Recent advances in amino acid metabolism have revealed that targeting amino acid metabolic enzymes in cancer therapy is a promising strategy for the development of novel therapeutic agents. There are currently several...Recent advances in amino acid metabolism have revealed that targeting amino acid metabolic enzymes in cancer therapy is a promising strategy for the development of novel therapeutic agents. There are currently several drugs in clinical trials that specifically target amino acid metabolic pathways in tumor cells. In the context of the tumor microenvironment,however,tumor cells form metabolic relationships with immune cells,and they oftencompete for common nutrients. Many tumors evolved to escape immune surveillance by taking advantage of their metabolic flexibility and redirecting nutrients for their own advantage. This review outlines the most recent advances in targeting amino acid metabolic pathways in cancer therapy while giving consideration to the impact these pathways may have on the anti-tumor immune response.展开更多
It has been reported that host defense responses,such as phagocytic function of neutrophils and natural killer(NK)cell activity of lymphocytes,are impaired in cirrhotic patients.This review will concentrate on the imp...It has been reported that host defense responses,such as phagocytic function of neutrophils and natural killer(NK)cell activity of lymphocytes,are impaired in cirrhotic patients.This review will concentrate on the impairment of innate immune responses in decompensated cirrhotic patients and the effect of the treatment by branched-chain amino acids(BCAA)on innate immune responses.We already reported that phagocytic function of neutrophils was significantly improved by3-mo BCAA supplementation.In addition,the changes of NK activity were also significant at 3 mo of supplementation compared with before supplementation.Also,Fisher’s ratios were reported to be significantly increased at 3 mo of BCAA supplementation compared with those before oral supplementation.Therefore,administration of BCAA could reduce the risk of bacterial and viral infection in patients with decompensated cirrhosis by restoring impaired innate immune responses of the host.In addition,it was also revealed that BCAA oral supplementation could reduce the risk of development of hepatocellular carcinoma in cirrhotic patients.The mechanisms of the effects will also be discussed in this review article.展开更多
Immune system activation begins a host of physiological responses. Infectious agents are recognized by monocytes and macrophages which in turn stimulate cytokine production. It is the hormone-like factors called cytok...Immune system activation begins a host of physiological responses. Infectious agents are recognized by monocytes and macrophages which in turn stimulate cytokine production. It is the hormone-like factors called cytokines that orchestrate the immune response. The classic responses observed with immune system activation and cytokine production include： anorexia, fever, lethargy, recruitment of other immune cells, and phagocytosis. While production of immune system components is known to require some amino acids, increases in amino acid requirements are more than offset by the associated decrease in protein accretion and increased muscle protein degradation that also accompanies immune system activation. However, the biggest impact of cytokine production is a decrease in feed intake. Therefore, as feed intake decreases, the energy needed to drive protein synthesis is also decreased. This suggests that diets should still be formulated on a similar calorie：lysine ratio as those formulated for non-immune challenged pigs. The evidence is sparse or equivocal for increasing nutrient requirements during an immune challenge. Nutritionists and swine producers should resist the pressure to alter the diet, limit feed, or add expensive feed additives during an immune challenge. While immune stimulation does not necessitate changes in diet formulation, when pigs are challenged with non-pathogenic diarrhea there are potential advantages on gut health with the increased use of crystalline amino acids rather than intact protein sources （i.e., soybean meal）. This is because reducing crude protein decreases the quantity of fermentable protein entering the large intestine, which lowers post weaning diarrhea. It also lowers the requirement for expensive specialty protein sources or other protein sources such as soybean meal that present immunological challenges to the gut. The objective of this review is two-fold. The first is to discuss immunity by nutrition interactions, or lack thereof, and secondly, to review amino acid requirement estimates for nursery pigs.展开更多
