| 1. |
- Nano, Rita, et al.
(författare)
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Human Pancreatic Islet Preparations Release HMGB1 : (Ir)Relevance for Graft Engraftment
- 2013
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Ingår i: Cell Transplantation. - 0963-6897 .- 1555-3892. ; 22:11, s. 2175-2186
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Tidskriftsartikel (refereegranskat)abstract
- High levels of donor-derived high-mobility group box 1 (HMGB1) protein have been associated with poor islet graft outcome in mouse models. The aim of our work was to determine whether HMGB1 released by human islets had independent proinflammatory effects that influence engraftment in humans. Human islet preparations contained and released HMGB1 in different amounts, as determined by Western blot and ELISA (median 17 pg/ml/IEQ/24 h; min-max 0-211, n=74). HMGB1 release directly correlated with brain death, donor hyper-amilasemia, and factors related to the pancreas digestion procedure (collagenase and digestion time). HMGB1 release was significantly positively associated with the release of other cytokines/chemokines, particularly with the highly released "proinflammatory" CXCL8/IL-8, CXCL1/GRO-alpha, and the IFN-gamma-inducible chemokines CXCL10/IP-10 and CXCL9/MIG. HMGB1 release was not modulated by Toll-like receptor 2,3,4,5, and 9 agonists or by exposure to IL-1 beta. When evaluated after islet transplantation, pretransplant HMGB1 release was weakly associated with the activation of the coagulation cascade (evaluated as serum cross-linked fibrin products), but not with the immediate posttransplant inflammatory response. Concordantly, HMGB1 did not affect short-term human islet function. Our data show that human islet HMGB1 release is a sign of "damaged" islets, although without any independent direct role in graft failure.
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| 2. |
- Sanna, Daria, et al.
(författare)
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Mendelian breeding units versus standard sampling strategies: Mitochondrial DNA variation in southwest Sardinia
- 2011
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Ingår i: Genetics and Molecular Biology. - 1678-4685. ; 34:2, s. 187-194
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Tidskriftsartikel (refereegranskat)abstract
- We report a sampling strategy based on Mendelian Breeding Units (MBUs), representing an interbreeding group of individuals sharing a common gene pool. The identification of MBUs is crucial for case-control experimental design in association studies. The aim of this work was to evaluate the possible existence of bias in terms of genetic variability and haplogroup frequencies in the MBU sample, due to severe sample selection. In order to reach this goal, the MBU sampling strategy was compared to a standard selection of individuals according to their surname and place of birth. We analysed mitochondrial DNA variation (first hypervariable segment and coding region) in unrelated healthy subjects from two different areas of Sardinia: the area around the town of Cabras and the western Campidano area. No statistically significant differences were observed when the two sampling methods were compared, indicating that the stringent sample selection needed to establish a MBU does not alter original genetic variability and haplogroup distribution. Therefore, the MBU sampling strategy can be considered a useful tool in association studies of complex traits.
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