Trimethylamine N-oxide(TMAO)is a risk factor of various chronic diseases,which was produced by metabolism from precursors to trimethylamine(TMA)in gut and the oxidation from TMA in liver.The TMA generation was influen...Trimethylamine N-oxide(TMAO)is a risk factor of various chronic diseases,which was produced by metabolism from precursors to trimethylamine(TMA)in gut and the oxidation from TMA in liver.The TMA generation was influenced by diet,mainly due to the rich TMAO precursors in diet.However,it was still unclear that the effects of different proportion and source of macronutrients in different dietary pattern on the production process of TMAO.Here,the generation of TMA from precursors and TMAO from TMA was determined after single oral choline chloride and intraperitoneal injection TMA,respectively,in mice fed with carbohydrates,proteins and fats in different proportion and sources.The results suggested that the generation of TMAO was increased by low non-meat protein and high fat via enhancing the production of TMAO from TMA,and decreased by plant protein and refined sugar via reducing TMA production from precursors in gut and TMAO transformation from TMA in liver.The high fat and high sugar diets accelerating the development of atherosclerosis did not increase the production of TMAO,the risk factor for atherosclerosis,which indicated that the dietary compositions rather than the elevated TMAO level might be a more key risk factor for atherosclerosis.展开更多
AIM:To provide the direct evidence for the crucial role of trimethylamine N-oxide(TMAO)in vascular permeability and endothelial cell dysfunction under diabetic condition.METHODS:The role of TMAO on the in vitro biolog...AIM:To provide the direct evidence for the crucial role of trimethylamine N-oxide(TMAO)in vascular permeability and endothelial cell dysfunction under diabetic condition.METHODS:The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells(HRMEC)under high glucose conditions was tested by a cell counting kit,wound healing,a transwell and a tube formation assay.The inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction(RT-PCR).The expression of the cell junction was measured by Western blotting(WB)and immunofluorescence staining.In addition,two groups of rat models,diabetic and non-diabetic,were fed with normal or 0.1%TMAO for 16wk,and their plasma levels of TMAO,vascular endothelial growth factor(VEGF),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere tested.The vascular permeability of rat retinas was measured using FITC-Dextran,and the expression of zonula occludens(ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence staining.RESULTS:TMAO administration significantly increased the cell proliferation,migration,and tube formation of primary HRMEC either in normal or high-glucose conditions.RT-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation,while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO treatment.Diabetic rats showed higher plasma levels of TMAO as well as retinal vascular leakage,which were even higher in TMAO-feeding diabetic rats.Furthermore,TMAO administration increased the rat plasma levels of VEGF,IL-6 and TNF-αwhile decreasing the retinal expression levels of ZO-1 and claudin-5.CONCLUSION:TMAO enhances the proliferation,migration,and tube formation of HRMEC,as well as destroys their vascular integrity and tight connection.It also regulates the expression of VEGF,IL-6,and TNF-α.展开更多
BACKGROUND Trimethylamine N-oxide (TMAO) has been shown to be involved in cardiovascular disease (CVD). However, its role in nonalcoholic steatohepatitis (NASH) is unknown. AIM To determine the effect of TMAO on the p...BACKGROUND Trimethylamine N-oxide (TMAO) has been shown to be involved in cardiovascular disease (CVD). However, its role in nonalcoholic steatohepatitis (NASH) is unknown. AIM To determine the effect of TMAO on the progression of NASH. METHODS A rat model was induced by 16-wk high-fat high-cholesterol (HFHC) diet feeding and TMAO was administrated by daily oral gavage for 8 wk. RESULTS Oral TMAO intervention attenuated HFHC diet-induced steatohepatitis in rats. Histological evaluation showed that TMAO treatment significantly alleviated lobular inflammation and hepatocyte ballooning in the livers of rats fed a HFHC diet. Serum levels of alanine aminotransferase and aspartate aminotransferase were also decreased by TMAO treatment. Moreover, hepatic endoplasmic reticulum (ER) stress and cell death were mitigated in HFHC diet-fed TMAOtreated rats. Hepatic and serum levels of cholesterol were both decreased by TMAO treatment in rats fed a HFHC diet. Furthermore, the expression levels of intestinal cholesterol transporters were detected. Interestingly, cholesterol influxrelated Niemann-Pick C1-like 1 was downregulated and cholesterol efflux-related ABCG5/8 were upregulated by TMAO treatment in the small intestine. Gut microbiota analysis showed that TMAO could alter the gut microbial profile and restore the diversity of gut flora. CONCLUSION These data suggest that TMAO may modulate the gut microbiota, inhibit intestinal cholesterol absorption, and ameliorate hepatic ER stress and cell death under cholesterol overload, thereby attenuating HFHC diet-induced steatohepatitis in rats. Further studies are needed to evaluate the influence on CVD and define the safe does of TMAO treatment.展开更多
