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Liver-specific drug delivery platforms: Applications for the treatment of alcohol-associated liver disease

World Journal of Gastroenterology 2022年第36期28卷 5280-5299页

作者： Jeffrey Barr Warner Steven Corrigan Guenthner Josiah Everett Hardesty Craig James McClain Dennis Ray Warner irina andreyevna kirpich Department of Medicine Division of GastroenterologyHepatology and NutritionUniversity of Louisville School of MedicineLouisvilleKY 40202United States Department of Pharmacology and Toxicology University of Louisville School of MedicineLouisvilleKY 40202United States Alcohol Research Center University of Louisville School of MedicineLouisvilleKY 40202United States Hepatobiology and Toxicology Center University of Louisville School of MedicineLouisvilleKY 40202United States Veterans Health Administration Robley Rex Veterans Medical CenterLouisvilleKY 40206United States Department of Microbiology and Immunology University of Louisville School of MedicineLouisvilleKY 40202United States

Alcohol-associated liver disease(ALD)is a common chronic liver disease and major contributor to liver disease-related deaths *** its prevalence,there are few effective pharmacological options for the severe stages of this *** much pre-clinical research attention is paid to drug development in ALD,many of these experimental therapeutics have limitations such as poor pharmacokinetics,poor efficacy,or off-target side effects due to systemic *** means of addressing these limitations is through liver-targeted drug delivery,which can be accomplished with different platforms including liposomes,polymeric nanoparticles,exosomes,bacteria,and adenoassociated viruses,among *** platforms allow drugs to target the liver passively or actively,thereby reducing systemic circulation and increasing the‘effective dose’in the *** many studies,some clinical,have applied targeted delivery systems to other liver diseases such as viral hepatitis or hepatocellular carcinoma,only few have investigated their efficacy in *** review provides basic information on these liver-targeting drug delivery platforms,including their benefits and limitations,and summarizes the current research efforts to apply them to the treatment of ALD in rodent *** also discuss gaps in knowledge in the field,which when addressed,may help to increase the efficacy of novel therapies and better translate them to humans.

关键词： Liver targeted delivery Nanoparticles Liposomes Polymeric nanoparticles Precision medicine Alcohol associated liver disease

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Histone modifications and alcohol-induced liver disease:Are altered nutrients the missing link?

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World Journal of Gastroenterology 2011年第20期17卷 2465-2472页

作者： Akshata Moghe Swati Joshi-Barve Smita Ghare Leila Gobejishvili irina kirpich Craig J McClain Shirish Barve University of Louisville Alcohol Research Center Department of Pharmacology and Toxicology University of Louisville Department of Internal Medicine Division of GastroenterologyHepatology and NutritionUniversity of Louisville Robley Rex Veterans Affairs Medical Center

Alcoholism is a major health problem in the United States and worldwide,and alcohol remains the single most significant cause of liver-related diseases and *** is known to influence nutritional status at many levels including nutrient intake,absorption,utilization,and excretion,and can lead to many nutritional disturbances and *** can dramatically affect gene expression and alcohol-induced nutrient imbalance may be a major contributor to pathogenic gene expression in alcohol-induced liver disease(ALD).There is growing interest regarding epigenetic changes,including histone modifications that regulate gene expression during disease ***,modifications of core histones in the nucleosome regulate chromatin structure and DNA methylation,and control gene *** review highlights the role of nutrient disturbances brought about during alcohol metabolism and their impact on epigenetic histone modifications that may contribute to *** review is focused on four critical metabolites,namely,acetate,S-adenosylmethionine,nicotinamide adenine dinucleotide and zinc that are particularly relevant to alcohol metabolism and ALD.

