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1.
Environ Toxicol Pharmacol ; 83: 103581, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33412297

RESUMO

To evaluate the different characteristics of cognitive impairment caused by occupational aluminium exposure at different ages, we surveyed 1660 workers in Shanxi Aluminium Plant, China, and assessed their cognitive function and plasma aluminium concentration. In multiple linear regression, the scores of the digit-span test (DST) and digit-span backward test (DSBT) were negatively correlated with plasma aluminium concentration when concentration reached 34.52 µg/L in younger group (<40 years), while in the middle-aged group (≥40 years) only found when concentration reached 42.25 µg/L (ß<0, P < 0.05). In logistic regression, when plasma aluminum concentration reached 42.25µg/L, odds ratios (95 % confidence interval) were 1.695 (1.062-2.705) and 3.270 (1.615-6.620) for DST, 7.644 (3.846-15.192) and 15.308 (4.180-56.059) for DSBT in middle-aged group and younger group, respectively. These results showed that aluminium exposures were associated with cognitive impairment among aluminium-exposed workers, particularly for young workers who were more susceptible.


Assuntos
Poluentes Ocupacionais do Ar/efeitos adversos , Alumínio/efeitos adversos , Cognição/efeitos dos fármacos , Disfunção Cognitiva/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Adulto , Poluentes Ocupacionais do Ar/sangue , Alumínio/sangue , Monitoramento Biológico , Disfunção Cognitiva/sangue , Estudos Transversais , Humanos , Masculino , Metalurgia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Exposição Ocupacional/análise , Adulto Jovem
2.
Food Chem ; 348: 129091, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33508603

RESUMO

Phospholipids are critical for milk digestion and infant development. But the profile of phospholipid molecular species in human milk and its dynamic changes during the lactation period have never been reported. The present study elucidated precise qualitative and quantitative analysis of 258 phospholipid molecular species in 486 human milk samples. Phosphatidylcholine is the most abundant class, followed by phosphatidylserine, phosphatidylethanolamine and sphingomyelin as the second abundant class in different lactation period. The plasmalogens declined along the lactation period, and the polyunsaturated-phospholipids decreased after 10-15 days. The decrease of phosphatidylcholines and phosphatidylglycerols, and the increase of lysophosphatidylethanolamines and lysophosphatidylcholines are critical changes from 0 to 5 days to 10-15 days; increase of phosphatidylinositols, phosphatidylserines, lysophosphatidylethanolamines and lysophosphatidylcholines is the key changes from 10-15 days to 40-45 days; the decrease of most phospholipid molecular species is the characteristic change from 40-45 days to 200-240 days; and the phospholipid profile achieved stability after 200 days.


Assuntos
Lactação , Lipidômica , Leite Humano/química , Mães , Fosfolipídeos/análise , Animais , China , Feminino , Humanos , Lactente
3.
Chemosphere ; 271: 129569, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33453483

RESUMO

OBJECTIVE: To explore the effects of occupational aluminium(Al) exposure on workers' cognition through a longitudinal study. METHODS: The study population consisted of 276 workers in an Al factory. In 2014, we used inductively coupled plasma mass spectrometry (ICP-MS) to determine the plasma aluminium (P-Al) concentration of the workers, and a combined questionnaire to test the workers' cognitive function. Followed-up in 2016, the workers were tested again for cognitive function. Generalized linear regression was used to assess the association between P-Al concentration and cognitive scores, and multivariable logistic regression was used to assess the risk of cognitive decline caused by Al exposure. RESULTS: Generalized linear regression results showed that a non-significant association was found between the P-Al concentration and cognitive test scores (P > 0.05) in 2014. Two years later, each 10-fold increase in P-Al concentration was inversely associated with the score of Mini-Mental state examination (MMSE) (ß: -0.53, 95% CI: -0.86, -0.20) and Fuld object memory evaluation (FOME) (ß: -0.93, 95% CI: -1.62, -0.24). Each 10-fold increase in P-Al concentration was inversely associated with MMSE2016-2014 (ß: -0.38, 95% CI: -0.74, -0.01) and FOME2016-2014 (ß: -1.20, 95% CI: -1.95, -0.45). There was a statistically significant difference in the average annual rate of change of MMSE and FOME with the tertile of P-Al concentration increase (P < 0.05). The multivariable logistic regression results showed that as the P-Al concentration increased, the risk of a FOME score decline increased (Ptrend = 0.009). CONCLUSIONS: Continuous occupational Al exposure can damage workers' overall cognitive ability, especially episodic memory function.


