Age and immunity

Longitudinal studies are defining progressive alterations to the immune system associated with increased mortality in the very elderly. Many of these changes are exacerbated by or even caused by chronic T cell stimulation by persistent antigen, particularly from Cytomegalovirus. The composition of T cell subsets, their functional integrity and representation in the repertoire are all markedly influenced by age and by CMV. How these findings relate to epidemiological, functional, genetic, genomic and proteomic studies of human T cell immunosenescence was the subject of intense debate at an international conference held just before Christmas 2005 in the Black Forest

Zinc, oxidative stress, genetic background and immunosenescence: implications for healthy ageing

The relevance of zinc for proper functioning of the entire immune system is already well documented. However, the identification of individuals who really need zinc supplementation is still debated in view of the fact that excessive zinc may also be toxic. The risk of developing zinc deficiency in people from industrialized countries is relatively low, except for elderly subjects where zinc intake may be suboptimal and inflammation is chronic. Thus, the role of zinc on the immune system and on the health of European elderly people is becoming of paramount importance, considering also that the elderly population is rapidly increasing. In particular, the factors contributing to and the biochemical markers of zinc deficiency in the elderly are still remain to be established. Epidemiological, functional, and genetic studies aimed at formulating a rationale for the promotion of healthy ageing through zinc supplementation was the subject of an International Conference held in Madrid from 11–13 February 2006 (3(rd )ZincAge Meeting) at the CNIO Institute (local organizer: Maria Blasco, partner of ZincAge

Randomized controlled clinical trials in orthopedics: difficulties and limitations

Os ensaios clínicos controlados e randomizados (ECCR) são considerados o padrão ouro da medicina baseada em evidências na atualidade, sendo importantes para direcionar a conduta médica através de observações científicas consistentes. Passos como seleção dos pacientes, randomização e cegamento são fundamentais na realização de um ECCR e apresentam algumas dificuldades extras nos ensaios que envolvem procedimentos cirúrgicos, como é comum na Ortopedia. O objetivo deste artigo é destacar e discutir algumas dificuldades e eventuais limitações dos ECCR na área cirúrgica.Randomized controlled clinical trials (RCTs) are considered to be the gold standard for evidence-based medicine nowadays, and are important for directing medical practice through consistent scientific observations. Steps such as patient selection, randomization and blinding are fundamental for conducting an RCT, but some additional difficulties are presented in trials that involve surgical procedures, as in common in orthopedics. The aim of this article was to highlight and discuss some difficulties and possible limitations on RCTs within the field of surgery

Are zinc-bound metallothionein isoforms (I+II and III) involved in impaired thymulin production and thymic involution during ageing?

BACKGROUND: With advancing age, thymic efficiency shows progressive decline due to thymic involution allowing impaired cell-mediated immunity and the appearance of age-related diseases. The intrinsic cause of thymic involution is still undefined. Chronic inflammation and high glucocorticoids (GCs) may be involved. However, transgenic mice, with increased GC sensitivity and over expression of GC receptors, display delayed age-associated thymic involution. This fact suggests that other substances may affect thymic involution. Among them, both isoforms of metallothioneins (MTs) I+II and III are the major candidates because their increments leads to organ atrophy in constant stress and are induced by IL-6, which increases in ageing. Enhanced MTs in ageing allows constant sequester of zinc ions and no subsequent zinc release leading to low zinc ion bioavailability for thymic efficiency. This sequester is very limited in very old age. Thus, we have investigated the MTmRNA (I+II and III) in the thymus from young, old and very old mice. METHODS: MTmRNA and IL-6mRNA (RT-PCR) in the thymus from different donors were tested. Concomitantly, TECs proliferation, zinc ion bioavailability (ratio total thymulin/active thymulin), thymulin activity and corticosterone were tested from different donors. RESULTS: Both isoforms of MTmRNA and IL-6mRNA increase in old thymus coupled with low zinc ion bioavailability, reduced TECs proliferation, impaired thymulin activity and enhanced plasma corticosterone in comparison with young. Conversely, although the thymus is involuted in very old mice because of no changes in thymus weight in comparison to old mice, reduced MTmRNA, especially MT-I+II isoforms, and low IL6mRNA occur. Concomitantly, good zinc ion bioavailability, maintained TECs proliferation, satisfactory thymulin activity and reduced corticosterone are observed in very old mice. CONCLUSIONS: The concomitant increments by high IL-6 of both MT isoforms in the thymus from old mice may be involved in thymic involution because provoking low zinc ion bioavailability, which is relevant for thymic efficiency. By contrast, the limited increments of MTs by low IL-6 induce good zinc ion bioavailability and satisfactory thymic efficiency in very old mice. Therefore, abnormal increased MTs may provoke complete thymic involution during ageing and the possible appearance of age-related diseases. If their increments are instead limited by low inflammation, healthy ageing and longevity may be reached

