Impaired DNA repair efficiency in systemic lupus erythematosus (SLE) patients has been reported in some studies, mainly regarding the repair of oxidative damage, but little is known about repair kinetics towards primarily single-stranded DNA breaks. In the present study, we aimed to investigate: (a) the efficiency of SLE peripheral blood leucocytes in repairing DNA damage induced by ionizing radiation and (b) the association of DNA repair gene (XRCC1 Arg399Gln, XRCC3 Thr241Met and XRCC4 Ile401Thr) polymorphisms in SLE patients, considering the whole group, or stratified sub-groups according to clinical and laboratory features. A total of 163 SLE patients and 125 healthy controls were studied. The kinetics of DNA strand break repair was evaluated by the comet assay, and genotyping for DNA repair genes was performed by PCR-RFLP. Compared with controls, SLE leucocytes exhibited decreased efficiency of DNA repair evaluated at 30 min following irradiation. A significant association with DNA repair gene polymorphisms was not observed for the whole group of SLE patients; however, the XRCC1Arg399Gln polymorphism was associated with the presence of anti-dsDNA antibody. The concomitance of two DNA repair polymorphic sites was associated with the presence of neuropsychiatric manifestations and antiphospholipid antibody syndrome. Taken together, these results indicated that SLE leucocytes repair less efficiently the radiation-induced DNA damage, and DNA repair polymorphic sites may predispose to the development of particular clinical and laboratory features.

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As the mechanisms leading to the persistence of hepatitis B virus (HBV) infection are poorly understood and as the histocompatibility leucocyte antigen (HLA)-G is well described as a tolerogenic molecule, we evaluated HLA-G expression in 74 specimens of HBV liver biopsies and in 10 specimens obtained from previously healthy cadaver liver donors. HBV specimens were reviewed and classified by the METAVIR score, and HLA-G expression was assessed by immunohistochemistry. No HLA-G expression was observed in control hepatocytes. In contrast, 57 (77%) of 74 HBV specimens showed soluble and membrane-bound HLA-G expression in hepatocytes, biliary epithelial cells or both. No associations between the intensity of HLA-G expression and patient age or gender, HBeAg status, severity of liver fibrosis, and grade of histological findings were observed. Although significance was not reached (P = 0.180), patients exhibiting HLA-G expression presented a higher median HBV DNA viral load (10⁵ copies/mL) than those who did not express HLA-G (10(3.7) copies/mL). These results indicate that HLA-G is expressed in most cases of chronic HBV infection in all stages and may play a role in the persistency of HBV infection.

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Pancreatic cancer related cachexia and muscle wasting are associated with poor outcome. Body muscle mass can be assessed by CT-imaging. Intermuscular adipose tissue and intermyofibrillar fat accumulation (reflected by the 'muscle attenuation index') are increased in cancer patients independent of sarcopenia, and might be indicators of muscle loss and muscle quality. This study aimed to assess the impact of fat accumulation in muscle on postoperative outcome in surgical patients with pancreatic cancer. Methods: A prospective cohort of pancreatic cancer patients operated between 2008e2013 was analysed by CTimage analysis at the L3 level to measure cross-sectional surface area of 1) skeletal muscle, 2) intermuscular adipose tissue, and 3) visceral adipose tissue; the muscle attenuation index, reflecting intermyofibrillar fat, was defined by the average muscle signal intensity in Hounsfield units. Results: Low muscle attenuation index, indicating high intermyofibrillar fat, was associated with low survival compared with middle and high muscle attenuation index (median survival 46.5, 77.1, and 67.1 weeks, respectively; p < 0.001) and was associated with an increased risk of major complications (OR: 2.3, 95%-CI: 1.4e5.6). Muscle attenuation index was negatively correlated with intermuscular adipose tissue (rp = À0.68, p < 0.001). Increased visceral adipose tissue was related to an increased risk of development of pancreatic fistula (OR: 2.5, 95%-CI: 1.1e6.1) and postoperative infections (OR: 2.7, 95%-CI: 1.4e5.2). Conclusions: A low muscle attenuation index is associated with reduced survival and increased severe postoperative complications. The strong correlation between intermyofibrillar fat and intermuscular adipose tissue suggests a common mechanism of origin, warranting further investigation. Preoperative CT-image analysis of body tissue compartments may prove to be clinically useful in identifying patients with an increased risk of complications.

These results corroborate the presence of genomic instability in SSc peripheral blood cells, as evaluated by increased DNA damage, and show that polymorphic sites of the XRCC1 and XRCC4 DNA repair genes may differentially influence DNA damage and the development of autoantibodies.

Glioblastoma multiforme (GBM) is a highly invasive and radioresistant brain tumor. Aiming to study how glioma cells respond to γ-rays in terms of biological processes involved in cellular responses, we performed experiments at cellular context and gene expression analysis in U343-MG-a GBM cells irradiated with 1 Gy and collected at 6 h post-irradiation. The survival rate was approximately 61% for 1 Gy and was completely reduced at 16 Gy. By performing the microarray technique, 859 cDNA clones were analyzed. The Significance Analysis of Microarray algorithm indicated 196 significant expressed genes (false discovery rate (FDR) = 0.42%): 67 down-regulated and 97 up-regulated genes, which belong to several classes: metabolism, adhesion/cytoskeleton, signal transduction, cell cycle/apoptosis, membrane transport, DNA repair/DNA damage signaling, transcription factor, intracellular signaling, and RNA processing. Differential expression patterns of five selected genes ( HSPA9B, INPP5A, PIP5K1A, FANCG, and TPP2) observed by the microarray analysis were further confirmed by the quantitative real time RT-PCR method, which demonstrated an up-regulation status of those genes. These results indicate a broad spectrum of biological processes (which may reflect the radio-resistance of U343 cells) that were altered in irradiated glioma cells, so as to guarantee cell survival.

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