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STING mediates microglial pyroptosis via interaction with NLRP3 in cerebral ischaemic stroke

Stroke & Vascular neurology 2024年第2期9卷 153-164页

作者： Wenyu Li Nan Shen Lingqi Kong Hongmei Huang Xinyue Wang Yan Zhang Guoping Wang Pengfei Xu Wei Hu Department of neurology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhuiChina

background Ischaemia-evoked neuroinflammation is a critical pathogenic event following ischaemic *** D(GSDMD)-associated pyroptosis represents a type of inflammation-associated programmed cell death,which can exacerbate neuroinflammatory responses and brain *** of interferon genes(STING)was recently described as a vital innate immune adaptor protein associated with ***,the regulatory effects of STING on microglial pyroptosis post-stroke have not been well *** STING-knockout and wild-type(WT)mice were subjected to middle cerebral artery occlusion(MCAO).STING small interfering RNA(siRNA)was transfected into BV2 cells before oxygen-glucose deprivation/reoxygenation(OGD/R).STING-overexpressing adeno-associated virus(AAV)and NOD-like receptor family pyrin domain containing 3(NLRP3)siRNA were administered by stereotaxic injection.2,3,5-Triphenyl tetrazolium chloride(TTC)staining,TdT-mediated dUTP nick end labeling(TUNEL)staining,Fluoro-Jade C(FJC)staining,neurobehavioural tests,immunohistochemistry,cytokine antibody array assay,transmission electron microscopy,immunoblot,Enzyme-linked immunosorbent assay(ELISA)and quantitative real-time polymerase chain reaction(qRT-PCR)were carried ***-immunoprecipitation assays were used to investigate the interplay between STING and *** STING expression was increased after MCAO and mainly detected on *** deletion alleviated brain infarction,neuronal damage and neurobehavioural impairment in mice subjected to *** knockout suppressed microglial activation and the secretion of inflammatory chemokines,accompanied by mitigation of microglial *** upregulation of microglial STING by AAV-F4/80-STING aggravated brain injury and microglial ***,co-immunoprecipitation showed that STING bound to NLRP3 in *** of NLRP3 siRNA reversed AAV-F4/80-STING-induced deterioration of microglial pyropt

关键词： NLRP3 cerebral inflammation

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Is medical management useful in Moyamoya disease?

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World Journal of Clinical Cases 2024年第3期12卷 466-473页

作者： Sombat Muengtaweepongsa Vatcharasorn Panpattanakul Center of Excellence in Stroke Division of NeurologyDepartment of MedicineFaculty of MedicineThammasat UniversityRangsit CampusKlonglaung 12120Pathum ThaniThailand division of neurology Department of Internal MedicineSchool of MedicineUniversity of PhayaoPhayao 56000Thailand

Moyamoya disease(MMD),characterized by progressive internal carotid artery stenosis and collateral vessel formation,prompts cerebral perfusion complications and is stratified into idiopathic and Moyamoya syndrome subtypes.A multifa-ceted approach toward MMD management addresses cerebral infarctions through revascularization surgery and adjunctive medical therapy,while also navigating risks such as intracranial hemorrhage and cerebral infarction resulting from arte-rial stenosis and fragile collateral *** antithrombotic management reveals a potential role for treatments like antiplatelet agents and anticoagulants,despite the ambiguous contribution of thrombosis to MMD-related infarctions and the critical balance between preventing ischemic events and averting hemo-rrhagic *** doppler has proven useful in thromboembolic detection,despite persisting challenges concerning the efficacy and safety of an-tithrombotic ***,antihypertensive interventions aim to ma-nage blood pressure meticulously,especially during intracerebral hemorrhage,with recommendations and protocols varying based on the patient’s hypertension ***,lipid-lowering therapeutic strategies,particularly employing statins,are appraised for their possible beneficial role in MMD management,even as comprehensive data from disease-specific clinical trials remains ***-prehensive guidelines and protocols to navigate the multifaceted therapeutic ave-nues for MMD,while maintaining a delicate balance between efficacy and safety,warrant further meticulous research and *** protocol manuscript seeks to elucidate the various aspects and challenges imbued in managing and navigating through the complex landscape of MMD treatment.

