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
Multidisciplinary Sciences
Michael Ziemba, Molly Barkhouse, Kitipong Uaesoontrachoon, Mamta Giri, Yetrib Hathout, Utkarsh J. Dang, Heather Gordish-Dressman, Kanneboyina Nagaraju, Eric P. Hoffman
Summary: Duchenne muscular dystrophy is caused by dystrophin deficiency, leading to downstream pathophysiological pathways that drive disability. Dystrophin replacement strategies may trigger these pathways, so combination therapies targeting multiple downstream pathways are crucial. Blood biomarkers could be used to assess drug combinations for treating DMD in both mouse models and human studies.
Article
Biochemistry & Molecular Biology
Yusuke Kawamura, Tetsuro Hida, Bisei Ohkawara, Masaki Matsushita, Takeshi Kobayashi, Shinya Ishizuka, Hideki Hiraiwa, Satoshi Tanaka, Mikito Tsushima, Hiroaki Nakashima, Kenyu Ito, Shiro Imagama, Mikako Ito, Akio Masuda, Naoki Ishiguro, Kinji Ohno
Summary: The anti-histamine drug meclozine promotes the proliferation and survival of human myogenic progenitor cells but inhibits myotube formation. In a mouse model of muscular dystrophy, meclozine improves muscle mass, exercise performance, and reduces ERK1/2 phosphorylation.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Basma A. Al-Mshhdani, Miranda D. Grounds, Peter G. Arthur, Jessica R. Terrill
Summary: Research has shown that oxidation of albumin Cys34 is a sensitive blood biomarker that reflects oxidative stress in muscle tissue of DMD patients. Plasma albumin oxidation reflects muscle dystropathology, supporting its use as a blood biomarker to assist with advancing clinical development of therapies for DMD.
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
Biochemistry & Molecular Biology
Keryn G. Woodman, Chantal A. Coles, Shireen R. Lamande, Jason D. White
Summary: Resveratrol at a lower dosage showed potential efficacy in reducing muscle damage and inflammatory cell markers associated with Duchenne muscular dystrophy, suggesting it as a candidate drug for treating DMD.
Article
Biochemistry & Molecular Biology
Agnese Bonato, Giada Raparelli, Siro Luvisetto, Flavia Forconi, Marianna Cosentino, Felice Tirone, Emanuele Rizzuto, Maurizia Caruso
Summary: We found that cyclin D3-null mice exhibit a shift towards oxidative muscle fibers and improved endurance in response to exercise, as well as enhanced response to fasting. In a model of Duchenne muscular dystrophy (DMD), cyclin D3-deficient mice displayed a higher proportion of oxidative fibers, reduced muscle degeneration/regeneration, and reduced muscle fatigue. This suggests that depletion of cyclin D3 may be a promising therapeutic strategy against DMD.
Article
Neurosciences
Priscila Mantovani Nocetti, Adriano Alberti, Viviane Freiberger, Leticia Ventura, Leoberto Ricardo Grigollo, Cristina Salar Andreau, Rudy Jose Nodari Junior, Daniel Fernandes Martins, Clarissa M. Comim
Summary: The study showed that a swimming protocol for 4 weeks significantly reduced oxidative stress levels and prevented memory impairment in an animal model of DMD.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Cell Biology
Laetitia Marcadet, Emma Sara Juracic, Nasrin Khan, Zineb Bouredji, Hideo Yagita, Leanne M. Ward, A. Russell Tupling, Anteneh Argaw, Jerome Frenette
Summary: Cardiomyopathy is a leading cause of death in DMD patients. Inhibition of RANKL-RANK interaction improves muscle and bone functions in mdx mice. Anti-RANKL treatment prevents cardiac hypertrophy and dysfunction by inhibiting NF-κB and PI3K pathways.
Article
Pharmacology & Pharmacy
Malgorzata Myszka, Olga Mucha, Paulina Podkalicka, Urszula Wasniowska, Jozef Dulak, Agnieszka Loboda
Summary: This study investigated the effects of hydrogen sulfide (H2S) on muscle pathology in dystrophin-deficient mice. The results showed that H2S reduced muscle damage markers, decreased oxidative stress, regulated the expression of disease-related molecules, and promoted angiogenesis. These findings suggest that H2S could be a promising therapeutic factor for Duchenne muscular dystrophy (DMD).
