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Immunosuppression for in vivo research： state-of-the-at protocols and experimental approaches

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Cellular & Molecular Immunology 2017年第2期14卷 146-179页

作者： Rita Diehl Fabienne Ferrara Claudia Müller Antje Y Dreyer Damian D McLeod Stephan Fricke johannes boltze Fraunhofer-lnstitute for Cell Therapy and Immunology Leipzig 04103 Germany Institute of Vegetative Physiology Charite University Medicine and Center for Cardiovascular Research Berlin 10115 Germany University of Newcastle Callaghan NSW 2308 Australia Fraunhofer Research Institution for Marine Biotechnolegy and Institute for Medical and Marine Bietechnolegy University of LObeck LObeck 23562 Germany These authors contributed equally to this work

Almost every experimental treatment strategy using non-autologous cell, tissue or organ transplantation is tested in small and large animal models before clinical translation. Because these strategies require immunosuppression in most cases, immunosuppressive protocols are a key element in transplantation experiments. However, standard immunosuppressive protocols are often applied without detailed knowledge regarding their efficacy within the particular experimental setting and in the chosen model species. Optimization of such protocols is pertinent to the translation of experimental results to human patients and thus warrants further investigation. This review summarizes current knowledge regarding immunosuppressive drug classes as well as their dosages and application regimens with consideration of species-specific drug metabolization and side effects. It also summarizes contemporary knowledge of novel immunomodulatory strategies, such as the use of mesenchymal stem cells or antibodies. Thus, this review is intended to serve as a state-of-the-art compendium for researchers to refine applied experimental immunosuppression and immunomodulation strategies to enhance the predictive value of preclinical transplantation studies.

关键词： animal models immunomodulation immunosuppression transplantation translational research

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 *** 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 *** the contrary.

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

Mononuclear cell therapy of neonatal hypoxic-ischemic encephalopathy in preclinical versus clinical studies:A systematic analysis of therapeutic efficacy and study design

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Neuroprotection 2023年第2期1卷 143-159页

作者： Alexander M.Scrutton Francesca Ollis johannes boltze School of Life Sciences University of WarwickCoventryUK Neurobiology Division MRC Laboratory of Molecular BiologyUniversity of CambridgeCambridgeUK

Background:Hypoxic-ischemic encephalopathy(HIE)is a devastating condition affecting around 8.5 in 1000 newborns *** hypothermia(TH)can reduce mortality and,to a limited extent,disability after ***,there is a need for new and effective treatment ***-based treatments using mononuclear cells(MNCs),which can be sourced from umbilical cord blood,are currently being *** promising preclinical results,there is currently no strong indicator for the clinical efficacy of the *** analysis aimed to provide potential explanations for this ***:A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis *** and clinical studies were retrieved from PubMed,Web of Science,Scopus,and *** using a predefined search strategy.A total of 17 preclinical and 7 clinical studies were *** analyzed overall MNC efficacy in preclinical trials,the methodological quality of preclinical trials,and relevant design features in preclinical versus clinical ***:There was evidence for MNC therapeutic efficacy in preclinical models of *** methodological quality of preclinical studies was not optimal,and statistical design quality was particularly ***,methodological quality was above the standard in other *** were significant differences in preclinical versus clinical study design including the use of TH as a baseline treatment(only in clinical studies)and much higher MNC doses being applied in preclinical ***:Based on the analyzed data,it is unlikely that therapeutic effect size is massively overestimated in preclinical *** is more plausible that the many design differences between preclinical and clinical trials are responsible for the so far lacking proof of the efficacy of MNC treatments in *** preclinical and clinical research is required

关键词： cell therapy hypoxic-ischemic encephalopathy mononuclear cells translational research treatment efficacy

Activation of neurogenesis in the hippocampus is a novel therapeutic target for Alzheimer's disease

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Neuroprotection 2023年第2期1卷 139-142页

作者： Akihiko Taguchi Yuka Okinaka Akiko Takeda Takayuki Okamoto johannes boltze Carsten Claussen Sheraz Gul Department of Regenerative Medicine Research Foundation for Biomedical Research and Innovation at KobeHyogoJapan Department of Pharmacology Faculty of MedicineShimane UniversityIzumoShimaneJapan School of Life Sciences University of WarwickCoventryUK Fraunhofer Institute for Translational Medicine and Pharmacology ITMP HamburgGermany Fraunhofer Cluster of Excellence for Immune-Mediated Diseases CIMD HamburgGermany

The pathologies associated with age-related brain dysfunction,including Alzheimer's disease(AD),Parkinson's disease,Lewy body dementia,and vascular dementia,often share similarities across multiple diseases.1 While various factors,such as amyloidβ,Tau protein,α-synuclein,chronic inflammation,and impaired cerebral microcirculation have been suggested as potential therapeutic targets,addressing a single factor is unlikely to be sufficient in preventing or treating age-related brain *** from these observations.

