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TM6SF2 E167K variant predicts severe liver fibrosis for human immunodeficiency/hepatitis C virus co-infected patients, and severe steatosis only for a non-3 hepatitis C virus genotype

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World Journal of Gastroenterology 2016年第38期22卷 8509-8518页

作者： Caterina Sagnelli Marco Merli Caterina Uberti-Foppa Hamid Hasson Anna Grandone Grazia Cirillo Stefania Salpietro Carmine Minichini Mario Starace emanuela messina Patrizia Morelli Emanuele Miraglia Del Giudice Adriano Lazzarin Nicola Coppola Evangelista Sagnelli Department of Clinical and Experimental Medicine and Surgery F. Magrassi e A. LanzaraSecond University of Naples 80131 Naples Italy Department of Infectious Diseases Vita-Salute University San Raffaele Scientific Institute 20127 Milan Italy Department of Pediatrics Second University of Naples 80131 Naples Italy Department of Mental Health and Public Medicine Section of Infectious Diseases Second University of Naples 80131 Naples Italy

AIM To evaluate the impact of the Glu167Lys(E167K) transmembrane 6 superfamily member 2(TM6SF2) variant on the biochemical and morphologic expression of liver lesions in human immunodeficiency virus(HIV)/hepatitis C virus(HCV) co-infected *** The study comprised 167 consecutive patients with HIV/HCV coinfection and biopsy-proven chronic hepatitis. A pathologist graded liver fibrosis and necroinflammation using the Ishak scoring system, and steatosis using Kleiner's scoring system. Patients were genotyped for TM6SF2 E167K(rs58542926) by real-time Polymerase chain reaction. The 167 patients, 35 therapy-naive and 132 receiving ART, were prevalently males(73.6%), the median age was 40.7 years and the immunological condition good(median CD4+ cells/mm3 = 505.5).RESULTS The 17 patients with the TM6SF2 E167 K variant, compared with the 150 with TM6SF2-E/E, showed higher AST(P = 0.02) and alanine aminotransferase(P = 0.02) and higher fibrosis score(3.1 ± 2.0 vs 2.3 ± 1.5, P = 0.05). In a multivariate analysis, TM6SF2 E167 K was independently associated with severe fibrosis. The same analysis showed that HCV-genotype 3, present in 42.2% of patients was an independent predictor of severe steatosis. The association of TM6SF2 E167 K with severe steatosis, absent for the whole group of 167 patients, was re-evaluated separately for HCVgenotype 3 and non-3 patients: No factor was independently associated with severe steatosis in the HCV-genotype-3 subgroup, whereas an independent association was observed between severe steatosis and TM6SF2 E167 K in non-3 HCV genotypes. No association between the TM6SF2 E167 K variant and severe liver necroinflammation was *** In HIV/HCV coinfection the TM6SF2 E167 K variant is an independent predictor of severe fibrosis, but appears to be independently associated with severe steatosis only for patients with a non-3 HCV genotype.

关键词： Human immunodeficiency virus/hepatitis C virus co-infection TM6SF2 Liver histology Liver steatosis Liver biopsy

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Can cannabinoids be a potential therapeutic tool in amyotrophic lateral sclerosis？

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Neural Regeneration Research 2016年第12期11卷 1896-1899页

作者： Sabrina Giacoppo emanuela Mazzon IRCCS Centro Neurolesi"Bonino-Pulejo" Via Provinciale PalermoContrada CasazzaMessinaItaly

Amyotrophic lateral sclerosis（ALS） is the most common degenerative disease of the motor neuron system. Over the last years, a growing interest was aimed to discovery new innovative and safer therapeutic approaches in the ALS treatment. In this context, the bioactive compounds of Cannabis sativa have shown antioxidant, anti-inflammatory and neuroprotective effects in preclinical models of central nervous system disease. However, most of the studies proving the ability of cannabinoids in delay disease progression and prolong survival in ALS were performed in animal model, whereas the few clinical trials that investigated cannabinoids-based medicines were focused only on the alleviation of ALS-related symptoms, not on the control of disease progression. The aim of this report was to provide a short but important overview of evidences that are useful to better characterize the efficacy as well as the molecular pathways modulated by cannabinoids.

关键词： amyotrophic lateral sclerosis cannabinoids symptomatic ALS treatment experimental ALS model clinical trials mechanisms of neuroprotection

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Au,Pd and maghemite nanofunctionalized hydroxyapatite scaffolds for bone regeneration

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Regenerative Biomaterials 2020年第5期7卷 461-469页

作者： Giovanna Calabrese Salvatore Petralia Claudia Fabbi Stefano Forte Domenico Franco Salvatore Guglielmino emanuela Esposito Salvatore Cuzzocrea Francesco Traina Sabrina Conoci Department of Chemistry Biology Pharmacy and Environmental Science University of MessinaPiazza Pugliatti198122 MessinaSiciliaItaly Research and Development Applied Chemical WorksPaternoCataniaItaly Department of Chemical Science Fin-Ceramica FaenzaVia Granarolo 177/3Faenza 48018Italy Istituto Oncologico del Mediterraneo Ricerca ViagrandeCatania 95029Italy Dipartimento Biomorf Universita degli Studi di MessinaMessinaItaly Rizzoli Orthopedic Institute IRCSSBolognaItaly Distretto Tecnologico Micro e Nano Sistemi Sicilia CataniaItaly

Nanotechnology plays a key role in the development of innovative scaffolds for bone tissue engineering(BTE)allowing the incorporation of nanomaterials able to improve cell proliferation and *** this study,Mg-HA-Coll type I scaffolds(Mg-HA-based scaffolds)were nanofunctionalized with gold nanorods(Au NRs),palladium nanoparticles(Pd NPs)and maghemite nanoparticles(MAG NPs).Nanofunctionalized Mg-HA-based scaffolds(NF-HA-Ss)were tested for their ability to promote both the proliferation and the differentiation of adipose-derived mesenchymal stem cells(hADSCs).Results clearly highlight that MAG nanofunctionalization substantially improves cell proliferation up to 70% compared with the control(Mg-HA-based scaffold),whereas both Au NRs and Pd NPs nanofunctionalization induce a cell growth inhibition of 94% and 89%,*** evidences were found for the osteoinductive properties showing relevant calcium deposits(25% higher than the control)for MAG nanofunctionalization,while a decreasing of cell differentiation(20% lower than the control)for both Au NRs and Pd NPs *** results are in agreement with previous studies that found cytotoxic effects for both Pd NPs and Au *** excellent improvement of both osteoconductivity and osteoinductivity of the MAG NF-HA-S could be attributed to the high intrinsic magnetic field of superparamagnetic MAG *** findings may pave the way for the development of innovative nanostructured scaffolds for BTE.

关键词： bone regeneration hydroxyapatite scaffold tissue engineering gold nanoroads Pd nanoparticles maghemite nanoparticles

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