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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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Exposure of juvenile Chinook salmon to effluent from a large urban wastewater treatment *** *** profiling

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Aquaculture and Fisheries 2024年第3期9卷 367-377页

作者： james P.Meador Suzanne C.Ball C.Andrew james Jenifer K.McIntyre Dept.of Environmental and Occupational Health Sciences School of Public Health4225 Roosevelt Way NESuite 100SeattleWA98105-6099USA Washington State University School of the EnvironmentPuyallup Research and Extension Center2606 W Pioneer AvePuyallupWA98371USA University of Washington Tacoma Center for Urban Waters326 East D StreetTacomaWA98421-1801USA

Targeted metabolomic analysis was conducted on juvenile Chinook salmon exposed for 10 days to wastewater effluent(WWE)from a large urban treatment *** included five dilutions of WWE(20%,5.3%,1.4%,0.4%,and 0.1%)and a control with 7 replicates per *** was extracted from fish and analyzed via liquid chromatography–mass spectrometry(LC-MS)for 361 endogenous metabolites,of which 185 were ***-versus-treatment comparisons identified several metabolites that were associated with altered biochemical pathways observed for all treatments,including several that are important for energy generation and *** altered pathways are crucial for fish health and may be an early indicator of potential adverse effects on growth,reproduction,behavior,and immune *** ocean-type Chinook salmon spend several days to weeks in the nearshore estuary where they may encounter high concentrations of WWE *** are exposed to a wide range of potent pharmaceuticals,personal care products,and industrial compounds from WWE that have the potential to affect physiological homeostasis and disrupt their normal life cycle.

关键词： Wastewater effluent Metabolomics Physiology Chinook salmon Pharmaceuticals Metabolic pathways Estuary

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Correcting for spatially dependent intrinsic efficiency on a germanium double-sided strip detector to improve nuclear forensics response

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Radiation Detection Technology and Methods 2022年第1期6卷 78-87页

作者： Timothy Jacomb-Hood james Fast craig Department of Nuclear Engineering Texas A&M UniversityCollege StationTXUSA Pacific Northwest National Laboratory RichlandWAUSA

Purpose The Germanium Gamma-ray Imager(GeGI)is a planar high-purity germanium(HPGe)imaging detector developed by PHDS Co for far-field *** research investigates the detector’s ability for measuring heterogeneous sources in the near field,placed directly on the detector’s faceplate,to perform isotopic mapping for nuclear forensic *** The intrinsic efficiency is strongly dependent on where the photons interact within the *** efficiency varies by up to 20%within the sensitive volume of the *** efficiency was mapped using eight different photons from 123 to 1274 keV emitted from a collimated 154Eu *** were measured at 108 locations to interpolate the efficiency at any point on the detector’s *** The position and energy dependence are uncorrelated,and thus,the absolute efficiency at any position and for any gamma-ray energy can be calculated by the convolution of the spatial and energy *** The results on this research show that detection efficiency for a planar two-sided strip HPGe is spatially dependent and shows typical energy *** spatial dependence,which does not have any additional energy dependence,can be corrected.A 154Eu source was used in this research and was able to spatially calibrate for photon energies ranging from 100 to 1300 *** method is applicable for sources with higher gamma *** advantages of the method demonstrated that after initial in-laboratory calibration,a single measurement in the field can be used to efficiently calibrate the HPGe as a function of photon interaction on the crystal.

关键词： Nuclear forensics Radiation detection Gamma-ray imaging

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Could titin have a role in strain-induced injuries？

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Journal of Sport and Health Science 2017年第2期6卷 143-144页

作者： craig Perrin Kazunori Nosaka james Steele School of Sport Health and Social SciencesSouthampton Solent University Ringgold Standard InstitutionSouthamptonS014 OYNUK School of Exercise and Health Sciences Edith Cowan UniversityJoondalupWA 6027Australia

It has been known for some time that strain injuries occur through the excessive lengthening of a muscle.^(1–3)However,the precise mechanism for strain injury remains elusive and has been the subject of recent debate in the Journal of Sport and Health Science,^(4–9)but it seems sensible to consider mechanisms at the level of the muscle *** was previously believed that damage was the result of non-uniform stretching of

关键词：肌联蛋白损伤机制应变诱导肌肉纤维最佳长度肌原纤维最大变形力曲线

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Infrastructure-based localisation of automated coal mining equipment

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International Journal of Coal Science & Technology 2017年第3期4卷 252-261页

作者： Chad O. Hargrave craig A. james Jonathon C. Ralston Mining and Processing Technologies Research Group CoalMining Research Program CSIRO Energy BrisbaneAustralia

