objective: To observe the changes of soluble intercellular adhesion molecule-1(sICAM-1) in the serum of patients with acute cerebral infarctlon (ACI) and their clinical significance. Methods: The concen-tration of sIC...objective: To observe the changes of soluble intercellular adhesion molecule-1(sICAM-1) in the serum of patients with acute cerebral infarctlon (ACI) and their clinical significance. Methods: The concen-tration of sICAM-1 in the serum of 91 patients with ACI was determined with ELISA and then the results were compared wlth those of 43 patients with cerebral hemorrhage and 30 healthy individuals. Results: In the 24th hour after infarction. the concentration of sICAMu-1 in the serum was significantly higher in patients with ACI than in patients with cerebral hemorrhage and normal controls (P< 0. 01). In the patients with ACI, the concentration exhibited an decreasing tendency in the period from the 24th hour to the 14th day andwas correlated with the focal size of cerebral infarction. During the first 14 days after infarction, the concen-tration was significantly higher in the patients with the complication of infection than in those without. Con-clusion: sICAM-1 is closely correlated with clinical manifestation of ACI.展开更多
Objective:To explore the relationship of plasma homocysteine(Hcy),soluble intercellular adhesion molecule-1(sICAM-1)and high mobility group box 1 protein(HMGB1)with carotid intima-media thickness(c-IMT)in elderly pati...Objective:To explore the relationship of plasma homocysteine(Hcy),soluble intercellular adhesion molecule-1(sICAM-1)and high mobility group box 1 protein(HMGB1)with carotid intima-media thickness(c-IMT)in elderly patients with type 2 diabetes mellitus.Methods:A total of 100 elderly patients who were diagnosed as type 2 diabetes mellitus in Baogang Hospital of Inner Mongolia from June 2017 to May 2020 were chosen as research objects.According to c-IMT,they were divided into the normal group(n=35),the mild to moderate group(n=41)and the severe group(n=24).The expression levels of plasma Hcy,sICAM-1 and HMGB1 were compared between groups respectively.Pearson’s correlation coefficient was used to analyze the relationship of plasma Hcy,sICAM-1,HMGB1 with c-IMT.Results:The comparison in plasma Hcy,sICAM-1,HMGB1 and c-IMT among the three groups of patients was of statistical significance(p<.05).The results of correlation analysis showed that the expression levels of plasma Hcy,sICAM-1 and HMGB1 were positively correlated with c-IMT in elderly patients with type 2 diabetes mellitus(r=.627,.598,.614;p<.05).Conclusions:The expression levels of plasma Hcy,sICAM-1 and HMGB1 are abnormally increased in elderly patients with type 2 diabetes mellitus,and related to c-IMT,which can provide a strong evidence for clinical diagnosis and treatment by detecting their levels in clinical practice.展开更多
Objective To investigate effects of electroacupuncture （EA） on expression of intercellular adhesion molecule-1 （ICAM-1） in the rat of local cerebral ischemia-reperfusion. Methods Eighty SD rats were randomly divid...Objective To investigate effects of electroacupuncture （EA） on expression of intercellular adhesion molecule-1 （ICAM-1） in the rat of local cerebral ischemia-reperfusion. Methods Eighty SD rats were randomly divided into a normal control group, a sham operation group, a model group and an EA treatment group, 20 rats in each group. The thread-obstruction method was used for preparation of ischemia-reperfusion model. Zea-Longa rating criteria were used for evaluation of nervous function disorder; Immunohistochemical SABC method was used for detection of ICAM-1 expression in the microvascular endothelial cell of the ischemic brain region, and ELISA method for the soluble ICAM-1 （slCAM-1） content in peripheral blood. Re. suits After cerebral ischemia-reperfusion, both ICAM-1 expression level in the microvascular endethelium cell of the ischemic brain region and slCAM-1 content in the peripheral blood significantly increased in the model group as compared with the normal group and the sham operation group （P〈0.01）; After EA treatment, the ICAM-1 expression level in the microvascular endothelial cell of the ischemic brain region and slCAM-1 content in the peripheral blood were significantly down-regulated in the EA treatment group as com- pared with the model group （P〈 0.05）. Conclusion After cerebral ischemia-reperfusion, the microvascular endothelial cell of the ischemic brain region releases ICAM-1, which induces inflammatory injury of cerebral tissues; EA treatment can decease the expression of ICAM-1, so as to prevent the brain from the injury.展开更多
