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OBJECTIVE: In recent years, coronary heart disease (CHD) has become a disease that cannot be ignored by residents of our country, because CHD will not only endanger people's quality of life, but also threaten their lives. Therefore, this research mainly explores the correlation between myocardial infarction (MI) with endoplasmic reticulum (ER) stress and apoptosis. MATERIALS AND METHODS: First, we constructed a model of myocardial ischemia and hypoxia (I/H) in vivo and in vitro, and examined the change of CACNA1H expression. At the same time, in order to research the role of CACNA1H, we chose CACNA1H-specific inhibitor ABT-639 to next research and detect changes in heart injury by detecting changes in creatine kinase (CK) content and lactate dehydrogenase (LDH) activity. Next, we used TUNEL staining and immunofluorescence staining to detect changes in apoptosis and ER stress, and analyzed changes in ER stress and apoptotic pathway expression by Western blotting and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). RESULTS: At 28 days after MI, the cardiac function of the mice was significantly reduced, the myocardial cell apoptosis rate was dramatically increased, and CACNA1H expression was dramatically increased in vivo and in vitro. In addition, we treated the model group with the ABT-639, and found that ABT-639 can partially protect myocardial function and relieve myocardial cell apoptosis. At the same time, ABT-639 may reduce H9c2 injury after I/H by reducing the degree of ER stress, because we found that the use of ABT-639 can dramatically reduce ER stress-related factors expression, and can inhibit the expression of apoptosis-related factors Caspase-3 and Caspase-9. CONCLUSIONS: The CACNA1H inhibitor ABT-639 can alleviate myocardial cell apoptosis caused by MI by reducing the ER stress response.
Assuntos
Canais de Cálcio Tipo T/metabolismo , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Apoptose , Células Cultivadas , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/patologia , Miócitos Cardíacos/patologiaRESUMO
OBJECTIVE: The aim of this study was to investigate the effect of micro ribonucleic acid (miR)-497 on myocardial cell apoptosis in rats with myocardial ischemia/reperfusion (I/R) through the mitogen-activated protein kinase (MAPK)/extracellular regulated protein kinase (ERK) signaling pathway. MATERIALS AND METHODS: A rat model of myocardial I/R was established, myocardial cells were extracted, and miR-497 was inhibited by inhibitors and overexpressed using miRNA mimics. The cell apoptosis rate was detected by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The interaction between miR-497 and ERK was determined by dual-luciferase reporter gene assay. The change in the protein level was measured via Western blotting (WB). RESULTS: Up-regulation of miR-497 promoted myocardial cell apoptosis, and the 3'-untranslated region (3'-UTR) of ERK was highly conserved to combine with miR-497. The luciferase reporter gene assay showed that the transfection of miR-497 could significantly inhibit the relative luciferase activity in cells. CONCLUSIONS: MiR-497 overexpression significantly down-regulated the ERK expression at messenger RNA (mRNA) and protein levels in cells. MiR-497 plays an important role in regulating I/R injury-induced myocardial cell apoptosis by targeting the ERK-induced apoptosis pathway.
Assuntos
Apoptose , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , MicroRNAs/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Isquemia Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Isquemia Miocárdica/patologia , Miócitos Cardíacos/patologia , Transdução de SinaisRESUMO
OBJECTIVE: To evaluate the safety and efficacy of a new technique for accurate ostial/non-ostial coronary stenting in percutaneous coronary intervention (PCI). BACKGROUND: Accurate stent localization is a key factor impacting the postoperative success of patients undergoing PCI. However, the accurate localization of some lesions, especially ostial lesions, is very difficult to achieve, because they are often complicated by bobbing or to-and-fro movement of the stent during cardiac contractions. METHODS: We report a novel technique of precise ostial/non-ostial stenting based on the buddy balloon anchor stent (BBAS) technique. Between May 2014 and July 2017, 47 patients with significant ostial/non-ostial coronary stenosis that required accurate stenting were included in this study. Of them, 23 patients were treated using the conventional method and the remaining 24 patients were treated using (BBAS) technique. Evaluation was then performed using intravascular ultrasound (IVUS) in the procedural, or coronary computed tomography angiography (CCTA) in the follow up. RESULTS: Using the BBAS technique, the procedural success was achieved in all 24 (100%) cases. IVUS was performed in seven patients (29.17%) and no procedural complications occurred. All six failed cases that occurred among patients with right coronary artery and left anterior descending artery ostial stenosis treated using the conventional method, the lesions were subsequently successfully re-stented using the BBAS technique. After a follow-up of 3-36 months, CCTA was performed in 11 patients (45.83%), all the stents were in the accurate position. There were no major cardiovascular events of death, myocardial infarction, or target lesion revascularization. CONCLUSION: BBAS is a simple, highly successful and safe technique for accurate stenting of difficult ostial/nonostial coronary stenosis lesions.
