Soluble Intercellular Adhesion Molecule-1 Research Articles

A Comprehensive Analysis of Renal and Endothelium Dysfunction Markers Fourteen Years after Hemorrhagic Fever with Renal Syndrome Contraction.

While the pathology of acute hemorrhagic fever with renal syndrome (HFRS) has been widely researched, details on the chronic HFRS sequelae remain mainly unexplored. In this study, we analyzed the clinical and laboratory characteristics of 30 convalescent HFRS patients 14 years after the disease contraction, mainly emphasizing several endothelial dysfunction parameters. Convalescent HFRS patients exhibited significantly higher serum levels of erythrocyte sedimentation rate, von Willebrand factor, uric acid, C-reactive protein and immunoglobulin A when compared to healthy individuals. Furthermore, 24 h urine analyses revealed significantly lower sodium and potassium urine levels, as well as significantly higher proteinuria, microalbumin levels and β2-microglobulin levels when compared to healthy individuals. First morning urine analysis revealed significantly higher levels of hematuria in convalescent HFRS patients. None of the additional analyzed endothelium dysfunction markers were significantly different in post-HFRS patients and healthy individuals, including serum and urine P-selectin, E-selectin, soluble intercellular adhesion molecule 1, vascular intercellular adhesion molecule 1 (sVCAM-1) and vascular endothelial growth factor (VEGF). However, binary logistic regression revealed a weak association of serum sVCAM-1 and urine VEGF levels with HFRS contraction. Generally, our findings suggest mild chronic inflammation and renal dysfunction levels in convalescent HFRS patients 14 years after the disease contraction.

Dietary acid load and markers of malnutrition, inflammation, and oxidative stress in hemodialysis patients.

The present study was conducted to examine the association between dietary acid load (DAL) and markers of inflammation, oxidative stress, and malnutrition in a group of Iranian hemodialysis (HD) patients. This cross-sectional study was performed on individuals aged ≥18 years who were on HD at least 6 months before their enrollment in the study. A 4-day dietary recall was used for the evaluation of dietary intake. DAL was calculated using two methods including potential renal acid load (PRAL) and net endogenous acid production (NEAP). For assessing the malnutrition status, we used the subjective global assessment (SGA), dialysis malnutrition score (DMS), and malnutrition inflammation score (MIS). Fasting blood samples were collected from each participant to assess serum levels of high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), sE-selectin, malondialdehyde (MDA), nitric oxide (NO), and endothelin-1. In total, 291 patients with a mean age of 57.73 ± 0.88 years and HD vintage of 4.27 ± 0.25 months were enrolled in the current study. Significant positive associations were observed between PRAL and hs-CRP (β = 1.77, 95% CI: 0.88, 2.65), sICAM-1 (β = 83.21, 95% CI: 10.39, 156.04), sVCAM-1 (β = 194.63, 95% CI: 74.68, 314.58), and sE-selectin (β = 6.66, 95% CI: 1.81, 11.50) among participants with the highest PRAL scores, compared to those with the lowest PRAL scores. NEAP was positively correlated with hs-CRP (β = 1.34, 95% CI: 0.46, 2.22), sICAM-1 (β = 88.83, 95% CI: 16.99, 160.67), and MDA (β = 0.35, 95% CI: 0.005, 0.71). Additionally, marginally significant higher odds of SGA (OR = 1.98, 95% CI: 0.95, 4.11) and DMS (OR = 1.94, 95% CI: 0.92, 4.05) were observed in individuals in the third tertile of PRAL vs. the first tertile of PRAL. NEAP had also a marginally significant positive correlation with DMS (OR = 2.01, 95% CI: 0.93, 4.31). This study illustrates that higher consumption of acidic foods is correlated with markers of inflammation, oxidative stress, and malnutrition in HD patients.

Dynamic YAP expression in the non-parenchymal liver cell compartment controls heterologous cell communication

