Soluble L-selectin Research Articles

Abstract B082: A pro-tumorigenic, aged microenvironment may aid in worsened disease progression in an HGSOC model

Abstract Over 70% of HGSOC patients are diagnosed after 55 and the average patient succumbs to disease at 70 years old. Despite this, most ovarian cancer research, and cancer studies generally, utilize young mice that are mimetic of human teenagers and/or do not investigate age as a variable despite it being the top cancer risk factor. An improved understanding of how age affects HGSOC progression may enable development of alternative treatment strategies aimed at intercepting metastasis and preventing cancer cells from establishing in the peritoneum. Our preliminary studies show tumor burden and disease severity are significantly higher in aged versus young animals. We developed an epithelial cell line derived from C57Bl/6 oviducts and used CRISPR-Cas9 genome editing to develop a syngeneic tumorigenic line harboring Trp53, Pten, and Brca2 deletions. After intraperitoneal injection into 6-week and 14-month-old immunocompetent C57Bl/6 mice, we observed a stark increase in tumor burden in aged mice. Furthermore, older mice died at a faster rate; all aged mice succumbed to disease within 1-month of inoculation compared to young mice surviving up to 3 months. Total RNA-sequencing of tumors harvested from aged and young mice is ongoing. Characterization of the tumor-naïve peritoneal compartment revealed the aged microenvironment to be highly inflammatory. When assessed via cytokine array, peritoneal fluid of aged mice had higher concentrations of inflammatory markers including soluble TNF receptor-1 (sTNFR-1), L-selectin, and VCAM-1. Flow cytometry of peritoneal lavage indicated an over 2-fold increase in the number CD45+ cells present in the peritoneal cavity, coinciding with cytokine array results. Within this population, there was nearly complete depletion of macrophage and neutrophil populations and a significant increase in B cells and CD4+ and CD8+ T cells. The percentage of PD-1+ CD8+ cells also increased. In addition to increased signs of inflammation, a significantly higher concentration of insulin-like growth factor-1 (IGF-I) and higher concentrations of the associated IGF binding proteins -3 and -6 were found in peritoneal fluid of aged mice. In addition, during tissue collection, organs of the aged mice were found to be much larger than young mice, a common effect of elevated IGF-I; aged omentum weighed 2-4 times that of young. Notably, IGF-I is known to inhibit apoptosis and promote proliferation and increased IGF-I is correlated with increased risk of breast, prostate, and lung cancer. A drastic difference in disease severity occurs when identical cancer cells are injected into 6-week and 14-month-old mice. To identify possible microenvironmental differences in the two populations, a broad panel of cytokines was assessed, and immune populations were quantified in pre-cancerous mice. Overall, multiple pro-inflammatory markers and the number of lymphocytes were upregulated in the aged peritoneal cavity, and markers of immune fatigue were present. Further work is aimed at identifying immune cell state via further cytometry and sequencing. Citation Format: Katherine A. Cummins, Ronny I. Drapkin, Matthew Knarr. A pro-tumorigenic, aged microenvironment may aid in worsened disease progression in an HGSOC model [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B082.

Early detection and correlation of tear fluid inflammatory factors that influence angiogenesis in premature infants with and without retinopathy of prematurity.