BACKGROUND: Traditional Chinese medicine is a potent agent in the management of clinical and experimental acute pancreatitis (AP), but the molecular mechanism of its the- rapeutic action is unclear. Numerous experimen...BACKGROUND: Traditional Chinese medicine is a potent agent in the management of clinical and experimental acute pancreatitis (AP), but the molecular mechanism of its the- rapeutic action is unclear. Numerous experimental and clinical studies have shown that platelet endothelial cell ad- hesion molecule-1 (PECAM-1) is pivotal to leukocyte re- cruitment, which results in microcirculatory injury during inflammation, but its role in acute pancreatitis is poorly un- derstood. We investigated the effects of a compound of tra- ditional Chinese medicine pancreatitis-1 (TCMP-1) on the changes of platelet endothelial cell adhesion molecule-1 (PECAM-1) expression on polymorphonuclear leukocytes (PMNs) in acute edematous pancreatitis (AEP). METHODS: The model of acute pancreatitis was estab- lished by subcutaneous injection of caerulein, and TCMP-1 treated groups were given TCMP-1 by catheterization from mouth to stomach (20 ml/kg) immediately after first time subcutaneous injection of caerulein. The changes of expres- sion of PECAM-1 on leukocytes from the blood of the splenic vein and inferior vena cava were determined by flow cytometry. RESULTS: In the AEP group, expression of PECAM-1 on PMNs was not significantly different between pancreatic microcirculation and systemic circulation at AEP2h and AEP4h time point. Then from AEP4h time point to AEP8h time point, expression of PECAM-1 was up-regulated in systemic circulation while it was down-regulated in pancre- atic microcirculation and was significantly different be- tween pancreatic microcirculation and systemic circulation at AEP8h time point (P<0.05). In the TCMP-1 treated group, compared with the AEP group, expression of PE-CAM-1 on PMNs decreased in different levels between pan- creatic microcirculation and systemic circulation and was of significant difference at AEP8h time point (P <0.05). CONCLUSION: Inhibition of PECAM-1 expression on PMNs may prevent PMNs from transmigration through the endo- thelium and may be one of the treatment mechanisms of TCMP-1 decoction on AEP.展开更多
AIM: To investigate the changes of platelet endothelial cell adhesion molecule-1 (PECAM-1) expression on polymorphonuclear leukocytes (PMNs) in peripheral circulation and pancreatic microcirculation in cerulein-induce...AIM: To investigate the changes of platelet endothelial cell adhesion molecule-1 (PECAM-1) expression on polymorphonuclear leukocytes (PMNs) in peripheral circulation and pancreatic microcirculation in cerulein-induced acute edematous pancreatitis (AEP).METHODS: Fifty Wistar rats were randomly divided into control group (n=10) and AEP group (n=40). A model of AEP was established by subcutaneous injection of cerulein 5.5 and 7.5 μg/kg at 0 and 1 h after the beginning of experiment respectively. PECAM-1 expression on PMNs from splenic vein and inferior vena cava was determined by RT-PCR at mRNA level and determined by flow cytometry at protein level.RESULTS: In experimental rats, an increased PECAM-1mRNA expression was seen from 4 to 8 h of AEP in peripheral circulation (0.77±0.25%, 0.76±0.28%, 0.89±0.30%,1.00±0.21% ), while in pancreatic microcirculation,expression decreased from 2 h and reached the lowest level at 6 h of AEP (0.78±0.29%, 0.75±0.26%, 0.62±0.28%,0.66±0.20%). There were significant differences at 8-h time point of AEP between peripheral circulation and pancreatic microcirculation (1.00±0.21% vs0.66±0.20%, P＜0.05).Meanwhile,the difference at protein level was also found.CONCLUSION: A reverse expression of PECAM-1 on PMNs was found between peripheral circulation and pancreatic microcirculation, suggesting that inhibition of PECAM-1expression may improve the pathological change of AEP.展开更多