IntroductionThe Hippo pathway and its transcriptional effectors yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are targets for cancer therapy. It is important to determine if the activation of one factor compensates for the inhibition of the other. Moreover, it is unknown if YAP/TAZ-directed perturbation affects cell–cell communication of non-malignant liver cells.Materials and MethodsTo investigate liver-specific phenotypes caused by YAP and TAZ inactivation, we generated mice with hepatocyte (HC) and biliary epithelial cell (BEC)-specific deletions for both factors (YAPKO, TAZKO and double knock-out (DKO)). Immunohistochemistry, single-cell sequencing, and proteomics were used to analyze liver tissues and serum.ResultsThe loss of BECs, liver fibrosis, and necrosis characterized livers from YAPKO and DKO mice. This phenotype was weakened in DKO tissues compared to specimens from YAPKO animals. After depletion of YAP in HCs and BECs, YAP expression was induced in non-parenchymal cells (NPCs) in a cholestasis-independent manner. YAP positivity was detected in subgroups of Kupffer cells (KCs) and endothelial cells (ECs). The secretion of pro-inflammatory chemokines and cytokines such as C-X-C motif chemokine ligand 11 (CXCL11), fms-related receptor tyrosine kinase 3 ligand (FLT3L), and soluble intercellular adhesion molecule-1 (ICAM1) was increased in the serum of YAPKO animals. YAP activation in NPCs could contribute to inflammation via TEA domain transcription factor (TEAD)-dependent transcriptional regulation of secreted factors.ConclusionYAP inactivation in HCs and BECs causes liver damage, and concomitant TAZ deletion does not enhance but reduces this phenotype. Additionally, we present a new mechanism by which YAP contributes to cell–cell communication originating from NPCs.

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.

Angiopoietin-2 is associated with sickle cell complications, including stroke risk, and decreases with hydroxyurea therapy

AbstractHydroxyurea reduces morbidity and mortality in children with sickle cell anemia (SCA). The endothelium is central to SCA-related complications including stroke. However, hydroxyurea’s impact on the endothelium is not well described. To address this gap, we measured plasma levels of endothelial activation markers (angiopoietin-2, P-selectin, soluble endothelial selectin [sE-selectin], soluble intercellular cellular adhesion molecule 1, and soluble vascular endothelial cellular adhesion molecule) by enzyme-linked immunosorbent assay after initiation of hydroxyurea therapy. Samples were collected from Ugandan children with SCA enrolled in a clinical trial evaluating hydroxyurea vs placebo (NOHARM trial). Samples were collected at enrollment; and then after 2, 4, and 12 months of follow-up. Longitudinal changes in biomarker levels were evaluated using linear mixed effects models. Transcranial Doppler (TCD) velocities were measured at 10 to 12 months follow-up to assess cerebral blood flow and primary stroke risk. Mediation analysis was used to explore causal pathways of hydroxyurea-mediated effects on TCD velocities. In total, 798 plasma samples were tested from 205 children (mean enrollment age, 2.2 years). At enrollment, higher levels of angiopoietin-2 were associated with a previous medical history of dactylitis, vaso-occlusive crises, acute chest syndrome, and transfusion (P < .05 for all). Hydroxyurea therapy at a fixed dose of 20 mg/kg per day decreased plasma angiopoietin-2, P-selectin, and sE-selectin levels over the study period (P < .05 for all). Angiopoietin-2 and sE-selectin were associated with higher TCD velocities. Mediation analysis suggests that hydroxyurea decreases TCD velocities through an increase in fetal and total hemoglobin. Increased fetal and total hemoglobin, and decreased white blood cell count may decrease TCD velocity, in part, through an angiopoiten-2–mediated pathway. This trial was registered at www.ClinicalTrials.gov as #NCT01976416.

Innate immune responsive inflammation in development of progressive myopia.

Inflammation has been implicated for development of myopia. It is not clear when inflammation is kicked in during the course of myopia, and what characteristics of the inflammation. In this study, we tested for cytokines from aqueous humour of eyes with wide spectrum of refractive status for profiling the inflammation. Aqueous humour of 142 patient eyes were tested for soluble intercellular adhesion molecule 1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-beta 2 (TGF-β2) using an enzyme-linked immunosorbent assay (ELISA). Eye globe axial length of these patients ranged from emmetropia to high myopia. Of 142 patients, an average axial length is 25.51 ± 3.31 mm, with a range of 21.56-34.37 mm. There are 36 cases in lower 25 percentile, 37 cases in upper 25 percentile, and 69 case in the middle 50 percentile. sICAM-1 and MCP-1 were significantly higher in the eyes with staphyloma (407.48 pg/mL, 312.31 pg/mL, n = 33) or macular schisis (445.86 pg/mL,345.33 pg/mL, n = 19) than that in the eyes without these changes (206.44 pg/mL, 244.76 pg/mL, n = 107). All three cytokines level was significantly associated with eye globe axial in a positive mode while adjusting for the age and sex. Strength of the association was the greatest for sICAM-1 and the weakest for TGF- β2. MCP-1 was in between. sICAM-1 and MCP-1 in ocular fluid may be indicative biomarkers for progressive high myopia and the underneath autoimmune inflammation. sICAM-1 may be used as a monitoring biomarker for development of pathologic myopia.

