Intercellular Adhesion Molecule-1 Levels Research Articles

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.

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.

Blood Adhesion Molecules as Biomarkers in Children with Chronic Urticaria.

The prevailing etiological model of both acute and chronic urticaria implicates specific allergen exposure that triggers the local release of vasoactive factors and inflammatory adhesion molecules, including vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), endothelial leukocyte adhesion molecule 1 (ELAM-1), P-selectin and E-selectin in the superficial dermis. This study focused on the possible role of VCAM-1 and ICAM-1 as biomarkers in children with acute and chronic urticaria. This study involved 184 children, 40 with acute urticaria, 71 with chronic urticaria, and 73 matched comparison subjects. The serum levels of ICAM-1 and VCAM-1 were determined in venous blood in all the participants on enrollment. Antihistamine treatment was administered to all the patients. In the children with chronic urticaria, the Urticaria Activity Score Questionnaire (UAS7) was completed daily by the parents. In 16 of the patients with acute urticaria and 43 with chronic urticaria, the serum levels of ICAM-1 and VCAM-1 were determined at follow-up after 6-8 weeks of treatment. The mean serum levels of both VCAM-1 and ICAM-1 were higher in both groups of children with urticaria than in the comparison subjects at the start of the study. In the chronic urticaria group, the levels decreased significantly (p = 0.03 and p = 0.01, respectively) following treatment. Similarly, the acute urticaria group exhibited significant reduction in the mean levels of VCAM and ICAM (p < 0.001). In both groups, the mean level of ICAM after treatment was comparable with that of the comparison group. VCAM-1 and ICAM-1 are suggested as promising biomarkers for monitoring both acute and chronic urticaria in children. Future research should explore their utility in larger cohorts and investigate their role in personalized treatment strategies.

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.

Resveratrol Suppresses “Metabolic Memory” by Inhibiting Inflammation and Apoptosis Through the ROS/TXNIP/NLRP3 Signaling Pathway

Aim: This research endeavored to explore the impact and underlying mechanisms of resveratrol on the phenomenon of “metabolic memory” in cultured human retinal vascular endothelial cells (HRVECs) under high-glucose (HG) conditions. Materials and Methods: According to the glucose level and treatment, cultured HRVECs were divided into seven groups: normal glucose (NG), HG, high glucose followed by NG (HN), mannitol (Man), resveratrol, thioredoxin-interacting protein (TXNIP)-small interfering ribonucleic acid (siRNA), and N-acetylcysteine (NAC). The expression levels of TXNIP, nucleotide oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, intercellular adhesion molecule 1 (ICAM-1), caspase-1, interleukin-1β (IL-1β), B-cell lymphoma 2 (Bcl-2), caspase-3, and Bcl-2-associated X (BAX), as well as reactive oxygen species (ROS) production, were measured. Cell apoptosis was assessed through a terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Results: In HRVECs from the HG group, expression levels of TXNIP, NLRP3, caspase-1, ICAM-1, and IL-1β were upregulated. However, in the HN group, the above upregulations were not reversed. After the administration of resveratrol, the expression levels of TXNIP, NLRP3, and other inflammatory cytokines were significantly reduced. Resveratrol mitigated the elevated ROS production induced by HG conditions. In the NAC group, the expression of TXNIP and inflammatory cytokines was downregulated. TXNIP-siRNA treatment showed similar effects. Resveratrol inhibited apoptosis as well as reversed the downregulation of BCL-2 and the upregulation of caspase-3 and BAX induced by HG conditions. Conclusion: Resveratrol mitigated the HG-induced phenomenon of “metabolic memory” by inhibiting inflammation and apoptosis via modulation of the ROS/TXNIP/NLRP3 signaling pathway in cultured HRVECs. Therefore, resveratrol may have therapeutic potential to treat diabetic retinopathy and related metabolic memory complications.

The effect of eight weeks combined training with omega-3 supplementation on the levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in older women

The effect of eight weeks combined training with omega-3 supplementation on the levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in older women

Cardiac Autonomic and Endothelial Function in Acute Lymphoblastic Leukaemia Patients Immediately After Chemotherapy and at the Three-Month Follow-up.

