Serum sCD40L Research Articles

Can Vitamin D Supplementation Improve Inflammation in Relapsing-Remitting Multiple Sclerosis Patients?

(1) Background: Studies indicate that vitamin D (VitD) may reduce inflammation in multiple sclerosis (MS). The aim of the study was to assess the effect of supplementation with different doses of VitD on inflammation in relapsing-remitting MS (RRMS) patients. (2) Methods: The effect of 6-month supplementation with different doses of oral VitD (2000 IU/day) in a high-dose group (HD, n = 23) and a low-dose group (15,960 IU/month) (LD, n = 29) on selected markers of inflammation was assessed in 52 RRMS patients. (3) Results: Females constituted the majority of participants (63.46%). The median age [years] was 39.5 [34.5-49.8] and 47 [40.0-55.0] in the HD and LD groups, respectively. Significant differences were observed in age (p = 0.028), body weight (p = 0.014) and height (p = 0.001) between the study groups. Considering the BMI, statistically significant differences were not found (p = 0.496). The median 25(OH)D concentration [ng/mL] increased from 23.023 [15.578-25.76] in the HD group and 28.318 [20.644-32.232] in the LD group to 29.819 [24.937-38.064] and 30.837 [25.382-36.789], respectively (p < 0.01), and the increase was significantly higher in the HD group (p = 0.01). Hypovitaminosis D was found in most patients (71.2%) initially, and serum VitD levels were still <30.0 ng/mL in 46.2% of the participants at the follow-up. A significant increase in the levels of IL-4, IL-6, IL-17A, IL-22, IL-23 and TNF -α [pg/mL] and a decrease in IL-10 levels were reported during the study (p < 0.01). A significant positive correlation was observed between 25(OH)D serum levels and sCD40L (R = 0.33; p < 0.05) and TNF-α (R = 0.28; p < 0.05), and a significant negative correlation was reported between 25(OH)D and IL-23 (R = -0.32; p < 0.01) at the beginning of the study. (4) Conclusions: In RRMS patients, the doses of VitD were probably too low to induce beneficial effects on inflammation. Further studies are warranted to determine the effect of VitD supplementation on inflammatory markers in MS patients.

Impact of heat-not-burn cigarette passive smoking on children's oxidative stress, endothelial and platelet function

Growing global use of heat-not-burn cigarettes (HNBC) prompts investigation. Prior studies assessed HNBC's effects on cardiovascular health, revealing heightened oxidative stress, platelet activation, and endothelial dysfunction. However, limited understanding exists regarding passive smoking's impact on children exposed to HNBC.This study aims to assess levels of oxidative stress, endothelial and platelet function among children exposed to passive smoke from HNBC, traditional tobacco (TT) cigarettes and unexposed subjects.Seventy-eight children (2–18 years) were divided into three groups: HNBC passive smokers (n = 26), TT cigarette exposed (n = 26), and control (CNT) group (n = 26, unexposed).Oxidative stress was evaluated by serum NADPH oxidase-2 (NOX2) activity, assessed by soluble Nox2-derived peptide (sNOX2-dp), isoprostanes, hydrogen peroxide (H2O2) production, hydrogen break-down activity (HBA) and NO bioavailability. Endothelial function was assessed by brachial flow-mediated dilation (FMD). Platelet function was evaluated by soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin) and thrombus formation by T-TAS analysis.Passive smoking-exposed children (both HNBC and TT) exhibited significantly increased serum sNOX2-dp, isoprostanes, H2O2, sCD40L sP-selectin and thrombus formation versus controls. Conversely, exposed children displayed reduced brachial FMD and serum NO bioavailability. No significant differences were found between children exposed to passive smoking of HNBC vs TT.Multivariable regression linked sNOX2 (standardized coefficient β: 0.284; SE: 0.040; p = 0.01) and H2O2 (standardized coefficient β: 0.243; SE: 0.0; p = 0.02) as independent predictors of FMD, and isoprostanes (standardized coefficient β:0.388; SE: 0.022; p < 0.001) and serum cotinine (standardized coefficient β:0.270; SE: 0.048; p = 0.01) with sNOX2-dp levels.Exposure to HNBC smoke heightened oxidative stress, endothelial dysfunction, platelet activation, and thrombus formation in children. Findings suggest avenues for interventions to curb childhood passive smoking exposure.

