Intercellular Adhesion Molecule-1 Concentrations Research Articles

Serum metabolic changes link metal mixture exposures to vascular endothelial inflammation in residents living surrounding rivers near abandoned lead–zinc mines

Metal exposure is associated with vascular endothelial inflammation, an early pathological phenotype of atherosclerotic cardiovascular events. However, the underlying mechanism linking exposure, metabolic changes, and outcomes remains unclear. We aimed to investigate the metabolic changes underlying the associations of chronic exposure to metal mixtures with vascular endothelial inflammation. We recruited 960 adults aged 20–75 years from residential areas surrounding rivers near abandoned lead–zinc mine and classified them into river area and non-river area exposure groups. Urine levels of 25 metals, Framingham risk score (FRS), and serum concentrations of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), as biomarkers of vascular endothelial inflammation, were assessed. A “meet-in-the-middle” approach was applied to identify causal intermediate metabolites and metabolic pathways linking metal exposure to vascular endothelial inflammation in representative metabolic samples from 64 participants. Compared to the non-river area exposure group, the river area exposure group had significantly greater urine concentrations of chromium, copper, cadmium, and lead; lower urine concentrations of selenium; elevated FRS; and increased concentrations of ICAM-1 and VCAM-1. In total, 38 differentially abundant metabolites were identified between the river area and non-river area exposure groups. Among them, 25 metabolites were significantly associated with FRS, 8 metabolites with ICAM-1 expression, and 10 metabolites with VCAM-1 expression. Furthermore, fructose, ornithine, alpha-ketoglutaric acid, urea, and cytidine monophosphate, are potential mediators of the relationship between metal exposure and vascular endothelial inflammation. Additionally, the metabolic changes underlying these effects included changes in arginine and proline metabolism, pyrimidine metabolism, starch and sucrose metabolism, galactose metabolism, arginine biosynthesis, and alanine, aspartate, and glutamate metabolism, suggesting the disturbance of amino acid metabolism, the tricarboxylic acid cycle, nucleotide metabolism, and glycolysis. Overall, our results reveal biomechanisms that may link chronic exposure to multiple metals with vascular endothelial inflammation and elevated cardiovascular risk.

Serum Levels of Intercellular Adhesion Molecule 1 and Vascular Cell Adhesion Molecule 1 as Biomarkers to Predict Radiotherapy Sensitivity in Cervical Cancer.

Cervical cancer is a significant global health burden, and individualized treatment approaches are necessary due to its heterogeneity. Radiotherapy is a common treatment modality; however, the response varies among patients. The identification of reliable biomarkers to predict radiotherapy sensitivity is crucial. A cohort of 189 patients with stage IB2-IVA cervical cancer, treated with radiotherapy alone or concurrent chemoradiotherapy, was included. Serum samples were collected before treatment, and intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) concentrations were determined. Patients were categorized into radiotherapy-sensitive (RS) and radiotherapy-resistant (RR) groups based on treatment response. Clinicopathological characteristics and survival rates were analyzed. The analysis of clinicopathological characteristics showed that age, family history of cervical cancer and post-menopausal status did not significantly differ between RS and RR groups. Tumor size demonstrated a borderline significant association with radiotherapy response, while differentiation degree was significantly associated. Serum ICAM-1 and VCAM-1 concentrations were significantly higher in the RR group compared to the RS group. Combined detection of ICAM-1 and VCAM-1 improved the predictive ability for radiotherapy sensitivity. Higher serum ICAM-1 and VCAM-1 levels were observed in patients with lower tumor differentiation. Five-year overall survival rates differed significantly between patients with high and low ICAM-1 and VCAM-1 levels. Serum ICAM-1 and VCAM-1 levels show potential as predictive biomarkers for radiotherapy sensitivity in cervical cancer.

Effects of marine-derived n–3 PUFA supplementation on soluble adhesion molecules: A systematic review and dose-response meta-analysis of randomized controlled trials

