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BACKGROUND: As a result of climate change (reduced the oxygen content and food available in the waters) and overfishing, ever larger batches of the herring catch are classified as low‐value fish and used for feedstuff or canned food production. Fast and complete ripening of marinated fillets, especially from low‐value Baltic herring, poses a problem because of the low muscle protease activity and changes in muscle tissue proteins. RESULTS: For the first time, a crude digestive proteases preparation (CDPP) was obtained from herring viscera using a two‐stage method consisting of ethanol extraction and then salt precipitation. CDPP had a reduced hemoglobin content, with optimum activity at pH 7.5–8.8 or 60–120 g kg−1 NaCl. At pH 4–5, it still exhibited 24–68% of proteolytic activity. CDPP was used for 4–24 h of brining of fresh and frozen–thawed fillets or injection of fresh fillets before marinating. CDPP‐brining increased especially cathepsin D and carboxypeptidase A activities, whereas it decreased cathepsin B and L activities in the marinades. CDPP‐brining mitigated the negative effect of freezing–thawing on mass‐yield, protease activity, protein hydrolysis, texture profile, colour and sensory quality of the marinated fillets. CDPP‐injection was found to be the best method because it increased mass‐yield and ripeness of the marinated fillets to a greater extent than CDPP‐brining did. The marinades from the CDPP‐treated fillets had no bitter taste as a result of the presence of hemoglobin or chymotrypsin, and there were no results indicating lipid oxidation. CONCLUSION: The application of CDPP in marinating technology is a viable approach to enable the use of low‐value herring in food production, shorten the marinating time, and improve the ripeness and sensory quality of meat. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Identifying effective treatment(s) for sarcopenia and sarcopenic obesity is of paramount importance as the global population advances in age and obesity continues to be a worldwide concern. Evidence has shown that a ketogenic diet can be beneficial for the preservation of muscle quality and function in older adults, but long-term adherence is low due in part to the high-fat (≥80%), very low carbohydrate (<5%) composition of the diet. When provided in adequate amounts, exogenous ketone esters (KEs) can increase circulating ketones to concentrations that exceed those observed during prolonged fasting or starvation without significant alterations in the diet. Ketone esters first emerged in the mid-1990s and their use in preclinical and clinical research has escalated within the past 10–15 years. We present findings from a narrative review of the existing literature for a proposed hypothesis on the effects of exogenous ketones as a therapeutic for preservation of skeletal muscle and function within the context of sarcopenic obesity and future directions for exploration. Much of the reviewed literature herein examines the mechanisms of the ketone diester (R,S-1,3-butanediol diacetoacetate) on skeletal muscle mass, muscle protein synthesis, and epigenetic regulation in murine models. Additional studies are needed to further examine the key regulatory factors producing these effects in skeletal muscle, examine convergent and divergent effects among different ketone ester formulations, and establish optimal frequency and dosing regimens to translate these findings into humans. [ABSTRACT FROM AUTHOR]

Rugby athletes consume large amounts of animal protein in accordance with conventional dietary guidance to increase muscle mass and strength. This misaligns with national dietary guidelines, which suggest limiting meat consumption for chronic disease prevention. The ability of completely plant-based diets to satisfy the nutritional needs of rugby players has not been explored. This study scaled nutrient data from a large population consuming completely plant-based diets with limited supplemental protein to meet the calorie requirements of adult male rugby athletes to assess whether protein and leucine recommendations for muscular development and athletic performance would be achieved. Calorie requirements were estimated from research that employed the doubly labeled water method, and dietary data from the Adventist Health Study-2 were scaled to this level. The modeled protein level was 1.68 g/kg/day, which meets recommendations for maximal gains in muscle mass, strength, and athletic performance. The modeled leucine level was 2.9 g/meal for four daily meals, which exceeds the threshold proposed to maximally stimulate muscle protein synthesis in young men. These results indicate that consuming large portions of completely plant-based meals can satisfy protein and leucine requirements for maximal muscular development and athletic performance in adult male rugby athletes while aligning with public health recommendations. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor α (TNFα) exhibits diverse biological functions; however, its regulatory roles in myogenesis are not fully understood. In the present study, we explored the function of TNFα in myoblast proliferation, differentiation, migration, and myotube fusion in primary myoblasts and C2C12 cells. To this end, we constructed TNFα muscle-conditional knockout (TNFα-CKO) mice and compared them with flox mice to assess the effects of TNFα knockout on skeletal muscles. Results indicated that TNFα-CKO mice displayed phenotypes such as accelerated muscle development, enhanced regenerative capacity, and improved exercise endurance compared to flox mice, with no significant differences observed in major visceral organs or skeletal structure. Using label-free proteomic analysis, we found that TNFα-CKO altered the distribution of several muscle development-related proteins, such as Hira, Casz1, Casp7, Arhgap10, Gas1, Diaph1, Map3k20, Cfl2, and Igf2, in the nucleus and cytoplasm. Gene set enrichment analysis (GSEA) further revealed that TNFα deficiency resulted in positive enrichment in oxidative phosphorylation and MyoD targets and negative enrichment in JAK-STAT signaling. These findings suggest that TNFα-CKO positively regulates muscle growth and development, possibly via these newly identified targets and pathways. [ABSTRACT FROM AUTHOR]

Background: Thyroid cancer is a slow-growing tumor with excellent oncological outcomes. However, few patients with unexpectedly severe outcomes are usually ignored. Current Concepts: Radioactive iodine therapy is the mainstay treatment for differentiated thyroid cancer with distant metastasis. The refractoriness to radioactive iodine therapy has been overcome by the emergence of targeted agents. First, multikinase inhibitors (sorafenib and lenvatinib) targeting the growth factor pathway were developed and approved as anticancer agents for patients with advanced differentiated thyroid cancer, regardless of their genetic features. With progress in sequencing techniques, the genetic backgrounds of tumors have unveiled new targets, including rearrangements during transformation and tropomyosin receptor kinase. Special attention should be paid to the national health insurance coverage of systemic therapeutics and genetic studies. Discussion and Conclusion: New drugs were introduced to treat previously untreatable advanced thyroid cancers. However, the cost of these drugs has increased with new developments, and only first-line drugs for thyroid cancer are still covered by insurance. These medical advances will remain an illusion for clinics and patients if improvements in healthcare policies do not accompany them. [ABSTRACT FROM AUTHOR]

