N-Acetylcysteine Alleviates Impaired Muscular Function Resulting from Sphingosine Phosphate Lyase Functional Deficiency-Induced Sphingoid Base and Ceramide Accumulation in Caenorhabditis elegans.

Sphingosine-1-phosphate lyase (SPL) resides at the endpoint of the sphingolipid metabolic pathway, catalyzing the irreversible breakdown of sphingosine-1-phosphate. Depletion of SPL precipitates compromised muscle morphology and function; nevertheless, the precise mechanistic underpinnings remain elusive. Here, we elucidate a model of SPL functional deficiency in Caenorhabditis elegans using spl-1 RNA interference. Within these SPL-deficient nematodes, we observed diminished motility and perturbed muscle fiber organization, correlated with the accumulation of sphingoid bases, their phosphorylated forms, and ceramides (collectively referred to as the "sphingolipid rheostat"). The disturbance in mitochondrial morphology was also notable, as SPL functional loss resulted in heightened levels of reactive oxygen species. Remarkably, the administration of the antioxidant N-acetylcysteine (NAC) ameliorates locomotor impairment and rectifies muscle fiber disarray, underscoring its therapeutic promise for ceramide-accumulation-related muscle disorders. Our findings emphasize the pivotal role of SPL in preserving muscle integrity and advocate for exploring antioxidant interventions, such as NAC supplementation, as prospective therapeutic strategies for addressing muscle function decline associated with sphingolipid/ceramide metabolism disruption.

Toxicity of cigarette butts (CBs) leachate on Nile tilapia (Oreochromis niloticus): Blood biochemical parameters, oxidative stress biomarkers, and metabolic profile.

The aim of this study is to evaluate the toxic effects of different concentrations of cigarette butt leachate (CBL) (0.0, 0.5, 1, 1.5, and 2.0 µL L-1) on blood biochemistry, oxidative stress biomarkers, and the biochemical profile of the liver and muscle of Nile tilapia fish (Oreochromis niloticus) after 21 days. Increased activity of lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), and aspartate aminotransferase (AST) in plasma, and decreased activity of alkaline phosphatase (ALP) in fish exposed to CBL, indicated cytotoxicity. Elevated cholesterol, triglycerides, and glucose levels, coupled with reduced total protein, albumin, and globulin levels in the plasma, indicated impaired liver function in the fish. An increase in creatinine showed kidney damage. Increased superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities, along with the decrease in liver glutathione (GSH) content and total antioxidant capacity in the hepatocytes of fish exposed to CBL, indicated the occurrence of oxidative stress. Malondialdehyde (MDA) elevation indicated heightened lipid peroxidation in CBL-exposed fish hepatocytes. Raman spectroscopy revealed altered biochemical profiles in fish liver and muscle post-CBL exposure. The results demonstrated that exposure to CBL led to a decrease in phospholipid levels, collagen destruction, changes in phenylalanine levels, and a decrease in the levels of lipids, proteins, and nucleic acids in fish liver and muscle tissue. Furthermore, the metabolites and compounds of cigarette butt juice were detectable in the liver and muscle tissue of fishes. In conclusion, this study showed that exposure to CBL can have adverse effects on fish health.

Anti-Melanogenic Effects of Takifugu flavidus Muscle Hydrolysate in B16F10 Melanoma Cells and Zebrafish.

