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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal j.Goldschmidt-Clermont Aisha Khan George jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera Alexander j.P.Goldschmidt Damien D.Pearse W.Dalton Dietrich Allan D.Levi james D.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

Assessing effect of interaction between the FTO A/T polymorphism(rs9939609)and physical activity on obesity-related traits

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journal of Sport and Health Science 2018年第4期7卷 459-464页

作者： Agata Leonska-Duniec Zbigniew jastrzebski Aleksandra Zarebska Agnieszka Maciejewska krzysztof Ficek Pawel Cieszczyk Faculty of Physical Culture and Health Promotion Centre for Human Structural and Functional ResearchUniversity of SzczecinSzczecin 71-065Poland Faculty of Tourism and Recreation Gdansk University of Physical Education and SportGdansk 80-336Poland Faculty of Physical Education Gdansk University of Physical Education and SportGdansk 80-336Poland Galen Medical Center Bierun 43-150Poland E-mail address： leonska.duniec@***

Background： The first described obesity-susceptibility gene was the fat mass and obesity-associated （FTO） gene. However, knowledge about FTO＇s potential modifying effect on changes in body weight achieved through a training program is still limited. We decided to study the association between the FTO A/T polymorphism （rs9939609） and obesity-related traits. Additionally, we investigated whether body mass and body composition, as well as metabolic variables observed in physically active participants, are modulated by the FTO polymorphism. Methods： A group of 201 young Polish women were recruited for the study. The genotype distribution was examined in participants measured for selected changes before and after the completion of a 12-week training program. Results： Our results confirm the association between the common FTO A/T polymorphism and increased body mass index （BMI）. Subjects with AA and AT genotypes had higher BMI during the entire study period compared with the TT genotype. Although parameters such as BMI, basal metabolism rate, tissue independence, fat mass percentage, fat mass, fat-free mass, total body water, high-density lipoprotein, and glucose changed significantly during the training program, none of the examined parameters changed significantly across the FTO genotypes （genotype × training interaction）. Conclusion： We confirm an association between the FTO A/T polymorphism and increased BMI; this polymorphism is therefore a candidate for influencing obesity and other disease-related phenotypes. Although the gene x physical activity interaction was not shown, we want to point out that promoting physical activity is an important approach to controlling the increasing obesity epidemic.2018 Published by Elsevier B.V. on behalf of Shanghai University of Sport. This is an open access article under the CC BY-NC-ND license. （http：//***/licenses/by-nc-nd/4.0/）.

关键词： Exercise FTO gene Gene x physical activity interaction Obesity-related traits Polish women Sport genetics

Microwave absorption properties of carbonyl iron-based paint coatings for military applications

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Defence Technology（防务技术） 2023年第4期22卷 1-9页

作者： Wojciech Przybyl Adam januszko Norbert Radek Marcin Szczepaniak krzysztof A.Bogdanowicz Ireneusz Plebankiewicz Bogusława Szczodrowska Robert Mazurczuk Military Institute of Engineer Technology ul.Obornicka 136Wrocław50-961Poland Kielce University of Technology Faculty of Mechatronics and Mechanical EngineeringAl.1000-lecia P.P.7Kielce25-314Poland

The paper explores the possibilities of using carbonyl iron in the form of a powder for the manufacture of radar-absorbing paints-reducing the radar signature of the objects that they *** attenuation values in the range of 4-18 GHz for various coating thicknesses,ranging from 0.5 to 2.00 mm with 0.5 mm increment,and for different absorber content-75%and 80%,as well as the use of two different binders in the form of epoxy resins with hardeners,were *** the frequency of 18 GHz and a 1.5 mm thick coating with a 75%absorber content,Epidian 112 resin and Saduramid 10/50 hardener used as a binder,and the maximum attenuation level obtained equalled 20.2 d B at 16 ***,the absorber particle size ranging from 3 to 4μm and its higher mass content resulted in achieving the reflection loss above-12 d B in the entire 8-12.5 GHz range for layers between 1-and 1.5 mm *** qualitative assessment of the tested samples in the context of camouflage in the radar range was also performed,using statistical analysis.

