,among the proteins downstream of signaling pathway, expression of Akt increased (0. 952±0.060 vs 0.835±0.029,t=4.9150, P=0.0001), phospho-Akt set473 increased (0.800±0.075 vs 0.657± 0.025,t=4.5598, P=0.0002), phospho-GSK-3α decreased (0.604±0.062 vs 0.726±0.041, t= 3.5871, P=0.0018 ), and the expression of mature BACE1 and β-CTF significantly decreased. In wortmannin group, the expression of Akt and phospho-Akt ser473 were inhibited; phospho-GSK-3α increased ; mature BACEI (1.004±0.096) and β-CTF (1.031±0.048) increased (t=11.5980, P= 0.0000 and t =4.2194, P =0.0004, respectively). Conclusions PI3K/Akt signaling pathway might effect the expression of BACE1, in which impaired signaling pathway may cause the amyloid precursor protein to be easily processed by BACE1, and thus involves the pathology of Alzheimer' s disease.
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OBJECTIVE: To introduce the research progression of fMRI in brain functional localization in China or abroad in the recent 15 years, so as to further comprehend the effect and value of fMRI.DATA SOURCES: A computer-based online search of Medline database was undertaken to identify English articles about fMRI published from 1990 to 2005 with the keywords "functional magnetic resonance imaging (fMRI), brain".STUDY SELECTION: The articles about experimental studies of fMRI articles irrelative to motor function, sensory function, hearing function, visuEnglish title.DATA EXTRACTION: Totally 6 144 relevant articles were collected, 18 articles were involved according to the inclusive criteria, and the others were excluded. cles about sensory function, including 1 about simple tactile stimulation,ry function, including 2 about simple visual stimulation, and 1 about binoction, including about hearing stimulation by various methods, and 1 about comparison between normal and abnormal subjects by the same stimulation.language function, 1 about visual language function, and 1 about listening basic principle.CONCLUSION: fMRI was more accurate, convenient and direct than other methods. It can not only show localization, size and dimension of the activated areas in different cerebral regions, but also show accurate anatomical position. Many aspects still need to be consummated, for example, exploration of the stimulating method, design of advanced hardware, post processing of the image and the effect of visualization. With the development of hardware, software and the endless endeavor of scientists, fMRI dooms to play an important role in illustrating the function of human brain.