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PURPOSE: Endurance exercise induces muscle fiber-type shifting and autophagy; however, the potential role of autophagy in muscle fiber-type transformation remains unclear. This study examined the relationship between muscle fiber-type shifting and autophagy in the soleus (SOL) and extensor digitorum longus (EDL) muscles, which are metabolically discrete muscles. METHODS: Male C57BL/6J mice were randomly assigned to sedentary control (CON) and exercise (EXE) groups. After 1 week of acclimation to treadmill running, the mice in the EXE group ran at 12-15 m/min, 60 min/day, 5 days/week for 6 weeks. All mice were sacrificed 90 min after the last exercise session, and the targeted tissues were rapidly dissected. The right side of the tissues was used for western blot analysis, whereas the left side was subjected to immunohistochemical analysis. RESULTS: Endurance exercise resulted in muscle fiber-type shifting (from type IIa to type I) and autophagy (an increase in LC3-II) in the SOL muscle. However, muscle fiber-type transformation and autophagy were not correlated in the SOL and EDL muscles. Interestingly, in contrast to the canonical autophagy signaling pathways, our study showed that exercise-induced autophagy concurs with enhanced anabolic (increased p-AKTSer473/AKT and p-mTOR/mTORSer2448 ratios) and suppressed catabolic (reduced p-AMPKThr172/AMPK ratio) states. CONCLUSION: Our findings demonstrate that chronic endurance exercise-induced muscle fiber-type transformation and autophagy occur in a muscle-specific manner (e.g., SOL). More importantly, our study suggests that endurance training-induced SOL muscle fiber-type transition may underlie metabolic modulations caused by the AMPK and AKT/mTOR signaling pathways rather than autophagy.
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PURPOSE: Maternal and postnatal overnutrition has been linked to an increased risk of cardiometabolic diseases in offspring. This study investigated the impact of adult-onset voluntary wheel running to counteract cardiometabolic risks in female offspring exposed to a life-long high-fat, high-sucrose (HFHS) diet. METHODS: Dams were fed either an HFHS or a low-fat, low-sucrose (LFLS) diet starting from 8 wk before pregnancy and continuing throughout gestation and lactation. Offspring followed their mothers' diets. At 15 wk of age, they were divided into sedentary (Sed) or voluntary wheel running (Ex) groups, resulting in four groups: LFLS/Sed ( n = 10), LFLS/Ex ( n = 5), HFHS/Sed ( n = 6), HFHS/Ex ( n = 5). Cardiac function was assessed at 25 wk, with tissue collection at 26 wk for mitochondrial respiratory function and protein analysis. Data were analyzed using two-way ANOVA. RESULTS: Although maternal HFHS diet did not affect the offspring's body weight at weaning, continuous HFHS feeding postweaning resulted in increased body weight and adiposity, irrespective of the exercise regimen. HFHS/Sed offspring showed increased left ventricular wall thickness and elevated expression of enzymes involved in fatty acid transport (CD36, FABP3), lipogenesis (DGAT), glucose transport (GLUT4), oxidative stress (protein carbonyls, nitrotyrosine), and early senescence markers (p16, p21). Their cardiac mitochondria displayed lower oxidative phosphorylation (OXPHOS) efficiency and reduced expression of OXPHOS complexes and fatty acid metabolism enzymes (ACSL5, CPT1B). However, HFHS/Ex offspring mitigated these effects, aligning more with LFLS/Sed offspring. CONCLUSIONS: Adult-onset voluntary wheel running effectively counteracts the detrimental cardiac effects of a lifelong HFHS diet, improving mitochondrial efficiency, reducing oxidative stress, and preventing early senescence. This underscores the significant role of physical activity in mitigating diet-induced cardiometabolic risks.
