Background Intrauterine growth retardation(IUGR)affects intestinal growth,morphology,and function,which leads to poor growth performance and high mortality.The present study explored whether maternal dietary methyl do...Background Intrauterine growth retardation(IUGR)affects intestinal growth,morphology,and function,which leads to poor growth performance and high mortality.The present study explored whether maternal dietary methyl donor(MET)supplementation alleviates IUGR and enhances offspring’s growth performance by improving intestinal growth,function,and DNA methylation of the ileum in a porcine IUGR model.Methods Forty multiparous sows were allocated to the control or MET diet groups from mating until delivery.After farrowing,8 pairs of IUGR and normal birth weight piglets from 8 litters were selected for sampling before suckling colostrum.Results The results showed that maternal MET supplementation tended to decrease the IUGR incidence and increased the average weaning weight of piglets.Moreover,maternal MET supplementation significantly reduced the plasma concentrations of isoleucine,cysteine,urea,and total amino acids in sows and newborn pig-lets.It also increased lactase and sucrase activity in the jejunum of newborn piglets.MET addition resulted in lower ileal methionine synthase activity and increased betaine homocysteine S-methyltransferase activity in the ileum of newborn piglets.DNA methylation analysis of the ileum showed that MET supplementation increased the methyla-tion level of DNA CpG sites in the ileum of newborn piglets.Down-regulated differentially methylated genes were enriched in folic acid binding,insulin receptor signaling pathway,and endothelial cell proliferation.In contrast,up-regulated methylated genes were enriched in growth hormone receptor signaling pathway and nitric oxide biosyn-thetic process.Conclusions Maternal MET supplementation can reduce the incidence of IUGR and increase the weaning litter weight of piglets,which may be associated with better intestinal function and methylation status.展开更多
BACKGROUND Dietary methyl donors might influence DNA methylation during carcinogenesis of colorectal cancer(CRC).However,whether the influence of methyl donor intake is modified by polymorphisms in such epigenetic reg...BACKGROUND Dietary methyl donors might influence DNA methylation during carcinogenesis of colorectal cancer(CRC).However,whether the influence of methyl donor intake is modified by polymorphisms in such epigenetic regulators is still unclear.AIM To improve the current understanding of the molecular basis of CRC.METHODS A literature search in the Medline database,Reference Citation Analysis(https://www.referencecitationanalysis.com/),and manual reference screening were performed to identify observational studies published from inception to May 2022.RESULTS A total of fourteen case-control studies and five cohort studies were identified.These studies included information on dietary methyl donors,dietary components that potentially modulate the bioavailability of methyl groups,genetic variants of methyl metabolizing enzymes,and/or markers of CpG island methylator phenotype and/or microsatellite instability,and their possible interactions on CRC risk.CONCLUSION Several studies have suggested interactions between methylenetetrahydrofolate reductase polymorphisms,methyl donor nutrients(such as folate)and alcohol on CRC risk.Moreover,vitamin B6,niacin,and alcohol may affect CRC risk through not only genetic but also epigenetic regulation.Identification of specific mechanisms in these interactions associated with CRC may assist in developing targeted prevention strategies for individuals at the highest risk of developing CRC.展开更多
Free Fatty acid is an end-product of hepatic metabolism of fructose. Most of past studies have demonstrated significant relationship between gestational high fat diet and metabolic and physiology outcomes in offspring...Free Fatty acid is an end-product of hepatic metabolism of fructose. Most of past studies have demonstrated significant relationship between gestational high fat diet and metabolic and physiology outcomes in offspring. However, there is a scarce of data extended to the effects of high fructose diet-fed dams on juveniles’ progeny. Therefore, the present experiment was designed to examine the later effects of maternal high fructose diet intake during pregnancy and lactation on juvenile offspring rats emotional behaviors and memory abilities. We tested whether methyl donors supplemented to that high fructose diet could reverse the adverse effects. We found at two months of age, anxiety-like behavior and depression-like behavior were elevated in off springs of mother fed to high fructose diet and a sex difference effect with males were more affected than females. In addition, behavioral outcomes indicated that the high fructose diet also impaired spatial working and recognition memories in the Y-maze and object recognition test respectively. Blood glucose intolerance increased significantly in juvenile males rats of dams fed with high fructose diet when compared to females. However, a supplementation of the maternal diet with methyl donors attenuated all these changes. Our study suggested a controlled fructose diet supplemented to methyl donors during critical period of brain developing (in utero and pre-weaning stage), otherwise that could induced irreversible detrimental effects on offspring behavior and cognitive health.展开更多