Long-chain n–3 poly unsaturated fatty acids have anti-inflammatory effects but their effects on serum levels of adhesion molecules are inconsistent and contradictory. In this updated systematic review and meta-analysis, marine sources of omega-3 fatty acids were pooled up to determine the effects of omega-3 supplementation on adhesion molecules. PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases (from inception to April 2023) were searched and all RCTs investigating the effects of marine sources of omega-3, on blood concentrations of adhesion molecules were included and a meta-analysis undertaken. Forty-two RCTs were included involving 3555 participants aged from 18 to 75 years. Meta-analysis of 38 arms from 30 RCTs reporting serum concentrations of vascular cell adhesion molecule-1 (VCAM-1) showed a significant reduction after omega-3 supplementation (WMD: −1.26, 95% CI: −1.88 to −0.64 ng/mL, P < 0.001). Meta-analysis of 40 arms from 30 RCTs reporting serum concentrations of intercellular adhesion molecule-1 (ICAM-1) revealed a reduction following omega-3 supplementation, although it was not significant (WMD: −1.76, 95%CI: −3.68 to 0.16 ng/mL, P = 0.07). Meta-analysis of 27 arms from 21 trials showed no effect on E-selectin (WMD: 0.01, 95%CI: −0.02 to 0.04 ng/mL, P = 0.62). Pooling 15 arms from 11 RCTs showed a marginally significant reducing effect on P-selectin concentrations (WMD: −2.67, 95%CI: −5.53 to 0.19 ng/mL, P = 0.06). A considerable decrease in VCAM concentration was observed after omega-3 supplementation in this meta-analysis with a trend to decreases in both ICAM and P-selectin levels, with effects that may be significant depending on study design, and there was no effect on E-selectin.

The effects of mango consumption on vascular health and immune function

ObjectivesHeart disease, caused by atherosclerosis, is the leading cause of death. Maintaining vascular integrity is crucial to reducing atherosclerosis risk. Mangos are rich in fiber, vitamins, minerals, and phytochemicals that may offer cardioprotective and immune-boosting benefits. However, their effects on the vasculature and immune system in adults with overweight and obesity remain unclear. The objective of this study was to investigate the effects of mango consumption on vascular health and immune function in adults with overweight and obesity. MethodsIn a 12-week, crossover study, 27 overweight and obese participants consumed either 100 kcals of mangos daily or isocaloric low-fat cookies daily. Fasting blood samples were collected at baseline, week 4, and week 12 and analyzed for vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), P-selectin, E-selectin, sCD4, sCD8, sCD3E, and sCD45, tumor necrosis factor-alpha (TNF-α), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). ResultsMango consumption significantly decreased VCAM-1 between baseline and week 4 (P = 0.046) and week 12 (P = 0.004). CAT increased between baseline and week 12 (P = 0.035) with mango consumption. GPx increased at week 12 compared to baseline and week 4 (P < 0.05). At week 12, SOD was higher after mango consumption compared to low-fat cookie consumption (P = 0.046). There were no significant differences in ICAM-1, P-selectin, E-selectin, sCD4, sCD8, sCD3E, sCD45 or TNF-α concentrations (P > 0.05 for all non-significant results). ConclusionsThis study suggests that 100 kcals of mangos may benefit the integrity of the vasculature by reducing VCAM-1 and increasing SOD, CAT, and GPx levels. Mangos can be an alternative snack for improving atherosclerosis and oxidative stress risk factors.

Impact of treatment on blood-brain barrier impairment in Wilson's disease.

Our study assessed changes in concentrations of serum markers for brain damage and blood-brain barrier (BBB) dysfunction in untreated and treated Wilson's disease (WD) patients, and examined correlations between these changes and neurological impairment. These results hold the potential to determine BBB impairment and neurological advancement in WD to develop the most effective treatment for patients with severe neurological deterioration. The study groups included 171 patients with WD (77 with hepatic and 94 with neurological manifestations), treated either for up to 5 or 15 years, and 88 healthy controls. Serum concentrations of intercellular adhesion molecule 1 (ICAM1), P-selectin, matrix metallopeptidase 9 (MMP9), glial fibrillary acidic protein (GFAP), and S100 calcium-binding protein B (S100B) were measured before and during anti-copper treatment. The Unified Wilson's disease Rating Scale (UWDRS) was used to assess neurological advancement. ICAM1 concentrations were elevated before and during anti-copper treatment compared to controls (p < 0.01), but therapy led to substantial decreases both in patients with hepatic (p < 0.01) and in patients with neurological manifestations (p < < 0.05). P-selectin concentrations remained elevated before and during treatment (p < 0.05) regardless of the treatment duration and disease form. MMP9 concentrations before treatment were lower (p < 0.05), but reached control levels during treatment. GFAP concentrations were significantly elevated only in untreated patients with neurological symptoms in the longer-treated group compared to controls (p < 0.05). A significant reduction during treatment was observed only in the shorter-treated neurological group (p < 0.05). No substantial changes were observed in S100B. Only ICAM1 concentrations positively correlated (r = 0.27, p < 0.001) with the UWDRS. Our results provide evidence of endothelial activation in WD. However, inconclusive GFAP results, and no increase in S100B, do not allow us to conclude whether the reactive gliosis is not prominent or alternatively whether the BBB is disrupted. Elevated ICAM1 concentrations and their correlation with neurological advancement indicate BBB impairment. A decrease in ICAM1 during treatment suggests that the inflammatory process is reduced, and the BBB partially repaired. Decreased MMP9 concentrations may be the result of active liver fibrosis and higher copper concentrations. Elevated P-selectin concentrations indicate a systemic inflammatory process.

