Accurate Noninvasive Assessment of Myocardial Iron Load in Advanced Heart Failure Patients.

BACKGROUND: Heart failure patients presenting with iron deficiency can benefit from systemic iron supplementation; however, there is the potential for iron overload to occur, which can seriously damage the heart. Therefore, myocardial iron (M-Iron) content should be precisely balanced, especially in already failing hearts. Unfortunately, the assessment of M-Iron via repeated heart biopsies or magnetic resonance imaging is unrealistic, and alternative serum markers must be found. This study is aimed at assessing M-Iron in patients with advanced heart failure (HF) and its association with a range of serum markers of iron metabolism. METHODS: Left ventricle (LV) myocardial biopsies and serum samples were collected from 33 consecutive HF patients (25 males) with LV dysfunction (LV ejection fraction 22 (11) %; NT-proBNP 5464 (3308) pg/ml) during heart transplantation. Myocardial ferritin (M-FR) and soluble transferrin receptor (M-sTfR1) were assessed by ELISA, and M-Iron was determined by Instrumental Neutron Activation Analysis in LV biopsies. Nonfailing hearts (n = 11) were used as control/reference tissue. Concentrations of serum iron-related proteins (FR and sTfR1) were assessed. RESULTS: LV M-Iron load was reduced in all HF patients and negatively associated with M-FR (r = -0.37, p = 0.05). Of the serum markers, sTfR1/logFR correlated with (r = -0.42; p = 0.04) and predicted (in a step-wise analysis, R 2 = 0.18; p = 0.04) LV M-Iron. LV M-Iron load (µg/g) can be calculated using the following formula: 210.24-22.869 × sTfR1/logFR. CONCLUSIONS: The sTfR1/logFR ratio can be used to predict LV M-Iron levels. Therefore, serum FR and sTfR1 levels could be used to indirectly assess LV M-Iron, thereby increasing the safety of iron repletion therapy in HF patients.

Topical Wound Healing Activity of Myricetin Isolated from Tecomaria capensis v. aurea.

Wounds and burn injury are major causes of death and disability worldwide. Myricetin is a common bioactive flavonoid isolated naturally from the plant kingdom. Herein, a topical application of naturally isolated myricetin from the shoots of Tecomaria capensis v. aurea on excisional wound healing that was performed in albino rats. The wounded rats were treated every day with 10 and 20% myricetin for 14 days. During the experiment, the wound closure percentage was estimated at days 0, 7, and 14. Effects of myricetin on the inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and cluster of differentiation 68 (CD68) in the serum were evaluated using immunosorbent assay kits. The percentage of wound closure and contraction was delayed in wounded rats (67.35%) and was remarkably increased after treatment of wounded rats with myricetin; the treatment with 20% myricetin was the most potent (98.76%). Histological findings exhibited that 10% myricetin caused the formation of a large area of scarring at the wound enclosure and stratified squamous epithelium without the formation of papillae as in the control group. Treatment with 20% myricetin exhibited less area of scarring at the wound enclosure as well as re-epithelialization with a high density of fibroblasts and blood capillaries in the wound. Level elevations of serum pro-inflammatory cytokines, IL-1ß, and TNF-α and macrophage CD68 were decreased in wounded rats treated with myricetin. Thus, it can be suggested that the enhancements in inflammatory cytokines as well as systemic reorganization after myricetin treatment may be recommended to play a crucial part in the promotion of wound healing. The findings suggest that treatment with a higher dose of myricetin was better in improving wound curing in rats. It could serve as a potent anti-inflammatory agent and can be used as an adjunctive or alternative agent in the future.

Phenotypical and functional abnormalities of circulating neutrophils in patients with ß-thalassemia.

