ICAM-1 Concentrations Research Articles

Safety and Effectiveness of Acceleration Training as Cardiac Rehabilitation Immediately After Open Heart Surgery - A Pilot Study.

We examined the safety and efficacy of acceleration training (AT) in patients immediately after cardiac surgery. This randomized controlled study included patients who underwent open-heart surgery using cardiopulmonary bypass. Of these patients, 31 received regular cardiac rehabilitation (CR) and 39 received AT in addition to regular CR (AT group). AT was provided using a vibration platform (Power Plate®Pro7TMand Power plate®personal; Performance Health System, Chicago, IL, USA). The AT group performed 5 static resistance training sessions: squats, wide stance squats, toe stands, banded squats, and front lunges. Each vibration session lasted 30 s. We evaluated the short physical performance battery, anterior mid-thigh thickness, maximum voluntary isometric contraction of the knee extensors, and serum intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) concentrations as indicators of endothelial function. The observation period was during hospitalization and lasted approximately 20 days. No adverse events occurred during AT. Ultrasound revealed a significantly lower reduction in muscle mass at discharge in the AT group. No significant differences were observed in ICAM-1 and VCAM-1 concentrations between the 2 groups preoperatively, postoperatively, or at discharge. AT is considered safe and effective for patients immediately after open-heart surgery. AT, along with regular CR, may prevent skeletal muscle mass loss, muscle weakness, and physical function loss immediately after open-heart surgery.

ROLE OF INTERCELLULAR ADHESION MOLECULES (ICAM-1), VASCULAR CELL ADHESION (VCAM-1) AND CALPROTECTIN (MRP8/14) IN PATHOGENESIS OF DIABETIC RETINOPATHY

Aim of the research. The aim is to study the content of intercellular adhesion molecules (ICAM-1), vascular cell adhesion molecule (VCAM-1) and calprotectin in the blood serum of patients with type 2 diabetes mellitus and various stages of diabetic retinopathy. The aim is also to evaluate the role of these molecules in the pathogenesis of the disease. Materials and methods. Four groups of people were formed: first group (control group) included 21 healthy individuals; second group included 21 patients with prediabetes, third group 21 patients with type 2 diabetes. The fourth group included 63 patients with diabetic retinopathy, and this group was further divided into 3 groups of 21 people each: with non-proliferative stage of DR, with preproliferative stage, with proliferative stage.. The concentrations of ICAM-1, VCAM-1 and calprotectin (MRP8/14) in blood serum were determined using Human Vascular Inflammation Panel 1 multiplex analysis kits from Biolegend (USA). The results were assessed using CytoFlex flow cytometer (USA). The results were calculated using Jamovi version 2.3. Results. In individuals with prediabetes, the content of MRP8/14 was increased by 111,7% (p < 0,001) relative to the control group. In type 2 diabetes without retinopathy, the values of MRP8/14 protein exceed the control group values by 2,7 times (p < 0,001) and those in individuals with prediabetes by 29,2% (p = 0,049). In the group of patients who had non-proliferative stage of DR, the levels of ICAM-1, VCAM-1 and MRP8/14 are higher than control group values in the groups of people with prediabetes and patients with diabetes without complications. During the preproliferative stage, the number of adhesion molecules increases even more; during the proliferative stage, the concentrations of VCAM-1 and calprotectin remain high, and the level of ICAM-1 increases relative to the previous stages. Conclusion. Increasing of MRP8/14 level in diabetes and increasing of ICAM-1 and VCAM-1 concentrations in the initial stage of DR demonstrate the role of these molecules in the initiation of DR in type 2 diabetes. Researching the relationship between these markers and the development of DR can provide additional information to develop strategies for prevention and treatment of DR as well as predicting its complications.

Precision symptom phenotyping identifies early clinical and proteomic predictors of distinct COVID-19 sequelae.

Post-COVID conditions (PCC) are difficult to characterize, diagnose, predict, and treat due to overlapping symptoms and poorly understood pathology. Identifying inflammatory profiles may improve clinical prognostication and trial endpoints. 1,988 SARS-CoV-2 positive U.S. Military Health System beneficiaries with quantitative post-COVID symptom scores were included in this analysis. Among participants who reported moderate-to-severe symptoms on surveys collected 6-months post-SARS-CoV-2 infection, principal component analysis (PCA) followed by K-means clustering identified distinct clusters of symptoms. Three symptom-based clusters were identified: a sensory cluster (loss of smell and/or taste), a fatigue/difficulty thinking cluster, and a difficulty breathing/exercise intolerance cluster. Individuals within the sensory cluster were all outpatients during their initial COVID-19 presentation. The difficulty breathing cluster had a higher likelihood of obesity and COVID-19 hospitalization compared to those with no/mild symptoms at 6-months post-infection. Multinomial regression linked early post-infection D-dimer and IL-1RA elevation to fatigue/difficulty thinking, and elevated ICAM-1 concentrations to sensory symptoms. We identified three distinct symptom-based PCC phenotypes with specific clinical risk factors and early post-infection inflammatory predictors. With further validation and characterization, this framework may allow more precise classification of PCC cases and potentially improve the diagnosis, prognostication, and treatment of PCC.

