Abstract： Stem cell paracrine has been considered as the main mechanism to promote infarcted myocardium regeneration and repair of damaged cardiomyocytes. With further research, secreted frizzled-related protein 2 （Sfrp 2） and stem cell paracrine are closely linked to each other. Sfrp 2 can competitively bind to the specific receptor Fz in Wnt signaling pathway, inhibit Wnt signaling pathway to regulates apoptosis, differentiation, and other life processes of stem cells, and therefore becomes a research hotspot in recent years. This review focuses on the mechanism of Sfrp 2/Wnt signal way in stem cell therapy for myocardial infarction.
OBJECTIVE: To study the effect of simvastatin on the expression of bone morphogenetic protein-2 (BMP-2) and alkaline phosphates (ALP) activity in the primary cultured bone marrow stromal cells, and to elucidate the mechanism of the anabolic osteogenetic effect of simvastatin. METHODS: Bone marrow stromal cells in femur and tibia of adult mouse were cultured in vitro. after treated with different concentrations of simvastatin (0, 0.1, 0.2, 0.5 and 1.0 mumol/L) or recombinant human BMP-2 for 72 hours, ALP activity of bone marrow stromal cells was determined. BMP-2 expression of bone marrow stromal cells was analyzed by using immunocytochemistry and Western blotting. RESULTS: After treated with simvastatin for 72 hours, BMP-2 expression increased, while little BMP-2 expression could be observed in the control group. ALP activity also increased in a dose-dependent manner; t-test showed that ALP activity in the group which concentrations of simvastatin were 0.5 mumol/L (t = 2.35, P = 0.041), 1.0 mumol/L (t = 2.348, P = 0.041) had significant difference when compared with control group. CONCLUSION: Simvastatin lead to high expression of BMP-2 in bone marrow stromal cells, via the increased auto- or para-crine of BMP-2, and ALP activity increased. These may be parts of the mechanism on the anabolic osteogenetic effect of simvastatin.
摘要:目的: 探討益活清下法治療重癥急性胰腺炎(severe acute pancreatitis, SAP)對血清單核趨化蛋白1及對器官功能不全的影響。 方法 : 依據納入和排除標準,選取SAP患者24例,按1︰1隨機分為治療組和對照組,在接受相同西醫治療的基礎上,治療組使用中藥“益活清下”法治療,對照組同時接受中藥安慰劑治療。測定患者第0、1、3、5、7天血清MCP1的濃度水平,比較各器官功能不全的發生率與持續時間。 結果 :兩組入院時Rason評分、CT評分、急性生理和慢性健康評價指標Ⅱ評分無統計學差異(〖WTBX〗P gt;005)。對照組第3天MCP1濃度水平明顯高于治療組,差異有統計學意義(〖WTBX〗P lt;005),對照組腸、肝功能不全的發生率高于治療組,持續時間長于治療組,但無統計學差異(〖WTBX〗P gt;005)。 結論 :益活清下法治療重癥急性胰腺炎,可降低患者血清MCP1的水平。Abstract: Objective: To investigated the impact of Yihuo Qingxia method on the serum monocyte chemoattractant protein1 of severe acute pancreatitis (SAP)and on the organs disfunction. Methods : Twentyfour SAP patients who admitted to hospital within 72h after onset were randomized into treatment group (n=12) and control group (n=12). The patients in the treatment group were treated by Yihuo Qingxia method, and the control group were administrated with placebo.The level of the serum mcp1 of the patients on the first,3rd,5th,7thday were measured, as well as the incidence and the duration of disfunction of the organs were compared.〖WTHZ〗Results :There were no statistical significance in admission Rason scores, CT scores, Acute physiology and chronic health evaltionⅡscores(APACHEⅡscores)(Pgt;005). The level of the serum Monocyte chemoattractant protein1 of the treatment group was lower than that of the placebo group generally(Plt;005).At the 3rd day after onset,the serum mcp1 level of the control group was significantly higher than that of the treament group(Plt;005).The incidence of the control group of the intestin disfunction and hepatic inadequacy was obviously higher than those of the treatment group,and the duration of the former was longer than that of the latter,but with no satistical significance. Conclusion :Yihuo Qingxia method can effectively cut down the level of the serum mcp1 of severe pancreatitis patients.