Nutrition contributes to honey bee caste differentiation,but the role of individual nutrients is still unclear.Most essential amino acid contents,except that of methionine(Met),are greater in royal jelly than worker j...Nutrition contributes to honey bee caste differentiation,but the role of individual nutrients is still unclear.Most essential amino acid contents,except that of methionine(Met),are greater in royal jelly than worker jelly.After〜3.5 i the Met content in the latter was slightly greater than in the former.Met is the major raw material used in the synthesis of S-adenosyl-L-methionine,an active methyl donor for DNA methylation,which is an epigenetic driver of caste differentiation.Here,we tested whether Met regulates caste differentiation in honey bees by determining its effects on the caste development of bees receiving four diets:the basic,basic+0.2%Met,basic+0.2%Met+20 mg/kg 5-azacytidine,and basic+20 mg/kg 5-azacytidine.The presence of Met decreased the adult bee body length and the numbers of ovarioles,indicating that Met may direct the development of female larvae toward worker bees.The upregulated expression of SAMS,Dnmtl,and Dnmt3 caused by Met exposure in 4-d-old larvae indicated that the worker-inductive effects of Met may occur through the promotion of DNA methylation.We investigated the co-effects of Met and glucose on bee development,and found that the effects of an increased glucose level on the number of ovarioles and body length did not strengthen the worker-inductive effects caused by Met.Our results contribute to caste development theory and suggest that Met-as a methyl donor一plays a regulatory,but not decisive,role in caste differentiation.展开更多
Theoretical calculations were carried out using the DFT/B3LYP/6-31+G(d) methodology in an attempt to predict the preferred interaction site of a polyfunctional heterocyclic base 3-methyl-4- pyrimidone molecule with a ...Theoretical calculations were carried out using the DFT/B3LYP/6-31+G(d) methodology in an attempt to predict the preferred interaction site of a polyfunctional heterocyclic base 3-methyl-4- pyrimidone molecule with a series of proton donors of different acidic strength, i.e. water, methanol, phenol, 1-naphtol, 2,4,5 trichlorophenol, pentachlorophenol, picric acid and hydrogen chlordide. Computed H-bond interaction energies (ΔEc), internuclear and intermolecular distances r(O…H) and r(O…O), infrared frequency shifts Δv(C=O) and (Δv(OH) are proved to be reliable parameters for predicting the preferred interaction site of 3-methyl-4-pyrimidone. These computational data suggest that the O-H…O=C complex is preferred with water, methanol, phenol, 1-naphtol, 2,4,5 trichlorophenol and pentachlorophenol. However, for H-bonding with stronger acids such as picric acid or hydrochloric acid, the computational data suggest that the H-bonding occurs at the N1 ring atom of 3-methyl-4-pyrimidone. In the O-H…O=C com- plex, where the H-bond at the carbonyl O-atom can be oriented “anti” (Ha) and “syn” (Hb) with respect to the N3 atom, the same computational data suggest a higher stability of the “anti-O” compared to the “syn-O” orientation.展开更多
This article reviews the evidence that ties the development of hepatocellular carcinoma (HCC) to the natural immune pro-inflammatory response to chronic liver disease, with a focus on the role of Toll-like receptor (T...This article reviews the evidence that ties the development of hepatocellular carcinoma (HCC) to the natural immune pro-inflammatory response to chronic liver disease, with a focus on the role of Toll-like receptor (TLR) signaling as the mechanism of liver stem cell/progenitor transformation to HCC. Two exemplary models of this phenomenon are reviewed in detail. One model applies chronic ethanol/lipopolysaccharide feeding to the activated TLR4 signaling pathway. The other applies chronic feeding of a carcinogenic drug, in which TLR2 and 4 signaling pathways are activated. In the drug-induced model, two major methyl donors, S-adenosylmethionine and betaine, prevent the upregulation of the TLR signaling pathways and abrogate the stem cell/progenitor proliferation response when fed with the carcinogenic drug. This observation supports a nutritional approach to liver cancer prevention and treatment. The observation that upregulation of the TLR signaling pathways leads to liver tumor formation gives evidence to the popular concept that the chronic pro-inflammatory response is an important mechanism of liver oncogenesis. It provides a nutritional approach, which could prevent HCC from developing in many chronic liver diseases.展开更多
