Search Results (180)

This study investigated the effects of dietary carbohydrate levels (control 8.13%, HG1 12.03%, and HG2 14.15%) on growth performance and glutamate metabolism in Chinese perch (S. chuatsi) (initial weight: 39.12 ± 0.25 g) reared at 12–15 °C. Diets were isonitrogenous (49% protein). After 8 weeks, the HG1 group optimized weight gain rate (WGR), specific growth rate (SGR), and protein efficiency ratio (PER), while reducing feed conversion ratio (FCR). HG1 and HG2 groups reduced liver glutamate/glutamine levels while downregulating the expression of key ammonia-metabolizing genes (gs, gdh, and ampd), collectively suppressing glutamate-mediated ammonia excretion. HG1 and HG2 groups enhanced glycolysis (upregulated gk and pk) coupled with suppressed gluconeogenesis (decreased PEPCK and G6Pase activities) in the liver. Concurrent downregulation of proteolytic markers (mafbx and murf1) in the muscle indicated improved protein conservation efficiency in the HG1 and HG2 groups. The HG1 diet optimally enhances growth by promoting glycolysis, reducing ammonia excretion, and improving feed efficiency. The insights gained from this research will be used to refine the low-temperature culture feed for Chinese perch, aiming to decrease ammonia and nitrogen emissions, thereby advancing the practice of low-ammonia emission culture for this species. Full article

Platycladus orientalis, an evergreen tree belonging to the Cupressaceae family, has been traditionally used to treat various ailments, including fever, cough, diarrhea, diuresis, cold symptoms, and gastrointestinal disorders in folk medicine. As part of our ongoing investigation aimed at discovering bioactive natural products and elucidating their mechanisms of action from various natural sources, we investigated a methanol (MeOH) extract of P. orientalis leaves. This investigation led to the isolation and identification of a labdane-type diterpene, lambertianic acid (LA), via column chromatography and HPLC purification. The structure of LA was elucidated using LC/MS and NMR spectroscopic analyses, including HR-ESIMS, while its absolute configuration was confirmed through electronic circular dichroism (ECD) calculations. Recent studies have reported that labdane-type diterpenes exhibit diverse pharmacological activities, such as anticancer, anti-inflammatory, anti-obesity, and hypolipidemic effects. Notably, LA has been shown to modulate adipocyte metabolism via AMPK signaling; however, its role in skeletal muscle atrophy remains unexplored. Therefore, in this study, we investigated the effects of LA on dexamethasone (Dex)-induced muscle atrophy in C2C12 myotubes. Treatment with LA at concentrations of 25 µM and 50 µM significantly rescued myotube diameter and reduced the expression of atrophy-related proteins, including MuRF-1 and atrogin-1/MAFbx, without compromising cell viability at these moderate concentrations. These findings suggest that LA derived from P. orientalis exerts protective effects against skeletal muscle atrophy, highlighting its potential as a promising natural therapeutic candidate for muscle-wasting disorders. Full article

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract, defined by intestinal epithelial cell death. While ferroptosis and disulfidptosis have been linked to IBD pathogenesis, the functional significance of disulfidptosis-related ferroptosis genes (DRFGs) in this disease remains poorly characterized. This investigation sought to pinpoint DRFGs as diagnostic indicators and clarify their mechanistic contributions to IBD progression. Methods: Four IBD datasets (GSE65114, GSE87473, GSE102133, and GSE186582) from the GEO database were integrated to identify differentially expressed genes (DEGs) (|log2FC| > 0.585, adj. p < 0.05). A Pearson correlation analysis was used to link disulfidptosis and ferroptosis genes, followed by machine learning (LASSO and RF) to screen core DRFGs. The immune subtypes and single-cell sequencing (GSE217695) results were analyzed. A DSS-induced colitis Mus musculus (C57BL/6) model was used for validation. Results: Transcriptomic profiling identified 521 DEGs, with 16 defined as DRFGs. Nine hub genes showed diagnostic potential (AUC: 0.71–0.91). Functional annotation demonstrated that IBD-associated genes regulate diverse pathways, with a network analysis revealing their functional synergy. The PPI networks prioritized DUOX2, NCF2, ACSL4, GPX2, CBS, and LPCAT3 as central hubs. Two immune subtypes exhibited divergent DRFG expression. Single-cell mapping revealed epithelial/immune compartment specificity. The DSS-induced murine colitis model confirmed differential expression patterns of DRFGs, with concordant results between qRT-PCR and RNA-seq, emphasizing their pivotal regulatory roles in disease progression and potential for translational application. Conclusions: DRFGs mediate IBD progression via multi-signal pathway regulation across intestinal cell types, demonstrating diagnostic and prognostic potential. Full article