BACKGROUND:Platelet endothelial cell adhesion molecule-1(PECAM-1),also known as CD31,is mainly distributed in vascular endothelial cells.Studies have shown that PECAM-1 is a very significant indicator of angiogenesis,...BACKGROUND:Platelet endothelial cell adhesion molecule-1(PECAM-1),also known as CD31,is mainly distributed in vascular endothelial cells.Studies have shown that PECAM-1 is a very significant indicator of angiogenesis,and has been used as an indicator for vascular endothelial cells.The present study aimed to explore the relationship between the expression of PECAM-1 and the degree of acute lung injury(ALI) and fibrosis in paraquat(PQ) induced lung injury in rabbits.METHODS:Thirty-six adult New Zealand rabbits were randomly divided into three groups(12rabbits in each group) according to PQ dosage:8 mg/kg(group A),16 mg/kg(group B),and 32 mg/kg(group C).After PQ infusion,the rabbits were monitored for 7 days and then euthanized.The lungs were removed for histological evaluation.Masson staining was used to determine the degree of lung fibrosis(LF),and semi-quantitative immune-histochemistry analysis to determine the expression of PECAM-1.Pearson's product-moment correlation analysis was performed to evaluate the relationship between the expression of PECAM-1 and the extent of lung injuries expressed by ALI score and degree of LF.RESULTS:Rabbits in the three groups showed apparent poisoning.The rabbits survived longer in group A than in groups B and C(6.47±0.99 days vs.6.09±1.04 days vs.4.77±2.04 days)(P<0.05).ALI score was lower in group A than in groups B and C(8.33±1.03 vs.9.83±1.17 vs.11.50±1.38)(P<0.05),and there was statistically significant difference between group B and group C(P=0.03).LF was slighter in group A than in groups B and C(31.09%±2.05%vs.34.37%±1.62%vs.36.54%±0.44%)(P<0.05),and there was statistically significant difference between group B and group C(P=0.026).The PEACAM-1 expression was higher in group A than in groups B and C(20.31%±0.70%vs.19.34%±0.68%vs.18.37%±0.46%)(P<0.05),and there was statistically significant difference between group B and group C(P=0.017).Pearson's correlation analysis showed that the expression of PECAM-1 was negatively correlated to both ALI score(Coe=-0.732,P=0.001)and degree of LF(Coe=-0.779,P<0.001).CONCLUSIONS:The PECAM-1 expression significantly decreases in New Zealand rabbits after PQ poisoning,and the decrease is dose-dependent.The PECAM-1 expression is negatively correlated with ALI score and LF,showing a significant role in the development of lung injuries induced by PQ.展开更多
AIM:To explain the role of Monocyte chemotactic protein-1 (MCP-1) and soluble adhesion molecules in chronic hepatitis C during the treatment of interferon alpha (IFNα) 2 b and ribavirin (RBV). METHODS:Concentrations ...AIM:To explain the role of Monocyte chemotactic protein-1 (MCP-1) and soluble adhesion molecules in chronic hepatitis C during the treatment of interferon alpha (IFNα) 2 b and ribavirin (RBV). METHODS:Concentrations of MCP-1,soluble adhesion molecules intercellular adhesion molecule-1 (sICAM-1),sP- selectin,interleukin (IL) 6,and IL10 in serum were estimated in the group of 40 patients with chronic hepatitis C treated with IFNalpha2 b and RBV in 0,16,32,48 wk of the therapy, RESULTS:In chronic hepatitis C,before and during the treatment,the serum levels of MCP-1 and sP-selectin in responders were similar to those of healthy subjects.In non- responders (NR),MCP-1 increased in the course of IFNc^+RBV treatment,differences were statistically significant as compared to responders.MCP-1 correlated statistically with the activity of periportal inflammation (r=0.35,P<0.05) but not with staging of liver fibrosis,sICAM-1 positively correlated with inflammatory activity and fibrosis in NR.sP-selectin did not correlate with histological findings in the liver.The MCP-1 correlated with the soluble form of sP-selectin concentrations (r= 6,P<0.001) and with IL-10 level in NR (r=0.4,P<0.05).There was no correlation observed between the concentration of MCP-1 and sICAM-1,IL-6 during the treatment. CONCLUSION:MCP-1 concentration may be a prognostic marker of the efficacy of IFN+RBV therapy in patients with chronic hepatitis C.展开更多
Regulation of the adhesion molecules expression by cytokine in vascular endothelial cells was investigated. Human umbilical vein endothelial cells (HUVEC) were stimulated with cytokines, TNF α (1-250 U/ml) or IL 1...Regulation of the adhesion molecules expression by cytokine in vascular endothelial cells was investigated. Human umbilical vein endothelial cells (HUVEC) were stimulated with cytokines, TNF α (1-250 U/ml) or IL 1β (0.1-50 U/ml) for 24 h. HUVEC were also cultured with cytokines, TNF α (100 U/ml) or IL 1β (10 U/ml), for 4-72 h, cell surface expression of adhesion molecules (ICAM 1 and VCAM 1) were detected and quantitated by immunocytochemical methods and computerized imaging analysis technique. Adhesion molecules expression were up regulated by TNF α, IL 1β in a concentration and time dependent manner. Some significant differences were observed between the effects of cytokines on the ICAM 1 and on VCAM 1 expression. Cytokines might directly induce the expression of ICAM 1 and VCAM 1 in vascular endothelial cells. Our observations indicate differential functions of the two adhesion molecules during the evolution of inflammatory responses in stroke.