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Signal Transduction and Targeted Therapy 2021年第8期6卷 2257-2258页

作者： Sabrina Ehnert Tina Histing andreas k.nussler Department of Trauma and Reconstructive Surgery Eberhard karls University Tubingen Siegfried Weller Research InstituteBG Trauma Center TubingenTubingenGermany

In a study recently published in Nature,Shen and colleagues characterized a peri-arteriolar niche in the bone marrow with highly proliferative,short-lived,leptin receptor-and osteolectin(Oln)positive stromal cells,which improved bone regeneration and supported bacterial clearance after *** proving that maintenance of these cells critically required mechanical stimulation,which in turn was affected by age,1 the authors identified possible therapeutic targets for bone healing and regeneration.

关键词： stimulation healing clearance

DNA origami-based nano-hunter enriches low-abundance point mutations by targeting wild-type gene segments

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Chinese Chemical Letters 2022年第4期33卷 2052-2056页

作者： Longjie Li kejun Dong Xinyu Wang Meizhou Zhang Jun Li andreas knussler Xianjin Xiao Hongbo Wang Yuzhou Wu School of Life Science and Technology Wuhan Polytechnic UniversityWuhan 430023China Hubei key Laboratory of Bioinorganic Chemistry and Materia Medica Hubei Engineering Research Center for Biomaterials and Medical Protective MaterialsSchool of Chemistry and Chemical EngineeringHuazhong University of Science and TechnologyWuhan 430074China Department of Obstetrics and Gynecology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Institute of Reproductive Health Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Breast Surgery Second Hospital of Jilin UniversityChangchun 130041China Siegfried Weller Institute for Trauma Research Eberhard-Karls-Universitat TubingenSchnarrenbergstr.95D-72076TubingenGermany

Point mutations can be used as biomarkers to perform diagnosis for diseases. In this study, a nanorobot for low-abundance point mutation enrichment was constructed using DNA origami. The novel design achieved limits of detection of 0.1% and 1% for synthesized DNA samples and clinical gene samples, respectively. Resettability was a key property of this method, which also involved a simpler process, lower cost and shorter detection duration than traditional enrichment methods. This novel DNA nanorobot may enable the detection of tumor markers, potentially facilitating early cancer diagnosis.

关键词： Low-abundance point mutation Cancer diagnosis DNA nano-hunter Enrichment Resettability

Microglia:a promising therapeutic target in spinal cord injury

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Neural Regeneration Research 2025年第2期20卷 454-463页

作者： Xiaowei Zha Guoli Zheng Thomas Skutella karl kiening andreas Unterberg Alexander Younsi Department of Neurosurgery Heidelberg University HospitalHeidelbergGermany Department of Neuroanatomy Institute for Anatomy and Cell BiologyHeidelberg UniversityHeidelbergGermany

Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal *** a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal *** this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor *** a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive *** review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target.

关键词： astrocytes cytokines functional recovery immune regulation M1/M2 activation macrophages microglia neuroinflammation spinal cord injury therapy

Assessment of tobacco heating system 2.4 on osteogenic differentiation of mesenchymal stem cells and primary human osteoblasts compared to conventional cigarettes

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World Journal of Stem Cells 2020年第8期12卷 841-856页

作者： Romina H Aspera-Werz Sabrina Ehnert Monja Müller Sheng Zhu Tao Chen Weidong Weng Johann Jacoby andreas k.nussler Department of Traumatology BG Trauma ClinicSiegfried Weller Institute for Trauma ResearchEberhard Karls Universität TübingenTübingen 72076Germany Department of Traumatology BG Trauma ClinicSiegfried Weller Institute for Trauma ResearchEberhard Karls Universität TübingenTübingen 71076Germany Institute for Clinical Epidemiology and Applied Biometry Eberhard Karls Universität TübingenTübingen 71076Germany