MuRF1 [muscle RING (Really Interesting New Gene)-finger protein-1] is an ubiquitin-protein ligase (E3), which encode by TRIM63 (tripartite motif containing 63) gene, playing a crucial role in regulating cardiac muscle size and function through ubiquitylation. Among hypertrophic cardiomyopathy (HCM) patients, 24 TRIM63 variants have been identified, with 1 additional variant linked to restrictive cardiomyopathy. However, only three variants have been previously investigated for their functional effects. The structural impacts of the 25 variants remain unexplored. This study investigated the effects of 25 MuRF1 variants on ubiquitylation activity using in vitro ubiquitylation assays and structural predictions using computational approaches. The variants were generated using site-directed PCR (Polymerase Chain Reaction) mutagenesis and subsequently purified with amylose affinity chromatography. In vitro ubiquitylation assays demonstrated that all 25 variants compromised the ability of MuRF1 to monoubiquitylate a titin fragment (A168-A170), while 17 variants significantly impaired or completely abolished auto-monoubiquitylation. Structural modelling predicted that 10 MuRF1 variants disrupted zinc binding or key stabilising interactions, compromising structural integrity. In contrast, three variants were predicted to enhance the structural stability of MuRF1, while six others were predicted to have no discernible impact on the structure. This study underscores the importance of functional assays and structural predictions in evaluating MuRF1 variant pathogenicity and provides novel insights into mechanisms by which these variants contribute to HCM and related cardiomyopathies. Full article

This study investigates the effects of pilot scale Alnus japonica hot water extract (AJHW) on muscle loss and muscle atrophy. Building on previous in vitro studies, in vivo experiments were conducted to evaluate muscle strength, mass, fiber size, protein synthesis, and antioxidant activity. The results showed that AJHW significantly restored muscle strength, increased muscle mass, enhanced the expression of muscle synthesis markers, such as Akt and mTOR, and apoptosis inhibition markers, such as Bcl-2, compared to the muscle atrophy control. Muscle degradation markers, such as Atrogin1, MuRF1, FoxO3α, and the apoptosis activation marker Bax, were decreased compared to the muscle atrophy control. Additionally, AJHW significantly boosted the activity of antioxidant factors like SOD, catalase, and Gpx, suggesting its protective role against oxidative stress-induced muscle damage. The enhanced effects were attributed to the high content of hirsutanonol and hirsutenone, which synergized with oregonin, compounds, identified through phytochemical analysis. While these findings support the potential of AJHW as a candidate for preventing muscle loss, further studies are needed to confirm its efficacy across diverse atrophy models and to elucidate its exact mechanisms. Full article

Muscle atrophy leads to decreased muscle mass, weakness, inactivity, and increased mortality. E3 ubiquitin ligases, key regulators of protein degradation via the ubiquitin–proteasome system, play a critical role in atrophic mechanisms. This meta-analysis followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, and its objective was to evaluate the association between E3 ligases Muscle Atrophy F-box (MAFbx)/Atrogin-1 (Fbxo32) and Muscle RING-finger protein 1 (MuRF-1) (TRIM63) E3 ligase mRNA levels, reductions in skeletal muscle CSA measures, and atrophy conditions. We examined papers published on PubMed^®, Scopus, and Web of Science that studied E3 ligase gene expression signatures for Fbxo32 (MAFbx/Atrogin-1) and Trim63 (MuRF1) in different types of muscle atrophy and hypertrophy murine models. Twenty-nine studies selected by two independent raters were analyzed. Standardized mean differences (SMDs)/effect sizes (ESs) and 95% confidence intervals (CIs) were calculated for the outcomes using fixed-effects models. We found that 6- and 4.8-fold upregulation, respectively, of Fbxo32 and Trim63 was sufficient to reduce the ES to −3.89 (95% CI: −4.45 to −3.32) for the muscle fiber cross-sectional area and the development of skeletal muscle atrophy. I² and Q test statistics did not indicate heterogeneous data. There was a low probability of bias after both the funnel plot and Egger’s test analyses. These results were sustained independently of the atrophic model and muscle type. Therefore, the magnitude of the increase in muscle Fbxo32 and Trim63 mRNA is a feasible, reliable molecular marker for skeletal muscle atrophy in mice. The next step for the Ubiquitin-proteasome system (UPS) field involves elucidating the targets of E3 ligases, paving the way for diagnostic and treatment applications in humans. Full article