ß-Thalassemia is an inherited single gene disorder related to reduced synthesis of the ß-globin chain of hemoglobin. Patients with ß-thalassemia present variable clinical severity ranging from asymptomatic trait to severe transfusion-dependent anemia and multiple organs complications. Moreover, multiple immune abnormalities are a major concern in ß-thalassemia patients. Aberrant neutrophil effector function plays a pivotal role in infection susceptibility in these patients. In severe and persistent inflammation, immature neutrophils are released from the bone marrow and are functionally different compared with mature ones. Despite some abnormalities reported for thalassemia patient's immune system, few data exist on the characterization of human neutrophils in ß-thalassemia. The aim of this study was to investigate the phenotype and function of circulating neutrophil subsets in patients with ß-thalassemia major and with ß-thalassemia intermedia divided in transfusion-dependent and non-transfusion-dependent. By the use of immunochemical and cytofluorimetric analyses, we observed that patients' CD16+ neutrophils exhibit abnormalities in their phenotype and functions and the abnormalities vary according to the clinical form of the disease and to the neutrophil subset (CD16bright and CD16dim). Abnormalities include altered surface expression of the innate immune receptor CD45, Toll-like receptor 4, and CD32, reduced ability to produce an oxidative burst, and elevated levels of membrane lipid peroxidation, especially in patients with a more severe form of the disease. Overall, our results indicating the occurrence of an immuno-senescent phenotype on circulating neutrophils from thalassemia patients suggest the usefulness of neutrophil feature assessment as a tool for better clinical management of ß-thalassemia.

Berberis aristata, Elaeis guineensis and Coffea canephora Extracts Modulate the Insulin Receptor Expression and Improve Hepatic Steatosis in NAFLD Patients: A Pilot Clinical Trial.

Non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance and diabetes. A reduction in insulin receptor (IR) expression has been reported in these patients. The aims of this study were to evaluate the effects of a mixture of plant extracts consisting of Berberis aristata, Elaeis guineensis and decaffeinated green coffee by Coffea canephora on the improvement of glycaemic profile, through the modulation of IR levels, and of hepatic steatosis in NAFLD patients. Forty-nine patients with a grade of steatosis S1-S2 were randomly allocated to the treatment with plant extracts or placebo for six months. Hepatic steatosis was evaluated using transient elastography with CAP (controlled attenuation parameter). Glucose, insulin, and IR levels were measured in serum samples. At the end of the study, patients treated with plant extracts displayed a significant reduction of serum glucose (p < 0.001), insulin levels (p < 0.01), homeostatic model assessment for insulin resistance (HOMA-IR) index (p < 0.001), and CAP value (p < 0.01) compared to placebo. Moreover, the IR expression was increased significantly in the plant extracts group compared to the placebo group (p < 0.05). The combination of plant extracts increases serum IR levels, determining amelioration of glycemic profile and improvement of hepatic steatosis in NAFLD patients.

Yangxin Tongmai Formula ameliorates impaired glucose tolerance in children with Graves' disease through upregulation of the insulin receptor levels.

Graves' disease (GD) is the leading cause of hyperthyroidism, and the majority of GD patients eventually develop disorders of glucose handling, which further affects their quality of life. Yangxin Tongmai formula (YTF) is modified from a famous formula of traditional Chinese medicine for the treatment of cardiovascular diseases. In this study we investigated the potential effects of YTF in the treatment of pediatric GD patients with impaired glucose tolerance. Forty pediatric GD patients and 20 healthy children were recruited for this clinical study. Based on the glucose tolerance, the GD patients were divided into two groups: 20 patients displayed impaired glucose tolerance, while the other 20 patients displayed normal glucose tolerance. YTF was orally administered for 60 days. YTF administration significantly ameliorated the abnormal glucose tolerance and insulin sensitivity in the GD patients with impaired glucose tolerance. To determine the molecular mechanisms of this observation, the number of plasma insulin receptors was determined by ELISA. Before treatment, the fasting and postprandial levels of the insulin receptor were significantly lower in patients with impaired glucose tolerance compared with those in patients with normal glucose tolerance and healthy children. After YTF treatment, both the fasting and the postprandial circulating insulin receptor levels were upregulated, and close to those in healthy children. Therefore, YTF is a potential effective treatment to enhance glucose handling in GD children with impaired glucose tolerance.

Plant-based Food Cyanidin-3-Glucoside Modulates Human Platelet Glycoprotein VI Signaling and Inhibits Platelet Activation and Thrombus Formation.

