Bushen Jianpi Jiedu Liyan Formula Regulates Homing-associated Cell Adhesion Molecules in Rat Model of IgA Nephropathy / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Bushen Jianpi Jiedu Liyan formula on the expression of integrin alpha 4 beta 1 （α4 β1）， vascular cell adhesion molecule-1 （VCAM-1）， stromal-derived factor-1 （SDF-1）， and chemokine receptor-4 （CXCR4） in the small intestine and bone marrow of the rat model of immunoglobulin A（IgA） nephropathy. MethodA total of 120 male SD rats were used to establish the IgA nephropathy model by intragastric administration of bovine serum albumin （BSA）， subcutaneous injection of CCl4， and tail vein injection of lipopolysaccharide （LPS）. The successfully modeled rats were randomized into blank， model， lotensin （63 mg·kg-1）， and low-， medium-， and high-dose （10.4， 20.81， 41.62 g·kg-1， respectively） Bushen Jianpi Jiedu Liyan formula groups （n=16）. The rats were treated with corresponding drugs according to their body weight. After 7 weeks of administration， the rats were sacrificed for the collection of samples， and the protein and mRNA levels of α4 β1， VCAM-1， SDF-1， and CXCR4 in the small intestine and bone marrow were determined by immunohistochemistry and real-time fluorescence quantitative polymerase chain reaction， respectively. ResultCompared with the blank group， the model group showed increased red blood cell count in the urine at the 10th， 12th， 14th， 16th weeks （P<0.01）， and such increases were reduced in the drug intervention groups （P<0.05）， especially in the medium-dose Bushen Jianpi Jiedu Liyan formula group （P<0.05）. Compared with those in the blank group， the protein levels of α4 β1， VCAM-1， SDF-1， and CXCR4 in the intestinal lamina propria in the model group were up-regulated （P<0.05）， and such un-regulations were inhibited in the drug intervention groups （P<0.05）. Compared with the model group， medium-dose Bushen Jianpi Jiedu Liyan formula down-regulated the protein levels of SDF-1 and CXCR4 in the intestinal lamina propria （P<0.05）. Compared with the blank group， the model group showed down-regulated mRNA levels of α4 β1 and SDF-1 and up-regulated mRNA levels of VCAM-1 and CXCR4 （P<0.05）. Compared with the model group， the drug intervention groups showed down-regulated mRNA levels of SDF-1 and CXCR4 （P<0.05）. ConclusionBushen Jianpi Jiedu Liyan formula regulates the expression of α4 β1， VCAM-1， SDF-1， and CXCR4 in the intestinal lamina propria to inhibit the homing effect of plasma cells， which may be associated with the Toll-like receptor-mediated activation of immune response. Bushen Jianpi Jiedu Liyan formula can down-regulate the expression of adhesion molecules to inhibit the proliferation of plasmocytes in circulation， so as to reduce the renal injury of IgA nephropathy.

Cognitive impairment related to arterial stiffness in cardiovascular disease patients with severe periodontitis / Deterioro cognitivo relacionado a la rigidez arterial en pacientes con enfermedad cardiovascular y periodontitis grave

ABSTRACT Severe periodontal disease (SPD) associated with systemic peripheral inflammation, cognitive impairment (CI) and arterial stiffness (AS) has been recognized. The aim of this study was to investigate whether CI and arterial stiffness (AS) occur in cardiovascular disease (CVD) patients with SPD. A crosssectional case-control study included hospitalized patients with CVD. Demographic characteristics, CVD and atherogenic risk factors were recorded. SPD was diagnosed by clinical and radiographic dental examinations. Dental clinical attachment level (CAL) and CAL % were recorded. A Mini-Mental State Examination test (MMSE) assessed cognition, a MMSE score of < 27 was set as the cut-off point of CI; a score > 27 was considered as no CI. Patients were categorized into: MMSE<27 (cases) and MMSE>27 (controls). AS was evaluated by pulse wave velocity (PWV). Serum VCAM-1 levels were determined in a random sample. Results: This study comprised 91 patients (cases, n=26; 29.6%; controls, n=65, 71.4%); aged 73±8 vs. 73±7 years, respectively (p=0.73), of whom 53.8% and 36.9% respectively, were women; SPD was found to be a risk factor for CI; the presence of SPD increased the risk for MMSE <27 by an average 5.39 times (model 1). PWV was associated with MMSE < 27 in the three models. The risk of having MMSE < 27 increased an average of2.404-fold for each 1-unit increase in PWV SPD and AS had significant and independent associations on the risk for development CI. MMSE negatively correlated with CAL% (r=0.69) and PWV (r=0.70). PWV positively correlated with CAL% (r=0.67). Serum VCAM-1 levels were higher in SPD with lower MMSE scores. In conclusion, SPD increases the risk of development of cognitive decline in CVD patients. PWV was directly associated with the risk of cognitive decline. These findings denote a significant opportunity to improve periodontal health in order to avert CI in CVD patients.

