RESUMO
BACKGROUND: This study sought to ascertain whether a staged approach involving carotid artery stenting (CAS) and coronary artery bypass grafting (CABG) holds superiority over the synchronous (Syn) strategy of CAS or carotid endarterectomy (CEA) and CABG in patients necessitating combined revascularization for concurrent carotid and coronary artery disease. METHOD: Studies were identified through 3 databases: PubMed, EMBASE, and the Cochrane Library. Statistical significance was defined as a P value of less than .05 for all analyses, conducted using STATA version 12.0. RESULTS: In the comparison between staged versus Syn CAS and CABG for patients with concomitant severe coronary and carotid stenosis, 4 studies were analyzed. The staged procedure was associated with a lower rate of 30-day stroke (ORâ =â 8.329, 95% CIâ =â 1.017-69.229, Pâ =â .048) compared to Syn CAS and CABG. In the comparison between staged CAS and CABG versus Syn CEA and CABG for patients with concomitant severe coronary and carotid stenosis, 5 studies were examined. The staged CAS and CABG procedure was associated with a lower rate of mortality (ORâ =â 2.046, 95% CIâ =â 1.304-3.210, Pâ =â .002) compared to Syn CEA and CABG. CONCLUSION: The Syn CAS and CABG was linked to a higher risk of peri-operative stroke compared to staged CAS and CABG. Additionally, patients undergoing staged CAS and CABG exhibited a significantly decreased risk of 30-day mortality compared to Syn CEA and CABG. Future randomized trials or prospective cohorts are essential to confirm and validate these findings.
Assuntos
Estenose das Carótidas , Ponte de Artéria Coronária , Stents , Humanos , Estenose das Carótidas/cirurgia , Estenose das Carótidas/complicações , Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/complicações , Endarterectomia das Carótidas/métodos , Acidente Vascular Cerebral/etiologia , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To investigate the situation of women's dietary quality during pregnancy and explore the correlations between maternal dietary index and fetal immune function. METHODS: From September 2010 to February 2011, pregnant women who had routine physical examination in Yuexiu District and Baiyun District Maternal and Child Health Hospital of Guangzhou were recruited as study objects to use 3-day 24-hour dietary review to investigate diet during pregnancy, and general demographic information of pregnant women was collected through questionnaire, and the neonatal umbilical cord blood was collected during delivery. Laboratory detection of immunological indicators included IgG, IgA, IgM, IFN-γ and IL-6. The quality of diet during pregnancy was evaluated by diet quality index for pregnancy(DQI-P), dietary balance index for pregnancy(DBI-P) and alternate Medierranean diet score(aMED). Spearman correlation analysis and multiple linear regression analysis were used to explore the correlations between dietary quality during pregnancy and fetal immune function. RESULTS: The mean score of total DQI-P score of the study subjects was 55.8±10.0, and the mean score of overall food diversity and protein food source diversity was as high as 12.0±2.4 and 4.8±0.7. The mean score of nutrient energy ratio and fatty acid energy ratio was only 0.3±1.0 and 0.4±1.0, indicating that the population had good dietary diversity during pregnancy, but the dietary adequacy, suitability and balance were poor. The total score of DBI-P score was-19.2±9.4. The positive end score was 4.6±2.9, only 7.2% of the subjects had a high degree of dietary intake during pregnancy. The negative end score was 23.9±7.9, indicating the status of moderate dietary intake. Dietary quality was 28.5±7.1. Only 0.6% of the study population had a balanced dietary situation, and more than 67.9% of pregnant women had high intake imbalance. The mean total score of aMED score was 4.9±1.3, and the proportion of the food intake of beans and nuts was less than the median population was 62.5% and 79.1%, respectively, indicating that the food intake of beans and nuts was insufficient in this population. After adjusting for confounding factors such as maternal age, parity, parity, prepregnancy BMI, weight gain during pregnancy, and mode of delivery, multiple linear regression analysis showed DQI-P during pregnancy and negatively with IL-6(ß=0.143, ß=-0.155, P<0.05). DBI-P was negatively associated with IL-6(ß=-0.177, P<0.01) and aMED and IFN-γ(ß=-0.161, P<0.01). CONCLUSION: The dietary quality of women in late pregnancy in Guangzhou is low, the dietary structure is unbalanced. Higher dietary quality during pregnancy can promote the development of fetal immune system and improve fetal immune function.