Predictive value of soluble CD40L combined with APACHE II score in elderly patients with sepsis in the emergency department

BackgroundThe prognostic performance of soluble CD40L (sCD40L) for illness severity in infectious diseases is rarely reported. We investigated the ability of sCD40L combined with Acute Physiology and Chronic Health Evaluation II (APACHE II) score to evaluate mortality in septic patients in the emergency department(ED).MethodsWe enrolled 222 septic patients in the ED of Beijing Chao-Yang Hospital from October 2020 to April 2021. Their serum sCD40L, PCT, lactate (Lac), Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation II (APACHE II) score were used to predict the prognosis of septic patients in terms of 28-day mortality. Serum sCD40L was detected by Human XL Cytokine Luminex. Logistic regression analysis and receiver operating characteristic (ROC) curves were used to assess the prognostic value of the variables.ResultsOne hundred ninety-five patients met the inclusion criteria, divided into survival group (55 cases) and non-survival group (140 cases). sCD40L, PCT, Lac, SOFA and APACHE II score were found to independently predict 28-day mortality (P < 0.05). The AUC values of sCD40L, PCT, Lac, SOFA and APACHE II score were 0.662,0.727,0.704, 0.719 and 0.716, respectively. There was no difference in the diagnostic value of sCD40L compared with the PCT, Lac, SOFA score or APACHE II score (Z1 = 1.19, P = 0.234; Z2 = 0.77, P = 0.441; Z3 = 1.05, P = 0.294; Z4 = 0.97, P = 0.332). However, the combined evaluation of sCD40L + APACHE II (AUC:0.772, Z = 2.10, P = 0.036) was much better than sCD40L alone in predicting 28-day mortality.ConclusionThe predictive value of sCD40L + APACHE II is better than sCD40L alone for 28-day mortality. sCD40L combined with APACHE II score is valuable for predicting 28-day mortality in elderly patients with sepsis.

Reduced Relapse-Free Survival in Colorectal Cancer Patients with Elevated Soluble CD40 Ligand Levels Improved by Vitamin D Supplementation.

Although elevated serum levels of soluble CD40 ligand (sCD40L) were reported in patients with cancer, the importance of high sCD40L levels in clinical oncology remains unknown. We conducted a post hoc analysis of the AMATERASU randomized clinical trial of vitamin D3 supplementation (2000 IU/day) in patients with digestive tract cancer to assess its significance. Serum sCD40L levels were measured by ELISA in 294 residual samples, and were divided into tertiles. In patients with colorectal cancer (CRC), 5-year relapse-free survival (RFS) rates in the middle and highest tertiles were 61.6% and 61.2%, respectively, which was significantly lower than 83.8% in the lowest tertile. A Cox proportional hazard analysis showed that the lowest tertile had a significantly lower risk of relapse or death than the highest tertile even with multivariate adjustment (hazard ratio (HR), 0.30; 95% confidence interval (CI), 0.11-0.80; p = 0.016). In the subgroup of CRC patients with the highest tertile of sCD40L, the 5-year RFS rate in the vitamin D group was 77.9%, which was significantly higher than 33.2% in the placebo group (HR, 0.30; 95% CI, 0.11-0.81; p = 0.018 [Pinteraction = 0.04]). In conclusion, elevated sCD40L might be a biomarker of poor prognosis in patients with CRC, but vitamin D supplementation might improve RFS in patients with high sCD40L.

Relationship among serum TIMP-1, sCD40L and peripheral neuropathy in type 2 diabetes

Purpose: To determine the correlation of serum TIMP-1 and sCD40L with peripheral neuropathy in type 2 diabetes (T2DM), and potential targets for pharmacological intervention.Methods: The study enrolled 97 subjects with T2DM. The 41 subjects with simple diabetes were classified as T2DM group, while 56 subjects with diabetic peripheral neuropathy (DPN) were included in the DPN group. A control group consisting of 50 healthy volunteers who conducted health checks during a similar time-period was also included. Clinical data and parameters were compared among the three groups, and TIMP-1 and sCD40L levels were determined. Univariate and multivariate logistic regression analyses were conducted to identify factors affecting DPN. The diagnostic value of TIMP-1 and sCD40L in DPN was also determined.Results: Body mass index (BMI) varied among the three groups (p &lt; 0.05), but age or gender were not significantly different (p &lt; 0.05). Duration of diabetes was longer in DPN group than in T2DM group (p &lt; 0.05). The study also revealed statistically significant differences in fasting blood glucose (FBS), postprandial blood glucose, and glycosylated hemoglobin among the three groups. Tissue inhibitor of metalloproteinase-1 (TIMP-1) and soluble CD40 ligand (sCD40L) were important factors that affected the occurrence of diabetic peripheral neuropathy (p &lt; 0.05).Conclusion: TIMP-1 and sCD40L levels reflect neurovascular injury in patients with diabetes, with potential as targets for pharmacological intervention for peripheral neuropathy. These findings espouse crucial clinical implications for early identification and treatment in type 2 diabetes.

