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3篇 您的检索式:作者名="Jan Tuckermann"
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1Inhibition of Cdk5 increases osteoblast differentiation and bone mass and improves fracture healing显示文摘Identification of regulators of osteoblastogenesis that can be pharmacologically targeted is a major goal in combating osteoporosis,a common disease of the elderly population. Here, unbiased kinome RNAi screening in primary murine osteoblasts identified cyclin-dependent kinase 5(Cdk5) as a suppressor of osteoblast differentiation in both murine and human preosteoblastic cells. Cdk5 knockdown by si RNA, genetic deletion using the Cre-lox P system, or inhibition with the small molecule roscovitine enhanced osteoblastogenesis in vitro. Roscovitine treatment significantly enhanced bone mass by increasing osteoblastogenesis and improved fracture healing in mice. Mechanistically, downregulation of Cdk5 expression increased Erk phosphorylation, resulting in enhanced osteoblast-specific gene expression. Notably, simultaneous Cdk5 and Erk depletion abrogated the osteoblastogenesis conferred by Cdk5 depletion alone, suggesting that Cdk5 regulates osteoblast differentiation through MAPK pathway modulation. We conclude that Cdk5 is a potential therapeutic target to treat osteoporosis and improve fracture healing.Mubashir Ahmad Benjamin Thilo Krüger Torsten Kroll Sabine Vettorazzi Ann-Kristin Dorn Florian Mengele Sooyeon Lee Sayantan Nandi Dilay Yilmaz Miriam Stolz Naveen Kumar Tangudu David Carro Vázquez Johanna Pachmayr Ion Cristian Cirstea Maja Vujic Spasic Aspasia Ploubidou Anita Ignatius Jan Tuckermann 2022Bone Research2022,10,3:2
2Could a phase model help to improve translational animal research?显示文摘Background:Animal models are widely applied in medical research for different purposes.In particular,results from translational experiments may be used for subsequent clinical development.However,transferability of these findings to the human organism is controversial.Among other factors,this may be traced back to a lack of clear differentiation of the evidence(explorative vs.confirmatory)provided by such experimental results.In general,inferential statistics(i.e.p values)should not be interpreted in as confirmatory unless crucial methodological requirements are met.Methods:Therefore,we propose a phase model which reflects the well-established process of clinical research,and we discuss its potential to improve decision making in translational research.The model aims to clarify the reliability of results derived from animal models.Results:The phase model proposes subdividing translational,pre-clinical research into pilot,exploration,and confirmation phases.Experiments for which there is no valid estimation of the expected effect size are designated as pilot studies.Based on these data,experiments in subsequent phases may be planned using both appropriate design and statistical methods.Conclusion:Separating the entire process of translational animal research into three phases could contribute to improved transparency of the evidence derived from such experiments.Benjamin Mayer Jan Tuckermann Rainer Muche 2022Animal Models and Experimental Medicine2022,5,6:1
3Cell:新分子或可有效清除肝脏和血液中的脂肪显示文摘肥胖和糖尿病持续上升代表着我们的社会所面临的一个重大的负担。脂肪肝和动脉粥样硬化是这些代谢疾病常见的后果,但是开发一种高效且又安全的能够逆转肥胖、胰岛素抵抗性、脂肪肝和动脉粥样硬化的药物仍然是全球头等的一项重大的科学挑战。Brian Finan Christoffer Clemmensen Zhimeng Zhu Kerstin Stemmer Karine Gauthier Luisa M uuml ller Meri De Angelis Kristin Moreth Frauke Neff Diego Perez-Tilve Katrin Fischer Dominik Lutter Miguel A. S aacute nchez-Garrido Peng Liu Jan Tuckermann Mohsen Malehmir Marc E. Healy Achim Weber Mathias Heikenwalder Martin Jastroch Maximilian Kleinert Sigrid Jall Sara Brandt Fr eacute d eacute ric Flamant Karl-Werner Schramm Heike Biebermann Yvonne D ouml ring Christian Weber Kirk M. Habegger Michaela Keuper Vasily Gelfanov Fa Liu Josef K ouml hrle Jan Rozman Helmut Fuchs Valerie Gailus-Durner Martin Hrabě de Angelis Susanna M. Hofmann Bin Yang Matthias H. Tsch ouml p Richard DiMarchi Timo D. M uuml ller 2017现代生物医学进展2017,17,4:0
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