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.

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.

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.

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.

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.

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.

Effect of Polyphenol-Rich Foods, Juices, and Concentrates on Recovery from Exercise Induced Muscle Damage: A Systematic Review and Meta-Analysis.

Objectives. To determine the effects of consuming polyphenol-rich foods, juices and concentrates on recovery from exercise-induced muscle damage (EIMD). Method. Eligibility criteria. Randomised and quasi-randomised placebo-controlled trials with a parallel or cross-over design evaluating the effects of consuming polyphenol-rich foods, juices and concentrates on recovery from EIMD in humans. Eligible studies included at least one of the primary outcome measures: maximal isometric voluntary contraction; MIVC, delayed onset muscle soreness; DOMS, or countermovement jump; CMJ. Information sources. AMED, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, PUBMED, SCOPUS (Elsevier), SPORTDiscus (EBSCO), and the UK Clinical Trials Gateway were searched from inception to September 2020. Risk of bias and quality of evidence. Risk of bias was assessed using Cochrane Risk of Bias 2 tool. Quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation framework. Synthesis of results. Random effects models were used to determine the effect of polyphenol supplementation on recovery from EIMD. Data are presented as standardised mean differences (SMD) with 95% confidence intervals (CI). Results. Included studies. Twenty-five studies were included; 15 had a parallel, and 10 had a cross-over design. A total of 527 participants (male: n = 425; female: n = 102) were included in the meta-analysis. Synthesis of results. Consumption of polyphenol-rich foods, juices and concentrates accelerated recovery of MIVC immediately post-exercise (SMD = 0.23, 95% CI 0.04, 0.42; p = 0.02; low-quality evidence), 24 h (SMD = 0.39, 95% CI 0.15, 0.62; p = 0.001; low-quality evidence), 48 h (SMD = 0.48, 95% CI 0.28, 0.67; p < 0.001; moderate-quality evidence), 72 h (SMD = 0.29, 95% CI 0.11, 0.46; p = 0.001; low-quality evidence) and 96 h post-exercise (SMD = 0.50, 95% CI 0.16, 0.83; p = 0.004; very low-quality evidence). DOMS was reduced at 24 h (SMD = -0.29, 95% CI -0.47, -0.11; p = 0.002; low-quality evidence), 48 h (SMD = -0.28, 95% CI -0.46, -0.09; p = 0.003; low-quality evidence) and 72 h post-exercise (SMD = -0.46, 95% CI -0.69, -0.24; p < 0.001; very low-quality evidence). CMJ height was greater immediately post-exercise (SMD = 0.27, 95% CI 0.01, 0.53; p = 0.04; low-quality evidence), at 24 h (SMD = 0.47, 95% CI 0.11, 0.83; p = 0.01; very low-quality evidence), 48 h (SMD = 0.58, 95% CI 0.24, 0.91; p < 0.001; very low-quality evidence) and 72 h post-exercise (SMD = 0.57, 95% CI 0.03, 1.10; p = 0.04; very low-quality evidence). Polyphenol supplementation did not alter creatine kinase, c-reactive protein, and interleukin-6 at any time points. At 72 h post-exercise, protein carbonyls (SMD = -0.64, 95% CI -1.14, -0.14; p = 0.01) were reduced. Discussion. Limitations of evidence. Risk of bias was high for 10 studies and moderate for 15. Sensitivity analyses excluding the high risk of bias studies reduced the SMDs for MIVC and DOMS, and for CMJ effects at 24 and 48 h were no longer statistically significant. Interpretation. Consuming polyphenol-rich foods, juices and concentrates accelerated recovery of muscle function while reducing muscle soreness in humans. Maximal benefit occurred 48-72 h post-exercise, however, the certainty of the evidence was moderate to very low. Supplementation could be useful when there is limited time between competitive events and impaired recovery could negatively impact performance.

Ecotoxicity of losartan potassium in aquatic organisms of different trophic levels.

The intensive use of the antihypertensive losartan potassium (LOS) has culminated in its high occurrence in aquatic environments. However, insufficient studies had investigated its effects in non-target organisms. In this study, ecotoxicity of LOS was assessed in aquatic organisms from distinct trophic levels (Desmodesmus subspicatus, Daphnia magna, and Astyanax altiparanae). Genotoxicity was assessed by the comet assay in D. magna and A. altiparanae, and biochemical biomarkers for the fish. LOS was more toxic to D. subspicatus (EC50(72h) = 27.93 mg L-1) than D. magna (EC50 = 303.69 mg L-1). Subsequently, this drug showed to induce more DNA damage in D. magna than A. altiparanae, when exposed to 2.5 mg L-1. No significant stress responses were observed by the fish biomarkers, suggesting that higher trophic levels organisms are more tolerant to LOS toxicity. LOS showed relatively low toxic potential for a short period of exposure, but with different patterns of toxicity for the organisms from distinct trophic levels, contributing to further risk assessment of LOS.