Serum sCD40L and IL-31 in Association with Early Phase of IgA Nephropathy

IgA nephropathy (IgAN) is a major cause of chronic glomerulonephritis worldwide. T cell dysregulation has been reported to contribute to the pathogenesis of IgAN. Methods We measured a broad range of Th1, Th2 and Th17 cytokines in the serum of IgAN patients. We searched for significant cytokines, which were associated with clinical parameters and histological scores in IgAN patients. Among 15 cytokines, the levels of soluble CD40L (sCD40L) and IL-31 were higher in IgAN patients and were significantly associated with a higher estimated glomerular filtration rate (eGFR), a lower urinary protein to creatinine ratio (UPCR), and milder tubulointerstitial lesions (i.e., the early phase of IgAN). Multivariate analysis revealed that serum sCD40L was an independent determinant of a lower UPCR after adjustment for age, eGFR, and mean blood pressure (MBP). CD40, a receptor of sCD40L, has been reported to be upregulated on mesangial cells in IgAN. The sCD40L/CD40 interaction may directly induce inflammation in mesangial areas and may therefore be involved in the development of IgAN. The present study demonstrated the significance of serum sCD40L and IL-31 in the early phase of IgAN. Serum sCD40L may be a marker of the beginning of inflammation in IgAN.

Sphingosine 1-Phosphate and Apolipoprotein M Levels and Their Correlations with Inflammatory Biomarkers in Patients with Untreated Familial Hypercholesterolemia.

High-density lipoprotein (HDL)-bound apolipoprotein M/sphingosine 1-phosphate (ApoM/S1P) complex in cardiovascular diseases serves as a bridge between HDL and endothelial cells, maintaining a healthy endothelial barrier. To date, S1P and ApoM in patients with untreated heterozygous familial hypercholesterolemia (HeFH) have not been extensively studied. Eighty-one untreated patients with HeFH and 32 healthy control subjects were included in this study. Serum S1P, ApoM, sCD40L, sICAM-1, sVCAM-1, oxLDL, and TNFα concentrations were determined by ELISA. PON1 activities were measured spectrophotometrically. Lipoprotein subfractions were detected by Lipoprint. We diagnosed FH using the Dutch Lipid Clinic Network criteria. Significantly higher serum S1P and ApoM levels were found in HeFH patients compared to controls. S1P negatively correlated with large HDL and positively with small HDL subfractions in HeFH patients and the whole study population. S1P showed significant positive correlations with sCD40L and MMP-9 levels and PON1 arylesterase activity, while we found significant negative correlation between sVCAM-1 and S1P in HeFH patients. A backward stepwise multiple regression analysis showed that the best predictors of serum S1P were large HDL subfraction and arylesterase activity. Higher S1P and ApoM levels and their correlations with HDL subfractions and inflammatory markers in HeFH patients implied their possible role in endothelial protection.

SCD40L Is Increased and Associated with the Risk of Gestational Diabetes Mellitus in Pregnant Women with Isolated TPOAb Positivity.

Background Autoimmune disorders are associated with gestational diabetes mellitus (GDM) in pregnant women who were positive for thyroid peroxidase antibody (TPOAb). Soluble CD40 ligand (sCD40L) and soluble interleukin-2 receptor (sCD25) are abnormally expressed in autoimmune diseases and are reliable markers of inflammation. The purpose of this study was to evaluate sCD40L and sCD25 in early pregnancy and investigate their correlation with GDM and TPOAb. Methods A total of 126 pregnant women in the first trimester were enrolled for analysis: 93 were positive for TPOAb and 33 were negative for TPOAb. Demographical and clinical data in early pregnancy were collected. A total of 123 participants underwent a 75 g oral glucose tolerance test in the second trimester. Serum sCD40L and sCD25 levels were measured by ELISA. Results The incidence of GDM was 24.4% in pregnant women with isolated TPOAb positivity in our study. Both sCD40L and sCD25 were positively correlated with TPOAb (r = 0.476, P < 0.001; r = 0.188, P < 0.05). sCD40L was highest in (P < 0.001) Ab-positive women with GDM group (P < 0.05). After adjusting for TPOAb, age, TSH, FT4, triglycerides, and low-density lipoprotein cholesterol, multivariate logistic regression analysis showed that sCD40L was an independent risk factor for GDM in pregnant women with TPOAb positivity (odds ratio = 3.235, 95% confidence interval 1.024–10.218, P < 0.05). Conclusions About a quarter of pregnant women with isolated positive TPOAb might have GDM. sCD40L was an independent risk factor for GDM in women with isolated TPOAb positivity.