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is associated with obesity,insulin resistance and dyslipidaemia and currently is estimated to affect up to a third of all individuals in developed countries.Current s...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is associated with obesity,insulin resistance and dyslipidaemia and currently is estimated to affect up to a third of all individuals in developed countries.Current standard of care for patients varies according to disease stage,but includes lifestyle interventions common insulin sensitizers,antioxidants and lipid modifiers.However,to date specific therapies have shown little histological or fibrosis stage improvement in large clinical trials,and there is still no licensed therapy for NAFLD.Given the high prevalence,limited treatment options and significant screening costs for the general population,new treatments are urgently required.AIM To assess the potential for inhibition of the amine oxidase enzyme vascular adhesion protein-1(VAP-1)to modify hepatic lipid accumulation in NAFLD.METHODS We have used immunochemical and qPCR analysis to document expression of VAP-1 and key functional proteins and transporters across the NAFLD spectrum.We then utilised hepatocytes in culture and human precision cut liver slices in concert with selective enzyme activity inhibitors to test the effects of activating the semicarbazide-sensitive amine oxidase activity of VAP-1 on hepatic lipid uptake and triglyceride export.A murine model of NAFLD was also used to determine the consequences of VAP-1 knockout and gene expression arrays were used to quantify the effects of VAP-1 activity on key lipid modifying and proinflammatory gene expression.RESULTS We confirmed that increasing severity of NAFLD and progression to cirrhosis was associated with a significant increase in hepatocellular VAP-1 expression.Hepatocytes in vitro exposed to recombinant VAP-1 and its substrate methylamine showed increased lipid accumulation as determined by quantification of Oil Red O uptake.This was recapitulated using hydrogen peroxide,and lipid accumulation was accompanied by changes in expression of the lipid transporter molecules FABP3,FATP6,insulin receptor subunits and PPARα.Human liver tissue exposed to recombinant VAP-1 or substrates for endo/exogenous VAP-1 produced less triglyceride than untreated tissue and demonstrated an increase in steatosis.This response could be inhibited by using bromoethylamine to inhibit the SSAO activity of VAP-1,and mice deficient in VAP-1/AOC3 also demonstrated reduced steatosis on high fat diet.Exposure of human liver tissue to methylamine to activate VAP-1 resulted in increased expression of FABP2 and 4,FATP3-5,caveolin-1,VLDLR,PPARGC1 and genes associated with the inflammatory response.CONCLUSION Our data confirm that the elevations in hepatic VAP-1 expression reported in nonalcoholic steatohepatitis can contribute to steatosis,metabolic disturbance and inflammation.This suggests that targeting the semicarbazide sensitive amine oxidase capacity of VAP-1 may represent a useful adjunct to other therapeutic strategies in NAFLD.展开更多
INTRODUCTIONMultiple organ dysfunction syndrome (MODS) isthought to be a frequent consequence of sepsis[1-3].Despite substantial advances in our knowledge and understanding of the basic pathophysiologic mechanisms[4-7...INTRODUCTIONMultiple organ dysfunction syndrome (MODS) isthought to be a frequent consequence of sepsis[1-3].Despite substantial advances in our knowledge and understanding of the basic pathophysiologic mechanisms[4-7], in critically ill patients infections and sepsis are still associated with a high mortality[8,9].展开更多
Pingyangmycin (bleomycin A5 hydrochloride,PYM) is one of the anti-neoplastic agents which have been commonly used to treat venous malformations.However,the underlying mechanism by which PYM treats venous malformations...Pingyangmycin (bleomycin A5 hydrochloride,PYM) is one of the anti-neoplastic agents which have been commonly used to treat venous malformations.However,the underlying mechanism by which PYM treats venous malformations remains poorly understood.It was reported that venous endothelial cells could recruit neutrophils via adhesion molecules (E-selectin,ICAM-1,ICAM-3,VCAM-1) during the acute/chronic inflammation and subsequent histological fibrosis after sclerotherapy with PYM.This study explored if the expression of E-selectin,ICAM-1,ICAM-3 and VCAM-1 in human venous malformation endothelial cells could be affected by PYM.HVMECs were cultured from human venous malformation tissue.Expressions of E-selectin,ICAM-1,ICAM-3 and VCAM-1 on HVMECs in response to PYM were analyzed by cell ELISA.The relative levels of mRNA expression in the cells were semi-quantified.The results showed that PYM up-regulated the expressions of E-selectin,ICAM-3,VCAM-1 and ICAM-1 in both time-and concentration-dependent manner.Our findings suggested that PYM could induce the expression of adhesion molecules in HVMECs,which might be a possible mechanism by which sclerotherapy by intralesional injection of PYM treats venous malformations.展开更多
