Intercellular Adhesion Molecule-1 Levels Research Articles

Dynamics of Ischemia/Reperfusion Injury Markers During Normothermic Liver Machine Perfusion

Background. A comprehensive mechanistic assessment of normothermic machine perfusion (NMP) is an essential step toward identifying biomarkers to assess liver viability. Although some studies have evaluated the effect of NMP on inflammation markers, there are other key pathological mechanisms involved in ischemia/reperfusion injury (IRI) that have not yet been evaluated. Methods. Eight human donor livers preserved by NMP were included to analyze IRI during preservation. Concentrations of several biomarkers involved in different biological processes of IRI were measured in the perfusate. Results. Perfusate levels of intercellular adhesion molecule 1, P-selectin, vascular cell adhesion molecule 1, metalloproteinase with thrombospondin motif type 1, member 13, phospholipase A2 group VII, and syndecan-1 progressively increased during NMP. Noteworthy, perfusate lactate levels showed a strong correlation with C-X-C motif chemokine ligand 10 (P = 0.001), intercellular adhesion molecule 1 (P = 0.01), and urokinase plasminogen activator (P = 0.001). Conclusions. Perfusate lactate correlates with the main underlying biological mechanisms occurring in the NMP environment. Moreover, several IRI biomarkers accumulate during NMP, which may limit the extent of the benefits of this technology.

The effect of eight weeks of circuit resistance training on Apo-B/A ratio and inflammatory status of sedentary postmenopausal women

Abstract Exercise can be an effective non-pharmacological method to reduce the complications of menopause. This study aimed to investigate the effect of 8 weeks of circuit resistance training (CRT) on the levels of C-reactive protein (CRP), intercellular adhesion molecule 1 (ICAM-1), apolipoprotein A (Apo-A), Apo-B, and their ratio in sedentary postmenopausal women. Thirty postmenopausal women (age 54 ± 3 years, body mass index 27.6 ± 1.97 kg/m2) without any serious diseases and no hormone therapy volunteered to participate in the research. The subjects were randomly divided into two groups: circuit resistance training (n = 15, CRT) and Control (n = 15) groups. Resistance training was performed for 8 weeks, 3 days a week, including 12 stations for the whole body in 3 sets and 8-12 repetitions. The exercises started at 40% of one repetition maximum (1RM) and gradually reached 75% of 1RM in the last week. Blood samples were taken before and 48 hours after the end of both interventions to measure CRP, ICAM-1, Apo-A-I, and Apo-B. To analyse the data, a two-way analysis of variance test was used. The CRT intervention by reducing Apo-B (−8.9% vs −0.1%; change percentage relative to pre-to-post values in each group) and increasing Apo-A1 (+4.7% vs −0.1%) led to a significant increase in the Apo-B/A ratio (−13.0% vs −0.08%) compared to the Control group. In addition, a substantial decrease in the inflammatory levels of CRP (−21.0% vs +6.3%) and ICAM-1 (−22.7% vs +1.6%) was observed after 8 weeks of CRT compared to the Control group. The observed changes were consistent with a reduction in body mass and an improvement in the waist-hip ratio (WHR). The findings indicated that CRT could reduce the complications of menopause by reducing inflammatory markers and improving the lipid profile.

Anti-inflammatory Activity of Clitoria ternatea L. and Hibiscus sabdariffa L. Extract Combination in Reducing VCAM-1 Levels in Atherosclerosis

Atherosclerosis occurs when plaque accumulates and hardens within the arterial walls, leading to blood vessel blockages and increasing the risk of coronary heart disease (CHD). The extracts of butterfly pea (Clitoria ternatea L.) and roselle (Hibiscus sabdariffa L.) contain flavonoids that possess strong antioxidant and anti-inflammatory properties. This study aims to assess the effects of the combined extract of butterfly pea and roselle (EKTR) on atherosclerosis biomarkers such as Vascular Cell Adhesion Molecules-1 (VCAM-1), Intercellular Adhesion Molecule-1 (ICAM-1), and Interleukin-6 (IL-6). The research employed a True Experimental Laboratory approach using a Post-Test Control Group Design. The subjects were 36 female Wistar rats (Rattus norvegicus L.), randomly divided into six groups through a Completely Randomized Design (CRD). Data were collected on the levels of VCAM-1, ICAM-1, and IL-6 in the serum of obese white rats, measured using an ELISA photometer. Data analysis was conducted using SPSS version 18, with statistical evaluation performed via one-way ANOVA and Tukey's post hoc test. The results showed that increasing doses of EKTR led to significant reductions in atherosclerosis biomarkers such as VCAM-1, ICAM-1, and IL-6 compared to the positive control and other groups. At a dose of 500 mg/kg BW, group F3 recorded IL-6 levels of 30.49 ± 1.60 ng/mL, VCAM-1 level of 29.42 ± 2.58 ng/mL, and ICAM-1 levels of 28.42 ± 1.72 ng/mL. In conclusion, butterfly pea and roselle, rich in flavonoids with potent antioxidant and anti-inflammatory properties, are effective as traditional remedies for reducing atherosclerosis biomarkers and for preventing and treating coronary heart disease (CHD) at an optimal dose of 500 mg/kg BW.