Dairy cattle undergo dramatic metabolic, endocrine, physiologic and immune changes during the peripartal period largely due to combined increases in energy requirements for fetal growth and development, milk productio...Dairy cattle undergo dramatic metabolic, endocrine, physiologic and immune changes during the peripartal period largely due to combined increases in energy requirements for fetal growth and development, milk production, and decreased dry matter intake. The negative nutrient balance that develops results in body fat mobilization,subsequently leading to triacylglycerol(TAG) accumulation in the liver along with reductions in liver function,immune dysfunction and a state of inflammation and oxidative stress. Mobilization of muscle and gluconeogenesis are also enhanced, while intake of vitamins and minerals is decreased, contributing to metabolic and immune dysfunction and oxidative stress. Enhancing post-ruminal supply of methyl donors is one approach that may improve immunometabolism and production synergistically in peripartal cows. At the cellular level, methyl donors(e.g. methionine, choline, betaine and folic acid) interact through one-carbon metabolism to modulate metabolism,immune responses and epigenetic events. By modulating those pathways, methyl donors may help increase the export of very low-density lipoproteins to reduce liver TAG and contribute to antioxidant synthesis to alleviate oxidative stress. Thus, altering one-carbon metabolism through methyl donor supplementation is a viable option to modulate immunometabolism during the peripartal period. This review explores available data on the regulation of one-carbon metabolism pathways in dairy cows in the context of enzyme regulation, cellular sensors and signaling mechanisms that might respond to increased dietary supply of specific methyl donors. Effects of methyl donors beyond the one-carbon metabolism pathways, including production performance, immune cell function,mechanistic target or rapamycin signaling, and fatty acid oxidation will also be highlighted. Furthermore, the effects of body condition and feeding system(total mixed ration vs. pasture) on one-carbon metabolism pathways are explored. Potential effects of methyl donor supply during the pepartum period on dairy calf growth and development also are discussed. Lastly, practical nutritional recommendations related to methyl donor metabolism during the peripartal period are presented. Nutritional management during the peripartal period is a fertile area of research, hence, underscoring the importance for developing a systems understanding of the potential immunometabolic role that dietary methyl donors play during this period to promote health and performance.展开更多
The transition period of dairy cattle is characterized by a number of metabolic, endocrine, physiologic, and immune adaptations, including the occurrence of negative energy balance, hypocalcemia, liver dysfunction, ov...The transition period of dairy cattle is characterized by a number of metabolic, endocrine, physiologic, and immune adaptations, including the occurrence of negative energy balance, hypocalcemia, liver dysfunction, overt systemic inflammatory response, and oxidative stress status. The degree and length of time during which these systems remain out of balance could render cows more susceptible to disease, poor reproductive outcomes, and less efficient for milk production and quality. Studies on both monogastrics and ruminants have reported the health benefits of nutraceuticals(e.g. probiotics, prebiotics, dietary lipids, functional peptides, phytoextracts) beyond nutritional value, interacting at different levels of the animal's physiology. From a physiological standpoint, it seems unrealistic to disregard any systemic inflammatory processes. However, an alternate approach is to modulate the inflammatory process per se and to resolve the systemic response as quickly as possible.To this aim, a growing body of literature underscores the efficacy of nutraceuticals(active compounds) during the critical phase of the transition period. Supplementation of essential fatty acids throughout a 2-month period(i.e. a month before and a month after calving) successfully attenuates the inflammatory status with a quicker resolution of phenomenon. In this context, the inflammatory and immune response scenario has been recognized to be targeted by the beneficial effect of methyl donors, such as methionine and choline, directly and indirectly modulating such response with the increase of antioxidants GSH and taurine. Indirectly by the establishment of a healthy gastrointestinal tract, yeast and yeast-based products showed to modulate the immune response, mitigating negative effects associated with parturition stress and consequent disorders.The use of phytoproducts has garnered high interest because of their wide range of actions on multiple tissue targets encompassing a series of antimicrobial, antiviral, antioxidant, immune-stimulating, rumen fermentation, and microbial modulation effects. In this review, we provide perspectives on investigations of regulating the immune responses and metabolism using several nutraceuticals in the periparturient cow.展开更多
基金This work was supported by Sichuan Provincial Science Fund for Distinguished Young Scholars(Grant No.2020JDJQ0041)CARS-35 and Sichuan Key Science and Technology Project(NO.2021ZDZX0009).