Objective To investigate the effect of lung volume reduction surgery （LVRS） on messenger RNA expression levels of cytoskeletal proteins in diaphragmatic muscle tissues of emphysematous rabbits. Methods A total of 40 rabbits were randomly divided into 4 groups （10 rabbits in each group） ：normal control group, emphysema group, sham operation group and LVRS group. Rabbits in control group were intratracheally administered with 0.9% normal sodium, but those in other groups were intratracheally administered with 0.4% papain at the dose of 0.5 ml/kg and inhaled cigarette smoke to induce emphysema model. Then, rabbits in emphysema group were fed routinely, however, after median sternotomy , bilateral LVRS was performed in LVRS group but not in sham operation group. The mRNA expression levels of titin and nebulin in the diaphragmatic muscles of rabbits in each group were detected by reverse transcription-polymerase chain reaction（RT-PCR）. Results Compared with control group, the mRNA expression levels of titin and nebulin in the rabbit diaphragm of emphysema groups and sham operation group decreased significantly （P〈0.01 ）, so did those in LVRS group （P〈0.05）. But it increased significantly in LVRS group compared with emphysema group and sham operation group （P〈0.05）. Conclusion LVRS can increase the mRNA expression levels of titin and nebulin in diaphragmatic muscle tissues of emphysematous rabbits, which may be the associated mechanisms at the molecular level in restoring the functions of the emphysematous diaphragm by LVRS.
Objective To study the relationship between metalloproteinases (MMPs) and breast cancer. Methods The literature in recent years on the relationship between the expression of MMPs and breast cancer was reviewed. Results The balance between MMPs and tissue inhibitors of metalloproteinases (TIMPs) is keeping normally kept in human body. Many of the studies showed that the expression of MMPs is increased in breast cancer. Conclusion The growth, invasion and metastasis of breast cancer is closely related with the increased expression of MMPs. This suggests that MMPs is a valuable prognostic marker and TIMPs would be a novel drug against cancer.
Objective To study the vascularization of the compositeof bone morphogenetic protein 2 (BMP-2) gene transfected marrow mesenchymal stem cells (MSCs) and biodegradable scaffolds in repairing bone defect. Methods Adenovirus vector carrying BMP-2 (Ad-BMP-2) gene transfected MSCs and gene modified tissue engineered bone was constructed. The 1.5 cm radial defect models were made on 60 rabbits, which were evenly divided into 4 groups randomly(n=15, 30 sides). Different materials were used in 4 groups: Ad-BMP-2 transfected MSCs plus PLA/PCL (group A), AdLacz transfected MSCs plus PLA/PCL (group B), MSCs plus PLA/PCL (group C) and only PLA/PCL scaffolds (group D). The X-ray, capillary vessel ink infusion, histology, TEM, VEGF expression and microvacular density counting(MVD) were made 4, 8, and 12 weeks after operation. Results In group A after 4 weeks, foliated formed bones image was observed in the transplanted bones, new vessels grew into the bones, the pores of scaffolds were filled with cartilage callus, osteoblasts with active function grew around the microvessels, and VEGF expression and the number of microvessels were significantly superior to those of other groups, showing statistically significant difference (Plt;0.01); after 8 weeks, increasingly more new bones grew in the transplanted bones, microvessels distended and connected with each other, cartilage callus changed into trabecular bones; after 12 weeks, lamellar bone became successive, marrow cavity recanalized, microvessels showed orderly longitudinal arrangement. In groups B and C, the capability of bone formation was weak, the regeneration of blood vessels was slow, after 12 weeks, defects were mostly repaired, microvessels grew among the new trabecular bones. In group D, few new vessels were observed at each time, after 12 weeks, broken ends became hardened, the defectedarea was filled with fibrous tissue. Conclusion BMP-2 gene therapy, by -upregulating VEGF expression, indirectly induces vascularization ofgrafts,promotes the living of seed cells, and thus accelerates new bone formation.
Objective To investigate the protective effects of estrogen on rabbit retinal damages induced by chronic ocular hypertension.Methods A total of 18 white New Zealand female rabbits were randomly divided into ovariectomized (OV) group and sham OV (SOV) group. Bilateral ovaries were remove in OV group while only the adipose tissue around ovarian were remove in SOV group. Chronic ocular hypertension was induced by anterior chamber injection of carbomer. Retinal cell apoptosis was measured by terminal deoxynucleotidyl transferasemediated dUTP nick end labeling (TUNEL), the expression of bcl-2, bax were detected by immunohistochemistry. The images were captured under microscope and analyzed with computer-image-analysis system. Results Four, six and eight weeks after ocular hypertension modeling, the OV retinas have less retinal ganglion cells, thinner optic nerve fiber layer and inner nuclear layer and more TUNEL positive cells (t=3.285，4.012，3.624；P＜0.01). The OV retinas also have less bcl-2 expression (t=4.256，3.867，3.459；P＜0.01), more bax positive cells (t=3.211，3.625，3.253；P＜0.01). Bcl-2 expression was negatively correlated with TUNEL positive cells indicating bcl-2 can inhibit apoptosis. Bax expression was positively correlated with TUNEL positive cells indicating bax induce apoptosis.ConclusionEstrogen has a neuroprotection role to rabbit retina under chronic ocular hypertension by reducing apoptosis.