Background: Platelets play an important role in hemostasis, thrombosis, and atherosclerosis. Glycoprotein VI (GPVI) is a major platelet receptor that interacts with exposed collagen on injured vessel walls. Our previous studies have shown that anthocyanins (a type of natural plant pigment) attenuate platelet function; however, whether anthocyanins affect collagen-induced GPVI signaling remains unknown.Objective: The objective of this study was to explore the effects of cyanidin-3-glucoside (Cy-3-g, one of the major bioactive compounds in anthocyanins) on platelet activation and thrombosis and the GPVI signaling pathway.Methods: Platelets from healthy men and women were isolated and incubated with different concentrations (0, 0.5, 5, and 50 µM) of Cy-3-g. The expression of activated integrin αIIbß3, P-selectin, CD63, and CD40L, fibrinogen binding to platelets, and platelet aggregation were evaluated in vitro. Platelet adhesion and aggregation in whole blood under flow conditions were assessed in collagen-coated perfusion chambers. Thrombosis and hemostasis were assessed in 3-4-wk-old male C57BL/6J mice through FeCl3-induced intravital microscopy and tail bleeding time. The effect of Cy-3-g on collagen-induced human platelet GPVI signaling was explored with Western blot.Results: Cy-3-g attenuated platelet function in a dose-dependent manner. The 0.5-µM dose of Cy-3-g inhibited (P < 0.05) human platelet adhesion and aggregation to collagen at both venous (-54.02%) and arterial (-22.90%) shear stresses. The 5-µM dose inhibited (P < 0.05) collagen-induced human platelet activation (PAC-1: -48.21%, P-selectin: -50.63%), secretion (CD63: -73.89%, CD40L: -43.70%), fibrinogen binding (-56.79%), and aggregation (-17.81%). The 5-µM dose attenuated (P < 0.01) thrombus growth (-66.67%) without prolonging bleeding time in mice. The 50-µM dose downregulated (P < 0.05) collagen-induced GPVI signaling in human platelets and significantly decreased phosphorylation of Syk-linker for activation of T cells (LAT)-SLP76 (Syk: -39.08%, LAT: -32.25%, SLP76: -40.00%) and the expression of Lyn (-31.89%), Fyn (-36.27%), and phospholipase C-γ2 (-39.08%).Conclusions: Cy-3-g inhibits human platelet activation, aggregation, secretion, and thrombus formation, and downregulates the collagen-GPVI signaling pathway. Supplementation of Cy-3-g may have protective effects against atherothrombosis.

Soluble form of transferrin receptor-1 level is associated with the age at first diagnosis and the risk of therapeutic intervention and iron overloading in patients with non-transfusion-dependent thalassemia.

We retrospectively evaluated the relationship between serum transferrin receptor-1 (sTfR1) and some fundamental events in the life and the management (the age at diagnosis, the age at the first red blood cells transfusion, the age at splenectomy, and the overall need of chelation therapy) of 111 patients with non-transfusion-dependent thalassemia (NTDT) subdivided in four genetic entities: patients with homozygous or compound heterozygous state for ß-thalassemia, patients with triplicated α genotype associated with ß heterozygosity, patients with deletional HbH, and patients with the combination of a ß defect plus a ß chain variant. We found that the group with homozygous or compound heterozygous state for ß-thalassemia had the highest sTfR1 levels and that the presence of increased sTfR1 levels (>5 times normal) was associated with a complex and severe history of disease requiring splenectomy, occasional red blood cells transfusions, and early start and continuous iron chelation therapy.The complexity in the management of NTDT patients is an emerging issue due to the wide heterogeneity of clinical behavior. Our data indicate that the measurement of sTfR1 levels, a common laboratory test, could contribute to correctly stratify disease history and the iron chelation strategy in NTDT patients.

The Effect of Selenium Supplementation on Glucose Homeostasis and the Expression of Genes Related to Glucose Metabolism.

