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| 1 | Biochemical mechanisms in drug-induced liver injury:Certainties and doubts显示文摘Drug-induced liver injury is a significant and still unresolved clinical problem.Limitations to knowledge about the mechanisms of toxicity render incomplete the detection of hepatotoxic potential during preclinical development.Several xenobiotics are lipophilic substances and their transformation into hydrophilic compounds by the cytochrome P-450 system results in production of toxic metabolites.Aging,preexisting liver disease,enzyme induction or inhibition,genetic variances,local O2 supply and,above all,the intrinsic molecular properties of the drug may affect this process.Necrotic death follows antioxidant consumption and oxidation of intracellular proteins,which determine increased permeability of mitochondrial membranes,loss of potential,decreased ATP synthesis,inhibition of Ca2+-dependent ATPase,reduced capability to sequester Ca2+ within mitochondria,and membrane bleb formation.Conversely,activation of nucleases and energetic participation of mitochondria are the main intracellular mechanisms that lead to apoptosis.Non-parenchymal hepatic cells are inducers of hepatocellular injury and targets for damage.Activation of the immune system promotes idiosyncratic reactions that result in hepatic necrosis or cholestasis,in which different HLA genotypes might play a major role.This review focuses on current knowledge of the mechanisms of drug-induced liver injury and recent advances on newly discovered mechanisms of liver damage.Future perspectives including new frontiers for research are discussed. | Ignazio Grattagliano Leonilde Bonfrate Catia V Diogo Helen H Wang David QH Wang Piero Portincasa | 2009 | World Journal of Gastroenterology2009，15，39： | 30 |
| 2 | Prunus genetics and applications after de novo genome sequencing:achievements and prospects显示文摘Prior to the availability of whole-genome sequences,our understanding of the structural and functional aspects of Prunus tree genomes was limited mostly to molecular genetic mapping of important traits and development of EST resources.With public release of the peach genome and others that followed,significant advances in our knowledge of Prunus genomes and the genetic underpinnings of important traits ensued.In this review,we highlight key achievements in Prunus genetics and breeding driven by the availability of these whole-genome sequences.Within the structural and evolutionary contexts,we summarize:(1)the current status of Prunus whole-genome sequences;(2)preliminary and ongoing work on the sequence structure and diversity of the genomes;(3)the analyses of Prunus genome evolution driven by natural and man-made selection;and(4)provide insight into haploblocking genomes as a means to define genome-scale patterns of evolution that can be leveraged for trait selection in pedigree-based Prunus tree breeding programs worldwide.Functionally,we summarize recent and ongoing work that leverages whole-genome sequences to identify and characterize genes controlling 22 agronomically important Prunus traits.These include phenology,fruit quality,allergens,disease resistance,tree architecture,and self-incompatibility.Translationally,we explore the application of sequence-based marker-assisted breeding technologies and other sequence-guided biotechnological approaches for Prunus crop improvement.Finally,we present the current status of publically available Prunus genomics and genetics data housed mainly in the Genome Database for Rosaceae(GDR)and its updated functionalities for future bioinformatics-based Prunus genetics and genomics inquiry. | Maria JoséAranzana Véronique Decroocq Elisabeth Dirlewanger Iban Eduardo Zhong Shan Gao Ksenija Gasic Amy Iezzoni Sook Jung Cameron Peace Humberto Prieto Ryutaro Tao Ignazio Verde Albert G.Abbott Pere Arús | 2019 | Horticulture Research2019，6，1： | 8 |