Environmental exposure to pesticides is widespread and commonly occurs in mixtures,and pregnant women are particularly concerned.Trimethylamine N-oxide(TMAO),a dietary-derived catabolite linked to cardiometabolic dise...Environmental exposure to pesticides is widespread and commonly occurs in mixtures,and pregnant women are particularly concerned.Trimethylamine N-oxide(TMAO),a dietary-derived catabolite linked to cardiometabolic disease,may be influenced by pesticide exposure.However,limited knowledge exists regarding the associations,and studies have primarily been restricted to single pesticides.To address this gap,we examined the associations of pesticide exposure with urinary TMA,TMAO,and TMAO-to-TMA ratio among 1067 pregnant women residing in a rural area.Latent class analysis(LCA)was applied to identify distinct patterns of pesticide exposure based on urinary metabolite concentrations.Multiple linear regression(MLR)models and Bayesian kernel machine regression(BKMR)models were employed to estimate the effects of single pesticides,exposure patterns,and combined exposure.Four distinct pesticide exposure patterns were identified.Higher concentrations of pesticide metabolites were found to be associated with increased urinary TMAO levels(β:0.043 to 0.254,p<0.05).In the MLR models for individual pesticides and exposure patterns,carbofuran phenol(CFP),pentachlorophenol(PCP),and 2-phenylphenol(OPP)exhibited positive associations with urinary TMA concentrations,while pyrethroid pesticide metabolites were correlated with the up-regulation of the TMAO-to-TMA ratio.Significant positive associations of pesticide mixtures with TMA,TMAO,and TMAO-to-TMA ratio were observed in the BKMR model,primarily driven by PCP and trans-DCCA.Our findings provided a perspective to reveal that the mechanisms and contributions to TMAO alterations may vary among different pesticides in mixture exposure.展开更多
Infrared-vacuum ultraviolet （IR-VUV） spectra of neutral trimethylamine dimer were mea- sured in the 2500-3800 cm-1 region. Quantum chemical calculations were performed to identify the structure of the low-lying isom...Infrared-vacuum ultraviolet （IR-VUV） spectra of neutral trimethylamine dimer were mea- sured in the 2500-3800 cm-1 region. Quantum chemical calculations were performed to identify the structure of the low-lying isomers and to assign the observed spectral features. The bands at 2975 and 2949 cm-1 were assigned to the antisymmetric C-H stretching and the band at 2823 cm-1 to the symmetric C-H stretching, respectively. The 2739 cm-1 band was due to the CH3 bending overtone, which disappeared at low IR laser power of 1 mJ/mm2. The extra band at 2773 cm-1 could be due to Fermi resonance behavior of the light isotopologue, these are often close in energy and can strongly mix through cubic terms in the potential function. Experimental and theoretical results indicate the likely coexistence of multiple structures. The peak widths of IR spectra of neutral trimethylamine dimer are not significantly affected by the structural transformation, allowing the stretching modes to be well resolved.展开更多
In this study,seven coal-based activated carbons(ACs)were adopted to remove trimethylamine(TMA)in an aqueous solution as environmentally friendly and harmless adsorbents.The results showed that columnar AC(CAC)had a c...In this study,seven coal-based activated carbons(ACs)were adopted to remove trimethylamine(TMA)in an aqueous solution as environmentally friendly and harmless adsorbents.The results showed that columnar AC(CAC)had a clear scale and honeycomb structures with few fragments and micropores,contributing to superior TMA removal capacity compared to granular AC(GAC)(71.67%for 6.0 mm CAC and 69.92%for 40–60 mesh GAC).In addition,the process of adsorption was accompanied by desorption,and the recommended absorbed time was 120–180 min.The short time to achieve equilibrium indicated that adsorption was kinetically controlled,and pseudo-second-order kinetics was more appropriate than pseudo-first-order kinetics in explaining the adsorption mechanism in both water and oyster enzymatic hydrolysate.The intraparticle diffusion model presented that the adsorption processes could be divided into three steps for GAC and two steps for CAC.The adsorption processes were consistent with the Freundlich model,indicating the existence of physisorption and chemisorption as multilayer adsorption.The results indicated that AC,especially CAC,has great potential for TMA elimination in aquatic product processing.展开更多
基金supported by the National Natural Science Foundation of China(32072145)。
文摘Trimethylamine N-oxide(TMAO)is a risk factor of various chronic diseases,which was produced by metabolism from precursors to trimethylamine(TMA)in gut and the oxidation from TMA in liver.The TMA generation was influenced by diet,mainly due to the rich TMAO precursors in diet.However,it was still unclear that the effects of different proportion and source of macronutrients in different dietary pattern on the production process of TMAO.Here,the generation of TMA from precursors and TMAO from TMA was determined after single oral choline chloride and intraperitoneal injection TMA,respectively,in mice fed with carbohydrates,proteins and fats in different proportion and sources.The results suggested that the generation of TMAO was increased by low non-meat protein and high fat via enhancing the production of TMAO from TMA,and decreased by plant protein and refined sugar via reducing TMA production from precursors in gut and TMAO transformation from TMA in liver.The high fat and high sugar diets accelerating the development of atherosclerosis did not increase the production of TMAO,the risk factor for atherosclerosis,which indicated that the dietary compositions rather than the elevated TMAO level might be a more key risk factor for atherosclerosis.