Effects of quercetin supplementation on endothelial dysfunction biomarkers and depression in post-myocardial infarction patients: A double-blind, placebo-controlled, randomized clinical trial

Endothelial dysfunction and depression are highly prevalent in patients who have experienced a myocardial infarction (MI). Epidemiological studies have pointed out that a diet rich in flavonoids, e.g., quercetin, can prevent the development of these biological phenomena. Therefore, we aimed to investigate the effects of quercetin supplementation on the levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) and on depression in post-MI subjects. Eighty-eight post-MI patients who had experienced their first MI (body mass index ≤35kg/m2, age 30-65 years) were recruited from the Rasool-e-Akram and Afshar Hospitals, Iran, and included in this randomized, placebo-controlled, double-blind parallel study. The participants were randomly assigned to receive a daily dose of 500mg quercetin (n=44) or placebo (n=44) for 8 weeks. Serum concentrations of ICAM-1 and VCAM-1 were quantified by ELISA and depression levels were assessed using the Beck's Depression Inventory (BDI-II) questionnaire at baseline and at 8-week follow-up. Seventy-six participants completed the study, but the intention-to-treat (ITT) analysis was conducted for all 88 participants who were randomized into the intervention groups. No significant changes in serum concentrations of ICAM-1 or VCAM-1 (P=0.21 and P=0.80, respectively) were observed after 8 weeks of quercetin supplementation versus placebo. In addition, depression levels did not differ significantly between the quercetin and placebo groups. Our findings demonstrated that in post-MI patients, daily supplementation with quercetin (500mg/day) for 8 weeks did not affect endothelial dysfunction biomarkers and depression levels. This trial was registered at IRCT.ir as IRCT20190428043405N1.

Multi-Targeting Anticancer Activity of a New 4-Thiazolidinone Derivative with Anti-HER2 Antibodies in Human AGS Gastric Cancer Cells

Combining chemotherapy with immunotherapy still remains a regimen in anticancer therapy. Novel 4-thiazolidinone-bearing hybrid molecules possess well-documented anticancer activity, and together with anti-HER2 antibodies, may represent a promising strategy in treating patients with gastric cancer with confirmed human epidermal growth factor receptor 2 (HER2) expression. The aim of the study was to synthesize a new 4-thiazolidinone derivative (Les-4367) and investigate its molecular mechanism of action in combination with trastuzumab or pertuzumab in human AGS gastric cancer cells. AGS cell viability and antiproliferative potential were examined. The effect of the tested combinations as well as monotherapy on apoptosis and autophagy was also determined. Metalloproteinase-2 (MMP-2), intercellular adhesion molecule 1 (ICAM-1), pro-inflammatory and anti-inflammatory cytokine concentrations were also demonstrated by the ELISA technique. We proved that pertuzumab and trastuzumab were very effective in increasing the sensitivity of AGS gastric cancer cells to novel Les-4367. The molecular mechanism of action of the tested combination is connected with the induction of apoptosis. Additionally, the anticancer activity is not associated with the autophagy process. Decreased concentrations of pro-inflammatory cytokines, MMP-2 and ICAM-1-were observed. The novel combination of drugs based on anti-HER2 antibodies with Les-4367 is a promising strategy against AGS gastric cancer cells.

Prophylactic Treatment with Hydrogen Sulphide Can Prevent Renal Ischemia-Reperfusion Injury in L-NAME Induced Hypertensive Rats with Cisplatin-Induced Acute Renal Failure.