关键词：组蛋白修饰酒精性营养物质肝病烟酰胺腺嘌呤二核苷酸 DNA甲基化代谢产物相关疾病

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Dietary fatty acids and bioactive fatty acid metabolites in alcoholic liver disease

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Liver Research 2019年第3期3卷 206-217页

作者： Kara H.Zirnheld Dennis R.Warner Jeffrey B.Warner Josiah E.Hardesty Craig J.McClain irina A.kirpich Division of Gastroenterology Hepatologyand NutritionDepartment of MedicineUniversity of Louisville School of MedicineLouisvilleKYUSA Department of Pharmacology and Toxicology University of Louisville School of MedicineLouisvilleKYUSA University of Louisville Alcohol Center University of Louisville School of MedicineLouisvilleKYUSA Robley Rex Veterans Medical Center LouisvilleKYUSA

Alcoholic liver disease(ALD)comprises a spectrum of liver pathology,including steatosis,steatohepatitis,and *** work from our group and others suggests that dietary fat,both the amount and composition,plays a pivotal role in ALD development and progression;however,the impact of specific dietary fatty acids on ALD pathogenesis is not fully *** rodent models of ALD revealed the deleterious effects of omega-6 polyunsaturated fatty acids(n-6 PUFAs),specifically linoleic acid(LA),and this may be partially attributed to the increased levels of pro-inflammatory oxidized LA *** is limited understanding regarding the role of omega-3 polyunsaturated fatty acids(n-3 PUFAs,such as alpha-linolenic acid,eicosapentaenoic acid,and docosahexaenoic acid),and bioactive n-3 PUFAderived lipid molecules in *** that majority of n-6 and n-3 PUFAs-derived metabolites are potent endogenous signaling molecules,knowledge regarding the changes in these lipid mediators may shed new light on the mechanisms contributing to ALD pathogenesis and reveal novel therapeutic targets and biomarkers of this *** current review summarizes relevant scientific literature regarding the role of dietary fat,distinct fatty acids,and bioactive fatty acid metabolites in ALD,and highlights recent advances in the field.

关键词： Dietary fatty acids Bioactive fatty acid metabolites Alcoholic liver disease(ALD) Omega-6 polyunsaturated fatty acids(n-6 PUFAs) Omega-3 polyunsaturated fatty acids(n-3 PUFAs)

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Aberrant post-translational protein modifications in the pathogenesis of alcohol-induced liver injury

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World Journal of Gastroenterology 2016年第27期22卷 6192-6200页

作者： Natalia A Osna Wayne G Carter Murali Ganesan irina A kirpich Craig J Mc Clain Dennis R Petersen Colin T Shearn Maria L Tomasi Kusum K Kharbanda Research Service Veterans Affairs Nebraska-Western Iowa Health Care System Omaha NE 68105 United States Department of Internal Medicine 982000 Nebraska Medical Center Omaha NE 68198 United States School of Medicine University of Nottingham Royal Derby Hospital Centre Derby DE22 3DT United Kingdom Division of Gastroenterology Hepatology and Nutrition Department of Medicine Department of Medicine and Pharmacology and Toxicology University of Louisville Louisville KY 40202 United States University of Colorado Denver School of Pharmacy Department of Pharmaceutical Sciences Aurora CO 80045 United States Division of Gastroenterology Department of Medicine Davis research building suite 2096/2035 Cedars-Sinai Medical Center Los Angeles CA 90048 United States Department of Biochemistry and Molecular Biology 985870 Nebraska Medical Center Omaha NE 68198 United States

It is likely that the majority of proteins will undergo post-translational modification, be it enzymatic or non-enzymatic. These modified protein(s) regulate activity, localization and interaction with other cellular molecules thereby maintaining cellular hemostasis. Alcohol exposure significantly alters several of these post-translational modifications leading to impairments of many essential physiological processes. Here, we present new insights into novel modifications following ethanol exposure and their role in the initiation and progression of liver injury. This critical review condenses the proceedings of a symposium at the European Society for the Biomedical Research on Alcoholism Meeting held September 12-15, 2015, in Valencia, Spain.

关键词： Alcohol Acetylation Liver Carbonylation methylation Dysfunction Methylation Glycosylation Phosphoryl

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