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Objective Mitochondrial dysfunction, cell energy metabolism, and oxidative stress play important roles in sepsis-induced acute brain injury.This study was to investigate the effects of Xingnaojing Injection (XNJ) on brain mitochondrial oxidative stress in rats with lipopolysaccharide (LPS)-induced sepsis.Methods Totally, 252 male SD rats were randomly divided into a normal control group, 3 LPS-induced sepsis model groups (LPS 6, 24, and 48 h), and 3 XNJ treatment groups (XNJ 6, 24, and 48 h), with 36 in each group.After treatment, the mitochondrial membrane potential (MMP) was monitored by flow cytometry and the levels of manganese superoxide dismutase (Mn-SOD), malondialdehyde (MDA), nitric oxide (NO), and nitric oxide synthase (NOS) were determined by chromatometry.Results The MMP was significantly increased in the XNJ 6 h group as compared with the LPS 6 h group (0.80±0.11 vs 0.54±0.19, P<0.05).In the LPS and XNJ groups, the levels of MDA and NOS reached the peak at 6 hours and then dropped gradually, while those of NO and Mn-SOD rose to the peak at 24 hours followed by a gradual fall.Statistically significant differences were observed in the levels of MDA, NOS and NO between the LPS 6h and XNJ 6 h groups (P<0.05), as well as in those of NOS, NO and Mn-SOD between the LPS 24 h and XNJ 24 h groups (P<0.05).Conclusion Xingnaojing Injection can elevate the level of the brain mitochondrial membrane potential, improve anti-oxidation indexes in the mitochondria, and protect brain mitochondria in sepsis rats.
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Objective To investigate whether single nucleotide polymorphisms(SNPs)in the ABCC4(rs7320375,rs7329490,rs7986087),FCGR2A(rs1801274)and BLK(rs2254546)region could be susceptibility locus for Kawasaki disease(KD)in children from southern China.Methods This study was performed as a case-control study.The samples,92 individuals with KD and 194 healthy controls from southern China,were collected at Guangzhou Women and Childrens′Medical Center from October,2013 to November,2015,and the SNPs were genotyped by using the Sequenom MassArray system.The genotype distribution and allele frequency of the SNPs were analyzed using chi-square test and Fisher′s exact test.Results The genotype distribution of FCGR2A(rs1801274)in patients with KD were as follows: GG 4.3%(4/92),AG 33.7%(31/92),AA 62%(57/92),correspondingly in healthy controls were GG 48.5%(94/194),AG 41.2%(80/194),AA 10.3%(20/194)respectively,and a significant difference was found between KD patients and controls(x2=98.17,P=0.000).A allele frequency of FCGR2A(rs1801274)in KD patients(78.8%,145/184)was higher than that in controls(30.9%,x2=0.120,P=0.000).The genotype distribution of BLK(rs2254546)in patients with KD were as follows: GG 67.4%(62/92),AG 28.3%(26/92),AA 4.3%(4/92),correspondingly in healthy controls were GG 52.1%(101/194),AG 43.8%(85/194),AA 4.1%(8/194)respectively,significant differences were found between KD patients and controls(x2=6.47,P=0.039).G allele frequency of BLK(rs2254546)in KD patients(81.5%,150/184)was higher than that in controls(74.0%,287/388,x2=1.553,P=0.047).Conclusions For the children in southern China,FCGR2A SNPs(rs1801274)may be associated with the susceptibility to KD,and the A allele may increase the risk of KD.BLK SNPs(rs2254546)is also found to be associated with the susceptibility to KD,and the G allele may increase the risk of KD.
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Objective To investigate the dynamics of white blood cell count (WBC),prealbumin(PA),high sensitive C-reactive protein (hs-CRP),and vascular endothelial growth factor (VEGF) in hand-foot-and-mouth disease (HFMD) complicated with or without encephalitis and in vitro inhibitory effects of artesunate on VEGF secretion of mononuclear cells from HFMD patients.Methods Peripheral blood mononuclear cells from healthy control group,HFMD group and HFMD combined with encephalitis group were isolated by Ficoll density gradient centrifugation and treated with different concentrations of artesunate (25,50,100 mg/L).The expression of VEGF in the supernatant was examined by ELISA double antibody sandwich method.The levels of WBC,PA and hs-CRP in the three groups were also detected.Multiple samples were compared by one-way analysis of variance.Multiple comparison was performed by Dunnett T3 test.Correlation of two variables was analyzed by Spearman correlation test.Results There were significant differences in the levels of WBC,hs-CRP,PA and VEGF between the HFMD combined with or without encephalitis group and health control group (F=172.69,366.02,166.32 and 5 941.89,respectively,all P<0.01).There were significant differences in the levels of VEGF secreted by mononuclear cells treated with three different concentrations of artesunate between the HFMD combined with or without encephalitis groups and health control group (F =194.265 and 4 750.69,respectively,both P<0.01).Correlation analysis showed that the VEGF level secretion by mononuclear cells from HFMD patients with or without encephalitis were both negatively correlated with different concentrations of artesunate (r=-0.903 and-0.969,both P<0.01).Conclusions Compared with HFMD without encephalitis,the secretion of VEGF by mononuclear cells,WBC and hs-CRP levels in HFMD complicated with encephalitis group all increase and PA decrease significantly.Artesunate can inhibit the secretion of VEGF by mononuclear cells of patients with hand-foot-and-mouth disease in a dosedependent manner in vitro.
