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Role of astrocytes and microglia in hepatic encephalopathy associated with advanced chronic liver disease:lessons from animal studies

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Neural Regeneration Research 2025年第12期20卷 3461-3475页

作者： Wouter Claeys Anja Geerts Lien Van Hoecke Christophe Van Steenkiste Roosmarijn E.Vandenbroucke Department of Internal Medicine and Paediatrics Hepatology Research UnitGhent UniversityGhentBelgium Liver Research Center Ghent Ghent UniversityGhent University HospitalGhentBelgium Barriers in Inflammation VIB-UGent Center for Inflammation ResearchVIBGhentBelgium Department of Biomedical molecular Biology Ghent UniversityGhentBelgium Department of Gastroenterology and hepatology Ghent University HospitalGhentBelgium Department of Gastroenterology and hepatology Antwerp UniversityAntwerpBelgium Department of Gastroenterology and hepatology Maria Middelares HospitalGhentBelgium

Hepatic encephalopathy,defined as neuropsychiatric dysfunction secondary to liver disease,is a frequent decompensating event in *** clinical impact is highlighted by a notable increase in patient mortality rates and a concomitant reduction in overall quality of ***,liver disease,liver function failure,portosystemic shunting,and associated multi-organ dysfunction result in the increase of disease-causing neurotoxins in the circulation,which impairs cerebral *** circulating neurotoxins are ammonia and inflammatory *** the brain,pathophysiology is less well understood,but is thought to be driven by glial cell *** are the only brain resident cells that have ammonia-metabolizing machinery and are therefore putatively most susceptible to ammonia *** on a large body of mostly in vitro evidence,ammonia-induced cellular and molecular disturbances include astrocyte swelling and oxidative ***,the brain resident macrophages,have been linked to the translation of systemic inflammation to the brain *** evidence from animal studies has provided novel insights into old and new downstream effects of astrocyte and microglial dysfunction such as toxin clearance disruption and myeloid cell attraction to the central nervous system ***,state of the art research increasingly implicates neuronal dysfunction and possibly even irreversible neuronal cell ***-type specific investigation in animal models highlights the need for critical revision of the contribution of astrocytes and microglia to well-established and novel cellular and molecular alterations in hepatic *** this review,we therefore give a current and comprehensive overview of causes,features,and consequences of astrocyte and microglial dysfunction in hepatic encephalopathy,including areas of interest for future investigation.

关键词： ammonia astrocytes cirrhosis hepatic encephalopathy microglia neuroinflammation osmotic stress oxidative stress systemic inflammation

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New aspects of a small GTPase RAB35 in brain development and function

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Neural Regeneration Research 2025年第7期20卷 1971-1980页

作者： Ikuko Maejima Ken Sato Laboratory of molecular Traffic Institute for Molecular and Cellular RegulationGunma UniversityMaebashiJapan

In eukaryotic cells,organelles in the secretory,lysosomal,and endocytic pathways actively exchange biological materials with each other through intracellular membrane trafficking,which is the process of transporting the cargo of proteins,lipids,and other molecules to appropriate compartments via transport vesicles or *** processes are strictly regulated by various small GTPases such as the RAS-like in rat brain(RAB)protein family,which is the largest subfamily of the RAS *** of membrane trafficking affects tissue homeostasis and leads to a wide range of diseases,including neurological disorders and neurodegenerative ***,it is important to understand the physiological and pathological roles of RAB proteins in brain ***35,a member of the RAB family,is an evolutionarily conserved protein in metazoans.A wide range of studies using cultured mammalian cells and model organisms have revealed that RAB35 mediates various processes such as cytokinesis,endocytic recycling,actin bundling,and cell ***35 is also involved in neurite outgrowth and turnover of synaptic *** generated brain-specific Rab35 knockout mice to study the physiological roles of RAB35 in brain development and *** mice exhibited defects in anxiety-related behaviors and spatial ***,RAB35 is required for the precise positioning of pyramidal neurons during hippocampal development,and thereby for normal hippocampal *** contrast,layer formation in the cerebral cortex occurred superficially,even in the absence of RAB35,suggesting a predominant role for RAB35 in hippocampal development rather than in cerebral cortex *** studies have suggested an association between RAB35 and neurodegenerative diseases,including Parkinson's disease and Alzheimer's *** this review,we provide an overview of the current understanding of subcellular functions of *** also provide insights into the phys