Abnormal melanogenesis can lead to hyperpigmentation. Tyrosinase (TYR), a key rate-limiting enzyme in melanin production, is an important therapeutic target for these disorders. We investigated the TYR inhibitory activity of hydrolysates extracted from the muscle tissue of Takifugu flavidus (TFMH). We used computer-aided virtual screening to identify a novel peptide that potently inhibited melanin synthesis, simulated its binding mode to TYR, and evaluated functional efficacy in vitro and in vivo. TFMH inhibited the diphenolase activities of mTYR, reducing TYR substrate binding activity and effectively inhibiting melanin synthesis. TFMH indirectly reduced cAMP response element-binding protein phosphorylation in vitro by downregulating melanocortin 1 receptor expression, thereby inhibiting expression of the microphthalmia-associated transcription factor, further decreasing TYR, tyrosinase related protein 1, and dopachrome tautomerase expression and ultimately impeding melanin synthesis. In zebrafish, TFMH significantly reduced black spot formation. TFMH (200 µg/mL) decreased zebrafish TYR activity by 43% and melanin content by 52%. Molecular dynamics simulations over 100 ns revealed that the FGFRSP (T-6) peptide stably binds mushroom TYR via hydrogen bonds and ionic interactions. T-6 (400 µmol/L) reduced melanin content in B16F10 melanoma cells by 71% and TYR activity by 79%. In zebrafish, T-6 (200 µmol/L) inhibited melanin production by 64%. TFMH and T-6 exhibit good potential for the development of natural skin-whitening cosmetic products.

Sensitivity of cholinesterases and carboxylesterases to pharmaceutical products in Tinca tinca.

Discharges to the aquatic environment of pharmaceuticals represent a hazard to the aquatic organisms. Subchronic assay with 17-alpha-ethinylestradiol (EE2) and in vitro essays with pharmaceuticals of environmental concern were conducted to examine the sensitivity of tissue acetylcholinesterase (AChE) and carboxylesterase (CbE) activities of Tinca tinca to them. Subchronic exposure to 17-alpha-EE2 caused significant effects on brain, liver, and muscle CbE, but no on AChE activities. Most of the pharmaceuticals tested in vitro were considered as weak inhibitors of tissular AChE activity. Depending on the tissues, some compounds were classified as moderate inhibitors of CbE activity while other were categorized as weak enzymatic inhibitors. An opposite trend was observed depending on the tissue, while brain and liver CbE activities were inhibited, the muscle CbE activity was induced. Changes experienced on enzymatic activities after exposure to pharmaceuticals might affect the physiological functions in which these enzymes are involved. In vitro exposure to 17-alpha-EE2 in tench could be an informative, but not a surrogate model to know the effect of this synthetic estrogen on AChE and CbE activities.

Superb bio-effectiveness of Cobalt (II) phthalocyanine and Ag NPs adorned Sm-doped ZnO nanorods/cuttlefish bone to annihilate Trichinella spiralis muscle larvae and adult worms: In-vitro evaluation.

Herein, innovative biocides are designed for the treatment of Trichinella spiralis muscle larvae (ML) and adult worms. Samarium-doped ZnO nanorods (Sm-doped ZnO) are stabilized onto the laminar structure of cuttlefish bone (CB) matrix and adorned by either Ag NPs or cobalt phthalocyanine (CoPc) species. Physicochemical characteristics of such nanocomposites are scrutinised. Adorning of Sm-doped ZnO/CB with Ag NPs shortens rod-like shaped Sm-doped ZnO nanoparticles and accrues them, developing large-sized detached patches over CB moiety. Meanwhile, adorning of Sm-doped ZnO/CB by CoPc species degenerates CB lamellae forming semi-rounded platelets and encourages invading of Sm-doped ZnO nanorods deeply inside gallery spacings of CB. Both nanocomposites possess advanced parasiticidal activity, displaying quite intoxication for ML and adult worms (≥88% mortality) within an incubation period of <48 h at concentrations around 200 µg/ml. CoPc@Sm-doped ZnO/CB nanocomposite exhibits faster killing efficiency of adult worms than that of Ag@Sm-doped ZnO/CB at a concentration of ∼75 µg/ml showing entire destruction of parasite after 24 h incubation with the former nanocomposite and just 60% worm mortality after 36 h exposure to the later one. Morphological studies of the treated ML and adult worms show that CoPc@Sm-doped ZnO/CB exhibits a destructive impact on the parasite body, creating featureless and sloughed fragments enriched with intensive vacuoles. Hybridization of cuttlefish bone lamellae by CoPc species is considered a springboard for fabrication of futuristic aggressive drugs against various food- and water-borne parasites.

