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Journal of Cellular Physiology Jun 2024Skeletal muscle injury affects the quality of life in many pathologies, including volumetric muscle loss, contusion injury, and aging. We hypothesized that the...
Skeletal muscle injury affects the quality of life in many pathologies, including volumetric muscle loss, contusion injury, and aging. We hypothesized that the nicotinamide phosphoribosyltransferase (Nampt) activator P7C3 improves muscle repair following injury. In the present study, we tested the effect of P7C3 (1-anilino-3-(3,6-dibromocarbazol-9-yl) propan-2-ol) on chemically induced muscle injury. Muscle injury was induced by injecting 50 µL 1.2% barium chloride (BaCl) into the tibialis anterior (TA) muscle in C57Bl/6J wild-type male mice. Mice were then treated with either 10 mg/kg body weight of P7C3 or Vehicle intraperitoneally for 7 days and assessed for histological, biochemical, and molecular changes. In the present study, we show that the acute BaCl-induced TA muscle injury was robust and the P7C3-treated mice displayed a significant increase in the total number of myonuclei and blood vessels, and decreased serum CK activity compared with vehicle-treated mice. The specificity of P7C3 was evaluated using Nampt mice, which did not display any significant difference in muscle repair capacity among treated groups. RNA-sequencing analysis of the injured TA muscles displayed 368 and 212 genes to be exclusively expressed in P7C3 and Veh-treated mice, respectively. There was an increase in the expression of genes involved in cellular processes, inflammatory response, angiogenesis, and muscle development in P7C3 versus Veh-treated mice. Conversely, there is a decrease in muscle structure and function, myeloid cell differentiation, glutathione, and oxidation-reduction, drug metabolism, and circadian rhythm signaling pathways. Chromatin immunoprecipitation-quantitative polymerase chain reaction (qPCR) and reverse transcription-qPCR analyses identified increased Pax7, Myf5, MyoD, and Myogenin expression in P7C3-treated mice. Increased histone lysine (H3K) methylation and acetylation were observed in P7C3-treated mice, with significant upregulation in inflammatory markers. Moreover, P7C3 treatment significantly increased the myotube fusion index in the BaCl-injured human skeletal muscle in vitro. P7C3 also inhibited the lipopolysaccharide-induced inflammatory response and mitochondrial membrane potential of RAW 264.7 macrophage cells. Overall, we demonstrate that P7C3 activates muscle stem cells and enhances muscle injury repair with increased angiogenesis.
PubMed: 38946152
DOI: 10.1002/jcp.31346 -
Journal of Cellular Physiology Jun 2024Skeletal muscle is crucial for animal movement and posture maintenance, and it serves as a significant source of meat in the livestock and poultry industry. The number...
Skeletal muscle is crucial for animal movement and posture maintenance, and it serves as a significant source of meat in the livestock and poultry industry. The number of muscle fibers differentiated from myoblast in the embryonic stage is one of the factors determining the content of skeletal muscle. Insulin-like growth factor 2 (IGF2), a well-known growth-promoting hormone, is crucial for embryonic and skeletal muscle growth and development. However, the specific molecular mechanism underlying its impact on chicken embryonic myoblast differentiation remains unclear. To elucidate the molecular mechanism by which IGF2 regulates chicken myoblast differentiation, we manipulated IGF2 expression in chicken embryonic myoblast. The results demonstrated that IGF2 was upregulated during chicken skeletal muscle development and myoblast differentiation. On the one hand, we found that IGF2 promotes mitochondrial biogenesis through the PGC1/NRF1/TFAM pathway, thereby enhancing mitochondrial membrane potential, oxidative phosphorylation, and ATP synthesis during myoblast differentiation. This process is mediated by the PI3K/AKT pathway. On the other hand, IGF2 regulates BNIP3-mediated mitophagy, clearing dysfunctional mitochondria. Collectively, our findings confirmed that IGF2 cooperatively regulates mitochondrial biogenesis and mitophagy to remodel the mitochondrial network and enhance mitochondrial function, ultimately promoting myoblast differentiation.
