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Neural Regeneration Research 2020年第10期15卷 1844-1845页

作者： krisztián Pajer Tamás Bellák Antal Nógrádi Department of Anatomy Histology and Embryology Faculty of Medicine University of Szeged

Pathophysiology of spinal cord injury:Injury to the spinal cord results in loss of gray and white matter i.e.,it produces a segmental spinal cord lesion and,as a consequence leads to a fatal loss of motor,sensory and autonomic functions.spinal cord injuries in humans and other mammals are not followed by the replacement of lost neurons and oligodendrocytes and regrowth of injured axons,instead they lead to permanent,fatal and incurable functional deficits.The primary physical injury is followed by a cascade of tissue-decaying events,called secondary injury,which leads to ischemia,vascular disruption,neuroinflammation,excitotoxicity,demyelination and death of neurons and glial cells(silva et al.,2014;Figure 1A).The direct mechanical disruption of the vasculature results in the increased permeability of the blood-spinal cord barrier.Due to the leakiness of blood-spinal cord barrier and production of cytokines by activated microglia,a number of various immune cells(T lymphocytes,neutrophils and monocytes)invade the injury site.The macrophages generate a set of inflammatory cytokines such as tumor necrosis factor-α,interleukin(IL)-1α,IL-1β,and IL-6,which may further augment the secondary events(Ahuja et al.,2017).In addition,a number of other disruptive processes contribute to the heterogeneous and time-sensitive pathophysiology of spinal cord injury.

关键词： mutual Figure injuries

Restoration of Motor Function through Delayed Intraspinal Delivery of Human IL-10-Encoding Nucleoside-Modified mRNA after spinal Cord Injury

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Research 2023年第4期2023卷 131-144页

作者： LászlóGál Tamás Bellák Annamária Marton Zoltán Fekécs Drew Weissman Dénes Török Rachana Biju Csaba Vizler Rebeka kristóf Mitchell B.Beattie Paulo J.C.Lin Norbert Pardi Antal Nógrádi krisztián Pajer Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary National Biotechnology Laboratory Institute of GeneticsBiological Research CentreSzegedHungary Institute of Biochemistry Biological Research CentreSzegedHungary Department of Medicine University of PennsylvaniaPhiladelphiaPA19104USA Acuitas Therapeutics VancouverBCV6T 1Z3Canada

Efficient in vivo delivery of anti-inflammatory proteins to modulate the microenvironment of an injured spinal cord and promote neuroprotection and functional recovery is a great challenge.Nucleoside-modified messenger RNA(mRNA)has become a promising new modality that can be utilized for the safe and efficient delivery of therapeutic proteins.Here,we used lipid nanoparticle(LNP)-encapsulated human interleukin-10(hIL-10)-encoding nucleoside-modified mRNA to induce neuroprotection and functional recovery following rat spinal cord contusion injury.Intralesional administration of hIL-10 mRNA-LNP to rats led to a remarkable reduction of the microglia/macrophage reaction in the injured spinal segment and induced significant functional recovery compared to controls.Furthermore,hIL-10 mRNA treatment induced increased expression in tissue inhibitor of matrix metalloproteinase 1 and ciliary neurotrophic factor levels in the affected spinal segment indicating a time-delayed secondary effect of IL-105 d after injection.Our results suggest that treatment with nucleoside-modified mRNAs encoding neuroprotective factors is an effective strategy for spinal cord injury repair.

关键词： protective Restoration utilized

Public Health Control Measures for the Co-circulation of Influenza and sARs-CoV-2 During Influenza seasons

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China CDC weekly 2022年第2期4卷 22-26页