The RU486-dependent activation of the GeneSwitch system in adult muscles leads to severe adverse effects in Drosophila.

Robust genetic systems to control the expression of transgenes in a spatial and temporal manner are a valuable asset for researchers. The GeneSwitch system induced by the drug RU486 has gained widespread use in the Drosophila community. However, some concerns were raised as negative effects were seen depending on the stock, transgene, stage, and tissue under study. Here, we characterized the adverse effects triggered by activating the GeneSwitch system in adult muscles using the MHC-GS-GAL4 driver. When a control, mock UAS-RNAi transgene was induced by feeding adult flies with RU486, we found that the overall muscle structure, including myofibrils and mitochondrial shape, was significantly disrupted and led to a significant reduction in the lifespan. Remarkably, lifespan was even shorter when 2 copies of the driver were used even without the mock UAS-RNAi transgene. Thus, researchers should be cautious when interpreting the results given the adverse effects we found when inducing RU486-dependent MHC-GS-GAL4 in adult muscles. To account for the impact of these effects we recommend adjusting the dose of RU486, setting up additional control groups, such as a mock UAS-RNAi transgene, as comparing the phenotypes between RU486-treated and untreated animals could be insufficient.

Urate-Lowering Drugs and Muscle Injury: A Systematic Review and Network Meta-Analysis.

Several urate-lowering drugs have been linked to muscle injury. This study investigated the association of oral urate-lowering drugs with the risk of muscle injury by performing a network meta-analysis of randomized and non-randomized controlled trials. A systematic search of MEDLINE, via PubMed, the ClinicalTrials.gov website, and the Cochrane Central Register of Controlled Trials was conducted to identify relevant studies with a primary outcome of "all muscle injuries." A random-effects model was used to perform a frequentist network meta-analysis to estimate whether there was significant heterogeneity among the studies. In total, 32 studies including 28,327 participants with 2694 (9.5%) "all muscle injuries" were assessed, and the overall risk of bias was judged to be low to moderate. No statistically significant differences were found between placebo and 6 urate-lowering therapies: allopurinol (risk ratio, RR, 1.05; 95% confidence interval, 95%CI, 0.63-1.73), febuxostat (RR 1.10, 95%CI 0.71-1.70), lesinurad (RR 7.00, 95%CI 0.31-160.36), lesinurad concomitant with allopurinol (RR 0.85, 95%CI 0.34-2.11), lesinurad concomitant with febuxostat (RR 1.97, 95%CI 0.55-7.03), and topiroxostat (RR 0.99, 95%CI 0.37-2.65). The findings suggest that there is little need to consider the risk of muscle injury when using urate-lowering drugs in the clinical setting.

Chemical characterization and effects of volatile oil of Alpinia zerumbet on the quality of collagen deposition and caveolin-1 expression in a muscular fibrosis murine model / Caracterização química e efeitos do óleo volátil de Alpinia zerumbet na qualidade da deposição do colágeno e expressão da caveolina-1 em modelo murino de fibrose muscular

Abstract This study evaluated the effect of the volatile oil of Alpinia zerumbet (VOAz) on caveolin-1 gene expression and muscular fibrosis. The rats were immobilized to induce fibrosis of the gastrocnemius muscle, and they were treated with VOAz. Collagen quality was assessed by histology and the expression of the caveolin-1 (CAV-1) gene was evaluated using qPCR. Histomorphological analysis indicated a significant reduction in the perimeter, width, and intensity of collagen in the treated groups, thus showing that the oil was effective in regulating the quality of collagen at the three concentrations. The results of expression levels suggested a decrease in the lesioned group and in two treatment groups (0.0115 µg/g and 0.009 µg/g). However, with the lowest concentration (0.0065 µg/g), no significant difference was observed, with levels similar to those found in healthy tissue. Therefore, the results showed that VOAz has the potential to be a non-invasive and low-cost alternative to aid in the treatment of muscular fibrosis.