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Dieta Hiperlipídica , Efeitos Tardios da Exposição Pré-Natal , Feminino , Dieta Hiperlipídica/efeitos adversos , Gravidez , Animais , Corrida/fisiologia , Sacarose Alimentar/efeitos adversos , Sacarose Alimentar/administração & dosagem , Adiposidade , Fatores de Risco Cardiometabólico , Condicionamento Físico Animal/fisiologia , Fenômenos Fisiológicos da Nutrição Materna , Mitocôndrias Cardíacas/metabolismo , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/etiologiaRESUMO
CONTEXT: Latency is a reliable temporal metric used to evaluate sensorimotor integration of the fibularis longus (FL) and fibularis brevis (FB) during lateral ankle sprain perturbations. Currently, no clinical recommendations exist to select appropriate thresholds to evaluate the closed-loop reflex response of the lateral ankle musculature. The purpose of this study was to assess threshold value on latency of the FL and FB during an unanticipated inversion perturbation that simulates the mechanism of a lateral ankle sprain. DESIGN: Descriptive laboratory study. METHODS: Twenty healthy adults with no history of lateral ankle sprain injury completed an unanticipated single-leg drop landing onto a 25° laterally inclined force platform from a height of 30 cm. Surface electromyography recorded muscle activity data from the FL and FB during the inversion perturbation. Latency was identified at points where muscle activity exceeded 2, 5, and 10 SD above the average muscle activity 200 milliseconds prior to foot contact, and compared across threshold value using a 1-way analysis of variance (P < .05). RESULTS: The 2 SD threshold was significantly shorter than both 5 SD and 10 SD thresholds for the FL (P < .01) and FB (P < .01). Likewise, the 5 SD threshold was significantly shorter than the 10 SD thresholds for FL (P = .004) and FB (P = .003). CONCLUSIONS: More sensitive thresholds results in a shorter closed-loop reflexive response compared to the more rigorous thresholds. We recommend that selection of the appropriate threshold to identify latency of the lateral ankle musculature should be based on the device used to simulate a lateral ankle sprain and the ankle inversion velocity produced during the ankle inversion perturbation.
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Traumatismos do Tornozelo , Tornozelo , Adulto , Humanos , Extremidade Inferior , Articulação do Tornozelo , ReflexoRESUMO
Children who have been sexually abused may experience various short- and long-term psychological sequelae and behavioral problems. This study assessed the mental health of sexually abused children using the Korean-Child Behavior Checklist (K-CBCL) and examined differences from a control group. The participants were 97 children who had been sexually abused and who visited a local Sunflower Center, and 178 control participants. Data were collected via the K-CBCL and analyzed using SPSS version 25.0. T-tests, cross-tabulation, and logistic regression analyses were performed. Scores from the K-CBCL Problem Behavior Syndrome scale were compared between sexually abused children and the control participants. Significant differences were observed between the 2 groups in all the subscales. Compared to the control group, children who were sexually abused showed statistically significant differences in the total problem behavior, internalization, anxiety/depression, withdrawal/depression (withdrawn), somatic symptoms, externalization, rule-breaking behavior (delinquency), aggressive behavior, social immaturity, thought problems, attention problems, and other subscale scores. Sexual violence hurts the overall mental health of children who are abused, including their emotional, behavioral, and social factors. Our findings suggest that multidisciplinary assessment and treatment are required for children who have experienced sexual abuse.
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Experiências Adversas da Infância , Abuso Sexual na Infância , Transtornos Mentais , Criança , Humanos , Agressão , Progressão da Doença , Transtornos Mentais/etiologia , Transtornos Mentais/psicologia , Comportamento Sexual/psicologia , Abuso Sexual na Infância/diagnóstico , Abuso Sexual na Infância/etnologia , Abuso Sexual na Infância/psicologia , População do Leste Asiático/psicologia , Experiências Adversas da Infância/etnologia , Experiências Adversas da Infância/psicologiaRESUMO
This study aimed to identify and compare central post-traumatic stress disorder (PTSD) symptoms experienced by rape and sexual harassment victims, and the differences between the 2 groups. This study included 935 female victims of sexual violence who visited Sunflower Center in Korea between 2014 and 2020. Of the 935 victims, 172 were rape victims and 763 were sexually harassed. The Korean version of the Post-traumatic Diagnosis Scale was used to evaluate PTSD symptoms, and network analysis was performed to examine the differences in symptoms. The central symptom was "Physical reactions (PDS05)" for the group of rape victims and Less interest in activities (PDS09)' for the group of sexual harassment victims. For the group of sexual harassment victims, the most distinct central edge was the one between "Being over alert (PDS16)" and "Being jumpy or easily startled (PDS17)," and for the group of rape victims, it was the edge between "Upset when reminded of the trauma (PDS04)," and "Physical reactions (PDS05)." Network analysis revealed differences in central PTSD symptoms and central edges between sexual harassment and rape victims. Although re-experiencing and avoidance symptom clusters were most central in both groups, the specific central symptoms and edges differed between the 2 groups.
