RESUMO
Cardiovascular diseases such as atherosclerosis and aortic valve sclerosis involve inflammatory reactions triggered by various stimuli, causing increased oxidative stress. This increased oxidative stress causes damage to the heart cells, with subsequent cell apoptosis or calcification. Currently, heart valve damage or heart valve diseases are treated by drugs or surgery. Natural antioxidant products are being investigated in related research, such as fucoxanthin (Fx), which is a marine carotenoid extracted from seaweed, with strong antioxidant, anti-inflammatory, and anti-tumor properties. This study aimed to explore the protective effect of Fx on heart valves under high oxidative stress, as well as the underlying mechanism of action. Rat heart valve interstitial cells under H2O2-induced oxidative stress were treated with Fx. Fx improved cell survival and reduced oxidative stress-induced DNA damage, which was assessed by cell viability analysis and staining with propidium iodide. Alizarin Red-S analysis indicated that Fx has a protective effect against calcification. Furthermore, Western blotting revealed that Fx abrogates oxidative stress-induced apoptosis via reducing the expression of apoptosis-related proteins as well as modulate Akt/ERK-related protein expression. Notably, in vivo experiments using 26 dogs treated with 60 mg/kg of Fx in combination with medical treatment for 0.5 to 2 years showed significant recovery in their echocardiographic parameters. Collectively, these in vitro and in vivo results highlight the potential of Fx to protect heart valve cells from high oxidative stress-induced damage.
Assuntos
Calcificação Fisiológica/efeitos dos fármacos , Cardiotônicos/farmacologia , Valvas Cardíacas/efeitos dos fármacos , Xantofilas/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Cães , Valvas Cardíacas/patologia , Peróxido de Hidrogênio , Estresse Oxidativo/efeitos dos fármacos , RatosRESUMO
BACKGROUND: Relatively few studies have investigated the effects of diet on behavior problems among preschoolers, particularly, physical aggression. In addition, children raised by poorly educated mothers usually have a higher probability of developing negative outcomes. Additionally, highly educated mothers have a higher probability of providing more healthy foods for their children. Thus, mothers providing healthy foods might mitigate children's behavior problems. The study aims to examine whether preschoolers' dietary pattern, as a manipulable factor, mediates the association between maternal education level and physical aggression. METHODS: Data came from the Taiwan Birth Cohort Study (TBCS), a nationally representative population-based cohort study, which included 18,513 five-year-old Taiwanese children. Mothers and primary caregivers reported the information on preschoolers' physical aggression and food consumption at age 5 and maternal education level at age 6 months. Two dietary patterns, namely a healthy diet and a high-fat-sugar-salt (HFSS) diet, were retrieved by exploratory factor analysis. Mediation hypotheses were tested by a series of multiple regression models conducted using the PROCESS macro of SAS 9.4. All models were adjusted for children's sex, parental marital status, household income, mental distress at age 5 and children's physical aggression at age 3. RESULTS: Maternal education positively linked to healthy dietary patterns (B = 0.014, p = 0.002) which was negatively associated with preschoolers' physical aggression (B = -0.096, p = 0.013), and it is negatively related to the HFSS dietary pattern (B = -0.042, p = 0.002) which was directly positively associated with preschoolers' physical aggression (B = 0.123, p = 0.008). The association between maternal education and preschoolers' physical aggression was partially mediated by preschoolers' healthy (B = -0.001, p < .001) and HFSS (B = -0.005, p = <.001) dietary patterns, respectively. The R-square of the mediation model is 0.178. CONCLUSIONS: Preschoolers' dietary patterns directly associate with their physical aggression. In addition, mothers with poor education may provide less healthy foods and more unhealthy foods to their children, which may increase the level of physical aggression. The results imply partial mediating effects of dietary patterns between maternal education and physical aggression. It is suggested that a parent-based nutritional education program focusing on healthy meal preparation for poor educated mothers might be beneficial for preschoolers' healthy development.