Resumo Este estudo avaliou o efeito do óleo volátil de Alpinia zerumbet (OVAz) na expressão do gene da caveolina-1 e na fibrose muscular. Os ratos foram imobilizados para induzir a fibrose do músculo gastrocnêmio, e foram tratados com OVAz. A qualidade do colágeno foi avaliada com histologia e à expressão do gene caveolina-1 (CAV-1) foi avaliada usando qPCR. A análise histomorfológica indicou uma redução significativa no perímetro, largura e intensidade do colágeno nos grupos tratados. Os resultados dos níveis de expressão sugeriram diminuição nos grupos de lesão e em dois grupos de tratamento (0,0115 µg/g e 0,009 µg/g). No entanto, com a menor concentração (0,0065 µg/g), não foi observada diferença significativa, apresentando níveis semelhantes aos encontrados em tecido saudável. O uso do OVAz foi eficaz para reverter as alterações do colágeno causadas pela fibrose, e sua menor concentração apresentou uma possível tendência de aumento na expressão do CAV-1. Portanto, os resultados mostraram que o OVAz tem potencial para ser uma alternativa não invasiva e de baixo custo para auxiliar no tratamento da fibrose muscular.

Marcadores bioquímicos propuestos para el estudio de la sarcopenia / Proposed biochemical markers for the study of sarcopenia

La sarcopenia asociada a la edad es una condición clínica caracterizada por una disminución en la fuerza, calidad y cantidad de masa muscular así como también en la función muscular. Un biomarcador se define como una característica que es medible objetivamente y evaluable como indicador de un proceso biológico normal, patológico o respuesta terapéutica a una intervención farmacológica. Los marcadores bioquímicos propuestos para el estudio de la sarcopenia pueden ser categorizados en dos grupos. El primero de ellos evalúa el estatus musculoesquelético; este panel de marcadores está formado por miostatina/folistatina, procolágeno aminoterminal tipo III e índice de sarcopenia. El segundo grupo de marcadores bioquímicos evalúa factores causales, para lo cual se sugiere medir el factor de crecimiento insulino-símil tipo 1 (IGF-1), dehidroepiandrosterona (DHEAS), cortisol, facto-res inflamatorios [proteína C reactiva (PCR), interleuquina 6 (IL-6) y factor de necrosis tu-moral (TNF-a)]. Las recomendaciones realiza-das están basadas en la evidencia científica disponible en la actualidad y la disponibilidad de la metodología apropiada para cada uno de los biomarcadores. (AU)

Sarcopenia is a progressive and generalized skeletal muscle disorder defined by decrease in the strength, quality and quantity of muscle mass as well as in muscle function. A biomarker is defined as a feature objectively measured and evaluated as an indicator of a normal biologic process, a pathogenic process or a pharmacologic response to therapeutic intervention. The biochemical markers proposed for the study of sarcopenia may be classified in two groups. The first group evaluates the musculoskeletal status, made up by myostatin/follistatin, N-terminal Type III Procollagen and the sarcopenia index. The second evaluates causal factors, where the measurement of the following is suggested: hormones insulin-like growth factor-1 (IGF-I), dehydroepiandrosterone sulphate (DHEAS), cortisol, inflammatory factors [C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-a)]. The recommendations made are based on scientific evidence currently available and the appropriate methodology availability for each biomarker. (AU)

Postoperative Use of the Muscle Relaxants Baclofen and/or Cyclobenzaprine Associated With an Increased Risk of Delirium Following Lumbar Fusion.

