Article
Multidisciplinary Sciences
Michael Stirm, Bachuki Shashikadze, Andreas Blutke, Elisabeth Kemter, Andreas Lange, Jan B. Stoeckl, Florian Jaudas, Laeticia Laane, Mayuko Kurome, Barbara Kessler, Valeri Zakhartchenko, Andrea Baehr, Nikolai Klymiuk, Hiroshi Nagashima, Maggie C. Walter, Wolfgang Wurst, Christian Kupatt, Thomas Froehlich, Eckhard Wolf
Summary: Skipping DMD exon 51 can restore dystrophin expression and improve cardiac function in DMD patients and animal models.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Medicine, Research & Experimental
Cedric Happi Mbakam, Joel Rousseau, Yaoyao Lu, Anne Bigot, Kamel Mamchaoui, Vincent Mouly, Jacques P. Tremblay
Summary: In this study, researchers used CRISPR-Cas9 prime editing technology to correct a mutation in the DMD gene, resulting in improved editing efficiency and restoration of dystrophin protein expression. Optimization of the reverse transcription template sequence led to a significant increase in the editing percentage of the target nucleotide.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Cell Biology
Michael Stirm, Lina Marie Fonteyne, Bachuki Shashikadze, Magdalena Lindner, Maila Chirivi, Andreas Lange, Clara Kaufhold, Christian Mayer, Ivica Medugorac, Barbara Kessler, Mayuko Kurome, Valeri Zakhartchenko, Arne Hinrichs, Elisabeth Kemter, Sabine Krause, Rudiger Wanke, Georg J. Arnold, Gerhard Wess, Hiroshi Nagashima, Martin Hrabe de Angelis, Florian Flenkenthaler, Levin Arne Kobelke, Claudia Bearzi, Roberto Rizzi, Andrea Baehr, Sven Reese, Kaspar Matiasek, Maggie C. Walter, Christian Kupatt, Sibylle Ziegler, Peter Bartenstein, Thomas Froehlich, Nikolai Klymiuk, Andreas Blutke, Eckhard Wolf
Summary: Creating a breeding cohort of DMD Delta 52 pigs by mating female DMD+/- carriers with DMD male animals has provided a valuable resource for studying disease mechanisms and testing treatment strategies. The DMDY/- piglets exhibited pathological features similar to human DMD disease, with progressive myocardial fibrosis and cognitive impairment observed. This cohort offers significant potential for future research in DMD.
DISEASE MODELS & MECHANISMS
(2021)
Article
Veterinary Sciences
Sarah M. Schneider, Garett T. Sansom, Lee-Jae Guo, Shinji Furuya, Brad R. Weeks, Joe N. Kornegay
Summary: This study systematically assessed cardiac lesions in carrier dogs, GRMD dogs, and normal dogs, and found that quantitative analysis of the cross-sectional area of fibrosis can distinguish the health status of different groups of dogs. The features identified in GRMD dogs are compatible with those of DMD, validating GRMD as an effective model for studying cardiomyopathy.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Article
Clinical Neurology
Giulio Gadaleta, Guido Urbano, Chiara Brusa, Rossella D'Alessandro, Enrica Rolle, Ilaria Cavallina, Alessio Mattei, Fulvia Ribolla, Claudia Raineri, Stefano Pidello, Liliana Vercelli, Federica S. Ricci, Tiziana E. Mongini
Summary: The clinical characteristics of adults with DMD include mechanical ventilation, swallowing and nutritional issues, and bone density alterations. Other issues include respiratory infections, gastrointestinal symptoms, metabolic acidosis, psychiatric symptoms, and chronic pain. Patients have a negative perception of their physical health but a more positive assessment of their mental health.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Matteo Giovarelli, Francesca Arnaboldi, Silvia Zecchini, Laura Brigida Cornaghi, Ambra Nava, Michele Sommariva, Emilio Giuseppe Ignazio Clementi, Nicoletta Gagliano
