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1.
Hepatology ; 72(1): 169-182, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31677282

RESUMO

BACKGROUND AND AIMS: Free and bioavailable 25-hydroxyvitamin D (25OHD) are emerging measurements of vitamin D status. It remains unclear whether circulating free or bioavailable 25OHD are relevant to hepatocellular carcinoma (HCC) prognosis. Our aim was to test the hypothesis that bioavailable 25OHD may be a better serum biomarker of vitamin D status than total 25OHD on the association with HCC survival. APPROACH AND RESULTS: We included 1,031 newly diagnosed, previously untreated patients with HCC from the Guangdong Liver Cancer Cohort enrolled between September 2013 and April 2017. Serum total 25OHD levels were measured using an electrochemiluminescence immunoassay. Serum-free 25OHD levels were measured using a two-step enzyme-linked immunosorbent assay. Bioavailable 25OHD levels were calculated from measured free 25OHD and albumin using a previously validated equation. Primary outcomes were liver cancer-specific (LCSS) and overall survival (OS). Cox proportional hazards models were performed to calculate the multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 726 days, 430 patients had deceased, including 393 deaths from HCC. In multivariable analyses, higher bioavailable 25OHD levels were significantly associated with better survival, independent of nonclinical and clinical prognostic factors including serum C-reactive protein, Barcelona Clinic Liver Cancer stage, and cancer treatment. The multivariable-adjusted HRs in the highest versus lowest quartile of bioavailable 25OHD levels were 0.69 (95% CI: 0.51, 0.93; P for trend = 0.014) for LCSS and 0.71 (95% CI: 0.53, 0.94; P for trend = 0.013) for OS. In contrast, neither total nor free 25OHD levels were associated with LCSS or OS. CONCLUSIONS: Higher bioavailable, rather than total, 25OHD levels were independently associated with improved survival in a population-based HCC cohort, suggesting a potential utility of bioavailable 25OHD in HCC prognosis.


Assuntos
Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Vitamina D/análogos & derivados , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Vitamina D/sangue
2.
Opt Express ; 29(6): 9465-9473, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33820374

RESUMO

We report the spatiotemporal mode-locked multimode fiber laser operating at 1.55 µm based on semiconductor saturable absorber mirrors with the mode-locking threshold as low as 104 mW. Benefiting from the multimode interference filtering effect introduced in the laser cavity not only the central wavelength can be continuously tuned from 1557 nm to 1567 nm, but also the number of the output pulses can be adjusted from 1 to 4 by simply adjusting the polarization controllers. This work provides a new platform for exploring the dynamic characteristics of spatiotemporal mode-locked pulses at negative dispersion regime. Moreover, this kind of tunable laser has potential applications in fields of all-optical signal processing, fiber sensing and information coding.

3.
Opt Lett ; 46(3): 588-591, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33528415

RESUMO

We report a switchable and spacing tunable dual-wavelength spatiotemporal mode-locked (STML) laser based on the multimode interference filtering effect in an all-fiber linear cavity. The dual-wavelength STML operations combined with different pulse patterns are achieved. By adjusting the polarization controllers, the dual-wavelength STML pulses can be switched to single wavelength operation, which is tunable up to 35 nm under certain pump powers. Moreover, the dual-wavelength spacing can also be tuned from 8 nm to 22 nm. The obtained results contribute to understanding and exploring the spatiotemporal characteristics operating in the multi-wavelength regime of STML fiber lasers. All-fiber STML lasers with lasing wavelength tunability and flexibility may have applications in the fields of optical communications and optical measurements.

4.
Br J Nutr ; 126(7): 1091-1099, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33308344

RESUMO

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


Assuntos
Diabetes Mellitus Tipo 2 , Dieta , Ferro da Dieta , Adulto , Idoso , China/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Heme , Humanos , Ferro da Dieta/administração & dosagem , Pessoa de Meia-Idade , Estudos Prospectivos , Carne Vermelha , Fatores de Risco
5.
Br J Nutr ; 125(4): 440-447, 2021 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32616104

RESUMO

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


Assuntos
Betaína/administração & dosagem , Dieta , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiologia , Envelhecimento , Composição Corporal , Índice de Massa Corporal , China , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ciências da Nutrição , Estado Nutricional , Estudos Prospectivos
6.
Eur J Nutr ; 60(2): 747-758, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32440731

RESUMO

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 Jovem
7.
Hepatol Res ; 50(10): 1164-1175, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32691459