Acute lymphoblastic leukemia (ALL) is a malignant uncontrolled overproduction of immature lymphoid cells in blood and bone marrow. The primary treatment of ALL is chemotherapy. Chemotherapy can have myriad systemic side effects, notably cardiovascular derangement. Autonomic derangement occurrence in cancer patients signifies cardiovascular risk in them and is a determinant of cardiovascular morbidity and mortality. Elevated soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) levels implicated in the regulation of inflammation indicate endothelial dysfunction. High levels of high-sensitivity C-reactive protein (hsCRP) can be indicative of low-grade inflammation. Hence, in this study the cardiac autonomic function and endothelial and inflammatory biomarker levels in adult patients with ALLwere assessed immediately and three months after chemotherapy. In this longitudinal study, 30 ALL patients (23 males, seven females) aged between 18 to 50 years, who had completed chemotherapy regimens, and 30 age and gender-matched healthy participants (controls) were recruited. Cardiac autonomic function tests (short-term heart rate variability (HRV), 30:15 ratio, synaptic excitation and inhibition (E/I) ratio, diastolic blood pressure (DBP) response to isometric hand grip), endothelial markers (sVCAM-1 and sICAM-1), and inflammatory marker (hsCRP) were assessed immediately and at three months after chemotherapy. Magnitudes of time domain and frequency domain indices, conventional autonomic function test indices, and biomarkers were deranged in ALL patients immediately after chemotherapy. After three months, cardiac autonomic function parameters were found to improve in the form of increased root mean square of successive differences between normal heartbeats (RMSSD), standard deviation of the interbeat intervals of normal sinus beats (SDNN), total power, high-frequency (HF)nu, and decreased low-frequency(LF)nu & LF-HF ratio. Endothelial (sVCAM-1) and inflammatory markers (hsCRP) were lower in the patient group as compared to the controls immediately after chemotherapy. Three months after chemotherapy, the levels of endothelial and inflammatory markers did not show much change. In this study, we found ALL patients showed higher sympathetic drive, decreased parasympathetic modulation, and sympathovagal imbalance immediately after chemotherapy as compared to the controls, indicating cardiovascular risk. After three months, improvement in cardiovascular autonomic function was observed. ALL itself is a state of inflammation with elevated endothelial and inflammatory markers; thus, the decreased endothelial and inflammatory markers could be attributed to the immediate effect of chemotherapy.

Association of serum levels of inflammatory cytokines with retinopathy of prematurity in preterm infants.

Retinopathy of prematurity (ROP) is a retinal vascular developmental disease associated with risks factors such as supplementary oxygen use or low birth weight/early gestational age. Multiple studies have reported associations between ROP and systemic inflammation. In this study, we investigated serum cytokines associated with ROP development and severity and assessed their applicability as potential biomarkers of ROP. This prospective study was conducted at an institutional referral center between 2019 and 2021. To measure the serum levels of 40 inflammatory cytokines in eligible premature patients, we collected their serum samples during the enrollment of patients or the intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents and after 2 and 4 weeks. Fifty patients were enrolled. In patients with type 1 ROP who received anti-VEGF agents (n = 22), the levels of serum intercellular adhesion molecule-1 decreased significantly (p < 0.05) at 4 weeks compared with the baseline level, whereas those of serum granulocyte-macrophage colony-stimulating factor increased significantly (p < 0.05). In patients with ROP who did not require any treatment (n = 14), no significant change was noted in the level of any of the 40 inflammatory cytokines. In control infants without ROP (n = 14), the serum levels of tumor necrosis factor-α, interleukin (IL)-15, and IL-12p40 increased significantly (p < 0.05) at 4 weeks. The changes in the levels of serum inflammatory cytokines did not vary significantly among the aforementioned three groups. A generalized estimating equation indicated that zone 1 ROP, stage 3 ROP, older postmenstrual age, respiratory distress syndrome, necrotizing enterocolitis, and sepsis were associated with the changes in serum cytokine levels. Although significant changes (compared with baseline) were observed in the serum levels of certain inflammatory cytokines in patients with type 1 ROP and infants without ROP, no significant difference in cytokine level fluctuations were noted among the three groups. Changes in serum inflammatory cytokine levels may not predict ROP development or severity. Additional comprehensive studies are warranted to establish their definitive role and significance in ROP, emphasizing the need for continued research in this area.