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Vítimas de Crime , Estupro , Delitos Sexuais , Transtornos de Estresse Pós-Traumáticos , Adulto , Feminino , Humanos , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/etiologia , Estupro/diagnóstico , Comportamento Sexual , EmoçõesRESUMO
BACKGROUND: The term, "multiple chronic diseases" (MCD), describes a patient with two or more chronic conditions simultaneously at the same time. Compared with general chronic diseases, it is linked to poorer health outcomes, more difficult clinical management, and higher medical expenses. Several existing MCD guidelines support a healthy lifestyle including regular physical activities but do not include specific exercise therapy recommendations. This study aimed to understand the prevalence and model of MCD in middle-aged and elderly South Koreans by comparing MCD characteristics with exercise habits, to provide a theoretical basis for the implementation of exercise therapy in these patients. METHODS: The data of 8477 participants aged > 45 years from the "2020 Korean Health Panel Survey" were used to analyze the current status of MCD in the middle-aged and elderly. The Chi-square test for categorical variables and the t-test for continuous variables. the used software was IBM SPSS Statistics 26.0 and IBM SPSS Modeler 18.0. RESULTS: In this study, the morbidity rate of MCD was 39.1%. Those with MCD were more likely to be female (p < 0.001), seniors over 65 years of age (p < 0.001), with low education level, no regular exercise behavior (p < 0.01). Chronic renal failure (93.9%), depression (90.4%), and cerebrovascular disease (89.6%) were the top three diseases identified in patients with MCD. A total of 37 association rules were identified for the group of individuals who did not engage in regular exercise. This equated to 61% more than that of the regular exercise group, who showed only 23 association rules. In the extra association rules, cardiovascular diseases (150%), spondylosis (143%), and diabetes (125%) are the three chronic diseases with the highest frequency increase. CONCLUSIONS: Association rule analysis is effective in studying the relationship between various chronic diseases in patients with MCD. It also effectively helps with the identification of chronic diseases that are more sensitive to regular exercise behaviors. The findings from this study may be used to formulate more appropriate and scientific exercise therapy for patients with MCD.
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População do Leste Asiático , Múltiplas Afecções Crônicas , Idoso , Pessoa de Meia-Idade , Humanos , Feminino , Masculino , Exercício Físico , Doença Crônica , Hábitos , AlgoritmosRESUMO
Cyberbullying among children is increasing every year, leading to serious public health problems. Victims suffer serious aftereffects such as depression and suicidal ideation; therefore, early and appropriate psychological intervention and the role of schools are emphasized. This study investigated the effects of school sandplay group therapy (SSGT) on children affected by cyberbullying. This study was designed as a parallel-group non-randomized controlled trial. The study subjects were 139 elementary school students (mean age 11.35 years; standard deviation, 0.479; age range 12-13 years) residing in Cheonan City, Korea, who were assigned to the intervention and comparison groups. The intervention group received 10 sessions of therapy on a weekly basis, for 40 minutes per session. No therapy was administered in the control group. The effectiveness of the intervention was assessed using the Children Depression Inventory, Suicidal Ideation Questionnaire-Junior, and Rosenberg Self-Esteem Scale. The assessment for the comparison group was performed concurrently with that of the intervention group. Data were analyzed using multivariate analysis of variance. In this study, the SSGT group showed a significant decrease in depression and suicidal ideation compared to the control group after sandplay group therapy (SGT), and a significant increase in self-esteem. It was confirmed that SSGT can mitigate the negative consequences of cyberbullying and strengthen protective factors. This suggests that the SSGT can be successfully used for crisis counseling.
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Bullying , Vítimas de Crime , Cyberbullying , Psicoterapia de Grupo , Humanos , Criança , Adolescente , Cyberbullying/psicologia , Ludoterapia , Ideação Suicida , Autoimagem , Vítimas de Crime/psicologiaRESUMO
BACKGROUND: The purpose of this study was to identify the prevalence of posttraumatic embitterment disorder (PTED) among soldiers, and examine its relation to stress, depression, self-esteem, impulsiveness, and suicidal ideation. METHODS: The subjects of this study were 200 soldiers and 197 control subjects, a total of 397 persons. Measurement tools used included the PTED self-rating scale, Stress Response Inventory, Beck Depression Inventory, Rosenberg Self-Esteem Inventory, Barratt Impulsiveness Scale, and Beck Scale of Suicide Ideation. RESULT: The major findings of the analysis are as follows: first, 11.5% of the soldiers were in the risk group for PTED, and 4% of them had PTED. Second, PTED in the soldiers was significantly associated with a number of variables such as their educational background, stress, depression, self-esteem, impulsiveness, and suicidal ideation, while it was not significantly associated with age. Third, through the hierarchical multiple regression analysis, it was found that academic background, stress, and depression had a statistically significant positive effect on the incidence of PTED in the soldiers. CONCLUSION: In order to prevent and effectively intervene in PTED in soldiers, there is a need for interventional efforts focused on depression and stress related to negative life events.
