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Exploring novel experimental treatments for major neurodegenerative disorders

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Neuroprotection 2023年第2期1卷 81-83页

作者： Xunming Ji piotr walczak Johannes Boltze Beijing Institute of Brain Disorders Capital Medical UniversityBeijingChina Department of Diagnostic Radiology and Nuclear Medicine Center for Advanced Imaging ResearchUniversity of MarylandBaltimoreMarylandUSA School of Life Sciences University of WarwickCoventryUK

Acute and chronic neurodegenerative disorders such as ischemic stroke or Alzheimer's disease(AD)impose a major burden on patients,their relatives,caregivers,and health care systems in general.The socioeconomic impact of neurodegenerative disorders is anticipated to escalate due to a globally ageing population and the increasing prevalence of sedentary lifestyle and inappropriate dietary habits.On the contrary.

关键词： Alzheimer's disease amyotrophic lateral sclerosis cell therapy cytoprotection extracellular vesicles neurodegeneration stroke

3D printing-based frugal manufacturing of glass pipettes for minimally invasive delivery of therapeutics to the brain

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Neuroprotection 2023年第1期1卷 58-65页

作者： Guanda Qiao David Gulisashvili Anna Jablonska Guiling Zhao Miroslaw Janowski piotr walczak Yajie Liang Department of Diagnostic Radiology and Nuclear Medicine University of Maryland School of MedicineBaltimoreMarylandUSA Laboratory of Molecular Cardiology Department of PhysiologyCenter for Biomedical Engineering and TechnologyUniversity of Maryland School of MedicineBaltimoreMarylandUSA

Objective:Intracerebral delivery of agents in liquid form is usually achieved through commercially available and durable metal needles.However,their size and texture may contribute to mechanical brain damage.Glass pipettes with a thin tip may significantly reduce injection-associated brain damage but require access to prohibitively expensive programmable pipette pullers.This study is to remove the economic barrier to the application of minimally invasive delivery of therapeutics to the brain,such as chemical compounds,viral vectors,and cells.Methods:We took advantage of the rapid development of free educational online resources and emerging low-cost 3D printers by designing an affordable pipette puller(APP)to remove the cost obstacle.Results:We showed that our APP could produce glass pipettes with a sharp tip opening down to 20μm or less,which is sufficiently thin for the delivery of therapeutics into the brain.A pipeline from pipette pulling to brain injection using low-cost and open-source equipment was established to facilitate the application of the APP.Conclusion:In the spirit of frugal science,our device may democratize glass pipette-puling and substantially promote the application of minimally invasive and precisely controlled delivery of therapeutics to the brain for finding more effective therapies of brain diseases.

关键词： 3D-printable brain injection frugal science glass pipette pulling

Join us on an amazing journey towards next-generation treatments for CNS disorders:Launch of Neuroprotection,a new high-quality journal in translational neuroscience

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Neuroprotection 2023年第1期1卷 5-8页

作者： Xunming Ji piotr walczak Heleen M.M.van Beusekom Ana I.Casas Andrew Clarkson Tracy Farr Jukka Jolkkonen Yajie Liang Michel M.Modo Paulo H.Rosado-de-Castro Karsten Ruscher Yan-Jiang Wang Haitao Wu Marietta Zille Shen Li Johannes Boltze Beijing Institute of Brain Disorders Capital Medical UniversityBeijingChina Department of Diagnostic Radiology and Nuclear Medicine Center for Advanced Imaging ResearchUniversity of MarylandBaltimoreMarylandUSA Department of Cardiology Erasmus MC RotterdamUniversity Medical Center RotterdamRotterdamThe Netherlands Department of Neurology Center for Translational Neuro‐and Behavioral Sciences(C‐TNBS)University Clinics EssenEssenGermany Department of Anatomy Brain Health Research Center and Brain Research New ZealandDunedinNew Zealand Medical School Queen's Medical CentreUniversity of NottinghamNottinghamUK A.I.Virtanen Institute for Molecular Sciences University of Eastern FinlandKuopioFinland McGowan Institute for Regenerative Medicine University of PittsburghPittsburghPennsylvaniaUSA Department of Radiology University of PittsburghPittsburghPennsylvaniaUSA Department of Bioengineering University of PittsburghPittsburghPennsylvaniaUSA Department of Anatomy and Department of Radiology School of MedicineInstitute of Biomedical SciencesFederal University of Rio de JaneiroRio de JaneiroBrazil Laboratory for Experimental Brain Research University of LundLundSweden Department of Neurology Daping HospitalCenter for Clinical NeuroscienceChongqingChina Department of Neurobiology Beijing Institute of Basic Medical SciencesBeijingChina Department of Pharmaceutical Sciences Division of Pharmacology and ToxicologyUniversity of ViennaViennaAustria Department of Neurology and Psychiatry Beijing Shijitan HospitalCapital Medical UniversityBeijingChina School of Life Sciences University of WarwickCoventryUK