Assuntos
Agressão , Mães , Criança , Pré-Escolar , Estudos de Coortes , Escolaridade , Feminino , Humanos , Lactente , TaiwanRESUMO
Amyloid beta (Aß) accumulation in the brain is one of the major pathological features of Alzheimer's disease. The active form of vitamin D (1,25(OH)2D3), which acts via its nuclear hormone receptor, vitamin D receptor (VDR), has been implicated in the treatment of Aß pathology, and is thus considered as a neuroprotective agent. However, its underlying molecular mechanisms of action are not yet fully understood. Here, we aim to investigate whether the molecular mechanisms of 1,25(OH)2D3 in ameliorating Aß toxicity involve an interplay of glial cell line-derived neurotrophic factor (GDNF)-signaling in SH-SY5Y cells. Cells were treated with Aß(25-35) as the source of toxicity, followed by the addition of 1,25(OH)2D3 with or without the GDNF inhibitor, heparinase III. The results show that 1,25(OH)2D3 modulated Aß-induced reactive oxygen species, apoptosis, and tau protein hyperphosphorylation in SH-SY5Y cells. Additionally, 1,25(OH)2D3 restored the decreasing GDNF and the inhibited phosphorylation of the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3ß (GSK-3ß) protein expressions. In the presence of heparinase III, these damaging effects evoked by Aß were not abolished by 1,25(OH)2D3. It appears 1,25(OH)2D3 is beneficial for the alleviation of Aß neurotoxicity, and it might elicit its neuroprotection against Aß neurotoxicity through an interplay with GDNF-signaling.
Assuntos
Peptídeos beta-Amiloides/toxicidade , Calcitriol/farmacologia , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Neurônios/citologia , Espécies Reativas de Oxigênio/metabolismo , Proteínas tau/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fosforilação/efeitos dos fármacos , Polissacarídeo-Liases/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: The present study analysed data derived from the 2004-2008 Nutrition and Health Survey in Taiwan, conducted by the Ministry of Health and Welfare, to understand the relationship among eating-out behaviour, related non-nutritional factors and osteopenia in the Taiwanese population. Design/Setting/Subjects Data of 1140 adults who had been evaluated with dual-energy X-ray absorptiometry in June 2007 were included. The data were analysed through descriptive and inferential statistics to determine the association of osteopenia with the frequency of eating out, demographic variables (i.e. age, sex, level of education, marital status and place of birth), BMI, waist circumference and food consumption. RESULTS: Gender, age, education level, personal income and waist circumference were all factors found to be significantly associated with eating-out frequency and the incidence of osteopenia. Eating-out frequency was negatively associated with the incidence of osteopenia. Individuals with BMI>27 kg/m2 had a lower frequency of eating out and a lower incidence of osteopenia. Individuals with a lower monthly income had a significantly greater chance of developing osteopenia. Men living without spouses had significantly higher chances of osteopenia. Ca intake was negatively associated with breakfast eating-out frequency. CONCLUSIONS: Eating-out frequency was not associated with an increasing incidence of osteopenia, but affected the Ca intake in the Taiwanese population. Having a balanced selection of food is crucial to reduce the incidence of osteopenia. Improving nutritional knowledge for those under higher risk of osteopenia is necessary to prevent osteopenia and Ca deficiency.
Assuntos
Densidade Óssea , Comportamento Alimentar , Absorciometria de Fóton , Adulto , Fatores Etários , Idoso , Estudos Transversais , Escolaridade , Feminino , Humanos , Renda/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Taiwan , Circunferência da Cintura , Adulto JovemRESUMO
OBJECTIVE: To investigate the reciprocal relationship between unhealthy eating behaviours and depressive symptoms from childhood to adolescence. DESIGN: Unhealthy eating behaviours were measured by the frequencies of eating foods with excess salt, sugar or fat in the past week. Depressive symptoms in the past two weeks were measured using a seven-item scale. Hierarchical linear growth models were used to analyse longitudinal associations between unhealthy eating behaviours and depressive symptoms. Time-fixed variables (sex, parents' education level and household monthly income) and time-varying variables (parents' marital status, family activities, body weight, vegetable or fruit consumption, exercising and smoking) were controlled for. SETTING: The Child and Adolescent Behaviors in Long-Term Evolution study, which commenced in 2001 and has annual follow-up. SUBJECTS: Students (n 2630) followed from 2nd grade (8 years old in 2002) to 11th grade. RESULTS: The frequency of unhealthy eating behaviours in the previous year and the difference between the frequency in the previous and successive year were positively associated with the initiation and growth rate of depressive symptoms. Depressive symptoms in the previous year and the difference in depressive symptoms between the previous and successive year were positively associated with the initial state and growth rate of unhealthy eating behaviours. CONCLUSIONS: Our results suggest a reciprocal relationship between depressive symptoms and unhealthy eating behaviours. This relationship should be considered when developing programmes targeting depressive symptoms and unhealthy diet in children and adolescents.
