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Introduction: Coenzyme Q10 (CoQ10) has gained attention as a potential therapeutic agent for improving endothelial function. Several randomized clinical trials have investigated CoQ10 supplementation's effect on endothelial function. However, these studies have yielded conflicting results, therefore this systematic review and meta-analysis were conducted. Aim: This systematic review and meta-analysis were conducted to assess the effects of CoQ10 supplementation on endothelial factors. Methods: A comprehensive search was done in numerous databases until July 19th, 2023. Quantitative data synthesis was performed using a random-effects model, with weight mean difference (WMD) and 95% confidence intervals (CI). Standard methods were used for the assessment of heterogeneity, meta-regression, sensitivity analysis, and publication bias. Results: 12 studies comprising 489 subjects were included in the meta-analysis. The results demonstrated significant increases in Flow Mediated Dilation (FMD) after CoQ10 supplementation (WMD: 1.45; 95% CI: 0.55 to 2.36; p < 0.02), but there is no increase in Vascular cell adhesion protein (VCAM), and Intercellular adhesion molecule (ICAM) following Q10 supplementation (VCAM: SMD: − 0.34; 95% CI: − 0.74 to − 0.06; p < 0.10) (ICAM: SMD: − 0.18; 95% CI: − 0.82 to 0.46; p < 0.57). The sensitivity analysis showed that the effect size was robust in FMD and VCAM. In meta-regression, changes in FMD percent were associated with the dose of supplementation (slope: 0.01; 95% CI: 0.004 to 0.03; p = 0.006). Conclusions: CoQ10 supplementation has a positive effect on FMD in a dose-dependent manner. Our findings show that CoQ10 has an effect on FMD after 8 weeks of consumption. Additional research is warranted to establish the relationship between CoQ10 supplementation and endothelial function. [ABSTRACT FROM AUTHOR]

Objective To investigate the causal association between intercellular adhesion molecule 5 (ICAM5) and neuro 一 immune system disorders using a two 一 sample Mendelian randomization method. Methods SNPs meeting correlation, independence, and exclusivity with ICAM5 and neuro 一 immune system diseases were selected from the GWAS database. Sensitivity analysis was performed in terms of pleiotropy, heterogeneity, and leave - one - out method using the inverse variance weighting (IVW) method for the primary analysis, supplemented by three methods - WME (weighted median method), MR Egger and MR Presso. Results ICAM5 had a possible causal association with Alzheimer' s disease (OR = 1. 05, 95% CI: 1. 02 -1. 09), Parkinson' s disease (OR = 1.05, 95% CI: 1. 02 -1. 09), encephalitis (OR = 1.23, 95% CI: 1. 08 -1. 39), systemic lupus erythematosus (OR = 1. 16, 95% CI: 1. 23 -1.57) and Crohn' s disease (OR = 1. 16, 95% CI: 1. 07 -1. 27). The sensitivity analysis further confirmed the accuracy of the study. Conclusion A possible causal association between ICAM5 and five neuroimmune disorders provides a reference for the in 一 depth study of ICAM5 protein. [ABSTRACT FROM AUTHOR]

Acute kidney injury is associated with increased risk of heart failure and mortality. This study demonstrates that acute kidney injury induces remote cardiac dysfunction, damage, injury, and fibrosis via a galectin-3 (Gal-3) dependent pathway. Gal-3 originates from bone marrow-derived immune cells. Cardiac damage could be prevented by blocking this pathway.

Acute kidney injury is associated with increased risk of heart failure and mortality. This study demonstrates that acute kidney injury induces remote cardiac dysfunction, damage, injury, and fibrosis via a galectin-3 (Gal-3) dependent pathway. Gal-3 originates from bone marrow-derived immune cells. Cardiac damage could be prevented by blocking this pathway.

The complement system is an evolutionarily conserved arm of innate immunity, which forms one of the first lines of host response to pathogens and assists in the clearance of debris. A deficiency in key activators/amplifiers of the cascade results in recurrent infection, whereas a deficiency in regulating the cascade predisposes to accelerated organ failure, as observed in colitis and transplant rejection. Given that there are over 60 proteins in this system, it has become an attractive target for immunotherapeutics, many of which are United States Food and Drug Administration-approved or in multiple phase 2/3 clinical trials. Moreover, there have been key advances in the last few years in the understanding of how the complement system operates locally in tissues, independent of its activities in circulation. In this review, we will put into perspective the abovementioned discoveries to optimally modulate the spatiotemporal nature of complement activation and regulation at mucosal surfaces., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Pluchea Indica is a shrub plant found in mangrove forests. The leaves are consumed as food and herbal tea and exhibit various biological effects, such as antioxidant and anti-inflammatory activities, in macrophages and animal models. However, the inhibitory activity of P. Indica leaf extract on vascular inflammation remains unknown. Therefore, this study investigated the effect of an ethanol extract from P. Indica herbal tea leaves (PIE) on tumor necrosis factor-α (TNF-α)-induced human vascular endothelial EA.hy926 cells. The cytotoxic effect of PIE was determined by thiazolyl blue tetrazolium bromide assays. PIE at concentrations of 12.5 - 50 μg/mL did not show significant cytotoxicity, whereas PIE at concentrations ≥ 100 μg/mL decreased cell viability. PIE inhibited the production of reactive oxygen species (ROS) in TNF-α-stimulated endothelial cells. To evaluate the PIE's anti-vascular inflammatory activity, the protein expression of cell adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), was determined by western blot. PIE significantly decreased TNF-α-induced ICAM-1 and VCAM-1 expression in a concentration-dependent manner. Furthermore, PIE upregulated heme oxygenase-1 (HO-1) in a concentration- and time-dependent manner. Inhibiting the activity of HO-1 by tin protoporphyrin IX significantly blocked the suppressive effect of PIE on ICAM-1 but not VCAM-1 expression. Therefore, PIE exerts anti-inflammatory activity on vascular endothelial cells, at least in part, by suppressing ROS production and the induction of HO-1. The obtained data suggest that PIE is a promising substance for developing therapeutic agents or as an ingredient of functional food. [ABSTRACT FROM AUTHOR]

Aims: With the specific pharmacological activities including anti-inflammation, anti-oxidant and hypoglycemic effects, Naringin may possess the potential to ameliorate diabetic nephropathy (DN). The purpose of this study was to investigate the anti-DN effect of Naringin and the molecular mechanism by which Naringin ameliorates diabetic renal fibrosis. Methods: The effects of Naringin on fibronectin (FN) and intercellular adhesion molecule (ICAM-1) as well as the MAPK signaling pathways were detected in streptozotocin (STZ)-induced diabetic mice and high glucose (HG)-cultured glomerular mesangial cells (GMCs) respectively. Results: Naringin significantly alleviated the renal fibrosis injury and suppressed the expression of FN and ICAM-1, with down-regulating the phosphorylation of ERK1/2 and JNK and inhibiting the activation of the downstream activating protein (AP-1). There were no meaningful difference between Naringin and the MAPK specific inhibitors. Conclusion: Inhibiting the ERK1/2 and JNK MAPK signaling pathways is probably a novel mechanism by which Naringin alleviates experimental diabetic renal fibrosis.

Abstract Objective Regulation of intercellular adhesion molecule (ICAM)-1 in retinal endothelial cells is a promising druggable target for retinal vascular diseases. The ICAM-1-related (ICR) long non-coding RNA stabilizes ICAM-1 transcript, increasing protein expression. However, studies of ICR involvement in disease have been limited as the promoter is uncharacterized. To address this issue, we undertook a comprehensive in silico analysis of the human ICR gene promoter region. Results We used genomic evolutionary rate profiling to identify a 115 base pair (bp) sequence within 500 bp upstream of the transcription start site of the annotated human ICR gene that was conserved across 25 eutherian genomes. A second constrained sequence upstream of the orthologous mouse gene (68 bp; conserved across 27 Eutherian genomes including human) was also discovered. Searching these elements identified 33 matrices predictive of binding sites for transcription factors known to be responsive to a broad range of pathological stimuli, including hypoxia, and metabolic and inflammatory proteins. Five phenotype-associated single nucleotide polymorphisms (SNPs) in the immediate vicinity of these elements included four SNPs (i.e. rs2569693, rs281439, rs281440 and rs11575074) predicted to impact binding motifs of transcription factors, and thus the expression of ICR and ICAM-1 genes, with potential to influence disease susceptibility. We verified that human retinal endothelial cells expressed ICR, and observed induction of expression by tumor necrosis factor-α.