The tumor microenvironment is an ecosystem composed of multiple types of cells, such as tumor cells, immune cells, and cancerassociated fibroblasts. Cancer cells grow faster than non-cancerous cells and consume larger...The tumor microenvironment is an ecosystem composed of multiple types of cells, such as tumor cells, immune cells, and cancerassociated fibroblasts. Cancer cells grow faster than non-cancerous cells and consume larger amounts of nutrients. The rapid growth characteristic of cancer cells fundamentally alters nutrient availability in the tumor microenvironment and results in reprogramming of immune cell metabolic pathways. Accumulating evidence suggests that cellular metabolism of nutrients, such as lipids and amino acids, beyond being essential to meet the bioenergetic and biosynthetic demands of immune cells, also regulates a broad spectrum of cellular signal transduction, and influences immune cell survival, differentiation, and anti-tumor effector function. The cancer immunometabolism research field is rapidly evolving, and exciting new discoveries are reported in high-profile journals nearly weekly. Therefore, all new findings in this field cannot be summarized within this short review. Instead, this review is intended to provide a brief introduction to this rapidly developing research field, with a focus on the metabolism of two classes of important nutrients-lipids and amino acids-in immune cells. We highlight recent research on the roles of lipids and amino acids in regulating the metabolic fitness and immunological functions of T cells, macrophages, and natural killer cells in the tumor microenvironment. Furthermore, we discuss the possibility of “editing” metabolic pathways in immune cells to act synergistically with currently available immunotherapies in enhancing anti-tumor immune responses.展开更多
High current findings indicate that a substitution with pyruvate can lead to significant alterations or even improvement in neutrophil immunonutrition. However, it is still unknown which intra-cellular pathways might ...High current findings indicate that a substitution with pyruvate can lead to significant alterations or even improvement in neutrophil immunonutrition. However, it is still unknown which intra-cellular pathways might be involved here. Hence, in this study, we investigated whether preincu-bation with an inhibitor of ·NO-synthase (L-NAME), an ·NO donor (SNAP), an analogue of taurine (beta-alanine), an inhibitor of ornithine-decarboxylase (DFMO) as well as a glutamine-analogue (DON), is able to alter the intragranulocytic metabolic response to pyruvate, here for example studied for neutrophil intracellular amino- and α-keto acid concentrations or important neutrophil immune functions [released myeloperoxidase (MPO), the formation of superoxide anions O2- and hydrogen peroxide (H2O2)]. In summary, the interesting first results presented here showed, that any damage of specific metabolic pathways or mechanisms, which seem directly or indirectly to be involved in relevant pyruvate dependent granulocytic nutrient content or specific cellular tasks, could lead to therapeutically desired, but also to unexpected or even fatal consequences for the affected cells. We therefore continue to believe that pyruvate, irrespective of which exact biochemical mechanisms were involved, in neutrophils may satisfy the substantial metabolic demands for a potent intracellular nutrient.展开更多
Agrobacterium-mediated plant transformation is widely used in plant genetic engineering.However,its efficiency is limited by plant immunity against Agrobacterium.Chili pepper(Capsicum annuum L.)is an important vegetab...Agrobacterium-mediated plant transformation is widely used in plant genetic engineering.However,its efficiency is limited by plant immunity against Agrobacterium.Chili pepper(Capsicum annuum L.)is an important vegetable that is recalcitrant to Agrobacterium-mediated transformation.In this work,Agrobacterium was found to induce a strong immune response in pepper,which might be the reason for T-DNA being difficult to express in pepper.An Agrobacterium mutant screen was conducted and a point mutation in the hisI gene was identified due to a weak immune response and enhanced transient expression mediated by this Agrobacterium mutant in pepper leaves.Further genetic analysis revealed that histidine biosynthesis deficiency caused by mutations in many genes of this pathway led to reduced pepper cell death,presumably due to reduced bacterial growth.However,mutation analysis of threonine and tryptophan biosynthesis genes showed that the biosynthesis of different amino acids may play different roles in Agrobacterium growth and stimulating the pepper immune response.The possible application of Agrobacterium amino acid biosynthesis mutations in plant biology was discussed.展开更多
Branched chain amino acids(BCAAs)have been shown to affect gene expression,protein metabolism,apoptosis and regeneration of hepatocytes,and insulin resistance.They have also been shown to inhibit the proliferation of ...Branched chain amino acids(BCAAs)have been shown to affect gene expression,protein metabolism,apoptosis and regeneration of hepatocytes,and insulin resistance.They have also been shown to inhibit the proliferation of liver cancer cells in vitro,and are essential for lymphocyte proliferation and dendritic cell maturation.In patients with advanced chronic liver disease,BCAA concentrations are low,whereas the concentrations of aromatic amino acids such as phenylalanine and tyrosine are high,conditions that may be closely associated with hepatic encephalopathy and the prognosis of these patients.Based on these basic observations,patients with advanced chronic liver disease have been treated clinically with BCAA-rich medicines,with positive effects.展开更多
