Individually Tailored Screening of Susceptibility to Sarcopenia Using p53 Codon 72 Polymorphism, Phenotypes, and Conventional Risk Factors

Background and Aim. p53 activity plays a role in muscle homeostasis and skeletal muscle differentiation; all pathways that lead to sarcopenia are related to p53 activities. We investigate the allelic frequency of the TP53 codon 72 in exon 4 polymorphism in the Italian female population and the association with appendicular skeletal muscle mass index in normal weight (NW), normal weight obese (NWO), and preobese-obese (Preob-Ob) subjects. Methods. We evaluated anthropometry, body composition, and p53 polymorphism in 140 women distinguished in NW, NWO, and Preob-Ob. Results. ∗Arg/∗Arg genotype increases sarcopenia risk up to 20% (∗Arg/∗Arg genotype OR = 1.20; 95% CI = 0.48–2.9; ∗proallele carriers OR = 0.83; 95% CI = 0.83–2.06). The risk of being sarcopenic for ∗Arg/∗Arg genotype in NWO and Preob-Ob is 31% higher than NW carriers of ∗proallele (RR = 0,31, 95% CI = 0,15–0,66, P = 0,0079). We developed a model able to predict sarcopenia risk based on age, body fat, and p53 polymorphism. Conclusion. Our study evidences that genotyping TP53 polymorphism could be a useful new genetic approach, in association with body composition evaluations, to assess sarcopenia risk

Novel insights on saccharin- and acesulfame-based carbonic anhydrase inhibitors: design, synthesis, modelling investigations and biological activity evaluation

A large library of saccharin and acesulfame derivatives has been synthesised and evaluated against four isoforms of human carbonic anhydrase, the two off-targets hCA I/II and the tumour related isoforms hCA IX/XII. Different strategies of scaffold modification have been attempted on both saccharin as well as acesulfame core leading to the obtainment of 60 compounds. Some of them exhibited inhibitory activity in the nanomolar range, albeit some of the performed changes led to either micromolar activity or to its absence, against hCA IX/XII. Molecular modelling studies focused the attention on the binding mode of these compounds to the enzyme. The proposed inhibition mechanism is the anchoring to zinc-bound water molecule. Docking studies along with molecular dynamics also underlined the importance of the compounds flexibility (e.g. achieved through the insertion of methylene group) which favoured potent and selective hCA inhibition

Altruism and sacrifice : mafia free gift giving in south Italy

As a social phenomenon that torments modern states, mafia receives considerable political and legal attention. The term mafia itself is often directly related to criminality and violence. Thus far violence has been employed as an analytical construct that could explain compliance with the mafia ethos. Nevertheless this schema fails to take into consideration possible discourses that make mafia tolerable. Drawing on fieldwork conducted in Reggio Calabria, South Italy, this paper explores distinctive mafia notions of giving and charity. Mafia free gifts, albeit rare, are paradoxical in the sense that through elaborate speech registers both the donor and the recipient debase the very act of gift-giving so as not to be bound in relations of reciprocity and obligation. These mafia gifts, which have so far escaped anthropological attention, are conceptualised as tropes of worldly imagining aspiring to non-worldly discourses. Status, umiltà, duty and sacrifice frame free gifting as accorded to the overt religious rhetoric of mafia hierarchy. In this paper I argue that a) free gifting embraces a series of complex non-violent discourses which relate closely to religious duty and altruism but work alongside capitalist systems b) in principal these gifts do not bind people, yet are imbued with the potential of a relation.PostprintPeer reviewe

4-Hydroxy-3-nitro-5-ureido-benzenesulfonamides selectively target the tumor-associated carbonic anhydrase isoforms IX and XII showing hypoxia-enhanced anti-proliferative profiles.

