Intercellular Adhesion Molecule-1 Levels Research Articles

Vascular injury is associated with repetitive head impacts and tau pathology in chronic traumatic encephalopathy.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head impacts (RHI) and characterized by perivascular hyperphosphorylated tau (p-tau) deposits. The role of vascular injury, blood-brain barrier leakage, and neuroinflammation in CTE pathogenesis is not well understood. We performed quantitative immunoassays for intercellular adhesion molecule 1 (ICAM1), vascular cellular adhesion molecule 1 (VCAM1), and C-reactive protein (CRP) within the postmortem dorsolateral frontal cortex of participants with and without a history of RHI and CTE (n = 156), and tested for associations with RHI, microgliosis, and tau pathology measures. Levels of vascular injury-associated markers ICAM1, VCAM1, and CRP were increased in CTE compared to RHI-exposed and -naïve controls. ICAM1 and CRP increased with RHI exposure duration (p < 0.01) and were associated with increased microglial density (p < 0.001) and tau pathology (AT8, p-tau396, p-tau202; p < 0.05). Histologically, there was significantly increased ICAM1 staining of the microvasculature, extracellular space, and astrocytes at the sulcal depths in high stage CTE compared to both low stage CTE and controls. Multifocal perivascular immunoreactivity for serum albumin was present in all RHI-exposed individuals. These findings demonstrate that vascular injury markers are associated with RHI exposure, duration, and microgliosis, are elevated in CTE, and increase with disease severity.

Mechanism of total flavonoids of Ziziphora clinopodioides in improving atherosclerosis by regulating PI3K/Akt/mTOR pathway

The present study observed the regulatory effect of total flavonoids of Ziziphora clinopodioides on autophagy and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathways in ApoE~(-/-) mice and explored the mechanism of total flavonoids of Z. clinopodioides against atherosclerosis(AS). ApoE~(-/-) mice were fed on a high-fat diet for eight weeks to induce an AS model. The model mice were randomly divided into a model group, a positive control group, and low-, medium-and high-dose groups of total flavonoids of Z. clinopodioides, while C57BL/6J mice fed on a common diet were assigned to the blank group. The serum and aorta samples were collected after intragastric administration for 12 weeks, and the serum levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C), and high density lipoprotein-cholesterol(HDL-C) were detected by an automatic biochemical analyzer. The serum expression levels of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), matrix metalloproteinase-2(MMP-2), and matrix metalloprotei-nase-9(MMP-9) were detected by enzyme-linked immunosorbent assay(ELISA). Oil red O staining was used to observe the aortic plaque area in mice. Hematoxylin-eosin(HE) staining was used to observe the aortic plaque and pathological changes in mice. The expression of P62 and LC3 in the aorta was detected by the immunofluorescence method. The protein expression of LC3Ⅱ/Ⅰ, Beclin-1, P62, p-PI3K, p-Akt, and p-mTOR in the aorta of mice was detected by Western blot. The results showed that compared with the blank group, the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2 and MMP-9 in the model group were significantly increased(P&lt;0.01 or P&lt;0.05), the content of HDL-C was decreased(P&lt;0.05), intra-aortic plaque area was enlarged(P&lt;0.01), the expression of LC3 in the aorta was significantly down-regulated, P62 expression was up-regulated(P&lt;0.01 or P&lt;0.05), the expressions of LC3Ⅱ/Ⅰ and Beclin-1 in the aortic lysate were significantly down-regulated, and the expressions of p-PI3K, p-Akt, p-mTOR and P62 were significantly increased(P&lt;0.01). The medium-and high-dose groups of total flavonoids of Z. clinopodioides could reduce the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2, and MMP-9 in AS model mice(P&lt;0.01 or P&lt;0.05), and increase the content of HDL-C(P&lt;0.01 or P&lt;0.05). The aortic plaque area of mice after middle and high doses of total flavonoids of Z. clinopodioides was significantly reduced(P&lt;0.01), the content of foam cells decrease, and the narrowing of the lumen decreased. The total flavonoids of Z. clinopodioides significantly increased the expression of LC3 in the aorta and the expression of LC3Ⅱ/Ⅰ and Beclin-1 in the lysate, and decreased the expression of P62 in the aorta and the expression of p-PI3K, p-Akt, p-mTOR and P62 in the lysate(P&lt;0.01 or P&lt;0.05). The results showed that the total flavonoids of Z. clinopodioides could improve the content of blood lipids and inflammatory factors, and reduce the generation of foam cells and plaques in aortic tissue, and the mechanism may be related to the regulation of PI3K/Akt/mTOR signaling pathway.