RESUMEN La enfermedad periodontal severa (EPS) podría estar asociada a la rigidez arterial (RA) y al deterioro cognitivo (DC). Se realizó un estudio transversal de casos y controles y se investigó la presencia de RA y DC en pacientes con enfermedad cardiovascular (ECV) y EPS. En pacientes hospitalizados con ECVse registraron las características demográficas y factores de riesgo aterogénicos. El DC se diagnosticó a través del Mini-Mental State Examination (MMSE). Punto de corte: MMSE<27 (casos); puntaje >27 ausencia de DC (controles). La EPS fue diagnosticada clínica y radiográficamente. Se registraron el nivel inserción clínica (NIC) y NIC %. La RA fue evaluada a través de la velocidad de onda de pulso (VOP). VCAM-1 sérico se determinó en una muestra aleatoria. Se incluyeron 91 pacientes (casos,n=26; 29.6%; controles,n=65, 71.4%); edad promedio: 73±8 vs. 73±7 años, respectivamente (p=0.73); % de mujeres: 53.8 vs. 36.9, respectivamente y EPS (n=54) y ausencia de EP (noEP) en 37. MMSE< 27 en 26 pacientes; 23 de ellos, con EPS. La presencia de EPS aumentó el riesgo de MMSE< 27 en 5.39 veces (modelo 1). La VOP se asoció a MMSE< 27 (Modelo 1, 2 y 3). El riesgo de MMSE< 27 incrementó en promedio en 2.40 veces por cada aumento de unidad de VOP. EPS y RA mostraron asociaciones significativas e independientes sobre el riesgo de DC. MMSE se correlacionó negativamente con NIC % (r=0.69) y POV (r=0.70); y POV, positivamente con NIC % (r=0.67). Los niveles séricos de VCAM-1 fueron más elevados en presencia de EPS y puntajes bajos de MMSE. Puede concluirse que en pacientes con ECV y EPS, el aumento en RA incrementaría el riesgo de DC. Estos hallazgos enfatizan la necesidad de promover y mantener la salud bucal para evitar el DC en pacientes con ECV.

Influences of Leptospira interrogans infection on the expression of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 / 中华微生物学和免疫学杂志

Objective To investigate the influences of Leptospira interrogans (L.interrogans) in-fection on the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion mole-cule-1 (VCAM-1) on endothelial cells. Methods Expression of ICAM-1 and VCAM-1 at mRNA level was detected by reverse transcription-polymerase chain reaction (RT-PCR) after infecting human umbilical vein endothelial cells (HUVEC) with L.interrogans strain Lai. Silver staining was used to detect leptospires in lung,liver and kidney tissues of L.interrogans-infected C3H/HeJ mice. Expression of ICAM-1 and VCAM-1 in lung,liver and kidney tissues of L.interrogans-infected mice was measured with immunohistochemistry. Results L.interrogans infection increased the expression of ICAM-1 and VCAM-1 on HUVEC(P<0.05). Moreover,the expression of VCAM-1 at mRNA level was significantly higher than that of ICAM-1 (P<0.05). Silver-stained leptospires could be found in lung,liver and kidney tissues of L.interrogans-infected C3H/HeJ mice. Results of the immunohistochemical examination showed that increased expression of both ICAM-1 and VCAM-1 could be detected in ling,liver and kidney tissues of L.interrogans-infected mice,and the VCAM-1 level was significantly higher than that of ICAM-1 in every tissue sample(P<0.05). Conclu-sion L.interrogans infection could induce the expression of ICAM-1 and VCAM-1 on endothelial cells and increase the expression of VCAM-1 to a level significantly higher than that of ICAM-1, which mediated the infiltration of specific inflammatory cells to the site of infection.

Relationship between circulating VCAM-1, ICAM-1, E-selectin and MMP9 and the extent of coronary lesions

OBJECTIVES: Inflammatory molecules play a role in the development of atherosclerosis, which is the primary origin of cardiovascular disorders. However, to the best of our knowledge, no study has attempted to investigate the relationship between these circulating molecules and the prediction of cardiovascular risk. The present study aimed to investigate the relationships of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and matrix metalloproteinase 9 serum concentrations with the extent of coronary lesions. METHODS: Seventy-four individuals who were undergoing coronary angiography for the first time for diagnostic purposes were enrolled in this study. The extent of the coronary lesion was assessed using the Friesinger Index, and subjects were classified into four groups: no lesions, minor lesions, intermediate lesions and major lesions. Serum biochemical parameters and serum concentrations of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and matrix metalloproteinase 9 were analyzed. RESULTS: The vascular cell adhesion molecule-1 concentration was higher than 876 ng/mL in individuals with intermediate and major lesions (p<0.001 and p=0.020, respectively). Moreover, logistic regression analysis showed that these patients had an increased risk of having an intermediate lesion (p=0.007). Interestingly, all individuals with major lesions had vascular cell adhesion molecule-1 concentrations higher than 876 ng/mL. No association was found between the concentrations of the other proteins and the Friesinger Index. CONCLUSIONS: Serum vascular cell adhesion molecule-1 may be associated with the extent of coronary lesions. Moreover, it may represent an alternative to improve the cardiovascular risk classification in patients without acute coronary syndrome.

