The choice of Milan. Smoking and air pollution

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Gallbladder stem/progenitor cells are able to repopulate and rescue the damaged liver in a experimental mouse model of liver cirrhosis

[No abstract available]The human biliary tree contains stem cells within peribiliary glands (Cardinale et al., 2011). Human Gallbladder contains stem/progenitors (hGSCs) located in mucosal crypts (Carpino et al., 2012). Our aim was to evaluate the capability of hGSCs to repopulate and rescue the damaged liver in a model of liver cirrhosis. hGSCs were selected for Epithelial Cell Adhesion Molecule. Cirrhosis was induced by intraperitoneal injection, twice a week, of carbon tetrachloride for 7 weeks. hGSCs were injected into the liver via the spleen of normal or cirrhotic SCID mice. As controls, cirrhotic SCID mice were injected only with the medium or with mature human hepatocytes. 2 months after the injection, the necrotic areas were lower in mice treated with hGSCs in comparison with controls. In hGSCs-injected cirrhotic mice, the expression of the human antigens indicated that ≈10% of the host hepatocyte mass was represented by in vivo differentiated human hepatocytes derived from injected hGSCs. This value was significantly higher with respect to mice injected with human adult hepatocytes. The presence of human cells in murine livers was confirmed by in situ hybridization for human chromosomes. hGSCs injection dictated an improvement of serum liver biochemistry with a significant reduction of transaminases and an improvement of synthetic functions. In this model, hGSC engraftment and differentiation determinate the improvement of histological liver damage and serum liver biochemistry. These data could open future perspectives for a role of gallbladder as a source of stem cells for liver regenerative medicine

Detection of colonic dysplasia in patients with ulcerative colitis using a targeted fluorescent peptide and confocal laser endomicroscopy: A pilot study

Targeted molecular probes have been used to detect sporadic colonic dysplasia during confocal laser endomicroscopy (CLE) with promising results. This is a feasibility pilot study aiming to assess the potential role of CLE combined with a fluorescent-labeled peptide to stain and detect dysplasia associated with Ulcerative Colitis

The Biological Role of Vitamins in Athletes’ Muscle, Heart and Microbiota

Physical activity, combined with adequate nutrition, is considered a protective factor against cardiovascular disease, musculoskeletal disorders, and intestinal dysbiosis. Achieving optimal performance requires a significantly high energy expenditure, which must be correctly supplied to avoid the occurrence of diseases such as muscle injuries, oxidative stress, and heart pathologies, and a decrease in physical performance during competition. Moreover, in sports activities, the replenishment of water, vitamins, and minerals consumed during training is essential for safeguarding athletes’ health. In this scenario, vitamins play a pivotal role in numerous metabolic reactions and some muscle biochemical adaptation processes induced by sports activity. Vitamins are introduced to the diet because the human body is unable to produce these micronutrients. The aim of this review is to highlight the fundamental role of vitamin supplementation in physical activity. Above all, we focus on the roles of vitamins A, B6, D, E, and K in the prevention and treatment of cardiovascular disorders, muscle injuries, and regulation of the microbiome

D-aspartate oxidase gene duplication induces social recognition memory deficit in mice and intellectual disabilities in humans

The D-aspartate oxidase (DDO) gene encodes the enzyme responsible for the catabolism of D-aspartate, an atypical amino acid enriched in the mammalian brain and acting as an endogenous NMDA receptor agonist. Considering the key role of NMDA receptors in neurodevelopmental disorders, recent findings suggest a link between D-aspartate dysmetabolism and schizophrenia. To clarify the role of D-aspartate on brain development and functioning, we used a mouse model with constitutive Ddo overexpression and D-aspartate depletion. In these mice, we found reduced number of BrdU-positive dorsal pallium neurons during corticogenesis, and decreased cortical and striatal gray matter volume at adulthood. Brain abnormalities were associated with social recognition memory deficit at juvenile phase, suggesting that early D-aspartate occurrence influences neurodevelopmental related phenotypes. We corroborated this hypothesis by reporting the first clinical case of a young patient with severe intellectual disability, thought disorders and autism spectrum disorder symptomatology, harboring a duplication of a chromosome 6 region, including the entire DDO gene

Metastatic group 3 medulloblastoma is driven by PRUNE1 targeting NME1-TGF-β-OTX2-SNAIL via PTEN inhibition.

