المؤلفون: Fabrizio Pin, Andrea Bonetto, Leah J. Novinger, Monte S. Willis, Joshua R. Huot, Ashok Narasimhan, Austin S Keith, Teresa A. Zimmers

المصدر: Journal of Cachexia, Sarcopenia and Muscle

مصطلحات موضوعية: Male, 0301 basic medicine, Cardiac function curve, medicine.medical_specialty, Cachexia, Skeletal muscle, Adipose tissue, Liver metastases, Mice, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Internal medicine, medicine, Animals, Orthopedics and Sports Medicine, Bone, Muscle, Skeletal, Wasting, Ejection fraction, business.industry, Liver Neoplasms, Cardiac muscle, Cancer, Heart, Original Articles, medicine.disease, Colorectal cancer, Disease Models, Animal, Activin signalling, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, 030220 oncology & carcinogenesis, Original Article, medicine.symptom, Colorectal Neoplasms, business

الوصف: Background Advanced colorectal cancer (CRC) is often accompanied by the development of liver metastases, as well as cachexia, a multi‐organ co‐morbidity primarily affecting skeletal (SKM) and cardiac muscles. Activin receptor type 2B (ACVR2B) signalling is known to cause SKM wasting, and its inhibition restores SKM mass and prolongs survival in cancer. Using a recently generated mouse model, here we tested whether ACVR2B blockade could preserve multiple organs, including skeletal and cardiac muscle, in the presence of metastatic CRC. Methods NSG male mice (8 weeks old) were injected intrasplenically with HCT116 human CRC cells (mHCT116), while sham‐operated animals received saline (n = 5–10 per group). Sham and tumour‐bearing mice received weekly injections of ACVR2B/Fc, a synthetic peptide inhibitor of ACVR2B. Results mHCT116 hosts displayed losses in fat mass ( − 79%, P

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b3b6050ae4d294bc7aff79e56474f1cdTest
https://doi.org/10.1002/jcsm.12642Test

المؤلفون: Fabrizio Pin, Joshua R. Huot, Andrea Bonetto, Alyson L. Essex

المصدر: International Journal of Molecular Sciences
Volume 22
Issue 3
International Journal of Molecular Sciences, Vol 22, Iss 1486, p 1486 (2021)

مصطلحات موضوعية: Male, Colorectal cancer, Muscle Fibers, Skeletal, Gastroenterology, bone, lcsh:Chemistry, Mice, Subcutaneous Tissue, Femur, Young adult, Wasting, lcsh:QH301-705.5, Spectroscopy, Muscle Weakness, Liver Neoplasms, digestive, oral, and skin physiology, General Medicine, musculoskeletal system, Computer Science Applications, Muscular Atrophy, medicine.anatomical_structure, Disease Progression, medicine.symptom, Colorectal Neoplasms, hormones, hormone substitutes, and hormone antagonists, Muscle Contraction, STAT3 Transcription Factor, medicine.medical_specialty, colorectal cancer, Adenocarcinoma, cachexia, Article, Catalysis, Cachexia, Inorganic Chemistry, Contractility, Atrophy, Cell Line, Tumor, Internal medicine, medicine, Animals, Physical and Theoretical Chemistry, skeletal muscle, Muscle, Skeletal, Molecular Biology, neoplasms, business.industry, Organic Chemistry, Skeletal muscle, X-Ray Microtomography, medicine.disease, digestive system diseases, Blockade, Mice, Inbred C57BL, lcsh:Biology (General), lcsh:QD1-999, business, liver metastases