Assuntos
Transtornos Cognitivos , Exposição Ocupacional , Alumínio/toxicidade , Cognição , Humanos , Estudos Longitudinais , Testes Neuropsicológicos , Exposição Ocupacional/efeitos adversos
4.
Br J Nutr ; : 1-9, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33308344

RESUMO

The association between dietary Fe intake and diabetes risk remains inconsistent. We aimed to explore the association between dietary Fe intake and type 2 diabetes mellitus (T2DM) risk in middle-aged and older adults in urban China. This study used data from the Guangzhou Nutrition and Health Study, an on-going community-based prospective cohort study. Participants were recruited from 2008 to 2013 in Guangzhou community. A total of 2696 participants aged 40-75 years without T2DM at baseline were included in data analyses, with a median of 5·6 (interquartile range 4·1-5·9) years of follow-up. T2DM was identified by self-reported diagnosis, fasting glucose ≥ 7·0 mmol/l or glycosylated Hb ≥ 6·5 %. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95 % CI. We ascertained 205 incident T2DM cases during 13 476 person-years. The adjusted HR for T2DM risk in the fourth quartile of haem Fe intake was 1·92 (95 % CI 1·07, 3·46; Ptrend = 0·010), compared with the first quartile intake. These significant associations were found in haem Fe intake from total meat (HR 2·74; 95 % CI 1·22, 6·15; Ptrend = 0·011) and haem Fe intake from red meat (HR 1·86; 95 % CI 1·01, 3·44; Ptrend = 0·034), but not haem Fe intake from processed meat, poultry or fish/shellfish. The association between dietary intake of total Fe or non-haem Fe with T2DM risk had no significance. Our findings suggested that higher dietary intake of haem Fe (especially from red meat), but not total Fe or non-haem Fe, was associated with greater T2DM risk in middle-aged and older adults.

5.
Hepatol Res ; 50(10): 1164-1175, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32691459

RESUMO

AIM: Adherence to dietary recommendations has been linked to a reduced risk of developing hepatocellular carcinoma (HCC) and dying of chronic liver disease. However, its role in the prognosis of HCC is still unclear. We prospectively investigated the association of two dietary quality indices, the Chinese Healthy Eating Index (CHEI) and the Healthy Eating Index-2015 (HEI-2015), with all-cause and HCC-specific mortality in a large prospective cohort of HCC survivors. METHODS: We included 887 patients with newly diagnosed, previously untreated HCC enrolled in the Guangdong Liver Cancer Cohort (GLCC) between September 2013 and April 2017 in the analysis. CHEI and HEI-2015 scores were calculated based on the dietary intake in the year before diagnosis of HCC. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for each index. RESULTS: During a median follow-up of 797 days, 389 deaths were identified, including 347 from HCC. Higher CHEI scores, reflecting favorable adherence to the 2016 Dietary Guidelines for Chinese, were associated with a lower risk of all-cause mortality (T3 vs. T1 : HR = 0.75, 95% CI: 0.58-0.98) and HCC-specific mortality (T3 vs. T1 : HR = 0.74, 95% CI: 0.56-0.98). Non-significant, inverse associations of HEI-2015 score with all-cause mortality (T3 vs. T1 : HR = 0.86, 95% CI: 0.67-1.11) and HCC-specific mortality (T3 vs. T1 : HR = 0.93, 95% CI: 0.71-1.21) were suggested. CONCLUSIONS: Our findings suggest that better adherence to the 2016 Dietary Guidelines for Chinese may reduce the risk of all-cause and HCC-specific mortality in patients with HCC.