To measure the levels of inflammatory factors in tear fluid of pre-term infants with and without retinopathy of prematurity (ROP). The cross-sectional pilot study included 29 pre-term infants undergoing routine ROP screening. Pre-term infants were grouped as those without ROP (no ROP; n = 14) and with ROP (ROP; n = 15). Sterile Schirmer's strips were used to collect the tear fluid from pre-term infants. Inflammatory factors such as interleukin (IL)-6, IL-8, MCP1 (Monocyte Chemoattractant Protein 1; CCL2), RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted; CCL5), and soluble L-selectin (sL-selectin) were measured by cytometric bead array using a flow cytometer. Birth weight (BW) and gestation age (GA) were significantly (P < 0.05) lower in pre-term infants with ROP compared with those without ROP. Higher levels of RANTES (P < 0.05) and IL-8 (P = 0.09) were observed in the tear fluid of pre-term infants with ROP compared with those without ROP. Lower levels of tear fluid IL-6 (P = 0.14) and sL-selectin (P = 0.18) were measured in pre-term infants with ROP compared with those without ROP. IL-8 and RANTES were significantly (P < 0.05) higher in the tear fluid of pre-term infants with stage 3 ROP compared with those without ROP. Tear fluid RANTES level was observed to be inversely associated with GA and BW of pre-term infants with ROP and not in those without ROP. Furthermore, the area under the curve and odds ratio analysis demonstrated the relevance of RANTES/BW (AUC = 0.798; OR-7.2) and RANTES/MCP1 (AUC = 0.824; OR-6.8) ratios in ROP. Distinct changes were observed in the levels of tear inflammatory factors in ROP infants. The status of RANTES in ROP suggests its possible role in pathobiology and warrants further mechanistic studies to harness it in ROP screening and management.

АНАЛИЗ МАРКЕРОВ СИСТЕМЫ ГЕМОСТАЗА У ПАЦИЕНТОВ С ФИБРИЛЛЯЦИЕЙ ПРЕДСЕРДИЙ НЕКЛАПАННОГО ГЕНЕЗА С ТРОМБОЭМБОЛИЧЕСКИМИ ОСЛОЖНЕНИЯМИ

Introduction. Atrial fibrillation (AF) is one of the most common heart rhythm disorders. The risk of developing thromboembolic complications, including ischemic stroke, in patients with AF is 5 times higher than that in patients with sinus rhythm; therefore, one of the main directions in the treatment of patients with this rhythm disorder is the prevention of thromboembolic complications. Objective: to study the markers of monitoring the blood coagulation system in the blood serum of patients with non-valvular AF receiving anticoagulant therapy and having a history of thrombotic and thromboembolic complications. Materials and methods. The study included 31 healthy volunteers (without a history of AF, thrombosis) and 31 patients over 18 years of age with a diagnosis of AF (mean age 66.2±8.1), receiving anticoagulant therapy and having a history of thrombotic and thromboembolic events. complications. Therapy taken by patients at the time of inclusion in the study was in line with current recommendations and included standard conventional antiarrhythmic and anticoagulant therapy, as well as therapy for the underlying cardiovascular disease. Biomarkers of thrombus formation and pro-inflammatory activation (L-selectin, thrombomodulin) were determined by enzyme immunoassay using diagnostic kits from BiomedicaGmbH, Austria. Results. During the screening of 2820 patients treated in the Department of CHLSRS&amp;EX for the nosology of AF in the period 01.2020-01.2023, 31 patients were included in the study, who were diagnosed with thrombotic and thromboembolic complications (0.01% of the total number of screened patients) against the background of regular anticoagulant therapy . Among all patients included in the study, thrombotic complications in AF were as follows: thrombosis of the left atrial appendage was noted in 17 patients (54%), spontaneous echo contrast of grade II or more in 5 patients (16%), cardioembolic stroke - in 3 patients (10%) , thrombosis of peripheral arteries (2 (6%)), thrombosis on EKS electrodes (2 (6%)). The concentration of soluble thrombomodulin in the blood serum of patients with thrombotic and thromboembolic complications was reduced compared with the group of healthy volunteers (2073.0±548.6 vs. 2845.3±726.4 pg/ml; p=0.004). Serum levels of L-selectin in patients with thrombotic and thromboembolic complications were reduced compared to healthy volunteers (1.5±0.6 vs. 2.4±1.3 µg/mL; p=0.04). Conclusion. In patients with thrombotic and thromboembolic complications that occurred against the background of adequate anticoagulant therapy, there was a decrease in serum soluble thrombomodulin and L-selectin, which may indicate damage to the endothelium, activation of thrombus formation and inflammation.

Increased endothelial biomarkers are associated with HIV antiretroviral therapy and C-reactive protein among a African rural population in Limpopo Province, South Africa.

