Soluble Form Of Receptor Research Articles

Serum soluble receptor of advanced glycation end products and risk of metabolic syndrome in Egyptian obese women.

Obesity is one of the diagnostic criteria of metabolic syndrome (MS). It is correlated with insulin resistance (IR) and high vascular risk as well. Advanced glycation end products (AGEs) and their receptor (RAGE) play an important role in abnormal metabolic components in obese women. This study aimed to explore the serum levels of sRAGE in Egyptian obese women and compare with healthy non-obese controls and investigate the relationship between serum sRAGE, metabolic parameters, and obesity complications. The soluble form of receptor for advanced glycation end products (sRAGE), anthropometry, metabolic and biochemical biomarkers were measured in 100 obese women and 100 age-matched healthy control non-obese women. The homeostasis model assessment estimate of insulin resistance (HOMA-IR) has been determined from serum insulin and glucose values. Serum sRAGE levels were significantly lower in obese cases than controls and inversely correlated with obesity and metabolic parameters. Results of univariate and multivariate analyses for determinants of serum sRAGE levels in obese cases showed that parameters statistically and significantly related were body mass index (BMI), waist circumference (WC), LDL-C, TG, BP, HOMA-IR, ALT and AST. sRAGE is a novel biomarker for metabolic dysfunction in Egyptian obese women and might predict the future cardio-metabolic events.

A Brief History of IL-1 and IL-1 Ra in Rheumatology.

The history of what, in 1979, was called interleukin-1 (IL-1), orchestrator of leukocyte inter-communication, began many years before then, initially by the observation of fever induction via the endogenous pyrogen (EP) (1974) and then in rheumatology on the role in tissue destruction in rheumatoid diseases via the induction of collagenase and PGE2 in human synovial cells by a mononuclear cell factor (MCF) (1977). Since then, the family has exploded to presently 11 members as well as many membrane-bound and soluble receptor forms. The discovery of a natural Interleukin-1 receptor antagonist (IL-1Ra) in human biological fluids has highlighted the importance of IL-1 and IL-1Ra in human diseases. Evidence delineating its role in autoinflammatory syndromes and the elucidation of the macromolecular complex referred to as “inflammasome” have been instrumental to our understanding of the link with IL-1. At present, the IL-1blockade as therapeutic approach is crucial for many hereditary autoinflammatory diseases, as well as for adult-onset Still’s disease, crystal-induced arthropathies, certain skin diseases including neutrophil-triggered skin diseases, Behçet’s disease and deficiency of IL-1Ra and other rare fever syndromes. Its role is only marginally important in rheumatoid arthritis and is still under debate with regard to osteoarthritis, type 2 diabetes mellitus, cardiovascular diseases and cancer. This brief historical review focuses on some aspects of IL-1, mainly IL-1β and IL-Ra, in rheumatology. There are many excellent reviews focusing on the IL-1 family in general or with regard to specific diseases or biological discoveries.

GENE POLYMORPHISM OF PROINFLAMMATORY CYTOKINES (TNF, IL6) AND THEIR RECEPTORS (TNFRSF1A, TNFRSF1B, IL6R): IMPLICATIONS FOR NON-ALCOHOLIC FATTY LIVER DISEASE

Proinflammatory cytokines (tumor necrosis factor alpha (TNFα) and interleukin 6 (IL6)) play an important role in the etiology and pathogenesis of non-alcoholic fatty liver disease (NAFLD), since they can promote inflammation and regulate apoptosis and necrosis of liver cells, induce fibrosis. Cytokines perform their functions through interaction with membrane-bound and soluble receptors on the cell surface, and the soluble forms of receptors may act as antagonists or as enhancers of their biological effects. Differences in the level of cytokines and soluble and membrane-bound cytokine receptors may be due to the presence of mutations in different regions of the corresponding genes. This may influence the formation of the signaling pathway that determines the fate of cells (i. e., survival, apoptosis or necrosis) and, accordingly, the development and progress of NAFLD, some forms of which, in particular steatohepatitis and cirrhosis, involve intensified hepatic cell death. However, the question of whether the polymorphism of TNF , IL6 genes and their receptors affects NAFLD development and progress currently remains largely uninvestigated. This paper presents current data from the literature investigating the relationship between TNF, IL6, TNFRSF1A, TNFRSF1B, IL6R gene polymorphism and the development of non-alcoholic fatty liver disease.