Objective: Fragmented QRS (fQRS) detected on a 12-lead electrocardiogram (ECG) has been demonstrated to be a marker of myocardial fibrosis. Intercellular adhesion molecule-1 (ICAM-1) is a protein which plays an important role in fibro-inflammatory processes. In this study, we aimed to investigate the relationship between ICAM-1 levels and the presence of fQRS in hypertensive patients. Methods: Ninety consecutive patients who were diagnosed with hypertension were included in the study. ECG and transthoracic echocardiography were performed to all patients. fQRS was defined as additional R' wave or notching/splitting of S wave in two contiguous ECG leads. Serum ICAM-1 levels were measured using the enzyme-linked immunosorbent assay method. Patients were divided into two groups according to the presence of fQRS. Results: A total of 90 patients (female, 65%; mean age: 54.6 ± 8.5 years) were included in the study. fQRS was detected on ECG recordings of 47 (52.2%) patients. The demographic characteristics were similar between the groups. Left atrial diameter (p =.003), interventricular septal thickness (p =.013), posterior wall thickness (p =.01), left ventricular mass (p =.002), left ventricular mass index (p <.001), left ventricular hypertrophy (p =.001), and ICAM-1 levels (p <.001) were found to be significantly increased in fQRS(+) group. In multivariate analysis, only high ICAM-1 level was observed to be an independent predictor for the presence of fQRS (odds ratio: 1.029; 95%Confidence Interval: 1.013–1.045, p <.001). Conclusion: A significant association exists between serum ICAM-1 levels and the presence of fQRS in hypertensive patients. The presence of fQRS may be used as an indicator of inflammation in hypertensive patients. [ABSTRACT FROM AUTHOR]

Inflammation plays an important role in the development of many diseases and health conditions. Because walnut has rich antioxidant content such as polyphenols, α-tocopherol and melatonin, walnuts against these diseases may be at least partially attributed to their anti-inflammatory effect. When comprehensive prospective studies were evaluated, vascular endothelial molecules such as intracellular adhesion molecule 1 and vascular cell adhesion molecule 1 and eicosanoid levels such as prostaglandin E2 and thromboxane A2 were found to be decreased after walnut-containing diet. In randomized controlled trials, it was found that c-reactive protein, interleukin-6, interleukin-1 and fibrinogen were reduced by approximately 5% in walnuts consumption of 30 - 65 grams per day. It has been found that walnut consumption in healthy, obese or diabetic individuals increases the concentration of adiponectin, which is anti-inflammatory cytokine, and consequently contributes to decrease in pro-inflammatory precursor molecules. Walnut can also increase nitric oxide synthesis, which can prevent oxygen mediated inflammation, due to its rich arginine content. Given the small number of studies examining the effects walnuts, more trials are needed to address the effects of walnuts on inflammation or cardiovascular risk. Although some pharmacologic treatments and exercise appear to be effective in reducing inflammation, healthy diets that include regular consumption of walnuts may protect against the possible consequences of low-grade inflammation. Finally, walnut contain alpha linolenic acid, polyphenol, melatonin and arginine. Lysine rate is higher than other different types of nuts, so it is important to conduct research on the effect of walnut consumption on inflammation. [ABSTRACT FROM AUTHOR]

Purpose: Pterygium, one of the most common ocular surface diseases, is characterized by inflammatory infiltrates, proliferation, angiogenesis, fibrosis, and extracellular matrix breakdown. The objective of this study was to elucidate the levels of the intercellular adhesion molecule (ICAM)-2, and ICAM-3 gene and protein expressions in pterygium. Methods: A total of 59 patients with pterygium were included in this study. mRNA from pterygial and conjunctival autograft tissues were extracted, and real-time polymerase chain reaction on the BioMark HD dynamic array system was performed for the ICAM-2 and ICAM-3 gene expressions. ICAM-2 and ICAM-3 protein expressions using western blot and immunohistochemistry methods were also investigated in pterygial and conjunctival autograft tissues. Results: ICAM-2 and ICAM-3 gene expressions were markedly augmented in pterygial tissues (P = 0.0018 and P = 0.0023, respectively). Significant increases in protein expressions in pterygial tissues were also detected for ICAM-2 and ICAM-3 (P = 0.0116 and P = 0.0252, respectively). In the immunohistochemical studies, there was a marked increase in ICAM-3 (P = 0.0152), but not in ICAM-2 (P = 0.1041), protein expressions in pterygial tissues. Significant positive correlations between pterygia grading with ICAM-2 protein expression (P = 0.0398) and ICAM-3 immunohistochemical scores (P = 0.0138) were observed. Conclusion: These results demonstrate, for the first time, the expressions of ICAM-2 and ICAM-3 in the pterygium. These findings may help to understand the signal transduction mechanisms in the pterygium formation and provide a new therapy strategy for pterygium treatment. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights: • Naringin significantly alleviated the diabetic renal fibrosis injury. • Naringin inhibited the activation of ERK and JNK MAPK signaling pathways in high glucose condition. • Naringin inhibited the transcriptional activity of AP-1. • Naringin alleviated diabetic renal fibrosis by inhibiting the ERK and JNK MAPK signaling pathways. Abstract Aims With the specific pharmacological activities including anti-inflammation, anti-oxidant and hypoglycemic effects, Naringin may possess the potential to ameliorate diabetic nephropathy (DN). The purpose of this study was to investigate the anti-DN effect of Naringin and the molecular mechanism by which Naringin ameliorates diabetic renal fibrosis. Methods The effects of Naringin on fibronectin (FN) and intercellular adhesion molecule (ICAM-1) as well as the MAPK signaling pathways were detected in streptozotocin (STZ)-induced diabetic mice and high glucose (HG)-cultured glomerular mesangial cells (GMCs) respectively. Results Naringin significantly alleviated the renal fibrosis injury and suppressed the expression of FN and ICAM-1, with down-regulating the phosphorylation of ERK1/2 and JNK and inhibiting the activation of the downstream activating protein (AP-1). There were no meaningful difference between Naringin and the MAPK specific inhibitors. Conclusion Inhibiting the ERK1/2 and JNK MAPK signaling pathways is probably a novel mechanism by which Naringin alleviates experimental diabetic renal fibrosis. [ABSTRACT FROM AUTHOR]

ObjectivesRespiratory epithelial cells are the first site of interaction of allergens with the immune system. The aim of this study was to examine the effect of epithelial cells, which were stimulated with house dust mite (HDM) extracts, on the immune response of peripheral blood mononuclear cells (PBMCs).MethodsPrimary nasal polyp epithelial cells were exposed to dermatophagoides pteronyssinus and dermatophagoides farina for 48 hr, and then the supernatant and cells were collected. After stimulation with HDM extract, the epithelial cells were co-cultured with PBMCs for 72 hr and then the supernatant was collected. We measured the interleukin (IL)-8 and granulocyte-macrophage colony stimulating factor to determine the activation of the epithelial cells. The tumor necrosis factor (TNF)-α, IL-5 and interferon-γ were measured to evaluate the interaction between the epithelial cells and the PBMCs. The mRNA expression of intercellular adhesion molecule 1 (ICAM-1) was assessed using the anti-ICAM-1 antibody.ResultsThe HDM extracts activated the nasal epithelial cells and enhanced the expression of ICAM-1 mRNA and cell membrane ICAM-1. When the activated epithelial cells were co-cultured with PBMCs, the PBMCs produced lager amounts of TNF-α and IL-5. However the cytokine production was not inhibited by pretreatment with ICAM-1 antibody.ConclusionHDM allergens induce allergic inflammation by activating nasal epithelial cells, yet the interaction of the epitheila cells and the PBMCs may not be associated with an ICAM-1 medicated mechanism.