الوصف: Colorectal cancer (CRC) is a leading cause of cancer-related death, and the prevalence of CRC in young adults is on the rise, making this a largescale clinical concern. Advanced CRC patients often present with liver metastases (LM) and an increased incidence of cachexia, i.e., musculoskeletal wasting. Despite its high incidence in CRC patients, cachexia remains an unresolved issue, and animal models for the study of CRC cachexia, in particular, metastatic CRC cachexia, remain limited
therefore, we aimed to establish a new model of metastatic CRC cachexia. C57BL/6 male mice (8 weeks old) were subcutaneously (MC38) or intrasplenically injected (mMC38) with MC38 murine CRC cells to disseminate LM, while experimental controls received saline (n = 5–8/group). The growth of subcutaneous MC38 tumors was accompanied by a reduction in skeletal muscle mass (−16%
quadriceps muscle), plantarflexion force (−22%) and extensor digitorum longus (EDL) contractility (−20%) compared to experimental controls. Meanwhile, the formation of MC38 LM (mMC38) led to heighted reductions in skeletal muscle mass (−30%
quadriceps), plantarflexion force (−28%) and EDL contractility (−35%) compared to sham-operated controls, suggesting exacerbated cachexia associated with LM. Moreover, both MC38 and mMC38 tumor hosts demonstrated a marked loss of bone indicated by reductions in trabecular (Tb.BV/TV: −49% in MC38, and −46% in mMC38) and cortical (C.BV/TV: −12% in MC38, and −8% in mMC38) bone. Cell culture experiments revealed that MC38 tumor-derived factors directly promote myotube wasting (−18%) and STAT3 phosphorylation (+5-fold), while the pharmacologic blockade of STAT3 signaling was sufficient to preserve myotube atrophy in the presence of MC38 cells (+21%). Overall, these results reinforce the notion that the formation of LM heightens cachexia in an experimental model of CRC.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fe0dd57bf24453f7ec34f115eaa54579Test

المؤلفون: Marion E. Couch, Andrea Bonetto, Joshua R. Huot, Leah J. Novinger, Thomas M. O’Connell, Fabrizio Pin, Robert A. Harris

المصدر: The FASEB Journal. 33:7778-7790

مصطلحات موضوعية: Male, 0301 basic medicine, medicine.medical_specialty, Cachexia, Pyruvate dehydrogenase kinase, PDK4, Biochemistry, Cell Line, Mice, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Internal medicine, Genetics, medicine, Animals, Myocyte, Muscle, Skeletal, Molecular Biology, business.industry, Research, Pyruvate Dehydrogenase Acetyl-Transferring Kinase, Skeletal muscle, medicine.disease, Muscle atrophy, Mitochondria, Muscle, Muscular Atrophy, Protein catabolism, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Pirinixic Acid, medicine.symptom, business, Oxidation-Reduction, 030217 neurology & neurosurgery, Biotechnology

الوصف: Cachexia is frequently accompanied by severe metabolic derangements, although the mechanisms responsible for this debilitating condition remain unclear. Pyruvate dehydrogenase kinase (PDK)4, a critical regulator of cellular energetic metabolism, was found elevated in experimental models of cancer, starvation, diabetes, and sepsis. Here we aimed to investigate the link between PDK4 and the changes in muscle size in cancer cachexia. High PDK4 and abnormal energetic metabolism were found in the skeletal muscle of colon-26 tumor hosts, as well as in mice fed a diet enriched in Pirinixic acid, previously shown to increase PDK4 levels. Viral-mediated PDK4 overexpression in myotube cultures was sufficient to promote myofiber shrinkage, consistent with enhanced protein catabolism and mitochondrial abnormalities. On the contrary, blockade of PDK4 was sufficient to restore myotube size in C2C12 cultures exposed to tumor media. Our data support, for the first time, a direct role for PDK4 in promoting cancer-associated muscle metabolic alterations and skeletal muscle atrophy.-Pin, F., Novinger, L. J., Huot, J. R., Harris, R. A., Couch, M. E., O'Connell, T. M., Bonetto, A. PDK4 drives metabolic alterations and muscle atrophy in cancer cachexia.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6a6d9cb764e9d78940286b810086b8a7Test
https://doi.org/10.1096/fj.201802799rTest

المؤلفون: Elena A. Goncharova, Gunner Halliday, Taijyu Satoh, Timothy N. Bachman, Jian Hu, Charles F. McTiernan, Joshua R. Huot, Dmitry A. Goncharov, Yang Bai, Rebecca Vanderpool, Roberto Machado, Longfei Wang, Amanda Fisher, Robert V. Considine, Jeffrey J. Baust, Ana L. Mora, Mark T. Gladwin, Todd G. Cook, Andrea Sebastiani, Jiangning Tan, Yen Chun Lai, T. Avolio, Andrea Bonetto

