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An optimized derivative of an endogenous CXCR4 antagonist prevents atopic dermatitis and airway inflammation

Acta Pharmaceutica Sinica B 2021年第9期11卷 2694-2708页

作者： Mirja Harms Monica MWHabib Simona Nemska Antonella Nicolò Andrea Gilg Nico Preising Pandian Sokkar Sara Carmignani martina raasholm Gilbert Weidinger Gönül Kizilsavas Manfred Wagner Ludger Ständker Ashraf HAbadi Hassan Jumaa Frank Kirchhoff Nelly Frossard Elsa Sanchez-Garcia Jan Münch Institute of Molecular Virology Ulm University Medical CenterUlm 89081Germany Department of Pharmaceutical Chemistry Faculty of Pharmacy and BiotechnologyGerman University in CairoCairo 11835Egypt Laboratoire D'Innovation Thérapeutique UMR7200 CNRS/Universitéde Strasbourg and LabEx MEDALISFacultéde PharmacieIllkirch 67412France Institute of Immunology Ulm University Medical CenterUlm 89081Germany Core Facility Functional Peptidomics Ulm University Medical CenterUlm 89081Germany Center of Medical Biotechnology University of Duisburg-EssenDuisburg 47057Germany Max-Planck-Institute for Coal Research Düsseldorf 45470Germany Faculty of Allied Health Sciences Chettinad Hospital and Research InstituteChettinad Academy of Research and EducationKelambakkam 603103India Max-Planck-Institut für Molekulare Physiologie Dortmund 44227Germany Institute of Biochemistry and Molecular Biology Ulm UniversityUlm 89081Germany Max Planck Institute for Polymer Research Mainz 55128Germany

Aberrant CXCR4/CXCL12 signaling is involved in many pathophysiological processes such as cancer and inflammatory diseases.A natural fragment of serum albumin,named EPI-X4,has previously been identified as endogenous peptide antagonist and inverse agonist of CXCR4 and is a promising compound for the development of improved analogues for the therapy of CXCR4-associated *** generate optimized EPI-X4 derivatives we here performed molecular docking analysis to identify key interaction motifs of EPI-X4/*** rational drug design allowed to increase the anti-CXCR4 activity of *** EPI-X4 derivative JM#21 bound CXCR4 and suppressed CXCR4-tropic HIV-1 infection more efficiently than the clinically approved small molecule CXCR4 antagonist ***-X4 JM#21 did not exert toxic effects in zebrafish embryos and suppressed allergen-induced infiltration of eosinophils and other immune cells into the airways of animals in an asthma mouse ***,topical administration of the optimized EPI-X4 derivative efficiently prevented inflammation of the skin in a mouse model of atopic ***,rationally designed EPIX4 JM#21 is a novel potent antagonist of CXCR4 and the first CXCR4 inhibitor with therapeutic efficacy in atopic *** clinical development of this new class of CXCR4 antagonists for the therapy of atopic dermatitis,asthma and other CXCR4-associated diseases is highly warranted.

关键词： CXCR4 antagonist Asthma Allergy Inflammation Atopic dermatitis

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Role of copper in central nervous system physiology and pathology

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Neural Regeneration Research 2025年第4期20卷 1058-1068页

作者： martina Locatelli Cinthia Farina Institute of Experimental Neurology Division of NeuroscienceIstituto di Ricovero e Cura a Carattere Scientifico(IRCCS)San Raffaele Scientific InstituteMilanItaly Vita-Salute San Raffaele University MilanItaly

Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous *** copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple *** review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper ***,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.

关键词： astrocytes central nervous system copper cuprizone multiple sclerosis myelin neurodegenerative disorders

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Targeting Epac2 and GluA3-containing AMPARs:a novel therapeutic strategy for Alzheimer's disease

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Neural Regeneration Research 2025年第11期20卷 3223-3224页

作者： Tong Zhang martina Schmidt Department of Molecular Pharmacology Groningen Research Institute of PharmacyUniversity of GroningenGroningenThe Netherlands School of Pharmacy Tianjin Medical UniversityTianjinChina

Alzheimer's disease(AD)is a neurodegenerative disease that manifests progressive decline in memory and *** the early stage of AD,memory retrieval is impaired preceding memory acquisition and consolidation(Roy et al.,2016).Prior to the onset of symptoms,pathological amyloid-β(Aβ)plagues and tau protein tangles accumulate in extracellular and intracellular spaces,respectively,leading to *** these hallmark pathologies,Aβ is proposed to be the primary etiology by triggering a cascade of pathogenic events,including neuroinflammation,oxidative stress,tau hyperphosphorylation,synaptic/neuronal dysfunction,and neuronal death(Zhang et al.,2023b).