A novel radar-based system for longwall coal mine machine localisation is described. The system, based on a radar-ranging sensor and designed to localise mining equipment with respect to the mine tunnel gate road infrastructure, is developed and trialled in an underground coal mine. The challenges of reliable sensing in the mine environment are considered, and the use of a radar sensor for localisation is justified. The difficulties of achieving reliable positioning using only the radar sensor are examined. Several probabilistic data processing techniques are explored in order to estimate two key localisation parameters from a single radar signal, namely along-track position and across-track position, with respect to the gate road structures. For the case of across-track position, a conventional Kalman filter approach is sufficient to achieve a reliable estimate. However for along-track position estimation, specific infrastructure elements on the gate road rib-wall must be identified by a tracking algorithm. Due to complexities associated with this data processing problem, a novel visual analytics approach was explored in a 3D interactive display to facilitate identification of significant features for use in a classifier algorithm. Based on the classifier output, identified elements are used as location waypoints to provide a robust and accurate mining equipment localisation estimate.

关键词： Localisation · Waypoint navigation · Machine learning · Radar ·Underground · Longwall mining· Automation

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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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Characterization and transcriptional analyses of cDNAs encoding three trypsin- and chymotrypsin-like proteinases in CrylAb-susceptible and CrylAb-resistant strains of sugarcane borer, Diatraea saccharalis

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Insect Science 2013年第4期20卷 485-496页

作者： Yunlong Yang Yu Cheng Zhu james Ottea Claudia Husseneder B. Rogers Leonard craig Abel Randall Luttrell Fangneng Huang Department of Entomology Louisiana State University Agricultural Center Baton Rouge Louisiana Southern Insect Management Research Unit Agricultural Research Service United States Department of Agriculture Stoneville Mississippi Corn Insects and Crop Genetics Research Unit Agricultural Research Service United States Department of Agriculture Ames Iowa USA

Diatraea saccharalis is a major corn borer pest. Midgut serine proteinases are essential for insect growth and development. Alteration of midgut proteinases is re- sponsible for Bt resistance development in some species. To clone midgut trypsin and chymotrypsin cDNAs and to test if the CrylAb resistance in D. saccharalis is associ- ated with changes in midgut proteinases, total midgut tryptic and chymotryptic activities, cDNA sequences, and gene expressions of three trypsin and three chymotrypsin genes were comparatively examined between Cry 1 Ab-susceptible （Cry 1 Ab- S S） and Cry 1 Ab-resistant （Cry 1 Ab-RR） strains. Full-length cDNAs encoding three trypsin- and three chymotrypsin- like proteinases were sequenced from CrylAb-SS and CrylAb-RR larvae. These cDNAs code for active forms of midgut serine proteinases with all fimctional motifs, includ- ing signal peptide, conserved His-Asp-Ser for the catalytic triad, three pairs of cysteines for disulfide bridge configurations, and conserved substrate specificity determination residues. In general, cDNA and putative protein sequences are highly similar between CrylAb-SS and CrylAb-RR strains, except for a few nucleotide and predicted amino acid substitutions, whose function need to be further clarified. Total trypsin and chymotrypsin activities were also similar between CrylAb-SS and CrylAb-RR strains. Transcriptional levels of the trypsin and chymotrypsin genes had numerical difference between Cry 1 Ab-SS and CrylAb-RR strains, but the difference was not statistically significant. Data suggest that the development of CrylAb resistance in D. saccharalis was not significantly as- sociated with these trypsins and chymotrypsins. Results clarified the role of six midgut proteinases and provided a foundation for continuing examination of potential involvement of other midgut proteinases in Bt resistance development and other important biochemical processes.

关键词： Bt cDNA chymotrypsin enzymatic activity resistance trypsin

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Proton-pump inhibitor use does not affect semen luality in subfertile men

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Asian Journal of Andrology 2018年第3期20卷 290-293页

作者： Sorena Keihani james R craig Chong Zhang Angela P Presson Jeremy B Myers William O Brant Kenneth I Aston Benjamin R Emery Timothy G Jenkins Douglas T Carrell james M Hotaling Division of Urology Department of Surgery University of Utah Salt Lake City Utah 84132 USA Division of Epidemiology Department of Internal Medicine University of Utah Salt Lake City Utah 84132 USA Andrology and IVF Laboratory Department of Surgery (Urology) University of Utah Salt Lake City Utah 84108 USA

