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1. The challenges of research data management in cardiovascular science: a DGK and DZHK position paper—executive summary

Author

Steffens, Sabine, Schröder, Katrin, Krüger, Martina, Maack, Christoph, Streckfuss-Bömeke, Katrin, Backs, Johannes, Backofen, Rolf, Baeßler, Bettina, Devaux, Yvan, Gilsbach, Ralf, Heijman, Jordi, Knaus, Jochen, Kramann, Rafael, Linz, Dominik, Lister, Allyson L., Maatz, Henrike, Maegdefessel, Lars, Mayr, Manuel, Meder, Benjamin, Nussbeck, Sara Y., Rog-Zielinska, Eva A., Schulz, Marcel H., Sickmann, Albert, Yigit, Gökhan, and Kohl, Peter

Published
2024
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8. Sodium-Glucose-Cotransporter-2 Inhibitor Therapy and Intermitted Fasting in Cardiorenal Syndrome: The Role of Glucose-Mediated Oxidative Stress.

Author

Schröder, Katrin

Subjects
*INSULIN regulation, *INTERMITTENT fasting, *CARDIO-renal syndrome, *INSULIN sensitivity, *METABOLIC regulation
Abstract

Cardiorenal syndrome (CRS) is a complex clinical disorder characterized by the interplay between heart and kidney dysfunction. This condition is exacerbated by comorbidities such as diabetes mellitus, which contribute to glucose-mediated oxidative stress, further complicating the management of CRS. The management of CRS has evolved with the discovery of sodium-glucose-cotransporter-2 (SGLT2) inhibitors, which have been established as effective agents in reducing hyperglycemia and demonstrated cardiorenal protective effects. Concurrently, intermittent fasting has gained attention as an intervention without pharmacological treatment for its metabolic benefits, including improved glucose metabolism and insulin regulation and sensitivity, both with a potential reduction in oxidative stress. This review provides a summary of current findings on the roles of SGLT2 inhibitors and intermittent fasting in managing CRS, with a particular focus on glucose-mediated oxidative stress. We evaluate the mechanisms by which these interventions exert their effects, identify gaps in current research, and offer recommendations for future studies. While both SGLT2 inhibitors and intermittent fasting demonstrate potential in managing CRS, more research is needed to elucidate their long-term efficacy, safety, and potential synergistic effects. [ABSTRACT FROM AUTHOR]

Published
2025
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10. Genetic deletion of Nox4 enhances cancerogen-induced formation of solid tumors

Author

Helfinger, Valeska, von Gall, Florian Freiherr, Henke, Nina, Kunze, Michael M., Schmid, Tobias, Rezende, Flavia, Heidler, Juliana, Wittig, Ilka, Radeke, Heinfried H., Marschall, Viola, Anderson, Karen, Shah, Ajay M., Fulda, Simone, Brüne, Bernhard, Brandes, Ralf P., and Schröder, Katrin

Published
2021

17. Enhancement of a one-step membrane technique for the treatment of large bone defects by pre-seeding the membrane with CD8 lymphocyte depleted bone marrow mononuclear cells in a rat femoral defect model.

Author

Penna-Martinez, Marissa, Kammerer, Andreas, Stützle, Pia, Fees, Sabatian, Behr, Savina, Schaible, Inna, Schröder, Katrin, Verboket, René Danilo, Neijhoft, Jonas, Marzi, Ingo, Nau, Christoph, and Henrich, Dirk

Subjects
BONE marrow cells, BONE density, BONE growth, CELL populations, BONE regeneration
Abstract

