Review
Biochemistry & Molecular Biology
Trace Thome, Kyoungrae Kim, Gengfu Dong, Terence E. E. Ryan
Summary: Chronic kidney disease (CKD) affects 700 million people worldwide and leads to the loss of muscle mass and function. Mitochondrial and redox alterations have been found to be involved in CKD-associated myopathy, but the underlying mechanisms are not well understood. Effective treatments to improve muscle health in CKD are still lacking.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Article
Geriatrics & Gerontology
Alessia Geremia, Roberta Sartori, Martina Baraldo, Leonardo Nogara, Valeria Balmaceda, Georgia Ana Dumitras, Stefano Ciciliot, Marco Scalabrin, Hendrik Nolte, Bert Blaauw
Summary: During cancer cachexia, impaired mTORC1 signaling leads to reduced protein synthesis rates in skeletal muscle. Conversely, activation of Akt-mTORC1 signaling can completely reverse muscle loss and force reduction, and prevent the increase in protein degradation observed in muscles from tumor-bearing animals. These findings suggest that skeletal muscle maintains its anabolic capacities during cancer cachexia, potentially explaining the beneficial effects of exercise in cancer patients.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2022)
Article
Food Science & Technology
Pengfei Ren, Xinyue Yu, Qingjuan Tang, Yuchen Huan, Jie Xu, Yuming Wang, Changhu Xue
Summary: This study aimed to assess whether astaxanthin ameliorates weight loss and skeletal muscle atrophy in sorafenib-treated hepatocellular carcinoma mice. The results showed that astaxanthin significantly delayed weight loss and skeletal muscle atrophy in sorafenib-treated mice, without affecting food intake. Astaxanthin enhanced glucose competition in skeletal muscle by targeting the PI3K/Akt/GLUT4 signaling pathway, thereby slowing skeletal muscle atrophy. These findings indicate the significant potential of astaxanthin as a nutritional supplement for cancer patients and the importance of implementing nutritional interventions at the initiation of cancer treatment rather than waiting for cachexia to occur.
MOLECULAR NUTRITION & FOOD RESEARCH
(2023)
Review
Cell Biology
Ming-Ming Chen, Yan Li, Shou-Long Deng, Yue Zhao, Zheng-Xing Lian, Kun Yu
Summary: Mitochondria in skeletal muscle play an important role in producing ATP for muscle contraction, but also produce reactive species as byproducts. Traditionally, an increase in reactive oxygen/nitrogen species (RONS) is associated with oxidative stress and muscle dysfunction, but recent studies have highlighted the physiological significance of an optimal RONS level in skeletal muscle under the influence of antioxidants.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Agriculture, Dairy & Animal Science
Victoria Favorit, Wendy R. Hood, Andreas N. Kavazis, Patricia Villamediana, Kang Nian Yap, Hailey A. Parry, Amy L. Skibiel
Summary: Lactation requires increased nutrient and energy usage. Mitochondrial efficiency and biogenesis in the liver are positively associated with milk yield, while skeletal muscle mitochondrial efficiency remains consistent but experiences oxidative damage.
Article
Multidisciplinary Sciences
Jun-Ha Hwang, Kyung Min Kim, Ho Taek Oh, Gi Don Yoo, Mi Gyeong Jeong, Hyun Lee, Joori Park, Kwon Jeong, Yoon Ki Kim, Young-Gyu Ko, Eun Sook Hwang, Jeong-Ho Hong
Summary: This study reveals that TAZ is a novel stimulator for mitochondrial biogenesis and exercise-induced muscle adaptation. TAZ stimulates the translation of mitochondrial transcription factor A via the Rheb/Rhebl1-mTOR pathway. The knockout of TAZ in mice results in decreased mitochondrial biogenesis, respiratory metabolism, and exercise ability.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Paul A. Roberson, Leonard S. Jefferson, Scot R. Kimball
Summary: This study investigated the mechanisms through which leucine and IGF-1 regulate protein synthesis in skeletal muscle via the mTORC1 pathway. The results demonstrated that IGF-1 promoted phosphorylation of AKT, TSC2, and mTOR, while leucine stimulated protein synthesis.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Jordan M. Johnson, Alek D. Peterlin, Enrique Balderas, Elahu G. Sustarsic, J. Alan Maschek, Marisa J. Lang, Alejandro Jara-Ramos, Vanja Panic, Jeffrey T. Morgan, Claudio J. Villanueva, Alejandro Sanchez, Jared Rutter, Irfan J. Lodhi, James E. Cox, Kelsey H. Fisher-Wellman, Dipayan Chaudhuri, Zachary Gerhart-Hines, Katsuhiko Funai
Summary: Phosphatidylethanolamine (PE) modulates the proton conductance of UCP1, regulating thermogenesis in brown adipose tissue (BAT).