(Background and Objectives): Renal ischemia perfusion injury is one of the major issues in kidney transplant. The aim of the study was to investigate the hypothesis that prophylactic treatment-with a hydrogen sulphide donor to an acute renal failure case of hypertensive rats-can minimize the ischemia reperfusion injury of the kidney which is beneficial for kidney transplant. To check this hypothesis, the present study was designed to investigate the effect of chronic administration of a hydrogen sulphide (H2S) donor and sodium hydrosulfide (NaHS) on nuclear factor kappa B (NF-kB) and inter cellular adhesion molecule-1 (ICAM-1) concentration in non-renal failure (NRF) and acute renal failure (ARF) rats in the ischemia-reperfusion injury (IRI) model of the kidney in both normotensive WKY and hypertensive rats (L-nitro arginine methyl ester (L-NAME-induced); (Materials and Methods): A total number of 48 Sprague-Dawley rats were recruited into eight groups each consisting of six animals. Each of these eight groups was used to measure systemic and renal parameters, H2S, antioxidant parameters in plasma, plasma concentration of NF-kB and ICAM-1 and renal cortical blood pressure. ARF was induced by single intraperitoneal (i.p.) cisplatin injection (5 mg/kg). Hypertension was induced by oral administration of L-NAME in drinking water for four weeks at 40 mg/kg/day. NaHS was administered (i.p) at 56 µmol/kg for five weeks while dL-propargylglycine (PAG), a H2S generation inhibitor, was administered as a single intra-peritoneal injection (50 mg/kg). An acute surgical experiment was performed for the induction of renal ischemia for 30 min by renal artery clamping followed by reperfusion for three hours; (Results): Chronic administration of NaHS attenuated the severity of ARF in both normotensive and hypertensive animals (L-NAME) along with lowering the blood pressure in hypertensive groups. NaHS improved the oxidative stress parameters such as total superoxide dismutase (T-SOD), glutathione (GSH) and reduced the malondialdehyde (MDA) concentration along with reduction of NF-kB and ICAM-1 following renal IRI; Conclusions: These findings demonstrate that H2S not only reduced the severity of cisplatin induced ARF but also reduced the severity of renal IRI by upregulating antioxidants along with decreased concentrations of NF-kB and ICAM-1 in normotensive and L-NAME induced hypertensive rats.

Analysis of the Cytokine Expression in the Aqueous Humor of Individuals with BRVO-Associated Macular Edema.

Purpose This study aimed to determine the expression levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in the aqueous humor of patients with macular edema (ME) caused by branch retinal vein occlusion (BRVO), as well as to investigate the relationship between the cytokines as mentioned earlier and best-corrected visual acuity (BCVA), ME, and the degree of ME from the molecular level. Methods In a prospective observational study, fluorescein fundus angiography (FFA) and optical coherence tomography (OCT) were used to classify 58 patients with non-ischemic BRVO-ME into three groups according to the degree of ME: 14-mild, 17-moderate, and 27-severe. The specific concentration of IL-6, VEGF, ICAM-1, and VCAM-1 in the aqueous humor was detected using the BD CSCanto™ II Flow Cytometer (US). Spearman or Pearson correlation analysis was used to test the correlation between the levels of BCVA and severity of ME and the expression levels of IL-6, VEGF, ICAM-1, and VCAM-1 in the aqueous humor. Results According to the obtained data, BCVA did not correlate with the severity of ME, and these four cytokines expression levels in patients' aqueous humor (P > 0.05). Moreover, BCVA did not correlate with mild, moderate, or severe ME as well (P > 0.05). However, the levels of these four cytokines were correlated with the severity of the ME. These underlined cytokines were linked to the mild, moderate, and severe degrees of ME. VEGF was also significantly correlated (r > 0.8, P < 0.0001) with the severity of ME. Conclusions This study suggests that the severity of ME in BRVO-ME patients is significantly correlated with the expression levels of IL-6, VEGF, ICAM-1, and VCAM-1 in the aqueous humor. Lowering the level of disease-associated cytokines may potentially reduce the degree of ME. Therefore, an in-depth study of the levels and the relationship may provide some evidence for the pathogenesis, treatment, and prevention of BRVO-ME.