关键词： endocytosis endosomes hippocampal development neurodegenerative diseases RAB35

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Mitochondrial therapeutics and mitochondrial transfer for neurodegenerative diseases and aging

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Neural Regeneration Research 2025年第3期20卷 794-796页

作者： Neville Ng Michelle Newbery Nicole Miles Lezanne Ooi molecular Horizons and School of Chemistry and molecular Bioscience University of WollongongWollongongNSWAustralia

Mitochondrial dysfunction and neurodegeneration:Progressive neurodegenerative diseases affect a significant proportion of the population;in a single year,there are as many as 276 million disabilities and 9 million dea... 详细信息

关键词： degenerative diseases Mitochondrial

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Redefining endoluminal biliary drainage:Challenges and innovations in endosonography-guided techniques

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World Journal of Gastroenterology 2025年第1期31卷 146-151页

作者： Marcel Razpotnik Department of Gastroenterology and hepatology Campus Virchow/Campus MitteCharitéBerlinBerlin 10117Germany

Endoscopic retrograde cholangiopancreatography is considered the gold standard for treating benign and malignant biliary ***,its use in complex biliary obstructions is *** the past decades,therapeutic endosonography(EUS)and emerging technologies such as lumen-apposing metal stents have enabled endoscopic treatment of conditions previously requiring nonendoscopic or surgical *** show that EUS-guided choledochoduodenostomy is a reliable alternative to endoscopic retrograde cholangiopancreatography in the treatment of distal malignant biliary obstructions and can be considered a primary drainage modality in centers with adequate *** malignant hilar biliary obstructions,draining at least 50%of viable liver tissue often requires combining different *** treatment strategy in these patients should be individualized,depending on the Bismuth classification,patient physical status,and intended systemic *** to the lack of evidence,general recommendations cannot be made for EUS-guided hepaticoduodenostomy or combined procedures with transhepatic bridging *** novel techniques should be limited to selected palliative cases where conventional methods have failed and conducted within clinical trials to generate evidence before broader application.

关键词： Endoscopic biliary drainage Interventional endosonography Lumen-apposing metal stent Malignant hilar biliary obstruction Malignant distal biliary obstruction

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Gastric polyps are not created equal: Know your enemy

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World Journal of Gastroenterology 2025年第2期31卷 144-146页

作者： Fady Daniel Department of Gastroenterology and hepatology American University of Beirut Medical CenterBeirut 11072020Lebanon

Gastric polyps are commonly detected during upper gastrointestinal *** are most often benign and rarely become ***,adequate knowledge,diagnostic modalities,and management strategies should be the endoscopist’s readily available“weapons”to defeat the potentially malignant“enemies”.This article sheds light on the valuable effort by Costa et al to generate a new classification system of gastric polyps as“good”,“bad”,and“ugly”.This comprehensive overview provides clinicians with a simplified decision-making process.

关键词： Gastric polyps Polypoid subepithelial lesions Early gastric cancer Endoscopic ultrasonography Electronic chromoendoscopy

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Gut microbiota shifts in hepatitis B-related portal hypertension after transjugular intrahepatic portosystemic shunt:Mechanistic and clinical implications

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World Journal of Gastroenterology 2025年第3期31卷 134-137页

作者： Qi-Rong Jiang Da-Wu Zeng Department of hepatology Hepatology Research InstituteThe First Affiliated HospitalFujian Medical UniversityFuzhou 350005Fujian ProvinceChina Department of Infectious Diseases The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350004Fujian ProvinceChina