Assuntos
Dieta , Humanos , Feminino , Gravidez , China , Adulto , Feto/imunologia , Inquéritos e Questionários , Sangue Fetal/imunologia , Sangue Fetal/química , Fenômenos Fisiológicos da Nutrição Materna , Inquéritos sobre Dietas , Interleucina-6/sangueRESUMO
Insulin resistance (IR) is a global health challenge, often initiated by dysfunctional adipose tissue. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may have different effects on IR, but the mechanisms are unknown. This study aims to evaluate the protective effect of EPA and DHA against IR in a high-fat diet (HFD) mice model and investigate whether EPA and DHA alter IR modulate the G-protein-poupled receptor 120/peroxisome proliferator-activated receptor γ (GPR120/PPARγ) pathway in macrophages and adipocytes, which may affect IR in adipocytes. The findings of this study show that 4% DHA had a better effect in improving IR and reducing inflammatory cytokines in adipose tissue of mice. Additionally, in the cell experiment, the use of AH7614 (a GPR120 antagonist) inhibited the glucose consumption increase and the increasable expression of PPARγ and insulin signaling molecules mediated by DHA in adipocytes. Furthermore, GW9662 (a PPARγ antagonist) hindered the upregulation of glucose consumption and insulin signaling molecule expression induced by EPA and DHA in adipocytes. DHA exhibited significant effects in reducing the number of migrated cells and inflammation. The compounds AH7614 and GW9662 hindered the suppressive effects of EPA and DHA on macrophage-induced IR in adipocytes. These findings suggest that DHA has a stronger potential in improving IR in adipocytes through the GPR120/PPARγ pathway in macrophages, when compared to EPA.
Assuntos
Tecido Adiposo , Dieta Hiperlipídica , Ácidos Docosa-Hexaenoicos , Ácido Eicosapentaenoico , Inflamação , Resistência à Insulina , Camundongos Endogâmicos C57BL , PPAR gama , Receptores Acoplados a Proteínas G , Transdução de Sinais , Animais , Ácidos Docosa-Hexaenoicos/farmacologia , PPAR gama/metabolismo , Ácido Eicosapentaenoico/farmacologia , Receptores Acoplados a Proteínas G/metabolismo , Camundongos , Masculino , Tecido Adiposo/metabolismo , Tecido Adiposo/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Inflamação/metabolismo , Transdução de Sinais/efeitos dos fármacos , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Células 3T3-L1 , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Células RAW 264.7 , Anilidas/farmacologia , Compostos de Bifenilo , FenilpropionatosRESUMO
BACKGROUND: Myokines have a prominent effect on improving insulin resistance (IR) by inducing browning of white adipose tissue (WAT). Although docosahexaenoic acids (DHA) and eicosapentaenoic acids (EPA) play roles in improving IR and stimulating browning, whether they mediate myokines directly remains unknown. OBJECTIVE: This study aims to investigate the effects of DHA and EPA on browning-related myokines under IR and clarify the mechanism via Ca2+ signaling. METHODS: The expression and secretion levels of myokines in IR mice and IR myotubes were detected after DHA/EPA treatment. The crosstalk between myotubes and adipocytes was evaluated through a method in which IR adipocytes were treated with the culture medium supernatant of myotubes treated with DHA/EPA. The expression of browning markers in the WAT of IR mice and adipocytes was determined. A calcium chelator was used to determine whether DHA and EPA regulate myokine production through a calcium ion-dependent pathway. RESULTS: In vivo experiments: 3:1 and 1:3 DHA/EPA promoted the mRNA levels of Irisin, IL-6, IL-15, and FGF21 in skeletal muscle, stimulated WAT browning, reduced lipid accumulation; 3:1 DHA/EPA upregulated the serum concentration of Irisin; 1:3 DHA/EPA upregulated the serum concentrations of Irisin, IL-6, and FGF21. In vitro experiments: the levels of Irisin and IL-6 in C2C12 myotubes and their medium supernatant were significantly elevated in the 3:1 and 1:3 groups and the upregulation of browning markers and reduction in fat accumulation were observed in adipocytes treated with the medium supernatant of C2C12 myotubes in the 3:1 and 1:3 groups. However, the above phenomena disappeared when Ca2+ signaling was inhibited. CONCLUSIONS: Treatment with DHA and EPA at composition ratios of 3:1 and 1:3 induces browning of WAT in IR mice, which is likely related to the promotion of the accumulation of myokines, especially Irisin and IL-6, via Ca2+ signaling.
Assuntos
Resistência à Insulina , Insulina , Camundongos , Animais , Insulina/metabolismo , Miocinas , Interleucina-6/genética , Interleucina-6/metabolismo , Ácido Eicosapentaenoico/farmacologia , Fibronectinas/metabolismo , Sinalização do Cálcio , Insulina Regular Humana , Ácidos Docosa-Hexaenoicos/farmacologiaRESUMO
OBJECTIVE: To explore the relationship between dietary inflammatory index(DII), serum interleukin-6(IL-6) of late pregnant women and infant birth weight. METHODS: This study was conducted in late pregnant women who received antenatal care at the Maternal and Children& apos; s Hospital of Baiyun and Yuexiu District in Guangzhou, China between September 2010 and February 2011. Tree consecutive 24-h diet recalls, pre-pregnancy body mass index, maternal education level and etc were collected. DII score was calculated based on data of dietary surveys. Participant were dived into anti-inflammatory group(T1), neutral group(T2) and pro-inflammatory group(T3) according to the tertiles of DII score. Maternal and infant anthropometric profile(n=456) and level of maternal serum IL-6(n=308) were measured. Structrural equation modeling(SEM) was used to explore the relationship between DII, IL-6 and birth weight. RESULTS: In 456 women, the mean DII score was 0. 02±1. 08. Women performed anti-inflammatory diet had higher intake of grain and potato, vegetables, energy, fiber, minerals, vitamins and unsaturated fatty acids, but lower intakes of fruits, diary, fat(% energy) and protein from animal food(P& lt; 0. 05). Average infant birth weight and level of maternal serum IL-6 were(3238. 1±376. 4)g and 4. 05(2. 02, 10. 14) pg/mL respectively. DII of pregnant women was positively correlated with maternal serum IL-6(r=0. 144, P& lt; 0. 05), and IL-6 was negatively correlated with birth weight(r=-0. 184, P& lt; 0. 05). SEM indicated that maternal serum IL-6 may be a mediator in the association between DII and birth weight. CONCLUSION: The diet of pregnant women may change the serum level of IL6, and then affect infant birth weight.
