Elevated Urine Heparanase Levels Are Associated with Proteinuria and Decreased Renal Allograft Function

Heparanase is an endo-β-glucuronidase that cleaves heparan sulfate side chains, leading to structural modifications that loosen the extracellular matrix barrier and associated with tumor metastasis, inflammation and angiogenesis. In addition, the highly sulfated heparan sulfate proteoglycans are important constituents of the glomerular basement membrane and its permselective properties. Recent studies suggest a role for heparanase in several experimental and human glomerular diseases associated with proteinuria such as diabetes, minimal change disease, and membranous nephropathy. Here, we quantified blood and urine heparanase levels in renal transplant recipients and patients with chronic kidney disease (CKD), and assessed whether alterations in heparanase levels correlate with proteinuria and renal function. We report that in transplanted patients, urinary heparanase was markedly elevated, inversely associated with estimated glomerular filtration rate (eGFR), suggesting a relationship between heparanase and graft function. In CKD patients, urinary heparanase was markedly elevated and associated with proteinuria, but not with eGFR. In addition, urinary heparanase correlated significantly with plasma heparanase in transplanted patients. Such a systemic spread of heparanase may lead to damage of cells and tissues alongside the kidney.The newly described association between heparanase, proteinuria and decreased renal function is expected to pave the way for new therapeutic options aimed at attenuating chronic renal allograft nephropathy, leading to improved graft survival and patient outcome.     

Serum IgG Antibody Levels to Periodontal Microbiota Are Associated with Incident Alzheimer Disease

Background

Periodontitis and Alzheimer disease (AD) are associated with systemic inflammation. This research studied serum IgG to periodontal microbiota as possible predictors of incident AD.

Methods

Using a case-cohort study design, 219 subjects (110 incident AD cases and 109 controls without incident cognitive impairment at last follow-up), matched on race-ethnicity, were drawn from the Washington Heights-Inwood Columbia Aging Project (WHICAP), a cohort of longitudinally followed northern Manhattan residents aged >65 years. Mean follow-up was five years (SD 2.6). In baseline sera, serum IgG levels were determined for bacteria known to be positively or negatively associated with periodontitis (Porphyromonas gingivalis, Tannerella forsythia, Actinobacillus actinomycetemcomitans Y4, Treponema denticola, Campylobacter rectus, Eubacterium nodatum, and Actinomyces naeslundii genospecies-2). In all analyses, we used antibody threshold levels shown to correlate with presence of moderate-severe periodontitis.

Results

Mean age was 72 years (SD 6.9) for controls, and 79 years (SD 4.6) for cases (p<0.001). Non-Hispanic Whites comprised 26%, non-Hispanic Blacks 27%, and Hispanics 48% of the sample. In a model adjusting for baseline age, sex, education, diabetes mellitus, hypertension, smoking, prior history of stroke, and apolipoprotein E genotype, high anti-A. naeslundii titer (>640 ng/ml, present in 10% of subjects) was associated with increased risk of AD (HR = 2.0, 95%CI: 1.1–3.8). This association was stronger after adjusting for other significant titers (HR = 3.1, 95%CI: 1.5–6.4). In this model, high anti-E. nodatum IgG (>1755 ng/ml; 19% of subjects) was associated with lower risk of AD (HR = 0.5, 95%CI: 0.2–0.9).

Conclusions

Serum IgG levels to common periodontal microbiota are associated with risk for developing incident AD.     

Decreased Reactive Oxygen Species Production in Cells with Mitochondrial Haplogroups Associated with Longevity

