Genital infection by high risk Human Papillomavirus (HR-HPV), although recognized as the main etio-pathogenetic factor of cervical cancer, is not per se sufficient to induce tumour development. Oxidative stress (OS) represents an interesting and under-explored candidate as a promoting factor in HPV-initiated carcinogenesis. To gain insight into the role of OS in cervical cancer, HPV-16 positive tissues were collected from patients with invasive squamous cervical carcinoma, from patients with High Grade dysplastic HPV lesions and from patients with no clinical evidence of HPV lesions. After virological characterization, modulation of proteins involved in the redox status regulation was investigated. ERp57 and GST were sharply elevated in dysplastic and neoplastic tissues. TrxR2 peaked in dysplastic samples while iNOS was progressively reduced in dysplastic and neoplastic samples. By redox proteomic approach, five proteins were found to have increased levels of carbonyls in dysplastic samples respect to controls namely: cytokeratin 6, actin, cornulin, retinal dehydrogenase and GAPDH. In carcinoma samples the peptidyl-prolyl cis-trans isomerase A, ERp57, serpin B3, Annexin 2 and GAPDH were found less oxidized than in dysplastic tissues. HPV16 neoplastic progression seems associated with increased oxidant environment. In dysplastic tissues the oxidative modification of DNA and proteins involved in cell morphogenesis and terminal differentiation may provide the conditions for the neoplastic progression. Conversely cancer tissues seem to attain an improved control on oxidative damage as shown by the selective reduction of carbonyl adducts on key detoxifying/pro-survival proteins.

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system. Several evidences suggest that MS can be considered a multi-factorial disease in which both genetics and environmental factors are involved. Among proposed candidates, growing results support the involvement of oxidative stress (OS) in MS pathology. The aim of this study was to investigate the role of OS in event of exacerbations in MS on serum of relapsing-remitting (RR-MS) patients, either in relapsing or remitting phase, with respect to serum from healthy subjects. We applied proteomics and redox proteomics approaches to identify differently expressed and oxidatively modified proteins in the low-abundant serum protein fraction. Among differently expressed proteins ceruloplasmin, antithrombin III, clusterin, apolipoprotein E, and complement C3, were up-regulated in MS patients compared with healthy controls. Further by redox proteomics, vitamin D-binding protein showed a progressive trend of oxidation from remission to relapse, respect with controls. Similarly, the increase of oxidation of apolipoprotein A-IV confirmed that levels of OS are elevated with the progression of the disease. Our findings support the involvement of OS in MS and suggest that dysfunction of target proteins occurs upon oxidative damage and correlates with the pathology.

HPV circulation is a key feature for the rational design of prevention and screening campaigns. 36A cross-sectional, virological study was conducted on adult Albanian women living either in the 37 Tirana area or in the Duress prefecture. Clinical and gynaecological evaluations were performed 38 according to current standard criteria. HPV detection and typing were carried out by a combined 39 MY09/MY11 and GP5+/GP6+ PCR followed by direct sequencing of generated amplicons. 40Virological data were obtained from 402 out of 452 patients enrolled between January 2004 and 41December 2007. Sixty-one patients (15.1 % of the cohort) were found to be infected with a genital 42 HPV. As expected, viral prevalence was higher among women younger than 30 years of age 43 (25.2%) in comparison to those aged 30 or older (13.6%). HPV 16 was found to be the most 44 frequent type (41% of cases), followed by HPV 53 (7.2%), HPV 31 (5.8%) and HPV 18 (4.3%). 45 HPV 81 and HPV 84, were the most prevalent low risk types detected with prevalences of 11.6 and 46 5.8 %, respectively. No differences were noted in any type specific prevalence between young and 47 mature women. 48The circulation of HPV types is far more complex than assumed generally. Detailed knowledge of 49 HPV type circulating patterns in specific local geographical areas is essential for appropriate 50 implementation of screening, prevention and surveillance campaigns. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59