RESUMO

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

8.
Int J Cancer ; 144(11): 2823-2832, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30426509

RESUMO

Copper and zinc are essential micronutrients, whose imbalance may be involved in the development and progression of cancer. However, the role of copper and/or zinc imbalance in the prognosis of hepatocellular carcinoma (HCC) is currently unclear. Our objective was to investigate the association between serum levels of copper, zinc and their ratio (copper/zinc) at diagnosis with HCC survival. We included 989 patients with incident HCC in this prospective cohort study, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study within 30 days of diagnosis between September 2013 and February 2017. Serum copper and zinc were measured using inductively coupled plasma mass spectrometry. Primary outcomes were liver cancer-specific survival (LCSS) and overall survival (OS). Cox proportional hazards models were used to calculate the multivariable hazard ratios (HRs) and 95% confidence interval (CI). Higher serum copper levels were strongly associated with worse LCSS (Q4 vs. Q1: HR = 1.87, 95% CI: 1.22-2.86; p < 0.01 for trend) and OS (Q4 vs. Q1: HR = 2.06, 95% CI: 1.36-3.11; p < 0.01 for trend). The calculated copper/zinc ratio was positively associated with LCSS (Q4 vs. Q1: HR = 1.31, 95% CI: 0.89-1.92; P = 0.04 for trend) and OS (Q4 vs. Q1: HR = 1.43, 95% CI: 0.99-2.08; P = 0.01 for trend). No overall associations were observed between serum zinc levels and LCSS or OS in the entire cohort. The results suggest that higher serum copper and copper in relation to zinc levels (i.e., higher copper/zinc ratio) may be associated with worse HCC survival, but serum zinc levels may be not associated with HCC survival.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/mortalidade , Cobre/sangue , Neoplasias Hepáticas/mortalidade , Zinco/sangue , Adulto , Carcinoma Hepatocelular/sangue , China/epidemiologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida
9.
Opt Express ; 27(20): 28507-28522, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31684601

RESUMO

Pulsating behavior is a universal phenomenon in versatile fields. In nonlinear dissipative systems, the solitons also pulsate under proper conditions and show many interesting dynamics. However, the pulsation dynamics are generally concerned with single-soliton cases. Herein, by utilizing real-time spectroscopy technique, namely, dispersive Fourier-transform (DFT), we reveal the distinct dynamical diversity of pulsating solitons in a fiber laser. In particular, the weak to strong explosive behaviors of pulsating solitons, as well as the rogue wave generation during explosions are observed. Moreover, the concept of soliton pulsation is extended to the multi-soliton case. It is found that the simultaneous pulsations of energy, separation and relative phase difference could be observed for solitons inside the molecule, while the pulsations of each individual in a multi-soliton bunch could be regular or irregular. These findings will shed new insights into the complex nonlinear behavior of solitons in ultrafast fiber lasers as well as dissipative optical systems.

10.
Br J Nutr ; 121(12): 1376-1388, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30935429

RESUMO

Existing data on folate status and hepatocellular carcinoma (HCC) prognosis are scarce. We prospectively examined whether serum folate concentrations at diagnosis were associated with liver cancer-specific survival (LCSS) and overall survival (OS) among 982 patients with newly diagnosed, previously untreated HCC, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study between September 2013 and February 2017. Serum folate concentrations were measured using chemiluminescent microparticle immunoassay. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95 % CI by sex-specific quartile of serum folate. Compared with patients in the third quartile of serum folate, patients in the lowest quartile had significantly inferior LCSS (HR = 1·48; 95 % CI 1·05, 2·09) and OS (HR = 1·43; 95 % CI 1·03, 1·99) after adjustment for non-clinical and clinical prognostic factors. The associations were not significantly modified by sex, age at diagnosis, alcohol drinking status and Barcelona Clinic Liver Cancer (BCLC) stage. However, there were statistically significant interactions on both multiplicative and additive scale between serum folate and C-reactive protein (CRP) levels or smoking status and the associations of lower serum folate with worse LCSS and OS were only evident among patients with CRP > 3·0 mg/l or current smokers. An inverse association with LCSS were also observed among patients with liver damage score ≥3. These results suggest that lower serum folate concentrations at diagnosis are independently associated with worse HCC survival, most prominently among patients with systemic inflammation and current smokers. A future trial of folate supplementation seems to be promising in HCC patients with lower folate status.


Assuntos
Carcinoma Hepatocelular/mortalidade , Ácido Fólico/sangue , Neoplasias Hepáticas/mortalidade , Adulto , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , China , Feminino , Humanos , Neoplasias Hepáticas/sangue , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos
11.
J Natl Cancer Inst ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830043

RESUMO

BACKGROUND: Little is known about the role of vitamin D receptor polymorphisms and their interaction with vitamin D status in hepatocellular carcinoma (HCC) prognosis. METHODS: We evaluated the association of TaqI, BsmI, Cdx-2, and ApaI polymorphisms, individually and in combination, with liver cancer-specific (LCSS) and overall survival (OS) among 967 patients with newly diagnosed HCC. Subsequently, we examined whether these polymorphisms modified the association between serum bioavailable 25-hydroxyvitamin D (25OHD) concentrations and survival. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 1017 days, 393 deaths occurred, with 360 attributed to HCC. Having TaqI G allele (HRper allele = 1.30, 95% CI = 1.08 to 1.57) or BsmI T allele (HRper allele = 1.41, 95% CI = 1.01 to 1.99) was associated with worse LCSS. Carrying increasing numbers of protective alleles was associated with superior LCSS (HR6-8 vs 0-3 = 0.52, 95% CI = 0.34 to 0.80). The inverse association of bioavailable 25OHD with LCSS was only significant in patients with TaqI AA (HRQuartile 4 vs Quartile 1 = 0.63, 95% CI = 0.44 to 0.92), BsmI CC (HRQuartile 4 vs Quartile 1 = 0.62, 95% CI = 0.44 to 0.88), and 6 to 8 protective alleles (HRQuartile 4 vs Quartile 1 = 0.45, 95% CI = 0.23 to 0.87). Similar associations were observed for OS. CONCLUSIONS: Patients carrying wild-type TaqI, BsmI, or more protective alleles had improved survival and might benefit from optimizing bioavailable 25OHD status.

