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Driver genomic mutations in tumors define specific molecular subtypes that display distinct malignancy competence, therapeutic resistance and clinical outcome. Although TP53 mutation has been identified as the most common mutation in hepatocellular carcinoma (HCC), current understanding on the biological traits and therapeutic strategies of this subtype has been largely unknown. Here, we reveal that fatty acid ß oxidation (FAO) is remarkable repressed in TP53 mutant HCC and which links to poor prognosis in HCC patients. We further demonstrate that carnitine palmitoyltransferase 1 (CPT1A), the rate-limiting enzyme of FAO, is universally downregulated in liver tumor tissues, and which correlates with poor prognosis in HCC and promotes HCC progression in the de novo liver tumor and xenograft tumor models. Mechanically, hepatic Cpt1a loss disrupts lipid metabolism and acetyl-CoA production. Such reduction in acetyl-CoA reduced histone acetylation and epigenetically reprograms branched-chain amino acids (BCAA) catabolism, and leads to the accumulation of cellular BCAAs and hyperactivation of mTOR signaling. Importantly, we reveal that genetic ablation of CPT1A renders TP53 mutant liver cancer mTOR-addicted and sensitivity to mTOR inhibitor AZD-8055 treatment. Consistently, Cpt1a loss in HCC directs tumor cell therapeutic response to AZD-8055. CONCLUSION: Our results show genetic evidence for CPT1A as a metabolic tumor suppressor in HCC and provide a therapeutic approach for TP53 mutant HCC patients.
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Carcinoma Hepatocelular , Carnitina O-Palmitoiltransferase , Neoplasias Hepáticas , Mutação , Proteína Supressora de Tumor p53 , Humanos , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Carnitina O-Palmitoiltransferase/antagonistas & inibidores , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Animais , Camundongos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Aminoácidos de Cadeia Ramificada/metabolismo , Linhagem Celular Tumoral , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Metabolismo dos Lipídeos/genética , Transdução de Sinais , Acetilcoenzima A/metabolismo , Regulação Neoplásica da Expressão Gênica , MasculinoRESUMO
BACKGROUND AND AIMS: The immunosuppressive tumor microenvironment (TME) plays an essential role in cancer progression and immunotherapy response. Despite the considerable advancements in cancer immunotherapy, the limited response to immune checkpoint blockade (ICB) therapies in patients with hepatocellular carcinoma (HCC) remains a major challenge for its clinical implications. Here, we investigated the molecular basis of the protein O-fucosyltransferase 1 (POFUT1) that drives HCC immune evasion and explored a potential therapeutic strategy for enhancing ICB efficacy. METHODS: De novo MYC/Trp53-/- liver tumor and the xenograft tumor models were used to evaluate the function of POFUT1 in immune evasion. Biochemical assays were performed to elucidate the underlying mechanism of POFUT1-mediated immune evasion. RESULTS: We identified POFUT1 as a crucial promoter of immune evasion in liver cancer. Notably, POFUT1 promoted HCC progression and inhibited T-cell infiltration in the xenograft tumor and de novo MYC/Trp53-/- mouse liver tumor models. Mechanistically, we demonstrated that POFUT1 stabilized programmed death ligand 1 (PD-L1) protein by preventing tripartite motif containing 21-mediated PD-L1 ubiquitination and degradation independently of its protein-O-fucosyltransferase activity. In addition, we further demonstrated that PD-L1 was required for the tumor-promoting and immune evasion effects of POFUT1 in HCC. Importantly, inhibition of POFUT1 could synergize with anti-programmed death receptor 1 therapy by remodeling TME in the xenograft tumor mouse model. Clinically, POFUT1 high expression displayed a lower response rate and worse clinical outcome to ICB therapies. CONCLUSIONS: Our findings demonstrate that POFUT1 functions as a novel regulator of tumor immune evasion and inhibition of POFUT1 may be a potential therapeutic strategy to enhance the efficacy of immune therapy in HCC.
