92 research outputs found

    Serum or Plasma (and Which Plasma), That Is the Question

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    Blood derivatives are the biofluids of choice formetabolomic clinical studies since blood can be collected with lowinvasiveness and is rich in biological information. However, the choiceof the blood collection tubes has an undeniable impact on the plasmaand serum metabolic content. Here, we compared the metabolomicand lipoprotein profiles of blood samples collected at the same timeand place from six healthy volunteers but using different collectiontubes (each enrolled volunteer provided multiple blood samples at adistance of a few weeks/months): citrate plasma, EDTA plasma, andserum tubes. All samples were analyzed via nuclear magnetic resonancespectroscopy. Several metabolites showed statistically significantalterations among the three blood matrices, and also metabolites'correlations were shown to be affected. The effects of blood collectiontubes on the lipoproteins'profiles are relevant too, but less marked. Overcoming the issue associated with different blood collectiontubes is pivotal to scale metabolomics and lipoprotein analysis at the level of epidemiological studies based on samples frommulticenter cohorts. We propose a statistical solution, based on regression, that is shown to be efficient in reducing the alterationsinduced by the different collection tubes for both the metabolomic and lipoprotein profile

    Serum or Plasma (and Which Plasma), That Is the Question

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    Blood circulating miR-28-5p and let-7d-5p associate with premature ageing in Down syndrome

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    Persons with Down syndrome (DS) undergo a premature ageing with early onset of age-related diseases. The main endpoint of this study was the identification of blood circulating microRNAs (c-miRs) signatures characterizing DS ageing process. A discovery phase based on array was performed in plasma samples obtained from 3 young (31 ± 2 years-old) and 3 elderly DS persons (66 ± 2 years-old). Then, a validation phase was carried out for relevant miRs by RT-qPCR in an enlarged cohort of 43 DS individuals (from 19 up to 68 years-old). A group of 30 non-trisomic subjects, as representative of physiological ageing, was compared. In particular miR-628-5p, miR-152-3p, miR-28-5p, and let-7d-5p showed a lower level in younger DS persons (age ≤ 50 years) respect to the age-matched controls. Among those, miR-28-5p and let-7d-5p were found significantly decreased in physiological ageing ( oldest group ), thus they emerged as possible biomarkers of premature ageing in DS. Moreover, measuring blood levels of beta amyloid peptides, Aβ-42 was assessed at the lowest levels in physiological ageing and correlated with miR-28-5p and let-7d-5p in DS, while Aβ-40 correlated with miR-628-5p in the same cohort. New perspectives in terms of biomarkers are discussed

    Circulating perilipin 2 levels are associated with fat mass, inflammatory and metabolic markers and are higher in women than men.

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    Perilipin 2 (PLIN2) is a protein involved in lipid storage and metabolism in non-adipose tissues. Detectable levels of circulating PLIN2 (cPLIN2) have been reported to be associated with some types of cancer, but no systematic analysis of age-related modifications in cPLIN2 levels has ever been performed. We measured serum cPLIN2 in a group of old people including centenarians in comparison with young subjects and tested possible correlations with parameters of body composition, fat and glucose metabolism, and inflammation. We found that: i. levels of cPLIN2 do not change with age, but women have higher levels of cPLIN2 with respect to men; ii. cPLIN2 levels strongly correlate to BMI, as well as fat and lean mass; iii. cPLIN2 levels strongly correlate with the proinflammatory adipokine leptin. Due to the adipogenic activity of leptin, it is hypothesized that cPLIN2 is affected and possibly regulated by this pleiotropic adipokine. Moreover, these results suggest that cPLIN2 (possibly together with leptin) could be assumed as a proxy for body adiposity

    Transcultural body spaces: re-inventing and performing headwrap practice among young Congolese women in London

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    This article examines embodied representation of race, ethnicity, and gender, questioning ideas of cultural appropriation. Using the London-based Congolese transnational fashion brand Kiyana Wraps as a case study, the article addresses how young Congolese designers re-invent their cultural heritage to conceive the label stylisation and construct meanings of Blackness/Africanness. The article also explores the brand’s social spaces, where the headwrap ritual is used by different actors to perform hybrid identities. In addition, wearing the headwrap reveals symbolic metaphors of empowerment, through which intertwined ‘feminist’ and ‘feminine’ identities are evoked. The paper examines how Congolese women are creatively taking inspiration from the environment of London to produce innovative fashion trajectories as lived socio-cultural experiences. It argues how the headwrap ritual signifies an aesthetic and material process through which specific racial and ethnic boundaries are transcended, fabricating transcultural body spaces which encompass individuals with diverse cultural backgrounds