PS-B03-10: EPLERENONE INHIBITS ICAM-1 FROM MACROPHAGES AND MACROPHAGE-TO-MYOFIBROBLAST TRANSITION IN TYPE 4 CARDIORENAL SYNDROME RATS INDUCED WITH UUO

Objective: The type 4 cardiorenal syndrome (CRS) represents the kidney-heart relationship in a pathological situation where cardiovascular complications dominate all causes of death in patients with chronic kidney disease (CKD), but the underlying mechanism of CKD-induced cardiac disease have not been fully clarified. We reported that aldosterone directly stimulates cardiac fibrosis, whereas macrophage-to-myofibroblast (MMT) is associated with fibrosis. However, the mechanistic basis of this pathogenic pathway that promotes cardiac fibrosis remains to be elucidated. Design and method: We used a 180-day rat model of unilateral ureteral obstruction (UUO) to replicate the CRS model and RAW264.7 cells in-vitro studies. Using eplerenone, a blocker of mineralocorticoid receptor (MR), to test the effect of aldosterone in cardiac fibrosis induced by UUO. The levels of intercellular adhesion molecule (ICAM)-1 and monocyte chemoattractant protein (MCP)-1 were examined to verify the role of macrophage infiltration and inflammatory injury. Co-expression of macrophage marker CD68 and myofibroblast marker -SMA to identify MMT contributing to cardiac fibrosis. Results: We identified cardiac injury in UUO rats, and eplerenone can inhibit UUO-induced cardiac fibrosis. We found that macrophages can co-express the myofibroblast marker alpha-SMA for phenotypic transformation and participate in cardiac fibrosis by secreting collagen III, while eplerenone inhibits this process. Activated MR enhanced macrophage infiltration and secretion of ICAM-1 and MCP-1, which stimulated inflammatory injury in the heart, whereas aldosterone stimulation and eplerenone treatment with RAW264.7 revealed a role for aldosterone in cardiac fibrosis. Conclusions: Our results identified the role of aldosterone in promoting macrophage infiltration and MMT through MR/SGK-1 pathway. These findings provide a new mechanism for macrophage involvement in the pathogenesis of UUO-induced cardiac fibrosis and reveal novel therapeutic targets.

Efekat kalcijum dobesilata u kombinaciji sa hipoglikemijskim lekovima u lečenju NPDR katarakte i njegov uticaj na mikrocirkulaciju fundusa i nivoe ICAM-1, MCP-1 i MIF u krvi

Background: To explore the effect of calcium dobesilate combined with hypoglycemic drugs in the treatment of cataract complicated with non-proliferative diabetic retinopathy (NPDR) and its effects on fundus microcirculation, intercellular adhesion molecule 1 (ICAM-1), mono - cyte chemoattractant protein 1 (MCP-1), and macrophage migration inhibitory factor (MIF). Methods: From March 2019 to January 2021, a total of 114 patients with cataract and NPDR were included, and the patients were assigned into the control and the observation groups by random number table method, with 57 cases/group. The control was given hypoglycemic drugs, and the observation was given calcium dobesilate combined therapy. The therapeutic efficacy, blood glucose and blood lipid levels, fluorescein fundus angiography results, fundus microcirculation indexes, retinal neovascularizationrelated factors, and ICAM-1, MCP-1, and MIF levels before and after treatment were compared between the two groups. Results: The total effective rate of treatment in the observation was higher vs. the control (P &lt; 0.05); Fasting blood glucose (FBG), 2 h postprandial blood glucose (2hPG), glycosylated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC) and low density lipoprotein (LDL) in the observation after treatment were reduced vs. the control (P &lt; 0.05); The number of micro-hemangiomas in the observation after treatment was less vs. the control, and the area of hemorrhage, the area of exudation and the thickness of the yellow plate were smaller vs. the control (P &lt; 0.05); The resistance index (RI) value of the observation after treatment was lower than the control, and the end-diastolic blood flow velocity (EDV) and the peak systolic blood flow velocity (PSV) of the observation were higher vs. the control (P &lt; 0.05). ICAM-1, MCP-1, MIF, vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF1) in the observation after treatment were reduced vs. the control, but pigment epithelium-derived factor (PEDF) were higher vs. the control (P &lt; 0.05); one case of gastrointestinal reaction took place in the observation, but no adverse reaction occurred in the control, and no clear difference exhibited in the incidence of adverse reactions between the two groups (P &gt; 0.05). Conclusions: Calcium dobesilate combined with hypoglycemic drugs has good clinical efficacy in the treatment of cataract complicated with NPDR, which can effectively reduce the level of blood glucose and blood lipids, reduce inflammation, and mitigate the microcirculation of branch retinal vein occlusion lesions.

E prostanoid receptor-3 promotes oxidized low-density lipoprotein-induced human aortic smooth muscle cells inflammation.