Mitochondrial DNA (mtDNA) is highly polymorphic, and its variations in humans may contribute to individual differences in function. Zhang and colleagues found a strikingly higher frequency of a C150T transition in the D-loop of mtDNA from centenarians and twins of an Italian population, and also demonstrated that this base substitution causes a remodeling of the mtDNA 151 replication origin in human leukocytes and fibroblasts [1]. The C150T transition is a polymorphism associated with several haplogroups. To determine whether haplogroups that carry the C150T transition display any phenotype that may be advantageous for longevity, we analyzed cybrids carrying or not the C150T transition. These cybrids were obtained by fusing cytoplasts derived from human fibroblasts with human mtDNA-less cells (ρ⁰ cells). We chose for cybrid construction and analysis haplogroup-matched pairs of fibroblast strains containing or not the C150T transition. In particular, we used, as one pair of mtDNA donors, a fibroblast strain of the U3a haplogroup, carrying the C150T transition and a strain of the U-K2 haplogroup, without the C150T transition, and as another pair, fibroblasts of the J2b haplogroup, carrying the C150T transition and of the J1c haplogroup, without the C150T transition. We have found no association of respiratory capacity, mtDNA level, mitochondrial gene expression level, or growth rate with the presence of the C150T transition. However, we have found that the cybrids with haplogroups that include the C150T transition have in common a lower reactive oxygen species (ROS) production rate than the haplogroup-matched cybrids without that transition. Thus, the lower ROS production rate may be a factor in the increased longevity associated with the U and the J2 haplogroups. Of further interest, we found that cybrids with the U3a haplogroup exhibited a higher respiration rate than the other cybrids examined.     

Bisecting GlcNAc mediates the binding of annexin V to Hsp47

The bisecting N-acetylglucosamine (GlcNAc) structure, formed through catalysis by UDP-N-acetylglucosamine : beta-D-mannoside beta-1,4-N-acetylglucosaminyltansferase III (GnT-III), is responsible for a variety of biological functions. We have previously shown that annexin V, a member of the calcium/phospholipid-binding annexin family of proteins, has binding activity toward the bisecting GlcNAc structure. In this study, we reported on a search for potential target glycoproteins for annexin V in a rat hepatoma cell line, M31. Using a glutathione S-transferase (GST)-annexin V immobilized sepharose 4B affinity column to trap interacting proteins produced by the GnT-III-transfected M31 cells, we isolated a 47 kDa protein. It was identified as Hsp47 by an N-terminal sequence analysis. Immunoprecipitation experiments showed that annexin V interacted with Hsp47. The association of annexin V and Hsp47 was abolished by treatment with N-glycosidase F or preincubation with sugar chains containing bisecting GlcNAc, suggesting that the bisecting GlcNAc plays an important role in the interaction. An oligosaccharide analysis of Hsp47 purified from GnT-III-transfected M31 cells was shown to have the bisecting GlcNAc structure, as detected by erythroagglutinating phytohemagglutinin (E4-PHA) and matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MS) analysis. Surface plasmon resonance analysis showed that annexin V was bound to Hsp47, bearing a bisecting GlcNAc with a Kd of 5.5 microM, whereas no significant binding was observed in the case of Hsp47 without a bisecting GlcNAc. In addition, immunofluorescence microscopy revealed the colocalization of annexin V, Hsp47, and a bisecting GlcNAc sugar chain around the Golgi apparatus. Collectively, these results suggest that the binding of annexin V to Hsp47 is mediated by a bisecting GlcNAc oligosaccharide structure and that Hsp47 is an intracellular ligand glycoprotein for annexin V.     

Placental Cadmium Levels Are Associated with Increased Preeclampsia Risk

Environmental exposure to heavy metals is a potentially modifiable risk factor for preeclampsia (PE). Toxicologically, there are known interactions between the toxic metal cadmium (Cd) and essential metals such as selenium (Se) and zinc (Zn), as these metals can protect against the toxicity of Cd. As they relate to preeclampsia, the interaction between Cd and these essential metals is unknown. The aims of the present study were to measure placental levels of Cd, Se, and Zn in a cohort of 172 pregnant women from across the southeast US and to examine associations of metals levels with the odds of PE in a nested case-control design. Logistic regressions were performed to assess odds ratios (OR) for PE with exposure to Cd controlling for confounders, as well as interactive models with Se or Zn. The mean placental Cd level was 3.6 ng/g, ranging from 0.52 to 14.5 ng/g. There was an increased odds ratio for PE in relationship to placental levels of Cd (OR = 1.5; 95% CI: 1.1–2.2). The Cd-associated OR for PE increased when analyzed in relationship to lower placental Se levels (OR = 2.0; 95% CI: 1.1–3.5) and decreased with higher placental Se levels (OR = 0.98; 95% CI: 0.5–1.9). Similarly, under conditions of lower placental Zn, the Cd-associated OR for PE was elevated (OR = 1.8; 95% CI: 0.8–3.9), whereas with higher placental Zn it was reduced (OR = 1.3; 95% CI: 0.8–2.0). Data from this pilot study suggest that essential metals may play an important role in reducing the odds of Cd-associated preeclampsia and that replication in a larger cohort is warranted.     

