The Beneficial Impact of Zinc Supplementation on the Vascular Tissue of the Abdominal Aorta under Repeated Intoxication with Cadmium: A Study in an In Vivo Experimental Model.

In an in vivo rat model of human exposure to cadmium (Cd; 5 and 50 mg/L, 6 months), whether the supplementation with zinc (Zn; 30 and 60 mg/L, increasing its daily intake by 79% and 151%, respectively) protects against the unfavourable impact of this xenobiotic on the vascular tissue of the abdominal aorta was investigated. The treatment with Cd led to oxidative stress and increased the concentrations of pro-inflammatory interleukin 1ß (IL-1ß), total cholesterol (TC), triglycerides (TG), and endothelial nitric oxide synthase (eNOS) and decreased the concentration of anti-inflammatory interleukin 10 (IL-10) in the vascular tissue. Cd decreased the expression of intercellular adhesion molecule-1 (ICAM-1), platelet endothelial cell adhesion molecule-1 (PECAM-1), and L-selectin on the endothelial cells. The administration of Zn prevented most of the Cd-induced alterations or at least weakened them (except for the expression of adhesive molecules). In conclusion, Zn supplementation may protect from the toxic impact of Cd on the blood vessels and thus exert a beneficial influence on the cardiovascular system. The increase in the intake of Zn by 79% may be sufficient to provide this protection and the effect is related to the antioxidative, anti-inflammatory, and antiatherogenic properties of this essential element.

c-Myc participates in high glucose-mediated endothelial inflammation via upregulation of IRAK1 expression in diabetic nephropathy.

Diabetic nephropathy (DN) is a common vascular complication of diabetes. Endothelial adhesion molecules are involved in physiopathology of DN. Interleukin-1 receptor-associated kinase 1 (IRAK1) and c-Myc participate in inflammation in DN. We hypothesized c-Myc modulates IRAK1 expression, contributing to hyperglycemia-mediated endothelial inflammation. The expression of endothelial adhesion molecules and IRAK1 were increased in glomerular endothelium of DN patients and rats. Our cellular experiments indicated high glucose-induced endothelial cell inflammation was inhibited by si-IRAK1. Additionally, high glucose increased c-Myc expression. si-c-Myc inhibited high glucose-mediated increase of IRAK1 levels and endothelial cell inflammation. c-Myc overexpression-mediated endothelial cell inflammation was counteracted by si-IRAK1. c-Myc also interacted with lysine methyltransferase 5A (KMT5A). Furthermore, high glucose decreased KMT5A expression and histone H4 lysine 20 methylation (H4K20me1). KMT5A upregulation decreased high glucose-mediated increase of IRAK1 levels as well as endothelial inflammation. KMT5A silencing-mediated endothelial inflammation was reversed by si-IRAK1. Mechanistic research indicated that c-Myc and H4K20me1 occupied IRAK1 promoter region. KMT5A silencing augmented the active action of c-Myc on IRAK1 levels. Our in vivo experiments represented KMT5A is downregulated and c-Myc is upregulated in DN patients and rats. KMT5A interacts with c-Myc to modulate IRAK1 expression, thus contributing to hyperglycemia-mediated endothelial inflammation in DN.

MiR-520b inhibits endothelial activation by targeting NF-κB p65-VCAM1 axis.

