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Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

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Neural Regeneration Research 2025年第8期20卷 2348-2360页

作者： Mohamed Aghyad Al Kabbani Christoph Köhler Hans Zempel Institute of Human Genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for Molecular medicine cologne(CMMC) University of CologneCologneGermany Center Anatomy Department ⅡMedical FacultyUniversity of CologneCologneGermany

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the *** is missorted and aggregated in an array of diseases known as *** are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing *** impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule *** therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to *** investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic *** sum,P301L-TAU results in changes in micr

关键词： human induced pluripotent stem cell microtubules P301L pR5 mice TAU tauopathy tubulin code

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Amyloid-β-induced disruption of axon-initial-segment mitochondria localization:consequences for TAU missorting in Alzheimer's disease pathology

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Neural Regeneration Research 2025年第5期20卷 1407-1408页

作者： Daniel Adam Felix Langerscheidt Hans Zempel Institute of Human Genetics University Hospital CologneCologneGermany Center for Molecular medicine cologne(CMMC) University of CologneCologneGermany

TAU is a neuronal microtubule-associated protein preferentially located in *** a battery of neurodegenerative diseases termed"tauopathies,"including Alzheimer's disease (AD),TAU is missorted and abnormally phosphorylated,leading to filamentous accumulations of hyperphosphorylated TAU,a pathological hallmark and potential disease driver of AD and related tauopathies (Zempel,2024).

关键词： Alzheimer tau diseases

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Vedolizumab serum trough concentrations with and without thiopurines in ulcerative colitis: The prospective VIEWS pharmacokinetics study

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World Journal of Gastroenterology 2025年第2期31卷 102-112页

作者： Thanaboon Chaemsupaphan Aviv Pudipeddi Hui-Yu Lin Sudarshan Paramsothy Viraj C Kariyawasam Melissa Kermeen Rupert W Leong Department of Gastroenterology and Liver Services Concord Repatriation General HospitalSydney 2139New South WalesAustralia faculty of medicine Siriraj HospitalMahidol UniversityBangkok 10700Thailand faculty of medicine and Health University of SydneySydney 2139New South WalesAustralia Department of Gastroenterology Tan Tock Seng HospitalSingapore 308433Singapore faculty of medicine and Health Sciences Macquarie UniversitySydney 2139New South WalesAustralia Department of Gastroenterology and Hepatology Blacktown HospitalSydney 2148New South WalesAustralia Blacktown Clinical School Western Sydney UniversitySydney 2148New South WalesAustralia

BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory condition requiring continuous treatment and *** is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is *** To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance *** This is a post-hoc analysis of prospective randomized clinical trial(VIEWS)involving UC patients across 8 centers in Australia from 2018 to *** in clinical and endoscopic remission were randomized to continue or withdraw thiopurine while receiving *** evaluated vedolizumab serum trough concentrations,presence of anti-vedolizumab antibodies,and clinical outcomes over 48 weeks to assess exposure-response asso-ciation and impact of thiopurine *** There were 62 UC participants with mean age of 43.4 years and 42%were *** participants received vedolizumab as maintenance therapy with 67.7%withdrew *** serum trough concentrations remained stable over 48 weeks regardless of thiopurine use,with no anti-vedolizumab antibodies ***-tients with clinical remission had higher trough concentrations at week *** quartile analysis,a threshold of>11.3μg/mL was associated with sustained clinical remission,showing a sensitivity of 82.4%,specificity of 60.0%,and an area of receiver operating characteristic of 0.71(95%CI:0.49-0.93).Patients discontinuing thiopurine required higher vedolizumab concentrations for achieving *** A positive exposure-response relationship between vedolizumab trough concentrations and UC outcomes suggests that monitoring drug levels may be *** thiopurine did not influence vedolizumab levels,its with-drawal may necessitate higher vedolizumab trough concentrations to maintain remi

关键词： Pharmacokinetic Vedolizumab Thiopurine Ulcerative colitis Trough concentration Antibody Inflammatory bowel diseases

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Mechanisms behind elevated serum levels of plasminogen activator inhibitor-1 in frontotemporal lobar degeneration

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Neural Regeneration Research 2025年第8期20卷 2317-2318页

作者： Francesco Angelucci Jakub Hort Memory Clinic Department of NeurologySecond Faculty of MedicineCharles University and Motol University HospitalPragueCzech Republic International Clinical Research Centre St.Anne’s University HospitalBrnoCzech Republic

Frontotemporal lobar degeneration(FTLD)is a form of progressive dementia characterized by degeneration of the frontal and temporal lobes of the *** pathology involves a series of cognitive,behavioral,and neurological ... 详细信息

关键词： degeneration elevated pathology

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Mycoplasma pneumoniae pneumonia in children

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World Journal of Clinical Cases 2025年第5期13卷 61-67页

作者： Thakoon Butpech Prakarn Tovichien Department of Pediatrics Faculty of Medicine Siriraj HospitalMahidol UniversityBangkok 10700Thailand

Mycoplasma pneumoniae(***)is a common pathogen that causes community-acquired pneumonia in *** clinical presentation of this pathogen can range from mild self-limiting illness to severe and refractory *** may occur,such as necrotizing pneumonia and respiratory *** complications,including encephalitis,myocarditis,nephritis,hepatitis,or even multiple organ failure,can also *** this editorial,we dis-cuss the clinical implications of the significant findings from the article"Serum inflammatory markers in children with *** pneumonia and their predictive value for mycoplasma severity"published by Wang et *** reported that measuring lactic dehydrogenase,interleukin-6 levels,and D-dimer effectively predicts refractory *** pneumonia cases.