Assuntos
Angioplastia Coronária com Balão/métodos , Doença da Artéria Coronariana/terapia , Estenose Coronária/terapia , Idoso , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/instrumentação , Cateteres Cardíacos , Doença da Artéria Coronariana/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Stents , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Older adults experience age-related physiological changes that affect body weight and body composition. In general, nutrition and exercise have been identified as potent stimulators of protein synthesis in skeletal muscle. Milk proteins are excellent sources of all the essential amino acids and may represent an ideal protein source to promote muscle anabolism in older adults undergoing resistance training. However, several randomized control trials (RCTs) have yielded mixed results on the effects of milk proteins supplementation in combination with resistance training on body weight and composition. METHODS: PubMed, Web of Science and Cochrane databases were searched for literature that evaluated the effects of milk proteins supplementation on body weight and composition among older adults (age ≥ 60 years) undergoing resistance training up to September 2016. A random-effects model was used to calculate the pooled estimates and 95% confidence intervals (CIs) of effect sizes. RESULTS: The final analysis included 10 RCTs involving 574 participants (mean age range from 60 to 80.8 years). Overall, the combination of milk proteins supplementation and resistance training did not have significant effect on fat mass (0.30, 95% CI -0.25, 0.86 kg) or body weight (1.02, 95% CI: -0.01, 2.04 kg). However, a positive effect of milk proteins supplementation paired with resistance training on fat-free mass was observed (0.74, 95% CI 0.30, 1.17 kg). Greater fat-free mass gains were observed in studies that included more than 55 participants (0.73, 95% CI 0.30, 1.16 kg), and in studies that enrolled participants with aging-related medical conditions (1.60, 95% CI 0.92, 2.28 kg). There was no statistical evidence of publication bias among the studies. CONCLUSION: Our findings provide evidence that supplementation of milk protein, in combination with resistance training, is effective to elicit fat-free mass gain in older adults.
Assuntos
Composição Corporal/fisiologia , Peso Corporal/fisiologia , Suplementos Nutricionais/análise , Proteínas do Leite/uso terapêutico , Treinamento Resistido/métodos , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Epidemiologic evidence has shown inconsistent findings regarding the relationships between abdominal fatness, as measured by waist circumferences (WC) or waist-to-hip ratio (WHR), and risks of pre- and postmenopausal breast cancer (BC). A dose-response meta-analysis of prospective studies was conducted to address these issues. Potentially eligible studies were identified by searching PubMed and EMBASE databases, and by carefully reviewing the bibliographies of retrieved publications and related reviews. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. When the most fully adjusted RRs were combined, both WC (14 studies, RR per 10-cm increase = 1.06, 95% CI: 1.04-1.09, I2 = 29.9%) and WHR (15 studies, RR per 0.1-unit increase = 1.07, 95% CI: 1.01-1.14, I2 = 52.9%) were significantly positively associated with postmenopausal BC, but neither WC (eight studies, RR per 10-cm increase = 1.05, 95% CI: 0.99-1.10, I2 = 0%) nor WHR (11 studies, RR per 0.1-unit increase = 1.07, 95% CI: 0.95-1.21, I2 = 59.7%) were associated with premenopausal BC. The WHR-postmenopausal BC association lost statistical significance after correcting publication bias (RR per 0.1-unit increase = 1.06, 95% CI: 0.99-1.13). When considering BMI-adjusted RRs, WC was associated with both pre- (five studies, RR per 10-cm increase = 1.09, 95% CI: 1.02-1.16, I2 = 0%) and postmenopausal BC (seven studies, RR per 10-cm increase = 1.05, 95% CI: 1.02-1.08, I2 = 6.3%), whereas WHR was not associated with either pre- (seven studies, RR per 0.1-unit increase = 1.12, 95% CI: 0.94-1.34, I2 = 70.9%) or postmenopausal BC (eight studies, RR per 0.1-unit increase = 1.05, 95% CI: 0.98-1.13, I2 = 57.3%). Among non-current (former or never) users of hormone replacement therapy, the summary RR per 10-cm increase of postmenopausal BC associated with WC was 1.08 (95% CI: 1.03-1.05, I2 = 69.2%, seven studies; BMI-adjusted RR = 1.05, 95% CI: 1.02-1.09, I2 = 22.8%, four studies). This meta-analysis indicates that central obesity measured by WC, but not by WHR, is associated with modestly increased risks of both pre- and postmenopausal BC independent of general obesity.