Total and Fetal Circulating Cell-Free DNA, Angiogenic, and Antiangiogenic Factors in Preeclampsia and HELLP Syndrome.

Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by hypertension and proteinuria. The HELLP syndrome is the most severe form of PE. The aim of the present study was to determine different potential biomarkers that may help us perform an early diagnosis of the disease, assess on the severity of the disease, and/or predict maternal or fetal adverse outcomes. We measured serum levels of total and fetal circulating cell-free DNA (cfDNA), soluble endoglin, soluble form of vascular endothelial growth factor receptor, and placental growth factor in a healthy control group of pregnant women (n = 26), patients with mild (n = 37) and severe PE (n = 25), and patients with HELLP syndrome (n = 16). We observed a gradual and strong relationship between all the biomarkers mentioned and the range of severity of PE, with the highest levels in patients with HELLP syndrome. Nevertheless, only the values of total cfDNA were able to significantly differentiate severe PE and HELLP syndrome (20957 ± 2784 vs. 43184 ± 8647 GE/ml, P = 0.01). Receiver operating characteristic (ROC) curves were constructed (i) for the healthy group with respect to the groups with PE and (ii) for patients with PE with respect to the group with HELLP syndrome; sensitivity and specificity values at different cutoff levels were calculated in each case. The maximum ROC area under the curve value for PE and HELLP syndrome (with respect to controls) was 0.91 (P < 0.001). The measured biomarkers of cell damage, angiogenesis, and antiangiogenesis may reflect the severity of PE, with higher levels in patients who develop HELLP syndrome. In addition, these biomarkers may also help predict adverse fetal and maternal outcomes.

Pseudomonas aeruginosa GroEL Stimulates Production of PTX3 by Activating the NF-κB Pathway and Simultaneously Downregulating MicroRNA-9.

As one of the first lines of host defense, monocytes play important roles in clearing infected microbes. The defensive response is triggered by recognition of diverse microbial moieties, including released factors, which modulate host immune responses to establish a harsh environment for clinically important bacterial pathogens. In this study, we found that the expression of PTX3, a soluble form of pattern recognition receptor, was induced by infection with live Pseudomonas aeruginosa or treatment of cells with its supernatant. P. aeruginosa GroEL, a homolog of heat shock protein 60, was identified as one of the factors responsible for inducing the expression of PTX3 in host cells. GroEL induced PTX3 expression by activating the Toll-like receptor 4 (TLR4)-dependent pathway via nuclear factor-kappa B (NF-κB), while simultaneously inhibiting expression of microRNA-9, which targets the PTX3 transcript. Finally, by acting as an opsonin, GroEL-induced PTX3 promoted the association and phagocytosis of Staphylococcus aureus into macrophages. These data suggest that the host defensive environment is supported by the production of PTX3 in response to GroEL, which thus has therapeutic potential for clearance of bacterial infections.

Antiangiogenic Activity of rTRAIL is Potentiated by Sflt-1, a VEGF Trap

Objective: Anti-angiogenesis and pro-apoptosis are the two processes which are strategically used to target tumors. The soluble form of VEGF receptor 1 (Flt-1) is a modulator of VEGF activity and could be useful as a trap to intrinsically sequester VEGF in tumor cells. In the present study, we have investigated the role of rTRAIL in inhibiting VEGF-mediated angiogenesis and its synergistic potentiation by sFlt-1. Methods: We have expressed human recombinant TRAIL, to study its role in anti-angiogenesis and a 2-domain active variant of sFlt-1 by bacterial expression to be used as a trap for VEGF. 3[H] thymidine incorporation assay was used to confirm the inhibitory activity of sFlt-1 and/or rTRAIL on cell proliferation. The synergistic anti-migratory and anti-angiogenic activity of sFlt-1 and rTRAIL were assessed using endothelial cell wound healing and tube formation assay in-vitro and by rat corneal micropocket assay in-vivo. Results: Inhibition of cell proliferation was evident in sFlt-1 and rTRAIL treated cells in a dose -dependent manner with more than 60% reduction in proliferation rate as compared to the tumor cells treated with sFlt-1 and rTRAIL alone. Furthermore, the anti-metastatic and anti-angiogenic activity of sFlt-1 and rTRAIL in combination was evident in endothelial wound healing and tube formation with a significant reduction in the number of cells migrated into the wounded area and the number of honey comb-like structures with the length of the tubes formed to mimic blood vessel formation in-vitro respectively. The in-vivo corneal micropocket assay confirmed the anti-angiogenic effect of sFlt-1 and rTRAIL in combination. Conclusion: The synergistic role of sFlt-1 and rTRAIL as the potential inhibitors of VEGF- mediated angiogenesis could be therapeutically exploited.