Circulating markers of endothelial activation in canine parvoviral enteritis

Canine parvovirus (CPV) is a common cause of enteritis, immune suppression and systemic inflammation in young dogs. Endothelial markers, such as intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and molecules that upregulate their expression, such as high mobility group box 1 protein (HMGB-1), provide insight into the state of the endothelium during inflammation. This study aimed to determine if circulating concentrations of ICAM-1, VCAM-1 and HMGB-1 were altered in CPV enteritis compared to healthy controls, and whether a correlation existed between these molecules and the degree of inflammation. Thirty dogs with naturally occurring CPV enteritis and ten control dogs were included. Physical examinations, complete blood count and C-reactive protein (CRP) measurements were performed on all dogs at presentation. The concentrations of ICAM-1, VCAM-1 and HMGB-1 were measured using commercially available canine-specific enzyme-linked immunosorbent assay (ELISA) kits. In dogs with CPV enteritis, ICAM-1 concentrations were significantly lower (median: 5.9 [IQR: 4.3-8.3]) and CRP higher (134 [IQR: 85-195]) compared to controls (8.0 [IQR: 6.9-10.3], p = 0.008; 1 [IQR: 0-7], p < 0.001). No significant difference was found for VCAM- 1 and HMGB-1. A strong correlation was identified between VCAM-1 and segmented neutrophil count (r = 0.612, p < 0.001). Despite the presence of systemic inflammation in CPV enteritis, evidenced by high CRP concentrations, our results suggest circulating concentrations of ICAM-1, VCAM-1 and HMGB-1 failed to show an increase. Endothelial activation with subsequent leukocyte adhesion and transmigration through the endothelium may be affected in CPV enteritis and these findings require further investigation.

Changes in plasma total saturated fatty acids and palmitic acid are related to pro-inflammatory molecule IL-6 concentrations after nutritional intervention for one year.

Systemic inflammation is associated with an increased risk of non-communicable diseases, such as cardiovascular diseases and diabetes. Circulating fatty acids (FA) are known to be related to these conditions, possibly through their role in inflammation, although different types of FAs can have opposite effects on inflammatory mediators. The aim of the present study was to analyze the association of plasma FAs with inflammatory biomarkers in a PREDIMED trial subsample after one year of intervention. In a one-year longitudinal study of 91 participants of the PREDIMED trial (Barcelona-Clinic center), plasma FAs and inflammatory biomarkers were analyzed using gas chromatography and ELISA, respectively. In baseline plasma, a multivariable-adjusted ordinary least squares regression model showed that n-3 polyunsaturated FAs concentrations were inversely associated with concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and E-selectin, whereas the level of the most abundant saturated FA, palmitic acid, was directly associated with concentrations of interleukin-6 (IL-6) (β=0.48pg/mL, 95% CI: 0.03, 0.93 per 1-SD increase, p-value = 0.037). After one year of nutritional intervention, changes of plasma diet-derived total saturated FAs and palmitic acid were directly associated with changes in IL-6 (β=0.59pg/mL [95% CI: 0.28, 0.89] per 1-SD, p-value = 0.001; β=0.64pg/mL, 95% CI: 0.31, 0.98, p-value = 0.001), respectively, after correction for multiple testing. Our findings suggest that saturated FAs of dietary origin, especially palmitic acid, are directly involved in the increase of IL-6 in plasma.

Association of Inflammatory Cytokines With Non-Alcoholic Fatty Liver Disease.

BackgroundInflammatory cytokines have been considered to be significant factors contributing to the development and progression of non-alcoholic fatty liver disease (NAFLD). However, the role of inflammatory cytokines in NAFLD remains inconclusive.ObjectiveThis study aimed to evaluate the association between inflammatory cytokines and NAFLD.MethodsPubMed, Web of Science, the Cochrane Library, and EMBASE databases were searched until 31 December 2021 to identify eligible studies that reported the association of inflammatory cytokine with NAFLD and its subtypes. We pooled odds ratios (ORs) and hazard risk (HRs) with 95% confidence intervals (CIs) and conducted heterogeneity tests. Sensitivity analysis and analysis for publication bias were also carried out.ResultsThe search in the databases identified 51 relevant studies that investigated the association between 19 different inflammatory cytokines and NAFLD based on 36,074 patients and 47,052 controls. The results of the meta-analysis showed significant associations for C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) with NAFLD (ORs of 1.41, 1.08, 1.50, 1.15 and 2.17, respectively). In contrast, we observed non-significant associations for interferon-γ (IFN-γ), insulin-like growth factor (IGF-II), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-7 (IL-7), interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-12 (IL-12), monocyte chemoattractant protein-1(MCP-1), and transforming growth factor-β (TGF-β) with NAFLD. Our results also showed that CRP, IL-1β, and TNF-α were significantly associated with non-alcoholic steatohepatitis (NASH) and hepatic fibrosis.ConclusionsOur results indicated that increased CRP, IL‐1β, IL-6, TNF‐α, and ICAM-1 concentrations were significantly associated with increased risks of NAFLD. These inflammatory mediators may serve as biomarkers for NAFLD subjects and expect to provide new insights into the aetiology of NAFLD as well as early diagnosis and intervention.

Trigeminal Nerve Stimulation Improves Cerebral Macrocirculation and Microcirculation After Subarachnoid Hemorrhage: An Exploratory Study.