Background: The one-step membrane technique, using a human acellular dermal matrix (hADM), is an experimental method for treating large bone defects. This eliminates the need for the Masquelet membrane induction step, shortening the procedure while maintaining effectiveness. However, previous studies showed that colonizing hADM with bone marrow mononuclear cells (BMC) worsens healing, likely due to the presence of CD8+ lymphocytes, which negatively affect bone regeneration. This study aims to investigate whether the negative impact of BMC on bone healing in this technique is due to the CD8+ cell population. Materials and methods: A 5 mm femoral defect was created in 25 male Sprague-Dawley rats, divided into three groups (G1-G3). BMC were isolated from syngenic donor rats, with CD8+ lymphocytes removed magnetically from the BMC fraction in one group. The defects were filled with bone chips and wrapped with differently treated hADM: G1 received native hADM, G2 received hADM+BMC, and G3 received hADM+BMC-CD8. After 8 weeks, the femurs were evaluated through radiological, biomechanical, and histological examinations. Results: Bone defects and bone mineral density (BMD) were significantly improved in G3 (hADM+BMC-CD8) compared to G2 (hADM+BMC). Bone volume, bone formation, and median bending stiffness were higher in G3. Immunohistological analysis showed a significant decrease in CD8 cell count in G3, with a lower percentage of IFNγ-producing cells compared to G2. Conclusion: Depleting CD8+ cells from BMC before colonizing hADM significantly improved bone healing, likely due to changes in the local mediator environment. This suggests that preoperative colonization with CD8+-depleted BMC could enhance the one-step membrane technique. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Skeletal Phenotyping of Period‐1‐Deficient Melatonin‐Proficient Mice.

Author

Bahlmann, Olaf, Taheri, Shahed, Spaeth, Manuela, Schröder, Katrin, Schilling, Arndt F., Dullin, Christian, and Maronde, Erik

Subjects
BONE density, CLOCK genes, MOLECULAR clock, HINDLIMB, BODY size
Abstract

In mice, variability in adult bone size and density has been observed among common inbred strains. Also, in the group of genes regulating circadian rhythmicity in mice, so called clock genes, changes in body size and skeletal parameters have been noted in knockout mice. Here, we studied the size and density of prominent bones of the axial and appendicular skeleton of clock gene Period‐1‐deficient (Per1‐/‐) mice by means of microcomputed tomography. Our data show shorter spinal length, smaller and less dense femora and tibiae, but no significant changes in the shape of the skull and the length of the head. Together with the significantly lower total body weight of Per1‐/‐ mice, we conclude that Per1‐deficiency in a melatonin‐proficient mouse strain is associated with an altered body phenotype with smaller appendicular (hind limb) bone size, shorter spine length and lower total body weight while normal head length and brain weight. The observed changes suggest an involvement of secondary bone mineralisation with impact on long bones, but lesser impact on those of the skull. Evidence and overall physiological implications of these findings are discussed. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Physiologists as medical scientists: An early warning from the German academic system.

Author

Streckfuss‐Bömeke, Katrin, Kränkel, Nicolle, Maack, Christoph, Schnabel, Renate B., Zelarayán, Laura C., Frey, Norbert, Jezzard, Peter, Krüger, Martina, Lachmann, Nico, Lutz, Susanne, Noack, Claudia, Schoger, Eric, Schröder, Katrin, Sommerfeld, Laura C., Steffens, Sabine, Winkels, Holger, Würtz, Christina, Zeller, Tanja, Rog‐Zielinska, Eva A., and Kohl, Peter

Subjects
CAREER development, MEDICAL scientists, ACADEMIC employment, PHYSIOLOGISTS, ADMINISTRATIVE reform
Abstract

"Medical scientists" are postgraduate investigators who are engaged in biomedical research, and either hold a biomedical PhD or are qualified in medicine but do not participate in patient care. Medical scientists constitute ~40% of staff at medical faculties and >90% at nonuniversity medical research institutions in Germany. However, medical scientists in Germany face limited long‐term career prospects and a lack of dedicated training and support programmes. They also face time limits on their career progression arising from national academic employment legislation, and imminent reforms by the German government are likely to make this worse. Nevertheless, recent developments in the educational landscape including the introduction of increasingly focused MSc, pre‐PhD, and doctoral programmes to train medically aware basic scientists, as well as improved general recognition of the roles and relevance of medical scientists in health research, are encouraging. Physiologists have taken essential steps to improve the recognition of medical scientists in Germany by introducing a "specialist physiologist" qualification; this initiative could be applied to support medical scientists in other fields and countries. In this review, we describe the particular challenges facing medical scientists in Germany and make recommendations that may apply to other academic systems. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Redox Signaling in Endosomes Using the Example of EGF Receptors: A Graphical Review.

