Background:1,2,3,4,6-penta-O-galloyl-beta-D-glucose(PGG)is a natural polyphenolic compound derived from multiple medicinal plants with favorable anticancer activity.Methods:In this study,the mechanisms of PGG against ...Background:1,2,3,4,6-penta-O-galloyl-beta-D-glucose(PGG)is a natural polyphenolic compound derived from multiple medicinal plants with favorable anticancer activity.Methods:In this study,the mechanisms of PGG against gastric cancer were explored through network pharmacology and molecular docking.First,the targets of PGG were searched in the Herbal Ingredients’Targets(HIT),Similarity Ensemble Approach(SEA),and Super-PRED databases.The potential targets related to gastric cancer were predicted from the Human Gene Database(GeneCards)and DisGeNET databases.The intersecting targets of PGG and gastric cancer were obtained by Venn diagram and then subjected to protein-protein interaction analysis to screen hub targets.Functional and pathway enrichment of hub targets were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway databases.The differential expression and survival analysis of hub targets in gastric cancer were performed based on The Cancer Genome Atlas database.Finally,the affinity of PGG with hub targets was visualized by molecular docking.Results:Three hub targets were screened,including mitogen-activated protein kinase 14(MAPK14),BCL2 like 1(BCL2L1),and vascular endothelial growth factor A(VEGFA).MAPK14 had a higher expression,while BCL2L1 and VEGFA had lower expression in gastric cancer than in normal conditions.Enrichment analysis indicated enrichment of these hub targets in MAPK,neurotrophin,programmed death-ligand 1(PD-L1)checkpoint,phosphatidylinositol 3-kinases/protein kinase B(PI3K-Akt),Ras,and hypoxia-inducible factor-1(HIF-1)signaling pathways.Conclusion:Therefore,network pharmacology and molecular docking analyses revealed that PGG exerts a therapeutic efficacy on gastric cancer by multiple targets(MAPK14,BCL2L1,and VEGFA)and pathways(MAPK,PD-L1 checkpoint,PI3K-Akt,Ras,and HIF-1 pathways).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
Leucine can affect intestinal protein expressions, and improve mucosal immune function. However, little study has been conducted to determine the change of protein component by leucine treatment in intestine epithelia...Leucine can affect intestinal protein expressions, and improve mucosal immune function. However, little study has been conducted to determine the change of protein component by leucine treatment in intestine epithelial cells. The present study was to cover the key proteins and cell pathways that could be regulated by leucine treatment in porcine intestinal epithelial cell line(IPEC-J2) cells with the approach of proteome analysis. A total number of 3,211 proteins were identified in our approach by searching the database of Uniprot sus scrofa. Among identified proteins, there were 101 proteins expressed differently between control group and leucine group. Compared with the control group, there were 50 up-regulated proteins and 51 down-regulated proteins in leucine group. In these proteins, leucine treatment decreased the expression of some proteins including pyruvate kinase, glyceraldehyde-3-phosphate dehydrogenase,E3 ubiquitin ligase, cathepsin D, caspase 3 and caspase 6, and increased the levels of some proteins, such as some eukaryotic translation initiation factors, ubiquitin carboxyl-terminal hydrolase, DNA-related RNA polymerase II, urokinase plasminogen activator, cyclin-dependent kinase inhibitor 2 b, Mut L homolog 1,5-methylcytosine binding domain 4, polymerase d, a-tubulin, syntaxin 18, Ras homolog D, actin related protein 2/3 complex and cofilin. Via the analysis of Gene Ontology and pathways, these proteins in IPECJ2 cells were related with some physiological functions, such as protein metabolism, glycolysis, cell proliferation, apoptosis and phagocytosis. Thus, these results suggest that leucine affects gut barrier function possibly via regulating cell proliferation and apoptosis, metabolism and phagocytosis.展开更多
基金supported by the Natural Science Foundation of Gansu Province[Grant Numbers 22JR5RA930,22JR5RA894]the Talent Project of Lanzhou Science and Technology Bureau[Grant Number 2022-3-44]+1 种基金the projects managed by the Administration of Traditional Chinese Medicine[Grant Number GZKG-2022-54]Intra Hospital Fund of the First Hospital of Lanzhou University[Grant Number ldyyyn2021101].
