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Objective: It is aimed to be a technique that can be used for diagnosis and to prevent maternal deaths in cases where the serum levels of cell adhesion molecules are different in patients with abnormal placentation compared to healthy pregnant women., Materials and Methods: Patients between March 2020 and September 2021 were included in the study. While 56 patients, out of 153 cases formed the placental adhesion and/or localization anomaly group, 55 cases without placental adhesion anomaly (placental invasion anomaly and/or previa pathology) constituted the cesarean section group and 42 cases constituted the vaginal birth control group. Demographic characteristics and histories of 153 patients were questioned. I-CAM-1, V-CAM-1, E-Selectin, P-Selectin, LRG-1 levels were studied. The parameters measured by the ELISA method were studied in the Thermo Fisher Scientific Multiscan Go (Finland) device at the Hatay Mustafa Kemal University Medical Faculty Medical Biochemistry USA ELISA Laboratory. Wholehouse and One Way Anova analysis methods were used to compare the results., Results: There were significant differences in E-Selectin, P-Selectin, ICAM-1 and LRG-1 values between the groups (p < 0.05). There was a significant difference between the vaginal birth (VB) and previa/percreata (PP) groups in terms of E-Selectin (p = 0.038). In terms of P-Selectin, there was a significant difference between the C/S and previa/percreata (PP) groups (p < 001). P-Selectin was higher in the previa/percreata (PP) group. There was a significant difference between the Vaginally birth (VB), C/S group (p = 0.041) and the vaginal birth (VB), previa/percreata (PP) group (p = 0.013) in terms of ICAM-1, but there was no significant difference between the C/S and previa/percreata (PP) groups. In terms of LRG-1, there was a significant difference between all 3 groups (p < 0.05)., Discussion: A recent study investigated the potential modulatory effects of trans-resveratrol (RSV), arginase and endothelial dysfunction biomarkers in patients with PE. Another reflection of endothelial dysfunction in PE is increased endothelial activation biomarkers such as intercellular adhesion molecule-1 (ICAM-1), von Willebrand factor (vWF), and Caspase-3 (CASP-3). The study, regarding vWF expression, the preeclampsia (PE) group showed higher levels compared to endothelial cells incubated with healty pregnant (HP) plasma [Bueno-Pereira et al 2022 Antioxidants 2111]. From this and similar studies, the hypothesis that the role of cell adhesion molecules in endothelial damage may be the underlying cause of invasion and location anomalies emerges. This hypothesis is the starting point of our study., Conclusions: In our study, all adhesion molecules except V-CAM-1 were found to be significantly higher in the previa/percreata (PP) group. E-Selectin and LRG-1 adhesion molecules were found to be significantly higher even in C/S patients compared to normal delivery. As a result; these adhesion molecules can be studied as a marker in previa/percreata (PP) patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The phytochemical investigation of the EtOAc extract from the aerial parts of Isodon eriocalyx afforded seventeen diterpenoids, including eight undescribed compounds. Eriocalyxins H-L have unique structural characteristics featuring a 5-epi-ent-kaurane diterpenoid scaffold with eriocalyxins H-K also possess an unusual 6,11-epoxyspiro-lactone ring while eriocalyxin L, a 1,7:3,20-diepoxy-ent kaurene, features an 1,7-oxygen linkage. The structures of these compounds were elucidated by spectroscopic data interpretation, and the absolute configurations of eriocalyxins H, I, L, and M were confirmed by single-crystal X-ray diffraction. The isolates were screened for their inhibitory activities against VCAM-1 and ICAM-1 at 5 μM. While eriocalyxin O, coetsoidin A and laxiflorin P were found to significantly inhibit both VCAM-1 and ICAM-1, 8 (17),13-ent-labdadien-15 → 16-lactone-19-oic acid displayed evidently inhibitory effect against ICAM-1., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: To investigate the relationship between the levels of soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-1β (IL-1β) and hypoxia-inducible factor-1α (HIF-1α) in gingival sulcus fluid and peri-implantitis (PI) in patients with implant restoration., Methods: A total of 198 patients with implant restoration admitted to Fengcheng Hospital from January 2019 to December 2021 were selected, the patients were divided into PI and non-PI group according to whether the implant restoration was complicated by PI 3 months after restoration. The levels of sICAM-1, IL-1β and HIF-1α in the gingival sulcus fluid prior to implant restoration were measured by enzyme-linked immunosorbent assay. Multi-factor logistic regression was used to analyze the factors influencing concurrent PI in patients with implant restoration. ROC curves were used to analyze the predictive value of sICAM-1, IL-1β and HIF-1α levels in gingival sulcus fluid on concurrent PI in patients with implant restoration. SPSS 28.0 software package was used for statistical processing of the data., Results: The incidence of PI in 198 patients with implant restoration was 17.68% (35/198) 3 months after implant restoration. The levels of sICAM-1, IL-1β and HIF-1α in the gingival sulcus fluid were significantly higher in the PI group than in the non-PI group (P＜0.05). Multi-factor logistic regression analysis showed that elevated sICAM-1(OR=1.135, 95%CI: 1.066-1.208), IL-1β (OR=1.106, 95%CI: 1.054-1.161) and HIF-1α (OR=1.008, 95%CI: 1.004-1.012) were independent risk factors for complications of PI in prosthetic patients(P＜0.05). ROC curve analysis showed that the area under the curve for sICAM-1, IL-1β and HIF-1α levels in gingival sulcus fluid alone and in combination for the diagnosis of concurrent PI in patients with implantation was 0.787, 0.785, 0.794 and 0.930, respectively, with sensitivity of 80.00%, 74.29%, 62.86% and 88.57% and specificity of 66.87%, 74.85%, 78.53% and 85.28%, respectively., Conclusions: Elevated levels of sICAM-1, IL-1β and HIF-1α in gingival sulcus fluid are independent risk factors for PI complications in patients with implant restoration and can be used as an auxiliary predictor of PI complications in patients with implant restoration.

Background and Objective: Endothelial cell activation plays a critical role in leukocyte recruitment during inflammation and infection. We previously found that cholinergic stimulation (via vagus nerve stimulation) attenuates vascular endothelial impairment and reduces the inflammatory profile in ovariectomized rats. However, the specific molecular mechanism is unclear. This study was designed to explore the effects and molecular mechanisms of cholinergic agonists (acetylcholine [ACh]) on lipopolysaccharide (LPS)-induced endothelial cell activation in vitro., Methods: Human umbilical vein endothelial cells (HUVECs) were treated with different concentrations of LPS (10/100/1000 ng/mL) to activate endothelial cells. HUVECs were untreated, treated with ACh (10-5 M) alone, treated with 100 ng/mL LPS alone, or treated with different concentrations of ACh (10-9/10-8/10-7/10-6/10-5 M) before LPS stimulation. HUVECs were also pre-treated with 10-6 M ACh with or without mecamylamine (an nAChR blocker) (10 μΜ) and methyllycaconitine (a specific α7 nAChR blocker) (10 μΜ) and incubated with or without LPS. ELISA, western blotting, cell immunofluorescence, and cell adhesion assays were used to examine inflammatory cytokine production, adhesion molecule expression, monocyte-endothelial cell adhesion and activation of the MAPK/NF-κB pathways., Results: LPS (at 10 ng/mL, 100 ng/mL and 1,000 ng/mL) increased VCAM-1 expression in HUVECs in a dose-dependent manner (with no significant difference between LPS at 100 ng/mL and 1,000 ng/mL). ACh (10-9 M-10-5 M) blocked adhesion molecule expression (VCAM-1, ICAM-1, and E-selectin) and inflammatory cytokine production (TNF-α, IL-6, MCP-1, IL-8) in response to LPS in a dose-dependent manner (with no significant difference between 10-5 and 10-6 M Ach). LPS was also shown to significantly enhance monocyte-endothelial cell adhesion, which was largely abrogated by treatment with ACh (10-6M). VCAM-1 expression was blocked by mecamylamine rather than methyllycaconitine. Lastly, ACh (10-6 M) significantly reduced LPS-induced phosphorylation of NF-κB/p65, IκBα, ERK, JNK and p38 MAPK in HUVECs, which was blocked by mecamylamine., Conclusions: ACh protects against LPS-induced endothelial cell activation by inhibiting the MAPK and NF-κB pathways, which are mediated by nAChR, rather than α7 nAChR. Our results may provide novel insight into the anti-inflammatory effects and mechanisms of ACh.