Assuntos
Comportamento do Adolescente , Comportamento Infantil , Depressão/epidemiologia , Dieta , Comportamento Alimentar , Adolescente , Criança , Feminino , Seguimentos , Humanos , MasculinoRESUMO
Ageing accompanied by a decline in cognitive performance may be a result of the long-term effects of oxidative stress on neurologic processes. It has been shown that high-cholesterol contents in the blood and brain may lead to the deposition of the ß-amyloid (Aß) protein in the brain, which damages brain cells. The present study was designed to observe the effect of polyphenol-rich Oriental plums on cognitive function and cerebral neurodegeneration-related protein expression in mice that were fed a high-cholesterol diet for 5 months. The study consisted of four groups: the control (Ctrl) group, which was fed the American Institute of Nutrition (AIN)-93M diet; the high cholesterol (HC) group, which was fed the AIN-93M diet with 5% cholesterol; the high cholesterol + low Oriental plum (LOP) group, which was fed the AIN-93M diet with 5% cholesterol and 2% Oriental plum powder; and the high cholesterol + high Oriental plum (HOP) group, which was fed the AIN-93M diet with 5% cholesterol and 5% Oriental plum powder. Measurements of cognitive function were assessed using the Morris water maze, and the mRNA expression of cholesterol hydroxylase (Cyp46), Aß and ß-secretase 1 (BACE1) were analysed. The results showed that cholesterol concentrations in both the blood and the brain were significantly higher in the HC group than in the Ctrl and HOP groups at the end of the trial. The high-cholesterol diet per se produced significant cognitive deficits, which were accompanied by a significantly increased mRNA expression of Cyp46, BACE1, Aß and 24-hydroxycholesterol in the brain cortex and hippocampus. However, all of these variables were non-significantly increased in the HOP group as compared to the Ctrl group. In conclusion, incorporating polyphenol-enriched Oriental plum into a high-cholesterol diet can ameliorate some of the symptoms of neurodegenerative conditions.
Assuntos
Anticolesterolemiantes/uso terapêutico , Encéfalo/metabolismo , Transtornos Cognitivos/prevenção & controle , Hipercolesterolemia/prevenção & controle , Proteínas do Tecido Nervoso/metabolismo , Nootrópicos/uso terapêutico , Polifenóis/uso terapêutico , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Anticolesterolemiantes/administração & dosagem , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/metabolismo , Comportamento Animal , Colesterol/sangue , Colesterol/metabolismo , Colesterol 24-Hidroxilase , Transtornos Cognitivos/sangue , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/metabolismo , Suplementos Nutricionais , Frutas/química , Regulação da Expressão Gênica , Hipercolesterolemia/sangue , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Masculino , Aprendizagem em Labirinto , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/genética , Neurônios/metabolismo , Nootrópicos/administração & dosagem , Polifenóis/administração & dosagem , Prunus/química , Distribuição Aleatória , Esteroide Hidroxilases/genética , Esteroide Hidroxilases/metabolismoRESUMO
BACKGROUND: Osteopontin (OPN) is a pro-inflammatory cytokine which is expressed in various tissues. It participates in the bone remodeling process and stimulates bone resorption by osteoclasts. It is also a core protein of cholesterol gallstones. We hypothesized osteoporotic patients might have higher risk in developing gallstones and conducted a population-based study to examine the risk of developing gallstone in osteoporotic patients in Taiwan. METHODS: A total of 1,638 patients diagnosed with osteoporosis between 2003 and 2005 were identified in the National Health Insurance Research Database. A comparison cohort without osteoporosis (n =6,552) was randomly matched to each osteoporosis patient at a ratio of 4: 1 based on age and sex. A Cox proportional-hazards regression analysis was performed to evaluate the 5-year gallstone-free survival rates for the 2 cohorts. RESULTS: During the 5-year follow-up period, 114 and 311 cases of gallstone occurred in the osteoporosis and comparison cohorts, respectively. After adjusting for the confounders, the Cox regression analysis of the risk of gallstone in the osteoporosis and comparison cohorts yielded a hazard ratio of 1.35 (95% confidence interval: 1.07 - 1.69; p < 0 .01). CONCLUSION: Patients with osteoporosis in Taiwan have a higher risk of developing gallstone than the general population.