Changes of aqueous humor cytokine profiles of patients with high intraocular pressure after PPV for retinal detachment

High intraocular pressure (IOP) is one of the early complications after pars plana vitrectomy (PPV), which may cause glaucoma and poor visual prognosis secondary to surgery. Proliferative vitreoretinopathy (PVR) is one of the complications of retinal detachment (RD) and is the main reason for the poor prognosis, which is related to different kinds of cytokines. It’s essential for the basic mechanism to analyze the relative aqueous humor cytokine profiles with IOP after PPV for RD. In this study, we have collected the aqueous humor of 16 patients and qualified 27 cytokines using Luminex and compared biomarkers with the high IOP group and the normal group. As a result, the concentrations of VEGF, IL-6, FGF2, and G-CSF upregulated significantly (P < 0.05), while VEGFR2 downregulated significantly (P < 0.05) in the high IOP group. IL-6 was positively correlated with high IOP (r = 0.561, P = 0.041). Meanwhile, the concentrations of IL-6 (r = 0.543, P = 0.03), IL-5 (r = 0.576, P = 0.019), IL-15 (r = 0.614, P = 0.011), IL-4 (r = 0.517, P = 0.04), ICAM-1 (r = 0.611, P = 0.012), and G-CSF (r = 0.636, P = 0.008) were significantly associated with preoperative PVR classification, and the aqueous humor levels of IL-4 (r = 0.567, P = 0.022), HGF (r = 0.701, P = 0.005), and MCP-1 (r = 0.565, P = 0.035) are significant relative to laser points. Hence, cytokines might potentially be the therapeutic target of high IOP after PPV.

Effect of GLP-1RA Treatment on Adhesion Molecules and Monocyte Chemoattractant Protein-1 in Diabetic Patients with Atherosclerosis.

Cardiovascular disease (CVD) remains a prominent cause of global mortality, primarily driven by atherosclerosis. Diabetes mellitus, as a modifiable risk factor, significantly contributes to atherogenesis. Monocyte recruitment to the intima is a critical step in atherosclerotic plaque formation, involving chemokines and adhesion molecules such as selectins, ICAM-1, and MCP-1. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are a promising group of drugs for reducing cardiovascular risk in diabetic patients, prompting investigation into their mechanisms of action. This interventional study enrolled 50 diabetes patients with atherosclerotic plaque, administering GLP-1RA for 180 days. Serum concentrations of MCP-1, ICAM-1, and L-selectin were measured before and after treatment. Anthropometric and biochemical parameters were also assessed. GLP-1RA treatment resulted in significant improvements in anthropometric parameters, glycemic control, blood pressure, and biochemical markers of liver steatosis. Biomarker laboratory analysis revealed higher baseline levels of MCP-1, ICAM-1, and L-selectin in diabetic patients with atherosclerotic plaque compared to healthy controls. Following treatment, MCP-1 and L-selectin levels decreased significantly (p < 0.001), while ICAM-1 levels increased (p < 0.001). GLP-1RA treatment in diabetic patients with atherosclerotic plaque leads to favorable changes in serum molecule levels associated with monocyte recruitment to the endothelium. The observed reduction in MCP-1 and L-selectin suggests a potential mechanism underlying GLP-1RA-mediated cardiovascular risk reduction. Further research is warranted to elucidate the precise mechanisms and clinical implications of these findings in diabetic patients with atherosclerosis.