Continuous flow quartz crystal microbalance (QCM) was utilized to study binding kinetics between EV subpopulations (exomere- and exosome-sized EVs) and four affinity ligands: monoclonal antibodies against tetraspanins (anti-CD9, anti-CD63, and anti-CD81) and recombinant intercellular adhesion molecule-1 (ICAM-1) or CD54 protein). High purity CD9 + , CD63 + , and CD81 + EV subpopulations of <50 nm exomeres and 50-80 nm exosomes were isolated and fractionated using our recently developed on-line coupled immunoaffinity chromatography - asymmetric flow field-flow fractionation system. Adaptive Interaction Distribution Algorithm (AIDA), specifically designed for the analysis of complex biological interactions, was used with a four-step procedure for reliable estimation of the degree of heterogeneity in rate constant distributions. Interactions between exomere-sized EVs and anti-tetraspanin antibodies demonstrated two interaction sites with comparable binding kinetics and estimated dissociation constants K d ranging from nM to fM. Exomeres exhibited slightly higher affinity compared to exosomes. The highest affinity with anti-tetraspanin antibodies was achieved with CD63 + EVs. The interaction of EV subpopulations with ICAM-1 involved in cell internalization of EVs was also investigated. EV - ICAM-1 interaction was also of high affinity (nM to pM range) with overall lower affinity compared to the interactions of anti-tetraspanin antibodies and EVs. Our findings proved that QCM is a valuable label-free tool for kinetic studies with limited sample concentration, and that advanced algorithms, such as AIDA, are crucial for proper determination of kinetic heterogeneity. To the best of our knowledge, this is the first kinetic study on the interaction between plasma-derived EV subpopulations and anti-tetraspanin antibodies and ICAM-1., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Meninges, or the membranous coverings of the brain and spinal cord, play host to dozens of morbid pathologies. In this study we provide a method to isolate the leptomeningeal cell layer, identify leptomeninges in histologic slides, and maintain leptomeningeal fibroblasts in in vitro culture. Using an array of transcriptomic, histological, and cytometric analyses, we identified ICAM1 and SLC38A2 as two novel markers of leptomeningeal cells in vivo and in vitro. Our results confirm the fibroblastoid nature of leptomeningeal cells and their ability to form a sheet-like layer that covers the brain and spine parenchyma. These findings will enable researchers in central nervous system barriers to describe leptomeningeal cell functions in health and disease., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Flow cytometry (FC) is a popular method to detect bone marrow (BM) involvement in patients with B-cell non-Hodgkin lymphoma (B-NHL). The majority of screen panels of FC still rely on finding monoclonal B-cells, e.g., B-cells with immunoglobin (Ig) light-chain restriction, which has many limitations. Therefore, exploring new markers is warranted., Methods: A total of 52 cases of B-NHL with BM involvement were collected. The median age was 60 years. Out of these 52 cases, 34 were male, and 18 were female. A 10-color FC panel was used to detect the expression of CD54 on lymphoma cells. The expression of CD54 was calculated as the mean fluorescence index ratio (MFIR) and was described as the mean ± standard error of the mean (SEM)., Results: Up to 18/52 (34.62%) of BM specimens abnormally expressed an increased level of CD54, including 1/10 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 9/13 cases of mantle cell lymphoma (MCL), 2/14 cases of follicular lymphoma (FL), 5/9 cases of marginal zone lymphoma (MZL), and 1/3 cases of high-grade B-NHL (HG B-NHL). The expression level of CD54 was significantly increased in MCL cases (53.41 ± 11.04) compared with CLL/SLL cases (11.66 ± 2.79) and FL cases (13.49 ± 2.81). The lowest percentage of CD54-positive B-cells attained 0.13%. In 5/9 cases of MZL and 1/3 cases of HG B-NHL, increased expression of CD54 was the only abnormal immunophenotype detected besides Ig light-chain restriction. No aberrant CD54 expression was identified by FC in lymphoplasmacytic lymphoma (LPL) (0/2) and Burkitt lymphoma (BL) (0/1) cases. Aberrant expression of CD54 was not related to plasma cell differentiation., Conclusion: Lymphoma cells, especially in MCL and MZL cases, frequently show increased expression of CD54. Such aberrant expression is not related to plasma cell differentiation. We highly recommend adding CD54 to the FC screening panel to detect BM involvement in patients with B-NHL., (© 2021. The Author(s).)

Background: Evidence show that Matrix metalloproteinases (MMPs) have been associated with neurological complications in the viral infections. Here in the current investigation, we intended to reveal if MMPs are potentially involved in the development of neurological symptoms in the patients with Coronavirus disease 2019 (COVID-19)., Methods: The levels of MMPs, inflammatory cytokines, chemokines, and adhesion molecules were evaluated in the serum and cerebrospinal fluid (CSF) samples from 10 COVID-19 patients with neurological syndrome (NS) and 10 COVID-19 patients lacking NS. Monocytes from the CSF samples were treated with TNF-α and the secreted levels of MMPs were determined., Results: The frequency of monocytes were increased in the CSF samples of COVID-19 patients with NS compared to patients without NS. Levels of inflammatory cytokines IL-1β, IL-6, and TNF-α, chemokines CCL2, CCL3, CCL4, CCL7, CCL12, CXCL8, and CX3CL1, MMPs MMP-2, MMP-3, MMP-9, and MMP-12, and adhesion molecules ICAM-1, VCAM-1, and E-selectin were significantly increased in the CSF samples of COVID-19 patients with NS compared with patients without NS. Treatment of CSF-derived monocytes obtained from COVID-19 patients with NS caused increased production of MMP-2, MMP-3, MMP-9, and MMP-12., Conclusions: Higher levels of inflammatory cytokines might promote the expression of adhesion molecules on blood-CSF barrier (BCSFB), resulting in facilitation of monocyte recruitment. Increased levels of CSF chemokines might also help to the trafficking of monocytes to CSF. Inflammatory cytokines might enhance production of MMPs from monocytes, leading to disruption of BCSFB (and therefore further infiltration of inflammatory cells to CSF) in COVID-19 patients with NS., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Flow cytometry plays a key role in detecting bone marrow (BM) involvement in patients with diffuse large B-cell lymphoma (DLBCL). To improve its detection sensitivity, we need to explore novel markers. In this study, we detected the expression CD54 on lymphoma cells in BM specimens from DLBCL patients and clarified its diagnostic significance in BM involvement by DLBCL., Methods: We collected BM specimens from 76 patients with DLBCL (germinal center B-cell (GCB) = 25, non-GCB = 51) and 10 control patients without lymphoma. We detected and compared the expression of CD54 on lymphoma cells and normal mature B cells by using 10-color panels., Results: Normal plasma cells expressed a higher level of CD54 as compared with hematogones (p < 0.05) and normal mature B cells (p < 0.05). Among 76 patients, 23 of them (GCB = 12, non-GCB = 11) had BM involvement. Lymphoma B cells from 12 cases (GBC = 4, non-GCB = 8) expressed a higher level of CD54 compared to normal mature B cells (p < 0.05). Additionally, lymphoma cells of the non-GCB subtype frequently expressed a higher level of CD54 in comparison to the GCB subtype (p < 0.05). And the high expression of CD54 was not related to plasmacytoid differentiation., Conclusion: Aberrant expression of CD54 on lymphoma cells is frequently seen in patients' BM specimens involved by DLBCL, especially in the non-GCB subtype. CD54 could be used as a new marker to gate on lymphoma cells and improve the detection sensitivity of BM involvement in patients with DLBCL., (© 2021. The Author(s).)

Background: Biomarkers can be used to detect the presence of endothelial and/or alveolar epithelial injuries in case of ARDS. Angiopoietin-2 (Ang-2), soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion protein-1 (VCAM-1), P-selectin and E-selectin are biomarkers of endothelial injury, whereas the receptor for advanced glycation end-products (RAGE) reflects alveolar epithelial injury. The aims of this study were to evaluate whether the plasma concentration of the above-mentioned biomarkers was different 1) in survivors and non-survivors of COVID-19-related ARDS and 2) in COVID-19-related and classical ARDS., Methods: This prospective study was performed in two COVID-19-dedicated Intensive Care Units (ICU) and one non-COVID-19 ICU at Ferrara University Hospital. A cohort of 31 mechanically ventilated patients with COVID-19 ARDS and a cohort of 11 patients with classical ARDS were enrolled. Ang-2, ICAM-1, VCAM-1, P-selectin, E-selectin and RAGE were determined with a bead-based multiplex immunoassay at three time points: inclusion in the study (T1), after 7 ± 2 days (T2) and 14 ± 2 days (T3). The primary outcome was to evaluate the plasma trend of the biomarker levels in survivors and non-survivors. The secondary outcome was to evaluate the differences in respiratory mechanics variables and gas exchanges between survivors and non-survivors. Furthermore, we compared the plasma levels of the biomarkers at T1 in patients with COVID-19-related ARDS and classical ARDS., Results: In COVID-19-related ARDS, the plasma levels of Ang-2 and ICAM-1 at T1 were statistically higher in non-survivors than survivors, (p = 0.04 and p = 0.03, respectively), whereas those of P-selectin, E-selectin and RAGE did not differ. Ang-2 and ICAM-1 at T1 were predictors of mortality (AUROC 0.650 and 0.717, respectively). At T1, RAGE and P-selectin levels were higher in classical ARDS than in COVID-19-related ARDS. Ang-2, ICAM-1 and E-selectin were lower in classical ARDS than in COVID-19-related ARDS (all p < 0.001)., Conclusions: COVID-19 ARDS is characterized by an early pulmonary endothelial injury, as detected by Ang-2 and ICAM-1. COVID-19 ARDS and classical ARDS exhibited a different expression of biomarkers, suggesting different pathological pathways. Trial registration NCT04343053 , Date of registration: April 13, 2020.

This monocentric prospective study of patient suffering from Amyotrophic lateral sclerosis (ALS) aims to evaluate the prognosis and diagnostic potential of both Neurofilament-Light (Nf-L) and neuroinflammatory biomarkers in serum and CSF. Candidate markers levels were measured using multiplex method in serum of 60 ALS patients, 94 healthy controls of 43 patients suffering from Inflammatory Peripheral Neuropathies (IPN). A comparative CSF analysis was performed for 20 ALS and 17 IPN patients. Among the altered biomarkers, CSF Nf-L level remains the best marker of ALS severity, while serum levels correlate strongly with disease progression. The combination of Nf-L and ICAM-1 concentrations in the CSF and IFN-γ concentration in the serum differentiate ALS patients from IPN patients with improved sensibility and specificity relative to individual biomarkers. A cutoff value of 0.49 for the fitted values of these 3 biomarkers discriminate ALS from IPN patients with a specificity of 100% (78.20-100%) and a sensibility of 85.71% (57.19-98.22%) with an AUC of 0.99 ± 0.01. The measure of Nf-L and neuroinflammatory biomarkers in CSF and serum can be useful biomarkers panel in the differential diagnosis of ALS.