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Antígeno B7-H1 , Fucosiltransferases , Imunoterapia , Neoplasias Hepáticas , Fucosiltransferases/metabolismo , Fucosiltransferases/genética , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/tratamento farmacológico , Humanos , Camundongos , Animais , Antígeno B7-H1/metabolismo , Imunoterapia/métodos , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Evasão Tumoral , Microambiente Tumoral , Evasão da Resposta Imune , Linhagem Celular TumoralRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the major causes of death from cancer and has a very poor prognosis with few effective therapeutic options. Despite the approval of lenvatinib for the treatment of patients suffering from advanced HCC, only a small number of patients can benefit from this targeted therapy. METHODS: Diethylnitrosamine (DEN)-CCL4 mouse liver tumour and the xenograft tumour models were used to evaluate the function of KDM6A in HCC progression. The xenograft tumour model and HCC cell lines were used to evaluate the role of KDM6A in HCC drug sensitivity to lenvatinib. RNA-seq and ChIP assays were conducted for mechanical investigation. RESULTS: We revealed that KDM6A exhibited a significant upregulation in HCC tissues and was associated with an unfavourable prognosis. We further demonstrated that KDM6A knockdown remarkably suppressed HCC cell proliferation and migration in vitro. Moreover, hepatic Kdm6a loss also inhibited liver tumourigenesis in a mouse liver tumour model. Mechanistically, KDM6A loss downregulated the FGFR4 expression to suppress the PI3K-AKT-mTOR signalling pathway, leading to a glucose and lipid metabolism re-programming in HCC. KDM6A and FGFR4 levels were positively correlated in HCC specimens and mouse liver tumour tissues. Notably, KDM6A knockdown significantly inhibited the efficacy of lenvatinib therapy in HCC cells in vitro and in vivo. CONCLUSIONS: Our findings revealed that KDM6A promoted HCC progression by activating FGFR4 expression and may be an essential molecule for influencing the efficacy of lenvatinib in HCC therapy.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Fosfatidilinositol 3-Quinases , Compostos de Fenilureia/farmacologia , Compostos de Fenilureia/uso terapêutico , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/genéticaRESUMO
BACKGROUND AND AIMS: Epigenetic plasticity is a major challenge in cancer-targeted therapy. However, the molecular basis governing this process has not yet been clearly defined. Despite the considerable success of poly(ADP-ribose) polymerase inhibitors (PARPi) in cancer therapy, the limited response to PARPi, especially in HCC, has been a bottleneck in its clinical implications. Herein, we investigated the molecular basis of the histone methyltransferase KMT5C (lysine methyltransferase 5C) that governs PARPi sensitivity and explored a potential therapeutic strategy for enhancing PARPi efficacy. APPROACH AND RESULTS: We identified KMT5C, a trimethyltransferase of H4K20, as a targetable epigenetic factor that promoted liver tumor growth in mouse de novo MYC/Trp53-/- and xenograft liver tumor models. Notably, induction of KMT5C by environmental stress was crucial for DNA repair and HCC cell survival. Mechanistically, KMT5C interacted with the pivotal component of homologous recombination repair, RAD51, and promoted RAD51/RAD54 complex formation, which was essential for the activation of dsDNA breaks repair. This effect depended on the methyltransferase activity of KMT5C. We further demonstrated that the function of KMT5C in promoting HCC progression was dependent on RAD51. Importantly, either a pharmacological inhibitor (A196) or genetic inhibition of KMT5C sensitized liver cancer cells to PARPi. CONCLUSIONS: KMT5C played a vital role in promoting liver cancer progression by activating the DNA repair response. Our results revealed a novel therapeutic approach using the KMT5C inhibitor A196, concurrent with olaparib, as a potential HCC therapy.