We investigated the effects of belt electrode-skeletal muscle electrical stimulation (B-SES) on muscle atrophy in collagen-induced arthritis (CIA) rats. Twenty-eight 8-week-old male Dark Agouti rats were immunized with type II collagen and Freund’s incomplete adjuvant (day 0). From days 14 to 28, 18 rats received B-SES (50 Hz) four times only on the right hindlimb (STIM), while the contralateral left hindlimb remained unstimulated. Both hindlimbs of 10 untreated CIA rats were defined as controls (CONT). Paw volume was measured every other day. On day 28, the muscle weight, histology, and gene expression of the soleus and extensor digitorum longus (EDL) were analyzed. B-SES did not worsen paw volume throughout the experimental period. Compared with CONT, the muscle weight and fiber cross-sectional area of the soleus were higher in STIM. The expression of muscle degradation markers (atrogin-1 and MuRF-1) in the soleus and EDL was lower in the STIM group than that in the CONT group. In contrast, B-SES did not significantly affect the expression of muscle synthesis (Eif4e and p70S6K) and mitochondrial (PGC-1α) markers. B-SES prevents muscle atrophy in CIA rats by reducing muscle degradation without exacerbating arthritis, demonstrating its promising potential as an intervention for RA-induced muscle atrophy. Full article

Sarcopenia, a serious consequence of chronic kidney disease (CKD), is driven by elevated myostatin (MSTN), a key inhibitor of muscle growth. This study explored the potential of an MSTN-specific antisense oligonucleotide (ASO) in reversing CKD-induced muscle wasting in a mouse model. Thirty-two male C57BL/6J mice were randomly assigned to a non-CKD group (n = 8, regular diet) and a CKD group (n = 24, adenine diet). CKD was induced using a 0.2% adenine-supplemented diet for 4 weeks. Following this, the mice were sub-grouped into CKD (saline, n = 8), CKD + Low-Dose ASO (25 mg/kg ASO, n = 8), and CKD + High-Dose ASO (50 mg/kg ASO, n = 8). ASO was administered via subcutaneous injections for 8 weeks. Muscle mass, treadmill performance, grip strength, and muscle fiber morphology were assessed alongside qPCR and Western blot analysis for MSTN, atrogin-1, and MuRF-1 expression. ASO therapy significantly enhanced muscle mass and function and enlarged muscle fibers while effectively downregulating muscle degradation markers. These improvements occurred without compromising renal function, as confirmed by BUN, creatinine, kidney weight, and histological analysis. This study is the first to demonstrate the efficacy of ASO therapy in mitigating CKD-induced sarcopenia, offering a promising targeted gene therapy with significant clinical implications for improving nutritional status and physical performance in CKD. Full article

Aucubin (AU) is one of the main components of the traditional Chinese medicine Eucommia ulmoides Oliv (EU). This study investigated the effects of AU on aging-related skeletal muscle atrophy in vitro and in vivo. The results of network pharmacology revealed the potential therapeutic effects of AU on muscle atrophy. In vitro, AU effectively attenuated D-gal-induced cellular damage, reduced the number of senescence-associated β-galactosidase (SA-β-Gal)-positive cells, down-regulated the expression levels of muscle atrophy-related proteins Atrogin-1 and MuRF1, and improved myotube differentiation, thereby mitigating myotube atrophy. Notably, AU was found to attenuate oxidative stress and apoptosis in skeletal muscle cells by reducing ROS production, regulating Cleaved caspase3 and BAX/Bcl-2 expression in apoptotic pathways, and enhancing Sirt1 and PGC-1α signaling pathways. In vivo studies demonstrated that AU treatment extended the average lifespan of Caenorhabditis elegans (C. elegans), increased locomotor activity, improved body wall muscle mitochondrial content, and alleviated oxidative damage in C. elegans. These findings suggested that AU can ameliorate aging-related muscle atrophy and show significant potential in preventing and treating muscle atrophy. Full article

