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BACKGROUND: Emerging evidence suggested that S-adenosylhomocysteine (SAH) may be a better serum biomarker for cardiovascular disease than homocysteine (Hcy). However, the role of SAH in hepatocellular carcinoma (HCC) prognosis remains unclear. OBJECTIVES: We aimed to prospectively explore the relationships between serum SAH and related metabolites [Hcy, S-adenosylmethionine (SAM)] with HCC survival, and to evaluate the effect modifications by gene polymorphisms in one-carbon metabolism key enzymes. METHODS: We included 1080 newly diagnosed patients with HCC from the Guangdong Liver Cancer Cohort. Serum SAH, Hcy, and SAM were measured utilizing high-performance liquid chromatography-tandem mass spectrometry. Gene polymorphisms in one-carbon metabolism key enzymes were identified using kompetitive allele-specific polymerase chain reaction. Primary outcomes were liver cancer-specific survival (LCSS) and overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using multivariate Cox proportional hazards models. RESULTS: After a median follow-up of 3.6 y, 601 deaths occurred, with 552 (92%) attributed to HCC. Multivariable analysis revealed that patients in the highest quartile of serum SAH concentrations were significantly associated with worse survival compared with those in the lowest quartile, with HRs of 1.58 (95% CI: 1.19, 2.10; P-trend = 0.002) for LCSS and 1.54 (95% CI: 1.18, 2.02; P-trend = 0.001) for OS. There were no significant interactions between serum SAH concentrations and genetic variants of one-carbon metabolism key enzymes. No significant associations were found between serum Hcy, SAM concentrations, and SAM/SAH ratio with LCSS or OS. CONCLUSIONS: Higher serum SAH concentrations, rather than Hcy, were independently associated with worse survival in patients with HCC, regardless of the genetic variants of one-carbon metabolism key enzymes. These findings suggest that SAH may be a novel metabolism-related prognostic biomarker for HCC.
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Carcinoma Hepatocelular , Homocisteína , Neoplasias Hepáticas , S-Adenosil-Homocisteína , Humanos , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , S-Adenosil-Homocisteína/sangue , Masculino , Feminino , Homocisteína/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , S-Adenosilmetionina/sangue , Estudos de Coortes , PrognósticoRESUMO
BACKGROUND: Trimethylamine-N-oxide (TMAO) is linked with obesity, while limited evidence on its relationship with body fat distribution. Herein, we investigated the associations between serum TMAO and longitudinal change of fat distribution in this prospective cohort study. METHODS: Data of 1964 participants (40-75y old) from Guangzhou Nutrition and Health Study (GNHS) during 2008-2014 was analyzed. Serum TMAO concentration was quantified by HPLC-MS/MS at baseline. The body composition was assessed by dual-energy X-ray absorptiometry at each 3-y follow-up. Fat distribution parameters were fat-to-lean mass ratio (FLR) and trunk-to-leg fat ratio (TLR). Fat distribution changes were derived from the coefficient of linear regression between their parameters and follow-up duration. RESULTS: After an average of 6.2-y follow-up, analysis of covariance (ANCOVA) and linear regression displayed women with higher serum TMAO level had greater increments in trunk FLR (mean ± SD: 1.47 ± 4.39, P-trend = 0.006) and TLR (mean ± SD: 0.06 ± 0.24, P-trend = 0.011). Meanwhile, for women in the highest TMAO tertile, linear mixed-effects model (LMEM) analysis demonstrated the annual estimated increments (95% CI) were 0.03 (95% CI: 0.003 - 0.06, P = 0.032) in trunk FLR and 1.28 (95% CI: -0.17 - 2.73, P = 0.083) in TLR, respectively. In men, there were no similar significant observations. Sensitivity analysis yielded consistent results. CONCLUSION: Serum TMAO displayed a more profound correlation with increment of FLR and TLR in middle-aged and older community-dwelling women in current study. More and further studies are still warranted in the future. TRIAL REGISTRATION: NCT03179657.