Intercellular adhesion molecule1 (ICAM1) is involved in adhesion and transmigration of leukocytes across endothelium, promoting brain inflammation and leading to brain diseases. Here, we studied the mechanism that regulates ICAM expression in response to proinflammatory cytokine tumor necrosis factor alpha (TNF-α). ICAM1 mRNA and protein levels in human brain microvascular endothelial cells dramatically increased after TNF-α treatment. TNF-α also upregulated histone demethylases KDM1B and KDM7A responsible for demethylation of H3K9me2, a well-known repression marker. Knockdown of KDM7A by a small interfering RNA reduced the ICAM1 protein level and leukocyte adhesion without an effect on ICAM1 mRNA expression. In contrast, a KDM1B knockdown did not affect TNF-α-induced ICAM1 expression. Thus, KDM7A-mediated ICAM1 protein upregulation is likely related to protein stability, not a histone-mediated epigenetic mechanism. Experiments with cycloheximide supported the role of KDM7A in ICAM1 protein stabilization. Further experiments suggest that KDM7A regulates ICAM1 protein stability via a lysosome-dependent pathway. Lysosome inhibitors increased the TNF-α-induced ICAM1 protein level and restored KDM7A knockdown-induced downregulation of ICAM1. In contrast, the KDM7A knockdown had no effect on proteasome-mediated ICAM1 degradation. We also found that the transcription factor EB protein level reduced in response to TNF-α but increased by the KDM7A knockdown. Immunocytochemical analysis revealed weak lysosome formation with high ICAM1 immunoreactivity after TNF-α treatment, but KDM7A knockdown reversed this response, resulting in strong lysosome formation with ICAM1 protein clustering in lysosomes. Taken together, our results show that KDM7A mediates TNF-α-induced ICAM1 protein upregulation and is mediated by induction of KDM7A, which regulates the TFEB-mediated lysosomal activity. [ABSTRACT FROM AUTHOR]

The elevated cardiovascular morbidity and mortality in chronic kidney disease (CKD) is linked with endothelial dysfunction secondary to the pro-inflammatory and pro-oxidative state typical of this pathology. In consideration of the well-known pleiotropic effect of statins, we investigated the effect of cholesterol lowering treatment on endothelial dysfunction markers (MED), asymmetric dimethylarginine (ADMA), vascular cell (VCAM) and intercellular (ICAM) adhesion molecule. Plasma MED concentrations, inflammation and oxidative stress indices [Kynurenine/Tryptophan (Kyn/Trp) ratio, malondialdehyde (MDA) and allantoin/uric acid (All/UA) ratio] were measured in 30 CKD patients randomized to three cholesterol lowering regimens for 12 months (simvastatin 40 mg/day, ezetimibe/simvastatin 10/20 mg/day, or ezetimibe/simvastatin 10/40 mg/day). Treatment significantly reduced ADMA concentrations in all patients [0.694 μmol/L (0.606–0.761) at baseline vs. 0.622 μmol/L (0.563–0.681) after treatment, p < 0.001]. ADMA reduction was paralleled by a significant decrease of MDA, All/AU ratio and Kyn/Trp ratio, but not VCAM and ICAM plasma concentrations. Cholesterol lowering treatment was associated with a significant reduction in plasma ADMA concentrations in CKD patients. This might be mediated by reduced oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

Objectives Matrix metallopeptidase 9 ( MMP9) and soluble intercellular adhesion molecule 1 ( sICAM-1) are both involved in the restructuring of connective tissues. Evidence also implicates MMP9 and sICAM in cardiovascular and neoplastic diseases, where blood levels may be a marker of disease severity or prognosis. In individuals with bipolar disorder ( BD), higher risk for cardiovascular illness has been extensively reported. Methods The aim of this investigation was to measure and compare peripheral levels of serum MMP9 and sICAM in adults with euthymic BD and healthy controls ( HC). Furthermore, we focussed on correlations with illness severity and metabolic parameters. Results MMP9 levels among the BD sample (n = 112) were significantly higher than among the HC (n = 80) ( MMP9: F = 9.885, p = 0.002, η2 = 0.058) after controlling for confounding factors. Patients with BD in a later, progressive stage of disease showed significantly higher MMP9 as well as sICAM-1 levels compared to patients with BD in an earlier stage of disease ( MMP9: F = 5.8, p = 0.018, η2 = 0.054; sICAM-1: F = 5.6, p = 0.020, η2 = 0.052). Correlation analyses of cognitive measures revealed a negative association between performance on the d2 Test of Attention and MMP9 ( r = −0.287, p = 0.018) in the BD sample. Despite the sample being euthymic (i.e., according to conventional criteria) at the time of analysis, we found significant correlations between MMP9 as well as sICAM-1 and subthreshold depressive/hypomanic symptoms. Conclusions A collection of disparate findings herein point to a role of MMP9 and cICAM-1 in the patho-progressive process of BD: the increased levels of serum MMP9 and sICAM-1, the correlation between higher levels of these parameters, progressive stage, and cognitive dysfunction in BD, and the positive correlation with subthreshold symptoms. As sICAM-1 and MMP9 are reliable biomarkers of inflammatory and early atherosclerotic disease, these markers may provide indications of the presence of occult cardiovascular disease in this highly at-risk population. [ABSTRACT FROM AUTHOR]

We performed this study to determine (1) whether the levels of inflammatory mediators, including matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-3 (ICAM-3), in gastric fluid (GF) in premature newborns are associated with those in amniotic fluid (AF) in their mothers and (2) whether the levels of the inflammatory mediators in newborn GF are associated with the presence of intrauterine inflammation (IUI). Methods: Sixty-two pairs of pregnant women and their premature newborns born at <35 weeks' gestation by cesarean delivery were enrolled in this study. AF and newborn GFs were obtained during cesarean section procedures. Levels of MMP-9, ICAM-3, interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF- α) were measured and compared between the AF and newborn GFs in each dyad, according to the presence or absence of chorioamnionitis (CA), preterm prelabor rupture of membranes (PPROM), and preterm labor (PTL). Results: The levels of MMP-9, ICAM-3, IL-6, IL-8, and TNF-α in newborn GF were significantly correlated with those in AF in each dyad. The premature newborns and their mothers with CA had significantly higher GF MMP-9, IL-8, and TNF-α levels than those without CA. Those with PPROM or PTL showed similar findings in terms of GF MMP-9, IL-8, and TNF-α levels. Conclusion: The newborn GF immediately after birth can be a useful alternative source of information on whether a premature infant has been exposed to IUI at the time of delivery. [ABSTRACT FROM AUTHOR]

Force transduction at cell-cell adhesions regulates tissue development, maintenance and adaptation. We developed computational and experimental approaches to quantify, with both sub-cellular and multi-cellular resolution, the dynamics of force transmission in cell clusters. Applying this technology to spontaneously-forming adherent epithelial cell clusters, we found that basal force fluctuations were coupled to E-cadherin localization at the level of individual cell-cell junctions. At the multi-cellular scale, cell-cell force exchange depended on the cell position within a cluster, and was adaptive to reconfigurations due to cell divisions or positional rearrangements. Importantly, force transmission through a cell required coordinated modulation of cell-matrix adhesion and actomyosin contractility in the cell and its neighbors. These data provide insights into mechanisms that could control mechanical stress homeostasis in dynamic epithelial tissues, and highlight our methods as a resource for the study of mechanotransduction in cell-cell adhesions.

