There is growing evidence that metabolic alterations play an important role in cancer development and progression.The metabolism of cancer cells is reprogrammed in order to support their rapid proliferation.Elevated f...There is growing evidence that metabolic alterations play an important role in cancer development and progression.The metabolism of cancer cells is reprogrammed in order to support their rapid proliferation.Elevated fatty acid synthesis is one of the most important aberrations of cancer cell metabolism.An enhancement of fatty acids synthesis is required both for carcinogenesis and cancer cell survival,as inhibition of key lipogenic enzymes slows down the growth of tumor cells and impairs their survival.Based on the data that serum fatty acid synthase(FASN),also known as oncoantigen 519,is elevated in patients with certain types of cancer,its serum level was proposed as a marker of neoplasia.This review aims to demonstrate the changes in lipid metabolism and other metabolic processes associated with lipid metabolism in pancreatic ductal adenocarcinoma(PDAC),the most common pancreatic neoplasm,characterized by high mortality.We also addressed the influence of some oncogenic factors and tumor suppressors on pancreatic cancer cell metabolism.Additionally the review discusses the potential role of elevated lipid synthesis in diagnosis and treatment of pancreatic cancer.In particular,FASN is a viable candidate for indicator of pathologic state,marker of neoplasia,as well as,pharmacological treatment target in pancreatic cancer.Recent research showed that,in addition to lipogenesis,certain cancer cells can use fatty acids from circulation,derived from diet(chylomicrons),synthesized in liver,or released from adipose tissue for their growth.Thus,the interactions between de novo lipogenesis and uptake of fatty acids from circulation by PDAC cells require further investigation.展开更多
Pharmacokinetics(PK)is the study of the absorption,distribution,metabolism,and excretion(ADME)processes of a drug.Understanding PK properties is essential for drug development and precision medication.In this review w...Pharmacokinetics(PK)is the study of the absorption,distribution,metabolism,and excretion(ADME)processes of a drug.Understanding PK properties is essential for drug development and precision medication.In this review we provided an overview of recent research on PK with focus on the following aspects:(1)an update on drug-metabolizing enzymes and transporters in the determination of PK,as well as advances in xenobiotic receptors and noncoding RNAs(ncRNAs)in the modulation of PK,providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy;(2)current status and trends in assessing drug-drug interactions,especially interactions between drugs and herbs,between drugs and therapeutic biologies,and microbiota-mediated interactions:(3)advances in understanding the effects of diseases on PK,particularly changes in metabolizing enzymes and transporters with disease progression;(4)trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies:(5)emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes,especially non-P450s.Existing challenges and perspectives on future directions are discussed,and may stimulate the development of new research models,technologies,and strategies towards the development of better drugs and improved clinical practice.展开更多
Post-silking high temperature is one of the abiotic factors that affects waxy maize(Zea mays L. sinensis Kulesh) growth in southern China. We conducted a pot trial in 2016–2017 to study the effects of post-silking da...Post-silking high temperature is one of the abiotic factors that affects waxy maize(Zea mays L. sinensis Kulesh) growth in southern China. We conducted a pot trial in 2016–2017 to study the effects of post-silking daytime heat stress(35°C) on the activities of enzymes involved in leaf carbon and nitrogen metabolisms and leaf reactive oxygen species(ROS) and water contents. This study could improve our understanding on dry matter accumulation and translocation and grain yield production. Results indicated that decreased grain number and weight under heat stress led to yield loss, which decreased by 20.8 and 20.0% in 2016 and 2017, respectively. High temperature reduced post-silking dry matter accumulation(16.1 and 29.5% in 2016 and 2017, respectively) and promoted translocation of pre-silking photoassimilates stored in vegetative organs, especially in leaf. The lower leaf water content and chlorophyll SPAD value, and higher ROS(H2O2 and O2^-·) content under heat stress conditions indicated accelerated senescent rate. The weak activities of phosphoenolpyruvate carboxylase(PEPCase), Ribulose-1,5-bisphosphate carboxylase(Ru BPCase), nitrate reductase(NR), and glutamine synthase(GS) indicated that leaf carbon and nitrogen metabolisms were suppressed when the plants suffered from a high temperature during grain filling. Correlation analysis results indicated that the reduced grain yield was mainly caused by the decreased leaf water content, weakened NR activity, and increased H2O2 content. The increased accumulation of grain weight and post-silking dry matter and the reduced translocation amount in leaf was mainly due to the increased chlorophyll SPAD value and NR activity. Reduced PEPCase and Ru BPCase activities did not affect dry matter accumulation and translocation and grain yield. In conclusion, post-silking heat stress down-regulated the leaf NR and GS activities, increased the leafwater loss rate, increased ROS generation, and induced pre-silking carbohydrate translocation. However, it reduced the post-silk展开更多
基金Supported by Medical University of Gdansk Grants ST-41,ST-40
文摘There is growing evidence that metabolic alterations play an important role in cancer development and progression.The metabolism of cancer cells is reprogrammed in order to support their rapid proliferation.Elevated fatty acid synthesis is one of the most important aberrations of cancer cell metabolism.An enhancement of fatty acids synthesis is required both for carcinogenesis and cancer cell survival,as inhibition of key lipogenic enzymes slows down the growth of tumor cells and impairs their survival.Based on the data that serum fatty acid synthase(FASN),also known as oncoantigen 519,is elevated in patients with certain types of cancer,its serum level was proposed as a marker of neoplasia.This review aims to demonstrate the changes in lipid metabolism and other metabolic processes associated with lipid metabolism in pancreatic ductal adenocarcinoma(PDAC),the most common pancreatic neoplasm,characterized by high mortality.We also addressed the influence of some oncogenic factors and tumor suppressors on pancreatic cancer cell metabolism.Additionally the review discusses the potential role of elevated lipid synthesis in diagnosis and treatment of pancreatic cancer.In particular,FASN is a viable candidate for indicator of pathologic state,marker of neoplasia,as well as,pharmacological treatment target in pancreatic cancer.Recent research showed that,in addition to lipogenesis,certain cancer cells can use fatty acids from circulation,derived from diet(chylomicrons),synthesized in liver,or released from adipose tissue for their growth.Thus,the interactions between de novo lipogenesis and uptake of fatty acids from circulation by PDAC cells require further investigation.