Anti-inflammatory Actions of Heshi Yangshen Recipe on Rat Model of Nephrotic Syndrome / 广州中医药大学学报

Objective To explore the anti-inflammatory action of Heshi Yangshen Recipe on rat model of nephrotic syndrome induced by adriamycin. Methods Rat model of nephrotic syndrome was established by tail venous injection of one-dose of adriamycin. SD rats were divided into normal group(N = 10),model group(N =11), positive control group (N = 12), and high-, middle- , low-dose Chinese medicine groups (N = 12, respectively). Two weeks after modeling,rats in the normal group and model group were given gastric gavage of same volume of normal saline, rats in positive control group were given gastric gavage of benazepril aqueous solution at a dose of 10 mg·kg-1·d-1 in the former period of 15 days and at 10 mg·kg-1·d-1 in the later period of 20 days, and rats in high-,middle- ,low-dose groups were given gastric gavage of Heshi Yangshen Recipe at a dosage of 33.26, 16.63, 8.32 g·kg-1·d-1 respectively, for 30 continuous groups. During the treatment period, the general situation of rats was observed. After the completion of medication, the levels of 24-hour urinary protein, urine total proteins, urine creatinine were measured by biochemical analyzer, serum high-sensitivity C-reactive protein (Hs-CRP) level was detected by enzyme-linked immunosorbent assay(ELISA),and the expression levels of intercellular adhesion molecule 1 (ICAM-1)and vascular cell adhesion molecule-1 (VCAM-1)in rat renal tissue of various groups were determined by immunohistochemistry. Results The increase of body mass in all of the modeled rats was significantly slowed down (P < 0.01 as compared with the normal group). Compared with the normal group, the levels of 24-hour urinary protein, serum hs-CRP, and the expression of ICAM-1 and VCAM-1 in rat renal tissue were increased in the model group (P < 0.05 or P <0.01). Compared with the model group, the level of 24-hour urinary protein in the positive control group and high-dose Chinese medicine group was decreased (P < 0.05), and the levels of serum Hs-CRP, and the expression of ICAM-1 and VCAM-1 in rat renal tissue of the positive control group and high-,middle-,low-dose Chinese medicine groups were decreased (P < 0.05 or P < 0.01). Conclusion Heshi Yangshen Recipe exerts certain anti-inflammatory action, and its mechanism may be related with the decrease of ICAM-1 and VCAM-1 expression. High dosage of Heshi Yangshen Recipe has the strongest therapeutic effect.

Effect of sitagliptin on atherosclerosis in ApoE-/-mice / 局解手术学杂志

Objective To investigate the effect of DPP-4 inhibitor sitagliptin on atherosclerosis and its mechanism.Methods Thirty male ApoE-/-mice were randomly divided into two groups:experimental group(n=15) and control group(n=15).The mice in the experimental group were fed with high-fat mixture of sitagliptin and the control group was fed with high fat.Collected blood in the eyeballs in order to analyze serum levels of blood lipids and blood glucose after 16 weeks of feeding,and detected serum nitric oxide synthase(eNOS),vascular adhesion molecule-1(VCAM-1) with ELISA method.Collected aortic tissue in order to analyze atherosclerotic plaque.Results There was no significant difference in blood glucose,triglyceride and total cholesterol level between the two groups(P>0.05).The serum high density lipoprotein in the experimental group was significantly higher than that in the control group(P<0.05).The atherosclerotic plaque in the experimental group(7.55±1.87)%, which was significantly smaller than that in the control group(11.67±1.32)%.The serum VCAM-1 in the experimental group was lower and the eNOS was higher than that in the control group(P<0.05).Conclusion DPP-4 sitagliptin can increase the expression of HDL and eNOS and inhibit the expression of VCAM-1,thereby inhibiting the progression of atherosclerosis in ApoE-/-mice.

Effect of Guizhi Gancao decoction on cardiac function and serum VCAM-1 and sE-selectin levels in patients with coronary heart disease / 中国生化药物杂志

