Effects of Wenxiao Decoction(稳消方) on the Expression of Interleukin-6,Intercellular Adhesion Molecular-1and Monocyte Chemoattractant Protein-1 in Experimental Atherosclerotic Rabbits

Objective： To observe the effects of different doses of Wenxiao Decoction （稳消方） on the expression of interleukin-6 （IL-6）, intercellular adhesion molecule-1 （ICAM-1）, and monocyte chemoattractant protein-1 （MCP-1） in experimental atherosclerotic rabbits and to explore the mechanism by which it alleviates atherosclerosis. Methods： Sixty New Zealand rabbits were randomly divided into six groups： a blank group, a model group, a Simvastatin group, and high-, medium-, and low-dosage Wenxiao Decoction groups. Except for those in the blank group, all rabbits were fed with a high-cholesterol diet. Carotid atherosclerosis was established by balloon-induced carotid artery endothelium injury in conjunction with the high-cholesterol diet. After 8 weeks, all animals were euthanized to evaluate levels of IL-6 and ICAM-1 expressions （by enzyme linked immunosorbent assay） and of MCP-1 （by immunohistochemistry staining）. Results： The expressions of IL-6, ICAM-1, and MCP-1 were significantly increased in all groups except the blank group （P〈0.05）. However, the rabbits in the Wenxiao Decoction groups and the Simvastatin group showed significantly lower levels of IL-6, ICAM-1, and MCP-1 expression than those in the model group （P〈0.05）. The expressions of IL-6, ICAM-1, and MCP-1 in the high- dosage Wenxiao Decoction group and the Simvastatin group were lower than those in the low-dosage Wenxiao Decoction group （P〈0.05）. The expression of MCP-1 in medium-dosage Wenxiao Decoction group was lower than that in the low-dosage group （P〈0.05）. Conclusions： High, medium, and low doses of Wenxiao Decoction can inhibit the expressions of IL-6, ICAM-1, and MCP-1, which may prevent and stabilize atherosclerotic plaques. There may be a direct relationship between dosage and therapeutic efficacy of Wenxiao Decoction.

血清IL-8、ESM-1、VAP-1在慢性阻塞性肺疾病临床诊断及病情评估中的应用

目的探讨慢性阻塞性肺疾病(COPD)患者血清白细胞介素-8(IL-8)、内皮特异性分子-1(ESM-1)、血管黏附蛋白-1(VAP-1)表达水平,分析其与病情程度相关性及其对COPD的诊断价值。方法选取2021年11月至2022年8月郑州大学第一附属医院收治的153例COPD患者为研究对象,其中COPD稳定期42例(设为SCOPD组)、COPD急性加重期111例(设为AECOPD组),同时选取同期于医院体检的健康志愿者51例为对照组。比较两组临床资料及血清IL-8、ESM-1、VAP-1水平。对比不同病情程度患者血清IL-8、ESM-1、VAP-1水平。分析血清各指标与肺功能、生化指标、病情程度相关性。评价血清各指标对SCOPD、AECOPD的诊断价值。结果AECOPD组、SCOPD组血清IL-8、ESM-1、VAP-1水平高于对照组,且AECOPD组高于SCOPD组(P<0.05);IL-8、ESM-1、VAP-1与生化指标、COPD评估测试表(CAT)、病情程度呈正相关,与肺功能呈负相关(P<0.05);血清各指标联合诊断SCOPD与AECOPD的曲线下面积(AUC)大于单独指标诊断(P<0.05)。结论血清IL-8、ESM-1、VAP-1与COPD病情严重程度相关,联合检测其水平对COPD具有一定诊断价值,可能作为疾病诊断、病情评估的重要指标。