المصدر: Arterioscler Thromb Vasc Biol
Arteriosclerosis, thrombosis, and vascular biology, vol 40, iss 6

مصطلحات موضوعية: Leptin, 0301 basic medicine, Male, Cardiorespiratory Medicine and Haematology, 030204 cardiovascular system & hematology, AMP-Activated Protein Kinases, Inbred C57BL, Cardiovascular, Mice, 0302 clinical medicine, Receptors, Lung, Metabolic Syndrome, Diabetes, Heart, Pulmonary, Metformin, Heart Disease, 5.1 Pharmaceuticals, 6.1 Pharmaceuticals, Hypertension, Cardiology, Receptors, Leptin, Left heart disease, Development of treatments and therapeutic interventions, Cardiology and Cardiovascular Medicine, medicine.drug, Cardiac function curve, medicine.medical_specialty, Hypertension, Pulmonary, Clinical Sciences, Diet, High-Fat, metabolic syndrome, Article, 03 medical and health sciences, Internal medicine, medicine, Humans, Animals, Hypoglycemic Agents, Obesity, Metabolic and endocrine, Antihypertensive Agents, Nutrition, Heart Failure, business.industry, treprostinil, Evaluation of treatments and therapeutic interventions, Stroke Volume, medicine.disease, Pulmonary hypertension, Epoprostenol, Diet, Rats, Mice, Inbred C57BL, High-Fat, 030104 developmental biology, glucose intolerance, Cardiovascular System & Hematology, Hyperglycemia, Metabolic syndrome, Insulin Resistance, Heart failure with preserved ejection fraction, business, Treprostinil

الوصف: Objective:Pulmonary hypertension (PH) due to left heart disease (group 2), especially in the setting of heart failure with preserved ejection fraction (HFpEF), is the most common cause of PH worldwide; however, at present, there is no proven effective therapy available for its treatment. PH-HFpEF is associated with insulin resistance and features of metabolic syndrome. The stable prostacyclin analog, treprostinil, is an effective and widely used Food and Drug Administration-approved drug for the treatment of pulmonary arterial hypertension. While the effect of treprostinil on metabolic syndrome is unknown, a recent study suggests that the prostacyclin analog beraprost can improve glucose intolerance and insulin sensitivity. We sought to evaluate the effectiveness of treprostinil in the treatment of metabolic syndrome-associated PH-HFpEF.Approach and Results:Treprostinil treatment was given to mice with mild metabolic syndrome-associated PH-HFpEF induced by high-fat diet and to SU5416/obese ZSF1 rats, a model created by the treatment of rats with a more profound metabolic syndrome due to double leptin receptor defect (obese ZSF1) with a vascular endothelial growth factor receptor blocker SU5416. In high-fat diet-exposed mice, chronic treatment with treprostinil reduced hyperglycemia and pulmonary hypertension. In SU5416/Obese ZSF1 rats, treprostinil improved hyperglycemia with similar efficacy to that of metformin (a first-line drug for type 2 diabetes mellitus); the glucose-lowering effect of treprostinil was further potentiated by the combined treatment with metformin. Early treatment with treprostinil in SU5416/Obese ZSF1 rats lowered pulmonary pressures, and a late treatment with treprostinil together with metformin improved pulmonary artery acceleration time to ejection time ratio and tricuspid annular plane systolic excursion with AMPK (AMP-activated protein kinase) activation in skeletal muscle and the right ventricle.Conclusions:Our data suggest a potential use of treprostinil as an early treatment for mild metabolic syndrome-associated PH-HFpEF and that combined treatment with treprostinil and metformin may improve hyperglycemia and cardiac function in a more severe disease.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::15a606dca2088db7c61a4384a37d651fTest
https://pubmed.ncbi.nlm.nih.gov/32966132Test