The aim of the study was to evaluate the effect of selenium supplementation on the expression of genes associated with glucose metabolism in humans, in order to explain the unclear relationship between selenium and the risk of diabetes. For gene expression analysis we used archival samples of cDNA from 76 non-diabetic subjects supplemented with selenium in the previous study. The supplementation period was six weeks and the daily dose of selenium was 200 µg (as selenium yeast). Blood for mRNA isolation was collected at four time points: before supplementation, after two and four weeks of supplementation, and after four weeks of washout. The analysis included 15 genes encoding selected proteins involved in insulin signaling and glucose metabolism. In addition, HbA1c and fasting plasma glucose were measured at three and four time points, respectively. Selenium supplementation was associated with a significantly decreased level of HbA1c but not fasting plasma glucose (FPG) and significant down-regulation of seven genes: INSR, ADIPOR1, LDHA, PDHA, PDHB, MYC, and HIF1AN. These results suggest that selenium may affect glycemic control at different levels of regulation, linked to insulin signaling, glycolysis, and pyruvate metabolism. Further research is needed to investigate mechanisms of such transcriptional regulation and its potential implication in direct metabolic effects.

Acupoint Application for Asthma Therapy in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: To evaluate the evidence available on the effects of acupuncture point (acupoint) application for asthma therapy in adults. METHODS: Six electronic databases were searched up to May 2014 to identify relevant studies. Randomized controlled trials, which assessed the effects of acupoint application for asthma treatment in adults, were included in our review. The methodological quality of eligible studies was assessed by the Cochrane Collaboration's tool. The standardized mean difference (SMD) and 95% confidence intervals (CI) of a random-effects model were calculated. The heterogeneity was assessed using I2 statistics. RESULTS: Eight studies were included in our review. The aggregated results indicated that acupoint application improved forced expiratory volume in 1 second (FEV1) (SMD, 0.32; 95% CI 0.04-0.60; p = 0.03), FEV1/forced vital capacity (SMD, 0.89; 95% CI 0.70-1.09; p < 0.00001), interleukin (SMD, -0.26; 95% CI -0.50 to -0.01; p = 0.04) and immunoglobulin E (SMD, -0.49; 95% CI -0.83 to -0.16; p = 0.004) in patients with asthma, but not eosinophilic cation protein (SMD, -0.58; 95% CI -1.42 to 0.26; p = 0.18). There was no sufficient evidence for the follow-up effects of acupoint application for asthma therapy in adults. CONCLUSIONS: Acupoint application may be a valid complementary and alternative therapy for asthma in adults. It contributes especially to improving pulmonary function and reducing the levels of interleukin and immunoglobulin E. However, more studies with longer follow-ups are warranted to confirm the current findings.

Direct and maternal n-3 long-chain polyunsaturated fatty acid supplementation improved triglyceridemia and glycemia through the regulation of hepatic and muscle sphingolipid synthesis in offspring hamsters fed a high-fat diet.

PURPOSE: We recently reported that direct and maternal supplementation with n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) alleviates the metabolic disturbances in adult hamster pups fed with a high-fat diet (HFD). In this study, we hypothesized that these results involved a perinatal modulating effect of sphingolipids by n-3 LC-PUFA. METHODS: We studied the effect of direct and maternal n-3 LC-PUFA supplementation on sphingolipid contents in liver and muscle, hepatic triglycerides (TG) secretion and glucose tolerance. Offspring male hamsters born from supplemented (Cω) or unsupplemented (C) mothers were subjected after weaning to a HFD during 16 weeks, without (Cω-HF or C-HF) or with direct supplementation with n-3 LC-PUFA (C-HFω). RESULTS: Direct supplementation decreased sphingosine, sphinganine and ceramides in liver and decreased sphingosine, sphinganine, sphingosine-1-phosphate (S1P) and ceramides in muscle in C-HFω compared to C-HF (p < 0.05). Maternal supplementation decreased C20 ceramide and lactosylceramide in liver and sphinganine, S1P and lactosylceramide in muscle (p < 0.05). This supplementation tended to decrease glucosylceramide in liver (p < 0.06) and muscle (p < 0.07) in Cω-HF compared to C-HF. Direct supplementation increased glucose tolerance and decreased hepatic TG secretion and hepatic gene expression levels of diacylglycerol O-acyltransferase 2 (DGAT2), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase, stearoyl-CoA desaturase-1 (SCD1) and tumor necrosis factor α (TNFα). Maternal supplementation decreased basal glycemia and hepatic TG secretion. We observed a positive correlation between hepatic TG secretion and hepatic ceramide (p = 0.0059), and between basal glycemia and hepatic ceramide (p = 0.04) or muscle lactosylceramide contents (p = 0.001). CONCLUSION: We observed an improvement of lipids and glucose metabolism in hamster with n-3 LC-PUFA direct supplementation and a decrease in glycemia and hepatic TG secretion with maternal supplementation. These results are probably related to a decrease in both lipogenesis and sphingolipid contents in liver and muscle.