Background: Survival from pediatric critical illness in high‐income countries is high, and the focus now must be on optimizing the recovery of survivors. Muscle mass wasting during critical illness is problematic, so identifying factors that may reduce this is important. Therefore, the aim of this study was to examine the relationship between quadricep muscle mass wasting (assessed by ultrasound), with protein and energy intake during and after pediatric critical illness. Methods: A prospective cohort study in a mixed cardiac and general pediatric intensive care unit in England, United Kingdom. Serial ultrasound measurements were undertaken at day 1, 3, 5, 7, and 10. Results: Thirty‐four children (median age 6.65 [0.47–57.5] months) were included, and all showed a reduction in quadricep muscle thickness during critical care admission, with a mean muscle wasting of 7.75%. The 11 children followed‐up had all recovered their baseline muscle thickness by 3 months after intensive care discharge. This muscle mass wasting was not related to protein (P = 0.53, ρ = 0.019) (95% CI: −0.011 to 0.049) or energy intake (P = 0.138, ρ = 0.375 95% CI: −0.144 to 0.732) by 72 h after admission, nor with severity of illness, highest C‐reactive protein, or exposure to intravenous steroids. Children exposed to neuromuscular blocking drugs exhibited 7.2% (95% CI: −0.13% to 14.54%) worse muscle mass wasting, but this was not statistically significant (P = 0.063). Conclusion: Our study did not find any association between protein or energy intake at 72 h and quadricep muscle mass wasting. [ABSTRACT FROM AUTHOR]

Nitrogen balance (NB), the principal methodology used to derive recommendations for human protein and amino acid requirements, has been widely criticised, and calls for increased protein and amino acid requirement recommendations have been made, often on the basis of post-prandial amino acid tracer kinetic studies of muscle protein synthesis, or of amino acid oxidation. This narrative review considers our knowledge of the homeostatic regulation of the FFM throughout the diurnal cycle of feeding and fasting and what can and has been learnt from post-prandial amino acid tracer studies, about amino acid and protein requirements. Within the FFM, muscle mass in well fed weight-stable adults with healthy lifestyles appears fixed at a phenotypic level within a wide range of habitual protein intakes. However homoeostatic regulation occurs in response to variation in habitual protein intake, with adaptive changes in amino acid oxidation which influence the magnitude of diurnal losses and gains of body protein. Post-prandial indicator amino acid oxidation (IAAO) studies have been introduced as an alternative to NB and to the logistically complex 24 h [13C-1] amino acid balance studies, for assessment of protein and amino acid requirements. However, a detailed examination of IAAO studies shows both a lack of concern for homeostatic regulation of amino acid oxidation and  major flaws in their design and analytical interpretation, which seriously constrain their ability to provide reliable values. New ideas and a much more critical approach to existing work is needed if real progress is to be made in the area. [ABSTRACT FROM AUTHOR]

Key points Murine models lacking CLOCK/BMAL1 proteins in skeletal muscle (SkM) present muscle deterioration and mitochondria abnormalities. It is unclear whether humans with lower levels of these proteins in the SkM have similar alterations. Here we evaluated the association between BMAL1 and CLOCK protein mass with mitochondrial dynamics parameters and molecular and functional SkM quality markers in males. SkM biopsies were taken from the vastus lateralis of 16 male (non‐athletes, non‐obese and non‐diabetic) subjects (8–9 a.m.). The morphology of mitochondria and their interaction with the sarcoplasmic reticulum (mitochondria‐SR) were determined using transmission electron microscopy images. Additionally, protein abundance of the OXPHOS complex, mitochondria fusion/fission regulators, mitophagy and signalling proteins related to muscle protein synthesis were measured. To evaluate the quality of SkM, the cross‐sectional area and maximal SkM strength were also measured. The results showed that BMAL1 protein mass was positively associated with mitochondria‐SR distance, mitochondria size, mitochondria cristae density and mTOR protein mass. On the other hand, CLOCK protein mass was negatively associated with mitochondria‐SR interaction, but positively associated with mitochondria complex III, OPA1 and DRP1 protein mass. Furthermore, CLOCK protein mass was positively associated with the protein synthesis signalling pathway (total mTOR, AKT and P70S6K protein mass) and SkM strength. These findings suggest that the BMAL1 and CLOCK proteins play different roles in regulating mitochondrial dynamics and SkM function in males, and that modulation of these proteins could be a potential therapeutic target for treating muscle diseases. In murine models, reductions in BMAL1 and CLOCK proteins lead to changes in mitochondria biology and a decline in muscle function. However, this association has not been explored in humans. We found that in human skeletal muscle, a decrease in BMAL1 protein mass is linked to smaller intermyofibrillar mitochondria, lower mitochondria cristae density, higher interaction between mitochondria and sarcoplasmic reticulum, and reduced mTOR protein mass. Additionally, we found that a decrease in CLOCK protein mass is associated with a higher interaction between mitochondria and sarcoplasmic reticulum, lower protein mass of OPA1 and DRP1, which regulates mitochondria fusion and fission, lower protein synthesis signalling pathway (mTOR, AKT and P70S6K protein mass), and decreased skeletal muscle strength. According to our findings in humans, which are supported by previous studies in animals, the mitochondrial dynamics and skeletal muscle function could be regulated differently by BMAL1 and CLOCK proteins. As a result, targeting the modulation of these proteins could be a potential therapeutic approach for treating muscle diseases and metabolic disorders related to muscle. [ABSTRACT FROM AUTHOR]