Author

Hebchen, Dana Maureen and Schröder, Katrin

Subjects
EPIDERMAL growth factor receptors, SECOND messengers (Biochemistry), REACTIVE oxygen species, ENDOSOMES, LYSOSOMES
Abstract

Early endosomes represent first-line sorting compartments or even organelles for internalized molecules. They enable the transport of molecules or ligands to other compartments of the cell, such as lysosomes, for degradation or recycle them back to the membrane by various mechanisms. Moreover, early endosomes function as signaling and scaffolding platforms to initiate or prolong distinct signaling pathways. Accordingly, early endosomes have to be recognized as either part of a degradation or recycling pathway. The physical proximity of many ligand-binding receptors with other membrane-bound proteins or complexes such as NADPH oxidases may result in an interaction of second messengers, like reactive oxygen species (ROS) and early endosomes, that promote the correct recognition of individual early endosomes. In fact, redoxosomes comprise an endosomal subsection of signaling endosomes. One example of such potential interaction is epidermal growth factor receptor (EGFR) signaling. Here we summarize recent findings on EGFR signaling as a well-studied example for receptor trafficking and trans-activation and illustrate the interplay between cellular and endosomal ROS. [ABSTRACT FROM AUTHOR]

Published
2024
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21. NoxO1 Determines the Level of ROS Formation by the Nox1-Centered NADPH Oxidase.

Author

Hebchen, Dana Maureen, Spaeth, Manuela, Müller, Niklas, and Schröder, Katrin

Subjects
NADPH oxidase, REACTIVE oxygen species, CHARGE exchange, GENE expression, CELL lines
Abstract

The Nox1-centered NADPH oxidase complex facilitates the transfer of electrons from intracellular NADPH across the cell membrane to extracellular molecular oxygen, resulting in the formation of superoxide. The complex is comprised of two membrane-bound subunits, namely Nox1 and p22phox, and the cytosolic subunits, namely NoxA1 and NoxO1. The presence of NoxO1 facilitates the proximity of all components, thereby enabling the complex to exhibit constitutive activity. Despite the theoretical sufficiency of all subunits in a 1:1 ratio, the precise composition of the Nox1-centered NADPH oxidase remains unknown. Analyses of mRNA expression in different cell lines revealed an unequal expression of the components, with an excess of NoxO1. Furthermore, plasmid-based overexpression of individual components of the Nox1-centered NADPH oxidase resulted in an excess of NoxO1 mRNA. The objective of this study was to analyze the ability of NoxO1 to control the level of ROS formation by the Nox1 complex. To this end, we generated Hek293 cells for constitutive expression of Nox1 and NoxA1, which were then transfected with increasing concentrations of NoxO1. The data presented herein suggests that ROS formation by the Nox1-centered NADPH oxidase is dependent on the concentration of NoxO1. A surplus of NoxO1 has been observed to exert control over the activity of the complex in accordance with a dose-dependent mechanism. We thus conclude that the ratio of Nox1, NoxA1, and NoxO1 complexes does not adhere to a 1:1 ratio. Conversely, the availability of NoxO1 serves to regulate the formation of ROS by the Nox1-centered NADPH oxidase. [ABSTRACT FROM AUTHOR]

Published
2024
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28. The challenges of research data management in cardiovascular science:a DGK and DZHK position paper—executive summary