文摘objective: To observe the changes of soluble intercellular adhesion molecule-1(sICAM-1) in the serum of patients with acute cerebral infarctlon (ACI) and their clinical significance. Methods: The concen-tration of sICAM-1 in the serum of 91 patients with ACI was determined with ELISA and then the results were compared wlth those of 43 patients with cerebral hemorrhage and 30 healthy individuals. Results: In the 24th hour after infarction. the concentration of sICAMu-1 in the serum was significantly higher in patients with ACI than in patients with cerebral hemorrhage and normal controls (P< 0. 01). In the patients with ACI, the concentration exhibited an decreasing tendency in the period from the 24th hour to the 14th day andwas correlated with the focal size of cerebral infarction. During the first 14 days after infarction, the concen-tration was significantly higher in the patients with the complication of infection than in those without. Con-clusion: sICAM-1 is closely correlated with clinical manifestation of ACI.
文摘Objective:To explore the relationship of plasma homocysteine(Hcy),soluble intercellular adhesion molecule-1(sICAM-1)and high mobility group box 1 protein(HMGB1)with carotid intima-media thickness(c-IMT)in elderly patients with type 2 diabetes mellitus.Methods:A total of 100 elderly patients who were diagnosed as type 2 diabetes mellitus in Baogang Hospital of Inner Mongolia from June 2017 to May 2020 were chosen as research objects.According to c-IMT,they were divided into the normal group(n=35),the mild to moderate group(n=41)and the severe group(n=24).The expression levels of plasma Hcy,sICAM-1 and HMGB1 were compared between groups respectively.Pearson’s correlation coefficient was used to analyze the relationship of plasma Hcy,sICAM-1,HMGB1 with c-IMT.Results:The comparison in plasma Hcy,sICAM-1,HMGB1 and c-IMT among the three groups of patients was of statistical significance(p<.05).The results of correlation analysis showed that the expression levels of plasma Hcy,sICAM-1 and HMGB1 were positively correlated with c-IMT in elderly patients with type 2 diabetes mellitus(r=.627,.598,.614;p<.05).Conclusions:The expression levels of plasma Hcy,sICAM-1 and HMGB1 are abnormally increased in elderly patients with type 2 diabetes mellitus,and related to c-IMT,which can provide a strong evidence for clinical diagnosis and treatment by detecting their levels in clinical practice.
文摘Objective To investigate effects of electroacupuncture （EA） on expression of intercellular adhesion molecule-1 （ICAM-1） in the rat of local cerebral ischemia-reperfusion. Methods Eighty SD rats were randomly divided into a normal control group, a sham operation group, a model group and an EA treatment group, 20 rats in each group. The thread-obstruction method was used for preparation of ischemia-reperfusion model. Zea-Longa rating criteria were used for evaluation of nervous function disorder; Immunohistochemical SABC method was used for detection of ICAM-1 expression in the microvascular endothelial cell of the ischemic brain region, and ELISA method for the soluble ICAM-1 （slCAM-1） content in peripheral blood. Re. suits After cerebral ischemia-reperfusion, both ICAM-1 expression level in the microvascular endethelium cell of the ischemic brain region and slCAM-1 content in the peripheral blood significantly increased in the model group as compared with the normal group and the sham operation group （P〈0.01）; After EA treatment, the ICAM-1 expression level in the microvascular endothelial cell of the ischemic brain region and slCAM-1 content in the peripheral blood were significantly down-regulated in the EA treatment group as com- pared with the model group （P〈 0.05）. Conclusion After cerebral ischemia-reperfusion, the microvascular endothelial cell of the ischemic brain region releases ICAM-1, which induces inflammatory injury of cerebral tissues; EA treatment can decease the expression of ICAM-1, so as to prevent the brain from the injury.