Introduction: Tryptophan’s (Trp) metabolites are undervalued markers of human health. Their serum concentrations are modified by physical exercise and other factors, among which fasting has a well-documented role. Although this mechanism is hardly explored, thus, the study aimed to determine the effect of the 8-day fasting period and the impact of such a procedure on a single bout of an endurance exercise on the concentration of kynurenine pathway (KP) metabolites. Methods: 10 participants fasted for 8 days, and 10 as a control group participated in the study. The exercise was performed at baseline after an overnight fast and repeated post 8 days. Results: The 8 days of fasting increased the resting 3-hydroxy-L-kynurenine (3HK), picolinic acid (PA), kynurenic acid (KYNA), and xanthurenic acid (XA) serum concentration. Also elevated phenylalanine (Phe) and tyrosine (Tyr) levels were recorded, suggesting expanded proteolysis of muscle proteins. In turn, physical activity caused a decrease in the concentration of 3-hydroxyanthranilic acid (3HAA) and PA after fasting. The obtained results were not recorded in controls. Conclusion: The results of this study show that the health-promoting effects of fasting are associated with changes in the KYN pathway. The increase in the concentration of PA and XA metabolites following fasting is capable of penetrating the blood-brain barrier, and KYNA, which initiates several beneficial changes, supports this assumption. [ABSTRACT FROM AUTHOR]

Connectin (also known as titin) is a giant striated muscle protein that functions as a molecular spring by providing elasticity to the sarcomere. Novex-3 is a short splice variant of connectin whose physiological function remains unknown. We have recently demonstrated using in vitro analyses that in addition to sarcomere expression, novex-3 was also expressed in cardiomyocyte nuclei exclusively during fetal life, where it provides elasticity/compliance to cardiomyocyte nuclei and promotes cardiomyocyte proliferation in the fetus, suggesting a non-sarcomeric function. Here, we analyzed novex-3 knockout mice to assess the involvement of this function in cardiac pathophysiology in vivo. Deficiency of novex-3 compromised fetal cardiomyocyte proliferation and induced the enlargement of individual cardiomyocytes in neonates. In adults, novex-3 deficiency resulted in chamber dilation and systolic dysfunction, associated with Ca2+ dysregulation, resulting in a reduced life span. Mechanistic analyses revealed a possible association between impaired proliferation and abnormal nuclear mechanics, including stiffer nuclei positioned peripherally with stabilized circumnuclear microtubules in knockout cardiomyocytes. Although the underlying causal relationships were not fully elucidated, these data show that novex-3 has a vital non-sarcomeric function in cardiac pathophysiology and serves as an early contributor to cardiomyocyte proliferation. [ABSTRACT FROM AUTHOR]

Periods of skeletal muscle disuse lead to rapid declines in muscle mass (atrophy), which is fundamentally underpinned by an imbalance between muscle protein synthesis (MPS) and muscle protein breakdown (MPB). The complex interplay of molecular mechanisms contributing to the altered regulation of muscle protein balance during disuse have been investigated but rarely synthesised in the context of humans. This narrative review discusses human models of muscle disuse and the ensuing inversely exponential rate of muscle atrophy. The molecular processes contributing to altered protein balance are explored, with a particular focus on growth and breakdown signalling pathways, mitochondrial adaptations and neuromuscular dysfunction. Finally, key research gaps within the disuse atrophy literature are highlighted providing future avenues to enhance our mechanistic understanding of human disuse atrophy. [ABSTRACT FROM AUTHOR]

Mitochondria are essential, membrane-enclosed organelles that consist of ∼1100 different proteins, which allow for many diverse functions critical to maintaining metabolism. Highly metabolic tissues, such as skeletal muscle, have a high mitochondrial content that increases with exercise training. The classic western blot technique has revealed training-induced increases in the relatively small number of individual mitochondrial proteins studied (∼5% of the >1100 proteins in MitoCarta), with some of these changes dependent on the training stimulus. Proteomic approaches have identified hundreds of additional mitochondrial proteins that respond to exercise training. There is, however, surprisingly little crossover in the mitochondrial proteins identified in the published human training studies. This suggests that to better understand the link between training-induced changes in mitochondrial proteins and metabolism, future studies need to move beyond maximizing protein detection to adopting methods that will increase the reliability of the changes in protein abundance observed. [ABSTRACT FROM AUTHOR]

Oxidative stress is considered a contributor to declining muscle function and mobility during aging; however, the underlying molecular mechanisms remain poorly described. We hypothesized that greater levels of cysteine (Cys) oxidation on muscle proteins are associated with decreased measures of mobility. Herein, we applied a novel redox proteomics approach to measure reversible protein Cys oxidation in vastus lateralis muscle biopsies collected from 56 subjects in the Study of Muscle, Mobility and Aging (SOMMA), a community‐based cohort study of individuals aged 70 years and older. We tested whether levels of Cys oxidation on key muscle proteins involved in muscle structure and contraction were associated with muscle function (leg power and strength), walking speed, and fitness (VO2 peak on cardiopulmonary exercise testing) using linear regression models adjusted for age, sex, and body weight. Higher oxidation levels of select nebulin Cys sites were associated with lower VO2 peak, while greater oxidation of myomesin‐1, myomesin‐2, and nebulin Cys sites was associated with slower walking speed. Higher oxidation of Cys sites in key proteins such as myomesin‐2, alpha‐actinin‐2, and skeletal muscle alpha‐actin were associated with lower leg power and strength. We also observed an unexpected correlation (R = 0.48) between a higher oxidation level of eight Cys sites in alpha‐actinin‐3 and stronger leg power. Despite this observation, the results generally support the hypothesis that Cys oxidation of muscle proteins impairs muscle power and strength, walking speed, and cardiopulmonary fitness with aging. [ABSTRACT FROM AUTHOR]