Evaluation of Hypoxia and Microcirculation Factors in the Progression of Diabetic Retinopathy.

The purpose of this study was to evaluate comparatively the changes in HIF-1ɑ, EPO, sICAM-1, hemodynamic, and electrophysiological parameters during the progression of non-proliferative diabetic retinopathy (NPDR). This retrospective longitudinal study included 82 patients with NPDR, who were divided into 2 groups: group I (n=40) consisted of patients without progression of NPDR after 1 year and group II (n=42) included patients with the transition of NPDR to proliferative diabetic retinopathy (PDR). The hemodynamics of the eye was assessed by Doppler ultrasonography. The glial hypoxia index Cg was calculated using ERG. The serum levels of hypoxia-inducible factor 1-a (HIF1-α), soluble intercellular adhesion molecule-1 (sICAM-1), and erythropoietin (EPO) were determined by ELISA method. In group II, resistive index (RI), short posterior ciliary arteries (SPCAs) increased significantly from 0.62 ± 0.005 to 0.65 ± 0.007 (P=0.003), being higher than the corresponding parameter in group I (P=0.013). In group II, there was an increase in the hypoxia index Cg (5.56 ± 0.05) relative to the primary indicators and in group I (P<0.001). In group II, HIF1-ɑ, EPO, and sICAM-1 levels after a year significantly increased (0.213 ± 0.02 ng/mL, 37.7 ± 2.4mIU/mL, and 576.3 ± 11.9 ng/mL, respectively) both relative to the main indicators and the values in group I (P<0.001). When EPO exceeds 27.5mIU/mL, a high risk of progression of NPDR to the initial stages of PDR is predicted. The glial Cg index and the level of HIF1-a, EPO in the serum of patients with progression of NPDR were initially higher than in patients without progression of NPDR and have increased during the year, indicating the development of PDR due to more severe hypoxia.

Ateroprotective effects of Plinia cauliflora in. New Zealand rabbits: beyond the lipid-lowering effect.

Introduction: Plinia cauliflora [Mart.] Kausel (Myrtaceae), popularly known as "jabuticaba," is a fruit species native to Brazil. Despite extensive widespread usage, its antiatherosclerotic properties' impact remains unknown. Thus, the present study aimed to investigate the cardioprotective effects of a preparation obtained from the fruit peels of P. cauliflora (EEPC). Methods: Male New Zealand rabbits received a 1% cholesterol-supplemented diet for 60days. On the thirtieth day, the animals were divided into five experimental groups and received, once a day, by the oral route, the EEPC (10, 30, and 100mg/kg), simvastatin (2.5mg/kg), or vehicle for 30days. At the end of the experimental period, peripheral blood and arterial branch samples were collected. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), malondialdehyde (MDA), nitrotyrosine (NT), nitrite, interleukin 1 beta (IL-1b), interleukin 6 (IL-6), soluble inter-cellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels were measured. Moreover, the catalase and superoxide dismutase levels were measured on the arterial samples. Histopathological analysis and arterial morphometry were also performed. Results and discussion: The oral administration of ESEG significantly lowered the levels of lipids in rabbits that were fed a CRD diet. This treatment also adjusted the protective system against oxidation in the arteries by decreasing the oxidation of lipids and proteins. Additionally, the levels of IL-1b, IL-6, sICAM-1, and sVCAM-1 in the bloodstream decreased significantly, and this was accompanied by a reduction of atherosclerotic lesions in all branches of the arteries. The findings suggest that EEPC may be a possible option for additional management of atherosclerosis.

Coptisine Down-Regulates Soluble Intercellular Adhesion Molecule-1 by Inactivating Fas/FasL Signaling Pathway to Inhibit the Recurrence After Orthodontics

In this study, by constructing a rat model of orthodontic recurrence and intervening with coptisine, the IL-6, IL-8, TNF-α and soluble intercellular adhesion molecule-1 (sICAM-1) content were analyzed to assess the regulatory mechanism of coptisine on the health status of recurrent periodontal tissue after orthodontics and the occurrence of periodontal tissue inflammation. Male rats were assigned into three groups by constructing coptisine liposome nano-objects: blank group (Blank, 10 rats), orthodontic tooth movement model group (50 rats). The orthodontic tooth movement model group was randomly divided into model group (module), model control group (control-free), model coptisine treatment group (treatment-free), model blank functional liposome group (control-lip) and model functional coptisine liposome group (treatment-lip). Rats in model group were killed on the day after device was removed. Rats in other groups received equal doses of normal saline, coptisine, blank functional liposomes, and functional coptisine liposomes by intragastric administration on the day of device removal and then were killed after 7 days of continuous treatment. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, we found that Fas/FasL signaling pathway was enriched in pathways related to apoptosis, disease infection and inflammation. Western blot experiments confirmed that coptisine could inhibit Fas/FasL signaling activation in the process of relapse after orthodontics. Lipopolysaccharides (LPS) treatment significantly increased inflammatory cytokines and sICAM-1, as well as the level of Fas and FasL. Coptisine treatment inhibited LPS-induced Fas/FasL signaling pathway in periodontal ligament cells. Coptisine attenuated the relapsed inflammation after orthodontics by inhibiting Fas/FasL signaling.

