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Cellular models of stress resistance may pave ways to fight neurodegenerative diseases

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Neural Regeneration Research 2025年第9期20卷 2579-2580页

作者： Thu Nguyen Minh Pham christian Behl Institute of Pathobiochemistry University Medical Center of the Johannes Gutenberg UniversityMainzGermany

Alzheimer's disease(AD),the most common form of neurodegeneration,is characterized by selective neuronal vulnerability and brain regionselective neuron *** entorhinal cortex and hippoc,ampal CA1 projection neurons are at greater risk in AD whereas other regions display resistance to ***,the cerebellum,a phylogenetically very old region,is affected only very late in the disease progression.

关键词： cortex resistance Alzheimer

Many faces of neuronal activity manipulation in Drosophila

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Neural Regeneration Research 2025年第9期20卷 2574-2576页

作者： Amber Krebs Steffen Kautzmann christian Klämbt Institut für Neuro-und Verhaltensbiologie MünsterGermany

Animals exhibit complex responses to external and internal *** information is computed by interconnected neurons that express numerous ion channels,which modulate the neuronal membrane *** can neuronal activity orchestrate complex motor patterns or allow learning from previous experience?To answer such questions,we need the ability not only to record,but also to modulate neuronal activity in both space(e.g.,neuronal subsets)and time.

关键词： manipulation potential. neuronal

Checkpoint blockade therapy in Hodgkin lymphoma:improved response through combination with JAK inhibition

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Signal Transduction and Targeted Therapy 2024年第10期9卷 4165-4166页

作者： Marc A.weniger Ralf Küppers Institute of Cell Biology(Cancer Research) Medical FacultyUniversity of Duisburg-EssenEssenGermany

In a recently published article in Science,Zak et *** that the Janus kinase(JAK)inhibitor ruxolitinib alters innate and adaptive immune cells to an unanticipated,predominantly immune-stimulatory phenotype in mouse infection models.1 This finding motivated a clinical study,which showed that ruxolitinib treatment in combination with the anti-PD1 immune checkpoint inhibitor(ICI)nivolumab in a cohort of relapsed or refractory Hodgkin lymphoma(HL)patients demonstrated promising responses.

关键词： PD1 lymphoma

Complement-dependent neuroinflammation in spinal cord injury:from pathology to therapeutic implications

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Neural Regeneration Research 2025年第5期20卷 1324-1335页

作者： Hassan Saad Bachar El Baba Ali Tfaily Firas Kobeissy Juanmarco Gutierrez Gonzalez Daniel Refai Gerald R.Rodts christian Mustroph David Gimbel Jonathan Grossberg Daniel L.Barrow Matthew F.Gary Ali M.Alawieh Department of Neurosurgery Emory University School of MedicineAtlantaGAUSA Department of Neurology Yale UniversityNew HavenCTUSA Center for Neurotrauma Multiomics&Biomarkers(CNMB)Morehouse School of MedicineAtlantaGAUSA

Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this *** the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing *** this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the *** study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular *** effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord *** this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human *** review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.

关键词： complement neuroinflammation neuroplasticity regeneration spinal cord injury targeted therapy

Complications of dexamethasone implants:risk factors,prevention,and clinical management

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International Journal of Ophthalmology(English edition) 2020年第10期13卷 1612-1620页

作者： Nil Celik Ramin Khoramnia gerd.U Auffarth Saadettin Sel christian S Mayer Department of Ophthalmology University Hospital of HeidelbergHeidelberg 69120Germany