Article
Nutrition & Dietetics
Brandon N. VanderVeen, Thomas D. Cardaci, Patrice Cunningham, Sierra J. McDonald, Brooke M. Bullard, Daping Fan, E. Angela Murphy, Kandy T. Velazquez
Summary: Cachexia diagnosis is associated with prolonged hospital stay and increased healthcare cost for cancer patients, and most cachectic patients do not survive treatment. Treatment complexity is amplified by both the underlying malignancy and anti-cancer therapy, which can independently promote cachexia. Quercetin, a polyphenolic flavonoid, shows potential in protecting against cancer and chemotherapy-induced dysfunction, but its efficacy in maintaining muscle mass in tumor-bearing animals undergoing chemotherapy has not been studied. In this study, quercetin was found to protect against cancer and chemotherapy-induced muscle mass loss through improvement of mitochondrial homeostatic balance.
Article
Biochemistry & Molecular Biology
Hector G. Paez, Peter J. Ferrandi, Christopher R. Pitzer, Junaith S. Mohamed, Stephen E. Alway
Summary: The gene expression of NOR-1, a nuclear orphan receptor, is reduced in obesity and during muscle disuse. NOR-1 is responsive to exercise and its deficiency may contribute to altered metabolic signaling and insulin resistance. This study identifies metabolic targets regulated by NOR-1 and suggests it plays a role in mTORC1 signaling and insulin sensitivity pathways. Improving NOR-1 may offset the negative impact of inactivity, obesity, and type 2 diabetes on muscle metabolism.
Article
Biochemistry & Molecular Biology
Hector G. Paez, Peter J. Ferrandi, Christopher R. Pitzer, Junaith S. Mohamed, Stephen E. Alway
Summary: The study investigates the impact of NOR-1 deficiency on C2C12 metabolic signaling. The results reveal that NOR-1 acts as a modulator of mTORC1 signaling and its deficiency may contribute to insulin resistance and metabolic disease. Therefore, strategies that improve NOR-1 levels could be important in mitigating muscle metabolic abnormalities.
Article
Nutrition & Dietetics
Paul A. Roberson, Gregory N. Kincheloe, Jaclyn E. Welles, Dandan Xu, Mahalia Sam -Clarke, Paul S. MacLean, Charles H. Lang, Leonard S. Jefferson, Scot R. Kimball
Summary: This study confirms the role of Sestrins in glucose-induced mTORC1 activation and reveals the involvement of HK2 in this process in HEK293T cells. The effect of glucose on mTORC1 activation is independent of SESN-GATOR2 interaction and instead associated with alterations in SESNs' association with HK2.
JOURNAL OF NUTRITION
(2023)
Article
Multidisciplinary Sciences
Andrew L. Cangelosi, Anna M. Puszynska, Justin M. Roberts, Andrea Armani, Thao P. Nguyen, Jessica B. Spinelli, Tenzin Kunchok, Brianna Wang, Sze Ham Chan, Caroline A. Lewis, William C. Comb, George W. Bell, Aharon Helman, David M. Sabatini
Summary: This study reveals that Sestrin proteins play a crucial role in leucine sensing in mammals, showing their function in inhibiting mTORC1 activity, regulating white adipose tissue and muscle loss, and inducing FGF21 production in the liver. Moreover, it uncovers the zonated expression of Sestrin in the liver lobule, highlighting the spatial organization of nutrient sensing by the mTORC1 pathway.
Article
Cell Biology
John Noone, Keith D. Rochfort, Finbarr O'Sullivan, Donal J. O'Gorman
Summary: This study investigates the role of SIRT4 in regulating mitochondrial fusion and substrate utilization in human skeletal muscle cells. The results show that SIRT4 knockdown increases mitochondrial capacity to oxidize fatty acids and promotes mitochondrial elongation. The findings suggest a direct relationship between the mitochondrial phenotype and substrate oxidation in skeletal muscle cells.
CELLULAR SIGNALLING
(2023)
Review
Biochemistry & Molecular Biology
Wenlan Li, Kristy Swiderski, Kate T. Murphy, Gordon S. Lynch
Summary: Cancer cachexia is a progressive muscle wasting and weakness experienced by cancer patients, which can compromise treatment response and reduce quality of life. It has no effective treatment currently, but plant-derived antioxidants, especially polyphenols, show potential in attenuating cancer-related muscle loss.