STUDY DESIGN: Retrospective, single-center, cohort study. OBJECTIVE: Investigate whether the incidence of postoperative delirium in older adults undergoing spinal fusion surgery is associated with postoperative muscle relaxant administration. SUMMARY OF BACKGROUND DATA: Baclofen and cyclobenzaprine are muscle relaxants frequently used for pain management following spine surgery. Muscle relaxants are known to cause central nervous system side effects in the outpatient setting and are relatively contraindicated in individuals at high risk for delirium. However, there are no known studies investigating their side effects in the postoperative setting. METHODS: Patients over 65 years of age who underwent elective posterior lumbar fusion for degenerative spine disease were stratified into two treatment groups based on whether postoperative muscle relaxants were administered on postoperative day one as part of a multimodal analgesia regimen. Doubly robust inverse probability weighting with cox regression for time-dependent covariates was used to examine the association between postoperative muscle relaxant use and the risk of delirium while controlling for variation in baseline characteristics. RESULTS: The incidence of delirium was 17.6% in the 250 patients who received postoperative muscle relaxants compared with 7.9% in the 280 patients who did not receive muscle relaxants ( P=0.001 ). Multivariate analysis to control for variation in baseline characteristics between treatment groups found that patients who received muscle relaxants had a 2.00 (95% CI: 1.14-3.49) times higher risk of delirium compared with controls ( P=0.015 ). CONCLUSION: Postoperative use of muscle relaxants as part of a multimodal analgesia regimen was associated with an increased risk of delirium in older adults after lumber fusion surgery. Although muscle relaxants may be beneficial in select patients, they should be used with caution in individuals at high risk for postoperative delirium.

Pharmacogenomic Study of Statin-Associated Muscle Symptoms in the ODYSSEY OUTCOMES Trial.

BACKGROUND: Statin-associated muscle symptoms (SAMS) are the most frequently reported adverse events for statin therapies. Previous studies have reported an association between the p.Val174Ala missense variant in SLCO1B1 and SAMS in simvastatin-treated subjects; however, evidence for genetic predictors of SAMS in atorvastatin- or rosuvastatin-treated subjects is currently lacking. METHODS: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; n=18 924) was a double-blind, randomized, placebo-controlled study evaluating the efficacy and safety of alirocumab (a PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitor) in acute coronary syndrome patients receiving high-intensity statin therapy. The goal of this pharmacogenomic analysis was to identify genetic variants associated with atorvastatin- and rosuvastatin-mediated SAMS among ODYSSEY OUTCOMES subjects who consented to participate in the genetic study (n=11 880). We performed multi-ancestry exome-wide and genome-wide association studies and gene burden analysis across 2 phenotypes (clinical SAMS [n=10 617] and creatine kinase levels [n=9630]). RESULTS: A novel genome-wide significant association for an intronic variant (rs6667912) located within TMEM9 (odds ratio [95% CI], 1.39 [1.24-1.55]; P=3.71×10-8) for patients with clinical SAMS (cases=894, controls=9723) was identified. This variant is located ≈30 kb upstream of CACNA1S, a locus associated with severe SAMS. We replicated 2 loci, at LINC0093 and LILRB5, previously associated with creatine kinase levels during statin treatment. No association was observed between p.Val174Ala (rs4149056) in SLCO1B1 and SAMS (odds ratio [95% CI], 1.03 [0.90-1.18]; P=0.69). CONCLUSIONS: This study comprises the largest discovery exome-wide and genome-wide association study for atorvastatin- or rosuvastatin-mediated SAMS to date. These novel genetic findings may provide biological/mechanistic insight into this drug-induced toxicity, and help identify at-risk patients before selection of lipid-lowering therapies.

The inducing of caspase and Bcl-2 pathway with royal jelly decreases the muscle tissue damage exposed with fluoride in rats.

