Elevated levels of interleukin-12/23p40 may serve as a potential indicator of dysfunctional heart rate variability in type 2 diabetes.

BACKGROUND: Systemic inflammatory processes plausibly contribute to the development of cardiovascular complications, causing increased morbidity and mortality in type 2 diabetes. Circulating inflammatory markers, i.e., interleukin (IL)-6 and tumour necrosis factor-α, are associated with neurocardiac measures. We examined a broad panel of various inflammatory and inflammation-related serum markers to obtain more detailed insight into the possible neuro-immune interaction between cardiovascular regulation and systemic level of inflammation. METHODS: Serum samples from 100 participants with type 2 diabetes were analysed. Heart rate variability, cardiovascular autonomic reflex tests, and cardiac vagal tone tests were performed based on electrocardiographic readings. Data regarding covariates (demographic-, diabetes-, and cardiovascular risk factors) were registered. RESULTS: Increased serum levels of IL-12/IL-23p40 (p < 0.01) and intercellular adhesion molecule (ICAM)-1 (p < 0.007) were associated with diminished heart rate variability measures. After all adjustments, the associations between IL-12/23p40, SDANN and VLF persisted (p = 0.001). Additionally, serum levels of vascular endothelial growth factor (VEGF)-C were associated with response to standing (p = 0.005). DISCUSSION: The few but robust associations between neurocardiac regulation and serum markers found in this study suggest systemic changes in proinflammatory, endothelial, and lymphatic function, which collectively impacts the systemic cardiovascular function. Our results warrant further exploration of IL-12/IL-23p40, ICAM-1, and VEGF-C as possible cardiovascular biomarkers in T2D that may support future decisions regarding treatment strategies for improved patient care.

Relationship among Serum Homocysteine, Intercellular Adhesion Molecule-1, Monocyte Chemoattractant Protein-1, and Visual Impairment in Diabetic Macular Edema.

OBJECTIVE: To determine the relationship among serum homocysteine (Hcy), intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1) and visual impairment in patients with diabetic macular edema (DME). STUDY DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF STUDY: Yulin Second Hospital, China, from April 2018 to May 2021. METHODOLOGY: A total of 132 patients with diabetic retinopathy (DR), complicated with DME, were selected as observation group; and 132 patients with simple DR were included in the control group. According to visual examination, patients in observation group were divided into visual disability and non-visual disability. Serum Hcy, ICAM-1, MCP-1, and other indicators were measured. RESULTS: Duration of diabetes, levels of serum Hcy, ICAM-1 and MCP-1 in observation group were higher than those in control group (all p <0.001). Levels of serum Hcy, ICAM-1 and MCP-1 in patients with mild, moderate and severe DME were significantly different (all p <0.001). Levels of serum Hcy, ICAM-1 and MCP-1 in patients with visual disabilities were higher than those in patients with non-visual disabilities (all p <0.001). Levels of serum Hcy, ICAM-1 and MCP-1 in visually disabled patients were higher than those in non-visual disability patients (all p <0.001). CONCLUSION: Levels of serum Hcy, ICAM-1 and MCP-1 in patients with DR complicated with DME were higher than those without visual disability; and levels of Hcy, ICAM-1 and MCP-1 in patients with visual disability were higher than those without visual disability. In patients with DR complicated with DME, increase of these serum markers may play an important role in visual disability. Key Words: Diabetic retinopathy (DR), Diabetic macular edema (DME), Hcy, ICAM-1, MCP-1, Visual impairment.

Rapid and Effective Vitamin D Supplementation May Present Better Clinical Outcomes in COVID-19 (SARS-CoV-2) Patients by Altering Serum INOS1, IL1B, IFNg, Cathelicidin-LL37, and ICAM1.

