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Microbiome dysbiosis and alcoholic liver disease

Liver Research 2019年第3期3卷 218-226页

作者： Fengyuan Li craig J.mcclain Wenke Feng Department of Medicine Department of Pharmacology and ToxicologyAlcohol Research CenterUniversity of LouisvilleLouisvilleKYUSA

Microbiome dysbiosis is strongly associated with alcoholic liver disease(ALD).Recent studies on comprehensive analyses of microbiome compositional and functional changes have begun to uncover the mechanistic relation between microbiome and the pathogenesis of ***,targeting the microbiome has become a potential strategy for the prevention and treatment of *** this review,we summarize the clinical evidence of microbiome dysbiosis in ALD patients,and experimental advances in microbiome and metabolomic functional changes in animals with different species and genetic backgrounds in *** also summarize the studies in humanized intestinal microbiome and fecal microbiota transplantation in *** introduce new developments in the studies on the role of the circulating bacterial microbiome,oral bacterial microbiome and fungal microbiome in the development of *** highlight the potential mechanisms by which microbiome dysbiosis contributes to ALD,including short chain fatty acid changes,bile acid metabolism,intestinal barrier function,release of bacterial and fungal products,and *** addition,we summarize the recent developments targeting the microbiome in prevention and treatment of ALD,including dietary nutrient interference,herbal medicine,antibiotics,anti-fungal agents,probiotics,engineered bacterial therapy,fecal transplantation and oral *** recent preclinical studies have advanced our understanding of the microbiome and ALD,clinical studies,especially prospective studies with large samples,are needed to better understand the cause-effect of microbiome dysbiosis in *** new precision-based strategies targeting the microbiome are expected to be developed as more effective therapies in ALD.©2019 The Third Affiliated Hospital of Sun Yat-sen *** Services by Elsevier *** behalf of KeAi Communications Co.,*** is an open access article under the CC BY-NC-ND license.

关键词： Microbiome Dysbiosis Alcoholic liver disease(ALD)

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Generalization of Reference System for Calculating the Second Dimension Retention Index in GC×GC-MS

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Journal of Analysis and Testing 2018年第3期2卷 263-273页

作者： Md Aminul Islam Prodhan Ahmed A.Sleman Seongho Kim craig mcclain Xiang Zhang Department of Chemistry University of Louisville2320 South Brook StreetLouisvilleKY 40292USA University of Louisville Alcohol Research Center 505 South Hancock StreetLouisvilleKY 40202USA University of Louisville Hepatobiology and Toxicology Program 505 South Hancock StreetLouisvilleKY 40202USA Center for Regulatory and Environmental Analytical Metabolomics University of Louisville2210 South Brook StreetLouisvilleKY 40208USA Department of Computer Science and Computer Engineering University of LouisvilleLouisvilleKY 40208USA Department of Pharmacology and Toxicology University of Louisville323 East Chestnut StreetLouisvilleKY 40202USA Department of Medicine University of Louisville550 South Jackson StreetLouisvilleKY 40202USA Department of Oncology Biostatistics CoreKarmanos Cancer InstituteSchool of MedicineWayne State UniversityDetroitMI 48201USA Robley Rex Louisville VAMC LouisvilleKY 40292USA

Using C_(4)-C_(25)fatty acid methyl esters(C_(4)-C_(25)FAMEs)as a sample reference series,a method was developed to generalize the reference system for calculating the second dimension retention index(2I)of compounds analyzed by comprehensive two-dimensional gas chromatography-mass spectrometry(GC×GC-MS).The second dimension elution temperature(2Te),second dimension unadjusted retention time(2tR),and the linear retention index(IT)of C_(4)-C_(25)FAMEs were used to form a second dimension retention index surface(2IS)via a three-dimensional surface fitting *** 2I of an analyte analyzed by GC×GC-MS was then calculated from the 2IS based on its 2tR and *** developed method was validated by calculat-ing the 2I of n-alkanes,80 compounds,and two commercially available mixtures(MegaMix A and MegaMix B).Compared to the conventional method,the developed method keeps the 2I in n-alkane retention index scale,and enables using any compounds as references to obtain a much increased separation space in the second dimension GC.