Vitamin D Supplementation Decreases TGF-ß1 Bioavailability in PCOS: A Randomized Placebo-Controlled Trial.

CONTEXT: There is an abnormal increase in TGF-ß1 bioavailability in women with polycystic ovary syndrome (PCOS), which might play a role in the pathophysiology of this syndrome. Vitamin D (VD) supplementation improves various clinical manifestations of PCOS and decreases TGF-ß1 levels in several diseases including myelofibrosis. OBJECTIVE: The objective of the study was to determine the effect of VD supplementation on TGF-ß1 bioavailability in VD-deficient women with PCOS and assess whether changes in TGF-ß1/soluble endoglin (sENG) levels correlate with an improvement in PCOS clinical manifestations. DESIGN: This was a prospective, randomized, placebo-controlled trial. SETTING: The study was conducted at an academic-affiliated medical center. PARTICIPANTS: Sixty-eight VD-deficient women with PCOS who were not pregnant or taking any exogenous hormones were recruited between October 2013 and January 2015. INTERVENTIONS: Forty-five women received 50 000 IU of oral vitamin D3 and 23 women received oral placebo once weekly for 8 weeks. MAIN OUTCOMES MEASURES: Serum TGF-ß1, sENG, lipid profile, testosterone, dehydroepiandrosterone sulfate, and insulin resistance were measured. The clinical parameters were evaluated before and 2 months after treatment. RESULTS: The VD level significantly increased and normalized after VD supplementation (16.3 ± 0.9 [SEM] to 43.2 ± 2.4 ng/mL; P < .01), whereas it did not significantly change after placebo. After the VD supplementation, there was a significant decrease in the following: the interval between menstrual periods (80 ± 9 to 60 ± 6 d; P = .04), Ferriman-Gallwey score (9.8 ± 1.5 to 8.1 ± 1.5; P < .01), triglycerides (138 ± 22 to 117 ± 20 mg/dL; P = .03), and TGF-ß1 to sENG ratio (6.7 ± 0.4 to 5.9 ± 0.4; P = .04). In addition, the ΔTGF-ß1 to sENG ratio was positively correlated with Δtriglycerides (r = 0.59; P = .03). CONCLUSIONS: VD supplementation in VD-deficient women with PCOS significantly decreases the bioavailability of TGF-ß1, which correlates with an improvement in some abnormal clinical parameters associated with PCOS. This is a novel mechanism that could explain the beneficial effects of VD supplementation in women with PCOS. These findings may support new treatment modalities for PCOS, such as the development of anti-TGF-ß drugs.

Decrease of serum adenine nucleotide hydrolysis in an irritant contact dermatitis mice model: potential P2X7R involvement.

Extracellular adenosine 5'-triphosphate (ATP) has significant effects on a variety of pathological conditions and it is the main physiological agonist of P2X7 purinergic receptor (P2X7R). It is known that ATP acting via purinergic receptors plays a relevant role on skin inflammation, and P2X7R is required to neutrophil recruitment in a mice model of irritant contact dermatitis (ICD).The present study investigated the effects of chemical irritant croton oil (CrO) upon ATP, ADP, and AMP hydrolysis in mice blood serum, and the potential involvement of P2X7R. The topical application CrO induced a decrease on soluble ATP/ADPase activities (~50 %), and the treatment with the selective P2X7R antagonist, A438079, reversed these effects to control level. Furthermore, we showed that CrO decreased cellular viability (52.6 % ± 3.9) in relation to the control and caused necrosis in keratinocytes (PI positive cells). The necrosis induced by CrO was prevented by the pre-treatment with the selective P2X7R antagonist A438079. The results presented herein suggest that CrO exerts an inhibitory effect on the activity of ATPDase in mouse serum, reinforcing the idea that ICD has a pathogenic mechanism dependent of CD39. Furthermore, it is tempting to suggest that P2X7R may act as a controller of the extracellular levels of ATP.