Delayed cerebral ischemia (DCI) is the most consequential secondary insult after aneurysmal subarachnoid hemorrhage (SAH). It is a multifactorial process caused by a combination of large artery vasospasm and microcirculatory dysregulation. Despite numerous efforts, no effective therapeutic strategies are available to prevent DCI. The trigeminal nerve richly innervates cerebral blood vessels and releases a host of vasoactive agents upon stimulation. As such, electrical trigeminal nerve stimulation (TNS) has the capability of enhancing cerebral circulation. To determine whether TNS can restore impaired cerebral macrocirculation and microcirculation in an experimental rat model of SAH. The animals were randomly assigned to sham-operated, SAH-control, and SAH-TNS groups. SAH was induced by endovascular perforation on Day 0, followed by KCl-induced cortical spreading depolarization on day 1, and sample collection on day 2. TNS was delivered on day 1. Multiple end points were assessed including cerebral vasospasm, microvascular spasm, microthrombosis, calcitonin gene-related peptide and intercellular adhesion molecule-1 concentrations, degree of cerebral ischemia and apoptosis, and neurobehavioral outcomes. SAH resulted in significant vasoconstriction in both major cerebral vessels and cortical pial arterioles. Compared with the SAH-control group, TNS increased lumen diameters of the internal carotid artery, middle cerebral artery, and anterior cerebral artery, and decreased pial arteriolar wall thickness. Additionally, TNS increased cerebrospinal fluid calcitonin gene-related peptide levels, and decreased cortical intercellular adhesion molecule-1 expression, parenchymal microthrombi formation, ischemia-induced hypoxic injury, cellular apoptosis, and neurobehavioral deficits. Our results suggest that TNS can enhance cerebral circulation at multiple levels, lessen the impact of cerebral ischemia, and ameliorate the consequences of DCI after SAH.

Hydrogen Sulphide Treatment Prevents Renal Ischemia-Reperfusion Injury by Inhibiting the Expression of ICAM-1 and NF-kB Concentration in Normotensive and Hypertensive Rats.

Our main objective was to investigate the effect of chronic administration of hydrogen sulphide donor (sodium hydrosulphide) on the expression of intercellular adhesion molecule-1 (ICAM-1) and concentration of nuclear factor-kappa B (NF-kB) in a renal ischemia-reperfusion injury (IRI) model of WKY and L-nitro-arginine-methyl-ester (L-NAME)-induced hypertensive rats. Sodium hydrosulphide (NaHS) was administered intraperitoneally (i.p.) for 35 days while cystathionine gamma lyase (CSE) inhibitor dL-propargylglycine (PAG) was administered at a single dose of 50 mg/kg. Animals were anesthetised using sodium pentobarbitone (60 mg/kg) and then prepared to induce renal ischemia by clamping the left renal artery for 30 min followed by 3 h of reperfusion. Pre-treatment with NaHS improved the renal functional parameters in both WKY and L-NAME-induced hypertensive rats along with reduction of blood pressure in hypertensive groups. Oxidative stress markers like malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione (GSH) were also improved by NaHS treatment following renal IRI. Levels of ICAM-1 and NF-kB concentration were reduced by chronic treatment with NaHS and increased by PAG administration after renal IRI in plasma and kidney. Treatment with NaHS improved tubular morphology and glomerulus hypertrophy. Pre-treatment with NaHS reduced the degree of renal IRI by potentiating its antioxidant and anti-inflammatory mechanism, as evidenced by decreased NF-kB concentration and downregulation of ICAM-1 expression.

Effect of a nut-enriched low-calorie diet on body weight and selected markers of inflammation in overweight and obese stable coronary artery disease patients: a randomized controlled study.

Weight loss through a low-calorie diet (LCD) could improve low-grade inflammation evident in the obese state. Few studies have evaluated the effect of the mixed nuts consumption in the context of a LCD on inflammatory biomarkers. This study compared the effects of a nut-enriched LCD (NELCD) with a nut-free LCD (NFLCD) on body weight and inflammatory markers in overweight or obese coronary artery disease (CAD) patients. In this randomized controlled parallel trial, patients with stable CAD of both genders were randomly allocated to 8-week NELCD or NFLCD. Body weight, plasma C-reactive protein (CRP), interleukin-6 (IL-6), interleukin 10 (IL-10), intercellular adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein (MCP-1) were assessed at baseline and 8 weeks. Overall, 67 patients (aged 58.8 ± 7.4 years; BMI 30.9 ± 3.9 kg/m2) completed the study. Participants in both groups lost weight to a comparable extent. Patients in the NELCD group showed a decrease in ICAM-1 (p = 0.04) and IL-6 (p = 0.02) concentrations compared to NFLCD group. No significant difference in concentrations of MCP-1, IL-10, or CRP was observed between diet groups. Nuts are healthy energy-dense foods that if included in controlled amounts in a weight management program can still result in weight reduction and may improve some plasma concentration of inflammatory factors, such as ICAM-1 and IL-6.