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Distribuição da Gordura Corporal , Metilaminas , Humanos , Metilaminas/sangue , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Prospectivos , Idoso , Distribuição da Gordura Corporal/métodos , Adulto , Absorciometria de Fóton/métodos , Composição Corporal , Estudos de Coortes , ChinaRESUMO
Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated death. Emerging evidence suggests that autophagy plays a critical role in HCC tumorigenesis, metastasis, and prognosis. Choline is an essential nutrient related to prolonged survival and reduced risk of HCC. However, it remains unclear whether this phenomenon is mediated by autophagy. Methods: Two HCC cell lines (HUH-7 and Hep3B) were used in the present study. Cell growth was evaluated by cell counting kit 8 (CCK-8), colony formation, and in vivo mouse xenografts assays. Cell motility was calculated by wound healing and transwell assays. Autophagosomes were measured by transmission electron microscope (TEM), and autophagy flux was detected by mRFP-GFP-labeled LC3 protein. The mRNA level of genes was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels were detected by Western blotting (WB). Results: We found that choline inhibited the proliferation, migration, and invasion of HCC cells by downregulating autophagy in vitro and in vivo. Upregulated expression of the solute carrier family 5 member 7 (SLC5A7), a specific choline transporter, correlated with better HCC prognosis. We further discovered that choline could promote SLC5A7 expression, upregulate cytoplasm p53 expression to impair the AMPK/mTOR pathway, and attenuate autophagy. Finally, we found that choline acted synergistically with sorafenib to attenuate HCC development in vitro and in vivo. Conclusions: Our findings provide novel insights into choline-mediated autophagy in HCC, providing the foothold for its future application in HCC treatment.
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BACKGROUND & AIMS: Increasing dietary protein intake can be an efficient strategy to prevent sarcopenia. Nevertheless, due to the discrepancy in the population and their dietary pattern, evidence suggested the effects of dietary protein amount or source on sarcopenia prevention varies. This prospective cohort study investigated the correlation between dietary protein intakes or sources and changes in muscle mass measurements. Additionally, the study explored the link between dietary protein and the prevalence of sarcopenia. METHODS: Participants aged 40 to 75 were from Guangzhou Nutrition and Health Study (GNHS) 2011-2013 and returned in 2014-2017. Validated 79-item food frequency questionnaires were applied to calculate the amount of total, animal, and plant protein intakes and animal-to-plant protein ratio (APR). The body composition was examined by dual-energy x-ray absorptiometry (DXA) to calculate the appendicular lean mass (ALM) and its index (ASMI). Sarcopenia was diagnosed based on the 2019 Asia Working Group of Sarcopenia's criteria. ANCOVA was utilized to compare the differences of Δ ALM and Δ ASMI across the quartiles of the dietary protein, and linear regression was employed to examine dose-response associations. Multilinear mixed-effect models were employed to evaluate whether protein intake relates to annual changes in ALM and ASMI. Multivariable logistic regressions were performed to analyze the associations between dietary protein and sarcopenia. RESULTS: In total, 2709 participants during the 3.2-year follow-up period were considered eligible for analysis. Higher dietary protein intakes (total, animal, plant) in both sexes could preserve more ALM and ASMI in a dose-response manner (all P-trend < 0.05). The annual estimated preservations of ASMI were greater in the highest dietary protein intakes (total, animal, plant) quartile than the lowest (0.05-0.13 kg/m2/y, all P < 0.05). In women, the risk of sarcopenia was reduced by 35%-50 % in the highest protein intake (total, animal, plant) quartile than the lowest. The APR did not display any significant associations. CONCLUSIONS: Higher dietary protein intake, regardless of animal or plant sources, is associated with less muscle loss and a lower prevalence of sarcopenia in middle-aged and older Chinese, particularly women. GOV IDENTIFIER: NCT03179657.