The progression of atherosclerosis can lead to the occurrence of multiple cardiovascular diseases (coronary heart disease, etc.). E prostanoid receptor-3 (EP3) is known to participate in the progression of atherosclerosis. This study aimed to investigate the mechanism by which EP3 modulates the development of atherosclerosis. ApoE-/- mice were used to construct in vivo model of atherosclerosis. Human aortic smooth muscle cells (HASMCs) were stimulated with oxidized low-density lipoprotein (ox-LDL) to construct in vitro model of atherosclerosis. mRNA expressions were assessed by qRT-PCR, and western blot was applied to assess the protein levels. CCK-8 assay was applied to assess the cell viability. The inflammatory cytokines levels were assessed by enzyme-linked immunosorbent assay, and flow cytometry was applied to assess cell apoptosis. In vivo experiment was constructed to investigate the impact of EP3 in atherosclerosis development. L-798106 (EP3 inhibitor) significantly inhibited the levels of pro-inflammatory cytokines in atherosclerosis in vivo. EP3 inhibitor (L-798106) significantly reversed ox-LDL-caused HASMCs injury via inhibiting the apoptosis and inflammatory responses (P<0.05). The levels of interleukin-17 (IL-17) and intercellular adhesion molecule-1 (ICAM-1) in HASMCs were elevated by ox-LDL, whereas L-798106 or knockdown of cyclic AMP (cAMP) response element-binding protein (CREB) notably restored this phenomenon (P<0.05). EP3 overexpression further aggravated ox-LDL-induced inflammation in HASMCs, and EP3 up-regulated the levels of IL-17 and ICAM-1 in ox-LDL-treated HASMCs (P<0.05). EP3 up-regulation promoted the inflammatory responses in ox-LDL-treated HASMCs through mediation of cAMP/protein kinase A (PKA)/CREB/IL-17/ICAM-1 axis (P<0.05). EP3 inhibitor alleviates ox-LDL-induced HASMC inflammation via mediation of cAMP/PKA/CREB/IL-17/ICAM-1 axis. Our study might shed new lights on discovering novel strategies against atherosclerosis.

Assessment of I-CAM1, V-CAM1, and E-selectin Serum Levels in Patients with Breast and Pelvic Cancer: A Case Control Study

Background: Breast and pelvic cancers are the most prevalent cancers among women globally. Several studies have reported on the effect of cell adhesion molecules on the growth, multiplication, invasion, and metastasis of tumor cells as well as inflammatory biomarkers, which are responsible for harmful inflammatory processes. Objectives: The purpose of the current study was to assess the serum levels of adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in patients with cancer before and after radiotherapy, compare these with the levels of healthy subjects, and consider the relationship of these levels with the tumor origin. Methods: The present case-control study investigated 14 patients with breast cancer and 14 patients with pelvic cancer who had been referred to Omid Teaching Hospital’s oncology clinic, Mashhad, Iran between 2015 and 2017. Evaluated by the ELISA method for ICAM-1, VCAM-1, and E-selectin were the serum samples of these 28 cancer patients before and after their course of radiotherapy treatment and the serum samples of the 28 healthy subjects who had no history of cancer, radiotherapy or the risk factor of coronary artery disease. Results: The ICAM-1, VCAM-1, and E-selectin serum levels of all patients with cancer before and after a course of radiotherapy were significantly higher than those of the control group (P-value ≤ 0.5). There was no significant difference between the two cancer groups before and after radiotherapy (P-value ≥ 0.05). Conclusions: The current study demonstrated that the serum levels of adhesion molecules in patients with cancer before and after radiotherapy increase significantly regardless of the initial location of the tumor.

Sustained therapeutic effect of an anti-inflammatory peptide encapsulated in nanoparticles on ocular vascular leakage in diabetic retinopathy.

Pigment epithelium-derived factor (PEDF), an endogenous Wnt signaling inhibitor in the serine proteinase inhibitors (SERPIN) super family, is present in multiple organs, including the vitreous. Significantly low levels of PEDF in the vitreous are found to associate with pathological retinal vascular leakage and inflammation in diabetic retinopathy (DR). Intravitreal delivery of PEDF represents a promising therapeutic approach for DR. However, PEDF has a short half-life after intravitreal injection, which represents a major hurdle for the long-term treatment. Here we report the prolonged therapeutic effects of a 34-mer peptide of the PEDF N-terminus, encapsulated in poly (lactic-co-glycolic acid) (PLGA) nanoparticles (PEDF34-NP), on DR. PEDF34-NP inhibited hypoxia-induced expression of vascular endothelial growth factor and reduced levels of intercellular adhesion molecule 1 (ICAM-1) in cultured retinal cells. In addition, PEDF34-NP significantly ameliorated ischemia-induced retinal neovascularization in the oxygen-induced retinopathy rat model, and significantly reduced retinal vascular leakage and inflammation in streptozotocin-induced diabetic rats up to 4weeks after intravitreal injection, as compared to PLGA-NP control. Intravitreal injection of PEDF34-NP did not display any detectable toxicities to retinal structure and function. Our findings suggest that PEDF34-NP can confer sustained therapeutic effects on retinal inflammation and vascular leakage, having considerable potential to provide long-term treatment options for DR.