Effects of Vitamin D Supplementation on Omentin-1 and Spexin Levels, Inflammatory Parameters, Lipid Profile, and Anthropometric Indices in Obese and Overweight Adults with Vitamin D Deficiency under Low-Calorie Diet: A Randomized Placebo Controlled Trial.

Background and Aims Improved vitamin D levels can have a favorable effect on some metabolic variables. The objective of the current study was to determine the effects of vitamin D supplementation during a weight-loss intervention on the levels of omentin-1, spexin, lipid profiles, and inflammatory factors in obese and overweight participants. Methods and Materials In this double-blind placebo-controlled randomized clinical trial, 70 overweight and obese participants with vitamin D deficiency (25(OH)D ≤ 20 nmol/L) were assigned into the intervention (a daily dose of 2,000 IU vitamin D + low-calorie diet) and placebo (placebo + low-calorie diet) groups for 8 weeks. Anthropometric parameters, serum levels of 25-hydroxy vitamin D (25(OH)D), lipid profiles, omentin-1 and spexin levels, high-sensitivity C-reactive protein (hs-CRP), and soluble intercellular adhesion molecule-1 (sICAM-1) concentrations were assessed before and after the intervention. Results Vitamin D supplementation after the intervention led to a significant decrease in triglycerides (TG) (P = 0.02), very-low-density lipoprotein-cholesterol (VLDL-C) (P = 0.02), and hs-CRP (P = 0.03) concentrations and a significant increase in the serum vitamin D level (P < 0.001). Furthermore, after adjusting for baseline values, age, and baseline BMI, the levels of serum high-density lipoprotein-cholesterol (HDL-C) (P = 0.01) increased significantly, and a significant reduction was observed in the concentration of sICAM-1 (P = 0.01) in the intervention group. However, we did not find any significant difference in serum omentin-1 and spexin concentrations between the groups after intervention. Conclusions Vitamin D supplementation along with a low-calorie diet (LCD) program for 8 weeks significantly decreased the inflammatory markers in obese individuals, while it did not alter serum omentin-1 and spexin concentrations.

Mitochondrial DNA drives noncanonical inflammation activation via cGAS\u2013STING signaling pathway in retinal microvascular endothelial cells

BackgroundPathological stimuli cause mitochondrial damage and leakage of mitochondrial DNA (mtDNA) into the cytosol, as demonstrated in many cell types. The cytosolic mtDNA then drives the activation of noninfectious inflammation. Retinal microvascular endothelial cells (RMECs) play an important role in the inner endothelial blood–retinal barrier (BRB). RMEC dysfunction frequently occurs in posterior-segment eye diseases, causing loss of vision. In this study, we investigated the involvement of cytosolic mtDNA in noninfectious immune inflammation in RMECs under pathological stimuli.MethodsRMECs were stimulated with 100 ng/ml lipopolysaccharide (LPS), 200 μM hydrogen peroxide (H2O2), or 25 mM d-glucose. After 24 h, immunofluorescent staining was used to detect the opening of the mitochondrial permeability transition pore (MPTP). Cytosolic mtDNA was detected with immunofluorescent staining and PCR after stimulation. mtDNA was then isolated and used to transfect RMECs in vitro, and the protein levels of cGAS were evaluated with western blotting. Real-time PCR was used to examine cGAS mRNA expression levels at different time points after mtDNA stimulation. The activation of STING was detected with immunofluorescent staining 6 h after mtDNA stimulation. Western blotting was used to determine the expression of STING and IFNβ, the phosphorylation status of TBK1, IRF3, and nuclear factor-κB (NF-κB) P65, and the nuclear translocation of IRF3 and NF-κB P65 at 0, 3, 6, 12, and 24 h. The mRNA expression of proinflammatory cytokines CCL4, CXCL10, and IFNB1, and transcription factor IRF1 were determined with real-time PCR, together with the concentrations of intercellular adhesion molecule 1 (ICAM-1) mRNA.ResultsPathological stimuli caused mtDNA to leak into the cytosol by opening the MPTP in RMECs after 24 h. Cytosolic mtDNA regulated the expression of cGAS and the distribution of STING in RMECs. It promoted ICAM-1, STING and IFNβ expression, TBK1, IRF3, and NF-κB phosphorylation and the nuclear translocation in RMECs at 12 and 24 h after its transfection. The mRNAs of proinflammatory cytokines CCL4, CXCL10, and IFNB1, and transcription factor IRF1 were significantly elevated at 12 and 24 h after mtDNA stimulation.ConclusionsPathological stimulation induces mtDNA escape into the cytosol of RMECs. This cytoplasmic mtDNA is recognized by the DNA sensor cGAS, increasing the expression of inflammatory cytokines through the STING–TBK1 signaling pathway.Ba7zzwjjDYYV6NH7beoBySVideo . (MP4 37490 kb)