MiR-520b belongs to the miR-373/520 family, is expressed only in human and nonhuman primates. Previous reports indicated that the expression of miR-520b was repressed in human atherosclerotic plaque tissue compared with healthy vessels. However, the role of miR-520b in coronary artery disease still remains to be uncovered. In this study, we demonstrated that endothelial cells (ECs) in human atherosclerotic plaques expressed miR-520b and aimed to elucidate the impact of miR-520b on EC activation and inflammatory response. To determine the potential targets of miR-520b, we performed RNA-seq analysis by transfecting miR-520b mimics in ECs. The quantitative real-time PCR (qPCR) validation suggested that miR-520b over-expression reduced pro-inflammatory gene expression (e.g. ICAM1, VCAM1, SELE) while the inhibition of miR-520b induced their expression. By combining bioinformatics prediction and functional assays, we identified that RELA (Nuclear Factor-κB (NF-κB) Transcription Factor P65) was a direct target of miR-520b. Moreover, miR-520b mimics attenuated monocyte adhesion and monocyte trans-endothelial migration (the initial steps of atherosclerotic formation) in response to lipopolysaccharides (LPS) stimulation. Re-expression of a non-miR-targetable version of p65 could rescue the reduced monocyte cell attachment, suggesting that this process is NF-κB p65 dependent. MiR-520b reduced the abundance of NF-κB p65 in cytoplasmic fractions without corresponding increase in nuclear fractions, indicating that this regulation is independent of p65 translocation process. MiR-520b mimics attenuated the activity of VCAM-1 promoter, whereas miR-520b inhibitor activated its activity. However, miR-520b inhibitor had no effect on promoter activity containing the mutated NF-κB p65 binding sites, strongly demonstrating that the impact of miR-520b on VCAM1 gene is mediated by NF-κB p65. Thus, we concluded that miR-520b suppressed EC inflammation and the cross-talk between monocytes and ECs by down-regulating NF-κB p65-ICAM1/VCAM1 axis and might serve as a potential therapeutic target for EC dysfunction and atherosclerosis.

The Altered Migration and Distribution of Systemically Administered Mesenchymal Stem Cells in Morphine-Treated Recipients.

Mesenchymal stem cells (MSCs) have the ability to migrate to the site of injury or inflammation, and to contribute to the healing process. Since patients treated with MSCs are often users of analgesic drugs, to relieve their uncomfortable pain associated with the tissue disorder, there is a possibility of negative effects of these drugs on the migration of endogenous and exogenous MSCs. Therefore, we tested the impact of acute and chronic treatment with morphine on the migration and organ distribution of exogenous adipose tissue-derived MSCs in mouse models. Firstly, we showed that the incubation of MSCs with morphine significantly reduced the expression of adhesive molecules CD44 (HCAM), CD54 (ICAM-1) and CD106 (VCAM-1) on MSCs. Using a model of systemic administration of MSCs labeled with vital dye PKH26 and by the application of flow cytometry to detect living CD45-PKH26+ cells, we found a decreased number of labeled MSCs in the lung, spleen and bone marrow, and a significantly increased number of MSCs in the liver of morphine-treated recipients. A skin allograft model was used to study the effects of morphine on the migration of exogenous MSCs to the superficial wound. Intraperitoneally administered MSCs migrated preferentially to the wound site, and this migration was significantly decreased in the morphine-treated recipients. The present results showed that morphine significantly influences the distribution of exogenous MSCs in the body, and decreases their migration to the site of injury.

Characterization of the role for cadherin 6 in the regulation of human endometrial receptivity.

BACKGROUND: The endometrial luminal epithelium is the first point of attachment of embryos during implantation. Failure of embryos to firmly adhere results in implantation failure and infertility. A receptive endometrial luminal epithelium is achieved through the expression of adhesion molecules in the mid-secretory phase and is a requirement for implantation. Cadherin 6 (CDH6) is an adhesion molecule localizing to the endometrial luminal epithelial cell surface in the mid-secretory/receptive phase and knockdown of CDH6 in the Ishikawa cells (receptive endometrial epithelial cell line) compromises cell integrity. However, there are no studies investigating the role of CDH6 on receptivity and infertility. This study aimed to investigate whether CDH6 is dysregulated in the endometrium of women with infertility during the receptive window and the effect of CDH6 on endometrial adhesion and receptivity. METHODS: The expression and the localization of CDH6 in the human endometrium were determined by immunohistochemistry. Ishikawa cells were used to investigate the functional consequences of CDH6 knockdown on endometrial adhesive capacity to HTR8/SVneo (trophoblast cell line) spheroids in vitro. CDH6 knockdown was assessed by qPCR and immunoblotting. After CDH6 knockdown, the expression of type II cadherin family members and CDH6 functional partners were assessed by qPCR. Two-tailed unpaired student's t-test or one-way ANOVA as appropriate were used for statistical analysis with a significance threshold of P < 0.05. RESULTS: A significant reduction of CDH6 immunolocalization was recorded in the luminal and glandular epithelium of endometrium from women with infertility (P < 0.05) compared to fertile group respective cellular compartments in the mid-secretory phase. Functional analysis using Ishikawa cells demonstrated that knockdown of CDH6 (treated with 50 nM CDH6 siRNA) significantly reduced epithelial adhesive capacity (P < 0.05) to HTR8/SVneo spheroids compared to control and other type II cadherin family members likely failed to compensate for the loss of CDH6. The expression levels of CDH6 functional partners, catenin family members were not changed after CDH6 knockdown in Ishikawa cells. CONCLUSION: Together, our data revealed that CDH6 was dysregulated in the endometrium from women with infertility and altered Ishikawa cell adhesive capacity. Our study supports a role for CDH6 in regulating endometrial adhesion and implantation.

