Article
Multidisciplinary Sciences
Michael J. Stec, Qi Su, Christina Adler, Lance Zhang, David R. Golann, Naveen P. Khan, Lampros Panagis, S. Armando Villalta, Min Ni, Yi Wei, Johnathon R. Walls, Andrew J. Murphy, George D. Yancopoulos, Gurinder S. Atwal, Sandra Kleiner, Gabor Halasz, Mark W. Sleeman
Summary: Using spatial transcriptomics and single-cell RNA sequencing datasets, a high-resolution cellular and molecular spatial atlas of the severely dystrophic D2-mdx mouse model was generated. Clustering analysis revealed the nonuniform distribution of unique cell populations associated with multiple regenerative timepoints, faithfully recapitulating the asynchronous regeneration observed in human DMD muscle. Through spatiotemporal gene expression signatures, it was found that propagation of inflammatory and fibrotic signals from locally damaged areas contributes to widespread pathology and identifying targetable pathways for DMD therapy within discrete microenvironments. Overall, this spatial atlas of dystrophic muscle provides a valuable resource for studying DMD disease biology and therapeutic target discovery.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Silvia Consalvi, Luca Tucciarone, Elisa Macri, Marco De Bardi, Mario Picozza, Illari Salvatori, Alessandra Renzini, Sergio Valente, Antonello Mai, Viviana Moresi, Pier Lorenzo Puri
Summary: Late-stage mdx FAPs exhibit abnormal HDAC activity and genome-wide alterations of histone acetylation that cannot be fully reversed by HDACi. HDACi show general resistance in inducing H3K9/14 hyperacetylation in late-stage mdx FAPs, but is effective in reducing promoter acetylation and blunting SASP gene activation.
Article
Medicine, Research & Experimental
Yan Wang, Yanfeng Xiao, Yanyan Zheng, Le Yang, Dong Wang
Summary: In this study, it was found that ADAMTS1 levels were increased in mdx mice lacking dystrophin and DMD patients. Treatment with anti-ADAMTS1 improved muscle function, reduced muscle fibrosis, and enhanced muscle strength in mdx mice. This suggests that ADAMTS1 may be a potential target for developing new biological therapies for DMD.
Article
Multidisciplinary Sciences
Ziad Al Tanoury, John F. Zimmerman, Jyoti Rao, Daniel Sieiro, Harold M. McNamara, Thomas Cherrier, Alejandra Rodriguez-delaRosa, Aurore Hick-Colin, Fanny Bousson, Charlotte Fugier-Schmucker, Fabio Marchiano, Bianca Habermann, Jerome Chal, Alexander P. Nesmith, Svetlana Gapon, Erica Wagner, Vandana A. Gupta, Rhonda Bassel-Duby, Eric N. Olson, Adam E. Cohen, Kevin Kit Parker, Oliver Pourquie
Summary: This study introduces an in vitro human model to investigate the pathology of Duchenne muscular dystrophy (DMD) and test new therapeutic approaches. The researchers describe an optimized protocol for differentiating human induced pluripotent stem cells (iPSC) to a late myogenic stage, which allows them to replicate classic DMD phenotypes in isogenic DMD-mutant iPSC lines. Treatment with prednisolone significantly improves muscle function in DMD iPSC lines, challenging the prevailing view that its benefits are solely due to anti-inflammatory properties.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biotechnology & Applied Microbiology
Ling Leng, Xue Dong, Xianjun Gao, Ning Ran, Mengyuan Geng, Bingfeng Zuo, Yingjie Wu, Wei Li, Hua Yan, Gang Han, HaiFang Yin
Summary: Duchenne muscular dystrophy (DMD) is a genetic disorder that compromises cellular membranes, but the use of exosomes can improve muscle membrane integrity, leading to functional improvements in DMD patients.