In Sub-Saharan Africa (SSA) endothelial dysfunction (ED) and chronic inflammation in the HIV-positive adults population who are on highly active antiretroviral therapy (HAART) are not fully explored. We determined the effect of HAART on chronic inflammation and ED among HAART-exposed adults in a rural setting. Weight and height were measured to quantify the body mass index (BMI). Lipid and Glucose levels were determined. C-reactive protein (CRP), L-selectin, soluble intercellular adhesion molecule (sICAM-1), and soluble vascular cell adhesion molecule (sVCAM-1) in serum samples were tested. The majority of the HAART-exposed group were on treatment for <5 years. Soluble intercellular adhesion molecules, sVCAM-1, L-selectin and CRP were elevated in the HIV-infected groups as compared to the control group. The multivariate analysis showed that HIV infection (HAART-naïve) associated with increased sICAM-1 (β = 0.350; 95% CI: 0.035-0.664, p = 0.029) and L-selectin (β = 0.236; 95% CI: 0.038-0.434, p = 0.019) but not sVCAM-1 (β = 0.009; 95% CI: 0.252-0.270, p = 0.468). The HAART-exposed group is associated with sVCAM-1 (β = 0.250; 95% CI: 0.015-0.486, p = 0.037) but not with sICAM-1- (β = 0.253; 95% CI: -0.083-0.590, p = 0.14) and L-selectin (β = 0.119; 95% CI: -0.016-0.253, p = 0.084). sVCAM-1 was associated with decreased alcohol consumption (β = -0.245; 95% CI: -0.469-0.021, p = 0.032) while L-selectin was associated with decreased total cholesterol (β = -0.061; 95% CI: -0.124-0.002, p = 0.05) and increased CRP (β = 0.015; 95% CI: 0.009-0.022, p < 0.001). Increased endothelial biomarkers were associated with HIV disease and HAART in a rural black adult population of African descent after controlling for CVD risk factors. Inflammation (as measured with CRP) may play an important role in endothelial activation. Further studies are needed to explore the association between endothelial dysfunction and inflammation especially among the HIV-positive population on HAART in similar settings.

Endothelial Nitric Oxide Synthase (eNOS) Gene Polymorphisms and Markers of Hemolysis, Inflammation and Endothelial Dysfunction in Brazilian Sickle Cell Anemia Patients.

The impaired bioavailability of endogenous nitric oxide (NO) in sickle cell anemia (SCA) may be influenced by polymorphisms in the endothelial nitric oxide synthase gene (eNOS). We compared allelic/genotypic frequencies of the eNOS polymorphisms T-786C, VNTR4a/b and G894T between 89 adult SCA patients and 100 healthy controls, and investigated the relationship between these SNPs and markers of hemolysis [lactate dehydrogenase (LDH), indirect bilirubin (IB) and reticulocyte counts], inflammation [interleukins IL-1β, IL-6, IL-8, Tumor Necrosis Factor (TNF-α) and C-reactive protein (CRP)] and endothelial dysfunction (ED) [soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble L-selectin (sL-selectin), von Willebrand Factor (vWF) antigen and D-dimers] in the patients. The frequencies of the mutant -786C allele and -786C/C genotype were significantly higher in patients (p = 0.02 and p = 0.04, respectively) but not significantly correlated with the markers. For VNTR4a/b and G894T, the allelic/genotypic frequencies did not statistically differ between patient and control groups. Patients carrying the 4a allele and those with the 894G/G genotype showed a significant decrease in IB (p = 0.02 and p = 0.04, respectively), and only patients with the 4a allele exhibited reduced IL-1β (p = 0.01). The correlation profiles between markers of inflammation and ED significantly differed between patients carrying the mutant alleles and those with wild-type genotypes. This appears to be the first report on the relationship between eNOS gene polymorphisms and markers of hemolysis, inflammation and ED in Brazilian SCA patients. Our results indicate that the SNPs analyzed may influence the phenotypic variability of these patients.