文摘Background:1,2,3,4,6-penta-O-galloyl-beta-D-glucose(PGG)is a natural polyphenolic compound derived from multiple medicinal plants with favorable anticancer activity.Methods:In this study,the mechanisms of PGG against gastric cancer were explored through network pharmacology and molecular docking.First,the targets of PGG were searched in the Herbal Ingredients’Targets(HIT),Similarity Ensemble Approach(SEA),and Super-PRED databases.The potential targets related to gastric cancer were predicted from the Human Gene Database(GeneCards)and DisGeNET databases.The intersecting targets of PGG and gastric cancer were obtained by Venn diagram and then subjected to protein-protein interaction analysis to screen hub targets.Functional and pathway enrichment of hub targets were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway databases.The differential expression and survival analysis of hub targets in gastric cancer were performed based on The Cancer Genome Atlas database.Finally,the affinity of PGG with hub targets was visualized by molecular docking.Results:Three hub targets were screened,including mitogen-activated protein kinase 14(MAPK14),BCL2 like 1(BCL2L1),and vascular endothelial growth factor A(VEGFA).MAPK14 had a higher expression,while BCL2L1 and VEGFA had lower expression in gastric cancer than in normal conditions.Enrichment analysis indicated enrichment of these hub targets in MAPK,neurotrophin,programmed death-ligand 1(PD-L1)checkpoint,phosphatidylinositol 3-kinases/protein kinase B(PI3K-Akt),Ras,and hypoxia-inducible factor-1(HIF-1)signaling pathways.Conclusion:Therefore,network pharmacology and molecular docking analyses revealed that PGG exerts a therapeutic efficacy on gastric cancer by multiple targets(MAPK14,BCL2L1,and VEGFA)and pathways(MAPK,PD-L1 checkpoint,PI3K-Akt,Ras,and HIF-1 pathways).
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.
基金financially supported by the grant from the National Basic Research Program(973 Program)of China(2013CB127306)the grant from National Natural Science Foundation of China(31201812)the earmarked fund for the China Agriculture Research System(CARS-35)
文摘Leucine can affect intestinal protein expressions, and improve mucosal immune function. However, little study has been conducted to determine the change of protein component by leucine treatment in intestine epithelial cells. The present study was to cover the key proteins and cell pathways that could be regulated by leucine treatment in porcine intestinal epithelial cell line(IPEC-J2) cells with the approach of proteome analysis. A total number of 3,211 proteins were identified in our approach by searching the database of Uniprot sus scrofa. Among identified proteins, there were 101 proteins expressed differently between control group and leucine group. Compared with the control group, there were 50 up-regulated proteins and 51 down-regulated proteins in leucine group. In these proteins, leucine treatment decreased the expression of some proteins including pyruvate kinase, glyceraldehyde-3-phosphate dehydrogenase,E3 ubiquitin ligase, cathepsin D, caspase 3 and caspase 6, and increased the levels of some proteins, such as some eukaryotic translation initiation factors, ubiquitin carboxyl-terminal hydrolase, DNA-related RNA polymerase II, urokinase plasminogen activator, cyclin-dependent kinase inhibitor 2 b, Mut L homolog 1,5-methylcytosine binding domain 4, polymerase d, a-tubulin, syntaxin 18, Ras homolog D, actin related protein 2/3 complex and cofilin. Via the analysis of Gene Ontology and pathways, these proteins in IPECJ2 cells were related with some physiological functions, such as protein metabolism, glycolysis, cell proliferation, apoptosis and phagocytosis. Thus, these results suggest that leucine affects gut barrier function possibly via regulating cell proliferation and apoptosis, metabolism and phagocytosis.
