Article
Geriatrics & Gerontology
Dengqiu Xu, Sijia Li, Lu Wang, Jingwei Jiang, Lei Zhao, Xiaofei Huang, Zeren Sun, Chunjie Li, Lixin Sun, Xihua Li, Zhenzhou Jiang, Luyong Zhang
Summary: This study found that TAK1 activation worsens fibrosis and muscle degeneration, while TAK1 inhibition can improve muscle quality and function, providing a potential new therapeutic approach for DMD.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2021)
Article
Biochemistry & Molecular Biology
Jacopo Morroni, Leonardo Schirone, Valentina Valenti, Clemens Zwergel, Carles Sanchez Riera, Sergio Valente, Daniele Vecchio, Sonia Schiavon, Rino Ragno, Antonello Mai, Sebastiano Sciarretta, Biliana Lozanoska-Ochser, Marina Bouche
Summary: Chronic cardiac muscle inflammation and subsequent fibrotic tissue deposition are key features in Duchenne Muscular Dystrophy (DMD). Corticosteroids are currently the treatment of choice for delaying DMD progression, but there is a need for new anti-inflammatory therapies due to the adverse effects associated with long-term corticosteroid use. In this study, the inhibition of PKC theta was found to significantly reduce immune cell infiltration, necrosis, and fibrosis in the heart. Functional improvements were also observed in left ventricle fractional shortening. These findings suggest that PKC theta pharmacological inhibition could be an attractive therapeutic approach for treating dystrophic cardiomyopathy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Lizzia Raffaghello, Elisa Principi, Serena Baratto, Chiara Panicucci, Sara Pintus, Francesca Antonini, Genny Del Zotto, Andrea Benzi, Santina Bruzzone, Paolo Scudieri, Carlo Minetti, Elisabetta Gazzerro, Claudio Bruno
Summary: In this study, the therapeutic effectiveness of a selective P2X7 purinoreceptor antagonist, A438079, was evaluated in limb-girdle muscular dystrophy R3. The results showed that the P2X7 antagonist improved clinical parameters, reduced muscle inflammation and fibrosis, and upregulated immunosuppressive regulatory T cells.
Article
Multidisciplinary Sciences
Pedro Gameiro dos Santos, Ana Rita Soares, Solveig Thorsteinsdottir, Gabriela Rodrigues
Summary: The extracellular matrix (ECM) is important for cell structure and signaling. Traditional 2D cell culture models cannot accurately represent in vivo processes. Deficiencies in ECM composition and cell-ECM interactions contribute to various diseases.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Multidisciplinary Sciences
Pedro Gameiro dos Santos, Ana Rita Soares, Solveig Thorsteinsdottir, Gabriela Rodrigues
Summary: The extracellular matrix (ECM) is important for cell structure and signaling. Two-dimensional cell culture models oversimplify cell-ECM interactions, while deficiencies in ECM and cell-ECM interactions contribute to disease progression.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Biochemistry & Molecular Biology
Viktorija Cernisova, Ngoc Lu-Nguyen, Jessica Trundle, Shan Herath, Alberto Malerba, Linda Popplewell
Summary: Duchenne muscular dystrophy (DMD) is a rare neuromuscular disease that primarily affects newborn males. Gene addition therapy using adeno-associated viral vectors has shown significant improvement in muscle function and prevention of fibrosis in a relevant animal model of DMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Darko Bosnakovski, David Oyler, Ana Mitanoska, Madison Douglas, Elizabeth T. Ener, Ahmed S. Shams, Michael Kyba
Summary: FSHD is a disease caused by loss of silencing of the DUX4 gene, but the presence of the DUX4 protein in affected muscle has not been directly detected. This study used an animal model to investigate the extent of muscle regeneration following DUX4-mediated degeneration. The results showed that muscle histology could recover significantly after DUX4 expression was switched off, but the fibroadipogenic progenitor compartment remained elevated and the recovered muscle had a propensity for severe fibrosis. These findings have potential implications for therapeutic approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Rekha Balakrishnan, Satvik Mareedu, Gopal J. Babu
Summary: The reduction or elimination of sarcolipin (SLN) expression improves muscle metabolism, reduces oxidative stress, improves muscle pathology, and protects mdx mice from glucose intolerance in the Duchenne muscular dystrophy (DMD) mouse model.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Juan Shugert Aguayo, John M. Shelton, Wei Tan, Dinesh Rakheja, Chunyu Cai, Ahmed Shalaby, Jeon Lee, Susan T. Iannaccone, Lin Xu, Kenneth Chen, Dennis K. Burns, Yanbin Zheng
Summary: A new mouse model of muscular dystrophies (MD) driven by ectopic expression of PLAG1 was reported, which showed dystrophic features similar to human MD pathology. The study confirmed the repression of Dmd gene by ectopic PLAG1 expression and suggested the potential contribution of excess IGF2 in this model. This research provides new insights into the pathogenesis of MD and potential new treatment strategies.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Alexander B. Andre, Liqiang Zhang, Jalen D. Nix, Nora Elmadbouly, Alexandra R. Lucas, Jeanne Wilson-Rawls, Alan Rawls
Summary: Duchenne muscular dystrophy is a rare disease that affects males and current treatment options have serious side effects. A study suggests that a new immune-modulating protein called Pegylated Serp-1 can improve inflammation and fibrosis, potentially providing a new therapeutic approach for Duchenne muscular dystrophy.