Correlation of oxidative stress and vascular endothelial dysfunction with hippocampal perfusion in atrial fibrillation patients with cognitive impairment.

To evaluate the correlation of oxidative stress and vascular endothelial dysfunction with hippocampal perfusion in patients with atrial fibrillation and cognitive impairment. In total, 41 atrial fibrillation patients with cognitive impairment were compared to 45 atrial fibrillation patients without cognitive impairment. Oxidative stress, vascular endothelial dysfunction, hippocampal perfusion, and cognitive function were measured. Serum level of oxidized low-density lipoprotein was significantly higher in the atrial fibrillation + cognitive impairment group than in the atrial fibrillation group. Serum levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were significantly higher, and nitric oxide was lower, in the atrial fibrillation + cognitive impairment group than in the atrial fibrillation group. The regional cerebral blood volume, mean transit time, and time to peak were significantly higher in the atrial fibrillation + cognitive impairment group than in the atrial fibrillation group. Moreover, regional cerebral blood flow was significantly lower in the atrial fibrillation + cognitive impairment group than in the atrial fibrillation group. Age, left atrial diameter, and regional cerebral blood volume were negatively correlated with the cognitive function score in the atrial fibrillation + cognitive impairment group. Serum levels of oxidized low-density lipoprotein, regional cerebral blood volume, regional cerebral blood flow, mean transit time, and time to peak were significantly correlated with cognitive impairment in atrial fibrillation patients after multivariate logistic regression analysis. Hippocampal perfusion and oxidative stress were significantly correlated with cognitive impairment in atrial fibrillation patients.

Levels of VCAM-1 and ICAM-1 in serum of active and inactive Systemic Lupus Erythematosus patients as biochemical markers for risk of cardiovascular disease

Background: Cardiovascular complications represent one of the consequences of chronic autoimmune diseases such as Systemic Lupus Erythematosus (SLE), which has significant rates of morbidity and mortality. Dyslipidemia can be brought on by steroid medications, which are frequently given to SLE patients and are considered to be one of the major risk factors for cardiovascular diseases. Objectives: This study attempted to investigate a potential association between circulating vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) as risk factors for atherosclerosis and their relationship to cardiovascular risk. Patients and methods: A total of 100 patients and 50 apparently healthy controls were included in the study. All patients were from the Department of Rheumatology, Baghdad Hospital / Medical City during the period from 1 December 2021 to 1 March 2022 who were all treated with antimalarial drugs as immunosuppressants such as chloroquine (CQ) or hydroxychloroquine HCQ). They were divided according to the SLE disease activity index 2000 (SLEDAI-2K) into the active group (SLEDAI ≥ 10) and the inactive group (SLEDAI). Results: Serum VCAM and ICAM were significantly high in all study groups of SLE patients. The VCAM mean ± SD were (271.9±63.90), (247.9±82.92) and (97.7±24.69) in the active, inactive controls respectively. The ICAM mean ± SD were (3.1±0.91), (2.7±0.79) and (1.8±0.22) in the active, inactive and controls respectively. The values have increased gradually with increasing disease activity. The area under curve (AUC) of ICAM and VCAM were (0.802), (0.776) in active SLE patients and (0.858), (0.674) in inactive SLE patients. However, the AUC of VCAM and ICAM in active group were the highest. Conclusion: In SLE patients, VCAM-1 and ICAM-1 serum levels may operate as disease detection and severity differentiation indicators, and they may be linked to the number of coronary lesions in people at risk of developing CVD. Received: Aug.,2022 Accepted: Sept., 2022 Published: April 2023

Эндотелиальная дисфункция и пародонтопатогенная микрофлора: аспекты патогенетической коррекции бактериофагом