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Militares , Ideação Suicida , Humanos , Depressão/complicações , Fatores de Risco , República da Coreia/epidemiologiaRESUMO
INTRODUCTION: Metabolic disorder promotes premature senescence and poses more severe cardiac dysfunction in females than males. Although endurance exercise (EXE) has been known to confer cardioprotection against metabolic diseases, whether EXE-induced cardioprotection is associated with mitigating senescence in females remains unknown. Thus, the aim of the present study was to examine metabolic disorder-induced cardiac anomalies (cellular senescence, metabolic signaling, and autophagy) using a mouse model of obese/type 2 diabetes induced by a high-fat/high-fructose (HFD/HF) diet. METHODS: Female C57BL/6 mice (10 wk old) were assigned to three groups ( n = 11/group): normal diet group (CON), HFD/HF group, and HFD/HF diet + endurance exercise (HFD/HF + EXE) group. Upon confirmation of hyperglycemia and overweight after 12 wk of HFD/HF diet, mice assigned to HFD/HF + EXE group started treadmill running exercise (60 min·d -1 , 5 d·wk -1 for 12 wk), with HFD/HF diet continued. RESULTS: EXE ameliorated HFD/HF-induced body weight gain and hyperglycemia, improved insulin signaling and glucose transporter 4 (GLUT4) levels, and counteracted cardiac disruption. EXE reversed HFD/HF-induced myocyte premature senescence (e.g., prevention of p53, p21, p16, and lipofuscin accumulation), resulting in suppression of a senescence-associated secretory phenotype such as inflammation (tumor necrosis factor α and interleukin-1ß) and oxidative stress (protein carbonylation). Moreover, EXE restored HFD/HF-induced autophagy flux deficiency, evidenced by increased LC3-II concomitant with p62 reduction and restoration of lysosome function-related proteins (LAMP2, CATHEPSIN L, TFEB, and SIRT1). More importantly, EXE retrieved HFD/HF-induced apoptosis arrest (e.g., increased cleaved CASPASE3, PARP, and TUNEL-positive cells). CONCLUSIONS: Our study demonstrated that EXE-induced antisenescence phenotypes, autophagy restoration, and promotion of propitiatory cell removal by apoptosis play a crucial role in cardiac protection against metabolic distress-induced cardiac disruption.
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Diabetes Mellitus Tipo 2 , Hiperglicemia , Doenças Metabólicas , Condicionamento Físico Animal , Animais , Masculino , Camundongos , Feminino , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , AutofagiaRESUMO
INTRODUCTION AND AIM: Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases in the United States. Metabolic distress (obese diabetes) is the main causative element of NAFLD. While there is no cure for NAFLD, endurance exercise (EEx) has emerged as a therapeutic strategy against NAFLD. However, mechanisms of EXE-induced hepatic protection especially in female subjects remain unidentified. Thus, the aim of the study is to examine molecular mechanisms of EXE-induced hepatic protection against diet-induced NAFLD in female mice. MATERIAL AND METHODS: Nine-week-old female C57BL/6J mice were randomly divided into three groups: normal-diet control group (CON, n=11); high-fat diet/high-fructose group (HFD/HF, n=11); and HFD/HF+EEx group (HFD/HF+EEx, n=11). The mice assigned to HFD/HF and HFD/HF+EEx groups were fed with HFD/HF for 12 weeks, after which the mice assigned to the EEx group began treadmill exercise for 12 weeks, with HFD/HF continued. RESULTS: EEx attenuated hepatic steatosis, reduced de novo lipogenesis (reduction in ATP-Citrate- Lyase and diacylglycerol-O-acyltransferase 1), and enhanced mitochondrial biogenesis and fatty-acid activation (oxidative phosphorylation enzymes and Acyl-CoA synthetase1). Also, EEx prevented upregulation of gluconeogenic proteins (glyceraldehyde-3-phosphate dehydrogenase, glucose-6-phosphatase, and phosphoenolpyruvate-carboxykinase1), premature senescence (suppression of p53, p22, and p16, tumor-necrosis-factor-α, and interleukin-1ß, and oxidative stress), and autophagy deficiency. Furthermore, EXE reversed apoptosis arrest (cleaved cysteine-dependent-aspartate-directed protease3 and Poly-(ADP-ribose)-polymerase1). CONCLUSION: EEx-mediated reparations of metabolic and redox imbalance (utilization of pentose phosphate pathway), and autophagy deficiency caused by metabolic distress critically contribute to preventing/delaying severe progression of NAFLD. Also, EEx-induced anti-senescence and cell turnover are crucial protective mechanisms against NAFLD.
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Hepatopatia Gordurosa não Alcoólica , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Feminino , Humanos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controleRESUMO
Luminescent inorganic lead halide perovskite nanoparticles lack stability in aqueous solutions, limiting their application to optical sensors. Here, hybrid CsPbBr3-loaded MIP nanogels were developed with enhanced stability in aqueous media. Multifunctional MIP nanogels with antioxidant function and hydrophobic cavities were synthesized from HEMA derivatives in the presence of roxithromycin as a template. The CsPbBr3 nanoparticles were loaded into pre-synthesized MIP nanogels via in-situ synthesis with a size distribution of 200 nm. The developed CsPbBr3-nanogel exhibits excellent stability to air/moisture and enhanced stability toward an aqueous solvent. The developed CsPbBr3-loaded MIP nanogels showed a selective and sensitive detection of ROX with a limit of detection calculated to be 1.7 × 10-5 µg/mL (20.6 pM). The developed CsPbBr3-loaded MIP antioxidant-nanogels were evaluated on practical application for the quantitative determination of ROX antibiotic in animal-derived food products with excellent analytical performance. The detection of ROX in animal-derived food products showed good recovery results, making them an ideal candidate for sensing ROX.