AIM:To evaluate major complications after intravitreal injection of dexamethasone implants(Ozurdex)and their clinical ***:In a retrospective observational study between 2014 and 2016 at two university hospitals,we reviewed the clinical records of 1241 consecutive macular edema patients treated with the dexamethasone implant,and separated severe adverse events in the injection procedure from those that were post-injection *** evaluated the cause and the outcomes in each ***:In twenty-one procedures(1.69%)we noticed significant complications during and after intravitreal injection of the dexamethasone *** related to the injection procedure were in one case,that a second implant was injected by mistake in the same eye on the same *** another case,the implant lodged in the sclera during retraction of the injector *** scleral tunnel at the injection site led to hypotony in another *** were 10 cases of post-injection displacement of the implant into the anterior chamber and one case with a migrated and trapped device between the intraocular lens and an artificial *** typically occurred in patients with preexisting risk factors:eyes with complicated intraocular lens implantation,iris reconstruction or iris defects or pseudophakic eyes after vitrectomy were prone to develop this *** led to secondary corneal decompensation with *** case developed an endophthalmitis,and we observed four cases of retinal *** eyes presented with long-lasting hypotony due to ciliary ***:Treatment with the dexamethasone implant may cause various expected or unexpected complications that may have serious consequences for the patient and require further *** reduce complications,clinicians should evaluate certain risk factors before scheduling patients for dexamethasone implant treatment and use proper injection techniques.

关键词： intravitreal implants dexamethasone implants Ozurdex intravitreal injection slow release drug

A Hierarchy of Compatibility and Comeasurability Levels in Quantum Logics with Unique Conditional Probabilities

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Communications in Theoretical Physics 2010年第12期54卷 974-980页

作者： gerd Niestegge Zillertalstrasse 39 81373 Muenchen Germany

In the quantum mechanical Hilbert space formalism, the probabilistic interpretation is a later ad-hocadd-on, more or less enforced by the experimental evidence, but not motivated by the mathematical model *** involving a clear probabilistic interpretation from the very beginning is provided by the quantum logics withunique conditional *** includes the projection lattices in von Neumann algebras and here probabilityconditionalization becomes identical with the state transition of the Lüders-von Neumann measurement *** the definition of a hierarchy of five compatibility and comeasurability levels in the abstract setting of thequantum logics with unique conditional *** meanings are: the absence of quantum interference orinfluence, the existence of a joint distribution, simultaneous measurability, and the independence of the final stateafter two successive measurements from the sequential order of these two measurements.A further level means that twoelements of the quantum logic (events) belong to the same Boolean *** the general case, the five compatibilityand comeasurability levels appear to differ, but they all coincide in the common Hilbert space formalism of quantummechanics, in von Neumann algebras, and in some other cases.

关键词： quantum measurement conditional probability quantum logic operator algebras

Epigenetic changes of DNA repair genes in cancer

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Journal of Molecular Cell Biology 2011年第1期3卷 51-58页

作者： Christoph Lahtz gerd P.Pfeifer Department of Cancer Biology Beckman Research InstituteCity of HopeDuarteCA 91010USA

‘Every Hour Hurts,The Last One Kills’.That is an old saying about getting *** day,thousands of DNA damaging events take place in each cell of our body,but efficient DNA repair systems have evolved to prevent ***,our DNA repair system and that of most other organisms are not as perfect as that of Deinococcus radiodurans,for example,which is able to repair massive amounts of DNA damage at one *** many instances,accumulation of DNA damage has been linked to cancer,and genetic deficiencies in specific DNA repair genes are associated with tumor-prone *** addition to mutations,which can be either inherited or somatically acquired,epigenetic silencing of DNA repair genes may promote *** review will summarize current knowledge of the epigenetic inactivation of different DNA repair components in human cancer.

关键词： DNA methylation DNA repair epigenetics

Ephrin-B2 is differentially expressed in the intestinal epithelium in Crohn's disease and contributes to accelerated epithelial wound healing in vitro

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World Journal of Gastroenterology 2005年第26期11卷 4024-4031页

作者： christian Hafner Stefanie Meyer Thomas Langmann gerd Schmitz Frauke Bataille Ilja Hagen Bernd Becker Alexander Roesch Gerhard Rogler Michael Landthaler Thomas Vogt Department of Dermatology University Hospital of Regensburg D-93042 Regensburg Germany Department of Clinical Chemistry University Hospital of Regensburg D-93042 Regensburg Germany Institute of Pathology University Hospital of Regensburg D-93042 Regensburg Germany Department of Internal Medicine University Hospital of Regensburg D-93042 Regensburg Germany