关键词： Alzheimer impaired Aβ

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Wilson's disease in two siblings from Ecuador:Two case reports

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World Journal of Clinical Cases 2025年第3期13卷 50-60页

作者： Enrique Carrera Jonathan Alvarado martina Astudillo Galo Pillajo Department of Gastroenterology and Hepatology Hospital de Especialidades Eugenio EspejoQuito 170136PichinchaEcuador Faculty of Medicine Pontificia Universidad Catolica del EcuadorQuito 170143PichinchaEcuador Department of Radiology Hospital de Especialidades Eugenio EspejoQuito 170136PichinchaEcuador

BACKGROUND Wilson's disease(WD)is a rare metabolic disorder of copper accumulation in organs such as liver,brain,and *** and treatments are challenging in settings,where advanced diagnostic tests are unavailable,copper chelating agents are frequently scarce,healthcare professionals lack disease awareness,and medical follow-ups are *** diagnoses and treatments help prevent complications,improve patients’quality of life,and ensure a normal life *** clinical presentations and outcomes of WD can vary within a single *** SUMMARY We present the cases of two siblings(19 and 27 years)from a consanguineous family in rural Ecuador,diagnosed as having WD during a family *** male patient,diagnosed at age 19 after his brother’s death from acute liver failure,presented with compensated cirrhosis,neurological symptoms,and bilateral Kayser-Fleischer *** developed progressive neurological deterioration during an irregular treatment with D-penicillamine due to medication *** condition improved upon switching to trientine tetrahydrochloride,and his neurological symptoms improved over an 8-year period of *** female patient,diagnosed at age 10,exhibited only biochemical *** treatment history was similar;however,she remained asymptomatic without disease progression over the same follow-up *** discuss the potential influence of epigenetic mechanisms and modifier genes on the various phenotypes,emphasizing the need for research in these areas to optimize therapeutic *** Our patients’medical histories show how early diagnosis and treatment can prevent disease progression;and,how suboptimal treatments impact disease outcomes.

关键词： Wilson disease Kayser-Fleischer rings Copper chelator D-penicillamine Trientine tetrahydrochloride Case report

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Promising new treatment targets in patients with fibrosing lung disorders

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World Journal of Clinical Cases 2014年第11期2卷 668-675页

作者： martina Sterclova martina Vasakova Department of Respiratory Medicine Thomayer Hospital and 1st Medical Faculty of Charles University Prague 14000 Czech Republic

The processes of lung fibrogenesis and fibrotic healing are common to a number of conditions with different etiologies. The lungs are the only affected organ in some cases, whereas in others, several organ systems are involved. Therapeutic options can be discussed from various perspectives. In this review, we address the localization of therapeutic targets with regard to cell compartments, including secreted ligands, cell surface, plasma membrane-cytosol interplay, cytosol and nucleus. Complex approach using stem cell therapy is also discussed. As the prognosis of patients with these disorders remains grim, treatment combinations targeting different molecules within the cell should sometimes be considered. It is reasonable to assume that blocking specific pathways will more likely lead to disease stabilization, while stem cell-based treatments could potentially restore lung architecture. Gene therapy could be a candidate for preventive care in families with proven specific gene polymorphisms and documented familial lung fibrosis. Chronobiology, that takes into account effect of circadian rhythm on cell biology, has demonstrated that timed drug administration can improve treatment outcomes. However, the specificrecommendations for optimal approaches are still under debate. A multifaceted approach to interstitial lung disorders, including cooperation between those doing basic research and clinical doctors as well as tailoring research and treatment strategies toward(until now) unmet medical needs, could improve our understanding of the diseases and, above all, provide benefits for our patients.