基金supported by National Natural Science Foundation of China(grants:81573489,81522047,81730103,81320108027,81660618,and 81773808)the National Key Research and Development Program(grant:2017YFE0109900 and 2017YFC0909303,China)+5 种基金the 111 project(grant:B16047,China)the Key Laboratory Foundation of Guangdong Province(grant:2017B030314030,China)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01Y093,China)National Engineering and Technology Research Center for New drug Druggability Evaluation(Seed Program of Guangdong Province,2017B090903004,China)Natural Science Foundation of Guangdong(grant:2017A030311018 and 2015A030313124,China)National Institutes of Health(grants No.R01CA225958 and R01GM113888 to Ai-Ming Yu,USA).
文摘Pharmacokinetics(PK)is the study of the absorption,distribution,metabolism,and excretion(ADME)processes of a drug.Understanding PK properties is essential for drug development and precision medication.In this review we provided an overview of recent research on PK with focus on the following aspects:(1)an update on drug-metabolizing enzymes and transporters in the determination of PK,as well as advances in xenobiotic receptors and noncoding RNAs(ncRNAs)in the modulation of PK,providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy;(2)current status and trends in assessing drug-drug interactions,especially interactions between drugs and herbs,between drugs and therapeutic biologies,and microbiota-mediated interactions:(3)advances in understanding the effects of diseases on PK,particularly changes in metabolizing enzymes and transporters with disease progression;(4)trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies:(5)emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes,especially non-P450s.Existing challenges and perspectives on future directions are discussed,and may stimulate the development of new research models,technologies,and strategies towards the development of better drugs and improved clinical practice.
基金the Engineering Project for Innovative Scholars of He-nan Province(2004107014).This work was carried out in He-nan Key Laboratory for Molecular Medicine.
基金supported by the National Key Research and Development Program of China (2016YFD0300109 and 2018YFD0200703)the National Natural Science Foundation of China (31771709 and 31471436)the Priority Academic Program Development of Jiangsu Higher Education Institutions, China
文摘Post-silking high temperature is one of the abiotic factors that affects waxy maize(Zea mays L. sinensis Kulesh) growth in southern China. We conducted a pot trial in 2016–2017 to study the effects of post-silking daytime heat stress(35°C) on the activities of enzymes involved in leaf carbon and nitrogen metabolisms and leaf reactive oxygen species(ROS) and water contents. This study could improve our understanding on dry matter accumulation and translocation and grain yield production. Results indicated that decreased grain number and weight under heat stress led to yield loss, which decreased by 20.8 and 20.0% in 2016 and 2017, respectively. High temperature reduced post-silking dry matter accumulation(16.1 and 29.5% in 2016 and 2017, respectively) and promoted translocation of pre-silking photoassimilates stored in vegetative organs, especially in leaf. The lower leaf water content and chlorophyll SPAD value, and higher ROS(H2O2 and O2^-·) content under heat stress conditions indicated accelerated senescent rate. The weak activities of phosphoenolpyruvate carboxylase(PEPCase), Ribulose-1,5-bisphosphate carboxylase(Ru BPCase), nitrate reductase(NR), and glutamine synthase(GS) indicated that leaf carbon and nitrogen metabolisms were suppressed when the plants suffered from a high temperature during grain filling. Correlation analysis results indicated that the reduced grain yield was mainly caused by the decreased leaf water content, weakened NR activity, and increased H2O2 content. The increased accumulation of grain weight and post-silking dry matter and the reduced translocation amount in leaf was mainly due to the increased chlorophyll SPAD value and NR activity. Reduced PEPCase and Ru BPCase activities did not affect dry matter accumulation and translocation and grain yield. In conclusion, post-silking heat stress down-regulated the leaf NR and GS activities, increased the leafwater loss rate, increased ROS generation, and induced pre-silking carbohydrate translocation. However, it reduced the post-silk