Bisecting GlcNAc Is a General Suppressor of Terminal Modification of N-glycan,

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Highlights

• •Loss of bisecting GlcNAc in N-glycan increases various terminal glycan modifications.
• •Glycosyltransferases commonly do not act well on glycans with bisecting GlcNAc.
• •Presence of bisecting GlcNAc alters overall conformation of N-glycan.
• •Bisecting GlcNAc serves as a general suppressor for terminal modification.

     

Circulating Docosahexaenoic Acid Levels Are Associated with Fetal Insulin Sensitivity

Background

Arachidonic acid (AA; C20∶4 n-6) and docosahexaenoic acid (DHA; C22∶6 n-3) are important long-chain polyunsaturated fatty acids (LC-PUFA) in maintaining pancreatic beta-cell structure and function. Newborns of gestational diabetic mothers are more susceptible to the development of type 2 diabetes in adulthood. It is not known whether low circulating AA or DHA is involved in perinatally “programming” this susceptibility. This study aimed to assess whether circulating concentrations of AA, DHA and other fatty acids are associated with fetal insulin sensitivity or beta-cell function, and whether low circulating concentrations of AA or DHA are involved in compromised fetal insulin sensitivity in gestational diabetic pregnancies.

Methods and Principal Findings

In a prospective singleton pregnancy cohort, maternal (32-35 weeks gestation) and cord plasma fatty acids were assessed in relation to surrogate indicators of fetal insulin sensitivity (cord plasma glucose-to-insulin ratio, proinsulin concentration) and beta-cell function (proinsulin-to-insulin ratio) in 108 mother-newborn pairs. Cord plasma DHA levels (in percentage of total fatty acids) were lower comparing newborns of gestational diabetic (n = 24) vs. non-diabetic pregnancies (2.9% vs. 3.5%, P = 0.01). Adjusting for gestational age at blood sampling, lower cord plasma DHA levels were associated with lower fetal insulin sensitivity (lower glucose-to-insulin ratio, r = 0.20, P = 0.036; higher proinsulin concentration, r = −0.37, P <0.0001). The associations remained after adjustment for maternal and newborn characteristics. Cord plasma saturated fatty acids C18∶0 and C20∶0 were negatively correlated with fetal insulin sensitivity, but their levels were not different between gestational diabetic and non-diabetic pregnancies. Cord plasma AA levels were not correlated with fetal insulin sensitivity.

Conclusion

Low circulating DHA levels are associated with compromised fetal insulin sensitivity, and may be involved in perinatally “programming” the susceptibility to type 2 diabetes in the offspring of gestational diabetic mothers.     