6.
Br J Nutr ; : 1-8, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32616104

RESUMO

A higher dietary intake or serum concentration of betaine has been associated with greater lean body mass in middle-aged and older adults. However, it remains unknown whether betaine intake is associated with age-related loss of skeletal muscle mass (SMM). We assessed the association between dietary betaine intake and relative changes in SMM after 3 years in middle-aged adults. A total of 1242 participants aged 41-60 years from the Guangzhou Nutrition and Health Study 2011-2013 and 2014-2017 with body composition measurements by dual-energy X-ray absorptiometry were included. A face-to-face questionnaire was used to collect general baseline information. After adjustment for potential confounders, multiple linear regression found that energy-adjusted dietary betaine intake was significantly and positively associated with relative changes (i.e. percentage loss or increase) in SMM of legs, limbs and appendicular skeletal mass index (ASMI) over 3 years of follow-up (ß 0·322 (se 0·157), 0·309 (se 0·142) and 0·303 (se 0·145), respectively; P < 0·05). The ANCOVA models revealed that participants in the highest betaine tertile had significantly less loss in SMM of limbs and ASMI and more increase in SMM of legs over 3 years of follow-up, compared with those in the bottom betaine tertile (all Ptrend < 0·05). In conclusion, our findings suggest that elevated higher dietary betaine intake may be associated with less loss of SMM of legs, limbs and ASMI in middle-aged adults.

7.
Appl Physiol Nutr Metab ; 45(7): 737-744, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31917604

RESUMO

Previous studies suggest that betaine and choline may be beneficial for body composition. However, no longitudinal study has been conducted to illustrate if choline and betaine have long-term effects on changes in body composition. This study aimed to prospectively investigate the association between serum choline and betaine concentrations and 3-year changes in body composition in community-dwelling Chinese adults. This present analysis used data from 1384 women and 554 men aged 40-75 years. Serum concentrations of betaine and choline at baseline were assessed using high-performance liquid chromatography-tandem mass spectrometry. Body composition parameters, i.e., muscle mass (MM), fat mass (FM), and body fat percentage (FM%) were measured using dual-energy X-ray absorptiometry at the first and the second follow-ups. After adjustment for potential cofounders, higher serum choline concentrations were associated with a lower decrease in MM in men (ß = 0.022, P = 0.025) and a lower increase in FM and FM% in women with baseline choline concentrations below 21.5 µmol/L (all P for nonlinearity = 0.007); higher serum betaine concentrations were associated with a lower decline in MM and a lower increase in FM and FM% among men whose betaine concentrations were lower than 55 µmol/L (all P for nonlinearity < 0.05). These findings suggest that higher concentrations of serum choline and betaine may be associated with favorable changes in body composition profiles among men and women who have relatively low concentrations, especially in men. Novelty Higher concentrations of serum choline and betaine were associated with favorable changes in body composition. Such favorable associations were more pronounced in men.

8.
Hum Gene Ther ; 31(1-2): 119-128, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31822134

RESUMO

Accumulating evidence indicates that the onset of myocardial infarction (MI) shows obvious circadian rhythmicity. Clinical studies have shown that MIs that occur in the early morning have a poor prognosis, but the mechanisms involved are still unknown. In this study, we showed that the expression level of Period 2 (per2) in the heart of mice is lower in the early morning than at noon and that increasing the expression of per2 in H9C2 cells and rat cardiomyocytes increases autophagy levels. Further studies indicated that overexpression of per2 after an MI improved cardiac function by increasing autophagy. In summary, this study has shown that the circadian clock protein, per2, may be a regulator of MI.

10.
PLoS One ; 14(8): e0220845, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31369643

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0098047.].