Comparison of biofilm production and virulence gene distribution among community- and hospital-acquired Staphylococcus aureus isolates from northwestern Iran.

INTRODUCTION: The emergence of antimicrobial-resistant isolates among Staphylococcus aureus and their genetic variations has become a major concern worldwide. The present study aims at comparing the biofilm formation and the genes encoding adhesion molecules in methicillin-susceptible, community- and hospital-acquired methicillin-resistant, vancomycin-intermediate and vancomycin-resistant S. aureus isolates. METHODOLOGY: The current study was conducted on 60 S.aureus isolates, collected at Urmia University of Medical Sciences, Iran, between the years 2014 and 2015. The modified Congo-red agar and Microtiter plate methods were used to determine biofilm production. PCR was used to detect the genes which were associated with a protein family of staphylococcal microbial surface components recognizing adhesive matrix molecules. The data were analyzed using SPSS (IBM SPSS Statistics, version 16). RESULTS: Of 60 isolates, 57 (95%) were biofilm producers. Unlike the bbp gene, which was only detected in 3 (5%) isolates, the eno and icaD genes were identified as the most prevalent as they were detected in 53 (88.3%) and 50 (85%) of 60 isolates, respectively. The dominant virulotype comprised eight genes (icaA, icaD, clfA, clfB, fnbA, cna, eno, ebpS) in eight isolates, six of which were community-acquired-MRSAs. CONCLUSION: A high percentage of the S. aureus isolates could produce a biofilm which is more common among methicillin-susceptible isolates. The high frequency of eno and icaD genes suggests that these genes may synergistically function in the onset and progression of bacterial colonization and biofilm formation. Meanwhile, this ability may help the bacteria resist the exposure of antibacterial agents and cause severe infections.

Interface of Phospholipid Polymer Grafting Layers to Analyze Functions of Immobilized Oligopeptides Involved in Cell Adhesion.

The aim of this study was to design a material surface for use in the analysis of the behavior of biomolecules at the interface of direct cell contact. A superhydrophilic surface was prepared with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), which was grafted onto a substrate with controlled polymer chain density. An arginine-glycine-aspartic acid (RGD) peptide was immobilized at the surface of the polymer graft surface (PMPC-RGD surface). Initial adhesion of the cells to this substrate was observed. The PMPC-RGD surface could enable cell adhesion only through RGD peptide-integrin interactions. The density and movability of the RGD peptide at the terminal of the graft PMPC chain and the orientation of the RGD peptide affected the density of adherent cells. Thus, the PMPC graft surface may be a good candidate for a new platform with the ability to immobilize biomolecules to a defined position and enable accurate analysis of their effects on cells.

Triorganotin Isothiocyanates Affect Migration and Immune Check-point Receptors in Human Triple-negative Breast Carcinoma MDA-MB-231 Cells.