INTRODUCTION: Alteration of the expression of intercellular adhesion molecules on the surface of endotheliocytes is associated with disorders of anticoagulant, antiplatelet, fibrinolytic and barrier functions of the endothelium. It results in derangement of microcirculation in periodontal tissues, and, together with adhesive, invasive toxic properties of the main periodontopathogenic bacteria Аggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Prevotella intermedia, leads to a chronic systemic periodontitis (CSP). AIM: To evaluate pathogenetic aspects of the effect of phagotherapy on the level of secretion of soluble forms of adhesive molecules and on periodontopathogenic microflora. MATERIALS AND METHODS: The study material was the discharge of the dentogingival/periodontal pocket (DG/PP) of patients with intact periodontium and with CSP. The first subgroup with CSP, in addition to therapeutic treatment, received a course of Phagodent bacteriophage applications, the subsecond group received only therapeutic treatment. RESULTS: A high frequency of isolation of periodontal pathogens (92.0%) in patients with CSP was reflected in the detection of P. gingivalis in 81% of cases, T. forsythia in 74% of cases, A. actinomycetemcomitans in 37.0% of cases. On the top of the administered therapy, a statistically significant (6.2 times) decrease in the level of A. actinomycetemcomitans was revealed in subgroup 1 (p = 0.03) and 1.58 times decrease in subgroup 2 (p = 0.045). The content of T. forsythia decreased by 3.9 (p = 0.034) and 2.4 (p = 0.02) times in the respective groups. A significant decrease in the level of T. denticola was detected only in subgroup 1 (p = 0.04). The levels of intercellular adhesion molecules during the therapy decreased in both groups, but most significantly when using a bacteriophage: sICAM-1 decreased 3.2 times in subgroup 1 (p &lt; 0.001) and 2.1 times in subgroup 2 (p &lt; 0.001), sVCAM — 6.4 times (p &lt; 0.001) and 4.6 times (p &lt; 0.001), respectively. The content of sL-selectin and sE-selectin in PP decreased 4.1-times (p &lt; 0.001) and 2.2 times, (p &lt; 0.001), respectively, in individuals receiving bacteriophage and 2.2 times (p &lt; 0.001) and 1.5 times (p &lt; 0.001) in patients with another method of treating CSP. CONCLUSION: The effectiveness of targeted pathogenetic correction using a bacteriophage for the treatment of CSP was confirmed by a decrease in the quantitative content of marker periodontopathogenic microorganisms in the DGP discharge and normalization of the concentration of adhesive molecules, which indicated reduction of the degree of endothelial dysfunction.

Sodium Selenite Ameliorates Silver Nanoparticles Induced Vascular Endothelial Cytotoxic Injury by Antioxidative Properties and Suppressing Inflammation Through Activating the Nrf2 Signaling Pathway.

Silver nanoparticles (AgNP) are the dominant nanomaterials in commercial products and the medical field, but the widespread occurrence of AgNP has become a global threat to human health. Growing studies indicate that AgNP exposure can induce vascular endothelial toxicity by excessive oxidative stress and inflammation, which is closely related to cardiovascular disease (CVD), but the potential intrinsic mechanism remains poorly elucidated. Thus, it has been crucial to control the toxicological effects of AgNP in order to improve their safety and increase the outcome of their applications.Multiple researches have demonstrated that sodium selenite (Se) possesses the capability to counteract the toxicity of AgNP, but the functional role of Se in AgNP-induced CVD is largely unexplored. The aim of this study was to explore the potential protective effect of Se on AgNP-induced vascular endothelial lesion and elucidate the underlying mechanisms. An in vivo model of toxicity in animals was established by the instillation of 200 µL of AgNP into the trachea of rats both with (0.2 mg/kg/day) and without Se treated. In vitro experiments, human umbilical vein endothelial cells (HUVECs) were incubated with AgNP (0.3 µg/mL ) and Se for a duration of 24 h. Utilizing transmission electron microscopy, we observed that the internalization of AgNP-induced endothelial cells was desquamated from the internal elastic lamina, the endoplasmic reticulum was dilated, and the medullary vesicle formed. Se treatment reduced the levels of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), inhibited the release of pro-inflammatory cytokines (specifically tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6), improved endothelial cell permeability, integrity, and dysfunction, and prevented damage to the aortic endothelium caused by AgNP. Importantly, we found that Se showed the capacity against AgNP with biological functions in guiding the intracellular reactive oxygen species (ROS) scavenging and meanwhile exhibiting anti-inflammation effects. Se supplementation decreased the intracellular ROS release and suppressed NOD-like receptor protein 3 (NLRP3) and nuclear factor kappa-B (NF-κB) mediated inflammation within AgNP-intoxicated rats and HUVECs. The anti-oxidant stress and anti-inflammatory effects of Se were at least partly dependent on nuclear factor erythroid 2-related factor 2 (Nrf2). Overall, our results indicated that the protectiveness of Se against AgNP-induced vascular endothelial toxicity injury was at least attributed to the inhibition of oxidative ROS and pro-inflammatory NF-κB/NLRP3 inflammasome by activating the Nrf2 and antioxidant enzyme (HO-1) signal pathway.