关键词： Radar Attenuation Carbonyl iron Coating Camouflage

Developmental Toxicity in Mice Following Paternal Exposure to Di-N-Butyl-Phthalate (DBP)

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Biomedical and Environmental Sciences 2011年第5期24卷 569-578页

作者： Malgorzata M.DOBRZY SKA Ewa j.TYRKIEL krzysztof A.PACHOCKI Department of Radiation Protection and Radiobiology National Institute of Public Health-National Institute of Hygiene00-791 WarsawPoland Department of Environmental Toxicology National Institute of Public Health-National Institute of Hygiene00-791 WarsawPoland

Objective The aim of the present study was to investigate the effects of paternal Di‐N‐butyl‐phthalate （DBP） exposure pre‐ and postnatally on F1 generation offspring,and prenatally on F2 generation *** Male mice were exposed to either 500 mg/kg or 2 000 mg/kg of DBP for 8 weeks,and mated with non‐exposed ***‐quarters of the females were sacrificed a day prior to parturition,and examined for the number of living and dead implantations,and incidence of gross *** from the remaining females were assessed for developmental markers,growth parameters,as well as sperm quantity and *** There were no changes in the fertility of parents and in intrauterine development of the *** of DBP‐exposed males demonstrated growth‐*** paternal exposure to 500 mg/kg bw of DBP,there were almost twice the number of males than females born in the F1 generation.F1 generation females had a 2.5‐day delay in vaginal *** exposure to 2 000 mg/kg bw of DBP increased the incidence of sperm head malformations in F1 generation males;however,there were no changes in the fertility and viability of foetuses in the F2 *** Paternal DBP exposure may disturb the sex ratio of the offspring,delay female sexual maturation,and deteriorate the sperm quality of F1 generation males.

关键词： Di‐n‐butyl phthalate Paternal exposure Pre‐ and postnatal effects Male‐mediated developmental toxicity

Numerical modeling of blast-induced rock fragmentation in deep mining with 3D and 2D FEM method approaches

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journal of Rock Mechanics and Geotechnical Engineering 2024年第11期16卷 4532-4553页

作者： MichałKucewicz MazurkiewiczŁukasz PawełBaranowski jerzy Małachowski krzysztof Fuławka Piotr Mertuszka Marcin Szumny Military University of Technology Faculty of Mechanical EngineeringInstitute of Mechanics and Computational Engineering2 Gen.S.Kaliskiego Street00-908WarsawPoland KGHM CUPRUM Ltd. Research and Development Center2-8 Sikorskiego Street53-659WrocławPoland

To optimize the excavation of rock using underground blasting techniques,a reliable and simplified approach for modeling rock fragmentation is *** paper presents a multistep experimentalnumerical methodology for simplifying the three-dimensional(3D)to two-dimensional(2D)quasiplane-strain problem and reducing computational costs by more than ***,in situ tests were conducted involving single-hole and free-face blasting of a dolomite rock mass in a 1050-m-deep *** results were validated by laser *** craters were then compared with four analytical models to calculate the radius of the crushing ***,a full 3D model for single-hole blasting was prepared and validated by simulating the crack length and the radius of the crushing *** on the stable crack propagation zones observed in the 3D model and experiments,a 2D model was *** properties of the high explosive(HE)were slightly reduced to match the shape and number of radial cracks and crushing zone radius between the 3D and 2D *** final methodology was used to reproduce various cut-hole blasting scenarios and observe the effects of residual cracks in the rock mass on further *** presence of preexisting cracks was found to be crucial for fragmentation,particularly when the borehole was situated near a free rock ***,an optimization study was performed to determine the possibility of losing rock continuity at different positions within the well in relation to the free rock face.