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Sarcopenia , Masculino , Pessoa de Meia-Idade , Humanos , Feminino , Idoso , Sarcopenia/epidemiologia , Sarcopenia/prevenção & controle , Sarcopenia/complicações , Proteínas Alimentares , Músculo Esquelético/fisiologia , Estudos Prospectivos , Vida Independente , Composição Corporal/fisiologia , Absorciometria de Fóton , Proteínas de PlantasRESUMO
The impact of betaine on the development of hypertension remains unclear, and prospective data are sparse. We aimed to investigate the association of serum betaine with repeated measurements of blood pressure (BP) and hypertension incidence. This study was based on the Guangzhou Nutrition and Health Study (GNHS), a community-based prospective cohort study in China. Baseline serum betaine was measured by high-performance liquid chromatography-tandem mass spectrometry. BP and hypertension status were assessed at the baseline and 3-year intervals. Linear mixed-effects models (LMEMs) were used to analyze the longitudinal association of serum betaine with BP (n = 1996). Cox proportional hazard models were used to evaluate the association of baseline serum betaine with hypertension incidence (n = 1339). LMEMs showed that compared with the lowest quartile group, the higher quartile groups had lower systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (all P-trend < 0.05). Each standard deviation (16.3 µmol L-1) increase in serum betaine was associated with -0.92 (-1.52, -0.32) mmHg of SBP, -0.49 (-0.84, -0.13) mmHg of DBP and -0.43 (-0.81, -0.05) mmHg of pulse pressure. During a median follow-up of 9.2 years, 371 incident cases of hypertension were identified. Serum betaine was associated with lower risk of hypertension only when comparing the third quartile level with the lowest quartile (HR, 0.74; 95% CI, 0.56-0.99). A nonlinear association between serum betaine and the risk of hypertension was found (P-nonlinear = 0.040). A higher serum betaine level was associated with lower risk of hypertension below 54.5 µmol L-1. Our findings suggested that higher serum betaine was associated with favorable blood pressure in middle-aged and older Chinese adults. Higher concentrations of serum betaine were related to lower hypertension risk in people with relatively low serum betaine concentrations.
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Hipertensão , Hipotensão , Pessoa de Meia-Idade , Humanos , Idoso , Pressão Sanguínea/fisiologia , Estudos Prospectivos , Betaína , Incidência , Hipertensão/epidemiologia , Fatores de RiscoRESUMO
We propose a scheme consisting of coupled nanomechanical cantilever resonators and superconducting flux qubits to engineer a parity-time- (P T-) symmetric phononic system formed by active and passive modes. The effective gain (loss) of the phonon mode is achieved by the longitudinal coupling of the resonator and the fast dissipative superconducting qubit with a blue-sideband driving (red-sideband driving). A P T-symmetric to broken-P T-symmetric phase transition can be observed in both balanced gain-to-loss and unbalanced gain-to-loss cases. Applying a resonant weak probe field to the dissipative resonator, we find that (i) for balanced gain and loss, the acoustic signal absorption to amplification can be tuned by changing the coupling strength between resonators; (ii) for unbalanced gain and loss, both acoustically induced transparency and anomalous dispersion can be observed around Δ = 0, where the maximum group delay is also located at this point. Our work provides an experimentally feasible scheme to design P T-symmetric phononic systems and a powerful platform for controllable acoustic signal transmission in a hybrid quantum system.
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PURPOSE: To test the hypothesis that daily supplementation with low-dose B vitamins plus betaine could significantly reduce plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia and free from background mandatory folic acid fortification. METHODS: One hundred apparently healthy adults aged 18-65 years with hyperhomocysteinemia were recruited in South China from July 2019 to June 2021. They were randomly assigned to either the supplement group (daily supplementation: 400 µg folic acid, 8 mg vitamin B6, 6.4 µg vitamin B12 and 1 g betaine) or the placebo group for 12 weeks. Fasting venous blood was collected at baseline, week 4 and week 12 to determine the concentrations of homocysteine, folate, vitamin B12 and betaine. Generalized estimation equations were used for statistical analysis. RESULTS: Statistically significant increments in blood concentrations of folate, vitamin B12 and betaine after the intervention in the supplement group indicated good participant compliance. At baseline, there were no significant differences in plasma homocysteine concentration between the two groups (P = 0.265). After 12-week supplementation, compared with the placebo group, there was a significant reduction in plasma homocysteine concentrations in the supplement group (mean group difference - 3.87; covariate-adjusted P = 0.012; reduction rate 10.1%; covariate-adjusted P < 0.001). In the supplement group, the decreased concentration of plasma homocysteine was associated with increments of blood concentrations of both folate (ß = -1.680, P = 0.004) and betaine (ß = -1.421, P = 0.020) after 12 weeks of supplementation. CONCLUSIONS: Daily supplementation with low-dose B vitamins plus betaine for 12 weeks effectively decreased plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov as NCT03720249 on October 25, 2018. Website: https://clinicaltrials.gov/ct2/show/NCT03720249 .