Context: Chloranthus serratus (Thunb.) Roem. et Schult. (Chloranthaceae) is an herb widely used as a folk medicine treating inflammatory diseases, although it is toxic., Objective: To investigate hepatotoxicity and related mechanisms induced by ethanol extracts of different parts of C. serratus in rats., Materials and Methods: Sprague Dawley rats were divided into control (Con), ethanol extract of roots (ER), stems (ES), and leaves (EL) groups, and acute oral toxicity studies were conducted. The rats received doses of 4.14, 3.20, and 1.16 g/kg/d extracts for 14 days, respectively. Liver index, liver function and oxidative stress biomarkers, liver pathology, ultrastructure, TNF-α, ICAM-1, and Nrf2/HO-1 proteins expression levels were determined., Results: The LD 50 of ER, ES, and EL were higher than 10.35, 8.05, and 2.90 g/kg/p.o., respectively. The liver indexes in the extract groups increased significantly. EL dramatically increased TP, GLB, AST, ALT, ALP, TBA, MDA, ICAM-1, and TNF-α levels ( p  < 0.01), and induced the most obvious pathological and ultrastructural changes. ES and EL obviously decreased the T-SOD, GSH, CAT, and CHOL levels. Nrf2 and HO-1 proteins expression was reduced significantly in ES (0.77 ± 0.06, 2.33 ± 0.20) and EL (0.23 ± 0.04, 2.14 ± 0.16) groups, and reduced slightly in ER (1.08 ± 0.10; 3.39 ± 0.21) group., Discussion and Conclusion: ES and EL induce stronger hepatotoxicity than ER through oxidative stress and the Nrf2/HO-1 pathway, and the root is a better medicinal part, which provides a basis for clinical research, safe applications, and reasonable development of C. serratus .

Endothelial dysfunction is a critical event in vascular inflammation characterized, in part, by elevated surface expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). ICAM-1 is heavily N-glycosylated, and like other surface proteins, it is largely presumed that fully processed, complex N-glycoforms are dominant. However, our recent studies suggest that hypoglycosylated or high mannose (HM)-ICAM-1 N-glycoforms are also expressed on the cell surface during endothelial dysfunction, and have higher affinity for monocyte adhesion and regulate outside-in endothelial signaling by different mechanisms. Whether different ICAM-1 N-glycoforms are expressed in vivo during disease is unknown. In this study, using the proximity ligation assay, we assessed the relative formation of high mannose, hybrid and complex α-2,6-sialyated N-glycoforms of ICAM-1 in human and mouse models of atherosclerosis, as well as in arteriovenous fistulas (AVF) of patients on hemodialysis. Our data demonstrates that ICAM-1 harboring HM or hybrid epitopes as well as ICAM-1 bearing α-2,6-sialylated epitopes are present in human and mouse atherosclerotic lesions. Further, HM-ICAM-1 positively associated with increased macrophage burden in lesions as assessed by CD68 staining, whereas α-2,6-sialylated ICAM-1 did not. Finally, both HM and α-2,6-sialylated ICAM-1 N-glycoforms were present in hemodialysis patients who had AVF maturation failure compared to successful AVF maturation. Collectively, these data provide evidence that HM- ICAM-1 N-glycoforms are present in vivo, and at levels similar to complex α-2,6-sialylated ICAM-1 underscoring the need to better understand their roles in modulating vascular inflammation., Competing Interests: Dr. Lee is a consultant for Proteon Therapeutics, Merck, and Boston Scientific. All other authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The aim of this study was to evaluate the inflammation process that resulted from the inoculation of Wistar Rats with Acanthamoeba griffini, a virulent T3 Acanthamoeba genotype that produces keratitis. Haematoxylin and eosin, periodic acid stain, immunohistochemistry and morphometry were used to analyse tissues from rats of an Acanthamoeba keratitis (AK) model. Two weeks after inoculating the rats with A griffini trophozoites, the thickness of the stroma had diminished, followed by an increase in thickness at 4 weeks. At the latter time, an abundance of inflammatory infiltrate cells was observed, some found to express IL-1β, IL-10 and/or caspase 3. Intercellular adhesion molecule-1 was expressed in corneal blood vessels amid the abundant vascularization characteristic of the development of AK. Through an immunohistochemical technique, trophozoites were detected at 2 and 4 weeks post-inoculation. By 8 weeks, there were a low number of trophozoites and cysts and the corneas of infected rats were similar in thickness to those of the controls. Thus, the rats were capable of healing experimental AK in the present rat model. Diverse immunological mechanisms regulated the inflammatory process in acute AK induced by A griffini in a murine model., (© 2019 John Wiley & Sons Ltd.)

Background: Sepsis is a pathological host response to infection leading to vascular barrier breakdown due to elevated levels of angiopoietin-2 (Angpt-2) and vascular endothelial growth factor-A (VEGF-A). Here, we tested a novel heterodimeric bispecific monoclonal IgG1-cross antibody of Angpt-2 and VEGF - termed "A2V.", Methods: Cecal ligation and puncture was used to induce murine polymicrobial sepsis. Organs and blood were harvested for fluorescence immunohistochemistry and RT-PCR, and survival was recorded. In vitro endothelial cells were stimulated with plasma from septic shock patients costimulated with A2V or IgG antibody followed by immunocytochemistry and real-time transendothelial electrical resistance., Results: Septic mice treated with A2V had a reduced induction of the endothelial adhesion molecule ICAM-1, leading to a trend towards less transmigration of inflammatory cells (A2V: 42.2 ± 1.0 vs. IgG 48.5 ± 1.7 Gr-1+ cells/HPF, p = 0.08) and reduced tissue levels of inflammatory cytokines (e.g., IL-6 mRNA: A2V 9.4 ± 3.2 vs. IgG 83.9 ± 36.7-fold over control, p = 0.03). Endothelial permeability was improved in vivo and in vitro in stimulated endothelial cells with septic plasma. Survival was improved by 38% (p = 0.02)., Conclusion: Dual inhibition of Angpt-2 and VEGF-A improves murine sepsis morbidity and mortality, making it a potential therapeutic against vascular barrier breakdown., (© 2019 S. Karger AG, Basel.)

Purpose: To determine the characteristics of diabetic macular edema (DME) patients with cotton-wool spots (CWS)., Methods: We classified 80 treatment-naïve DME patients according to whether or not they had CWS involving macula and then compared the concentrations of interleukin- (IL-) 1 β , IL-6, IL-8, IL-10, IL-17, placental growth factor, vascular endothelial growth factor (VEGF), and intercellular adhesion molecule (ICAM)-1 in the aqueous humor between the groups, as well as optical coherence tomography (OCT) findings, baseline characteristics, and intravitreal bevacizumab responsiveness., Results: Aqueous levels of ICAM-1 and VEGF in the group with CWS were significantly higher than those in the non-CWS (control) group ( p < 0.001 and p = 0.006, respectively). In multiple logistic regression analysis to identify factors associated with CWS, the aqueous ICAM-1 (≥0.36 ng/mL) was significantly associated with CWS (odds ratio = 13.26, p < 0.001). Based on OCT, ellipsoid zone (EZ) disruption distribution was significantly different between the two groups ( p = 0.038). Regarding responsiveness to treatment, although there was no significant difference in central subfield thickness between the two groups after treatments, the best-corrected visual acuity was worse in the group with CWS., Conclusions: The presence of CWS was accompanied by higher levels of aqueous ICAM-1. Based on OCT, EZ disruption was greater in DME patients with CWS, and their short-term visual prognosis was poorer., Competing Interests: No author has a financial and proprietary interest in any material or method mentioned., (Copyright © 2019 Young-Gun Park et al.)

The macrophage migration inhibitory factor (MIF)/CD74 signaling pathway is strongly implicated in inflammation and angiogenesis. We investigated the expression of MIF and its receptor CD74 in proliferative diabetic retinopathy (PDR) to reveal a possible role of this pathway in the pathogenesis of PDR. Levels of MIF, soluble (s)CD74, soluble intercellular adhesion molecule-1 (sICAM-1) and vascular endothelial growth factor (VEGF) were significantly increased in the vitreous from patients with PDR compared to nondiabetic control samples. We detected significant positive correlations between the levels of MIF and the levels of sICAM-1 ( r = 0.43; p = 0.001) and VEGF ( r = 0.7; p < 0.001). Through immunohistochemical analysis of PDR epiretinal membranes, significant positive correlations were also found between microvessel density (CD31 expression) and the numbers of blood vessels expressing MIF ( r = 0.56; p = 0.045) and stromal cells expressing MIF ( r = 0.79; p = 0.001) and CD74 ( r = 0.59; p = 0.045). Similar to VEGF, MIF was induced in Müller cells cultured under hypoxic conditions and MIF induced phosphorylation of ERK1/2 and VEGF production in Müller cells. Intravitreal administration of MIF in normal rats induced increased retinal vascular permeability and significant upregulation of phospho-ERK1/2, NF-κB, ICAM-1 and vascular cell adhesion molecule-1 expression in the retina. MIF induced migration and proliferation of human retinal microvascular endothelial cells. These results suggest that MIF/CD74 signaling is involved in PDR angiogenesis., (Copyright © 2019 Abu El-Asrar, Ahmad, Siddiquei, De Zutter, Allegaert, Gikandi, De Hertogh, Van Damme, Opdenakker and Struyf.)