基金Supported by the National Natural Science Foundation in China(No.81671641)Jiangsu Provincial Medical Innovation Team(No.CXTDA2017039)Gusu Health Talents Program(No.GSWS 2022018).
文摘AIM:To provide the direct evidence for the crucial role of trimethylamine N-oxide(TMAO)in vascular permeability and endothelial cell dysfunction under diabetic condition.METHODS:The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells(HRMEC)under high glucose conditions was tested by a cell counting kit,wound healing,a transwell and a tube formation assay.The inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction(RT-PCR).The expression of the cell junction was measured by Western blotting(WB)and immunofluorescence staining.In addition,two groups of rat models,diabetic and non-diabetic,were fed with normal or 0.1%TMAO for 16wk,and their plasma levels of TMAO,vascular endothelial growth factor(VEGF),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere tested.The vascular permeability of rat retinas was measured using FITC-Dextran,and the expression of zonula occludens(ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence staining.RESULTS:TMAO administration significantly increased the cell proliferation,migration,and tube formation of primary HRMEC either in normal or high-glucose conditions.RT-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation,while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO treatment.Diabetic rats showed higher plasma levels of TMAO as well as retinal vascular leakage,which were even higher in TMAO-feeding diabetic rats.Furthermore,TMAO administration increased the rat plasma levels of VEGF,IL-6 and TNF-αwhile decreasing the retinal expression levels of ZO-1 and claudin-5.CONCLUSION:TMAO enhances the proliferation,migration,and tube formation of HRMEC,as well as destroys their vascular integrity and tight connection.It also regulates the expression of VEGF,IL-6,and TNF-α.
基金Supported by National Key R and D Program of China,No.2017YFC0908903National Natural Science Foundation of China,No.81873565,No.81470840,and No.81800510Shanghai Sailing Program,No.18YF1415900
文摘BACKGROUND Trimethylamine N-oxide (TMAO) has been shown to be involved in cardiovascular disease (CVD). However, its role in nonalcoholic steatohepatitis (NASH) is unknown. AIM To determine the effect of TMAO on the progression of NASH. METHODS A rat model was induced by 16-wk high-fat high-cholesterol (HFHC) diet feeding and TMAO was administrated by daily oral gavage for 8 wk. RESULTS Oral TMAO intervention attenuated HFHC diet-induced steatohepatitis in rats. Histological evaluation showed that TMAO treatment significantly alleviated lobular inflammation and hepatocyte ballooning in the livers of rats fed a HFHC diet. Serum levels of alanine aminotransferase and aspartate aminotransferase were also decreased by TMAO treatment. Moreover, hepatic endoplasmic reticulum (ER) stress and cell death were mitigated in HFHC diet-fed TMAOtreated rats. Hepatic and serum levels of cholesterol were both decreased by TMAO treatment in rats fed a HFHC diet. Furthermore, the expression levels of intestinal cholesterol transporters were detected. Interestingly, cholesterol influxrelated Niemann-Pick C1-like 1 was downregulated and cholesterol efflux-related ABCG5/8 were upregulated by TMAO treatment in the small intestine. Gut microbiota analysis showed that TMAO could alter the gut microbial profile and restore the diversity of gut flora. CONCLUSION These data suggest that TMAO may modulate the gut microbiota, inhibit intestinal cholesterol absorption, and ameliorate hepatic ER stress and cell death under cholesterol overload, thereby attenuating HFHC diet-induced steatohepatitis in rats. Further studies are needed to evaluate the influence on CVD and define the safe does of TMAO treatment.