Objective To analyze the effect of guizhi gancao decoction on dardiac function and serum VCAM-1 and sE-selectin levels in patients with coronary heart diseaser. Methods Fifty-eight patients with coronary heart disease were enrolled in this study from September 2014 to June 2015. According to the different treatment methods, 40 patients were treated with conventional western medicine. The observation group of 40 cases were treated with conventional western medicine and Guizhi licorice soup. The effects of cardiac function, 6-minute walking test, cardiac parameters and serum sE-Selectin and ICAM-1 levels were observed. Results Observation group of patients with cardiac ultrasound parameters LVEF (43.27 ± 5.21)%, LVEDd (59.34 ± 5.43) mm, FS (26.32 ± 1.63)%, E / A (1.23 ± 0.22) and 6 min walking distance were better than those of the control group (t=2.3628,P =0.0206;t=2.4643,P=0.0159;t=2.7831,P =0.0068;t=2.5023,P =0.0144;t=3.7571,P =0.0006). The markedly effective rate was 47.50%, which was higher than that of the control group (25.00%), and there was significant difference (χ2 = 4.3813, P= 0.0363). In the observation group, 4 patients were ineffective and the inefficiency rate was 10.00%, which was significantly lower than that of the control group (χ2 = 4.0205,P= 0.0450). The levels of TC (5.21 ± 0.82) mmol / L, TG (1.22 ± 0.32) mmol / L and LDL-C (2.44 ± 0.52) mmol / L were significantly lower in the observation group than those in the control group (t= 3.2729, P = 0.0016; t= 3.5119, P = 0.0007; t= 3.5136, P= 0.0007). While the HDL-C (1.21 ± 0.17) mmol / L index was higher than that of the control group (t = 5.4575, P = 0.0000). There was no significant difference in serum index between the two groups before treatment . After treatment, the serum sE-Selectin (75.58 ± 9.97) ng / mL and VCAM-1 (662.43 ± 65.78) ng / mL were lower than those in the control group (t = 3.4082, P = 0.0010;t = 3.3088, P = 0.0014). Conclusion Treatment of CHF patients with CRT / CRT-D pacemaker implantation in the heart after surgery can effectively improve its clinical condition, and the effect is outstanding, side effects, and CRT-D better effect.

Taurine affects expression of ICAM-1, VCAM-1 by p38 pathway in hypoxic endothelial cells / 中国中药杂志

To investigate the effect of taurine(Tau) on ICAM-1, VCAM-1 by p-p38 pathway in bovine pulmonary artery endothelial cells(PAECs) and explore its mechanism of action. Generation 4-12 cells in primary cultures of PAECs were used in experiments and divided into five groups： control group, hypoxia(hyp) group, inhibitor(SB203580) group, treatment(Tau) group, and treatment+inhibitor(SB+Tau) group. The concentration of Tau：100 mmol•L⁻¹; p38 inhibitor SB203580： 20 μmol•L⁻¹; and the treatment time was 12 h. MTT assay was used to detect the inhibitory effect of different concentrations of Tau on PAECs. Western blot and Real-time PCR method were used to detect the p38 pathway proteins and ICAM-1, VCAM-1 expression levels. Immunofluorescence was used to investigate p38 nuclear displacement situation. The results of MTT showed that the inhibitory effect was gradually increased with increasing concentrations of Tau. Western blot and RT-PCR revealed that the protein and mRNA expression levels of ICAM-1, VCAM-1 were reduced by Tau. Western blot and immunofluorescence showed Tau can inhibit p38 activation. Tau may decrease the expression levels of VCAM-1 and ICAM-1 in endothelial cells induced by hypoxia through MAPK p38 pathway.

Angiogenesis-related factors expression in oral lichen planus / 口腔疾病防治

Objective@# To detect the expression of vascular endothelial growth factor (VEGF), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) in oral lichen planus (OLP).@*Methods @#Thirty OLP patients and fifteen healthy subjects were enrolled in the study. Serum were collected from 15 healthy volunteers as controls. Normal tissues were collected from surgical department as immunohistochemical analysis. The levels of VEGF, ICAM-1, VCAM-1 in serum were measured by ELISA. Immunohistochemical analysis of VEGF, ICAM-1, VCAM-1 were carried out by the means of primary antibodies and anti-VEGF, anti-CD106 antigen (VCAM-1) and anti-CD54 antigen (ICAM-1). @*Results@# ELISA results showed no expression differences for VEGF between the two groups. Whereas, the levels of ICAM-1, VCAM-1 in OLP group were significantly higher than those in control group (P < 0.05). Immunohistochemical results reveal the presence of a significant angiogenesis in OLP patients through the immunoexpression of VEGF, ICAM-1, VCAM-1 according to the percentage of stained cells (P < 0.05).@*Conclusion @# Regarding the results, it seems that high expression of VCAM-1 and ICAM-1 are related to oral lichen planus.

Evaluation of biochemical and clinical markers of endothelial dysfunction and their correlation with urinary albumin excretion in patients with type 1 diabetes mellitus