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Autophagy/mitophagy, a cellular catabolic process necessary for sustaining normal cellular function, has emerged as a potential therapeutic strategy against numerous obstinate diseases. In this regard, endurance exercise (EXE)-induced autophagy/mitophagy (EIAM) has been considered as a potential health-enriching factor in various tissues including the brain; however, underlying mechanisms of EIAM in the brain has not been fully defined yet. This study investigated the molecular signaling nexus of EIAM pathways in the cortex of the brain. C57BL/6 young male mice were randomly assigned to a control group (CON, n = 12) and an endurance exercise group (EXE, n = 12). Our data demonstrated that exercise-induced autophagy coincided with an enhanced anabolic state (p-AKT, p-mTOR, and p-p70S6K); furthermore, mitophagy concurred with enhanced mitochondrial turnover: increases in both fission (DRP1, BNIP3, and PINK1) and fusion (OPA1 and MFN2) proteins. In addition, neither oxidative stress nor sirtuins (SIRT) 1 and 3 were associated with EIAM; instead, the activation of AMPK as well as a JNK-BCL2 axis was linked to EIAM promotion. Collectively, our results demonstrated that EXE-induced anabolic enrichment did not hinder autophagy/mitophagy and that the concurrent augmentation of mitochondrial fusion and fusion process contributed to sustaining mitophagy in the cortex of the brain. Our findings suggest that the EXE-induced concomitant potentiation of the catabolic and anabolic state is a unique molecular mechanism that simultaneously contributes to recycling and rebuilding the cellular structure, leading to upholding healthy cellular environment. Thus, the current study provides a novel autophagy/mitophagy mechanism, from which groundbreaking pharmacological strategies of autophagy can be developed.
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Autofagia , Córtex Cerebral/metabolismo , Metabolismo/fisiologia , Renovação Mitocondrial/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Condicionamento Físico Animal , Quinases Proteína-Quinases Ativadas por AMP , Animais , Córtex Cerebral/ultraestrutura , MAP Quinase Quinase 4/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Mitocondriais/metabolismo , Mitofagia , Oxirredução , Estresse Oxidativo , Proteínas Quinases/metabolismo , Distribuição Aleatória , Corrida , Sirtuína 1/análise , Sirtuína 3/análise , Serina-Treonina Quinases TOR/metabolismoRESUMO
Trematode specimens were collected from the intestine of a herring gull, Larus argentatus, which was found in a critical condition on the shore of a small island (Yubu-do, Seocheon-gun, Chungcheongnam-do) located at the western coast of the Korean peninsula. Total 11 specimens of intestinal flukes, including 3 Cryptocotyle lingua (Heterophyidae), 1 Himasthla alincia (Echinostomatidae), 5 Cardiocephaloides medioconiger (Strigeidae), and 2 Diplostomum spathaceum (Diplostomidae), were recovered. C. lingua was morphologically characterized by the presence of a large ventrogenital apparatus and 2 obliquely tandem testes. H. alincia had an elongated body and a head collar equipped with 31 collar spines. C. medioconiger had a bisegmented body and a voluminous copulatory bursa containing the seminal vesicle and ejaculatory duct. D. spathaceum also had a bisegmented body and its vitellaria extended up to the anterior border of the tribocytic organ. It is of note that C. lingua is potentially zoonotic that can occur in birds and humans. Three of them, i.e., C. lingua, C. medioconiger, and D. spathaceum, are new trematode fauna in Korea. Studies on trematode fauna of migratory birds should be continued in Korea.