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Marco Ponzetti, Argia Ucci, Antonio Maurizi, Luca Giacchi, Anna Teti, Nadia Rucci
Summary: The study found that Lcn2 plays a significant role in DMD, with its overexpression being associated with bone loss. Ablating Lcn2 can reduce bone loss and improve muscle function, making it a potential therapeutic target for treating DMD-induced bone loss.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Brigida Boccanegra, Ornella Cappellari, Paola Mantuano, Daniela Trisciuzzi, Antonietta Mele, Lisamaura Tulimiero, Michela De Bellis, Santa Cirmi, Francesca Sanarica, Alessandro Giovanni Cerchiara, Elena Conte, Ramona Meanti, Laura Rizzi, Elena Bresciani, Severine Denoyelle, Jean-Alain Fehrentz, Gabriele Cruciani, Orazio Nicolotti, Antonella Liantonio, Antonio Torsello, Annamaria De Luca
Summary: Growth hormone secretagogues (GHSs) have multiple actions including activation of GHS-receptor 1a, control of inflammation and metabolism, enhancement of GH/IGF-1-mediated myogenesis, and inhibition of angiotensin-converting enzyme. This study provides preclinical evidence for the potential benefits of GHSs in Duchenne muscular dystrophy (DMD). The results show that GHSs can improve muscle strength, reduce fibrosis-related parameters, and improve muscle metabolism in mdx mice, suggesting that GHSs have potential as therapeutic agents for DMD.
FRONTIERS IN IMMUNOLOGY
(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
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
Cardiac & Cardiovascular Systems
Melanie Gartz, Margaret Haberman, Mariah J. Prom, Margaret J. Beatka, Jennifer L. Strande, Michael W. Lawlor
Summary: Nicorandil did not exert cardioprotective effects in aged mdx mice, in contrast to previous findings in young mice. This discrepancy may be due to the absence of cardiac disease manifestation in aged mdx mice compared to wild-type mice.
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS
(2022)
Article
Multidisciplinary Sciences
S. Tsimbalyuk, C. M. Donnelly, J. K. Forwood
Summary: The shuttling of macromolecules between the nucleus and cytoplasm is a regulated process mediated by specific interactions between cargo and nuclear transport proteins. In this study, the crystal structure of human importin alpha 7 was presented, providing insights into the structure-function relationships and isoform specificity within the importin alpha family.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Thilini S. Munasinghe, Megan R. Edwards, Sofiya Tsimbalyuk, Olivia A. Vogel, Kate M. Smith, Murray Stewart, Justin K. Foster, Loretta A. Bosence, David Aragao, Justin A. Roby, Christopher F. Basler, Jade K. Forwood
Summary: In this study, the authors biochemically and structurally characterized the interaction between MERS-CoV ORF4b and IMP alpha-family members. They found that mutations in ORF4b alter its binding mechanism with IMP alpha, which impairs nuclear import, interaction with IMP alpha, and inhibition of immune signaling pathways. The study also revealed that the binding sites of NF-kappa B component p50 and ORF4b overlap, suggesting a possible mechanism for inhibition.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Jenny Dunn, Robert D. McCuaig, Abel H. Y. Tan, Wen Juan Tu, Fan Wu, Kylie M. Wagstaff, Anjum Zafar, Sayed Ali, Himanshu Diwakar, Jane E. Dahlstrom, Elaine G. Bean, Jade K. Forwood, Sofiya Tsimbalyuk, Emily M. Cross, Kristine Hardy, Amanda L. Bain, Elizabeth Ahern, Riccardo Dolcetti, Roberta Mazzieri, Desmond Yip, Melissa Eastgate, Laeeq Malik, Peter Milburn, David A. Jans, Sudha Rao
Summary: The study found that a protein called nPKC-theta is enriched in circulating tumor cells (CTCs) in patients with triple-negative breast cancer (TNBC) brain metastases and immunotherapy-resistant metastatic melanoma, and is associated with poor survival in immunotherapy-resistant disease. A novel nPKC-theta inhibitor was designed to target nPKC-theta and showed potential in reducing mesenchymal cancer stem cell signatures in immunotherapy-resistant CTCs and TNBC xenografts.