BACKGROUND: We aimed to establish an acute treatment protocol to increase serum vitamin D, evaluate the effectiveness of vitamin D3 supplementation, and reveal the potential mechanisms in COVID-19. METHODS: We retrospectively analyzed the data of 867 COVID-19 cases. Then, a prospective study was conducted, including 23 healthy individuals and 210 cases. A total of 163 cases had vitamin D supplementation, and 95 were followed for 14 days. Clinical outcomes, routine blood biomarkers, serum levels of vitamin D metabolism, and action mechanism-related parameters were evaluated. RESULTS: Our treatment protocol increased the serum 25OHD levels significantly to above 30 ng/mL within two weeks. COVID-19 cases (no comorbidities, no vitamin D treatment, 25OHD <30 ng/mL) had 1.9-fold increased risk of having hospitalization longer than 8 days compared with the cases with comorbidities and vitamin D treatment. Having vitamin D treatment decreased the mortality rate by 2.14 times. The correlation analysis of specific serum biomarkers with 25OHD indicated that the vitamin D action in COVID-19 might involve regulation of INOS1, IL1B, IFNg, cathelicidin-LL37, and ICAM1. CONCLUSIONS: Vitamin D treatment shortened hospital stay and decreased mortality in COVID-19 cases, even in the existence of comorbidities. Vitamin D supplementation is effective on various target parameters; therefore, it is essential for COVID-19 treatment.

Serum and aqueous humor adiponectin levels correlate with diabetic retinopathy development and progression.

PURPOSE: To compare adiponectin (APN) levels in the serum and aqueous humor (AH) and evaluate their association with the development/progression of diabetic retinopathy (DR). METHODS: Diabetic patients with (group 3; n = 59) and without (group 2; n = 39) DR and age- and sex-matched normal subjects (group 1; n = 35) were compared. Duration of diabetes, body mass index, serum HbA1c, vascular endothelial growth factor (VEGF), APN, pentraxin 3 (PTX3), platelet derived growth factor (PDGF), intercellular adhesion molecule-1 (ICAM-1), and APN were measured and analyzed. RESULTS: One hundred and thirty-three participants were included. Compared to patients without diabetes, diabetic patients with DR had significantly elevated average serum APN levels (5.99±3.89 µg/ml versus 3.51±1.44 µg/ml, P = 0.002) and average AH APN levels (10.94±11.74 ng/ml versus 3.65±3.33 ng/ml, P<0.001). Serum APN was significantly correlated with AH APN (R = 0.512, P<0.001) and AH VEGF (R = 0.202, P = 0.020). The log serum APN was significantly correlated with intraocular cytokines, including log APN, log VEGF, log ICAM, log leptin, log PTX3, log PDGF, angiopoietin, C-reactive protein, and interleukins (IL)-5 and IL-10 (P<0.001, P = 0.020, P<0.001, P<0.001, P = 0.001, P<0.001, P = 0.008, P = 0.009, P<0.001, and P = 0.046, respectively). Log serum VEGF showed a significant correlation only with log AH VEGF (P = 0.001). Multivariate logistic analysis was performed to evaluate the association of DR progression and cytokine concentrations; log Serum APN and log AH APN showed good correlation with the DR progression in each model. CONCLUSIONS: AH APN levels correlated well with DR development and progression. Serum APN could be a better marker for estimating intraocular cytokines, including both intraocular APN and VEGF concentrations in clinical field, than serum VEGF in DR patients.

Intracellular Adhesion Molecule-1 (ICAM-1) Levels in Convalescent COVID-19 Serum: A Case Report.

OBJECTIVE: Intercellular adhesion molecule-1 (ICAM-1), an endothelial cell adhesion molecule, contributes to inflammation and immune-mediated responses. Viral infection of endothelial cells caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause vascular changes and elevate the expression of ICAM-1 in coronavirus disease 2019 (COVID-19) patients and may be used as a biomarker to measure disease severity or recovery. This study sought to identify the ICAM-1 levels in convalescent COVID-19 serum 2 to 33 weeks after the initial diagnosis. METHODS: ICAM-1 levels were measured 2-33 weeks after COVID-19 diagnosis (April 2020) in the serum from a subject in Brooklyn, New York who recovered from COVID-19 (ELISA). SARS-CoV-2 IgG antibody levels were also measured (ELISA). RESULTS: ICAM-1 levels were low 2 weeks after the initial COVID-19 diagnosis and increased 6-fold at 5 weeks. ICAM-1 levels decreased at 12 weeks (50%) and at 33 weeks (50%) after the initial COVID-19 diagnosis. SARS-CoV-2 IgG antibody levels were detected 4-5 weeks after the initial COVID-19 diagnosis. CONCLUSIONS: ICAM-1 levels in serum from a recovered COVID-19 patient were highest 5 weeks after the initial COVID-19 diagnosis. The presence of high levels of soluble markers such as ICAM-1, as measured by the anti-ICAM-1 antibody, may be due to their increased shedding from the cell surface. ICAM-1 may also be a prognostic indicator for late complications or sequelae due to COVD-19 infection.