Circulating immune signatures across clinical stages of chronic pancreatitis: a pilot study.

This pilot study seeks to identify serum immune signatures across clinical stages of patients with chronic pancreatitis (CP). We performed a cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies-study. CP subjects were categorised into three clinical stages based on the presence/absence of metabolic complications: (1) CP with no diabetes and exocrine pancreatic dysfunction (EPD), (2) CP with either diabetes or EPD, and (3) CP with diabetes and EPD. Blinded samples were analysed using an 80-plex Luminex assay of cytokines/chemokines/adhesion molecules. Group and pairwise comparisons were performed to characterise immune signatures across CP subgroups. A total of 135 CP subjects (evenly distributed between clinical stages) and 50 controls were studied. Interleukin-6 (IL-6), interleukin-8 (IL-8), and soluble intercellular adhesion molecule 1 (sICAM-1) were significantly elevated in CP subjects compared to controls. The levels of IL-6 and IL-8 increased with advancing disease stages, with the highest levels observed in CP with diabetes and EPD (clinical stage 3). Furthermore, hepatocyte growth factor and macrophage-derived chemokine were significantly increased in clinical stage 3 compared to controls. Our study reveals a progressive elevation in pro-inflammatory cytokines and chemokines with advancing clinical stages of CP. These findings indicate potential targets for the development of disease-modifying interventions.

A Phase II Study to Evaluate the Safety and Efficacy of Defibrotide and Changes in Plasma Biomarkers in Sickle Cell Disease-Related Acute Chest Syndrome (IND 127812)

Background: Acute Chest Syndrome (ACS) is the greatest contributor to the morbidity and mortality of Sickle Cell Disease (SCD) patients with a rate of 12.8 cases per 100 patient-years. The mortality rates of ACS are 4 times higher in adults than in children (Vichinsky et al, Blood, 1997). The root cause of ACS in SCD is related to endothelial dysfunction (Paul et al, European Journal of Hematology 2011). While existing therapies target infection, inflammation, and alveolar hypoxia, they do not address endothelial dysfunction, a major contributor to SCD associated ACS. Defibrotide is a polydisperse mixture of predominantly single stranded oligonucleotides derived from porcine intestinal mucosa. Several pre-clinical studies indicate that defibrotide primarily protects endothelium, particularly in small vessels, and reduces endothelial cell injury (Falanga et al, Leukemia, 2003) (Cairo/Cooke et al, British Journal of Haematology 2020). In a randomized phase III study, a decrease in incidence of SOS/VOD was observed in pediatric hematopoietic stem cell transplantation patients who received prophylactic defibrotide (Corbacioglu et al, Lancet, 2012). We hypothesized that Defibrotide would be safe and well tolerated in children and adolescents with SCD-associated ACS. Primary Aims: To determine the safety and efficacy of defibrotide in the treatment of patients with SCD-associated ACS. Design/Methods: Patients with SCD- (Homozygous Hemoglobin S disease, Hemoglobin SC Disease or Hemoglobin Sβ 0/+ Thalassemia) associated ACS 2 to 40 years of age were enrolled. Defibrotide, generously supplied by Jazz Pharmaceuticals, was administered at 6.25 mg/kg IV Q6H (total daily dose 25 mg/kg/day) within 24 hours of consent and continued for 7 days or until the patient was discharged from hospital (IND 127812) (NCT 03805581). All patients were treated with current standard of care, including antibiotics, analgesics, oxygen, intravenous fluids, and packed red blood cells (PRBC)/exchange transfusion. Complete blood counts and coagulation studies were performed at baseline, day 7 and day 30, while chest radiograph (CXR), CT chest angiogram (CTA), pulmonary function test, and transthoracic echocardiogram were performed at baseline and 30 days after defibrotide was first given. Blood plasma was collected from patients at baseline, day 7, day 30, and age matched SCD patients without ACS and analyzed for biomarkers of inflammation through ELISA and Luminex multiplex assays and significance was calculated using two-tailed T tests. Results: We have enrolled 20 patients (median age 9.5 years) with a gender ratio of M/F 8/12. Patients had hemoglobin SS (n=14), hemoglobin Sβ 0/+ (n=2), or hemoglobin SC (n=4). The median doses of defibrotide per patient was 18.5 (range 6-28) and the average hospital admission length was 6.1 days (range 3-13 days). There were no serious adverse events possibly, probably, or directly related to defibrotide, as judged by investigators. Two patients had a grade I/II epistaxis that did not disrupt defibrotide's course. Pulmonary infiltrate on CXR and/or CTA was the most common finding at diagnosis, detected in 18/20 study participants. Thirteen patients had fever as a presenting symptom, with an average fever duration of 2.8 days (range 1-6 days). Nine patients required O 2 supplementation, with an average duration of 4.1 days (range 2-7 days). Thirteen patients were treated with blood transfusions with a median of 1.9 units (PRBC unit was defined as 15ml/kg) transfused per patient (range, 1-5 units) and 1 patient underwent an exchange transfusion (Table 1). Soluble Intercellular Adhesion Molecule-1 (sICAM-1) was significantly elevated at the onset of ACS (p &amp;lt; 0.01) compared to control SCD plasma and was reduced by Day 30 after defibrotide treatment. Other markers of inflammation, including Angiopoetin-2 (Ang2), Interleukin-6 (IL-6), and Phospholipase A2-IIA (PLA2G2A) were elevated at baseline in patient plasma samples but were significantly decreased following defibrotide treatment (p &amp;lt; 0.05, 0.01, 0.01, respectively) (Figure 1). Conclusion: Our data suggests that defibrotide is safe and well tolerated in SCD patients with ACS. sICAM-1, Ang2, IL-6, and PLA2G2A may serve as important biomarkers in SCD associated ACS. A randomized phase II/III multi-center clinical trial will need to be conducted to further investigate efficacy of defibrotide in patients with SCD-associated ACS.