Aim: The etiologic role of inflammatory pathways in the development of diabetic complications, especially cardiovascular events, has been established. The anti-inflammatory role of metformin and pioglitazone has been described; however, no study to date has compared the efficacy of these common oral agents in this regard. In this study, the authors aimed to compare the anti-inflammatory properties of pioglitazone and metformin, with respect to their effect on serum concentrations of highly sensitive C-reactive protein (hsCRP), osteoprotegerin (OPG), intercellular adhesion molecule-1 (ICAM-1) and adiponectin. Methods: In an open-label randomized clinical trial, 117 patients with newly diagnosed type 2 diabetes mellitus were visited; 84 fulfilled the inclusion criteria, and were randomly allocated to 2 arms receiving either 1 000 mg/d metformin or 30 mg/d pioglitazone, respectively. Biochemical assessments were made at baseline and the end of the 3 months trial. Results: Significant reduction in FPG, insulin and HbA1c in women and men of both arms were observed. Log-hsCRP values significantly decreased in both arms. A decreasing, but non-significant trend in log-OPG levels was observed in women of the metformin arm (p = 0.063). A greater reduction in log-ICAM levels was identifiable in men receiving pioglitazone compared to the other arm (p = 0.008); in addition, the same trend was observed in log-OPG values (p = 0.029). Nonetheless, reduction in log-ICAM and log-OPG levels was comparable between the 2 arms. A significant increase in adiponectin was observed in both men and women in the pioglitazone arm (p < 0.001), whereas changes were non-significant in the metformin arm. Conclusion: Remarkably, patients receiving pioglitazone revealed more significant reduction in inflammatory markers. [ABSTRACT FROM AUTHOR]

OBJECTIVE: It has been shown that genetic factors have a role in the development of acromegaly. We aimed to investigate the association between intercellular adhesion molecule (ICAM)-1 E469K polymorphism and some cardiovascular clinical parameters of acromegalic patients. PATIENTS AND METHODS: We included 41 patients with acromegaly and 65 healthy subjects with similar age and sex to the study. Fasting plasma glucose (FPG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglyceride (TG) were analyzed. Genotyping was made by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The frequency of genotype and allel ICAM-1 E469K was not significantly different between control and patients (p > 0.05). Systolic blood pressure (SBP), diastolic blood pressure (DBP) and FPG levels were significantly higher, and HDL-C was significantly lower in patients with KK genotypes compared to patients with EE genotype in acromegaly group (p < 0.05). CONCLUSIONS: This is the first study to investigate the role of ICAM gene polymorphism in acromegaly and its cardiovascular characteristics. ICAM E469K may not be a risk factor for the acromegaly in Turkish population but may be associated with hypertension, higher FPG and lower HDL-C in acromegalic patients. [ABSTRACT FROM AUTHOR]

Upregulation of intercellular adhesion molecule 1 (ICAM-1) is an early event in lesion formation in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Monitoring its expression may provide a biomarker for early disease activity and allow validation of anti-inflammatory interventions. Our objective was therefore to explore whether ICAM-1 expression can be visualized in vivo during EAE with magnetic resonance imaging (MRI) using micron-sized particles of iron oxide (MPIO), and to compare accumulation profiles of targeted and untargeted MPIO, and a gadolinium-containing agent. Targeted αICAM-1-MPIO/untargeted IgG-MPIO were injected at two model-characteristic phases of EAE (in myelin oligodendrocyte glycoprotein35-55-immunized C57BL/6 J mice), that is, at the peak of the acute phase (14 ± 1 days post-immunization) and during the chronic phase (26 ± 1 days post-immunization), followed by T2*-weighted MRI. Blood-brain barrier (BBB) permeability was measured using gadobutrol-enhanced MRI. Cerebellar microvessels were analyzed for ICAM-1 mRNA expression using quantitative PCR (qPCR). ICAM-1 and iron oxide presence was examined with immunohistochemistry (IHC). During EAE, ICAM-1 was expressed by brain endothelial cells, macrophages and T-cells as shown with qPCR and (fluorescent) IHC. EAE animals injected with αICAM-1-MPIO showed MRI hypointensities, particularly in the subarachnoid space. αICAM-1-MPIO presence did not differ between the phases of EAE and was not associated with BBB dysfunction. αICAM-1-MPIO were associated with endothelial cells or cells located at the luminal side of blood vessels. In conclusion, ICAM-1 expression can be visualized with in vivo molecular MRI during EAE, and provides an early tracer of disease activity. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: In this study, we investigated the effect of melatonin administration on four markers of endothelial cell function including intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), C-reactive protein (CRP), and nitric oxide (NO) on patients with three vessels coronary disease. Materials and Methods: This double-blind, randomized, controlled trial study was conducted on 39 patients (32 men and 7 women) with three vessels coronary disease. The case group included 20 patients who received 10 mg oral melatonin 1 h before sleeping for 1 month. The control group included 19 patients who received placebo 1 h before sleeping for 1 month. The serum levels of CRP, ICAM, VCAM, and NO were compared after 1 month treatment. Results: After 1 month of melatonin treatment, the mean level of ICAM, VCAM, and CRP showed a statistically significant decrease in the case group. On the other hand, the mean level of VCAM increased significantly in the control group. The mean levels of CRP and ICAM were also increased in the control group, but the difference did not reach the significant threshold. With respect to NO, there was a statistically significant increase in the case group, while there was a statistically significant decrease in serum NO in the control group. Conclusions: The results of this study suggested that melatonin may have beneficial effects on endothelial oxidative stress even in patient with severe and advanced atherosclerosis.

Copyright of West Indian Medical Journal is the property of West Indian Medical Journal (WIMJ) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background Childhood asthma is characterized by chronic airway inflammation. Integrative genomic analysis of airway inflammation on genetic and protein level may help to unravel mechanisms of childhood asthma. We aimed to employ an integrative genomic approach investigating inflammation markers on DNA, mRNA, and protein level at preschool age in relationship to asthma development. Methods In a prospective study, 252 preschool children (202 recurrent wheezers, 50 controls) from the Asthma DEtection and Monitoring (ADEM) study were followed until the age of six. Genetic variants, mRNA expression in peripheral blood mononuclear cells, and protein levels in exhaled breath condensate for intercellular adhesion molecule 1 (ICAM1), interleukin (IL)4, IL8, IL10, IL13, and tumor necrosis factor α were analyzed at preschool age. At six years of age, a classification (healthy, transient wheeze, or asthma) was based on symptoms, lung function, and medication use. Results The ICAM1 rs5498 A allele was positively associated with asthma development (p = 0.02) and ICAM1 gene expression (p = 0.01). ICAM1 gene expression was positively associated with exhaled levels of soluble ICAM1 (p = 0.04) which in turn was positively associated with asthma development (p = 0.01). Furthermore, rs1800872 and rs1800896 in IL10 were associated with altered IL10 mRNA expression (p < 0.01). Exhaled levels of IL4, IL10, and IL13 were positively associated with asthma development (p < 0.01). Conclusions In this unique prospective study, we demonstrated that ICAM1 is associated with asthma development on DNA, mRNA, and protein level. Thus, ICAM1 is likely to be involved in the development of childhood asthma. [ABSTRACT FROM AUTHOR]

Background: Endocan is a novel human endothelial cell–specific molecule. The central role of leukocytes and endothelial dysfunction in the development of Behçet disease (BD) led us to hypothesize that endocan might be a marker of this disease. Objective: We investigated the relationship between serum levels of endocan and disease activity in patients with BD. Methods: In all, 33 patients (16 active, 17 inactive) with BD and 35 healthy persons were included in the study. Endocan and C-reactive protein were measured in all subjects. Results: Patients with BD had significantly higher serum endocan levels. Mean serum levels of endocan were 1.29 ± 0.60 ng/mL (range: 0.58-2.99) in patients with BD and 0.75 ± 0.16 ng/mL (range: 0.48-1.21) in control subjects (P < .001). In patients with BD, serum endocan levels correlated moderately but significantly with C-reactive protein, erythrocyte sedimentation rate, and disease activity. Receiver operating characteristic curve analysis suggested that the optimum endocan level cut-off point for patients with BD was 0.87 ng/mL, with a sensitivity and specificity of 75.8% and 80%, respectively (area under curve 0.835, 95% confidence interval 0.738-0.932). Limitations: The main limitation of our study is the relatively small sample size. Conclusions: Circulating endocan may be a marker of BD activity. [Copyright &y& Elsevier]