Background: Fibrosis is a significant pathological feature of chronic skeletal muscle injury, profoundly affecting muscle regeneration. Fibro-adipogenic progenitors (FAPs) have the ability to differentiate into myofibroblasts, acting as a primary source of extracellular matrix (ECM). the process by which FAPs differentiate into myofibroblasts during chronic skeletal muscle injury remains inadequately explored. Method: mouse model with sciatic nerve denervated was constructed and miRNA expression profiles between the mouse model and uninjured mouse were analyzed. qRT/PCR and immunofluorescence elucidated the effect of miR-27b-3p on fibrosis in vivo and in vitro. Dual-luciferase reporter identified the target gene of miR-27b-3p, and finally knocked down or overexpressed the target gene and phosphorylation inhibition of Smad verified the influence of downstream molecules on the abundance of miR-27b-3p and fibrogenic differentiation of FAPs. Result: FAPs derived from a mouse model with sciatic nerves denervated exhibited a progressively worsening fibrotic phenotype over time. Introducing agomiR-27b-3p effectively suppressed fibrosis both in vitro and in vivo. MiR-27b-3p targeted Transforming Growth Factor Beta Receptor 1 (TGF-βR1) and the abundance of miR-27b-3p was negatively regulated by TGF-βR1/Smad. Conclusion: miR-27b-3p targeting the TGF-βR1/Smad pathway is a novel mechanism for regulating fibrogenic differentiation of FAPs. Increasing abundance of miR-27b-3p, suppressing expression of TGF-βR1 and inhibiting phosphorylation of smad3 presented potential strategies for treating fibrosis in chronic skeletal muscle injury. [ABSTRACT FROM AUTHOR]

Chronic inflammation causes muscle wasting. Because most inflammatory cytokine signals are mediated via TGF-β-activated kinase-1 (TAK1) activation, inflammatory cytokine-induced muscle wasting may be ameliorated by the inhibition of TAK1 activity. The present study was undertaken to clarify whether TAK1 inhibition can ameliorate inflammation-induced muscle wasting. SKG/Jcl mice as an autoimmune arthritis animal model were treated with a small amount of mannan as an adjuvant to enhance the production of TNF-α and IL-1β. The increase in these inflammatory cytokines caused a reduction in muscle mass and strength along with an induction of arthritis in SKG/Jcl mice. Those changes in muscle fibers were mediated via the phosphorylation of TAK1, which activated the downstream signaling cascade via NF-κB, p38 MAPK, and ERK pathways, resulting in an increase in myostatin expression. Myostatin then reduced the expression of muscle proteins not only via a reduction in MyoD1 expression but also via an enhancement of Atrogin-1 and Murf1 expression. TAK1 inhibitor, LL-Z1640-2, prevented all the cytokine-induced changes in muscle wasting. Thus, TAK1 inhibition can be a new therapeutic target of not only joint destruction but also muscle wasting induced by inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Tunicate orthologs in the human genome comprise just 84 genes of the 19,872 protein-coding genes and 23 of the 16,528 non-coding genes, yet they stand at the base of the Olfactores clade, which radiated to generate thousands of tunicate and vertebrate species. What were the powerful drivers among these genes that enabled this process? Many of these orthologs are present in gene families. We discuss the biological role of each family and the orthologs' quantitative contribution to the family. Most important was the evolution of a second type of cadherin. This, a Type II cadherin, had the property of detaching the cell containing that cadherin from cells that expressed the Type I class. The set of such Type II cadherins could now detach and move away from their Type I neighbours, a process which would eventually evolve into the formation of the neural crest, "the fourth germ layer", providing a wide range of possibilities for further evolutionary invention. A second important contribution were key additions to the broad development of the muscle and nerve protein and visual perception toolkits. These developments in mobility and vision provided the basis for the development of the efficient predatory capabilities of the Vertebrata. [ABSTRACT FROM AUTHOR]

Background: Skeletal craniofacial morphology can be influenced by changes in masticatory muscle function, which may also change the functional profile of the muscles. Objectives: To investigate the effects of age and functional demands on the expression of Myosin Heavy‐Chain (MyHC) isoforms in representative jaw‐closing and jaw‐opening muscles, namely the masseter and digastric muscles respectively. Methods: Eighty‐four male Wistar rats were divided into four age groups, namely an immature (n = 12; 4‐week‐old), early adult (n = 24; 16‐week‐old), adult (n = 24; 26‐week‐old) and mature adult (n = 24; 38‐week‐old) group. The three adult groups were divided into two subgroups each based on diet consistency; a control group fed a standard (hard) diet, and an experimental group fed a soft diet. Rats were sacrificed, and masseter and digastric muscles dissected. Real‐time quantitative polymerase chain reaction was used to compare the mRNA transcripts of the MyHC isoforms—Myh7 (MyHC‐I), Myh2 (MyHC‐IIa), Myh4 (MyHC‐IIb) and Myh1 (MyHC‐IIx)—of deep masseter and digastric muscles. Results: In the masseter muscle, hypofunction increases Myh1 (26, 38 weeks; p <.0001) but decreases Myh4 (26 weeks; p =.046) and Myh2 (26 weeks; p <.0001) expression in adult rats. In the digastric muscle, hypofunction increases Myh1 expression in the mature adult rats (38 weeks; p <.0001), while Myh2 expression decreases in adult rats (26 weeks; p =.021) as does Myh4 (26 weeks; p =.001). Myh7 expression is increased in the digastric muscle of mature adult rats subjected to hypofunction (38 weeks; p = <.0001), while it is very weakly expressed in the masseter. Conclusion: In jaw‐opening and jaw‐closing muscles, differences in myosin expression between hard‐ and soft‐diet‐fed rats become evident in adulthood, suggesting that long‐term alteration of jaw function is associated with changes in the expression of MyHC isoforms and potential fibre remodelling. This may give insight into the role of function on masticatory muscles and the resultant craniofacial morphology. [ABSTRACT FROM AUTHOR]