المؤلفون: Alyson L. Essex, Fabrizio Pin, Joshua R. Huot, Lynda F. Bonewald, Lilian I. Plotkin, Andrea Bonetto

المصدر: Frontiers in Endocrinology, Vol 10 (2019)
Frontiers in Endocrinology

مصطلحات موضوعية: 0301 basic medicine, medicine.medical_specialty, muscle, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Osteoporosis, 030209 endocrinology & metabolism, chemotherapy, bone, cachexia, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Cachexia, 03 medical and health sciences, Endocrinology, 0302 clinical medicine, Atrophy, Internal medicine, medicine, Wasting, bisphosphonates, Original Research, Cisplatin, Chemotherapy, lcsh:RC648-665, business.industry, Bisphosphonate, medicine.disease, 3. Good health, 030104 developmental biology, Zoledronic acid, medicine.symptom, business, medicine.drug

الوصف: Chemotherapy is frequently accompanied by several side effects, including nausea, diarrhea, anorexia and fatigue. Evidence from ours and other groups suggests that chemotherapy can also play a major role in causing not only cachexia, but also bone loss. This complicates prognosis and survival among cancer patients, affects quality of life, and can increase morbidity and mortality rates. Recent findings suggest that soluble factors released from resorbing bone directly contribute to loss of muscle mass and function secondary to metastatic cancer. However, it remains unknown whether similar mechanisms also take place following treatments with anticancer drugs. In this study, we found that young male CD2F1 mice (8-week old) treated with the chemotherapeutic agent cisplatin (2.5 mg/kg) presented marked loss of muscle and bone mass. Myotubes exposed to bone conditioned medium from cisplatin-treated mice showed severe atrophy (-33%) suggesting a bone to muscle crosstalk. To test this hypothesis, mice were administered cisplatin in combination with an antiresorptive drug to determine if preservation of bone mass has an effect on muscle mass and strength following chemotherapy treatment. Mice received cisplatin alone or combined with zoledronic acid (ZA; 5 μg/kg), a bisphosphonate routinely used for the treatment of osteoporosis. We found that cisplatin resulted in progressive loss of body weight (-25%), in line with reduced fat (-58%) and lean (-17%) mass. As expected, microCT bone histomorphometry analysis revealed significant reduction in bone mass following administration of chemotherapy, in line with reduced trabecular bone volume (BV/TV) and number (Tb.N), as well as increased trabecular separation (Tb.Sp) in the distal femur. Conversely, trabecular bone was protected when cisplatin was administered in combination with ZA. Interestingly, while the animals exposed to chemotherapy presented significant muscle wasting (~-20% vs. vehicle-treated mice), the administration of ZA in combination with cisplatin resulted in preservation of muscle mass (+12%) and strength (+42%). Altogether, these observations support our hypothesis of bone factors targeting muscle and suggest that pharmacological preservation of bone mass can benefit muscle mass and function following chemotherapy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0e8f6b5f3a4c7fd57137bc5a29cbe374Test
https://www.frontiersin.org/article/10.3389/fendo.2019.00809/fullTest

المؤلفون: Joshua R. Huot, Andrea Bonetto, Fabrizio Pin, Leah J. Novinger

المصدر: Disease Models & Mechanisms
Disease Models & Mechanisms, Vol 13, Iss 1 (2020)

مصطلحات موضوعية: Male, Cachexia, Colorectal cancer, Medicine (miscellaneous), lcsh:Medicine, Skeletal muscle, STAT3, Mice, Liver metastases, 0302 clinical medicine, Immunology and Microbiology (miscellaneous), Wasting, 0303 health sciences, biology, Myogenesis, Liver Neoplasms, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cytokines, medicine.symptom, Colorectal Neoplasms, lcsh:RB1-214, Research Article, STAT3 Transcription Factor, medicine.medical_specialty, Neuroscience (miscellaneous), HCT116, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Atrophy, Internal medicine, medicine, lcsh:Pathology, Animals, Humans, Muscle, Skeletal, neoplasms, 030304 developmental biology, business.industry, Interleukin-6, Wasting Syndrome, lcsh:R, medicine.disease, HCT116 Cells, Protein ubiquitination, digestive system diseases, Mitochondria, Muscle, Disease Models, Animal, Endocrinology, biology.protein, business