Correction
Cell Biology
Sofiya Tsimbalyuk, Emily M. Cross, Mikayla Hoad, Camilla M. Donnelly, Justin A. Roby, Jade K. Forwood
Article
Virology
Mikayla Hoad, Emily M. M. Cross, Camilla M. M. Donnelly, Subir Sarker, Justin A. A. Roby, Jade K. K. Forwood
Summary: This study reveals the interaction between the AAV Cap protein and the nuclear transport protein importin alpha (IMP alpha) at an atomic resolution. The research identifies a bipartite nuclear localization signal (NLS) in the porcine AAV Cap that binds to IMP alpha. The findings provide a detailed molecular view of how AAV virions enter the host nucleus.
Article
Pharmacology & Pharmacy
Gualtiero Alvisi, Elisabetta Manaresi, Emily M. Cross, Mikayla Hoad, Nasim Akbari, Silvia Pavan, Daryl Ariawan, Gloria Bua, Gayle F. Petersen, Jade Forwood, Giorgio Gallinella
Summary: Human parvovirus B19 (B19V) is a major pathogen that primarily infects human progenitor cells in bone marrow. The non-structural protein NS1 plays a crucial role in viral replication and host gene expression. This study identified a specific sequence of amino acids as the nuclear localization signal responsible for NS1 nuclear import, which was found to be dependent on importin alpha/beta and energy. Ivermectin, an antiparasitic drug that interferes with importin alpha/beta-dependent nuclear import, inhibited NS1 nuclear accumulation and viral replication.
ANTIVIRAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Manjeet Kumar, Sarah L. Teakel, Crystall Swarbrick, Intifar S. Chowdhury, David C. Thorn, Margaret Sunde, John A. Carver, Jade K. Forwood
Summary: Acot enzymes play important roles in cell signaling, lipid metabolism, inflammation, and ion channel opening. Acot7 can spontaneously form amyloid fibrils under physiological conditions. The aggregation mechanism of Acot7 involves conformational rearrangement and the formation of enhanced beta-sheet structures in the initial phase, followed by the formation of amyloid fibrils.
Article
Veterinary Sciences
Babu K. Nath, Shubhagata Das, Naomie Tidd, Tridip Das, Jade K. Forwood, Shane R. Raidal
Summary: Coinfection of CoHV1 and PiCV in racing rock pigeons caused oral and upper respiratory tract lesions, encephalitis, and fatal systemic disease. Both viruses were found in high viral load in liver, oropharynx, and bursa of Fabricius. The lesions induced by CoHV1 may have been exacerbated by concomitant PiCV infection.
JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION
(2023)
Article
Virology
Camilla M. Donnelly, Olivia A. Vogel, Megan R. Edwards, Paige E. Taylor, Justin A. Roby, Jade K. Forwood, Christopher F. Basler
Summary: Nipah and Hendra viruses are highly pathogenic viruses that cause severe respiratory disease and encephalitis. This study investigates the interaction between viral proteins and cellular structures to gain a better understanding of viral transmission and develop potential therapeutics.
Letter
Microbiology
Peter Speck, Jason Mackenzie, Rowena A. Bull, Barry Slobedman, Heidi Drummer, Johanna Fraser, Lara Herrero, Karla Helbig, Sarah Londrigan, Gregory Moseley, Natalie Prow, Grant Hansman, Robert Edwards, Chantelle Ahlenstiel, Allison Abendroth, David Tscharke, Jody Hobson-Peters, Robson Kriiger-Loterio, Rhys Parry, Glenn Marsh, Emma Harding, David A. Jacques, Matthew J. Gartner, Wen Shi Lee, Julie McAuley, Paola Vaz, Frank Sainsbury, Michelle D. Tate, Jane Sinclair, Allison Imrie, Stephen Rawlinson, Andrew Harman, Jillian M. Carr, Ebony A. Monson, Merilyn Hibma, Timothy J. Mahony, Thomas Tu, Robert J. Center, Lok Bahadur Shrestha, Robyn Hall, Morgyn Warner, Vernon Ward, Danielle E. Anderson, Nicholas S. Eyre, Natalie E. Netzler, Alison J. Peel, Peter Revill, Michael Beard, Alistair R. Legione, Alexandra J. Spencer, Adi Idris, Jade Forwood, Subir Sarker, Damian F. J. Purcell, Nathan Bartlett, Joshua M. Deerain, Bruce J. Brew, Sassan Asgari, Helen Farrell, Alexander Khromykh, Daniel Enosi Tuipulotu, David Anderson, Sevim Mese, Yaman