ABSTRACT Objective Endothelial dysfunction (ED) plays an important role in the pathogenesis of diabetic nephropathy. The purpose of the study was to determine flow mediated endothelial dependent vasodilatation (FMD) measurements and serum soluble (s) endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1) levels in patients with type 1 diabetes mellitus (T1DM) with or without increased urinary albumin excretion (UAE) and compare them with the healthy controls. Subjects and methods Seventy three patients with T1DM were enrolled. Patients were divided into two subgroups according to microalbumin measurements in 24-hr urine collections. The diabetic patients without microalbuminuria (41 patients) were defined as Group I and those with microalbuminuria (32 patients) were defined as group II. A hundred age and sex matched healthy subjects participated as the control group (Group III). Serum sET-1, sICAM-1, sVCAM-1 levels and FMD measurements were determined in all participants. Results Median FMD measurement was significantly lower in the diabetic groups compared with the control group (6.6, 6.4 and 7.8% in Group I, II and III, respectively) (p < 0.05). FMD was negatively correlated with age (p = 0.042). Median serum sICAM-1 level was higher in the patient groups compared to the control group (p < 0.05). Median serum sVCAM-1 level was higher in the group of patients with increased albuminuria compared to the normoalbuinuric and the control group (p < 0.05). Serum sVCAM-1 level was found to be positively correlated with degree of urinary albumin excretion (p < 0.001). Conclusion We assume that sVCAM-1 may be used as a predictive marker for risk stratification for nephropathy development and progression.

Lobaric Acid Inhibits VCAM-1 Expression in TNF-alpha-Stimulated Vascular Smooth Muscle Cells via Modulation of NF-kappaB and MAPK Signaling Pathways

Lichens have been known to possess multiple biological activities, including anti-proliferative and anti-inflammatory activities. Vascular cell adhesion molecule-1 (VCAM-1) may play a role in the development of atherosclerosis. Hence, VCAM-1 is a possible therapeutic target in the treatment of the inflammatory disease. However, the effect of lobaric acid on VCAM-1 has not yet been investigated and characterized. For this study, we examined the effect of lobaric acid on the inhibition of VCAM-1 in tumor necrosis factor-alpha (TNF-alpha)-stimulated mouse vascular smooth muscle cells. Western blot and ELISA showed that the increased expression of VCAM-1 by TNF-alpha was significantly suppressed by the pre-treatment of lobaric acid (0.1-10 mug/ml) for 2 h. Lobaric acid abrogated TNF-alpha-induced NF-kappaB activity through preventing the degradation of IkappaB and phosphorylation of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), and p38 mitogen activated protein (MAP) kinase. Lobaric acid also inhibited the expression of TNF-alpha receptor 1 (TNF-R1). Overall, our results suggest that lobaric acid inhibited VCAM-1 expression through the inhibition of p38, ERK, JNK and NF-kappaB signaling pathways, and downregulation of TNF-R1 expression. Therefore, it is implicated that lobaric acid may suppress inflammation by altering the physiology of the atherosclerotic lesion.

Evaluation of Endothelial Cell Adhesion Molecules and Anti-C1q Antibody in Discriminating between Active and Non-Active Systemic Lupus Erythematosus

Background : Detecting the active state of systemic lupus erythematosus (SLE) is important but challenging. This study aimed to determine the diagnostic accuracy of serum endothelial cell adhesion molecules (ICAM-1 and VCAM-1) and anti-C1q antibody in discriminating between active and non-active SLE. Methods: Using SELENA-SLE disease activity index (SLEDAI), 95 SLE patients (45 active and 50 non-active) were assessed. A score above five was considered indicative of active SLE. The blood samples were tested for serum ICAM-1, VCAM-1 and anti-C1q antibody using enzyme-linked immunosorbent assay (ELISA). Results: The levels of serum VCAM-1 and anti-C1q antibody were significantly higher in active SLE patients. Both VCAM-1 and anti-C1q were able to discriminate between active and non-active SLE ( p -value < 0.001 and 0.005, respectively). From the receiver operating characteristic curves (ROCs) constructed, the optimal cut-off values for VCAM-1 and anti-C1q antibody in discriminating between active and non-active SLE were 30.5 ng/mL (69.0% sensitivity, 60.0% specificity, PPV 58.5%, NPV 66.7%) and 7.86 U/mL (75.6% sensitivity, 80% specificity, PPV 77.3%, NPV 78.4%), respectively. However, serum ICAM-1 level was unable to discriminate between the two groups ( p -value = 0.193). Conclusion: Anti-C1q antibody demonstrated the best diagnostic accuracy in discriminating between active and non-active SLE patients

Changes of intercellular adhesion molecular-l and vaseular cell adhesion molecular-l in patients with pancreatic cancer / 中国生化药物杂志

Objective To investigate the changes of VCAM-1 and ICAM-1 levels in tumor and peripheral blood in pancreatic cancer patients. Methods 28 cases with pancreatic cancer were selected from August 2013 to Octorber 2014 as experiment group,28 cases with acute pancreatitis who needed removal of pancreas as control group,28 healthy people as normal group.ICAM-1 and VCAM-1 in tissue were compared and sVCAM-1 and sICAM-1 in serum were compared.Results ICAM-1 and VCAM-1 in tissue of experiment group were significantly higher than normal group(P0.05;r=0.093,P>0.05),there were positive correlation between CA19-9 and sICAM-1,sVCAM-1 in serum of experiment group(r=0.573,P<0.01;r=0.435,P<0.05).Compared with pre-operation, the serum concentrations of sVCAM-1 and sICAM-1 were lower(P<0.05).Conclusion ICAM-1 and VCAM-1in pancreatic cancer patients are significantly higher than that in acute pancreatitis patients and healthy people, the correlation of ICAM-1 and VCAM-1 expression in pancreatic cancer, early diagnosis and treatment of pancreatic cancer has important significance.