DCZ19931, a novel multi-targeting kinase inhibitor, inhibits ocular neovascularization

Neovascularization is a prominent cause of irreversible blindness in a variety of ocular diseases. Current therapies for pathological neovascularization are concentrated on the suppression of vascular endothelial growth factors (VEGF). Despite the remarkable efficacy of anti-VEGF drugs, several problems still exist, including ocular complications and drug resistance. Thus, it is still required to design novel drugs for anti-angiogenic treatment. This study aimed to investigate the anti-angiogenic effects of a small molecule multi-target tyrosine kinase inhibitor, DCZ19931, on ocular neovascularization. The results showed that administration of DCZ19931 at the tested concentrations did not cause obvious cytotoxicity and tissue toxicity. DCZ19931 could reduce the size of choroidal neovascularization (CNV) lesions in laser-induced CNV model and suppress ocular neovascularization in oxygen-induced retinopathy (OIR) model. DCZ19931 could suppress VEGF-induced proliferation, migration, and tube formation ability of endothelial cells, exhibiting similar anti-angiogenic effects as Ranibizumab. DCZ19931 could reduce the levels of intercellular cell adhesion molecule-1 (ICAM-1) expression in vivo and in vitro. Network pharmacology prediction and western blots revealed that DCZ19931 exerted its anti-angiogenic effects through the inactivation of ERK1/2-MAPK signaling and p38-MAPK signaling. In conclusion, this study indicates that DCZ19931 is a promising drug for anti-angiogenic therapy for ocular diseases.

Immunostimulatory oncolytic activity of coxsackievirus A11 in human malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is an aggressive solid cancer with a poor prognosis, whereas coxsackievirus A11 (CVA11) is a potential oncolytic virus for cancer treatment. We here investigated the oncolytic activity of CVA11 with human MPM cell lines. CVA11 infection was cytotoxic in all six MPM cell lines examined and showed no or minimal cytotoxicity toward normal human normal cell lines. MPM cells with a higher surface level of intercellular adhesion molecule-1 (ICAM-1) expression tended to be more susceptible to CVA11-induced cytotoxicity, and a neutralizing antibody to ICAM-1 attenuated such cytotoxicity. CVA11 infection activated signaling by Akt and extracellular signal-regulated kinase (ERK) pathways, and inhibitors of such signaling also abrogated CVA11-mediated cytotoxicity. Furthermore, CVA11 infection-triggered multiple modes of tumor cell death including apoptosis, pyroptosis, and necroptosis, and such death was accompanied by the release or exposure of the proinflammatory cytokine interleukin-1β and damage-associated molecular patterns such as calreticulin, high-mobility group box-1, annexin A1, and heat shock protein 70, which are hallmarks of immunogenic cell death. Notably, in vivo treatment of human MPM xenografts with intratumoral CVA11 injection resulted in significant suppression of tumor growth in SCID mice, and all mice infected with CVA11 showed no significant change in body weight. Our findings collectively suggest that the oncolytic activity of CVA11 for MPM is dependent on ICAM-1 as a virus receptor, as well as on Akt and ERK signaling, and that oncolytic virotherapy with CVA11 is a promising treatment modality with immunostimulatory activity for human MPM.

Pretransplant serum levels of endothelial cell activation markers are associated with graft loss and mortality after kidney transplantation.

Long-term allograft survival remains a challenge in kidney transplantation. In this study, we aimed to identify biomarkers for potentially modifiable pathways involved in the outcome of kidney transplantation. We tested the hypothesis that a pre-existing systemic environment with endothelial cell activation in the recipient is associated with the outcome after kidney transplantation. In a retrospective study cohort of 611 kidney transplanted patients, we investigated associations between serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) before transplantation and delayed graft function, acute rejection, graft loss and mortality after transplantation. We adjusted associations for age, sex, preformed donor-specific antibodies (DSA), pretransplant diabetes, cardiovascular disease and dialysis. Additionally, we investigated if associations between endothelial cell activation markers and outcomes differed in recipients with and without preformed DSA. Serum levels of endothelial cell activation markers were associated with delayed graft function and mortality but not with rejection. Additionally, high levels of sICAM-1 were associated with graft loss. Associations were most pronounced in recipients without DSA, adjusted for potential confounders. Data suggest that endothelial cell activation at the time of transplantation is associated with graft loss and mortality after kidney transplantation, especially in transplant candidates without preformed DSA.