In this study, 42 Wistar albino male rats (n = 42, 8 weeks old) were used. Rats were divided into 6 groups and 7 rats included each group. Groups: (i) Control group: Standard diet; (ii) RJ (royal jelly) group: Standard diet + royal jelly; (iii) F50 group: Standard diet + 50 mg/kg fluoride; (iv): F100 group: Standard diet + 100 mg/kg fluoride; (v) F50+RJ group: Standard diet + 50 mg/kg fluoride + royal jelly; (vi): F100+RJ group: Standard diet + 100 mg/kg fluoride + royal jelly. After 8 weeks, the rats were decapitated, and their muscle tissues were removed. Expression levels of Caspase-3, Caspase-6, Bax, tumor necrosis factor-α (TNF-α), interleukin 1 alpha (IL1-α) and Bcl-2 proteins in muscle tissue were determined by western blotting method. Histopathological analyses were also performed on the muscle tissue. Malondialdehyde (MDA), glutathione (GSH) and catalase (CAT) analyses were determined by a spectrophotometer. According to the obtained results, Bcl-2, TNF-α and IL1-α protein expression was increased in damage groups compared to the control and royal jelly groups, while Caspase-3, Caspase-6 and Bax protein expression levels decreased in damage groups. MDA level increased in damage groups compared to the control and royal jelly groups, while CAT and GSH levels increased with royal jelly application in royal jelly-given group in comparison to the flouride-exposed group. According to histopathological analysis results, edema and inflammatory cell formations were found in the injury groups, a tendency to decrease in these injuries was observed in the treatment groups. Based on these results, we can say that royal jelly has protective effects on muscle tissue against fluoride damage.

Chemical characterization and effects of volatile oil of Alpinia zerumbet on the quality of collagen deposition and caveolin-1 expression in a muscular fibrosis murine model.

This study evaluated the effect of the volatile oil of Alpinia zerumbet (VOAz) on caveolin-1 gene expression and muscular fibrosis. The rats were immobilized to induce fibrosis of the gastrocnemius muscle, and they were treated with VOAz. Collagen quality was assessed by histology and the expression of the caveolin-1 (CAV-1) gene was evaluated using qPCR. Histomorphological analysis indicated a significant reduction in the perimeter, width, and intensity of collagen in the treated groups, thus showing that the oil was effective in regulating the quality of collagen at the three concentrations. The results of expression levels suggested a decrease in the lesioned group and in two treatment groups (0.0115 µg/g and 0.009 µg/g). However, with the lowest concentration (0.0065 µg/g), no significant difference was observed, with levels similar to those found in healthy tissue. Therefore, the results showed that VOAz has the potential to be a non-invasive and low-cost alternative to aid in the treatment of muscular fibrosis.

Potential Relevance of Bioactive Peptides in Sports Nutrition.

Bioactive peptides are physiologically active peptides mostly derived from proteins following gastrointestinal digestion, fermentation or hydrolysis by proteolytic enzymes. It has been shown that bioactive peptides can be resorbed in their intact form and have repeatedly been shown to have a positive effect on health-related parameters such as hypertension, dyslipoproteinemia, inflammation and oxidative stress. In recent years, there has been increasing evidence that biologically active peptides could also play an important role in sports nutrition. Current studies have shown that bioactive peptides could have a positive impact on changes in body composition and muscular performance, reduce muscle damage following exercise and induce beneficial adaptions within the connective tissue. In the following overview, potential mechanisms as well as possible limitations regarding the sports-related effect of bioactive peptides and their potential mechanisms are presented and discussed. In addition, practical applications will be discussed on how bioactive peptides can be integrated into a nutritional approach in sports to enhance athletic performance as well as prevent injuries and improve the rehabilitation process.

Effects of Vitamin D in Post-Exercise Muscle Recovery. A Systematic Review and Meta-Analysis.

Vitamin D is a key micronutrient modulating function and health in skeletal muscle. Therefore, we sought to systematically review the role of vitamin D in muscle recovery. A search in different databases (PubMed/MEDLINE, WOS, Google Scholar, and Scopus) was carried out following PRISMA® and PICOS. The search period was from inception to April 2020. Changes in post-exercise muscle damage were quantified comparing experimental group vs. placebo in each study by using number of participants, standardized mean difference (SMD), and standard error of the SMD. Hedges's g was used to calculate the SMDs for each study group and biased by the inverse of variance that allows calculating an overall effect and the 95% confidence interval (CI). The net vitamin D supplementation effect was calculated by subtracting the placebo SMD from SMD of the experimental group. The DerSimonian and Laird method was used as a random effect model, taking into account that the effect of vitamin D on muscular damage may vary according to the dose administered and additional moderators. Six studies were selected. In conclusion, regarding circulating levels of muscle biomarkers and additional limitations of the studies, it cannot be concluded that vitamin D supplementation exerts an effect in post-exercise muscle recovery. Likely, the anti-inflammatory action of vitamin D is quicker than the recovery of tissue structure and function. This aspect is pending verification in future research.