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Peixes/parasitologia , Trematódeos/isolamento & purificação , Animais , República da CoreiaRESUMO
PURPOSE: Endurance exercise (EXE) preconditioning before DOX treatment confers cardioprotection; however, whether EXE postconditioning (i.e., EXE intervention after the completion of DOX treatment) is cardioprotective remains unknown. Thus, the aim of the present study was to investigate if EXE postconditioning provides cardioprotection by testing the hypothesis that EXE-autophagy upregulation and NADPH oxidase 2 (NOX2) downregulation would be linked to cardioprotection against DOX-induced cardiotoxicity. METHODS: C57BL/6 male mice were assigned into three groups: control (CON, n = 10), doxorubicin (DOX, n = 10), and doxorubicin + endurance exercise (DOX + EXE, n = 10). Animals assigned to DOX and DOX + EXE groups were intraperitoneally injected with DOX (5 mg·kg each week for 4 wk). Forty-eight hours after the last DOX treatment, the mice assigned to DOX + EXE performed EXE on a motorized treadmill at a speed of 13-15 m·min for 60 min·d for 4 wk. RESULTS: EXE prevented DOX-induced apoptosis and mitigated tissue damages. Although DOX did not modulate auto/mitophagy, EXE significantly enhanced its flux (increased LC3-II levels, reduced p62 levels, and increased autophagosomes with mitochondria) along with increased mitochondrial fission (DRP1) and reduced fusion markers (OPA1 and MFN2). Interestingly, EXE-induced autophagy against DOX occurred in the absence of alterations of autophagy inducer AMPK or autophagy inhibitor mTOR signaling. EXE prohibited DOX-induced oxidative damages by suppressing NOX2 levels but without modulating other key antioxidant enzymes including MnSOD, CuZnSOD, catalase, and GPX1/2. CONCLUSION: Our data provide novel findings that EXE-induced auto/mitophagy promotion and NOX2 downregulation are linked to cardioprotection against DOX-induced cardiotoxicity. Importantly, our study shows that EXE postconditioning intervention is effective and efficacious to prevent DOX-induced cardiac injuries.
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Antibióticos Antineoplásicos/toxicidade , Cardiotoxicidade/prevenção & controle , Doxorrubicina/toxicidade , Condicionamento Físico Animal/fisiologia , Animais , Apoptose/efeitos dos fármacos , Autofagia/fisiologia , Cardiotoxicidade/fisiopatologia , Regulação para Baixo , Masculino , Camundongos Endogâmicos C57BL , Dinâmica Mitocondrial/fisiologia , Mitofagia/efeitos dos fármacos , NADPH Oxidase 2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Condicionamento Físico Animal/métodos , Resistência Física/efeitos dos fármacos , Regulação para CimaRESUMO
INTRODUCTION AND OBJECTIVES: Endurance exercise (EXE) has emerged as a potent inducer of autophagy essential in maintaining cellular homeostasis in various tissues; however, the functional significance and molecular mechanisms of EXE-induced autophagy in the liver remain unclear. Thus, the aim of this study is to examine the signaling nexus of hepatic autophagy pathways occurring during acute EXE and a potential crosstalk between autophagy and apoptosis. MATERIALS AND METHODS: C57BL/6 male mice were randomly assigned to sedentary control group (CON, n=9) and endurance exercise (EXE, n=9). Mice assigned to EXE were gradually acclimated to treadmill running and ran for 60min per day for five consecutive days. RESULTS: Our data showed that EXE promoted hepatic autophagy via activation of canonical autophagy signaling pathways via mediating microtubule-associated protein B-light chain 3 II (LC3-II), autophagy protein 7 (ATG7), phosphorylated adenosine mono phosphate-activated protein kinase (p-AMPK), CATHEPSIN L, lysosome-associated membrane protein 2 (LAMP2), and a reduction in p62. Interestingly, this autophagy promotion concurred with enhanced anabolic activation via AKT-mammalian target of rapamycin (mTOR)-p70S6K signaling cascade and enhanced antioxidant capacity such as copper zinc superoxide dismutase (CuZnSOD), glutathione peroxidase (GPX), and peroxiredoxin 3 (PRX3), known to be as antagonists of autophagy. Moreover, exercise-induced autophagy was inversely related to apoptosis in the liver. CONCLUSIONS: Our findings indicate that improved autophagy and antioxidant capacity, and potentiated anabolic signaling may be a potent non-pharmacological therapeutic strategy against diverse liver diseases.