11.
Curr Med Sci ; 39(2): 250-258, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31016518

RESUMO

Previous studies reported the association between interleukin-6 (IL-6) -174G/C gene polymorphism and the risk of diabetic nephropathy in type 2 diabetes mellitus (T2DN). However, the results remain controversial. In the present study, we conducted a meta-analysis to further examine this relationship between IL-6-174G/C gene polymorphism and T2DN. Three databases (PubMed, SinoMed and ISI Web of Science) were used to search clinical case-control studies about IL-6-174G/C polymorphism and T2DN published until Apr. 14, 2018. Fixed- or random-effects models were used to calculate the effect sizes of odds ratio (OR) and 95% confidence intervals (95% CI). Moreover, subgroup analysis was performed in terms of the excretion rate of albuminuria. All the statistical analyses were conducted using Stata 12.0. A total of 11 case-control studies were included in this study, involving 1203 cases of T2DN and 1571 cases of T2DM without DN. Meta-analysis showed that there was an association between IL-6-174G/C polymorphism and increased risk of T2DN under the allelic and recessive genetic models (G vs. C: OR=1.10, 95%CI 1.03-1.18, P=0.006; GG vs. CC+GC: OR=1.11, 95%CI 1.02-1.21 P=0.016). In the subgroup analysis by albuminuria, a significant association of IL-6-174G/C polymorphism with risk of T2DN was noted in the microalbuminuria group under the recessive model (OR=1.54, 95% CI 1.02-2.32, _P=0.038). In conclusion, this meta-analysis suggests that IL-6-174G/C gene polymorphism is associated with the risk of T2DN.


Assuntos
Diabetes Mellitus Tipo 2/genética , Nefropatias Diabéticas/genética , Predisposição Genética para Doença/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único/genética , Estudos de Casos e Controles , Humanos , Razão de Chances , Fatores de Risco
13.
Oncol Lett ; 16(2): 2668-2674, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30013663

RESUMO

Period 2 (per2) is a core circadian clock gene. Dysregulation of the per2 gene has been identified in a number of types of human cancer and may be associated with a poor prognosis. To confirm the influence of per2 gene on MNNG/HOS human osteosarcoma cells, small interfering (si)RNA against per2 or plasmids containing per2 were transfected into MNNG/HOS cells, and the proliferation, apoptosis and migration were observed. The present study demonstrated that per2 knockdown significantly enhanced MNNG/HOS cell proliferation and migration and protected MNNG/HOS cells from apoptosis. Per2 overexpression inhibited MNNG/HOS cell proliferation and migration and promoted apoptosis. Furthermore, the protein expression of phosphorylated (p)-protein kinase B (Akt) and Bcl-2 were inhibited in per2-overexpressing cells, while the expression of p27, p21 and cleaved caspase-3 was promoted. In contrast, the expression of p-Akt and Bcl-2 was promoted in per2-knockdown cells, and p27, p21 and cleaved caspase-3 were decreased. This initial study may provide an alternative therapeutic strategy for the treatment of osteosarcoma.

14.
Infect Dis Poverty ; 7(1): 28, 2018 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-29628017

RESUMO

BACKGROUND: Snail-borne parasitic diseases, such as angiostrongyliasis, clonorchiasis, fascioliasis, fasciolopsiasis, opisthorchiasis, paragonimiasis and schistosomiasis, pose risks to human health and cause major socioeconomic problems in many tropical and sub-tropical countries. In this review we summarize the core roles of snails in the life cycles of the parasites they host, their clinical manifestations and disease distributions, as well as snail control methods. MAIN BODY: Snails have four roles in the life cycles of the parasites they host: as an intermediate host infected by the first-stage larvae, as the only intermediate host infected by miracidia, as the first intermediate host that ingests the parasite eggs are ingested, and as the first intermediate host penetrated by miracidia with or without the second intermediate host being an aquatic animal. Snail-borne parasitic diseases target many organs, such as the lungs, liver, biliary tract, intestines, brain and kidneys, leading to overactive immune responses, cancers, organ failure, infertility and even death. Developing countries in Africa, Asia and Latin America have the highest incidences of these diseases, while some endemic parasites have developed into worldwide epidemics through the global spread of snails. Physical, chemical and biological methods have been introduced to control the host snail populations to prevent disease. CONCLUSIONS: In this review, we summarize the roles of snails in the life cycles of the parasites they host, the worldwide distribution of parasite-transmitting snails, the epidemiology and pathogenesis of snail-transmitted parasitic diseases, and the existing snail control measures, which will contribute to further understanding the snail-parasite relationship and new strategies for controlling snail-borne parasitic diseases.