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MAIN CONCLUSION: Overexpression of SaAQP can improve the salt tolerance of transgenic soybean hairy roots and A. thaliana. Salt stress severely affects crop yield and food security. There is a need to improve the salt tolerance of crops, but the discovery and utilization of salt-tolerance genes remains limited. Owing to its strong stress tolerance, Sophora alopecuroides is ideal for the identification of salt-tolerance genes. Therefore, we aimed to screen and identify the salt-tolerance genes in S. alopecuroides. With a yeast expression library of seedlings, salt-tolerant genes were screened using a salt-containing medium to simulate salt stress. By combining salt-treatment screening and transcriptome sequencing, 11 candidate genes related to salt tolerance were identified, including genes for peroxidase, inositol methyltransferase, aquaporin, cysteine synthase, pectinesterase, and WRKY. The expression dynamics of candidate genes were analyzed after salt treatment of S. alopecuroides, and salt tolerance was verified in yeast BY4743. The candidate genes participated in the salt-stress response in S. alopecuroides, and their overexpression significantly improved the salt tolerance of yeast. Salt tolerance mediated by SaAQP was further verified in soybean hairy roots and Arabidopsis thaliana, and it was found that SaAQP might enhance the salt tolerance of A. thaliana by participating in a reactive oxygen species scavenging mechanism. This result provides new genetic resources in plant breeding for salt resistance.
Assuntos
Tolerância ao Sal , Sophora , Regulação da Expressão Gênica de Plantas , Melhoramento Vegetal , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Tolerância ao Sal/genética , Sophora/genética , Sophora/metabolismo , Estresse FisiológicoRESUMO
Aim: We aimed to examine the association between baseline mean platelet volume/platelet count ratio (MPR) and all-cause mortality in patients with infective endocarditis (IE). Patients & methods: This study analyzed 218 consecutive patients with IE and divided them into four groups based on MPR quartiles. We used Kaplan-Meier survival curves to determine the cumulative survival and Cox proportional hazards models to investigate the association between MPR and all-cause mortality after hospital discharge. Results: Kaplan-Meier curves showed a gradual increase in mortality risk from the lowest MPR quartile to the highest quartile. Multivariate analysis revealed that MPR was an independent predictor of increased risk for all-cause death. Conclusion: Elevated MPR was independently associated with long-term all-cause mortality in patients with IE.
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Endocardite/diagnóstico , Endocardite/mortalidade , Volume Plaquetário Médio , Contagem de Plaquetas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Medição de RiscoRESUMO
Nitrogen (N), phosphorus (P), and potassium (K) exert various effects on adzuki bean yields. Our research was conducted in a semi-arid area, and four test sites were established in environments that have chernozem or sandy loam soils. During a five-year period, the effects of N, P, and K fertilizers on yield were comprehensively investigated in field trials (2014-2016) and for model-implementation trials (2017-2018), with models established prior to the latter. In the field trials, 23 treatments comprising different N, P, and K combinations significantly affected both yield and yield components, and regression analysis indicated that the experimental results were suitable for model establishment. The model subsequently demonstrated that the yield and the yield components were more sensitive to N and K fertilizer than to P fertilizer. Moreover, the yield and yield components increased. These yield increases were intense in response to the 0.5 to 1.34 levels in terms of the single effects; interaction effects; and the effects of combinations of N, P, and K fertilizers. Moreover, the effects of combinations of N, P, and K fertilizers were more significant on yield than were the single or interaction effects of N, P, and K fertilizers. The optimal fertilizer combination that resulted in high yields (≥1941.53 kg ha-1) comprised 57.23-68.43 kg ha-1 N, 36.04-47.32 kg ha-1 P2O5 and 50.29-61.27 kg ha-1 K2O. The fertilizer combination that resulted in the maximum yield was 62.98 kg ha-1 N, 47.04 kg ha-1 P2O5 and 59.95 kg ha-1 K2O (N:P2O5:K2O = 1:0.75:0.95), which produced the model-expected yield in trials at multiple sites. An economical fertilizer combination was determined on the basis of the best fertilizer measures in consideration of the cost of fertilizer and seed; this combination achieved yields of 2236.17 kg ha-1, the profit was 15,653.16 Yuan ha-1, and the corresponding rates were 57.60 kg ha-1 N, 47.03 kg ha-1 P2O5, and 31.64 kg ha-1 K2O (N:P2O5:K2O = 1:0.82:0.55).