TMIC-17. THE ROLE OF ICAM1 IN GLIOBLASTOMA TUMORIGENESIS UNDER HYPOXIC CONDITIONS

Abstract Glioblastoma (GBM) is a deadly brain cancer in adults with limited treatment options. Cell adhesion molecules (CAMs) mediate cell-cell interactions and migration. Intercellular adhesion molecule 1 (ICAM-1) is a CAM expressed by various cell types in solid tumors, including macrophages, tumor and endothelial cells. We previously demonstrated that ICAM-1 expression is linked to shorter overall survival in GBM patients. We observed elevated ICAM-1 levels in hypoxic regions of GBMs. Considering the role of tumor-associated macrophages (TAMs) in GBM tumorigenicity, our objective was to investigate how ICAM-1 expression in TAMs contributes to GBM growth within the hypoxic tumor microenvironment (TME). We employed a comprehensive approach utilizing in vitro and in vivo models, as well as genomic analyses at both bulk and single-cell levels, to elucidate the association between ICAM-1 and TAMs in tumorigenicity. Our findings demonstrated that injecting GBM cells into ICAM-1 knockout mice led to prolonged survival, smaller tumors, reduced macrophage infiltration, and enhanced M1-like polarization of TAMs. Additionally, bone marrow reconstitution experiments confirmed the tumor-promoting role of ICAM-1-expressing TAMs. Cell deconvolution, immunohistochemical, and flow cytometry analyses of mouse tumors supported these findings. Gene set enrichment analysis of differentially expressed genes in xenografted tumors revealed that ICAM-1 presence upregulated key tumorigenic pathways, including epithelial-mesenchymal transition, IL2-STAT5, TNF-α via NFκB, IL6-JAK-STAT3, and RAS/MAPK. In vitro analysis indicated that ICAM-1 promoted macrophage migration and polarization towards M2-like state, which was further augmented by hypoxia-induced ICAM1 expression. Flow cytometry, cytometry by time of flight (cyToF), and single-cell RNA sequencing analysis of human and mouse GBMs revealed elevated ICAM-1 expression in hypoxic TAMs, suggesting the hypoxic microenvironment promotes the tumorigenic functions of TAMs. In conclusion, ICAM1 likely enhances GBM tumorigenesis by promoting TAM migration into the TME. Furthermore, environmental factors such as hypoxia contribute to increased ICAM-1 expression in TAMs, further exacerbating GBM tumorigenicity.

Sex Differences and Cytokine Profiles among Patients Hospitalized for COVID-19 and during Their Recovery: The Predominance of Adhesion Molecules in Females and Oxidative Stress in Males.

The severity and mortality of coronavirus disease 2019 (COVID-19) are greater in males than in females, though the infection rate is the same in the two sexes. We investigated sex hormone differences associated with the hyperinflammatory immune response to SARS-CoV-2 on the basis of patients' cytokine profiles and vaccination statuses. Clinical and laboratory data of 117 patients with COVID-19 were collected to examine sex differences associated with oxidative stress markers, neutrophil extracellular traps (NETs), and plasma cytokine levels up to 5 months from hospital admission. The testosterone and free testosterone levels were low in male patients with COVID-19 and returned to normal values after recovery from the disease. The dihydrotestosterone (DHT) levels were transiently reduced, while the sex hormone-binding globulin levels were decreased in post-COVID-19 male patients. The levels of the inflammatory cytokines interleukin-6 (IL-6) and IL-10 appeared generally increased at diagnosis and decreased in post-COVID-19 patients. In females, the concentration of tumor necrosis factor-alpha was increased by four times at diagnosis. The levels of the coagulation markers intercellular adhesion molecule-1 (ICAM-1) and E-selectin were consistently upregulated in post-COVID-19 female patients, in contrast to those of vascular cell adhesion molecule-1 (VCAM-1), P-selectin, and chemokine IL-8. DHT increased the levels of reactive oxygen species in the neutrophils of male patients, while estradiol decreased them in females. Markers for NET, such as circulating DNA and myeloperoxidase, were significantly more abundant in the patients' plasma. Sex hormones have a potential protective role during SARS-CoV-2 infection, which is weakened by impaired testosterone synthesis in men.