In this article,we provide commentary on the recent article by Zhao et *** focus on the shifts in the gut microbiota of patients with hepatitis B virus(HBV)-associated cirrhosis/portal hypertension(PH)following transjugular intrahepatic portosystemic shunt(TIPS)and the implications for understanding the mechanisms,diagnosis,and *** comparing the gut microbiota composition and dynamic changes before and after TIPS in patients with and without hepatic encephalopathy,the authors found an increase in non-probiotic bacteria in those who developed hepatic encephalopathy post-TIPS,with Morganella species present only in the hepatic encephalopathy *** gut microbiota changes post-TIPS among patients without the occurrence of hepatic encephalopathy suggest potential therapeutic benefits through prophylactic microbiome ***,the specific gut microbiota alterations may hold promise to predict the risk of hepatic encephalopathy in individuals undergoing TIPS for HBVrelated *** these promising findings,future studies are needed to address limitations,including a small sample size,a relatively short evaluation period for gut microbiota alterations,the absence of data on dynamic alterations in gut microbiota post-TIPS and their correlation with blood ammonia levels,and the lack of validation in animal *** conclusion,Zhao et al's study has shed new light on the link of gut microbiota with post-TIPS hepatic encephalopathy,potentially through the intricate gut-liver axis,and has important clinical implications for improving the management of patients with HBV-related PH.

关键词： Hepatitis B virus Cirrhosis Portal hypertension Hepatic encephalopathy Transjugular intrahepatic portosystemic shunt Gut microbiota

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Association between autoimmune gastritis and gastric polyps:Clinical characteristics and risk factors

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 73-87页

作者： Jing-Zheng Jin Xiao Liang Shu-Peng Liu Rui-Lan Wang Qing-Wei Zhang Yu-Feng Shen Xiao-Bo Li Division of Gastroenterology and hepatology Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China Division of Gastroenterology and hepatology Shanghai Institute of Digestive DiseasesShanghai 200001China Division of Gastroenterology and hepatology Renji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China Division of Gastroenterology and hepatology Sichuan Armed Police Corps HospitalLeshan 610041Sichuan ProvinceChina Division of Gastroenterology and hepatology NHC Key Laboratory of Digestive DiseasesRenji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China Department of Gastroenterology Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai Institute of Digestive DiseasesShanghai 200127China

BACKGROUND The relationship between autoimmune gastritis(AIG)and gastric polyps(GPs)is not well *** To explore the clinical characteristics and risk factors of AIG with GPs in *** This double center retrospective study included 530 patients diagnosed with AIG from July 2019 to July *** collected clinical,biochemical,serological,and demographic data were of each *** regression analyses,both multivariate and univariate,were conducted to pinpoint independent risk factors for GPs in patients with AIG *** operating characteristic curves were utilized to establish the optimal cutoff values,sensitivity,and specificity of these risk factors for predicting GPs in patients with *** Patients with GPs had a higher median age than those without GPs[61(52.25-69)years vs 58(47-66)years,P=0.006].The gastrin-17 levels were significantly elevated in patients with GPs compared with those without GPs[91.9(34.2-138.9)pmol/mL vs 60.9(12.6-98.4)pmol/mL,P<0.001].Additionally,the positive rate of parietal cell antibody(PCA)antibody was higher in these patients than in those without GPs(88.6%vs 73.6%,P<0.001).Multivariate and univariate analyses revealed that PCA positivity[odds ratio(OR)=2.003,P=0.017],pepsinogen II(OR=1.053,P=0.015),and enterochromaffin like cells hyperplasia(OR=3.116,P<0.001)were significant risk factors for GPs,while pepsinogen I was identified as a protective *** PCA positivity and enterochromaffin like cells hyperplasia are significant risk factor for the development of GPs in patients with *** gastrin-17 levels may also play a role in this *** findings suggest potential targets for further research and therapeutic intervention in managing GPs in patients with AIG.