| 3 | A silybin-phospholipids complex counteracts rat fatty liver degeneration and mitochondrial oxidative changes显示文摘AIM:To investigate the effectiveness of antioxidant compounds in modulating mitochondrial oxidative alterations and lipids accumulation in fatty hepatocytes.METHODS:Silybin-phospholipid complex containing vitamin E(Realsil) was daily administered by gavage(one pouch diluted in 3 mL of water and containing 15 mg vitamin E and 47 mg silybin complexed with phospholipids) to rats fed a choline-deprived(CD) or a high fat diet [20% fat,containing 71% total calories as fat,11% as carbohydrate,and 18% as protein,high fat diet(HFD)] for 30 d and 60 d,respectively.The control group was fed a normal semi-purified diet containing adequate levels of choline(35% total calories as fat,47% as carbohydrate,and 18% as protein).Circulating and hepatic redox active and nitrogen regulating molecules(thioredoxin,glutathione,glutathione peroxidase),NO metabolites(nitrosothiols,nitrotyrosine),lipid peroxides [malondialdehyde-thiobarbituric(MDA-TBA)],and pro-inflammatory keratins(K-18) were measured on days 0,7,14,30,and 60.Mitochondrial respiratory chain proteins and the extent of hepatic fatty infiltration were evaluated.RESULTS:Both diet regimens produced liver steatosis(50% and 25% of liver slices with CD and HFD,respectively) with no signs of necro-inflammation:fat infiltration ranged from large droplets at day 14 to disseminated and confluent vacuoles resulting in microvesicular steatosis at day 30(CD) and day 60(HFD).In plasma,thioredoxin and nitrosothiols were not significantly changed,while MDA-TBA,nitrotyrosine(from 6 ± 1 nmol/L to 14 ± 3 nmol/L day 30 CD,P < 0.001,and 12 ± 2 nmol/L day 60 HFD,P < 0.001),and K-18(from 198 ± 20 to 289 ± 21 U/L day 30 CD,P < 0.001,and 242 ± 23 U/L day 60 HFD,P < 0.001) levels increased significantly with ongoing steatosis.In the liver,glutathione was decreased(from 34.0 ± 1.3 to 25.3 ± 1.2 nmol/mg prot day 30 CD,P < 0.001,and 22.4 ± 2.4 nmol/mg prot day 60 HFD,P < 0.001),while thioredoxin and glutathione peroxidase were initially increased and then decreased.Nitrosothiols were constantly increased.MDA-TBA levels were five-fold increased from 9.1 ± 1.2 nmol/g to 75.6 ± 5.4 nmol/g on day 30,P < 0.001(CD) and doubled with HFD on day 60.Realsil administration significantly lowered the extent of fat infiltration,maintained liver glutathione levels during the first half period,and halved its decrease during the second half.Also,Realsil modulated thioredoxin changes and the production of NO derivatives and significantly lowered MDA-TBA levels both in liver(from 73.6 ± 5.4 to 57.2 ± 6.3 nmol/g day 30 CD,P < 0.01 and from 27.3 ± 2.1 nmol/g to 20.5 ± 2.2 nmol/g day 60 HFD,P < 0.01) and in plasma.Changes in mitochondrial respiratory complexes were also attenuated by Realsil in HFD rats with a major protective effect on Complex Ⅱ subunit CII-30.CONCLUSION:Realsil administration effectively contrasts hepatocyte fat deposition,NO derivatives formation,and mitochondrial alterations,allowing the liver to maintain a better glutathione and thioredoxin antioxidant activity. | Ignazio Grattagliano Catia V Diogo Maria Mastrodonato Ornella de Bari Michele Persichella David QH Wang Adriana Liquori Domenico Ferri Maria Rosaria Carratù Paulo J Oliveira Piero Portincasa | 2013 | World Journal of Gastroenterology2013，19，20： | 6 |
| 4 | Muscle-in-vein nerve guide for secondary reconstruction in digital nerve lesions显示文摘 | Ignazio M Adolfo V | 2010 | J Hand Surg Am2010，35，9： | 1 |
| 5 | Downwind sailaerodynamics: a CFD investigation with high grid resolution 显示文摘 | IGNAZIO M V | 2009 | Ocean Engineering2009，，36： | 1 |
| 6 | A peach linkage map integration RFLPs, SSRs, RAPDs, and morphological markers 显示文摘 | MARIA T D ROBERTA Q IGNAZIO V | 2001 | Genome Ottawa2001，44，： | 1 |
| 7 | Food deprivation exacerbates mitochondrial oxidative stress in rat liver exposed to ischemia-reperfusion injury 显示文摘 | Marco D Paolo C Gianluigi V Ignazio G Bruno N Monia D A Bruno S Franco T Antonino C Emanuele A Mauro B | 2001 | J Nutr2001，131，： | 1 |
| 8 | Sail Aerodynamics: Understanding Pressure Distributions on Upwind Sails 显示文摘 | Ignazio M V Richard G J F | 2011 | Experimental Thermal and Fluid Science2011，35，： | 1 |
| 9 | A peach linkage map intergrating RFLPs,SSRs, RAPDs, and morphological markers 显示文摘 | Maria T D Roberta Q Ignazio V | 2001 | Genome2001，44，： | 1 |
| 10 | Muscle-in-vein nerve guide for seconda- ry reconstruction in digital nerve lesions 显示文摘 | Ignazio M Adolfo V | 2010 | J Hand Surg Am2010，35，： | 1 |
| 11 | A peach linkage map intergrating RFLPs, SSRs, BAPDs, and morphological markers显示文摘 | Maria TD Roberta Q Ignazio V | 2001 | Genome2001，44，： | 1 |
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