BACKGROUND/AIM: Triple-negative breast cancer (TNBC) constitutes 15-20% of all breast carcinomas, affecting younger women more often and has a worse prognosis than other types of breast cancer, due to the combination of more aggressive clinical behavior and lack of molecular targets for therapy. This study assessed the effects of non-genotoxic concentrations of tributyltin isothiocyanate (TBT-ITC) and triphenyltin isothiocyanate (TPT-ITC) on MDA-MB-231 cells. MATERIALS AND METHODS: MTT assay, comet assay, kinetic imaging and flow cytometry were used for analysis of MDA-MB-231 cells. RESULTS: The results showed that 100 nM concentration of TBT-ITC and TPT-ITC, that did not affect viability or DNA integrity, slowed-down migration by CD44 down-regulation. Moreover, both compounds demonstrated immunomodulatory properties, attenuating PD-L1 expression in MDA-MB-231 cells. CONCLUSION: TPT-ITC was more effective in down-regulating CD44 expression and reducing migration than TBT-ITC, while TBT-ITC was more potent in lowering PD-L1 expression in comparison with TPT-ITC.

Microgravity-Induced Alterations of Inflammation-Related Mechanotransduction in Endothelial Cells on Board SJ-10 Satellite.

Endothelial cells (ECs) are mechanosensitive cells undergoing morphological and functional changes in space. Ground-based study has provided a body of evidences about how ECs can respond to the effect of simulated microgravity, however, these results need to be confirmed by spaceflight experiments in real microgravity. In this work, we cultured EA.hy926 ECs on board the SJ-10 Recoverable Scientific Satellite for 3 and 10 days, and analyzed the effects of space microgravity on the ECs. Space microgravity suppressed the glucose metabolism, modulated the expression of cellular adhesive molecules such as ICAM-1, VCAM-1, and CD44, and depressed the pro-angiogenesis and pro-inflammation cytokine secretion. Meanwhile, it also induced the depolymerization of actin filaments and microtubules, promoted the vimentin accumulation, restrained the collagen I and fibronectin deposition, regulated the mechanotransduction through focal adhesion kinase and Rho GTPases, and enhanced the exosome-mediated mRNA transfer. Unlike the effect of simulated microgravity, neither three-dimensional growth nor enhanced nitric oxide production was observed in our experimental settings. This work furthers the understandings in the effects and mechanisms of space microgravity on ECs, and provides useful information for future spaceflight experimental design.

Impact of weight reduction on insulin resistance, adhesive molecules and adipokines dysregulation among obese type 2 diabetic patients.

BACKGROUND: Type 2 diabetes mellitus is usually related to vascular problems and is associated with impairment in endothelial function characterized by impaired endothelial-dependent vasodilation and increased platelet adhesion. There is limitation in clinical studies that have addressed the beneficial effects of weight reduction in modulating biomarkers of endothelial dysfunction and adipokines dysregulation for obesity associated with type 2 diabetes mellitus. OBJECTIVE: This study was designed to detect the effects of weight loss on insulin resistance, adhesive molecules and adipokines dysregulation in obese type 2 diabetic patients. METHODS: Eighty obese patients with type 2 diabetes mellitus, their age ranged from 35-55 years and their body mass index ranged from 31-37 kg/m2 were equally assigned into 2 groups: the weight reduction group received aerobic exercises in addition to diet regimen, where the control group received medical treatment only for 12 weeks. RESULTS: There was a 24.04%, 19.33%, 22.78% ,12.28%, 9.35%, 22.53% & 10.12 % reduction in mean values of Homeostasis Model Assessment-Insulin Resistance Index (HOMA-IR), Leptin, Adiponectin, Resistin, intercellular cell adhesion molecule -1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin & body mass index (BMI) respectively in addition to 26.20% & 24.58% increase in the mean values of adiponectin & the quantitative insulin-sensitivity check index (QUICKI) respectively in group (A) at the end of the study. The mean values of leptin, resistin, insulin, HOMA-IR, ICAM-1, VCAM-1, E-selectin & BMI were significantly decreased in addition to significant increase in the mean values of adiponectin & QUICKI in group (A) those that received aerobic exercise training in addition to diet regimen. While the results of group (B) those that received no treatment intervention were not significant. In addition, there were significant differences between mean levels of the investigated parameters in group (A) and group (B) after treatment (P<0.05). CONCLUSION: Within the limit of this study, 10% reduction in body mass index modulates insulin resistance, adhesive molecules and adipokines dysregulation among obese type 2 diabetic patients.

Neutrophil adhesion and crawling dynamics on liver sinusoidal endothelial cells under shear flow.