Serum inflammatory cell adhesion molecules predict malignant cerebral edema and clinical outcome early after mechanical thrombectomy in stroke

BackgroundEarly prediction of life-threatening malignant cerebral edema (MCE) after mechanical thrombectomy (MT) is of clinical importance. Although inflammatory cell adhesion molecules (CAMs) and anti-inflammation factor Kruppel-like transcription factor (KLF) 4 are induced after acute ischemic stroke (AIS), the relationship between expressions of these molecules after MT and MCE as well as outcome in AIS patients have rarely been explored. MethodsWe retrospectively reviewed the data of all AIS patients with large-vessel occlusion in anterior circulation who underwent MT from our stroke centers. The serum levels of CAMs and KLF4 were determined at 12 h after MT. MCE was assessed on follow-up head computed tomography within 5 days after MT. ResultsOf 91 included patients, 18 (19.8 %) patients experienced MCE. Patients with MCE were more likely to have higher levels of E-selectin and inter-cellular adhesion molecule 1 (ICAM-1) than those without MCE (P < 0.05). More specifically, elevated E-selectin, but not of vascular cell adhesion molecule 1 (VCAM-1), ICAM-1 and KLF4, was significantly associated with MCE after adjusting for hypertension, admission NIHSS, Alberta Stroke Program Early CT Scores, serum glucose, collateral circulation and onset to recanalization time respectively (P < 0.05). ROC curve suggested that E-selectin had considerable discrimination to predict MCE (AUC=0.7, 95 % CI: 0.55–0.83). Moreover, after adjusting by confounders, serum levels of E-selectin and ICAM-1 were independently associated with 3-month outcome in AIS patients after MT (both P < 0.05). ConclusionsThese data indicate that of three CAMs, serum E-selectin level early after MT is the best predictor for MCE and outcome in AIS.

VEGF promotes diabetic retinopathy by upregulating the PKC/ET/NF-κB/ICAM-1 signaling pathway.

Diabetic retinopathy (DR) is a common microvascular complication in patients with diabetes mellitus. DR is caused by chronic hyperglycemia and is characterized by progressive loss of vision because of damage to the retinal microvasculature. In this study, we investigated the regulatory role and clinical significance of the vascular endothelial growth factor (VEGF)/protein kinase C (PKC)/endothelin (ET)/nuclear factor-κB (NF-κB)/intercellular adhesion molecule 1 (ICAM-1) signaling pathway in DR using a rat model. Intraperitoneal injections of the VEGF agonist, streptozotocin (STZ) were used to generate the DR model rats. DR rats treated with the VEGF inhibitor (DR+VEGF inhibitor) were used to study the specific effects of VEGF on DR pathology and the underlying mechanisms. DR and DR+VEGF agonist rats were injected with the PKCβ2 inhibitor, GF109203X to determine the therapeutic potential of blocking the VEGF/PKC/ET/NF-κB/ICAM-1 signaling pathway. The body weights and blood glucose levels of the rats in all groups were evaluated at 16 weeks. DR-related retinal histopathology was analyzed by hematoxylin and eosin staining. ELISA assay was used to estimate the PKC activity in the retinal tissues. Western blotting and RT-qPCR assays were used to analyze the expression levels of PKC-β2, VEGF, ETs, NF-κB, and ICAM-1 in the retinal tissues. Immunohistochemistry was used to analyze VEGF and ICAM-1 expression in the rat retinal tissues. Our results showed that VEGF, ICAM-1, PKCβ2, ET, and NF-κB expression levels as well as PKC activity were significantly increased in the retinal tissues of the DR and DR+VEGF agonist rat groups compared to the control and DR+VEGF inhibitor rat groups. DR and DR+VEGF agonist rats showed significantly lower body weight and significantly higher retinal histopathology scores and blood glucose levels compared to the control and DR+VEGF inhibitor group rats. However, treatment of DR and DR+VEGF agonist rats with GF109203X partially alleviated DR pathology by inhibiting the VEGF/ PKC/ET/NF-κB/ICAM-1 signaling pathway. In summary, our data demonstrated that inhibition of the VEGF/ PKC/ET/NF-κB/ICAM-1 signaling pathway significantly alleviated DR-related pathology in the rat model. Therefore, VEGF/PKC/ET/NF-κB/ICAM-1 signaling axis is a promising therapeutic target for DR.