Article
Chemistry, Organic
Yongdong Su, Prithi Raguraman, Rakesh N. Veedu, Vyacheslav V. Filichev
Summary: 2'-O-Methyl antisense oligonucleotides with various modifications were designed to skip exon-23 in dystrophin pre-mRNA transcript in mdx mice myotubes. The study found that AOs with N+ modifications had increased thermal stability towards complementary mRNA, while AOs with Ts modifications showed better exon skipping effects.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Jorge Alonso-Perez, Ana Carrasco-Rozas, Maria Borrell-Pages, Esther Fernandez-Simon, Patricia Pinol-Jurado, Lina Badimon, Lutz Wollin, Cinta Lleixa, Eduard Gallardo, Montse Olive, Jordi Diaz-Manera, Xavier Suarez-Calvet
Summary: This study found that nintedanib has a positive effect on a murine model of alpha-sarcoglycanopathy. Nintedanib can improve muscle function and architecture by reducing muscle fibrosis and degeneration and reverting the chronic inflammatory environment.
Article
Cell Biology
Ariany Oliveira-Santos, Marisela Dagda, Jennifer Wittmann, Robert Smalley, Dean J. Burkin
Summary: LAMA2-CMD is a neuromuscular disease caused by mutations in the LAMA2 gene, leading to the loss of laminin-211/221 heterotrimers in skeletal muscle. Patients exhibit severe hypotonia and progressive muscle weakness, with no effective treatment currently available. The loss of laminin-alpha 2 results in muscle degeneration, defective muscle repair, and dysregulation of multiple signaling pathways. Vemurafenib, a serine/threonine kinase inhibitor, was found to partially restore signaling pathways and improve histopathology in a mouse model of LAMA2-CMD, but did not improve muscle function.
DISEASE MODELS & MECHANISMS
(2023)
Article
Cell Biology
Yu Zhang, Christopher Zeuthen, Carol Zhu, Fang Wu, Allison T. Mezzell, Thomas J. Whitlow, Hyojung J. Choo, Katherine E. Vest
Summary: Oculopharyngeal muscular dystrophy (OPMD) is a late-onset dominant disease primarily affecting craniofacial muscles with no current pharmacologic treatments available. Using a mouse model, this study discovered pathology in pharyngeal muscles and satellite cells, suggesting aberrant gain of PABPN1 function contributes to the craniofacial pathology in OPMD.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Kenji Rowel Q. Lim, Md Nur Ahad Shah, Stanley Woo, Harry Wilton-Clark, Pavel Zhabyeyev, Faqi Wang, Rika Maruyama, Gavin Y. Oudit, Toshifumi Yokota
Summary: The study showed that overexpression of Dp71 in del52;WT mice has a more detrimental effect on cardiac function than on skeletal muscles, providing insight into the role of Dp71 in DMD pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Francesca Giulimondi, Elisabetta Vulpis, Luca Digiacomo, Maria Valeria Giuli, Angelica Mancusi, Anna Laura Capriotti, Aldo Lagana, Andrea Cerrato, Riccardo Zenezini Chiozzi, Carmine Nicoletti, Heinz Amenitsch, Francesco Cardarelli, Laura Masuelli, Roberto Bei, Isabella Screpanti, Daniela Pozzi, Alessandra Zingoni, Saula Checquolo, Giulio Caracciolo
Summary: The study explores the use of DNA charge to generate unPEGylated liposome/DNA complexes that can slip past the human immune system, forming proteoDNAsomes which maintain their synthetic identity more efficiently and accumulate less in the body compared to PEGylated systems.
Article
Endocrinology & Metabolism
Fabiola Marino, Mariangela Scalise, Nadia Salerno, Luca Salerno, Claudia Molinaro, Donato Cappetta, Michele Torella, Marta Greco, Daniela Foti, Ferdinando C. Sasso, Pasquale Mastroroberto, Antonella De Angelis, Georgina M. Ellison-Hughes, Maurilio Sampaolesi, Marcello Rota, Francesco Rossi, Konrad Urbanek, Bernardo Nadal-Ginard, Daniele Torella, Eleonora Cianflone
Summary: Diabetes mellitus affects the biology of cardiac stem/progenitor cells, inhibiting their regenerative potential. By clearing senescent cells, the function of these cells can be restored, resulting in improved cardiac function in diabetic patients.