关键词： Moyamoya disease Cerebral infarction Antithrombotic management Transcranial doppler Revascularization Intracerebral hemorrhage Antihypertensive intervention Lipid-lowering therapies

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Use of donepezil for neurocognitive recovery after brain injury in adult and pediatric populations:a scoping review

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Neural Regeneration Research 2024年第8期19卷 1686-1695页

作者： Avery L.Miller Nathan K.Evanson J.Michael Taylor University of Cincinnati College of Medicine CincinnatiOHUSA Department of Pediatrics University of CincinnatiCincinnatiOHUSA Department of neurology and Rehabilitation Medicine University of CincinnatiCincinnatiOHUSA division of Pediatric Rehabilitation Medicine Cincinnati Children’s Hospital Medical CenterCincinnatiOHUSA division of neurology Cincinnati Children’s Hospital Medical CenterCincinnatiOHUSA

There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric *** inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury,but relatively less is known about the effect in pediatric *** goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibito rs as a potential a djuvant treatment fo r neurocognitive decline in pediatric patients with traumatic brain *** queried PubMed to identify literature published from database inception thro ugh June 2023 desc ribing the use of donepezil in young adult traumatic brain injury and pediatric patients with predefined *** on preselected search criteria,340 unique papers we re selected for title and abstra ct ***-two reco rds were reviewed in full after eliminating preclinical studies and pape rs outside the scope of the *** adult traumatic brain injury,we review results from 14 papers detailing 227 subjects where evidence suggests donepezil is well tole rated and shows both objective and patient-reported efficacy for reducing cognitive *** children,3 pape rs report on 5 children recovering from traumatic brain injury,showing limited *** additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age *** its promise for efficacy in adults with traumatic brain injury and tole rability in pediatric patients,we believe further study of donepezil for children and adolescents with traumatic brain injury is warranted.

关键词： acetylcholinesterase inhibitor adult cognition donepezil pediatrics traumatic brain injury

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Cerebral small vessel disease modifies outcomes after minimally invasive surgery for intracerebral haemorrhage

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Stroke & Vascular neurology 2024年第4期9卷 446-456,I0147页

作者： Yunke Li Sung-Min Cho Radhika Avadhani Hassan Ali Yi Hao Santosh B Murthy Joshua N Goldstein Fan Xia Xin Hu Natalie L Ullman Issam Awad Daniel Hanley Wendy C Ziai The George Institute for Global Health BeijingChina Department of neurology Division of Neurocritical CareJohns Hopkins Medical InstitutionsBaltimoreMarylandUSA Department of neurology Division of Brain Injury OutcomesJohns Hopkins Medical Institutions CampusBaltimoreMarylandUSA Department of neurology Weill Cornell Medical CollegeNew YorkNew YorkUSA Department of Emergency Medicine Massachusetts General HospitalBostonMassachusettsUSA Department of Neurosurgery West China Hospital of MedicineChengduSichuanChina Department of Neurosurgery University of Chicago Pritzker School of MedicineChicagoIllinoisUSA