Assessment of Serum Levels of E-Selectin and L-Selectin in Alopecia Areata

Background: Alopecia Areata (AA) is an immune system disease that invades anagen Hair Follicles (HFs) and shows multifactorial etiology. One of the essential histopathological features of AA is a lymphocytic intrusion that envelops HFs. Soluble forms of Endothelial (E), Lymphocytic (L), and Platelets (P)-selectins are known markers of persistent bothering. There are limited examinations for the assessment of serum levels of soluble E-selectin, L-selectin, and P-selectin in patients with AA. Objectives: We assessed serum levels of soluble E-selectin and L-selectin in patients with in association with the control group to determine their role in the pathogenesis of the disease. Methods: The study included 30 patients with AA and 10 healthy subjects who served as controls. Blood samples were taken from all patients and controls. The serum levels of soluble E-selectin and L-selectin were determined with the Enzyme-linked Immunosorbent Assay (ELISA) method. Results: Higher levels of sE-selectin and sL-selectin were found in AA patients than in controls. There was a significant relationship between the higher serum levels of sE-selectin and the increased size of lesions with time. There was a significant positive correlation between the serum levels of sE-selectin and sL-selectin and the percentage of hair loss. Conclusions: This study showed that sE-selectin and sL-selectin may play a significant role in the pathogenesis of AA and might open a way to future treatments for this disease.

L-Selectin Expression is Influenced by Phosphatase Activity in Chronic Lymphocytic Leukemia.

Adhesion receptors have important role in cellular invasiveness and L-selectin is a primary determinant in the binding of chronic lymphocytic leukemia (CLL) cells to several glycated proteins on endothelial cells. We investigated L-selectin expression on CLL cells and explored the mechanisms that lead to their shedding. Surface and soluble L-selectin expression levels were studied by flow cytometry and immunoassay, respectively. Magnetically isolated B-cells from patients and controls were investigated for total and protein phosphatase-2A activities. Flow cytometry of permeabilized cells was utilized for the determination of phosphorylated mitogen-activated protein kinase (pp38MAPK) and surface tumor necrosis factor alpha-converting enzyme expression (TACE). In CLL patients elevated absolute lymphocyte cell counts, high soluble and low surface L-selectin expression were observed. Similarly, TACE surface expression was significantly lower on B-CLL cells compared to normal B-cells. Both total phosphatase and protein phosphatase-2A activities were also significantly lower in B-CLL cells compared to normal B-cells and we found a consequently higher level of pp38 MAPK in B-CLL cells. Based on in vitro experiments a MAPK inhibitor could attenuate the phosphatase inhibitor's effect on L-selectin shedding. The lower phosphatase activity detectable in chronic lymphocytic leukemia, results in a downstream signaling cascade with subsequent reduction of surface L-selectin expression and this effect is mediated by enhanced phosphorylation of p38MAPK and an altered TACE expression. © 2019 The Authors. Cytometry Part B: Clinical Cytometry published by Wiley Periodicals, Inc. on behalf of International Clinical Cytometry Society.

The Role of Soluble L-Selectin with Polymorphism in Iraqi Arabs Patients with Diabetes Mellitus Type 2

Diabetes mellitus type 2 [DMT2] is a disturbance of metabolism and complex diseases influenced by environmental, genetic agents, and linked with inflammation, happens when the pancreas either does not use the insulin as it should or the body does not make enough insulin, lead to insulin resistance [IR] alongside with gradual loss of ß-cell secretory ability. The aim of this study was to investigate the role of soluble L-selectin (sL-selectin) in diabetes mellitus type 2 patients in Iraqi Arabs patient. Study includes seventy six Iraqi Arabs patients (male and female) having newly diagnosed type 2 diabetes mellitus (T2DM), with Fifty three Iraqi Arabs healthy subjects matched in age, sex and ethnic group. Patients and healthy subjects were genotyped, by PCR-RFLP analysis, and mesure serum level of L-selectin by enzyme-linked immunosorbent assay (sandwich ELISA) test include 65 patients and 23 controls. The statistical analysis of serum level of sL-selectin in study groups showed that the mean of sL-selectin level high significantly increased in patients group (10.708±1.1007) compared to control group (7.055±0.767) respectively. Thus, our results suggest soluble L-selectin play a role in the development of DMT2 in Iraqi Arabs patients. Present results showed that genotype PS associated with increase the susceptibility of DMT2.

