Plasma lipidomic profiling in patients with rheumatoid arthritis

Introduction

Rheumatoid arthritis (RA) is linked to increased cardiovascular morbidity and mortality, not completely explained by traditional risk factors. Importantly, the increased risk occurs despite lower levels of total and low-density lipoprotein cholesterol. Whilst systemic inflammation may be a factor, it is possible that changes in individual lipid species contribute to the increased cardiovascular risk.

Objectives

In the present study, we characterized plasma lipidomic profiles in patients with RA in comparison with healthy controls.

Methods

Patients with RA (n = 32) and age- and gender-matched healthy volunteers (n = 84) were recruited. Fasting plasma lipid profiles were measured using electrospray-ionisation tandem mass spectrometry. 24 lipid classes and subclasses were measured.

Results

Patients with RA had normal total, low-density lipoprotein and high-density lipoprotein cholesterol, but higher triglycerides than controls. Five lipid classes (dihydroceramides, alkylphosphatidylethanolamine, alkenylphosphatidylethanolamine, lysophosphatidylinositol, phosphatidylserine) differed between patients with RA and controls. Then we measured 36 lipid species within these 5 classes and found that 11 lipid species were different between patients with RA and controls. Three lipid classes (dihydroceramides, lysophosphatidylinositol, phosphatidylserine) and 10 lipid species remained significantly associated with RA after adjusting for age, sex, body mass index, current smoking, systolic blood pressure and anti-hypertensive treatment in a binary logistic regression model.

Conclusion

This study has identified lipid alterations in RA. These alterations of lipids warrant further investigation as they may be associated with accelerated atherosclerosis and joint inflammation in patient with RA.

     

Exploiting the natural poly(3-hydroxyalkanoates) production capacity of Antarctic Pseudomonas strains: from unique phenotypes to novel biopolymers

Journal of Industrial Microbiology & Biotechnology - Extreme environments are a unique source of microorganisms encoding metabolic capacities that remain largely unexplored. In this work, we...     

The effect of obesity management on body image in patients seeking treatment at medical centers

Objective: Body image dissatisfaction is common in treatment‐seeking patients with obesity. We aimed to investigate the effects of obesity management on body image in patients with obesity attending Italian medical centers for weight loss programs. Research Methods and Procedures: A total of 473 obese patients seeking treatment in 13 Italian medical centers (80% females; age, 45.9 ± standard deviation 11.0 years; BMI, 36.8 ± 5.7 kg/m²) were evaluated at baseline and after a 6‐month weight loss treatment. Body uneasiness, psychiatric distress, and binge eating were tested by Body Uneasiness Test (BUT, Part A), Symptom CheckList‐90 (SCL‐90), and Binge Eating Scale (BES), respectively. Results: At 6‐month follow‐up, the percentage weight loss was significantly higher in men (9.0 ± 6.3%) than in women (6.8 ± 7.3%; p = 0.010). Both men and women had a significant improvement in BUT Global Severity Index and in all of the BUT subscales with the exception of the Compulsive Self‐Monitoring subscale. Linear regression analysis selected baseline psychological and behavioral measures (global score of BUT and SCL‐90) and improved psychiatric distress and binge eating as independent predictors of changes in basal body dissatisfaction in females, whereas in males, changes were associated only with baseline BUT‐Global Severity Index score, binge eating, and its treatment‐associated improvement. Pre‐treatment BMI and BMI changes did not enter the regression. Discussion: Obesity treatment, even with a modest degree of weight loss, is associated with a significant improvement of body image, in both females and males. This effect depends mainly on psychological factors, not on the amount of weight loss.     

Structural characterization of the L0 cytoplasmic loop of human multidrug resistance protein 6 (MRP6)

ABCC6 is a member of the C subfamily of ATP-binding cassette transporters whose mutations are correlated to Pseudoxanthoma elasticum, an autosomal recessive, progressive disorder characterized by ectopic mineralization and fragmentation of elastic fibers. Structural studies of the entire protein have been hindered by its large size, membrane association, and domain complexity. Studies previously performed have contributed to shed light on the structure and function of the nucleotide binding domains and of the N-terminal region. Here we report the expression in E. coli of the polypeptide E₂₀₅-G₂₇₉ contained in the cytoplasmic L0 loop. For the first time structural studies in solution were performed. Far-UV CD spectra showed that L0 is structured, assuming predominantly α-helix in TFE solution and turns in phosphate buffer. Fluorescence spectra indicated some flexibility of the regions containing aromatic residues. ¹H NMR spectroscopy identified three helical regions separated by more flexible regions.     

Overexpression of sialidase NEU3 increases the cellular radioresistance potential of U87MG glioblastoma cells

The plasma membrane-associated sialidase NEU3 is known to play important roles in different physiological and pathophysiological processes such as proliferation, cellular differentiation and tumorigenesis. Up-regulation of NEU3 has been associated to several tumors and recently it was demonstrated that its down-modulation in glioblastoma cells promotes cell invasiveness. To date, no information concerning the possible role played by NEU3 in relation to tumor radioresistance is available. Here we show that overexpression of NEU3 in glioblastoma U87MG cells activates PI3K/Akt signaling pathway resulting in an increased radioresistance capacity and in an improved efficiency of double strand DNA-repair mechanisms after irradiation. Our results demonstrate for the first time that NEU3 contributes to the radioresistance features of U87MG cells, bringing to evidence a novel rand peculiar role of the enzyme in cancer biology.     

Solvent-mediated conformational transition in β-alanine containing cyclic peptides. VIII

In the present paper we describe the solution nmr structural analysis and restrained molecular dynamic simulation of the cyclic pentapeptide cyclo-(Pro-Phe-Phe-β-Ala-β-Ala). The conformational analysis carried out in CD₃CN and dimethylsulfoxide (DMSO) solutions by nmr spectroscopy was based on interproton distances derived from rotating frame nuclear Overhauser effect spectroscopy spectra and homonuclear coupling constants. A restrained molecular dynamic simulation in vacuo was also performed to build refined molecular models. The molecule is present in both solvent systems as two slowly interconverting conformers, characterized by a cis-trans isomerism around the β-Ala⁵-Pro¹ peptide bond. In CD₃CN solution, the conformer with a cis peptide bond is quite similar to that observed in the solid state, while the conformer containing all trans peptide bonds is characterized by an intramolecular hydrogen bond stabilizing a C₁₀- and a C₁₃-ring structure. In DMSO solution, the trans isomer is partly similar to that observed in CD₃CN solution while the cis isomer is different from that observed in the solid state. The effect of the solvent in stabilizing different conformations was also investigated in DMSO-CD₃CN solvent mixtures. © 1996 John Wiley & Sons, Inc.