Objective To construct a mammalian vector encoding angiostatin kringle 5 (K5) under the control of αfetoprotein （AFP） enhancer and albumin promoter, and to observe the expression of angiostatin by introducting angiostatin gene into hepatocellular carcinoma cells through gene transfection. Methods Angiostatin cDNA was amplified from normal human eukaryotic cells by using RTPCR. Meanwhile, AFP enhancer and albumin promoter sequences were directed cloned and were inserted into vector pcDNA3.1. The recombinant vector of pcDNA3.1AFABangiostatin K5His was constructed, which contained the angiostatin K5 cDNA sequence that was under the control of the AFP enhancer and promoter. Angiostatin K5 cDNA was introduced into human AFP positive hepatocellular carcinoma cell lines with the transfected cultured cells that were mediated with Lipofectamine 2000. The expression of angiostatin K5 was analyzed by Western blot and the protein was dectected with antiHis antibody. Results The 500base pair of angiostatin K5 was in accordance with the expected sequence and the recombinant vector of pcDNA3.1AFABangiostatin K5His was also confirmed as the anticipated sequence. The expression of angiostatin K5 in AFP positive hepatocellular carcinoma cells was detected both by SDSPAGE and Western blot. Conclusion Efficient construction and expression of angiostatin K5 to AFP positive cells make it possible for antiangiogenesis therapy of human hepatocellular carcinomas, which may provide a promising approach.
ObjectiveTo investigate the expression of CD133 protein in primary lesions of gastric cancer and its clinical significance. MethodsThe expressions of CD133 protein in the primary lesion of tumor and normal gastric mucosa tissues confirmed by using histopathologic examination of 99 patients were detected by immunohistochemical staining. The correlation of CD133 protein expression with the clinicopathologic parameters and features after operation were analyzed. ResultsPositive cells of CD133 protein were localized in the gland parietal and cell membrane surface. The expression of CD133 protein in the cancer and normal gastric mucosa tissues were 29.29% (29/99) and zero, respectively (P=0.000). Expression of CD133 protein in tumor with diameter gt;5 cm was significantly higher than that in the tumor with diameter ≤5 cm (P=0.041). The expression of CD133 protein was correlated with TNM stage (P=0.044), lymph node metastasis (P=0.017), lymphatic vessel invasion (P=0.000), and vascular invasion (P=0.000). Logistic regression analysis revealed that invasion depth of tumor (P=0.011), lymph node metastasis (P=0.043), and TNM stage (P＝0.049) were independent risk factors for CD133 protein expression. Survival time of patients with positive expression of CD133 protein was significantly shorter than that negative expression of CD133 protein (P＝0.046). Cox proportial hazard regression model analysis demonstrated that lymph node metastasis (P=0.042), TNM stage (P=0.046), and positive expression of CD133 protein (P=0.046) were independent risk factors for patients survival. ConclusionThe CD133 protein expression in primary lesions is closely related with development, metastasis, and prognosis of gastric cancer.
ObjectiveTo investigate the effect and significance of early coronary artery bypass graft (CABG) on the expression level of ionophorous protein at infracted border zone (IBZ) in dog with acute myocardial infarction. MethodsThe anterior descending coronary artery of all thirty healthy mongrel dogs were ligated into myocardial infarction model, whose successful criteria was that the regional myocardium supplied by ligated coronary artery became darker. Coronary artery bypass surgery performed at different time points after myocardial infarction (in the 1st week, the 2nd week, the 4th week, the 6th week respectively) was as an experimental group. While myocardial infarction without coronary artery bypass surgery was set up as a control group. Myocardial tissue without ligation of coronary artery was as a normal group. After 8 weeks, myocardial specimens were cut out in the experimental group and the control group. The local expression levels of ionophorous proteins such as Cav1.2, Kv4.3 and KchIP2 mRNA were detected by means of reverse transcription- polymerase chain reaction (RT-PCR) at normal myocardium and IBZ of the experimental group and the control group. ResultsFour dogs in every experimental group and all dogs in the control group survived to the end of the study. Three myocardial ion channel proteins expression in the control group were lower than those of the normal group or the experimental group significantly (P<0.01). Cav1.2 mRNA expression in the experimental group in the 4th week or the 6th week was lower than that in the normal group significantly (P<0.05). Kv4.3 and KchIP2 mRNA expression in the experimental group in the 4th week or the 6th week were lower than those in the normal group and the experimental group significantly in the 1st week or the 2nd week (P<0.05). ConclusionEarly CABG surgery for acute myocardial infarction could lessen the changes of expression level of ionophorous protein at infracted border zone (IBZ) of dog with acute myocardial infarction. Especially, CABG surgery among two weeks could improve expression level of ionophorous protein, and reduce the effect of ischemia for ionophorous protein and myocardial electrophysiology at IBZ.