The effects of statins on cardiovascular and inflammatory biomarkers in primary prevention: A systematic review and meta-analysis

Abstract Background Statins are well-established for their treatment of cardiovascular disease (CVD) due to their cholesterol-lowering effects and potential anti-inflammatory properties. Although previous systematic reviews demonstrate that statins reduce inflammatory biomarkers in the secondary prevention of CVD, none examine their effects on cardiac and inflammatory biomarkers in a primary prevention setting. Aims and Methods We conducted a systematic review and meta-analysis to examine the effects of statins on cardiovascular and inflammatory biomarkers among individuals without established CVD. The biomarkers included are: cardiac troponin, N-terminal pro B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule (sICAM), soluble E-selectin (sE-selectin) and endothelin-1 (ET-1). A literature search was performed through Ovid MEDLINE, Embase and CINAHL Plus for randomized controlled trials (RCTs) published up to June 2021. Results Overall, 35 RCTs with 26,521 participants were included in our meta-analysis. Data was pooled using random effects models presented as standardized mean differences (SMD) with 95% confidence intervals (CI). Combining 36 effect sizes from 29 RCTs, statin use resulted in a significant reduction in CRP levels (SMD -0.61; 95% CI -0.91, -0.32; P&amp;lt;0.001). This reduction was observed for both hydrophilic (SMD -0.39; 95% CI -0.62, -0.16; P&amp;lt;0.001) and lipophilic statins (SMD -0.65; 95% CI -1.01, -0.29; P&amp;lt;0.001). There were no significant changes in serum concentrations of cardiac troponin, NT-proBNP, TNF-α, IL-6, sVCAM, sICAM, sE-selectin and ET-1. Conclusions This meta-analysis demonstrates the effect of statins in reducing serum CRP concentrations in the context of CVD primary prevention, with no significant changes in the other cardiac and inflammatory biomarkers studied. The meta-analysis highlights the need for further high quality, large-scale trials evaluating the effects of statins on cardiac and inflammatory biomarkers in primary prevention.Figure 1.Effect of statins on CRP

Elevated indoleamine 2,3-dioxygenase activity is associated with endothelial dysfunction in people living with HIV and ROS production in human aortic endothelial cells in vitro.