Potentiality of α-fetoprotein (AFP) and soluble intercellular adhesion molecule-1 (sICAM-1) in prognosis prediction and immunotherapy response for patients with hepatocellular carcinoma.

ABSTRCTThe α-fetoprotein (AFP) and soluble intercellular adhesion molecule-1 (sICAM-1) have certain diagnostic value, but their potential value in prognosis prediction, especially immunotherapy response prediction, remains unclear in liver cancer. Through the tumor-free survival (TFS) and overall survival (OS) rates analyses of serum AFP and sICAM-1 levels in 87 patients with primary hepatocellular carcinoma (HCC), the patients whose AFP and sICAM-1 levels were normal (AFP < 20 µg/L or sICAM-1 < 1000 µg/L) before surgery or recovered to normal after surgery exhibited a lower tumor recurrence rate and better OS than patients with elevated serum levels of the two markers. Combined analysis showed that patients with synchronously elevated levels of AFP and sICAM-1 showed the lowest TFS and OS. In addition, the RNA-seq data and clinical information of The Cancer Genome Atlas Liver Hepatocellular Carcinoma were collected to analyze the predictive values of AFP and ICAM-1 in the diagnosis, prognosis and immunotherapy of HCC. The results indicated that the combined application of the two indicators had higher accuracy in both the diagnosis and prognostic prediction of HCC by receiver operating characteristic curves. AFP and ICAM-1 were significantly correlated with multiple immune cells in HCC samples but not in normal samples. The patients with low expression of the two indicators were most likely to benefit from the immune checkpoint blockade therapy. In conclusion, AFP and ICAM-1 play vital roles in the diagnosis, prognostic prediction, and immunotherapy of HCC, suggesting that they are considered as prognostic predictors in clinical practice.

Effects of Acute Fructose Loading on Markers of Inflammation-A Pilot Study.

Inflammation plays a role in development of diabetic complications. The postprandial state has been linked to chronic low grade inflammation. We therefore aimed to investigate the acute effects of fructose loading, with and without a pizza, on metabolic and inflammatory markers in patients with type 2 diabetes (T2D) (n = 7) and in healthy subjects (HS) (n = 6), age 47-76 years. Drinks consumed were blueberry drink (18 g fructose), Coca-Cola (17.5 g fructose), and fructose drink (35 g fructose). The levels of glucose, insulin, insulin-like growth factor binding protein-1 (IGFBP-1) and inflammatory markers: Interleukin-6 (IL-6), Monocyte chemoattractant protein-1 (MCP-1), Interleukin-18 (IL-18), Intercellular Adhesion Molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and bacterial lipopolysaccharides (LPS) were analyzed in blood. The postprandial responses were assessed using Wilcoxon's matched-pairs test, Friedman's ANOVA and Mann-Whitney U test. There was no difference in baseline levels of inflammatory markers between the groups. In T2D, MCP-1 decreased following blueberry drink and Coca-Cola (p = 0.02), Coca-Cola + pizza and fructose + pizza (p = 0.03). In HS, IL-6 increased following blueberry + pizza and fructose + pizza (p = 0.03), there was a decrease in MCP-1 following blueberry drink and Coca-Cola (p = 0.03), and in ICAM-1 following blueberry + pizza (p = 0.03). These results may indicate a role for MCP-1 as a link between postprandial state and diabetes complications, however further mechanistic studies on larger population of patients with T2D are needed for confirmation of these results.

Research on Association between Levels of Serum Adiponectin, Hs-CRP, and sICAM-1 and Hypertensive Cerebrovascular Complications.