Author

Steffens, Sabine, Schröder, Katrin, Krüger, Martina, Maack, Christoph, Streckfuss-Bömeke, Katrin, Backs, Johannes, Backofen, Rolf, Baeßler, Bettina, Devaux, Yvan, Gilsbach, Ralf, Heijman, Jordi, Knaus, Jochen, Kramann, Rafael, Linz, Dominik, Lister, Allyson L., Maatz, Henrike, Maegdefessel, Lars, Mayr, Manuel, Meder, Benjamin, Nussbeck, Sara Y., Rog-Zielinska, Eva A., Schulz, Marcel H., Sickmann, Albert, Yigit, Gökhan, Kohl, Peter, Steffens, Sabine, Schröder, Katrin, Krüger, Martina, Maack, Christoph, Streckfuss-Bömeke, Katrin, Backs, Johannes, Backofen, Rolf, Baeßler, Bettina, Devaux, Yvan, Gilsbach, Ralf, Heijman, Jordi, Knaus, Jochen, Kramann, Rafael, Linz, Dominik, Lister, Allyson L., Maatz, Henrike, Maegdefessel, Lars, Mayr, Manuel, Meder, Benjamin, Nussbeck, Sara Y., Rog-Zielinska, Eva A., Schulz, Marcel H., Sickmann, Albert, Yigit, Gökhan, and Kohl, Peter

Abstract

The sharing and documentation of cardiovascular research data are essential for efficient use and reuse of data, thereby aiding scientific transparency, accelerating the progress of cardiovascular research and healthcare, and contributing to the reproducibility of research results. However, challenges remain. This position paper, written on behalf of and approved by the German Cardiac Society and German Centre for Cardiovascular Research, summarizes our current understanding of the challenges in cardiovascular research data management (RDM). These challenges include lack of time, awareness, incentives, and funding for implementing effective RDM; lack of standardization in RDM processes; a need to better identify meaningful and actionable data among the increasing volume and complexity of data being acquired; and a lack of understanding of the legal aspects of data sharing. While several tools exist to increase the degree to which data are findable, accessible, interoperable, and reusable (FAIR), more work is needed to lower the threshold for effective RDM not just in cardiovascular research but in all biomedical research, with data sharing and reuse being factored in at every stage of the scientific process. A culture of open science with FAIR research data should be fostered through education and training of early-career and established research professionals. Ultimately, FAIR RDM requires permanent, long-term effort at all levels. If outcomes can be shown to be superior and to promote better (and better value) science, modern RDM will make a positive difference to cardiovascular science and practice. The full position paper is available in the supplementary materials.

Published
2024

29. NADPH oxidase subunit NOXO1 is a target for emphysema treatment in COPD

Author

Seimetz, Michael, Sommer, Natascha, Bednorz, Mariola, Pak, Oleg, Veith, Christine, Hadzic, Stefan, Gredic, Marija, Parajuli, Nirmal, Kojonazarov, Baktybek, Kraut, Simone, Wilhelm, Jochen, Knoepp, Fenja, Henneke, Ingrid, Pichl, Alexandra, Kanbagli, Zeki I., Scheibe, Susan, Fysikopoulos, Athanasios, Wu, Cheng-Yu, Klepetko, Walter, Jaksch, Peter, Eichstaedt, Christina, Grünig, Ekkehard, Hinderhofer, Katrin, Geiszt, Miklós, Müller, Niklas, Rezende, Flavia, Buchmann, Giulia, Wittig, Ilka, Hecker, Matthias, Hecker, Andreas, Padberg, Winfried, Dorfmüller, Peter, Gattenlöhner, Stefan, Vogelmeier, Claus F., Günther, Andreas, Karnati, Srikanth, Baumgart-Vogt, Eveline, Schermuly, Ralph T., Ghofrani, Hossein A., Seeger, Werner, Schröder, Katrin, Grimminger, Friedrich, Brandes, Ralf P., and Weissmann, Norbert

Published
2020
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38. List of contributors