关键词： Cytokine Mycoplasma pneumoniae pneumonia Children,Community-acquired pneumonia Lactic dehydrogenase Interleukin-6

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Acquired sensorineural hearing loss,oxidative stress,and microRNAs

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Neural Regeneration Research 2025年第9期20卷 2513-2519页

作者： Desmond A.Nunez Ru C.Guo Division of Otolaryngology–Head&Neck Surgery Department of SurgeryFaculty of MedicineThe University of British ColumbiaVancouverBCCanada Division of Otolaryngology–Head&Neck Surgery Gordon&Leslie Diamond Health Care CentreVancouver General HospitalVancouverBCCanada faculty of medicine–The university of British Columbia VancouverBCCanada

Hearing loss is the third leading cause of human ***-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health ***-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing *** etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental *** stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing *** non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic *** hair cell death is a central histopathological finding in sensorineural hearing *** these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing *** EMBASE,Ovid MEDLINE,Web of Science Core Collection,and *** databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical *** red clinical trials known to the senior author we re also assessed.A total of 222studies were thus *** excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text *** resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative *** miR-34a and miR-29b levels increase with age in *** miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P GC-1α),SIRT

关键词： hearing loss hypoxia microRNAs oxidative stress sensorineural

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Human endogenous retrovirus type-W and multiple sclerosis–related smoldering neuroinflammation

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Neural Regeneration Research 2025年第3期20卷 813-814页

作者： Joel Gruchot Laura Reiche Andrew Chan Robert Hoepner Patrick Küry Department of Neurology Medical Faculty and University Hospital DüsseldorfHeinrich Heine University DüsseldorfDüsseldorfGermany Department of Neurology InselspitalBern University Hospital and University of BernBernSwitzerland

Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.

关键词： endogenous inflammation Human

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Suppression of mature TAU isoforms prevents Alzheimer's disease-like amyloid-beta oligomer-induced spine loss in rodent neurons

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Neural Regeneration Research 2024年第8期19卷 1655-1657页

作者： Sarah Buchholz Hans Zempel Institute of Human Genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for Molecular medicine cologne(CMMC) Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany

Introduction:TAU isoforms as disease mediators:The microtubule-associated protein TAU is predominantly present in the axons of neurons under physiological *** Alzheimer’s disease(AD)and related tauopathies,TAU also mislocalizes("TAU missorting")to the soma and the dendrites,where it eventually forms aggregates,the so-called neurofibrillary tangles(for review see Zimmer-Bensch and Zempel,2021;Zempel,2023).

关键词： Alzheimer Zimmer tau

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The role of LIN28B in tumor progression and metastasis in solid tumor entities

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Oncology Research 2023年第2期31卷 101-115页

作者： TABEA GEWALT KA-WON NOH LYDIA MEDER Department I of Internal medicine Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for Molecular medicine cologne University of CologneCologneGermany Institute for Pathology Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Mildred Scheel School of Oncology Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany

LIN28B is an RNA-binding protein that targets a broad range of microRNAs and modulates their maturation and *** normal conditions,LIN28B is exclusively expressed in embryogenic stem cells,blocking differentiation and promoting *** addition,it can play a role in epithelial-to-mesenchymal transition by repressing the biogenesis of let-7 *** malignancies,LIN28B is frequently overexpressed,which is associated with increased tumor aggressiveness and metastatic *** this review,we discuss the molecular mechanisms of LIN28B in promoting tumor progression and metastasis in solid tumor entities and its potential use as a clinical therapeutic target and biomarker.

关键词： Cancer Metastasis LIN28B Let-7 Stemness EMT Resistance

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Gut virome:New key players in the pathogenesis of inflammatory bowel disease

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World Journal of Methodology 2025年第2期15卷 27-43页

作者： Helal F Hetta Rehab Ahmed Yasmin N Ramadan Hayam Fathy Mohammed Khorshid Mohamed M Mabrouk Mai Hashem Department of Medical Microbiology and Immunology Faculty of MedicineAssiut UniversityAssiut 71515Egypt Division of Microbiology Immunology and BiotechnologyFaculty of pharmacyUniversity of TabukTabuk 71491Saudi Arabia Division of Microbiology Immunology and BiotechnologyDepartment of Natural Products and Alternative MedicineFaculty of PharmacyUniversity of TabukTabuk 71491Saudi Arabia Department of Internal medicine Division HepatogastroenterologyAssiut UniversityAssiut 71515Egypt Department of Clinical Research Egyptian Developers of Gastroenterology and Endoscopy FoundationCairo 11936Egypt Department of Internal medicine Faculty of Medicine.Tanta UniversityTanta 31527Egypt Department of Tropical medicine Gastroenterology and HepatologyAssiut University HospitalAssiut 71515Egypt

Inflammatory bowel disease(IBD)is a chronic inflammatory illness of the *** the mechanism underlying the pathogenesis of IBD is not fully under-stood,it is believed that a complex combination of host immunological response,environmental exposure,particularly the gut microbiota,and genetic suscept-ibility represents the major *** gut virome is a group of viruses found in great frequency in the gastrointestinal tract of *** gut virome varies greatly among individuals and is influenced by factors including lifestyle,diet,health and disease conditions,geography,and *** majority of research has focused on the significance of gut bacteria in the progression of IBD,although viral populations represent an important component of the *** conducted this review to highlight the viral communities in the gut and their expected roles in the etiopathogenesis of IBD regarding published research to date.

关键词： Inflammatory bowel disease Pathogenesis Gut virome Bacteriophage Eukaryotic viruses

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