Summary: This study provides a comprehensive histological and molecular characterization of muscle fibrosis in Duchenne muscular dystrophy (DMD), showing that fibrosis mainly affects the diaphragm and quadriceps with higher collagen cross-linking and inhibition of MMPs. These findings may lead to new targeted therapeutic interventions for DMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Zeren Sun, Dengqiu Xu, Lei Zhao, Xihua Li, Sijia Li, Xiaofei Huang, Chunjie Li, Lixin Sun, Bing Liu, Zhenzhou Jiang, Luyong Zhang
Summary: The study found that fenofibrate can promote the differentiation of myofibers by down-regulating the expression of myostatin protein in myoblasts, significantly improving muscle function and reducing muscle damage in mdx mice, along with anti-inflammatory effects.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Immunology
Xuan Wu, Nan Dong, Liqiang Yu, Meirong Liu, Jianhua Jiang, Tieyu Tang, Hongru Zhao, Qi Fang
Summary: By integrating transcriptomic and proteomic methods, we identified differentially expressed mRNAs and proteins between DMD and Control groups, as well as key genes related to DMD. Through cell infiltration analysis, TF and miRNA prediction, and experimental verification, we found potential diagnostic biomarkers and therapeutic targets for DMD.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Olga Mucha, Malgorzata Myszka, Paulina Podkalicka, Bianka Swiderska, Agata Malinowska, Jozef Dulak, Agnieszka Loboda
Summary: This study investigated differentially expressed proteins in the diaphragm of 6-week-old mdx mice, a model for Duchenne muscular dystrophy (DMD), using label-free and tandem mass tag (TMT)-based methods. The comparison of both methods revealed 88 commonly changed proteins. Further analysis showed that 953 proteins significantly changed in dystrophic animals, with 867 increased and 86 decreased in expression. Interestingly, a significant decrease in the expression of enzymes generating hydrogen sulfide (H2S) was found in the dystrophic diaphragm, suggesting a potential role of H2S metabolism in modulating DMD progression.
Article
Clinical Neurology
Craig M. Zaidman, Crystal M. Proud, Craig M. Mcdonald, Kelly J. Lehman, Natalie L. Goedeker, Stefanie Mason, Alexander P. Murphy, Maitea Guridi, Shufang Wang, Carol Reid, Eddie Darton, Christoph Wandel, Sarah Lewis, Jyoti Malhotra, Danielle A. Griffin, Rachael A. Potter, Louise R. Rodino-Klapac, Jerry R. Mendell
Summary: The study ENDEAVOR demonstrated that the commercial process delandistrogene moxeparvovec is safe and effective in improving micro-dystrophin expression in patients with Duchenne muscular dystrophy. After 12 weeks of treatment, significant improvements were observed in micro-dystrophin expression, as well as patient's functional outcomes and quality of life at 1 year.
ANNALS OF NEUROLOGY
(2023)
Article
Materials Science, Multidisciplinary
Andre N. Tomiate, Gabriela K. Barbosa, Rose E. G. Rici, Sonia Regina Y. de Almeida, Ii-Sei Watanabe, Adriano P. Ciena
Summary: This study described the morphological, structural, and ultrastructural changes in the tongue mucosa and musculature of mdx mice, an experimental model of Duchenne muscular dystrophy. It was found that the muscular degeneration process indirectly led to higher wear of filiform papillae.
MICROSCOPY AND MICROANALYSIS
(2022)
Review
Cell Biology
Elisa Domi, Malvina Hoxha, Emanuela Prendi, Bruno Zappacosta
Summary: Duchenne muscular dystrophy is a muscular disease with no cure, and SIRT1 has been identified as a potential therapeutic target for the condition. Activation of SIRT1 improves muscle function, while its inhibition leads to muscle fragility.