BACkGROUND Cigarette smoking(CS)is the most common method of consuming *** effects on bone integrity,increased incidence of fractures,and delayed fracture healing are all associated with *** 150 of the 6500 molecular species contained in cigarette smoke and identified as toxic compounds are inhaled by CS and,via the bloodstream,reach the skeletal *** technologies designed to develop a reduced-risk alternative for smokers are based on electronic nicotine delivery systems,such as e-cigarettes and tobacco heating systems(THS).THS are designed to heat tobacco instead of burning it,thereby reducing the levels of harmful toxic compounds *** To examine the effects of THS on osteoprogenitor cell viability and function compared to conventional *** Human immortalized mesenchymal stem cells(n=3)and primary human preosteoblasts isolated from cancellous bone samples from BG Unfall klinik Tübingen(n=5)were osteogenically differentiated in vitro with aqueous extracts generated from either the THS 2.4“IQOS”or conventional“Marlboro”cigarettes for up to 21 *** viability was analyzed using resazurin conversion assay(mitochondrial activity)and calcein-AM staining(esterase activity).Osteogenic differentiation and bone cell function were evaluated using alkaline phosphatase(AP)activity,while matrix formation was analyzed through alizarin red *** cilia structure was examined by acetylatedα-tubulin immunofluorescent *** radical production was evaluated with 2’,7’-dichlorofluoresceindiacetate *** Our data clearly show that THS is significantly less toxic to bone cells than CS when analyzed by mitochondrial and esterase activity(P<0.001).No significant differences in cytotoxicity between the diverse flavors of THS were *** effects from THS on bone cell function were observed only at very high,non-physiological *** contrast,extracts from conventional cigarettes significantly reduced the A

关键词： Primary human osteoblast Cigarette smoke Tobacco heating system Mesenchymal stem cells Electronic nicotine delivery systems Bone

Effects of immune cells on mesenchymal stem cells during fracture healing

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World Journal of Stem Cells 2021年第11期13卷 1667-1695页

作者： Sabrina Ehnert Borna Relja katharina Schmidt-Bleek Verena Fischer Anita Ignatius Caren Linnemann Helen Rinderknecht Markus Huber-Lang Miriam kalbitz Tina Histing andreas k.nussler Siegfried Weller Research Institute at the BG Trauma Center Tübingen Department of Trauma and Reconstructive SurgeryUniversity of TübingenTübingen 72076Germany Experimental Radiology Department of Radiology and Nuclear MedicineOttovon-Guericke UniversityMagdeburg 39120Germany Julius Wolff Institute and Berlin Institute of Health Center of Regenerative Therapies Charité-University Medicine BerlinBerlin 13353Germany Institute of Orthopedic Research and Biomechanics Ulm University Medical CenterUlm 89091Germany Institute for Clinical and Experimental Trauma-Immunology(ITI) University Hospital UlmUlm 89091Germany Department of Trauma and Orthopedic Surgery University Hospital Erlangen Friedrich-Alexander University Erlangen-Nürnberg(FAU)Erlangen 91054Germany

In vertebrates,bone is considered an osteoimmune system which encompasses functions of a locomotive organ,a mineral reservoir,a hormonal organ,a stem cell pool and a cradle for immune *** osteoimmune system is based on cooperatively acting bone and immune cells,cohabitating within the bone *** are highly interdependent,a fact that is confounded by shared progenitors,mediators,and signaling *** fracture healing requires the participation of all the precursors,immune and bone cells found in the osteoimmune *** evidence demonstrated that changes of the immune cell composition and function may negatively influence bone *** this review,first the interplay between different immune cell types and osteoprogenitor cells will be elaborated more *** separate paragraphs focus on the specific cell types,starting with the cells of the innate immune response followed by cells of the adaptive immune response,and the complement system as mediator between ***,a brief overview on the challenges of preclinical testing of immunebased therapeutic strategies to support fracture healing will be given.