Assuntos
Cálculos Biliares/epidemiologia , Osteoporose/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Cálculos Biliares/complicações , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Osteoporose/complicações , Osteoporose/mortalidade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologiaRESUMO
Chronic amphetamine intake leads to neurogenic bladder and chronic urinary retention. The mechanism underlying persistent urinary retention is unclear. The pelvic-urethral reflex (PUR) is essential for the urethra to develop sufficient resistance to maintain urine continence, an important function of the urinary system. Recent studies on PUR activities have indicated that repetitive/tetanic stimulation of the pelvic afferent fibers induces spinal reflex potentiation (SRP) in PUR activities, which further increases urinary retention. In this study, results showed that test stimulation (TS, 1/30 Hz) evoked a baseline reflex activity, while repetitive stimulation (RS, 1 Hz) induced reflex potentiation in the external urethral sphincter. Intrathecal d-amphetamine (AMPH, 30 µM) did not but higher AMPH concentration (100 µM) induced SRP in TS-induced reflex activity. H89 (10 µM, a protein kinase A inhibitor), but not chelerythrine chloride (CTC, 10 µM, a protein kinase C inhibitor), prevented the 100 µM AMPH-elicited SRP. At 30 µM, forskolin, an activator of adenylyl cyclase, elicited SRP. The co-administration of 10 µM forskolin and 30 µM AMPH induced SRP in TS-induced reflex activity. These results implied that the repetitive/tetanic stimulation of the pelvic afferent fibers could induce SRP in PUR activities, so that the urethra can produce sufficient resistance and played a significant role in urinary retention. Findings in this study demonstrated that amphetamine could induce bladder dysfunction by triggering protein kinase A activation, and provide a practical basis for the development of treatment for amphetamine-associated urinary retention.
Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/complicações , Dextroanfetamina/farmacologia , Retenção Urinária/induzido quimicamente , Retenção Urinária/fisiopatologia , Micção/efeitos dos fármacos , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , Vias Aferentes/efeitos dos fármacos , Vias Aferentes/fisiologia , Amidinas/farmacologia , Animais , Benzofenantridinas/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Doença Crônica , Colforsina/farmacologia , Agonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Ácido Glutâmico/farmacologia , Isoquinolinas/farmacologia , N-Metilaspartato/farmacologia , Oxidantes/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Ratos Wistar , Reflexo/efeitos dos fármacos , Reflexo/fisiologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/fisiologia , Sulfonamidas/farmacologia , Micção/fisiologia , Valina/análogos & derivados , Valina/farmacologiaRESUMO
Obesity-related neurodegenerative diseases are associated with elevated saturated fatty acids (SFAs) in the brain. An increase in SFAs, especially palmitic acid (PA), triggers neuron cell apoptosis, causing cognitive function to deteriorate. In the present study, we focused on the specific mechanism by which PA triggers SH-SY5Y neuron cell apoptosis. We found that PA induces significant neuron cell cycle arrest in the G2/M phase in SH-SY5Y cells. Our data further showed that G2/M arrest is involved in elevation of endoplasmic reticular (ER) stress according to an increase in p-eukaryotic translation inhibition factor 2α, an ER stress marker. Chronic exposure to PA also accelerates beta-amyloid accumulation, a pathological characteristic of Alzheimer's disease. Interestingly, SFA-induced ER stress, G2/M arrest and cell apoptosis were reversed by treatment with 2-bromopalmitate, a protein palmitoylation inhibitor. These findings suggest that protein palmitoylation plays a crucial role in SFA-induced neuron cell cycle G2/M arrest, ER stress and apoptosis; this provides a novel strategy for preventing SFA-induced neuron cell dysfunction.
Assuntos
Estresse do Retículo Endoplasmático , Pontos de Checagem da Fase G2 do Ciclo Celular , Pontos de Checagem da Fase M do Ciclo Celular , Neurônios/metabolismo , Ácido Palmítico/metabolismo , Apoptose , Linhagem Celular Tumoral , Humanos , Lipoilação , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Neurônios/patologiaRESUMO
Midlife overweight and obesity are risk factors of cognitive decline and Alzheimer' s disease (AD) in late life. In addition to increasing risk of obesity and cognitive dysfunction, diets rich in fats also contributes to an imbalance of gut microbiota. Xylo-oligosaccharides (XOS) are a kind of prebiotic with several biological advantages, and can selectively promote the growth of beneficial microorganisms in the gut. To explore whether XOS can alleviate cognitive decline induced by high-fat diet (HFD) through improving gut microbiota composition, mice were fed with normal control or 60% HFD for 9 weeks to induce obesity. After that, mice were supplemented with XOS (30 g or 60 g/kg-diet) or without, respectively, for 12 weeks. The results showed that XOS inhibited weight gain, decreased epidydimal fat weight, and improved fasting blood sugar and blood lipids in mice. Additionally, XOS elevated spatial learning and memory function, decreased amyloid plaques accumulation, increased brain-derived neurotrophic factor levels, and improved neuroinflammation status in hippocampus. Changes in glycerolipids metabolism-associated lipid compounds caused by HFD in hippocampus were reversed after XOS intervention. On the other hand, after XOS intervention, increase in immune-mediated bacteria, Faecalibacterium was observed. In conclusion, XOS improved gut dysbiosis and ameliorated spatial learning and memory dysfunction caused by HFD by decreasing cognitive decline-associated biomarkers and changing lipid composition in hippocampus.