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Apoptose/fisiologia , Autofagia/fisiologia , Fígado/metabolismo , Condicionamento Físico Animal/fisiologia , Resistência Física , Adenilato Quinase/metabolismo , Animais , Antioxidantes/metabolismo , Proteína 7 Relacionada à Autofagia/metabolismo , Catepsina L/metabolismo , Glutationa Peroxidase/metabolismo , Fígado/patologia , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Lisossomos/metabolismo , Masculino , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Peroxirredoxina III/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Distribuição Aleatória , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Comportamento Sedentário , Transdução de Sinais , Superóxido Dismutase-1/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
PURPOSE: Metabolic disorder such as obesity and type 2 diabetes caused by excess caloric intake is associated with an increased risk of neurodegenerative diseases. Endurance exercise (EXE) has been suggested to exert neuroprotective effects against the metabolic distress. However, the exact underlying molecular mechanisms responsible for the exercise-induced neuroprotection have not been fully elucidated. In this study, we investigated whether EXE-induced neuroprotection is associated with cellular senescence, neuroinflammation, and oxidative stress using a mouse model of obesity induced by a high-fat/high-fructose diet. METHODS: C57BL/6 female mice (10 wk old) were randomly divided to three groups: normal chow diet group (CON, n = 11), high-fat diet/high-fructose (HFD/HF) group (n = 11), and high-fat diet/high-fructose + endurance exercise (HFD/HF + EXE) group (n = 11). HFD/HF + EXE mice performed treadmill running exercise for 60 min·d, 5 d·wk for 12 wk. RESULTS: Our data showed that EXE ameliorated HFD/HF-induced weight gain, fasting blood glucose levels, and visceral fat gain. More importantly, HFD/HF diet promoted cellular senescence, whereas EXE reversed it, evidenced by a reduction in the levels of p53, p21, p16, beta-galactosidase (SA-ß-gal), and lipofuscin. Furthermore, EXE prevented HFD/HF-induced neuroinflammation (e.g., tumor necrosis factor-α and interleukin-1ß) by inhibiting toll-like receptor 2 downstream signaling cascades (e.g., tumor necrosis factor receptor-associated factor 6, c-Jun N-terminal kinase, and c-Jun) in parallel with reduced reactive glial cells. This anti-inflammatory effect of EXE was associated with the reversion of HFD/HF-induced cellular oxidative stress. CONCLUSION: Our study provides novel evidence that EXE-induced antisenescence against metabolic distress in the hippocampus may be a key neuroprotective mechanism, preventing neuroinflammation and oxidative stress.
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Hipocampo/metabolismo , Obesidade/metabolismo , Resistência Física/fisiologia , Animais , Glicemia/metabolismo , Senescência Celular , Dieta Hiperlipídica , Modelos Animais de Doenças , Feminino , Frutose , Inflamação/fisiopatologia , Gordura Intra-Abdominal/metabolismo , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/patologia , Estresse Oxidativo/fisiologia , Aumento de PesoRESUMO
AIM: Endurance exercise (EE) has been reported to confer neuroprotection against Parkinson's disease (PD); however, underlying molecular mechanisms of the protection remain still unclear. Since mitochondrial impairment is commonly observed in the brain of PD patients and animals, this study investigated whether EE-induced neuroprotection is associated with mitochondrial phenotypes, using a mouse model of PD induced by intraperitoneal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MAIN METHODS: SH-SY5Y cells were cultured with a neurotoxin MPP+ known to cause PD-like symptoms to examine if modifications of mitochondrial morphology are linked to etiology of PD. For in vivo experiments, C57BL/6 male mice were randomly assigned to four groups: control (CON, nâ¯=â¯12), endurance exercise (EXE, nâ¯=â¯12), MPTP (MPTP, nâ¯=â¯12) and MPTP plus endurance exercise (MPTPâ¯+â¯EXE, nâ¯=â¯12). Mice assigned to endurance exercise performed treadmill running at 12â¯m/min for 60â¯min/day, 5â¯days/week for 6â¯weeks. KEY FINDINGS: SH-SY5Y cells exposed to a neurotoxin MPP+ exhibited mitochondrial fragmentation and diminished mitochondrial proteins, and cell death. Similarly, animals administered with MPTP displayed comparable impairments in the substantia nigra pars compacta (SNpc). In contrast, EE intervention restored motor function to control levels and reduced apoptosis. These propitious effects of EE were associated with mitochondrial phenotypic changes such as upregulated anti-apoptotic proteins (e.g., MCL-1 and BLC-2), reduced a pro-apoptotic protein (e.g., AIF), and improved mitochondrial biogenesis and fusion. SIGNIFICANCE: Our finding that EE-induced mitochondrial phenotypic changes that resist mitochondrial impairment and cell death against PD introduce potential insight into mitochondria as a new therapeutic target for PD.
Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/efeitos adversos , Modelos Animais de Doenças , Terapia por Exercício , Intoxicação por MPTP/terapia , Mitocôndrias , Neuroproteção , Doença de Parkinson/terapia , Animais , Apoptose , Intoxicação por MPTP/induzido quimicamente , Intoxicação por MPTP/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neuroblastoma/patologia , Neuroblastoma/terapia , Neurotoxinas/toxicidade , Doença de Parkinson/etiologia , Doença de Parkinson/patologia , Fenótipo , Células Tumorais CultivadasRESUMO
Soil-transmitted helminthiases (STH) are now no longer public health problems in the Republic of Korea (South Korea), but their status are unavailable in the residents of North Korea (NK) despite the expectation of large scale traffic and future reunification of the Korean Peninsula. A total of 20 female refugees from NK who had been admitted to the Division of Gastroenterology, Dankook University Hospital, were subjected in this study. Among them, 15 refugees were examined by the colonoscopy and 10 ones were examined with the stool examination (formalin-ether sedimentation). Both diagnostic methods were commonly adopted in 5 patients. Eggs of Trichuris trichiura were detected in 7 out of 10 refugees in the stool examination. In the colonoscopy, T. trichiura worms were found in 6 (40.0%) out of 15 refugees. Total 9 (45.0%) peoples were confirmed to be infected with human whipworms. Additionally, 1 case of clonorchiasis was diagnosed in the stool examination and a worm of Ascaris lumbricoides was discovered from a trichuriasis case. These findings suggested that STH is highly prevalent in NO, in which living conditions are not so good in the aspect of general hygiene and medical care.