Assuntos
Peso ao Nascer , Dieta , Interleucina-6 , Gestantes , China , Feminino , Humanos , Recém-Nascido , Inflamação , Interleucina-6/sangue , GravidezRESUMO
The structural characteristics of a novel Flammulina velutipes polysaccharide (FVP2) were explored in this study. Besides, immunomodulatory activities of FVP2 on RAW 264.7 cell and its impact on gut microbiota in rats were investigated. FVP2 has a molecular weight of 18.3 kD, and its main components include galactose (19.96%), glucose (60.66%) and mannose (19.38%). By NMR analysis, the main-chain structure consisted of (1 â 3)-linked-ß-D-Gal, (1 â 6) -linked-ß-D-Gal, (1 â 6)-linked-α-D-Glc and (1 â 3,6)-linked-α-D-Man was identified. Results of the in vitro assays on RAW 264.7 murine macrophage cells showed FVP2 could significantly up-regulate the expression of NO, TNF-α and IL-6. FVP2 was intragastrically administered to rats for 2 weeks. Compared with the control group, two caecal short-chain fatty acids (SCFAs) concentration (isobutyric acid and butyric acid) and the abundance of beneficial microbiota of the FVP2-treated group were significantly increased (p < .05) respectively. The results demonstrated that FVP2 could effectively enhance the level of butyric acid and increase beneficial gut microbiota, which could improve the intestinal barrier function and maintain the intestinal mucosal integrity, suggesting that FVP2 could potentially be an immunomodulators or a functional food to promote intestinal health.
Assuntos
Flammulina/química , Microbioma Gastrointestinal/efeitos dos fármacos , Polissacarídeos/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Polissacarídeos/química , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Testes de ToxicidadeRESUMO
The aim of the study was to investigate how maternal dietary patterns and maternal/fetal cytokines are associated with birth weight and whether cytokines mediate the association. A total of 469 pregnant women and their children were recruited for this prospective study. Dietary patterns in pregnancy were identified using factor analysis of data from three consecutive 24 h dietary recalls. Maternal and umbilical blood serum cytokines (adiponectin (APN), IL-6 and interferon-γ) were measured via ELISA. Path analysis was used to explore the relationships between maternal diet, cytokines and birth weight. Four dietary patterns were identified: a mainly fruit, dairy products and poultry diet (FDP); a mainly vegetables, beans and pork diet (VBP); a mainly fish, shrimp and soup diet (FS) and a mainly tuber and egg diet (TE). Path analysis showed the order of effects of dietary patterns on birth weight was FS>FDP>TE>VBP (ß=0·130, 0·109, -0·094 and 0·046, respectively). Only the TE pattern's effect was negative. Maternal and fetal APN were positively associated with birth weight (ß=0·045 and 0·226, respectively), and they mediated the association between the TE pattern and birth weight (indirect effect was 5·3 %). Maternal IL-6 was negatively associated with birth weight (ß=-0·067) and mediated the association between maternal FDP and VBP patterns and birth weight (indirect effects were 10·1 and 100·0 %, respectively). All variables in the path explained 33·6 % of variation. These results suggested that maternal dietary patterns in pregnancy are associated with birth weight and mediated directly and indirectly through some maternal/fetal serum cytokines.
Assuntos
Peso ao Nascer , Citocinas/sangue , Dieta/métodos , Fenômenos Fisiológicos da Nutrição Materna , Adiponectina/sangue , Adulto , Inquéritos sobre Dietas , Análise Fatorial , Comportamento Alimentar , Feminino , Sangue Fetal/química , Desenvolvimento Fetal , Humanos , Recém-Nascido , Interferon gama/sangue , Interleucina-6/sangue , Testes para Triagem do Soro Materno , Gravidez , Estudos ProspectivosRESUMO
A new water-soluble polysaccharide (FVP1) was extracted from Flammulina velutipes by traditional method "water extraction and alcohol precipitation" and purified by column chromatography. Physicochemical characterization showed that FVP1 was a homogeneous polysaccharide with a relative molecular weight of 54.78â¯kDa. It is composed of mannose (7.74%), glucose (70.41%), and galactose (16.38%). FVP1 (1000â¯mg/mL) possessed significant immune activity by increasing the secretion of nitric oxide (NO), tumour necrosis factor-α (TNF-α) (3183⯱â¯133.84â¯pg/mL), interleukin (IL)-6 (1133.21⯱â¯39.05â¯pg/mL), and IL-12 (579.96⯱â¯74.53â¯pg/mL) in macrophages. Furthermore, FVP1 showed significant hepatitis B surface antibody (anti-HBV) activity through reducing the expression of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA replication. These results suggest a novel role for FVP1 to be applied as an immunomodulators in dietary supplements to prevent HBV infection.