Translational medicine in neurodegenerative and neurovascular diseases is approaching a breakthrough point.Recent years have led to dramatic progress in both experimental and clinical research.Based on a much better and continuously increasing understanding of disease mechanisms,progression and pathophysiology,new therapies with an improved translational potential to protect tissue either against acute or chronic degeneration and even approaches potentially capable of repairing damaged brain tissue are emerging.

关键词： cytoprotection nervous system repair neurodegeneration neuroprotection neurovasculardiseases translational research

Preserving cognitive function in patients with Alzheimer's disease:The Alzheimer's disease neuroprotection research initiative(ADNRI)

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Neuroprotection 2023年第2期1卷 84-98页

作者： Jie Liu Heleen van Beusekom Xian-Le Bu Gong Chen Paulo Henrique Rosado de Castro Xiaochun Chen Xiaowei Chen Andrew N.Clarkson Tracy D.Farr Yuhong Fu Jianping Jia Jukka Jolkkonen Woojin Scott Kim Paula Korhonen Shen Li Yajie Liang Guang-Hui Liu Guiyou Liu Yu-Hui Liu Tarja Malm Xiaobo Mao Joaquim Miguel Oliveira Mike M.Modo Pedro Ramos-Cabrer Karsten Ruscher Weihong Song Jun Wang Xuanyue Wang Yun Wang Haitao Wu Lize Xiong Yi Yang Keqiang Ye Jin-Tai Yu Xin-Fu Zhou Marietta Zille Colin L.Masters piotr walczak Boltze Johannes Xunming Ji Yan-Jiang Wang Department of Neurology Daping HospitalThird Military Medical UniversityChongqingChina Chongqing Key Laboratory of Ageing and Brain Diseases ChongqingChina Division of Experimental Cardiology Department of CardiologyErasmus MCUniversity Medical CenterRotterdamThe Netherlands Institute of Brain and Intelligence Third Military Medical UniversityChongqingChina Guangdong-HongKong-Macao Institute of CNS Regeneration(GHMICR) Jinan UniversityGuangzhouGuangdongChina Institute of Biomedical Sciences Federal University of Rio de JaneiroRio de JaneiroRio de JaneiroBrazil Fujian Key Laboratory of Molecular Neurology Department of Neurology and GeriatricsFujian Institute of GeriatricsFujian Medical University Union HospitalInstitute of NeuroscienceFujian Medical UniversityFuzhouFujianChina Guangyang Bay Laboratory Chongqing Institute for Brain and IntelligenceChongqingChina Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghaiChina Department of Anatomy Brain Health Research Centre and Brain Research New ZealandUniversity of OtagoDunedinNew Zealand School of Life Sciences University of NottinghamNottinghamUK Brain and Mind Centre&School of Medical Sciences The University of SydneySydneyNew South WalesAustralia Innovation Center for Neurological Disorders and Department of Neurology Xuanwu HospitalNational Clinical Research Center for Geriatric DiseasesCapital Medical UniversityBeijingChina A.I.Virtanen Institute for Molecular Sciences University of Eastern FinlandKuopioFinland Department of Neurology and Psychiatry Beijing Shijitan HospitalCapital Medical UniversityBeijingChina Department of Diagnostic Radiology and Nuclear Medicine University of Maryland School of MedicineBaltimoreMarylandUSA University of Chinese Academy of Sciences BeijingChina State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Beijing Institute of Brain Disorders Laboratory of Brain DisordersMinistry of Sci