Association of endothelin-1 and cell surface adhesion molecules levels in patients with systemic sclerosis

Abstract Objectives Endothelin-1 (ET-1) has been implicated in the pathogenesis of inflammatory and fibrotic diseases, including systemic sclerosis. In addition to modulating vascular tone and extracellular matrix turnover, ET-1 up-regulates cell surface adhesion molecules–intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1).The aim of the study was to evaluate the diagnostic value of the detection of ET-1, VCAM-1 and ICAM-1 in the diagnosis of systemic sclerosis. Methods A total of 30 patients with systemic sclerosis from Vilnius University Hospital Santaros Clinics were included in the study. Serum levels of ICAM-1, VCAM-1 and ET-1 were assessed by enzyme immunoassay. Results ET-1 concentration was associated with VCAM-1 concentration (r=0.687; p&lt;0.001). No associations between ET-1 and ICAM-1 concentrations were detected. Depending on the duration of the disease no significant differences in the concentrations of ET-1, ICAM-1 and VCAM-1 were detected. Conclusions The results of this study indicated that ET-1 and VCAM-1 may be assessed together as markers of inflammation and the identification of patients at high risk for disease progression.

Evaluation of biomarkers related to endothelial dysfunction: proof of vasculopathy in anti-melanoma differentiation-associated gene 5 dermatomyositis.

We aimed to reveal evidence of endothelial dysfunction in the development of anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis (DM). Thirty anti-MDA5 DM patients were enrolled and compared with patients with polymyositis (PM) (n=10) and healthy controls (n=20). The concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelin-1 (ET-1) and von Willebrand factor (vWF) as well as interferon-alpha (IFN-α) and Galcetin-9 in the peripheral blood were tested by enzyme-linked immunosorbent assay (ELISA). Plasma levels of sICAM-1, sVCAM-1, ET-1 and vWF were higher in the anti-MDA5 DM patients than in either the healthy controls or the PM patients. In the anti-MDA5 DM cohort, the ET-1 and vWF levels were significantly lower in the cases without cutaneous ulcers and ILD than the other cases. There was a strong positive relationship between the concentrations of ET-1 and Galectin-9 in the anti-MDA5 DM group. Our data suggest that endothelial dysfunction may be involved in the development of anti-MDA5 DM.

Circulating cell adhesion molecules in metabolically healthy obesity

Background/ObjectivesPeople with metabolically healthy obesity (MHO) may still have an increased risk for cardiovascular mortality compared to metabolically healthy lean (MHL) individuals. However, the mechanisms linking obesity to cardiovascular diseases are not entirely understood. We therefore tested the hypothesis that circulating cell adhesion molecules (CAMs) are higher in MHO compared to MHL individuals.Subjects/MethodsSerum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), E-selectin and P-selectin were measured in age- and sex-matched groups of MHL (n = 32), MHO categorized into BMI-matched insulin sensitive (IS, n = 32) or insulin resistant (IR) obesity (n = 32) and people with metabolically unhealthy obesity (MUO, n = 32).ResultsIndeed, individuals with MHO have significantly higher sICAM-1, E-selectin, and P-selectin serum concentrations compared to MHL people. However, these CAMs are still significantly lower in IS compared to IR MHO. There was no difference between the groups in sVCAM-1 serum concentrations. Compared to all other groups, circulating adhesion molecules were significantly higher in individuals with MUO.ConclusionsThese findings suggest that obesity-related increased cardiovascular risk is reflected and may be mediated by significantly higher CAMs. The mechanisms causing elevated adhesion molecules even in the absence of overt cardio-metabolic risk factors and whether circulating CAMs could predict cardiovascular events need to be explored.