Tayyar, Kathryn Edenborough, Jasim Muhammad Uddin, Abrar Hussain, Connor J. Daymond, Jacinta Agius, Karyn N. Johnson, Paniz Shirmast, Mahdi Abedinzadeshahri, Robin MacDiarmid, Caroline L. Ashley, Jay Laws, Lucy L. Furfaro, Thomas D. Burton, Stephen M. R. Johnson, Zahra Telikani, Mary Petrone, Justin A. Roby, Carolyn Samer, Andreas Suhrbier, April van der Kamp, Anthony Cunningham, Celeste Donato, Jackie Mahar, Wesley D. Black, Subhash Vasudevan, Roman Lenchine, Kirsten Spann, Daniel J. Rawle, Penny Rudd, Jessica Neil, Richard Kingston, Timothy P. Newsome, Ki Wook Kim, Johnson Mak, Kym Lowry, Nathan Bryant, Joanne Meers, Jason A. Roberts, Nigel McMillan, Larisa I. Labzin, Andrii Slonchak, Leon E. Hugo, Bennett Henzeler, Natalee D. Newton, Cassandra T. David, Patrick C. Reading, Camille Esneau, Tatiana Briody, Najla Nasr, Donna McNeale, Brian McSharry, Omid Fakhri, Bethany A. Horsburgh, Grant Logan, Paul Howley, Paul Young
Article
Multidisciplinary Sciences
Seyed Mohammad Ghafoori, Gayle F. Petersen, Deborah G. Conrady, Brandy M. Calhoun, Matthew Z. Z. Stigliano, Ruth O. Baydo, Rena Grice, Jan Abendroth, Donald D. Lorimer, Thomas E. Edwards, Jade K. Forwood
Summary: Influenza virus causes annual outbreaks of flu, resulting in a significant economic burden on the healthcare system. It has caused several pandemics with millions of deaths in the past century. This study characterizes the structures of seven influenza A virus hemagglutinins (HAs) and identifies conserved residues involved in receptor binding. The study also shows that modifications in a certain region disrupt the binding of a specific antibody, providing new insights for anti-influenza vaccine development.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Seyed Mohammad Ghafoori, Soha Abdollahpour, Paniz Shirmast, Jade K. Forwood
Summary: Bacterial antibiotic resistance is a global problem and Acinetobacter baumannii is a significant antibiotic-resistant bacterium. Researchers have determined the structure of a protein from A. baumannii and evaluated its comparisons with other enzymes and cofactors, providing a foundation for future studies.
Article
Virology
Babu Kanti Nath, Tridip Das, Andrew Peters, Suman Das Gupta, Subir Sarker, Jade K. Forwood, Shane R. Raidal, Shubhagata Das
Summary: The study revealed that the genomes of Pigeon circovirus circulating in Australia lack host adapted population structure, but demonstrate natural spillover infection between different countries.
Article
Multidisciplinary Sciences
Wen Juan Tu, Michelle Melino, Jenny Dunn, Robert D. McCuaig, Helle Bielefeldt-Ohmann, Sofiya Tsimbalyuk, Jade K. Forwood, Taniya Ahuja, John Vandermeide, Xiao Tan, Minh Tran, Quan Nguyen, Liang Zhang, Andy Nam, Liuliu Pan, Yan Liang, Corey Smith, Katie Lineburg, Tam H. H. Nguyen, Julian D. J. Sng, Zhen Wei Marcus Tong, Keng Yih Chew, Kirsty R. R. Short, Roger Le Grand, Nabila Seddiki, Sudha Rao
Summary: In vitro, ACE2 can induce SARS-CoV-2 replication by translocating to the nucleus. However, a peptide inhibitor called NACE2i can inhibit viral replication, reduce inflammation and macrophage infiltration, and increase NK cell infiltration in lung tissues from infected Syrian hamsters. NACE2i treatment also leads to ACE2 methylation, decreased viral reservoir, and enhanced immune protection against SARS-CoV-2.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Sofiya Tsimbalyuk, Aleksander Shornikov, Parul Srivastava, Van Thi Bich Le, Imani Warren, Yogesh B. B. Khandokar, Misty L. L. Kuhn, Jade K. K. Forwood
Summary: Polyamines play diverse roles in numerous pathogenic and non-pathogenic organisms, affecting the transcription and translation of key genes and proteins. The bacterial SpeG enzyme exhibits a unique structure and function compared to other SSATs, and its role in different bacterial pathogens varies. This study provides new insight into the structure and function of the SpeG enzyme, shedding light on its molecular role in pathogenic and non-pathogenic bacteria.