Ativação endotelial na granulomatose com poliangeíte (granulomatose de Wegener) / Endothelial activation in granulomatosis with polyangiits

INTRODUÇÃO: Eventos vasculares e imunológicos são centrais na patogênese da granulomatose com poliangeíte (GPA). Moléculas de adesão celular tem papel fundamental no recrutamento de células inflamatórias do sangue para os tecidos. Diferentes leitos vasculares apresentam particularidades na expressão de moléculas de adesão celular explicando talvez parte da especificidade da GPA por determinados órgãos. A elevação no nível sérico de moléculas de adesão celular e aumento da expressão destas em amostras de biópsia renal já foram demonstrados em pacientes com vasculite ANCA associada. No entanto, o fenômeno ainda não foi estudado in situ no pulmão. OBJETIVO: O objetivo deste estudo foi analisar o padrão de expressão endotelial pulmonar de três moléculas de adesão celular na GPA, in situ: molécula de adesão intercelular 1 (ICAM-1), molécula e adesão vascular 1 (VCAM-1) e E-selectina. MÉTODOS: Examinou-se a expressão endotelial de ICAM-1, VCAM-1, E-selectina usando marcação imuno-histoquímica em secções de pulmão fixadas e parafinadas de lesões de GPA (n = 8 casos, 90 secções transversais de vasos analisados). Foram também analisados controles positivos: amostras de pulmão de doença intersticial associada à esclerodermia (SScl) (n = 8 casos, 96 secções transversais de vasos analisados) e controles negativos (n = 9 casos, 90 secções transversais de vasos analisados). A quantificação imuno-histoquímica foi realizada no aumento de 400x usando a técnica de point-counting. RESULTADOS: ICAM-1: A expressão endotelial mediana de ICAM-1 esteve aumentada de forma semelhante na GPA e na SScl (81% and 73%, respectivamente; p = 0.97). A comparação com o grupo controle (26.3%) revelou diferença estatisticamente significativa entre controle e GPA (p <0.001) quanto entre controle e SScl (p = 0.017). VCAM-1: A expressão mediana de VCAM-1 esteve significativamente aumentada na GPA se comparada a SScl (79.5% vs 41.4%; p = 0.012), no entanto, a expressão endotelial de VCAM-1 nos...

INTRODUCTION: Vascular and immunologic processes are central to the pathogenesis of granulomatosis with polyangiitis (GPA). Endothelial cellular adhesion molecules have a central role in recruiting leukocytes to sites of inflammation. Moreover, different vascular beds are phenotypically and functionally distinct with regard to expression of cellular adhesion molecules. They have been shown to be elevated in sera and in renal biopsies of patients with active ANCA-associated vasculitis. Despite of that, the expression of cellular adhesion molecules has not been studied in situ in the lungs. OBJECTIVE: Within this context, the aim of this study was to analyze the in situ pulmonary endothelial immunohistochemical pattern of expression of three cellular adhesion molecules in GPA: intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin . METHODS: For such, we examined formalin-fixed, paraffin-embedded sections of lung lesions of GPA (n = 8 cases, 90 transverse sections of pulmonary vessels), negative controls which were obtained from autopsies ( n = 9 cases, 90 transverse sections of pulmonary vessels analyzed) and positive controls which were cases of interstitial lung disease associated with systemic sclerosis (SScl) (n = 8 cases, 96 transverse sections of pulmonary vessels). The quantification of the immunohistochemical staining was performed at x400 magnification using the technique of point-counting, previously described. RESULTS: ICAM-1: Median endothelial expression of ICAM-1 was similarly enhanced in GPA and SScl (81% and 73%, respectively; p = 0.97). When compared to controls (26.3%), both GPA (p <0.001) and SScl (p = 0.017) had significantly higher endothelial expression of ICAM-1. VCAM-1: Median endothelial expression of VCAM-1 was significantly enhanced in GPA when compared to SScl (79.5% vs 41.4%; p = 0.012), however the endothelial expression of VCAM-1 in the controls was also moderately enhanced (49.8%)...