The study is aimed at studying the association between the levels of serum adiponectin (ADPN), high-sensitivity C-reactive protein (hs-CRP), and soluble intercellular adhesion molecule-1 (sICAM-1) and hypertensive cerebrovascular complications. 50 patients with hypertensive cerebrovascular disease treated in Gansu Provincial Hospital from December 2016 to December 2018 were selected as the experimental group, and 50 normal people who underwent physical examination were selected as the control group. The blood pressure, heart rate, and the complications were recorded, and the serum blood lipid indexes were detected. Moreover, the content of serum ADPN, hs-CRP, and sICAM-1; the neurological indexes; brain-derived neurotrophic factor (BNDF); and neurone-specific enolase (NSE) were also determined using ELISA. The content of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and serum creatinine (SCR) in the experimental group was significantly higher than that in control group (p < 0.05); the incidence of cerebrovascular complications, systolic blood pressure, diastolic blood pressure, and heart rate increased (p < 0.05); the content of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), hs-CRP, and sICAM-1 obviously rose (p < 0.05); and the content of ADPN and HDL obviously declined (p < 0.05). Besides, the experimental group had evidently lower systolic blood flow velocity (Vs), diastolic blood flow velocity (Vd), and mean blood flow velocity (Vm) and evidently higher pulsatility index (PI) (p < 0.05). The levels of S100 and NSE in the experimental group increased significantly, and the level of BNDF decreased significantly (p < 0.05). In patients with hypertensive cerebrovascular disease, the level of ADPN declines; the levels of hs-CRP and sICAM-1 rise; the incidence rate of cerebrovascular complications is elevated; and there are changes in the blood lipid, cerebrovascular hemodynamic, and neurological indexes, thereby further promoting the occurrence and development of hypertensive cerebrovascular disease.

Reduced frequency of perforin-positive CD8+ T cells in menstrual effluent of endometriosis patients.

Endometriosis is a widespread disease and commonly reduces the life quality of those affected. Scientific literature indicates different underlying immunological changes. Frequently examined tissues are peripheral blood, endometrial tissue and peritoneal fluid. Yet, knowledge on immunological differences in menstrual effluent (ME) is scarce. In this study, between January 2018 and August 2019, 12 women with endometriosis (rASRM classification: stages I-IV) and 11 healthy controls were included. ME was collected using menstrual cups and venous blood samples (PB) were taken. Mononuclear cells were obtained from ME (MMC) and PB (PBMC) and analyzed using flow cytometry. Concentrations of cell adhesion molecules (ICAM-I and VCAM-I) and cytokines (IL-6, IL-8 and TNF-α) were measured using ELISA. CD8 + T cells obtained from ME were significantly less often perforin-positive in women with endometriosis compared to healthy controls. A comparison between MMC and PBMC revealed that MMC contained significantly less T cells and more B cells. The CD4/CD8 ratio was significantly higher in MMC, and Tregs were significantly less frequently in MMC. In ME, T cells and NK cells expressed significantly more CD69. NK cells obtained from ME were predominantly CD56bright/CD16dim and had a lower frequency of perforin + cells compared to PBMC NK cells. Moreover, ICAM-1 plasma levels were significantly reduced in women with endometriosis compared to healthy controls. In conclusion, CD8 + T cells obtained from the ME were significantly less perforin-positive in endometriosis patients indicating a reduced cytotoxic potential. MMC are distinctively different from PBMC and, thus, seem to be of endometrial origin.

Resolvin-D1 attenuation of angiotensin II-induced cardiac inflammation in mice is associated with prevention of cardiac remodeling and hypertension.

AIMS: Despite the broad pharmacological arsenal to treat hypertension, chronic patients may develop irreversible cardiac remodeling and fibrosis. Angiotensin II, the main peptide responsible for the Renin-Angiotensin-Aldosterone-System, has been closely linked to cardiac remodeling, hypertrophy, fibrosis, and hypertension, and some of these effects are induced by inflammatory mediators. Resolvin-D1 (RvD1) elicits potent anti-inflammatory and pro-resolving effects in various pathological models. In this study, we aimed to examine whether RvD1 ameliorates cardiac remodeling and hypertension triggered by angiotensin II. METHODS AND RESULTS: Alzet® osmotic mini-pumps filled with angiotensin II (1.5 mg/kg/day) were implanted in male C57BL/6 J mice for 7 or 14 days. RvD1 (3 µg/kg/day, i.p) was administered one day after the surgery and during the complete infusion period. Blood pressure and myocardial functional parameters were assessed by echocardiography. At the end of the experimental procedure, blood and heart tissue were harvested, and plasma and histological parameters were studied. After 7 and 14 days, RvD1 reduced the increase of neutrophil and macrophage infiltration triggered by angiotensin II, and also reduced ICAM-1 and VCAM-1 expression levels. RvD1 also reduced cytokine plasma levels (IL-1ß, TNF-α, IL-6, KC, MCP-1), cardiac hypertrophy, interstitial and perivascular fibrosis, and hypertension. CONCLUSIONS: This study unveils novel cardioprotective effects of RvD1 in angiotensin II-induced hypertension and cardiac remodeling by attenuating inflammation and provides insights into a potential clinical application.