基金This work was supported by the grants from the National Natural ScienceFoundation of China (No. 39770722 and 39925032).
文摘BACKGROUND: Traditional Chinese medicine is a potent agent in the management of clinical and experimental acute pancreatitis (AP), but the molecular mechanism of its the- rapeutic action is unclear. Numerous experimental and clinical studies have shown that platelet endothelial cell ad- hesion molecule-1 (PECAM-1) is pivotal to leukocyte re- cruitment, which results in microcirculatory injury during inflammation, but its role in acute pancreatitis is poorly un- derstood. We investigated the effects of a compound of tra- ditional Chinese medicine pancreatitis-1 (TCMP-1) on the changes of platelet endothelial cell adhesion molecule-1 (PECAM-1) expression on polymorphonuclear leukocytes (PMNs) in acute edematous pancreatitis (AEP). METHODS: The model of acute pancreatitis was estab- lished by subcutaneous injection of caerulein, and TCMP-1 treated groups were given TCMP-1 by catheterization from mouth to stomach (20 ml/kg) immediately after first time subcutaneous injection of caerulein. The changes of expres- sion of PECAM-1 on leukocytes from the blood of the splenic vein and inferior vena cava were determined by flow cytometry. RESULTS: In the AEP group, expression of PECAM-1 on PMNs was not significantly different between pancreatic microcirculation and systemic circulation at AEP2h and AEP4h time point. Then from AEP4h time point to AEP8h time point, expression of PECAM-1 was up-regulated in systemic circulation while it was down-regulated in pancre- atic microcirculation and was significantly different be- tween pancreatic microcirculation and systemic circulation at AEP8h time point (P<0.05). In the TCMP-1 treated group, compared with the AEP group, expression of PE-CAM-1 on PMNs decreased in different levels between pan- creatic microcirculation and systemic circulation and was of significant difference at AEP8h time point (P <0.05). CONCLUSION: Inhibition of PECAM-1 expression on PMNs may prevent PMNs from transmigration through the endo- thelium and may be one of the treatment mechanisms of TCMP-1 decoction on AEP.
基金Supported by National Natural Science Foundation of China, No.39925032
文摘AIM: To investigate the changes of platelet endothelial cell adhesion molecule-1 (PECAM-1) expression on polymorphonuclear leukocytes (PMNs) in peripheral circulation and pancreatic microcirculation in cerulein-induced acute edematous pancreatitis (AEP).METHODS: Fifty Wistar rats were randomly divided into control group (n=10) and AEP group (n=40). A model of AEP was established by subcutaneous injection of cerulein 5.5 and 7.5 μg/kg at 0 and 1 h after the beginning of experiment respectively. PECAM-1 expression on PMNs from splenic vein and inferior vena cava was determined by RT-PCR at mRNA level and determined by flow cytometry at protein level.RESULTS: In experimental rats, an increased PECAM-1mRNA expression was seen from 4 to 8 h of AEP in peripheral circulation (0.77±0.25%, 0.76±0.28%, 0.89±0.30%,1.00±0.21% ), while in pancreatic microcirculation,expression decreased from 2 h and reached the lowest level at 6 h of AEP (0.78±0.29%, 0.75±0.26%, 0.62±0.28%,0.66±0.20%). There were significant differences at 8-h time point of AEP between peripheral circulation and pancreatic microcirculation (1.00±0.21% vs0.66±0.20%, P＜0.05).Meanwhile,the difference at protein level was also found.CONCLUSION: A reverse expression of PECAM-1 on PMNs was found between peripheral circulation and pancreatic microcirculation, suggesting that inhibition of PECAM-1expression may improve the pathological change of AEP.