Article
Biochemistry & Molecular Biology
Jacopo Morroni, Leonardo Schirone, Valentina Valenti, Clemens Zwergel, Carles Sanchez Riera, Sergio Valente, Daniele Vecchio, Sonia Schiavon, Rino Ragno, Antonello Mai, Sebastiano Sciarretta, Biliana Lozanoska-Ochser, Marina Bouche
Summary: Chronic cardiac muscle inflammation and subsequent fibrotic tissue deposition are key features in Duchenne Muscular Dystrophy (DMD). Corticosteroids are currently the treatment of choice for delaying DMD progression, but there is a need for new anti-inflammatory therapies due to the adverse effects associated with long-term corticosteroid use. In this study, the inhibition of PKC theta was found to significantly reduce immune cell infiltration, necrosis, and fibrosis in the heart. Functional improvements were also observed in left ventricle fractional shortening. These findings suggest that PKC theta pharmacological inhibition could be an attractive therapeutic approach for treating dystrophic cardiomyopathy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Valentina Piastra, Angelina Pranteda, Gianluca Bossi
Summary: Cancer target therapy relies on identifying new molecular factors to improve treatment outcomes. MKK3, an evolutionarily conserved protein kinase, has controversial roles in cancer. Analysis of recent literature reveals that MKK3 functions differently in various types of tumors, playing both oncogenic and tumor-suppressive roles. This suggests that MKK3 could be a potential molecular target for designing more effective anticancer therapies.
Article
Oncology
Rossella Loria, Valentina Laquintana, Stefano Scalera, Rocco Fraioli, Valentina Caprara, Italia Falcone, Chiara Bazzichetto, Marta Di Martile, Laura Rosano, Donatella Del Bufalo, Gianluca Bossi, Isabella Sperduti, Irene Terrenato, Paolo Visca, Silvia Soddu, Michele Milella, Gennaro Ciliberto, Rita Falcioni, Virginia Ferraresi, Giulia Bon
Summary: This study reveals that high expression of SEMA6A is associated with poor prognosis in BRAF-mutant melanoma and plays a critical role in promoting tumor aggressiveness and resistance to targeted therapies. SEMA6A may serve as a potential predictor for the efficacy of dual BRAF/MEK inhibition.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Francesco Millozzi, Andrea Papait, Marina Bouche, Ornella Parolini, Daniela Palacios
Summary: Skeletal muscle has strong regenerative ability under normal conditions, but it is diminished in physio-pathological conditions. Inflammation is a major characteristic of many muscle diseases and aging muscles, and immunomodulation shows promise as a therapeutic approach. Nano-sized materials are being explored as biocarriers to release immunomodulatory agents in damaged tissues, allowing effective doses with limited side effects. This review discusses the current use of nano-sized materials to modulate the immune response in muscle diseases and explores opportunities, challenges, and limitations in the field of nano-immunomodulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Tim Vervliet, Robin Duelen, Ankit Pradhan, Rita La Rovere, H. Llewelyn Roderick, Maurilio Sampaolesi
Summary: Bcl-2 plays a crucial role in the differentiation of cardiomyocytes, and its loss delays the induction of pluripotent stem cells into cardiomyocytes, leading to reduced expression and activity of the cardiomyocyte Ca2+ toolkit, as well as decreased c-Myc expression and nuclear localization in the early phase of cardiac differentiation.
JOURNAL OF CELL SCIENCE
(2023)
Review
Genetics & Heredity
Giulio Cossu, Rossana Tonlorenzi, Silvia Brunelli, Maurilio Sampaolesi, Graziella Messina, Emanuele Azzoni, Sara Benedetti, Stefano Biressi, Chiara Bonfanti, Laricia Bragg, Jordi Camps, Ornella Cappellari, Marco Cassano, Fabio Ciceri, Marcello Coletta, Diego Covarello, Stefania Crippa, M. Gabriella Cusella-De Angelis, Luciana De Angelis, Arianna Dellavalle, Jordi Diaz-Manera, Daniela Galli, Francesco Galli, Cesare Gargioli, Mattia F. M. Gerli, Giorgia Giacomazzi, Beatriz G. Galvez, Hidetoshi Hoshiya, Maria Guttinger, Anna Innocenzi, M. Giulia Minasi, Laura Perani, Stefano C. Previtali, Mattia Quattrocelli, Martina Ragazzi, Urmas Roostalu, Giuliana Rossi, Raffaella Scardigli, Dario Sirabella, Francesco Saverio Tedesco, Yvan Torrente, Gonzalo Ugarte
Summary: In 2002, we discovered a group of vessel-associated progenitors called mesoangioblasts (MABs). Studies over the past decade have shown that muscle development and regeneration are more complex than previously thought. We identified the origin of MABs as partly from the embryonic aorta and later from the microvasculature of skeletal muscle. MABs could be expanded in vitro and cross the vessel wall, making them a potential choice for cell therapy of muscular dystrophies.