Neutrophil (polymorphonuclear leukocyte, PMN) recruitment in the liver sinusoid takes place in almost all liver diseases and contributes to pathogen clearance or tissue damage. While PMN rolling unlikely appears in liver sinusoids and Mac-1 or CD44 is assumed to play respective roles during in vivo local or systematic inflammatory stimulation, the regulating mechanisms of PMN adhesion and crawling dynamics are still unclear from those in vivo studies. Here we developed a two-dimensional in vitro sinusoidal model with primary liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs) to investigate TNF-α-induced PMN recruitment under shear flow. Our data demonstrated that LFA-1 dominates the static or shear resistant adhesion of PMNs while Mac-1 decelerates PMN crawling on LSEC monolayer. Any one of LFA-1, Mac-1, and CD44 molecules is not able to work effectively for mediating PMN transmigration across LSEC monolayer. The presence of KCs only affects the randomness of PMN crawling. These findings further the understandings of PMN recruitment under shear flow in liver sinusoids.

The contributions of fasting and postprandial blood glucose increments to oxidative stress and inflammation in dyslipidemic type 2 diabetic patients with stable ischemic heart disease.

BACKGROUND/OBJECTIVES: Contributions of fasting and postprandial blood glucose increments on level of inflammation and oxidative stress biomarkers in patients with stable ischemic heart disease (IHD) and diabetes mellitus type 2 (T2DM) was evaluated. METHODOLOGY: Ninety T2DM patients (60 with IHD and 30 without IHD) treated with metformin and/or sulphonylurea were enrolled in cross-sectional nested case-control clinical study. The areas under the six-point daily glucose curve above the fasting glucose concentrations (AUCpp) and over 5.5mmol/L (AUCbg) were calculated to determine postprandial (AUCpp) and fasting (AUCbg-AUCpp) glucose increments. Malondialdehyde (MDA), protein carbonyl group (PCO), fibrinogen, C-reactive protein (hsCRP), leukocyte count and adhesion molecules ICAM-1 and VCAM-1 were determined. RESULTS: AUCbg-AUCpp 58.2 (95%CI 40.6-75.8) was higher in IHD group compared to non-IHD 36.9 (95%CI 23.5-50.2) mmol*h/L. They had significantly higher ICAM-1 (mean±SD) 72.70±30.6 vs. 60.22±22.6ng/mL and MDA 16.47±4.5 vs. 13.42±4.01µmol/g plasma proteins, but similar PCO, VCAM-1, fibrinogen, hsCRP concentration and leukocyte count. AUCpp positively correlated with MDA (r=0.45) and ICAM-1 (r=0.32) in the presence of IHD, and VCAM-1 (r=0.44) in the absence of IHD. AUCbg-AUCpp positively correlated with PCO (r=0.45) in the absence of IHD. The analysis revealed that AUCpp over turning point of 0mmol*h/L was associated with high MDA and ICAM-1 expression in diabetics with IHD. AUCbg-AUCpp over 30mmol*h/L leads to high oxidative protein modification in diabetics without IHD. CONCLUSION: In T2DM patients with stable IHD, AUCpp at any point, significantly contributes to increasing of MDA and ICAM-1 expression. Fasting blood glucose increment showed significant correlation with carbonyl content in diabetics without IHD.

[Connective tissue and inflammation]. / Kötoszövet és inflammatio.

The author summarizes the structure of the connective tissues, the increasing motion of the constituents, which determine the role in establishing the structure and function of that. The structure and function of the connective tissue are related to each other in the resting as well as inflammatory states. It is emphasized that cellular events in the connective tissue are part of the defence of the organism, the localisation of the damage and, if possible, the maintenance of restitutio ad integrum. The organism responds to damage with inflammation, the non specific immune response, as well as specific, adaptive immunity. These processes are located in the connective tissue. Sterile and pathogenic inflammation are relatively similar processes, but inevitable differences are present, too. Sialic acids and glycoproteins containing sialic acids have important roles, and the role of Siglecs is also highlighted. Also, similarities and differences in damages caused by pathogens and sterile agents are briefly summarized. In addition, the roles of adhesion molecules linked to each other, and the whole event of inflammatory processes are presented. When considering practical consequences it is stressed that the structure (building up) of the organism and the defending function of inflammation both have fundamental importance. Inflammation has a crucial role in maintaining the integrity and the unimpaired somato-psychological state of the organism. Thus, inflammation serves as a tool of organism identical with the natural immune response, inseparably connected with the specific, adaptive immune response. The main events of the inflammatory processes take place in the connective tissue.