Protective Effects of Human and Mouse Soluble Scavenger-Like CD6 Lymphocyte Receptor in a Lethal Model of Polymicrobial Sepsis.

Sepsis still constitutes an unmet clinical need, which could benefit from novel adjunctive strategies to conventional antibiotic therapy. The soluble form of the scavenger-like human CD6 lymphocyte receptor (shCD6) binds to key pathogenic components from Gram-positive and -negative bacteria and shows time- and dose-dependent efficacy in mouse models of monobacterial sepsis. The objective of the present work was to demonstrate the effectiveness of infusing mouse and human sCD6 by different systemic routes, either alone or as adjunctive therapy to gold standard antibiotics, in a lethal model of polymicrobial sepsis. To this end, C57BL/6 mice undergoing high-grade septic shock induced by cecal ligation and puncture (CLP; ≥90% lethality) were infused via the intraperitoneal (i.p.) or intravenous (i.v.) route with shCD6 at different doses and time points, either alone or in combination with imipenem/cilastatin (I/C) at a dose of 33 mg/kg of body weight every 8 h. Significantly reduced mortality and proinflammatory cytokine levels were observed by i.p. infusion of a single shCD6 dose (1.25 mg/kg) 1 h pre- or post-CLP. When using the i.v. route, mice survival was significantly extended by starting shCD6 infusion at later time points post-CLP (up to 6 h after CLP). Significant adjunctive effects on mouse survival were observed by i.p. or i.v. infusion of shCD6 in combination with i.p. I/C post-CLP. Similar results were obtained in mice expressing high sustained levels (5 to 10 μg/ml) of mouse sCD6 in serum by means of transduction with hepatotropic adeno-associated virus (AAV). Taken together, the data support the conserved antibacterial effects of human and mouse sCD6 and their use as adjunctive therapy in experimental models of complex and severe polymicrobial sepsis.

Clinical significance of GCF sIL-6R and calprotectin to evaluate the periodontal inflammation.

Background Periodontitis is an inflammatory disease. The aim of this study was to investigate whether the soluble form of interleukin-6 receptor (sIL-6R) and calprotectin concentrations in gingival crevicular fluid are useful biomarkers in the evaluation of periodontitis. Methods First, a cross-sectional study was performed. A total of 34 periodontitis patients were enrolled and the gingival crevicular fluid samples were collected from the healthy and inflamed sites of periodontal pockets in each patient. The relationship between periodontal condition and gingival crevicular fluid sIL-6R and calprotectin concentrations was analysed statistically. The cut-off values of gingival crevicular fluid sIL-6R and calprotectin concentrations for the evaluation of periodontitis were determined using a receiver operating characteristic curve. Next, by using enzyme-linked immunosorbent assay, it was examined whether calprotectin induces sIL-6R production in THP-1 macrophages. Results Both gingival crevicular fluid sIL-6R and calprotectin concentrations were significantly higher in the inflamed sites than in the healthy sites ( P < 0.0001). The cut-off values of gingival crevicular fluid sIL-6R and calprotectin concentrations for the evaluation of periodontal inflammation were as follows: sIL-6R: 43.5 pg/site; calprotectin: 134.3 ng/site. In the in vitro study, calprotectin significantly induced sIL-6R production in THP-1 macrophages ( P < 0.01). Conclusions Both gingival crevicular fluid sIL-6R and calprotectin concentrations are significant biomarkers in the evaluation of periodontal inflammation.

Soluble Tumor Necrosis Factor Receptors and Arterial Stiffness in Patients With Coronary Atherosclerosis.