Adhesion molecules and atherosclerosis in ankylosing spondylitis: implications for cardiovascular risk.

Ankylosing Spondylitis (AS) stands as a chronic inflammatory arthritis within the spondyloarthritis spectrum, notably increasing cardiovascular (CV) risk and mortality through accelerated atherosclerosis compared to the non-affected population. While evidence in some studies supports a higher cardiovascular morbidity in AS patients, results from other studies reveal no significant disparities in atherosclerotic markers between AS individuals and healthy controls. This discrepancy may arise from the complex interaction between traditional CV risk factors and AS inflammatory burden. Endothelial dysfunction, a recognized antecedent of atherosclerosis prevalent among most individuals with AS, demonstrates the synergistic impact of inflammation and conventional risk factors on endothelial injury, consequently hastening the progression of atherosclerosis. Remarkably, endothelial dysfunction can precede vascular pathology in AS, suggesting a unique relationship between inflammation, atherosclerosis, and vascular damage. The role of adhesion molecules in the development of atherosclerosis, facilitating leukocyte adherence and migration into vascular walls, underscores the predictive value of soluble intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels for cardiovascular events. Despite significant progress in comprehending the pathogenesis of AS and its associated cardiovascular implications, the interplay among inflammation, endothelial dysfunction, and atherosclerosis remains partially elucidated. Investigations into the efficacy of therapeutic approaches involving angiotensin receptor blockers and statins have demonstrated reduced cardiovascular risk in AS patients, underscoring the imperative for additional research in this domain.

Bacteriophage Therapy for Staphylococcus aureus Induced Postoperative Acute Endophthalmitis In Vivo

Background: Postoperative acute endophthalmitis is a rare but severe complication following cataract surgery, with bacterial pathogens such as Staphylococcus aureus being the leading cause. Despite declining incidence rates globally, visual outcomes remain poor in many cases. Recent studies have explored the potential of bacteriophage therapy to treat bacterial infections, particularly for antimicrobial-resistant strains. This study aimed to assess the therapeutic effectiveness of bacteriophage treatment in a rabbit model of S. aureus-induced acute postoperative endophthalmitis. Methods: The study employed a randomized, controlled, posttest-only design using New Zealand white rabbits. Following extracapsular lens extraction surgery, rabbits were injected with S. aureus intracamerally to induce endophthalmitis. The treatment group received additional bacteriophage therapy. Ocular inflammation was assessed by measuring two biomarkers, myeloperoxidase (MPO) and intercellular adhesion molecule-1 (ICAM-1), using enzyme-linked immunosorbent assay (ELISA) from vitreous fluid samples. Histopathological analysis of retinal and scleral structures was performed post-enucleation. Statistical analyses were conducted using independent t-tests. Results: The treatment group showed significantly lower ICAM-1 levels (p < 0.001), indicating reduced leukocyte infiltration and inflammation compared to the control group. MPO levels were slightly elevated in the treatment group but were not statistically significant (p = 0.261). Histopathological examination revealed that retinal structures in the treatment group were preserved with reduced inflammatory cell infiltration, whereas the control group displayed extensive retinal damage, including neovascularization and retinal detachment. Conclusion: Bacteriophage therapy significantly reduced ocular inflammation and tissue damage in S. aureus-induced endophthalmitis, as evidenced by lower ICAM-1 levels and better-preserved retinal structures in the treatment group. These findings suggest that bacteriophage therapy may be an effective alternative to conventional treatments for postoperative acute endophthalmitis, particularly in cases involving antibiotic-resistant bacteria. Further studies are warranted to explore its broader clinical applicability.