Background Minimally invasive surgery(MIS)for spontaneous supratentorial intracerebral haemorrhage(ICH)is controversial but may be beneficial if end-of-treatment(EOT)haematoma volume is reduced to≤15 *** explored whether MRI findings of cerebral small vessel disease(CSVD)modify the effect of MIS on long-term *** Prespecified blinded subgroup analysis of 288 subjects with qualified imaging sequences from the phase 3 Minimally Invasive Surgery Plus Alteplase for Intracerebral Haemorrhage Evacuation(MISTIE)*** tested for heterogeneity in the effects of MIS and MIS+EOT volume≤15 mL on the trial’s primary outcome of good versus poor function at 1 year by the presence of single CSVD features and CSVD scores using multivariable *** Of 499 patients enrolled in MISTIE III,288 patients had MRI,149(51.7%)randomised to MIS and 139(48.3%)to standard medical care(SMC).Median(IQR)ICH volume was 42(30–53)*** the full MRI cohort,there was no statistically significant heterogeneity in the effects of MIS versus SMC on 1-year outcomes by any specific CSVD feature or by CSVD scores(all P_(interaction)>0.05).In 94 MIS patients with EOT ICH volume≤15 mL,significant reduction in odds of poor outcome was found with cerebral amyloid angiopathy score<2(OR,0.14(0.05–0.42);P_(interaction)=0.006),absence of lacunes(OR,0.37(0.18–0.80);P_(interaction)=0.02)and absence of severe white matter hyperintensities(WMHs)(OR,0.22(0.08–0.58);P_(interaction)=0.03).Conclusions Following successful haematoma reduction by MIS,we found significantly lower odds of poor functional outcome with lower total burden of CSVD in addition to absence of lacunes and severe *** features may have utility for prognostication and patient selection in clinical trials of MIS.

关键词： Surgery surgery absence

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Haemorrhage after thrombectomy with adjuvant thrombolysis in unknown onset stroke depends on high early lesion water uptake

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Stroke & Vascular neurology 2024年第4期9卷 390-398页

作者： Gabriel Broocks Lukas Meyer Uta Hanning Tobias Djamsched Faizy Matthias Bechstein Helge Kniep Noel Van Horn Gerhard Schön Ewgenia Barow Götz Thomalla Jens Fiehler Andre Kemmling Department of Diagnostic and Interventional Neuroradiology University Medical Center Hamburg-EppendorfHamburgGermany Department of Medical Biometry and epidemiology University Medical Center Hamburg EppendorfHamburgGermany Department of neurology University Medical Center Hamburg-EppendorfHamburgGermany Department of Neuroradiology University MarburgMarburgGermany

Background and purpose In wake-up stroke,CT-based quantitative net water uptake(NWU)might serve as an alternative tool to MRI to guide intravenous thrombolysis with alteplase(IVT).An important complication after IVT is symptomatic intracerebral haemorrhage(sICH).As NWU directly implies ischaemic lesion progression,reflecting blood-brain barrier injury,we hypothesised that NWU predicts sICH in patients who had a ischaemic stroke undergoing thrombectomy with unknown *** Consecutive analysis of all patients who had unknown onset anterior circulation ischaemic stroke who underwent CT at baseline and endovascular treatment between December 2016 and October *** NWU was assessed on baseline *** primary endpoint was *** association of NWU and other baseline parameters to sICH was investigated using inverse-probability weighting(IPW)*** A total of 88 patients were included,of which 46 patients(52.3%)received *** median NWU was 10.7%(IQR:5.1–17.7).The proportion of patients with any haemorrhage and sICH were 35.2%and 13.6%.NWU at baseline was significantly higher in patients with sICH(19.1%vs 9.6%,p<0.0001)and the median Alberta Stroke Program Early CT Score(ASPECTS)was lower(5 vs 8,p<0.0001).Following IPW,there was no association between IVT and sICH in unadjusted ***,after adjusting for ASPECTS and NWU,there was a significant association between IVT administration and sICH(14.6%,95%CI:3.3%to 25.6%,p<0.01).Conclusion In patients with ischaemic stroke with unknown onset,the combination of high NWU with IVT is directly linked to higher rates of *** ASPECTS for evaluating the extent of the early infarct lesion,quantitative NWU could be used as an imaging biomarker to assess the degree of blood-brain barrier damage in order to predict the risk of sICH in patients with wake up stroke.