It is widely known that branched chain amino acids（BCAA） are not only elementary components for building muscle tissue but also participate in increasing protein synthesis in animals and humans. BCAA（isoleucine, le...It is widely known that branched chain amino acids（BCAA） are not only elementary components for building muscle tissue but also participate in increasing protein synthesis in animals and humans. BCAA（isoleucine, leucine and valine） regulate many key signaling pathways, the most classic of which is the activation of the m TOR signaling pathway. This signaling pathway connects many diverse physiological and metabolic roles. Recent years have witnessed many striking developments in determining the novel functions of BCAA including：（1） Insufficient or excessive levels of BCAA in the diet enhances lipolysis.（2） BCAA, especially isoleucine, play a major role in enhancing glucose consumption and utilization by up-regulating intestinal and muscular glucose transporters.（3）Supplementation of leucine in the diet enhances meat quality in finishing pigs.（4） BCAA are beneficial for mammary health, milk quality and embryo growth.（5） BCAA enhance intestinal development, intestinal amino acid transportation and mucin production.（6） BCAA participate in up-regulating innate and adaptive immune responses.In addition, abnormally elevated BCAA levels in the blood（decreased BCAA catabolism） are a good biomarker for the early detection of obesity, diabetes and other metabolic diseases. This review will provide some insights into these novel metabolic and physiological functions of BCAA.展开更多
Purpose: Special nutrients have an impact on common cold infections. In this trial we have investigated the effectiveness of the specific amino acid composition “aminoplus? immun” on the occurrence, duration and sev...Purpose: Special nutrients have an impact on common cold infections. In this trial we have investigated the effectiveness of the specific amino acid composition “aminoplus? immun” on the occurrence, duration and severity of common cold. Material and Methods: Our study is a controlled, randomised completely masked trial comparing genuine trial remedy versus placebo in parallel groups. Eligible subjects were people with recurrent and chronic infections of the ear, nose and pharyngeal area. The treatment period was 90 days. The primary outcome was the mean number of days that the patients had symptoms of infections. Results: From Oct. 2009 to Feb. 2010 a total of 145 patients were recruited, of whom 119 had no major protocol violation and were valid for assessment. Two thirds of the patients were female. The mean age of the patients was 45 years. 65% of participants had come into contact with many people and thereby an increased risk of infection. On average the patients had 11.1 infections during the 12 months before the study. Compliance for the intake of the study preparation was 98.9%. Due to randomisation, the groups were very similar and balanced. The primary and all 6 secondary outcome variables showed a clear superiority of the investigated amino acid composition over placebo (p Conclusion: The specific composition “aminoplus? immun is effective in preventing recurrent and chronic infections of the ear, nose and upper respiratory tract.展开更多
文摘Recent advances in amino acid metabolism have revealed that targeting amino acid metabolic enzymes in cancer therapy is a promising strategy for the development of novel therapeutic agents. There are currently several drugs in clinical trials that specifically target amino acid metabolic pathways in tumor cells. In the context of the tumor microenvironment,however,tumor cells form metabolic relationships with immune cells,and they oftencompete for common nutrients. Many tumors evolved to escape immune surveillance by taking advantage of their metabolic flexibility and redirecting nutrients for their own advantage. This review outlines the most recent advances in targeting amino acid metabolic pathways in cancer therapy while giving consideration to the impact these pathways may have on the anti-tumor immune response.
基金Supported by Grants(in part)from Ministry of Education,Culture,Sports,Science and Technology of Japan and the Ministry of Health,Labor and Welfare of Japan
文摘It has been reported that host defense responses,such as phagocytic function of neutrophils and natural killer(NK)cell activity of lymphocytes,are impaired in cirrhotic patients.This review will concentrate on the impairment of innate immune responses in decompensated cirrhotic patients and the effect of the treatment by branched-chain amino acids(BCAA)on innate immune responses.We already reported that phagocytic function of neutrophils was significantly improved by3-mo BCAA supplementation.In addition,the changes of NK activity were also significant at 3 mo of supplementation compared with before supplementation.Also,Fisher’s ratios were reported to be significantly increased at 3 mo of BCAA supplementation compared with those before oral supplementation.Therefore,administration of BCAA could reduce the risk of bacterial and viral infection in patients with decompensated cirrhosis by restoring impaired innate immune responses of the host.In addition,it was also revealed that BCAA oral supplementation could reduce the risk of development of hepatocellular carcinoma in cirrhotic patients.The mechanisms of the effects will also be discussed in this review article.