American ginseng regulates gene expression to protect against premature ovarian failure in rats.

Premature ovarian failure (POF) is defined as lost ovarian functions before the age of 40. Three possible molecular markers (PLA2G4A, miR-29a, and miR-144) have been identified in our previous study by integrated analysis of mRNA and miRNA expression profiles. The present study aimed to evaluate American ginseng root's protective potential against POF by studying transcriptional and protein variations between American ginseng treatments and controls in rats. 4-Vinylcyclohexene diepoxide (VCD) was administered to rats for 14 days to induce POF. Additionally, American ginseng was administered to POF rats for one month, and PLA2G4A, miR-29a, and miR-144 expressions were measured in rat ovaries by qRT-PCR. PLA2G4A protein expression was examined by Western Blot, and PGE2, LH, FSH, and E2 serum levels were detected by ELISA. PLA2G4A mRNA and protein were downregulated in American ginseng-treated rats, miR-29a and miR-144 levels increased, and PGE2 serum levels decreased, while LH, FSH, and E2 increased compared to POF induction alone. Analysis of transcriptional and protein variations suggested that American ginseng protects the ovary against POF by regulating prostaglandin biosynthesis, ovulation, and preventing ovarian aging. High hormone levels (PGE2, FSH, and LH) were reduced, and E2 secretion approached normal levels, leading to improved POF symptoms and abnormal ovulation.

Acupuncture for sleep quality, BDNF levels and immunosenescence: a randomized controlled study.

Poor sleep in elderly populations is associated with detrimental neuropsychological, and physiological changes including premature immunosenescence and reduced brain derived neurotrophic factor (BDNF). Here, we evaluated the effects of acupuncture on sleep quality, psychological distress and immunosenescence in elderly, as well as effects on BDNF levels. Forty-eight community-dwelling elderly were randomized into true or placebo acupuncture, and intervention consisted of ten sessions. Sleep quality, depression and stress scores were evaluated by the Pittsburgh sleep quality index (PSQI), beck depression inventory (BDI II) and perceived stress scale (PSS), respectively, before and after the intervention. Lymphocyte subsets commonly associated with stress, sleep impairment and immunosenescence were phenotyped by flow cytometry. BDNF plasma levels were assessed by ELISAs. Acupuncture was highly effective for improving sleep quality (-53.23%; p<0.01), depression (-48.41%; p<0.01), and stress (-25.46%; p<0.01). However, neither lymphocyte subpopulations nor BDNF levels changed following the intervention.

Vascular dysfunction in patients with young ß-thalassemia: relation to cardiovascular complications and subclinical atherosclerosis.

We aimed to study the endothelial dysfunction among children and adolescents with transfusion-dependent ß-thalassemia using von Willebrand factor antigen (VWF:Ag) and flow cytometric analysis of circulating CD144(+) endothelial microparticles (EMPs) and endothelial progenitor cells (CD34(+)VEGFR2(+)) and assess their relation to iron overload, erythropoietin and chelation therapy as well as echocardiographic parameters and carotid intima-media thickness. The VWF:Ag, EMPs, and CD34(+)VEGFR2(+) cells were significantly higher among patients with ß-thalassemia than controls (P < .001). The type of chelation and patients' compliance did not influence the results. No significant correlations were found between the studied vascular markers. Patients with evident heart disease had higher VWF: Ag, EMPs, and CD34(+)VEGFR2(+) cells than those without. Carotid intima-media thickness was increased among patients but not correlated with vascular markers. We suggest that procoagulant EMPs and VWF: Ag are involved in cardiovascular complications in patients with young ß-thalassemia. CD34(+)VEGFR2(+) cells were further increased in response to tissue injury contributing to reendothelialization and neovascularization.