关键词： throm thrombolysis high

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Star power: harnessing the reactive astrocyte response to promote remyelination in multiple sclerosis

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Neural Regeneration Research 2024年第3期19卷 578-582页

作者： Markley Silva Oliveira Junior Laura Reiche Emerson Daniele Ines Kortebi Maryam Faiz Patrick Küry Department of neurology Neuroregeneration laboratoryMedical FacultyHeinrich-Heine-UniversityDüsseldorfGermany Institute of Medical Science University of TorontoTorontoCanada division of Anatomy Department of SurgeryUniversity of TorontoTorontoCanada

Astrocytes are indispensable for central nervous system development and *** response to injury and disease,astrocytes are integral to the immunological-and the,albeit limited,repair *** this review,we will examine some of the functions reactive astrocytes play in the context of multiple sclerosis and related animal *** will consider the heterogeneity or plasticity of astrocytes and the mechanisms by which they promote or mitigate ***,we will discuss a set of biomedical strategies that can stimulate astrocytes in their promyelinating response.

关键词： astrocytes demyelination drug-based therapies myelin repair oligodendrocyte precursor cells reactive astrogliosis

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A comparative study on antimicrobial susceptibility of uroculturome of humans in health and urinary tract infections

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Infectious Diseases Research 2024年第3期5卷 9-21页

作者： Bhoj Raj Singh Himani Agri division of epidemiology ICAR-Indian Veterinary Research InstituteIzatnagar 243122India

Background:The uroculturome indicates the profile of culturable microbes inhabiting the urinary tract,and it is often required to do a urine culture to find an effective antimicrobial to treat urinary tract infections(UTIs).Methods:This study targeted to understand the profile of culturable pathogens in the urine of apparently healthy(128)and humans with clinical UTIs(161)and their antimicrobial *** the urine samples were analyzed to quantify microbial load and determine the diversity and antimicrobial susceptibility of microbes following standard microbiological ***:In urine samples from UTI cases,microbial counts were 1.2×10^(4)±6.02×10^(3) colony-forming units(cfu)/mL,while in urine samples from apparently healthy humans,the average count was 3.33±1.34×10^(3) cfu/*** eight samples(six from UTI cases and two from apparently healthy people,Candida(*** 3,*** 1,*** 1,*** 1,*** 1,*** 1)and Rhizopus species(1)were *** krusei was detected only in a single urine sample from a healthy person and *** was detected both in urine of healthy and clinical UTI ***-positive(G+ve)bacteria were more commonly(Odds ratio,1.98;CI99,1.01-3.87)detected in urine samples of apparently healthy humans,and Gram-negative(G−ve)bacteria(Odds ratio,2.74;CI99,1.44-5.23)in urines of UTI *** urine samples of 161 UTI cases,a total of 90 different types of microbes were detected and,73 samples had only a single type of *** contrast,49,29,3,4,1,and 2 samples had 2,3,4,5,6 and 7 types of bacteria,*** most common bacteria detected in urine of UTI cases was Escherichia coli(52 samples),in 20 cases as the single type of bacteria,other 34 types of bacteria were detected in pure form in 53 *** 128 urine samples of apparently healthy people,88 types of microbes were detected either singly or in association with others,from 64 urine samples only a single type of bact

关键词： uro-microbiome UTI antibiotic susceptibility testing herbal antimicrobials ESBL carbapenem resistance MDR multiple herbal drug resistance

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Function and dysfunction of GEMIN5:understanding a novel neurodevelopmental disorder

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Neural Regeneration Research 2024年第11期19卷 2377-2386页

作者： Charles H.Nelson Udai B.Pandey Department of Pediatrics Division of Child NeurologyChildren’s Hospital of PittsburghUniversity of Pittsburgh Medical CenterPittsburghPAUSA Children’s Neuroscience Institute Children’s Hospital of PittsburghUniversity of Pittsburgh Medical CenterPittsburghPAUSA

The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction(NEDCAM)has resulted in an increased interest in GEMIN5,a multifunction RNA-binding *** the largest member of the survival motor neuron complex,GEMIN5 plays a key role in the biogenesis of small nuclear ribonucleoproteins while also exhibiting translational regulatory functions as an independent *** many questions remain regarding both the pathogenesis and pathophysiology of this new disorder,considerable progress has been made in the brief time since its *** this review,we examine GEMIN5 within the context of NEDCAM,focusing on the structure,function,and expression of the protein specifically in regard to the disorder ***,we explore the current animal models of NEDCAM,as well as potential molecular pathways for treatment and future directions of *** review provides a comprehensive overview of recent advances in our understanding of this unique member of the survival motor neuron complex.