基金supported by grants from Guangdong Medical Research Fund(2010501)Guangzhou Pharmaceutical Health Science Fund(2009-YB-111)
文摘BACKGROUND:Platelet endothelial cell adhesion molecule-1(PECAM-1),also known as CD31,is mainly distributed in vascular endothelial cells.Studies have shown that PECAM-1 is a very significant indicator of angiogenesis,and has been used as an indicator for vascular endothelial cells.The present study aimed to explore the relationship between the expression of PECAM-1 and the degree of acute lung injury(ALI) and fibrosis in paraquat(PQ) induced lung injury in rabbits.METHODS:Thirty-six adult New Zealand rabbits were randomly divided into three groups(12rabbits in each group) according to PQ dosage:8 mg/kg(group A),16 mg/kg(group B),and 32 mg/kg(group C).After PQ infusion,the rabbits were monitored for 7 days and then euthanized.The lungs were removed for histological evaluation.Masson staining was used to determine the degree of lung fibrosis(LF),and semi-quantitative immune-histochemistry analysis to determine the expression of PECAM-1.Pearson's product-moment correlation analysis was performed to evaluate the relationship between the expression of PECAM-1 and the extent of lung injuries expressed by ALI score and degree of LF.RESULTS:Rabbits in the three groups showed apparent poisoning.The rabbits survived longer in group A than in groups B and C(6.47±0.99 days vs.6.09±1.04 days vs.4.77±2.04 days)(P<0.05).ALI score was lower in group A than in groups B and C(8.33±1.03 vs.9.83±1.17 vs.11.50±1.38)(P<0.05),and there was statistically significant difference between group B and group C(P=0.03).LF was slighter in group A than in groups B and C(31.09%±2.05%vs.34.37%±1.62%vs.36.54%±0.44%)(P<0.05),and there was statistically significant difference between group B and group C(P=0.026).The PEACAM-1 expression was higher in group A than in groups B and C(20.31%±0.70%vs.19.34%±0.68%vs.18.37%±0.46%)(P<0.05),and there was statistically significant difference between group B and group C(P=0.017).Pearson's correlation analysis showed that the expression of PECAM-1 was negatively correlated to both ALI score(Coe=-0.732,P=0.001)and degree of LF(Coe=-0.779,P<0.001).CONCLUSIONS:The PECAM-1 expression significantly decreases in New Zealand rabbits after PQ poisoning,and the decrease is dose-dependent.The PECAM-1 expression is negatively correlated with ALI score and LF,showing a significant role in the development of lung injuries induced by PQ.
文摘AIM:To explain the role of Monocyte chemotactic protein-1 (MCP-1) and soluble adhesion molecules in chronic hepatitis C during the treatment of interferon alpha (IFNα) 2 b and ribavirin (RBV). METHODS:Concentrations of MCP-1,soluble adhesion molecules intercellular adhesion molecule-1 (sICAM-1),sP- selectin,interleukin (IL) 6,and IL10 in serum were estimated in the group of 40 patients with chronic hepatitis C treated with IFNalpha2 b and RBV in 0,16,32,48 wk of the therapy, RESULTS:In chronic hepatitis C,before and during the treatment,the serum levels of MCP-1 and sP-selectin in responders were similar to those of healthy subjects.In non- responders (NR),MCP-1 increased in the course of IFNc^+RBV treatment,differences were statistically significant as compared to responders.MCP-1 correlated statistically with the activity of periportal inflammation (r=0.35,P<0.05) but not with staging of liver fibrosis,sICAM-1 positively correlated with inflammatory activity and fibrosis in NR.sP-selectin did not correlate with histological findings in the liver.The MCP-1 correlated with the soluble form of sP-selectin concentrations (r= 6,P<0.001) and with IL-10 level in NR (r=0.4,P<0.05).There was no correlation observed between the concentration of MCP-1 and sICAM-1,IL-6 during the treatment. CONCLUSION:MCP-1 concentration may be a prognostic marker of the efficacy of IFN+RBV therapy in patients with chronic hepatitis C.