Article
Biochemistry & Molecular Biology
Elena Gargaun, Sestina Falcone, Guilhem Sole, Julien Durigneux, Andoni Urtizberea, Jean Marie Cuisset, Sofia Benkhelifa-Ziyyat, Laura Julien, Anne Boland, Florian Sandron, Vincent Meyer, Jean Francois Deleuze, David Salgado, Jean-Pierre Desvignes, Christophe Beroud, Anatole Chessel, Alexia Blesius, Martin Krahn, Nicolas Levy, France Leturcq, France Pietri-Rouxel
Summary: This study found that long noncoding RNAs play important roles in Duchenne and Becker muscular dystrophy, particularly in regulating myocyte proliferation and differentiation with potential therapeutic implications. The research suggests that lncRNA44s2 may serve as an accelerator in muscle differentiation process and is associated with a favorable clinical phenotype.
Review
Clinical Neurology
Patricia Soblechero-Martin, Andrea Lopez-Martinez, Laura de la Puente-Ovejero, Ainara Vallejo-Illarramendi, Virginia Arechavala-Gomeza
Summary: Utrophin is a paralogue of dystrophin that can be overexpressed in the absence of dystrophin and may act as a surrogate to compensate for its deficiency. Various strategies to overexpress utrophin are being investigated, with many compounds showing promising results in preclinical studies by modulating utrophin expression and ameliorating the disease phenotype in animal models.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Krzysztof Zablocki, Dariusz C. Gorecki
Summary: Muscular dystrophies are inherited neuromuscular diseases that cause progressive disability and can reduce life expectancy. Loss of dystrophin or mutations in sarcoglycan-encoding genes lead to the loss of a-sarcoglycan ecto-ATPase activity, disrupting purinergic signaling and causing chronic inflammation in dystrophic muscles. Over-activation of P2X7 purinoceptors exacerbates pathology in dystrophic muscle cells. Blocking P2X7 receptors has shown promising results in mouse models and should be considered for the treatment of muscular dystrophies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Elena E. E. Wolf, Anne Steglich, Friederike Kessel, Hannah Kroeger, Jan Sradnick, Simone Reichelt-Wurm, Kathrin Eidenschink, Miriam C. C. Banas, Eckhard Wolf, Ruediger Wanke, Florian Gembardt, Vladimir T. T. Todorov
Summary: PLVAP serves as an early marker of glomerular endothelial injury in diabetic kidney disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Payel Sen, Bachuki Shashikadze, Florian Flenkenthaler, Esther Van de Kamp, Siyu Tian, Chen Meng, Michael Gigl, Thomas Froehlich, Daphne Merkus
Summary: Pulmonary vein stenosis (PVS) causes pulmonary hypertension (PH) by affecting flow and pressure in the pulmonary vasculature, leading to endothelial dysfunction and metabolic changes. Targeted therapy is recommended to relieve pressure and reverse flow-related changes in this type of PH.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Bachuki Shashikadze, Sophie Franzmeier, Isabel Hofmann, Martin Kraetzl, Florian Flenkenthaler, Andreas Blutke, Thomas Froehlich, Eckhard Wolf, Arne Hinrichs
Summary: This study investigated the histomorphological and molecular alterations associated with growth hormone receptor deficiency (GHRD). The results showed that GHRD pigs had reduced body weights, decreased pituitary volumes, and reduced volume density of GH-storing granules in somatotroph cells. Proteomic analysis revealed changes in protein expression related to protein production, transport, and endoplasmic reticulum (ER) stress. These findings provide insights into the molecular and histological changes caused by GHRD.