ОЦЕНКА ЛОКАЛЬНОГО ПРОФИЛЯ ЦИТОКИНОВ, ЭКСПРЕССИРУЕМЫХ НАТИВНЫМИ КЛАПАНАМИ СЕРДЦА, ПОЛУЧЕННЫМИ ОТ ПАЦИЕНТОВ С ПРИОБРЕТЕННЫМИ ПОРОКАМИ СЕРДЦА

Doing. The pathogenesis of acquired heart defects is a complex process involving many different factors. One of the triggers for the development of dysfunctions of native heart valves can be an inflammatory process caused by various types of pathogens. The aim of the study was to evaluate the local profile of cytokines expressed by native heart valves obtained from patients with acquired heart defects during cardiac surgery. Materials and Methods: As a material for the study, biopsies of native mitral heart valves were obtained from 4 patients with infective endocarditis and from 10 patients with rheumatic heart disease. RNA was isolated using a commercial RNeasy® Plus Universal Mini Kit (Qiagen, Germany), protein extraction was performed using T-PER™ Tissue Protein Extraction Reagent lysis buffer (ThermoScientific, USA) with the addition of protease inhibitors Halt™ Protease Inhibitor Cocktail (ThermoScientific, USA) and 0.5M EDTA solution (ThermoScientific, USA). The level of cytokines expressed by native valves was determined by dot blotting using the Proteome Profiler™ Human Cytokine Array Kit (ARY005B) (R&amp;D Systems, USA). Cytokine gene expression was assessed by qPCR using SYBR Green probes (JSC Evrogen, Russia) on a ViiA7 Real-Time PCR System amplifier (Applied Biosystems, USA). Statistical analysis of the results obtained was performed using the GraphPad Prism 8 program (GraphPad Software, USA). Results: The proteins MIF (macrophage migration inhibitory factor), PAI-1 (plasminogen activator inhibitor-1), ICAM-1 (intercellular adhesion molecule-1) and CXCL12 (stromal growth factor-1) were found to be registered in native valves, obtained from both patients with IE and patients with RHD. Semi-quantitative analysis showed that native valves obtained from patients with IE are characterized by a four-fold increase in the level of PAI-1 secretion and a two-fold decrease in the level of ICAM-1 and CXCL12 compared with the control. MIF was expressed at the same level in both studied groups. IL-1ra (interleukin 1 receptor antagonist), IL-6 (interleukin 6), IL-8 (interleukin 8), IL-16 (interleukin 16), CCL4 (chemokine ligand 4), CCL5 (chemokine ligand 5), and CXCL1 ( chemokine ligand 1) were found only in valves affected by IE. The expression of the MIF, IL6, and IL8 genes was increased in the experimental group relative to the control, and the expression of the PAI1, IL1RA, and CXCL1– genes was decreased in the experiment relative to the control. The gene expression of ICAM1, CXCL12, CCL4, CCL5 and IL16 was the same in both studied groups. Conclusions: The results of the study show that native heart valves affected by IE are characterized by a unique cytokine profile compared to valves obtained from patients with non-infectious endocardial pathology. Native heart valves affected by IE show nonspecific local inflammation, active neovascularization, and decreased resistance to pathogenic bacteremia.

Role of ICAM1 in tumor immunity and prognosis of triple-negative breast cancer.

