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
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
Background: Pregnancy and early life are critical periods of plasticity during which the fetus and neonate may be influenced by environmental factors such as nutrition.Maternal methionine(Met) supply in non-ruminants ...Background: Pregnancy and early life are critical periods of plasticity during which the fetus and neonate may be influenced by environmental factors such as nutrition.Maternal methionine(Met) supply in non-ruminants during pregnancy can affect offspring development and growth.Thus,the objective of this study was to investigate if increasing Met supply during late-pregnancy affects developmental parameters of the calf at birth and if either maternal Met or colostrum from Met-fed cows alters calf growth.Calves born to Holstein cows individually-fed a basal control [CON; 1.47 Mcal/kg dry matter(DM) and 15.3% crude protein] diet with no added Met or CON plus ethylcellulose rumen-protected Met(MET; Mepron? at 0.09% of diet DM; Evonik Nutrition & Care GmbH,Germany)during the last 28 ± 2 d of pregnancy were used.A total of 39 calves were in CON(n = 22 bulls,17 heifers) and 42 in MET(n = 20 bulls,22 heifers).At birth,calves were randomly allocated considering dam treatment and colostrum as fol ows: 1) calves from CON cows and colostrum from CON cows(n = 21); 2) calves from CON cows and colostrum from MET cows(n = 18); 3) calves from MET cows and colostrum from MET cows(n = 22); and 4) calves from MET cows and colostrum from CON cows(n = 20).Al calves were housed,managed,and fed individual y during the first 9 wk of life.Results: Despite greater daily DM intake pre-partum in cows fed MET(15.7 vs.14.4 ± 0.12 kg/d,P < 0.05),colostrum quality and quantity were not affected by maternal diet.At birth,MET calves had greater(P ≤ 0.05) body weight(BW,44.1 vs.42.1 ± 0.70 kg),hip height(HH,81.3 vs.79.6 ± 0.53 cm) and wither height(WH,77.8 vs.75.9 ± 0.47 cm).In contrast,concentrations of His,Lys,and Asn in plasma were lower(P ≤ 0.05) in MET calves.Regardless of colostrum source,the greater BW,HH,and WH in MET calves at birth persisted through 9 wk of age resulting in average responses of + 3.1 kg BW,+ 1.9 cm HH,and + 1.8 cm WH compared with CON.Average daily gain during the 9 wk was(P < 0.05) 0.72 ± 0.02 kg/d in MET compa展开更多
This editorial reviews the recent evidence showing that Mallory-Denk bodies(MDBs)form in hepatocytes as the result of a drug-induced shift from the 26s proteasome formation to the immunoproteasome formation.The shift ...This editorial reviews the recent evidence showing that Mallory-Denk bodies(MDBs)form in hepatocytes as the result of a drug-induced shift from the 26s proteasome formation to the immunoproteasome formation.The shift is the result of changes in gene expression induced in promoter activation,which is induced by the IFNγ and TNFa signaling pathway.This activates TLR 2 and 4 receptors.The TLR signaling pathway stimulates both the induction of a cytokine proinflammatory response and an up regulation of growth factors.The MDB-forming hepatocytes proliferate as a result of the increase in growth factor expression by the MDBforming cells,which selectively proliferate in response to drug toxicity.All of these mechanisms are induced by drug toxicity,and are prevented by feeding the methyl donors SAMe and betaine,supporting the epigenetic response of MDB formation.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
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.
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.
基金supported by a postdoctoral fellowship from the government of the Arab Republic of Egypt
文摘Background: Pregnancy and early life are critical periods of plasticity during which the fetus and neonate may be influenced by environmental factors such as nutrition.Maternal methionine(Met) supply in non-ruminants during pregnancy can affect offspring development and growth.Thus,the objective of this study was to investigate if increasing Met supply during late-pregnancy affects developmental parameters of the calf at birth and if either maternal Met or colostrum from Met-fed cows alters calf growth.Calves born to Holstein cows individually-fed a basal control [CON; 1.47 Mcal/kg dry matter(DM) and 15.3% crude protein] diet with no added Met or CON plus ethylcellulose rumen-protected Met(MET; Mepron? at 0.09% of diet DM; Evonik Nutrition & Care GmbH,Germany)during the last 28 ± 2 d of pregnancy were used.A total of 39 calves were in CON(n = 22 bulls,17 heifers) and 42 in MET(n = 20 bulls,22 heifers).At birth,calves were randomly allocated considering dam treatment and colostrum as fol ows: 1) calves from CON cows and colostrum from CON cows(n = 21); 2) calves from CON cows and colostrum from MET cows(n = 18); 3) calves from MET cows and colostrum from MET cows(n = 22); and 4) calves from MET cows and colostrum from CON cows(n = 20).Al calves were housed,managed,and fed individual y during the first 9 wk of life.Results: Despite greater daily DM intake pre-partum in cows fed MET(15.7 vs.14.4 ± 0.12 kg/d,P < 0.05),colostrum quality and quantity were not affected by maternal diet.At birth,MET calves had greater(P ≤ 0.05) body weight(BW,44.1 vs.42.1 ± 0.70 kg),hip height(HH,81.3 vs.79.6 ± 0.53 cm) and wither height(WH,77.8 vs.75.9 ± 0.47 cm).In contrast,concentrations of His,Lys,and Asn in plasma were lower(P ≤ 0.05) in MET calves.Regardless of colostrum source,the greater BW,HH,and WH in MET calves at birth persisted through 9 wk of age resulting in average responses of + 3.1 kg BW,+ 1.9 cm HH,and + 1.8 cm WH compared with CON.Average daily gain during the 9 wk was(P < 0.05) 0.72 ± 0.02 kg/d in MET compa
基金Supported by the NIH/NIAAA 8116Alcohol Center Grant on Liver and Pancreas P50-011999,Morphology Core
文摘This editorial reviews the recent evidence showing that Mallory-Denk bodies(MDBs)form in hepatocytes as the result of a drug-induced shift from the 26s proteasome formation to the immunoproteasome formation.The shift is the result of changes in gene expression induced in promoter activation,which is induced by the IFNγ and TNFa signaling pathway.This activates TLR 2 and 4 receptors.The TLR signaling pathway stimulates both the induction of a cytokine proinflammatory response and an up regulation of growth factors.The MDB-forming hepatocytes proliferate as a result of the increase in growth factor expression by the MDBforming cells,which selectively proliferate in response to drug toxicity.All of these mechanisms are induced by drug toxicity,and are prevented by feeding the methyl donors SAMe and betaine,supporting the epigenetic response of MDB formation.
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.