Assuntos
Flammulina/química , Vírus da Hepatite B/efeitos dos fármacos , Polissacarídeos/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , DNA Viral/antagonistas & inibidores , Relação Dose-Resposta a Droga , Células Hep G2 , Antígenos de Superfície da Hepatite B/biossíntese , Antígenos E da Hepatite B/biossíntese , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Peso Molecular , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Células RAW 264.7 , Relação Estrutura-Atividade , Replicação Viral/efeitos dos fármacosRESUMO
n-3PUFA consumption has been widely accepted as a nutritional strategy for the secondary prevention of cardiovascular events in patients at high risk of cardiovascular disease (CVD), but little is known about the dose-response relationship between dietary n-3PUFA and serum biomarkers associated with cardiovascular health in the general population. The present study involved a 12-week double-blind, randomized controlled trial to explore the effects of fish oil with different doses (0.31, 0.62 and 1.24 g d-1 of EPA and DHA) on serum fatty acids and cardio-metabolic biomarkers including adiponectin, inflammatory markers, lipid profiles and fasting glucose in healthy middle-aged and elderly Chinese people. 240 volunteers met our inclusion criteria. A total of 39 subjects dropped out and 201 finally completed the intervention. No significant differences in baseline characteristics and daily intakes of dietary nutrients were detected among all groups. After a 12-week intervention, fish oil dose-dependently enhanced serum EPA, DHA, n-3PUFA and adiponectin (except for 0.31 g d-1), but decreased serum n-6/n-3PUFA, TG and fasting glucose. Changes in the above indicators from the baseline to week 12 in fish oil groups significantly differed from those in the control. Meanwhile, all the doses of EPA and DHA led to decreases in serum CRP; only 1.24 g d-1 led to an increase in HDL-C with a concurrent decrease in TC/HDL-C even though these changes were not significantly different among all groups. All the findings suggested that fish oil dose-dependently regulated serum PUFA and cardio-metabolic biomarkers including adiponectin, CRP, lipid profiles and fasting glucose in healthy middle-aged and elderly Chinese people who consumed insufficient dietary n-3PUFA, and the most desirable changes were observed for 1.24 g d-1.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Ácidos Graxos Ômega-3/administração & dosagem , Óleos de Peixe/administração & dosagem , Adiponectina/sangue , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/metabolismo , China , Feminino , Óleos de Peixe/análise , Humanos , Masculino , Pessoa de Meia-Idade , Triglicerídeos/metabolismoRESUMO
BACKGROUND: Enhancing circulating adiponectin is considered as a potential approach for the prevention and treatment of non-communicable diseases (NCDs). Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were reported to increase adiponectin by previous studies using a mixture of them. However, their individual effects on adiponectin and the underlying mechanisms are still unclear. In the present study, we observed and compared the individual effect of DHA and EPA on adiponectin in 3T3-L1 adipocytes, and further tested whether DHA or EPA regulated adiponectin by peroxisome proliferator-activated receptor γ (PPARγ) and its phosphorylation at Ser273 to provide a plausible explanation for their distinct actions. METHODS: Firstly, 3T3-L1 adipocytes were treated with different doses of DHA or EPA for 24 h. Secondly, 3T3-L1 adipocytes were treated with DHA or EPA in the presence or absence of GW9662. Thirdly, 3T3-L1 adipocytes were pretreated with DHA or EPA for 24 h, followed by being respectively co-incubated with tumor necrosis factor α (TNF-α) or roscovitine for another 2 h. Bovine serum albumin treatment served as the control. After treatments, cellular and secreted adiponectin, cellular PPARγ and its phosphorylation at Ser273 were determined. RESULTS: Compared with the control, DHA increased cellular and secreted adiponectin at 50 and 100 µmol/L, while EPA increased them at 100 and 200 µmol/L. Adiponectin expressions in DHA treated groups were significantly higher than those in EPA treated groups at 50 and 100 µmol/L. Both DHA and EPA enhanced PPARγ expression, but DHA was more effective. GW9662 blocked DHA- and EPA-induced increases in PPARγ as well as adiponectin. Remarkably, an opposite regulation of PPARγ phosphorylation was detected after fatty acids treatment: DHA inhibited it but EPA stimulated it. TNF-α blocked DHA-induced decrease in PPARγ phosphorylation, which eventually led to a decrease in adiponectin. Roscovitine blocked EPA-induced increase in PPARγ phosphorylation, but the corresponding increase in adiponectin was non-significant. CONCLUSION: DHA compared with EPA led to a greater increase in cellular and secreted adiponectin at relative low concentrations by increasing PPARγ expression and inhibiting its phosphorylation at Ser273. DHA may be more beneficial than EPA in reducing risks of NCDs.