Soluble forms of tumor necrosis factor receptors (sTNFRs) are emerging target molecules of inflammatory disease. However, their role in vascular biology is not well known. This study was performed to investigate the association between serum concentrations of sTNFRs and arterial stiffness. A total of 117 consecutive patients with suspected coronary artery disease (CAD) (63.6 ± 11.0 years; men, 65%) who were referred for invasive coronary angiography (ICA) were prospectively enrolled. Arterial blood sTNFR1 and sTNFR2 were measured using commercially available ELISA kits. Brachial-ankle pulse wave velocity (baPWV) measurements were made within 24 hours of blood sampling for sTNFRs measurement. Most of the patients (86.3%) had significant CAD (stenosis ≥ 50%) in ICA. In simple linear regression analyses, there were significant positive correlations of baPWV with sTNFR1 (r = 0.483, P < 0.001) and sTNFR2 (r = 0.366, P < 0.001). In multiple linear regression analyses, sTNFR1 (β = 0.316, P < 0.001) and sTNFR2 (β = 0.235, P = 0.005) had independent association with baPWV even after controlling for potential confounders. sTNFR1 and sTNFR2 were independently associated with baPWV in patients undergoing ICA. This result may extend previous knowledge on close interactions between inflammation and arterial stiffening.

Activation of dengue virus-specific T cells modulates vascular endothelial growth factor receptor 2 expression.

The pathogenic mechanisms underlying the increased vascular permeability in dengue hemorrhagic fever (DHF) are not well understood. Enhanced cellular immune activation, especially activation of serotype-cross reactive T cells, has been implicated in plasma leakage in DHF. Changes in several biological markers and mediators including cytokines, chemokines, angiogenic factors and their receptors have been shown to correlate with disease severity. A decline in plasma levels of a soluble form of vascular endothelial growth factor receptor 2 (VEGFR2), a receptor of vascular endothelial growth factor (VEGF), has been associated with plasma leakage in dengue patients. We aimed to investigate the effect of dengue virus (DV)-specific CD8⁺ T cells on the expression of VEGFR2 on endothelial cells. An in vitro model was developed in which dengue virus-specific CD8⁺ T cells generated from peripheral blood mononuclear cells (PBMCs) of DHF patients were co-cultured with antigen-presenting cells, human umbilical vein endothelial cells (HUVECs) and activated with DV non-structural protein 3 (NS3) peptides. The expression of VEGFR2 by endothelial cells was measured. DV-specific CD8⁺ T cells were serotype cross-reactive. Activation of DV-specific CD8⁺ T cells resulted in down-regulation of soluble VEGFR2 production and an up-regulation of cell-associated VEGFR2. Our findings indicate that activation of DV-specific T cell is associated with modulation of VEGFR2 expression that may contribute to increased VEGF responsiveness and vascular permeability.

Predictors of Vascular Cognitive Impairment Poststroke in a Middle Eastern (Bahrain) Cohort: A Proposed Case-Control Comparison.

BackgroundPoststroke dementia and cognitive impairment are associated with poor long-term outcomes after stroke. The contribution of genetic factors such as the presence of apolipoprotein (ApoE) ɛ4 allele and its association with cognitive impairment poststroke remains inconclusive, particularly in Middle Eastern regions.ObjectiveThe aim of this study is to examine all correlates and potential predictors of cognitive impairment including self-awareness and regulation deficits in stroke patients and compare these functions with healthy older adults from a Middle Eastern population.MethodsA prospective stroke sample of 200 patients (case group) and 100 healthy aging individuals (control group) will be recruited from the largest medical complex in Bahrain. A neuropsychological battery of cognitive assessments (global, executive, and metacognition) will be conducted on all participants. Participants will be categorized into 4 subgroups (nonvascular cognitive impairment, vascular cognitive impairment with no dementia, vascular dementia, and mixed dementia) using standardized cognitive assessment scores and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, dementia criteria. Biomarkers will include ApoE genotype, soluble form of receptor for advanced glycation end products, neprilysin, beta-secretase 1, biochemistry, and hematology measurements.ResultsThe primary study outcome is to determine early risk factors for cognitive impairment after stroke in a Bahraini cohort. The study has received full ethical approval from the Bahrain Ministry of Health and from the affiliated university.ConclusionsWith increasing stroke incidence rates in the Middle East, this research study will provide useful biological and epidemiological data for future development and planning of health policies and guidelines for stroke care within the Gulf region.