Pathogenesis of respiratory failure in COVID-19 due to coagulopathy and endothelial dysfunction

Respiratory failure is known to be the main clinical manifestation of COVID-19. However, the mechanism of its development has not been sufficiently studied. The originality of the study is that for the first time, coagulation, fibrinolysis and endothelial dysfunction indicators were studied depending on the SpO2/FiO2 index in patients with COVID-19.The aim of the work. To assess the role of impaired activity of the blood coagulation system and the development of endothelial dysfunction in patients with COVID-19 in the pathogenesis of respiratory failure.Methods. The study included 134 patients infected with SARS-CoV-2 virus having varying severity of the clinical picture. They were divided into three groups according to the SpO2/FiO2 index. We determined the number of venous blood cells and studied the level of transferrin (TF), D-dimer, tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), inter-cellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in the blood serum.Results. The study revealed that the tissue factor content increased by 24 % in patients of the third group compared to the first. The PAI-1 level was high in the second group and significantly decreased in the third (p < 0.001). An increase in the D-dimer level was recorded in the second and third groups. The levels of ICAM-1 and VCAM-1 molecules increased significantly in the third group of patients (p = 0.021 and p = 0.028, respectively). A moderate positive correlation was found between the SpO2/FiO2 index and the VCAM-1 level (p < 0.001), a weak positive correlation with PAI-1 (p = 0.012), and a weak negative correlation with TF (p = 0.027).Conclusion. Respiratory failure in patients with COVID-19 is caused by disorders in the hemostasis and fibrinolysis systems, as evidenced by an increase in the level of tissue factor and D-dimer, “consumption” of tissue activator and plasminogen activator inhibitor. Developing endothelial dysfunction, accompanied by increased secretion of adhesion molecules, aggravates the pathogenesis of respiratory failure.

Regulatory role and molecular mechanism of METTL14 in vascular endothelial cell injury in preeclampsia.

Preeclampsia (PE) is a pregnancy-related disease characterized by vascular endothelial cell injury. This study aimed to investigate the role of methyltransferase-like protein 14 (METTL14) in vascular endothelial cell injury in PE. The PE cell model was established by treating human umbilical vein endothelial cells (HUVECs) with tumor necrosis factor-alpha (TNF-α) in vitro. METTL14 and forkhead box protein 1 (FOXP1) were silenced, and miR-34a-5p was overexpressed in HUVECs to evaluate their effects. HUVEC viability, apoptosis, and the levels of intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and endothelin-1 were measured. The N6-methyladenosine (m6A) modification of pri-miR-34a-5p was quantified. The interactions between miR-34a-5p, DiGeorge syndrome critical region 8, and m6A enrichment in miR-34a-5p were analyzed. The relationship between miR-34a-5p and FOXP1 was also verified. The results showed that the expressions of METTL14, FOXP1, and miR-34a-5p were determined. METTL14 expression was elevated in the TNF-α-induced HUVEC injury model. Silencing METTL14 improved HUVEC viability, inhibited apoptosis, and reduced endothelial inflammation. METTL14 promoted miR-34a-5p expression through m6A modification. Overexpression of miR-34a-5p or silencing of FOXP1 reversed the protective effects of METTL14 silencing on cell injury in the PE model. In conclusion, METTL14 mediated m6A modification to promote miR-34a-5p expression, leading to the inhibition of FOXP1 expression, which aggravated endothelial cell damage in the PE cell model.

Hyaluronate functionalized Span-Labrasol nanovesicular transdermal therapeutic system of ferulic acid targeting diabetic nephropathy

Diabetic kidney disease, known as diabetic nephropathy (DN), is a widespread severe diabetes complication leading to kidney failure. Due to the lack of efficacious therapies, this study endeavors to enhance DN therapeutic effectiveness of ferulic acid (FRA), a natural phenolic with poor oral bioavailability, by developing a transdermal kidney-targeted spanlastic formulation. Spanlastics (SP) nanovesicles were prepared using Span 60 and Labrasol or Brij35 as edge activators (EA). Cationic guar (CG) and hyaluronic acid (HA) were employed as coatings. The formulations were assessed for entrapment efficiency (EE), particle size (PS) and zeta potential (ZP). A 21 × 31 factorial optimization of FRA spanlastic formulations revealed the desirable nanoformula was FRA-L-H-SP comprising Labrasol and hyaluronate coating. Transmission electron microscopy (TEM), Fourier-transform infrared (FT-IR), Diphenylpicrylhydrazyl (DPPH) antioxidant activity, in-vitro release, and rat skin ex-vivo permeation assessed this formula and the uncoated one (FRA-L-SP). Biochemical indicators and histopathology for diabetes and kidney injury were evaluated in the Streptozotocin (STZ)-induced DN rat model. Results showed significant improvements after treatment with FRA-L-H-SP compared to FRA-L-SP and free FRA, with decreased blood glucose, creatinine, and intercellular adhesion molecule-1 (ICAM-1) levels and increased insulin, AMP-activated protein kinase (AMPK), and sirtuins (SIRT). This enhancement can be acknowledged as passive targeting of SP and active targeting properties of hyaluronic to cluster of differentiation 44 (CD44) receptors, revealing the potential to improve DN pathophysiology.