JOURNAL OF NEUROENDOCRINOLOGY
(2023)
Article
Multidisciplinary Sciences
Ken Ikeuchi, Nives Ivic, Robert Buschauer, Jingdong Cheng, Thomas Froehlich, Yoshitaka Matsuo, Otto Berninghausen, Toshifumi Inada, Thomas Becker, Roland Beckmann
Summary: This study reveals the impact of Otu2-driven deubiquitylation of ribosomal protein eS7 on translational efficiency and provides insights into its role in translation reset. The authors found that eS7 in actively translating 80S ribosomes is monoubiquitinated by the E3 ligase Not4 and deubiquitinated by Otu2 upon ribosomal subunit recycling. Cryo-electron microscopy analysis showed that Otu2 mainly binds to the 40S subunit surface at sites not occupied by other factors.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Valerie Pauly, Julia Vlcek, Zhihao Zhang, Nora Hesse, Ruibing Xia, Julia Bauer, Simone Loy, Sarah Schneider, Simone Renner, Eckhard Wolf, Stefan Kaeaeb, Dominik Schuettler, Philipp Tomsits, Sebastian Clauss
Summary: Atrial fibrillation (AF) is a common arrhythmia caused by myocardial ischemia/infarction (MI). Men have a higher prevalence of AF, while women have a higher risk of new onset AF after MI. The impact of sex on AF pathophysiology is largely unknown. In pigs with/without ischemic heart failure (IHF), both male and female pigs showed increased vulnerability to AF. Male pigs had more and longer AF episodes, while female pigs had sinus node dysfunction.
Article
Biochemistry & Molecular Biology
Marie-Christin Schilloks, Isabella-Maria Giese, Arne Hinrichs, Lucia Korbonits, Stefanie M. Hauck, Eckhard Wolf, Cornelia A. Deeg
Summary: This study investigated the effects of impaired GHR signaling on immune functions and immunometabolism in GHR-KO pigs. The results showed significant differences in the relative proportion of the CD4(+)CD8a(-) subpopulation and IFN-a levels between GHR-KO pigs and WT controls. However, no significant difference was found in the respiratory capacity and the capacity for polyclonal stimulation in PBMCs between the two groups. Proteome analysis revealed multiple significant protein abundance differences related to amino acid metabolism, beta-oxidation of fatty acids, insulin secretion signaling, and oxidative phosphorylation between GHR-KO pigs and WT pigs.
Article
Environmental Sciences
Federica Lamberto, Bachuki Shashikadze, Radwa Elkhateib, Salvo Danilo Lombardo, Alex Horanszky, Andrea Balogh, Kornel Kistamas, Melinda Zana, Joerg Menche, Thomas Froehlich, Andras Dinnyes
Summary: This study investigated the effects of environmentally relevant doses of Bisphenol A (BPA) on developing cardiomyocytes using a human induced pluripotent stem cell (hiPSC)-derived model. The results showed that long-term treatment with low doses of BPA interferes with hiPSC-CMs functionality and alters the surrounding cellular environment, leading to potential diseases. This study contributes to the understanding of BPA effects on developing human foetal cardiomyocytes and provides a suitable model for environmental chemical hazard and risk assessment.
ENVIRONMENTAL POLLUTION
(2023)
Article
Multidisciplinary Sciences
Michael Stirm, Bachuki Shashikadze, Andreas Blutke, Elisabeth Kemter, Andreas Lange, Jan B. Stoeckl, Florian Jaudas, Laeticia Laane, Mayuko Kurome, Barbara Kessler, Valeri Zakhartchenko, Andrea Baehr, Nikolai Klymiuk, Hiroshi Nagashima, Maggie C. Walter, Wolfgang Wurst, Christian Kupatt, Thomas Froehlich, Eckhard Wolf
Summary: Skipping DMD exon 51 can restore dystrophin expression and improve cardiac function in DMD patients and animal models.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Developmental Biology
Pia Sessenhausen, Karolina M. Caban, Nicole Kreitmair, Mirko Peitzsch, Jan B. Stoeckl, Marie C. Meinsohn, David Pepin, Bastian Popper, Thomas Froehlich, Artur Mayerhofer
Summary: The nicotinic acetylcholine receptor alpha 7 (nAChRa7), encoded by Chrna7, is expressed in various ovarian cells and plays a role in the local regulation of the ovary.