Author

Anderson, Alisha R., primary, Andersson, Martin N., additional, Ashourian, Kristen Taylor, additional, Blomquist, Gary J., additional, Bruckmann, Astrid, additional, Chertemps, Thomas, additional, Crewe, Robin M., additional, Fandino, Richard A., additional, Ferguson, Stephen T., additional, Fleischer, Jörg, additional, Ginzel, Matthew D., additional, Hansson, Bill S., additional, Hofferberth, John, additional, Jacquin-Joly, Emmanuelle, additional, Jurenka, R.A., additional, Kanzaki, Ryohei, additional, Keeling, Christopher I., additional, Keesey, Ian W., additional, Krieger, Jürgen, additional, Löfstedt, Christer, additional, MacLean, Marina, additional, Maïbèche, Martine, additional, Miazzi, Fabio, additional, Mitchell, Robert F., additional, Mitsuno, Hidefumi, additional, Montagne, Jacques, additional, Montagné, Nicolas, additional, Mumoki, Fiona N., additional, Namiki, Shigehiro, additional, Newcomb, Richard D., additional, Pinnelli, Govardhana R., additional, Plettner, Erika, additional, Ray, Anandasankar, additional, Ruther, Joachim, additional, Sakurai, Takeshi, additional, Schröder, Katrin, additional, Sparks, Jackson T., additional, Stengl, Monika, additional, Terrado, Mailyn, additional, Tholl, Dorothea, additional, Tittiger, Claus, additional, Vogt, Richard G., additional, Wanner, Kevin, additional, Wicher, Dieter, additional, Wicker-Thomas, Claude, additional, Xia, Yi-Han, additional, and Zwiebel, Laurence J., additional

Published
2021
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43. Redox stress in Marfan syndrome: Dissecting the role of the NADPH oxidase NOX4 in aortic aneurysm

Author

Jiménez-Altayó, Francesc, Meirelles, Thayna, Crosas-Molist, Eva, Sorolla, M. Alba, del Blanco, Darya Gorbenko, López-Luque, Judit, Mas-Stachurska, Aleksandra, Siegert, Ana-Maria, Bonorino, Fabio, Barberà, Laura, García, Carolina, Condom, Enric, Sitges, Marta, Rodríguez-Pascual, Fernando, Laurindo, Francisco, Schröder, Katrin, Ros, Joaquim, Fabregat, Isabel, and Egea, Gustavo

Published
2018
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44. Lung Ischaemia–Reperfusion Injury: The Role of Reactive Oxygen Species

Author

Pak, Oleg, Sydykov, Akylbek, Kosanovic, Djuro, Schermuly, Ralph T., Dietrich, Alexander, Schröder, Katrin, Brandes, Ralf P., Gudermann, Thomas, Sommer, Natascha, Weissmann, Norbert, COHEN, IRUN R., Series editor, LAJTHA, ABEL, Series editor, LAMBRIS, JOHN D., Series editor, PAOLETTI, RODOLFO, Series editor, REZAEI, NIMA, Series editor, and Wang, Yong-Xiao, editor

Published
2017
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46. The challenges of research data management in cardiovascular science: a DGK and DZHK position paper—executive summary

Author

Steffens, Sabine, primary, Schröder, Katrin, additional, Krüger, Martina, additional, Maack, Christoph, additional, Streckfuss-Bömeke, Katrin, additional, Backs, Johannes, additional, Backofen, Rolf, additional, Baeßler, Bettina, additional, Devaux, Yvan, additional, Gilsbach, Ralf, additional, Heijman, Jordi, additional, Knaus, Jochen, additional, Kramann, Rafael, additional, Linz, Dominik, additional, Lister, Allyson L., additional, Maatz, Henrike, additional, Maegdefessel, Lars, additional, Mayr, Manuel, additional, Meder, Benjamin, additional, Nussbeck, Sara Y., additional, Rog-Zielinska, Eva A., additional, Schulz, Marcel H., additional, Sickmann, Albert, additional, Yigit, Gökhan, additional, and Kohl, Peter, additional

Published
2023
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48. European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)