Analysis of Risk Factors of Coronary Heart Disease and Its Correlation with Inflammatory Factors in Patients with Type 2 Diabetes Mellitus.

In this paper, we propose a new method to analyze the risk factors of coronary heart disease (CHD) and their correlation with inflammatory factors in patients with type 2 diabetes mellitus (T2DM). To verify and implement this idea, we have selected a total of 165 patients with T2DM treated in our hospital from March 2019 to October 2021 that were divided into CHD group (n = 72) and non-CHD group (n = 93) according to the results of coronary angiography. Patients with CHD were divided into three groups according to SYNTAX score: low-risk group, medium-risk group, and high-risk group. The clinical data of all patients were collected. Univariate and multivariate analyses were used to screen the risk factors of CHD in patients with T2DM. The related inflammatory factors such as C-reactive protein (CRP), interleukin-6 (IL-6), and water-soluble CD40 ligand (sCD40L) were detected in all patients. Pearson's linear correlation analysis was used to analyze the correlation between the expression levels of CRP, IL-6, and sCD40L and CHD in patients with T2DM. The receiver working curve (ROC) was used to evaluate the efficacy of IL-6, CRP, and sCD40L in predicting high risk of CHD in patients with T2DM. Multivariate analysis showed that age and course of T2DM, FFA, UA, and Hcy were risk factors for CHD in patients with T2DM. The serum levels of IL-6, CRP, and sCD40L in patients with CHD were significantly higher than those in patients without CHD. According to SYNTAX score, 72 patients with CHD were divided into low-risk group (n = 36), medium-risk group (n = 26), and high-risk group (n = 10). Compared with the low-risk group, the expression levels of serum IL-6 CRP and sCD40L in the middle-risk group and high-risk group were significantly higher than those in the low-risk group. The expression levels of IL-6 CRP and sCD40L in the high-risk group were also significantly higher than those in the medium-risk group. There is a positive correlation between syntactic score and IL-6 expression in patients with T2DM complicated with coronary heart disease (r = 0.778, P < 0.001), with the expression of CRP (r = 0.756, P < 0.001) and with the expression of sCD40L (r = 0.748, P < 0.001). Advanced age, long course of T2DM, elevated levels of FFA, UA, and Hcy are all risk factors of CHD in patients with type 2 diabetes. T2DM patients with the above risk factors should be vigilant and pay attention to monitoring the related indexes of coronary heart disease to avoid the occurrence of serious cardiovascular disease. CRP, IL-6, and sCD40L are involved in the progression of CHD in patients with T2DM. The more severe CHD is, the higher the expression of IL-6, CRP, and sCD40L in serum.

Evaluation of platelet activation marker expression and its correlation with tumorigenesis and tumor progression in patients with gastric cancer.

Gastric cancer (GC) remains responsible for over one million new cases in 2020. Activated platelets express the CD40 ligand (CD40L) and CD62P in the cytoplasmic membrane, and interaction with the vascular endothelium can induce the production of tumor growth factors and metastases. We aimed to characterize the soluble levels of sCD40L and sCD62P in GC patients. A cross-sectional study was performed on 83 GC patients and 20 healthy controls. High levels of sCD40L were obtained in GC patients compared to healthy controls (p = 0.003) and in the I/II compared with III and IV stages (p < 0.0001 and p = 0.007, respectively). Low levels of sCD62P in the GC patients compared to healthy controls (p = 0.009). High soluble levels of sCD62P in I/II compared with III and IV stages (p = 0.002 and p = 0.01, respectively). There are no significant differences in the levels of sCD40L and sCD62P were observed between intestinal, diffuse, and mixed types. We concluded that sCD40L and sCD62P molecules may be predictive biomarkers since the increase in plasma levels was associated with disease progression and metastasis in GC. In addition, the serum sCD40L and sCD62P can potentially be used as an indicator of response to anticancer therapy.