FRONTIERS IN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Martina Gatti, Katarina Stoklund Dittlau, Francesca Beretti, Laura Yedigaryan, Manuela Zavatti, Pietro Cortelli, Carla Palumbo, Emma Bertucci, Ludo van den Bosch, Maurilio Sampaolesi, Tullia Maraldi
Summary: Neuromuscular junctions are important for communication between spinal motor neurons and skeletal muscle, and their vulnerability in degenerative diseases like muscle atrophy is poorly understood. Recent studies have shown the regenerative potential of stem cells and extracellular vesicles in muscle fiber regeneration, but their role in counteracting NMJ perturbations is not clear. In this study, a co-culture system was used to investigate the effects of AFSC-derived EVs on NMJ alterations induced by muscle atrophy. The presence of EVs reduced morphological and functional defects and prevented oxidative stress in atrophic myotubes. This study provides a valuable tool for studying MN and myotube interactions and demonstrates the efficacy of AFSC-EVs in counteracting NMJ perturbations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Chiara Della Peruta, Biliana Lozanoska-Ochser, Alessandra Renzini, Viviana Moresi, Carles Sanchez Riera, Marina Bouche, Dario Coletti
Summary: Thanks to precision medicine, personalized treatments based on sex have emerged in recent years. Male and female skeletal muscles have significant differences, which impacts diagnosis and therapy. Men have more muscle and exhibit different inflammation responses, leading to different treatment outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Physiology
Laura Yedigaryan, Maurilio Sampaolesi
Summary: Duchenne muscular dystrophy (DMD) is a severe disorder caused by mutations in the dystrophin gene, leading to muscle fiber degradation and weakness. Extracellular vesicles (EVs), secreted by cells, may play a role in DMD pathology and could serve as biomarkers for specific pathological processes. Additionally, EVs can be used for targeted cargo delivery and inhibition of EV secretion, providing potential therapeutic strategies for DMD.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Medicine, Research & Experimental
Angelina Pranteda, Valentina Piastra, Martina Serra, Roberta Bernardini, Federica Lo Sardo, Silvia Carpano, Maria Grazia Diodoro, Armando Bartolazzi, Michele Milella, Giovanni Blandino, Gianluca Bossi
Summary: Understanding the molecular mechanisms of BRAF inhibitor resistance is crucial for the treatment of CRC patients with BRAF mutations. In this study, higher levels of MKK3 transcript were observed in CRC lines with acquired resistance to BRAF inhibitors. Additionally, MKK3 was found to interact with and stabilize the c-Myc protein, preventing the effects of dabrafenib in drug-resistant CRC cells.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Cell Biology
M. Corvelyn, J. Meirlevede, J. Deschrevel, E. Huyghe, E. De Wachter, G. Gayan-Ramirez, M. Sampaolesi, A. Van Campenhout, K. Desloovere, D. Costamagna
Summary: Cerebral palsy (CP) is a common condition causing lifelong physical disability in children. Previous studies have shown changes in muscle properties, such as decreased number of satellite cells and altered fusion capacity. However, these observations vary widely among studies, possibly due to differences in patient population, lack of control data, methodology, and muscle assessment. This study aimed to further investigate CP muscle pathology and confirm previous findings of increased satellite cell fusion capacity.
Article
Cell Biology
Domiziana Costamagna, Valeria Bastianini, Marlies Corvelyn, Robin Duelen, Jorieke Deschrevel, Nathalie De Beukelaer, Hannah De Houwer, Maurilio Sampaolesi, Ghislaine Gayan-Ramirez, Anja Van Campenhout, Kaat Desloovere
Summary: This study aims to clarify the impact of BoNT on growing muscles by analyzing the effect of BoNT on muscle stem cells in vitro, and by following the effect of in vivo BoNT administration on these cells obtained from children with CP. The results show that in vitro BoNT does not affect muscle differentiation or collagen production, but it does affect neuromuscular junctions. Further studies are needed to understand the long-term and collateral effects of BoNT in the muscles of children with CP.
Article
Biology
Giulia Buonaiuto, Valeria Taliani, Carmine Nicoletti, Fabio Desideri, Monica Ballarino
Summary: The interaction between RNA and specific RNA-binding proteins plays a crucial role in gene expression regulation through complex networks. Understanding the exact environment in which this interaction occurs is important, as it can vary depending on the organism and cellular context. This study presents an optimized protocol to identify the RNA interactome of specific RNA-binding proteins, focusing on long non-coding RNAs in mouse embryonal hearts.