الوصف: Colorectal cancer (CRC) is often accompanied by formation of liver metastases (LM) and skeletal muscle wasting, i.e. cachexia. Despite affecting the majority of CRC patients, cachexia remains underserved, understudied and uncured. Animal models for the study of CRC-induced cachexia, in particular models containing LM, are sparse; therefore, we aimed to characterize two new models of CRC cachexia. Male NSG mice were injected subcutaneously (HCT116) or intrasplenically (mHCT116) with human HCT116 CRC tumor cells to disseminate LM, whereas experimental controls received saline (n=5-8/group). Tumor growth was accompanied by loss of skeletal muscle mass (HCT116: −20%; mHCT116: −31%; quadriceps muscle) and strength (HCT116: −20%; mHCT116: −27%), with worsened loss of skeletal muscle mass in mHCT116 compared with HCT116 (gastrocnemius: −19%; tibialis anterior: −22%; quadriceps: −21%). Molecular analyses revealed elevated protein ubiquitination in HCT116, whereas mHCT116 also displayed elevated Murf1 and atrogin-1 expression, along with reduced mitochondrial proteins PGC1α, OPA1, mitofusin 2 and cytochrome C. Further, elevated IL6 levels were found in the blood of mHCT116 hosts, which was associated with higher phosphorylation of STAT3 in skeletal muscle. To clarify whether STAT3 was a main player in muscle wasting in this model, HCT116 cells were co-cultured with C2C12 myotubes. Marked myotube atrophy (–53%) was observed, along with elevated phospho-STAT3 levels (+149%). Conversely, inhibition of STAT3 signaling by means of a JAK/STAT3 inhibitor was sufficient to rescue myotube atrophy induced by HCT116 cells (+55%). Overall, our results indicate that the formation of LM exacerbates cachectic phenotype and associated skeletal muscle molecular alterations in HCT116 tumor hosts.
Summary: Colorectal cancer-derived liver metastases exacerbate cachexia, in line with activation of STAT3 signaling. STAT3 inhibition may improve cancer-associated muscle wasting.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::349243284d3324470b591013a4bf4dc2Test
https://pubmed.ncbi.nlm.nih.gov/31915140Test

المؤلفون: Teresa A. Zimmers, Andrea Bonetto, Joseph E. Rupert, Joshua R. Huot, Daenique H A Jengelley, Ashok Narasimhan

المصدر: Cancer Research. 81:969-969

مصطلحات موضوعية: Cancer Research, medicine.medical_specialty, Myogenesis, Chemistry, Adipose tissue, Inflammation, medicine.disease, Muscle atrophy, Cachexia, Endocrinology, Atrophy, Oncology, Internal medicine, medicine, Muscular dystrophy, medicine.symptom, Protein kinase C