Increased serum levels of sCD40L were associated with rapidly progressive interstitial lung disease in idiopathic inflammatory myopathies.

Whether coagulopathy exists in development of idiopathic inflammatory myopathies associated rapidly progressive interstitial lung disease (IIMs-RPILD) is unclear. In this study, we aimed to investigate soluble CD40 ligand and D-dimer levels in RPILD patients. Patients with IIMs-ILD were enrolled and classified as RPILD and stable-ILD group. Clinical data, laboratory examinations including coagulation-associated parameters and the myositis antibodies status, chest high-resolution computed tomography (HRCT) findings and treatment regimens were collected and serum levels of sCD40L were detected by ELISA. Univariable and adjusted multivariable cox regression were performed to identify risk factors for 6-month mortality, and further to select predictors for establishing predictive model for RPILD. Eighty patients with IIMs-ILD were enrolled and 34 of them were diagnosed as RPILD while 46 as stable-ILD. Multivariable cox regression showed that albumin<32.4 g/L and sCD40L<1658.55 pg/ml were independent risk factors of short-term mortality in RPILD. A SMAD model consisting of serum sCD40L>1054 pg/ml, anti-MDA5 positivity, albumin<32.4 g/L and D-dimer>0.865 mg/L were generated. The odds for RPILD with SMAD score of 0, 1, 2, 3 and 4 were 0, 26.9%, 66.7%, 91.7% and 100%. The 6-month survival stratified by mild (SMAD score 0), moderate (SMAD score 1 and 2) and severe group (SMAD score 3 and 4) were 100%, 79.5% and 20%, respectively. We established a predictive model for IIMs-RPILD, which provided a clue that coagulopathy might exist in IIMs-RPILD and could help to better treat patients with RPILD. This model awaits further validations.

CD38 Deficiency Ameliorates Chronic Graft-Versus-Host Disease Murine Lupus via a B-Cell-Dependent Mechanism.

The absence of the mouse cell surface receptor CD38 in Cd38−/− mice suggests that this receptor acts as a positive regulator of inflammatory and autoimmune responses. Here, we report that, in the context of the chronic graft-versus-host disease (cGVHD) lupus inducible model, the transfer of B6.C-H2bm12/KhEg(bm12) spleen cells into co-isogenic Cd38−/− B6 mice causes milder lupus-like autoimmunity with lower levels of anti-ssDNA autoantibodies than the transfer of bm12 spleen cells into WT B6 mice. In addition, significantly lower percentages of Tfh cells, as well as GC B cells, plasma cells, and T-bet+CD11chi B cells, were observed in Cd38−/− mice than in WT mice, while the expansion of Treg cells and Tfr cells was normal, suggesting that the ability of Cd38−/− B cells to respond to allogeneic help from bm12 CD4+ T cells is greatly diminished. The frequencies of T-bet+CD11chi B cells, which are considered the precursors of the autoantibody-secreting cells, correlate with anti-ssDNA autoantibody serum levels, IL-27, and sCD40L. Proteomics profiling of the spleens from WT cGVHD mice reflects a STAT1-driven type I IFN signature, which is absent in Cd38−/− cGVHD mice. Kidney, spleen, and liver inflammation was mild and resolved faster in Cd38−/− cGVHD mice than in WT cGVHD mice. We conclude that CD38 in B cells functions as a modulator receptor that controls autoimmune responses.

Serum Soluble CD40 Ligand in Predicting Simple Appendicitis and Complicated Appendicitis at Different Time Points in Children.

Objectives: Appendicitis is a common abdominal emergency in children. It is difficult for clinicians to distinguish between simple appendicitis (SA), gangrenous appendicitis (GA), and ruptured appendicitis (RA) in children based on physical and current laboratory tests. Abdominal computed tomography with the disadvantage of excess radiation exposure is usually used in the emergency room for appendicitis surveys. Serum soluble CD40 ligand (sCD40L) is an inflammatory biomarker. This study aimed to use sCD40L to distinguish SA, GA, and RA.Methods: All patients aged <18 years old with suspected appendicitis were tested once for serum sCD40L within 72 h of appendicitis symptoms. We compared sCD40L levels of SA, GA, and RA individually on days 1, 2, and 3 in patients with normal appendix (NA), a total of nine subgroups. Thereafter, the diagnostic performance of sCD40L in predicting appendicitis and the receiver operating characteristic curves were carried out.Results: Of 116 patients, 42 patients had SA, 20 GA, 44 RA, and 10 NA. We found six subgroups with significant p-values of sCD40L predicting appendicitis as follows: SA on day 2, GA on days 2 and 3, and RA on days 1–3. The sensitivity and specificity of sCD40L at the best cutoff point with 178 pg/mL in these six subgroups range from 0.75 to 1.00 and 0.90, respectively.Conclusions: SCD40L is a good predictor of pediatric appendicitis. Clinicians can use sCD40L to distinguish from SA, GA, and RA in children with suspected appendicitis.