CORRELATION OF THE SHEDDING OF LYMPHOCYTES RECEPTORS WITH PARAMETERS OF IMMUNOLOGIC REACTIVITY IN RESIDENTS OF THE NORTH

The study retrospectively investigated correlation characteristics of membrane and soluble forms of lymphocyte receptors in 78 healthy people living in the city of Arkhangelsk. The results of a statistical analysis allowed to evaluate the relationship of dynamic indices of shedding lymphocyte receptors CD23 and CD80 to the immunological reactivity indices. It was found that the receptors' shedding was not associated with the processes of proliferation and activation of immune cells, and the receptors abscission occurred by postmitotic mature cells. A high ratio reflecting the relationship of shedding activity of membrane forms of lymphocyte with cytokine IL-1 and IL-10 in the extracellular medium was a reflection of the biological processes regulating the in the form of feedback: increasing of receptor concentration in the extracellular medium by means of cytokine blocked cell receptor expression. Low values of the analyzed indices for CD95 receptor indicated that the cells got free from unnecessary receptor substances in the course of performing its function did not undergo apoptosis. Accumulation of receptors extracellular pool was provided by phagocytosis deficiency. Increase of phagocytosis intensity at a maximum concentration of free receptors was due to the necessity of urgent prevention of unwanted substances accumulation in the blood serum.

Recombinant soluble IFN receptor (sIFNAR2) exhibits intrinsic therapeutic efficacy in a murine model of Multiple Sclerosis

Endogenous interferon beta (IFNβ) is an important cytokine involved in several chronic inflammatory diseases, such as Multiple Sclerosis (MS). In spite of the numerous therapeutic approaches available for MS patients, the administration of recombinant IFNβ continues being one of the first line treatment to these patients. The soluble form of IFNβ receptor (sIFNAR2) could act as critical regulator of the endogenous and the systemically administered IFNβ, but whether it functions as an agonist or antagonist of its ligand is not completely elucidated. Morover, the possible role of sIFNAR2 in autoimmune diseases like MS is still unknown and so far overlooked. Here we evaluated the efficacy of the combined therapy of IFNβ and our recombinant protein analogous to human sIFNAR2 as a treatment in a chronic mice model of MS (CP-EAE). We also tested the effect of the sIFNAR2 administered as a monotherapy over these EAE-animals. The results showed that our recombinant sIFNAR2 protein potentiates the immunomodulatory effects of exogenous IFNβ in CP-EAE by increasing the reduction of the induced inflammation and the tissue damage. Furthermore, we demonstrate for the first time that sIFNAR2 shows intrinsic properties by modulating the CP-EAE progression and the neuroinflammation processes related to this disease. Another intrinsic activity showed by sIFNAR2 is the inhibition of the T cells proliferation, which increase its potential as therapeutic molecule.

The Potentials of Fas Receptors and Ligands in Monitoring HIV-1 Disease in Children in Yaoundé, Cameroon

Difficulties in systematically monitoring HIV viral load in resource-limited settings prompt the search for alternate approaches. The authors aimed at assessing the correlation between the plasma levels of soluble forms of Fas receptors (Fas) and Fas ligands (FasL) with standard indicators of HIV disease progression in children. Twenty-two HIV-1-positive children were enrolled in Yaounde. CD4 counts, CD4% counts, plasma levels of Fas, FasL, and HIV-1 RNA levels were assayed. The correlation coefficients (P values) between FasL levels and each of HIV-1 viral load, CD4 counts, and CD4% were, respectively, .56 (.01), -.29 (.18), and .30 (.18). On the other hand, the respective correlation coefficients (P values) with Fas levels were .12 (.60), -.30 (.18), and -.29 (.19). The significant correlation between levels of HIV-1 viral load and FasL suggests that the latter needs to be further studied as a potential biomarker to monitor HIV-1 disease progression in children in resource-limited setting.

The Prognostic Significance of Soluble Urokinase Plasminogen Activator Receptor in Acute Myeloid Leukemia.