The global trend toward aging populations has resulted in an increase in the occurrence of Alzheimer's disease(AD)and associated socioeconomic burdens.Abnormal metabolism of amyloid-β(Aβ)has been proposed as a significant pathomechanism in AD,supported by results of recent clinical trials using anti-Aβantibodies.Nonetheless,the cognitive benefits of the current treatments are limited.The etiology of AD is multifactorial,encompassing Aβand tau accumulation,neuroinflammation,demyelination,vascular dysfunction,and comorbidities,which collectively lead to widespread neurodegeneration in the brain and cognitive impairment.Hence,solely removing Aβfrom the brain may be insufficient to combat neurodegeneration and preserve cognition.To attain effective treatment for AD,it is necessary to(1)conduct extensive research on various mechanisms that cause neurodegeneration,including advances in neuroimaging techniques for earlier detection and a more precise characterization of molecular events at scales ranging from cellular to the full system level;(2)identify neuroprotective intervention targets against different neurodegeneration mechanisms;and(3)discover novel and optimal combinations of neuroprotective intervention strategies to maintain cognitive function in AD patients.The Alzheimer's Disease Neuroprotection Research Initiative's objective is to facilitate coordinated,multidisciplinary efforts to develop systemic neuroprotective strategies to combat AD.The aim is to achieve mitigation of the full spectrum of pathological processes underlying AD,with the goal of halting or even reversing cognitive decline.

关键词： Alzheimer's disease early intervention neural regeneration neuroprotection systematic perspective

Effects of small molecules on neurogenesis:Neuronal proliferation and differentiation

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Acta Pharmaceutica Sinica B 2024年第1期14卷 20-37页

作者： MichałK Jastrze˛bski piotr Wo´jcik piotr Ste˛pnicki Agnieszka A.Kaczor Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modeling Laboratory Medical University of LublinFaculty of PharmacyLublin PL-20093Poland School of Pharmacy University of Eastern FinlandKuopio FI-70211Finland

Neurons are believed to be non-proliferating cells.However,neuronal stem cells are still present in certain areas of the adult brain,although their proliferation diminishes with age.Just as with other cells,their proliferation and differentiation are modulated by various mechanisms.These mechanisms are foundational to the strategies developed to induce neuronal proliferation and differentiation,with potential therapeutic applications for neurodegenerative diseases.The most common among these diseases are Parkinson's disease and Alzheimer's disease,associated with the formation ofβ-amyloid(Aβ)aggregates which cause a reduction in the number of neurons.Compounds such as LiCl,4-aminothiazoles,Pregnenolone,ACEA,harmine,D2AAK1,methyl 3,4-dihydroxybenzoate,and shikonin may induce neuronal proliferation/differentiation through the activation of pathways:MAPK ERK,PI3K/AKT,NFκB,Wnt,BDNF,and NPAS3.Moreover,combinations of these compounds can potentially transform somatic cells into neurons.This transformation process involves the activation of neuron-specific transcription factors such as NEUROD1,NGN2,ASCL1,and SOX2,which subsequently leads to the transcription of downstream genes,culminating in the transformation of somatic cells into neurons.Neurodegenerative diseases are not the only conditions where inducing neuronal proliferation could be beneficial.Consequently,the impact of pro-proliferative compounds on neurons has also been researched in mouse models of Alzheimer's disease.