Evaluation of Pre-miRNA-146a rs2910164 Variations and sCD40 Ligand in Egyptian Patients with Rheumatoid Arthritis

Abstract Background: Patients with Rheumatoid Arthritis (RA) are at greater risk of developing Cardiovascular (CV) events with higher rate of subsequent mortality. MicroRNAs (miR-NAs) such as MiR-146a are thought to have an important role in the pathogenesis of RA. CD40-CD40L interaction is poten-tially involved in atherogenesis and plaque rupture in RA, it can be a risk factor in development of accelerated vascular complications in RA patients. Aim of Work: Our aim is to evaluate the level of sCD40L, investigate the genetic variations (polymorphisms) in pre-miRNA-146a rs2910164 in a cohort of Egyptian RA patients and detect their possible relation to CV risk in RA. Methods: 108 RA patients were enrolled in our study and were divided into 2 groups according to presence and absence of CV risk along with 49 controls. Genotyping of pre-microRNA-146a rs2910164 polymorphism was done by Taq-Man real-time PCR and serum sCD40L levels were measured using human soluble CD40L ELISA assay. Results: sCD40L concentration was significantly lower in RA patients without CV risk and RA patients with CV risk when compared to control group (p < 0.001), but there was no statistically significant difference when comparing both patients' groups (p=0.5). The genotype and allele frequencies of pre-microRNA-146a rs2910164 did not show a statistically significant difference between the studied groups. When comparing RA group without CV risk, RA group with CV risk and control group, GG genotype was 41.8%, 39.6% and 32.7%, GC was 40%, 49.1% and 51% and CC was 18.2%, 11.3% and 16.3%, respectively. G allele frequency in RA without CV risk group, RA with CV risk group and control group was 35.2%, 35.2% and 29.5% and C allele frequency was 34.7%, 31.4% and 33.9%, respectively. Conclusion: Pre-miRNA-146a rs2910164 gene variations were not associated with RA and does not increase the sus-ceptibility to cardiovascular disease. Low serum levels of sCD40L were detected in RA patients irrespective of the presence of cardiovascular risk. Evaluating sCD40L in patients not receiving any treatment and comparing them with post-treatment levels is recommended.

Curcumin's Effect on Inflammatory Response following Percutaneous Coronary Intervention in Adult Patients with Stable Coronary Heart Disease.

Cardiovascular diseases play major roles in the health problems worldwide especially in Indonesia. Percutaneous coronary intervention (PCI) is a minimally invasive procedure with relatively low complications. However, high inflammatory response post-PCI has showed adverse events even after administration of standard medication. Previous studies showed that curcumin was able to reduce inflammatory response in adult patients with stable coronary heart disease (CHD). This article determines the efficacy of oral administration of curcumin in reducing inflammatory response post-PCI with stable CHD. A double-blind randomized controlled trial on 50 adult patients comparing curcumin and placebo was performed in Cipto Mangunkusumo General Hospital and Jakarta Heart Center within April and June 2015. Either curcumin (45 mg/day) or placebo was given 7 days prior to PCI until 2 days after PCI. Inflammatory markers (high-sensitivity C-reactive protein [hsCRP] and soluble CD40 ligand [sCD40L]) were measured in three phases (7 days prior PCI, 24 hours post-PCI, and 48 hours post-PCI). There were no significant differences in the reduction of hsCRP and sCD40L between curcumin and placebo groups in three phases of measurement. Curcumin significantly reduce the serum hsCRP ( p = 0.006) and sCD40L ( p = 0.002) 7 days before PCI to 48 hours post-PCI. The decrement of hsCRP (-14.2% vs. -7.4%) and sCD40L (-24.3% vs. -13.2%) from 24 to 48 hours post-PCI was higher in the curcumin group than placebo group. The administration of curcumin 45 mg dose daily for 7 days prior PCI until 48 hours post-PCI is useful in reducing inflammatory response post-PCI with stable CHD.