Assuntos
Dieta Hiperlipídica , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Oligossacarídeos , Prebióticos , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Oligossacarídeos/farmacologia , Oligossacarídeos/administração & dosagem , Masculino , Camundongos , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Obesidade/metabolismo , Obesidade/microbiologia , Glucuronatos/farmacologia , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Lipídeos/sangue , Disfunção Cognitiva/prevenção & controle , Disbiose , Metabolismo dos Lipídeos/efeitos dos fármacosRESUMO
Hypoglycemia has been known as a potential contributory factor to neurodegenerative diseases, such as Alzheimer's disease. There may be shared pathogenic mechanisms underlying both conditions, and the ketone body, ß-hydroxybutyrate (BHB), as an alternative substrate for glucose may exert neuroprotection against hypoglycemia-induced injury. To investigate this, Neuro-2a cells were subjected to a 24 h period of glucose deprivation with or without the presence of BHB. Cell viability, reactive oxygen species (ROS) production, apoptosis, autophagy, and adenosine triphosphate (ATP) and beta-amyloid peptide (Aß) levels were evaluated. The results show that Neuro-2a cells deprived of glucose displayed a significant loss of cell survival with a corresponding decrease in ATP levels, suggesting that glucose deprivation was neurotoxic. This effect was likely attributed to the diverse mechanisms including raised ROS, defective autophagic flux and reduced basal Aß levels (particularly monomeric Aß). The presence of BHB could partially protect against the loss of cell survival induced by glucose deprivation. The mechanisms underlying the neuroprotective actions of BHB might be mediated, at least in part, through restoring ATP, and modulating ROS production, autophagy flux efficacy and the monomeric Aß level. Results imply that a possible link between the basal monomeric Aß and glucose deprivation neurotoxicity, and treatments designed for the prevention of energy impairment, such as BHB, may be beneficial for rescuing surviving cells in relation to neurodegeneration.
RESUMO
The present study examined the effect of the isocaloric low-carbohydrate ketogenic diet (LCKD) with or without exercise training for 6 weeks on postpartum weight retention (PPWR), body composition, metabolic profile and physical activity performance in postpartum mice. Postpartum mice were assigned to four groups (n=8/group) as follows: (1) those on a control diet without aerobic exercise (CN); (2) those on a control diet with aerobic exercise (CN+EX), (3); those on a LCKD without aerobic exercise (LCKD); (4) those on a LCKD with aerobic exercise (LCKD+EX). CN+EX and LCKD+EX mice performed 6 weeks of exercise training on a treadmill. After the 6-week intervention, physical activity performance was determined. Postpartum mice in all groups experienced progressive reductions in body weight over the study period. The LCKD group had the smallest reduction in PPWR (P<.05). The LCKD group had significantly higher total cholesterol, low-density lipoprotein cholesterol and lactate dehydrogenase levels, and liver lipid concentrations with a worsened glucose tolerance, compared to the CN group (P<.05). The LCKD group showed significant reductions in physical activity performance, whilst the LCKD+EX group showed significant improvement in endurance performance, and paralleled the concomitant elevation in blood ketone levels. Six-week LCKD feeding on its own was less effective for reducing PPWR, and more detrimental to the postpartum metabolic outcomes and physical activity performance of the postpartum mice. The feasibility of a LCKD with or without exercise during the postpartum period as a strategy for managing PPWR and improving postpartum metabolic profiles should be carefully considered.