Endothelial Dysfunction Biomarkers and CKD Incidence in the REGARDS Cohort

IntroductionChronic kidney disease (CKD) is only partly caused by traditional risk factors. Endothelial dysfunction is common in CKD and may contribute to CKD incidence. We studied the association of circulating biomarkers reflecting endothelial dysfunction with incident CKD. MethodsREGARDS is a prospective cohort of 30,239 Black or White adults aged ≥45 years. Baseline levels of ICAM-1, VCAM-1, factor VIII, and E-selectin were measured in 3,300 participants without baseline CKD or albuminuria who attended a second visit 9.4 years later. Kidney outcomes were incident CKD (eGFR <60 mL/min/1.73m2 and ≥40% decline or onset of new end stage kidney disease), incident ≥30% eGFR decline, and incident albuminuria (albumin-to-creatinine ratio (ACR) ≥30 mg/g). Sequentially adjusted logistic regression models assessed the association of biomarkers with kidney outcomes. ResultsMedian age of participants was 62, 49% were women, and 46% identified as Black. 228 (6.9%) developed CKD, 613 (18.9%) experienced ≥30% decline in eGFR, and 356 (11.4%) developed albuminuria. The adjusted odds ratios for incident CKD per 1 standard deviation increment biomarker was 1.12 for ICAM-1 (95% CI 1.02-1.22), 1.10 for VCAM-1 (95% CI 1.01-1.20), 1.15 for factor VIII (95% CI 1.06-1.24), and 1.10 for E-selectin (95% CI 1.01-1.20). Results were similar for incident ≥30% eGFR decline but not albuminuria, where only higher factor VIII was positively associated. ConclusionsHigher concentration of ICAM-1, VCAM-1, factor VIII, and E-selectin were associated with incident CKD and ≥30% eGFR decline in a large cohort study. Higher factor VIII was also associated with incident albuminuria.

Study of IL-17 and Intercellular Adhesion Molecule-1 in Conjunctivochalasis Using Correlation Analysis.

The aim of this study was to observe the expression of interleukin (IL)-17 and intercellular adhesion molecule (ICAM)-1 in conjunctivochalasis (CCH) and to analyze the correlations between cytokines and the severity of CCH. Serum samples were collected from 22 patients with CCH and 18 normal controls (NCs). The Ocular Surface Disease Index, tear film break-up time, Schirmer I test, and corneal fluorescein staining were used to evaluate the ocular surface signs and symptoms. The concentrations of IL-17, IL-23, and ICAM-1 in serum and cellular supernatants were measured by enzyme-linked immunosorbent assays, and the gene expression levels of cytokines were measured by a quantitative real-time polymerase chain reaction. The relationships between serum concentrations of IL-17, IL-23, and ICAM-1 with clinical ocular surface parameters in CCH were analyzed using the Spearman correlation analysis. The concentrations of IL-17 and ICAM-1 in serum and cellular supernatants of CCH were significantly higher than those of NCs (all P < 0.001). The concentrations of IL-23 in serum and cellular supernatants of CCH showed no significant difference from those of NCs ( P > 0.05). The mRNA expression levels of IL-17 and ICAM-1 in conjunctival fibroblasts of CCH were significantly higher than those of NCs (all P < 0.001). The mRNA expression of IL-23 in conjunctival fibroblasts of CCH was higher than that of NCs, without a significant difference ( P > 0.05). Furthermore, the serum concentrations of IL-17 and ICAM-1 were positively correlated with Ocular Surface Disease Index and fluorescein staining (all P < 0.05), and negatively correlated with break-up time and Schirmer I test of CCH (all P < 0.05). The expression levels of IL-17 and ICAM-1 were significantly increased in CCH serum and associated with the disease severity. We postulate that IL-17 and ICAM-1 may play a role in the pathogenesis of CCH. IL-17 and ICAM-1 antagonists may be a potential treatment option for CCH in the future.

Systemic concentrations of IL-18, TFG-β, RANTES, ICAM-1 and uPAR as combined pathway-related factors may help in identification of patients suffering from depressive disorder.

Systemic concentrations of IL-18, TFG-β, RANTES, ICAM-1 and uPAR as combined pathway-related factors may help in identification of patients suffering from depressive disorder.

Labetalol Ameliorates Experimental Colitis in Rat Possibly Through its Effect on Proinflammatory Mediators and Oxidative Stress.

Members of beta blockers drugs possess significant antioxidant activities. The current research is to assess the effect of the labetalol on acetic acid (AA-induced) colitis in rat model. Forty adult Wistar rats were separated into 4 groups, including the negative control group, AA group, AA + sulfasalazine (100 mg/kg/day) group, and AA + labetalol (300 mg/kg/day) group. Colitis was induced in rats by the interrectal installation of 2 mL of 4% (v/v) AA. Sulfasalazine and labetalol were administered orally for 7 days after 2 hours of induction. The following parameters were measured: disease activity index (DAI), histopa-thological changes and colon tissue homogenate concentrations of proinflammatory mediators IL-1β, adhesion molecules ICAM-1, and oxidative stress marker myeloperoxidase (MPO). The treatment with labetalol significantly reduced DAI and histopathological changes induced by AA. Also, labetalol markedly decreased the concentrations of IL-1β, ICAM-1, and MPO in colonic tissue that were increased by AA. The effects of labetalol were significantly lower than that produced by sulfasalazine as standard drug. Labetalol exerts ameliorative effects on disease activity and histopathological features of AA-induced colitis in rats possibly through antioxidant effects and inhibition of inflammatory mediators.