Complementary metal oxide semiconductor compatible silicon nanowires-on-a-chip: fabrication and preclinical validation for the detection of a cancer prognostic protein marker in serum.

An integrated translational biosensing technology based on arrays of silicon nanowire field-effect transistors (SiNW FETs) is described and has been preclinically validated for the ultrasensitive detection of the cancer biomarker ALCAM in serum. High-quality SiNW arrays have been rationally designed toward their implementation as molecular biosensors. The FET sensing platform has been fabricated using a complementary metal oxide semiconductor (CMOS)-compatible process. Reliable and reproducible electrical performance has been demonstrated via electrical characterization using a custom-designed portable readout device. Using this platform, the cancer prognostic marker ALCAM could be detected in serum with a detection limit of 15.5 pg/mL. Importantly, the detection could be completed in less than 30 min and span a wide dynamic detection range (∼10(5)). The SiNW-on-a-chip biosensing technology paves the way to the translational clinical application of FET in the detection of cancer protein markers.

Serum sCD163 levels are associated with type 2 diabetes mellitus and are influenced by coffee and wine consumption: results of the Di@bet.es study.

OBJECTIVE: Serum levels of soluble TNF-like weak inducer of apoptosis (sTWEAK) and its scavenger receptor CD163 (sCD163) have been linked to insulin resistance. We analysed the usefulness of these cytokines as biomarkers of type 2 diabetes in a Spanish cohort, together with their relationship to food consumption in the setting of the Di@bet.es study. RESEARCH DESIGN AND METHODS: This is a cross-sectional, matched case-control study of 514 type 2 diabetes subjects and 517 controls with a Normal Oral Glucose Tolerance Test (NOGTT), using data from the Di@bet.es study. Study variables included clinical and demographic structured survey, food frequency questionnaire and physical examination. Serum concentrations of sTWEAK and sCD163 were measured by ELISA. Linear regression analysis determined which variables were related to sTWEAK and sCD163 levels. Logistic regression analysis was used to estimate odd ratios of presenting type 2 diabetes. RESULTS: sCD163 concentrations and sCD163/sTWEAK ratio were 11.0% and 15.0% higher, respectively, (P<0.001) in type 2 diabetes than in controls. Following adjustment for various confounders, the OR for presenting type 2 diabetes in subjects in the highest vs the lowest tertile of sCD163 was [(OR), 2,01 (95%CI, 1,46-2,97); P for trend <0.001]. Coffee and red wine consumption was negatively associated with serum levels of sCD163 (P = 0.0001 and; P = 0.002 for coffee and red wine intake, respectively). CONCLUSIONS: High circulating levels of sCD163 are associated with type 2 diabetes in the Spanish population. The association between coffee and red wine intake and these biomarkers deserves further study to confirm its potential role in type 2 diabetes.

Dietary flavanol intervention lowers the levels of endothelial microparticles in coronary artery disease patients.

Current evidence suggests that regenerative v. degenerative endothelial responses can be integrated in a clinical endothelial phenotype, reflecting the net result between damage from risk factors and endogenous repair capacity. We have previously shown that a cocoa flavanol (CF) intervention can improve endothelial function and increase the regenerative capacity of the endothelium by mobilising circulating angiogenic cells in patients with coronary artery disease (CAD). The aim of the present study was to investigate whether CF can lower the levels of circulating endothelial microparticles (EMP), markers of endothelial integrity, along with improvements in endothelial function. The levels of EMP in the frozen plasma samples of CAD patients were measured along with endothelial function (flow-mediated vasodilation, FMD); n 16, FMD data published previously), and these data were compared with those of young (n 12) and age-matched (n 12) healthy control subjects. The CAD patients exhibited significantly increased levels of EMP along with impaired FMD when compared with the healthy control subjects. The levels of CD144⁺ and CD31⁺/41⁻ EMP were inversely correlated with FMD (r -0.67, P=0.01 and r -0.59, P=0.01, respectively). In these CAD patients, the levels of EMP were measured after they had consumed a drink containing 375 mg of CF (high-CF intervention, HiFI) or 9 mg of CF (macro- and micronutrient-matched low-CF control, LoFl) twice daily over a 30-d period in a randomised, double-blind, cross-over study. After 1 month of HiFI, the levels of CD31⁺/41⁻ and CD144⁺ EMP decreased (-25 and -23%, respectively), but not after LoFl. Our data show that flavanols lower the levels of EMP along with higher endothelial function, lending evidence to the novel concept that flavanols may improve endothelial integrity.