Assuntos
Dieta Cetogênica , Ganho de Peso na Gestação , Animais , Carboidratos , Colesterol , Feminino , Humanos , Metaboloma , Camundongos , Período Pós-PartoRESUMO
Alzheimer's disease (AD) is a common neurodegenerative disorder that causes dementia and affects millions of people worldwide. The mechanism underlying AD is unclear; however, oxidative stress and mitochondrial biogenesis have been reported to be involved in AD progression. Previous research has also reported the reduction in mitochondrial biogenesis in the brains of patients with AD. Quercetin (QE), a type of polyphenol, has been found to be capable of increasing mitochondrial biogenesis in the body. Accordingly, we explored whether QE could reduce amyloid beta (Aß) accumulation caused by hydrogen peroxide (H2O2)-induced oxidative stress in SH-SY5Y cells. Our results revealed that QE stimulated the expression of mitochondrial-related proteins such as SIRT1, PGC-1α, and TFAM and subsequently activated mitochondrial biogenesis. Additionally, QE increased ADAM10 expression but reduced H2O2-induced reactive oxygen species production, apoptosis, ß-site amyloid precursor protein cleaving enzyme 1 expression, and Aß accumulation in the SH-SY5Y cells. These findings indicate that QE can effectively elevate mitochondrial biogenesis-related proteins and reduce the damage caused by oxidative stress, making it a promising option for protecting neuronal cells.
Assuntos
Doença de Alzheimer , Neuroblastoma , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Linhagem Celular Tumoral , Humanos , Peróxido de Hidrogênio/farmacologia , Proteínas Mitocondriais/metabolismo , Neuroblastoma/tratamento farmacológico , Biogênese de Organelas , Estresse Oxidativo , Quercetina/farmacologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
We found the main effects of harm avoidance temperament in predicting bipolar I and II, but the interaction between novelty seeking and Ser9Gly polymorphisms of dopamine D3 receptor gene was demonstrated in bipolar-I patients only. This study provided evidence that differences existed between BP-I and BPII in gene and temperament interactions.
Assuntos
Transtorno Bipolar , Polimorfismo Genético/genética , Receptores de Dopamina D3/genética , Temperamento/fisiologia , Transtorno Bipolar/classificação , Transtorno Bipolar/genética , Transtorno Bipolar/fisiopatologia , Análise Mutacional de DNA , Comportamento Exploratório/fisiologia , Feminino , Genótipo , Glicina/genética , Humanos , Masculino , Inventário de Personalidade , Escalas de Graduação Psiquiátrica , Análise de Regressão , Serina/genética , Taiwan/etnologiaRESUMO
BACKGROUND: Small-cell lung cancer (SCLC) represents a group of highly fatal diseases with a tendency toward fast growth, early metastasis, and easy development of chemotherapy resistance. In the past 30 years, few advances have been made in the systemic treatment of SCLC, and cisplatin/etoposide has remained the standard of care for limited-stage SCLC and, in combination with radiotherapy, extensive-stage SCLC. The preferred metastatic sites of SCLC include the brain, liver, adrenal glands, bone, and bone marrow. However, bowel metastasis caused by SCLC is extremely rarely proved in patients while they are still alive (although autopsy studies suggest that silent metastases to the bowel are more common), and the standard treatment for bowel metastasis has never been reported. The mean time between the identification of gastrointestinal metastasis and mortality in patients with lung cancer is 100.6 days, with a range of 21-145 days. CASE: We report the case of a patient with extensive SCLC (including brain metastasis), in which exon 19 deletion of epidermal growth factor receptor (EGFR) was detected. She initially refused chemotherapy and cranial radiotherapy and instead only agreed to oral target therapy. The second-generation EGFR-tyrosine kinase inhibitor (TKI), afatinib, was administered to the patient, and partial remission, including smaller metastatic brain tumors, was noted. Even though the subsequent development of rare metastatic lesions in the ascending and sigmoid colon was proved by colonoscopic biopsies, the prolonged overall survival (400 days) without standard treatment was marked in this case. CONCLUSION: The patient with extensive metastasis of SCLC did not receive standard systemic chemotherapy. Instead, she initially received second-generation EGFR-TKI afatinib alone and later on whole brain radiotherapy as well (3 weeks before she expired). The prolonged overall survival of 400 days was marked and is worthy of sharing and further investigation.