Expression of cell adhesion molecules in laryngeal carcinoma - preliminary analysis.

AIM OF THE STUDY: Intercellular adhesion molecules present in immunocompetent cells as well as endothelium and tumour cells can regulate cell migration, angiogenesis, apoptosis, proliferation, and metastases in solid tumours. The aim of this study was to analyse the sICAM-1 (soluble intercellular adhesion molecule 1) and sVCAM-1 (soluble vascular cell adhesion molecule 1) expression in peripheral blood mononuclear cell (PBMC) cultures, and to find their relationships with clinicomorphological characteristics in laryngeal cancer. MATERIALS AND METHODS: The analysis included a group of 50 patients with verified squamous cell carcinoma of the larynx. The control group constituted 30 healthy volunteers. The pathological assessment included pTNM, stage, histological grade, and type of invasion according to the tumour front grading. The expression of adhesion molecules was assessed using the enzyme-linked immunosorbent assay (ELISA). RESULTS: Increased expression of sICAM-1 and sVCAM-1 was an indicator of more aggressive laryngeal carcinomas. More advanced local changes evaluated on the pT feature were connected with a higher sVCAM-1 (p = 0.017), but not sICAM-1 level. The presence of lymph node metastases correlated with a higher expression of adhesion molecules (p = 0.012 and p = 0.003, for sICAM-1 and sVCAM-1, respectively). Tumours with more diffuse growth and infiltrating with small cell groups (< 15/hpf) was characterised by the highest level of adhesive proteins (p = 0.001 and p = 0.02 for sICAM and sVCAM, respectively). Moreover, lower levels of sICAM-1 and sVCAM-1 were observed more frequently in patients who lived longer than five years after treatment. CONCLUSIONS: The study indicates the importance of the sICAM and sVCAM expression as indicators of advanced changes and prognosis in patients with laryngeal carcinoma.

The influence of β peptide dimmer modified by polyethylene glycol on anti-metastasis activity / 肿瘤

Objective: To observe the influence of β peptide dimmer modified by PEG on anti-metastasis activity. Methods: Cell culture plates were coated with fibronectin (FN) as extracellular matrix (ECM). The influence of β 2 and β 2-PEG peptides on the adhesion of tumor cells to FN were observed. The effects of β 2 and β 2-PEG peptides on migration and invasion ability of tumor cells in reconstituted basement membrane were measured by using Transwell Boyden and Matrigel method. Results: Compared with negative control, β 2 and β 2-PEG peptide significantly inhibited the adhesion of SMMC-7721 and HCCLM 6 tumor cells to FN in a time- and dose-dependent manner (P < 0.05). The inhibitory effects of β 2-PEG were stronger than β 2 peptides (P < 0.05). The mobility and invasion of HCCLM 6 and SMMC-7721 cells were obviously inhibited by β 2 peptide and β 2-PEG (P < 0.05). For HCCLM 6 cells, β 2 peptide and β 2-PEG inhibited cell migration were 54.6% and 56.3% and suppressed cell invasion were 36. 8% and 46.6%, respectively. For SMMC-7721 cells, the migration inhibitory rate were 43.6% and 45.7% and invasion inhibitory rate was 33.6% and 35.9% by β 2 and β 2-PEG peptide, respectively. The difference were not significant before and after PEGylation. Conclusions: The β 2 and β 2-PEG peptides specifically inhibite the adhesion of tumor cells to FN in a time- and dose-dependent manner. The anti-adhesion effects are enhanced after PEG modification. The β 2 and β 2-PEG peptides obviously suppress migration and invasion of the two kinds of tumor cells. The difference is not significant before and after PEG modification.