Assuntos
Vetores de Doenças , Interações Hospedeiro-Parasita , Doenças Parasitárias , Caramujos/parasitologia , Animais , Humanos , Doenças Parasitárias/epidemiologia , Doenças Parasitárias/prevenção & controle , Doenças Parasitárias/transmissão
15.
Psychosom Med ; 79(9): 1036-1044, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28691995

RESUMO

OBJECTIVE: Psychological stress in chronic heart failure (CHF) is associated with systemic neurohormonal and immune system responses and increased mortality. Autophagy refers to the biological process of degradation and recycling of dysfunctional cellular components. We investigated the role of psychological stress on autophagy function in CHF mice. METHODS: C57BL/6 mice underwent transverse aortic constriction, with or without combined acoustic and restraint stress, and cardiac function was assessed by echocardiography analysis. Serum corticosterone and angiotensin II (Ang II) were determined using enzyme-linked immunosorbent assay (ELISA). Autophagy and oxidative stress were measured with immunohistochemistry and quantitative polymerase chain reaction, and chloroquine and rapamycin were used to detect autophagy flux. In vivo, cardiomyocytes were cultured with or without Ang II or N-acetylcysteine, and autophagy and oxidative stress were also detected. RESULTS: A 1-week stress exposure significantly increased serum levels of corticosterone and Ang II (p = .000), increased levels of oxidative stress, induced overt heart failure, and increased mortality (p = .002). Furthermore, stress exposure unregulated messenger RNA expression of Bcl-2-interacting coiled-coil protein 1 (10.891 [3.029] versus 4.754 [1.713], p = .001), cysteine-rich domain containing beclin-1 interacting (6.403 [1.813] versus 3.653 [0.441], p = .006), and autophagy 7 (111.696 [4.049] versus 6.189 [1.931], p = .017), increased expression of autophagosomal, and decreased clearance of autophagosomes. In vitro, Ang II significantly increased autophagy flux in cultured cardiomyocytes, which could be partly inhibited by N-acetylcysteine. CONCLUSIONS: Psychological stress may contribute to the development of CHF by enhancing heart oxidative stress and impairing autophagy flux.


Assuntos
Angiotensina II/sangue , Autofagia/fisiologia , Corticosterona/sangue , Insuficiência Cardíaca , Miócitos Cardíacos , Estresse Oxidativo/fisiologia , Estresse Psicológico , Animais , Células Cultivadas , Modelos Animais de Doenças , Ecocardiografia , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Estresse Psicológico/complicações , Estresse Psicológico/metabolismo
16.
Clin Imaging ; 39(6): 1068-72, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26318916

RESUMO

Increased uptake of Tc-99m-methylene diphosphonate in the area of jaw is a common finding on the whole body bone scan. To study its incidence, causes and clinical significance, we performed static anterior and bilateral head views on 52 consecutive patients, followed by a dental examination and a panoramic radiograph. We demonstrated that increased uptake of bone tracer in the area of jaw was observed at a high incidence, as well as its characteristic distribution. The mainly causes are some common dental diseases. These findings would better guide the diagnosis and treatment for patients.


Assuntos
Arcada Osseodentária/efeitos dos fármacos , Compostos Radiofarmacêuticos , Medronato de Tecnécio Tc 99m , Imagem Corporal Total , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Chin J Integr Med ; 21(4): 259-65, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24599820