Relation of ICAM-1 and VCAM-1 markers in COVID-19 patients in Kirkuk province.

The advent of the Coronavirus Disease 2019 (COVID-19) has presented a substantial and urgent global public health issue. Biomarkers have the potential to be utilized for the identification of endothelium and/or alveolar epithelial damage in instances of COVID-19 infection. to evaluate the levels of Intercellular adhesion molecule-1 (ICAM-1) and Vascular cell adhesion molecule (VCAM-1) biomarkers in hospitalized patients who tested positive for COVID-19 infection using Polymerase Chain Reaction (PCR) with the virus specific Immunoglobulins; IgM, and IgG testing. This can help with improved clinical management and treatment programs. A case-control study that involved 90 hospitalized patients who tested positive for COVID-19 and 40 apparently healthy control patients, subjects in both groups underwent nasopharyngeal swabs for PCR and blood sample collection for evaluation of serum; IgM, IgG, ICAM-1 and VCAM-1 levels. Males made up the vast majority of the patients (78.9%), with only a minor percentage of females (21.1%) P value 0.1641. Furthermore, every patient in this study had a minimum of one risk factor for COVID-19. The investigator's results show that COVID-19 patients had higher amounts of endothelial cell adhesion indicators (ICAM-1 and VCAM-1) with mean values of 126.27 ± 89.51 ng/mL and 109.74 ± 96.57 ng/mL respectively. While, ICAM-1 and VCAM-1, were present at normal levels in the control group with difference P value 0.0028 and 0.0032 in comparison to the patient's group respectively. The adhesive markers ICAM and VCAM play a crucial role in the development of COVID-19 and the strong endothelial activation and dysfunction linked to both acute and persistent immunological responses is shown by the substantial correlation found in COVID-19 patients between the presence of IgM and IgG antibodies and higher levels of ICAM-1 and VCAM-1.

Systematic pan-cancer analysis insights into ICAM1 as an immunological and prognostic biomarker.

Intercellular adhesion molecule 1 (ICAM1) is a cell surface adhesion glycoprotein in the immunoglobulin supergene family. It is associated with several epithelial tumorigenesis processes, as well as with inflammation. However, the function of ICAM1 in the prognosis of tumor immunity is still unclear. This study aimed to examine the immune function of ICAM1 in 33 tumor types and to investigate the prognostic value of tumors. Using datasets from the Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), Cancer Cell Lines Encyclopedia (CCLE), Human Protein Atlas (HPA), and cBioPortal, we investigated the role of ICAM1 in tumors. We explored the potential correlation between ICAM1 expression and tumor prognosis, gene mutations, microsatellite instability, and tumor immune cell levels in various cancers. We observed that ICAM1 is highly expressed in multiple malignant tumors. Furthermore, ICAM1 is negatively or positively associated with different malignant tumor prognoses. The expression levels of ICAM1 were correlated with the tumor mutation burden (TMB) in 11 tumors and with MSI in eight tumors. ICAM1 is a gene associated with immune infiltrating cells, such as M1 macrophages and CD8+ T cells in gastric and colon cancer. Meanwhile, the expression of ICAM1 is associated with several immune-related functions and immune-regulation-related signaling pathways, such as the chemokine signaling pathway. Our study shows that ICAM1 can be used as a prognostic biomarker in many cancer types because of its function in tumorigenesis and malignant tumor immunity.

An evaluation of inflammatory and endothelial dysfunction markers as determinants of peripheral arterial disease in those with diabetes mellitus

The most serious long-term effects of diabetes is peripheral artery disease (PAD) which increases the chance of developing diabetic foot ulcers, gangrene and even lower limb amputation. The clinical manifestations of PAD which are typically not revealed until symptoms like intermittent claudication, rest pain and ischemic gangrene develop, are not present in majority of diabetes mellitus patients with PAD due to diabetic peripheral neuropathy. Therefore, current study is aimed to evaluate the inflammatory and endothelial dysfunction markers with their correlation to biomarkers that can help for in-time diagnosis and efficient prognosis of developing diabetes-associated PAD. Enzyme-linked immunosorbent assay was used to evaluate the interlukin-6, interlukin-8, intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in PAD with diabetes group, diabetic group and healthy individual group while biomarkers were measured by kit method. It was observed that serum IL-6, IL-8, ICAM and VCAM levels in type II diabetes mellitus (T2DM) with PAD patients were increased significantly (85.93, 597.08, 94.80 and 80.66) as compared to T2DM patients (59.52, 231.34, 56.88 and 50.19) and healthy individuals (4.81, 16.93, 5.55 and 5.16). The overall means for the parameters, IL-6, IL-8, ICAM, VCAM, urea, S/creatinine, CK-MB, AST, ALT, cholesterol, triglyceride, HDL, LDL, PT, aPTT, INR, HbA1C, and CRP within all groups were significantly (P < 0.05) different from each other. Therefore, it was concluded that the change in IL-6, IL-8, ICAM and VCAM can serve as an accurate diagnostic indicator and successful treatment.