Objective:The soluble urokinase plasminogen activator receptor (suPAR) is a soluble form of the urokinase plasminogen activator receptor expressed in various immune and cancer cells. The levels of suPAR have been demonstrated to correlate with prognosis in various cancers. This study was intended to investigate serum suPAR levels and their effect on prognosis in patients with acute myeloid leukemia (AML).Materials and Methods:Thirty newly diagnosed patients with AML and 29 healthy individuals were enrolled. Serum suPAR levels were analyzed by enzyme-linked immunosorbent assay.Results:Serum suPAR levels were significantly higher in patients with AML than in healthy individuals (9±5.9 ng/mL and 2.4±1.4 ng/mL, respectively; p<0.001). Positive correlation was determined between suPAR levels and white blood cell counts (p<0.01). Serum suPAR levels were lower in patients who achieved complete response than in patients not achieving complete response (5.5±2.2 ng/mL and 12±6.6 ng/mL, respectively; p<0.001). The median overall survival was longer in patients with serum suPAR levels below 6.71 ng/mL than in those with serum suPAR levels above 6.71 ng/mL (12.6±13.2 months and 1.71±0.6 months, respectively; p=0.02). Multivariate Cox regression analysis showed that suPAR had independent prognostic value (95% confidence interval: 1.029-6.259; p<0.05) in AML.Conclusion:Serum suPAR levels can be used as a prognostic marker in AML.

217. Combinatorial Anti-Angiogenic Gene Therapy in a Human Malignant Mesothelioma Model

Anti-angiogenic gene therapy represents a promising strategy for cancer; however, it has rarely been tested in malignant mesothelioma, a highly aggressive tumor associated with asbestos that has poor prognosis. In this study, we investigated whether anti-angiogenic factors such as angiostatin, endostatin, and the soluble form of vascular endothelial growth factor receptor 2 (sFlk1) were able to inhibit endothelial cell proliferation via lentivirus-mediated gene transfer into malignant mesothelioma cells in culture. We also assessed whether a dual-agent strategy had greater therapeutic benefit. Human malignant pleural mesothelioma MSTO-211H cells were transduced using lentiviral vectors that individually expressed angiostatin, endostatin, and sFlk1 and linked to enhanced green fluorescent protein (EGFP) marker gene expression via an internal ribosome entry site. The lentivirus expressing EGFP alone was used as a control. The resultant cells designated as MSTO-A, MSTO-E, MSTO-F, and MSTO-C were confirmed by Western blot and fluorescence microscopy to stably express the corresponding proteins. No differences were observed in the in vitro growth rates between any of these cells. However, coculture of MSTO-A, MSTO-E, and MSTO-F showed significant suppression of human umbilical endothelial cell growth in vitro compared with that of MSTO-C. Furthermore, a combination of any two among MSTO-A, MSTO-E, and MSTO-F significantly enhanced efficacy. These results suggest that combinational anti-angiogenic gene therapy targeting different pathways of endothelial growth factor signaling has the potential for greater therapeutic efficacy than that of a single-agent regimen.

Glabridin Alleviates the Toxic Effects of Methylglyoxal on Osteoblastic MC3T3-E1 Cells by Increasing Expression of the Glyoxalase System and Nrf2/HO-1 Signaling and Protecting Mitochondrial Function.

Methylglyoxal (MG) contributes to the pathogenesis of age- and diabetes-associated complications. The present study investigated the effects of glabridin on MG-induced cytotoxicity in MC3T3-E1 osteoblastic cells. MC3T3-E1 cells were treated with glabridin in the presence of MG, and markers of mitochondrial function and oxidative damage were examined. Pretreatment of MC3T3-E1 osteoblastic cells with glabridin prevented MG-induced cell death, the production of intracellular reactive oxygen species and mitochondrial superoxides, cardiolipin peroxidation, and the production of inflammatory cytokines. The soluble form of receptor for advanced glycation end products (sRAGEs)/RAGE ratio increased upon MG treatment, but less so after pretreatment with glabridin, which also increased the level of reduced glutathione and the activities of glyoxalase I and heme oxygenase-1, all of which were reduced by MG. In addition, glabridin elevated the level of nuclear factor erythroid 2-related factor 2. These findings suggest that glabridin protects against MG-induced cell damage by inhibiting oxidative stress and increasing MG detoxification. Pretreatment of MC3T3-E1 osteoblastic cells with glabridin reduced MG-induced mitochondrial dysfunction. Additionally, the nitric oxide level significantly increased upon glabridin pretreatment. Together, these data show that glabridin may potentially serve to prevent the development of diabetic bone disease associated with MG-induced oxidative stress.

