1,721,020 research outputs found
Selectivity hot-spots of sirtuin catalytic cores
No full textSirtuins are NAD(+)-dependent deacetylases with several biological roles in DNA regulation, genomic stability, metabolism, longevity and immune cell functions. Numerous disease conditions are linked to sirtuins including metabolic disorders, inflammatory and autoimmune processes and cancer. Although few specific small molecule modulators have been reported to date, the need to identify selective ligands would be crucial not only for the development of active pharmaceutical ingredients for new targeted therapies but also as a tool for dissecting the biological roles of sirtuin family members. Herein, we report a comprehensive study aimed to classify and identify the selectivity hot-spots for targeting the catalytic cores of human sirtuins using small molecule modulators. Our selectivity analysis suggests that catalytic cores can be divided into different clusters that can constitute the basis for the development of selective ligands. The ensemble of hot-spot information is expected to be helpful to devise new selective chemicals targeting sirtuin family members
Prevenzione degli eventi infortunistici e stress lavoro-correlato:correlazione tra fattori di rischio e biomarcatori di stress
No full textLiterature review in support of adjuvanticity/immunogenicity assessment of proteins
Full text linkBased on the risk assessment of genetically modified plants, according to Implementing Regulation (EU) No 503/201321 “In cases when known functional aspects of the newly expressed protein or structural similarity to known strong adjuvants may indicate possible adjuvant activity, the applicant shall assess the possible role of these proteins as adjuvants”. To further investigate the topic, an EFSA procurement was launched requesting a comprehensive literature review and critically appraisal on adjuvanticity and immunogenicity of proteins. A systematic literature search and critical review was performed, identifying 299 relevant publications. From the evaluation of the relevant literature emerged that: i) a clear classification of adjuvant and immunogens of proteins cannot be done; ii) structural features able to modulate adjuvanticity and immunogenicity are mainly ascribed to therapeutic proteins and in the context of allergenicity and cross-reactivity; iii) factors affecting the propensity of a protein to stimulate immune response are aggregation, thermal processing, digestion, food matrix, among others; iv) different proteins are described to have immunomodulatory effects; v) risk assessment of adjuvant and immunogenic behaviour of proteins requires specific methodologies that can be adapted from other fields; vi) adjuvanticity and immunogenicity of Cry proteins in certain experimental conditions seems plausible but due to low dosage, oral route of administration, food and feed processing and digestion, it is unlikely to emerge as a safety issue in food and feed; vii) eliciting an immune response is a very complex matter as the body responds to immune offence by inducing many processes. Based on these considerations, it is expected that the availability of new humanized animal models and the possibility to deploy artificial intelligent systems on the vastity of human data will become a general direction aiming to help answering specific questions relating to the immune systems, including the adjuvanticity and immunogenicity of food/feed proteins
Morfologia dell’elettrocardiogramma in lavoratori turnisti
No full textBACKGROUND:
Besides a significant deterioration in their family and personal life, shift workers also suffer health problems ranging from chronic fatigue to gastro-intestinal disorders, changes in sleep rhythm and cardiovascular disease, including arrhythmia and ischaemic heart disease.
OBJECTIVES:
The aim of the study was to assess the prevalence of electrocardiographic changes, such as conduction disorders, alterations in the repolarization phase and frequency-adjusted QT interval (QTc) in relation to shift work.
METHODS:
We conducted a cross sectional survey of 125 male subjects, 60 of whom worked fixed hours, and 65 were shift workers on two different schedules: 32 were on duty for 24 hours followed by 96 hours rest, and 33 worked 8-hour shifts (3 x 8). During periodical health assessment we examined their electrocardiograms (ECG), classified the morphology and measured the QTc interval.
RESULTS:
The QTc interval did not differ by type of work shift or by the presence of morphological changes in the ECG, including concurrent conduction disorders, or alterations in the repolarization phase. However, unlike day workers and 24-h shift workers, the QTc interval tended to increase with age among 8-h shift workers (r = 0.338; p = 0.05). Also, risk of conduction disorders was moderately, but not significantly, elevated among 8-h shift workers compared with subjects working fixed hours (OR = 1.9; I.E 95% 0.6, 5.7).
CONCLUSIONS:
Our study did not reveal significant changes in the ECG morphology in relation to the type of work shift
Structure-Based Design of Potent Aromatase Inhibitors by High-Throughput Docking
No full textCytochrome P450 aromatase catalyzes the conversion of androgen substrates into estrogens. Aromatase inhibitors (AIs) have been used as first-line drugs in the treatment of estrogen-dependent breast cancer in postmenopausal women. However, the search for new, more potent, and selective AIs still remains necessary to avoid the risk of possible resistances and reduce toxicity and side effects of current available drugs. The publication of a high resolution X-ray structure of human aromatase has opened the way to structure-based virtual screening to identify new small-molecule inhibitors with structural motifs different from all known AIs. In this context, a high-throughput docking protocol was set up and led to the identification of nanomolar AIs with new core structures
Electrospinning of immiscible systems: The wool keratin/polyamide-6 case study
No full textBlends of wool keratin and polyamide 6 (PA6) have shown interesting adsorbent properties in filtration. In this work, the miscibility of keratin and PA6 was studied for the first time through rheological measurements of diluted blend solutions. In particular, the immiscibility between the two polymers in different blend proportions was observed by the segregation of phases in the cast films. Nevertheless, notwithstanding the immiscibility, we demonstrate here that homogeneous keratin/PA6 blend nanofibers can be obtained by electrospinning as a result of rapid solvent evaporation, where kinetic effects prevail on thermodynamic effects, thereby avoiding phase segregation. The obtained nanofibers have diameters ranging from 100 to 250 nm, depending on the experimental conditions. We show, through a principal component analysis (PCA) that the percentage of keratin represents the most important variable to determine nanofiber diameters. Collectively, this study represents a successful case of immiscible electrospinning system for production of useful nanofibers as adsorbent material for different applications
Risultati di un programma di sorveglianza sanitaria post-esposizione in operatori sanitari esposti a mycobacterium tuberculosis
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