ITRAQ Coupled with 2DLC-MS/MS to Screen and Identify Speci-fic Bio-markers of T-Cell Acute Lymphoblastic Leukemia

To screen and identify potential biomarkers specific for T-cell acute lymphoblastic leukemia (T-ALL). Sera were collected from 20 newly diagnosed B-cell acute lymphoblastic leukemia (B-ALL) patients and 20 T-ALL patients. Proteins were extracted, purified and digested with trypsin. All specimens were analyzed by isobaric tags for relative and absolute quantification (iTRAQ) and two-dimensional liquid chromatography-tandem mass spectrometry (2DLC-MS/MS) in a data-dependent mode. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the expression of serum soluble L-selectin (sL-selectin). A total of 468 proteins were identified from distinct peptides. Compared with B-ALL group, 31 proteins were significantly differentially up-regulated while 7 proteins were significantly down-regulated in T-ALL group, sL-selectin was the higher up-regulated in these differential expression proteins. The overexpression of sL-selectin in T-ALL was verified by ELISA. There are the differentially expressed proteins between T-ALL and B-ALL, and the sL-selectin is specific for T-ALL, which can not only become a new biomarker for the diagnosis and prognosis of T-ALL, but also can be used as a potential target for therapy of this leukemia.

Flow Cytometric Bead Sandwich Assay Based on a Split Aptamer.

A few aptamers still bind their targets after being split into two moieties. Split aptamers have shown great potential in the development of aptameric sensors. However, only a few split aptamers have been generated because of lack of knowledge on the binding structure of their parent aptamers. Here, we report the design of a new split aptamer and a flow cytometric bead sandwich assay using a split aptamer instead of double antibodies. Through DMS footprinting and mutation assay, we figured out the target-binding moiety and the structure-stabilizing moiety of the l-selectin aptamer, Sgc-3b. By separating the duplex strand in the structure-stabilizing moiety, we obtained a split aptamer that bound l-selectin. After optimization of one part of the split sequence to eliminate the nonspecific binding of the split sequence pair, we developed a split-aptamer-based cytometric bead assay (SACBA) for the detection of soluble l-selectin. SACBA showed good sensitivity and selectivity to l-selectin and was successfully applied for the detection of spiked l-selectin in the human serum. The strategies for generating split aptamers and designing the split-aptamer-based sandwich assay are simple and efficient and show good practicability in aptamer engineering.

Evaluation of Soluble L-Selectin (CD 62L)Level in Embryo Culture Media to Embryo Quality and Implantation Rate

Evaluation of Soluble L-Selectin (CD 62L)Level in Embryo Culture Media to Embryo Quality and Implantation Rate

A novel and accurate microfluidic assay of CD62L in bladder cancer serum samples.

We report a low-cost, sensitive, bead-based electrochemical immunoarray for soluble L-selectin (or CD62L protein), a potential biomarker for staging bladder cancer. We used a semi-automated modular microfluidic array with online antigen capture on superparamagnetic beads, which were subsequently delivered to a detection chamber housing multiple sensors. The assay was designed to accurately detect CD62L in diluted serum with a limit of detection (LOD) of 0.25 ng mL-1 and a dynamic range of 0.25-100 ng mL-1. The microfluidic array gave significantly better accuracy and higher sensitivity than a standard ELISA kit, which was shown to be subject to significant systematic error at high and low concentration ranges. 31 serum samples from patients with varying grades of bladder cancer and cancer-free controls were analyzed by the immunoarray and ELISA, and the CD62L levels correlated. This work establishes a new accurate assay for determining CD62L levels and highlights the potential of this protein as a biomarker for detecting locoregional progression of bladder cancer.