Role of ICAM-1 in impaired retinal circulation in rhegmatogenous retinal detachment.

Many studies have demonstrated that rhegmatogenous retinal detachment (RRD) leads to impaired retinal circulation. However, the involvement of inflammation in the RRD-induced worsening of retinal circulation was obscure. This retrospective observational study included 150 patients with primary RRD (macula-on, n = 63; macula-off, n = 87) who underwent 25-gauge microincision vitrectomy surgery (25G MIVS). Total retinal blood flow was represented by the mean blur rate (MBR) of the optic nerve head vessel, measured by laser speckle flowgraphy preoperatively and until 6 months postoperatively. Aqueous humor samples were obtained during surgery to determine cytokine concentrations by enzyme-linked immunosorbent assay. At 3 and 6 months postoperatively, there were no significant differences between eyes with macula-on RRD and fellow eyes. However, in macula-off RRD, MBR remained significantly lower in RRD eyes 6 months postoperatively (P < 0.05). Log-transformed levels of soluble intercellular adhesion molecule-1 (sICAM-1) were negatively correlated with relative MBR (r-MBR, RRD eye/fellow eye) before surgery (r = - 0.47, P = 0.01) in macula-on, but not macula-off, RRD. Six months postoperatively, r-MBR correlated significantly with sICAM-1 levels (r = - 0.36, P = 0.02) in macula-off RRD. ICAM-1 may play a role in RRD-induced deterioration of retinal circulation.

Trimetazidine ameliorates hindlimb ischaemic damage in type 2 diabetic mice.

BACKGROUND: Ischaemia caused by lower extremity artery stenosis is the main cause of peripheral artery disease (PAD) in patients with diabetes. Trimetazidine (TMZ) has traditionally been used as an anti-ischaemic drug for coronary artery disease. The effect of TMZ on PAD in a diabetic animal model and the underlying molecular mechanisms remain unclear. METHODS: The db/db mice were challenged with femoral artery ligation (FAL), followed by TMZ treatment for 2 weeks. Scores on hindlimb ischaemia and function were evaluated. Histological and capillary density analyses of gastrocnemius were performed. The expression of vascular endothelial growth factor (VEGF) and myogenic regulators was also confirmed by Western blotting. We also detected serum intercellular adhesion molecule 1 (ICAM-1) level through ELISA. RESULTS: Diabetic mice exhibited limb ulceration and motor dysfunction after FAL while TMZ-treated db/db mice exhibited milder ischaemic impairment. Furthermore, decreased capillary density in the gastrocnemius muscles of ischaemic hindlimb and reduced expressions of VEGF, myogenic markers, and serum ICAM-1 could be partially reversed by TMZ treatment. CONCLUSION: TMZ may alleviate hindlimb ischaemic damage in db/db mice, at least partly, through enhancing angiogenesis and promoting myogenesis in ischaemia region.Key messagesTMZ intervention could alleviate hindlimb ischaemic damage in db/db mice.TMZ intervention could enhance angiogenesis and stimulate myogenesis in ischaemia region.

The effect of vitamin D supplementation on flow-mediated dilatation, oxidized LDL and intracellular adhesion molecule 1 on type 2 diabetic patients with hypertension: A randomized, placebo-controlled, double-blind trial.

AIMS: Current study aimed to evaluate the effect of vitamin D supplementation on flow-mediated dilatation (FMD), oxidized LDL (oxLDL) and intracellular adhesion molecule 1 (ICAM1) in type 2 diabetic patients with hypertension. METHODS: In a double-blinded, placebo-controlled trial, 44 patients were randomly divided into vitamin D group (2000 IU/d, n = 23) and placebo group (control, n = 21) for 12 weeks. Vascular function with FMD, Serum 25-OH vitamin D, oxLDL and ICAM1 were assessed at the baseline and after the intervention. This clinical trial was registered at Iranian Registry of Clinical Trials (IRCT20191223045861N1). RESULTS: In intervention group serum level of vitamin D increased from 32.42 ± 10.56 to 40.45 ± 12.94 (p < 0.001). In the vitamin D group, oxLDL and ICAM1 significantly decreased and FMD increased significantly in both groups (p < 0.001). The level of oxLDL (p = 0.017) and ICAM1 (p < 0.001) were significantly lower in the vitamin D group than the placebo group and FMD (p < 0.001) was significantly higher in the vitamin D group. CONCLUSIONS: Vitamin D supplementation of 2000 IU/d for 12 weeks can improve endothelial function and decrease ICAM1 and oxLDL in type 2 diabetic patients with hypertension.