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Clima Desértico , Fertilizantes , Nitrogênio/farmacologia , Fósforo/farmacologia , Potássio/farmacologia , Vigna/crescimento & desenvolvimento , China , Fertilizantes/economia , Modelos Teóricos , Análise de Regressão , Vigna/efeitos dos fármacosRESUMO
Mung bean (Vigna radiata L.) is an important edible bean in the human diet worldwide. However, its growth, development, and yield may be restricted or limited by insufficient or unbalanced nitrogen (N), phosphorus (P), and potassium (K) fertilization. Despite this, there are few long-term studies of the effects of varying levels of N, P, and K combined fertilizers and the optimal fertilization for improving mung bean yield and quality. This study was conducted to optimize the fertilization strategies for high yield and to improve yield components (pods per plant, seeds per pod, and 100-seed weight) in the Bailv9 mung bean cultivar, 23 treatments were tested in 2013-2015, using a three-factor (N, P, and K fertilizers), five-level quadratic orthogonal rotation combination design. Our studies showed that, the N, P, and K fertilizers significantly influenced the pods per plant and yield, which increased and then decreased with the increasing N, P, and K fertilizers. The 100-seed weight was significantly affected by the N and P fertilization, and it was increased consistently with the increasing N fertilizer, and decreased significantly with the increasing P fertilizer. Whereas, the seeds per pod significantly decreased with the increasing N and K fertilizers, and the P fertilizer had no significant effect on it. The NP interaction had a significant effect on yield and pods per plant at high N levels, while the NK interaction had a significant but opposite effect on yield at low N levels. The optimal fertilization conditions to obtain yield >2,141.69 kg ha-1 were 34.38-42.62 kg ha-1 N, 17.55-21.70 kg ha-1 P2O5, and 53.23-67.29 kg ha-1 K2O. Moreover, the optimal N, P, and K fertilization interval to achieve pods per plant > 23.41 and the optimal N fertilization to achieve a 100-seed weight > 6.58 g intersected with the interval for yield, but the seeds per pod did not. The fertilizer ratio for the maximum yield was N:P2O5:K2O = 1:0.5:1.59. Following three years experimentation, the optimal fertilization measures were validated in 2016-2017, the results indicated that yield increased by 19.6% than that obtained using conventional fertilization. The results of this study provide a theoretical basis and technical guidance for high-yield mung bean cultivation using the optimal fertilization measures.
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Fertilizantes , Nitrogênio/metabolismo , Fósforo/metabolismo , Potássio/metabolismo , Vigna/crescimento & desenvolvimento , Agricultura/métodos , Produtos Agrícolas/crescimento & desenvolvimentoRESUMO
AIM: To study the expression of Rho kinase (Rho associated coil forming protein kinase-1, ROCK-1) and its substrate myosin phosphatase target subunit 1 (myosin phosphatase target subunit-1, MYPT-1), connexin 40 (Cx40) and connexin 43 (Cx43) in the left atrial appendage of patients with atrial fibrillation, and explore the role of ROCK signaling pathway in patients with atrial fibrillation and its underlying mechanism. Methods: 40 patients undergoing open heart surgery were divided into two groups; atrial fibrillation group (AF group) and sinus rhythm group (SR group). About 100 mg of left atrial appendage tissue was taken during surgery and quickly frozen in liquid nitrogen. Immunohistochemistry and western blot were performed to evaluate the expression and location of ROCK-1, MYPT-1, Cx40 and Cx43 in the left atrial appendage tissue. Results: The results indicated that the expression of ROCK-1, MYPT-1, and Cx40 in the left atrial appendage in patients with atrial fibrillation was significantly upregulated (P < .01), the difference in the two groups was statistically significant, and ROCK-1, Cx40, and MYPT-1 expression in the AF group were higher than those in sinus rhythm group; there was a weakly positive expression of Cx43 protein in the AF group and sinus rhythm group, the difference was not statistically significant, and ROCK-1 and MYPT-1 expression showed a significant positive correlation (r = 0.968, P < .05), MYPT 1 and Cx40 protein expression was also positively correlated (r = 0.983, P < .05). Evidence in the left atrial appendage tissue of patients with atrial fibrillation showed that some proteins in Rho/ROCK pathway were upregulated, and MYPT-1 and Cx40 protein expression in AF group were significantly higher than that of SR group, which was also positively correlated; Cx43 showed a weak positive expression in both the SR group and AF group, which indicates that Rho kinase may induce expression of Cx40 by phosphorylation of MYPT-1; Cx43 may not be involved, suggesting that Rho kinase signaling pathway may activate and play an important role in the pathogenesis of atrial fibrillation lesions.