TREM-1 SNP rs2234246 regulates TREM-1 protein and mRNA levels and is associated with plasma levels of L-selectin.

High levels of TREM-1 are associated with cardiovascular and inflammatory diseases risks and the most recent studies have showed that TREM-1 deletion or blockade is associated with up to 60% reduction of the development of atherosclerosis. So far, it is unknown whether the levels of TREM-1 protein are genetically regulated. Moreover, TREM family receptors have been suggested to regulate the cellular adhesion process. The goal of this study was to investigate whether polymorphisms within TREM-1 are regulating the variants of serum TREM-1 levels and the expression levels of their mRNA. Furthermore, we aimed to point out associations between polymorphisms on TREM-1 and blood levels of selectins. Among the 10 SNPs studied, the minor allele T of rs2234246, was associated with increased sTREM-1 in the discovery population (p-value = 0.003), explaining 33% of its variance, and with increased levels of mRNA (p-value = 0.007). The same allele was associated with increased soluble L-selectin levels (p-value = 0.011). The higher levels of sTREM-1 and L-selectin were confirmed in the replication population (p-value = 0.0007 and p-value = 0.018 respectively). We demonstrated for the first time one SNP on TREM-1, affecting its expression levels. These novel results, support the hypothesis that TREM-1 affects monocytes extravasation and accumulation processes leading to atherogenesis and atherosclerotic plaque progression, possibly through increased inflammation and subsequent higher expression of sL-selectin.

The effect of adhesives on inflammatory immune-markers during renal injury healing.

Renal injury is common in abdominal trauma. Adhesives and sealants can be used to repair and preserve damaged organs. We describe the effect of three biomaterial treatments (TachoSil, GelitaSpon, and Adhflex) on injured renal tissue. Renal traumatic injuries were experimentally induced in male Wistar rats (n = 90) using a punch. Animals were divided into five groups: (1) sham noninjured (n = 3) and punch injury groups; (2) nontreated (n = 6); (3) TachoSil (n = 27); (4) GelitaSpon (n = 27); and (5) Adhflex (n = 27). Wound healing was evaluated 2, 6, and 18 days postinjury by inflammatory cytokines response, histopathological evolution of lesions, inflammatory reaction markers (CD68), and vascular neoformation (CD31). The TachoSil group showed the least inflammatory reaction among the three treated groups, which showed similarly low inflammatory reaction 18 days postinjury. Ciliary neurotrophic factor, soluble intercellular adhesion molecule-1, L-selectin, thymus chemokine, and TIMP metallopeptidase inhibitor 1 expression peaked between 2 and 6 days postinjury. TachoSil promoted the highest cytokine expression. The Adhflex group had the highest CD31 inflammatory immune-marker levels at 2 and 6 days postinjury, but there was a similar decrease in CD31 levels in all three groups at 18 days postinjury. The results show that all three sealant treatments induced a normal healing process with the typical pattern of proinflammatory cytokine and immune-marker expression. Each tested sealant substance could be suitable treatment for renal lacerations. The findings of this study indicate that Adhflex® elastic cyanoacrylate does not induce an adverse inflammatory reaction, and therefore, could be considered as one of the first-line treatments for renal injuries. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1444-1455, 2018.

Influence of haplotypes, gene expression and soluble levels of L-selectin on the risk of acute coronary syndrome