升阳除湿防风汤联合化疗治疗晚期胃癌疗效及对患者血清CA72-4、sICAM-1的影响

目的:观察升阳除湿防风汤联合化疗治疗晚期胃癌患者的临床疗效及血清糖类抗原72-4(CA72-4)、可溶性细胞间黏附分子-1(sICAM-1)变化。方法:选择86例晚期胃癌患者,根据治疗方法将其分为两组,各43例,化疗组给予常规化疗治疗,观察组在化疗组基础上给予升阳除湿防风汤治疗,比较两组客观缓解率(ORR)、疾病控制率(DCR)、中医症状积分、血清CA72-4、sICAM-1水平、T淋巴细胞亚群指标(CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))、不良反应总发生率。结果:观察组ORR、DCR均较化疗组更高(P<0.05)。观察组治疗后畏寒肢冷、脘腹胀满、恶心呕吐、神疲乏力积分均较化疗组更低(P<0.05)。观察组治疗后血清CA72-4、sICAM-1水平均较化疗组更低(P<0.05)。观察组治疗后CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)均较化疗组更高(P<0.05),CD8^(+)较化疗组更低(P<0.05)。观察组血小板减少、贫血、脱发、恶心、呕吐总发生率与化疗组比较,差异无统计学意义(P>0.05)。结论:升阳除湿防风汤联合化疗可有效提高晚期胃癌客观缓解率、疾病控制率,缓解脘腹胀满等症状,改善免疫功能,纠正免疫失衡,降低血清CA72-4、sICAM-1表达量,且未增加不良反应发生率。

Clinical significance of serum intercellular adhesion molecule-1 detection in patients with hepatocellular carcinoma

INTRODUCTION Since the late 1980s,studies on the expression ofintercellular adhesion molecule-1(ICAM-1)inpatients with malignancies have demonstrated thatICAM-1 may strongly express in two forms in suchdiseases:membranous one on the surface of tumorcells(membrane-bound ICAM-1)and soluble one incirculation(soluble ICAM-1,sICAM-1).

Luteolin prevents f MLP-induced neutrophils adhesion via suppression of LFA-1 and phosphodiesterase 4 activity

Luteolin is an active ingredient found early from Fofium perillae and Flos Ionicerae, and has a specific inhibition on phosphodiesterase 4 （PDE4） activity in vitro. Researches show luteolin has pharmacological effects of anti-inflammation, anti-anaphylaxis, antitumor, antioxidant, protection of nervous system and so on, and has mainly been used for the treatment of respiratory inflammatory diseases, cancer and cardiovascular disease in clinic. PDE4, specific to hydrolyze cyclic AMP （cAMP）, is considered to be a new anti-inflammatory target due to the decisive role on cAMP signal in inflammatory cells such as neutrophils. In order to explore the anti-inflammatory mechanism, we further studied the effects of luteolin on the activity and expression of PDE4, the expression of lymphocyte function-associated antigen-1 （LFA-1） and macrophage-1 （MAC-l） in neutrophils, and the adhesion of neutrophils and endothelial cells. The results showed that luteolin had a dose-dependent inhibition on both bare PDE4 activity and PDE4 in cultured neutrophils, and had an obviously promotive effect on gene expressions of PDE4A, 4B and 4D in later period. Luteolin had a significant inhibitory effect on neutrophils adhesion and LFA-1 expression in early stage, and had no obvious effect on MAC-1 expression. Therefore, luteolin can inhibit LFA-1 expression of neutrophils, then inhibit the adhesion of neutrophils and endothelial cells, and the mechanism is at least related with the inhibition of PDE4 activity.

The Value of the Soluable Intercellular Adhesion Molecule-1 Levels in Matermal Serum for Determination of Occult Chorioamnionitis in Premature Rupture of Membranes

To compare the diagnostic value of soluble intercellular adhesion molecule 1 (sICAM-1) with that of c-reactive protein (CRP) for detecting chorioamnionitis (CAM) in serum of women with premature rupture of membranes (PROM), 55 pregnant women with PROM, including 18 pregnant women with preterm premature rupture of membranes (PPROM) and 20 normal pregnant women at term (TPROM) were studied. Maternal serum were measured by Sandwish enzyme-linked immunoabsorbent assay (ELISA) for sICAM. CAM was histologically confirmed after delivery. The results revealed that (1) maternal serum levels of sICAM-1 and CRP were significantly higher in women with PROM than those without it; (2) maternal serum levels of sICAM-1 and CRP were significantly higher in women with CAM than those without it; (3) serum levels of sICAM-1 in PPROM women were similar to those in TPROM women, whereas serum levels of CRP in PPROM women were significantly higher than those in TPROM women; (4) the sensitivity, specificity, positive predictive value, negative predictive value, Kappa index and area under receiver operating characteristic (ROC) curve of maternal serum sICAM-1 (cutoff 104.7 ng/ml) and CRP(cutoff 1.03 mg/dl) for diagnosing CAM were 100 %, 91.2 %, 87.5 %, 100 %, 0.20, 0.995 and 81.0 %, 73.5 %, 65.4 %, 86.2 %, 0.13, 0.811, respectively; (5) among the mild histological CAM group, severe histological CAM group and clinical CAM group, the difference in maternal serum levels of sICAM-1 were significantly (P<0.001), with the order of concentration from high level to low level corresponding to the severity of CAM. It is concluded that maternal serum level of ICAM-1 is superior to that of CRP as biomarker for diagnosing intraamniotic infection in pregnant women with PROM.