Calcium /3-hydroxy-/3-methylbutyrate (CaHMB), as a new food raw material, has obtained approval in multiple countries, including China. In China, CaHMB is allowed to be used in foods for special medical purposes. However, despite being approved in China for over a decade, no products containing CaHMB have been introduced as foods for special medical purposes to the market. Thus, there is a need to form a consensus on the health benefits, safety, dosage and other aspects of CaHMB to facilitate its application in the relevant food industry, regulatory authorities and consumer understanding, thereby advancing its application to better address the nutritional and health needs of the publication. This article provided comprehensive analysis of the global research and application of CaHMB, engaging relevant academic and industrial experts to form the scientific consensus on the application of CaHMB via literature analysis and scientific discussions, as: 1) CaHMB, as new food raw material and the calcium salt form of HMB, plays a crucial role to supplement HMB in promoting muscle protein synthesis and reducing muscle protein breakdown; 2) CaHMB supplementation is beneficial to correct the negative nitrogen balance and improving muscle health in the elderly and people with various diseases (such as sarcopenia syndrome, oncology, etc.); 3) The safety of CaHMB is widely recognized, and appropriate increase its maximal daily intake limit locally can better support target population to receive health benefits and promote industrial application development. Recommendations: At the policy level, proactive measures can guide the appropriate increase in the maximal daily intake limit of CaHMB to better address the nutritional and health needs of the population; further strengthen scientific research and innovation on CaHMB to provide scientific and technical evidence supporting its optimal application and related policy development; promote CaHMB application in food industry, especially in foods for special medical purposes, to further forest high-quality development of related industries. [ABSTRACT FROM AUTHOR]

Background and objective: Forkhead box‐O 1 (FOXO1) is a transcription factor actively involved in oral wound healing at the epithelial barrier. However, less is known regarding the role of FOXO1 during the tissue repair response in the connective tissue compartment. This study explored the involvement of FOXO1 in the modulation of fibroblast activity related to wound healing. Methods: Primary cultures of human gingival fibroblasts were obtained from four healthy young donors. Myofibroblastic differentiation, collagen gel contraction, cell migration, cell spreading, and integrin activation were evaluated in the presence or absence of a FOXO1 inhibitor (AS1842856). Variations in mRNA and proteins of interest were evaluated through qRT‐PCR and western blot, respectively. Distribution of actin, α‐smooth muscle actin, and β1 integrin was evaluated using immunofluorescence. FOXO1 and TGF‐β1 expression in gingival wound healing was assessed by immunohistochemistry in gingival wounds performed in C57BL/6 mice. Images were analyzed using ImageJ/Fiji. ANOVA or Kruskal‐Wallis test followed by Tukey's or Dunn's post‐hoc test was performed. All data are expressed as mean ± SD. p <.05 was considered statistically significant. Results: FOXO1 inhibition caused a decrease in the expression of the myofibroblastic marker α‐SMA along with a reduction in fibronectin, type I collagen, TGF‐β1, and β1 integrin mRNA level. The FOXO1 inhibitor also caused decreases in cell migration, cell spreading, collagen gel contraction, and β1 integrin activation. FOXO1 and TGF‐β1 were prominently expressed in gingival wounds in fibroblastic cells located at the wound bed. Conclusion: The present study indicates that FOXO1 plays an important role in the modulation of several wound‐healing functions in gingival fibroblast. Moreover, our findings reveal an important regulatory role for FOXO1 on the differentiation of gingival myofibroblasts, the regulation of cell migration, and collagen contraction, all these functions being critical during tissue repair and fibrosis. [ABSTRACT FROM AUTHOR]

To better understand the genetic basis of heart disease, we identified a variant in the Flightless-I homolog (FLII) gene that generates a R1243H missense change and predisposes to cardiac remodeling across multiple previous human genome-wide association studies (GWAS). Since this gene is of unknown function in the mammalian heart we generated gain- and loss-of-function genetically altered mice, as well as knock-in mice with the syntenic R1245H amino acid substitution, which showed that Flii protein binds the sarcomeric actin thin filament and influences its length. Deletion of Flii from the heart, or mice with the R1245H amino acid substitution, show cardiomyopathy due to shortening of the actin thin filaments. Mechanistically, Flii is a known actin binding protein that we show associates with tropomodulin-1 (TMOD1) to regulate sarcomere thin filament length. Indeed, overexpression of leiomodin-2 in the heart, which lengthens the actin-containing thin filaments, partially rescued disease due to heart-specific deletion of Flii. Collectively, the identified FLII human variant likely increases cardiomyopathy risk through an alteration in sarcomere structure and associated contractile dynamics, like other sarcomere gene-based familial cardiomyopathies.

BackgroundAlthough survival rates for infants born extremely preterm (gestation

Simple Summary: Cancer cachexia (CC) is a syndrome affecting advanced cancer patients, causing inflammation, metabolic dysfunction, and a decline in quality of life. It increases the risk of mortality. Nutritional therapies are being tested for improving muscle metabolism in cancer patients, but no special therapies have been validated in clinical practice. Studies suggest increasing muscle protein synthesis through amino acids or protein intake, and physical activity can reduce muscle atrophy. This manuscript provides an overview of the preclinical and clinical approaches for the use of amino acids with and without exercise therapy to improve muscle metabolism in cachexia. Cancer cachexia is a multifaceted syndrome that impacts individuals with advanced cancer. It causes numerous pathological changes in cancer patients, such as inflammation and metabolic dysfunction, which further diminish their quality of life. Unfortunately, cancer cachexia also increases the risk of mortality in affected individuals, making it an important area of focus for cancer research and treatment. Several potential nutritional therapies are being tested in preclinical and clinical models for their efficacy in improving muscle metabolism in cancer patients. Despite promising results, no special nutritional therapies have yet been validated in clinical practice. Multiple studies provide evidence of the benefits of increasing muscle protein synthesis through an increased intake of amino acids or protein. There is also increasing evidence that exercise can reduce muscle atrophy by modulating protein synthesis. Therefore, the combination of protein intake and exercise may be more effective in improving cancer cachexia. This review provides an overview of the preclinical and clinical approaches for the use of amino acids with and without exercise therapy to improve muscle metabolism in cachexia. [ABSTRACT FROM AUTHOR]