关键词： Retention index Second dimension retention index GC-MS GC×GC-MS

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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： Alcohol Liver disease Nutrients Metabolism Histone Epigenetic modifications S-adenosylmethionine Acetate Zinc NAD

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

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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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Microbiome data analysis with applications to pre-clinical studies using QIIME2: Statistical considerations

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Genes & Diseases 2021年第2期8卷 215-223页

作者： Shesh N.Rai Chen Qian Jianmin Pan Jayesh P.Rai Ming Song Juhi Bagaitkar Michael Merchant Matthew Cave Nejat K.Egilmez craig J.mcclain Biostatistics and Bioinformatics Facility James Graham Brown Cancer CenterUniversity of LouisvilleLouisvilleKY40202USA Department of Biostatistics and Bioinformatics University of LouisvilleLouisvilleKY40202USA University of Louisville Alcohol Research Center University of LouisvilleLouisvilleKY40202USA University of Louisville Hepatobiology&Toxicology Center University of LouisvilleLouisvilleKY40202USA Department of Oral Immunology&Infectious Diseases University of LouisvilleLouisvilleKY40202USA Department of Medicine University of LouisvilleLouisvilleKY40202USA Robley Rex Louisville VAMC LouisvilleKY40206USA Department of Microbiology&Immunology University of LouisvilleLouisvilleKY40202USA

Diversity analysis and taxonomic profiles can be generated from marker-gene sequence data with the help of many available computational *** Quantitative Insights into Microbial Ecology Version 2(QIIME2)has been widely used for 16S rRNA data *** many articles have demonstrated the use of QIIME2 with suitable datasets,the application to preclinical data has rarely been talked *** issues involved in the pre-clinical data include the low-quality score and small sample size that should be addressed properly during *** addition,there are few articles that discuss the detailed statistical methods behind those alpha and beta diversity significance tests that researchers are eager to *** the program without knowing the logic behind it is extremely *** this article,we first provide a guideline for analyzing 16S rRNA data using *** we will talk about issues in pre-clinical data,and how they could impact the ***,we provide brief explanations of statistical methods such as group significance tests and sample size calculation.

关键词： 16S rRNA gene Alpha diversity ANOVA Beta diversity Bioinformatics Microbiome data QIIME Sample size calculation

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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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Elevated Linoleic Acid (A Pro-Inflammatory PUFA) and Liver Injury in a Treatment Naive HIV-HCV Co-Infected Alcohol Dependent Patient

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Journal of Biosciences and Medicines 2016年第7期4卷 23-27页

作者： Vatsalya Vatsalya Shirish S. Barve craig J. mcclain Vijay A. Ramchandani Division of Gastroenterology Hepatology and Nutrition Department of Medicine University of Louisville School of Medicine Louisville USA Section on Human Psychopharmacology LCTS/DICBR/NIAAA at National Institutes of Health Bethesda USA Department of Pharmacology and Toxicology University of Louisville School of Medicine Louisville USA Robley Rex VA Medical Center Louisville USA

HIV and HCV co-infection is a unique disease condition, and medical management of such condition is difficult due to severity and systemic complications. Added with heavy alcohol drinking, risk of liver injury increases due to several pro-inflammatory responses that subsequently get involved with alcohol metabolism. Elevated levels of fatty acids have been reported both in viral infections as well as alcoholic liver disease though such investigations have not addressed the adverse event with dual viral infection of HIV and HCV along with heavy drinking. This case report of a patient with excessive alcohol drinking and first time diagnosis of HIV and HCV dual infection, elaborating concurrent alteration in Linoleic Acid (LA) levels and pro-inflammatory shift in ω-6/ω-3 ratio along with the elevations in liver injury markers. Elevated LA has been recently studied extensively for its role in alcoholic liver disease;and in the present case, we also found it to be clinically relevant to liver injury.