Assuntos
Afatinib/efeitos adversos , Colo Ascendente/patologia , Colo Sigmoide/patologia , Neoplasias do Colo/patologia , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Idoso , Antineoplásicos/efeitos adversos , Colo Ascendente/efeitos dos fármacos , Colo Sigmoide/efeitos dos fármacos , Neoplasias do Colo/induzido quimicamente , Feminino , Humanos , Neoplasias Pulmonares/patologia , Prognóstico , Carcinoma de Pequenas Células do Pulmão/secundárioRESUMO
ß-amyloid formation in the brain is one of the characteristics of Alzheimer's disease. Exposure to this peptide may result in reentry into the cell cycle leading to cell death. The phytoestrogen equol has similar biological effects as estrogen without the side effects. This study investigated the possible mechanism of the neuron cell-protecting effect of equol during treatment with Aß. SH-SY5Y neuroblastoma cells were treated with either 1 µM S-equol or 10 nM 17ß-estradiol for 24 h prior to 1 µM Aß (25-35) exposure. After 24 h exposure to Aß (25-35), a significant reduction in cell survival and a reentry into the cell cycle process accompanied by increased levels of cyclin D1 were observed. The expressions of estrogen receptor alpha (ERα) and its coactivator, steroid receptor coactivator-1 (SRC-1), were also significantly downregulated by Aß (25-35) in parallel with activated extracellular signal-regulated kinase (ERK)1/2. However, pretreatment of cells with S-equol or 17ß-estradiol reversed these effects. Treatment with the ER antagonist, ICI-182,780 (1 µM), completely blocked the effects of S-equol and 17ß-estradiol on cell viability, ERα, and ERK1/2 after Aß (25-35) exposure. These data suggest that S-equol possesses a neuroprotective potential as it effectively antagonizes Aß (25-35)-induced cell cytotoxicity and prevents cell cycle reentry in SH-SY5Y cells. The mechanism underlying S-equol neuroprotection might involve ERα-mediated pathways.
Assuntos
Peptídeos beta-Amiloides/farmacologia , Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Equol/farmacologia , Receptor alfa de Estrogênio/genética , Neurônios/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Doença de Alzheimer , Peptídeos beta-Amiloides/antagonistas & inibidores , Linhagem Celular Tumoral , Ciclina D1/genética , Estradiol/farmacologia , Receptor alfa de Estrogênio/antagonistas & inibidores , Receptor alfa de Estrogênio/fisiologia , Expressão Gênica/efeitos dos fármacos , Humanos , Neuroblastoma , Neurônios/citologia , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/antagonistas & inibidores , Fitoestrógenos/farmacologiaRESUMO
We investigated the effects of high-fructose-high-fat diets with different fat compositions on metabolic parameters, hippocampal-dependent cognitive function, and brain leptin (as well as stearoyl-CoA desaturase (SCD1) mRNA expressions). Thirty-two male Wistar rats were divided into 3 groups, a control group (n = 8), a high-fructose soybean oil group (37.5% of fat calories, n = 12), and a high-fructose coconut oil group (37.5% of fat calories, n = 12) for 20 weeks. By the end of the study, the coconut oil group exhibited significantly higher serum fasting glucose, fructosamine, insulin, leptin, and triglyceride levels compared to those of the control and soybean oil groups. However, hippocampal leptin expression and leptin receptor mRNA levels were significantly lower, while SCD1 mRNA was significantly higher in rats fed the high-fructose-high-coconut oil diet than in rats fed the other experimental diets. In addition, the coconut oil group spent significantly less time in the target quadrant on the probe test in the Morris water maze (MWM) task. Rats fed the high-fructose-high-coconut oil diet for 20 weeks were prone to develop hyperglycemia, hyperinsulinemia, hyperleptinemia, and hypertriglyceridemia. These metabolic consequences may contribute to hippocampal-dependent memory impairment, accompanied by a lower central leptin level, and a higher SCD1 gene expression in the brain.
Assuntos
Óleo de Coco/administração & dosagem , Frutose/administração & dosagem , Hipocampo/metabolismo , Leptina/metabolismo , Memória Espacial/efeitos dos fármacos , Estearoil-CoA Dessaturase/metabolismo , Ração Animal/análise , Animais , Glicemia , Peso Corporal , Óleo de Coco/efeitos adversos , Dieta/veterinária , Carboidratos da Dieta/administração & dosagem , Carboidratos da Dieta/efeitos adversos , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/efeitos adversos , Frutosamina/sangue , Frutose/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Leptina/sangue , Masculino , Ratos , Ratos Wistar , Estearoil-CoA Dessaturase/genéticaRESUMO
Abnormal glucose metabolism in the brain is recognized to be associated with cognitive decline. Because grapes are rich in polyphenols that produce antioxidative and blood sugar-lowering effects, we investigated how grape consumption affects the expression and/or phosphorylation of neurodegeneration-related brain proteins in aged rats fed a high-fructose-high-fat (HFHF) diet. Wistar rats were maintained on the HFHF diet from the age of 8 weeks to 66 weeks, and then on an HFHF diet containing either 3% or 6% grape powder as an intervention for 12 weeks. Western blotting was performed to measure the expression/phosphorylation levels of several cortical and hippocampal proteins, including amyloid precursor protein (APP), tau, phosphatidylinositol-3-kinase (PI3K), extracellular signal-regulated kinase (ERK), receptor for advanced glycation end products (RAGEs), erythroid 2-related factor 2 (Nrf2) and brain-derived neurotrophic factor (BDNF). Inclusion of up to 6% grape powder in the diet markedly reduced RAGE expression and tau hyperphosphorylation, but upregulated the expression of Nrf2 and BDNF, as well as the phosphorylation of PI3K and ERK, in the brain tissues of aged rats fed the HFHF diet. Thus, grape powder consumption produced beneficial effects in HFHF-diet-fed rats, exhibiting the potential to ameliorate changes in neurodegeneration-related proteins in the brain.
