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The infection rate of Epstein-Barr virus(EBV)in the population is as high as 95%.It is the first carcinogenic virus found by human beings.Children infected with EBV often cause non-neoplastic diseases, including infectious mononucleosis, chronic active EBV infection and hemophagocytic lymphohistiocytosis.Most of the diseases related to non-neoplastic EBV infection in children are self-limited diseases, and a few of them are complicated with serious complications or develop into neoplastic diseases.The pathogenesis of this kind of disease is complex, the condition is varied, and some children with gene defects have a poor prognosis.Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is an effective treatment for refractory children.At the same time, the condition of some critically ill children is progressing rapidly, so it is very important to create the opportunity of allo-HSCT for such children.
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FimA has been characterized as an important virulence factor for Porphyromonas gingivalis (Pg). These structures play a major role in the mechanisms of adhesion and invasion of Pg to host cells, and can induce cellular activation and cytokines release. FimA can also promote biofilm formation and induce immuno-inflammatory response of host cells. Many studies have characterized FimA to be associated with periodontitis and cardiovascular disease. Pg strains are classified into six types based on divergent nucleotide sequences of the fimA gene (types Ⅰ、Ⅰb、Ⅱ、Ⅲ、Ⅳ andⅤ). The expression of fimbriae is regulated by the fimA gene, which may be the key factor that leads to virulence diversities of Pg, At present, the research on the pathogenesis of FimA mainly focuses on periodontitis and atherosclerosis, which is of great significance for the prevention and treatment of diseases. This paper reviewed the pathogenic effect of FimA in the development of above mentioned two diseases and its application in the prevention.
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Objective:To explore the influence of treatment with HMG-CoA reductase inhibitors ( sta-tins) on the expression profile of microRNAs ( miRNAs) in the plasma of patients with unstable angina ( UA) .Methods:The Taqman low-density miRNA array ( TLDA) and significance analysis of microar-rays ( SAM) were used to identify distinct miRNA expression profiles in the plasma of UA patients treated with long-term and regular statins ( UA receiving statins , n=6 ) compared with UA patients who had not received statins therapy before ( UA received no statins , n=6 ) .These differentially expressed miRNAs discovered in the profiling were further validated by real-time PCR in another 20 controls with non-cardiac chest pain , 26 UA patients received no statins , and 19 UA patients received statins .Results: By using TLDA and SAM , significantly decreased expression levels of 21 miRNAs were observed in the UA pa-tients receiving statins compared with those who received no statins ( fold change >3 and false discovery rate<0 .0001%) .The unsupervised hierarchical clustering based on miRNA expression clearly separa-ted the UA patients receiving statins from those who received no statins .Consistent with the profiling da-ta, the levels of 5 inflammation-associated miRNAs (miR-106b, miR-21, miR-25, miR-451, and miR-92a) were down regulated (P<0.05) in the UA patients receiving statins compared with those who re-ceived no statins.Conclusion: A group of inflammation-associated miRNAs, consisting of miR-106b, miR-21, miR-25, miR-451, and miR-92a, could be decreased by treatment with statins and may be used as a novel biomarker for effectiveness of statins therapy in patients with UA .
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Objective To study whether miR-106b is involved in endothelial cells-mediated angio-genesis .Methods miR-106b cultured and transfected with endothelial cells was divided into miR-106b group ,blank control group and positive control group .RNA was extracted from miR-106b .The transfection efficiency was confirmed by inverse transcription .Endothelial cell tubes formed in matrigel were observed .Apoptosis of transfected miR-106b was assayed by TUNEL assay .Target genes of miR-106b were detected .Expressions of miR-106b and candidate genes were detected by RT-PCR and Western blot ,respectively .Results The number of endothe-lial cell tubes formed in matrigel was significantly less in miR-106b group than in blank control group and positive control group .The ratio of formed tubes ,signal transduction and mRNA ex-pression level were significantly lower in miR-106b group than in positive control group ( P0 .05) .Conclusion miR-106b inhibits endothelial cells-medi-ated angiogenesis by down-regulating the signal transduction and STAT 3 ,which is not directly re-lated with VEGFA .