Association of Helicobacter Pylori Infection with Endothelial Dysfunction in Metabolic Syndrome

Background: Metabolic risk factors play a critical role in metabolic syndrome (MetS), and endothelial dysfunction is important in its development. On the other hand, Helicobacter pylori (H. pylori) infection has an essential role in MetS. The goal of present study was to evaluate the effect of H. pylori infection on endothelial dysfunction in MetS patients.&#x0D; Methods: Based on the International Diabetes Federation (IDF) criteria, 80 MetS patients (59 females and 21 males, mean age: 48.94 ± 10.00 years) were selected. Plasma samples were assayed for H. pylori IgG using the ELISA method. Endothelial function was also evaluated by measuring plasma concentrations of endothelin-1 (ET- 1), E-selectin, and intracellular adhesion molecule (ICAM-1) using ELISA method. Also, NO2 −− and NO3 −− concentrations were measured by Griess method.&#x0D; Results: Fifty patients (62.5%) had H. pylori infection. Plasma concentrations of ET-1, NO2−−, and NO3−− were significantly higher in MetS patients with positive H. pylori infection than in MetS patients with negative H. pylori infection (ET-1: 2.92 ± 2.33 vs 1.9 ± 1.4 pg/ml; P = 0.037; NO2 −−:19.46 ± 7/11 vs 15.46 ± 4.56 μM; P = 0.003; NO3 −−: 20.8 ± 10.53 vs 16.85 ± 6.03 μM, P = 0.036). However, plasma concentrations of ICAM-1 and E-selectin did not show any significant difference in the two groups.&#x0D; Conclusion: The results showed a relationship between H. pylori infection and endothelial dysfunction. Helicobacter pylori infection can lead to atherosclerosis by causing chronic inflammation and affecting the factors contributing to the MetS.

The impact of macrosomia on cardiometabolic health in preteens: findings from the ROLO longitudinal birth cohort study

BackgroundMacrosomia (birthweight ≥ 4 kg or ≥ 4.5 kg) is strongly associated with a predisposition to childhood obesity, which in turn is linked with adverse cardiometabolic health. Despite this, there is a lack of longitudinal investigation on the impact of high birthweight on cardiometabolic outcomes in youth. The preteen period represents an important window of opportunity to further explore this link, to potentially prevent cardiometabolic profiles worsening during puberty.MethodsThis is a secondary analysis of 9–11-year-olds (n = 405) born to mothers in the ROLO longitudinal birth cohort study, who previously delivered an infant with macrosomia. Preteens were dichotomised into those born with and without macrosomia, using two common cut-off criteria (birthweight ≥ 4 kg (n = 208) and < 4 kg; ≥ 4.5 kg (n = 65) and < 4.5 kg). Cardiometabolic health was assessed using anthropometry, dual-energy x-ray absorptiometry, blood pressure, heart rate, cardiorespiratory endurance (20-m shuttle run test), and non-fasting serum biomarkers for a subgroup (n = 213). Statistical comparisons between the two groups were explored using independent t-tests, Mann–Whitney U tests, and Chi-square tests. Crude and adjusted linear regression models investigated associations between macrosomia and preteen cardiometabolic outcomes.ResultsIn total, 29.3% (n = 119) of preteens had overweight/obesity based on their BMI z-score. Preteens born ≥ 4 kg had lower median (IQR) C3 concentrations (1.38 (1.22, 1.52) g/L vs. 1.4 (1.26, 1.6) g/L, p = 0.043) and lower median (IQR) ICAM-1 concentrations (345.39 (290.34, 394.91) ng/mL vs. 387.44 (312.91, 441.83) ng/mL, p = 0.040), than those born < 4 kg. Those born ≥ 4.5 kg had higher mean (SD) BMI z-scores (0.71 (0.99) vs. 0.36 (1.09), p = 0.016), and higher median (IQR) lean mass (24.76 (23.28, 28.51) kg vs. 23.87 (21.9, 26.79) kg, p = 0.021), than those born < 4.5 kg. Adjusted linear regression analyses revealed birthweight ≥ 4 kg was negatively associated with C3 concentration (g/L) (B = − 0.095, 95% CI = − 0.162, − 0.029, p = 0.005) and birthweight ≥ 4.5 kg was positively associated with weight z-score (B = 0.325, 95% CI = 0.018, 0.633, p = 0.038), height z-score (B = 0.391, 95% CI = 0.079, 0.703, p = 0.014), lean mass (kg) (B = 1.353, 95% CI = 0.264, 2.442, p = 0.015) and cardiorespiratory endurance (B = 0.407, 95% CI = 0.006, 0.808, p = 0.047).ConclusionThis study found no strong evidence to suggest that macrosomia is associated with adverse preteen cardiometabolic health. Macrosomia alone may not be a long-term cardiometabolic risk factor.Trial registration ISRCTN54392969 registered at www.isrctn.com.