关键词： Neurogenesis Proliferation Differentiation Maturation Small-molecules Drug coctail Alzheimer’s disease Parkinson’s disease

Odd-even effects in the structure and properties of aryl-substituted aliphatic self-assembled monolayers

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Nano Research 2024年第5期17卷 4231-4243页

作者： piotr Cyganik Andreas Terfort Michael Zharnikov Jagiellonian University Faculty of PhysicsAstronomy and Applied Computer ScienceSmoluchowski Institute of PhysicsŁojasiewicza 1130-348 KrakówPoland Institut für Anorganische und Analytische Chemie Universität FrankfurtMax-von-Laue-Straße 760438 FrankfurtGermany Applied Physical Chemistry Heidelberg UniversityIm Neuenheimer Feld 25369120 HeidelbergGermany

Self-assembled monolayers(SAMs)represent an important tool in context of nanofabrication and molecular engineering of surfaces and interfaces.The properties of functional SAMs depend not only on the character of the tail groups at the SAM-ambient interface,but are also largely defined by their structure.In its turn,the latter parameter results from a complex interplay of the structural forces and a variety of other factors,including so called odd-even effects,viz.dependence of the SAM structure and properties on the parity of the number(odd or even)of individual building blocks in the backbone of the SAM constituents.The most impressive manifestation of the odd-even effects is the structure of aryl-substituted alkanethiolate SAMs on Au(111)and Ag(111),in which,in spite of the fact that the intermolecular interaction is mostly determined by the aryl part of the monolayers,one observes a pronounced dependence of molecular inclination and,consequently,the packing density of the SAM-forming molecules on the parity of number of methylene units in the alkyl linker.Here we review the properties of the above systems as well as address fundamental reasons behind the odd-even effects,including the existence of a so-called bending potential,which is frequently disregarded in analysis of the structure-building forces.The generality of the odd-even effects in SAMs is additionally supported by the recent data for SAMs on GaAs,scanning tunneling microscopy data for SAMs on Ag(111),and the data for the monolayers with selenolate and carboxyl anchoring groups on Au(111)and Ag(111).The implications of these effects in terms of the control over the packing density and orientation of the tail groups at the SAM-ambient interface,structural perfection,polymorphism,temperature-driven phase transitions,and SAM stability toward such factors as ionizing radiation,exchange reaction,and electrochemical desorption are discussed.These implications place the odd-even effects as an important tool for the design of functional SAMs in context of

关键词： self-assembled monolayers molecular films surface and interface engineering odd-even-effects

Early response of understory vegetation to the mass dieback of Norway spruce in the European lowland temperate forest

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Forest Ecosystems 2024年第2期11卷 214-225页

作者： Jan Marek Matuszkiewicz Andrzej N.Affek piotr Zaniewski Ewa Kołaczkowska Faculty of Geography and Regional Studies University of WarsawPoland Institute of Geography and Spatial Organization Polish Academy of SciencesPoland Institute of Forest Sciences Warsaw University of Life SciencesPoland

Spruce-dominated forests are commonly exposed to disturbances associated with mass occurrences of bark beetles.The dieback of trees triggers many physical and chemical processes in the ecosystem resulting in rapid changes in the vegetation of the lower forest layers.We aimed to determine the response of non-tree understory vegetation to the mass dieback of Norway spruce(Picea abies)in the first years after the disturbance caused by the European spruce bark beetle(Ips typographus)outbreak.Our study area was the Białowieża Biosphere Reserve covering the Polish part of the emblematic Białowieża Forest,in total 597km^(2).The main data source comprised 3,900 phytosociological relevés(combined spring and summer campaigns)collected from 1,300 systematically distributed forest sites in 2016–2018–the peak years of the bark beetle outbreak.We found that the understory responded immediately to mass spruce dieback,with the most pronounced changes observed in the year of the disturbance and the subsequent year.Shade-tolerant forest species declined in the initial years following the mass spruce dieback,while hemicryptophytes,therophytes,light-demanding species associated with non-forest seminatural communities,as well as water-demanding forest species,expanded.Oxalis acetosella,the most common understory species in the Białowieża Forest,showed a distinct fluctuation pattern,with strong short-term expansion right after spruce dieback,followed by a gradual decline over the next 3–4 years to a cover level 5 percentage points lower than before the disturbance.Thus,our study revealed that mass spruce dieback selectively affects individual herb species,and their responses can be directional and non-directional(fluctuation).Furthermore,we demonstrated that the mass dieback of spruce temporarily increases plant species diversity(α-diversity).

