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The bumpy road of purinergic inhibitors to clinical application in immune-mediated diseases

Neural Regeneration Research 2024年第6期19卷 1206-1211页

作者： Matihias T.wyss Christine Heuer Marina Herwerth Institute of Pharmacology and Toxicology University of Zurich Neuroscience Center zurich (ZNZ) University of Zurich and ETH Zurich 3. Neurology Department University Hospital of Zurich

Purinergic signaling plays important roles throughout the body in the regulation of organ functions during and following the disruption of homeostasis. This is also reflected by the widespread expression of two families of purinergic receptors(P1 and P2) with numerous subtypes. In the last few decades, there has been increasing evidence that purinergic signaling plays an important role in the regulation of immune functions. Mainly, signals mediated by P2 receptors have been shown to contribute to immune system-mediated pathologies. Thus, interference with P2 receptors may be a promising strategy for the modulation of immune responses. Although only a few clinical studies have been conducted in isolated entities with limited success, preclinical work suggests that the use of P2 receptor inhibitors may bear some promise in various autoimmune diseases. Despite the association of P2 receptors with several disorders from this field, the use of P2 receptor antagonists in clinical therapy is still very scarce. In this narrative review, we briefly review the involvement of the purinergic system in immunological responses and clinical studies on the effect of purinergic inhibition on autoimmune processes. We then open the aperture a bit and show some preclinical studies demonstrating a potential effect of purinergic blockade on autoimmune events. Using suramin, a non-specific purinergic inhibitor, as an example, we further show that off-target effects could be responsible for observed effects in immunological settings, which may have interesting implications. Overall, we believe that it is worthwhile to further investigate this hitherto underexplored area.

关键词： autoimmune diseases neurological disorders purinergic system P2 receptor inhibitors suramin

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Liver transplantation for malignant liver tumors

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iLIVER 2022年第1期1卷 3-11页

作者： Richard X.Sousa Da Silva Beat Muellhaupt Philipp Dutkowski Pierre-Alain Clavien Department of Surgery and Transplantation Swiss Hepato-Pancreato-Biliary(HPB)and Transplant CenterUniversity Hospital ZurichRaemistrasse 1008091 ZurichSwitzerland wyss zurich ETH ZurichUniversity of ZurichWeinbergstrasse 358006 ZurichSwitzerland Department of Gastroenterology and Hepatology University Hospital ZurichRaemistrasse 1008091 ZurichSwitzerland

Liver transplantation is a highly effective treatment not only for acute or chronic liver failure but also for primary liver cancer such as hepatocellular carcinoma,perihilar cholangiocarcinoma,intrahepatic cholangiocarcinoma,and metastatic tumors such as from neuroendocrine or colorectal liver *** success strongly relies on strict adherence to stringent selection criteria,which lead to excellent outcomes,while previously regarded as contraindication for liver *** impressive results are,however,mostly achieved with a combination of pretreatment strategies and convincing control of the tumor growth prior to transplantation,as well as minimizing long-term *** this emergence of oncologic liver transplantation,we expect an increasing need of grafts,and therefore included in this report strategies to improve the number of available grafts by maximizing liver utilization *** machine liver perfusion approaches may play in this respect an important role.

关键词： Liver transplantation Selection criteria Malignant tumor Machine perfusion Tumor recurrence

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Axon degeneration:new actor in an old play

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Neural Regeneration Research 2023年第3期18卷 547-548页

作者： Marina Herwerth Matthias T.wyss Institute of Pharmacology and Toxicology University of ZurichNeuroscience Center ZurichUniversity and ETH ZurichZürichSwitzerland Institute of Neuronal Cell Biology Department of NeurologyTechnische Universität MünchenMunichGermany

After an insult of white matter tracts,*** the spinal cord or optic nerve,axons react in general by the activation of a tightly regulated self-destruction *** so-called axon degeneration cascade can be triggered by various causes,including injury,toxins,and genetic defects,and is a shared pathway in many different neurological diseases(Coleman and Hoke,2020).Axonal degeneration is thought to be responsible for disease progression and accumulation of disability across many neurological *** hallmark of early axonal injury is the appearance of local spheroid formations along the axon,often referred to as a“pearl-on-string”pattern or axonal beading or *** this striking shape change has been observed after various types of injury,such as mechanical,chemical,or inflammatory stimuli,we know little about its exact mechanism and its immediate impact on axonal *** this perspective,we would like to contrast the classical calcium-dependent form of axonal degeneration with a recently described form of a calcium-independent mechanism underlying axonal beading.

关键词： degeneration swelling injury

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颈髓MR波谱成像在慢性脊髓损伤中的应用

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国际医学放射学杂志 2019年第3期 363-363页

作者：景瑞 P.O.wyss E.Huber A.Curt S.Kollias P.Freund A.Henning Institute for Biomedical Engineering University and ETH Zurich

摘要目的探讨颈髓MR波谱成像在研究慢性脊髓损伤(SCI)代谢改变中的作用。材料与方法应用单立体像素短回旋光谱前瞻性研究2016—2017年期间健康志愿者与上颈

关键词：慢性脊髓损伤波谱成像 MR

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