The precise role of indoleamine 2,3-dioxygenase (IDO) in cardiovascular diseases (CVD) among people living with HIV (PLWH) is still under debate, despite recognized links. This study aimed to investigate the impact of elevated IDO activity on endothelial dysfunction in PLWH. A total of 38 PLWH, who had not previously received anti-retroviral therapy (ART), were enrolled in the study. These participants were monitored for 36 months following the initiation of ART. Measurements including plasma levels of IDO activity, markers of endothelial dysfunction, inflammatory factors, and lipids. In vitro, human aortic endothelial cells (HAEC) were exposed to interferon-γ, an IDO inhibitor, a kynurenine 3-hydroxylase (KMO) inhibitor, as well as different concentrations of kynurenine. Pre-ART, PLWH demonstrated notably elevated plasma concentrations of soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1(sVCAM-1), and IDO activity in comparison to healthy controls. Post-ART, both IDO activity and sICAM-1 levels experienced a significant decrease, with IDO activity reaching levels comparable to those observed in healthy controls. Furthermore, a positive correlation was observed between IDO activity and sICAM-1 (p = 0.0002), as well as sVCAM-1 (p < 0.0001) before ART. In vitro, the augmentation of kynurenine concentration in the medium and the induction of IDO expression in HAEC resulted in increased production of reactive oxygen species (ROS), with minimal impact on endothelial dysfunction. From these findings, it can be concluded that long-term ART has the potential to restore the heightened IDO activity observed in PLWH. The overexpression of IDO primarily influences the expression of ROS in HAEC.

Endothelial dysfunction in patients with obesity and type 2 diabetes mellitus or normoglycemia: assessment of specific markers

BACKGROUND: One of the function of the endothelium is the maintenance of body's homeostasis. Endothelial dysfunction is known to be profoundly implicated in the pathogenesis of cardiovascular diseases (CVD). The presence of diabetes mellitus significantly increases the risks of CVD. Type 2 diabetes mellitus (T2DM) is often observed in obesity, however, there is a population of people with obesity, who do not develop T2DM for a long time.AIM: To compare the level of markers of endothelial dysfunction in two groups of individuals (without T2DM and with T2DM), as well as to evaluate the impact of cardioprotective medication (GPP-1 and SGLT-2) on these markers.MATERIALS AND METHODS: We recruited 2 groups of patients with obesity into this study: the 1st group with no carbohydrate metabolism disorders, the 2nd with T2DM. Several markers of endothelial dysfunction were evaluated: human von Willebrand factor (VWF), vascular endothelial growth factor A (VEGF-A), soluble form E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM1).RESULTS: A significant increase in sE-Selectin was seen in the group of patients with obesity and T2DM compared with those without carbohydrate metabolism disorders (46.65 [36.23; 66.66] vs 33.05 [22.1;53.31] ng/ml). There were no differences in the level of markers of endothelial dysfunction in the subgroups of patients with T2DM with HbA1c &lt; 8% and &gt;8%. There was also no effect of cardioprotective drugs (SGLT-2 and / or GPP-1) on any of endothelial dysfunction markers in individuals with T2DM.CONCLUSION: We suggest that an increase in sE-selectin may be an early marker of endothelial dysfunction in obese individuals and T2DM.

The effects of exercise training on circulating adhesion molecules in adults: A systematic review and meta-analysis.

The current meta-analysis investigated the effects of exercise training on circulating adhesion molecules i.e. soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in adults. PubMed, Web of Science, Scopus and Embase were searched to identify original articles, published in English languages journal from inception up to 31 August 2023 that compared the effects of exercise training with non-exercising control on sICAM-1 and sVCAM-1 in adults. Standardized mean differences (SMDs) and 95% CIs were calculated using random-effect models. Twenty-three studies including 31 intervention arms and involving 1437 subjects were included in the meta-analysis. Exercise training effectively reduced sICAM-1 [SMD: -0.33 (95% CI -0.56 to -0.11), p = 0.004; I2 = 56.38%, p = 0.001; 23 intervention arms]. Subgroup analyses showed that sICAM-1 decreased in adults with age <60 years (p = 0.01) and BMI ≥ 27 kg/m2 (p = 0.002) and those with metabolic disorders (p = 0.004) and cardiovascular diseases (p = 0.005). In addition, aerobic (p = 0.02) and resistance training (p = 0.007) are effective in reducing sICAM-1. However, exercise training did not indicate a superior effect on sVCAM-1 [SMD: -0.12 (95% CI -0.29 to 0.05), p = 0.17; I2 = 36.29%, p = 0.04; 23 intervention arms]. Our results show that exercise training reduces sICAM-1, but not for sVCAM-1, where both aerobic and resistance training is effective in reducing sICAM-1 in adults with metabolic disorders and cardiovascular diseases. The current meta-analysis was registered at www.crd.york.ac.uk/prospero with ID registration number: CRD42023410474.

Efficacy and anti-inflammatory analysis of glucocorticoid, antihistamine and leukotriene receptor antagonist in the treatment of allergic rhinitis.