BackgroundL-selectin gene (SELL) is a candidate gene for the development of acute coronary syndrome (ACS) that contributes to endothelial dysfunction. The −642C>T (rs2205849) and 725C>T (rs2229569) polymorphisms have been associated with changes in gene expression, ligand affinity and increased risk of cardiovascular disease. The aim of this study was to investigate the association between the haplotypes constructed with the −642C>T and 725C>T polymorphisms of the SELL gene, the expression levels of its mRNA and the serum levels of soluble L-selectin with ACS. MethodsWe recruited 615 individuals of Mexican origin matched by age, including 342 patients with ACS and 273 individuals without personal history of ischemic cardiopathy as control group (CG). Genotyping was performed by PCR-RFLP. The qPCR technique was used to analyze the expression of mRNA using TaqMan® UPL probes. The levels of soluble L-selectin were measured with ELISA. ResultsThe allele variants in both polymorphisms were over-represented in the CG compared to the ACS (OR range: 0.371–0.716, p<0.006). The CT and TT haplotypes had a protective effect against the development of ACS (OR=0.401, p<0.0001; OR=0.628, p<0.0001, respectively). SELL expression was 3.076 times higher in the ACS group compared to CG (p<0.001). The levels of soluble L-selectin were similar between ACS and CG. ConclusionsBoth polymorphisms had no effect on mRNA expression and soluble protein levels. The polymorphisms −642C>T and 725C>T of the SELL gene are protective factors against the development of ACS. There is an increased gene expression of L-selectin in ACS compared to CG in the population of Western Mexico.

Plasma soluble L-selectin in medicated patients with schizophrenia and healthy controls.

Immune dysfunction has been implicated in the pathophysiology of schizophrenia. Leukocyte migration to the site of inflammation is a fundamental step of immune response which involves P-, E-, and L-selectins. Elevated selectin levels have been reported in un-medicated first-episode patients with schizophrenia but not in medicated patients with multi-episode schizophrenia. We measured fasting plasma soluble P-, E-, and L-selectin in 39 medicated patients with multi-episode schizophrenia and 19 healthy controls. In patients, psychotic symptom severity and cognitive function were assessed with the Positive and Negative Syndrome Scale (PANSS) and the NIH Toolbox Cognitive Test Battery respectively. C-reactive protein (CRP) and Body Mass Index (BMI) were measured in patients and controls. Comparison of selectin levels between patients and controls was done with t-tests and linear regression. Pearson correlation coefficients between plasma selectins and PANSS and cognitive measures were calculated. Geometric mean plasma soluble L-selectin level was lower in patients compared to controls from unadjusted (606.7 ± 1.2 ng/ml vs. 937.7 ± 1.15 ng/ml, p < 0.001) and adjusted analyses (β = 0.59; CI 0.41 to 0.88, p = 0.011). There was a trend towards higher plasma soluble P-selectin in patients compared to controls (90.4 ± 1.2ng/ml vs. 71.8 ± 1.2ng/ml, p = 0.059) in the unadjusted analysis. There was no association between the selectins and psychotic symptoms or cognitive function in the patients. In addition, the selectins were not significantly associated with CRP or BMI. The limitations of this study include small sample size and unavailability of information on medications and blood cell counts. The potential utility of soluble L-selectin as a biomarker of antipsychotic exposure in patients with schizophrenia and the concomitant change in immune response with the use of antipsychotics should be further evaluated.

Effects of Almond- and Olive Oil-Based Docosahexaenoic- and Vitamin E-Enriched Beverage Dietary Supplementation on Inflammation Associated to Exercise and Age.

n-3-polyunsaturated fatty acids and polyphenols are potential key factors for the treatment and prevention of chronic inflammation associated to ageing and non-communicable diseases. The aim was to analyse effects of an almond and olive oil beverage enriched with α-tocopherol and docosahexaenoic, exercise and age on inflammatory plasma markers, and immune gene expression in peripheral blood mononuclear cells (PBMCs). Five young and five senior athletes who were supplemented for five weeks with a functional beverage performed a stress test under controlled conditions before and after beverage supplementation. Blood samples were taken immediately before and 1 h after each test. Plasma, erythrocytes and PBMCs were isolated. Beverage supplementation increased plasmatic Tumour Necrosis Factor α (TNFα) levels depending on age and exercise. Exercise increased plasma non esterified fatty acids (NEFAs), soluble Intercellular adhesion molecule 3 (sICAM3) and soluble L-selectin (sL-Selectin), and this increase was attenuated by the supplementation. Exercise increased PGE2 plasma levels in supplemented young and in senior placebo athletes. Exercise increased NFkβ-activated levels in PBMCs, which are primed to a pro-inflammatory response increasing pro-inflammatory genes expression after the exercise mainly in the young group after the supplementation. The functional beverage supplementation to young athletes enhances a pro-inflammatory circulating environment in response to the exercise that was less evident in the senior group.