Predictive Value of High ICAM-1 Level for Poor Treatment Response to Low-Dose Decitabine in Adult Corticosteroid Resistant ITP Patients.

Primary immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease. Endothelial cell activation/injury has been found in some autoimmune diseases including SLE, systemic sclerosis, and rheumatoid arthritis, but its role in ITP pathogenesis remains unclear. This study attempted to elucidate the correlation between endothelial dysfunction and disease severity of ITP and find related markers to predict response to low-dose decitabine treatment. Compared with healthy volunteers, higher plasma levels of soluble intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF), and Angiopoietin-2 were found in adult corticosteroid resistant ITP patients. Notably, ICAM-1 levels were negatively correlated with the platelet count, and positively associated with the bleeding score. Recently, we have reported the efficacy and safety of low-dose decitabine in adult patients with ITP who failed for the first line therapies. Here, we evaluated the correlation of plasma ICAM-1 level with the efficacy of low-dose decitabine therapy for corticosteroid resistant ITP. A total of 29 adult corticosteroid resistant ITP patients who received consecutive treatments of low-dose decitabine were enrolled in this study. Fourteen patients showed response (nine showed complete response and five showed partial response). The levels of ICAM-1 before and after treatment were significantly higher in the non-responsive ITP patients than in the responsive patients. As shown in the multivariable logistic regression model, the odds of developing no-response to low-dose decitabine increased by 36.8% for per 5 ng/ml increase in plasma ICAM-1 level [odds ratio (OR) 1.368, 95% confidence interval (CI): 1.060 to 1.764]. In summary, this was the first study to elucidate the relationship between endothelial dysfunction and corticosteroid resistant ITP and identify the potential predictive value of ICAM-1 level for response to low-dose decitabine.

Gastrodia remodels intestinal microflora to suppress inflammation in mice with early atherosclerosis.

Atherosclsis is a critical actuator causing cardiac-cerebral vascular disease with a complicated pathogeneon, refered to the disorders of intestinal flora and persistent inflammation. Gastrodin (4-(hydroxymethyl) phenyl-ß-D- Glucopyranoside) is the most abundant glucoside extracted from the Gastrodiaelata, which is a traditional Chinese herbal medicine for cardiac-cerebral vascular disease, yet its mechanisms remain little known. In the present study, the gastrodia extract and gastrodin attenuate the lipid deposition and foam cells on the inner membrane of the inner membrane of the thoracic aorta in the early atherosclerosis mice. Blood lipid detection tips that TC and LDL-C were reduced in peripheral blood after treatment with the gastrodia extract and gastrodin. Furthermore, unordered gut microbes are remodeled in terms of bacterial diversity and abundance at family and genus level. Also, the intestinal mucosa damage and permeability were reversed, accompaniedwith the reducing of inflammatory cytokines. Our findings revealed that the functions of gastrodia extract and gastrodin in cardiac-cerebral vascular disease involved to rescued gut microbes and anti-inflammation may be the mechanismof remission lipid accumulation.

Mechanisms of Ischemic Stroke in Patients with Cancer: A Prospective Study.