Fishmeal is an important protein source in aquafeed. However, due to the limited natural resources, fishmeal is in short supply, resulting in a price surge for fishmeal. Here, we reported a kind of Chinese medicine residue, endothelium corneum gigeriae galli residue (ECGGR), as a fishmeal substitute in the diets of Trachinotus ovatus. Six isonitrogenous and isolipidic diets were formulated, substituting fishmeal at 0%, 6.25%, 12.5%, 18.75%, 25%, and 31.25%. There was no significant difference in the growth performance when the fishmeal substitution level was no more than 25%. The smallest FCR was obtained at the 18.75% substitution level. Furthermore, substituting ECGGR for fishmeal had no effect on whole-body and muscle proximate compositions, except when the replacement level exceeded 25%, which led to a decrease in whole-body moisture and an increase in whole-body crude protein. The contents of Gly, Cys, Ile, Tyr, Pro, and EAAs/TAAs were altered as the substitution level varied. However, dietary replacement of fishmeal with ECGGR did not degrade muscle protein quality, according to a nutritional evaluation of muscle essential amino acid composition. In terms of hepatic antioxidant capacity, neither the overall antioxidant status nor the expression of genes in the Nrf2-ARE pathway was altered by dietary ECGGR. Moreover, the expressions of p65, TNF-α, and IL-8 in the intestine were upregulated at the 31.25% substitution level. Also, more goblet cells were observed in the intestine at substitution levels of 25% and 31.25%. In conclusion, ECGGR can substitute for fishmeal at the optimal level of 18.75% without adversely affecting the growth performance, protein quality, or hepatic and intestinal health of golden pompano. [ABSTRACT FROM AUTHOR]

Background: Myocarditis refers to an autoimmune inflammatory response of the myocardium with characterization of self-reactive CD4+ T cell activation, which lacks effective treatment and has a poor prognosis. Acacetin is a natural flavonoid product that has been reported to have anti-inflammatory effects. However, acacetin has not been investigated in myocarditis. Methods: Oral acacetin treatment was administered in an experimental autoimmune myocarditis model established with myosin heavy chain-alpha peptide. Echocardiography, pathological staining, and RT-qPCR were used to detect cardiac function, myocardial injury, and inflammation levels. Flow cytometry was utilized to detect the effect of acacetin on CD4+ T cell function. RNA-seq, molecular docking, and microscale thermophoresis (MST) were employed to investigate potential mechanisms. Seahorse analysis, mitoSOX, JC-1, and mitotracker were utilized to detect the effect of acacetin on mitochondrial function. Results: Acacetin attenuated cardiac injury and fibrosis as well as heart dysfunction, and reduced cardiac inflammatory cytokines and ratio of effector CD4+ T and Th17 cells. Acacetin inhibited CD4+ T cell activation, proliferation, and Th17 cell differentiation. Mechanistically, the effects of acacetin were related to reducing mitochondrial complex II activity thereby inhibiting mitochondrial respiration and mitochondrial reactive oxygen species in CD4+ T cells. Conclusion: Acacetin may be a valuable therapeutic drug in treating CD4+ T cell-mediated myocarditis. [ABSTRACT FROM AUTHOR]

Background: The study objective was to test the hypothesis that low crude protein (CP) diet with crystalline amino acids (CAA) supplementation improves Lys utilization efficiency for milk production and reduces protein turnover and muscle protein breakdown. Eighteen lactating multiparous Yorkshire sows were allotted to 1 of 2 isocaloric diets (10.80 MJ/kg net energy): control (CON; 19.24% CP) and reduced CP with "optimal" AA profile (OPT; 14.00% CP). Sow body weight and backfat were recorded on d 1 and 21 of lactation and piglets were weighed on d 1, 14, 18, and 21 of lactation. Between d 14 and 18, a subset of 9 sows (CON = 4, OPT = 5) was infused with a mixed solution of 3-[methyl-2H3]histidine (bolus injection) and [13C]bicarbonate (priming dose) first, then a constant 2-h [13C]bicarbonate infusion followed by a 6-h primed constant [1-13C]lysine infusion. Serial blood and milk sampling were performed to determine plasma and milk Lys enrichment, Lys oxidation rate, whole body protein turnover, and muscle protein breakdown. Results: Over the 21-d lactation period, compared to CON, sows fed OPT had greater litter growth rate (P < 0.05). Compared to CON, sows fed OPT had greater efficiency of Lys (P < 0.05), Lys mammary flux (P < 0.01) and whole-body protein turnover efficiency (P < 0.05). Compared to CON, sows fed OPT tended to have lower whole body protein breakdown rate (P = 0.069). Muscle protein breakdown rate did not differ between OPT and CON (P = 0.197). Conclusion: Feeding an improved AA balance diet increased efficiency of Lys and reduced whole-body protein turnover and protein breakdown. These results imply that the lower maternal N retention observed in lactating sows fed improved AA balance diets in previous studies may be a result of greater partitioning of AA towards milk rather than greater body protein breakdown. [ABSTRACT FROM AUTHOR]

Adverse experiences (e.g., acute stress) and alcohol misuse can both impair skeletal muscle homeostasis, resulting in reduced protein synthesis and greater protein breakdown. Exposure to acute stress is a significant risk factor for engaging in alcohol misuse. However, little is known about how these factors together might further affect skeletal muscle health. To that end, this study investigated the effects of acute stress exposure followed by a period of binge-patterned alcohol drinking on signaling factors along mouse skeletal muscle protein synthesis (MPS) and degradation (MPD) pathways. Young adult male C57BL/6J mice participated in the Drinking in the Dark paradigm, where they received 2–4 h of access to 20% ethanol (alcohol group) or water (control group) for four days to establish baseline drinking levels. Three days later, half of the mice in each group were either exposed to a single episode of uncontrollable tail shocks (acute stress) or remained undisturbed in their home cages (no stress). Three days after stress exposure, mice received 4 h of access to 20% ethanol (alcohol) to model binge-patterned alcohol drinking or water for ten consecutive days. Immediately following the final episode of alcohol access, mouse gastrocnemius muscle was extracted to measure changes in relative protein levels along the Akt-mTOR MPS, as well as the ubiquitin-proteasome pathway (UPP) and autophagy MPD pathways via Western blotting. A single exposure to acute stress impaired Akt singling and reduced rates of MPS, independent of alcohol access. This observation was concurrent with a potent increase in heat shock protein seventy expression in the muscle of stressed mice. Alcohol drinking did not exacerbate stress-induced alterations in the MPS and MPD signaling pathways. Instead, changes in the MPS and MPD signaling factors due to alcohol access were primarily observed in non-stressed mice. Taken together, these data suggest that exposure to a stressor of sufficient intensity may cause prolonged disruptions to signaling factors that impact skeletal muscle health and function beyond what could be further induced by periods of alcohol misuse. [ABSTRACT FROM AUTHOR]