Assuntos
Neoplasias da Mama/etiologia , Obesidade Abdominal/complicações , Índice de Massa Corporal , Neoplasias da Mama/patologia , Feminino , Humanos , Obesidade Abdominal/fisiopatologia , Pós-Menopausa/fisiologia , Pré-Menopausa/fisiologia , Estudos Prospectivos , Receptores de Estrogênio/fisiologia , Receptores de Progesterona/fisiologia , Fatores de Risco , Circunferência da Cintura , Relação Cintura-QuadrilRESUMO
BACKGROUND: A growing body of evidence has shown that microRNA-29 (miR-29) plays a central role in the progression of fibrosis. However, the mechanisms underlying the role of miR-29 in keloid fibrogenesis remain unknown. AIM: To investigate the roles of miR-29 in dermal fibroblasts in the pathogenesis of keloids. METHODS: Primary fibroblasts from 9 patients with keloid and 6 healthy controls (HCs) were cultured and pretreated with transforming growth factor (TGF)-ß1. Next, fibroblasts were transfected with precursor miRNA and anti-miR-29a miRNA. TGF-ß1-associated miR-29 alterations were investigated by quantitative real-time PCR. Collagen I and collagen III protein levels were analysed by western blotting. RESULTS: miR-29a, miR-29b and miR-29c levels were significantly lower in keloid compared with healthy fibroblasts (P < 0.05), and in particular, miR-29a was especially markedly reduced (P < 0.001). Type I and type III collagen mRNA and protein levels were decreased in keloid fibroblasts transfected with pre-miR-29a (P < 0.05), whereas knockdown with anti-miR-29a increased type I and type III collagen mRNA and protein expression (P < 0.05) in the fibroblasts. Interestingly, pretreatment of fibroblasts with TGF-ß1 significantly decreased miR-29a (P < 0.05), whereas miR-29b and miR-29c were reduced to a lesser extent, which was not significant. CONCLUSIONS: These findings show that miR-29a exerts as a novel regulator in the fibrogenesis of keloid, suggesting that miR-29a might be a novel marker for keloid.
Assuntos
Queloide/etiologia , Queloide/genética , MicroRNAs/genética , Adolescente , Adulto , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Feminino , Fibroblastos/metabolismo , Humanos , Masculino , Fator de Crescimento Transformador beta1/genéticaRESUMO
Epidermal growth factor receptor (EGFR) regulates multiple signaling cascades essential for cell proliferation, growth and differentiation. Using a genetic approach, we found that Drosophila FERM and PDZ domain-containing protein tyrosine phosphatase, dPtpmeg, negatively regulates border cell migration and inhibits the EGFR/Ras/mitogen-activated protein kinase signaling pathway during wing morphogenesis. We further identified EGFR pathway substrate 15 (Eps15) as a target of dPtpmeg and its human homolog PTPN3. Eps15 is a scaffolding adaptor protein known to be involved in EGFR endocytosis and trafficking. Interestingly, PTPN3-mediated tyrosine dephosphorylation of Eps15 promotes EGFR for lipid raft-mediated endocytosis and lysosomal degradation. PTPN3 and the Eps15 tyrosine phosphorylation-deficient mutant suppress non-small-cell lung cancer cell growth and migration in vitro and reduce lung tumor xenograft growth in vivo. Moreover, depletion of PTPN3 impairs the degradation of EGFR and enhances proliferation and tumorigenicity of lung cancer cells. Taken together, these results indicate that PTPN3 may act as a tumor suppressor in lung cancer through its modulation of EGFR signaling.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Movimento Celular , Proliferação de Células , Receptores ErbB/metabolismo , Neoplasias Pulmonares/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 3/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Animais Geneticamente Modificados , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular , Linhagem Celular Tumoral , Endocitose , Feminino , Células HEK293 , Humanos , Immunoblotting , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Microdomínios da Membrana/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Microscopia Confocal , Mutação , Fosforilação , Proteína Tirosina Fosfatase não Receptora Tipo 3/genética , Interferência de RNA , Transplante HeterólogoRESUMO