Role of intercellular adhesion molecule-1 in adhesion and migration of mesenchymal stem cells in ankylosing spondylitis and its mechanisms

Objective: To investigate the role and underlying mechanisms of intercellular adhesion molecule-1 (ICAM-1) in the adhesion and migration of mesenchymal stem cells (MSCs) in patients with ankylosing spondylitis (AS). Methods: Bone marrow and ligament tissues were collected during surgery from patients with AS and thoracolumbar fractures (as controls, HC) treated from October 2021 to October 2022 at Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital. MSCs were isolated and cultured from the bone marrow using the Ficoll separation method. Cell morphology was observed under high-resolution microscopy, and differences in the cytoskeletal features between AS-and HC-MSCs were analyzed through immunofluorescence staining. The expression of ICAM-1 was quantified in both groups using real-time quantitative polymerase chain reaction (RT-qPCR) and flow cytometry. Transwell migration assays and wound healing experiments were conducted to evaluate the differences in migration rates between the two groups of MSCs. Results: The interspinous ligament and bone marrow was acquired in AS (2 males and 1 female; 33, 37, 32 years old, respectively) and no-AS patients (2 males and 1 female; 35, 32, 38 years old, respectively). AS-MSCs exhibited broader cell morphology compared to HC-MSCs under bright field and fluorescence microscopy. Immunofluorescence staining of the interspinous ligament showed higher expression of ICAM-1 (68.38±3.42 vs 48.31±2.43) and CD105 (37.97±2.16 vs 23.36±2.06) in AS patients (both P<0.001). Western blot and RT-qPCR analysis revealed significantly stronger protein expression and transcription levels of ICAM-1 in AS-MSCs when compared to those in HC-MSCs (both P<0.001). Flow cytometry confirmed greater mean fluorescence intensity of ICAM-1 in AS-MSCs than in that in HC-MSCs (924.30±54.99 vs 636.47±40.03, P=0.002). Regarding cell adhesion efficiency, it showed no significant difference between AS-MSCs and HC-MSCs in the early stage of adhesion (0.5 h: 1 496±213 vs 1 205±163, P=0.133), but they were all significantly higher in AS-MSCs in the later stage (1 h: 2 894±172 vs 1 908±155, P=0.002; 2 h: 4 540±286 vs 3 334±188, P=0.004; 3 h: 5 212±281 vs 4 208±303, P=0.014). Finally, cell migration experiments demonstrated a stronger migration capability of AS-MSCs compared to HC-MSCs (5 449±172 vs 4 016±155, P<0.001), and the inhibition efficiency of A-205804 on the migration rate of AS-MSCs was stronger than that on HC-MSCs (2 145±239 vs 3 539±316, P=0.004). Conclusions: The aberrant expression of ICAM-1 markedly influences the adhesion and migration dynamics of MSCs. Elevated ICAM-1 levels in MSCs derives from patients with AS significantly enhance their migratory capabilities.

Study of Adhesion Molecules in Diabetes Mellitus Type2 Iraqi Patients with Dyslipidemia

