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Effects of apical sodium-bile acid transporter inhibitor and obeticholic acid co-treatment in experimental non-alcoholic steatohepatitis

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Liver Research 2022年第4期6卷 276-283页

作者： david j.matye Xuan Qin Mohammad Nazmul Hasan Lijie Gu Yung Dai Clayton Feng Li Tiangang Li Harold Hamm Diabetes Center Department of PhysiologyUniversity of Oklahoma Health Sciences CenterOklahoma CityOKUSA Department of Pathology and Immunology Baylor College of MedicineHoustonTXUSA NMR and Drug Metabolism Core Baylor College of MedicineHoustonTXUSA

Background and aims:Several bile acids-based monotherapies have been developed for non-alcoholic steatohepatitis(NASH)treatment but clinical trial findings suggest that they do not satisfactorily improve NASH and liver fibrosis in many ***,we have shown that combining a gut-restricted apical sodium-bile acid transporter(ASBT)inhibitor GSK2330672(GSK)with adeno-associated virus(AAV)-mediated liver fibroblast growth factor 15(FGF15)overexpression provides significantly improved efficacy than either single treatment against NASH and liver fibrosis in a high fat,cholesterol,and fructose(HFCFr)diet-induced NASH mouse *** beneficial effects of the com-bined treatment can be attributed to the markedly reduced bile acid pool that reduces liver bile acid burden and intestinal lipid *** aim of this study is to further investigate if combining GSK treatment with the orally bioavailable obeticholic acid(OCA),which induces endogenous FGF15 and inhibits hepatic bile acid synthesis,can achieve similar anti-NASH effect as the GSKþAAV-FGF15 co-treatment in HFCFr-diet-fed *** and methods:Male C57BL/6j mice were fed HFCFr diet to induce NASH and liver *** effect of GSK,OCA,and GSKþOCA treatments on NASH development was compared and contrasted among all ***:Findings from this study showed that the GSKþOCA co-treatment did not cause persistent reduction of obesity over a 12-week treatment *** single treatment nor the GSKþOCA co-treatment reduce hepatic steatosis,but all three treatments reduced hepatic inflammatory cytokines and fibrosis by a similar *** GSKþOCA co-treatment caused a higher degree of total bile acid pool reduction(~55%)than either GSK or OCA treatment ***,such bile acid pool reduction was insufficient to cause increased fecal lipid *** GSKþOCA co-treatment prevented GSK-mediated induction of hepatic cholesterol 7alpha-hydroxylase but failed to induce ileal FGF15 expression.

关键词： Bile acids Farnesoid X receptor(FXR) Fibroblast growth factor 15(FGF15) Apical sodium-bile acid transporter(ASBT) Non-alcoholic steatohepatitis(NASH) Liver fibrosis

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Women in visual neural regeneration research

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Neural Regeneration Research 2025年第2期20卷 489-490页

作者： Tonia S.Rex david j.Calkins Vanderbilt Eye Institute Vanderbilt University Medical CenterNashvilleTNUSA

The year 2024 marks the 60^(th)anniversary of Title IX and 25 years since the New York Times revealed bias against female faculty members at the Massachusetts Institute of *** take an opportunity here to examine the state of gender bias in a relatively new yet already prominent field,neural regeneration in the visual system,for which there is a well-defined context useful for this *** National Eye Institute(NEI)provided the first round of research funding for its Audacious Goals Initiative(AGI)on visual neural regeneration in 2013 and the last round in ***,we focus on this *** sources included PubMed,the National Science Foundation(NSF),the NEI,the Blue Ridge Institute for Medical Research and data from the major professional organization for eye and vision research,the Association for Research in Vision and Ophthalmology(ARVO).

关键词： neural visual Times

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Liver-specific microRNA-185 knockout promotes cholesterol dysregulation in mice

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Liver Research 2021年第4期5卷 232-238页

作者： Cheng Chen david matye Yifeng Wang Tiangang Li Harold Hamm Diabetes Center Department of PhysiologyUniversity of Oklahoma Health Sciences CenterOklahoma CityOKUSA

Background:The liver plays a key role in regulating whole body cholesterol *** cholesterol accumulation causes liver injury in fatty liver disease and hypercholesterolemia increases the risk of cardiovascular ***(miRNAs,miRs)have been shown to regulate various pathways in cholesterol ***,miR-185 has been shown to regulate sterol regulatory element-binding protein 2(SREBP2)and low-density lipoprotein receptor(LDLR)to modulate cholesterol syn-thesis and *** and methods:The role of miR-185 in regulating diet-induced metabolic disorders were studied in liver-specific miRNA-185 knockout(L-miR-185 KO)***:L-miR-185 KO mice developed worsened hepatic steatosis upon high-fat high-cholesterol Western diet feeding with accumulation of triglyceride and cholesterol in the *** addition,L-miR-185 KO mice developed hypercholesterolemia upon Western diet *** expression analysis showed that L-miR-185 KO mice did not show increased hepatic mRNA expression of SREBP2 or its targets LDLR and HMG-CoA reductase(HMGCR).Although expression of miR-185 mimic inhibited the mRNA of SREBP2,HMGCR and LDLR in HepG2 cells,miR-185 inhibitor did not increase the mRNA of SREBP2,HMGCR or LDLR in HepG2 ***:In conclusion,we reported that L-miR-185 KO mice were more sensitive to Western diet induced hepatic steatosis and *** molecular mechanisms underlying these metabolic changes remain to be investigated in future studies.

关键词： MicroRNA(miRNA) MicroRNA-185(miR-185) Cholesterol Fatty liver

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Apples to oranges:environmentally derived,dynamic regulation of serotonin neuron subpopulations in adulthood?