文摘Background Intrauterine growth retardation(IUGR)affects intestinal growth,morphology,and function,which leads to poor growth performance and high mortality.The present study explored whether maternal dietary methyl donor(MET)supplementation alleviates IUGR and enhances offspring’s growth performance by improving intestinal growth,function,and DNA methylation of the ileum in a porcine IUGR model.Methods Forty multiparous sows were allocated to the control or MET diet groups from mating until delivery.After farrowing,8 pairs of IUGR and normal birth weight piglets from 8 litters were selected for sampling before suckling colostrum.Results The results showed that maternal MET supplementation tended to decrease the IUGR incidence and increased the average weaning weight of piglets.Moreover,maternal MET supplementation significantly reduced the plasma concentrations of isoleucine,cysteine,urea,and total amino acids in sows and newborn pig-lets.It also increased lactase and sucrase activity in the jejunum of newborn piglets.MET addition resulted in lower ileal methionine synthase activity and increased betaine homocysteine S-methyltransferase activity in the ileum of newborn piglets.DNA methylation analysis of the ileum showed that MET supplementation increased the methyla-tion level of DNA CpG sites in the ileum of newborn piglets.Down-regulated differentially methylated genes were enriched in folic acid binding,insulin receptor signaling pathway,and endothelial cell proliferation.In contrast,up-regulated methylated genes were enriched in growth hormone receptor signaling pathway and nitric oxide biosyn-thetic process.Conclusions Maternal MET supplementation can reduce the incidence of IUGR and increase the weaning litter weight of piglets,which may be associated with better intestinal function and methylation status.
基金The Basque Government(BIOMICs Research Group,MICROFLUIDICs&BIOMICs Cluster of the University of the Basque Country UPV/EHU),No.IT1633-22.
文摘BACKGROUND Dietary methyl donors might influence DNA methylation during carcinogenesis of colorectal cancer(CRC).However,whether the influence of methyl donor intake is modified by polymorphisms in such epigenetic regulators is still unclear.AIM To improve the current understanding of the molecular basis of CRC.METHODS A literature search in the Medline database,Reference Citation Analysis(https://www.referencecitationanalysis.com/),and manual reference screening were performed to identify observational studies published from inception to May 2022.RESULTS A total of fourteen case-control studies and five cohort studies were identified.These studies included information on dietary methyl donors,dietary components that potentially modulate the bioavailability of methyl groups,genetic variants of methyl metabolizing enzymes,and/or markers of CpG island methylator phenotype and/or microsatellite instability,and their possible interactions on CRC risk.CONCLUSION Several studies have suggested interactions between methylenetetrahydrofolate reductase polymorphisms,methyl donor nutrients(such as folate)and alcohol on CRC risk.Moreover,vitamin B6,niacin,and alcohol may affect CRC risk through not only genetic but also epigenetic regulation.Identification of specific mechanisms in these interactions associated with CRC may assist in developing targeted prevention strategies for individuals at the highest risk of developing CRC.
文摘Free Fatty acid is an end-product of hepatic metabolism of fructose. Most of past studies have demonstrated significant relationship between gestational high fat diet and metabolic and physiology outcomes in offspring. However, there is a scarce of data extended to the effects of high fructose diet-fed dams on juveniles’ progeny. Therefore, the present experiment was designed to examine the later effects of maternal high fructose diet intake during pregnancy and lactation on juvenile offspring rats emotional behaviors and memory abilities. We tested whether methyl donors supplemented to that high fructose diet could reverse the adverse effects. We found at two months of age, anxiety-like behavior and depression-like behavior were elevated in off springs of mother fed to high fructose diet and a sex difference effect with males were more affected than females. In addition, behavioral outcomes indicated that the high fructose diet also impaired spatial working and recognition memories in the Y-maze and object recognition test respectively. Blood glucose intolerance increased significantly in juvenile males rats of dams fed with high fructose diet when compared to females. However, a supplementation of the maternal diet with methyl donors attenuated all these changes. Our study suggested a controlled fructose diet supplemented to methyl donors during critical period of brain developing (in utero and pre-weaning stage), otherwise that could induced irreversible detrimental effects on offspring behavior and cognitive health.