关键词： therapeutic Alzheimer impaired

Application of dynamic image analysis to the optical characterisation of fibrous bulk material

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Particuology 2024年第7期90卷 51-60页

作者： johannes Lunewski Eberhard Schmidt Institute of Particle Technology University of WuppertalGermany

Dynamic image analysis provides an automated evaluation method to determine the size and shape of multiple particles. This method represents a common application for ordinary bulk material. The latest draft of ISO 13322–2:2021 describes the state of the art, but lacks instructions for handling fibrous bulk material. Interlocking fibres complicate the measurement conditions and require a disentanglement of fibrous samples during a pre-dispersion step. A further error source includes the fibre orientation inside the measurement zone of the device. If the thresholding algorithm fails to differentiate between the fibre projection area and the background, a subsequent image optimisation solves the problem. This article addresses the mentioned problems by analysing cotton cellulose and polyacrylonitrile fibres. Besides the execution of a pre-dispersion step, the experiments compare the discrepancies between dry and wet dispersion. Here, the software packages PAQXOS and ImageJ perform the image evaluation. In this case, the wet dispersion setup with a subsequent image evaluation by ImageJ provides comprehensible results.

关键词： Bootstrap method Dynamic image analysis Fibre diameter Fibre length distribution Natural fibres Synthetic fibres

Training muscles to keep the aging brain fit

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Journal of Sport and Health Science 2024年第6期13卷 761-763页

作者： johannes Burtscher Martin Burtscher Department of Biomedical Sciences University of LausanneLausanne CH-1005Switzerland Institute of Sport Sciences University of LausanneLausanne CH-1015Switzerland Department of Sport Science University of InnsbruckInnsbruck A-6020Austria

*** and exercise Aging is associated with the decline of cellular,tissue,and systemic functions and is characterized by at least 7 highly interdependent molecular pillars of aging1(Fig.1).Besides compromised genetic functions(telomer shortening and epigenetic dysregulation),metabolic efficiency(impaired mitochondrial functions and nutrient sensing),and cellular stress responses *** disruption of normal protein regulation(proteostasis)in combination with impaired cellular waste clearance leads to the accumulation of macromolecular damage(and in some cases to specific protein aggregation pathologies,like in Alzheimer’s dementia brains).

关键词： impaired aging aggregation

Unveiling the culprit:the fusobacterium lineage that populates colorectal cancer

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2349-2350页

作者： johannes Betge Matthias P.Ebert Department of Medicine Ⅱ Medical Faculty MannheimHeidelberg UniversityMannheimGermany Junior Clinical Cooperation Unit Translational Gastrointestinal Oncology and Preclinical Models German Cancer Research Center(DKFZ)HeidelbergGermany DKFZ Hector Cancer Institute at University Medical Center MannheimGermany MMPU Microbiota Drug Metabolism and Cancer Therapy European Molecular Biology LaboratoryHeidelbergGermany

In a recent study published in Nature,Zepeda-Rivera et al.1 discovered that one distinct clade of Fusobacterium nucleatum animalis(Fna)dominates the colorectal cancer(CRC)tumor *** work unravels a more precise understanding of a major bacterial species associated with CRC progression,thereby establishing a new focus for future studies,which may aid to develop improved microbiome-based diagnostics and treatments(Fig.1).

关键词： colorectal al. cancer

Wear dependent virtual flow rate sensor for progressing cavity pumps with deformable stator

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Petroleum Science 2024年第2期21卷 1346-1353页

作者： Jens Müller Sebastian Leonow johannes Schulz Christian Hansen Martin Monnigmann Ruhr-Universitat Bochum Universit atsstraûe 150Bochum44801Germany SEEPEX GmbH Scharnh olzstraûe 344Bottrop46240Germany

This contribution presents a novel wear dependent virtual flow rate sensor for single stage single lobe progressing cavity pumps. We study the wear-induced material loss of the pump components and the impact of this material loss on the volumetric efficiency. The results are combined with an established backflow model to implement a backflow calculation procedure that is adaptive to wear. We use a laboratory test setup with a highly abrasive fluid and operate a pump from new to worn condition to validate our approach. The obtained measurement data show that the presented virtual sensor is capable of calculating the flow rate of a pump being subject to wear during its regular operation.

关键词： Backflow Progressing cavity pump Virtual sensor Wear

The emerging role of tranexamic acid and its principal target,plasminogen,in skeletal health

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2869-2884页

作者： Weixin Xie Antonia Donat Shan Jiang Anke Baranowsky johannes Keller Department of Trauma and Orthopedic Surgery University Medical Center Hamburg-EppendorfHamburg 20246Germany

The worldwide burden of skeletal diseases such as osteoporosis,degenerative joint disease and impaired fracture healing is steadily *** acid(TXA),a plasminogen inhibitor and anti-fibrinolytic agent,is used to reduce bleeding with high effectiveness and safety in major surgical *** its widespread clinical application,the effects of TXA beyond anti-fibrinolysis have been noticed and prompted renewed interest in its *** clinical trials have characterized the effects of TXA on reducing postoperative infection rates and regulating immune responses in patients undergoing ***,several animal studies suggest potential therapeutic effects of TXA on skeletal diseases such as osteoporosis and fracture *** a direct effect of TXA on the differentiation and function of bone cells in vitro was shown,few mechanisms of action have been ***,we summarize recent findings of the effects of TXA on skeletal diseases and discuss the underlying plasminogen-dependent and-independent mechanisms related to bone metabolism and the immune *** furthermore discuss potential novel indications for TXA application as a treatment strategy for skeletal diseases.

关键词： Tranexamic acid Osteoporosis Osteoarthritis Fracture healing Bone metabolism Inflammation Plasminogen Fibrinolysis