The Relationship of Carotid Intima-Media Thickness with Cell Adhesion Molecules and Pentraxin-3 in Patients with Psoriatic Arthritis

Abstract Aim Cardiovascular morbidity is increased in patients with psoriatic arthritis (PsA) compared to the general population. Several recent studies have indicated that pentraxin 3 (PTX-3) and cell adhesion molecules (CAMs) might be independent biomarkers of subclinical atherosclerosis. In this study, we aimed to determine the relationship of CAMs and PTX-3 with carotid intima media thickness (CIMT) in patients with PsA and to compare CIMT and serum levels of these biomarkers in patients with healthy controls (HCs). Method PsA patients fulfilling the CASPAR (Classification criteria for Psoriatic Arthritis) criteria without traditional cardiovascular (CV) comorbidity and HCs without autoimmune and/or CV disease were included in this cross-sectional study. Carotid artery Doppler ultrasound examinations were conducted by a single radiologist blinded to the participants’ clinical characteristics. Serum vascular adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin, and PTX-3 concentrations were analized. Results 43 PsA patients (27 females, mean age 42.49±11.70 years, and a mean disease duration of 9.37±7.96 years) and 37 HCs (28 females, mean age 42.16±11.38 years) were included. In regression analyses, age and PTX-3 were found to be the best predictors of CIMT in patients with PsA. CIMT was significantly higher in PsA patients compared with HCs (0.63±0.18 vs. 0.49±0.10 mm, p&lt;0.01). In te PsA group, serum levels of PTX-3, ICAM-1, and VCAM-1 were also significantly higher than HCs. CIMT correlated positively with age, disease duration, PTX-3, ICAM-1, and VCAM-1 (p&lt;0.05). Conclusion In our study, age and serum level of PTX-3 were found to be the predictors of CIMT in patients with PsA without CV comorbidity. This outcome highlights the importance of monitoring CIMT and serum level of PTX-3 as CV risk factors in PsA patients.

Evaluation of Blood Intercellular Adhesion Molecule-1 (ICAM-1) Level in Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis.

Background and objective: Intercellular adhesion molecule-1 (ICAM-1) appears to be an active and important biomarker for decreasing the risk of cardiovascular issues among individuals with obstructive sleep apnea (OSA). Herein, a systematic review and meta-analysis was designed to probe whether plasma/serum ICAM-1levels are different in adults with OSA compared to adults with no OSA, as well as adults with severe OSA compared to adults with mild/moderate OSA. Materials and methods: A thorough and systematic literature search was performed in four databases (PubMed/Medline, Web of Science, Scopus, and Cochrane Library) until 17 July 2022, without any age and sample size restrictions to retrieve the relevant articles. The standardized mean difference (SMD) along with a 95% confidence interval (CI) of plasma/serum of ICAM-1 levels was reported. Analyses, including sensitivity analysis, subgroup analysis, trial sequential analysis, meta-regression, and a funnel plot analysis, were performed in the pooled analysis. Results: A total of 414 records were identified in the databases, and 17 articles including 22 studies were entered into the meta-analysis. The pooled SMD of serum/plasma ICAM-1 levels in adults with OSA compared to controls was 2.00 (95%CI: 1.41, 2.59; p < 0.00001). The pooled SMD of serum/plasma ICAM-1 levels in adults with severe compared to mild/moderate OSA was 3.62 (95%CI: 1.74, 5.51; p = 0.0002). Higher serum/plasma ICAM-1 levels were associated with a higher mean age of controls, higher scores for the apnea-hypopnea index, and with a lower mean age of adults with OSA and with smaller sample sizes. Conclusions: Th results of the present meta-analysis showed that serum/plasma ICAM-1 levels in adults with OSA was higher than serum/plasma ICAM-1 levels in controls. Similarly, serum/plasma ICAM-1 levels in adults with severe OSA were higher compared to serum/plasma ICAM-1 levels of adults with mild or moderate OSA. Therefore, ICAM-1 may be used as an additional diagnostic and therapeutic biomarker in adults with OSA.

Modulation of salivary ICAM-1 and SIRT1 by disease modifying drugs in undepressed relapsing-remitting multiple sclerosis patients

BackgroundThe pathophysiology of Multiple Sclerosis (MS) is multifactorial where the correlation between inflammation and MS is evident. Adhesion molecules such as Intercellular adhesion molecule-1 (ICAM-1) are implicated in MS. SIRT1 is a member of surtins family that play a protective role in neurodegenerative and inflammatory diseases. Although previously studied in Relapsing-Remitting Multiple Sclerosis (RRMS) patients, however the salivary expression of ICAM-1 and SIRT1 have not been yet studied in patients receiving fingolimod or interferon-β. Therefore, the present research aimed to investigate the expression of salivary ICAM-1 and SIRT1 in RRMS patients treated with fingolimod or interferon-β compared to controls. MethodsRRMS patients attending the neurology department of AL-Bashir Hospital were recruited. Patients’ demographics, clinical information, and psychiatric status were evaluated (depression, anxiety and stress). Afterward, matched controls were recruited, then unstimulated whole saliva was obtained from the participants. The salivary expression of ICAM-1 and SIRT1 was investigated using western blot and normalized with β-actin. ResultsData were analyzed from 53 participants: 26 on fingolimod, 14 on interferon-β, and 13 control. The interferon-β treated patients showed a significantly (p < 0.001) higher ICAM-1 expression and lower SIRT1 expression (p < 0.05) compared to the control. Levels of ICAM-1 and SIRT1 did not vary between fingolimod and control. ConclusionICAM-1 and SIRT1 expression might be affected with fingolimod or INF- β treatment which should be investigated more in the future.