Brain S-Adenosylmethionine Levels Are Severely Decreased in Alzheimer's Disease

Abstract: S -Adenosylmethionine is an essential ubiquitous metabolite central to many biochemical pathways, including transmethylation and polyamine biosynthesis. Reduced CSF S -adenosylmethionine levels in Alzheimer's disease have been reported; however, no information is available regarding the status of S -adenosylmethionine or S -adenosylmethionine-dependent methylation in the brain of patients with this disorder. S -Adenosylmethionine concentrations were measured in postmortem brain of 11 patients with Alzheimer's disease. We found decreased levels of S -adenosylmethionine (−67 to −85%) and its demethylated product S -adenosylhomocysteine (−56 to −79%) in all brain areas examined (cerebral cortical subdivisions, hippocampus, and putamen) as compared with matched controls (n = 14). S -Adenosylmethionine and S -adenosylhomocysteine levels were normal in occipital cortex of patients with idiopathic Parkinson's disease (n = 10), suggesting that the decreased S -adenosylmethionine levels in Alzheimer's disease are not simply a consequence of a chronic, neurodegenerative condition. Reduced S -adenosylmethionine levels could be due to excessive utilization in polyamine biosynthesis. The severe reduction in levels of this essential biochemical substrate would be expected to compromise seriously metabolism and brain function in patients with Alzheimer's disease and may provide the basis for the observations of improved cognition in some Alzheimer's patients following S -adenosylmethionine therapy.     

Lower Low-Density Lipoprotein Cholesterol Levels Are Associated with Severe Dengue Outcome

Dengue virus (DENV) is a flavivirus of worldwide importance, with approximately 4 billion people across 128 countries at risk of infection, and up to 390 million infections and 96 million clinically apparent cases estimated annually. Previous in vitro studies have shown that lipids and lipoproteins play a role in modifying virus infectivity. However, the relationship between development of severe dengue and total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, is unclear. We analyzed data from 789 laboratory-confirmed dengue cases and 447 other febrile illnesses (OFI) in a prospective pediatric hospital-based study in Managua, Nicaragua between August 2005 and January 2013, using three different classifications of dengue severity: World Health Organization (WHO) 1997, WHO 2009, and standardized intervention categories. Total serum cholesterol and LDL-C levels decreased over the course of illness and were generally lower with increasing dengue severity, regardless of classification scheme. Greater decreases in LDL-C than HDL-C were observed among dengue-positive patients compared to patients with OFI and among severe dengue compared to mild dengue cases. Furthermore, daily cholesterol levels declined with daily albumin blood levels. To examine the effect of cholesterol at presentation on subsequent risk of development of severe dengue, relative risks and 95% confidence intervals were calculated using multivariable modified Poisson models. We found that lower total serum cholesterol and LDL-C levels at presentation were associated with subsequent risk of developing dengue hemorrhagic fever/dengue shock syndrome using the WHO 1997 dengue severity classification, and thus that the reduction in LDL-C is likely driving the decreases observed in total serum cholesterol levels among dengue-positive patients. Our results suggest that cholesterol blood levels are important correlates of dengue pathophysiology and should be explored as part of a prognostic biomarker panel for severe dengue.     

Plasma Adiponectin Levels Are Not Associated with Fat Oxidation in Humans

Objective: To test the hypothesis that low adiponectin is associated with low fat oxidation in humans. Research Methods and Procedures: We measured plasma adiponectin concentrations in 75 healthy, nondiabetic Pima Indians (age, 28 ± 7 years; 55 men and 20 women; body fat, 29.7 ± 7.5%) and 18 whites [(age, 33 ± 8 years; 14 men and 4 women; body fat, 28.2 ± 10.8% (means ± SD)] whose body composition was measured by DXA and 24-hour energy expenditure (24-hour EE) by a respiratory chamber. Respiratory quotient (an estimate of whole-body carbohydrate/lipid oxidation rate) was calculated over 24 hours (24-hour RQ). Results: Before correlational analyses, waist-to-thigh ratio (WTR) and percentage of body fat (PFAT) were adjusted for age, sex, and race; 24-hour EE was adjusted for fat mass and fat-free mass, and 24-hour RQ were adjusted for energy balance. Plasma adiponectin concentrations were negatively correlated with WTR (r = −0.42, p < 0.0001) and PFAT (r = −0.46, p < 0.0001). There was no correlation between plasma adiponectin concentrations and 24-hour RQ, (r = 0.09, p = 0.36) before or after adjustment for PFAT (r = 0.001, p = 0.99, respectively, partial correlation), and no correlation was found between plasma adiponectin concentrations and 24-hour EE (r = −0.12, p = 0.27). Discussion: Our cross-sectional data do not suggest physiological concentrations of fasting plasma adiponectin play a role in the regulation of whole-body fat oxidation or energy expenditure in resting conditions. Whether administration of adiponectin to individuals with low levels of this hormone will increase their fat oxidation rates/energy expenditure remains to be established.     