The antitumor activity of an inhibitor of 26S proteasome bortezomib (Velcade) has been observed in various malignancies, including colon cancer, prostate cancer, breast cancer, and ovarian cancer. Bortezomib has been proposed to stimulate autophagy, but scientific observations did not always support this. Interactions between ERK activity and autophagy are complex and not completely clear. Autophagy proteins have recently been shown to regulate the functions of ERK, and ERK activation has been found to induce autophagy. On the other hand, sustained activation of ERK has also been shown to inhibit the maturation step of the autophagy process. In this study, we sought to identify the mechanism of autophagy regulation in cancer cells treated with bortezomib. Our results indicate that bortezomib blocked the autophagic flux without inhibiting the fusion of the autophagosome and lysosome. In ovarian cancer, as well as endometrial cancer and hepatocellular carcinoma cells, bortezomib inhibited protein degradation in lysosomes by suppressing cathepsins, which requires the participation of ERK phosphorylation, but not JNK or p38. Our findings that ERK phosphorylation reduced cathepsins further explain how ERK phosphorylation inhibits the autophagic flux. In conclusion, bortezomib may induce ERK phosphorylation to suppress cathepsin B and inhibit the catalytic process of autophagy in ovarian cancer and other solid tumors. The inhibition of cisplatin-induced autophagy by bortezomib can enhance chemotherapy efficacy in ovarian cancer. As we also found that bortezomib blocks the autophagic flux in other cancers, the synergistic cytotoxic effect of bortezomib by abolishing chemotherapy-related autophagy may help us develop strategies of combination therapies for multiple cancers.
Assuntos
Antineoplásicos/farmacologia , Ácidos Borônicos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/genética , Regulação Neoplásica da Expressão Gênica , Inibidores de Proteassoma/farmacologia , Pirazinas/farmacologia , Autofagia/efeitos dos fármacos , Autofagia/genética , Bortezomib , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Humanos , Leupeptinas/farmacologia , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Fagossomos/efeitos dos fármacos , Fagossomos/metabolismo , Fosforilação/efeitos dos fármacos , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
This meta-analysis aimed to assess the gender-specific differences in the relationship between circulating leptin levels and risk of type 2 diabetes. Published prospective studies that reported the association of leptin levels with risk of type 2 diabetes for a certain gender or those that reported gender-specific associations were considered. Dose-response relationships were assessed by the generalized least squares trend estimation and summary relative risks (RRs) with 95% confidence interval (CI) were computed with the random-effects model. Stratified and sensitivity analyses were also performed to investigate potential sources of heterogeneity. Overall, 11 prospective studies were identified. The summary RR for an increment in leptin levels of 1-log ng mL(-1) was 1.37 (95% CI, 1.13-1.66) for men and 0.96 (95% CI, 0.90-1.03) for women. The differences between genders were statistically significant (P for interaction = 0.006). Subgroup and sensitivity analyses generally confirmed the robustness of these findings. Furthermore, the increased risk in men appeared non-linear, with a tendency to plateau at high levels (P for non-linearity = 0.03). Little evidence of publication bias was found. Collectively, higher leptin levels were found to be associated with elevated risk of type 2 diabetes in men but not in women.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Leptina/sangue , Obesidade/sangue , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Feminino , Humanos , Masculino , Obesidade/epidemiologia , Estudos Prospectivos , Fatores de Risco , Fatores SexuaisRESUMO
Spatial and seasonal variations in litter production and C, N, and P concentrations were compared between the 24 and 48 year old Kandelia obovata mangrove forests in the Jiulongjiang estuary, China. The 24 yr forest had significantly higher production of total, leaf and branch litter, but lower flower and fruit litter than the 48 yr forest. Total, leaf and branch litter production were significantly positively correlated to monthly temperature and rainfall. Spatial patterns of litter production among the inner, mid and outer zones in the same forest were similar to those of tree heights. C, N and P concentrations of leaf litter showed significant seasonality but varied little among these three forest zones. C/N and N/P ratios of leaf litter were significantly lower for the 24 yr forest than those for the 48 yr forest. During the entire sampling year, total litter of the 24 and 48 yr forests contained 590.31 and 437.31 g C m(-2) yr(-1), 8.46 and 5.47 g N m(-2) yr(-1), 1.92 and 1.16 g P m(-2) yr(-1), respectively.