Curcumin and Resveratrol Improve Muscle Function and Structure through Attenuation of Proteolytic Markers in Experimental Cancer-Induced Cachexia.

Muscle wasting and cachexia are prominent comorbidities in cancer. Treatment with polyphenolic compounds may partly revert muscle wasting. We hypothesized that treatment with curcumin or resveratrol in cancer cachectic mice may improve muscle phenotype and total body weight through attenuation of several proteolytic and signaling mechanisms in limb muscles. In gastrocnemius and soleus muscles of cancer cachectic mice (LP07 adenocarcinoma cells, N = 10/group): (1) LC-induced cachexia, (2) LC-cachexia+curcumin, and (3) LC-cachexia + resveratrol, muscle structure and damage (including blood troponin I), sirtuin-1, proteolytic markers, and signaling pathways (NF-κB and FoxO3) were explored (immunohistochemistry and immunoblotting). Compared to nontreated cachectic mice, in LC-cachexia + curcumin and LC-cachexia + resveratrol groups, body and muscle weights (gastrocnemius), limb muscle strength, muscle damage, and myofiber cross-sectional area improved, and in both muscles, sirtuin-1 increased, while proteolysis (troponin I), proteolytic markers, and signaling pathways were attenuated. Curcumin and resveratrol elicited beneficial effects on fast- and slow-twitch limb muscle phenotypes in cachectic mice through sirtuin-1 activation, attenuation of atrophy signaling pathways, and proteolysis in cancer cachectic mice. These findings have future therapeutic implications as these natural compounds, separately or in combination, may be used in clinical settings of muscle mass loss and dysfunction including cancer cachexia.

Exposure to pollutants present in Iguaçu River Southern Brazil affect the health of Oreochromis niloticus (Linnaeus, 1758): Assessment histological, genotoxic and biochemical.

Urban sewage is a source of major contamination in aquatic systems and contributes to environmental and human health disturbances. This study investigates the effects of sewage-polluted waters from Iguaçu River on the health of juvenile Oreochromis niloticus. Two hundred four specimens were exposed to riverine water in four groups: no diluted, 25 and 50 % diluted water and a control group without tested water for 72 days. Biological samples were obtained for histopathological, neurotoxicity, antioxidant defenses, genotoxicity, metallothionines expression and polycyclic aromatic hydrocarbons (PAHs) metabolites. The results showed histopathological alterations in liver and gills, genotoxic alteration in erythrocytes, reduction of acetylcholinesterase activity in brain and muscle, activation of antioxidant defenses in the liver, recruitment of metals by metallothionein and the detection of PAHs metabolites in bile. These results demonstrate that juveniles of O. niloticus are susceptible to Iguaçu River exposure water and they can be used as indicator of water quality.

Effects of trophic 2,2', 4,4'-tetrabromodiphenyl ether (BDE-47) exposure in Oreochromis niloticus: A multiple biomarkers analysis.

Polybrominated diphenyl esters are emerging environmental contaminants with few toxicological data, being a concern for the scientific community. This study evaluated the effects of BDE-47 on the health of Oreochromis niloticus fish. The animals were exposed to three doses of BDE-47 (0, 0.253, 2.53, 25.3 ng g-1) every 10 days, for 80 days. The BDE-47 affected the hepatosomatic and gonadosomatic index in female and the condition factor by intermediate dose in both sexes. The levels of estradiol decreased and the T4 are increased, but the vitellogenin production was not modulated in male individuals. Changes in AChE, GST, LPO and histopathology were observed while the integrated biomarker response index suggests that the lowest dose of BDE-47 compromised the activity of antioxidant enzymes. The oral exposure to BDE-47 in environmental concentrations is toxic to O. niloticus and the use of multiple biomarkers is an attribution in ecotoxicology studies and biomonitoring programs.

Secondary protein in the muscle of exercised rats that received creatine supplementation / Proteína secundaria en el músculo de ratones ejercitados que recibieron suplemento de creatina / Proteína secundária no músculo de ratos exercitados que receberam suplemento de creatina

ABSTRACT Introduction: Currently there is a lack of clarity around the use of Fourier transform infrared (FT-IR) spectroscopy to analyze the effect of creatine (Cr) supplementation on the secondary structures of skeletal muscle tissue protein subjected to exercise. Objective: The objective of this study was to evaluate the spectral characteristics of the tibialis anterior muscle in rats subjected to exercise in a pool and to Cr supplementation. Methods: Experiment 1. First, an experiment was conducted to ensure that FT-IR would be able to detect change in the secondary structures of skeletal muscle tissue protein in the group of sedentary rats (SED) and in the group of rats that received creatine supplementation (CRE). Experiment 2. Next, the effect of physical exercise on the spectral characteristics of muscle tissue, especially when compared to the groups without exercise practice, was examined. Results: It was possible to verify that the peaks centered on 1658 cm-1 (amide I) and 1546 cm-1 (amide II) are characteristic spectra and indicated as markers of protein content. Conclusion: Thus, FT-IR spectroscopy proved to be able to monitor changes in secondary structures of skeletal muscle protein in both animals that received supplements and in those subjected to exercise and both cases reconciled. Furthermore, the FT-IR technique proved to be a viable method for the nondestructive evaluation of skeletal muscle protein structures. Level of evidence II, Investigation of treatment results.