Increased Serum Levels of IL-17A and IL-23 Are Associated with Decreased Vitamin D3 and Increased Pain in Osteoarthritis

IntroductionOsteoarthritis (OA) is the most common type of arthritis and proinflammatory cytokines have been considered as the main etiologic factor in the pathogenesis of the disease. Serum levels of cytokines, that are associated with innate immunity and TH1 cells, have been analyzed in OA patients, however, there is limited research that profiles cytokines associated with Th17 cells and their relation to vitamin D3 and pain.ResultsSerum levels of IL-17A, and IL-23 were statistically higher in OA patients than in healthy controls, while IL-21 and vitamin D3 were significantly lower in OA patients when compared to controls. A significant positive correlation was found between the serum levels of IL-17A and IL-23 using WOMAC pain scores and vitamin D3 serum levels.DiscussionThe results suggest that IL-17A plays a significant role in OA pathogenesis and the induction of pain. Decreased serum levels of vitamin D3 may reflect a positive role played by the factor in the regulation of immune responses in OA patients.     

Soluble ST2 Levels Are Associated with Bleeding in Patients with Severe Leptospirosis

Background

Severe leptospirosis features bleeding and multi-organ failure, leading to shock and death. Currently it is assumed that both exaggerated inflammation and immune suppression contribute to mortality in sepsis. Indeed, several proinflammatory cytokines are reported to be induced during leptospirosis. Toll-like receptors, which play an important role in the initiation of an innate immune response, are inhibited by negative regulators including the membrane-bound ST2 (mST2) receptor. Soluble ST2 (sST2) has been implicated to inhibit signaling through mST2. The aim of this study was to determine the extent of sST2 and (pro-) inflammatory cytokine release in patients with severe leptospirosis.

Methodology and Principal Findings

In an observational study, 68 consecutive cases of severe leptospirosis were included. Soluble ST2 and cytokines (TNF-α, IL-1β, IL-6, IL-8, and IL-10) were repeatedly measured. To determine whether blood cells are a source of sST2 during infection, we undertook an in vitro experiment: human whole blood and peripheral blood mononuclear cells (PBMC) were stimulated with viable pathogenic Leptospira. All patients showed elevated sST2, IL-6, IL-8, and IL-10 levels on admission. Admission sST2 levels correlated with IL-6, IL-8, and IL-10. Thirty-four patients (50%) showed clinical bleeding. Soluble ST2 levels were significantly associated with bleeding overall (OR 2.0; 95%CI: 1.2–3.6) and severe bleeding (OR 5.1; 95%CI: 1.1–23.8). This association was unique, since none of the cytokines showed this correlation. Moreover, sST2 was associated with mortality (OR 2.4; 95%CI: 1.0–5.8). When either whole blood or isolated PBMCs were stimulated with Leptospira in vitro, no sST2 production could be detected.

Conclusions

Patients with severe leptospirosis demonstrated elevated plasma sST2 levels. Soluble ST2 levels were associated with bleeding and mortality. In vitro experiments showed that (white) blood cells are probably not the source. In this regard, sST2 could be an indicative marker for tissue damage in patients suffering from severe leptospirosis.     

Serum Interleukin-18 Levels Are Associated with Physical Activity in Japanese Men

Objective

To investigate the link between serum interleukin-18 (IL-18) levels and physical activity in Japanese men.

Methods

A total of 81 men (45.7±17.6 years old) was enrolled in this cross-sectional investigation study. We assessed anthropometric and body composition parameters. Serum IL-18 levels, physical activity by uniaxial accelerometers, peak oxygen uptake and metabolic risk parameters were also evaluated.

Results

Serum IL-18 levels were 179.4±84.7 pg/mL. Physical activity evaluated by Σ[metabolic equivalents × h per week (METs⋅h/w)]was significantly and negatively correlated with serum IL-18 levels (r = −0.252, p = 0.0235). These associations remained even after adjusting for age, peak oxygen uptake and other confounding factors.