Persistently higher serum sCD40L levels are associated with outcome in septic patients

BackgroundSoluble CD40 ligand (sCD40L) exhibits proinflammatory and procoagulant effects. Recent data indicated that sCD40L plays a significant role in septic patients. The aim of the present study was to determine sCD40L changes in surgical patients without sepsis (SWS) and surgical sepsis patients (SS) during the first 3 days after intensive care unit (ICU) admission and to observe the association between sCD40L and mortality.MethodsTime changes in sCD40L levels were assessed for 3 days after ICU admission in 49 patients with SS and compared with those in 19 SWS patients. Serum sCD40L concentration was detected by ELISA. Survival at 28 days served as the endpoint.ResultsSS had significantly higher sCD40L levels than SWS and control patients. We observed an association between sCD40L levels ≥1028.75 pg/mL at day 2 and 28-day mortality (odds ratio = 7.888; 95% confidence interval = 1.758 to 35.395; P = 0.007). We could not discover any significant differences in sex, presence of septic shock, site of infection, length of stay in the ICU, PaO2/FiO2 ratio, incidence of AKI, ARDS, or type of surgery between nonsurvivors and survivors.ConclusionsSeptic patients show persistently higher circulating sCD40L levels in the first 3 days after ICU admission, and serum sCD40L levels are associated with the mortality of patients with sepsis. Thus, serum sCD40L may be used as a reliable biomarker and therapeutic target in sepsis.

The Proinflammatory Soluble CD40 Ligand Is Associated with the Systemic Extent of Stable Atherosclerosis.

Background and objectives: Polyvascular atherosclerosis is frequent and associated with a high cardiovascular risk, although the mechanisms regulating the atherosclerosis extent to single or multiple arterial territories are still poorly understood. Inflammation regulates atherogenesis and soluble CD40 ligand (sCD40L) is an inflammatory mediator associated with the presence of single-territorial atherosclerosis. We assessed whether the sCD40L expression is associated with the atherosclerosis extent to single or multiple arterial territories and with the atherosclerosis severity in different territories. Materials and Methods: We prospectively enrolled 94 participants with no atherosclerosis (controls, n = 26); isolated coronary atherosclerosis (group 1, n = 20); coronary and lower extremity (LE) atherosclerosis (group 2, n = 18); coronary and carotid atherosclerosis (group 3, n = 12); and coronary, LE, and carotid atherosclerosis (group 4, n = 18). Serum sCD40L levels were quantified. Results: The sCD40L levels (ng/mL, mean (standard deviation)) were 4.0 (1.5), 5.6 (2.6), 7.2 (4.2), 5.9 (3.7), and 5.1 (2.4) in controls and groups 1 to 4, respectively (ANOVA p = 0.012). In nonrevascularized patients, the sCD40L levels were significantly higher in group 2 than in group 1 and were correlated with the number of LE diseased segments. Prior LE bypass surgery was associated with lower sCD40L levels. Coexistence of coronary and LE atherosclerosis was independently associated with the sCD40L levels. Conclusions: The sCD40L levels were increased in stable atherosclerosis, particularly in polyvascular coronary and LE atherosclerosis. The number of LE diseased segments and prior LE revascularization were associated with sCD40L expression. To our knowledge, these are novel data, which provide insights into the mechanisms underlying multi-territorial atherosclerosis expression. sCD40L may be a promising noninvasive tool for refining the stratification of the systemic atherosclerotic burden.

A study of Serum Soluble CD40 Ligand level and its correlation with serum CK-MB and lipid profile in patients with acutecoronary syndrome

Introduction: Coronary heart disease is an impairment of heart function due to inadequate blood flow to the heart. It is the most common cause of death worldwide. Serum sCD40L is an inflammatory marker. It is released from the platelets as soon as the onset of the chest pain. It is a strong predictor of cardio vascular risk factor. Objectives: To estimate Serum sCD40Ligand, Serum CK-MB, Serum Lipid Parameters, Serum LDH, and Serum AST levels in patients with ACS. Materials and Methods:Study group comprised of 50 subjects were admitted in ICCU with ACS. 50 healthy sex and age matched subjects were taken as control groups. Venous blood samples were collected. Serum Soluble CD40Ligand was estimated by ELISA technique, Serum CK-MB estimated by Immunoinhibition method, Serum Lipid profile by enzymatic assay methods. Serum LDH by DKGC method, Serum AST by Modified IFCC method. Results:There was significant increase in Serum sCD40L(psignificant decrease in the Sr. HDL-C levels in the ACS patients compared to control group. There was no significant change in Sr. LDH levels and Sr. AST levels in ACS patients compared to control group. There was a significant positive correlation between Serum sCD40L and Serum CK-MB, Serum TC, Serum TGL, Serum LDL-C, Serum VLDL and a negative correlation between Serum sCD40L and Serum HDL-C while no significant correlation was found between Serum sCD40L with Serum LDH and Serum AST levels. Conclusion:Serum sCD40L can be used as a marker in individuals with Acute Coronary Artery disease. Keywords: sCD40L, ACS, MI, CK-MB, Lipid Parameters