Role of Epigallocatechin Gallate in Glucose, Lipid, and Protein Metabolism and L-Theanine in the Metabolism-Regulatory Effects of Epigallocatechin Gallate.

Epigallocatechin gallate (EGCG) and L-theanine (LTA) are important bioactive components in tea that have shown promising effects on nutrient metabolism. However, whether EGCG alone or combined with LTA can regulate the glucose, lipid, and protein metabolism of healthy rats remains unclear. Therefore, we treated healthy rats with EGCG or the combination of EGCG and LTA (EGCG+LTA) to investigate the effects of EGCG on nutrient metabolism and the role of LTA in the metabolism-regulatory effects of EGCG. The results showed that compared with the control group, EGCG activated insulin and AMP-activated protein kinase (AMPK) signals, thus regulating glucose, lipid, and protein metabolism. Compared with EGCG, EGCG+LTA enhanced hepatic and muscle glycogen levels and suppressed phosphorylation of AMPK, glycogen synthase 2, mammalian target of rapamycin, and ribosomal protein S6 kinase. In addition, EGCG+LTA inhibited the expression of liver kinase B1, insulin receptor and insulin receptor substrate, and promoted the phosphorylation level of acetyl-CoA carboxylase. Furthermore, both EGCG and EGCG+LTA were harmless for young rats. In conclusion, EGCG activated AMPK and insulin pathways, thereby promoting glycolysis, glycogen, and protein synthesis and inhibiting fatty acid (FA) and cholesterol synthesis. However, LTA cooperated with EGCG to promote glycogen metabolism and suppressed the effect EGCG on FA and protein synthesis via AMPK signals.

20-Hydroxyecdysone activates the protective arm of the RAAS via the MAS receptor.

20-Hydroxyecdysone (20E) is a steroid hormone that plays a key role in insect development through nuclear ecdysteroid receptors (EcR/RXR complex) and at least one membrane GPCR receptor (DopEcR). It also displays numerous pharmacological effects in mammals, where its mechanism of action is still debated, involving either an unidentified GPCR or the estrogen ERß receptor. The goal of this study was to better understand 20E mechanism of action in mammals. A mouse myoblast cell line (C2C12) and the gene expression of myostatin (a negative regulator of muscle growth) were used as a reporter system of anabolic activity. Experiments using protein-bound 20E established the involvement of a membrane receptor. 20E-like effects were also observed with angiotensin(1-7), the endogenous ligand of MAS. Additionally, the effect on myostatin gene expression was abolished by Mas receptor knock-down using siRNA or pharmacological inhibitors. 17ß-Estradiol (E2) also inhibited myostatin gene expression, but protein-bound E2 was inactive, and E2 activity was not abolished by angiotensin(1-7) antagonists. A mechanism involving cooperation between the MAS receptor and a membrane-bound palmitoylated estrogen receptor is proposed. The possibility to activate the MAS receptor with a safe steroid molecule is consistent with the pleiotropic pharmacological effects of ecdysteroids in mammals and, indeed, the proposed mechanism may explain the close similarity between the effects of angiotensin(1-7) and 20E. Our findings open up many possible therapeutic developments involving stimulation of the protective arm of the renin-angiotensin-aldosterone system (RAAS) with 20E.

Dietary chitosan promotes the growth, biochemical composition, gut microbiota, hematological parameters and internal organ morphology of juvenile Barbonymus gonionotus.