OBJECTIVE: The objective of this study was to examine the pathophysiology of ischemic stroke with cancer. METHODS: We conducted a prospective cross-sectional study from 2016 to 2020 at 2 hospitals. We enrolled 3 groups of 50 adult participants each. The main group included patients with active solid tumor cancer and acute ischemic stroke. The control groups included patients with acute ischemic stroke only or active cancer only. The patients with stroke-only and patients with cancer-only were matched to the patients with cancer-plus-stroke by age, sex, and cancer type, if applicable. The outcomes were prespecified hematological biomarkers and transcranial Doppler microemboli detection. Hematological biomarkers included markers of coagulation (D-dimer and thrombin-antithrombin), platelet function (P-selectin), and endothelial integrity (thrombomodulin, soluble intercellular adhesion molecule-1 [sICAM-1], and soluble vascular cell adhesion molecule-1 [sVCAM-1]). Hematological biomarkers were compared between groups using the Kruskal-Wallis and Wilcoxon Rank-Sum tests. In multivariable linear regression models, we adjusted for race, number of stroke risk factors, smoking, stroke severity, and antithrombotic use. Transcranial Doppler microemboli presence was compared between groups using chi-square tests. RESULTS: Levels of all study biomarkers were different between groups. In univariate between-group comparisons, patients with cancer-plus-stroke had higher levels of D-dimer, sICAM-1, sVCAM-1, and thrombomodulin than both control groups; higher levels of thrombin-antithrombin than patients with cancer-only; and higher levels of P-selectin than patients with stroke-only. Findings were similar in multivariable analyses. Transcranial Doppler microemboli were detected in 32% of patients with cancer-plus-stroke, 16% of patients with stroke-only, and 6% of patients with cancer-only (p = 0.005). INTERPRETATION: Patients with cancer-related stroke have higher markers of coagulation, platelet, and endothelial dysfunction, and more circulating microemboli, than matched controls. ANN NEUROL 2021;90:159-169.

Serum ICAM-1 as a Predictor of Prognosis in Patients with Acute Ischemic Stroke.

OBJECTIVE: Inflammation is one of the key mechanisms involved in functional impairment after stroke. Intercellular adhesion molecule-1 (ICAM-1) is an important inflammatory molecule in the body. The purpose of our study was to determine the correlation between ICAM-1 and the prognosis of acute ischemic stroke (AIS). METHODS: 286 AIS patients treated at Beijing Tiantan Hospital were continuously included in the study. The demographic data of the patients were collected, and the fasting blood within 24 hours of admission was collected to detect the clinical indicators. The functional prognosis was measured using the modified Rankin Scale (mRS) 3 months after stroke. The poor prognosis is defined as mRS ≥ 3. The enzyme-linked immunosorbent assay (ELISA) was used to determine the serum ICAM-1 levels. RESULTS: The serum ICAM-1 levels of patients with poor prognosis were significantly higher than that of patients with good prognosis (144.2 ± 14.8 vs 117.5 ± 12.1 pg/ml). Receiver operating characteristic curve (ROC) analysis showed that the sensitivity and specificity of serum ICAM-1 for predicting the prognosis of AIS were 74% and 76%, respectively. In logistic regression analysis, the serum ICAM-1 level is still an independent predictor of poor prognosis (odds ratio [OR]: 0.52; 95% confidence interval [CI]: 0.318-0.839). CONCLUSIONS: Higher serum ICAM-1 levels on admission in AIS patients might increase the risk of poor prognosis.

Long-term physical training in adolescent sprint and middle distance swimmers alters the composition of circulating T and NK cells which correlates with soluble ICAM-1 serum concentrations.

PURPOSE: It remains unknown how different training intensities and volumes chronically impact circulating lymphocytes and cellular adhesion molecules. First, we aimed to monitor changes in NK and T cells over a training season and relate these to training load. Second, we analyzed effects of training differences between swimmers on these cells. Finally, we examined if changes in lymphocytes were associated with sICAM-1 concentrations. METHODS: We analyzed weekly training volume, training intensity, proportions of T and NK cells and serum sICAM-1 in eight sprint (SS) and seven middle-distance swimmers (MID) at three points over a 16-week training period: at the start (t0), after 7 weeks of increased training load (t7) and after 16 weeks, including 5-day taper (t16). RESULTS: Training volume of all swimmers was statistically higher and training intensity lower from t0-t7 compared to t7-t16 (p = 0.001). Secondly, training intensity was statistically higher in SS from t0-t7 (p = 0.004) and t7-t16 (p = 0.015), while MID had a statistically higher training volume from t7-t16 (p = 0.04). From t0-t7, NK (p = 0.06) and CD45RA+CD45RO+CD4+ cells (p < 0.001) statistically decreased, while CD45RA-CD45RO+CD4+ cells (p = 0.024) statistically increased. In a subgroup analysis, SS showed statistically larger increases in NK cells from t7-t16 than MID (p = 0.012). Lastly, sICAM-1 concentrations were associated with changes in CD45RA-CDRO+CD4+ cells (r = - 0.656, p = 0.08). CONCLUSION: These results indicate that intensified training in swimmers resulted in transient changes in T and NK cells. Further, NK cells are sensitive to high training volumes. Lastly, sICAM-1 concentrations may be associated with the migration and maturation of CD4+ cells in athletes.