Inflammation and emotion regulation: Findings from the MIDUS II study

Emotion regulation (ER) strategies are thought to contribute to mental as well as physical health outcomes. Two common ER strategies include expressive suppression, or inhibition of emotional expression, and cognitive reappraisal, which involves changing how to think about an emotion-eliciting event in order to change its emotional impact. Recent reports have hypothesized that one potential way in which ER may be linked to health outcomes is via the immune system. However, information on this putative link is scarce. The present study aims to explore whether peripheral inflammatory biomarkers are associated with individual differences in ER-strategy use. Participants (n = 117) from the Midlife in the United States II (MIDUS II) study completed the Emotion Regulation Questionnaire (ERQ), and provided a blood sample for immune biomarker extraction including interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), E-selectin, Intercellular Adhesion Molecule-1 (ICAM-1), and fibrinogen. Results showed higher levels of expressive suppression were associated with decreased IL-10, TNF-α, and ICAM-1 levels (controlling for age, sex, BMI, total prescribed medications, and depressive symptoms). Consistent with these findings, hierarchical regression results identified TNF-α as a significant predictor of expressive suppression use. In contrast, no inflammatory markers were associated with predicted use of cognitive reappraisal. Our findings suggest a link between inflammation and specific ER-strategy use. Future research should consider the effects of pro-vs. anti-inflammatory cytokines on adaptive ER and subsequent mental and physical health.

Endothelial dysfunction and atherosclerosis related miRNA-expression in patients with haemophilia.

Elevated markers of endothelial dysfunction and inflammation indicate worse endothelial function in the aging haemophilia population. MicroRNAs (miRNAs) regulate gene expression post-transcriptionally. Several miRNAs have been shown to be involved in the process of endothelial dysfunction and atherosclerosis. The aim of this study was to determine the underlying molecular pathways of endothelial dysfunction and inflammation in haemophilia patients. A total of 25 patients with severe or moderate haemophilia A (20 patients) or B (5 patients), 14 controls and 18 patients with coronary artery disease (CAD) after myocardial infarction were included in this study. Expression of miRNA-126, -155, -222, -1, -let7a, -21 and -197 were analysed using a real time polymerase chain reaction. Network-based visualisation and analysis of the miRNA-target interactions were performed using the MicroRNA ENrichment TURned NETwork (MIENTURNET). Expression of miRNA-126 (p<.05) and miRNA-let7a (p<.05) were significantly higher in CAD patients compared to haemophilia patients and controls. MiRNA-21 (p<.05) was significantly elevated in CAD patients compared to controls. MiRNA-155 (p<.05), miRNA-1 (p<.05) and miRNA-197 (p<.05) were significantly higher expressed in CAD and haemophilia patients compared to controls and showed a strong correlation with increased levels of interleukin-6 (IL-6) and soluble intercellular adhesion molecule-1 (sICAM-1). The network analysis revealed interactions in the cytokine signalling, focal adhesion and VEGFA-VEGFR2 pathway (Vascular endothelial growth factor, -receptor). This study characterises miRNA expression in haemophilia patients in comparison to CAD patients and healthy controls. The results imply comparable biological processes in CAD and haemophilia patients.

Connexin 43 (Cx43) regulates high-glucose-induced retinal endothelial cell angiogenesis and retinal neovascularization.

Diabetic retinopathy (DR) is an important microvascular complication of type 1 and type 2 diabetes mellitus (DM) and a major cause of blindness. Retinal neovascularization plays a critical role in the proliferative DR. In this study, high glucose-induced connexin 43 (Cx43) expression in human retinal endothelial cells (hRECs) in a dose-dependent manner. Compared with hRECs under normal culture conditions, high-glucose (HG)-stimulated hRECs showed promoted tubule formation, increased ROS release, and elevated levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), vascular endothelial growth factor A (VEGFA), and intercellular adhesion molecule 1 (ICAM-1) in the culture medium. HG-induced alterations were further magnified after Cx43 overexpression, whereas partially eliminated after Cx43 knockdown. Finally, in the DR mouse model, impaired retinal structure, increased CD31 expression, and elevated mRNA levels of TNF-α, IL-1β, VEGFA, and ICAM-1 were observed; in-vivo Cx43 knockdown partially reversed these phenomena. Conclusively, Cx43 knockdown could inhibit hREC angiogenesis, therefore improving DR in the mouse model.