PubMed: 38946060
DOI: 10.1002/jcp.31351 -
Journal of Medical Case Reports Jul 2024Necrotizing myopathies and muscle necrosis can be caused by immune-mediated mechanisms, drugs, ischemia, and infections, and differential diagnosis may be challenging.
BACKGROUND
Necrotizing myopathies and muscle necrosis can be caused by immune-mediated mechanisms, drugs, ischemia, and infections, and differential diagnosis may be challenging.
CASE PRESENTATION
We describe a case of diabetic myonecrosis complicated by pyomyositis and abscess caused by Escherichia coli. A white woman in her late forties was admitted to the hospital with a 1.5 week history of bilateral swelling, weakness, and mild pain of the lower extremities and inability to walk. She had a history of type 1 diabetes complicated by diabetic retinopathy, neuropathy, nephropathy, and end-stage renal disease. C-reactive protein was 203 mg/l, while creatinine kinase was only mildly elevated to 700 IU/l. Magnetic resonance imaging of her lower limb muscles showed extensive edema, and muscle biopsy was suggestive of necrotizing myopathy with mild inflammation. No myositis-associated or myositis-specific antibodies were detected. Initially, she was suspected to have seronegative immune-mediated necrotizing myopathy, but later her condition was considered to be explained better by diabetic myonecrosis with multifocal involvement. Her symptoms alleviated without any immunosuppressive treatment. After a month, she developed new-onset and more severe symptoms in her right posterior thigh. She was diagnosed with emphysematous urinary tract infection and emphysematous myositis and abscess of the right hamstring muscle. Bacterial cultures of drained pus from abscess and urine were positive for Escherichia coli. In addition to abscess drainage, she received two 3-4-week courses of intravenous antibiotics. In the discussion, we compare the symptoms and findings typically found in pyomyositis, immune-mediated necrotizing myopathy, and diabetic myonecrosis (spontaneous ischemic necrosis of skeletal muscle among people with diabetes). All of these diseases may cause muscle weakness and pain, muscle edema in imaging, and muscle necrosis. However, many differences exist in their clinical presentation, imaging, histology, and extramuscular symptoms, which can be useful in determining diagnosis. As pyomyositis often occurs in muscles with pre-existing pathologies, the ischemic muscle has likely served as a favorable breeding ground for the E. coli in our case.
CONCLUSIONS
Identifying the etiology of necrotizing myopathy is a diagnostic challenge and often requires a multidisciplinary assessment of internists, pathologists, and radiologists. Moreover, the presence of two rare conditions concomitantly is possible in cases with atypical features.
Topics: Humans; Pyomyositis; Female; Abscess; Escherichia coli Infections; Necrosis; Magnetic Resonance Imaging; Anti-Bacterial Agents; Escherichia coli; Diabetes Mellitus, Type 1; Urinary Tract Infections
PubMed: 38946001
DOI: 10.1186/s13256-024-04614-z -
Experimental & Molecular Medicine Jul 2024Neutrophils are emerging as an important player in skeletal muscle injury and repair. Neutrophils accumulate in injured tissue, thus releasing inflammatory factors,... (Review)
Review
Neutrophils are emerging as an important player in skeletal muscle injury and repair. Neutrophils accumulate in injured tissue, thus releasing inflammatory factors, proteases and neutrophil extracellular traps (NETs) to clear muscle debris and pathogens when skeletal muscle is damaged. During the process of muscle repair, neutrophils can promote self-renewal and angiogenesis in satellite cells. When neutrophils are abnormally overactivated, neutrophils cause collagen deposition, functional impairment of satellite cells, and damage to the skeletal muscle vascular endothelium. Heterotopic ossification (HO) refers to abnormal bone formation in soft tissue. Skeletal muscle injury is one of the main causes of traumatic HO (tHO). Neutrophils play a pivotal role in activating BMPs and TGF-β signals, thus promoting the differentiation of mesenchymal stem cells and progenitor cells into osteoblasts or osteoclasts to facilitate HO. Furthermore, NETs are specifically localized at the site of HO, thereby accelerating the formation of HO. Additionally, the overactivation of neutrophils contributes to the disruption of immune homeostasis to trigger HO. An understanding of the diverse roles of neutrophils will not only provide more information on the pathogenesis of skeletal muscle injury for repair and HO but also provides a foundation for the development of more efficacious treatment modalities for HO.