Background: Cell adhesion molecules are protein entities that are located on the cell surface. The vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression is related to type 2 diabetes mellitus (T2DM) with dyslipidemia. Objectives: To determine the levels of VCAM-1 and ICAM-1 in T2DM patients with dyslipidemia and to explore the relationship between VCAM-1 and ICAM-1 and the development of dyslipidemia in T2DM patients. Patients and methods: The study included 150 individuals with an age range of (35-55) years. Patients with diabetes for more than 5 years were excluded. Fifty healthy individuals constituted Group 1 (G1), fifty patients with T2DM constituted Group 2 (G2), and fifty T2DM patients with dyslipidemia constituted Group 3 (G3). Whole blood samples were drawn to measure HbA1c based on fluorescence immunoassay technology. The serum was separated to measure fasting blood glucose (FBG), triglycerides (TG), total cholesterol (TC), and high-density lipoproteins (HDL) by manual methods, while VCAM-1, and ICAM-1 were determined using the ELISA test. The study was conducted between November 2022 and April 2023 at the National Center for Diabetes Treatment and Research, Baghdad, Iraq. Results: Significantly higher levels of FSG and HbA1c were detected in G2 and G3 compared to G1, but non-significantly so when G3 was compared to G2. Significant higher levels of TG and TC levels were detected for G3 when compared to G1 and G2, but non-significantly so when G2 was compared to G1. HDL levels were significantly lower in G3 compared to G2 and G1, but non-significantly so when G2 was compared to G1. VCAM-1, and ICAM-1 were significantly higher in G2 compared to G1, and VCAM-1 level was significantly higher in G3 compared to G2. Non-significant differences in ICAM-1 levels were found between G3 and G2. Conclusion: VCAM-1 and ICAM-1 are potentially significant factors in the development of dyslipidemia in diabetes patients. They might serve as biomarkers to accurately predict the progression of cardiovascular disease.

Association Between Soluble Cell Adhesion Molecules (sP-Selectin, sE-Selectin, and sICAM-1) and Antibodies Against the Antigens of Proteus mirabilis in Rheumatoid Arthritis Patients.

Objective The purpose of this study was to examine the association between the serum concentration of soluble cell adhesion molecules (CAMs) and antibodies against antigens of Proteus mirabilis (P. mirabilis) in rheumatoid arthritis (RA) patients, taking into consideration the implication of P. mirabilis in the etiopathogenesis of RA. Methods The serum levels of soluble P-selectin (sP-selectin), soluble E-selectin (sE-selectin), and soluble intercellular adhesion molecule-1 (sICAM-1) were determined by sandwich enzyme-linked immunosorbent assay (ELISA) in 59 RA patients and 36 healthy controls. Using the same ELISA method, the serum levels of class-specific antibodies against hemolysin (HpmB), urease C (UreC), and urease F (UreF) enzymes of P. mirabilis were also measured. Results In this study, increased levels of sP-selectin and sICAM-1 were observed in RA patients, while the levels of sE-selectin were increased in comparison with healthy controls but did not present a statistically significant difference. Moreover, increased levels of antibodies against HpmB, UreC, and UreF of P. mirabilis were found. Additionally, it was observed that the sE-selectin levels presented a significant correlation with IgG antibodies against the UreF antigen (there is no corresponding antigen in human tissue) in all the RA patients. A statistically significant correlation was observed between levels of soluble CAMs and antibodies against P. mirabilis in the different subgroups. Conclusion The observed correlation between soluble CAMs and antibodies against antigens of P. mirabilis, specifically in the subgroup of biologic therapy, indicates that P. mirabilis exists and provokes refractory in the treatment of RA.

Investigating the therapeutic effects of nimodipine on vasogenic cerebral edema and blood-brain barrier impairment in an ischemic stroke rat model

Vasogenic brain edema, a potentially life-threatening consequence following an acute ischemic stroke, is a major clinical problem. This research aims to explore the therapeutic benefits of nimodipine, a calcium channel blocker, in mitigating vasogenic cerebral edema and preserving blood-brain barrier (BBB) function in an ischemic stroke rat model. In this research, animals underwent the induction of ischemic stroke via a 60-min blockage of the middle cerebral artery and treated with a nonhypotensive dose of nimodipine (1 mg/kg/day) for a duration of five days. The wet/dry method was employed to identify cerebral edema, and the Evans blue dye extravasation technique was used to assess the permeability of the BBB. Furthermore, immunofluorescence staining was utilized to assess the protein expression levels of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1). The study also examined mitochondrial function by evaluating mitochondrial swelling, succinate dehydrogenase (SDH) activity, the collapse of mitochondrial membrane potential (MMP), and the generation of reactive oxygen species (ROS). Post-stroke administration of nimodipine led to a significant decrease in cerebral edema and maintained the integrity of the BBB. The protective effects observed were associated with a reduction in cell apoptosis as well as decreased expression of MMP-9 and ICAM-1. Furthermore, nimodipine was observed to reduce mitochondrial swelling and ROS levels while simultaneously restoring MMP and SDH activity. These results suggest that nimodipine may reduce cerebral edema and BBB breakdown caused by ischemia/reperfusion. This effect is potentially mediated through the reduction of MMP-9 and ICAM-1 levels and the enhancement of mitochondrial function.

Early Effects of Modern Radiotherapy for Lung Cancer on Endothelial Damage and Myocardial Fibrosis: A Prospective Single-Center Study.