In this study, we determined the effects of dietary chitosan on the growth, biochemical composition, gut microbiota, and hematological and histological parameters of juvenile Barbonymus gonionotus. Three test diets containing three different concentrations (1, 2, and 3 g kg-1 feed) of dietary chitosan were formulated. A basal diet without dietary chitosan was considered a control, and the fish were reared for 60 days. Comparing the effects of the dietary chitosan-containing diets with those of the control diet, we found that dietary chitosan significantly improved the muscle growth, nutrient and mineral contents, hematological parameters, lactic acid bacterium abundance, and digestive enzyme activities of B. gonionotus. Moreover, dietary chitosan significantly inhibited the growth of pathogenic bacteria in fish. Interestingly, an increase in the dietary chitosan level significantly enhanced the protein contents of the muscles and inversely significantly decreased the lipid contents compared to those with the basal diet. Quantitative study revealed that dietary chitosan significantly enhanced the length of intestinal villi, and qualitative study showed that dietary chitosan considerably reduced the fat content in the liver and improved the morphology of the kidney compared to those with the basal diet. Taken together, our results suggest that the application of dietary chitosan at a dose of 1 g kg-1 feed produced the highest benefit to treated B. gonionotus, indicating its potential for safe use in aquaculture.

Peimine, an Anti-Inflammatory Compound from Chinese Herbal Extracts, Modulates Muscle-Type Nicotinic Receptors.

Fritillaria bulbs are used in Traditional Chinese Medicine to treat several illnesses. Peimine (Pm), an anti-inflammatory compound from Fritillaria, is known to inhibit some voltage-dependent ion channels and muscarinic receptors, but its interaction with ligand-gated ion channels remains unexplored. We have studied if Pm affects nicotinic acetylcholine receptors (nAChRs), since they play broad functional roles, both in the nervous system and non-neuronal tissues. Muscle-type nAChRs were incorporated to Xenopus oocytes and the action of Pm on the membrane currents elicited by ACh (IAChs) was assessed. Functional studies were combined with virtual docking and molecular dynamics assays. Co-application of ACh and Pm reversibly blocked IACh, with an IC50 in the low micromolar range. Pm inhibited nAChR by: (i) open-channel blockade, evidenced by the voltage-dependent inhibition of IAch, (ii) enhancement of nAChR desensitization, revealed by both an accelerated IACh decay and a decelerated IACh deactivation, and (iii) resting-nAChR blockade, deduced from the IACh inhibition elicited by Pm when applied before ACh superfusion. In good concordance, virtual docking and molecular dynamics assays demonstrated that Pm binds to different sites at the nAChR, mostly at the transmembrane domain. Thus, Pm from Fritillaria bulbs, considered therapeutic herbs, targets nAChRs with high affinity, which might account for its anti-inflammatory actions.

Choline acts during preimplantation development of the bovine embryo to program postnatal growth and alter muscle DNA methylation.

The preimplantation period of embryonic development can be a key window for programming of postnatal development because extensive epigenetic remodeling occurs during this time. It was hypothesized that modification of one-carbon metabolism of the bovine embryo by addition of the methyl-donor choline to culture medium would change postnatal phenotype through epigenetic modification. Embryos produced in vitro were cultured with 1.8 mM choline chloride or control medium. Blastocysts were transferred into females and pregnancy outcomes and postnatal phenotype of the resultant calves determined. Exposure of embryos to choline increased gestation length and calf birth weight. Calves derived from choline-treated embryos were also heavier at weaning and had increased ratio of body weight to hip height than control calves. Choline altered muscle DNA methylation of calves 4 months after birth. A total of 670 of the 8149 CpG examined were differentially methylated, with the predominant effect of choline being hypomethylation. Among the genes associated with differentially methylated CpG were ribosomal RNAs and genes in AMPK, mTOR, integrin, and BEX2 canonical pathways and cellular functions involved in growth and proliferation. Results demonstrate that provision of the methyl-donor choline to the preimplantation embryo can alter its developmental program to increase gestation length, birth weight, and weaning weight and cause postnatal changes in muscle DNA methylation including those associated with genes related to anabolic processes and cellular growth. The importance of the nutritional status of the embryo with respect to one-carbon metabolism for ensuring health and well-being after birth is emphasized by these observations.