文摘Regulation of the adhesion molecules expression by cytokine in vascular endothelial cells was investigated. Human umbilical vein endothelial cells (HUVEC) were stimulated with cytokines, TNF α (1-250 U/ml) or IL 1β (0.1-50 U/ml) for 24 h. HUVEC were also cultured with cytokines, TNF α (100 U/ml) or IL 1β (10 U/ml), for 4-72 h, cell surface expression of adhesion molecules (ICAM 1 and VCAM 1) were detected and quantitated by immunocytochemical methods and computerized imaging analysis technique. Adhesion molecules expression were up regulated by TNF α, IL 1β in a concentration and time dependent manner. Some significant differences were observed between the effects of cytokines on the ICAM 1 and on VCAM 1 expression. Cytokines might directly induce the expression of ICAM 1 and VCAM 1 in vascular endothelial cells. Our observations indicate differential functions of the two adhesion molecules during the evolution of inflammatory responses in stroke.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is associated with obesity,insulin resistance and dyslipidaemia and currently is estimated to affect up to a third of all individuals in developed countries.Current standard of care for patients varies according to disease stage,but includes lifestyle interventions common insulin sensitizers,antioxidants and lipid modifiers.However,to date specific therapies have shown little histological or fibrosis stage improvement in large clinical trials,and there is still no licensed therapy for NAFLD.Given the high prevalence,limited treatment options and significant screening costs for the general population,new treatments are urgently required.AIM To assess the potential for inhibition of the amine oxidase enzyme vascular adhesion protein-1(VAP-1)to modify hepatic lipid accumulation in NAFLD.METHODS We have used immunochemical and qPCR analysis to document expression of VAP-1 and key functional proteins and transporters across the NAFLD spectrum.We then utilised hepatocytes in culture and human precision cut liver slices in concert with selective enzyme activity inhibitors to test the effects of activating the semicarbazide-sensitive amine oxidase activity of VAP-1 on hepatic lipid uptake and triglyceride export.A murine model of NAFLD was also used to determine the consequences of VAP-1 knockout and gene expression arrays were used to quantify the effects of VAP-1 activity on key lipid modifying and proinflammatory gene expression.RESULTS We confirmed that increasing severity of NAFLD and progression to cirrhosis was associated with a significant increase in hepatocellular VAP-1 expression.Hepatocytes in vitro exposed to recombinant VAP-1 and its substrate methylamine showed increased lipid accumulation as determined by quantification of Oil Red O uptake.This was recapitulated using hydrogen peroxide,and lipid accumulation was accompanied by changes in expression of the lipid transporter molecules FABP3,FATP6,insulin receptor subunits and PPARα.Human liver tissue exposed to recombinant VAP-1 or substrates for endo/exogenous VAP-1 produced less triglyceride than untreated tissue and demonstrated an increase in steatosis.This response could be inhibited by using bromoethylamine to inhibit the SSAO activity of VAP-1,and mice deficient in VAP-1/AOC3 also demonstrated reduced steatosis on high fat diet.Exposure of human liver tissue to methylamine to activate VAP-1 resulted in increased expression of FABP2 and 4,FATP3-5,caveolin-1,VLDLR,PPARGC1 and genes associated with the inflammatory response.CONCLUSION Our data confirm that the elevations in hepatic VAP-1 expression reported in nonalcoholic steatohepatitis can contribute to steatosis,metabolic disturbance and inflammation.This suggests that targeting the semicarbazide sensitive amine oxidase capacity of VAP-1 may represent a useful adjunct to other therapeutic strategies in NAFLD.
基金Supported by the National Natural Science Foundation of China, No. 39870796
文摘INTRODUCTIONMultiple organ dysfunction syndrome (MODS) isthought to be a frequent consequence of sepsis[1-3].Despite substantial advances in our knowledge and understanding of the basic pathophysiologic mechanisms[4-7], in critically ill patients infections and sepsis are still associated with a high mortality[8,9].
基金supported by the Natural Science Foundation of Hubei province,China (No.2010CDB07907)
文摘Pingyangmycin (bleomycin A5 hydrochloride,PYM) is one of the anti-neoplastic agents which have been commonly used to treat venous malformations.However,the underlying mechanism by which PYM treats venous malformations remains poorly understood.It was reported that venous endothelial cells could recruit neutrophils via adhesion molecules (E-selectin,ICAM-1,ICAM-3,VCAM-1) during the acute/chronic inflammation and subsequent histological fibrosis after sclerotherapy with PYM.This study explored if the expression of E-selectin,ICAM-1,ICAM-3 and VCAM-1 in human venous malformation endothelial cells could be affected by PYM.HVMECs were cultured from human venous malformation tissue.Expressions of E-selectin,ICAM-1,ICAM-3 and VCAM-1 on HVMECs in response to PYM were analyzed by cell ELISA.The relative levels of mRNA expression in the cells were semi-quantified.The results showed that PYM up-regulated the expressions of E-selectin,ICAM-3,VCAM-1 and ICAM-1 in both time-and concentration-dependent manner.Our findings suggested that PYM could induce the expression of adhesion molecules in HVMECs,which might be a possible mechanism by which sclerotherapy by intralesional injection of PYM treats venous malformations.