    Discordance in glycemic categories and regression to normality at baseline in 10,000 people in a Type 2 diabetes prevention trial

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    The world diabetes population quadrupled between 1980 and 2014 to 422 million and the enormous impact of Type 2 diabetes is recognised by the recent creation of national Type 2 diabetes prevention programmes. There is uncertainty about how to correctly risk stratify people for entry into prevention programmes, how combinations of multiple ‘at high risk’ glycemic categories predict outcome, and how the large recently defined ‘at risk’ population based on an elevated glycosylated haemoglobin (HbA1c) should be managed. We identified all 141,973 people at highest risk of diabetes in our population, and screened 10,000 of these with paired fasting plasma glucose and HbA1c for randomisation into a very large Type 2 diabetes prevention trial. Baseline discordance rate between highest risk categories was 45.6 %, and 21.3 - 37.0 % of highest risk glycaemic categories regressed to normality between paired baseline measurements (median 40 days apart). Accurate risk stratification using both fasting plasma glucose and HbA1c data, the use of paired baseline data, and awareness of diagnostic imprecision at diagnostic thresholds would avoid substantial overestimation of the true risk of Type 2 diabetes and the potential benefits (or otherwise) of intervention, in high risk subjects entering prevention trials and programmes

    Regulatory T-cells from pancreatic lymphnodes of patients with type-1 diabetes express increased levels of microRNA miR-125a-5p that limits CCR2 expression

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    Autoimmune type 1 diabetes (T1D) is thought to be caused by a defective immune regulation with regulatory T (Treg) cells playing a fundamental role in this process. Tolerance mechanisms depend on tunable responses that are sensitive to minor perturbations in the expression of molecules that can be carried out by multiple epigenetic mechanisms, including regulation by microRNAs. In this study, microRNA expression profile was investigated in Treg cells isolated from peripheral blood (PB) and from pancreatic draining lymph nodes (PLN) of T1D patients and non-diabetic subjects. Among 72 microRNAs analyzed, miR-125a-5p resulted specifically hyper-expressed in Treg cells purified from PLN of T1D patients. TNFR2 and CCR2 were identified as miR-125a-5p target genes. Elevated miR-125a-5p was detected in Treg cells isolated from PLN but not from PB of donors with T1D and was associated with reduced CCR2 expression. A specific beta-cell expression of the CCR2-ligand (CCL2) was observed in the pancreata of cadaveric donors, suggesting that beta-cells are prone to attract CCR2+ Treg cells. These novel data propose a mechanism, occurring in PLNs of T1D patients, involving increased expression of miR-125a-5p on Treg cells which results into reduced expression of CCR2, thus limiting their migration and eventual function in the pancreas

    Goettingen Minipigs (GMP): Comparison of Two Different Models for Inducing Diabetes

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    Purpose: Preclinical experiments on large animals are indispensable for evaluating the effectiveness of diabetes therapies. Miniature swine are well suited for such studies due to their physiological and pathophysiological responses. Methods: We compare two methods for inducing diabetes in Goettingen minipigs (GMP), in five with the beta cell toxin streptozotocin (STZ) and in five other GMP by total pancreatectomy (PE). Glucose homeostasis was assessed with the intravenous glucose-tolerance test (IVGTT) and continual monitoring of interstitial glucose levels. At conclusion of the observation period, the pancreata were examined histologically. Three non-diabetic GMP served as control group. Results: The IVGTT revealed markedly diabetic profiles in both GMP groups. STZ-GMP were found to harbor residual C-peptides and scattered insulin-positive cells in the pancreas. PE-GMP survived the total pancreatectomy only with intensive postoperative care. Conclusions: Although both methods reliably induced diabetes in GMP, the PE-GMP clearly had more health problems and required a greater expenditure of time and resources. The PE-GMP model, however, was better at eliminating endogenous insulin and C-peptide than the STZ-GMP model
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