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Neural Regeneration Research 2025年第9期20卷 2596-2597页

作者： Christopher j.O’Connell Matthew j.Robson Department of Genetics College of MedicineHarvard UniversityBostonMAUSA james L.Winkle College of Pharmacy Division of Pharmaceutical SciencesUniversity of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program College of MedicineUniversity of CincinnatiCincinnatiOHUSA

Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).

关键词： sustained orange dynamic

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Gene therapy for spinal muscular atrophy:perspectives on the possibility of optimizing SMN1 delivery to correct all neurological and systemic perturbations

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Neural Regeneration Research 2025年第7期20卷 2011-2012页

作者： Sharon j.Brown Rafael j.Yáñez-Muñoz Heidi R.Fuller School of Pharmacy and Bioengineering Keele UniversityKeeleUK Wolfson Center for Inherited Neuromuscular Disease TORCH BuildingRJAH Orthopaedic HospitalOswestryUK *** Center of Gene and Cell TherapyDepartment of Biological SciencesSchool of Life Sciences and the EnvironmentRoyal Holloway University of LondonEghamUK

Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and *** genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(Lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of SMA-specific gene *** was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between ***,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of SMA,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe SMA phenotypes and vice ***,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.

关键词： atrophy traditionally absolute

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Generation of brain vascular heterogeneity:recent advances from the perspective of angiogenesis

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Neural Regeneration Research 2025年第7期20卷 2013-2014页

作者： Nathanael j.Lee Ryota L.Matsuoka Department of Neurosciences Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Molecular Medicine Cleveland Clinic Lerner College of MedicineCase Western Reserve UniversityClevelandOHUSA

Heterogeneous proper t i es of vascular endothelial cells in the brain:The brain displays large energy dynamics and consumption,and this high level of metabolic demands is fulfilled by a continuous supply of glucose and oxygen through its vascular *** vasculature consists of highly divergent blood vessel branches,giving rise to a dense network of capillaries that supply blood to all cells across the *** elaborated vascular network is thought to develop via angiogenesis,a process in which new blood vessels grow from pre-existing *** capillaries exhibit organotypic features distinct from other tissues and are formed primarily by two major endothelial cell(EC)types:those that form the semi-permeable blood-brain barrier(BBB)and those that develop highly permeable pores known as fenestrae(Matsuoka et al.,2022).The structural and functional differences between BBB and fenestrated vascular ECs represent a fundamental feature of brain vasculature and form the foundation for both brain function and homeostasis.

关键词： angiogenesis homeostasis network

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Neuroprotection by resveratrol-glucuronide and quercetin-glucuronide via binding to polyphenol-and glycosaminoglycan-binding sites in the laminin receptor

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Neural Regeneration Research 2025年第3期20卷 819-820页

作者： Rayudu Gopalakrishna jennifer Aguilar Emily Lee William j.Mack Department of Integrative Anatomical Sciences Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA Department of Neurological Surgery Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA

The dietary polyphenolic compounds resveratrol and quercetin prevent neurodegenerative diseases in experimental models;however, they reach the brain only in nanomolar concentrations in the glucuronidated and sulfated ... 详细信息

关键词： resveratrol molar dated

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Natural products and drug discovery

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National Science Review 2022年第11期9卷 37-57页

作者： david j.Newman NIH Special Volunteer

This review covers the recent history of a series of very important natural products and their derivatives that are currently in use or under evaluation in the areas of anti-infectives, important cancer treatments that include antibody drug conjugates, followed by a discussion of type 2 diabetes(T2DM) drugs and angiotensin converting enzyme inhibitors. The current structures of the agents are shown, though in the case of some peptides used in T2DM drugs the standard single leTher abbreviation for an amino acid is used.

关键词： artemisinin glycopeptides anthracyclines dolastatin diabetes 2 ACE inhibitors

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Brain-penetrating neurotrophic factor mimetics: HER-096 as a disease-modifying therapy for Parkinson’s disease

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Neural Regeneration Research 2025年第4期20卷 1094-1095页

作者： Natalia Kulesskaya Kira M.Holmström Henri j.Huttunen Herantis Pharma Plc EspooFinland

Neurotrophic factors as a therapeutic approach in neurodegenerative diseases:A major unmet need in the field of central nervous system diseases is disease-modifying *** for decades there have been various symptomatic treatments available to alleviate the symptoms of the disease,disease-modification,*** that stop,significantly delay,or reverse the progression of the disease,has been turned out to a difficult goal to achieve.

关键词： diseases treatment therapeutic

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Positron emission particle tracking——Application and labelling techniques

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Particuology 2008年第1期6卷 16-23页

作者： david j. Parker School of Physics and Astronomy the University of Birmingham Edgbaston Birmingham B15 2TT UK

The positron emission particle tracking （PEPT） technique has been widely used in science and engineering to obtain detailed information on the motion and flow fields of fluids or granular materials in multiphase systems, for example, fluids in rock cracks, chemical reactors and food processors; dynamic behaviour of granular materials in chemical reactors, granulators, mixers, dryers, rotating kilns and ball mills. The information obtained by the PEPT technique can be used to optimise the design, operational conditions for a wide range of industrial process systems, and to evaluate modelling work. The technique is based on tracking radioactively labelled particles （up to three particles） by detecting the pairs of backto-back 511 keV γ-rays arising from annihilation of emitted positrons. It therefore involves a positron camera, location algorithms for calculating the tracer location and speed, and tracer labelling techniques. This paper will review the particle tracking technique from tracking algorithm, tracer labelling to their application.

关键词： PEPT Tracer Algorithm Tracking

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