The anti-inflammatory potential of eight indigenous probiotic Lactobacillus isolates was evaluated in vitro in terms of modulating the expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in human acute monocytic leukemia (THP-1) cells under inflammatory conditions. Amongst these, Lactobacillus plantarum Lp91 was the most potent anti-inflammatory strain as it evoked a significant ( P < 0.001) down-regulation of TNF-α by −1.45-fold relative to the control in THP-1 cells. However, in terms of IL-6 expression, all the strains could up-regulate its expression considerably at different levels. Hence, based on in vitro expression of TNF-α, Lp91 was selected for in vivo study in lipopolysaccharide (LPS)-induced mouse model to look at the expression of TNF-α, IL-6, monocyte chemotactic protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule (ICAM-1) and E-selectin in mouse aorta. In LPS challenged (2 h) mice group fed with Lp91 for 10 days, TNF-α, IL-6, MCP-1, VCAM-1, ICAM-1 and E-selectin expressions were significantly down-regulated by 3.10-, 10.02-, 4.22-, −3.14-, 2.28- and 5.71-fold relative to control conditions. In conclusion, Lp91 could serve as a candidate probiotic strain to explore it as a possible biotherapeutic anti-inflammatory agent against inflammatory diseases including cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background Babesia infections in dogs can result in a wide range of clinical and laboratory presentations, including coagulopathy. Expression of intercellular adhesion molecule-1 (ICAM-1) and von Willebrand factor ( vWF) in dogs with babesiosis is unknown. Objectives Whether inflammation in babesiosis triggers activation of ICAM-1 and the coagulation system. Animals Twelve and 10 dogs with naturally occurring babesiosis before and after antiparasitic treatment, respectively, were compared with 10 healthy dogs. Methods In this prospective study, diagnosis was made by blood smear examination and confirmed by PCR. C-reactive protein (CRP), soluble intercellular adhesion molecule 1 ( sICAM-1), and von Willebrand factor ( vWF) levels were measured by a canine ELISA kit, fibrinogen (FIB) and factor VIII activity levels were measured by coagulometric methods, and blood cell counts (WBC, RBC, PLT) were determined with an automatic analyzer. Results Compared to healthy dogs, the CRP, sICAM-1, and FIB concentrations were significantly increased before therapy and remained high for 3 days after therapy in dogs with babesiosis. vWF activity was significantly decreased in dogs with babesiosis before treatment. FVIII activity did not differ between dogs with babesiosis and healthy dogs. WBC; RBC and PLT were significantly lower before treatment and normalized by 3 days after treatment. Conclusion and Clinical Importance A proinflammatory condition in babesiosis appears to influence endothelial dysfunction and hemostatic activity . Although clearly beneficial for the parasite, sequestered blood cells can obstruct blood flow in small vessels, promote an inflammatory state, and could increase the severity of babesiosis. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To examine CD99 expression and its functional role in ICAM-1 induction in human gingival fibroblasts (HGFs) and human gingival epithelial cells (HGECs) by activating cells with anti-CD99 monoclonal antibody, MT99/3. Background: Engagement of CD99 with agonistic antibodies has been shown to regulate immune responses, cell adhesion and migration, and cell death in several studies. Particularly, this engagement results in transendothelial migration of leukocytes mediated by intercellular adhesion molecule-1 (ICAM-1) induction in endothelial cells. Methods: Total mRNA and protein were isolated from HGFs and HGECs for analyses of CD99 and ICAM-1 expression. Surface expression of CD99 and ICAM-1 was analysed by flow cytometry, and the detection of soluble ICAM-1 was assayed by immunoprecipitation and ELISA. Results: CD99 surface expression was constitutive on HGFs to a greater extent than that on HGECs. CD99 ligation with MT99/3 induced ICAM-1 mRNA expression in HGFs, but not in HGECs. Interestingly, CD99 ligation led to an increased level of soluble ICAM-1 detected in culture supernatant, whereas interleukin-1β (IL-1β) treatment induced expression of membrane-bound ICAM-1. Furthermore, ICAM-1 induction by CD99 engagement was demonstrated to involve the activation of the p50 subunit of nuclear factor-kappaB (NF-κB), extracellular signal-regulated kinase, and p46 c-Jun N-terminal kinase that differed from that by IL-1β treatment. Conclusion: Our study has shown the involvement of CD99 ligation in the up-regulation of ICAM-1 expression and its secretion in gingival fibroblasts, which may be essential for better understanding of the pathogenesis of periodontal disease. [Copyright &y& Elsevier]

Release and activation of pro-inflammatory mediators are among the most important induced factors that are involved in the scorpion envenomation pathogenesis. Inflammatory response and lung reactivity were studied in mice following subcutaneous injection with Androctonus australis hector (Aah) venom. Venom immunodetection in lungs and sequestered cell population in the airways were determined. Cytokines, cellular peroxidase activities (eosinophil peroxidase, myeloperoxydase), and IgE antibodies were also assessed. Immunohistochemical study revealed a positive detection of the Aah venom in the alveolar wall, venule lumens, and inside inflammatory cells. Severe lung edema associated with rapid inflammatory response was observed after animal envenomation. Lung neutrophilia and eosinophilia were accompanied with IL-4, IL-5 release, and IgE synthesis. In conclusion, high cytokine levels, recruitment of inflammatory cells (eosinophils and neutrophils), and increased IgE concentration may contribute to the exacerbation and maintenance of the induced inflammatory response in lungs by scorpion venom. These results lead to the better understanding of this induced pathogenesis and could help the physicians to take care of envenomed patients. [ABSTRACT FROM AUTHOR]

The explosive development of nanotechnology has caused an increase in unintended biohazards in humans and in the ecosystem. Similar to particulate matter, nanoparticles (NPs) are strongly correlated with the increase in incidences of cardiovascular diseases, yet the mechanisms behind this correlation remain unclear. Within the testing concentrations of 0.1–10 μg/ml, which did not cause a marked drop in cell viability, zinc oxide NPs (ZnO-NPs) induced intercellular adhesion molecule-1 (ICAM-1) messenger RNA, and protein expression in both concentration- and time-dependent manner in treated human umbilical vein endothelial cells (HUVECs). ZnO-NPs treatment cause the activation of Ras-related C3 botulinum toxin substrate 1 (Rac1)/cell division control protein 42 homolog (Cdc42) and protein accumulation of mixed lineage kinase 3 (MLK3), followed by c-Jun N-terminal kinase (JNK) and transcription factor c-Jun activation. Induction of ICAM-1 and phosphorylation of JNK and c-Jun could be inhibited by either JNK inhibitor SP600125 or Rac guanosine triphosphatase inhibitor NSC23766 pretreatment. In addition, pretreatment with NSC23766 significantly reduced MLK3 accumulation, suggesting the involvement of Rac1/Cdc42-MLK3-JNK-c-Jun signaling in the regulation of ZnO-NPs–induced ICAM-1 expression, whereas these signaling factors were not activated in zinc oxide microparticles (ZnO-MPs)–treated HUVECs. The increase of ICAM-1 expression on ZnO-NPs–treated HUVECs enables leukocytes to adhere and has been identified as an indicator of vascular inflammation. Our data are essential for safety evaluation of the clinical usage of ZnO-NPs in daily supplements, cosmetics, and biomedicines. [ABSTRACT FROM PUBLISHER]