Assuntos
Apêndice Atrial/enzimologia , Fibrilação Atrial/genética , Regulação da Expressão Gênica , RNA/genética , Quinases Associadas a rho/biossíntese , Adulto , Idoso , Fibrilação Atrial/enzimologia , Biomarcadores/metabolismo , Western Blotting , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Isoflavonoids are secondary metabolites that play a variety of roles in plant-microbe interactions and plant defenses against abiotic stresses. Here we report a new MYB transcription factor (TF) gene, GmMYBJ3, that is involved in the isoflavonoids biosynthesis. The GmMYBJ3 gene is 1,002 bp long and encodes a protein of 333 amino acids. Amino acid sequence analysis showed that GmMYBJ3 is a typical R2R3 MYB TF. Yeast expression experiment demonstrated that GmMYBJ3 has its transcription activity in the nucleus and is transiently expressed in onion epidermal cells. The GmMYBJ3 gene was transformed into soybean and the expression activity of the GmMYBJ3 gene was significantly positively correlated with total isoflavonoid accumulation in soybean. Transient expression assays indicated that GmMYBJ3 can activate CHS8 expression. Furthermore, we analyzed the expressions of several genes known involved in the isoflavonoid biosynthesis, including CHS8, CHI1A, PAL1, IFS2 and F3H, in the GmMYBJ3 transgenic plants. The results showed that the expression levels of CHS8 and CHI1A were significantly increased in the transgenic plants compared to wild-type plants, but those of PAL1, IFS2 and F3H remained similar between the transgenic and wild-type plants. These results suggest that GmMYBJ3 participates in the isoflavonoid biosynthesis through regulation of CHS8 and CHI1A in soybean.
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Regulação da Expressão Gênica de Plantas , Glycine max/metabolismo , Isoflavonas/metabolismo , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Glycine max/genética , Fatores de Transcrição/genéticaRESUMO
Aim We aimed to identify clinical characteristics and risk factors associated with onset of high-altitude headache (HAH) after acute exposure at 3700 m. Method In two hours, 163 individuals ascended by plane to 3700 m. Demographic information, physiological and psychological measurements, cognitive function, physical work capacity tests and profile of mood states within one week prior to the departure and within 24 hours after arrival were examined. Results HAH patients featured significantly higher vertebral artery diastolic velocity (Vd), heart rate (HR) and pulmonary artery diameter. HAH was also associated with a more negative mood state, including scores for tension anxiety, depression, hostility, fatigue and confusion, as well as lower vigor (all p values <0.05). Furthermore, negative emotions were positively related to HAH severity. HAH slightly decreased cognitive functioning. HR, Vd, lack of vigor, confusion and self-reported anxiety (all p values <0.05) were independent risk factors for HAH. We have identified three independent baseline predictors for HAH including internal diameter of the left ventricle (LVD), Athens Insomnia Scale (AIS) and confusion score. Conclusions Higher HR, Vd, confusion and self-reported anxiety and insufficient vigor were independent risk factors for HAH. Furthermore, higher baseline LVD, AIS and confusion score are independent predictors of HAH.