Treating triple-negative breast cancer (TNBC) is a difficult landscape owing to its short survival times and high risk of metastasis and recurrence among patients. Although involved in tumor invasion and metastasis, the mechanism of action of intercellular adhesion molecule 1 (ICAM1), a trans-membrane glycoprotein, in TNBC is ambiguous. We examined ICAM1's role in TNBC, focusing on its expression, cell survival, mutation, and tumor immunity. Then, a risk score model was created utilizing co-expressed genes associated with ICAM1. According to their respective risk scores, we divided patients into high- and low-risk groups. Immune function, drug susceptibility differences, and somatic variants were analyzed in the high-and low-risk groups. And we used the CMap database to predict potential medications. Then, TNBC cells with low expression of ICAM-1 were co-cultured with PMA-treated THP-1 cells and CD8 T cells. In addition, We detected the expression of PD-1 and CTLA4 of low ICAM-1 expressing TNBC cells when they were cocultured with CD8 T cells. ICAM1 was found to be involved in leukocyte cell adhesion, motility, and immune activation. Patients with low-ICAM1 group had shorter disease-free survival (DFS) than those with high-ICAM1 group. The group with elevated levels of ICAM1 exhibited significantly increased levels of T-cell regulation, quiescence in natural killer (NK) cells, and M1 macrophage. ICAM1 expression was correlated with immune checkpoint drugs. The prognostic ability of the risk score model was found to be superior to that of individual genes. Patients categorized as high-risk exhibited elevated clinical stages, showed higher M1 macrophage numbers, and were able to benefit better from immunotherapy. Individuals belonging to the high-risk group exhibit significantly elevated mutation rates in TP53, TTN, and SYNE1 genes, along with increased TMB and PD-L1 levels and decreased TIDE scores. These findings suggest that immunotherapy may be advantageous for the high-risk group. Furthermore, low expression of ICAM1 was found to promote polarization to M2 macrophages along with T-cell exhaustion. In conclusion, Low ICAM1 expression may be related to immune escape, leading to poor treatment response and a worse prognosis.

In Vitro and In Vivo Evaluation of Epidermal Growth Factor (EGF) Loaded Alginate-Hyaluronic Acid (AlgHA) Microbeads System for Wound Healing.

The management of skin injuries is one of the most common concerns in medical facilities. Different types of biomaterials with effective wound-healing characteristics have been studied previously. In this study, we used alginate (Alg) and hyaluronic acid (HA) composite (80:20) beads for the sustained release of epidermal growth factor (EGF) delivery. Heparin crosslinked AlgHA beads showed significant loading and entrapment of EGF. Encapsulated beads demonstrated biocompatibility with rat L929 cells and significant migration at the concentration of AlgHAEGF100 and AlgHAEGF150 within 24 h. Both groups significantly improved the expression of Fetal Liver Kinase 1 (FLK-1) along with the Intercellular Adhesion Molecule-1 (ICAM-1) protein in rat bone Mesenchymal stem cells (rbMSCs). In vivo assessment exhibited significant epithelialization and wound closure gaps within 2 weeks. Immunohistochemistry shows markedly significant levels of ICAM-1, FLK-1, and fibronectin (FN) in the AlgHAEGF100 and AlgHAEGF150 groups. Hence, we conclude that the EGF-loaded alginate-hyaluronic acid (AlgHA) bead system can be used to promote wound healing.

Effect of serum adropin levels on circulating endothelial dysfunction biomarkers in COVID-19 patients

Purpose: Several studies show that the symptoms of severe COVID-19 infection reflect the clinical phenotype of endothelial dysfunction and share common pathophysiological mechanisms with endothelial dysfunction. Therefore, the aim of the study was to investigate the effect of serum adropin levels on endothelial dysfunction biomarkers and determine whether adropin could be a new biomarker for COVID-19.&#x0D; Materials and Methods: The study included 40 patients with mild/moderate COVID-19, 48 patients with severe/critical COVID-19, and 37 controls. Serum adropin and circulating biomarkers of endothelial dysfunction including asymmetric dimethylarginine (ADMA), endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), soluble intercellular adhesion molecule-1 (sICAM-1) and plasminogen activator inhibitor-1 (PAI-1) levels were determined by micro-ELISA.&#x0D; Results: Serum adropin levels were found to be significantly higher in COVID-19 patients (165.2±11.49 pg/ml) than in controls (85.46±12.08 pg/ml). Serum adropin levels of patients with severe/critical symptoms (194±16.23 pg/ml) were significantly higher than the patients with mild/moderate symptoms (130.6 ±14.53). In addition, serum ADMA, eNOS, and, ET-1 levels were significantly higher in the COVID-19 subjects (150.5±8.67 ng/ml, 172.4±14.01 pg/ml, 159.3±10.19 pg/ml, respectively) than that those in the controls (104.5±9.182 ng/ml, 141.4±17.74 pg/ml, 100.1±11.37 pg/ml, respectively). Significant positive correlations were found between adropin and ADMA, eNOS, ET-1, sICAM-1, and PAI-1 levels in the patients.&#x0D; Conclusion: We suggest that adropin may be a new potential biomarker for COVID-19 and an important molecule in restoring endothelial cell damage. Positive correlations between serum adropin levels and ADMA, eNOS, ET-1, sICAM-1 and PAI-1 levels in patients suggest that adropin may compensate for damage to endothelial cells.