PubMed: 38945957
DOI: 10.1038/s12276-024-01270-7 -
Journal of Nutritional Science and... 2024The purpose of this study was to examine whether 4 wk of daily ingestion of milk fat globule membrane (MFGM) combined with exercise training improves physical... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of Milk Fat Globule Membrane Supplementation Following Exercise Training on Physical Performance in Healthy Young Adults: A Randomized Double-Blind, Placebo-Controlled Pilot Trial.
The purpose of this study was to examine whether 4 wk of daily ingestion of milk fat globule membrane (MFGM) combined with exercise training improves physical performance-muscle strength, agility and muscle power-in healthy young adults. The study was designed as a randomized, double-blind, and placebo-controlled trial. Twenty healthy young adults received either an MFGM powder containing 1.6 g of fat and 160 mg of sphingomyelin or an isocaloric placebo powder daily throughout 4 wk of power or agility training. Physical performance tests and body composition measurements were conducted before and after the 4-wk intervention. Ingestion of MFGM did not affect isometric or isokinetic muscle strength, but it was associated with a greater increase in vertical jump peak power compared with placebo. There were no significant changes in body weight or lean body mass during the intervention period in either group, and no significant differences between groups. We conclude that daily MFGM supplementation combined with exercise training has the potential to improve physical performance in young adults; however, further studies with larger sample sizes should be conducted to obtain more evidence supporting achievement of improved physical performance through MFGM supplementation.
Topics: Humans; Double-Blind Method; Glycolipids; Lipid Droplets; Glycoproteins; Male; Young Adult; Female; Dietary Supplements; Muscle Strength; Body Composition; Exercise; Pilot Projects; Adult; Physical Functional Performance; Body Weight; Sphingomyelins; Muscle, Skeletal
PubMed: 38945893
DOI: 10.3177/jnsv.70.273 -
Journal of Nutritional Science and... 2024Alaska pollack protein (APP), has been reported as a protein source that can enhance muscle hypertrophy more than other protein sources in animal studies. This study... (Randomized Controlled Trial)
Randomized Controlled Trial
Alaska pollack protein (APP), has been reported as a protein source that can enhance muscle hypertrophy more than other protein sources in animal studies. This study aimed to examine the effects of APP ingestion on muscle quantity and quality in young adults. Fifty-five young college students were assigned to two groups: APP and placebo (whey protein: WP) groups, and instructed to ingest 4.5 g of each protein in addition to daily meals, and to maintain their usual daily physical activities for 3 mo. Twenty-one and 23 students completed the intervention and were analyzed in APP and WP groups, respectively. The maximum knee extension torque significantly increased in both groups during the intervention. The motor unit discharge rate, which is an indicator of activation, for a given force level significantly decreased in both groups during the intervention, but its decrease in the APP group was significantly greater than in the WP group. Echo intensity of the vastus lateralis evaluated by ultrasound images significantly decreased in both groups. The muscle thickness and skeletal muscle mass did not change. Small amount of additional APP intake induces greater effects on neural activation than WP, suggesting the greater neural economy of generation of force.
Topics: Humans; Young Adult; Male; Female; Muscle, Skeletal; Dietary Proteins; Adult; Adaptation, Physiological; Gadiformes; Torque; Quadriceps Muscle; Muscle Strength; Double-Blind Method
PubMed: 38945888
DOI: 10.3177/jnsv.70.228 -
Muscle-Protective Effect of Carnosine against Dexamethasone-Induced Muscle Atrophy in C2C12 Myotube.Journal of Nutritional Science and... 2024This study investigated the protective effect of carnosine and its components (L-histidine and β-alanine [HA]) against dexamethasone (Dex)-induced muscle atrophy in...