Article
Medicine, Research & Experimental
Anastasia Milusev, Jianfang Ren, Alain Despont, Jane Shaw, Matthias Laengin, Martin Bender, Jan-Michael Abicht, Maren Mokelke, Julia Radan, Elisabeth Neumann, Elisabeth Kemter, Nikolai Klymiuk, David Ayares, Eckhard Wolf, Bruno Reichart, Nicoletta Sorvillo, Robert Rieben
Summary: Xenotransplantation is a promising solution to organ shortage, and genetic modification of donor pigs has reduced the immunogenic burden. However, organ rejection remains a challenge. This study investigated the dynamics of the glycocalyx, a sugar-rich surface on endothelial cells, in genetically modified porcine arterial and venous cells after activation. The results showed that arterial cells, as well as venous cells, did not shed the glycocalyx after activation, and this was associated with reduced complement deposition. However, simultaneous perfusion with human serum and TNF? resulted in glycocalyx shedding and increased complement deposition, suggesting a proinflammatory phenotype in genetically modified endothelial cells in an inflammatory xenotransplantation setting.
XENOTRANSPLANTATION
(2023)
Article
Endocrinology & Metabolism
Bachuki Shashikadze, Libera Valla, Salvo Danilo Lombardo, Cornelia Prehn, Mark Haid, Fabien Riols, Jan Bernd Stoeckl, Radwa Elkhateib, Simone Renner, Birgit Rathkolb, Joerg Menche, Martin Hrabe de Angelis, Eckhard Wolf, Elisabeth Kemter, Thomas Froehlich
Summary: This study investigates the effects of maternal hyperglycemia on the liver of neonates using multi-omics analysis. The findings suggest that maternal hyperglycemia can lead to lipid accumulation and abnormal choline metabolism in the liver of newborns.
MOLECULAR METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Diana M. Bessa de Sousa, Rodolphe Poupardin, Saul A. Villeda, Adam B. Schroer, Thomas Froehlich, Vanessa Frey, Wolfgang Staffen, Heike Mrowetz, Barbara Altendorfer, Michael S. Unger, Bernhard Iglseder, Bernhard Paulweber, Eugen Trinka, Janne Cadamuro, Martin Drerup, Katharina Schallmoser, Ludwig Aigner, Kathrin M. Kniewallner
Summary: Alzheimer's disease (AD) and aging are associated with platelet hyperactivity, but the mechanisms underlying abnormal platelet function in AD and aging are poorly understood. This study investigated the molecular profile of platelet activation in AD patients, non-demented elderly, and young controls. The results showed increased platelet activation in AD and aged individuals compared to young controls based on proteomic analysis, and dysregulation of proteolytic machinery and autophagy in AD and aging based on transcriptomic profiling.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Developmental Biology
Katja Eubler, Karolina M. Caban, Gregory A. Dissen, Ulrike Berg, Dieter Berg, Carola Herrmann, Nicole Kreitmair, Astrid Tiefenbacher, Thomas Frohlich, Artur Mayerhofer
Summary: This study discovered the expression of TRPV2 in the ovary and its involvement in inflammatory and immunological processes. The TRPV2 agonist CBD was found to induce Ca2+ fluxes and the production of inflammatory factors, as well as interfere with progesterone synthesis and alter the proteome and secretome.
MOLECULAR HUMAN REPRODUCTION
(2023)
Article
Cell & Tissue Engineering
Kazutoshi Okamoto, Hitomi Matsunari, Kazuaki Nakano, Kazuhiro Umeyama, Koki Hasegawa, Ayuko Uchikura, Shuko Takayanagi, Masahito Watanabe, Jun Ohgane, Michael Stirm, Mayuko Kurome, Nikolai Klymiuk, Masaki Nagaya, Eckhard Wolf, Hiroshi Nagashima
Summary: This study demonstrated that DMD-XKOXWT pigs could serve as a suitable large animal model for understanding the pathogenic mechanism in DMD carriers and developing therapies for female DMD carriers.
REGENERATIVE THERAPY
(2023)