Background: Coronary heart disease is related to sudden death caused by multi-factors and a major threat to human health.This study explores the role of OX40L and ICAM-1 in the stability of coronary plaques and their relationship with sudden coronary death., Methods: A total of 118 human coronary arteries with different degrees of atherosclerosis and/or sudden coronary death comprised the experimental group and 28 healthy subjects constituted the control group were isolated from patients. The experimental group was subdivided based on whether the cause of death was sudden coronary death and whether it was accompanied by thrombosis, plaque rupture, plaque outflow and other secondary changes: group I: patients with coronary atherosclerosis but not sudden coronary death, group II: sudden coronary death without any of the secondary changes mentioned above, group III: sudden coronary death with coronary artery atherosclerotic lesions accompanied by either of the above secondary changes. The histological structure of the coronary artery was observed under a light microscope after routine HE staining, and the related indexes of atherosclerotic plaque lesions were assessed by image analysis software. The expressions of OX40L and ICAM-1 were detected by real-time quantitative PCR (RT-PCR), immunohistochemistry (IHC) and Western blotting, and the correlations between the expressions and the stability of coronary atherosclerotic plaque and sudden coronary death were analyzed., Results: (1) The expression of OX40L protein in the control group and the three experimental groups showed an increasing trend, and the difference between groups was statistically significant (P < 0.05). (2) The expression of the ICAM-1 protein in the control group and the three experimental groups showed a statistically significant (P < 0.05) increasing trend. (3) The expression of OX40L and ICAM-1 mRNAs increased in the control and the three experimental groups and the difference was statistically significant (P < 0.05)., Conclusion: The expression of OX40L and ICAM-1 proteins and mRNAs is positively correlated with the stability of coronary atherosclerotic plaque and sudden coronary death.

Scope: The objectives are to evaluate the anti-inflammatory and anti-atherosclerotic effects of digested total protein and digested protein fractions from chia seed in macrophages in vitro., Methods and Results: Total protein and protein fractions (albumin, globulin, glutelin, and prolamin) are isolated from chia seed and digested using simulated gastrointestinal conditions, resulting in digested total protein (DTP) and digested protein fractions (DPF). DTP and DPF are applied (1.0 mg mL -1 ) in RAW 264.4 macrophages stimulated with LPS (1 µg mL -1 ) for inflammation or ox-LDL (80 µg mL -1 ) for atherosclerosis. In the inflammatory process, DTP and DPF reduce p-NF-κB, iNOS, p-JNK, and AP-1. Digested glutelin reduces the secretion of nitric oxide (65.1%), reactive oxygen species (19.7%), prostaglandins (34.6%), TNF-α (24.1%), MCP-1 (18.9%), IL-6 (39.6%), and IL-10 (68.7%). DTP and DPF reduce the NF-κB translocation to nuclei. DTP and digested glutelin reduce iCAM expression (86.4%, 80.8%), LOX-1 (37.3%, 35.7%), iNOS (67.0%, 42.2%), and NF-κB (57.5%, 71.1%). DTP is effective in reducing secretion of nitric oxide (43.4%), lipid accumulation (41.9%), prostaglandins (41.9%), TNF-α (43.3%), MCP-1 (47.6%), and IL-6 (50.5%). Peptides from chia DTP and DPF are also characterized., Conclusion: DTP and digested glutelin from chia seed reduce expression and secretion of markers related to inflammation and atherosclerosis pathways., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Human IgA antibodies effectively engage myeloid cells for the FcαRI-dependent antibody-dependent cell-mediated cytotoxicity (ADCC) of tumor cells. Established methods to investigate ADCC are the 51 chromium and Calcein release assays. Their critical limitations are the end-point measurement, the unspecific release of the probes, the requirement of target cells in suspension and thus do not reflect physiologic conditions of adherently growing cells. Here we report the label-free real-time monitoring of granulocyte-mediated ADCC using an impedance-based method. We investigated the efficacy of an engineered epidermal growth factor receptor (EGFR)-directed IgA2 antibody to engage neutrophils for ADCC against a panel of adherently growing EGFR-expressing cancer cell lines majorly head and neck squamous cell carcinoma (HNSCC). The impedance assay allowed the documentation of the IgA-neutrophil-and FcαRI-signaling dependent ADCC of adherently growing target cells. While at a short-term it provided comparable results to release assays, in the long run real time monitoring also revealed cell-line specific kinetics and long-term efficacy. Although short-term results may depend on EGFR expression, long-term efficacy did not correlate with the surface level of EGFR nor of the myeloid checkpoint CD47 pointing to additional critical parameters to predict the treatment efficacy. Real-time monitoring of neutrophil-mediated ADCC allowed documenting effector cell activity and exhaustion. Along with excess expression of Mac-1 ligands, which may explain the target cell resistance, this eventually leads to tumor cell outgrowth at later time points. In conclusion, the impedance assay provides valuable information on the kinetics, effector cell performance, efficacy and critical parameters of IgA-dependent granulocyte-mediated cytotoxicity and is expected to become an important tool in its evaluation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Microparticles (MPs) are biomarkers and mediators of disease through their expression of surface receptors, reflecting activation or stress in their parent cells. Endothelial markers, ICAM-1 and VCAM-1, are implicated in atherosclerosis and associated with cardiovascular risk. Chronic kidney disease (CKD) patients have endothelial dysfunction and high levels of endothelial derived MPs. Vitamin D treatment has been reported to ameliorate endothelial function in CKD patients. We aimed to examine cell specific MP profiles and concentrations of MPs expressing the atherosclerotic markers ICAM-1 and VCAM-1 after treatment with paricalcitol in patients with CKD stage 3-4., Methods: Sub-study of the previously reported SOLID trial where 36 patients were randomly assigned to placebo, 1 or 2 μg paricalcitol, for 12 weeks. MPs were measured by flow cytometry after labelling with antibodies against endothelial (CD62E), platelet (CD62P, CD41, CD154) leukocyte (CD45) and vascular (CD54, CD106) markers., Results: Patients had a mean age of 65 years with a mean eGFR of 40 mL/min/1.73m 2 . Concentrations of ICAM-1 positive MPs were significantly reduced by treatment (repeated measures ANOVA p = 0.04). Repeated measures MANOVA of concentrations of endothelial, platelet and leukocyte MPs showed sustained levels in the 2 μg treatment group (p = 0.85) but a decline in the 1 μg (p = 0.04) and placebo groups (p = 0.005)., Conclusions: Treatment with paricalcitol reduces concentrations of ICAM-1 positive MPs. This is accompanied by sustained concentrations of all cell specific MPs in the 2 μg group, and decreasing concentrations in the other groups, possibly due to a more healthy and reactive endothelium with paricalcitol treatment.

Previous studies have demonstrated that excess aldosterone impairs glucose metabolism. However, the underlying mechanism is still misty. Aldosterone has been proved a risk factor of fibrosis and inflammation. And the histology of islets from patients with type 2 diabetes (T2D) also displays inflammation and fibrosis. But it is unclear whether aldosterone has direct impact on islet inflammation and fibrosis in T2D. Islet endothelium plays a significant role in the maintenance of islet beta cell function and has a close relationship with islet fibrosis and inflammation. Therefore, we focused on the effect of aldosterone on the islet endothelium. In this study, we utilized a diabetic db/db mouse model and examined serum aldosterone levels, islet macrophages infiltration, and islet fibrosis. After we confirmed that there was an increased expression of intercellular cell adhesion molecule-1 (ICAM-1) and endothelin-1 (ET-1) in islet of diabetic mice compared with wild type mice. We next determined that aldosterone increased expression of ICAM-1 and ET-1 in both mRNA and protein levels in islet endothelium in vitro. And then we tested the expression of mineralocorticoid receptor (MR) in islet endothelium in vitro and in vivo. Our results showed that aldosterone can up-regulate the expression levels of ICAM-1 and ET-1 through MR. These findings suggest excess aldosterone might participate in islet inflammation and fibrosis in T2D., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The purpose of this study is to investigate whether airborne exposure to endotoxins, hydrogen sulphide (H2S), and inhalable particles negatively impacts the respiratory system and inflammatory blood proteins in sewage plant and sewer net system workers and, further, to determine dose-response associations between exposure and health outcomes., Methods: In total, 148 waste water workers (WWWs) from urban and rural sewage plants and the sewer net system participated. One hundred and twenty-one workers were exposed to sewage, 46 from sewage plants and 75 from the sewer net system. Twenty-seven workers were characterized as little or not exposed and served as an internal reference group. Personal inhalable samples were analysed for endotoxins (Limulus assay), particle dust (gravimetrically) and Salmonella and Yersinia spp. (polymerase chain reaction method, PCR). Levels of H2S were measured using personal electro chemical sensors. Intercellular adhesion molecule 1 (ICAM-1), interleukin 8 (IL-8), surfactant protein D (SP-D), club cell protein 16 (CC16), and macrophage inflammatory protein (MIP) were determined by enzyme-linked immunosorbent assay and C-reactive protein (CRP) by an HS-MicroCRP assay in blood samples., Results: Workers in sewage plants were exposed to significantly higher levels of endotoxins compared to workers in the sewer net system [median 55 EU m-3 (4-262 EU m-3) and median 27 EU m-3 (1-304 EU m-3), respectively]. The estimated H2S index showed higher values when working in the sewer net system [median 3.1 (0.5-78.1)] compared to workers at the sewage plants [median 1.3 (0.5-9.3)], and the most excessive exposure was collecting sewage from cesspools (273 p.p.m.). No viable airborne Salmonella and Yersinia spp. were detected. The exposed workers had significantly higher CRP compared to the referents [1.2 µg ml-1 (0.1-19.0 µg ml-1) and 0.8 µg ml-1 (0.1-5.0 µg ml-1), respectively] and lower forced expiratory volume in 1 s (FEV1)% [92.6%, standard deviation (SD) 14.6 and 102.0%, SD 10.1, respectively], with numbers given as mean and SD. The serum concentration of CRP was significantly and negatively associated with FEV1% (β = -7.7, R2 = 0.05) and forced vital capacity % (β = -8.5, R2 = 0.08), and the serum concentration of ICAM-1 with the estimated exposure to H2S (β = -19.9, R2 = 0.07)., Conclusion: Despite moderate levels of endotoxin and H2S exposure, the results indicate an impact of these agents on lung function and the adhesion molecule ICAM-1, and a low-grade systemic inflammation was indicated in increased levels of CRP., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Inflammatory cytokine, adipokine and adhesion molecules are known to play a key role in pathogenesis of diabetic kidney disease (DKD). In this study, our aim was to investigate the role of fetuin-A in relation with pro-inflammatory cytokines (IL-6, IL-18), adipokines (adiponectin, leptin), chemokine (MCP-1), and adhesion molecules (ICAM-1, VCAM-1) in control and DKD subjects. We recruited a total of 224 type 2 diabetic (T2D) subjects. The control subjects were T2D with a normal albumin excrete (albumin-to-creatinine ratio-ACR ≤ 30 mg/g creatinine) and estimated glomerular filtration rate (eGFR) ≥ 60 (ml/min/1.73 m 2 ), while cases were T2D subjects with albumin excrete (ACR ≥ 30 mg/g creatinine) and eGFR ≤ 60 (ml/min/1.73 m 2 ). FBS, HbA1c, lipid profile (TC, LDL, HDL, triglyceride), ALT, AST, GGT, serum creatinine, BMI, blood pressure was evaluated in all the study subjects. Randox evidence biochip analyzer was used for measuring inflammatory cytokines, adipokines, and adhesion molecules by chemiluminescent assay. Serum fetuin-A and IL-18 were measured by ELISA kits. Serum fetuin-A levels were significantly decreased in DKD cases compare to control group [456.8 (299.2-649.0) µg/ml versus 670.6 (573.0-726.1) µg/ml; p < 0.001)]. Serum fetuin-A levels correlates significantly with IL-6, IL-18, TNF-α, PAI-1, leptin, resistin and ACR (p < 0.001). This study concludes that serum fetuin-A and pro-inflammatory markers (IL-18, IL-6, IL-1α and TNF-α) might play an important role in the pathophysiology and inflammatory process of DKD.