Assuntos
Monitoramento Ambiental , Estuários , Folhas de Planta/química , Rhizophoraceae/química , Rhizophoraceae/fisiologia , Árvores , China , Conservação dos Recursos Naturais , Estações do Ano , Fatores de TempoRESUMO
BACKGROUND/OBJECTIVES: Epidemiological evidence is suggestive, but inconclusive, for an association between consumption of red and processed meat and risk of stroke. We aimed to assess this association by conducting a meta-analysis of prospective cohort studies. SUBJECTS/METHODS: We performed a literature search on PubMed database through June 2012 to identify prospective cohort studies of red and processed meat intake in relation to risk of stroke. Reference lists of the retrieved articles were also reviewed. Both fixed-effects and random-effects model were assumed to compute the summary risk estimates. RESULTS: Five large independent prospective cohort studies were identified. These studies contained a total of 2 39 251 subjects and 9593 stroke events. Comparing the highest category of consumption with lowest category, the pooled relative risks (RRs) of total stroke were 1.15 (95% confidence interval (CI), 1.05-1.25) for total meat (red and processed meat combined) (n=4), 1.09 (95% CI, 1.01-1.18) for red meat (n=5) and 1.14 (95% CI, 1.05-1.25) for processed meat (n=5); the corresponding RRs of ischemic stroke (highest vs lowest quintile) were 1.15 (95% CI, 1.04-1.28), 1.13(95% CI, 1.01-1.25) and 1.19 (95% CI, 1.08-1.31). Consumption of red and/or processed meat was not associated with hemorrhagic stroke. In the dose-response analysis, the risk of stroke increased significantly by 10% and 13% for each 100 g per day increment in total and red meat consumption, respectively, and by 11% for each 50 g per day increment in processed meat consumption. CONCLUSION: Findings from this meta-analysis indicate that consumption of red and/or processed meat increase risk of stroke, in particular, ischemic stroke.
Assuntos
Alimentos em Conserva/efeitos adversos , Produtos da Carne/efeitos adversos , Carne/efeitos adversos , Acidente Vascular Cerebral/etiologia , Animais , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/etiologia , Isquemia Encefálica/prevenção & controle , Bovinos , Estudos de Coortes , Humanos , Estudos Prospectivos , Risco , Carneiro Doméstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Sus scrofaRESUMO
BACKGROUND/OBJECTIVES: Epidemiological studies have suggested that dietary fiber intake may be associated with a decreased risk of stroke, but the findings have been inconsistent. We aimed to assess this association by conducting a meta-analysis of prospective cohort studies. SUBJECTS/METHODS: We performed a literature search on PubMed database through July 2012 to identify prospective studies of dietary fiber intake in relation to risk of stroke. We also comprehensively reviewed the reference lists of the retrieved articles to identify additional studies. We used a random-effects model to compute the summary risk estimates. RESULTS: Six prospective cohort studies containing a total of 314 864 subjects and 8920 stroke cases were included. The summary relative risk (RR) of stroke for the highest vs lowest category of dietary fiber intake was 0.87 (95% confidence interval (CI), 0.77-0.99). The corresponding RR in the subgroup analyses for men and women was 0.95 (95% CI, 0.83-1.08) and 0.80 (95% CI, 0.66-0.96), respectively; and for ischemic stroke and hemorrhagic stroke was 0.83(95% CI, 0.72-0.96) and 0.86 (95% CI, 0.70-1.06), respectively. Meta-regression indicated no significant difference between gender (P-interaction=0.18), or stroke subtypes (P-interaction =0.85). The dose-response analysis suggested a 12% (RR=0.88; 95% CI, 0.79-0.97) reduction in risk of stroke for each 10 g per day increment in dietary fiber intake. Moderate heterogeneity emerged in some of analyses, but disappeared after removing one study substantially contributing to the heterogeneity. Little evidence of publication bias was detected. CONCLUSION: Findings of this meta-analysis indicate a significant inverse dose-response relationship between dietary fiber intake and risk of stroke.