关键词： Interstitial lung disease Treatment Idiopathic pulmonary fibrosis Connective tissue disease Cell compartments Signaling molecules Signal transducers Transcription factors

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Rheology of Poly(vinyl butyral)Solution Containing Fumed Silica in Correlation with Electrospinning

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Chinese Journal of Polymer Science 2018年第6期36卷 742-748页

作者： Petra Peer martina Polaskova Pavol Suly Institute of Hydrodynamics of the Czech Academy of Sciences Pod Patankou 5166 12 Prague 6Czech Republic Centre of Polymer Systems Tomas Bata University in Zlintrida Tomase Bati 5678760 O1 ZlinCzech Republic Department of Polymer Engineering Faculty of TechnologyTomas Bata University in ZlinVavreckova 27576001 ZlinCzech Republic

The rheological properties in question are influenced by many factors, ranging from the characteristics of the given polymer or solvent to the flowing conditions. The primary focus of this study is to analyse the rheological behaviour of poly（vinyl butyral）—Mowital B 60 H—（PVB） solutions dissolved in methanol and a blend of these with fumed silica nanoparticles. The preparation of the nanofibrous web and the quality of nanofibres were correlated with the rheology of the polymer solution. It was discerned that drastically intensifying shear viscosity and the elasticity of the solution exerted a negligible effect on the formation of fibres, a finding which has rarely been discussed in the literature. The morphologies and structures of the PVB/silica nanofibrous membranes were investigated by scanning electron microscopy, thermogravimetric analysis and Fourier transform infrared spectroscopy.

关键词： Electrospinning Nanofibres Poly(vinyl butyral) Fumed silica Rheology

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The combined influence of grain size distribution and dislocation density on hardness of interstitial free steel

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Journal of Materials Science & Technology 2020年第10期42卷 35-43页

作者： Wei Li martina Vittorietti Geurt Jongbloed Jilt Sietsma Department of Materials Science and Engineering Delft University of TechnologyMekelweg 22628 CDDelftthe Netherlands Department of Applied Mathematics Delft University of TechnologyVan Mourik Broekmanweg 62628 XEDelftthe Netherlands Materials Innovation Institute(M2i) Van der Burghweg 1.2628 CSDelftthe Netherlands

Understanding the relationship between microstructure features and mechanical properties is of great significance for the improvement and specific adjustment of steel *** relationship between mean grain size and yield strength is established by the well-known Hall-Petch *** due to the complexity of the grain configuration within materials,considering only the mean value is unlikely to give a complete representation of the mechanical *** classical Taylor equation is often used to account for the effect of dislocation density,but not thoroughly tested in combination with grain size *** the present study,systematic heat treatment routes and cold rolling followed by annealing are designed for interstitial free(IF)steel to achieve ferritic microstructures that not only vary in mean grain size,but also in grain size distribution and in dislocation density,a combination that is rarely studied in the *** microscopy is applied to determine the grain size *** dislocation density is determined through XRD *** hardness is analyzed on its relation with the mean grain size,as well as with the grain size distribution and the dislocation *** the help of the variable selection tool LASSO,it is shown that dislocation density,mean grain size and kurtosis of grain size distribution are the three features which most strongly affect hardness of IF steel.

关键词： Interstitial free steel Hardness Grain size distribution Dislocation density

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A strategy for uncovering germline variants altering anti-tumor CD8 T cell response

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Journal of Genetics and Genomics 2023年第5期50卷 353-361页

作者： Vijay Kumar Ulaganathan martina H.Vasileva Klinik fur Dermatologie&Allergology Universitatsmedizin GottingenGottingen 37075Germany Institut fuir Multiple Sklerose Forschung NeuroimmunologieUniversitatsmedizin GottingenGottingen 37075Germany University of Lorraine NGERE UnitFaculte de Medecine9 Avenue de La Foret de HayeVandoeuvre-les-Nancy 54505France