Lung inflammatory responses in the absence of infection are considered to be one of primary mechanisms of ventilator-induced lung injury. Here, we determined the role of calpain in the pathogenesis of lung inflammation attributable to mechanical ventilation. Male C57BL/6J mice were subjected to high (28 ml/kg) tidal volume ventilation for 2 h in the absence and presence of calpain inhibitor I (10 mg/kg). To address the isoform-specific functions of calpain 1 and calpain 2 during mechanical ventilation, we utilized a liposome-based delivery system to introduce small interfering RNAs targeting each isoform in pulmonary vasculature in vivo. Mechanical ventilation with high tidal volume induced rapid (within minutes) and persistent calpain activation and lung inflammation as evidenced by neutrophil recruitment, production of TNF-α and IL-6, pulmonary vascular hyperpermeability, and lung edema formation. Pharmaceutical calpain inhibition significantly attenuated these inflammatory responses caused by lung hyperinflation. Depletion of calpain 1 or calpain 2 had a protective effect against ventilatorinduced lung inflammatory responses. Inhibition of calpain activity by means of siRNA silencing or pharmacological inhibition also reduced endothelial nitric oxide (NO) synthase (NOS-3)-mediated NO production and subsequent ICAM-1 phosphorylation following high tidal volume ventilation. These results suggest that calpain activation mediates early lung inflammation during ventilator-induced lung injury via NOS-3/NO-dependent ICAM-1 phosphorylation and neutrophil recruitment. Inhibition of calpain activation may therefore provide a novel and promising strategy for the prevention and treatment of ventilator-induced lung injury. [ABSTRACT FROM AUTHOR]

Abstract: β2 agonists reduce the frequency of exacerbations in patients with bronchial asthma and chronic obstructive pulmonary disease caused by respiratory virus infection. β2 agonists reduce the production of pro-inflammatory cytokines. However, the inhibitory effects of β2 agonists on the infection of rhinovirus, the major cause of exacerbations, have not been well studied. To examine the effects of a β2 agonist, procaterol, on rhinovirus infection and rhinovirus infection-induced airway inflammation, human tracheal epithelial cells were infected with a major group rhinovirus, type 14 rhinovirus. Rhinovirus infection increased viral titers and the content of pro-inflammatory cytokines, including interleukin-1β and interlukin-6, in supernatant fluids and rhinovirus RNA in the cells. Procaterol reduced rhinovirus titers and RNA, cytokine concentrations, and susceptibility to rhinovirus infection. Procaterol reduced the expression of intercellular adhesion molecule-1 (ICAM-1), the receptor for type 14 rhinovirus, and the number of acidic endosomes in the cells from which rhinovirus RNA enters into the cytoplasm. Procaterol inhibited the activation of nuclear factor kappa-B (NF-κB) proteins including p50 and p65 in the nuclear extracts, while it increased the cytosolic amount of the inhibitory kappa B-α and intracellular cyclic AMP (cAMP) levels. A selective β2-adrenergic receptor antagonist ICI 118551 [erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol] reversed the inhibitory effects of procaterol on rhinovirus titers and RNA, susceptibility to rhinovirus infection, pro-inflammatory cytokines production, ICAM-1 expression, acidic endosomes, and NF-κB. ICI 118551 also reversed the effects of procaterol on cAMP levels. Procaterol may inhibit rhinovirus infection by reducing ICAM-1 and acidic endosomes as well as modulate airway inflammation in rhinovirus infection. [Copyright &y& Elsevier]

Lewis DF., Canzoneri BJ., Gu Y, Zhao S, Wang Y. Maternal Levels of Prostacyclin, Thromboxane, ICAM, and VCAM in normal and preeclamptic pregnancies. Am J Reprod Immunol 2010; 64: 376-383 To evaluate whether impaired endothelial function and endothelial inflammatory response occur in parallel in the women with preeclampsia. Venous blood was drawn from normal ( n = 40) and severe preeclamptic (sPE) ( n = 40) pregnant women when they were admitted to the L&D Unit and 24 hrs after delivery. Plasma and serum samples were extracted and measured for 6-keto PGF1α and TXB (stable metabolites of PGI2 and TXA2), and intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) by ELISA. Data are analyzed by Mann-Whitney test and paired t-test. The statistical significance is set as P < 0.05. Plasma 6-keto PGF1α levels were significantly reduced at admission and 24 hr after delivery in sPE compared to normal pregnant controls, P < 0.01. The ratio of 6-keto PGF1α and TXB was significant less in sPE than that in normal pregnant controls before delivery. There was no significant difference for ICAM and VCAM levels between normal and patients with sPE before and after delivery. Maternal 6-keto PGF1α levels and the ratio of 6-keto PGF1α and TXB were decreased in patients with sPE compared to normal pregnant controls. In contrast, maternal ICAM and VCAM levels were not different between the two groups. These data suggest that serum ICAM and VCAM levels may not be sensitive inflammatory biomarkers for preeclampsia. [ABSTRACT FROM AUTHOR]

Familial Mediterranean fever (FMF) is a disease of unknown etiology characterized by recurrent attacks of polyserositis and fever. Intercellular adhesion molecule-1 (ICAM-1) is known to contribute inflammatory conditions by regulating leukocyte localization at inflammatory sites. The aim of this study was to evaluate the probable association of ICAM-1 G/R 241 and ICAM-1 E/K 469 polymorphisms according to susceptibility with FMF. Sixty-seven FMF patients and 83 healthy volunteers were included in the study. Genomic DNA was extracted from EDTA-preserved whole blood of whole series of patients and controls, and genotyped by polymerase chain reaction (PCR) and allele-specific oligonucleotide techniques for ICAM-1 polymorphisms G/R at codon 241 and E/K at codon 469. The ICAM-1 241 genotype and allele frequencies of FMF patients and healthy volunteers were similar. The frequency of ICAM-1 K469 homozygosity was significantly lower in FMF patients than in the controls (32.8% vs 50.7% subsequently, p=0.03). Moreover, ICAM-1 E469 allele was more frequent in FMF patients than in controls (44.8% vs 32.3%, p:0.03). Our results showed that ICAM-1 469 gene polymorphism could contribute to the pathogenesis of FMF. [ABSTRACT FROM AUTHOR]

Endothelin (ET) 1 is a potent vasoactive peptide implicated in the pathogenesis of hypertension and renal disease. The aim of the current study was to test the hypotheses that ET-1 increases albumin permeability of glomeruli isolated from normal rats and that chronic ET-1 infusion will increase glomerular permeability and inflammation independent of blood pressure. Glomerular permeability to albumin was determined from the change in glomerular volume induced by exposing isolated glomeruli to oncotic gradients. Incubation of glomeruli taken from normal rats with ET-1 at a concentration that did not produce direct glomerular contraction (1 nmol/L) significantly increased glomerular permeability to albumin, reaching a maximum after 4 hours. Chronic ET-1 infusion for 2 weeks in Sprague-Dawley rats significantly increased glomerular permeability to albumin and nephrin excretion rate, effects that were attenuated in rats given an ET(A) receptor antagonist (ABT-627, 5 mg/kg per day). Urinary protein and albumin excretion and mean arterial pressure (telemetry) were not changed by ET-1 infusion. Acute incubation of glomeruli isolated from ET-1-infused rats with the selective ET(A) antagonist significantly reduced glomerular permeability to albumin, an effect not observed with acute treatment with a selective ET(B) antagonist. Chronic ET-1 infusion increased glomerular and plasma soluble intercellular adhesion molecule 1 and monocyte chemoattractant protein 1 and elevated the number of macrophages and lymphocytes in renal cortices (ED-1 and CD3-positive staining, respectively). These effects were all attenuated in rats given an ET(A) selective antagonist. These data support the hypothesis that ET-1 directly increases glomerular permeability to albumin and renal inflammation via ET(A) receptor activation independent of changes in arterial pressure. [ABSTRACT FROM AUTHOR]