الوصف: Approximately 80% of patients with pancreatic ductal adenocarcinoma (PDAC) suffer cachexia, involuntary loss of fat and muscle due to inflammation and dysmetabolism that increases treatment toxicity, reduces treatment response and promotes mortality. Most research has focused on muscle and adipose individually while neglecting tissue crosstalk. Recently, we reported that IL6 trans-signaling from muscle to fat in PDAC cachexia augments adipose lipolysis, leading to increased muscle lipid accumulation (myosteatosis) and promoting activation of lipid sensitive signaling pathways and metabolic substrate shifts in muscle. The lipid sensitive protein kinase C theta (PKC-θ) modulates myopathic phenotypes including muscular dystrophy, atrophy, and insulin resistance. PKC-θ is activated by diacylglycerol, which binds to PKC-θ promoting its translocation to the plasma membrane, phosphorylation, and activation. Activated PKC-θ modulates pathways with known roles in muscle atrophy including inhibition of insulin signaling, activation of NF-κB, and increased shedding of the IL-6R. We used in vitro and in vivo models to study the role of PKC-θ in PDAC cachexia. Here 50,000 tumor cells of a line derived from the KPC (LSL-KrasG12D:LSL-Trp53R172H:Pdx1-Cre) genetically engineered model of PDAC were implanted in the pancreases of male C57BL/6J mice. Tissues were collected when mice displayed severe cachexia (~25% muscle loss). Phospho-Thr538-PKC-θ was increased 1.8-fold (p=0.002) in muscle of mice with KPC cachexia and phosphorylation of PKC-θ substrates was correspondingly increased (p=0.048). Plasma from KPC-tumor bearing mice was used to treat C2C12 myotubes, with or without the PKC inhibitor Sotrastaurin. After 48 hours, KPC plasma caused a significant decrease in average myotube diameter compared to no tumor plasma (18%, p=0.002), whereas addition of 500nM Sotrastaurin prevented KPC plasma-induced myotube atrophy. KPC tumor growth was not different between wildtype mice and mice with germline deletion of the PKC-θ gene, Prkcq. However, Prkcq null tumor-bearing mice demonstrated greater in vivo muscle force production (p Citation Format: Joseph E. Rupert, Joshua R. Huot, Ashok Narasimhan, Daenique H. Jengelley, Andrea Bonetto, Teresa A. Zimmers. PKC-theta modulates myosteatosis, muscle function, atrophy, and survival in murine pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 969.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::0b5e0e3780df4bb53d8a6238e034b409Test
https://doi.org/10.1158/1538-7445.am2021-969Test

المؤلفون: Lilian I. Plotkin, Maya Gutierrez, David L. Waning, Alyson L. Essex, Rafael Barreto, Andrea Bonetto, Meijing Wang, Joshua R. Huot

المصدر: Cancers
Cancers, Vol 11, Iss 4, p 571 (2019)
Volume 11
Issue 4

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, medicine.medical_specialty, chemotherapy, lcsh:RC254-282, Article, Cachexia, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Regorafenib, Internal medicine, medicine, PI3K/AKT/mTOR pathway, business.industry, Autophagy, Cardiac muscle, Skeletal muscle, Muscle weakness, cardiac cachexia, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Muscle atrophy, 3. Good health, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Oncology, chemistry, 030220 oncology & carcinogenesis, skeletal muscle wasting, sorafenib, regorafenib, medicine.symptom, business

الوصف: Despite recent progress, chemotherapy remains the preferred treatment for cancer. We have shown a link between anticancer drugs and the development of cachexia, i.e., body wasting accompanied by muscle loss. The multi-kinase inhibitors (MKIs) regorafenib and sorafenib, used as second-line treatment for solid tumors, are frequently accompanied by several side effects, including loss of muscle mass and strength. In the present study we aimed to investigate the molecular mechanisms associated with the occurrence of muscle toxicities in in vivo conditions. Hence, we treated 8-week old healthy CD2F1 male mice with MKIs for up to six weeks and observed decreased skeletal and cardiac muscle mass, consistent with muscle weakness. Modulation of ERK1/2 and GSK3&beta
as well as increased expression of markers of autophagy, previously associated with muscle atrophy conditions, were shown in skeletal muscle upon treatment with either drug. MKIs also promoted cardiac abnormalities consistent with reduced left ventricular mass, internal diameter, posterior wall thickness and stroke volume, despite unchanged overall function. Notably, different signaling pathways were affected in the heart, including reduced expression of mitochondrial proteins, and elevated AKT, GSK3&beta
mTOR, MEK1/2 and ERK1/2 phosphorylation. Combined, our data demonstrate detrimental effects on skeletal and cardiac muscle in association with chronic administration of MKIs, although different mechanisms would seem to contribute to the cachectic phenotype in the two tissues.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1c44ce6b7d74c50c690cf29a8c9a0bfcTest
http://europepmc.org/articles/PMC6520777Test

المؤلفون: Marcus M. Lawrence, David C. Nieman, Kevin A. Zwetsloot, Mary Ann Lila, Joshua R. Huot, Mary H. Grace, Chase A. Sherman, R. Andrew Shanely, Vladimir Badmaev, Susan T Arthur