RESUMO
This study was aimed to explore the combined effects of Exendin-4 with dipeptidyl peptidase-IV (DPP-4) silencing on vascular endothelial growth factor (VEGF)-induced cell proliferation and angiogenesis in Human Coronary Artery Endothelial Cells (HCAECs), as well as the underlying molecular mechanisms which were involved in this process. HCAECs were treated by exendin-4, small interfering RNA (siRNA) targeting DPP-4 (DPP-4-siRNA) or exendin-4 plus DPP-4-siRNA, respectively. Cell migration, proliferation and angiogenesis in vitro were assessed by scratch-wound assay, MTT, tran swell assay, and matrigel tube formation, respectively. Cell apoptosis was investigated by TUNEL assay. Expression of apoptosis and PI3K/Akt related proteins were assessed by Western blotting. Incubation of HCAECs with exendin-4 and silencing of DPP-4 both caused an increase in cell proliferation, migration and tube formation, while a significant decrease in apoptosis (all p<0.05). Furthermore, the combination of the exendin-4 and silencing of DPP-4 had additional effects on HCAECs. Protein levels of p-Akt and p-PI3K were markedly increased by exendin-4 incubation, silencing of DPP-4 in HCAECs. These results suggest that combination of exendin-4 and silencing of DPP-4 had additional promoted effects on angiogenesis of HCAECs via activation of PI3K/Akt pathway. Our study indicated an alternative therapeutic strategy for atherosclerotic neovascularization.
Assuntos
Vasos Coronários/citologia , Dipeptidil Peptidase 4/deficiência , Células Endoteliais/citologia , Exenatida/farmacologia , Inativação Gênica , Neovascularização Fisiológica , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Apoptose/efeitos dos fármacos , Apoptose/genética , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Dipeptidil Peptidase 4/genética , Células Endoteliais/enzimologia , Células Endoteliais/metabolismo , Humanos , Neovascularização Fisiológica/efeitos dos fármacos , Neovascularização Fisiológica/genética , RNA Interferente Pequeno/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genéticaRESUMO
BACKGROUND AND OBJECTIVES: We aimed to investigate the prevalence of maternal health problems in the postpartum period and their association with traditional Chinese postpartum diets and behaviours in three selected regions in Hubei province, China. METHODS AND STUDY DESIGN: A cross-sectional study was conducted in urban, suburban and rural areas. A total of 2100 women who had given birth to full-term single infants in the past two years were enrolled. Their postpartum diet, personal behaviours, and health problems were surveyed by trained interviewers. RESULTS: During the puerperium women consumed plentiful eggs, fish, poultry and meats; however, fruit, vegetable and milk consumption were limited. A high prevalence of health problems potentially related to pregnancy and the puerperium were found. At least one such problem was reported by 59.3% of women. The putative postpartum problems were backaches (29.6%), arthralgia or leg clonus (12.7%), breast problems (19.6%), constipation (18.7%), haemorrhoids (11.7%), dizziness or headaches (14.8%), anaemia (10.0%). Multiple logistic regression analysis showed that leafy vegetable intake and frequent recipe change in the puerperium were positively associated with less anal diseases. Bathing or hair washing did not increase the risk of maternal infection as belief would have suggested. However, bathing was a risk factor for backache or arthralgia, and tooth brushing was a risk factor for bleeding gums. Excessive housework was a risk factor for anal diseases and disordered uterine involution. CONCLUSION: Postpartum maternal health problems were prevalent in Hubei province. These were in part associated with postpartum traditional Chinese diets and behaviours.