Cachexia is a multifactorial syndrome characterized by severe muscle wasting and is a debilitating condition frequently associated with cancer. Previous studies from our group revealed that withaferin A (WFA), a steroidal lactone, mitigated muscle cachexia induced by ovarian tumors in NSG mice. However, it remains unclear whether WFA’s protective effects are direct or secondary to its antitumor properties. We developed a cachectic model through continuous angiotensin II (Ang II) infusion in C57BL/6 mice to address this issue. Ang II infusion resulted in profound muscle atrophy, evidenced by significant reductions in grip strength and in the TA, GA, and GF muscle mass. Molecular analyses indicated elevated expression of inflammatory cytokines (TNFα, IL-6, MIP-2, IL-18, IL-1β), NLRP3 inflammasome, and genes associated with the UPS (MuRF1, MAFBx) and autophagy pathways (Bacl1, LC3B), along with suppression of anti-inflammatory heme oxygenase-1 (HO-1) and myogenic regulators (Pax7, Myod1). Strikingly, WFA treatment reversed these pathological changes, restoring muscle mass, strength, and molecular markers to near-normal levels. These findings demonstrate that WFA exerts direct anti-cachectic effects by targeting key inflammatory and atrophic pathways in skeletal muscle, highlighting its potential as a novel therapeutic agent for cachexia management. Full article

Clinical symptoms of monocled cobra (Naja kaouthia) envenoming include the paralysis of extraocular muscles, local tissue necrosis and death through respiratory failure. These neurotoxic outcomes are mainly due to the inhibitory action of postsynaptic neurotoxins to nicotinic acetylcholine receptors. However, injuries involving respiratory muscles have rarely been investigated. In this study, we determined the effect of N. kaouthia envenoming on morphological changes in the rat diaphragm. The efficacy of cobra monovalent antivenom in neutralising the histopathological effects of N. kaouthia venom was also evaluated. The intramuscular (i.m.) administration of N. kaouthia venom (2 mg/kg) caused skeletal muscle fibre atrophy and ruptures of myofibrils shown via a light microscope study. Transmission electron microscopy (TEM) revealed the zig-zagging of the Z-band, mitochondrial damages and degeneration of the synaptic fold of the neuromuscular junction following experimental cobra envenoming for 4 h. Intravenous administration of cobra antivenom at manufacturer-recommended doses diminished histopathological changes in the diaphragm following the administration of cobra venom. The expression of NF-kB and MuRF1 in the experimentally N. kaouthia-envenomed diaphragm indicated inflammation and tissue atrophy in the immunofluorescence analysis, respectively. In this study, we found that there were respiratory muscle injuries following N. kaouthia envenoming. The early administration of monovalent N. kaouthia antivenom is capable of neutralising neurotoxic outcomes following cobra envenoming. Full article

The chemotherapeutic agent doxorubicin (DOX) leads to the loss of skeletal muscle and adipose tissue mass, contributing to cancer cachexia. Experimental research on the molecular mechanisms of long-term DOX treatment is modest, and its effect on both skeletal muscle and adipose tissue has not been studied in an integrative manner. Dexrazoxane (DEXRA) is used to prevent DOX-induced cancer-therapy-related cardiovascular dysfunction (CTRCD), but its impact on skeletal muscle and adipose tissue remains elusive. Therefore, this study aimed to investigate the long-term effects of DOX on adipose tissue and skeletal muscle metabolism, and evaluate whether DEXRA can mitigate these effects. To this end, 10-week-old male C57BL6/J mice (n = 32) were divided into four groups: (1) DOX, (2) DOX-DEXRA combined, (3) DEXRA and (4) control. DOX (4 mg/kg weekly) and DEXRA (40 mg/kg weekly) were administered intraperitoneally over 6 weeks. Indirect calorimetry was used to assess metabolic parameters, followed by a molecular analysis and histological evaluation of skeletal muscle and adipose tissue. DOX treatment led to significant white adipose tissue (WAT) loss (74%) and moderate skeletal muscle loss (Gastrocnemius (GAS): 10%), along with decreased basal activity (53%) and energy expenditure (27%). A trend toward a reduced type IIa fiber cross-sectional area and a fast-to-slow fiber type switch in the Soleus muscle was observed. The WAT of DOX-treated mice displayed reduced Pparg (p < 0.0001), Cd36 (p < 0.0001) and Glut4 (p < 0.05) mRNA expression—markers of fat and glucose metabolism—compared to controls. In contrast, the GAS of DOX-treated mice showed increased Cd36 (p < 0.05) and Glut4 (p < 0.01), together with elevated Pdk4 (p < 0.001) mRNA expression—suggesting reduced carbohydrate oxidation—compared to controls. Additionally, DOX increased Murf1 (p < 0.05) and Atrogin1 (p < 0.05) mRNA expression—markers of protein degradation—compared to controls. In both the WAT and GAS of DOX-treated mice, Ppard mRNA expression remained unchanged. Overall, DEXRA failed to prevent these DOX-induced changes. Collectively, our results suggest that DOX induced varying degrees of wasting in adipose tissue and skeletal muscle, driven by distinct mechanisms. While DEXRA protected against DOX-induced CTRCD, it did not counteract its adverse effects on skeletal muscle and adipose tissue. Full article