关键词： Autoimmune gastritis Gastric polyps Neuroendocrine tumor Risk factors Nomogram

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A-kinase anchoring protein-mediated compartmentalization of pro-survival signaling in the retina

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Neural Regeneration Research 2025年第2期20卷 479-480页

作者： Joanna Mackiewicz Tomasz Boczek Department of molecular Neurochemistry Medical University of LodzLodzPoland

The retina plays a fundamental role in the process of vision,serving as the primary interface between external visual stimuli and the central nervous *** the retina is exposed to a variety of environmental stresses and deleterious insults,it is susceptible to a spectrum of pathological conditions that can detrimentally affect *** often leads to irreversible vision loss due to the injury of specific cell *** instance,inherited retinal degeneration and age-related macular degeneration can lead to the death of photoreceptors,while conditions like glaucoma and optic nerve injury can result in the loss of ganglion *** precise pathological mechanisms driving retinal degeneration remain largely elusive,although research utilizing mouse models suggests that disruptions in intracellular signal transduction pathways may play a pivotal *** pathways within the retina orchestrate various aspects of retinal physiology,including phototransduction,synaptic transmission,and neuronal survival.

关键词： degeneration utilizing irreversible

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Phosphodiesterase 9 localization in cytoplasm and nucleus:the gateway to selective targeting in neuroprotection?

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Neural Regeneration Research 2025年第6期20卷 1701-1702页

作者： Giovanni Ribaudo Matteo Giannangeli Margrate Anyanwu Alessandra Gianoncelli Department of molecular and Translational Medicine University of BresciaBresciaItaly

The umbrella term"neurodege ne rative disorders"(NDDs) refers to several conditions characterized by a progressive loss of structure and function of cells belonging to the nervous *** diseases affect more than 50million people *** disorders are characterized by sundry factors and pathophysiological mechanisms that a re challenging to be fully *** of these rely on cell signaling pathways to preserve homeostasis,involving second messengers such as cyclic adenosine monophosphate (cAMP)and cyclic guanosine 3',5'-monophosphate(cGMP).Their ability to control the duration and amplitude of the signaling cascade is given by the presence of several common and uncommon *** kinases A and G (PKA and PKG),phosphodiesterases (PDEs),and scaffold proteins are among them.

关键词： gateway homeostasis preserve

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Unraveling post-growth mechanisms of monolayer CsPbBr3 nanocubes:Laser-enhanced transformations and cathodoluminescence-electron microscopy correlations

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Journal of Energy Chemistry 2025年第1期100卷 146-156页

作者： Mingxing Li Xiaoge Wang Xiaofan Cao Zhiqun He Chunjun Liang Mingxing Chen Jing Ju Fangtian You Key Laboratory of Luminescence and Optical Information Ministry of EducationInstitute of Optoelectronic TechnologyBeijing Jiaotong UniversityBeijing 100044China Beijing National Laboratory for molecular Sciences(BNLMS) College of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China

Lead-halide perovskite nanoparticles(LHP NPs) are highly promising materials for next-generation displays and solid-state lighting due to their exceptional optical properties. However, their inherent instability presents a significant challenge. Recent advances have demonstrated that optoelectronic devices based on monolayer nanoparticle films exhibit both high luminescence efficiency and long-term *** research demonstrates that mobility limitations and anisotropic alignments in CsPbBr3nanocube monolayer films are key to their stabilization, hindering spontaneous growth through face-to-face fusion and resulting in the formation of connecting necks in a diagonal direction. Introducing laser irradiation confirmed this by significantly accelerating nanocubes growth, increasing mobility, and enhancing local structural ordering, leading to larger and more regularly shaped nanosheets. Fourier transform infrared spectroscopy and energy dispersive spectroscopy line-scan analyses indicated that laser irradiation did not disrupt the ligand structure. Transmission electron microscopy and correlative cathodoluminescence electron microscopy revealed the effects of post-growth and heterogeneous structures, including enhanced luminescence and inhomogeneous intensity in the nanosheets. These findings deepen the understanding of the post-growth mechanism of monolayer nanoparticles and the structure-emission correlation and highlight the unique role of laser irradiation in directing the formation of well-defined and regular nanostructures.

关键词： CsPbBr3 nanocubes Post-growth mechanism Heterogeneous structure Single-particle spectroscopy Laser irradiation

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