Assuntos
Cultura , Dieta , Comportamentos Relacionados com a Saúde , Transtornos Puerperais/epidemiologia , Adulto , Artralgia/epidemiologia , Dor nas Costas/epidemiologia , Doenças Mamárias/epidemiologia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Saúde Materna , Medicina Tradicional Chinesa , Doenças da Boca/epidemiologia , Doenças Retais/epidemiologia , População Rural , Autorrelato , População Suburbana , População Urbana , Doenças Uterinas/epidemiologiaRESUMO
PURPOSE: Butyrate, a short-chain fatty acid derived from dietary fiber, inhibits proliferation and induces cell death in colorectal cancer cells. However, clinical trials have shown mixed results regarding the anti-tumor activities of butyrate. We have previously shown that sodium butyrate increases endoplasmic reticulum stress by altering intracellular calcium levels, a well-known autophagy trigger. Here, we investigated whether sodium butyrate-induced endoplasmic reticulum stress mediated autophagy, and whether there was crosstalk between autophagy and the sodium butyrate-induced apoptotic response in human colorectal cancer cells. METHODS: Human colorectal cancer cell lines (HCT-116 and HT-29) were treated with sodium butyrate at concentrations ranging from 0.5-5mM. Cell proliferation was assessed using MTT tetrazolium salt formation. Autophagy induction was confirmed through a combination of Western blotting for associated proteins, acridine orange staining for acidic vesicles, detection of autolysosomes (MDC staining), and electron microscopy. Apoptosis was quantified by flow cytometry using standard annexinV/propidium iodide staining and by assessing PARP-1 cleavage by Western blot. RESULTS: Sodium butyrate suppressed colorectal cancer cell proliferation, induced autophagy, and resulted in apoptotic cell death. The induction of autophagy was supported by the accumulation of acidic vesicular organelles and autolysosomes, and the expression of autophagy-associated proteins, including microtubule-associated protein II light chain 3 (LC3-II), beclin-1, and autophagocytosis-associated protein (Atg)3. The autophagy inhibitors 3-methyladenine (3-MA) and chloroquine inhibited sodium butyrate induced autophagy. Furthermore, sodium butyrate treatment markedly enhanced the expression of endoplasmic reticulum stress-associated proteins, including BIP, CHOP, PDI, and IRE-1a. When endoplasmic reticulum stress was inhibited by pharmacological (cycloheximide and mithramycin) and genetic (siRNA targeting BIP and CHOP) methods, the induction of BIP, PDI, IRE1a, and LC3-II was blocked, but PARP cleavage was markedly enhanced. DISCUSSION: Taken together, these results suggested that sodium butyrate-induced autophagy was mediated by endoplasmic reticulum stress, and that preventing autophagy by blocking the endoplasmic reticulum stress response enhanced sodium butyrate-induced apoptosis. These results provide novel insights into the anti-tumor mechanisms of butyric acid.
Assuntos
Adenocarcinoma/patologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Ácido Butírico/farmacologia , Neoplasias Colorretais/patologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Western Blotting , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Humanos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Células Tumorais CultivadasRESUMO
Chrysophyllum cainito L., a traditional herbal medicine, could have the potential for management of hypertension due to presence of polyphenolic compounds. The extracts and fractions of the pulp of plant were evaluated for in vitro (inhibition of angiotensin I converting enzyme/ACE assay), ex vivo (isolated aorta relaxation assay) and in vivo (salt induced hypertensive rat assay). The alcoholic and aqueous extract (ALE and AQE respectively) of fruit of plant C. cainito was having 14.8 and 9.2% yield respectively. The fractionation with ethyl alcohol (EAF) and butanol (BTF) yielded 2.52 & 2.17% respectively from ALE and 0.46 & 0.31% respectively from AQE with respect to fruit pulp dry weight. More phenolic content was found in ALE (3.75±0.15 mg gallic acid equivalent or GAE g(-1) of dry power of fruit pulp) compared to AQE and maximum in ethyl acetate fraction of ALE (ALE-EAF) (2.32±0.21 mg GAE g(-1) of dry power of fruit pulp) among all fractions. ACE inhibition activity was found to be maximum in ALE-EAF 62.5±7.34%. While ex vivo study using isolated tissue of aorta showed again showed maximum activity (62.82±6.19 and 46.47±8.32% relaxation with 50 µg mL(-1) and 10 µg mL(-1) GAE concentration respectively). ALE-EAF reduced the elevated arterial pressure of salt induced hypertensive rat significantly to the level of normotensive animal group. Results of ALE-EAF have shown its potential as a source for novel constituent for the treatment hypertension and should further be studied for isolation of specific constituent for more effectiveness.
RESUMO
It appears to be more practical and effective to prevent carcinogenesis by targeting the tumor promotion stage. Gap junctional intercellular communication (GJIC) is strongly involved in carcinogenesis, especially the tumor promotion stage. Considerable interest has been focused on the chemoprevention activities of soyasaponin (SS), which are major phytochemicals found in soybeans and soy products. However, less is known about the preventive effects of SS (especially SS with different chemical structures) against tumor promoter-induced inhibition of GJIC. We investigated the protective effects of SS-A1, SS-A2, and SS-I against hydrogen peroxide (H2O2)-induced GJIC inhibition and reactive oxygen species (ROS) production in Buffalo rat liver (BRL) cells. The present results clearly show for the first time that SS-A1, SS-A2, and SS-I prevent the H2O2-induced GJIC inhibition by scavenging ROS in BRL cells in a dose-dependent manner at the concentration range of from 25 to 100 µg/mL. Soyasaponins attenuated the H2O2-induced ROS through potentiating the activities of superoxide dismutase and glutathione peroxidase. This may be an important mechanism by which SS protects against tumor promotion. In addition, various chemical structures of SS appear to exhibit different protective abilities against GJIC inhibition. This may partly attribute to their differences in ROS-scavenging activities.