关键词： Alcohol Fatty Acids HCV HIV Liver Injury

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Commentary on“Desialylated Platelets Maintain Immune Quiescence through Regulating Kupffer Cells”

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Research 2024年第3期6卷 621-623页

作者： Chen Li craig N.Morrell Aab Cardiovascular Research Institute University of Rochester School of Medicine and DentistryRochesterNYUSA Department of Pharmacology and Physiology University of Rochester School of Medicine and DentistryRochesterNYUSA Department of Medicine University of Rochester School of Medicine and DentistryRochesterNYUSA Department of Microbiology and Immunology University of Rochester School of Medicine and DentistryRochesterNYUSA Department of Pathology and Laboratory Medicine University of Rochester School of Medicine and DentistryRochesterNYUSA.

Platelets have long been studied for their roles in hemostasis and vascular injury repair. However, there is a continually evolving and deepening understanding that platelets initiate and regulate responses to tissue injury and pathogens, leading to platelets now being considered immune modulatory cells [1]. Platelets actively participate in host immune responses directly through pathogen engulfing and killing, or by regulating both innate and adaptive immune responses to infection or tissue injury [2]. Activated platelets promote inflammatory responses to tissue injury or infection by direct contact dependent interactions with immune cells and through indirect interactions via released soluble factors. However, mice that are deficient in platelets have skewed T helper cell differentiation [3] and increased vascular permeability [4], implying poorly defined roles for platelets in maintaining healthy immune homeostasis.

关键词： Platelet homeostasis Immune

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Sleep-based neuronal oscillations as a physiological biomarker for Alzheimer's disease:is night time the right time?

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Neural Regeneration Research 2024年第7期19卷 1417-1418页

作者： Jonathan Witton Erica S.Brady Michael T.craig Department of Clinical and Biomedical Sciences Faculty of Health and Life SciencesUniversity of ExeterExeterEnglandUK Gladstone Institute for Neurological Disease San FranciscoCAUSA School of Psychology and Neuroscience College of MedicalVeterinary and Life SciencesUniversity of GlasgowGlasgowScotlandUK

Dementia is a devastating syndrome characterized by memory problems,confusion,and behavior changes that prevent people from performing everyday *** is the leading cause of dependency and disability amongst older people,resulting in a global economic cost of ~$1.3 *** 58 million people are currently afflicted by dementia worldwide,with Alzheimer s disease(AD) causing most(60-70%) of these cases.

关键词： Alzheimer everyday performing

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Rheological properties of rare earth minerals flotation pulp in the presence of anions

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Journal of Rare Earths 2024年第11期42卷 2172-2182页

作者： Moonchul Jung Bogale Tadesse craig Dick Alex Logan Laurence Dyer Boris Albijanic Western Australia School of Mines Curtin University Lynas Rare Earths Ltd

Water quality has been found to significantly influence the flotation operations due to the alteration of surface properties of *** effect of cations on the flotation of RE minerals has been studied,however,there are still very limited information regarding the effect of *** present study examined the impact of specific anions such as Cl-,SO42-,and HCO3-on the flotation performance of rare earth（RE） *** study integrates flotation experiments,rheology measurements,entrainment experiments,zeta potential measurements and settling *** is observed that an increase in the concentration of these anions lead to a decrease in the recovery of RE minerals and an increase in the recovery of FeO minerals and thus negatively affecting flotation *** adverse effect is most pronounced with Cl-and least noticeable with HCO3-.An increase in the non-selective entrainment of gangue minerals is observed when the flotation pulp has higher *** reduction in the zeta potential of fine particles in the presence of these results in a higher pulp viscosity due to increased attractive forces between *** findings were verified by settling experiments and calculations based on the DLVO theory.

关键词： Flotation Rare earth ore Anions Pulp rheology Entrainment DLVO theory

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