基金Funds of Shandong Province"Double Tops"Program(2016-2020)Shandong Province Agricultural Fine Varieties Breeding Projects(2017LZN006)the earmarked fund for the China Agriculture Research System(No.CARS-44).
文摘Nutrition contributes to honey bee caste differentiation,but the role of individual nutrients is still unclear.Most essential amino acid contents,except that of methionine(Met),are greater in royal jelly than worker jelly.After〜3.5 i the Met content in the latter was slightly greater than in the former.Met is the major raw material used in the synthesis of S-adenosyl-L-methionine,an active methyl donor for DNA methylation,which is an epigenetic driver of caste differentiation.Here,we tested whether Met regulates caste differentiation in honey bees by determining its effects on the caste development of bees receiving four diets:the basic,basic+0.2%Met,basic+0.2%Met+20 mg/kg 5-azacytidine,and basic+20 mg/kg 5-azacytidine.The presence of Met decreased the adult bee body length and the numbers of ovarioles,indicating that Met may direct the development of female larvae toward worker bees.The upregulated expression of SAMS,Dnmtl,and Dnmt3 caused by Met exposure in 4-d-old larvae indicated that the worker-inductive effects of Met may occur through the promotion of DNA methylation.We investigated the co-effects of Met and glucose on bee development,and found that the effects of an increased glucose level on the number of ovarioles and body length did not strengthen the worker-inductive effects caused by Met.Our results contribute to caste development theory and suggest that Met-as a methyl donor一plays a regulatory,but not decisive,role in caste differentiation.
文摘Theoretical calculations were carried out using the DFT/B3LYP/6-31+G(d) methodology in an attempt to predict the preferred interaction site of a polyfunctional heterocyclic base 3-methyl-4- pyrimidone molecule with a series of proton donors of different acidic strength, i.e. water, methanol, phenol, 1-naphtol, 2,4,5 trichlorophenol, pentachlorophenol, picric acid and hydrogen chlordide. Computed H-bond interaction energies (ΔEc), internuclear and intermolecular distances r(O…H) and r(O…O), infrared frequency shifts Δv(C=O) and (Δv(OH) are proved to be reliable parameters for predicting the preferred interaction site of 3-methyl-4-pyrimidone. These computational data suggest that the O-H…O=C complex is preferred with water, methanol, phenol, 1-naphtol, 2,4,5 trichlorophenol and pentachlorophenol. However, for H-bonding with stronger acids such as picric acid or hydrochloric acid, the computational data suggest that the H-bonding occurs at the N1 ring atom of 3-methyl-4-pyrimidone. In the O-H…O=C com- plex, where the H-bond at the carbonyl O-atom can be oriented “anti” (Ha) and “syn” (Hb) with respect to the N3 atom, the same computational data suggest a higher stability of the “anti-O” compared to the “syn-O” orientation.
基金Supported by NIH/NIAAA 8116Alcohol Center Grant on Liver and Pancreas P50-011999, Morphology Core
文摘This article reviews the evidence that ties the development of hepatocellular carcinoma (HCC) to the natural immune pro-inflammatory response to chronic liver disease, with a focus on the role of Toll-like receptor (TLR) signaling as the mechanism of liver stem cell/progenitor transformation to HCC. Two exemplary models of this phenomenon are reviewed in detail. One model applies chronic ethanol/lipopolysaccharide feeding to the activated TLR4 signaling pathway. The other applies chronic feeding of a carcinogenic drug, in which TLR2 and 4 signaling pathways are activated. In the drug-induced model, two major methyl donors, S-adenosylmethionine and betaine, prevent the upregulation of the TLR signaling pathways and abrogate the stem cell/progenitor proliferation response when fed with the carcinogenic drug. This observation supports a nutritional approach to liver cancer prevention and treatment. The observation that upregulation of the TLR signaling pathways leads to liver tumor formation gives evidence to the popular concept that the chronic pro-inflammatory response is an important mechanism of liver oncogenesis. It provides a nutritional approach, which could prevent HCC from developing in many chronic liver diseases.