12.
Mol Nutr Food Res ; 65(15): e2100157, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34061446

RESUMO

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.


Assuntos
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 fármacos
13.
Appl Physiol Nutr Metab ; 45(7): 737-744, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31917604

RESUMO

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


Assuntos
Betaína/sangue , Composição Corporal , Colina/sangue , Absorciometria de Fóton , Adulto , Idoso , Índice de Massa Corporal , China , Cromatografia Líquida de Alta Pressão , Feminino , Seguimentos , Humanos , Vida Independente , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espectrometria de Massas em Tandem
14.
Mol Nutr Food Res ; 63(17): e1900257, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31095863

RESUMO

SCOPE: Trimethylamine N-oxide (TMAO), the metabolite of choline generated by gut microbiota, is associated with nonalcoholic fatty liver disease (NAFLD) and could influence bile acid (BA) metabolism. However, whether TMAO aggravates liver steatosis by modulating BA metabolism and the related mechanisms has not been investigated. METHODS AND RESULTS: A case-control study including biopsy-proven NAFLD patients (n = 34) and controls (n = 14) is conducted to determine the correlation between TMAO and BA metabolism. Serum levels of total BA and the percentage of farnesoid X receptor (FXR)-antagonistic BA species are markedly higher in NAFLD patients than in the controls. Serum levels of TMAO positively correlated with the serum levels of total BA and hepatic mRNA expression of cholesterol 7 alpha hydroxylase (CYP7A1). In a murine model, it is found that 18 weeks administration of TMAO impairs liver function and increases hepatic triglyceride accumulation and lipogenesis in mice fed with a high-fat diet. TMAO increases BA synthesis and shifted hepatic BA composition toward FXR-antagonistic activity. Knockdown of CYP7A1 via small interfering RNA or activation of FXR by GW4064 blocks the effect of TMAO-induced lipogenesis in palmitic acid-treated HepG2 cells. CONCLUSION: TMAO aggravates liver steatosis by suppressing BA-mediated hepatic FXR signaling.


Assuntos
Ácidos e Sais Biliares/metabolismo , Metilaminas/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Adulto , Animais , Ácidos e Sais Biliares/sangue , Estudos de Casos e Controles , Colesterol 7-alfa-Hidroxilase/genética , Colesterol 7-alfa-Hidroxilase/metabolismo , Dieta Hiperlipídica/efeitos adversos , Feminino , Células Hep G2 , Humanos , Lipogênese/efeitos dos fármacos , Masculino , Metilaminas/sangue , Metilaminas/toxicidade , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Palmitatos/farmacologia , Transdução de Sinais/efeitos dos fármacos
15.
Nutr Metab (Lond) ; 15: 81, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30479648

RESUMO

BACKGROUND: Evidence has suggested a potential link exists between trimethylamine-N-oxide (TMAO), a choline-derived metabolite produced by gut microbiota, and some cancers, but little is known for primary liver cancer (PLC). METHODS: A case-control study was designed including 671 newly diagnosed PLC patients and 671 control subjects frequency-matched by age (±5 years) and sex, in Guangdong province, China. High-performance liquid chromatography with online electrospray ionization tandem mass spectrometry (HPLC-MS/MS) was used to measure serum TMAO and choline. The associations between these biomarkers and PLC risk were evaluated using logistic regression models. RESULTS: Serum TMAO concentrations were greater in the PLC group than the control group (P = 0.002). Logistic regression analysis showed that the sex- and age-adjusted odds ratio (OR) and (95% confidence interval [CI]) was 3.43 (2.42-4.86) when comparing the top and bottom quartiles (Q4 vs Q1). After further adjusting for more selected confounders, the OR (95% CI) remained significant but was attenuated to 2.85 (1.59-5.11) (Q4 vs Q1). The multivariable-adjusted ORs (95% CIs) across quartiles of choline were 0.35-0.15 (P -trend < 0.001). CONCLUSION: Higher serum levels of TMAO were associated with increased PLC risk. The association was stronger in those with lower serum levels of choline. Additional large prospective studies are required to confirm these findings. TRIAL REGISTRATION: This study was registered at clinicaltrials.gov as NCT 03297255.

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