Nafamostat Mesilate Inhibits TNF-alpha-Induced Vascular Endothelial Cell Dysfunction by Inhibiting Reactive Oxygen Species Production

Nafamostat mesilate (NM) is a serine protease inhibitor with anticoagulant and anti-inflammatory effects. NM has been used in Asia for anticoagulation during extracorporeal circulation in patients undergoing continuous renal replacement therapy and extra corporeal membrane oxygenation. Oxidative stress is an independent risk factor for atherosclerotic vascular disease and is associated with vascular endothelial function. We investigated whether NM could inhibit endothelial dysfunction induced by tumor necrosis factor-alpha (TNF-alpha). Human umbilical vein endothelial cells (HUVECs) were treated with TNF-alpha for 24 h. The effects of NM on monocyte adhesion, vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) protein expression, p38 mitogen-activated protein kinase (MAPK) activation, and intracellular superoxide production were then examined. NM (0.01~100 microg/mL) did not affect HUVEC viability; however, it inhibited the increases in reactive oxygen species (ROS) production and p66shc expression elicited by TNF-alpha (3 ng/mL), and it dose dependently prevented the TNF-alpha-induced upregulation of endothelial VCAM-1 and ICAM-1. In addition, it mitigated TNF-alpha-induced p38 MAPK phosphorylation and the adhesion of U937 monocytes. These data suggest that NM mitigates TNF-alpha-induced monocyte adhesion and the expression of endothelial cell adhesion molecules, and that the anti-adhesive effect of NM is mediated through the inhibition of p66shc, ROS production, and p38 MAPK activation.

Estudio inmunohistoquímico de moléculas de adhesión en placentas de niños de bajo peso al nacer en el Hospital Universidad del Norte, Barranquilla (Colombia) / Immunohistochemical studies of adhesion molecules in placentas from low birth infants at Hospital Universidad of the Norte, Barranquilla (Colombia)

Objetivo: Observar la expresión de moléculas de adhesión VCAM-1, ICAM-1 en placentas de niños de bajo peso al nacer. Se estudiaron 21 placentas de pacientes atendidas en el Hospital Universidad del Norte en el periodo de mayo a diciembre de 2006. Materiales y métodos: Se realizó estudio macroscópico de las placentas: forma, peso, diámetro grosor, consistencia, color, olor. Para estudios microscópicos se realizaron 5 cortes de la placa corial, uno del rollo de membrana y otro del cordón umbilical. Los cortes fueron fijados en formol al 10 %, incluidos en parafina, coloreados con hematoxilia - eosina para estudios morfológicos. Para estudios inmunohistoquímicos se usaron anticuerpos mono-clonales Nova Castra para ICAM-1, VCAM-1, macrófagos. Resultados: Dieciocho placentas de forma redonda, 3 ovaladas; el peso varió entre 240 -400 gramos; 3 presentaron infarto en los cotiledones. En la micro 18 presentaron necrosis hialina de la media, hiperplasia de la intima, macrófagos xantomatosos, infiltrado linfoci-tario en tres. En la inmunohistoquímica se observó expresión de ICAM-1, VCAM-1, en la basal de las vellosidades coriales, en la basal de los vasos sanguíneos y macrófagos en el estroma conjuntivo Conclusiones: En dieciocho de los casos los cambios fueron compatibles con preeclampsia, tres con proceso virales. La expresión de moléculas de adhesión y macrófago en la inmunohistoquímica nos sugiere que estas moléculas son fundamentales en los proceso fisiopatológicos de la placenta.

Objective: To observe the expression of adhesion molecules VCAM -1, ICAM -1 in placentas of infants with low birthweight 21 placentas of patients treated at the University Hospital North in the period from May to December were studied 2006. Materials and methods: Macroscopic study of the placentas was performed; shape, weight, diameter, thickness, consistency, color, and odor: For five cuts microscopic studies chorionic plate, one membrane roll and another cord were performed. The sections were fixed in 10 % formalin, embedded in paraffin, stained with hematoxylin-eosin for morphological studies. For immunohistochemical studies monoclonal antibodies were used castra nova for ICAM1, VCAM1, macrophages. Results: 18 placentas round, three oval, the various weight between 240-400 grams, 3 had infarction in the cotyledons. In the micro 18 presented hyaline medial necrosis, hyperplasia of the intima, xanthomatous macrophages, lymphocytic infiltrate in three . In the immunohistochemical expression of ICAM-1, VCAM-1 was observed in the basal of chorionic villi in the basal blood vessel and macrophages in stroma. Conclusions: cases changes are compatible with pre -eclampsia, three viral process. The expression of adhesion molecules and macrophage in immunohistochemistry suggests that these molecules are critical in the pathophysiological process of the placenta.

Effect of Kangxin Capsule on Stability of Atherosclerotic Plaque in Rabbits / 中国中医药信息杂志

Objective To investigate the effect of Kangxin Capsule on the stability of atherosclerotic plaque in rabbits. Methods Forty purebred male New Zealand white rabbits were randomly divided into model group, atorvastatin group, Kangxin Capsule high and low dose groups, and normal control group, 8 rabbit for each group, and were given corresponding administration. Atherosclerosis model was made by intimal injury and high cholesterol diet except for normal control group. After 6 W, aortic vascular pathomorphology were observed, and immunohistochemical method was used to detect the expression of MMP-2 and VCAM-1 in atherosclerotic plaques. Results Compared with model group, the ratio of the thickness of wall to the area of lumina (W/L), average optical density, and the percentage of positive area of Kangxin Capsule groups were less, also, the expression of MMP-2 and VCAM-1 were reduced. The differences were significant (P<0.05 or P<0.01), especially in the high-dose group. Conclusion Kangxin Capsule can reduce the expression of MMP-2 and VCAM-1, which is the possible mechanism of stabilizing the atherosclerotic plaque.