Levels of proinflammatory cytokines and vascular endothelial growth factor in patients with Alzheimer's disease and mild cognitive impairment

to evaluate the levels of cytokines (IFNα, IFNγ, IL-2, Il-4, IL-6, IL-8, IL-10, IL-12, IL-15), IL-1β receptor antagonist (IL-1RA), vascular endothelial growth factor (VEGF) and its antagonist, the soluble form of receptor 1 (sVEGFR1) in the blood serum of patients with Alzheimer's disease, with early onset (ADEO) and late onset (ADLO), and in patients with mild cognitive impairment (MCI). Levels of interleukins, IL-1RA, VEGF and sVEGFR1 were measured in 20 patients with AD and 11 patients with MCI using ELISA. These parameters were compared to the severity of cognitive impairment assessed by the performance on neurocognitive tests. The levels of key cytokines (IL-8, TNFα, IL-12), VEGF and sVEGFR1 as well as anti-inflammatory proteins were different in patients with ADEO, ADLO and MCI. These differences suggest the phenotypic and genotypic heterogeneity of the disease that demands further research.

Soluble Human Intestinal Lactoferrin Receptor: Ca(2+)-Dependent Binding to Sepharose-Based Matrices.

A soluble form of human intestinal lactoferrin receptor (shLFR) is identical to human intelectin-1 (hITLN-1), a galactofuranose-binding protein that acts as a host defense against invading pathogenic microorganisms. We found that recombinant shLFR, expressed in mammalian cells (CHO DG44, COS-1, and RK13), binds tightly to Sepharose 4 Fast Flow (FF)-based matrices in a Ca(2+)-dependent manner. This binding of shLFR to Sepharose 4 FF-based matrices was inhibited by excess D-galactose, but not by D-glucose, suggesting that shLFR recognizes repeating units of α-1,6-linked D-galactose in Sepharose 4 FF. Furthermore, shLFR could bind to both Sepharose 4B- and Sepharose 6B-based matrices that were not crosslinked in a similar manner as to Sepharose 4 FF-based matrices. Therefore, shLFR (hITLN-1) binds to Sepharose-based matrices in a Ca(2+)-dependent manner. This binding property is most likely related to the ability, as host defense lectins, to recognize sepharose (agarobiose)-like structures present on the surface of invading pathogenic microorganisms.

Thrombocytopenia in critically ill patients with severe sepsis/septic shock: Prognostic value and association with a distinct serum cytokine profile

PurposeThe purpose of the study is to evaluate the incidence, association with serum cytokine profile, and prognostic value of thrombocytopenia, in critically ill patients with severe sepsis/septic shock. MethodsA cohort of 105 consecutive patients admitted in intensive care unit was included in our analysis. Serum levels of intercellular adhesion molecule, vascular cell adhesion molecule, interferon γ, interleukin 8, and soluble form of the urokinase-type plasminogen activator receptor (suPAR) were measured. ResultsThrombocytopenia was observed in 53% of patients at the time of admission. Platelet counts showed a statistically significant negative correlation with serum levels of intercellular adhesion molecule, suPAR, and interleukin 8 (P < .0001). In multivariate analysis, high Acute Physiological and Chronic Health Evaluation II score, high serum suPAR, and low platelet counts were associated with increased mortality, and receiver operating characteristic curve analysis was used to determine the best cutoff value for mortality prediction. Each variable with a value above or below the predefined cutoff levels were given 1 point. Patients were categorized in risk groups based on total point score. High-risk (2-3), intermediate-risk (1), and low-risk (0 points) groups consisted of 43%, 22%, and 35% and 28-day mortality was observed in 69%, 26%, and 3% of the patients in each group, respectively. ConclusionThrombocytopenia is associated with poor prognosis and a distinct serum cytokine profile.