RESUMO

OBJECTIVE: To investigate the mechanism of Panax notoginseng saponins (PNS), an effective component extracted from Panax notoginseng, on atherosclerotic plaque angiogenesis in atherosclerosis-prone apolipoprotein E-knockout (ApoE-KO) mice fed with high-fat, high-cholesterol diet. METHODS: Twenty ApoE-KO mice were divided into two groups, the model group and the PNS group. Ten normal C57BL/6J mice were used as a control group. PNS (60 mg/kg) was orally administered daily for 12 weeks in the PNS group. The ratio of plaque area to vessel area was examined by histological staining. The tissue sample of aortic root was used to detect the CD34 and vascular endothelial growth factor (VEGF) expression areas by immunohistochemistry. The expression of VEGF and nicotinamide adenine dinucleotide phosphate oxidase subunit 4 (NOX4) were measured by reverse transcription polymerase chain reaction and Western blotting respectively. RESULTS: After treatment with PNS, the plaque areas were decreased (P<0.05). CD34 expressing areas and VEGF expression areas in plaques were significantly decreased (P<0.05). Meanwhile, VEGF and NOX4 mRNA expression were decreased after treatment with PNS. VEGF and NOX4 protein expression were also decreased by about 72% and 63%, respectively (P<0.01). CONCLUSION: PNS, which decreases VEGF and NOX4 expression, could alleviate plaque angiogenesis and attenuate atherosclerosis.


Assuntos
NADPH Oxidases/genética , Neovascularização Patológica/prevenção & controle , Panax notoginseng , Placa Aterosclerótica/prevenção & controle , Saponinas/farmacologia , Fator A de Crescimento do Endotélio Vascular/genética , Animais , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Medicamentos de Ervas Chinesas/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NADPH Oxidase 4 , NADPH Oxidases/metabolismo , Neovascularização Patológica/patologia , Panax notoginseng/química , Placa Aterosclerótica/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
PLoS One ; 9(9): e107851, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25233229

RESUMO

BACKGROUND: Ectopic angiogenesis within the intima and media is considered to be a hallmark of advanced vulnerable atherosclerotic lesions. Some studies have shown that specific matrix metalloproteinases (MMPs) might play different roles in angiogenesis. Therefore, we investigated the predominant effects of specific MMPs in intraplaque angiogenesis and plaque instability in a rabbit model of atherosclerosis. METHODS AND RESULTS: New Zealand rabbits underwent balloon injury of the abdominal artery and ingestion of a high-cholesterol (1%) diet to establish an atherosclerotic animal model. At weeks 4, 6, 8, 10, and 12 after balloon injury, five rabbits were euthanized and the abdominal aorta was harvested. Blood lipid analysis, intravascular ultrasound imaging, pathologic and immunohistochemical expression studies, and western blotting were performed. From weeks 4 to 12, the expression of MMP-1, -2, -3, and -9 and vascular endothelial growth factor A (VEGF-A) increased with atherosclerotic plaque development in the abdominal aorta, while the expression of MMP-14 substantially decreased. The vulnerability index (VI) gradually increased over time. Intraplaque neovessels appeared at week 8. The microvessel density (MVD) was greater at week 12 than at week 8. The VI, MVD, and VEGF-A level were positively correlated with the MMP-1, -2,-3, and -9 levels within plaques. Negative correlations were noted between the MMP-14 level and the VI, MVD, and VEGF-A level. CONCLUSION: Upregulation of MMP-1, -2, -3, and -9 and downregulation of MMP-14 may contribute to intraplaque angiogenesis and plaque instability at the advanced stage of atherosclerosis in rabbits.


Assuntos
Aterosclerose/enzimologia , Metaloproteinases da Matriz/fisiologia , Neovascularização Patológica/enzimologia , Placa Aterosclerótica/enzimologia , Animais , Aterosclerose/fisiopatologia , Masculino , Microvasos/patologia , Microvasos/fisiopatologia , Placa Aterosclerótica/fisiopatologia , Coelhos
19.
PLoS One ; 9(6): e98047, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24887083