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Hiper-Homocisteinemia , Complexo Vitamínico B , Adulto , Humanos , Betaína , Suplementos Nutricionais , Método Duplo-Cego , População do Leste Asiático , Ácido Fólico , Homocisteína , Vitamina B 12 , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , IdosoRESUMO
Alzheimer's disease (AD) is the most common form of dementia in elderly people with a high incidence rate and complicated pathogenesis, and causes progressive cognitive deficit and memory impairment. Some natural products and bioactive compounds from natural sources show great potential in the prevention and treatment of AD, such as apple, blueberries, grapes, chili pepper, Monsonia angustifolia, cruciferous vegetables, Herba epimedii, Angelica tenuissima, Embelia ribes, sea cucumber, Cucumaria frondosa, green tea, Puer tea, Amanita caesarea and Inonotus obliquus, via reducing amyloid beta (Aß) deposition, decreasing Tau hyperphosphorylation, regulating cholinergic system, reducing oxidative stress, inhibiting apoptosis and ameliorating inflammation. This review mainly summarizes the effects of some natural products and their bioactive compounds on AD with the potential molecular mechanisms.
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Doença de Alzheimer , Produtos Biológicos , Disfunção Cognitiva , Humanos , Idoso , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/metabolismo , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Estresse OxidativoRESUMO
Cancer is the leading cause of death in the world. Curcumin is the main ingredient in turmeric (Curcuma longa L.), and is widely used in the food industry. It shows anticancer properties on different types of cancers, and the underlying mechanisms of action include inhibiting cell proliferation, suppressing invasion and migration, promoting cell apoptosis, inducing autophagy, decreasing cancer stemness, increasing reactive oxygen species production, reducing inflammation, triggering ferroptosis, regulating gut microbiota, and adjuvant therapy. In addition, the anticancer action of curcumin is demonstrated in clinical trials. Moreover, the poor water solubility and low bioavailability of curcumin can be improved by a variety of nanotechnologies, which will promote its clinical effects. Furthermore, although curcumin shows some adverse effects, such as diarrhea and nausea, it is generally safe and tolerable. This paper is an updated review of the prevention and management of cancers by curcumin with a special attention to its mechanisms of action.
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BACKGROUND: The role of trimethylamine-N-oxide (TMAO) in the development of diabetes remains controversial, and prospective data are few. We aimed to investigate the association between serum TMAO and incident type 2 diabetes in middle-aged and older adults. METHODS: This study was based on the Guangzhou Nutrition and Health Study (GNHS), a community-based prospective cohort study in China. A total of 2088 diabetes-free participants aged 40-75 years were included from 2008 to 2010. Incident type 2 diabetes was ascertained during follow-up visits. Baseline serum TMAO was measured by high-performance liquid chromatography with online electrospray ionization tandem mass spectrometry. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for diabetes across tertiles of serum TMAO were calculated using Cox proportional hazard models. Prospective associations of serum TMAO with changes in glycemic traits (fasting glucose, HbA1c, insulin, HOMA-IR) over time were estimated using linear mixed-effects models (LMEMs). RESULTS: We ascertained 254 incident type 2 diabetes cases during a median follow-up of 8.9 years. The median (interquartile range) of serum TMAO was 1.54 (0.86-2.91) µmol/L. From the first to the third tertile of serum TMAO, the multivariable-adjusted HRs for diabetes were 1.00 (reference), 1.17 (95% CI: 0.84-1.61), and 1.42 (95% CI: 1.03-1.96) (P-trend = 0.031). LMEMs showed that the estimated yearly change in fasting glucose was 0.011 (0.001-0.022) mmol/L/y in the highest tertile of serum TMAO, compared with the lowest tertile (P-interaction = 0.044). Serum TMAO was not associated with longitudinal changes in HbA1c, insulin or HOMA-IR. CONCLUSIONS: Our findings suggested that higher serum TMAO was associated with a higher risk of type 2 diabetes and an increase in fasting glucose among middle-aged and older Chinese adults. TRIAL REGISTRATION: NCT03179657. https://clinicaltrials.gov/ct2/show/NCT03179657?term=NCT03179657&draw=2&rank=1.