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Doença da Altitude/fisiopatologia , Doença da Altitude/psicologia , Cefaleia/etiologia , Hemodinâmica/fisiologia , Adolescente , Povo Asiático , Ventrículos do Coração/anatomia & histologia , Humanos , Masculino , Fatores de RiscoRESUMO
This study aims to evaluate the effect of the duration of high-altitude (HA) pre-exposure on human neurobehavioral parameters including mood states and cognitive performance at HA. One hundred and eleven healthy individuals (ranging in age from 18 to 35 years) were recruited to participate in this study. They were divided into two groups: a 4-day short-term HA pre-exposure group (n=57) and a 3-month long-term HA pre-exposure group (n=54). All participants lived in the area at 400 m altitude above sea level before pre-exposure to HA. They were then transported to 3700 m plateau for either a 4-day or a 3-month HA pre-exposure, and finally delivered to 4400 m plateau. On the last day of pre-exposure at 3700 m and on the 10th day at 4400 m, neurobehavioral parameters of the participants in the two groups were evaluated. At the end of pre-exposure and on the 10th day of HA exposure, participants in the short-term group had significantly lower negative mood states, better cognitive performance with higher sensorimotor, attention, and psychomotor abilities, and less acute mountain sickness in comparison with the participants in the long-term pre-exposure group. Our field study with large samples showed that in comparison with 3-month long-term pre-exposure, 4-day short-term HA pre-exposure at 3700 m has a better effect in improving human neurobehavioral parameters including mood states and cognitive performance and reducing acute mountain sickness when exposed to a HA at 4400 m.
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Afeto/fisiologia , Altitude , Cognição/fisiologia , Adolescente , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Militares , Testes Neuropsicológicos , Estudos Retrospectivos , Estatística como Assunto , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Oral glucocorticoids can prevent acute mountain sickness (AMS). Whether inhaled budesonide (BUD) can prevent AMS remains unknown. OBJECTIVE: Our aim was to investigate the effectiveness of BUD in AMS prevention. METHODS: Eighty subjects were randomly assigned to receive budesonide (BUD, inhaled), procaterol tablet (PT), budesonide/formoterol (BUD/FM, inhaled), or placebo tablet (n = 20 in each group). Subjects were treated for 3 days before ascending from 500 m to 3700 m within 2.5 h by air. Lake Louis AMS questionnaire, blood pressure, heart rate, and oxygen saturation (SpO2) were examined at 20, 72, and 120 h after high-altitude exposure. Pulmonary function was measured at 20 h after exposure. RESULTS: Compared with placebo, BUD significantly reduced the incidence of AMS (70% vs. 25% at 20 h, p < 0.05; both 10% vs. 5% at 72 and 120 h, both p > 0.05) without side effects. The relative risk was 0.357, and the risk difference was 0.45. Mean SpO2 was higher in BUD, BUD/FM, and PT groups than in the placebo group at 20 h (p < 0.05). SpO2 in all 80 subjects dropped after ascent (98.1% to 88.12%, p < 0.01) and increased gradually, but it was still lower at 120 h than at baseline (92.04% vs. 98.1%, p < 0.01). Pulmonary function did not differ among the four groups at 20 h. CONCLUSION: BUD can prevent AMS without side effects. The alleviation of AMS may be related to increased blood oxygen levels rather than pulmonary function.
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Doença da Altitude/prevenção & controle , Broncodilatadores/administração & dosagem , Budesonida/administração & dosagem , Glucocorticoides/administração & dosagem , Doença Aguda , Adolescente , Adulto , Doença da Altitude/fisiopatologia , Pressão Sanguínea/fisiologia , China , Volume Expiratório Forçado/fisiologia , Frequência Cardíaca/fisiologia , Humanos , Masculino , Consumo de Oxigênio/fisiologia , Capacidade Vital/fisiologia , Adulto JovemRESUMO
INTRODUCTION: Epidemiological studies evaluating the association of nut with risk of coronary artery disease (CAD) have produced inconsistent results. We conducted a meta-analysis to summarize the evidence from prospective cohort studies regarding the association between nut consumption and risk of CAD. MATERIALS AND METHODS: Pertinent studies were identified by searching Web of Knowledge, Pubmed and Wan Fang Med Online up to January 2014. Random-effect model was used to combine the results. Dose-response relationship was assessed by restricted cubic spline. Publication bias was estimated using Begg' funnel plot and Egger's regression asymmetry test. RESULTS: Nine articles with 13 prospective studies involving 6,127 CAD cases and 347,477 participants were included in this meta-analysis. Pooled results suggested that highest nut consumption amount versus lowest amount was significantly associated with the risk of CAD [summary relative risk (RR)=0.660, 95%CI=0.581-0.748, I(2)=39.6%]. Linear dose-response relationship was found between nut consumption and CAD risk, and the risk of CAD decreased by 5% for every 1 serving/week increase intake of nut. A protective effect for CAD was found when consumed more than 2 servings/week of nut. The RR of CAD was 0.96 (0.89-1.02), 0.91 (0.82-0.99), 0.85 (0.77-0.95), 0.80 (0.72-0.89), 0.75 (0.65- 0.85) and 0.70 (0.58-0.83) for 1, 2, 3, 4, 5 and 6 servings/week of nut consumption, respectively. CONCLUSIONS: Our analysis indicated that nut consumption has a protective effect on CAD.