المصدر: International Journal of Environmental Research and Public Health
Volume 18
Issue 2
International Journal of Environmental Research and Public Health, Vol 18, Iss 370, p 370 (2021)

مصطلحات موضوعية: Male, Aging, medicine.medical_specialty, Anabolism, Health, Toxicology and Mutagenesis, Phytoecdysteroid, lcsh:Medicine, Myostatin, Article, Muscle hypertrophy, atrogenes, Mice, Phosphatidylinositol 3-Kinases, 03 medical and health sciences, Anabolic Agents, 0302 clinical medicine, Internal medicine, medicine, Animals, skeletal muscle, Muscle, Skeletal, p70S6K, Protein kinase B, 030304 developmental biology, 0303 health sciences, biology, Akt, lcsh:R, Public Health, Environmental and Occupational Health, Skeletal muscle, Rats, Mice, Inbred C57BL, Endocrinology, medicine.anatomical_structure, biology.protein, Phosphorylation, 20-hydroxyecdysone, hypertrophy, C2C12, 030217 neurology & neurosurgery

الوصف: Skeletal muscle mass and strength are lost with aging. Phytoecdysteroids, in particular 20-hydroxyecdysone (20E), increase protein synthesis in C2C12 skeletal muscle cells and muscle strength in young rats. The objective of this study was to determine whether an extract from Ajuga turkestanica (ATE), enriched in phytoecdysteroids, and 20E affect skeletal muscle mass and fiber size, fiber type, activation of the PI3K&ndash
Akt signaling pathway, and the mRNA levels of MAFbx, MuRF-1, and myostatin in sedentary aging mice. Aging male C57BL/6 mice (20 months old) received ATE, 20E, or vehicle (CT) once per day for 28 days or a single acute dose. Treatment did not alter body, muscle, or organ mass
fiber cross-sectional area
or fiber type in the triceps brachii or plantaris muscles. Likewise, protein synthesis signaling markers (i.e., phosphorylation of AktSer473 and p70S6kThr389) measured after either 28 days or acutely were unchanged. Neither ATE nor 20E treatment for 28 days affected the mRNA levels of MAFbx, MuRF-1, and myostatin. In conclusion, these data indicate that phytoecdysteroid treatment does not alter muscle mass or fiber type, nor does it activate protein synthesis signaling in the skeletal muscle of sedentary aging mice.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::622d1e7db406876663dd8735b0b5c110Test
https://doi.org/10.3390/ijerph18020370Test

المؤلفون: Joseph S. Marino, Erik A. Wikstrom, Tricia Hubbard-Turner, Sophie Guderian, Joshua R. Huot, Bailey Peck, Susan T Arthur, Michael J. Turner

المصدر: AGE. 38

مصطلحات موضوعية: Male, Aging, medicine.medical_specialty, Physical Exertion, Diastole, Male mice, 030204 cardiovascular system & hematology, Ventricular Function, Left, Article, Mice, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Animals, Ankle Injuries, Sedentary lifestyle, E/A ratio, business.industry, 030229 sport sciences, General Medicine, Surgery, Disease Models, Animal, Isoflurane, Sedentary group, Mice, Inbred CBA, Cardiology, Velocity ratio, Geriatrics and Gerontology, business, Ankle sprain, Blood Flow Velocity, medicine.drug

الوصف: We assessed the impact of differing physical activity levels throughout the lifespan, using a musculoskeletal injury model, on the age-related changes in left ventricular (LV) parameters in active mice. Forty male mice (CBA/J) were randomly placed into one of three running wheel groups (transected CFL group, transected ATFL/CFL group, SHAM group) or a SHAM Sedentary group (SHAMSED). Before surgery and every 6 weeks after surgery, LV parameters were measured under 2.5 % isoflurane inhalation. Group effects for daily distance run was significantly greater for the SHAM and lesser for the ATLF/CFL mice (p = 0.013) with distance run decreasing with age for all mice (p

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::739aef6b244aa2568c07de99d5a65859Test
https://doi.org/10.1007/s11357-016-9877-2Test