文摘Dairy cattle undergo dramatic metabolic, endocrine, physiologic and immune changes during the peripartal period largely due to combined increases in energy requirements for fetal growth and development, milk production, and decreased dry matter intake. The negative nutrient balance that develops results in body fat mobilization,subsequently leading to triacylglycerol(TAG) accumulation in the liver along with reductions in liver function,immune dysfunction and a state of inflammation and oxidative stress. Mobilization of muscle and gluconeogenesis are also enhanced, while intake of vitamins and minerals is decreased, contributing to metabolic and immune dysfunction and oxidative stress. Enhancing post-ruminal supply of methyl donors is one approach that may improve immunometabolism and production synergistically in peripartal cows. At the cellular level, methyl donors(e.g. methionine, choline, betaine and folic acid) interact through one-carbon metabolism to modulate metabolism,immune responses and epigenetic events. By modulating those pathways, methyl donors may help increase the export of very low-density lipoproteins to reduce liver TAG and contribute to antioxidant synthesis to alleviate oxidative stress. Thus, altering one-carbon metabolism through methyl donor supplementation is a viable option to modulate immunometabolism during the peripartal period. This review explores available data on the regulation of one-carbon metabolism pathways in dairy cows in the context of enzyme regulation, cellular sensors and signaling mechanisms that might respond to increased dietary supply of specific methyl donors. Effects of methyl donors beyond the one-carbon metabolism pathways, including production performance, immune cell function,mechanistic target or rapamycin signaling, and fatty acid oxidation will also be highlighted. Furthermore, the effects of body condition and feeding system(total mixed ration vs. pasture) on one-carbon metabolism pathways are explored. Potential effects of methyl donor supply during the pepartum period on dairy calf growth and development also are discussed. Lastly, practical nutritional recommendations related to methyl donor metabolism during the peripartal period are presented. Nutritional management during the peripartal period is a fertile area of research, hence, underscoring the importance for developing a systems understanding of the potential immunometabolic role that dietary methyl donors play during this period to promote health and performance.
基金support from the “Romeo and Enrica Invernizzi Foundation” (Milan, Italy)Università Cattolica del Sacro Cuore (Piacenza, Italy)。
文摘The transition period of dairy cattle is characterized by a number of metabolic, endocrine, physiologic, and immune adaptations, including the occurrence of negative energy balance, hypocalcemia, liver dysfunction, overt systemic inflammatory response, and oxidative stress status. The degree and length of time during which these systems remain out of balance could render cows more susceptible to disease, poor reproductive outcomes, and less efficient for milk production and quality. Studies on both monogastrics and ruminants have reported the health benefits of nutraceuticals(e.g. probiotics, prebiotics, dietary lipids, functional peptides, phytoextracts) beyond nutritional value, interacting at different levels of the animal's physiology. From a physiological standpoint, it seems unrealistic to disregard any systemic inflammatory processes. However, an alternate approach is to modulate the inflammatory process per se and to resolve the systemic response as quickly as possible.To this aim, a growing body of literature underscores the efficacy of nutraceuticals(active compounds) during the critical phase of the transition period. Supplementation of essential fatty acids throughout a 2-month period(i.e. a month before and a month after calving) successfully attenuates the inflammatory status with a quicker resolution of phenomenon. In this context, the inflammatory and immune response scenario has been recognized to be targeted by the beneficial effect of methyl donors, such as methionine and choline, directly and indirectly modulating such response with the increase of antioxidants GSH and taurine. Indirectly by the establishment of a healthy gastrointestinal tract, yeast and yeast-based products showed to modulate the immune response, mitigating negative effects associated with parturition stress and consequent disorders.The use of phytoproducts has garnered high interest because of their wide range of actions on multiple tissue targets encompassing a series of antimicrobial, antiviral, antioxidant, immune-stimulating, rumen fermentation, and microbial modulation effects. In this review, we provide perspectives on investigations of regulating the immune responses and metabolism using several nutraceuticals in the periparturient cow.