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Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/prevenção & controle , Nozes/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/metabolismo , Comportamento Alimentar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVE: The clinical evidence regarding the influence of tailored antiplatelet strategy on adverse outcomes has been controversial. The aim of the study was to evaluate the significance of tailored antiplatelet therapy with respect to clinical adverse events in antiplatelet-resistant patients. METHODS: Randomised studies that assess clinical relevance of personalised antiplatelet treatment in antiplatelet-resistant patients were identified through a literature search: PubMed, EMBASE, Web of Science and the Cochrane Library. The primary endpoint was the composite of death from any cause and stent thrombosis. All total clinical adverse events and bleeding complications were evaluated. RESULTS: Data were combined across seven randomised studies comprising 12 048 subjects, of whom 3738 (31.0%) were found to be antiplatelet-resistant. Antiplatelet-resistant patients provided with tailored antiplatelet therapy showed less risk of death or stent thrombosis than those assigned conventional antiplatelet treatment (0.5% vs. 2.2%; OR (95% CI) 0.25 (0.13 to 0.49), p<0.0001). A significant benefit in terms of total adverse event risk reduction was observed during follow-up for tailored vs conventional antiplatelet therapy (5.5% vs. 10.0%; OR (95% CI) 0.40 (0.20 to 0.77), p=0.006). No statistical difference in bleeding complications was observed between these two groups (p=0.08). CONCLUSIONS: In the study, personalised antiplatelet treatment for antiplatelet resistance was found to be associated with less occurrence of death or stent thrombosis and the less risk of total clinical adverse events than conventional treatment, without increasing the risk of bleeding complications.
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Doenças Cardiovasculares/prevenção & controle , Hemorragia/induzido quimicamente , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Hemorragia/epidemiologia , Humanos , IncidênciaRESUMO
AIM: Previous meta-analyses have demonstrated an increased risk of adverse events in aspirin-resistant patients. In this meta-analysis, we aimed to update clinical evidence regarding the relationship between aspirin resistance and major adverse cardiovascular events (MACEs) in patients with coronary heart disease (CHD) on confirmed aspirin adherence. METHODS: An electronic literature search of PubMed, EMBASE, Web of Science and the Cochrane Library and a hand search of bibliographies through April 2013 were conducted. Studies were included if they prospectively investigated the association between aspirin resistance and the risk of adverse cardiovascular events during follow-up in CHD patients, mentioned confirmed compliance and provided adequate data for a statistical analysis. RESULTS: Nine prospective studies with a total 1,889 CHD patients who were followed for one month to 2.5 years and study sample sizes ranging from 86 to 496 patients were identified. Overall, 622 of the 1,889 CHD patients (33.0%) were classified as being aspirin resistant with confirmed aspirin adherence. The aspirin-resistant patients exhibited a significantly higher risk of adverse events than the aspirin-sensitive patients (odds ratio 2.44, 95% confidence interval 1.81 to 3.30; pï¼0.00001). CONCLUSIONS: Among CHD patients, approximately one in three individuals can be diagnosed as aspirin resistant on confirmed aspirin adherence. Patients identified as having laboratory aspirin resistance exhibit a 2.4-fold increased risk of MACE compared with aspirin-sensitive patients.