Indicators of endothelial dysfunction and the rate of thrombotic complications in patients with type 2 diabetes mellitus at different periods after COVID-19

Introduction. Damage to the vascular endothelium and hypercoagulation are two of the main causes of post-­COVID-19 complications. The aim of our study was to evaluate endothelial dysfunction and thrombotic complications at different periods after COVID-19 in patients with type 2 diabetes mellitus. Patients and methods. We conducted a cross-­sectional study of 135 patients with type 2 diabetes mellitus who applied for inpatient treatment at the RSSPMCE clinic (Tashkent, Uzbekistan) in the period from 3 to 24 months after the acute period of COVID-19. The following laboratory parameters were assessed: fibrinogen, INR, APTT, D-dimer, von Willebrand factor, and cell adhesion molecules (VCAM-1, ICAM-1). Results. Despite normal or near-normal INR, APTT and fibrinogen levels, many patients had elevated levels of D-dimer (41.4 % of cases), von Willebrand factor (27.6 % of cases) and vascular cell molecules up to 24 months after infection. The concentrations of ICAM-1 and VCAM-1 did not have statistically significant correlations with the degree of compensation of diabetes mellitus (HbA1c level). At various times after COVID-19, cases of ischemic forms of diabetic foot syndrome and thrombosis affecting the cavernous sinus and upper extremities were recorded. Conclusion. Taking into account the results obtained, patients with type 2 diabetes mellitus after SARS-CoV-2 infection require careful monitoring, and, in addition to assessing standard coagulation parameters, determining the level of cell adhesion molecules may have diagnostic value.

Functional activity of the oral endothelium in persons, with chronic periodontitis during treatment with plasmolifting

Chronic periodontitis as an osteoimmune disease of the oral cavity is accompanied by a change in the functional activity of endotheliocytes. Moreover, abnormal vascularization exacerbates periodontal inflammation, as it promotes the transmigration of a larger number of immunocompetent cells, the influx of inflammatory mediators and cytokines.The aim of our work was to study the functional activity of the endothelium of the vessels of the oral cavity in persons suffering from chronic periodontitis in the treatment of plasmolifting.Materials and methods. Under observation were 30 patients diagnosed with chronic generalized periodontitis of moderate severity at the age of 35 (32.50; 40.00) years, with no severe somatic pathology (main group). The comparison group included 20 people aged 38 (34.00; 45.00) years with no inflammatory diseases in the oral cavity. All patients underwent local anti-inflammatory therapy and sanitation of periodontal pockets, correction of occlusal contacts, curettage, plasma lifting. Oral fluid concentration of soluble adhesion molecules ICAM-1 and VCAM-1, endothelin-1, qualitative and quantitative composition of microflora were determined.Results. After the treatment with plasmolifting, a noticeable relief of the activity of the inflammatory process was observed. In patients with chronic periodontitis, Porphyromonas gingivalis was found in 100 % of cases in a titer of 5.73 (4.9; 6.7) lg (gEq/sample), in 62.5 % – Prevotella intermedia in a titer of 4.5 (3.0; 5.5) lg (gEq/sample). Against the background of therapy, decrease of the occurrence of the microorganism and of the number of microorganisms was observed. The concentration of the soluble form of VCAM-1 in the oral fluid of patients with chronic periodontitis exceeded the values of the control group by 38.3 times (p = 0.000001), and ICAM-1 – by 18.1 times (p = 0.00001). Against the background of plasmolifting therapy, the level of the studied substances decreased, but exceeded the control values by 25.2 and 6.4 times, respectively. The content of endothelin in the oral fluid in patients with periodontitis exceeded the values of healthy individuals by 40.7 % (p = 0.003), during therapy its values decreased, but did not reach the level of healthy volunteers (p = 0.04).

High levels of endothelial ICAM-1 prohibit natalizumab mediated abrogation of CD4+ T cell arrest on the inflamed BBB under flow in vitro