Genetic modifications during development of paediatric groups 3 and 4 medulloblastoma are responsible for their highly metastatic properties and poor patient survival rates. PRUNE1 is highly expressed in metastatic medulloblastoma group 3, which is characterized by TGF-β signalling activation, c-MYC amplification, and OTX2 expression. We describe the process of activation of the PRUNE1 signalling pathway that includes its binding to NME1, TGF-β activation, OTX2 upregulation, SNAIL (SNAI1) upregulation, and PTEN inhibition. The newly identified small molecule pyrimido-pyrimidine derivative AA7.1 enhances PRUNE1 degradation, inhibits this activation network, and augments PTEN expression. Both AA7.1 and a competitive permeable peptide that impairs PRUNE1/NME1 complex formation, impair tumour growth and metastatic dissemination in orthotopic xenograft models with a metastatic medulloblastoma group 3 cell line (D425-Med cells). Using whole exome sequencing technology in metastatic medulloblastoma primary tumour cells, we also define 23 common 'non-synonymous homozygous' deleterious gene variants as part of the protein molecular network of relevance for metastatic processes. This PRUNE1/TGF-β/OTX2/PTEN axis, together with the medulloblastoma-driver mutations, is of relevance for future rational and targeted therapies for metastatic medulloblastoma group 3

Electronic cigarette use as an aid to quit smoking in the representative Italian population PASSI survey

This study explored electronic cigarette (e-cigarette) use as an aid to quit smoking and compared abstinence rates for different quitting methods in a representative sample of the Italian population. In the 2014–2015 PASSI survey, the ongoing Italian behavioural risk factor surveillance system, 6112 adults who smoked and made at least one quit attempt in the previous 12 months, were categorized into three groups according to the method used in their most recent quit attempt: e-cigarette only, no aid, other quitting methods (medications; programmes delivered in smoking cessation services; other unspecified methods). The primary outcome was self-reported abstinence for a period ≥ 6 months, adjusted for potential confounders. Eleven percent used e-cigarettes only, 86% no aid, 3% other quitting methods. Smoking abstinence was reported among 9% of those using no aid; 8% of e-cigarette users; 15% of those using other methods. No significant differences in abstinence were observed for e-cigarette users compared with those reporting no aid (adjusted Prevalence Ratio [aPR] = 0.81; 95%Confidence Interval (CI) = 0.58–1.14). Changing the reference group to e-cigarette users, those using other quitting methods were significantly more likely to report abstinence than e-cigarette users (aPR = 1.76; 95%CI = 1.07–2.88). One out of ten smokers who attempted to quit in 2014–2015 in Italy used e-cigarettes. E-cigarettes users were as likely to report abstinence as those using no aid, but were less likely to report abstinence than users of established quitting methods. Further studies are needed to understand the relationship between e-cigarette types used to quit and abstinence rates

Le nuove strategie dell'industria del tabacco

L’industria del tabacco recentemente per promuovere i nuovi prodotti a tabacco riscaldato, ritenuti meno nocivi, ha cambiato strategia coinvolgendo alcune Società medico-scientifiche . Nella prima metà del ‘900, quando si iniziarono ad avere evidenze scientifiche che il fumo di tabacco provocava il cancro del polmone ed altre malattie, le multinazionali del tabacco utilizzarono la strategia di “insinuare il dubbio” sostenendo che le prove scientifiche non fossero ancora definitive. Il “Frank Statement” è un eccellente esempio di questa campagna di disinformazione: un comunicato stampa redatto appositamente per contrastare l’evidenza scientifica e per tranquillizzare l’opinione pubblica. Tra la fine del vecchio e l’inizio del nuovo Millennio, si verificarono due importanti eventi che costrinsero l’industria del tabacco a cambiare retorica. Il primo fu il “Master Settlement Agreement” che, in seguito alla citazione in giudizio delle multinazionali da parte di molti Stati USA, obbligò queste ultime a pubblicare oltre 30 milioni di pagine di documenti interni, dai quali emerse chiaramente come fossero consapevoli dei danni causati dal tabacco e come avessero cercato di insabbiare la verità con tutti i mezzi, inclusi la corruzione. Dovendo così ammettere la tossicità e la dipendenza causate dai prodotti del tabacco, l’industria ristrutturò la sua retorica attorno al valore della libertà, sia individuale (tabacco scelto liberamente da adulti consenzienti) che del libero mercato (libertà di informare con pubblicità, sponsorizzazioni, promozioni). Un paradosso, visto che il tabacco dà dipendenza, paradosso che tuttavia ha funzionato. Il secondo evento importante è stata la “Convenzione Quadro per il Controllo del Tabacco”, un trattato internazionale, creato dall’OMS e sottoscritto dalla maggior parte degli stati del mondo, che individua misure regolatorie efficaci per ridurre il consumo di tabacco e tutelare la salute dei non fumatori. Fumare è così diventato via via “meno normale” e l’industria ha nuovamente cambiato strategia: ha continuato a vendere i prodotti tradizionali nel Terzo Mondo e ha sviluppato nuovi prodotti tecnologici a “tabacco riscaldato o fumo freddo” nei Paesi ad economia avanzata dove era in difficoltà. Per promuoverli ha sponsorizzato e partecipato a convegni medico-scientifici per convincere i medici a raccomandare ai pazienti di usare questi prodotti per ridurre i danni da fumo (invece che convincerli a smettere). Le società scientifiche che accettano finanziamenti dall’industria del tabacco e ne permettono la partecipazione nei propri congressi, corrono il grave rischio di perdere la propria indipendenza. Il mondo medico e scientifico deve restare libero da conflitti di interessi per tutelare la salute pubblica e individuale