Conclusion

Serum IL-18 levels were closely associated with physical activity independent of peak oxygen uptake in Japanese men.     

Low Serum 25-Hydroxyvitamin D Levels Are Associated with Dry Eye Syndrome

Background

Dry eye syndrome (DES) is a common tear film and ocular surface disease that results in discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. Systemic diseases associated with DES include diabetes mellitus, rheumatoid arthritis, depression, anxiety, thyroid disease, allergic diseases, irritable bowel syndrome, chronic pain syndrome, and hyperlipidemia. Interestingly, it has been found that most of these are associated with low levels of serum 25-hydroxyvitamin D (25(OH)D) or inadequate sunlight exposure.

Methods

In this cross-sectional data analysis, noninstitutionalized adults aged ≥19 years (N = 17,542) who participated in Korean National Health and Nutrition Examination Survey 2010–2012 were included. Information regarding duration of sunlight exposure was collected from the survey participants. Serum 25(OH)D and zinc levels were measured. The confounding variables were age, gender, sunlight exposure time, region of residence, obesity, serum 25(OH)D level, diabetes mellitus, rheumatoid arthritis, depression, thyroid disorder, atopic dermatitis, history of ocular surgery, regular exercise, and walking exercise.

Results

Mean serum 25(OH)D levels of subjects with and without DES were 16.90 ± 6.0 and 17.52 ± 6.07 (p<0.001). Inadequate sunlight exposure time (odds ratio [OR], 1.554; 95% confidence interval [CI], 1.307–1.848), urban residence (OR, 1.669; 95% CI, 1.456–1.913), indoor occupation (OR, 1.578; 95% CI, 1.389–1.814), and low serum 25(OH)D level (OR, 1.158; 95% CI, 1.026–1.308) were the risk factors for DES. After adjusting for age, sex, obesity, diabetes mellitus, rheumatoid arthritis, depression, thyroid disorder, atopic dermatitis, history of ocular surgery, regular exercise, and occupation, low serum 25(OH)D level (OR, 1.178; 95% CI, 1.010–1.372) and deficient sunlight exposure time (OR, 1.383; 95% CI, 1.094–1.749) were the risk factors for diagnosed DES.

Conclusion

Low serum 25(OH)D levels and inadequate sunlight exposure are associated with DES in Korean adults. These results suggest that sufficient sunlight exposure or vitamin D supplementation may be useful in DES treatment.     

Hepatitis C Viremia Is Associated with Cytomegalovirus IgG Antibody Levels in HIV-Infected Women

Background

Individuals with HIV infection exhibit high cytomegalovirus (CMV) IgG levels, but there are few data regarding the association of hepatitis C virus (HCV) with the immune response against CMV.

Methods

Associations of HCV with CMV seropositivity and CMV IgG levels were studied in 635 HIV-infected women, 187 of whom were HCV-seropositive, with adjustment in multivariable models for age, race/ethnicity, and HIV disease characteristics. Eighty one percent of the women reported receipt of highly active antiretroviral therapy (HAART) prior to or at CMV testing.

Results

In adjusted models women with chronic HCV had higher CMV IgG levels than those without HCV RNA (β = 2.86, 95% CI:0.89 – 4.83; P = 0.004). The association of HCV RNA with CMV IgG differed by age (P _interaction = 0.0007), with a strong association observed among women in the low and middle age tertiles (≤45.3 years of age; β = 6.21, 95% CI:3.30 – 9.11, P<0.0001) but not among women in the high age tertile. CMV IgG levels were not associated with non-invasive measures of liver disease, APRI and FIB-4, or with HCV RNA level and adjustment for Epstein-Barr virus (EBV) IgG levels did not affect the association between HCV and CMV.

Conclusions

CMV IgG levels are higher in HCV/HIV co-infected women than in HIV mono-infected women. Further research on the association of HCV with CMV IgG is indicated because prior studies have found CMV IgG to be associated with morbidity and mortality in the general population and subclinical carotid artery disease in HIV-infected patients.     