关键词： Trauma Bones Immune response Mesenchymal stem cells Fracture healing

Hepatotropic growth factors protect hepatocytes during inflammation by upregulation of antioxidative systems

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World Journal of Gastroenterology 2011年第17期17卷 2199-2205页

作者： Matthias Glanemann Daniel knobeloch Sabrina Ehnert Mihaela Culmes Claudine Seeliger Daniel Seehofer andreas k.nussler Department of General- Visceral-and Transplantation SurgeryCharitéCampus Virchow KlinikumUniversittsmedizin Berlin13353 BerlinGermany Department of Traumatology Klinikum rechts der IsarTechnische Universitt München81675 MunichGermany

AIM:To investigate effects of hepatotropic growth factors on radical production in rat hepatocytes during ***:Rat hepatocytes,isolated by collagenase perfusion,were incubated with a lipopolysaccharide(LPS)-containing cytokine mixture of interleukin-1β,tumor necrosis factor-α and interferon-γ to simulate sepsis and either co-incubated or pre-incubated with hepatotropic growth factors,*** growth factor,epidermal growth factor and/or transforming growth factor-α.Cells were analyzed for glutathione *** supernatants were assayed for produc-tion of reactive oxygen intermediates(ROIs) as well as NO2-,NO3-and *** determine cellular damage,release of aspartate aminotransferase(AST) into the culture medium was *** of nuclear factor(NF)-κB was measured by electrophoretic mobility shift ***:Rat hepatocytes treated with the LPS-containing cytokine mixture showed a significant increase in ROI and nitrogen oxide intermediate *** leakage was not significantly increased in cells treated with the LPS-containing cytokine mixture,independent of growth-factor ***,pretreatment with growth factors significantly reduced AST leakage and ROI formation while increasing cellular *** of growth factors did not result in increased NF-κB *** with growth factors further increased formation of NO2-,NO3-and S-nitrosothiols in hepatocytes stimulated with LPS-containing cytokine ***,we propose that,together with an increase in glutathione increased NO2-,NO3-formation might shift their metabolism towards non-toxic ***:Our data suggest that hepatotropic growth factors positively influence sepsis-induced hepatocellular injury by reducing cytotoxic ROI formation via induction of the cellular protective antioxidative systems.

关键词： Primary human hepatocytes Hepatocyte proliferation Cytokines Hepatotropic growth factors Nitric oxide Glutathione

Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

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Neural Regeneration Research 2025年第6期20卷 1789-1800页

作者： Carina Hromada Patrick Heimel Markus kerbl LászlóGál Sylvia Nürnberger Barbara Schaedl James Ferguson Nicole Swiadek Xavier Monforte Johannes C.Heinzel Antal Nógrádi andreas H.Teuschl-Woller David Hercher Department Life Science Engineering University of Applied Sciences Technikum WienViennaAustria Austrian Cluster for Tissue Regeneration ViennaAustria Ludwig Boltzmann Institute for Traumatology The Research Center in Cooperation with AUVAViennaAustria University Clinic of Dentistry Medical University of ViennaViennaAustria Department of Plastic Reconstructive and Aesthetic SurgeryLandesklinikum Wiener Neustadt2700 Wiener NeustadtAustria Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Medical University of Vienna Department of Orthopedics and Trauma SurgeryDevision of Trauma SurgeryViennaAustria Department of Hand- PlasticReconstructive and Burn SurgeryBG Unfallklinik TuebingenUniversity of TuebingenTuebingenGermany

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimizatio

关键词： axon regeneration blood vessel functional recovery macroporous nerve lesion peripheral nerve repair sciatic nerve silk-based nerve guidance conduit vascularization

No evidence for female discrimination against male house mice carrying a selfish genetic element

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Current Zoology 2016年第6期62卷 675-685页

作者： andreas SUTTER Anna k. LINDHOLM Institute of Evolutionary Biology and Environmental Studies University of Zurich Winterthurerstrasse 190 Zurich 8057 Switzerland