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Diabetes Mellitus Tipo 2 , Idoso , Glicemia , Diabetes Mellitus Tipo 2/epidemiologia , Hemoglobinas Glicadas , Humanos , Insulina , Metilaminas , Pessoa de Meia-Idade , Óxidos , Estudos Prospectivos , Fatores de RiscoRESUMO
Dietary intake of one-carbon metabolism-related nutrients has been linked to cancer-related outcomes, but their effects on hepatocellular carcinoma (HCC) mortality are still unknown. The objective was to assess whether pre-diagnostic dietary intakes of methionine, folate, Vitamin B6, Vitamin B12, riboflavin and niacin are associated with HCC survival in this prospective cohort study. In total, 905 newly diagnosed HCC patients were recruited in the Guangdong Liver Cancer Cohort study between September 2013 and April 2017. Dietary intake was assessed using a validated 79-item food frequency questionnaire. Cox proportional hazard regression models were utilized to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the overall and HCC-specific mortality. During a median of 791 days of follow-up, we documented 395 deaths, 353 (89%) of which resulted from HCC. The multivariate-adjusted HRs in the highest vs. the lowest quartile of methionine intake were 0.59 (95% CI: 0.42-0.80; P for trend = 0.001) for overall mortality and 0.68 (95% CI: 0.49-0.93; P for trend = 0.027) for HCC-specific mortality. However, no significant association of other micronutrients involved in one-carbon metabolism with HCC survival was observed. Our research suggests that a high level of methionine intake, but no other one-carbon metabolism-related nutrients, may improve survival in patients with newly diagnosed HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carbono/metabolismo , Estudos de Coortes , Dieta , Ingestão de Alimentos , Ácido Fólico/metabolismo , Humanos , Metionina , Nutrientes , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND & AIMS: Epidemiological evidence linking fibroblast growth factor 21 (FGF21) with hepatocellular carcinoma (HCC) prognosis lacked. We aimed to evaluate the associations between serum FGF21 levels and HCC survival in a large prospective cohort. METHODS: 825 newly diagnosed, previously untreated HCC patients from the Guangdong Liver Cancer Cohort were enrolled between September 2013 and April 2017. Serum FGF21 levels were measured by ELISA. Liver cancer-specific survival (LCSS) and overall survival (OS) were calculated. Multivariable Cox proportional hazards models were performed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Compared with patients in the lowest tertile of serum FGF21 levels, patients in the highest tertile had inferior survival outcomes. HRs in the fully adjusted models were 1.44 (95% CI: 1.07, 1.94; P-trend = .014) and 1.48 (95% CI: 1.12, 1.97; P-trend = .002) for LCSS and OS, respectively. The associations were not significantly modified by selected metabolic disorder diseases or state such as arterial hypertension, diabetes, dyslipidemia, fatty liver, cirrhosis, and body mass index ≥25.0 kg/m2 , except for that stronger associations were observed in patients co-occurred more than three metabolic disorder diseases (P-interaction = .046 for OS and .151 for LCSS), with an HR of 2.01 (95% CI: 1.04, 3.85; P-trend = .009) for OS and 1.51 (95% CI: 0.73, 3.10; P-trend = .195) for LCSS. CONCLUSIONS: Higher serum FGF21 levels were associated with worse survival in HCC patients, suggesting that serum FGF21 may be used as a novel metabolism-related prognostic biomarker for HCC.