文摘Environmental exposure to pesticides is widespread and commonly occurs in mixtures,and pregnant women are particularly concerned.Trimethylamine N-oxide(TMAO),a dietary-derived catabolite linked to cardiometabolic disease,may be influenced by pesticide exposure.However,limited knowledge exists regarding the associations,and studies have primarily been restricted to single pesticides.To address this gap,we examined the associations of pesticide exposure with urinary TMA,TMAO,and TMAO-to-TMA ratio among 1067 pregnant women residing in a rural area.Latent class analysis(LCA)was applied to identify distinct patterns of pesticide exposure based on urinary metabolite concentrations.Multiple linear regression(MLR)models and Bayesian kernel machine regression(BKMR)models were employed to estimate the effects of single pesticides,exposure patterns,and combined exposure.Four distinct pesticide exposure patterns were identified.Higher concentrations of pesticide metabolites were found to be associated with increased urinary TMAO levels(β:0.043 to 0.254,p<0.05).In the MLR models for individual pesticides and exposure patterns,carbofuran phenol(CFP),pentachlorophenol(PCP),and 2-phenylphenol(OPP)exhibited positive associations with urinary TMA concentrations,while pyrethroid pesticide metabolites were correlated with the up-regulation of the TMAO-to-TMA ratio.Significant positive associations of pesticide mixtures with TMA,TMAO,and TMAO-to-TMA ratio were observed in the BKMR model,primarily driven by PCP and trans-DCCA.Our findings provided a perspective to reveal that the mechanisms and contributions to TMAO alterations may vary among different pesticides in mixture exposure.
文摘Infrared-vacuum ultraviolet （IR-VUV） spectra of neutral trimethylamine dimer were mea- sured in the 2500-3800 cm-1 region. Quantum chemical calculations were performed to identify the structure of the low-lying isomers and to assign the observed spectral features. The bands at 2975 and 2949 cm-1 were assigned to the antisymmetric C-H stretching and the band at 2823 cm-1 to the symmetric C-H stretching, respectively. The 2739 cm-1 band was due to the CH3 bending overtone, which disappeared at low IR laser power of 1 mJ/mm2. The extra band at 2773 cm-1 could be due to Fermi resonance behavior of the light isotopologue, these are often close in energy and can strongly mix through cubic terms in the potential function. Experimental and theoretical results indicate the likely coexistence of multiple structures. The peak widths of IR spectra of neutral trimethylamine dimer are not significantly affected by the structural transformation, allowing the stretching modes to be well resolved.
基金the National Key R&D Program of China(No.2018YFC0311202)the Key-Area Research and Development Program of Guang-dong Province(No.2020B1111030004)+4 种基金the Science and Technology Program of Guangzhou,China(Nos.201804010364 and 201804010321)the Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou)(No.GML2019ZD0406)the National Key R&D Program of China(No.2018YFC0311202)the Natural Science Foun-dation of Guangdong Province,China(Nos.2018A030313088,2018A030313626)the Academician Work-station Foundation for Young Scientists of Chinese Aca-demy of Sciences Guangzhou Branch(No.20180313).
文摘In this study,seven coal-based activated carbons(ACs)were adopted to remove trimethylamine(TMA)in an aqueous solution as environmentally friendly and harmless adsorbents.The results showed that columnar AC(CAC)had a clear scale and honeycomb structures with few fragments and micropores,contributing to superior TMA removal capacity compared to granular AC(GAC)(71.67%for 6.0 mm CAC and 69.92%for 40–60 mesh GAC).In addition,the process of adsorption was accompanied by desorption,and the recommended absorbed time was 120–180 min.The short time to achieve equilibrium indicated that adsorption was kinetically controlled,and pseudo-second-order kinetics was more appropriate than pseudo-first-order kinetics in explaining the adsorption mechanism in both water and oyster enzymatic hydrolysate.The intraparticle diffusion model presented that the adsorption processes could be divided into three steps for GAC and two steps for CAC.The adsorption processes were consistent with the Freundlich model,indicating the existence of physisorption and chemisorption as multilayer adsorption.The results indicated that AC,especially CAC,has great potential for TMA elimination in aquatic product processing.