CD144+ endothelial microparticles as a marker of endothelial injury in neonatal ABO blood group incompatibility.

BACKGROUND: ABO antigens are expressed on the surfaces of red blood cells and the vascular endothelium. We studied circulating endothelial microparticles (EMP) in ABO haemolytic disease of the newborn (ABO HDN) as a marker of endothelial activation to test a hypothesis of possible endothelial injury in neonates with ABO HDN, and its relation with the occurrence and severity of haemolysis. MATERIAL AND METHODS: Forty-five neonates with ABO HDN were compared with 20 neonates with Rhesus incompatibility (Rh HDN; haemolytic controls) and 20 healthy neonates with matched mother and infant blood groups (healthy controls). Laboratory investigations were done for markers of haemolysis and von Willebrand factor antigen (vWF Ag). EMP (CD144(+)) levels were measured before and after therapy (exchange transfusion and/or phototherapy). RESULTS: vWF Ag and pre-therapy EMP levels were higher in infants with ABO HDN or Rh HDN than in healthy controls, and were significantly higher in babies with ABO HDN than in those with Rh HDN (p<0.05). In ABO HDN, pre-therapy EMP levels were higher in patients with severe hyperbilirubinaemia than in those with mild and moderate disease or those with Rh HDN (p<0.001). Post-therapy EMP levels were lower than pre-therapy levels in both the ABO HDN and Rh HDN groups; however, the decline in EMP levels was particularly evident after exchange transfusion in ABO neonates with severe hyperbilirubinaemia (p<0.001). Multiple regression analysis revealed that the concentrations of haemoglobin, lactate dehydrogenase and indirect bilirubin were independently correlated with pre-therapy EMP levels in ABO HDN. DISCUSSION: Elevated EMP levels in ABO HDN may reflect an IgG-mediated endothelial injury parallel to the IgG-mediated erythrocyte destruction and could serve as a surrogate marker of vascular dysfunction and disease severity in neonates with this condition.

Repeated supra-maximal sprint cycling with and without sodium bicarbonate supplementation induces endothelial microparticle release.

Under normal homeostatic conditions, the endothelium releases microparticles (MPs), which are known to increase under stressful conditions and in disease states. CD105 (endoglin) and CD106 (vascular cell adhesion molecule-1) are expressed on the surface of endothelial cells and increased expression in response to stress may be observed. A randomised-controlled double-blinded study aimed to examine the use of endothelial MPs as a marker for the state of one's endothelium, as well as whether maintaining acid-base homeostasis affects the release of these MPs. This study tested seven healthy male volunteers, who completed a strenuous cycling protocol, with venous blood analysed for CD105+ and CD106+ MPs by flow cytometry at regular intervals. Prior to each trial participants consumed either 0.3 g·kg(-1) body mass of sodium bicarbonate (NaHCO3), or 0.045 g·kg(-1) body mass of sodium chloride (NaCl). A significant rise in endothelial CD105+ MPs and CD106+ MPs (p<0.05) was observed at 90 min post-exercise. A significant trend was shown for these MPs to return to resting levels 180 min post-exercise in both groups. No significance was found between experimental groups, suggesting that maintaining acid-base variables closer to basal levels has little effect upon the endothelial stress response for this particular exercise mode. In conclusion, strenuous exercise is accompanied by MP release and the endothelium is able to rapidly recover in healthy individuals, whilst maintaining acid-base homeostasis does not attenuate the MP release from the endothelium after exercise.