关键词： Forest disturbance Bark beetle outbreak Picea abies Ips typographus Response of understory vegetation Herbaceous species Biaowieza Forest

Role of gut-liver axis and glucagon-like peptide-1 receptor agonists in the treatment of metabolic dysfunction-associated fatty liver disease

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World Journal of Gastroenterology 2024年第23期30卷 2964-2980页

作者： Jakub Rochoń piotr Kalinowski Ksenia Szymanek-Majchrzak MichałGrąt Department of General Transplant and Liver SurgeryMedical University of WarsawWarsaw 02-097Poland Department of Medical Microbiology Medical University of WarsawWarsaw 02-004Poland

Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries.MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma.Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis.The mechanisms involved in maintaining gut-liver axis homeostasis are complex.One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gutliver axis functionality.An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis.Moreover,alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis.Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)are a class of drugs developed for the treatment of type 2 diabetes mellitus.They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis.The mechanisms reported to be involved in this effect include an improved regulation of glycemia,reduced lipid synthesis,β-oxidation of free fatty acids,and induction of autophagy in hepatic cells.Recently,multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment.A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD.This review presents the current understanding of the role of the gutliver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.

关键词： Metabolic dysfunction-associated fatty liver disease Metabolic dysfunction-associated steatohepatitis Nonalcoholic fatty liver disease Non-alcoholic steatohepatitis Metabolic syndrome Obesity Gastrointestinal microbiota Glucagon-like peptide-1 Glucagon-like peptide-2 Bariatric surgery

A dual-beam piezo-magneto-elastic wake-induced vibration energy harvesting system for high-performance wind energy harvesting

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Science China(Technological Sciences) 2024年第1期67卷 221-239页

作者： MA XiaoQing ZHANG Hang MARGIELEWICZ Jerzy GĄSKA Damian WOLSZCZAK piotr LITAK Grzegorz ZHOU ShengXi School of Aeronautics Northwestern Polytechnical UniversityXi’an 710072China Research&Development Institute in Shenzhen Northwestern Polytechnical UniversityShenzhen 518057China Faculty of Transport and Aviation Engineering Silesian University of TechnologyKrasińskiego 8Katowice 40-019Poland Department of Automation Lublin University of TechnologyNadbystrzycka 36Lublin 20-618Poland

Wind-induced vibration energy harvesting has a great potential for utilizing wind energy to supply power for low-powered devices.To improve the working performance of energy harvesters effectively,a suitable structural design is crucial.This paper proposes a dual-beam piezo-magneto-elastic wake-induced vibration energy harvesting system to enhance the functional performance of aeroelastic energy harvesters in environments with variable wind speeds.The system contains two piezoelectric beams coupled by magnets(forming upstream and downstream energy harvesters),and each beam is attached with a foam cylinder.A corresponding dynamic model is provided,and output characteristics are obtained at different wind speeds.Results and experimental verification indicate that both upstream and downstream energy harvesters can realize efficient energy harvesting.When the wind speed exceeds a certain critical value,the amplitudes of the system’s displacement and voltage are high.The wind speed threshold value is approximately 1.25 m/s.When the wind speed and magnet spacing are 10.2 m/s and 20 mm,respectively,the output power of the system reaches 4.9×10^(−4)W.Moreover,the wind speed threshold value of the proposed system can be adjusted by an equivalent nonlinear restoring force.

关键词： dual-beam structure piezoelectric energy harvester theoretical model nonlinear dynamics