Article
Sport Sciences
Brittany R. Counts, Jessica L. Halle, James A. Carson
Summary: This study found that cancer-induced skeletal muscle mass loss is a critical characteristic of cachexia. It also found that early-onset physical inactivity and altered systemic lipid oxidation in LLC tumor-bearing mice were associated with the eventual development of cachexia.
MEDICINE & SCIENCE IN SPORTS & EXERCISE
(2022)
Article
Critical Care Medicine
Geremy Clair, Lisa M. Bramer, Ravi Misra, Matthew D. McGraw, Soumyaroop Bhattacharya, Joseph A. Kitzmiller, Song Feng, Vincent G. Danna, Gautam Bandyopadhyay, Harsh Bhotika, Heidie L. Huyck, Gail H. Deutsch, Thomas J. Mariani, James P. Carson, Jeffrey A. Whitsett, Gloria S. Pryhuber, Joshua N. Adkins, Charles Ansong
Summary: This study provides a comprehensive analysis of the human lung proteome during development, revealing distinct molecular substages of alveolar development and evidence of post-transcriptional control in early postnatal development. The study also supports the extensive remodeling of the lung proteome during development and the concept of immune system maturation as an inherent part of normal lung development.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Review
Oncology
Sierra J. McDonald, Brandon N. VanderVeen, Kandy T. Velazquez, Reilly T. Enos, Ciaran M. Fairman, Thomas D. Cardaci, Daping Fan, E. Angela Murphy
Summary: Emodin, a Chinese herb-derived compound, shows anti-tumor effects in colon, liver, and pancreatic cancers by manipulating multiple signaling pathways. This review highlights its anti-cancer mechanisms, potential as a complementary treatment to chemotherapy, efficacy and bioavailability of emodin derivatives, and safety evaluation.
INTEGRATIVE CANCER THERAPIES
(2022)
Article
Biochemistry & Molecular Biology
Ashley J. Ovens, Yi Sing Gee, Naomi X. Y. Ling, Dingyi Yu, Justin P. Hardee, Jin D. Chung, Kevin R. W. Ngoei, Nicholas J. Waters, Nolan J. Hoffman, John W. Scott, Kim Loh, Katrin Spengler, Regine Heller, Michael W. Parker, Gordon S. Lynch, Fei Huang, Sandra Galic, Bruce E. Kemp, Jonathan B. Baell, Jonathan S. Oakhill, Christopher G. Langendorf
Summary: AMPK is a cellular energy sensor and regulator of energy homeostasis. Activating AMPK shows potential for treating type 2 diabetes and insulin resistance. Recent studies suggest that the ??202??1 isoform combination is primarily responsible for these effects. Structure/function analysis of SC4 activator led to the discovery of MSG010 and MSG011, which show greater potency in activating ??202??1 AMPK compared to MK-8722. These findings guide the development of selective AMPK activators.
BIOCHEMICAL JOURNAL
(2022)
Article
Oncology
Mehdi Chaib, Laura M. M. Sipe, Johnathan R. R. Yarbro, Margaret S. S. Bohm, Brittany R. R. Counts, Ubaid Tanveer, Ajeeth K. K. Pingili, Deidre Daria, Tony N. N. Marion, James A. A. Carson, Paul G. G. Thomas, Liza Makowski
Summary: This study investigates the effect of PKC agonists on MDSC expansion, differentiation, and recruitment to the tumor microenvironment. The results demonstrate that PKC agonists decrease MDSC expansion and induce their differentiation to an APC-like phenotype. Additionally, PKC agonists enhance MDSC cross-priming capacity and reduce their suppressive activity. Furthermore, the combination of PKC agonists with CD40 agonist leads to reduced tumor growth and increased activated CD8(+) T cells in a breast cancer mouse model.
Review
Physiology
C. David Hughes, P. Justin Hardee, S. David Waddell, A. Craig Goodman
Summary: Gene delivery strategy has been used to study muscular disorders and muscle physiology. This review provides a detailed protocol on how to efficiently electroporate plasmid DNA into rodent skeletal muscles, discussing key parameters and tissue processing methods.