We assessed the effects of two levels of calorie restriction (CR; eating either 15% or 35% less than ad libitum, AL, food intake for 8 weeks) by 24-month-old female and male rats on glucose uptake (GU) and phosphorylation of key signaling proteins (Akt; AMP-activated protein kinase, AMPK; Akt substrate of 160 kDa, AS160) measured in isolated skeletal muscles that underwent four incubation conditions (without either insulin or AICAR, an AMPK activator; with AICAR alone; with insulin alone; or with insulin and AICAR). Regardless of sex: (1) neither CR group versus the AL group had greater GU by insulin-stimulated muscles; (2) phosphorylation of Akt in insulin-stimulated muscles was increased in 35% CR versus AL rats; (3) prior AICAR treatment of muscle resulted in greater GU by insulin-stimulated muscles, regardless of diet; and (4) AICAR caused elevated phosphorylation of acetyl CoA carboxylase, an indicator of AMPK activation, in all diet groups. There was a sexually dimorphic diet effect on AS160 phosphorylation, with 35% CR exceeding AL for insulin-stimulated muscles in male rats, but not in female rats. Our working hypothesis is that the lack of a CR-effect on GU by insulin-stimulated muscles was related to the extended duration of the ex vivo incubation period (290 min compared to 40–50 min that was previously reported to be effective). The observed efficacy of prior treatment of muscles with AICAR to improve glucose uptake in insulin-stimulated muscles supports the strategy of targeting AMPK with the goal of improving insulin sensitivity in older females and males. [ABSTRACT FROM AUTHOR]

This study investigated the preventive effects of whey protein fermented with Lactobacillus gasseri IM13 (F-WP) against dexamethasone (DEX)-induced muscle atrophy. C2C12 muscle cells were treated with F-WP followed by DEX treatment. Dexamethasone treatment inhibited myotube formation and the expression of myogenic regulatory factors; however, pretreatment with F-WP attenuated DEX-induced damage. The F-WP significantly activated the phosphorylation of the IGF-1/PI3K/AKT pathway and improved muscle homeostasis suppressed by DEX. Moreover, F-WP alleviated the phosphorylation of mTOR, S6K1, and 4E-BP1 and enhanced muscle protein synthesis. Muscle-specific ubiquitin ligases and autophagy lysosomes, which were activated by the dephosphorylation of FOXO3a by DEX treatment, were significantly attenuated by F-WP pretreatment of myotubes. For peptidomic analysis, F-WP was fractionated using preparative HPLC (prep-HPLC), and the AA sequences of 11 peptides were identified using MALDI-TOF/MS/MS. In conclusion, fermentation of whey protein by the specific probiotic strain IM13 produced bioactive peptides with high antioxidant and anti-sarcopenic-sarcopenic effects, which markedly enhanced myogenesis and muscle protein synthesis while diminishing muscle protein degradation compared with intact whey protein. [Display omitted] [ABSTRACT FROM AUTHOR]

The goal of this narrative review is to summarize the effects of prolonged fasting on various metabolic health measures, including body weight, blood pressure, plasma lipids, and glycemic control. Prolonged fasting is characterized by consciously eating little to no food or caloric beverages for several days to weeks. Results reveal that prolonged fasting for 5–20 days produces potent increases in circulating ketones, and mild to moderate weight loss of 2–10%. Approximately two-thirds of the weight lost is lean mass, and one-third is fat mass. The excessive lean mass loss suggests that prolonged fasting may increase the breakdown of muscle proteins, which is a concern. Systolic and diastolic blood pressure consistently decreased with prolonged fasting. However, the impact of these protocols on plasma lipids is less clear. While some trials demonstrate decreases in LDL cholesterol and triglycerides, others show no benefit. With regard to glycemic control, reductions in fasting glucose, fasting insulin, insulin resistance, and glycated hemoglobin (HbA1c) were noted in adults with normoglycemia. In contrast, these glucoregulatory factors remained unchanged in patients with type 1 or type 2 diabetes. The effects of refeeding were also examined in a few trials. It was shown that 3–4 months after the fast was completed, all metabolic benefits were no longer observed, even when weight loss was maintained. With regard to adverse events, metabolic acidosis, headaches, insomnia, and hunger were observed in some studies. In summary, prolonged fasting appears to be a moderately safe diet therapy that can produce clinically significant weight loss (>5%) over a few days or weeks. However, the ability of these protocols to produce sustained improvements in metabolic markers warrants further investigation. [ABSTRACT FROM AUTHOR]

As the economy develops and living standards improve, overweight and obesity are increasingly prevalent. Currently, weight-loss medications are primarily administered orally or intravenously, which can result in poor targeting, low bioavailability, frequent administration, and high toxicity and side effects. The study aimed to address these challenges by preparing polylactic acidpolyethylene glycol staple fibers that carry the browning drug pioglitazone hydrochloride using electrostatic spinning and freeze-cutting techniques. Animal experiments were conducted to test the effectiveness of these fibers. Additionally, the study investigated the expression of uncoupling protein genes in rats exposed to different water temperatures by measuring changes in serum urea nitrogen and mRNA expression levels of skeletal muscle uncoupling protein genes. The physiological and genetic effects of low-temperature swimming exercise on changes in energy metabolism in rats were also analyzed at both the individual and molecular levels. The results revealed that serum urea nitrogen remained more stable in hypothermic swimming rats compared to rats in the swimming group. Furthermore, the study observed an induced up-regulation of uncoupling proteins in the skeletal muscle of Wistar rats in response to external temperature stimulation, and the expression of mRNA for skeletal muscle uncoupling proteins significantly increased as the temperature decreased. And the prepared short nanofibers also had a significant promotive effect on uncoupling protein gene, COX7A1, while suppressing the expression of lipogenic gene. [ABSTRACT FROM AUTHOR]