关键词： cerebellar atrophy GEMIN5 neurodevelopmental disorder neurological disease SMN complex

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Comparative antimicrobial activity in Murrah buffalo (Bubalus bubalis) Heifers’ urine and urine distillate

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Infectious Diseases Research 2024年第1期5卷 32-39页

作者： Bhoj R Singh Himani Agri Dayanath Balusamy Akanksha Yadav Varsha Jayakumar division of epidemiology ICAR-Indian Veterinary Research InstituteBareilly 243122India.

Background:Murrah buffalo is a breed of water buffalo(Bubalus bubalis)reared for milk and meat,especially in Northern *** are so many studies on the antimicrobial potential of the cow(Bos indicus)urine but buffalo urine has rarely been *** study was aimed to evaluate the antimicrobial activity in whole buffalo urine and its ***:Urine specimens were collected from seven Murrah buffalo heifers in the morning over three days from all seven heifers and distillated to prepare urine distillate(UD).The antimicrobial activity was determined through 96 well microplate method diluting(1:1)urine and UD in Mueller Hinton liquid medium against 919 microbial strains belonging to 148 species of 49 genera(Candia,11 genera of Gram+ve bacteria,37 genera of Gram-ve bacteria).The test strains were taken from the repository,revived and tested for purity before *** test strains were of clinical origin(372),environmental origin(496)and also from reference strain repositories(51).Results:Of the 919 test strains,a total of 57.89%and 56.04%of the tested strains were susceptible to UD and urine,*** was a no significant(p>0.4)difference in the antimicrobial activity of UD and urine against 919 strains of microbes,regardless of their genus,species,and Gram staining ***,there was no significant(p>0.4)difference between the susceptibility of bacterial and Candida strains to UD or ***,strains of clinical origin were more often resistant to buffalo UD and urine(p0.05).A significantly(p<0.01)higher proportion of reference strains was susceptible to UD and urine than microbial strains of clinical and environmental *** buffalo urine and UD,the most susceptible strains were Stenotrophomonas maltophilia(13/13)followed by Citrobacter freundii(8/10);Salmonella enterica ***(21/27),Geobacillus stearothermo

关键词： Bubalus bubalis Edwardsiella tarda Entereococcus faecium Escherichia coli Klebsiella pneumoniae Raoultella terrigena Salmonella enteric

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Disclosing the true impact of screening endoscopy in colorectal cancer prevention

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Cancer Communications 2024年第4期44卷 504-507页

作者： Thomas Heisser Carlo Senore Michael Hoffmeister Lina Jansen Hermann Brenner division of Clinical epidemiology and Aging Research German Cancer Research Center(DKFZ)HeidelbergBaden-WürttembergGermany epidemiology and Screening Unit Reference Centre for Epidemiology and Cancer PreventionUniversity Hospital Cittàdella Salute e della ScienzaTurinPiedmontItaly Epidemiological Cancer Registry Baden-Württemberg German Cancer Research Center(DKFZ)HeidelbergBaden-WürttembergGermany division of Preventive Oncology German Cancer Research Center(DKFZ)and National Center for Tumor Diseases(NCT)HeidelbergBaden-WürttembergGermany German Cancer Consortium(DKTK) German Cancer Research Center(DKFZ)HeidelbergBaden-WürttembergGermany

Preprint:https://***/10.1101/*** trials,cohort and modeling studies have consistently demonstrated a major impact of screening endoscopies on reducing colorectal cancer(CRC)inci-dence and mortality[1].Over time,CRC mortality starts to be lower in those who underwent screening compared to those who did not due to earlier detection of prevalent.

关键词： prevention endoscopy impact CRC

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