This study investigated the protective effect of carnosine and its components (L-histidine and β-alanine [HA]) against dexamethasone (Dex)-induced muscle atrophy in C2C12 myotubes. Myotubes were treated with Dex (10 μM) to induce muscle atrophy manifested by decreased myotube diameter, low myosin heavy chain content, and increased expression of muscle atrophy-associated ubiquitin ligases (Atrogin-1, MuRF-1, and Cbl-b). Carnosine (20 mM) treatment significantly improved the myotube diameter and MyHC protein expression level in Dex-treated C2C12 myotubes. It also downregulated the expression of Atrogin-1, MuRF-1, and Cbl-b and suppressed the expression of forkhead box O3 (FoxO3a) mediated by Dex. Furthermore, reactive oxygen species production was increased by Dex but was ameliorated by carnosine treatment. However, HA (20 mM), the component of carnosine, treatment was found ineffective in preventing Dex-induced protein damage. Therefore, based on above results it can be suggested that carnosine could be a potential therapeutic agent to prevent Dex-induced muscle atrophy compared to its components HA.
Topics: Carnosine; Dexamethasone; Muscular Atrophy; Muscle Fibers, Skeletal; Animals; Mice; Muscle Proteins; Cell Line; Reactive Oxygen Species; SKP Cullin F-Box Protein Ligases; Ubiquitin-Protein Ligases; Forkhead Box Protein O3; Tripartite Motif Proteins; Myosin Heavy Chains
PubMed: 38945887
DOI: 10.3177/jnsv.70.219 -
Food Research International (Ottawa,... Aug 2024Microplastics (MPs) pose a significant threat to livestock health. Yet, the roles of polystyrene MPs (PS-MPs) on meat quality and skeletal muscle development in pigs...
Microplastics (MPs) pose a significant threat to livestock health. Yet, the roles of polystyrene MPs (PS-MPs) on meat quality and skeletal muscle development in pigs have not been fully determined. To investigate the effect of PS-MPs on skeletal muscle, piglets were given diets supplementation with 0 mg/kg (CON group), 75 mg/kg (75 mg/kg PS-MPs group), and 150 mg/kg PS-MPs (150 mg/kg PS-MPs group), respectively. The results indicated that the average daily gain (ADG) of piglets in the 150 mg/kg PS-MPs group was significantly lower than that in the CON group. No significant differences were observed in the final body weight and ADG between the CON group and the 75 mg/kg PS-MPs group. Piglets in the 150 mg/kg PS-MPs group exhibited decreased meat redness index and type I muscle fiber density. Metabolomic analysis revealed that the contents of meat flavor compounds carnosine, beta-alanine, palmitic acid, and niacinamide in muscle were lower in the 150 mg/kg PS-MPs group than in the CON group. Additionally, piglets subjected to 150 mg/kg PS-MPs exhibited impaired muscle angiogenesis. Further analysis indicated that PS-MPs exposure up-regulated thrombospondin 1 (THBS1) expression by inhibiting THBS1 mRNA and protein degradation, thereby disrupting skeletal muscle angiogenesis. These findings indicate that PS-MPs exposure adversely affects meat quality and hinders skeletal muscle angiogenesis in pigs, providing deeper insights into the detrimental effects of PS-MPs on meat quality and skeletal muscle development.
Topics: Animals; Polystyrenes; Microplastics; Muscle, Skeletal; Thrombospondin 1; Swine; Meat; Neovascularization, Physiologic; Carnosine; Animal Feed; Food Quality; Food Contamination; Male; Angiogenesis
PubMed: 38945601
DOI: 10.1016/j.foodres.2024.114581 -
Comparative Biochemistry and... Jun 2024Animals living at high-altitude are faced with unremitting low oxygen availability. This can make it difficult to perform daily tasks that require increases in aerobic...