作者： John s tam Yuelong shu Department of Applied Biology and Chemical Technology Hong Kong Polytechnic UniversityHong KongChina Asia Pacific Alliance for the Control of Influenza(APACI) South MelbourneVICAustralia school of Public Health(shenzhen) Sun Yat-sen UniversityGuangzhouGuangdongChina

sEAsONAL INFLUENZA IN THE MIDsT OF COVID-19 The World Health Organization(WHO)named the disease caused by severe acute respiratory syndrome coronavirus 2(sARs-CoV-2)as coronavirus disease 2019(COVID-19)and declared the outbreak a Public Health Emergency of International Concern(PHEIC)on January 30,2020 and a pandemic on March 11,2020.Globally,there have been 239,437,517 confirmed cases of COVID-19 reported to WHO,including 4,879,235(2.1%)deaths as of October 15,2021(1).The COVID-19 pandemic continues to cause an unparalleled impact on global public health security and economic well-being in the context of previous influenza pandemics as well as other emerging infectious diseases in history(2).As the epidemiology,clinical presentations,and control measures for sARs-CoV-2 and influenza share many features,there is a need to develop strategies to address additional challenges arising in the continued surveillance,prevention,and clinical management of influenza in conjunction with COVID-19 pandemic responses.

关键词： epidemiology prevention acute

On the relationship between the activity at point of interests and road traffic

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Communications in Transportation Research

Communications in Transportation Research 2023年第1期3卷 150-160页

作者： Mátékolat tamás Tettamanti tamásBécsi Domokos Esztergár-kiss Department of Control for Transportation and Vehicle systems Faculty of Transportation Eng.and Vehicle Eng.Budapest University of Technology and EconomicsBudapest1111PestHungary systems and Control Laboratory Institute for Computer Science and Control of the Eötvös Lorand Research NetworkBudapest1053PestHungary Department of Transport Technology and Economics Faculty of Transportation Eng.and Vehicle Eng.Budapest University of Technology and EconomicsBudapest1111PestHungary

The estimation and analysis of road traffic represent the preliminary steps towards satisfying the current needs for smooth,safe,and green transportation.Therefore,effective traffic monitoring is an essential topic alongside the planning of sustainable transportation systems and the development of new traffic management concepts.In contrast to classical traffic detection solutions,this study investigates the correlation between travelers'social activities and road traffic.The s's primary goal is to investigate the presence of the relationship between social activity and road traffic,which might allow an infrastructure-independent traffic monitoring technique as well.People's general activities at Point of Interest(POI)locations(measured as occupancy parameter)are correlated with traffic data so that,finally,proper proxys can be defined for link-level average traffic speed estimation.The method is tested and evaluated using real-world traffic and POI occupancy data from Budapest(District XI.).The results of the correlation investigation justify an indirect relationship between activity at POIs and road traffic,which holds promise for future practical applicability.

关键词： Road traffic estimation Google popular times(GPT) Point of interest(POI) POI occupancy Genetic algorithm(GA)

Tinnitus characteristics and associated variables on Tinnitus Handicap Inventory among a Hungarian population

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Journal of Otology 2022年第3期17卷 136-139页

作者： Panayiota Mavrogeni stefani Maihoub László tamás András Molnár Tóth Ilona Health service Clinical Medical Institute Gorgey Artúr tér 8.H-1212BudapestHungary Department of Otolaryngology and Head and Neck surgery Semmelweis UniversitySzigony u.36H-1083BudapestHungary

Background:Tinnitus is a sound precepted without an external sound stimulus.Its background can be categorised into primary and secondary cases.The secondary cases include pathologies of the external,middle and inner ear.Tinnitus can be objective or subjective;the latter can only identified by the sufferer.Previous research results have shown that tinnitus significantly affects the quality of life and daily functioning.Objectives:To analyse the impact of tinnitus on the daily functioning and the possible influence of demographical data and tinnitus duration on it.Methods:630 patients(265 males and 365 females,25e85 years of age)suffering from primary tinnitus were enrolled.In the Hungarian language,these patients completed the Tinnitus Handicap Inventory(THI)questionnaire and underwent a complete otorhinolaryngological examination.IBM sPss V24 software was used for data processing;correlation tests,the Mann-Whitney U and kruskal-Wallis nonparametric tests were used.Results:According to the THI questionnaires outcomes,most patients(62.5%)were presented with a mild handicap.Based on statistical analysis,no significant correlation was observed between the total THI points and the age of the patients,along with the duration and localisation of the symptoms.However,the total THI scores of male and female patients significantly differed,indicating higher THI values in the female group(p=0.00052*).Conclusions:The tinnitus severity was not affected by the duration,localisation of the symptoms and age but by gender,indicating higher values in the case of females.