RESUMEN Introducción: Actualmente, no hay claridad en lo que se refiere al uso de la técnica de espectroscopia de Infrarrojo con transformada de Fourier (FT-IR) para análisis del efecto de la suplementación de creatina (Cr) sobre las estructuras secundarias de la proteína del tejido muscular esquelético sometido a ejercicio. Objetivo: El objetivo de este estudio fue evaluar las características espectrales del músculo tibial anterior de ratones sometidos a ejercicio en piscina y a la suplementación con Cr. Métodos: Experimento 1. En primer lugar, fue realizada una experiencia para asegurar que la FT-IR sería capaz de detectar la variación en las estructuras secundarias de la proteína del tejido muscular esquelético en el grupo de ratones sedentarios (SED) y el grupo de ratones que sólo recibieron suplemento de creatina (CRE). Experimento 2. A continuación, fue examinado el efecto del ejercicio físico sobre las características espectrales del tejido muscular, especialmente cuando comparado con los grupos sin práctica de ejercicio. Resultados: Fue posible verificar que los picos centrados en 1658 cm−1 (amida I) y 1546 cm−1 (amida II) son espectros característicos e indicados como marcadores del tenor proteico. Conclusión: Siendo así, la técnica de espectroscopia de FT-IR mostró ser capaz de monitorizar las variaciones en las estructuras secundarias de la proteína del tejido muscular esquelético, tanto en animales que recibieron suplementos, como en los que fueron sometidos a ejercicio y ambos casos conciliados. Además, la técnica FT-IR probó ser un método viable para la evaluación no destructiva de las estructuras proteicas en el músculo esquelético. Nivel de evidencia II, Investigación de los resultados del tratamiento.

RESUMO Introdução: Atualmente, não há clareza no que diz respeito ao uso da técnica de espectroscopia de infravermelho com transformada de Fourier (FT-IR) para análise do efeito da suplementação de creatina (Cr) sobre as estruturas secundárias da proteína do tecido muscular esquelético submetido a exercício. Objetivo: O objetivo deste estudo foi avaliar as características espectrais do músculo tibial anterior de ratos submetidos a exercício em piscina e à suplementação com Cr. Métodos: Experimento 1. Em primeiro lugar, foi realizada uma experiência para assegurar que a FT-IR seria capaz de detectar a variação nas estruturas secundárias da proteína do tecido muscular esquelético no grupo de ratos sedentários (SED) e no grupo de ratos que só receberam suplemento de creatina (CRE). Experimento 2. Em seguida, foi examinado o efeito do exercício físico sobre as características espectrais do tecido muscular, especialmente quando comparado com os grupos sem prática de exercício. Resultados: Foi possível verificar que os picos centrados em 1658 cm−1(amida I) e 1546 cm−1(amida II) são espectros característicos e indicados como marcadores do teor proteico. Conclusão: Assim sendo, a técnica de espectroscopia de FT-IR mostrou ser capaz de monitorar as variações nas estruturas secundárias da proteína do tecido muscular esquelético tanto em animais que receberam suplementos, quanto nos que foram submetidos a exercício e ambos os casos conciliados. Além disso, a técnica FT-IR provou ser um método viável para a avaliação não destrutiva de estruturas proteicas no músculo esquelético. Nível de evidência II, Investigação dos resultados do tratamento.

Pathological Downstaging and Survival Outcomes Associated with Neoadjuvant Chemotherapy for Variant Histology Muscle Invasive Bladder Cancer.