RESUMO

BACKGROUND: It has been demonstrated that Tongxinluo (TXL), a traditional Chinese medicine compound, improves ischemic heart disease in animal models via vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS). The present study aimed to investigate whether TXL protects against pressure overload-induced heart failure in mice and explore the possible mechanism of action. METHODS AND RESULTS: Transverse aortic constriction (TAC) surgery was performed in mice to induce heart failure. Cardiac function was evaluated by echocardiography. Myocardial pathology was detected using hematoxylin and eosin or Masson trichrome staining. We investigated cardiomyocyte ultrastructure using transmission electron microscopy. Angiogenesis and oxidative stress levels were determined using CD31 and 8-hydroxydeoxyguanosine immunostaining and malondialdehyde assay, respectively. Fetal gene expression was measured using real-time PCR. Protein expression of VEGF, phosphorylated (p)-VEGF receptor 2 (VEGFR2), p-phosphatidylinositol 3-kinase (PI3K), p-Akt, p-eNOS, heme oxygenase-1 (HO-1), and NADPH oxidase 4 (Nox4) were measured with western blotting. Twelve-week low- and high-dose TXL treatment following TAC improved cardiac systolic and diastolic function and ameliorated left ventricular hypertrophy, fibrosis, and myocardial ultrastructure derangement. Importantly, TXL increased myocardial capillary density significantly and attenuated oxidative stress injury in failing hearts. Moreover, TXL upregulated cardiac nitrite content and the protein expression of VEGF, p-VEGFR2, p-PI3K, p-Akt, p-eNOS, and HO-1, but decreased Nox4 expression in mouse heart following TAC. CONCLUSION: Our findings indicate that TXL protects against pressure overload-induced heart failure in mice. Activation of the VEGF/Akt/eNOS signaling pathway might be involved in TXL improvement of the failing heart.


Assuntos
Cardiotônicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Óxido Nítrico Sintase Tipo III/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo , 8-Hidroxi-2'-Desoxiguanosina , Animais , Capilares/efeitos dos fármacos , Capilares/patologia , Capilares/fisiopatologia , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Cardiotônicos/farmacologia , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Testes de Função Cardíaca , Masculino , Camundongos Endogâmicos C57BL , Miocárdio/patologia , Miocárdio/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Ultrassonografia
20.
J Cell Mol Med ; 18(8): 1599-611, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24889822

RESUMO

Autophagic dysfunction is observed in diabetes mellitus. Resveratrol has a beneficial effect on diabetic cardiomyopathy. Whether the resveratrol-induced improvement in cardiac function in diabetes is via regulating autophagy remains unclear. We investigated the mechanisms underlying resveratrol-mediated protection against heart failure in diabetic mice, with a focus on the role of sirtuin 1 (SIRT1) in regulating autophagic flux. Diabetic cardiomyopathy in mice was induced by streptozotocin (STZ). Long-term resveratrol treatment improved cardiac function, ameliorated oxidative injury and reduced apoptosis in the diabetic mouse heart. Western blot analysis revealed that resveratrol decreased p62 protein expression and promoted SIRT1 activity and Rab7 expression. Inhibiting autophagic flux with bafilomycin A1 increased diabetic mouse mortality and attenuated resveratrol-induced down-regulation of p62, but not SIRT1 activity or Rab7 expression in diabetic mouse hearts. In cultured H9C2 cells, redundant or overactive H2O2 increased p62 and cleaved caspase 3 expression as well as acetylated forkhead box protein O1 (FOXO1) and inhibited SIRT1 expression. Sirtinol, SIRT1 and Rab7 siRNA impaired the resveratrol amelioration of dysfunctional autophagic flux and reduced apoptosis under oxidative conditions. Furthermore, resveratrol enhanced FOXO1 DNA binding at the Rab7 promoter region through a SIRT1-dependent pathway. These results highlight the role of the SIRT1/FOXO1/Rab7 axis in the effect of resveratrol on autophagic flux in vivo and in vitro, which suggests a therapeutic strategy for diabetic cardiomyopathy.


Assuntos
Antioxidantes/farmacologia , Autofagia/efeitos dos fármacos , Diabetes Mellitus Experimental/fisiopatologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Estilbenos/farmacologia , Acetilação , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Células Cultivadas , Diabetes Mellitus Experimental/tratamento farmacológico , Técnicas Imunoenzimáticas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica/patologia , Oxirredução , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Resveratrol , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sirtuína 1/antagonistas & inibidores , Sirtuína 1/genética , Sirtuína 1/metabolismo , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/metabolismo
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