IntroductionThe humanized anti-α4 integrin blocking antibody natalizumab (NTZ) is an effective treatment for relapsing–remitting multiple sclerosis (RRMS) that is associated with the risk of progressive multifocal leukoencephalopathy (PML). While extended interval dosing (EID) of NTZ reduces the risk for PML, the minimal dose of NTZ required to maintain its therapeutic efficacy remains unknown.ObjectiveHere we aimed to identify the minimal NTZ concentration required to inhibit the arrest of human effector/memory CD4+ T cell subsets or of PBMCs to the blood–brain barrier (BBB) under physiological flow in vitro.ResultsMaking use of three different human in vitro BBB models and in vitro live-cell imaging we observed that NTZ mediated inhibition of α4-integrins failed to abrogate T cell arrest to the inflamed BBB under physiological flow. Complete inhibition of shear resistant T cell arrest required additional inhibition of β2-integrins, which correlated with a strong upregulation of endothelial intercellular adhesion molecule (ICAM)-1 on the respective BBB models investigated. Indeed, NTZ mediated inhibition of shear resistant T cell arrest to combinations of immobilized recombinant vascular cell adhesion molecule (VCAM)-1 and ICAM-1 was abrogated in the presence of tenfold higher molar concentrations of ICAM-1 over VCAM-1. Also, monovalent NTZ was less potent than bivalent NTZ in inhibiting T cell arrest to VCAM-1 under physiological flow. In accordance with our previous observations ICAM-1 but not VCAM-1 mediated T cell crawling against the direction of flow.ConclusionTaken together, our in vitro observations show that high levels of endothelial ICAM-1 abrogate NTZ mediated inhibition of T cell interaction with the BBB. EID of NTZ in MS patients may thus require consideration of the inflammatory status of the BBB as high levels of ICAM-1 may provide an alternative molecular cue allowing for pathogenic T cell entry into the CNS in the presence of NTZ.

Association between Aqueous Humor Cytokines and Structural Characteristics Based on Optical Coherence Tomography in Patients with Diabetic Macular Edema.

To investigate the relationship between aqueous humor cytokines and structural characteristics based on optical coherence tomography (OCT) in patients with diabetic macular edema (DME). Forty eyes of 28 patients with DME diagnosed in the Affiliated Eye Hospital of Wenzhou Medical University at Hangzhou were included. All patients collected aqueous humor during anti-VEGF treatment, and the IL-6, IL-8, IL-10, VEGF, VCAM-1, ICAM-1, TGF-β1, FGF, and MCP-1 concentrations were detected. OCT examination was performed before anti-VEGF treatment and 1 month after anti-VEGF operation. Central macular thickness (CMT), macular volume (MV), choroidal thickness (CT), and the number of hyperreflective foci (HRF) were obtained for analysis. Each eye was determined whether there is subretinal effusion (SRD), cystoid macular edema (CME), and diffuse retinal thickening (DRT). The levels of IL-6 and FGF in DME patients with SRD were significantly higher than those without SRD (all P < 0.05). The level of VEGF in DME patients with CME was significantly higher than that in DME patients without CME (P = 0.005); IL-6, TGF-β1, and MCP-1 were significantly higher in DME patients with DRT than that without DRT (all P < 0.05). There was no significant correlation between aqueous humor cytokines and retinal thickness and retinal volume. However, the thinner the CT, the higher the level of aqueous humor cytokines IL-6 (r = -0.313, P = 0.049) and FGF (r = -0.361, P = 0.022). A multivariate linear regression analysis showed that IL-6 was significantly correlated with CT (P = 0.002) and SRD (P = 0.017), FGF was also significantly correlated with CT (P = 0.002) and SRD (P = 0.005), and TGF-β1 was correlated with triglycerides (P = 0.030) and HRF (P = 0.021). DME patients with significant macular cystoid edema changes may be related to high VEGF concentrations and thin CT; meanwhile, the presence of SRD or a high number of HRF on OCT macular scans in DME patients may indicate high levels of intraocular inflammatory factors. Thus, OCT morphology characteristics to some extent reflect intraocular inflammatory factors and VEGF levels and may guide treatment alternatives.

Ornithine Aspartate and Vitamin-E Combination Has Beneficial Effects on Cardiovascular Risk Factors in an Animal Model of Nonalcoholic Fatty Liver Disease in Rats.