Assuntos
Comunicação Celular/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Junções Comunicantes/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Saponinas/farmacologia , Animais , Catalase/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Junções Comunicantes/metabolismo , Glutationa Peroxidase/metabolismo , Hepatócitos/metabolismo , Peróxido de Hidrogênio/efeitos adversos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/citologia , Fígado/efeitos dos fármacos , Malondialdeído/metabolismo , Ratos , Glycine max/química , Superóxido Dismutase/metabolismoRESUMO
We and others have recently shown that soyasaponins abundant in soybeans can decrease inflammation by suppressing the nuclear factor kappa B (NF-kB)-mediated inflammation. However, the exact molecular mechanisms by which soyasaponins inhibit the NF-kB pathway have not been established. In this study in macrophages, soyasaponins (A1, A2 and I) inhibited the lipopolysaccharide (LPS)-induced release of inflammatory marker prostaglandin E2 (PGE2) to a similar extent as the NF-kB inhibitor (BAY117082). Soyasaponins (A1, A2 and I) also suppressed the LPS-induced expression of cyclooxygenase 2 (COX-2), another inflammatory marker, in a dose-dependent manner by inhibiting NF-kB activation. In defining the associated mechanisms, we found that soyasaponins (A1, A2 and I) blunted the LPS-induced IKKα/ß phosphorylation, IkB phosphorylation and degradation, and NF-kB p65 phosphorylation and nuclear translocation. In studying the upstream targets of soyasaponins on the NF-kB pathway, we found that soyasaponins (A1, A2 and I) suppressed the LPS-induced activation of PI3K/Akt similarly as the PI3K inhibitor LY294002, which alone blocked the LPS-induced activation of NF-kB. Additionally, soyasaponins (A1, A2 and I) reduced the LPS-induced production of reactive oxygen species (ROS) to the same extent as the anti-oxidant N-acetyl-L-cysteine, which alone inhibited the LPS-induced phosphorylation of Akt, IKKα/ß, IkBα, and p65, transactivity of NF-kB, PGE2 production, and malondialdehyde production. Finally, our results show that soyasaponins (A1, A2 and I) elevated SOD activity and the GSH/GSSG ratio. Together, these results show that soyasaponins (A1, A2 and I) can blunt inflammation by inhibiting the ROS-mediated activation of the PI3K/Akt/NF-kB pathway.
Assuntos
Macrófagos/imunologia , Ácido Oleanólico/análogos & derivados , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Espécies Reativas de Oxigênio/antagonistas & inibidores , Saponinas/farmacologia , Animais , Linhagem Celular , Cromonas/farmacologia , Ciclo-Oxigenase 2/biossíntese , Dinoprostona/metabolismo , Quinase I-kappa B/metabolismo , Inflamação/tratamento farmacológico , Lipopolissacarídeos , Malondialdeído/metabolismo , Camundongos , Morfolinas/farmacologia , Nitrilas/farmacologia , Ácido Oleanólico/farmacologia , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Glycine max/metabolismo , Sulfonas/farmacologia , Superóxido Dismutase/biossíntese , Fator de Transcrição RelA/metabolismoRESUMO
The aim of the present study was to determine the expression of p-Akt in ovarian serous carcinoma (OSC) and its association with proliferation and apoptosis. Paraffin-embedded tissues of patients aged between 35 and 64 years old without history of radiotherapy, chemotherapy and hormone therapy prior to surgery were collected. In total, samples included 12 ovarian serous cystadenomas (OSAs), 18 ovarian serous borderline tumors (OS-BTs) and 46 OSCs. Of the 46 OSC samples, 16 were well-differentiated, 20 were moderately differentiated and 10 were poorly differentiated, while 22 developed lymphatic metastases and 24 were metastasis-free. An additional 10 paraffin-embedded normal ovarian tissues (NOTs) were used as controls. Streptavidin-peroxidase immunohistochemistry assays were used to investigate the expression of p-Akt and cyclin D1 in the collected samples. Compared with NOT, p-Akt expression in the OS-BT and OSC groups, as well as cyclin D1 expression in the OSA and OSC groups, was significantly elevated (P<0.05). Compared with the OSA group, p-Akt expression in the OSC group was significantly elevated (P<0.01) and reversely associated with tumor differentiation (P<0.01), whereas cyclin D1 expression showed no correlation with tumor differentiation (P>0.05). The expression of p-Akt, caspase-3 and cyclin D1 was positively associated with lymphatic metastasis (r=0.334; P=0.023). The expression of p-Akt gradually increased with carcinoma development and was associated with differentiation and metastasis of OSC, revealing that the activation of the PI3K/Akt signaling pathway is involved in the development of OSC. Furthermore, the expression of cyclin D1 gradually increased in the NOT, OSA, OS-BT and OSC groups and was associated with tumor metastasis.