Background and Aims: Aortic valve calcification (AVC) may be associated with atherogenic processes arising from endothelial dysfunction (ED). Limited data is available about the relationship between ED, defined by flow mediated dilation (FMD%) and biomarkers, and the prevalence and progression of AVC in a multiethnic population., Methods: A sample of 3475 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA), with both initial and repeat CT scans at a mean of 2.65 ± 0.84 years and FMD% and serologic markers of ED [ C-reactive protein (CRP), Von Willebrand factor (vWF), Plasminogen Activator Inhibitor (PAI), fibrinogen, Interleukin 6 (IL6), E-selectin and ICAM-1 (Intercellular Adhesion Molecule 1)], were analyzed. Multivariate modeling evaluated the association between ED and the prevalent AVC and AVC progression., Results: The median levels of FMD% was lower and vWF%, fibrinogen, IL6 and ICAM-1 were significantly higher in the AVC prevalence group versus no AVC prevalence (all p < 0.001). In the fully adjusted model for established risk factors, decreasing FMD% or increasing biomarkers was not independently associated with AVC prevalence [OR FMD% 1.028 (0.786, 1.346), CRP 0.981 (0.825, 1.168), vWF 1.132 (0.559, 2.292), PAI 1.124 (0.960, 1.316), fibrinogen 1.116 (0.424, 2.940), IL6 1.065 (0.779, 1.456), E-selectin 0.876 (0.479, 1.602) and ICAM-1 1.766 (0.834, 3.743)]. In the AVC progression group, FMD%, vWF%, fibrinogen and IL6 were significantly different (p < 0.05). After adjusting for cardiac risk factors, AVC progression was not independently associated with decreasing FMD% or increasing biomarkers [OR FMD% 1.105 (0.835, 1.463), CRP 1.014 (0.849, 1.210), vWF% 1.132 (0.559, 2.292), PAI 1.124 (0.960, 1.316), fibrinogen 0.909 (0.338, 2.443), IL6 1.061 (0.772, 1.459), E-selectin 0.794 (0.426, 1.480) and ICAM-1 0.998 (0.476, 2.092)]., Conclusions: Endothelial dysfunction by FMD% and biomarkers is not significantly associated with the prevalence or progression of aortic valve calcification after adjustment for cardiac risk factors., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Microvascular free flap reconstruction has become a standard technique in head and neck reconstructive surgery. Pre-operative radiotherapy is associated with a higher incidence of free flap malperfusion and the need for operative revision. Irradiated vessels present characteristic histomorphological and structural changes. Alterations in endothelial cells of irradiated arteries remain incompletely investigated especially with regard to long-term changes in endothelial dysfunction supporting an intraluminal pro-thrombotic and pro-inflammatory milieu., Methods: Endothelial expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E‑ and P‑selectin, endothelial NO-synthase (eNOS), thrombomodulin and plasminogen activator inhibitor-1 (PAI-1) in irradiated and non-irradiated arteries was analysed using immunohistochemistry and Remmele scale grading. The average radiation dose was 58.7 ± 7.0 Gy; the time interval between end of radiation and tissue sampling was 106.0 ± 86.8 months., Results: Endothelial expression of ICAM-1, VCAM-1, E‑ and P‑selectin as well as PAI-1 was significantly increased in previously irradiated arteries compared with non-irradiated controls, whereas thrombomodulin and eNOS expression did not show any differences. However, when comparing non-irradiated free flap arteries with irradiated arteries from the head and neck area in respective individuals, eNOS expression was significantly lower in irradiated vessels whereas ICAM-1, VCAM-1, E‑/p-Selectin and PAI-1 showed significantly higher expression levels., Conclusion: There is ongoing endothelial dysfunction in terms of increased expression of pro-thrombotic and pro-inflammatory markers in irradiated arteries even years after radiotherapy. Treating this endothelial dysfunction might reduce the complication rates associated with microvascular free flap reconstructions in irradiated patients.

Background: Lung cancer is a leading cause of morbidity and mortality worldwide and there is an urgent need for sensitive, specific, and reliable biomarkers., Methods: The study population included 60 patients (31 with lung cancer and 29 with chronic obstructive pulmonary disease [COPD]) and thirty healthy individuals comprised the control group. Measurements of neutrophil, beclin-1, VEGF, ICAM, VCAM, and TNF-alpha levels in induced sputum were analyzed as possible biomarkers for lung cancer., Results: Neutrophil, beclin-1, VEGF, ICAM and TNF-alpha levels of lung cancer patients differed significantly compared to those of COPD patients and healthy controls. A novel combined-score was created which was found to increase the likelihood to belong to the cancer group by 70% (odds-ratio 1.70 CI = 1.310-2.224,p < 0.001)., Conclusion: Biomarkers of autophagy, angiogenesis and inflammation in lung-cancer patients are significantly different from controls, and combination of these markers may be an indicator for lung cancer., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The detrimental consequences of obesity on female fertility are well known, but the functional changes that occur in the ovary in response to elevated BMI are not clear. Obesity induces multiple components of a systemic inflammatory state that is a key pathway by which it initiates tissue dysfunction in adipose, liver and muscle; however whether obesity induces similar inflammatory changes in the ovary has not been fully investigated. This is important to understand because it is increasingly clear that obesity at conception impacts not only pregnancy rates but also influences pre-implantation embryo development. To further understand the characteristics of inflammation in the ovaries of obese women we analysed a panel of cytokines (IL6, IL10 and TNFα), adipokines (adiponectin, leptin and monocyte chemotactic factor 1 (MCP-1)) and acute phase proteins (C-Reactive Protein (CRP) and sICAM-1) in the ovarian follicular fluid obtained at oocyte aspiration from women (n = 48) who were lean, overweight or obese. We hypothesised that adipokines and pro-inflammatory cytokines would be correlated with and/or dysregulated by increasing Body Mass Index (BMI). Surprisingly however, the majority were not related to BMI but instead were positively correlated with lipid levels in follicular fluid, namely triglycerides and free fatty acids. Further, as is typical of metabolic inflammation, the inflammatory markers that were associated with intra-follicular lipids included both pro-inflammatory (CRP, IL6, TNFα) and anti-inflammatory (adiponectin, IL10) mediators. The direct consequences of an ovarian microenvironment containing high levels of lipids and inflammatory mediators are not known but could impact luteinisation, ovulation and/or oocyte developmental competence., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective and Design: The aim of this study is to investigate the inflammatory alterations due to the use of smokeless tobacco and dual use of smokeless tobacco and cigarettes, relative to smoking., Subjects: Plasma and saliva samples were collected from healthy smokers (SMK-100 subjects), moist snuff users (MSC-89 subjects), the dual users (DUSMK-49 subjects), and non-tobacco consumers (NTC-99 subjects) from two cross-sectional studies., Methods: Luminex Human InflammationMAP® 1.0 panel, a multiplex immunoassay., Results: SMK and DUSMK exhibited larger number of alterations in the expression of inflammatory analytes compared to NTC. Eight analytes were significantly elevated (p ≤ .05) within plasma samples of SMK compared to NTC, while one 1 analyte was elevated between the MSC and NTC groups. DUSMK exhibited different levels of 11 analytes, relative to NTC. MSC displayed fewer alterations in inflammatory protein expression compared to smoker groups, and the inflammatory profile of MSC resembles NTC. Five analytes (ICAM-1, VEGF, MMP-9, ferritin and fibrinogen) emerged as potential biomarkers distinguishing tobacco consumers (p < .02)., Conclusions: We identified a set of five proteins as potential biomarkers that can inform of inflammation status due to tobacco usage. Our findings contribute a better understanding of how the use of different tobacco products contributes to inflammation., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate whether exogenous agmatine inhibits lipopolysaccharide (LPS)-induced activation and dysfunction of human umbilical vein endothelial cells (HUVECs) by modulating nuclear factor-κB (NF-κB) and MAPK signal pathways and the production of reactive oxygen species (ROS)., Methods: Cultured HUVECs were treated with agmatine at the optimized concentration of 1.0 mmolγL, LPS (10 µgγmL), and LPS + agmatine, with or without pretreatment with the inhibitors of NF-κB (PDTC), p38 (SB203580), and ERK (PD98059) for 1 h. The levels of soluble vascular cell adhesion molecule 1 (VCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin and monocyte chemoattractant protein 1 (MCP-1) in the supernatant were determined using ELISA, and their mRNA expressions, along with heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO-1), were assessed using real-time PCR. ROS production in the cells was determined using 2, 7-dichlorofluoresce in diacetate (DCFH-DA) as the fluorescence probe. The protein expressions of VCAM-1, ICAM-1, p65, phospho-p65 (p-p65), IκBα, p-IκBα, ERK, p-ERK, p38, p-p38, JNK, and p-JNK were detected using Western blotting., Results: LPS stimulation for 6 and 24 h significantly increased the levels of sVCAM-1, sICAM-1, sE-selectin and MCP-1 in the supernatant, intracellular ROS production, and the mRNA expressions of these molecules (P<0.05). Intervention with 1 mmolγL agmatine, similar with pretreatment with p38, ERK and NF-κB inhibitors, obviously inhibited such effects of LPS in HUVECs (P<0.05). Agmatine significantly up-regulated the mRNA expression of HO-1 (P<0.05), inhibited LPS-induced phosphorylation of p38, ERK, nuclear p65 and cytoplasmic IκBα, and up-regulated the protein expression of cytoplasmic IκBα., Conclusion: Agmatine inhibits LPS-induced activation and dysfunction of HUVECs by modulating NF-κB and MAPK signal pathways to down-regulate the expressions of adhesion molecules and chemokines and by up-regulating the expression of HO-1 to reduce ROS production.