Background/Objectives: Muscle-specific RING finger protein 1 (MuRF-1) is a pivotal regulator of muscle protein breakdown, an essential process for post-exercise muscle adaptation. This systematic review aimed to evaluate the effects of physical exercise on MuRF-1 mRNA expression in humans. Methods: A literature search was conducted in PubMed, Scopus, Cochrane Library, Google Scholar, and Web of Science following the PRISMA guidelines. The search was limited to studies published from 1 January 2001 to 1 December 2024. The inclusion and exclusion criteria were defined using the PICOS strategy. Two investigators independently performed the study selection, data extraction, and assessment of methodological quality, with any disagreements resolved by a third investigator. The PEDro scale was used to evaluate the risk of bias. Results: Forty-six studies met the eligibility criteria and were included. The findings evidenced that physical exercise significantly modulates MuRF-1 mRNA expression in humans. Resistance exercise induces transient increases, typically peaking between 1 and 4 h, whereas endurance exercise elicits similar responses within 40 min to 4 h post-exercise. Combined exercise protocols that include resistance and endurance exercises significantly increased MuRF-1 mRNA expression at 3 h post-exercise. The effects of physical exercise on MuRF-1 mRNA expression are influenced by factors such as exercise order, intensity, contraction mode, age, sex, and fitness level. Conclusions: This systematic review shows that MuRF-1 mRNA expression is significantly modulated by physical exercise in humans and is sensitive to different exercise modalities. These findings suggest that this key protein involved in muscle protein breakdown and turnover is essential for exercise-induced adaptations, contributing to skeletal muscle recovery and remodeling after exercise. Full article

Stress is recognized as an adaptive response to potentially harmful environmental stimuli. The primary physiological adaptation to stress is an increase in circulating cortisol levels, which, in excess, can be transferred and incorporated into the oocytes of maturing females, affecting the embryonic developmental program. Additionally, maternal energy availability is an essential environmental factor that modulates this program. Based on this background, we investigated the effects of maternal cortisol on the development of the somatotropic axis in zebrafish offspring and juveniles. Zebrafish mothers were divided into two groups based on diet: Group 1 received a cortisol-enriched diet, to mimic maternal stress, while Group 2 (control) received a standard diet, for five days. On the third day after treatment, the control and treated females were bred with untreated males. Offspring were assessed at 0, 24, 48, 72, 96, 120, and 144 h post-fertilization (hpf). Morphological analyses were performed during embryonic development, including survival rate, body length, the presence of pericardial edema, and heartbeat. We examined the gene expression of key somatotropic axis components, including mtor, foxo3a, mafbx, murf1, mstna, gh, igf1, igf2a, igf2b, 11hsdb2, and fkbp5. The study demonstrated that cortisol-treated females significantly influenced offspring development, resulting in higher mortality rates and increased morphological abnormalities, particularly pericardial edema. Gene expression analysis revealed alterations in transcripts related to the somatotropic axis, especially genes involved in protein synthesis, with signs of accelerated growth in the first hour post-fertilization. At 30 days post-fertilization, juveniles from cortisol-treated females displayed a marked increase in muscle bundle size and cross-sectional diameter compared to the control group. Our findings provide valuable insights into the intricate interaction between maternal factors and the development of the somatotropic axis in offspring. Full article

During skeletal muscle unloading, phosphoinositide 3-kinase (PI3K), and especially PI3K gamma (PI3Kγ), can be activated by changes in membrane potential. Activated IP3 can increase the ability of Ca²⁺ to enter the nucleus through IP3 receptors. This may contribute to the activation of transcription factors that initiate muscle atrophy processes. LY294002 inhibitor was used to study the role of PI3K in the ATP-dependent regulation of skeletal muscle signaling during three days of unloading. Inhibition of PI3K during soleus muscle unloading slows down the atrophic processes and prevents the accumulation of ATP and the expression of the E3 ubiquitin ligase MuRF1 and ubiquitin. It also prevents the increase in the expression of IP3 receptors and regulates the activity of Ca²⁺-dependent signaling pathways by reducing the mRNA expression of the Ca²⁺-dependent marker calcineurin (CaN) and decreasing the phosphorylation of CaMKII. It also affects the regulation of markers of anabolic signaling in unloaded muscles: IRS1 and 4E-BP. PI3K is an important mediator of skeletal muscle atrophy during unloading. Developing strategies for the localized skeletal muscle release of PI3K inhibitors might be one of the future treatments for inactivity and disease-induced muscle atrophy. Full article