Cardiovascular (CV) disease is the main cause of death in nonalcoholic fatty liver disease (NAFLD), a clinical condition without any approved pharmacological therapy. Thus, we investigated the effects of ornithine aspartate (LOLA) and/or Vitamin E (VitE) on CV parameters in a steatohepatitis experimental model. Adult Sprague Dawley rats were randomly assigned (10 animals each) and treated from 16 to 28 weeks with gavage as follows: controls (standard diet plus distilled water (DW)), NAFLD (high-fat choline-deficient diet (HFCD) plus DW), NAFLD+LOLA (HFCD plus LOLA (200 mg/kg/day)), NAFLD+VitE (HFCD plus VitE (150 mg twice a week)) or NAFLD+LOLA+VitE in the same doses. Atherogenic ratios were higher in NAFLD when compared with NAFLD+LOLA+VitE and controls (p < 0.05). Serum concentration of IL-1β, IL-6, TNF-α, MCP-1, e-selectin, ICAM-1, and PAI-1 were not different in intervention groups and controls (p > 0.05). NAFLD+LOLA decreased miR-122, miR-33a, and miR-186 (p < 0.05, for all) in relation to NAFLD. NAFLD+LOLA+VitE decreased miR-122, miR-33a and miR-186, and increased miR-126 (p < 0.05, for all) in comparison to NAFLD and NAFLD+VitE. NAFLD+LOLA and NAFLD+LOLA+VitE prevented liver collagen deposition (p = 0.006) in comparison to NAFLD. Normal cardiac fibers (size and shape) were lower in NAFLD in relation to the others; and the inverse was reported for the percentage of regular hypertrophic cardiomyocytes. NAFLD+LOLA+VitE promoted a significant improvement in atherogenic dyslipidemia, liver fibrosis, and paracrine signaling of lipid metabolism and endothelial dysfunction. This association should be further explored in the treatment of NAFLD-associated CV risk factors.

Optimizing the interaction between a new complex of platinum and copper with immunoproteins

New two complexes of Platinum IV and Cupper II were synthesized and characterized in this research, Mannich base derivative L was synthesized as ligand containing 2-thion 1,3,4oxadiaol ring. A bidentate ligand was characterized by UV, FT-IR, CHNS, 1HNMR and 13C-NMR techniques while the complexes were characterized by UV, FTIR, CHNS, flame atomic absorption, molar conductivity and Magnetic susceptibilities. Supported by theoretical calculations which completed by MOE program for molecular docking of the complexes with ICAM-1 and IL-1 Immunoproteins, the optimizing conditions for this binding were carried out to establish the best concentration of ICAM-1 and IL-1, volume ratio for both complexes and proteins, incubation time and temperature for the binding. The pointed optimal conditions for ICAM-1 were : concentration 300 ng/mL, volume ratio 40:60, time 90 min and 35oC for binding it’s with platinum complex, concentration 300ng/mL, 60:40 volume ratio, time 60 min and 35 oC to bind with Cu complex.

Complement and endothelial cell activation in COVID-19 patients compared to controls with suspected SARS-CoV-2 infection: A prospective cohort study.

BackgroundThromboinflammation may influence disease outcome in COVID-19. We aimed to evaluate complement and endothelial cell activation in patients with confirmed COVID-19 compared to controls with clinically suspected but excluded SARS-CoV-2 infection.MethodsIn a prospective, observational, single-center study, patients presenting with clinically suspected COVID-19 were recruited in the emergency department. Blood samples on presentation were obtained for analysis of C5a, sC5b-9, E-selectin, Galectin-3, ICAM-1 and VCAM-1.Results153 cases and 166 controls (suffering mainly from non-SARS-CoV-2 respiratory viral infections, non-infectious inflammatory conditions and bacterial pneumonia) were included. Hospital admission occurred in 62% and 45% of cases and controls, respectively. C5a and VCAM-1 concentrations were significantly elevated and E-selectin concentrations decreased in COVID-19 out- and inpatients compared to the respective controls. However, relative differences in outpatients vs. inpatients in most biomarkers were comparable between cases and controls. Elevated concentrations of C5a, Galectin-3, ICAM-1 and VCAM-1 on presentation were associated with the composite outcome of ICU- admission or 30-day mortality in COVID-19 and controls, yet more pronounced in COVID-19. C5a and sC5b-9 concentrations were significantly higher in COVID-19 males vs. females, which was not observed in the control group.ConclusionsOur data indicate an activation of the complement cascade and endothelium in COVID-19 beyond a nonspecific inflammatory trigger as observed in controls (i.e., “over”-activation).

Metabolomic analysis of serum from pure coronary artery ectasia patients based on UPLC-QE/MS technique