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
Geriatrics & Gerontology
Francesca M. Alves, Kai Kysenius, Marissa K. Caldow, Justin P. Hardee, Jin D. Chung, Jennifer Trieu, Dominic J. Hare, Peter J. Crouch, Scott Ayton, Ashley Bush, Gordon S. Lynch, Rene Koopman
Summary: Muscle tissues from dystrophic mice showed increased iron levels and dysregulated iron-related proteins associated with the pathology. Muscle iron levels were manipulated by iron chelation and iron-enriched feed, with chelation reducing fibrosis and reactive oxygen species but suppressing certain proteins, while iron supplementation increased specific proteins without altering other aspects of pathology.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2022)
Article
Multidisciplinary Sciences
Chady H. Hakim, Sandeep R. P. Kumar, Dennis O. Perez-Lopez, Nalinda B. Wasala, Dong Zhang, Yongping Yue, James Teixeira, Xiufang Pan, Keqing Zhang, Emily D. Million, Christopher E. Nelson, Samantha Metzger, Jin Han, Jacqueline A. Louderman, Florian Schmidt, Feng Feng, Dirk Grimm, Bruce F. Smith, Gang Yao, N. Nora Yang, Charles A. Gersbach, Shi-jie Chen, Roland W. Herzog, Dongsheng Duan
Summary: The study investigates the immune responses induced by AAV-CRISPR therapy in canine models of DMD, indicating that the Cas9-specific T cell response may pose a critical barrier to treatment.
NATURE COMMUNICATIONS
(2021)
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
Biochemistry & Molecular Biology
Arkady Uryash, Alfredo Mijares, Eric Esteve, Jose A. A. Adams, Jose R. R. Lopez
Summary: Duchenne muscular dystrophy (DMD) is a genetic muscular disorder caused by mutations in the dystrophin gene. This study found anomalous regulation of resting intracellular Ca2+ in vascular smooth muscle cells (VSMCs) from a mouse model of DMD. Hypoxia leads to Ca2+ overload in VSMCs, and the lack of dystrophin makes them more susceptible to this overload.
Article
Physiology
Thomas G. George, Laurin M. Hanft, Maike Krenz, Timothy L. Domeier, Kerry S. McDonald
Summary: Dystrophic cardiomyopathy is caused by mutations in the dystrophin gene, particularly in Duchenne muscular dystrophy (DMD). This study aimed to investigate the role of myofilament function in dystrophic cardiomyopathy using a mouse model. The results suggest that dystrophin helps mitigate length dependence of activation, and that mavacamten could be a potential treatment for DMD-associated dystrophic cardiomyopathy.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Physiology
William J. Valentine, Sherif A. Mostafa, Suzumi M. Tokuoka, Fumie Hamano, Natsuko F. Inagaki, Joel Z. Nordin, Norio Motohashi, Yoshihiro Kita, Yoshitsugu Aoki, Takao Shimizu, Hideo Shindou
Summary: In Duchenne muscular dystrophy (DMD), changes in phosphatidylcholine (PC) levels, specifically higher levels of PC 34:1 and lower levels of PC 34:2, are associated with muscle wasting. The study found that PC 34:1 levels were elevated in regenerated mdx muscles, while PC 34:2 levels were also elevated in mdx muscles. Experimental factors such as muscle types, mouse ages, and diets were found to impact the PC alterations.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Clinical Neurology
Daniel Natera-de Benito, Sergio Aguilera-Albesa, Laura Costa-Comellas, Mar Garcia-Romero, Maria Concepcion Miranda-Herrero, Julia Rubies Olives, Oscar Garcia-Campos, Elena Martinez del Val, Maria Josefa Martinez Garcia, Inmaculada Medina Martinez, Ramon Cancho-Candela, Miguel A. Fernandez-Garcia, Samuel Ignacio Pascual-Pascual, David Gomez-Andres, Andres Nascimento
Summary: This study described the clinical characteristics and outcomes of COVID-19 in 29 children with neuromuscular disorders, showing that no severe complications were observed and the majority of cases were asymptomatic or mild.
JOURNAL OF NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Martina Sandona, Federica Esposito, Anna Cargnoni, Antonietta Silini, Pietro Romele, Ornella Parolini, Valentina Saccone
Summary: This study demonstrates that the secretome and extracellular vesicles derived from mesenchymal stromal cells from the amniotic membrane (hAMSCs) can promote muscle regeneration by stimulating proliferation and differentiation of muscle stem cells. It also shows that these factors can modulate the muscle stem cell niche and reduce fibrosis and muscle exhaustion. These findings suggest a potential novel treatment for Duchenne muscular dystrophy (DMD).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Francesca Florio, Sara Vencato, Filomena T. Papa, Michela Libergoli, Eyemen Kheir, Imen Ghzaiel, Thomas A. Rando, Yvan Torrente, Stefano Biressi
Summary: Fibrosis in Duchenne muscular dystrophy (DMD) is caused by the crosstalk between the complement and the WNT signaling pathways, as well as the functional interactions of fibro-adipogenic progenitors and macrophages. Inhibiting the C1r/s subunits can reduce WNT signaling activation and mitigate fibrogenic characteristics, providing new insights into therapeutic strategies for muscular dystrophy fibrosis.