Objective: We sought to determine whether cerebral inflammation in ischemic rats was reduced by a neuroprotective action of pre-ischemic tumor necrosis factor-α up-regulation, which down-regulated matrix metalloproteinase-9 activity via extracellular signal-regulated kinase 1/2 phosphorylation. Material and methods: Adult male Sprague–Dawley rats were subjected to 30 minutes of exercise on a treadmill for 3 weeks. Stroke was induced by a 2 hour middle cerebral artery occlusion using an intraluminal filament. The exercised animals were treated with tumor necrosis factor-α antibody, UO126 (extracellular signal-regulated kinase 1/2 inhibitor), or both UO126 and doxycycline (matrix metalloproteinase-9 inhibitor). Brain infarct volume was assessed using Nissl staining. Leukocyte infiltration was evaluated using myeloperoxidase immunostaining. Intercellular adhesion molecule-1 and matrix metalloproteinase protein levels were determined by Western blot, and enzyme activity was evaluated using zymography. Results: There was a significant decrease in neurological deficits, brain infarct volume and leukocyte infiltration, in association with reduction in matrix metalloproteinase-9 and intercellular adhesion molecule-1 expression in exercised animals. Exercised animals treated with either tumor necrosis factor-α antibody or with UO126 showed a reversal of neurological outcome, infarct volume and leukocyte infiltration. Matrix metalloproteinase-9 activity was reversed, at least partially, but the intercellular adhesion molecule-1expression was not. Neuroprotection remained when the exercised ischemic rats were treated with both UO126 and doxycycline. Conclusion: These results suggest that exercise-induced up-regulation of tumor necrosis factor-α before stroke and extracellular signal-regulated kinase 1/2 phosphorylation play a role in decreasing brain inflammation by regulating matrix metalloproteinase-9 activity. [ABSTRACT FROM AUTHOR]

Endothelial activation and vascular inflammation are thought to be the mechanisms of pulmonary hypertension. Increased expression of the intercellular adhesion molecule (ICAM-1) and raised serum level of its soluble form (sICAM-1) are found in various conditions associated with endothelial activation. Serum samples from 31 children (14 boys and 17 girls; age, 4.9 ± 4.6 years) with congenital heart disease (CHD) collected at the time of cardiac catheterization were analyzed for sICAM-1 level. Uni- and multivariable stepwise linear regression analyses were performed for the following variables against the sICAM-1 level: age, hemoglobin, serum creatinine, systemic arterial pressure (SAP), pulmonary arterial pressure (PAP), pulmonary blood flow (Qp) and resistance (Rp), systemic blood flow (Qs) and resistance (Rs), Qp/Qs, Rp/Rs, and pulmonary and systemic oxygen saturation. The sICAM-1 levels in children who had CHD with and without pulmonary hypertension were 411 ± 110 and 344 ± 81 ng/ml, respectively ( p = 0.11). In the univariable models, age, serum creatinine, systolic PAP, mean PAP, diastolic PAP, Rp, and Rp/Rs were significantly correlated with sICAM-1 level. In the multiple stepwise regression model, only mean PAP remained as an independent predictor of sICAM-1 level ( r = 0.55; p = 0.002). Children with CHD and pulmonary hypertension had a trend toward elevated sICAM-1 compared with CHD children who had no pulmonary hypertension. A linear correlation was found between mean pulmonary arterial pressure and sICAM-1 level. [ABSTRACT FROM AUTHOR]

Summary: Celiac disease (CD) is a chronic intestinal inflammatory disease that develops in genetically susceptible individuals after gluten ingestion. The ICAM1 gene, located in the CD linkage region 19p13, encodes an intercellular adhesion molecule (ICAM-1) involved in inflammatory processes. Increased levels of ICAM-1 were observed in intestinal biopsies and in sera of CD patients. In addition, an association between the ICAM1 polymorphism G241R and CD patients has been recently described in a French population. Our aim in this study was to analyze the role of ICAM1 polymorphisms in CD susceptibility in the Spanish population. We performed a case–control study with 608 CD patients and 537 healthy control individuals and a family study including 231 trios. Four ICAM1 single nucleotide polymorphisms (SNPs) were analyzed: three nonsynonymous, R478W (rs5030400), P352L (rs1801714) and G241R (rs1799969); and one intronic, rs281432. Despite having above 98% statistical power to detect the association described in the French population (odds ratio = 1.7), we did not find any differences in genotypic or allelic frequencies of the G241R polymorphism between our CD patients and controls, and no differences were observed when the other SNPs were analyzed. Therefore, in our population our results discard the important previously described role of ICAM1 G241R in celiac disease. [Copyright &y& Elsevier]

Abstract: Both circulating and urinary tumor necrosis factor (TNF)-α levels have been shown to increase in inflammatory chronic kidney diseases and TNF-α can induce secretion of other inflammatory mediators from many cell types. Chemokine, mononuclear chemoattractant protein-1 (CCL2/MCP-1), and cell surface adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), in renal proximal tubular epithelial cells (PTEC) are important for promoting recruitment and adhesion of infiltrating macrophages and lymphocytes to inflamed renal tissue. This study aimed to investigate the effect of TNF-α on the expression of these inflammation-related molecules of human PTEC and the underlying intracellular mitogen-activated protein kinase (MAPK) regulatory signaling mechanisms. Cytokine expression profile of TNF-α-activated PTEC was assayed by protein array. The concentration of CCL2 was analyzed by ELISA, while the expression of cell surface ICAM-1 and VCAM-1 and intracellular phosphorylated p38 MAPK, c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) was assessed using flow cytometry. TNF-α could significantly induce CCL2, ICAM-1 and VCAM-1 expression of PTEC. Selective inhibitors of p38 MAPK (SB203580), JNK (SP600125) and ERK (PD98059) could suppress TNF-α-induced CCL2 and ICAM-1 expression, while only p38 MAPK and ERK inhibitors could suppress TNF-α-induced VCAM-1 expression. JNK inhibitor was found to up-regulate VCAM-1 expression but did not elicit any additive effect with TNF-α on VCAM-1 expression. Moreover, p38 MAPK inhibitor was found to abrogate the TNF-α-induced ERK phosphorylation, suggesting that there was a one-way interaction between p38 MAPK and ERK pathways during the TNF-α activation. TNF-α can play a crucial role in the immunopathogenesis of nephritis by the induction of CCL2, ICAM-1 and VCAM-1 expression via the activation of the intracellular MAPK signaling pathway, which may contribute to macrophage and lymphocyte infiltration. [Copyright &y& Elsevier]

Early-onset type 2 diabetes (T2DM) may lead to very early vascular complications. Cardiovascular mortality is two to five times higher in adults with diabetes than in people without diabetes. The cardiovascular risk of young people with T2DM is unknown. T2DM in young people is associated with marked visceral obesity, insulin resistance and microalbuminuria. We recently showed that these subjects did not improve in either fitness (maximum volume of oxygen consumption, VO2max) or glucose disposal after exercise training.Seven subjects with early-onset T2DM (aged 26.1±0.9 years, body mass index [BMI] 35.6±1.2 kg/m2) and 14 age-matched obese subjects with normal glucose tolerance (aged 25. 6±0.9 years, BMI 34. 3±1.4 kg/m2) underwent aerobic training for 12 weeks. Serum vascular inflammatory markers (high-sensitivity C-reactive protein [hsCRP], soluble intercellular adhesion molecule [sICAM-1], soluble vascular cell adhesion molecule [sVCAM-1], E-Selectin and P-Selectin) were measured before and after the training programme.At baseline, plasma concentrations of vascular inflammatory markers were significantly elevated in both groups. They did not improve after exercise. [ABSTRACT FROM PUBLISHER]