Radiotherapy (RT) may have a cardiotoxic effect on the heart and cardiovascular system. Postulated mechanisms mediating these complications include vascular endothelium damage and myocardial fibrosis. The aim of our study was to assess endothelial damage and myocardial fibrosis in the early period after RT on the basis of cardiac biomarkers and in relation to the radiation dose applied to individual heart structures in patients treated for non-small-cell lung cancer. This single-center prospective study included consecutive patients with lung cancer (LC) who were referred for treatment with radiochemotherapy (study group) or chemotherapy (control group). The study protocol included performing an echocardiographic examination, a standard ECG examination, and collecting blood samples for laboratory tests before starting treatment for lung cancer in the first week after completing RT (after four cycles of chemotherapy in the control group) and after 12 weeks from the end of treatment. The study included 23 patients in the study group and 20 patients in the control group. Compared to the baseline values, there was a significant increase in total cholesterol concentration in the study group immediately after the end of RT, which persisted for three months after the end of therapy. After taking into account the use of statins in the analysis, it was found that an increase in total cholesterol concentration after oncological treatment was observed only among patients who did not use statins. Taking into account the assessment of myocardial fibrosis markers, there were no significant changes in the concentration of matrix metallopeptidase 9 (MMP-9) and tissue inhibitors of metalloproteinases 1 (TIMP-1) in the study group. In patients treated with radiochemotherapy, there was a significant increase in the concentration of intercellular adhesion molecule 1 (ICAM-1) immediately after RT, when compared to the baseline. After taking into account the use of statins, an increase in ICAM-1 concentration immediately after RT was observed only in patients who did not use statins. There was also a significant correlation between the radiation dose received by the left anterior descending coronary artery (LAD) and left circumferential coronary artery, and vascular cell adhesion protein 1 (VCAM-1) concentration measured at three months after the end of RT. Immediately after completion of radiotherapy, a significant increase in the level of ICAM-1 is observed indicating endothelial damage. The radiation dose to coronary arteries should be minimized, as it correlates with the concentration of VCAM-1. The use of statins may prevent the increase in total cholesterol and ICAM-1 concentration after irradiation for lung cancer; however, further studies designed for this specific purpose are necessary to confirm the effectiveness of statins in this area.

B7-H3 and ICAM-1 are potentially therapeutic targets for thyroid carcinoma

Although most differentiated thyroid carcinoma has a clinically favorable prognosis, some of specific types of thyroid cancer (such as anaplastic thyroid carcinoma and advanced papillary thyroid carcinoma) show fatal outcomes and require novel treatments. Immunotherapy is a promising avenue for the treatment of advanced thyroid carcinoma. B7-H3 (B7 homolog 3 protein) and ICAM-1 (intercellular adhesion molecule 1), as two important immune checkpoints (ICPs), is becoming hopeful target spots for immunotherapy. A growing amount of evidence has suggested that B7-H3 and ICAM-1 are upregulated in papillary thyroid carcinoma. However, their expression level in specific types of thyroid cancer remains largely unclear. In the present study, we explored the expression level of B7-H3 and ICAM-1 in different types of thyroid carcinoma. In the groups of the TCGA cohort, both B7-H3 and ICAM-1 mRNA were highly expressed in thyroid carcinoma. Furthermore, the patients with Stage2, 61-80y, Follicular thyroid papillary carcinoma and N0 had lower B7-H3 and ICAM-1 mRNA expression. In the groups of our cohort, PTCs and ATCs showed frequently moderate to strong expression of B7-H3 and ICAM-1 protein expression. The significant relevance of B7-H3 staining score with ICAM-1 staining score was observed in TCGA database and our cohort, which might open avenues for the combination therapy in advanced thyroid cancer.

Unveiling the crucial role of intercellular adhesion molecule-1 in secondary diabetic complications.

Diabetes mellitus is associated with secondary complications such as diabetic retinopathy (DR), nephropathy (DN), and cardiomyopathy (DCM), all of which significantly impact patient health. Intercellular adhesion molecule-1 (ICAM-1) has been implicated in inflammatory responses and endothelial dysfunction, both crucial in the pathogenesis of these complications. The goal of this review is to investigate at potential therapy methods that target ICAM-1 pathways and to better understand the multifaceted role of ICAM-1 in secondary diabetic problems. A meticulous analysis of scholarly literature published globally was conducted to examine ICAM-1involvement in inflammatory processes, endothelial dysfunction, and oxidative stress related to diabetes and its complications. Elevated ICAM-1 levels are strongly associated with augmented leukocyte adhesion, compromised microvascular function, and heightened oxidative stress in diabetes. These pathways contribute significantly to DR, DN, and DCM pathogenesis, highlighting ICAM-1 as a key player in their progression. Understanding ICAM-1 role in secondary diabetic complications offers insights into novel therapeutic strategies. Targeting ICAM-1 pathways may mitigate inflammation, improve endothelial function, and ultimately attenuate diabetic complications, thereby enhancing patient health outcomes. Continued research in this area is crucial for developing effective targeted therapies.