Proton-pump inhibitors （PPIs） are among the most widely used drugs worldwide. PPI use has recently been linked to adverse changes in semen quality in healthy men; however, the effects of PPI use on semen parameters remain largely unknown specifically in cases with male factor infertility. We examined whether PPI use was associated with detrimental effects on semen parameters in a large population of subfertile men. We retrospectively reviewed data from 12 257 subfertile men who had visited our fertility clinic from 2003 to 2013. Patients who reported using any PPIs for 〉3 months before semen sample collection were included; 7698 subfertile men taking no medication served as controls. Data were gathered on patient age, medication use, and conventional semen parameters; patients taking any known spermatotoxic medication were excluded. Linear mixed-effect regression models were used to test the effect of PPI use on semen parameters adjusting for age. A total of 248 patients （258 samples） used PPIs for at least 3 months before semen collection. In regression models, PPI use （either as the only medication or when used in combination with other nonspermatotoxic medications） was not associated with statistically significant changes in semen parameters. To our knowledge, this is the largest study to compare PPI use with semen parameters in subfertile men. Using PPIs was not associated with detrimental effects on semen quality in this retrospective study.

关键词： infertility proton-pump inhibitors semen analysis sperm quality spermatozoa

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Co-Localization of Alpha1-Adrenoceptors and GPR55: A Novel Prostate Cancer Paradigm?

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Pharmacology & Pharmacy 2015年第4期6卷 212-220页

作者： Kalyani Chimajirao Patil Laura McPherson craig james Daly College of Medical Veterinary & Life Sciences School of Life Sciences University of Glasgow Glasgow UK

α1-adrenoceptors (α1-ARs) and “cannabinoid-like” G Protein Coupled Receptor 55 (GPR55) belong to the G-protein coupled receptor (GPCR) family and play a crucial role in regulating prostate function. Although physical and functional interactions between the cannabinoid and adrenergic systems have been reported, analysis of functional interactions between α1-AR and GPR55 in normal and neoplastic prostate has not been reported. Since GPR55 levels are high in rodent adrenal gland, we propose a function link between the adrenergic system and GPR55 receptor. Confocal Laser Scanning Microscopy (CLSM) was employed to examine the endogenous α1-AR and GPR55 expression and their co-localization, expressed as fluorescence, in vitro in human andro-gen-insensitive PC-3 and androgen-sensitive LNCaP prostatic carcinoma cell lines, using the fluo-rescent ligands—Syto 62 (nuclear stain), BODIPY FL-Prazosin (QAPB;fluorescent quinazoline α1-AR ligand) and Tocriflour (T1117;a novel fluorescent diarylpyrazole cannabinoid/GPR55 ligand). Fluorescent ligand binding in untreated PC-3 cells and LNCaP cells and spheroids showed hetero-geneous expression of both α1-ARs and GPR55. A small proportion of cells had both α1-ARs and GPR55 in relatively equal numbers indicating a degree of co-localization. Co-localization of fluo-rescent ligand binding exhibited a stronger correlation in LNCaP (0.87) as compared to PC-3 (0.63) cells. Upregulation of α1-AR was observed in PC-3 cells following chronic doxazosin incubation. Robust T1117 binding, suggestive of GPR55 upregulation, was also observed in these cells. The presence of subtype-rich cells with a degree of co-localization between α1-ARs and GPR55 indicates a possibility for dimerisation or functional interaction and a new paradigm for functional synergism in which interactions may be either between cells or involve converging intracellular signaling processes.

关键词： Prostate α1-Adrenoceptor GPR55 Doxazosin

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First principles materials design of novel functional oxides

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Journal of Advanced Dielectrics 2016年第2期6卷 61-69页

作者： Valentino R.Cooper Brian K.Voas craig A.Bridges james R.Morris Scott P.Beckman Materials Science and Technology Division Oak Ridge National Laboratory Oak RidgeTN 37831USA Department of Materials Science and Engineering Iowa State University AmesIA 50011USA Chemical Sciences Division Oak Ridge National Laboratory Oak RidgeTN 37831USA School of Mechanical and Materials Engineering Washington State University PulmannWA 99196USA

We review our efforts to develop and implement robust computational approaches for exploring phase stability to facilitate the prediction-to-synthesis process of novel functional *** efforts focus on a synergy between(i)electronic structure calculations for properties predictions,(ii)phenomenological/empirical methods for examining phase stability as related to both phase segregation and temperature-dependent transitions and(iii)experimental validation through synthesis and characteri*** illustrate this philosophy by examining an inaugural study that seeks to discover novel functional oxides with high piezoelectric *** results show progress towards developing a framework through which solid solutions can be studied to predict materials with enhanced properties that can be synthesized and remain active under device relevant conditions.

关键词： First principles materials design and discovery oxide solid solutions.

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