关键词： Tinnitus Tinnitus handicap inventory Tinnitus characteristics Daily functioning Hungarian population

Pathological mechanisms and therapeutic strategies for Alzheimer's disease

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Neural Regeneration Research 2022年第3期17卷 543-549页

作者： Yaojun Ju kin Yip tam Faculty of Health sciences University of MacaoAvenida de UniversidadeTaipaMacao Special Adiministrative RegionChina

Alzheimer's disease is a rather complex neurodegenerative disease,which is attributed to a combination of multiple factors.Among the many pathological pathways,synaptic dysfunctions,such as synapses loss and deficits in synaptic plasticity,were thought to be strongly associated with cognitive decline.The deficiencies in various sorts of neurotransmissions are responsible for the multifarious neurodegenerative symptoms in Alzheimer's disease,for example,the cholinergic and glutamatergic deficits for cognitive decline,the excitatory and inhibitory neurotransmission dyshomeostasis for synaptic plasticity deficits and epileptiform symptoms,and the monoamine neurotransmission for neuropsychiatric symptoms.Amyloid cascade hypothesis is the most popular pathological theory to explain Alzheimer's disease pathogenesis and attracts considerable attention.Multiple lines of genetic and pathological evidence support the predominant role of amyloid beta in Alzheimer's disease pathology.Neurofibrillary tangles assembled by microtubule-associated protein tau are other important histopathological characteristics in Alzheimer's disease brains.Cascade of tau toxicity was proved to lead to neuron damage,neuroinflammation and oxidative stress in brain.Ageing is the main risk factor of neurodegenerative diseases,and is associated with inflammation,oxidative stress,reduced metabolism,endocrine insufficiencies and organ failures.These aging related risk factors were also proved to be some of the risk factors contributing to Alzheimer's disease.In Alzheimer's disease drug development,many good therapeutic strategies have been investigated in clinical evaluations.However,complex mechanism of Alzheimer's disease and the interplay among different pathological factors call for the come out of allpowerful therapies with multiple curing functions.This review seeks to summarize some of the representative treatments targeting different pathological pathways currently under clinical evaluations.Multi-target therapies as an emerging strategy for A

关键词： Alzheimer's disease pathological pathways drug development multiple pathologies

Activation of human fibroblast-like synoviocytes by uric acid crystals in rheumatoid arthritis

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Cellular & Molecular Immunology 2011年第6期8卷 469-478页

作者： Da P Chen Chun k Wong Lai s tam Edmund k Li Christopher Wk Lam Department of Chemical Pathology The Chinese University of Hong KongPrince of Wales HospitalShatinNTHong KongChina Department of Clinical Laboratory Children’s Hospital of Chongqing Medical UniversityChongqingChina Department of Medicine and Therapeutics The Chinese University of Hong KongPrince of Wales HospitalNgan Shing StreetShatinNTHong KongChina Macao Institute for Applied Research in Medicine and Health Macao University of Science and TechnologyAvenida Wai LongTaipaMacaoChina

Hyperuricemia-mediated uric acid crystal formation may cause joint inflammation and provoke the destruction of joints through the activation of inflammasome-mediated innate immune responses.However,the immunopathological effects and underlying intracellular regulatory mechanisms of uric acid crystal-mediated activation of fibroblast-like synoviocytes(FLs)in rheumatoid arthritis(RA)have not been elucidated.Therefore,we investigated the in vitro effects of monosodium urate crystals,alone or in combination with the inflammatory cytokines tumor-necrosis factor(TNF)-a or interleukin(IL)-1b,on the activation of human FLs from RA patients and normal control subjects and the underlying intracellular signaling mechanisms of treatment with these crystals.Monosodium urate crystals were able to significantly increase the release of the inflammatory cytokine IL-6,the chemokine CXCL8 and the matrix metalloproteinase(MMP)-1 from both normal and RA-FLs(all P,0.05).Moreover,the additive or synergistic effect on the release of IL-6,CXCL8 and MMP-1 from both normal and RA-FLs was observed following the combined treatment with monosodium urate crystals and TNF-a or IL-1b.Further experiments showed that the release of the measured inflammatory cytokine,chemokine and MMP-1 stimulated by monosodium urate crystals were differentially regulated by the intracellular activation of extracellular signal-regulated kinase and c-Jun N-terminal kinase pathways but not the p38 mitogen-activated protein kinase pathway.Our results therefore provide a new insight into the uric acid crystal-activated immunopathological mechanisms mediated by distinct intracellular signal transduction pathways leading to joint inflammation in RA.