Acupuncture affects the apoptosis of eosinophilic granulocytes in lung tissue of asthmatic rats by regulating the P38MAPK signaling pathway

To investigate the effects of acupuncture on phosphorylated P38 mitogen-activated protein kinase (p-P38MAPK), intercellular adhesion molecule-1 (ICAM-1), interferon γ (IFN-γ), and eosinophilic granulocytes (EOS) in lung tissue of asthmatic rats, and to explore the mechanism of acupuncture in regulating the apoptosis of EOS. Clean-grade male Wistar rats were randomly divided into normal, model, dexamethasone and acupuncture groups, 8 rats in each group. The asthmatic model was established by intraperitoneal injection of mixture suspension (1 mL) of 10% ovalbumin and 10% Al(OH)_3+ normal saline, followed by inhalation of atomized 1% ovalbumin solution for 30 min, once daily for 2 weeks to trigger occurrence of asthmatic symptoms. The rats in dexamethasone group were intraperitoneally injected with 0.9 mg/kg dexamethasone since day 15 once a day for two consecutive weeks. In the acupuncture group, bilateral "Feishu" (BL13), "Pishu" (BL20), "Shenshu" (BL23), "Dingchuan" (EX-B1), and "Danzhong" (CV17) were selected for acupuncture treatment once every other day since day 15 for two consecutive weeks. Uniform reinforcing and reducing manipulation was carried out, and the needles were retained for 30 min. The pathological changes of the lung tissue were observed by hematoxylin-eosin (HE) staining. The apoptosis of EOS in the lung tissue of rats was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. The expression of p-P38MAPK in the lung tissue was detected by Western blot. The protein and mRNA levels of ICAM-1 and IFN-γ in the lung tissue were determined by immunohistochemistry and real-time PCR, respectively. The results of HE staining showed that the pulmonary alveoli and surrounding tissues were intact with no inflammatory cell infiltration in the normal group. The model group showed massive exudation of inflammatory materials and thickened pulmonary interstitium. The dexamethasone group and acupuncture group showed less damage of the alveolar structure and only a small number of inflammatory cells around the airway. Compared with the normal group, the apoptosis rate of EOS in lung tissue was decreased (P<0.01), the expression levels of p-P38MAPK and ICAM-1 proteins and mRNAs in the lung tissue were up-regulated (P<0.01), while the expression levels of IFN-γ protein and mRNA in the lung tissue were down-regulated (P<0.01) in the model group. Compared with the model group, the apoptosis rate of EOS in the lung tissue was increased (P<0.05), the expression levels of p-P38MAPK and ICAM-1 proteins and mRNAs in the lung tissue were down-regulated (P<0.01, P<0.05), while the expression levels of IFN-γ protein and mRNA were up-regulated (P<0.05, P<0.01) in the dexamethasone and acupuncture groups. Acupuncture may inhibit the P38MAPK signaling pathway, down-regulate ICAM-1 expression, and up-regulate IFN-γ expression to promote the apoptosis of EOS and reduce EOS aggregation, thus alleviating the inflammatory response of airway in asthma.

Periodontal ligament cells derived small extracellular vesicles are involved in orthodontic tooth movement.

Small extracellular vesicles (EVs) from human periodontal ligament cells (hPDLCs) are closely associated with periodontal homeostasis. Far less is known about EVs association with orthodontic tooth movement (OTM). This study aimed to explore the role of small EVs originated from hPDLCs during OTM. Adult C57BL/6 mice were used. Springs were bonded to the upper first molars of mice for 7 days to induce OTM in vivo. To block small EVs release, GW4869 was intraperitoneally injected and the efficacy of small EVs inhibition in periodontal ligament was verified by transmission electron microscope (TEM). Tooth movement distance and osteoclastic activity were studied. In vitro, hPDLCs were isolated and administered compressive force in the EV-free culture media. The cell morphologies and CD63 expression of hPDLCs were studied. Small EVs were purified and characterized using a scanning electron microscope, TEM, western blot, and nanoparticle tracking analysis. The expression of proteins in the small EVs was further processed and validated using a human immuno-regulated cytokines array and an enzyme-linked immunosorbent assay (ELISA). The small EV depletion significantly decreased the distance and osteoclastic activity of OTM in the mice. The hPDLCs displayed different morphologies under force compression and CD63 expression level decreased verified by western blot and immunofluorescence staining. Small EVs purified from supernatants of the hPDLCs showed features with <200 nm diameter, the positive EVs marker CD63, and the negative Golgi body marker GM130. The number of small EVs particles increased in hPDLCs suffering force stimuli. According to the proteome array, the level of soluble intercellular adhesion molecule-1 (sICAM-1) displayed the most significant fold change in small EVs under compressive force and this was further confirmed using an ELISA. Further mechanism studies are warranted to validate the hPDLC-originated small EVs function in OTM through proteins delivery. The notable decrease in the OTM distance after small EV blocking and the significant alteration of the sICAM-1 level in the hPDLC-originated small EVs under compression provide a new vista into small EV-related OTM biology.