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Objective To learn the gene mutation type and prevalence of thalassemia in the Taishan area and to provide basis for the prevention and treatment of local thalassemia .Methods 1 383 patients who visited the hospital for thalassemia genetic test from January to December 2014 were enrolled for this study .α‐andβ‐genes were determined by using PCR and membrane hybridization methods .Results Of the 1 383 patients ,595 were diagnosed with thalassemia (positive rate was 43 .02% ) ,including 386 cases (27 .91% ) of α‐thalassemia ,183 cases(13 .23% ) of β‐thalassemia and 26 cases(1 .88% ) of αβ‐thalassemia .- -SEA/αα(accounted for 64 .25% ) was the major genotype of α‐thalassemia ,the major genotype of β‐thalassemia wasβ41 -42/β(accounted for 28 .42% ) , and - -SEA/αα,β41 -42/βwas the major genotype of αβ‐thalassemia (accounted for 19 .23% ) .Conclusion Taishan is located in a high risk area of thalassemia ,it is of great significance to perform genetic diagnosis of thalassemia among reproductive population so as to reduce the birth rate of children with thalassemia in the area .
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Uncoupling protein 2 (UCP2) is a proton transporter which presents in the mitochondrial inner membrane.Recently studies found that UCP2 plays important roles in regulation of reactive oxygen species production,maintenance of mitochondrial function,as well as inflammation and blood glucose control.These features have important relevance with the pathophysiologic mechanism of sepsis.
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<p><b>OBJECTIVE</b>To study the effect of uncoupling protein 2 (UCP2)-siRNA on the inflammatory response of rat cardiomyocytes (H9C2) induced by septic serum and to investigate the possible role of UCP2 in the development of septic cardiomyopathy.</p><p><b>METHODS</b>Serum samples were separately collected from normal rats and septic rats. Cultured rat cardiac cells (H9C2) were randomly divided into blank control, normal serum, 10% septic serum, UCP2-siRNA+10% septic serum and negative siRNA+10% septic serum groups. Stimulation with 10% septic serum was performed for 12 hours in relevant groups. The mRNA expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) was measured by RT-PCR. The expression of phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and nuclear factor-kappa B (NF-κB) was measured by Western blot.</p><p><b>RESULTS</b>The expression levels of p-p38 and NF-κB in the UCP2-siRNA+10% septic serum group were significantly higher than in the 10% septic serum group (P<0.05). The UCP2-siRNA+10% septic serum group had a significantly higher TNF-α mRNA expression than the 10% septic serum group (P<0.01), but IL-1β mRNA expression showed no significant difference between the two groups.</p><p><b>CONCLUSIONS</b>UCP2 plays a regulatory role in the activation of p38 MAPK and NF-κB and the expression of downstream inflammatory mediators in H9C2 cells stimulated with septic serum.</p>
Sujets)
Animaux , Mâle , Rats , Cardiomyopathies , Cellules cultivées , Inflammation , Interleukine-1 bêta , Génétique , Canaux ioniques , Génétique , Physiologie , Protéines mitochondriales , Génétique , Physiologie , Myocytes cardiaques , Métabolisme , Facteur de transcription NF-kappa B , Métabolisme , Petit ARN interférent , Génétique , Rat Sprague-Dawley , Sepsie , Sang , Facteur de nécrose tumorale alpha , Génétique , Protéine-2 de découplage , p38 Mitogen-Activated Protein Kinases , MétabolismeRésumé
Sepsis is the systemic inflammatory respond syndrome and autoimmunity injury caused by pathogenic microorganism or any other immunogenicity.Mitochondria,an important organelle,which has an essential role in cellular growth,metabolism,occurrence and development of disease by generating ATP following the oxidative phosphorylation from glycolysis.There had been some progresses on the research of sepsis in several decades.A number of studies had shown that the degree of mitochondrial dysfunction was related to the eventual outcome of sepsis.microRNA are endogenous small noncoding RNAs that post-transcriptionally regulate gene and bio-protein expression,and then adjust mitochondrial oxidative stress,has important influence on the process of sepsis and prognosis.Here,a current review of how microRNA impinge on mitochondrial dysfunction in sepsis was performed.