Assuntos
Encéfalo/metabolismo , Hiperglicemia/fisiopatologia , Vitis/química , Animais , Peso Corporal , Encéfalo/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Transtornos Cognitivos/dietoterapia , Transtornos Cognitivos/etiologia , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Frutose/efeitos adversos , Hiperglicemia/dietoterapia , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Doenças Neurodegenerativas/metabolismo , Pós/farmacologia , Ratos Wistar , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Proteínas tau/metabolismoRESUMO
Research has suggested that the consumption of foods rich in polyphenols is beneficial to the cognitive functions of the elderly. We investigated the effects of grape consumption on spatial learning, memory performance and neurodegeneration-related protein expression in aged rats fed a high-fructose-high-fat (HFHF) diet. Six-week-old Wistar rats were fed an HFHF diet to 66 weeks of age to establish a model of an HFHF dietary pattern, before receiving intervention diets containing different amounts of grape powder for another 12 weeks in the second part of the experiment. Spatial learning, memory performance and cortical and hippocampal protein expression levels were assessed. After consuming the HFHF diet for a year, results showed that the rats fed a high grape powder-containing diet had significantly better spatial learning and memory performance, lower expression of ß-amyloid and ß-secretase and higher expression of α-secretase than the rats fed a low grape powder-containing diet. Therefore, long-term consumption of an HFHF diet caused a decline in cognitive functions and increased the risk factors for neurodegeneration, which could subsequently be ameliorated by the consumption of a polyphenol-rich diet.
Assuntos
Envelhecimento , Disfunção Cognitiva/prevenção & controle , Suplementos Nutricionais , Regulação da Expressão Gênica no Desenvolvimento , Proteínas do Tecido Nervoso/metabolismo , Nootrópicos/uso terapêutico , Vitis/química , Animais , Comportamento Animal , Córtex Cerebral/metabolismo , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Dieta da Carga de Carboidratos/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais/análise , Liofilização , Frutose/efeitos adversos , Frutas/química , Hipocampo/metabolismo , Masculino , Proteínas do Tecido Nervoso/genética , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/prevenção & controle , Neurônios/metabolismo , Nootrópicos/análise , Nootrópicos/química , Polifenóis/análise , Polifenóis/uso terapêutico , Ratos Wistar , Aprendizagem EspacialRESUMO
It has been indicated that probiotics can be nourished by consuming prebiotics in order to function more efficiently, allowing the bacteria to stay within a healthy balance. In this study, we investigated the effects of xylooligosaccharides- (XOS-) enriched rice porridge consumption on the ecosystem in the intestinal tract of human subjects. Twenty healthy subjects participated in this 6-week trial, in which 10 subjects received XOS-enriched rice porridge while the others received placebo rice porridge. Fecal samples were collected at the end of weeks 0, 1, 3, 4, 6, and 7 for microorganism examination. The results showed that 6-week daily ingestion of the XOS-enriched rice porridge induced significant increases in fecal bacterial counts of Lactobacillus spp. and Bifidobacterium spp., as well as decreases in Clostridium perfringens without changing the total anaerobic bacterial counts, compared to that of placebo rice porridge. However, fluctuations in the counts of coliforms were observed in both groups during the 6-week intervention. In conclusion, the intestinal microbiota balance was improved after daily consumption of 150 g of rice porridge containing XOS for 6 weeks, demonstrating the prebiotic potential of XOS incorporated into foods. This also indicates the effectiveness of XOS as a functional ingredient in relation to its role as a prebiotic compound.