Meiotic drivers distort transmission to the next generation in their favor, with detrimental effects on the fitness of their homologues and the rest of the genome. Male carriers of meiotic drivers commonly inflict costs on their mates through genetic incompatibility, reduced fecundity, or biased brood sex ratios. Given these costs, evidence for female discrimination against male carriers is surprisingly rare. One of few examples is the t haplotype in house mice, a meiotic driver that shows strong transmission distortion in males and is typically homozygote lethal. As a consequence, mating between 2 t heterozygous （＋/t） mice leads to high embryo mortality. Previous experiments showing that＋/t females avoid this incompatibility cost by preferring ＋/＋ versus ＋/t males have inferred preference based on olfactory cues or brief social interactions. Evidence from mating contexts in laboratory settings and semi-natural populations has been inconclusive. Here, we investigated female choice from a large number of no-choice mating trials. We found no evidence for discrimination against＋/t males based on mating, remating, and copulatory behavior. Further, we found no evidence for avoidance of incompatibility through selective interactions between game- tes. The likelihood of mating showed significant effects of female weight and genotype, suggesting that our test paradigm enabled females to exhibit mate choice. We discuss the strengths and limitations of our approach. By explicitly considering selection at both the individual and gene level, we argue why precopulatory female discrimination by＋/t females may be less evolutionarily stable than discrimination by all females based on postcopulatory mechanisms.

关键词： cryptic female choice female preference indirect benefits mate choice segregation distortion t haplotype

Putting On The Breaks:Regulating Organelle Movements in Plant Cells

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Journal of Integrative Plant Biology 2012年第11期54卷 868-874页

作者： Julianna k.Vick andreas Nebenfhr Department of Biochemistry and Cellular and Molecular Biology University of TennesseeKnoxvilleTN 37996USA

A striking characteristic of plant cells is that their organelles can move rapidly through the cell. This movement, commonly referred to as cytoplasmic streaming, has been observed for over 200 years, but we are only now beginning to decipher the mechanisms responsible for it. The identification of the myosin motor proteins responsible for these movements allows us to probe the regulatory events that coordinate organelle displacement with normal cell physiology. This review will highlight several recent developments that have provided new insight into the regulation of organelle movement, both at the cellular level and at the molecular level.

关键词： Cytoplasmic streaming cytoskeleton myosin organelle.

Heterologous Expression of the Mevalonic Acid Pathway in Cyanobacteria Enhances Endogenous Carbon Partitioning to Isoprene

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Molecular Plant 2014年第1期7卷 71-86页

作者： Fiona k. Bentley andreas Zurbriggen Anastasios Melis Department of Plant and Microbial Biology University of California 111 Koshland Hall Berkeley CA 94720-3102 USA

Heterologous expression of the isoprene synthase gene in the cyanobacterium Synechocystis PCC 6803 conferred upon these microorganisms the property of photosynthetic isoprene （C5H8） hYdrocarbons production. Continuous production of isoprene from CO2 and H2O was achieved in the light, occurring via the endogenous methylerythritolphosphate （MEP） pathway, in tandem with the growth of Synechocystis. This work addressed the issue of photosynthetic carbon partitioning between isoprene and biomass in Synechocystis. Evidence is presented to show heterologous genomic integration and cellular expression of the mevalonic acid （MVA） pathway genes in Synechocystis endowing a non-native pathway for carbon flux amplification to isopentenyl-diphosphate （IPP） and dimethylallyl-diphosphate （DMAPP） precursors of isoprene. Heterologous expression of the isoprene synthase in combination with the MVA pathway enzymes resulted in photosynthetic isoprene yield improvement by approximately 2.5-fold, compared with that measured in cyanobacteria transformed with the isoprene synthase gene only. These results suggest that the MVA pathway introduces a bypass in the flux of endogenous cellular substrate in Synechocystis to IPP and DMAPP, overcoming flux limitations of the native MEP pathway. The work employed a novel chromosomal integration and expression of synthetic gene operons in Synechocystis, comprising up to four genes under the control of a single promoter, and expressing three operons simultaneously. This is the first time an entire biosynthetic pathway with seven recombinant enzymes has been heterologously expressed in a photosynthetic microorganism. It constitutes contribution to the genetic engineering toolkit of photosynthetic microorganisms and a paradigm in the pursuit of photosynthetic approaches for the renewable generation of high-impact products.

关键词： biofuels cyanobacteria isoprene isoprene synthase metabolic engineering photosynthesis Synechocystis.