AIM:Eph receptor tyrosine kinases and their membrane bound receptor-like ligands, the ephrins, represent a bi-directional cell-cell contact signaling system that directs epithelial movements in development. The meaning of this system in the adult human gut is unknown. We investigated the Eph/ephrin mRNA expression in the intestinal epithelium of healthy controls and patients with inflammatory bowel disease (IBD). METHODS: mRNA expression profiles of all Eph/ephrin family members in normal small intestine and colon were established by real-time RT-PCR. In addition, differential expression in IBD was investigated by cDNA array technology, and validated by both real-time RT-PCR and immunohistochemistry. Potential effects of enhanced EphB/ephrin-B signaling were analyzed in an in vitro IEC-6 cell scratch wound model. RESULTS: Human adult intestinal mucosa exhibits a complex pattern of Eph receptors and ephrins. Beside the known prominent co-expression of EphA2 and ephrinAl, we found abundantly co-expressed EphB2 and ephrin-B1/2. Interestingly, cDNA array data, validated by real-time PCR and immunohistochemistry, showed upregulation of ephrin-B2 in both perilesional and lesional intestinal epithelial cells of IBD patients, suggesting a role in epithelial homeostasis. Stimulation of ephrin-B signaling in ephrin- B1/2 expressing rat IEC-6-cells with recombinant EphB1-Fc resulted in a significant dose-dependent acceleration of wound closure. Furthermore, fluorescence microscopy showed that EphB1-Fc induced coordinated migration of wound edge cells is associated with enhanced formation of lamellipodial protrusions into the wound, increased actin stress fiber assembly and production of laminin at the wound edge. CONCLUSION: EphB/ephrin-B signaling might represent a novel protective mechanism that promotes intestinal epithelial wound healing, with potential impact on epithelial restitution in IBD.

关键词： Ephrin-B2 Crohn's disease IBD IEC-6 Wound healing Epithelial restitution

Tracking morphologies at the nanoscale： Self-assembly of an amphiphilic designer peptide into a double helix superstructure

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Nano Research 2015年第6期8卷 1822-1833页

作者： Karin Kornmueller Ilse Letofsky-Papst Kerstin Gradauer christian Mikl Fernando Cacho-Nerin Mario Leypold Walter Keller gerd Leitinger Heinz Amenitsch Ruth Prassl Institute of Biophysics Medical University ofGraz BioTechMed-Graz 8010 Graz Austria Institute for Electron Microscopy and Nanoanalysis Graz University of Technology and Graz Centre for Electron Microscopy 80 10 Graz A us tria Institute of Inorganic Chemistry Graz University of Technology 8010 Graz Austria Institute of Organic Chemistry Graz University of Technology 8010 Graz Austria Institute for Molecular Biosciences KarI-Franzens-University Graz 8010 Graz Austria Research Unit Electron Microscopic Techniques Institute of Cell Biology Histology and Embryology Medical University of Graz 80 10 Graz A us tria Center for Medical Research Medical University of Graz 8010 Graz Austria

Hierarchical self-assembly is a fundamental principle in nature, which gives rise to astonishing supramolecular architectures that are an inspiration for the development of innovative materials in nanotechnolog）a Here, we present the unique structure of a cone-shaped amphiphilic designer peptide. While tracking its concentration-dependent morphologies, we observed elongated bilayered single tapes at the beginning of the assembly process, which further developed into novel double-helix-like superstructures at high concentrations. This architecture is characterized by a tight intertwisting of two individual helices, resulting in a periodic pitch size over their total lengths of several hundred nanometers. Solution X-ray scattering data revealed a marked 2-layered internal organization. All these characteristics remained unaltered for the investigated period of almost three months. In their collective morphology, the assemblies are integrated into a network with hydrogel characteristics. Such a peptide-based structure holds promise as a building block for next-generation nanostructured biomaterials.

关键词： double helix amphiphilic designerpeptide self-assembl)~SAXS TEM spectroscopy