Human carbonic anhydrases (CA, EC, 4.2.1.1) IX and XII are overexpressed in cancer cells as adaptive response to hypoxia and acidic conditions characteristic of many tumors. In addition, hypoxia facilitates the activity of specific oxido-reductases that may be exploited to selectively activate bioreductive prodrugs. Here, new selective CA IX/XII inhibitors, as analogues of the antitumor phase II drug SLC-0111 are described, namely ureido-substituted benzenesulfonamides appended with a nitro-aromatic moiety to yield an antiproliferative action increased by hypoxia. These compounds were screened for the inhibition of the ubiquitous hCA I/II and the target hCA IX/XII. Six X-ray crystallographies with CA II and IX/mimic allowed for the rationalization of the compounds inhibitory activity. The effects of some such compounds on the viability of HT-29, MDA-MB-231, and PC-3 human cancer cell lines in both normoxic and hypoxic conditions were examined, providing the initiation toward the development of hypoxia-activated antitumor CAIs

C677T gene polymorphism of MTHFR and metabolic syndrome: response to dietary intervention

Background: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms were found associated with body mass index (BMI)-defined obesity and lean mass. The aim of our study was to examine the role of the C677T MTHFR gene polymorphism in the response to diet in the management of metabolic syndrome. We investigated the body composition and metabolic factor changes after an hysocaloric balanced diet (HBD), in Italian obese women affected by metabolic syndrome (MS). Methods: Forty four obese women affected by MS were eligible for the study. A HBD for 12 weeks was assigned. Study participation included a complete screening for dietary habits, anthropometry, body composition, blood biochemical markers and C677T MTHFR polymorphism genotyping. The study has been registrated by ClinicalTrials. gov Id: NCT01890070. Results: The highest number of responders to HBD nutritional intervention were T(-) carriers (p 64 0.05). In the 81% of the total population a loss of Total Body Lean was observed. A significative loss (p 64 0.05) of Total Body Lean was observed in the 47% of T(-) carriers and in the 53% of T(+) carriers. Diastolic and systolic blood pressure, and waist circumference were reduced (p 64 0.05). The prevalence of MS parameters decreased by 84% for systolic and diastolic blood pressure; 79,5% for HDL cholesterol, 82% for fasting glucose and 77% for triglycerides. Conclusions: MTHFR genetic variations analysis would be an innovative tool for the nutritional assessment. Our data provide the basis for personalized dietary recommendations based on the individual's genetic makeup and nutritional status

A Hazelnut-Enriched Diet Modulates Oxidative Stress and Inflammation Gene Expression without Weight Gain

Introduction. Inflammation is associated with obesity condition and plays a pivotal role in the onset and progression of many chronic diseases. Among several nutraceutical foods, hazelnuts (Corylus avellana L.) are considered an excellent anti-inflammatory and hypolipidemic food being the second richest source of monounsaturated fatty acids among nuts and because they are rich in vitamins, minerals, and phenolic compounds.Materials and Methods. A prospective pilot clinical trial on 24 healthy volunteers who consumed daily, as a snack, 40 g of hazelnuts (261.99 kcal/1096.17 kJ) for six weeks was conducted. Anthropometric measurements, body composition analysis, and nutrigenomic analysis on 12 anti-inflammatory and antioxidant genes were evaluated at baseline (T0) and after hazelnut intervention (T1).Results. No significant changes were detected on body composition analysis after hazelnut consumption. Conversely, significant upregulation was detected for SOD1(2−ΔΔCt=242), CAT (2−ΔΔCt=241), MIF (2−ΔΔCt=412), PPARγ(2−ΔΔCt=589), VDR (2−ΔΔCt=361), MTHFR (2−ΔΔCt=240),and ACE (2−ΔΔCt=216) at the end of the study.Conclusions. According to emerging evidences, hazelnut consumption does not lead to weight gain probably due to the improvement of the body’s antioxidant capacity by the upregulation of genes implied in oxidant reactions and inflammation

The evolution of the Australian ‘ndrangheta. An historical perspective

This paper explores the phenomenon of the ‘ndrangheta – a criminal organisation from Calabria, South of Italy and allegedly the most powerful among the Italian mafias – through its migrating routes. In particular, by focusing on the peculiar case of Australia, the paper aims to show the overlapping of migrating flows with criminal colonisation, which has proven to be a strategy of this particular mafia. The paper uses the very thin literature on the subject alongside official reports and newspaper articles on migration and crime, mainly from Italian sources, to trace an historical journey on the migration of people from Calabria to Australia in various moments of the last century. The aim is to present the evolution and growth of Calabrian clans in Australia. The topic is largely unexplored and is still underreported among Australian institutions and scholars, which is why the paper chooses an historical approach to describe the principal paths in this very new field of research