Effect of Tangerine Peel and Pinellia Ternata on Expression of VCAM-1 and MMP-9 in Carotid Atherosclerosis Rabbits / 中国中医药信息杂志

Objective To research the influence of tangerine peel and pinellia ternata on the expression of VCAM-1 and MMP-9 in carotid atherosclerosis rabbits, and explore its mechanism. Methods Totally 25 male rabbits were divided into control group, model group and Chinese medicine group. Control group was treated with basic diet, model group and Chinese medicine group were treated with both high-fat diet and carotid artery intima-air drying technique. Chinese medicine decoction group was treated with tangerine peel and pinellia ternata decoction, as 10, 8, 6 mL/kg, for 4 weeks. Then the right carotid was cut and fixed, and pathological changes were observed by HE staining. The expressions of VCAM-1 and MMP-9 were observed by immunol histochemistry SABC method. Results Compared with control group, the expression of VCAM-1 and MMP-9 in model group was significantly increased (P<0.01). And compared with model group, tangerine peel and pinellia ternata decoction significantly restrained VCAM-1 and MMP-9 expression (P<0.05). Conclusion Tangerine peel and pinellia ternata could restrained VCAM-1 and MMP-9 expression in carotid atherosclerosis rabbits, suggesting that its mechanism may be related with inhibiting vascular inflammatory reaction and stabilizing plaques.

Resistance of Berberine on Lung Inflammatory Injury in Mice with Viral Pneumonia Caused by Influenza Virus / 中国中医药信息杂志

Objective To observe the effects of berberine on ICAM-1, VCAM-1 expression and inflammatory cells exudation in mice with viral pneumonia caused by influenza virus, and explore its anti-injury effect. Methods Totally 108 BALB/c mice were randomly divided into control group, model group, and berberine group. 25 μL 50 LD50 influenza virus, mouse lung-adapted strain, was intranasally inoculated to model group and berberine group. 1 h after infection, control and model group were intragastrically given 25 μL distilled water, berberine group was treated by intraperitoneal injection with berberine at a dose of 0.005 g/(kg·d) for 5 days, twice per day. On day 2, 4 and 6 after infection, immunocytochemical method was used to detect ICAM-1 and VCAM-1 expression, and sorting cell count of leukocytes in bronchoalveolar lavage fluid (BALF) were counted. Results The expression of ICAM-1 and VCAM-1 in model group increased obviously on day 2, 4, 6, and which in berberine group decreased compared with model group (P<0.01). WBC, mononuclear cell, eosinophile cell and neutrophil cell number in model group increased significantly. WBC and neutrophil cell number decreased in berberine group on day 6 (P<0.01), and the mononuclear cell number decreased on day 4 (P<0.01). Conclusion Berberine inhibited the expression of ICAM-1 and VCAM-1, and decreased the inflammatory cells exudation in lung of mice with viral pneumonia caused by influenza virus. Berberine has protective effect on inflammatory injury of lung tissue in mice with viral pneumonia caused by influenza virus.

Ginsenoside Rg2 Inhibits Lipopolysaccharide-Induced Adhesion Molecule Expression in Human Umbilical Vein Endothelial Cell

Vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), P- and E-selectin play a pivotal role for initiation of atherosclerosis. Ginsenoside, a class of steroid glycosides, is abundant in Panax ginseng root, which has been used for prevention of illness in Korea. In this study, we investigated the mechanism(s) by which ginsenoside Rg2 may inhibit VCAM-1 and ICAM-1 expressions stimulated with lipopolysaccharide (LPS) in human umbilical vein endothelial cell (HUVEC). LPS increased VCAM-1 and ICAM-1 expression. Ginsenoside Rg2 prevented LPS-mediated increase of VCAM-1 and ICAM-1 expression. On the other hand, JSH, a nuclear factor kappa B (NF-kappaB) inhibitor, reduced both VCAM-1 and ICAM-1 expression stimulated with LPS. SB202190, inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), and wortmannin, phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, reduced LPS-mediated VCAM-1 but not ICAM-1 expression. PD98059, inhibitor of mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) did not affect VCAM-1 and ICAM-1 expression stimulated with LPS. SP600125, inhibitor of c-Jun N-terminal kinase (JNK), reduced LPS-mediated ICAM-1 but not VCAM-1 expression. LPS reduced IkappaBalpha (IkappaBalpha) expression, in a time-dependent manner within 1 hr. Ginsenoside Rg2 prevented the decrease of IkappaBalpha expression stimulated with LPS. Moreover, ginsenoside Rg2 reduced LPS-mediated THP-1 monocyte adhesion to HUVEC, in a concentration-dependent manner. These data provide a novel mechanism where the ginsenoside Rg2 may provide direct vascular benefits with inhibition of leukocyte adhesion into vascular wall thereby providing protection against vascular inflammatory disease.