The Interplay Between Innate Immunity (TLR-4) and sCD40L in the Context of an Animal Model of Colitis-associated Cancer.

Several studies have found elevated soluble CD40 Ligand (sCD40L) in the serum of patients with malignancies as well as those with inflammatory bowel disease (IBD). Our goal was to determine the possible causal role of sCD40L in colitis-associated colorectal cancer (CAC) by using the well-established azoxymethane/dextran sulfate sodium (AOM/DSS) protocol. Twelve wild type (WT) and twelve TLR4 knock out (KO) female C57BL6 mice were divided into 4 experimental groups. Six WT and six TLR4 KO mice were treated with a single intraperitoneal dose (10 mg/kg of body weight) of AOM followed by three 7-day cycles of oral 2.5% DSS. The other two groups included 6 WT and 6 TLR4 KO mice that received only water and served as the control groups. The mice were sacrificed after 84 days. All mice in the AOM/DSS WT group developed CAC while all mice from the AOM/DSS TLR4 KO group were protected from CAC. We measured the serum and pathologic tissue levels of sCD40L with quantitative sandwich enzyme-linked immunoassay (ELISA) and found that serum sCD40L was significantly higher in wild-type mice that developed CAC compared to their healthy counterparts (wild-type and TLR-4 KO controls). In comparison, serum sCD40L levels were comparable between TLR-4 KO mice, which are protected from developing CAC, and their healthy counterparts (wild-type and TLR-4 KO controls). Of note, tissue levels of sCD40L were not affected by the development of CAC. Our findings point to the presence of an axis between TLR-4 and sCD40L, which may lead to decreased immunosurveillance and the subsequent development of colitis-associated cancer.

Role of inflammation in initiation and maintenance of atrial fibrillation in rheumatic mitral stenosis - An analytical cross-sectional study.

BackgroundInflammation has been implicated in the initiation and perpetuation of non‐valvular atrial fibrillation (AF). However, there is a lack of similar data on AF in rheumatic heart disease (RHD). The objective of this study was to analyze the association of inflammation as measured by serum inflammatory biomarkers with AF in rheumatic mitral stenosis (Rh‐MS).MethodsA comparative cross‐sectional analytical study was conducted on 181 Rh‐MS patients in normal sinus rhythm (NSR; n = 69), subclinical transient AF (SCAF; detected by 24‐hours Holter monitoring; n = 30) and chronic AF (n = 82). Serum hs‐CRP, IL‐6, and sCD‐40L were assessed using ELISA immunoassay and compared in all groups of Rh‐MS with or without AF.ResultsWe found significantly higher serum hs‐CRP and sCD‐40L levels in the overall AF (Chronic AF + SCAF) group (hs‐CRP: 4.5 ± 3.4 vs 2.3 ± 2.9 mg/L, P < .01; sCD‐40L: 6.4 ± 4.8 vs 3.1 ± 3.4 ng/mL, P < .01) and chronic AF subgroup (hs‐CRP: 4.9 ± 3.4 vs 2.3 ± 2.9 mg/L, P < .01; sCD‐40L: 6.9 ± 5.1 vs 3.1 ± 3.4 ng/mL, P < .01) compared to patients with sinus rhythm. There was a statistically significant graded increase of serum IL‐6 level from the NSR to the SCAF (vs NSR: 6.8 ± 3.9 vs 4.0 ± 2.2 pg/mL, P = .03), and chronic AF subgroups (vs NSR: 9.3 ± 6.5 vs 4.0 ± 2.2 pg/mL, P < .01; vs SCAF: 9.3 ± 6.5 vs 6.8 ± 3.9, P = .05) of atrial fibrillation.ConclusionsElevated levels of serum hs‐CRP, IL‐6, and sCD‐40L were strongly associated with overall AF and also with SCAF and chronic AF in Rh‐MS patients indicating a potential role of inflammation in the pathophysiology of rheumatic AF.