A clinical evaluation of serum concentrations of intercellular adhesion molecule-1 in patients with gastric cancer

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Different expression pattern of serum soluble intercellular adhesion molecules-1 and neutrophilic expression of CD18 in patients with diabetic retinopathy

AIM: To investigate the levels of serum soluble intercellular adhesion molecules-1 (sICAM-1) and neutrophilic expression of CD18 in patients with various stages of diabetic retinopathy and to determine their different expression pattern in the development of diabetic retinopathy(DR). METHODS: Levels of serum sICAM-1 and CD18 on the surface of neutrophile were measured in 41 DR patients, they were classified in three subgroups according to the stage of retinopathy as determined by fund's ophthalmoscopy; 10 control subjects were also studied. sICAM-1 were measured by enzyme-linked immunosorbent assay and CD18 by flow cytometry. RESULTS: The neutrophilic CD18 expression and serum sICAM-1 level were all significantly elevated in all diabetic subgroups compared to control subjects (P <0.01). The differences of CD18 and sICAM-1 among the diabetic subgroups were significant in CD18 but not in sICAM-1. The progression of retinopathy was associated with an increase both in CD18 and in sICAM-1 levels by simple correlation analysis (beta =0.74, P<0.001; beta =0.38, P<0.01, respectively). But stepwise multiple regression analysis revealed that only CD18 Was independent determinant of retinopathy (beta =1.04, P<0.01). CONCLUSION: Our results confirm the contribution of endothelial and neutrophilic activation in the development of DR as indicated by increased levels of CD18 and sICAM-1. However, a direct implication of CD18 and ICAM-1 in the progression of DR can be supported only in the CD18 but not ICAM-1. CD18 and ICAM-1 may play different role in the development of diabetic retinopathy.

Expression of platelet endothelial cell adhesion molecule-1 between pancreatic microcirculation and peripheral circulation in rats with acute edematous pancreatitis

OBJECTIVE: To study the ehanges of platelet endothelial cell adhesion molecule-1 (PECAM-1) expression on polymorphonuclear leukocytes (PMNs) in peripheral circulation anti pancreatic microcirculation in rats with acute edematous pancreatitis (AEP). METHODS: The model of AEP was established with 50 Wistar rats, and the changes of PECAM-1 expression on PMNs from the splenic vein and inferior vena cava were determined by flow cytometry. RESULTS: PECAM-I expression on PMNs showed no significant difference between pancreatic microcirculation and peripheral circulation at AEP2h and AEP4h time points. From the AEP4h to the AEP8h time point, PECAM-1 expression in peripheral circulation was up-regulated, but PECAM-1 expression in pancreatic microcirculation was down-regulated. PECAM-1 expression had a significant difference between pancreatic microcirculation and peripheral circulation at the AEP8h time point (P<0.05). CONCLUSION: PECAM-1 expression on PMNs is in a converse way between pancreatic microcirculation and peripheral circulation in AEP.

Expression of Metadherin/AEG-1 Gene Is Positively Related to Orientation Chemotaxis and Adhesion of Human Hepatocellular Carcinoma Cell Lines of Different Metastatic Potentials