RESUMO
The anti-inflammatory properties of soyasaponins (especially soyasaponins with different chemical structures) have scarcely been investigated. We investigated the inhibitory effects of five structural types of soyasaponins (soyasaponin A(1), A(2), I and soyasapogenol A, B) on the induction of nitric oxide (NO) and inducible NO synthase (iNOS) in murine RAW 264.7 cells activated with lipopolysaccharide (LPS). Soyasaponin A(1), A(2) and I (25-200 µg/mL) dose-dependently inhibited the production of NO and tumor necrosis factor α (TNF-α) in LPS-activated macrophages, whereas soyasapogenol A and B did not. Furthermore, soyasaponin A(1), A(2) and I suppressed the iNOS enzyme activity and down-regulated the iNOS mRNA expression both in a dose-dependent manner. The reporter gene assay revealed that soyasaponin A(1), A(2) and I decreased LPS-induced nuclear factor kappa B (NF-κB) activity. Soyasaponin A(1), A(2) and I exhibit anti-inflammatory properties by suppressing NO production in LPS-stimulated RAW 264.7 cells through attenuation of NF-κB-mediated iNOS expression. It is proposed that the sugar chains present in the structures of soyasaponins are important for their anti-inflammatory activities. These results have important implication for using selected soyasaponins towards the development of effective chemopreventive and anti-inflammatory agents.
Assuntos
Anti-Inflamatórios/química , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/metabolismo , Saponinas/química , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular Tumoral , Lipopolissacarídeos/toxicidade , Camundongos , Óxido Nítrico Sintase Tipo II/genética , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Saponinas/farmacologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: "Doing the month", or "sitting month", is a traditional practice for postpartum women in China and other Asian countries, which includes some taboos against well-accepted healthy diet and lifestyles in general population. Previous studies have shown this practice may be associated with higher prevalence of postpartum problems. The current multicenter randomized controlled trial (RCT) aims to evaluate outcomes of diet and lifestyle interventions in Chinese postpartum women. METHODS/DESIGN: The current multicenter RCT will be conducted in three representative areas in China, Shandong province, Hubei province and Guangdong province, which locate in northern, central and southern parts of China, respectively. Women who attend routine pregnancy diagnosis in hospitals or maternal healthcare centers will be invited to take part in this study. At least 800 women who meet our eligibility criteria will be recruited and randomly assigned to the intervention group (n > = 400) and the control group (n > = 400). A three-dimension comprehensive intervention strategy, which incorporates intervention measures simultaneously to individual postpartum woman, their family members and community environment, will be utilized to maximize the effectiveness of intervention. Regular visiting and follow-up will be done in both group; nutrition and health-related measurements will be assessed both before and after the intervention. DISCUSSION: To our knowledge, this current study is the first and largest multicenter RCT which focus on the effectiveness of diet and lifestyle intervention on reducing the incidence rate of postpartum diseases and improving health status in postpartum women. We hypothesize that the intervention will reduce the incidence rates of postpartum diseases and improve nutrition and health status due to a balanced diet and reasonable lifestyle in comparison with the control condition. If so, the results of our study will provide especially important evidence for changes in both the concept and action of traditional postpartum practice in China. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT01039051.
Assuntos
Dieta , Estilo de Vida , Serviços de Saúde Materna , Período Pós-Parto , Serviços Preventivos de Saúde/métodos , Adulto , China , Testes Diagnósticos de Rotina , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Nível de Saúde , Humanos , Necessidades Nutricionais , Seleção de Pacientes , Gravidez , Garantia da Qualidade dos Cuidados de Saúde/normas , Projetos de Pesquisa , Inquéritos e QuestionáriosRESUMO
BACKGROUND: 'Sitting month' is the Chinese tradition for postpartum customs. Available studies indicate that some of the traditional postpartum practices are potentially harmful for women's health. However, no intervention study aiming at postpartum practices has been performed. In this paper we evaluated the effect of a health and nutrition education intervention, which focused on improving postpartum dietary quality and optimal health behaviors. METHODS: The study design was a randomized controlled trial conducted in both urban and rural area of Hubei between August 2003 and June 2004. A total of 302 women who attended the antenatal clinic during the third trimester with an uncomplicated pregnancy were recruited. Women randomized to the education intervention group in both urban and rural area received two two-hour prenatal education sessions and four postpartum counseling visits. Control group women received usual health care during pregnancy and postpartum period. Women were followed up until 42 days postpartum. Outcome measures were nutrition and health knowledge, dietary behavior, health behavior and health problems during the postpartum period. RESULTS: Women in the intervention groups exhibited significantly greater improvement in overall dietary behaviors such as consumption of fruits, vegetables, soybean and soybean products as well as nutrition and health knowledge than those in the control groups. Significantly more women in the intervention groups give up the traditional behavior taboos. The incidence of constipation, leg cramp or joint pain and prolonged lochia rubra was significantly lower in the intervention groups as compared with the control groups. CONCLUSION: The study shows that health and nutrition education intervention enable the women take away some of the unhealthy traditional postpartum practices and decrease the prevalence of postpartum health problems. The intervention has potential for adaptation and development to large-scale implementation. TRIAL REGISTRATION NUMBER: klACTRN12607000549426.