Hamartomas, a focal excess of normal tissue usually presenting as isolated masses, are rarely found in the head and neck region. The purpose of this report is to discuss a rare case of an intra-oral angioleiomyomatous hamartoma in a 14-year-old male who presented with a congenital nodule over the anterior palatal mucosa. The confirmatory diagnosis was done based on histopathology and immunohistochemistry using various markers. A brief review of the literature and clinical differential diagnoses are discussed, along with the clinical significance of hamartomas associated with syndromes. Hence, the identification of such hamartomas may lead to early diagnosis of associated syndromes in pediatric patients. [ABSTRACT FROM AUTHOR]

Antifreeze peptides have become effective antifreeze agents for frozen products, but their low quantity of active ingredients and high cost limit large-scale application. This study used the glycosylation of fish collagen peptides with glucosamine hydrochloride catalyzed by transglutaminase to obtain a transglutaminase-catalyzed glycosylation product (TGP) and investigate its antifreeze effect on tilapia. Compared with the blank group, the freshness (pH value of 6.31, TVB-N value of 21.7 mg/100 g, whiteness of 46.28), textural properties (especially hardness and elasticity), and rheological properties of the TGP groups were significantly improved. In addition, the protein structures of the samples were investigated using UV absorption and fluorescence spectroscopy. The results showed that the tertiary structure of the TGP groups changed to form a dense polymer. Therefore, this approach can reduce the denaturation and decomposition of muscle fibers and proteins in fish meat more effectively and has a better protective effect on muscle structure and protein aggregation, improving the stability of fish meat. This study reveals an innovative method for generating antifreeze peptides by enzymatic glycosylation, and glycosylated fish collagen peptide products can be used as new and effective green antifreeze agents in frozen foods. [ABSTRACT FROM AUTHOR]

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Circadian regulation and temperature dependency are important orchestrators of molecular pathways. How the integration between these two drivers is achieved, is not understood. We monitored circadian-and temperature-dependent effects on transcription dynamics of cold-response protein RNA Binding Motif 3 (Rbm3). Temperature changes in the mammalian master circadian pacemaker, the suprachiasmatic nucleus (SCN), induced Rbm3 transcription and regulated its circadian periodicity, whereas the core clock gene Per2 was unaffected. Rbm3 induction depended on a full Brain And Muscle ARNT-Like Protein 1 (Bmal1) complement: reduced Bmal1 erased Rbm3 responses and weakened SCN circuit resilience to temperature changes. By focusing on circadian and temperature dependency, we highlight weakened transmission between core clock and downstream pathways as a potential route for reduced circadian resilience. [ABSTRACT FROM AUTHOR]

The purpose of this study was to study and analyze the composition and content of routine nutrients, amino acids, fatty acids, and mineral elements in muscle of three cultured populations of Cipangopaludina cathayensis, so as to provide a reference for the development and utilization of Cipangopaludina cathayensis germplasm resources. A total of 180 Cipangopaludina cathayensis with an average weight of (32.12±0.17) g were randomly divided into three groups with 60 Cipangopaludina cathayensis in each group. After shelling, the muscles were taken to test their nutritional components. The results showed that the crude protein, total amino acids, essential amino acids, and delicious amino acids in muscle of Luchuan County population were significantly higher than those of other populations (P<0.05). The amino acid score, chemical score, and essential amino acid index of Liujiang population were the highest. The contentrations of unsaturated fatty acids and polyunsaturated fatty acids in muscle of Luchuan County population were significantly higher than those of other populations, and the atherosclerosis index (IA) and thrombosis index (IT) were lower than those of other populations (P<0.05). The ratio of sigma-n-3/sigma-n-6PUFA of the three populations was in line with the recommended value of FAO/WHO for human diet (0.1~0.2). The contentrations of P and Ca in muscle of Rongshui County population were significantly higher than those of other populations (P<0.05). The study indicates that the muscle protein content of the three cultured populations is higher, the fat content is lower, and the delicious amino acids and unsaturated fatty acids are higher. The nutritional value of the muscle of Luchuan County population are better than those of other populations. [ABSTRACT FROM AUTHOR]

Skeletal muscle plays a critical role in metabolic diseases, such as obesity and type 2 diabetes mellitus (T2DM). Muscle atrophy, characterized by a decrease in muscle mass and function, occurs due to an imbalance between the rates of muscle protein synthesis and degradation. This study aimed to investigate the molecular mechanisms that lead to muscle atrophy in obese and T2DM mouse models. Additionally, the effect of nerve growth factor (NGF) on the protein synthesis and degradation pathways was examined. Male mice were divided into three groups: a control group that was fed a standard chow diet, and two experimental groups that were fed a Western diet. After 8 weeks, the diabetic group was injected with streptozotocin to induce T2DM. Each group was then further divided into NGF-treated or non-treated control group. In the gastrocnemius muscles of the Western diet group, increased expressions of myostatin, autophagy markers, and ubiquitin ligases were observed. Skeletal muscle tissue morphology indicated signs of muscle atrophy in both obese and diabetic mice. The NGF-treated group showed a prominent decrease in the protein levels of myostatin and autophagy markers. Furthermore, the NGF-treated group showed an increased Cyclin D1 level. Western diet-induced obesity and T2DM may be linked to muscle atrophy through upregulation of myostatin and subsequent increase in the ubiquitin and autophagy systems. Moreover, NGF treatment may improve muscle protein synthesis and cell cycling. [ABSTRACT FROM AUTHOR]