Metastasis contributes to the poor prognosis of hepatocellular carcinoma （HCC）. However, the mechanism through which a primary HCC cell develops into a metastatic phenotype is not well understood. The purpose of this study was to examine the correlation between metadherin （MTDH）/ astrocyte elevated gene-1 （AEG-1） expression in HCC cell lines of different metastatic potentials and such metastatic phenotypes as orientation chemotaxis and adhesion. MTDH/AEG-1 expression was detected by RT-PCR and western blotting in HCC cell lines （HepG2, Huh7, Sk-HEP-1, MHCC-97H）. Distribution of MTDH/AEG-1 was observed by immunofluorescence staining and confocal laser scanning microscopy. The abilities of orientation chemotaxis and adhesion and the index of interaction between HCC cell lines and microvascular endothelial cell lines （MVECs, including HUVECs and HPMECs） were measured by chemotaxis assay and adhesion assay, respectively. The results showed that MTDH/AEG-1 protein expression was significantly higher in high metastatic potential cancer cell lines （Sk-HEP-1, MHCC-97H ） than in low metastatic potential cell lines （HepG2, Huh7） （P〈0.05）. The MTDH/AEG-1 protein was localized in the perinuclear region of HCC cells. Furthermore, the abilities of orientation chemotaxis and adhesion of HCC cells to HPMECs were increased as compared with those of HCC cells to HUVECs （P〈0.05）. The abilities of orientation chemotaxis and adhesion were much stronger in Sk-HEP-1 and MHCC-97H cells with MTDH/AEG-1 highly expressed than in HepG2 and Huh7 cells with MTDH/AEG-1 lowly expressed （P〈0.05）. These results suggested that the expression of MTDH/AEG-1 gene in HCC cell lines of different metastatic potentials was closely positively related to the abilities of orientation chemotaxis and adhesion of HCC cells. It was deduced that MTDH/AEG-1 might play a pivotal role in the lung-specific metastasis of HCC, which may be medi-ated through orientation chemotaxis and adhesion abilities of HCC cells. MTDH/AEG-1 may serve as a potential therapeutic target for HCC.

Effects of TCMP-1 on the changes of platelet endothelial cell adhesion molecule-1 expression in acute edematous pancreatitis

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.

The relationship between platelet endothelial cell adhesion molecule-1 and paraquat-induced lung injury in rabbits

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.

Focal adhesion kinase-related non-kinase ameliorates liver fibrosis by inhibiting aerobic glycolysis via the FAK/Ras/c-myc/ENO1 pathway

BACKGROUND Hepatic stellate cell(HSC)hyperactivation is a central link in liver fibrosis development.HSCs perform aerobic glycolysis to provide energy for their activation.Focal adhesion kinase(FAK)promotes aerobic glycolysis in cancer cells or fibroblasts,while FAK-related non-kinase(FRNK)inhibits FAK phosphorylation and biological functions.AIM To elucidate the effect of FRNK on liver fibrosis at the level of aerobic glycolytic metabolism in HSCs.METHODS Mouse liver fibrosis models were established by administering CCl4,and the effect of FRNK on the degree of liver fibrosis in the model was evaluated.Transforming growth factor-β1 was used to activate LX-2 cells.Tyrosine phosphorylation at position 397(pY397-FAK)was detected to identify activated FAK,and the expression of the glycolysis-related proteins monocarboxylate transporter 1(MCT-1)and enolase1(ENO1)was assessed.Bioinformatics analysis was performed to predict putative binding sites for c-myc in the ENO1 promoter region,which were validated with chromatin immunoprecipitation(ChIP)and dual luciferase reporter assays.RESULTS The pY397-FAK level was increased in human fibrotic liver tissue.FRNK knockout promoted liver fibrosis in mouse models.It also increased the activation,migration,proliferation and aerobic glycolysis of primary hepatic stellate cells(pHSCs)but inhibited pHSC apoptosis.Nevertheless,opposite trends for these phenomena were observed after exogenous FRNK treatment in LX-2 cells.Mechanistically,the FAK/Ras/c-myc/ENO1 pathway promoted aerobic glycolysis,which was inhibited by exogenous FRNK.CONCLUSION FRNK inhibits aerobic glycolysis in HSCs by inhibiting the FAK/Ras/c-myc/ENO1 pathway,thereby improving liver fibrosis.FRNK might be a potential target for liver fibrosis treatment.