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<p><b>BACKGROUND</b>Endothelial cells derived microRNAs can be detected in plasma and serum and there is evidence that inflammatory disease states may affect the levels of circulating microRNAs. However, there is no direct proof that inflammation induces endothelial cells to release microRNAs into circulation. This study aimed to explore whether inflammation could induce endothelial cells to release microRNAs into circulation and to investigate whether these released microRNAs derived from endothelial cells were transported in microparticles.</p><p><b>METHODS</b>Microparticles were isolated from human atherosclerotic plaques with an active inflammatory phenotype and normal vascular tissue. Flow cytometry and real-time PCR were used to detect the levels of microparticles and microRNAs. Human umbilical vein endothelial cells (HUVEC) was treated with tumour necrosis factor a (TNF-α, 10 ng/ml) for 24 hours, and then HUVEC and the culture medium were respectively collected.</p><p><b>RESULTS</b>By comparing microparticles isolated from human atherosclerotic plaques with an active inflammatory phenotype (n = 9) and those from normal vascular tissues (n = 9), we found levels of annexin V(+) microparticles and annexin V(+) CD144(+) microparticles were significantly increased in plaques and angiogenesis associated microRNAs (106b, 25, 92a and 21) were also significantly increased in microparticles from plaques. After exposure to TNF-α at a concentration of 10 ng/ml (TNF-α group, n = 3) or DMEM (control group, n = 3) for 24 hours, counts of microparticles and expressions of microRNAs 106b, 25, 92a and 21 in microparticles isolated from medium significantly increased. However, there were no differences in the intracellular levels of microRNAs 25, 92a or 21 isolated from HUVEC between TNF-α group and control group, while microRNA 106b decreased in TNF-α group.</p><p><b>CONCLUSION</b>Inflammation could induce endothelial cells to release angiogenesis associated microRNAs into circulation, causing higher levels of circulating endothelial cells derived microRNAs in atherosclerosis.</p>
Subject(s)
Humans , Annexin A5 , Metabolism , Cell-Derived Microparticles , Metabolism , Cells, Cultured , Gene Expression Regulation , Human Umbilical Vein Endothelial Cells , Metabolism , Inflammation , Genetics , Allergy and Immunology , MicroRNAs , Genetics , Metabolism , Real-Time Polymerase Chain Reaction , Tumor Necrosis Factor-alpha , PharmacologyABSTRACT
Objective To determine whether acute withdrawal of simvastatin treatment in healthy normocholesterolemic men impairs the brachial artery endothelial function.Methods The study was performed on 16 healthy,young male subjects with desirable serum levels of cholesterol.They were administered with simvastatin(20 mg/d)for 4 weeks.Endothelial dependent flow-mediated vasodilation (FMD)was assessed on the brachial artery using high-resolution ultrasound,and fasting serum lipid profiles as well as vasoactive substances[NO,endothelin(ET)and 6-keto-PGF1α] were measured.The parameters mentioned above were obtained at indicated time points before and after simvastatin treatment. Resuts Simvastatin treatment for 4 weeks significantly improved FMD and reduced low density LDL-C and total TC levels.Withdrawal of simvastatin.however,resulted in dramatic impairment of endothelium- dependent relaxation on the first day after with drawal [(4.6±0.48)%and(10.9±0.89)%,P＜0.01 ], Furthermore,FMD decreased significantly as compared with baseline level[(4.6±0.48)%vs(6.4±0.47)%,P＜<0.01].Serum NO level varied according to the change of endothelial-dependent relaxation(γ=0.496,P＜0.01).After discontinuing simvastatin therapy,plasma ET increased and plasma 6-keto-PGF1α decreased progressively.In addition,serum TC and LDL-C were not significantly modified during the initial 2 days.No correlation was shown between FMD and serum LDL-C level(γ=-0.172,P=0.101). Conclusions Withdrawal of simvastatin not only abrogates the beneficial effect on endothelial function of healthy normocholesterolemic men rapidly,but also induces further endothelial deterioration as compared with pretreatment status.This adverse effect is independent of serum cholesterol.The underlying mechanism may be related to the suppression of endothelial NO production.
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Objective:To investigate the effect of acute mixed hyperlipidemia on acute myocardial infarct size and the potential mechanism.Methods: Fifty-three Sprague-Dawley(SD) rats were divided into three groups: the control group(n=15) was injected with 1.0 mL 0.9% sodium chloride,the low dose group(n=17) and high dose group(n=21) were injected with 0.5 mL and 1.0 mL 10% Triton WR-1339 solution respectively.Acute myocardial infarction was produced 24 hours after the injection.Serum lipid and the activity of lipoprotein-associated phospholipase A2(Lp-PLA2) were measured before and 24 hours after the injection.Rats were killed 24 hours after ligation and their hearts were excised to evaluate the myocardial infarct size.Results: Serum total cholesterol(TC) and trig1ycerides(TG) concentrations were(6.92?1.48) mmol/L and(11.76?2.76) mmol/L in the low dose group 24 hours after injection,(11.91?0.87) mmol/L and(33.97?5.85) mmol/L in the high dose group,and both increased significantly compared with the baseline.Also serum low density lipoprotein cholesterol(LDL-C) concentration increased(P0.05).Myocardial infarct size was significantly(P
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Objective:To evaluate the efficacy and safety of micronised fenofibrate on lipid and uric acid metabolism in patients with hyperlipidemia.Methods: A total of 116 patients with hypertriglyceridemia and hyperuricemia received 200 mg micronised fenofibrate for 4 weeks.Physical and laboratory investigations of lipid profiles,serum uric acid,and 24 h urine uric acid,for adverse effects were assessed.Results:(1) Serum triglyceride(TG) was significantly reduced by 51%,whilst high density lipoprotein cholesterol(HDL-C) increased 24% after 4-week fenofibrate treatment.Moreover,serum total cholesterol(TC) and low density lipoprotein cholesterol(LDL-C) were reduced by 10% and 12%,respectively.(2) Serum uric acid levels were significantly reduced by 28.3% [from(462.8?73.5) ?mol/L to(320.1?83.0) ?mol/L] after fenofibrate treatment,independent of baseline uric acid le-vels.There was no difference in serum uric acid changes between male gender and female gender(29.8% and 25.1%,respectively).(3) Urine uric acid levels were increased by 36.0% [from(2 874.2?503.4) ?mol/L to(3 604.2?769.7) ?mol/L].The urine uric acid changes were 41.1% in male gender group and 33.4% in female gender group.The uric acid clearance/creatinin clearance ratio was increased in all cases after treatment.Conclusion: Micronised fenofibrate treatment could significantly improve lipid and uric acid metabolism in patients with hypertriglyceridemia and hyperuricemia,and is ge-nerally safe and well tolerated.The anti-hyperuricemic effect of fenofibrate is a result of increasing the urinary excertion of uric acid,independent of baseline level and gender.