EMBO MOLECULAR MEDICINE
(2023)
Letter
Critical Care Medicine
Ryota Sato, Daisuke Hasegawa, Siddharth Dugar
INTENSIVE CARE MEDICINE
(2022)
Article
Hematology
Takaya Honda, Masayoshi Yamaoka, Yoko Mikami Terao, Daisuke Hasegawa, Tadashi Kumamoto, Masatoshi Takagi, Kenichi Yoshida, Seishi Ogawa, Hiroaki Goto, Masaharu Akiyama
Summary: Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of peripheral T-cell lymphoma that mainly affects adolescents and young adults. This case report presents a 3-year-old girl with HSTCL who achieved remission with salvage chemotherapy and umbilical cord blood transplantation. Molecular genetic characteristics play a crucial role in selecting individualized treatment regimens for HSTCL patients.
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2022)
Article
Health Care Sciences & Services
Tomomi Hayase, Makiko N. Mieno, Kyoko Kobayashi, Naoko Mori, Adam Jon Lebowitz, Yoko Kato, Yuya Saito, Yuki Yuza, Hirozumi Sano, Shinya Osone, Tsukasa Hori, Yuichi Shinkoda, Nobuyuki Yamamoto, Daiichiro Hasegawa, Michihiro Yano, Miho Ashiarai, Daisuke Hasegawa, Akihisa Sawada, Takuhiro Yamaguchi, Akira Morimoto, Keitaro Fukushima
Summary: The study translated and validated the use of the Memorial Symptom Assessment Scale (MSAS) in Japanese pediatric cancer patients. The MSAS-J was found to be a reliable and valid instrument for assessing symptoms in this population.
JOURNAL OF PAIN AND SYMPTOM MANAGEMENT
(2022)
Editorial Material
Pediatrics
Daisuke Hasegawa
PEDIATRICS INTERNATIONAL
(2022)
Letter
Veterinary Sciences
Satoshi Mizuno, Rikako Asada, Daisuke Hasegawa
VETERINARY MEDICINE AND SCIENCE
(2022)
Article
Veterinary Sciences
Daisuke Hasegawa, Miyoko Saito, Masato Kitagawa
Summary: This article summarizes the current standards of intracranial epilepsy surgery in human medicine and discuss its current status and expectation in veterinary medicine. Corpus callosotomy is the most common disconnection surgery for drug-resistant epilepsy in dogs. However, other types of disconnection and resection surgeries for focal epilepsy are limited to experimental studies and anecdotal case reports. Veterinary epilepsy surgery is a new and challenging field, but with the development of advanced presurgical evaluations, it may become more widespread.
VETERINARY JOURNAL
(2022)
Review
Radiology, Nuclear Medicine & Medical Imaging
Yuko Tsujioka, Taiki Nozaki, Yasunari Niimi, Jay Starkey, Daisuke Hasegawa, Mutsuko Kondo, Mikako Enokizono, Akari Makidono, Tatsuo Kono, Masahiro Jinzaki
Summary: Vascular malformations are a complex group of disorders that can enlarge over time, impacting quality of life and posing a risk of fatality. Gene mutations responsible for vascular anomalies have been identified, and molecular agents targeting these mutations are currently being developed. Diagnostic imaging findings can guide genetic testing and enable specific diagnosis.
Article
Veterinary Sciences
Naoko Yayoshi, Karin Yoshida, Masashi Terao, Tsuyoshi Ozawa, Hiroaki Kamishina, Fumitaka Takahashi, Yasushi Hara, Yoshihiko Yu, Daisuke Hasegawa
Summary: This study describes three cases of spinal epidural arteriovenous fistula in young adult cats. The presence of vein dilatation in the epidural space was observed through magnetic resonance imaging and computed tomography angiography. Surgical treatment involving dorsal laminectomy and occlusion of interarcuate branches resulted in symptom relief and no recurrence during the follow-up period.