血浆ET-1、D-D、sVCAM-1、ICAM-1水平预测突发性耳聋患者预后的价值

目的探讨血浆内皮素-1(ET-1)、D-二聚体(D-D)、血浆可溶性血管细胞黏附分子-1(sVCAM-1)、细胞间黏附因子-1(ICAM-1)在预测突发性耳聋患者预后方面的价值。方法选取2020年6月—2022年6月上海市杨浦区控江医院收治的老年突发性耳聋患者130例,作为观察组。选取同期检查的健康体检者120例,作为对照组。采用酶联免疫法(ELISA)测量2组患者血浆ET-1、D-D、sVCAM-1、ICAM-1水平。采用受试者工作特征(ROC)曲线评估血浆ET-1、D-D、sVCAM-1、ICAM-1水平预测突发性耳聋患者预后的价值。结果观察组血浆ET-1、D-D、sVCAM-1、ICAM-1水平显著高于对照组,差异有统计学意义(P<0.05)。与高频突发性耳聋相比,低频突发性耳聋患者血浆ET-1、D-D、sVCAM-1、ICAM-1水平更高,差异有统计学意义(P<0.05)。随着突发性耳聋患者听力损失的加重,血浆ET-1、D-D、sVCAM-1、ICAM-1水平显著升高,差异有统计学意义(P<0.05)。与治疗有效组相比,治疗无效组血浆ET-1、D-D、sVCAM-1、ICAM-1水平显著提升,差异有统计学意义(P<0.05)。血浆ET-1、D-D、sVCAM-1和ICAM-1联合应用时预测治疗有效的灵敏度、特异度高于单一指标预测(P<0.05)。结论血浆ET-1、D-D、sVCAM-1、ICAM-1水平升高与突发性耳聋的发生及预后有一定的关系。上述治疗联合检测将有助于临床更好地评价突发性耳聋患者的预后。

In vivo expression of thrombospondin-1 suppresses the formation of peritoneal adhesion in rats

BACKGROUND Formation of intraperitoneal adhesions is one of the major complications after abdominal surgery, which may lead to bowel obstruction. Thrombospondin 1(TSP-1) is an extracellular matrix modulating glycoprotein during tissue regeneration and collagen deposition.AIM To evaluated the therapeutic potential of overexpressed TSP-1 in suppressing pelvic adhesion formations in rat models.METHODS Pelvic adhesion was induced in anesthetized rats by laparotomy cecal abrasion.The animals were randomly assigned to treatment of local application with Seprafilm(an antiadhesive bioresorbable membrane) or adenoviral vectors encoding mouse TSP-1(AdTSP-1) on the surfaces of the injured cecum. The severity of the peritoneal adhesions was evaluated by blinded observers 14 d later.RESULTS Compared with control(no treatment) group, the application of Sperafilm significantly reduced the formation of adhesion band, and local administration of AdTSP-1 on the injured cecum the also attenuated the severity of peritoneal adhesion score. However, systemic delivery of AdTSP-1 did not affect the formation of adhesion.CONCLUSION We conclude that therapeutic approaches in inducing regional overexpression of TSP-1 may serve as alternative treatment strategies for preventing postoperative peritoneal adhesion.

Effect of BRM S1 expression on proliferation, migration and adhesion of mouse forestomach carcinoma

Objective: To discuss the ef ect of BRMS1 on the proliferation, migration and adhesion of mouse forestomach carcinoma(MFC). Methods: The constructed p CMV-myc-BRMS1 recombinant plasmid and blank plasmid were transfected into mouse forestomach carcinoma. MTT method was employed to measure the activity of gastric cancer cell; the scratch assay and Transwell assay to measure the migration and invasion of gastric cancer cell; the adhesion assay to measure the adhesion of gastric cancer cell; while the Western blot assay to measure the expression of The NF-毷B signal pathway, downstream matrix metalloproteinase(MMP-2), MMP-9 and osteopontin and E-cadherin in the gastric cancer cell. Besides, the transplanted animal model of gastric cancer in mice was constructed to measure the size of tumor xenograft. Results: Results of MTT assay showed that, compared with the empty vector control group, the activity of gastric cancer cell was not af ected in the BRMS1 transfection group. The improved expression of BRMS1 could inhibit the adhesion, migration and invasion of gastric cancer cell(P<0.01). Besides, compared with the empty vector control group, the phosphorylation of NF-毷B p65 and I毷Bα was reduced in the BRMS1 transfection group, with the decreased expression of MMP 2, MMP 9 and osteopontin and the increased expression of E-cadherin(P<0.01). Results of animal experiment also showed that the expression of BRMS1 did not af ect the transplanted tumor. Conclusions: The expression of BRMS1 can signii cantly inhibit the adhesion, migration, invasion and metastasis of MCF gastric cancer cell, which is related to The NF-毷B signal pathway.