High salivary soluble L-selectin and interleukin-7 levels in Asian Indian patients with primary Sjögren’s syndrome

In present study, we aimed to study salivary soluble L-selectin (sL-selectin), interleukin-7(IjL-7), and lymphotoxin-α levels in primary Sjögren's syndrome (pSS) and their clinical as well as serological correlations. pSS patients fulfilling either the American European Consensus Group (AECG) and/or the American college of Rheumatology (ACR) criteria were recruited. Age- and sex-matched hospital staff were recruited as healthy controls. Unstimulated saliva was collected by the spitting method; sL-selectin, IL-7, and lymphotoxin-α were measured in the saliva using commercial ELISA kits. Forty-three patients with pSS and 31 healthy controls were included in the study. Increased levels of sL-selectin and IL-7 were found in the saliva of patients as compared to controls. Lymphotoxin-α was undetectable in the saliva of pSS patients and controls. Salivary sL-selectin positively correlated with rheumatoid factor (r=0.47; p<0.003). No other variable including ESSDAI was significantly associated with salivary sL-selectin and IL-7 levels. Indian patients with primary Sjögren's syndrome have higher salivary sL-selectin and IL-7 levels than healthy controls.

Technical Approach Determines Inflammatory Response after Surgical and Transcatheter Aortic Valve Replacement.

ObjectiveTo investigate the periprocedural inflammatory response in patients with isolated aortic valve stenosis undergoing surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) with different technical approaches.Material and MethodsPatients were prospectively allocated to one of the following treatments: SAVR using conventional extracorporeal circulation (CECC, n = 47) or minimized extracorporeal circulation (MECC, n = 15), or TAVI using either transapical (TA, n = 15) or transfemoral (TF, n = 24) access. Exclusion criteria included infection, pre-procedural immunosuppressive or antibiotic drug therapy and emergency indications. We investigated interleukin (IL)-6, IL-8, IL-10, human leukocyte antigen (HLA-DR), white blood cell count, high-sensitivity C-reactive protein (hs-CRP) and soluble L-selectin (sCD62L) levels before the procedure and at 4, 24, and 48 h after aortic valve replacement. Data are presented for group interaction (p-values for inter-group comparison) as determined by the Greenhouse-Geisser correction.ResultsSAVR on CECC was associated with the highest levels of IL-8 and hs-CRP (p<0.017, and 0.007, respectively). SAVR on MECC showed the highest descent in levels of HLA-DR and sCD62L (both p<0.001) in the perioperative period. TA-TAVI showed increased intraprocedural concentration and the highest peak of IL-6 (p = 0.017). Significantly smaller changes in the inflammatory markers were observed in TF-TAVI.ConclusionSurgical and interventional approaches to aortic valve replacement result in inflammatory modulation which differs according to the invasiveness of the procedure. As expected, extracorporeal circulation is associated with the most marked pro-inflammatory activation, whereas TF-TAVI emerges as the approach with the most attenuated inflammatory response. Factors such as the pre-treatment patient condition and the extent of myocardial injury also significantly affect inflammatory biomarker patterns. Accordingly, TA-TAVI is to be classified not as an interventional but a true surgical procedure, with inflammatory biomarker profiles comparable to those found after SAVR. Our study could not establish an obvious link between the extent of the periprocedural inflammatory response and clinical outcome parameters.

Association between soluble L-selectin and anti- JCV antibodies in natalizumabtreated relapsing-remitting MS patients

Association between soluble L-selectin and anti- JCV antibodies in natalizumabtreated relapsing-remitting MS patients