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Carcinoma Hepatocelular , Fatores de Crescimento de Fibroblastos/sangue , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Estudos de Coortes , Humanos , Neoplasias Hepáticas/diagnóstico , Prognóstico , Estudos ProspectivosRESUMO
Dietary protein has been linked with all-cause and cancer mortality. However, the relationship between dietary protein and the prognosis of hepatocellular carcinoma (HCC) is still unknown. The purpose of this study was to investigate whether dietary protein intake was related to HCC mortality using data from the Guangdong Liver Cancer Cohort (GLCC), a prospective cohort study of HCC survivors established at the Sun Yat-sen University Cancer Center. Dietary information one year before the diagnosis of HCC was obtained through a 79-item semi-quantitative food frequency questionnaire (FFQ). A total of 883 patients with newly diagnosed HCC who were recruited between September 2013 and April 2017 were included in this study. The hazard ratio (HR) and 95% confidence intervals (95% CIs) were estimated by Cox proportional hazard models. The multivariate-adjusted HRs in the highest vs. the lowest tertile of total protein intake were 0.68 (95% CI: 0.52-0.91, P-trend = 0.007) for all-cause mortality and 0.74 (95% CI: 0.55-0.99, P-trend = 0.040) for HCC-specific mortality. However, the associations of animal protein intake, plant protein intake, and animal-to-plant protein ratio with all-cause and HCC-specific mortality were not significant (all P-trend >0.05). Our research suggests that higher prediagnostic dietary intake of total protein was associated with reduced all-cause and HCC-specific mortality.
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Carcinoma Hepatocelular , Dieta/estatística & dados numéricos , Proteínas Alimentares/análise , Neoplasias Hepáticas , Adulto , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos ProspectivosRESUMO
BACKGROUND: The importance of alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) in hepatocellular carcinoma (HCC) has been studied extensively in Japan, where hepatitis C virus is the predominant aetiology of HCC. The clinical profiles of HCC regarding the state of AFP and DCP in a hepatitis B virus epidemic area have not been comprehensively investigated, and the value of these tumour markers in evaluating the response to treatment and the detection of recurrence has yet to be determined. PATIENTS AND METHODS: A total of 4792 patients treated in our centre were continuously analysed regarding accessible AFP and DCP data pre- and posttreatment. Baseline characteristics were summarized, and comparisons of progression-free survival (PFS) and overall survival (OS) rates were made independently. The prognostic significance of each factor was tested with the Cox proportional hazards model. Patients who had AFP and DCP data pretreatment, pre- and posttreatment, and those who were continuously monitored more than twice were analysed separately. RESULTS: A total of 2600 patients (53.4%) were positive for AFP and DCP; 362 (7.6%) and 1211 (25.3%) patients were AFP- or DCP-positive, respectively, and 619 patients (12.9%) were negative for both AFP and DCP. Patients in the AFP single-positive or double-negative groups had the best OS (P<0.001). Patients with less than 50% responses in AFP and DCP after treatments suffered from worse prognostic survival (P<0.001). In the multivariate analysis, elevated AFP and DCP were identified as independent prognostic factors of PFS and OS. In addition, different tumour markers were related to different clinical and pathological traits. CONCLUSION: The present study comprehensively explored the clinical value of classical tumour markers for HCC using the "point-to-line" method. Positivity of pretreatment AFP and DCP or less than 50% treatment response rates exhibited more aggressive HCC, resulting in poor PFS and OS in HCC patients.
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SCOPE: The muscle loss during aging results from the blunt of protein synthesis and poses threat to the elderly health. This study aims to investigate whether betaine affects muscle loss by improving protein synthesis. METHODS AND RESULTS: Male C57BL/6J mice are raised from age 12 or 15 months. Mice are fed with AIN-93M diet without or with 2% w/v betaine in distilled water as control group or betaine intervention group (Bet), respectively. Betaine supplementation to mice demonstrates better body composition, grip strength, and motor function. Muscle morphology upregulates expression of myogenic regulate factors, and elevates myosin heavy chain and also improves in Bet group. Betaine promotes muscle protein synthesis via tethering mammalian target of rapamycin complex1 protein kinase (mTORC1) on the lysosomal membrane thereby activating mTORC1 signaling. All these effects aforementioned are time-dependent (p < 0.05). Ultrahigh-performance liquid chromatography results show that betaine increases S-adenosyl-l-methionine (SAM) via methionine cycle. SAM sensor-Samtor-overexpression in C2C12 cells could displace mTORC1 from lysosome thereby inhibiting the mTORC1 signaling. Addition of betaine attenuates this inhibition by increasing SAM level and then disrupting interaction of Samtor complex. CONCLUSIONS: These observations indicate that betaine could promisingly promote protein synthesis to delay age-related muscle loss.