Mild hypothermia effects on intercellular adhesion molecule-1 and serum interleukin-6 expression in brain tissues of a rat focal ischemia model

BACKGROUND： Previous studies have confirmed the neuroprotective effect of mild hypothermia on ischemic brain injury. OBJECTIVE： To investigate the effects of mild hypothermia on intercellular adhesion molecule-1 expression and serum interleukin-6 levels in ischemic brain tissues of focal brain ischemia rats, and to explore the neuroprotective effects of mild hypothermia on ischemic brain injury. DESIGN, TIME AND SETTING： A randomized, controlled, neurobiological experiment was performed at the Central Laboratory, First Affiliated Hospital, Xinxiang Medical College, China from February to July 2006. MATERIALS： Thirty healthy, adult, Sprague Dawley rats were used to establish middle cerebral artery occlusion models using the suture method, The immunohistochemistry （streptavidin-biotin-peroxidase complex method） kit was purchased from Boster, China. Interleukin-6 radioimmunoassay was supplied by Institute of Radioimmunity, Technology Development Center, General Hospital of Chinese PLA. METHODS： The rats were equally and randomly assigned into mild hypothermia and control groups, and middle cerebral artery occlusion models were established. The rectal temperature was maintained at （37 ±0.5）℃ in the control group. In the mild hypothermia group, the rectal temperature was maintained at （33±1）℃. MAIN OUTCOME MEASURES： At 12 hours after model establishment, the ischemic brain hemispheres were coronally sliced at the level of the optic chiasm. The number of intercellular adhesion molecule-1-positive vessels per high-power field was observed with an optical microscope. Serum interleukin-6 levels were measured by radioimmunoassay. RESULTS： Compared with the control group, intercellular adhesion molecule-1 and serum interleukin-6 expressions were significantly decreased in ischemic brain tissues of the mild hypothermia group （P 〈 0.01）. CONCLUSION： Mild hypothermia exhibits a neuroprotective effect by reducing serum interleukin-6 and intercellular adhesion molecule-1 expression following cerebral ischemia.

InterInterleukin (IL)-4 Induces Production of Cytokine-induced Neutrophil Chemoattractants (CINCs) and Intercellular Adhesion Molecule (ICAM)-1 in Lungs of Asthmatic Rats

Summary： The present study aimed to examine the effect of intedeukin （IL）-4 on neutrophil chemo- taxis in airway inflammation in asthmatic rats and the possible mechanism. Male Wistar rats were intranasally instilled with recombinant rat （rr） IL-4 （rrlL-4） at different doses [2, 4 or 8μ g/animal, dis- solved in 200 μL normal saline （NS）] or rrlL-4 at 4 μg/animal （dissolved in 200 μL NS）. NS （200 μL） and LPS （6 mg/kg/animal, dissolved in 200 IxL NS） were intranasally given respectively in the negative and positive control groups. Moreover, the asthmatic lung inflammation was induced in rats which were then intranasally treated with rrlL-4 （4 μg/animal） or LPS （6 mg/kg/animal）. The normal rats treated with different doses of rrlL-4 and those asthmatic rats were sacrificed 6 h later. And animals instilled with rrlL-4 at 4 μg were sacrificed 6, 12 or 24 h later. The bronchoalveolar lavage fluid （BALF） and lungs were harvested for detection of leukocyte counts by Wright-Giemsa staining and lung histopa- thology by haematoxylin-eosin （HE） staining. The levels of cytokine-induced neutrophil chemoattrac- tant （CINC）-I and intercellular adhesion molecule （ICAM）-I in BALF were determined by ELISA. Real-time PCR was used to measure the mRNA expression of C1NCs （CINC-1, CINC-2u, CINC-2a, CINC-3） and ICAM-1 in lung tissues. The results showed that the intranasal instillation of IL-4 did not induce a recruitment of neutrophils in BALF in rats. However, IL-4 could increase the CINC-1 level in BALF in a dose-dependent manner at 6 h. But the mRNA expression levels of CINC-1, C1NC-2a, CINC-2, CINC-3 were not significantly increased in lungs of IL-4-treated rats relative to NS negative control group. Moreover, IL-4 was found to augment the mRNA expression oflCAM-1 in lungs and the ICAM-1 level in BALF at 6 h. However, the increase in CINC-1 and ICAM-1 levels in BALF of IL-4-treated asthmatic rats was not significantly different from that in untreated asthmatic rats. These findings indicate that IL-4 does not directly recruit neutrophils in the rat lungs, but it may contribute to airway neutrophilia through up-regulation of CINC-1 and ICAM-1.