JOURNAL OF VETERINARY INTERNAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Amane Hori, Ryuji Saito, Kenichi Suijo, Michael R. Kushnick, Daisuke Hasegawa, Koji Ishida, Norio Hotta
Summary: This study aimed to investigate whether blood flow restriction (BFR) during moderate-intensity aerobic training can accelerate the adaptation of the time constant (tau) of phase II oxygen uptake (<(V) over dot>O-2) kinetics in the moderate-intensity exercise domain. The results showed that tau significantly decreased in the BFR group at the mid-point of training, while the CON group showed a decrease at the end of training. The BFR group had significantly lower tau than the CON group at the mid-point, but there was no significant difference between the two groups at the end of training.
SCIENTIFIC REPORTS
(2022)
Article
Immunology
Masato Kobayashi, Honami Sekine, Yushi Ogawa, Shin Toyama, Yuki Komukai, Moto Nakamura, Ryusuke Mitanda, Marina Hayashi, Masanori Kobayashi, Tatsuya Hori
Summary: The elevation of MDSCs in the peripheral blood of pregnant canines may contribute to reducing maternal immune activity. Relaxin induces monocytic MDSCs and inhibits T cell activation, highlighting its novel role in pregnancy and maternal-fetal immune tolerance.
JOURNAL OF REPRODUCTIVE IMMUNOLOGY
(2023)
Article
Veterinary Sciences
Tatsuya Hori, Hideo Tajima, Shinichi Sasaki, Mizuki Karasawa, Madoka Yoshizawa, Takuya Kuribara, Hidemasa Hori, Fujio Yamamoto, Etsuo Narushima, Kiyoshi Nagai, Kazuaki Nippashi, Yurie Sataka, Masato Kobayashi, Masanori Kobayashi, Toshihiko Tsutsui
Summary: This study collected cauda epididymal sperm from Amur leopard cats and Tsushima leopard cats and compared them with domestic cats. It was found that similar numbers of sperm to those in domestic cats could be collected from the cauda epididymis of Amur leopard cats. However, no or very few cauda epididymal sperm were recovered from older leopard cats, although there were no differences in sperm motility and abnormality. There were no significant differences in sperm quality between cauda epididymal sperm and domestic cats, both immediately after collection and after freezing-thawing.
JOURNAL OF VETERINARY MEDICAL SCIENCE
(2023)
Article
Veterinary Sciences
Masanori Kobayashi, Moe Onozawa, Shiho Watanabe, Tomokazu Nagashima, Kyoichi Tamura, Yoshiaki Kubo, Akiko Ikeda, Kazuhiko Ochiai, Masaki Michishita, Makoto Bonkobara, Masato Kobayashi, Tatsuya Hori, Eiichi Kawakami
Summary: The aim of this study was to establish a novel cPCa cell line and to clarify the antitumor effects of MEK inhibitors on cPCa in vitro and in vivo. The results showed that MEK inhibitors effectively suppressed cell proliferation in cPCa and induced cell cycle arrest by inhibiting ERK activation, leading to tumor regression. MEK inhibitors may be a potential targeted therapy for cPCa with the BRAF V595E mutation.
VETERINARY AND COMPARATIVE ONCOLOGY
(2023)
Article
Veterinary Sciences
Kazumasa Nakatsuka, Brian Zanghi, Daisuke Hasegawa
Summary: This study found that feeding a commercially available MCT-enriched diet concurrently with ZNS is safe for dogs with IE and does not affect ZNS concentration.
BMC VETERINARY RESEARCH
(2023)
Article
Veterinary Sciences
Satoshi Mizuno, Rikako Asada, Yoshihiko Yu, Yuji Hamamoto, Daisuke Hasegawa
Summary: In recent years, EEG in veterinary medicine has become important in diagnosing and determining the epileptogenic focus. Cats with temporal lobe epilepsy were administered ketamine to induce sedation and immobilization for EEG recordings, and it was found that ketamine induced more pronounced interictal epileptiform discharges compared to medetomidine. However, caution should be used due to the risk of seizures in cats with TLE.
FRONTIERS IN VETERINARY SCIENCE
(2023)