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Betaína/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Metiltransferases/antagonistas & inibidores , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiopatologia , S-Adenosilmetionina/metabolismo , Envelhecimento/efeitos dos fármacos , Envelhecimento/patologia , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Membranas Intracelulares/efeitos dos fármacos , Membranas Intracelulares/metabolismo , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Masculino , Metionina/metabolismo , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Biossíntese de Proteínas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
Due to the outbreak of coronavirus disease 2019 (COVID-19), the Chinese government implemented strict lockdown measures to control the spread of infection. The impact of the COVID-19 lockdown on eating habits and lifestyles in the general population is unclear. This cross-sectional study was conducted via an online survey to obtain an overview of the food access, food intake, and physical activity of Chinese residents during the initial stage of the COVID-19 lockdown, and to investigate the association between staying at home/working from home and changes in eating habits and lifestyles. A total of 2702 participants (70.7% women) were included. Most of the participants maintained their habitual diet, while 38.2% increased their snack intake, 54.3% reported reduced physical activity, and 45.5% had increased sleep duration. Most people (70.1%) reported no change in body weight, while 25.0% reported an increase. Always staying at home/working from home was associated with an increase in animal product, vegetable, fruit, mushroom, nut, water, and snack intake, as well as sleep duration and frequency of skipping breakfast (odds ratio (OR) 1.54, 1.62, 1.58, 1.53, 1.57, 1.52, 1.77, 2.29, and 1.76 respectively). Suggestions should be made to encourage people to reduce their snack intake, maintain the daily consumption of breakfast, and increase physical activity during future lockdown periods.
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COVID-19/psicologia , Controle de Doenças Transmissíveis , Comportamento Alimentar , Estilo de Vida , Adolescente , Adulto , COVID-19/epidemiologia , China/epidemiologia , Controle de Doenças Transmissíveis/métodos , Controle de Doenças Transmissíveis/estatística & dados numéricos , Estudos Transversais , Dieta/psicologia , Dieta/estatística & dados numéricos , Ingestão de Alimentos/psicologia , Exercício Físico , Comportamento Alimentar/psicologia , Feminino , Abastecimento de Alimentos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
PURPOSE: Docosahexaenoic acid (DHA) plays an essential role in brain, and its status is dependent on dietary intakes. School-aged children in rural China, who consume diets low in omega-3 polyunsaturated fatty acids, may benefit from DHA supplementation. Therefore, this trial was performed to examine the effect of 6-month DHA supplementation on executive functions (EFs) among healthy school-aged children in rural China. METHODS: A randomized, double-blind, placebo-controlled trial was conducted among 106 primary school children aged 7-12 years in rural China. Participants were randomized to receive either 300 mg/d DHA or placebo for 6 months. EFs including working memory and cognitive flexibility were evaluated at baseline, at 3 months and at 6 months, using Digit Span Backwards and Wisconsin card sorting test, respectively. Socio-demographic data were collected at baseline, and erythrocyte membrane fatty acids and serum neurotransmitters were measured at baseline and after 6-month intervention. RESULTS: Ninety-four children (88.7%) completed the study according to the protocol. Changes in erythrocyte membrane fatty acids indicated good compliance of the participants. There was no significant intervention effect on serum neurotransmitters. In two-factor ANCOVA, both groups showed a significant improvement in the Digit Span Backwards and the Wisconsin card sorting test from baseline to endpoint. However, no significant intervention effect was found on any EF scores. Linear regression analysis suggested no significant association between changes in erythrocyte DHA level with changes in any EF scores. CONCLUSIONS: Supplementation with 300 mg/d DHA for 6 months had no benefit on EFs including working memory and cognitive flexibility among healthy school-aged children. This trial was registered at clinicaltrials.gov as NCT02308930 on December 5, 2014.