JOURNAL OF APPLIED PHYSIOLOGY
(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)
Review
Cell Biology
Justin P. Hardee, James A. Carson
Summary: Skeletal muscle atrophy and dysfunction are significant factors contributing to increased morbidity and mortality in cancer patients. The complex pathophysiology of cachexia involves disruptions to the systemic cancer environment and interactions with various tissues. This article provides an overview of the current understanding of how resistance-type exercise impacts mechanisms involved in cancer-induced muscle wasting, particularly focusing on the role of IL-6 and gp130 receptors. The authors also discuss the gaps in knowledge and future research directions to improve preclinical studies and translate findings to human patients with cancer.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Oncology
Brandon N. VanderVeen, Thomas D. Cardaci, Sierra J. McDonald, Sarah S. Madero, Christian A. Unger, Brooke M. Bullard, Reilly T. Enos, Kandy T. Velazquez, Jason L. Kubinak, Daping Fan, E. Angela Murphy
Summary: Fluorouracil/5-flourouracil (5FU) is a commonly used first-line chemotherapy drug, but its toxicities can negatively affect patient's quality of life and treatment outcomes. Obesity may exacerbate the toxicities of 5FU, and obese mice show increased susceptibility to 5FU-induced cytotoxicity.
CANCER BIOLOGY & THERAPY
(2022)
Review
Health Care Sciences & Services
Brooke M. Bullard, Sierra J. McDonald, Thomas D. Cardaci, Brandon N. VanderVeen, E. Angela Murphy
Summary: Nonpharmacological strategies, including natural products, dietary patterns, and probiotic treatment, show great potential in preventing and treating chemotherapy-induced mucositis. Behavioral interventions such as psychological interventions and exercise interventions also hold promise in reducing the side effects of mucositis. Further research is needed to explore these approaches in more depth.
CURRENT OPINION IN SUPPORTIVE AND PALLIATIVE CARE
(2022)
Review
Gastroenterology & Hepatology
Brooke M. Bullard, Brandon N. VanderVeen, Sierra J. McDonald, Thomas D. Cardaci, E. Angela Murphy
Summary: Ulcerative colitis is a chronic disease characterized by inflammation of the colonic and rectal mucosa. The pathogenesis involves various factors including genetics, environment, and immune-mediated components. Nonpharmacological and behavioral interventions are proposed as safe and effective treatments to alleviate UC.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Article
Physiology
Brandon N. VanderVeen, Thomas D. Cardaci, Sarah S. Madero, Sierra J. McDonald, Brooke M. Bullard, Robert L. Price, James A. Carson, Daping Fan, E. Angela Murphy
Summary: Research has shown that 5-fluorouracil (5FU) monotherapy leads to weight loss and muscle mass reduction, along with negative impact on skeletal muscle immune cells. Additionally, 5FU decreases immune cells in skeletal muscle and impairs infiltration following damage, contributing to disrupted muscle repair processes. These findings provide insights into the impact of 5FU on skeletal muscle and offer a potential explanation for impaired tissue repair in some patients.
JOURNAL OF APPLIED PHYSIOLOGY
(2022)
Article
Cell Biology
Sierra J. McDonald, Taryn L. Cranford, Brandon N. VanderVeen, Thomas D. Cardaci, Kandy T. Velazquez, Reilly T. Enos, Ioulia Chatzistamou, Daping Fan, E. Angela Murphy
Summary: miR155 plays an important role in breast cancer development, but its specific role as an oncogenic or tumor suppressive factor is still unclear. This study found that the deficiency of miR155 in a transgenic mouse model of breast cancer resulted in reduced tumor growth and improved tumor microenvironment.
PHYSIOLOGICAL GENOMICS
(2022)
Article
Physiology
Sierra J. McDonald, Brandon N. VanderVeen, Brooke M. Bullard, Thomas D. Cardaci, Sarah S. Madero, Ioulia Chatzistamou, Daping Fan, E. Angela Murphy
Summary: The study found that surgical wounding can accelerate tumor progression and lung metastasis in a mouse model of triple negative breast cancer, leading to increased presence of macrophages in both the primary tumor and lungs which promote tumor development and metastasis.
PHYSIOLOGICAL REPORTS
(2022)
Article
Nutrition & Dietetics
Brandon N. VanderVeen, Thomas D. Cardaci, Patrice Cunningham, Sierra J. McDonald, Brooke M. Bullard, Daping Fan, E. Angela Murphy, Kandy T. Velazquez
Summary: Cachexia diagnosis is associated with prolonged hospital stay and increased healthcare cost for cancer patients, and most cachectic patients do not survive treatment. Treatment complexity is amplified by both the underlying malignancy and anti-cancer therapy, which can independently promote cachexia. Quercetin, a polyphenolic flavonoid, shows potential in protecting against cancer and chemotherapy-induced dysfunction, but its efficacy in maintaining muscle mass in tumor-bearing animals undergoing chemotherapy has not been studied. In this study, quercetin was found to protect against cancer and chemotherapy-induced muscle mass loss through improvement of mitochondrial homeostatic balance.