There are many adverse reactions in the treatment of allergic rhinitis (AR) mainly with conventional drugs. Leukotriene receptor antagonists, glucocorticoids and nasal antihistamines can all be used as first-line drugs for AR, but the clinical effects of the three drugs are not clear. To examine the impact of glucocorticoids, antihistamines, and leukotriene receptor antagonists on individuals diagnosed with AR, specifically focusing on their influence on serum inflammatory indexes. The present retrospective study focused on the clinical data of 80 patients diagnosed and treated for AR at our hospital between May 2019 and May 2021. The participants were categorized into the control group and the observation group. The control group received leukotriene receptor antagonists, while the observation group was administered glucocorticoids and antihistamines. Conducted an observation and comparison of the symptoms, physical sign scores, adverse reactions, and effects on serum inflammatory indexes in two distinct groups of patients, both before and after treatment. Subsequent to treatment, the nasal itching score, sneeze score, runny nose score, nasal congestion score, and physical signs score exhibited notable discrepancies (P < 0.05), with the observation group demonstrating superior outcomes compared to the control group (P < 0.05). The interleukin (IL)-6, IL-10, tumor necrosis factor-alpha, Soluble Intercellular Adhesion Molecule-1, Leukotriene D4 after treatment were significantly different and the observation group It is better than the control group, which is statistically significant (P < 0.05). Following the intervention, the incidence of adverse reactions in the observation group, including symptoms such as nasal dryness, discomfort in the throat, bitter taste in the mouth, and minor erosion of the nasal mucosa, was found to be 7.5%. This rate was significantly lower compared to the control group, which reported an incidence of 27.5%. The difference between the two groups was statistically significant (P < 0.05). Glucocorticoids and antihistamines have obvious therapeutic effects, reduce serum inflammatory index levels, relieve symptoms and signs of patients, and promote patients' recovery, which can provide a reference for clinical treatment of AR.

TIAM2S-positive microglia enhance inflammation and neurotoxicity through soluble ICAM-1-mediated immune priming.

TIAM Rac1-associated GEF 2 short form (TIAM2S) as an oncoprotein alters the immunity of peripheral immune cells to construct an inflammatory tumor microenvironment. However, its role in the activation of microglia, the primary innate immune cells of the brain, and neuroinflammation remains unknown. This study investigated the mechanism underlying TIAM2S shapes immune properties of microglia to facilitate neuron damage. Human microglial clone 3 cell line (HMC3) and human brain samples were applied to determine the presence of TIAM2S in microglia by western blots and double immunostaining. Furthermore, TIAM2S transgenic mice combined with multiple reconstituted primary neuron-glial culture systems and a cytokine array were performed to explore how TIAM2S shaped immune priming of microglia and participated in lipopolysaccharide (LPS)-induced neuron damage. TIAM2S protein was detectable in HMC3 cells and presented in a small portion (~11.1%) of microglia in human brains referred to as TIAM2S-positive microglia. With the property of secreted soluble factor-mediated immune priming, TIAM2S-positive microglia enhanced LPS-induced neuroinflammation and neural damage in vivo and in vitro. The gain- and loss-of-function experiments showed soluble intercellular adhesion molecule-1 (sICAM-1) participated in neurotoxic immune priming of TIAM2S+ microglia. Together, this study demonstrated a novel TIAM2S-positive microglia subpopulation enhances inflammation and neurotoxicity through sICAM-1-mediated immune priming.

COVID-19 promotes endothelial dysfunction and thrombogenicity: role of proinflammatory cytokines/SGLT2 prooxidant pathway