ЗАСТОСУВАННЯ В СХЕМАХ ЗБАГАЧЕННЯ ТОНКОПОДРІБНЕНОЇ СИРОВИНИ УДОСКОНАЛЕНОГО МАГНІТНОГО ГІДРОЦИКЛОНУ

Проблема та її зв'язок з науковими і практичними задачами. Необхідна ступінь подрібнення руди перед її переробленням визначається характером вкраплення рудних мінералів, використанням різних методів збагачення сиро-вини, вимогами до якості концентратів, послідовністю технологічних процесів, що застосовуються у схемах переробки корисних копалин. Чим тонше кінцева крупність подрібнення руди, тим менше залишається мінеральних зростків і тим більше вірогідність отримання якісних концентратів

Speciation of trace elements in human serum by micro anion exchange chromatography coupled with inductively coupled plasma mass spectrometry

n/

DNA hydroxymethylation levels are altered in blood cells from Down syndrome persons enrolled in the MARK-AGE project

Down syndrome (DS) is caused by the presence of part or an entire extra copy of chromosome 21, a phenomenon that can cause a wide spectrum of clinically defined phenotypes of the disease. Most of the clinical signs of DS are typical of the ageing process including dysregulation of immune system. Beyond the causative genetic defect, DS persons display epigenetic alterations, particularly aberrant DNA methylation patterns that can contribute to the heterogeneity of the disease. In the present work we investigated the levels of 5-hydroxymethylcytosine (5hmC) and of the TET dioxygenase enzymes, which are involved in DNA demethylation processes and are often deregulated in pathological conditions as well as in ageing. Analyses were carried out on peripheral blood mononuclear cells of DS volunteers enrolled in the context of the MARK-AGE study, a large-scale cross-sectional population study with subjects representing the general population in eight European countries. We observed a decrease of 5hmC, TET1 and other components of the DNA methylation/demethylation machinery in DS subjects, indicating that aberrant DNA methylation patterns in DS, which may have consequences on the transcriptional status of immune cells, may be due to a global disturbance of methylation control in DS

Machine Learning Aided Molecular Modelling of Taste to Identify Food Fingerprints

Nature has developed fascinating mechanisms for selecting and monitoring nutrients through refined systems for food intake and uptake. One of the most important is the sense of taste. Taste is an emergent property involving a complex network of multilevel biological interactions beginning with the activation of specific protein receptors as a consequence of interaction with food molecules. In this context, crucial information about the mechanisms underlying the functioning of taste can be obtained by using molecular mechanistic modelling and machine learning tools borrowed from the field of drug design and the study of structural biology and protein biophysics. The ultimate goal is to develop predictive models capable of studying the intricate connection of molecular, sub-cellular and cellular phenomena underlying the complex biological mechanisms that regulate the relationships between food constituents and perceived taste. Artificial intelligence-driven digital tools for taste prediction and the study of molecular features of the interaction between food molecules and taste receptors have been recently developed by our group. Such tools are the operating engines of the decision support tool developed during the VIRTUOUS project (https://virtuoush2020.com). In this work, these tools were used to generate molecular fingerprints of coffee starting from its chemical composition. Through methods that integrate molecular modelling techniques and machine learning, molecules extracted from coffee were characterized in terms of binding affinity, specificity, and selectivity toward bitter receptors. The targeting ability of coffee-extracted molecules for human TAS2Rs was studied with an atomistic resolution to obtain a virtual fingerprint that links the molecular structure of food ingredients with their bitter profile. The study fits within the digital transition vision that leverages modelling and computational approaches to develop decision-supporting tools for developing solutions in the areas of nutrition, health and the modern food industry