Assuntos
Fibras na Dieta/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Estudos de Coortes , Fibras na Dieta/administração & dosagem , Humanos , Estudos Prospectivos , Risco , Acidente Vascular Cerebral/epidemiologiaRESUMO
Epidemiologic studies have suggested that magnesium intake may be associated with a decreased risk of colorectal cancer (CRC), but the findings have been inconsistent. We aimed to assess this association by conducting a meta-analysis of prospective studies. We performed a literature search on PubMed database through July 2012 to identify prospective studies of magnesium intake in relation to CRC risk. Reference lists of the retrieved articles were also reviewed. A random-effects model was used to compute the summary risk estimates. Eight prospective studies containing 338,979 participants and 8000 CRC cases met the inclusion criteria. The summary relative risk (RR) for the highest vs lowest category of magnesium intake for CRC was 0.89 (95% CI, 0.79-1.00), with little evidence of heterogeneity. Restricting the analysis to six studies that have adjusted for calcium intake yielded a similar result. For colon and rectal cancer, the pooled RR was 0.81 (95% CI, 0.70-0.93) and 0.94 (95% CI, 0.72-1.24), respectively. In the dose-response analyses, the summary RRs for an increment of magnesium intake of 50 mg/day for colorectal, colon and rectal cancer were, respectively, 0.95 (95% CI, 0.89-1.00), 0.93 (95% CI, 0.88-0.99) and 0.93 (95% CI, 0.83-1.04), and there was some evidence of heterogeneity; omitting one study that substantially contributed to the heterogeneity yielded generally similar results, but with low heterogeneity. We detected no indication of publication bias. On the basis of the findings of this meta-analysis, a higher magnesium intake seems to be associated with a modest reduction in the risk of CRC, in particular, colon cancer.
Assuntos
Neoplasias do Colo/prevenção & controle , Neoplasias Colorretais/prevenção & controle , Dieta , Ingestão de Energia , Magnésio/uso terapêutico , Neoplasias Retais/prevenção & controle , Oligoelementos/uso terapêutico , Animais , Neoplasias do Colo/epidemiologia , Neoplasias Colorretais/epidemiologia , Humanos , Neoplasias Retais/epidemiologia , RiscoRESUMO
INTRODUCTION: Long bone surgery represents a significant surgical insults, and may cause severe local and systemic sequalae following both planned and emergent surgery. Glutamine offers pharmacological modulation of injury through clinically acceptable preconditioning. This effect has not been previously demonstrated in an orthopaedic model. AIMS: The aim of the study was to test the hypothesis that glutamine preconditioning protects against the local and systemic effects of long bone trauma in a rodent model. METHODS: Thirty two adult male Sprague-Dawley rats were randomised into four groups: Control group which received trauma without preconditioning; Normal Saline preconditioning 1 hour before trauma; Glutamine preconditioning 1 hour before trauma; Glutamine preconditioning 24 hours prior to trauma. Trauma consisted of bilateral femoral fracture following intramedullary instrumentation. Blood samples were taken before the insult, and at an interval four hours following this. Bronchioalveolar lavage (BAL) was performed, with skeletal muscle and lung harvested for evaluation. RESULTS: Glutamine pre-treated rats had lower Creatine Kinase levels, less creatinine elevation, and a significant reduction in neutrophil infiltration into BAL fluid. Glutamine pre-treated rats showed less muscle and lung oedema. This effect was more pronounced for the group which received glutamine 24 hours before trauma. CONCLUSION: Preconditioning with a single bolus of intravenous glutamine prior to planned orthopaedic intervention affords loco-regional and distal organ protection. We believe these finding have significant implications for elective orthopaedic surgery where significant soft tissue and long bone manipulation is anticipated.