Genetic incorporation of biologically orthogonal functional groups into macromolecules has the potential to yield efficient, controlled, reproducible, site-specific conjugation of affinity ligands, contrast agents, or therapeutic cargoes. Here, we applied this approach to ferritin, a ubiquitous iron-storage protein that self-assembles into multimeric nanocages with remarkable stability, size uniformity (12 nm), and endogenous capacity for loading and transport of a variety of inorganic and organic cargoes. The unnatural amino acid, 4-azidophenylalanine (4-AzF), was incorporated at different sites in the human ferritin light chain (hFTL) to allow site-specific conjugation of alkyne-containing small molecules or affinity ligands to the exterior surface of the nanocage. The optimal positioning of the 4-AzF residue was evaluated by screening a library of variants for the efficiency of copper-free click conjugation. One of the engineered ferritins, hFTL-5X, was found to accommodate ∼14 small-molecule fluorophores (AlexaFluor 488) and 3-4 IgG molecules per nanocage. Intravascular injection in mice of radiolabeled hFTL-5X carrying antibody to cell adhesion molecule ICAM-1, but not control IgG, enabled specific targeting to the lung due to high basal expression of ICAM-1 (43.3 ± 6.99 vs 3.48 ± 0.14%ID/g for Ab vs IgG). Treatment of mice with endotoxin known to stimulate inflammatory ICAM-1 overexpression resulted in 2-fold enhancement of pulmonary targeting (84.4 ± 12.89 vs 43.3 ± 6.99%ID/g). Likewise, injection of fluorescent, ICAM-targeted hFTL-5X nanocages revealed the effect of endotoxin by enhancement of near-infrared signal, indicating potential utility of this approach for both vascular targeting and imaging.

Cardiovascular calcification is associated with high risk of vascular disease. This involves macrophage infiltration of injured vascular tissue and osteoclast-related processes. Splenic monocytes from mice, that are predisposed (C3H) or resistant (B6) to calcification, were isolated and differentiated in vitro with M-CSF to generate macrophages, which aggregate to form multinucleated (MN) cells in the presence of RANKL. MN cell formation was significantly decreased in monocytes from resistant compared with calcifying mice. Conditioned media from C3H macrophages strongly induced calcification in vitro. However, medium from B6 macrophages inhibited calcification. An increase in ICAM-1 was detected in conditioned media from C3H macrophages compared with B6, suggesting a key role for this molecule in calcification processes. Due to natural genetic loss of Abcc6, the causal gene for cardiac calcification, C3H mice have reduced plasma levels of inorganic pyrophosphate (PPi), a potential calcification inhibitor. Supplementation of C3H mice with PPi or Etidronate prevented but did not completely reverse cardiac calcification. Our data provide strong evidence of the pathogenesis of macrophages and MNs during tissue calcification and suggest PPi or its analogue Etidronate as a potential inhibitor of MN formation and calcification. Furthermore, the adhesion molecule ICAM-1 was shown to play a key role in calcification.

Endothelial progenitor cells (EPCs) are an important component of stem-cell niches, which are able to promote the self-renewal and pluripotency of mesenchymal stem cells (MSCs). The biological functions of these two cell types is dependent on adhesion, and the adhesion between MSCs and EPCs is important due to their critical role in neovascularization and bone regeneration in tissue engineering. Intercellular adhesion molecule-1 (ICAM-1, also known as cluster of differentiation 54), is a member of the immunoglobulin supergene family, which functions in cell-cell and cell-matrix adhesive interactions. Compared with other adhesion molecules, ICAM-1 is expressed in hematopoietic and nonhematopoietic cells, and can mediate adhesive interactions. The present study aimed to investigate the importance of ICAM-1 in the adhesion of MSCs and EPCs, and demonstrated that adhesion between these cells could be regulated by interleukin (IL)-1β via the p38 mitogen‑activated protein kinase pathway. In addition, the results confirmed that ICAM-1 served a critical role in regulation of adhesion between MSCs and EPCs. ELISA, cell immunofluorescence, western blot analysis and adhesion assay were used to confirm our theory from phenomenon to essence. The present study provided evidence to support and explain the adhesion between MSCs and EPCs. Furthermore, the present findings provide a theoretical basis for further stem‑cell niche transplantation to increase understanding of the function of MSCs and the crosstalk between MSCs and EPCs in the stem-cell niche.

The objective of this study was to develop and validate the method based on micro-liquid chromatography-tandem mass spectrometry (microLC/MS-MRM) for simultaneous determination of adiponectin (ADN), von Willebrand factor (vWF), soluble form of vascular cell adhesion molecule 1 (sVCAM-1), soluble form of intercellular adhesion molecule 1 (sICAM-1) and syndecan-1 (SDC-1) in mouse plasma. The calibration range was established from 2.5pmol/mL to 5000pmol/mL for ADN; 5pmol/mL to 5000pmol/mL for vWF; 0.375pmol/mL to 250pmol/mL for sVCAM-1 and sICAM-1; and 0.25pmol/mL to 250pmol/mL for SDC-1. The method was applied to measure the plasma concentration of selected proteins in mice fed high-fat diet (HFD), and revealed the pro-thrombotic status by increased concentration of vWF (1.31±0.17 nmol/mL (Control) vs 1.98±0.09 nmol/mL (HFD), p <0.05) and the dysregulation of adipose tissue metabolism by decreased concentration of ADN (0.62±0.08 nmol/mL (Control) vs 0.37±0.06 nmol/mL (HFD), p <0.05). In conclusion, the microLC/MS-MRM-based method allows for reliable measurements of selected protein biomarkers of endothelial dysfunction in mouse plasma., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Amyloid β (Aβ) deposition is a hallmark of Alzheimer's disease (AD). Vascular modifications, including altered brain endothelial cell function and structural viability of the blood-brain barrier due to vascular pulsatility, are implicated in AD pathology. Pulsatility of phenomena in the cerebral vasculature are often not considered in in vitro models of the blood-brain barrier. We demonstrate, for the first time, that pulsatile stretch of brain vascular endothelial cells modulates amyloid precursor protein (APP) expression and the APP processing enzyme, β-secretase 1, eventuating increased-Aβ generation and secretion. Concurrent modulation of intercellular adhesion molecule 1 and endothelial nitric oxide synthase (eNOS) signaling (expression and phosphorylation of eNOS) in response to pulsatile stretch indicates parallel activation of endothelial inflammatory pathways. These findings mechanistically support vascular pulsatility contributing towards cerebral Aβ levels.