Author

Egea, Javier, Fabregat, Isabel, Frapart, Yves M., Ghezzi, Pietro, Görlach, Agnes, Kietzmann, Thomas, Kubaichuk, Kateryna, Knaus, Ulla G., Lopez, Manuela G., Olaso-Gonzalez, Gloria, Petry, Andreas, Schulz, Rainer, Vina, Jose, Winyard, Paul, Abbas, Kahina, Ademowo, Opeyemi S., Afonso, Catarina B., Andreadou, Ioanna, Antelmann, Haike, Antunes, Fernando, Aslan, Mutay, Bachschmid, Markus M., Barbosa, Rui M., Belousov, Vsevolod, Berndt, Carsten, Bernlohr, David, Bertrán, Esther, Bindoli, Alberto, Bottari, Serge P., Brito, Paula M., Carrara, Guia, Casas, Ana I., Chatzi, Afroditi, Chondrogianni, Niki, Conrad, Marcus, Cooke, Marcus S., Costa, João G., Cuadrado, Antonio, My-Chan Dang, Pham, De Smet, Barbara, Debelec–Butuner, Bilge, Dias, Irundika H.K., Dunn, Joe Dan, Edson, Amanda J., El Assar, Mariam, El-Benna, Jamel, Ferdinandy, Péter, Fernandes, Ana S., Fladmark, Kari E., Förstermann, Ulrich, Giniatullin, Rashid, Giricz, Zoltán, Görbe, Anikó, Griffiths, Helen, Hampl, Vaclav, Hanf, Alina, Herget, Jan, Hernansanz-Agustín, Pablo, Hillion, Melanie, Huang, Jingjing, Ilikay, Serap, Jansen-Dürr, Pidder, Jaquet, Vincent, Joles, Jaap A., Kalyanaraman, Balaraman, Kaminskyy, Danylo, Karbaschi, Mahsa, Kleanthous, Marina, Klotz, Lars-Oliver, Korac, Bato, Korkmaz, Kemal Sami, Koziel, Rafal, Kračun, Damir, Krause, Karl-Heinz, Křen, Vladimír, Krieg, Thomas, Laranjinha, João, Lazou, Antigone, Li, Huige, Martínez-Ruiz, Antonio, Matsui, Reiko, McBean, Gethin J., Meredith, Stuart P., Messens, Joris, Miguel, Verónica, Mikhed, Yuliya, Milisav, Irina, Milković, Lidija, Miranda-Vizuete, Antonio, Mojović, Miloš, Monsalve, María, Mouthuy, Pierre-Alexis, Mulvey, John, Münzel, Thomas, Muzykantov, Vladimir, Nguyen, Isabel T.N., Oelze, Matthias, Oliveira, Nuno G., Palmeira, Carlos M., Papaevgeniou, Nikoletta, Pavićević, Aleksandra, Pedre, Brandán, Peyrot, Fabienne, Phylactides, Marios, Pircalabioru, Gratiela G., Pitt, Andrew R., Poulsen, Henrik E., Prieto, Ignacio, Rigobello, Maria Pia, Robledinos-Antón, Natalia, Rodríguez-Mañas, Leocadio, Rolo, Anabela P., Rousset, Francis, Ruskovska, Tatjana, Saraiva, Nuno, Sasson, Shlomo, Schröder, Katrin, Semen, Khrystyna, Seredenina, Tamara, Shakirzyanova, Anastasia, Smith, Geoffrey L., Soldati, Thierry, Sousa, Bebiana C., Spickett, Corinne M., Stancic, Ana, Stasia, Marie José, Steinbrenner, Holger, Stepanić, Višnja, Steven, Sebastian, Tokatlidis, Kostas, Tuncay, Erkan, Turan, Belma, Ursini, Fulvio, Vacek, Jan, Vajnerova, Olga, Valentová, Kateřina, Van Breusegem, Frank, Varisli, Lokman, Veal, Elizabeth A., Yalçın, A. Suha, Yelisyeyeva, Olha, Žarković, Neven, Zatloukalová, Martina, Zielonka, Jacek, Touyz, Rhian M., Papapetropoulos, Andreas, Grune, Tilman, Lamas, Santiago, Schmidt, Harald H.H.W., Di Lisa, Fabio, and Daiber, Andreas

Published
2017
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