Animals living at high-altitude are faced with unremitting low oxygen availability. This can make it difficult to perform daily tasks that require increases in aerobic metabolism. An activity important for survival is aerobic locomotion, and the rapid recovery of muscle metabolism post exercise. Past work shows that hypoxia acclimated high-altitude mice (Peromyscus maniculatus) have a greater reliance on carbohydrates to power exercise than low altitude mice. However, it is unclear how quickly after aerobic exercise these mice can recovery and replenish muscle glycogen stores. The gastrocnemius muscle of high-altitude deer mice has a more aerobic phenotype and a greater capacity to oxidize lipids than low altitude deer mice. This suggests that high altitude mice may recover more rapidly from exercise than their lowland counterparts due to a greater capacity to support glycogen replenishment using intramuscular triglycerides (IMTG). To explore this possibility, we used low- and high-altitude native deer mice born and raised in common lab conditions and acclimated to chronic hypoxia. We determined changes in oxygen consumption following 15 min of aerobic exercise in 12% O and sampled skeletal muscles and liver at various time points during recovery to examine changes in key metabolites, including glycogen and IMTG. We found depletion in glycogen stores during exercise only in lowlanders, which returned to resting levels following 90 min of recovery. In contrast, IMTG's did not change significantly with exercise or during recovery in either population. These data suggest that exercise recovery is influenced by altitude ancestry in deer mice.
PubMed: 38945522
DOI: 10.1016/j.cbpb.2024.111004 -
The Lancet. Rheumatology Jun 2024Autoimmune rheumatic diseases have distinct pathogenic mechanisms and are causes of disability and increased mortality worldwide. In this study, we aimed to examine...
Annual trends in pain management modalities in patients with newly diagnosed autoimmune rheumatic diseases in the USA from 2007 to 2021: an administrative claims-based study.
BACKGROUND
Autoimmune rheumatic diseases have distinct pathogenic mechanisms and are causes of disability and increased mortality worldwide. In this study, we aimed to examine annual trends in pain management modalities among patients with autoimmune rheumatic diseases.
METHODS
We identified newly diagnosed patients with ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis, or systemic lupus erythematosus (SLE) in the Merative Marketscan Research Databases from 2007 to 2021. The database includes deidentified inpatient and outpatient health encounters with employment-sponsored health insurance claims in the USA. We found minimal occurrences of multiple overlapping conditions and included only the initial recorded diagnosis for each patient. We determined the annual incidence of patients treated with opioids, anticonvulsants, antidepressants, skeletal muscle relaxants, non-steroidal anti-inflammatory drugs (NSAIDs), topical analgesics, and physical therapy in the year following diagnosis. Logistic regression was used to estimate the association between calendar year and outcomes, adjusted for age, sex, and region.
FINDINGS
We included 141 962 patients: 10 927 with ankylosing spondylitis, 21 438 with psoriatic arthritis, 71 393 with rheumatoid arthritis, 16 718 with Sjögren's syndrome, 18 018 with SLE, and 3468 with systemic sclerosis. 107 475 (75·7%) were women and 34 487 (24·3%) were men. Overall, the incidence of opioid use increased annually until 2014 by 4% (adjusted odds ratio [aOR] 1·04 [95% CI 1·03-1·04]) and decreased annually by 15% after 2014 (0·85 [0·84-0·86]). The incidence of physical therapy use increased annually by 5% until 2014 (aOR 1·05 [95% CI 1·04-1·06]), with a slight decrease annually by 1% after 2014 (0·99 [0·98-1·00]). The incidence of anticonvulsant use increased annually by 7% until 2014 (aOR 1·07 [95% CI 1·07-1·08]) and did not significantly change after 2014 (1·00 [0·99-1·00]). Before 2014, the incidence of NSAIDs use increased by 2% annually (aOR 1·02 [95% CI 1·02-1·03]); however, after 2014, the incidence decreased annually by 5% (0·95 [0·95-0·96]). These trends did not differ by sex except for NSAID use before 2014 (p=0·02) and topical analgesic use after 2014 (p=0·0100).
INTERPRETATION
Since 2014, the use of non-opioid pain management modalities has increased or stabilised, whereas opioid and NSAID use has declined. Future studies are needed to evaluate the effectiveness of these changes, and the effects they have had on outcomes such as quality of life, disability, and function.
FUNDING
National Institute of Arthritis and Musculoskeletal and Skin Diseases.
PubMed: 38945137
DOI: 10.1016/S2665-9913(24)00120-6