Anthocyanins, the naturally occurring pigments responsible for most red to blue colours of flowers, fruits and vegetables, have also attracted interest because of their potential health effects. With the aim of contributing to major insights into their structure-activity relationship (SAR), we have evaluated the radical scavenging and biological activities of selected purified anthocyanin samples (PASs) from various anthocyanin-rich plant materials: two fruits (mahaleb cherry and blackcurrant) and two vegetables (black carrot and "Sun Black" tomato), differing in anthocyanin content (ranging from 4.9 to 38.5 mg/g DW) and molecular structure of the predominant anthocyanins. PASs from the abovementioned plant materials have been evaluated for their antioxidant capacity using Trolox Equivalent Antioxidant Capacity (TEAC) and Oxygen Radical Absorbance Capacity (ORAC) assays. In human endothelial cells, we analysed the anti-inflammatory activity of different PASs by measuring their effects on the expression of endothelial adhesion molecules VCAM-1 and ICAM-1. We demonstrated that all the different PASs showed biological activity. They exhibited antioxidant capacity of different magnitude, higher for samples containing non-acylated anthocyanins (typical for fruits) compared to samples containing more complex anthocyanins acylated with cinnamic acid derivatives (typical for vegetables), even though this order was slightly reversed when ORAC assay values were expressed on a molar basis. Concordantly, PASs containing non-acylated anthocyanins reduced the expression of endothelial inflammatory antigens more than samples with aromatic acylated anthocyanins, suggesting the potential beneficial effect of structurally diverse anthocyanins in cardiovascular protection., Competing Interests: The authors declare no conflict of interest.

This chapter describes the methodologies which may be used in evaluating in vitro endothelial cell dysfunction in preeclampsia.

Objective: To investigate the expression of intercellular adhesion molecule-1 (ICAM-1) in serum and induced sputum supernatant in children with bronchiolitis, as well as its role in the pathogenesis of bronchiolitis in children., Methods: A total of 67 children with bronchiolitis who were diagnosed and hospitalized between July 2015 and January 2017 were enrolled. According to the diagnostic criteria, these children were divided into mild group with 22 children, moderate group with 24 children, and severe group with 21 children. A total of 20 children who underwent physical examination were enrolled as healthy control group. ELISA was used to measure the level of ICAM-1 in serum and induced sputum supernatant in the children with bronchiolitis in the acute stage and recovery stage and the children in the healthy control group., Results: Compared with the healthy control group, the mild, moderate, and severe bronchiolitis groups had a significant increase in the level of ICAM-1 in serum and sputum (P<0.01). Compared with the mild group, the moderate and severe groups had a significant increase in the level of ICAM-1 in serum and sputum (P<0.01). Compared with the moderate group, the severe group had a significant increase in the level of ICAM-1 in serum and sputum (P<0.01). Compared with the children with bronchiolitis in the acute stage, the children in the recovery stage had a significant reduction in the level of ICAM-1 in serum and sputum (P<0.01). The correlation analysis showed that in the acute stage, the level of ICAM-1 in serum was positively correlated with that in sputum in children with bronchiolitis (r=0.875, P<0.001)., Conclusions: ICAM-1 is involved in the pathogenesis of bronchiolitis and is associated with disease severity.

Brassinin, a phytoalexin firstly identified as a constituent of Chinese cabbage, has been demonstrated to exhibit antiproliferative effects on various cancer cell lines, by reducing reactive oxygen species (ROS) production via regulation of the antioxidant pathway. The present study aimed to explore the protective effects of brassinin in TNF‑α‑induced vascular inflammation in human umbilical vein endothelial cells (HUVECs). Pretreatment with brassinin significantly inhibited adhesion of U937 cells to TNF‑α‑induced HUVECs in a dose‑dependent manner. Brassinin treatment decreased the expression levels of cell adhesion molecules, including intracellular adhesion molecule‑1 (ICAM‑1), vascular cell adhesion molecule‑1 (VCAM‑1), and endothelial‑selectin (E‑selectin) following stimulation with TNF‑α in HUVECs. In addition, pretreatment with brassinin decreased the protein expression levels of nuclear factor (NF)‑κB p65 in the nucleus, suggesting that brassinin inhibited NF‑κB p65 nuclear translocation. Brassinin treatment also markedly decreased the mRNA expression levels of interleukin‑8 in a dose‑dependent manner. Finally, brassinin pretreatment significantly decreased TNF‑α‑induced intracellular reactive oxygen species (ROS) production in HUVECs compared with control. The present results therefore suggest that brassinin may serve as a potential therapeutic agent for atherosclerosis.

The present study aimed to identify whether FK506 suppresses hypoxia‑induced inflammation and protects tight junction function via the calcineurin‑nuclear factor of activated T‑cells 1 (CaN‑NFATc1) signaling pathway in mouse retinal microvascular endothelial cells (mRMECs). The mRMECs were treated with FK506 at different concentrations following the induction of hypoxia. Trans‑epithelial electrical resistance (TEER) and cell permeability were examined to measure the integrity of the tight junctions. The concentrations of inflammatory cytokines were measured using reverse transcription‑quantitative polymerase chain reaction analysis and enzyme‑linked immunosorbent assays. The protein expression levels of zonula occludens‑1 (ZO‑1) and nuclear factor of activated T‑cell 1 (NFATc1) were identified using immunofluorescent microscopy and western blot analysis. The TEER value was decreased following hypoxia, but increased following treatment with FK506 (1 and 10 µM) for 24 and 48 h. The protein expression of ZO‑1 was also increased following FK506 treatment for 24 h at 1 and 10 µM. By contrast, following treatment with FK506 (1 and 10 µM) for 24 and 48 h, the elevated cell permeability in the hypoxia group was significantly downregulated. Similarly, the concentrations of inflammatory cytokines, including cyclooxygenase‑2, inducible nitric oxide synthase, monocyte chemoattractant protein‑1, interleukin‑6, intercellular adhesion molecule‑1 and vascular cell adhesion molecule‑1, were downregulated following treatment with FK506 for 24 h at 1 and 10 µM. Following treatment with FK506, the level of total NFATc1 was downregulated and the level of phosphorylated NFATc1 was upregulated. Taken together, FK506 suppressed injury to the tight junctions and downregulated the expression of inflammatory cytokines in hypoxia‑induced mRMECs via the CaN‑NFATc1 signaling pathway. This suggests a potentially effective therapy for hypoxia‑induced retinal microangiopathy.

Psoriasis is a chronic disease, characterized by erythematous scaly lesions, presented in eight different forms: plaques, guttate, pustular, erythrodermic, inverse, nail and scalp psoriasis, and psoriatic arthritis. Its development depends on genetic factors, external stimulus and immune response alteration.1 Proinflammatory cytokines such as TNF-alpha, IL-12 and 23 may also be involved. In the worst cases, systemic complications linked to endothelial alterations may occur. A literature review was conducted for a better understanding of what roles VEGF (vascular endothelial growth factor) and ICAM-1 (intercellular adhesion molecule) have, among other cytokines, in systemic capillary leak syndrome, involved in erythrodermic and pustular psoriasis, the most unstable forms of the disease.

Background: Acute ischaemic stroke (AIS) triggers both systemic and neurovascular inflammation, influencing poststroke recovery. In smokers with AIS, inflammation might be further upregulated, increasing ischaemia/reperfusion injury. Here, the predictive value of leucocyte and adhesion molecules levels on poststroke outcomes was investigated., Materials and Methods: A total of 89 patients with AIS (n = 30 smokers and n = 59 nonsmokers) were recruited and evaluated 1, 7 and 90 days after the onset to assess stroke severity by the National Institute of Health Stroke Scale (NIHSS) score as well as clinical recovery at 90 days by the modified Rankin Scale (mRS). Lesion volume was assessed by noncontrast computed tomography. Haematological parameters, blood chemistry and soluble adhesion molecules were measured., Results: Smokers experienced a more severe stroke and at a younger age with respect to nonsmokers, moreover, they had higher circulating levels of monocytes, neutrophils and soluble adhesion molecules. Baseline monocytes positively correlated with stroke severity and disability across all time points in the overall cohort. No correlation was shown between adhesion molecules and poststroke outcomes. A monocyte count >0·63 × 10 9 /L predicted worse stroke severity (defined as NIHSS ≥5) at day 90 independently of age, hypertension, thrombolysis and active smoking in the overall cohort. Similarly, a monocyte count >0·64 × 10 9 /L predicted poor neurological recovery at day 90 (defined as mRS > 2)., Conclusions: Smoker had more severe AIS and higher leucocytes and adhesion molecule levels. In the overall cohort, monocyte count was an independent predictor of worse poststroke outcome. Although larger trials are needed, monocyte count might be a cheap prognostic parameter in AIS., (© 2017 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Varicose vein (VV) disease is a frequently occurring pathology of the lower extremities. Although the pathogenesis of varicosity development is not clearly defined, the final common pathway leading to chronic venous insufficiency is the development of venous hypertension, which is associated with severe changes in the venous wall. The aim of this study was to clarify the histological and immunohistochemical changes in great saphenous veins (GSVs) in chronic venous insufficiency., Methods: A histopathological study was conducted on 20 patients with VVs (4 males, 16 females) and 4 (1 male, 3 females) patients undergoing distal bypass surgery. Tissues were processed for histological routine straining and immunohistochemical studies of vascular endothelial growth factor (VEGF), intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, protein gene product 9.5 (PGP 9.5), and collagen type IV, laminin, and fibronectin. A semiquantitative evaluation method was used., Results: Compared with the normal SV, VV sections showed the damaged endothelium areas, significant disorganization of the smooth muscle bundles, and highest density of the vasa vasorum in the tunica media and tunica adventitia, as well as sclerotic blood vessels and neoangiogenesis in almost all specimens. Immunohistochemistry study showed statistically significant difference between the VVs and the control group of several parameters, such as PGP 9.5 positive structures (P < 0.05; 1-tailed significance) and laminin positive structures in subendothelial layer of VVs (P < 0.05; 1-tailed significance). There is also the tendency in increasing of VEGF expression and decreasing of collagen IV structures. Our study did not show statistically significant difference in VEGF, ICAM-1, and VCAM-1 positive structures between varicose and normal veins; however, it could be explained by the limitations of the study., Conclusions: Varicose GSVs represent nonhomogeneous integrity of the basement membrane, smooth muscle disorganization, and active neoangiogenesis, suggesting remodulation of blood vessels. Changes in the appearance of PGP 9.5-containing innervation, laminin, and collagen IV in tunica intima confirm the remodulation of damaged blood vessels., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Glucosamine is a possible cause of vascular endothelial injury in the initial stages of atherosclerosis, through endoplasmic reticulum (ER) stress resulting in fatty streaks in the vascular wall. Quercetin is an anti‑diabetic and cardiovascular protective agent that has previously been demonstrated to reduce ER stress in human umbilical vein endothelial cells (HUVECs). The present study aimed to investigate whether quercetin prevents glucosamine‑induced apoptosis and inflammation via ER stress pathway in HUVECs. The effect of quercetin on cell viability, apoptosis, and protein expression levels of inflammatory cytokines and ER stress markers was investigated in glucosamine‑supplemented HUVECs. Quercetin was demonstrated to protect against glucosamine‑induced apoptosis, improved cell viability, and inhibited expression of pro‑inflammatory factors and endothelin‑1. Quercetin treatment also reduced the expression levels of glucose‑regulated protein 78, phosphorylated protein kinase‑like ER kinase, phosphorylated c‑Jun N‑terminal kinase and C/EBP homologous protein. In conclusion, quercetin may have auxiliary therapeutic potential against glucosamine‑induced cell apoptosis and inflammation, which may be partially due to alleviation of ER stress.