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Ácidos Docosa-Hexaenoicos , Ácidos Graxos Ômega-3 , Criança , China , Suplementos Nutricionais , Método Duplo-Cego , Função Executiva , Humanos , Instituições AcadêmicasRESUMO
PURPOSE: To explore whether probiotic supplementation could attenuate serum trimethylamine-N-oxide (TMAO) level and impact the intestinal microbiome composition. DESIGN: Forty healthy males (20-25 years old) were randomized into the probiotic group (1.32 × 1011 CFU live bacteria including strains of Lactobacillus acidophilus, Lactobacillus rhamnosus GG, Bifidobacterium animalis, and Bifidobacterium longum daily) or the control group for 4 weeks. All participants underwent a phosphatidylcholine challenge test (PCCT) before and after the intervention. Serum TMAO and its precursors (TMA, choline and betaine) were measured by UPLC-MS/MS. The faecal microbiome was analyzed by 16S rRNA sequencing. RESULTS: Serum TMAO and its precursors were markedly increased after the PCCT. No statistical differences were observed in the probiotic and the control group in area under the curve (AUC) (14.79 ± 0.97 µmol/L 8 h vs. 19.17 ± 2.55 µmol/L 8 h, P = 0.106) and the pre- to post-intervention AUC alterations (∆AUC) (- 6.33 ± 2.00 µmol/L 8 h vs. - 0.73 ± 3.04 µmol/L 8 h, P = 0.131) of TMAO; however, higher proportion of participants in probiotic group showed their TMAO decrease after the intervention (78.9% vs. 45.0%, P = 0.029). The abundance of Faecalibacterium prausnitzii (P = 0.043) and Prevotella (P = 0.001) in the probiotic group was significantly increased after the intervention but without obvious differences in α- and ß-diversity. CONCLUSIONS: The current probiotic supplementation resulted in detectable change of intestinal microbiome composition but failed to attenuate the serum TMAO elevation after PCCT. CLINICALTRIALS. GOV IDENTIFIER: NCT03292978. CLINICALTRIALS.GOV WEBSITE: https://clinicaltrials.gov/ct2/show/NCT03292978 .
Assuntos
Microbioma Gastrointestinal , Probióticos , Adulto , Cromatografia Líquida , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Masculino , Metilaminas , Óxidos , RNA Ribossômico 16S/genética , Espectrometria de Massas em Tandem , Adulto JovemRESUMO
A higher dietary intake or serum concentration of betaine has been associated with greater lean body mass in middle-aged and older adults. However, it remains unknown whether betaine intake is associated with age-related loss of skeletal muscle mass (SMM). We assessed the association between dietary betaine intake and relative changes in SMM after 3 years in middle-aged adults. A total of 1242 participants aged 41-60 years from the Guangzhou Nutrition and Health Study 2011-2013 and 2014-2017 with body composition measurements by dual-energy X-ray absorptiometry were included. A face-to-face questionnaire was used to collect general baseline information. After adjustment for potential confounders, multiple linear regression found that energy-adjusted dietary betaine intake was significantly and positively associated with relative changes (i.e. percentage loss or increase) in SMM of legs, limbs and appendicular skeletal mass index (ASMI) over 3 years of follow-up (ß 0·322 (se 0·157), 0·309 (se 0·142) and 0·303 (se 0·145), respectively; P < 0·05). The ANCOVA models revealed that participants in the highest betaine tertile had significantly less loss in SMM of limbs and ASMI and more increase in SMM of legs over 3 years of follow-up, compared with those in the bottom betaine tertile (all Ptrend < 0·05). In conclusion, our findings suggest that elevated higher dietary betaine intake may be associated with less loss of SMM of legs, limbs and ASMI in middle-aged adults.