Abstract 2084: Endothelial Cells With Silenced Flrt2 Expression Exhibit Enhanced Retention On Vascular Graft Materials Under Fluid Shear Stress In Vitro

Myocardial infraction is a leading cause of death, and surgical intervention is often required to treat severe coronary artery disease. Autologous vessel grafts are the only option for bypass graft procedures. Synthetic vascular grafts less than 6 mm diameter fail due to unacceptable patency rates (~60% at 1 year). The loss of patency is accredited to platelet activation, thrombosis, and neointimal hyperplasia. A promising strategy to improve patency is to endothelialize synthetic vascular grafts ex-vivo, but previous attempts have met with modest success due to detachment of cells upon exposure to fluid shear stress. We previously used RNA-seq to characterized gene expression of endothelial cells (ECs) which remained adherent to synthetic grafts post shear stress. We found that fibronectin leucine-rich transmembrane protein 2 (FLRT2) was significantly downregulated in adherent subpopulations. We therefore hypothesize that suppressing FLRT2 expression in ECs will result in better retention on synthetic vascular grafts upon exposure to shear stress. We used silencing RNA approach using lipofectamine and confirmed successful knockdown of FLRT2 expression (Si-FLRT2). We then seeded Si-FLRT2 cells onto a commercially available Goretex graft material and subjected them to fluid shear stress of for 20 min. We then stained the samples with DAPI. We observed increased retention of Si-FLRT2 ECs on Goretex graft material in comparison to non-specifically targeted scramble siRNA containing ECs. In addition, we compared both vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) levels to assess endothelial cell activation and found that silencing of FLRT2 lead to decreased levels of both VCAM-1 (by 49.2%±3.5%) and ICAM-1 (by 57.1%±3.4%) suggestive of decreased endothelial cell activation. In conclusion, we show that FLRT2 plays an important role in adhesion of ECs onto a commercially available synthetic graft material and silencing its expression ex-vivo may have beneficial clinical outcomes. In addition, we found that FLRT2 silencing may lead to decreased endothelial cell activation and we would like to further investigate the molecular mechanisms underlying the role of FLRT2 in both EC adhesion and activation.

Brief research report: ETS-1 blockade increases ICAM-1 expression in activated human retinal endothelial cells.

Intercellular adhesion molecule 1 (ICAM-1) is a central cell adhesion molecule for retinal transendothelial migration of the leukocytes in non-infectious posterior uveitis. Inhibiting ICAM1 gene transcription reduces induction of ICAM-1 in inflamed retinal endothelium. Based on published literature implicating transcription factor ETS-1 as an activator of ICAM1 gene transcription, we investigated the effect of ETS-1 blockade on ICAM-1 levels in cytokine-stimulated human retinal endothelial cells. We first examined ICAM1 and ETS1 transcript expression in human retinal endothelial cells exposed to tumor necrosis factor-alpha (TNF-α) or interleukin-1beta (IL-1β). ICAM1 and ETS1 transcripts were increased in parallel in primary human retinal endothelial cell isolates (n = 5) after a 4-hour stimulation with TNF-α or IL-1β (p ≤ 0.012 and ≤ 0.032, respectively). We then assessed the effect of ETS-1 blockade by small interfering (si)RNA on cellular ICAM1 transcript and membrane-bound ICAM-1 protein. ETS1 transcript was reduced by greater than 90% in cytokine-stimulated and non-stimulated human retinal endothelial cell monolayers following a 48-hour treatment with two ETS-1-targeted siRNA, in comparison to negative control non-targeted siRNA (p ≤ 0.0002). The ETS-1 blockade did not reduce ICAM1 transcript expression nor levels of membrane-bound ICAM-1 protein, rather it increased both for a majority of siRNA-treatment and cytokine-stimulation conditions (p ≤ 0.018 and ≤ 0.004, respectively). These unexpected findings indicate that ETS-1 blockade increases ICAM-1 transcript and protein levels in human retinal endothelial cells. Thus ETS-1-targeting would be expected to promote rather than inhibit retinal transendothelial migration of leukocytes in non-infectious posterior uveitis.