A shock-and-kill approach involving the simultaneous treatment of HIV-1-infected patients with latency-reversing agents (LRAs) and combination antiretroviral therapy was proposed as a means to eradicate viral reservoirs. Currently available LRAs cannot discriminate between HIV-1-infected and uninfected cells. Therefore, the risks and benefits of using broad-spectrum LRAs need to be carefully evaluated, particularly in the CNS, where inflammation and leukocyte transmigration must be tightly regulated. We used a real-time impedance-sensing system to dynamically record the impact of different classes of LRAs on the integrity of tight monolayers of the immortalized human cerebral microvascular endothelial cell line hCMEC/D3. Results show that prostratin and bryostatin-1 can significantly damage the integrity of an endothelial monolayer. Moreover, prostratin and bryostatin-1 induce secretion of some proinflammatory cytokines and an increase of ICAM-1 expression. Additional studies demonstrated that prostratin and bryostatin-1 also affect adhesion and transmigration of CD4 + and CD8 + T cells as well as monocytes in an in vitro human blood-brain barrier (BBB) model. Prostratin and bryostatin-1 could thus be considered as potent regulators of BBB permeability and inflammation that influence leukocyte transport across the BBB. Altogether, these findings contribute to a better understanding of the potential risks and benefits of using a shock-and-kill approach with LRAs on the normal physiological functions of the BBB., (Copyright © 2017 by The American Association of Immunologists, Inc.)

Background/aims: This study aimed to screen microRNAs and their corresponding target genes that are associated with vascular injury in type two diabetes mellitus (T2DM), investigate the effects of differentially expressed miRNAs and their target genes on high glucose-induced vascular injury and establish the mechanism underlying these effects., Methods: A high-throughput digital gene expression (DGE) sequencing was performed to sequence microRNAs (miRNAs) and messenger RNAs (mRNAs) and determine their differential expression in human umbilical vein endothelial cells (HUVECs) incubated with serum samples from patients with T2DM and healthy volunteers. The HUVECs were transfected with si-TNF-α (tumor necrosis factor α) and a miR-149-5p inhibitor or mimic in vitro and then treated with normal or high glucose. The relative content of nitric oxide (NO) in the cells was detected using the Griess Reagent System. The mRNA and protein expression of endothelial nitric oxide synthase (eNOS) were determined by qRT-PCR and Western blotting. The content of endothelin-1 (ET-1), von Willebrand factor (vWF), and intercellular adhesion molecular-1 (ICAM-1) were detected using an enzyme-linked immunosorbent assay (ELISA) kit. Apoptosis was determined by flow cytometry using the Annexin V/PI apoptosis detection kit. The mRNA and protein expression levels of ER stress (ERS) markers were determined by qRT-PCR and Western blotting., Results: Based on the high-energy sequencing and in vitro pre-experiment studies, we determined that miR-149-5p and TNF-α were a differentially expressed mRNA/miRNA pair in T2DM with vascular injury. The luciferase reporter assay results demonstrated that miR-149-5p could directly target TNF-α. The upregulation of miR-149-5p reduced the high glucose-induced dysfunction in the HUVECs by significantly decreasing the levels of ET-1, vWF, and ICAM-1 and increasing the level of NO and the expression of eNOS. Additionally, we found that miR-149-5p can improve cell injury and reduce apoptosis by restoring the ameliorated high glucose-induced expression of ERS markers., Conclusion: TNF-α and miR-149-5p were differentially expressed in T2DM vascular endothelial injury. The over-expression of miR-149-5p ameliorates the high glucose-induced injury in the HUVECs by regulating the expression of TNF-α and ERS markers., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

Background/aims: To investigate the regulation of LaCl3 on lipopolysaccharides (LPS)-induced pro-inflammatory cytokines and adhesion molecules in human umbilical vein endothelial cells (HUVECs)., Methods: Primary cultured HUVECs were pretreated with 2.5 µM LaCl3 for 30 min followed by 1 µg/ml LPS for 2 h. Pro-inflammatory cytokine and adhesion molecule expressions were determined by real-time RT-PCR and ELISA. NF-κB/p65 nuclear translocation was examined by immunofluorescence and immuno-blot, and its DNA-binding activity was measured by chemiluminescence. Recruitment of NF-κB/p65, Jmjd3, and H3K27me3 to gene promoter regions was determined by ChIP-qPCR., Results: LaCl3 exhibited no cytotoxic effects to primary HUVECs at concentrations ≤ 50 µM. LPS-mediated TNF-α, IL-1β, IL-6, MMP-9, and ICAM-1 production, nuclear translocation, and DNA-binding activity of NF-κB/p65, as well as Jmjd3 expression, were all reduced significantly by LaCl3. Furthermore, LaCl3 treatment significantly impaired LPS-induced enrichment of NF-κB/p65 to the promoter regions of TNF-α, MMP-9, IL-1β, ICAM-1, and IL-6; and of Jmjd3 to the promoter regions of TNF-α, MMP-9, IL-1β, and IL-6. H3K27me3 abundance in the promoter regions of TNF-α and ICAM-1 increased significantly in following LaCl3 treatment., Conclusion: LaCl3 inhibits pro-inflammatory cytokine and adhesion molecule expressions induced by LPS in HUVECs. NF-κB and histone demethylase Jmjd3 are involved in this effect., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

Inflammation has been linked to clinical cognitive impairment, including Alzheimer's disease. Less is known, however, about the relationship between inflammation and normal, age-associated cognitive decline. An understanding of the determinants of all types of cognitive decline is important for improving quality of life in an aging world. This study investigated whether biomarkers of inflammation were associated with cognitive function and decline in older Taiwanese adults. Data were from the Taiwan Longitudinal Study of Aging and the Social Environment and Biomarkers of Aging Study. Inflammation was measured in 2000 and 2006 as C-reactive protein, interleukin-6, soluble e-selectin, soluble intercellular adhesion molecule-1, and white blood cell count. Cognition was assessed by 10 cognitive and memory tasks, measured in 2006, 2007, and 2011. Growth curve models were used to examine the relationship between inflammation and cognitive score over this time period. Higher levels of inflammation were associated with lower baseline cognitive scores, but not with longitudinal change in cognitive score. This study did not support a causal link between inflammation and cognitive decline among this older cohort. The observed cross-sectional relationship could reflect a causal relationship that arises earlier in life, or confounding; additional research across the life course is warranted.

Background: Biliary cirrhosis (BC) is a chronic cholestatic liver disease, in which hepatic fibrosis is an early symptom. This study aimed to identify the biological function and the therapeutic effect of a Chinese traditional medicine, HuaGanTongLuoFang (HGTLF), in a mouse model of BC., Methods: The mice (n = 72) were randomly divided into a sham group (n =12) and BC group (n = 60). The animals in the BC group were then randomly divided into five groups (n = 12 in each) and treated with three different doses of HGTLF, ureodeoxycholic acid (UDCA), or normal saline (the model group). Four weeks later, serum and liver tissues were obtained from all the animals for analyses. Hematoxylin and eosin (H&E) staining was used to quantify the hepatic morphology, while real-time PCR and Enzyme-linked immunosorbent assay (ELISA) were used to determine the level of hepatic fibrosis-related genes., Results: Compared with the model group, all three doses of HGTLF improved hepatic function, as well as reducing inflammation and fibrogenesis. The best therapeutic effect was observed in the high-dose HGTLF group. Furthermore, HGTLF contributed to down-regulation of hepatic fibrosis-related genes (platelet-derived growth factor [PDGF], transforming growth factor-β [TGF-β], p38, nuclear factor-κB [NF-kB], intercellular adhesion molecular-1 [ICAM-1], and tissue inhibitor of metalloproteinase-1 [TIMP-1])., Conclusion: The data suggested that HGTLF effectively improved liver function and the morphology of the liver tissue in a mouse model of BC, possibly via suppression of hepatic fibrosis-related signals., (© 2017 The Author(s). Published by S. Karger AG, Basel.)