关键词： cytokines fibroblast-like synoviocytes rheumatoid arthritis signal transduction uric acid

A simple human cell model for TAU trafficking and tauopathy-related TAU pathology

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Neural Regeneration Research 2022年第4期17卷 770-772页

作者： Michael bell Hans Zempel Institute of Human Genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCenter for Molecular Medicine Cologne(CMMC)University of CologneCologneGermany

The microtubule(MT)-associated protein TAU is highly abundant in the axon of human brain neurons,where it binds to and stabilizes MT filaments.Thereby,TAU regulates the dynamic(dis)assembly of MT strands and is involved in a wide range of neuronal functions.In Alzheimer's disease(AD)and other tauopathies,TAU is missorted into the somatodendritic compartment.TAU missorting is accompanied by(or leads to)abnormal TAU phosphorylation,MT destabilization,and loss of dendritic spines and mitochondria,eventually resulting in TAU aggregation,neuronal dysfunction and cell death(Arendt et al.,2016).strikingly,the mechanisms of TAU sorting,and the detrimental cascade upon its failure,are still not fully understood.

关键词： tau sorting eventually

The shanghai Cooperation Organization on Turkey’s Energy Agenda

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Asian Journal of Middle Eastern and Islamic studies 2019年第1期13卷 50-64,I0004页

作者： tamás kozma Antall József knowledge Centre BudapestHungary Doctoral school of Earth sciences University of PécsPécsHungary

Turkey’s energy policy has attracted a growing scholarly interest.In line with this tendency,this article aims at the assessment of Turkey’s energy relations with the shanghai Cooperation Organization(sCO).As the sCO has appeared more frequently in Turkish foreign policy discourse in the recent years,it can be considered a relevant direction where Turkey’s active energy diplomacy can be assessed.Provided that Turkey’s energy aspirations are predominantly assessed from a Western point of view,the uniqueness of this article is that it combines the study of Turkey’s advancing Eastern relations and its energy policy endeavours.A central argument in this article is about the existing number of energy connections established between Turkey and the member states,observers and dialogue partners of sCO,which overwhelmingly operate at the bilateral level,while the energy framework of the sCO is yet to be filled with multilateral meaning for Turkey.

关键词： Energy policy natural gas shanghai Cooperation Organization Turkey

Managing type 2 diabetes:targeting a microbial enzyme as a novel treatment option

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signal Transduction and Targeted Therapy 2024年第1期9卷 3-5页

作者： Anikó keller-Pintér tamás korcsmáros Tibor Vellai Department of Biochemistry Albert Szent-Györgyi Medical SchoolUniversity of SzegedSzeged6720Hungary Department of Metabolism Digestion and ReproductionImperial College LondonLondonW120NNUK Quadram Institute Bioscience Norwich Research ParkNorwichNR47UQUK Department of Genetics Eötvös Loránd University(ELTE)Budapest1117Hungary Hungarian Research Network HUN-REN-ELTE Genetics Research Group Budapest1117Hungary

In a recent science article,Wang and colleagues showed that the dipeptidyl peptidase 4(DPP4)enzyme produced by the gut microbiota can interfere with the effect of host glucagon-like peptide-1(GLP-1)involved in stimulating insulin secretion,and the specific inhibitor of microbial DPP4(mDPP4),combined with clinical inhibitors of host DPP4 isoenzymes,further promotes blood glucose homeostasis.1 These results point out why certain patients respond inadequately to an antidiabetic medication.

关键词： homeostasis stimulating clinical