文摘Immune system activation begins a host of physiological responses. Infectious agents are recognized by monocytes and macrophages which in turn stimulate cytokine production. It is the hormone-like factors called cytokines that orchestrate the immune response. The classic responses observed with immune system activation and cytokine production include： anorexia, fever, lethargy, recruitment of other immune cells, and phagocytosis. While production of immune system components is known to require some amino acids, increases in amino acid requirements are more than offset by the associated decrease in protein accretion and increased muscle protein degradation that also accompanies immune system activation. However, the biggest impact of cytokine production is a decrease in feed intake. Therefore, as feed intake decreases, the energy needed to drive protein synthesis is also decreased. This suggests that diets should still be formulated on a similar calorie：lysine ratio as those formulated for non-immune challenged pigs. The evidence is sparse or equivocal for increasing nutrient requirements during an immune challenge. Nutritionists and swine producers should resist the pressure to alter the diet, limit feed, or add expensive feed additives during an immune challenge. While immune stimulation does not necessitate changes in diet formulation, when pigs are challenged with non-pathogenic diarrhea there are potential advantages on gut health with the increased use of crystalline amino acids rather than intact protein sources （i.e., soybean meal）. This is because reducing crude protein decreases the quantity of fermentable protein entering the large intestine, which lowers post weaning diarrhea. It also lowers the requirement for expensive specialty protein sources or other protein sources such as soybean meal that present immunological challenges to the gut. The objective of this review is two-fold. The first is to discuss immunity by nutrition interactions, or lack thereof, and secondly, to review amino acid requirement estimates for nursery pigs.
基金supported by a CRI Lloyd J. Old STAR Award(Grant No. 3914)a Helmholtz Young Investigator Award(Grant No. VH-NG-1113)+7 种基金an EMBO Young Investigator Awardan Exploration Grant of the Boehringer Ingelheim Foundation (BIS)the German Research Foundation (DFG,Grant Nos. CU375/5-1, CU375/5-2, CU375/7-1, CU375/9-1, and 259332240/RTG2099)the German Cancer Aid Foundation (DKH, Grant Nos. 70113343 and 70114224)the Helmholtz Zukunftsthema Ageing and Metabolic Programming (AMPro, Grant No. ZT0026)HI-TRON KickStart Seed Funding (Grant No. HITR-2021-08)the Hector Foundation (Grant No. M20102)an ERC Consolidator Award (Grant No. 101045416)
文摘The tumor microenvironment is an ecosystem composed of multiple types of cells, such as tumor cells, immune cells, and cancerassociated fibroblasts. Cancer cells grow faster than non-cancerous cells and consume larger amounts of nutrients. The rapid growth characteristic of cancer cells fundamentally alters nutrient availability in the tumor microenvironment and results in reprogramming of immune cell metabolic pathways. Accumulating evidence suggests that cellular metabolism of nutrients, such as lipids and amino acids, beyond being essential to meet the bioenergetic and biosynthetic demands of immune cells, also regulates a broad spectrum of cellular signal transduction, and influences immune cell survival, differentiation, and anti-tumor effector function. The cancer immunometabolism research field is rapidly evolving, and exciting new discoveries are reported in high-profile journals nearly weekly. Therefore, all new findings in this field cannot be summarized within this short review. Instead, this review is intended to provide a brief introduction to this rapidly developing research field, with a focus on the metabolism of two classes of important nutrients-lipids and amino acids-in immune cells. We highlight recent research on the roles of lipids and amino acids in regulating the metabolic fitness and immunological functions of T cells, macrophages, and natural killer cells in the tumor microenvironment. Furthermore, we discuss the possibility of “editing” metabolic pathways in immune cells to act synergistically with currently available immunotherapies in enhancing anti-tumor immune responses.
文摘High current findings indicate that a substitution with pyruvate can lead to significant alterations or even improvement in neutrophil immunonutrition. However, it is still unknown which intra-cellular pathways might be involved here. Hence, in this study, we investigated whether preincu-bation with an inhibitor of ·NO-synthase (L-NAME), an ·NO donor (SNAP), an analogue of taurine (beta-alanine), an inhibitor of ornithine-decarboxylase (DFMO) as well as a glutamine-analogue (DON), is able to alter the intragranulocytic metabolic response to pyruvate, here for example studied for neutrophil intracellular amino- and α-keto acid concentrations or important neutrophil immune functions [released myeloperoxidase (MPO), the formation of superoxide anions O2- and hydrogen peroxide (H2O2)]. In summary, the interesting first results presented here showed, that any damage of specific metabolic pathways or mechanisms, which seem directly or indirectly to be involved in relevant pyruvate dependent granulocytic nutrient content or specific cellular tasks, could lead to therapeutically desired, but also to unexpected or even fatal consequences for the affected cells. We therefore continue to believe that pyruvate, irrespective of which exact biochemical mechanisms were involved, in neutrophils may satisfy the substantial metabolic demands for a potent intracellular nutrient.