PURPOSE: Patients with muscle invasive bladder cancer (MIBC) of variant histology have a poor prognosis. It is unclear if neoadjuvant chemotherapy prior to radical cystectomy is associated with pathological downstaging or improved overall survival (OS) for patients with variant histology. Our objective was to assess for associations between receipt of neoadjuvant chemotherapy, pathological downstaging and OS for patients with variant histology MIBC. MATERIALS AND METHODS: Patients were identified in the National Cancer Database from 2004 to 2017 with MIBC, without metastases, who underwent radical cystectomy. Patients were stratified by histological subgroup, and receipt or nonreceipt of neoadjuvant chemotherapy. Pathological downstaging was defined as pT0N0 or pT ≤1N0, and OS from the time of diagnosis to date of death or censoring at last followup. Multivariable logistic regression analysis determined associations between neoadjuvant chemotherapy and pathological downstaging. Multivariable Cox regression analysis determined associations between neoadjuvant chemotherapy and OS. RESULTS: A total of 31,218 patients were included in the final study population (urothelial carcinoma [UC]: 27,779; sarcomatoid UC: 501; micropapillary UC: 418; squamous cell carcinoma: 1,141; neuroendocrine carcinoma: 629; adenocarcinoma: 750). Neoadjuvant chemotherapy was associated with pathological downstaging to pT0N0 in all histological subgroups (UC: OR 5.1 [4.6-5.6]; sarcomatoid UC: OR 13.8 [5.5-39.0]; micropapillary UC: OR 9.7 [2.8-46.8]; squamous cell carcinoma: OR 7.4 [2.1-24.5]; neuroendocrine: OR 4.7 [2.6-9.2]; adenocarcinoma: OR 23.3 [8.0-74.2]). Neoadjuvant chemotherapy was associated with improved OS for UC (HR 0.8 [0.77-0.84]), sarcomatoid UC (HR 0.64 [0.44-0.91]) and neuroendocrine carcinoma (HR 0.55 [0.43-0.70]). CONCLUSIONS: Neoadjuvant chemotherapy was associated with pathological downstaging for all MIBC histological variants, with improved OS for patients with UC, sarcomatoid variant UC and neuroendocrine carcinoma.

Dietary therapeutic dose of oxytetracycline negatively influences the antioxidant capacity and immune-related genes expression in Nile tilapia Oreochromis niloticus (L.).

Effects of the dietary therapeutic dose of oxytetracycline (OTC) at 80 mg/kg biomass/day for consecutive 10 days on the behaviour, feed intake, mortality, residue accumulation and depletion, antioxidant capacity and immune-related genes expression in juvenile Nile tilapia Oreochromis niloticus were evaluated. OTC-dosing caused mortalities, reduced feed intake, and biomass reduction at 24.5-28.5 °C. OTC residues recorded on day 10 (161.40 ± 11.10 ng/g) were within the maximum residue limits of the Codex Alimentarius. The withdrawal period was 7 days as per the European Commission's regulation. Traces of residues were present even on day 42 post-OTC-dosing. Dietary OTC reduced the antioxidant capacity of the liver and muscle tissues and down-regulated the expression of tumour necrosis factor-α, interleukin-1ß, and heat shock protein-70 genes in the liver significantly during the dosing period. The data generated on the biosafety of OTC-dosing may offer inputs for the development of management strategies in maintaining fish health and food safety.

An oral absorbent, AST-120, restores vascular growth and blood flow in ischemic muscles in diabetic mice via modulation of macrophage transition.

Background Diabetes has a pronounced effect on the peripheral vasculature. The accumulation of advanced glycation end products (AGEs) is regarded as the crucial mechanism responsible for vascular damage in diabetes, but it is not easy to be avoided from food. In this study, we aimed to investigate the effects of an oral absorbent, AST-120, on the accumulation of AGEs and changes in blood flow recovery in diabetic mice. Methods The mice were divided into four groups, wild-type (WT) mice without treatment, WT mice treated with 5% AST-120 mixed into pulverized chow, streptozotocin-induced diabetes mellitus (DM) mice, and DM mice treated with 5% AST-120. Six weeks after hind-limb ischemia surgery, blood flow reperfusion, histology, plasma AGE, and cytokine were examined. Bone marrow cells were cultured and derived into macrophages to evaluate the effects of AGEs on macrophage polarization. Results Plasma AGEs were significantly increased in diabetic mice. AST-120 could bind to AGEs and reduced their plasma concentrations. Histological analysis revealed fewer collateral vessels with corresponding impairment of blood flow recovery in diabetic mice. In these mice, AGE-positive and AGE receptor-positive macrophages were numerous in ischemic limbs compared with non- diabetic mice. In diabetic mice, macrophages in ischemic tissues demonstrated greater M1 polarization than M2 polarization; this pattern was reversed in the AST-120 treatment group. The change in macrophage polarization was associated with the corresponding expression of pro-inflammatory cytokines in the ischemic tissues. In cell cultures, AGEs triggered the transformation of bone marrow-derived macrophages into the M1 phenotype. The alterations in the polarization of macrophages were reversed after treatment with AST-120. Conclusions Oral administration of AST-120 decreased the serum levels of AGEs in diabetic mice and improved neovascularization of ischemic limbs. This benefit may be due to, at least partially, the alterations in macrophage polarization and the associated changes in inflammatory cytokines.