Among many factors known to alter the outcomes of T cell receptor(TCR)-induced proximal signaling,the role of human germline variants in dictating the individuality of the anti-tumor CD8 T cell response has remained challenging to ***,we describe a convenient strategy for molecular and functional characterization of phosphotyrosine-altering non-synonymous single nucleotide variations(pTyr-SNVs)that directly impact TCR-induced proximal phosphotyrosine motif-based signaling *** devise an experimental co-cultivation set-up comprising a C57BL/6 mouse-derived metastatic melanoma cell line engineered to constitutively present ovalbumin(OVA)antigens and retrovirally engineered syngeneic major histocompatibility complex(MHC)Class I restricted OVA TCR-transgenic CD8 T cells(OT-I).Using the synthetic version of pTyr-SNV rs1178800678-G/T-encoding integrin alpha 4(ITGA4)p.S1027I variant as a prototype,we show that under identical TCR stimulation conditions,genetically determined membrane-proximal immunoreceptor tyrosin activation motif(ITAM)results in increased tyrosine phosphorylation of 70 kDa zeta-chain-associated protein(ZAP70)and the levels of cytotoxic effector molecule granzyme B(GZMB),which in turn result in enhanced cytotoxic activity against metastatic melanoma cell *** strategy paves the way for rapid molecular and functional characterization of anti-tumor immune response-linked germline pTyr-SNVs so as to improve our understanding of the genetic basis of individual-to-individual differences in anti-tumor CD8 T cell response.

关键词： Non-synonymous single nucleotide variants(nsSNVs) Membrane-proximal phosphotyrosine signalling motifs Phosphotyrosine-altering non-synonymous single nucleotide variants(pTyr-SNVs) Immunoreceptor tyrosine activation motif(ITAM) CD8 T cells Melanoma B16-F10

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Facing different predators： adaptiveness of behavioral and morphological traits under predation

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Current Zoology 2017年第3期63卷 249-257页

作者： martina HEYNEN Nils BUNNEFELD Jost BORCHERDING Department of General Ecology and Limnology Ecological Field Station Grietherbusch Zoological Institute of the University of Cologne Rees Germany Department of Chemistry Umea University Umea Sweden Department of Ecology and Environmental Sciences Umea University Umea Sweden Department of Life Sciences Biological and Environmental Sciences School of Natural Sciences University of Stirling Stirling UK

Predation is thought to be one of the main structuring forces in animal communities. However, se- lective predation is often measured on isolated traits in response to a single predatory species, but only rarely are selective forces on several traits quantified or even compared between different predators naturally occurring in the same system. In the present study, we therefore measured be- havioral and morphological traits in young-of-the-year Eurasian perch Perca fluviatilis and com- pared their selective values in response to the 2 most common predators, adult perch and pike Esox lucius. Using mixed effects models and model averaging to analyze our data, we quantified and compared the selectivity of the 2 predators on the different morphological and behavioral traits. We found that selection on the behavioral traits was higher than on morphological traits and perch predators preyed overall more selectively than pike predators. Pike tended to positively se- lect shallow bodied and nonvigilant individuals （i.e. individuals not performing predator inspec- tion）. In contrast, perch predators selected mainly for bolder juvenile perch （i.e. individuals spend- ing more time in the open, more active）, which was most important. Our results are to the best of our knowledge the first that analyzed behavioral and morphological adaptations of juvenile perch facing 2 different predation strategies. We found that relative specific predation intensity for the di- vergent traits differed between the predators, providing some additional ideas why juvenile perch display such a high degree of phenotypic plasticity.

关键词： behavior morphological variation Perca f/uviatilis perch pike predator-specific defenses selective predation

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Particle penetration in fiber filters

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Particuology 2018年第5期16卷 70-79页

作者： Norbert Riefler martina Ulrich Marko Morshaiuser Udo Fritsching Process Engineering Institute of Materials ScienceBadgasteiner Strasse 328359BremenGermany Lydall Gutsche GmbH & Co.KG Hermann-Muth-Str.836039FuldaGermany Particles and Process Engineering University of BremenBibliothekstrasse 128359BremenGermany

Particle separation from gases is an important unit operation in manifold industrial applications,such as those conducted in environmental *** analysis of particle penetration and separation in fiber filters,standard dust particles (Al2O3)were loaded in the gas flow of a filter test facility and deposited within new and uncharged fiber *** loaded filters were analyzed by micro-computer tomography and scanning electron ***-dimensional tomograms of the samples show an exponential decay of the penetration depth of the *** dependency is confirmed by simulations conducted using the discrete element method coupled with computational fluid dynamics within unloaded and loaded fiber *** processes of particle separation at the fibers as well as the filtration efficiency and time-dependent filtering process are derived from the *** particle clustering in the filter medium and partial filter clogging are thus identified.

关键词： Particle filtration Fiber filter X-ray microtomography Computational fluid dynamics-discrete element method coupling High-fidelity simulation Transient mesh morphing

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