Differential effect of ramadan fasting on intercellular adhesion molecule-1 (ICAM-1) in diabetes mellitus and non-diabetes mellitus patients

BackgroundThe month of Ramadan is a holy month for Muslims. During this month, Muslims do not eat, drink, or smoke from sunrise to sunset. Patients with type 2 diabetes mellitus (T2DM) will also fast from dawn to dusk, creating a unique opportunity to study the effects of dietary changes during fasting period. One of the interesting results of Ramadan fasting is its effect on endothelial dysfunction, measured using Intercellular Adhesion Molecule-1 (ICAM-1) as a biological marker of endothelial function. AimTo determine the changes ICAM-1 levels in T2DM and non-DM patients during Ramadan fasting. MethodsA retrospective cohort study was performed on 26 T2DM patients and 21 non-DM, age-matched patients (aged 19–60 years). Measurement of metabolic parameters (systolic and diastolic blood pressure, total calorie intake, and intensity of physical activity), anthropometry (body weight, body mass index (BMI) and abdominal circumference), total dietary intake, and laboratory analysis (blood glucose fasting, HbA1c, lipid profile, ICAM-1) were done at 4 weeks before (T0) and 14 days after Ramadan fasting (T1). ResultThe median ICAM-1 level in T2DM patients at T0 was 340.9 (193–505) ng/mL and at T1 was 312.3 (158–581) ng/mL, while the ICAM-1 level in non-DM patients at T0 was 482 (305–653) and at T1 was 398.4 (202–526) ng/mL. There was no significant difference of ICAM-1 level between study groups at both T0 and T1 (p > 0.05). Both T2DM and non-DM patients had lower ICAM-1 level following Ramadan fasting. However, only non-DM patients had significantly lower post Ramadan ICAM-1 (p = 0.008) ConclusionThere was a significant decrease in ICAM-1 level in both T2DM and non-DM patients after Ramadan fasting.

Low-moderate dose whole-brain γ-ray irradiation modulates the expressions of glial fibrillary acidic protein and intercellular adhesion molecule-1 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine–induced Parkinson’s disease mouse model

The anti-inflammatory efficacy of radiation therapy (RT) with single fractions below 1.0 Gy has been demonstrated in Alzheimer’s disease mouse models. As neuroinflammation is also a major pathological feature of Parkinson’s disease (PD), RT may also be effective in PD treatment. Therefore, this study aimed to investigate the anti-inflammatory effect of low-moderate dose RT (LMDRT, 0.6 Gy/single dose, for 5 days) exposure in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 30 mg/kg, intraperitoneally, for 5 consecutive days)-induced PD mouse model. Importantly, LMDRT reduced the levels of glial fibrillary acidic protein and intercellular adhesion molecule-1 (CD54) in the striatum region, which increased following MPTP administration. LMDRT also modulated inflammatory gene expression patterns in the substantia nigra region of the MPTP-treated mice. However, LMDRT had no direct effects on the severe loss of dopaminergic neurons and impaired motor behavior in the rotarod test. These results indicate that LMDRT has anti-inflammatory effects by modulating neuroinflammatory factors, including glial fibrillary acidic protein and intercellular adhesion molecule-1, but showed no behavioral improvements or neuroprotection in the MPTP-induced mouse model of PD.