基金supported by the National Key Research and Development Program of China(Grant No.2018YFD1000800)National Natural Science Foundation of China(Grant No.32172600)。
文摘Agrobacterium-mediated plant transformation is widely used in plant genetic engineering.However,its efficiency is limited by plant immunity against Agrobacterium.Chili pepper(Capsicum annuum L.)is an important vegetable that is recalcitrant to Agrobacterium-mediated transformation.In this work,Agrobacterium was found to induce a strong immune response in pepper,which might be the reason for T-DNA being difficult to express in pepper.An Agrobacterium mutant screen was conducted and a point mutation in the hisI gene was identified due to a weak immune response and enhanced transient expression mediated by this Agrobacterium mutant in pepper leaves.Further genetic analysis revealed that histidine biosynthesis deficiency caused by mutations in many genes of this pathway led to reduced pepper cell death,presumably due to reduced bacterial growth.However,mutation analysis of threonine and tryptophan biosynthesis genes showed that the biosynthesis of different amino acids may play different roles in Agrobacterium growth and stimulating the pepper immune response.The possible application of Agrobacterium amino acid biosynthesis mutations in plant biology was discussed.
文摘Branched chain amino acids(BCAAs)have been shown to affect gene expression,protein metabolism,apoptosis and regeneration of hepatocytes,and insulin resistance.They have also been shown to inhibit the proliferation of liver cancer cells in vitro,and are essential for lymphocyte proliferation and dendritic cell maturation.In patients with advanced chronic liver disease,BCAA concentrations are low,whereas the concentrations of aromatic amino acids such as phenylalanine and tyrosine are high,conditions that may be closely associated with hepatic encephalopathy and the prognosis of these patients.Based on these basic observations,patients with advanced chronic liver disease have been treated clinically with BCAA-rich medicines,with positive effects.
基金supported by the National Key Basic Research Program(S.Y.Q.,Grant Number 2012CB124704)
文摘It is widely known that branched chain amino acids（BCAA） are not only elementary components for building muscle tissue but also participate in increasing protein synthesis in animals and humans. BCAA（isoleucine, leucine and valine） regulate many key signaling pathways, the most classic of which is the activation of the m TOR signaling pathway. This signaling pathway connects many diverse physiological and metabolic roles. Recent years have witnessed many striking developments in determining the novel functions of BCAA including：（1） Insufficient or excessive levels of BCAA in the diet enhances lipolysis.（2） BCAA, especially isoleucine, play a major role in enhancing glucose consumption and utilization by up-regulating intestinal and muscular glucose transporters.（3）Supplementation of leucine in the diet enhances meat quality in finishing pigs.（4） BCAA are beneficial for mammary health, milk quality and embryo growth.（5） BCAA enhance intestinal development, intestinal amino acid transportation and mucin production.（6） BCAA participate in up-regulating innate and adaptive immune responses.In addition, abnormally elevated BCAA levels in the blood（decreased BCAA catabolism） are a good biomarker for the early detection of obesity, diabetes and other metabolic diseases. This review will provide some insights into these novel metabolic and physiological functions of BCAA.
文摘Purpose: Special nutrients have an impact on common cold infections. In this trial we have investigated the effectiveness of the specific amino acid composition “aminoplus? immun” on the occurrence, duration and severity of common cold. Material and Methods: Our study is a controlled, randomised completely masked trial comparing genuine trial remedy versus placebo in parallel groups. Eligible subjects were people with recurrent and chronic infections of the ear, nose and pharyngeal area. The treatment period was 90 days. The primary outcome was the mean number of days that the patients had symptoms of infections. Results: From Oct. 2009 to Feb. 2010 a total of 145 patients were recruited, of whom 119 had no major protocol violation and were valid for assessment. Two thirds of the patients were female. The mean age of the patients was 45 years. 65% of participants had come into contact with many people and thereby an increased risk of infection. On average the patients had 11.1 infections during the 12 months before the study. Compliance for the intake of the study preparation was 98.9%. Due to randomisation, the groups were very similar and balanced. The primary and all 6 secondary outcome variables showed a clear superiority of the investigated amino acid composition over placebo (p Conclusion: The specific composition “aminoplus? immun is effective in preventing recurrent and chronic infections of the ear, nose and upper respiratory tract.