Increasing evidence indicates that replicative senescence and premature endothelial senescence could contribute to endothelial dysfunction. This study aims at testing the hypothesis that a high-fat diet may lead to premature vascular endothelial senescence in a nonhuman primate model. We isolated endothelial cells from left and right femoral arteries in 10 baboons before and after a 7-wk high-fat dietary treatment. We compared the morphological alterations, replicative capacities, and senescence-associated β-galactosidase activities (SA-β-gal) at these two time points. We found that high-fat diet increased the prevalence of endothelial senescence. Endothelial replicative capacities declined dramatically, and SA-β-gal activities increased significantly in postdietary challenge. There was no change in telomeric length using quantitative flow fluorescence in situ hybridization analysis, suggesting that some stressors lead to cell senescence independent of telomere dysfunction. Our findings that high-fat diet causes endothelial damage through the premature senescence suggest a novel mechanism for the diet-induced endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Background and purpose:A traditional Japanese herbal medicine, hochu-ekki-to, has been used for the symptomatic treatment of the common cold and to reduce the frequency of colds in patients with chronic obstructive pulmonary disease. However, the inhibitory effects of hochu-ekki-to on infection by rhinovirus (RV), the major cause of common colds, have not been studied.Experimental approach:Human tracheal epithelial cells in culture were infected with a major group rhinovirus-RV14. Virus output and viral RNA were measured along with interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF)-α), mRNA for intercellular adhesion molecule (ICAM)-1 and acidic endosomes in cells.Key results:RV14 infection increased virus titers, the content of cytokines in supernatants and RV14 RNA in the cells. Hochu-ekki-to decreased virus output, RV14 RNA in the cells, susceptibility to RV infection and supernatant cytokine concentrations after RV14 infection. Hochu-ekki-to reduced mRNA for ICAM-1, the receptor for RV14, the concentration of the soluble form of ICAM-1 and the number and fluorescence intensity of acidic endosomes in the cells, from which RV RNA enters into the cytoplasm, at RV14 infection. Glycyrrhizin, one of the chemical constituents of hochu-ekki-to, reduced supernatant virus titers dose-dependently.Conclusion and implications:Hochu-ekki-to inhibited RV14 infection by decreasing ICAM-1 and by blocking entry of viral RNA into the cytoplasm from the endosomes, in airway epithelial cells. Glycyrrhizin may be partly responsible for inhibition of RV infection by hochu-ekki-to. Hochu-ekki-to could modulate airway inflammation by reducing production of cytokines in RV infections.British Journal of Pharmacology (2007) 150, 702–710. doi:10.1038/sj.bjp.0707135; published online 19 February 2007 [ABSTRACT FROM AUTHOR]

Neutrophil recruitment into lung constitutes a major response to airborne endotoxins. In many tissues endothelial intercellular adhesion molecule-1 (ICAM-1) interacts with lymphocyte function associated antigen-1 (LFA-1) on neutrophils, and this interaction plays a critical role in neutrophil recruitment. There are conflicting reports about the role of ICAM-1 in neutrophil recruitment into lungs. We studied neutrophil recruitment into alveolar space in a murine model of aerosolized LPS-induced lung inflammation. LPS induces at least a 100-fold increase in neutrophil numbers in alveolar space, as determined by flow cytometry of bronchoalveolar lavage fluid. Neutrophil recruitment was reduced by 54% in ICAM-1 null mice and by 45% in LFA-1 null mice. In wild-type mice treated with anti-ICAM-1 and anti-LFA-1 antibodies, there was 51 and 58% reduction in the neutrophil recruitment, respectively. In chimeric mice, generated by the transplantation of mixtures of bone marrows from LFA-1 null and wild-type mice, the normalized recruitment of LFA-1 null neutrophils was reduced by 60% compared with wild-type neutrophils. Neither the treatment of ICAM-1 null mice with a function-blocking antibody to LFA-1 nor the treatment of LFA-1 null mice with anti-ICAM-1 antibody resulted in further reduction in the recruitment compared with untreated ICAM-1 null and LFA-1 null mice. We conclude that ICAM-1 and LFA-1 play critical roles in the recruitment of neutrophils into the alveolar space in aerosolized LPS-induced lung inflammation, and LFA-1 serves as a ligand of ICAM-1 in the lung. [ABSTRACT FROM AUTHOR]

Although the link between obstructive sleep apnea syndrome and risk for cardiovascular disorders has yet to be fully described, the hypothetical involvement of endothelial dysfunction is pathophysiologically plausible. In order to test this hypothesis, we measured plasma levels of endothelial markers in 82 male subjects (41 subjects with obstructive sleep apnea syndrome and a 41-subject control group). Obstructive sleep apnea syndrome patients presented higher circulating levels of intercellular cell adhesion molecule-1, E-selectin, and endothelin-1 than the control group. On the other hand, no differences were found in the von Willebrand factor. Levels of E-selectin and intercellular cell adhesion molecule-1 were significantly correlated to total oxygen desaturation. However, no significant correlation was found in either endothelin-1 or von Willebrand factor. We conclude that obstructive sleep apnea syndrome is associated with changes in levels of adhesion molecules, and that this could be the result of obstructive sleep apnea syndrome-induced hypoxia. [Copyright &y& Elsevier]

Abstract: Objective: The objective of this study was to determine whether oral conjugated equine estrogen (CEE) alone or with one of the three progestin regimens causes changes in biomarkers predictive of adverse cardiovascular events: C-reactive protein (CRP), interleukin-6 (IL-6), intercellular adhesion molecule (ICAM) and matrix metalloproteinase-9 (MMP-9). Methods and results: The analysis included 271 postmenopausal women from the postmenopausal estrogen progestin intervention (PEPI) trial. Plasma levels of biomarkers were measured on frozen samples obtained at baseline, 1- and 3-year follow-up visits. Multivariable linear mixed effects models were used to estimate changes in CRP, IL-6, ICAM and MMP-9 levels from baseline to follow-up visits by treatment groups. Women assigned to CEE only or CEE plus a progestin had 121 and 150% 1-year increase in CRP levels, respectively. In contrast, these treatments caused no significant change in IL-6 levels. Women assigned to CEE with or without a progestin had a 6–8% decline in ICAM and a 26–33% decline in MMP-9. Conclusions: The linkage between CEE alone or with a progestin and increased cardiovascular events may be associated with a rise in CRP level, but not through the mechanisms of IL-6-mediated inflammation, endothelial dysfunction or increased MMP activity. [Copyright &y& Elsevier]

Abstract: The infiltration of autoreactive T cells into the central nervous system (CNS) requires a complex molecular interplay between immune cells and the blood–brain barrier (BBB), especially involving adhesion molecules like intercellular adhesion molecule (ICAM)-1. Here we study the molecular expression at the BBB during adoptively transferred (AT) myelin basic protein (MBP)-experimental autoimmune encephalomyelitis (EAE) in vivo by sensitive particle acoustic quantification (SPAQ)-enhanced ultrasound after intravenous application of specific gas-filled MP (MP) targeted against ICAM-1 (ICAM-MP) as contrast agent. Our results reveal a clear periventricular and cerebellar upregulation of ICAM-1 expression at the disease maximum of AT-EAE. Moreover, SPAQ-enhanced ultrasound enables the sensitive quantification of ICAM-1 expression in vivo. This allows to monitor therapeutic changes as shown by suppression of ICAM-1 expression after pretreatment of rats with corticosteroids (P <0.008). All imaging results were confirmed by parallel immunohistochemistry. In vivo magnetic resonance imaging and albumin staining of rat brains after sonification did not reveal a disturbance of the BBB, thereby proving the safety of the method. Subsequent application of specific MP did not influence follow-up measurements, a prerequisite for sequential measurements in longitudinal studies. Based on these data, quantitative molecular imaging of adhesion molecules by SPAQ-enhanced ultrasound proves to be a safe and reliable technology to monitor changes at the BBB in vivo. [Copyright &y& Elsevier]