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- Ferri, F., et al.
(author)
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The Propensity of the Human Liver to Form Large Lipid Droplets Is Associated with PNPLA3 Polymorphism, Reduced INSIG1 and NPC1L1 Expression and Increased Fibrogenetic Capacity
- 2021
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In: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:11
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Journal article (peer-reviewed)abstract
- In nonalcoholic steatohepatitis animal models, an increased lipid droplet size in hepatocytes is associated with fibrogenesis. Hepatocytes with large droplet (Ld-MaS) or small droplet (Sd-MaS) macrovesicular steatosis may coexist in the human liver, but the factors associated with the predominance of one type over the other, including hepatic fibrogenic capacity, are unknown. In pre-ischemic liver biopsies from 225 consecutive liver transplant donors, we retrospectively counted hepatocytes with Ld-MaS and Sd-MaS and defined the predominant type of steatosis as involving >= 50% of steatotic hepatocytes. We analyzed a donor Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 polymorphism, hepatic expression of proteins involved in lipid metabolism by RT-PCR, hepatic stellate cell (HSC) activation by alpha-SMA immunohistochemistry and, one year after transplantation, histological progression of fibrosis due to Hepatitis C Virus (HCV) recurrence. Seventy-four livers had no steatosis, and there were 98 and 53 with predominant Ld-MaS and Sd-MaS, respectively. In linear regression models, adjusted for many donor variables, the percentage of steatotic hepatocytes affected by Ld-MaS was inversely associated with hepatic expression of Insulin Induced Gene 1 (INSIG-1) and Niemann-Pick C1-Like 1 gene (NPC1L1) and directly with donor PNPLA3 variant M, HSC activation and progression of post-transplant fibrosis. In humans, Ld-MaS formation by hepatocytes is associated with abnormal PNPLA3-mediated lipolysis, downregulation of both the intracellular cholesterol sensor and cholesterol reabsorption from bile and increased hepatic fibrogenesis.
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| 2. |
- Ferri, F., et al.
(author)
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Donor small-droplet macrovesicular steatosis affects liver transplant outcome in HCV-negative recipients
- 2019
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In: Canadian Journal of Gastroenterology. - : Hindawi Limited. - 0835-7900 .- 2291-2789 .- 2291-2797. ; 2019
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Journal article (peer-reviewed)abstract
- - Background. No data are available on liver transplantation (LT) outcome and donor liver steatosis, classified as large droplet macrovesicular (Ld-MaS), small-droplet macrovesicular (Sd-MaS), and true microvesicular (MiS), taking into account the recipient Hepatitis C virus (HCV) status. Aim. We investigate the impact of allograft steatosis reclassified according to the Brunt classification on early graft function and survival after LT. Methods. We retrospectively reviewed 204 consecutive preischemia biopsies of grafts transplanted in our center during the period 2001-2011 according to recipient HCV status. Results. The median follow-up after LT was 7.5 years (range: 0.0-16.7). In negative recipients (n=122), graft loss was independently associated with graft Sd-MaS, in multivariable Cox regression models comprehending only pre-/intraoperative variables (HR=1.03, 95%CI=1.01-1.05; P=0.003) and when including indexes of early postoperative graft function (HR=1.04, 95%CI=1.02-1.06; P=0.001). Graft Sd-MaS>15% showed a risk for graft loss > 2.5-folds in both the models. Graft Sd-MaS>15% was associated with reduced graft ATP content and, only in HCV-recipients, with higher early post-LT serum AST peaks. Conclusions. In HCV-negative recipients, allografts with >15% Sd-MaS have significantly reduced graft survival and show low ATP and higher AST peaks in the immediate posttransplant period. Donors with >15% Sd-MaS have significantly higher BMI, longer ICU stays, and lower PaO2. © 2019 Flaminia Ferri et al.
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| 3. |
- Dediu, V., et al.
(author)
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Room-temperature spintronic effects in Alq3 -based hybrid devices
- 2008
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In: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 78:11
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Journal article (peer-reviewed)abstract
- We report on efficient spin polarized injection and transport in long (102 nm) channels of Alq3 organic semiconductor. We employ vertical spin valve devices with a direct interface between the bottom manganite electrode and Alq3, while the top-electrode geometry consists of an insulating tunnel barrier placed between the "soft" organic semiconductor and the top Co electrode. This solution reduces the ubiquitous problem of the so-called ill-defined layer caused by metal penetration, which extends into the organic layer up to distances of about 50-100 nm and prevents the realization of devices with well-defined geometry. For our devices the thickness is defined with an accuracy of about 2.5 nm, which is near the Alq3 molecular size. We demonstrate efficient spin injection at both interfaces in devices with 100- and 200-nm-thick channels. We solve one of the most controversial problems of organic spintronics: the temperature limitations for spin transport in Alq3 -based devices. We clarify this issue by achieving room-temperature spin valve operation through the improvement of spin injection properties of both ferromagnetic/ Alq3 interfaces. In addition, we discuss the nature of the inverse sign of the spin valve effect in such devices proposing a mechanism for spin transport. © 2008 The American Physical Society.
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