Assuntos
Ascaríase/parasitologia , Ascaríase/transmissão , Ascaris lumbricoides/isolamento & purificação , Enteropatias Parasitárias/parasitologia , Enteropatias Parasitárias/transmissão , Refugiados/estatística & dados numéricos , Solo/parasitologia , Tricuríase/parasitologia , Tricuríase/transmissão , Trichuris/isolamento & purificação , Adolescente , Adulto , Animais , Ascaríase/epidemiologia , Colonoscopia , República Democrática Popular da Coreia/epidemiologia , República Democrática Popular da Coreia/etnologia , Fezes/parasitologia , Feminino , Humanos , Enteropatias Parasitárias/epidemiologia , Pessoa de Meia-Idade , Prevalência , República da Coreia , Tricuríase/epidemiologia , Adulto JovemRESUMO
PURPOSE: We investigated whether treadmill exercise (TE)-induced neuroprotection was associated with enhanced autophagy and reduced apoptosis in a mouse model of pharmacologically induced Parkinson's disease (PD). METHODS: PD was induced via the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). C57BL/6 male mice were randomly assigned to the following three groups: control (C57BL, n=10), MPTP with probenecid (MPTP/C, n=10), and MPTP/ C plus exercise (MPTP-TE, n=10). The MPTP-TE mice performed TE training (10 m/min, 60 min/day, 5 days/week) for 8 weeks. The rotarod test was used to assess motor function. RESULTS: TE restored MPTP/P-induced motor dysfunctionand increased tyrosine hydroxylase levels. Furthermore, TE diminished the levels of α-synuclein (α-syn), a neurotoxin; modulated the levels of autophagy-associated proteins, including microtubule-associated protein 1 light chain 3-II, p62, BECLIN1, BNIP3, and lysosomal-associated membrane protein-2, which enhanced autophagy; inhibited the activation of proapoptotic proteins (caspase-3 and BAX);and upregulated BCL-2, an antiapoptosis protein. CONCLUSION: Taken together, these results suggested that the TE-induced neuroprotection against MPTP-induced cell death was associated with enhanced autophagy and neuronal regeneration based on the findings of inhibited proapoptotic events in the brains of the TE-trained animals.
RESUMO
Parkinson's disease (PD) is a neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra, leading to motor dysfunction. Growing evidence has demonstrated that endurance exercise (EE) confers neuroprotection against PD. However, the exact molecular mechanisms responsible for exercise-induced protection of dopaminergic neurons in PD remain unclear. Since oxidative stress plays a key role in the degenerative process of PD. We investigated whether EE-induced neuroprotection is associated with enhanced antioxidative capacity and autophagy, using a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. C57BL/6 male mice were randomly assigned to four groups: control (CON, nâ¯=â¯12), exercise (EXE, nâ¯=â¯12), MPTP (MPTP, nâ¯=â¯12) and MPTPâ¯+â¯exercise (MPTPâ¯+â¯EXE, nâ¯=â¯12). Our data demonstrated that while MPTP treatment impaired motor function, EE restored MPTP-induced motor deficits. Our biochemical data showed that EE-induced neuroprotection occurs in combination with multiple synergic neuroprotective pathways: (1) increased neurogenesis shown by an increase in BrdU-positive neurons; (2) diminished loss of dopaminergic neurons evidenced by upregulated tyrosine hydroxylase (TH) and dopamine transporter (DAT) levels; (3) increased antioxidant capacity (e.g., CuZnSOD, CATALASE, GPX1/2, HO-1, DJ1 and PRXIII); and (4) enhanced autophagy (LC3 II, p62, BECLIN1, BNIP3, LAMP2, CATHEPSIN L and TFEB). Our study suggests that EE-induced multiple synergic protective pathways including enhanced neurogenesis, antioxidative capacity, and concordant autophagy promotion contribute to restoration of impaired dopaminergic neuronal function caused by PD. Thus, PD patients should be encouraged to actively participate in regular EE as a potent nonpharmacological therapeutic strategy against PD.