Plasma Levels of microRNA-145 Are Associated with Severity of Coronary Artery Disease

MethodsA total of 195 consecutive subjects who underwent coronary angiography for chest pain evaluation were enrolled in this study. In CAD patients severity of coronary lesions was assessed by the number of diseased vessels and the Synergy between PCI with Taxus and Cardiac surgery score (SYNTAX score). Plasma levels of miRNA-145 were quantified by real-time quantitative polymerase chain reaction test, and logarithmic transformation of miRNA-145 levels (Ln_miRNA-145) was used for analyses due to its skewed distribution.ResultsOf the 195 total subjects 167 patients were diagnosed as having CAD. Ln_miRNA-145 was significantly lower in CAD patients compared with the non-CAD group (-6.11±0.92 vs. -5.06±1.25; p <0.001). In multivariable linear regression analyses CAD was significantly associated with lower Ln_miRNA-145 (Estimate, -0.50; standard error (SE), 0.11; p <0.0001). Furthermore, among CAD patients, three-vessel disease, higher SYNTAX scores and STEMI were significantly associated with lower Ln_miRNA-145 ([Estimate, -0.40; SE, 0.07; p <0.0001]; [Estimate, -0.02, SE, 0.10; p = 0.005] and [Estimate, -0.35, SE, 0.10; p <0.001] respectively).ConclusionsLower plasma levels of miRNA-145 were significantly associated with the presence as well as severity of CAD. As a potential biomarker for CAD, plasma miRNA-145 may be useful in predicting CAD and its severity in patients presenting with chest pain.     

Primary Human Natural Killer Cells Retain Proinflammatory IgG1 at the Cell Surface and Express CD16a Glycoforms with Donor-dependent Variability

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Highlights

• •Enough CD16a from NK cells can be isolated from a single donor following apheresis.
• •NK cell CD16a shows variability between different donors.
• •NK cells preferentially bind IgG1 that lacks core fucosylation.

     

Increased Vaspin Levels Are Associated with Beneficial Metabolic Outcome Pre- and Post-Bariatric Surgery

Purpose

Vaspin (visceral-adipose-tissue-derived-serine-protease-inhibitor) is a recently identified adipokine with putative insulin-sensitizing properties. Plasma vaspin responses to surgery-induced weight loss are sparse and contradictory.

Design and Participants

We evaluated changes in vaspin levels and relationship to post-operative outcomes in men (n = 22) and women (n = 55) undergoing biliopancreatic-diversion/duodenal-switch bariatric surgery. Body composition and plasma parameters were measured at baseline, acutely (1 and 5 days) and medium-term (6 and 12 months) post-surgery.

Results

Fasting preoperative vaspin concentrations were comparable in men vs women. The distribution was biphasic (both men and women) with a nadir of 2.5 ng/ml. Subjects were divided into high (≥2.5 ng/mL, HI-group) and low (<2.5 ng/mL, LO-group) vaspin level. Both groups had comparable sex distribution, age and BMI, but the HI-vaspin group had lower insulin, HOMA, and triglyceride and higher HDL-cholesterol, acylation stimulating protein (ASP) and IL-6 levels (all p<0.05). Post-operatively, both groups decreased BMI comparably over 12 months; the HI-vaspin group maintained high vaspin levels, while the LO-vaspin group gradually increased their levels with weight loss over 12 months. The HI-vaspin group maintained a better glucose, insulin, HOMA, fructosamine, HDL-cholesterol, and triglyceride profile throughout. The HI-vaspin group also had higher gamma-glutamyltransferase and ASP profiles. Finally, baseline vaspin level inversely correlated significantly with baseline and 12-month insulin, HOMA, triglyceride and positively correlated with HDL and ASP. Twelve-month vaspin also correlated similarly, including an inverse correlation with BMI.

Conclusion

Globally, this study supports the concept of vaspin as a beneficial adipokine in obesity, which may potentially lead to possible therapeutic targets.