High level of intercellular adhesion molecule-1 affects prognosis of patients with hepatocellular carcinoma

AIM: To determine the cut-off value of intercellular adhesion molecule-1(ICAM-1) and assess the correlation of ICAM-1 with clinicopathological features and the prognosis of hepatocellular carcinoma(HCC)patients who underwent surgical resection.METHODS: We prospectively collected clinicopathological data from 236 HCC patients who had undergone successful hepatectomy. Receiver operating characteristic curve analysis was performed to determine the optimal cut-off value of ICAM-1. Enzymelinked immunosorbent assay was used to measure the concentration of ICAM-1 in 236 serum samples isolated from HCC patients and the stratified analysis was used to compare the serum level of ICAM-1 in different HCC subgroups. Immunohistochemistry was performed to test the expression level of the ICAM-1 protein in76 cases of HCC tissues and their adjacent normal liver tissues(ANLT). The survival probability of HCC patients was estimated using Kaplan-Meier plots and differences between the groups were obtained using the log-rank test. Furthermore, independent indicatorsof the prognosis were acquired using a stepwise Cox proportional hazard model to analyze a series of predictors that were associated with disease-free survival(DFS) and overall survival(OS) in HCC patients.RESULTS: Our findings suggested that ICAM-1promotes HCC metastasis and high serum ICAM-1 is significantly associated with alpha-fetoprotein(AFP)(P = 0.022), clinical tumor-node-metastasis stage(P< 0.001), portal vein tumor thrombus(P = 0.005),distant metastasis(P = 0.016) and recurrence(P= 0.034). We further detected the ICAM-1 protein in HCC specimens and found that 56 of 76(73.7%)HCC tissues had ICAM-1 positive staining while only23 of 76(30.3%) ANLT were positively stained(P <0.0001). Survival analysis indicated that HCC patients with increased ICAM-1 concentrations had significantly shorter DFS and OS after resection. A multivariate analysis showed that ICAM-1 > 684 ng/mL was an independent factor for DFS(HR = 1.643; 95%CI:1.125-2.401; P = 0.010) and OS(HR = 1.692; 95%CI:1.152-2.486; P = 0.007).CONCLUSION: ICAM-1 may be a promising serological biomarker for HCC diagnosis and an independent predictor of DFS and OS after surgical resection and may provide a useful reference for the prediction of intra- and extrahepatic metastasis.

Soluble intercellular adhesion molecule-1,D-lactate and diamine oxidase in patients with inflammatory bowel disease

AIM:To study the levels of serum soluble intercellular adhesion molecule-1 (sICAM-1), plasma D-lactate and diamine oxidase (DAO) in patients with inflammatory bowel disease (IBD), and the potential clinical signif icance.METHODS: Sixty-nine patients with IBD and 30 healthy controls were included in this study. The concentration of sICAM-1 was detected with enzyme-linked immu-nosorbent assay, the level of D-lactate and DAO was measured by spectroscopic analysis, and the number of white blood cells (WBC) was determined by routine procedure.RESULTS:The levels of sICAM-l, DAO, and WBC in IBD patients were significantly higher than those in the control group (P<0.01). sICAM-l in IBD patients was found to be closely related to the levels of DAO and D-lactate (212.94±69.89 vs 6.35±2.35, P=0.000), DAO 212.94±69.89 vs 8.65±3.54, P=0.000) and WBC (212.94±69.89 vs 7.40±2.61, P=0.000), but no signif icant difference was observed between patients with ulcerative colitis and patients with Crohn's disease. The post-treatment levels of sICAM-l, D-lactate and WBC were significantly lower than before treatment (sICAM-l 206.57±79.21 vs 146.21±64.43, P=0.000), (D-lactate 1.46±0.94 vs 0.52±0.32, P=0.000) and (WBC 7.24±0.2.33 vs 5.21±3.21, P=0.000).CONCLUSION: sICAM-1, D-lactate and DAO are closely related to the specific conditions of IBD, and thus could be used as a major diagnostic index.