BackgroundCOVID-19 is associated with an increased risk of cardiovascular complications. Although cytokines have a predominant role in endothelium damage, the precise molecular mechanisms are far from being elucidated. ObjectivesThe present study hypothesized that inflammation in patients with COVID-19 contributes to endothelial dysfunction through redox-sensitive SGLT2 overexpression and investigated the protective effect of SGLT2 inhibition by empagliflozin. MethodsHuman plasma samples were collected from patients with acute, subacute, and long COVID-19 (n = 100), patients with non-COVID-19 and cardiovascular risk factors (n = 50), and healthy volunteers (n = 25). Porcine coronary artery endothelial cells (ECs) were incubated with plasma (10%). Protein expression levels were determined using Western blot analyses and immunofluorescence staining, mRNA expression by quantitative reverse transcription-polymerase chain reaction, and the level of oxidative stress by dihydroethidium staining. Platelet adhesion, aggregation, and thrombin generation were determined. ResultsIncreased plasma levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, monocyte chemoattractant protein-1, and soluble intercellular adhesion molecule-1 were observed in patients with COVID-19. Exposure of ECs to COVID-19 plasma with high cytokines levels induced redox-sensitive upregulation of SGLT2 expression via proinflammatory cytokines IL-1β, IL-6, and tumor necrosis factor-α which, in turn, fueled endothelial dysfunction, senescence, NF-κB activation, inflammation, platelet adhesion and aggregation, von Willebrand factor secretion, and thrombin generation. The stimulatory effect of COVID-19 plasma was blunted by neutralizing antibodies against proinflammatory cytokines and empagliflozin. ConclusionIn patients with COVID-19, proinflammatory cytokines induced a redox-sensitive upregulation of SGLT2 expression in ECs, which in turn promoted endothelial injury, senescence, platelet adhesion, aggregation, and thrombin generation. SGLT2 inhibition with empagliflozin appeared as an attractive strategy to restore vascular homeostasis in COVID-19.

Effects of Butylphthalide Combined with Fasudil on Inflammatory Factors, Cognitive Function and Vascular Endothelial Function in Patients with Subarachnoid Hemorrhage Complicated with Cerebral Vasospasm.

To investigate the effect of butylphthalide combined with fasudil in the treatment of subarachnoid hemorrhage (SAH) with cerebral vasospasm (CVS) on inflammatory factors, cognitive function and vascular endothelial function. It is a retrospective study in which a total of 104 patients with SAH with CVS admitted to Baoding First Central Hospital from July 2020 to February 2022 were selected and randomly divided into two groups by drawing lots. Patients in the control group were treated with basic symptomatic treatment, while those in the observation group were treated with butylphthalide soft capsule combined with fasudil hydrochloride injection on the basis of the control group. Before and after treatment, serum neuron specific enolase (NSE), tumor necrosis factor-α(TNF-α), interleukin-8(IL-8), hypersensitive C-reactive protein (CRP), Birmingham Cognitive Screen test (BCoS) score, serum soluble intercellular adhesion molecule-1(ICAM-1), serum endothelin-1(ET-1), vascular endothelial growth factor (VEGF) levels, and endothelium-dependent vasodilation function (FMD) in the two groups were compared. After treatment, the expression levels of NSE, TNF-α, IL-8 and CRP in the two groups were significantly decreased, and the expression levels of all indicators in the observation group were lower than that in the control group (p<0.05). After treatment, the scores of orientations, attention, memory, language, practice and action in the two groups were significantly increased, and the scores of all dimensions in the observation group were higher than those in the control group (p<0.05). After treatment, S-ICAM-1, ET-1, VEGF, FMD decreased in both groups, and all indicators of the observation group were lower than those of the control group, with statistically significant differences (p<0.05). Butylphthalide combined with fasudil therapy was found as effective in reducing inflammatory factors, ameliorating cognitive function and vascular endothelial function in patients with subarachnoid hemorrhage complicated with cerebral vasospasm.

A near-infrared fluorescence-enhancing plasmonic biosensing microarray identifies soluble PD-L1 and ICAM-1 as predictive checkpoint biomarkers for cancer immunotherapy

Sensitive and accurate biomarker-driven assay guidance has been widely adopted to identify responsive patients for immune checkpoint blockade (ICB) therapy to impede disease progression and extend survival. However, most current assays are invasive, requiring surgical pathology specimens and only informing monochronic information. Here, we report a multiplexed enhanced fluorescence microarray immunoassay (eFMIA) based on a nanostructured gold nanoisland substrate (AuNIS), which macroscopically amplifies near-infrared fluorescence (NIRF) of a structurally symmetric IRDye78 fluorophore by over two orders of magnitude of 202.6-fold. Aided by non-contact piezo-driven micro-dispensing (PDMD), eFMIA simultaneously and semi-quantitatively detected intracellular and secreted programmed death-ligand 1 (PD-L1) and intercellular adhesion molecule-1 (ICAM-1) in human nasopharyngeal carcinoma (NPC) cells. The assay performance was superior to fluorescence immunoassays (FIA) and enzyme-linked immunosorbent assays (ELISA), with lower detection limits. Using eFMIA, we found significantly differential levels of soluble PD-L1 (sPD-L1) and sICAM-1 in the sera of 28 cancer patients, with different clinical outcomes following anti-PD-1 ICB therapy. With a well-characterized mechanism, the high-performance plasmonic multiplexed assay with the composite biomarkers may be a valuable tool to assist clinicians with decision-making and patient stratification to afford predictive ICB therapy responses.