BackgroundCoronary artery ectasia (CAE) is a cardiovascular disorder characterized by abnormal coronary artery dilation and disturbed coronary flow. The exact pathophysiology of CAE is still unclear. We aimed to investigate differences in metabolomic profiles between CAE patients and healthy controls. MethodsRadial artery blood samples were collected from 14 pure CAE patients, 12 mixed CAE patients with atherosclerosis, and 14 controls with normal angiography. Differential serum metabolites were analyzed by untargeted ultra-high performance liquid chromatography-mass spectrometry. Serum ICAM-1, VEGF, ROS, and glutathione levels were also measured. ResultsTen metabolites distinguished pure CAE patients from controls and mixed CAE, including 1-cyano-2-hydroxy-3-butene, 2,3-dihydro-6-methyl-5-(5-methyl-2-furanyl)-1H-pyrrolizine, 2-propionylpyrrole, 2-pyrrolidinone, 3-(2-furanylmethylene)pyrrolidine, D-alanine, furanofukinin, o-ethyltoluene, rotundine A, and SM(d18:1/18:1(9Z)). Related metabolic pathways include amino acid metabolism, sphingolipid dysfunction, energy metabolism, mitochondrial dysfunction, and oxidative stress. Serum concentrations of ICAM-1, VEGF and ROS were significantly elevated in CAE patients compared to controls, while glutathione decreased significantly in CAE patients. Moreover, ICAM-1 levels were negatively correlated with 2-propionylpyrrole, and VEGF levels were negatively correlated with SM(d18:1/18:1(9Z)), while GSH and ROS levels were correlated with the abundance of SM(d18:1/18:1(9Z)), further confirming systemic inflammation and oxidative stress in CAE. ConclusionsThis is the first report describing differential serum metabolomic profiles of pure CAE patients compared to mixed CAE and healthy controls, which revealed 10 potential biomarkers that can provide an early diagnosis of pure CAE. These discriminatory metabolites and related metabolic pathways can help to better understand the pathogenesis of pure CAE.

Abstract 5222: Biomarkers associated with complete metabolic response (CMR) to nivolumab and brentuximab vedotin (nivo + BV) for the treatment of children, adolescents, and young adults (CAYA) with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) in the CheckMate 744 study

Abstract Introduction: CAYA with R/R cHL without CMR have suboptimal outcomes. Biomarkers associated with poor outcomes in cHL include PD-L1 overexpression and presence of tumor-associated macrophages (TAMs). In the phase 2 CheckMate 744 study (NCT02927769), CAYA with R/R cHL treated with a risk-adapted approach using nivo + BV induction showed a CMR rate per BICR of 59% (26/44) in the standard risk cohort; 41% of patients (pts) did not achieve CMR (non-CMR). Here we compared biomarker data from pts achieving CMR vs non-CMR. Methods: Pts aged 5-30 y with R/R cHL received 4 cycles of nivo + BV induction. Tumor biopsy and peripheral blood samples were collected at baseline (BL) and 4 prespecified timepoints during induction. CD163+ CD68+ TAMs were quantified using multiplex immunohistochemistry. Cytokine expression in pts with CMR vs non-CMR was assessed by the limma workflow and a linear model based on changes from BL. Immune cells were analyzed by flow cytometry. Statistical testing was adjusted for repeated measures across visits; values are reported from 39/39 cytokines and 13/16 cell subsets tested. Cytokine ratios to BL were compared across all timepoints and between response groups by ANOVA. Results: Pts with CMR (n = 24/26) after nivo + BV induction had more CD163+ CD68+ TAMs than pts with non-CMR (n = 17/18) in the BL tumor microenvironment (P = 0.018). Hierarchical clustering of cytokine fold changes from BL to the indicated timepoint, between pts with CMR vs non-CMR, showed reduced levels of haptoglobin, RANTES, CRP, PARC, EN-RAGE, and TARC/CCL17, and increased levels of MCP-2, IFN-γ, IP-10, and MIG. In all pts, median concentrations of TARC, IL-2Rα, CRP, and ICAM-1 decreased significantly (all P &amp;lt; 0.05); a greater reduction in TARC and CRP was observed in early cycles in pts with CMR vs non-CMR. In contrast, IP-10 levels increased from BL in all pts (P = 0.0012). Four cytokines showed higher concentrations in pts with CMR vs non-CMR: TNFR2, MCP-2, vWF, and TIMP-1 (all P &amp;lt; 0.05). Increased numbers of lymphocytes and monocytes and decreased numbers of granulocytes were observed after induction in all pts (all P &amp;lt; 0.01). Pts with non-CMR had more naive (CCR7+ CD45RA+) CD4, and naive CD8 T cells than pts with CMR at BL, and more overall CD4 (CD3+ CD4+) T cells at the end of cycle 4 (all P &amp;lt; 0.05). Conclusions: This biomarker analysis from CheckMate 744 suggests that different immunological parameters are associated with CMR vs non-CMR to nivo + BV induction in CAYA with R/R cHL. These include increased TAMs at BL in pts with CMR, changes in cytokine levels associated with macrophage biology, and greater numbers of naive lymphocytes and CD4 T cells in pts with non-CMR. TAMs have been reported to express high PD-L1 levels; thus, increased TAM numbers may sensitize pts to nivo + BV. Citation Format: Charlie Garnett-Benson, Ron Ammar, Russell Crowe, Stephen Francis, Sahar Ansari, Alev Akyol. Biomarkers associated with complete metabolic response (CMR) to nivolumab and brentuximab vedotin (nivo + BV) for the treatment of children, adolescents, and young adults (CAYA) with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) in the CheckMate 744 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5222.