Expression of Leukocyte-Function-Associated Antigen-1 on Peripherial Blood Mononuclear Cells in Children with Febrile Seizures / 实用儿科临床杂志

Objective To observe the expression of leukocyte-function-associated antigen-1(LFA-1)immunoreaction in children with febrile seizures(FS),and explore the neuroimmunomodulation mechanisms in the pathogenesis of FS.Methods Adopting flow cytometry(FCM),the levels of LFA-1 contained in blood serum and peripheral blood mononuclear cells(PBMC)of 60 cases [simple FS(SFS)30 cases;complex FS(CFS)30 cases] with febrile convulsion were analyzed,and compared with those in a normal group(30 cases).Out of 60 children with FS group,the LFA-1 mRNA in 20 cases with SFS and 20 cases with CFS was analyzed,and LFA-1 mRNA in19 health children taken out from control group(30 cases)was analyzed.The real-time PCR was used to detect the expression of PBMC LFA-1 mRNA.Results The expression of LFA-1 in the surface of PBMC of the 3 groups,the highest LFA-1 level was in the SFS group(50.89?21.36),the lowest LFA-1 level was in the CFS group(34.35?11.45),and control group was(41.39?16.30).Significant differences were found in 3 groups(Pa

The inhibitive effects of resveratrol on adhesion of neutrophils to HUVECs induced by fMLP / 中国药理学通报

Aim To study the effects of resveratrol(Res)on the release of soluble adhesion molecules from human umbilical vein endothelial cells(HUVECs)induced by N-formyl-methionyl-leucyl-phenylal-anine(fMLP)and the adhesion between neutrophils and HUVECs.Methods The effects of Res on neutrophils adhesion to human umbilical endothelial cell(HUVECs)triggered by fMLP were examined.The soluble intercellular cell adhesive molecule-1(ICAM-1),the soluble vascular cell adhesive molecule-1(VCAM-1)and E-selectin release from fMLP(10 ?mol?L-1)stimulated HUVECs were determined by ELISA kits.The neutrophils isolated from human vein blood were loaded with Fluo-3,a fluorescent indicator,to detect intracellular free calcium concentration([Ca2+]i),and CLA was used as a chemiluminescent indicator to determine superoxide production in neutrophils.Results Res(1~50 ?mol?L-1)significantly inhibited neutrophil adhesion to fMLP-stimulated HUVECs and also obviously downregulated the levels of ICAM-1,VCAM-1 and E-selectin in supernatant of HUVECs culture stimulated by fMLP in the dose-dependent pattern.Res also suppressed fMLP-activated superoxide generation and[Ca2+]i increase in neutrophils.Conclusions Res involved in neutrophil adhesion to HUVECs intermediated by cell adhesive molecules expression trigged by[Ca2+]i and superoxide production in neutrophils,which means a lot to prevent inflammatory diseases.

Regulatory effect of iptakalim hydrochloride on excess expression of adhesive molecules in endothelial cells injury with high concentration of D-glucose / 中国药理学通报

Aim To investigate the regulatory effects of Iptakalim hydrochloride(Ipt) on excess expression of monocyte chemoattractant protein-1(MCP-1), intercellular cell adhesive molecule type-1(ICAM-1),vascular cell adhesive molecule1-1(VCAM-1) mRNA in bovine aortic endothelial cells cultured with high concentration D-glucose.Methods The endothelial cells were divided into three groups: control,model and Ipt group.The MCP-1,ICAM-1 and VCAM-1 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR).Results Compared with control group,MCP-1,ICAM-1 and VCAM-1 mRNA expres sion of model group all increased after treatments with 25 mmol?L~(-1) D-glucose for 16 h,respectively.Compare with model group,the excess expression of MCP-1,ICAM-1 mRNA was blocked by 1～10 ?mol?L~(-1) Ipt added for 20 h in advance,respectively but no significant effect was found in the expression of VCAM-1 mRNA.Conclusion High concentration of D-glucose induced excess expression of MCP-1,ICAM-1 and VCAM-1 mRNA,respectively.The excess expression of MCP-1,ICAM-1mRNA is inhibited by Ipt.