Assuntos
Glutamina/uso terapêutico , Precondicionamento Isquêmico , Procedimentos Ortopédicos/efeitos adversos , Substâncias Protetoras/uso terapêutico , Animais , Lavagem Broncoalveolar , Modelos Animais de Doenças , Fraturas do Fêmur/tratamento farmacológico , Fraturas do Fêmur/prevenção & controle , Masculino , Músculo Esquelético/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controleRESUMO
Esophageal capsule endoscopy (ECE) may offer an alternative approach to visualize esophageal lesions associated with gastroesophageal reflux (GER) disease. The objective of this study was to report the ECE findings in patients with GER symptoms and validate a new scoring system to assess ECE video quality. Five hundred two ECE were performed in patients with GER symptoms. We devised a new grading scale called ECE Utility score to assess the quality of images using five different parameters: anatomic landmarks visualized, esophageal transit time, image quality, illumination, and artifacts. The ECE cases were independently scored by two interpreters in a randomized, blinded fashion. Reflux esophagitis was diagnosed via ECE in 254 patients (50.5%). We identified 12 cases (2.4%) with suspected Barrett's esophagus and all of them had endoscopic evidence of Barrett's esophagus on esophagogastroduodenoscopy. Histologic confirmation Barrett's esophagus was found in six patients and dysplasia was found in one patient. From the 502 cases, mean ± standard deviation total ECE Utility score was 8.89 ± 0.96 for interpreter 1 and 8.96 ± 0.93 for interpreter 2. The concordance rate between the two interpreters for the ECE Utility score ranged from 75.9-96.8% across the parameters and the Pearson correlation rate of the total score was 0.81. ECE is shown to be a simple noninvasive valuable technique for evaluating esophageal mucosa and producing high quality images in patients with GER symptoms. ECE can help as an alternative screening tool for diagnosing Barrett's esophagus.
Assuntos
Esôfago de Barrett/diagnóstico , Endoscopia por Cápsula/métodos , Endoscopia do Sistema Digestório/métodos , Refluxo Gastroesofágico/complicações , Avaliação de Sintomas/métodos , Adulto , Pontos de Referência Anatômicos , Esôfago de Barrett/etiologia , Esofagite Péptica/diagnóstico , Feminino , Hérnia Hiatal/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Posicionamento do Paciente , Estudos RetrospectivosRESUMO
Death-associated protein kinase (DAPK) is a key player in several modes of neuronal death/injury and has been implicated in the late-onset Alzheimer's disease (AD). DAPK promotes cell death partly through its effect on regulating actin cytoskeletons. In this study, we report that DAPK inhibits microtubule (MT) assembly by activating MARK/PAR-1 family kinases MARK1/2, which destabilize MT by phosphorylating tau and related MAP2/4. DAPK death domain, but not catalytic activity, is responsible for this activation by binding to MARK1/2 spacer region, thereby disrupting an intramolecular interaction that inhibits MARK1/2. Accordingly, DAPK(-/-) mice brain displays a reduction of tau phosphorylation and DAPK enhances the effect of MARK2 on regulating polarized neurite outgrowth. Using a well-characterized Drosophila model of tauopathy, we show that DAPK exerts an effect in part through MARK Drosophila ortholog PAR-1 to induce rough eye and loss of photoreceptor neurons. Furthermore, DAPK enhances tau toxicity through a PAR-1 phosphorylation-dependent mechanism. Together, our study reveals a novel mechanism of MARK activation, uncovers DAPK functions in modulating MT assembly and neuronal differentiation, and provides a molecular link of DAPK to tau phosphorylation, an event associated with AD pathology.
Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Sistema de Sinalização das MAP Quinases , Microtúbulos/metabolismo , Neurônios/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas tau/metabolismo , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Animais , Diferenciação Celular , Linhagem Celular , Proteínas Quinases Associadas com Morte Celular , Drosophila , Ativação Enzimática , Humanos , Camundongos , Microtúbulos/ultraestrutura , Neurônios/ultraestrutura , FosforilaçãoRESUMO
The atmospheric fluxes of N(2)O, CH(4) and CO(2) from the soil in four mangrove swamps in Shenzhen and Hong Kong, South China were investigated in the summer of 2008. The fluxes ranged from 0.14 to 23.83 micromol m(-2)h(-1), 11.9 to 5168.6 micromol m(-2)h(-1) and 0.69 to 20.56 mmol m(-2)h(-1) for N(2)O, CH(4) and CO(2), respectively. Futian mangrove swamp in Shenzhen had the highest greenhouse gas fluxes, followed by Mai Po mangrove in Hong Kong. Sha Kong Tsuen and Yung Shue O mangroves in Hong Kong had similar, low fluxes. The differences in both N(2)O and CH(4) fluxes among different tidal positions, the landward, seaward and bare mudflat, in each swamp were insignificant. The N(2)O and CO(2) fluxes were positively correlated with the soil organic carbon, total nitrogen, total phosphate, total iron and NH(4)(+)-N contents, as well as the soil porosity. However, only soil NH(4)(+)-N concentration had significant effects on CH(4) fluxes.