Clinico-pathological associations of serum VCAM-1 and ICAM-1 levels in patients with lupus nephritis.

OBJECTIVE: We investigated the clinico-pathological associations of serum VCAM-1 and ICAM-1 levels in patients with biopsy-proven Class III/IV±V lupus nephritis (LN). METHODS: Serum VCAM-1 and ICAM-1 levels were determined by ELISAs. Sera from patients with non-renal SLE or non-lupus chronic kidney disease (CKD), and healthy subjects served as controls. RESULTS: Seropositivity rate for VCAM-1 and ICAM-1 was 93.10% and 37.93% respectively at the time of nephritic flare, and 44.83% and 13.79% respectively at remission, with both showing higher levels during flare (P < 0.05, for both). VCAM-1 level correlated with proteinuria, serum creatinine, and anti-dsDNA antibodies, and inversely correlated with C3. VCAM-1 level also correlated with leukocyte infiltration and fibrinoid necrosis/karyorrhexis scores in active LN kidney biopsies. ICAM-1 level correlated with proteinuria, but not anti-dsDNA or C3, nor histopathological features. VCAM-1 level increased 4.5 months before renal flare, while ICAM-1 increase coincided with flare, and both decreased after treatment. ROC analysis showed that VCAM-1 distinguished active LN from healthy subjects, LN in remission, active non-renal lupus, and CKD (ROC AUC of 0.98, 0.86, 0.93 and 0.90 respectively). VCAM-1 level in combination with either proteinuria or C3 was superior in distinguishing active LN from remission compared to the measurement of individual markers. Serum ICAM-1 level distinguished active LN from healthy subjects and LN patients in remission (ROC AUC of 0.75 and 0.66 respectively), but did not distinguish between renal versus non-renal lupus. ICAM-1 level in combination with markers of endothelial cell activation (syndecan-1, hyaluronan and thrombomodulin) was superior to proteinuria, anti-dsDNA, or C3 in distinguishing active LN from quiescent disease. CONCLUSION: Our findings suggest potential utility of serum VCAM-1 and ICAM-1 in clinical management. Monitoring VCAM-1 may facilitate early diagnosis of flare. Combining selected biomarkers may be advantageous in diagnosing active LN. VCAM-1 may have a pathogenic role in renal parenchymal inflammation in active LN.

Peripheral Markers of Vascular Endothelial Dysfunction Show Independent but Additive Relationships with Brain-Based Biomarkers in Association with Functional Impairment in Alzheimer's Disease.

BACKGROUND: Cerebrovascular dysfunction confers risk for functional decline in Alzheimer's disease (AD), yet the clinical interplay of these two pathogenic processes is not well understood. OBJECTIVE: We utilized Alzheimer's Disease Neuroimaging Initiative (ADNI) data to examine associations between peripherally derived soluble cell adhesion molecules (CAMs) and clinical diagnostic indicators of AD. METHODS: Using generalized linear regression models, we examined cross-sectional relationships of soluble plasma vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-Selectin to baseline diagnosis and functional impairment (clinical dementia rating sum-of-boxes, CDR-SB) in the ADNI cohort (n = 112 AD, n = 396 mild cognitive impairment (MCI), n = 58 cognitively normal). We further analyzed associations of these biomarkers with brain-based AD biomarkers in a subset with available cerebrospinal fluid (CSF) data (n = 351). p-values derived from main effects and interaction terms from the linear regressions were used to assess the relationship between independent and dependent variables for significance (significance level was set at 0.05 a priori for all analysis). RESULTS: Higher mean VCAM-1 (p = 0.0026) and ICAM-1 (p = 0.0189) levels were found in AD versus MCI groups; however, not in MCI versus cognitively normal groups. Only VCAM-1 was linked with CDR-SB scores (p = 0.0157), and APOE ɛ4 genotype modified this effect. We observed independent, additive associations when VCAM-1 and CSF amyloid-ß (Aß42), total tau, phosphorylated tau (P-tau), or P-tau/Aß42 (all < p = 0.01) were combined in a CDR-SB model; ICAM-1 showed a similar pattern, but to a lesser extent. CONCLUSION: Our findings indicate independent associations of plasma-based vascular biomarkers and CSF biomarkers with AD-related clinical impairment.