关键词： Dolomite rock Two-dimensional(2D)rock modeling Rock fragmentation Cut-hole blasting

Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

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Neural Regeneration Research 2025年第10期20卷 2913-2914页

作者： William j.Flerlage Mark L.Dell’Acqua Brian M.Cox Fereshteh S.Nugent Uniformed Services University of the Health Sciences Department of Pharmacology and Molecular TherapeuticsBethesdaMDUSA Department of Pharmacology University of Colorado School of MedicineAnschutz Medical CampusAuroraCOUSA

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).Diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).

关键词： function supporting

Kinetic studies of gold recovery from dilute aqueous solutions using Fe^(2+) chloride ions

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Transactions of Nonferrous Metals Society of China 2015年第6期25卷 2027-2036页

作者： Marek WOjNICKI krzysztof FITZNER Magdalena LUTY-BLOCHO Faculty of Non-Ferrous Metals AGH University of Science and Technology

The kinetics of Au3＋ chloride complex ions reduction using Fe2＋ chloride ions was investigated by stopped-flow method. The influence of initial concentrations of Au3＋ chloride ions, Fe2＋ ions, chloride ions, neutral salt （NaC104）, pH of the solution and temperature was investigated. Activation energy was determined to be 42.36 kj/mol. Moreover, the kinetic equation was postulated. Obtained solid phase was analyzed using SEM techniques. Particles size varies in the range from 0.5 to 5 gm. It was shown that gold can be removed from the solution by the reduction ofAu3＋ chloride ions and filtration of precipitant.

关键词： gold recovery reduction recycling electronic waste

Sustained activation of P2X7 induces MMP-2- evoked cleavage and functional purinoceptor inhibition

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journal of Molecular Cell Biology 2018年第3期10卷 229-242页

作者： Christopher N. j. Young Natalia Chira justyna Róg Rasha Al-Khalidi Magalie Benard Ludovic Galas Philippe Chan David Vaudry krzysztof Zablocki Dariusz C. Górecki School of Allied Health Sciences Faculty of Health and Life Sciences De Montfort University Leicester LE1 5RR UK Molecular Medicine Laboratory Institute of Biomedical and Biomolecular Sciences School of Pharmacy and Biomedical Sciences University of Portsmouth Portsmouth PO1 2DT UK Laboratory of Cellular Metabolism Department of Biochemistry Nencki Institute of Experimental Biology of the Polish Academy of Sciences Pasteur Str. 02- 093 Warsaw Poland PRIMACEN Cell Imaging Platform of Normandy Inserm IBiSA and PISSARO Proteomic Platform Institute for Research and Innovation in Biomedicine University of Rouen 76821 Mont-Saint-Aignan France

P2X7 purinoceptor promotes survival or cytotoxicity depending on extraceUular adenosine triphosphate （ATP） stimulus Intensity controlling its ion channel or P2X7-dependent large pore （LP） functions. Mechanisms governing this operational divergence and functional idiosyncrasy are ill-understood. We have discovered a feedback loop where sustained activation of P2X7 triggers release of active matrix metalloproteinase 2 （MMP-2）, which halts ion channel and LP responses via the MMP-2-dependent receptor cleavage. This mechanism operates in cells as diverse as macrophages, dystrophic myoblasts, P2X7-transfected HEK293, and human tumour cells. Given that serum-born MMP-2 activity also blocked receptor functions, P2X7 responses in vivo may decrease in organs with permeable capillaries. Therefore, this mechanism represents an Important fine-tuning of P2X7 functions, reliant on both cell-autonomous and extraneous factors. Indeed, it allowed evasion from the ATP-induced cvtotoxicity in macrophages and human cancer ceils with high P2X7 expression levels. Finally, we demonstrate that P2X7 ablation eliminated getatinase activity in inflamed dystrophic muscles in vivo. Thus, P2X7 antagonists could be used as an alternative to highly toxic MMP inhibitors in treatments of inflammatory diseases and cancers.

关键词： P2X7 MMP-2 DMD macrophage β-dystroglycan CD44 cancer

A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn j.W.So Konstantin Feinberg Marina Manoraj jenny Cheung jennifer Zhang Kaveh Mirmoeini jPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus