In previous experiment, we isolated a compound dibutyl phthalate (DBP) from Vaccaria segetalis which had galactopoietic function on mammary gland epithelial cells of dairy cow (DCMECs). In this experiment, we asce...In previous experiment, we isolated a compound dibutyl phthalate (DBP) from Vaccaria segetalis which had galactopoietic function on mammary gland epithelial cells of dairy cow (DCMECs). In this experiment, we ascertained the metabolic regulation function of DBP on DCMECs. Many genes related to lactation including Stat5, AMPK, b-casein, Glut1, SREBP-1, PEPCK, and ACC were detected by real-time PCR. Furthermore, Stat5 and AMPK were detected by Western blot and immunofluorescence co-localization, respectively. The results showed that DBP stimulates the expression of Stat5 and p-Stat5, thus activates Stat5 cell signal transduction pathway and stimulates b-casein synthesis. DBP also raises the activities of Glut1 and AMPK to stimulate glucose uptake and glycometabolism and activates the expression of AMPK downstream target genes PEPCK and ACC and expression of SREBP-1 to stimulate milk fat synthesis. In addition, the activities of HK, G-6-PDH, ICDH, ATPase, and energy charges were stimulated by DBP to increase the energy metabolism level of DCMECs. The results showed DBP stimulates energy metabolism related to galactopoietic function in DCMECs.展开更多
The use of traditional chemical catalysis to produce chemicals has a series of drawbacks,such as high dependence on fossil resources,high energy consumption,and environmental pollution.With the development of syntheti...The use of traditional chemical catalysis to produce chemicals has a series of drawbacks,such as high dependence on fossil resources,high energy consumption,and environmental pollution.With the development of synthetic biology and metabolic engineering,the use of renewable biomass raw materials for chemicals synthesis by constructing efficient microbial cell factories is a green way to replace traditional chemical catalysis and traditional microbial fermentation.This review mainly summarizes several types of bulk chemicals and high value-added chemicals using metabolic engineering and synthetic biology strategies to achieve efficient microbial production.In addition,this review also summarizes several strategies for effectively regulating microbial cell metabolism.These strategies can achieve the coupling balance of material and energy by regulating intracellular material metabolism or energy metabolism,and promote the efficient production of target chemicals by microorganisms.展开更多
The metabolic cycle firstly considered here is composed of a unique initial substrate, six enzymes, and five empty boxes to accommodate the substrates derived from the transformation of the initial substrate. This cyc...The metabolic cycle firstly considered here is composed of a unique initial substrate, six enzymes, and five empty boxes to accommodate the substrates derived from the transformation of the initial substrate. This cycle was considered as a pre-Closed Metabolic Cycle (CMC). Using this model, the influence of changing the kinetic constant values of any enzyme on the substrate concentration was explored. This model was transformed into an open metabolic cycle (OMC) by the input and output of two metabolites catalyzed by two external enzymes. In this case, the relative rates of input and output of metabolites were also examined;it can be concluded that the OMC cycles form delicate and fragile structures which can be theoretically disrupted, making them metabolically unfeasible.展开更多
The relevance of constipation to the development and progression of colorectal cancer(CRC)is currently a controversial issue.Studies have shown that changes in the composition of the gut microbiota,a condition known a...The relevance of constipation to the development and progression of colorectal cancer(CRC)is currently a controversial issue.Studies have shown that changes in the composition of the gut microbiota,a condition known as ecological imbalance,are correlated with an increasing number of common human diseases,including CRC and constipation.CRC is the second leading cause of cancerrelated deaths worldwide,and constipation has been receiving widespread attention as a risk factor for CRC.Early colonoscopy screening of constipated patients,with regular follow-ups and timely intervention,can help detect early intestinal lesions and reduce the risks of developing colorectal polyps and CRC.As an important regulator of the intestinal microenvironment,the gut microbiota plays a critical role in the onset and progression of CRC.An increasing amount of evidence supports the thought that gut microbial composition and function are key determinants of CRC development and progression,with alterations inducing changes in the expression of host genes,metabolic regulation,and local and systemic immunological responses.Furthermore,constipation greatly affects the composition of the gut microbiota,which in turn influences the susceptibility to intestinal diseases such as CRC.However,the crosstalk between the gut microbiota,constipation,and CRC is still unclear.展开更多
In addition to their pivotal roles in energy storage and expenditure,adipose tissues play a crucial part in the secretion of bioactive molecules,including peptides,lipids,metabolites,and extracellular vesicles,in resp...In addition to their pivotal roles in energy storage and expenditure,adipose tissues play a crucial part in the secretion of bioactive molecules,including peptides,lipids,metabolites,and extracellular vesicles,in response to physiological stimulation and met-abolic stress.These secretory factors,through autocrine and paracrine mechanisms,regulate various processes within adipose tissues.These processes include adipogenesis,glucose and lipid metabolism,inflammation,and adaptive thermogenesis,all of which are essential for the maintenance of the balance and functionality of the adipose tissue micro-environment.A subset of these adipose-derived secretory factors can enter the circulation and target the distant tissues to regulate appetite,cognitive function,energy expenditure,insulin secretion and sensitivity,gluconeogenesis,cardiovascular remodeling,and exercise capac-ity.In this review,we highlight the role of adipose-derived secretory factors and their signaling pathways in modulating meta-bolic homeostasis.Furthermore,we delve into the alterations in both the content and secretion processes of these factors under various physiological and pathological conditions,shedding light on potential pharmacological treatment strategies for related diseases.展开更多
This study examined the effect of insulin on the expression of very low density lipoprotein receptor (VLDLR) subtypes of SGC7901 cells and discussed its biological implication.In vitro, moderately or poorly-differenti...This study examined the effect of insulin on the expression of very low density lipoprotein receptor (VLDLR) subtypes of SGC7901 cells and discussed its biological implication.In vitro, moderately or poorly-differentiated human gastric adenocarcinoma cell line SGC7901 was incubated with insulin for different lengths of time, and then the expression of protein and RNA level in VLDLR subtypes were detected by Western blotting and real-time PCR, respectively.The results showed that, at certain time interval, insulin could down-regulate expression of type Ⅰ VLDLR and up-regulate the expression of type Ⅱ VLDLR in SGC7901 cells, at both protein and RNA level.We are led to conclude that insulin serves as a regulator in maintaining the balance between glucose and lipid metabolism in vivo, possibly through its effect on the differential expression of VLDLR subtypes.展开更多
Over 300 billion of cells die every day in the human body,producing a large number of endogenous apoptotic extracellular vesicles(apoEVs).Also,allogenic stem cell transplantation,a commonly used therapeutic approach i...Over 300 billion of cells die every day in the human body,producing a large number of endogenous apoptotic extracellular vesicles(apoEVs).Also,allogenic stem cell transplantation,a commonly used therapeutic approach in current clinical practice,generates exogenous apoEVs.It is well known that phagocytic cells engulf and digest apoEVs to maintain the body’s homeostasis.In this study,we show that a fraction of exogenous apoEVs is metabolized in the integumentary skin and hair follicles.Mechanistically,apoEVs activate the Wnt/β-catenin pathway to facilitate their metabolism in a wave-like pattern.The migration of apoEVs is enhanced by treadmill exercise and inhibited by tail suspension,which is associated with the mechanical force-regulated expression of DKK1 in circulation.Furthermore,we show that exogenous apoEVs promote wound healing and hair growth via activation of Wnt/β-catenin pathway in skin and hair follicle mesenchymal stem cells.This study reveals a previously unrecognized metabolic pathway of apoEVs and opens a new avenue for exploring apoEV-based therapy for skin and hair disorders.展开更多
Interactions between diet and the intestinal microbiome play an important role in human health and disease development.It is well known that such interactions,whether direct or indirect,trigger a series of metabolic r...Interactions between diet and the intestinal microbiome play an important role in human health and disease development.It is well known that such interactions,whether direct or indirect,trigger a series of metabolic reactions in the body.Evidence suggests that intestinal stem cells(ISCs),which are phenotypic precursors of various intestinal epithelial cells,play a significant role in the regulation of intestinal barrier function and homeostasis.The advent and evolution of intestinal organoid culture techniques have presented a key opportunity to study the association between the intestinal microenvironment and ISCs.As a result,the effects exerted by dietary factors,intestinal microbiomes,and their metabolites on the metabolic regulation of ISCs and the potential mechanisms underlying such effects are being gradually revealed.This review summarises the effects of different dietary patterns on the behaviour and functioning of ISCs and focuses on the crosstalk between intestinal microbiota,related metabolites,and ISCs,with the aim of fully understanding the relationship between these three factors and providing further insights into the complex mechanisms associated with ISCs in the human body.Gaining an understanding of these mechanisms may lead to the development of novel dietary interventions or drugs conducive to intestinal health.展开更多
In plants, vitamin B6 biosynthesis requires the activity of PDX1 and PDX2 proteins. Arabidopsis thaliana encodes for three PDX1 proteins, named PDXI.1, 1.2, and 1.3, but only one PDX2. Here, we show in planta complex ...In plants, vitamin B6 biosynthesis requires the activity of PDX1 and PDX2 proteins. Arabidopsis thaliana encodes for three PDX1 proteins, named PDXI.1, 1.2, and 1.3, but only one PDX2. Here, we show in planta complex assembly of PDX proteins, based on split-YFP and FPLC assays, and can demonstrate their presence in higher complexes of around 750 kDa. Metabolic profiling of plants ectopically expressing the different PDX proteins indicates a negative influence of PDX1.2 on vitamin Be biosynthesis and a correlation between aberrant vitamin B6 content, PDX1 gene expression, and light sensitivity specifically for PDX1.3. These findings provide first insights into in planta vitamin B6 synthase complex assembly and new information on how the different PDX proteins affect plant metabolism.展开更多
Thyroid hormone plays pivotal roles in growth,differentiation,development and metabolic homeostasis via thyroid hormone receptors(TRs)by controlling the expression of TR target genes.The transcriptional activity of TR...Thyroid hormone plays pivotal roles in growth,differentiation,development and metabolic homeostasis via thyroid hormone receptors(TRs)by controlling the expression of TR target genes.The transcriptional activity of TRs is modulated by multiple factors including various TR isoforms,diverse thyroid hormone response elements,different heterodimeric partners,coregulators,and the cellular location of TRs.In the present review,we summarize recent advance in understanding the molecular mechanisms of thyroid hormone action obtained from human subject research,thyroid hormone mimetics application,TR isoform-specific knock-in mouse models,and mitochondrion study with highlights in metabolic regulations.Finally,as future perspectives,we share our thoughts about current challenges and possible approaches to promote our knowledge of thyroid hormone action in metabolism.展开更多
Although a considerable increase in our knowledge concerning the importance of metabolic adjustments to unfavorable growth conditions has been recently provided, relatively little is known about the adjustments which ...Although a considerable increase in our knowledge concerning the importance of metabolic adjustments to unfavorable growth conditions has been recently provided, relatively little is known about the adjustments which occur in response to fluctuation in environmental factors. Evaluating the metabolic adjustments occurring under changing environmental conditions thus offers a good opportunity to increase our current understanding of the crosstalk between the major pathways which are affected by such conditions. To this end, plants growing under normal conditions were transferred to different light and temperature conditions which were anticipated to affect (amongst other processes) the rates of photosynthesis and photorespiration and characterized at the physiological, molecular, and metabolic levels following this transition. Our results revealed similar behavior in response to both treatments and imply a tight connec- tivity of photorespiration with the major pathways of plant metabolism. They further highlight that the majority of the regulation of these pathways is not mediated at the level of transcription but that leaf metabolism is rather pre-poised to adapt to changes in these input parameters.展开更多
Diterpenoid lactones(DLs),a group of furan-containing compounds found in Dioscorea bulbifera L.(DB),have been reported to be associated with hepatotoxicity.Different hepatotoxicities of these DLs have been observed in...Diterpenoid lactones(DLs),a group of furan-containing compounds found in Dioscorea bulbifera L.(DB),have been reported to be associated with hepatotoxicity.Different hepatotoxicities of these DLs have been observed in vitro,but reasonable explanations for the differential hepatotoxicity have not been provided.Herein,the present study aimed to confirm the potential factors that contribute to varied hepatotoxicity of four representative DLs(diosbulbins A,B,C,F).In vitro toxic effects were evaluated in various cell models and the interactions between DLs and CYP3 A4 at the atomic level were simulated by molecular docking.Results showed that DLs exhibited varied cytotoxicities,and that CYP3 A4 played a modulatory role in this process.Moreover,structural variation may cause different affinities between DLs and CYP3 A4,which was positively correlated with the observation of cytotoxicity.In addition,analysis of the glutathione(GSH)conjugates indicated that reactive intermediates were formed by metabolic oxidation that occurred on the furan moiety of DLs,whereas,GSH consumption analysis reflected the consistency between the reactive metabolites and the hepatotoxicity.Collectively,our findings illustrated that the metabolic regulation played a crucial role in generating the varied hepatotoxicity of DLs.展开更多
The progression of many diseases is accompanied by inflammation,in which inflammasomes play an important role.Inflammasomes are large multimolecular complexes present in the cytosol of stimulated immune cells,which me...The progression of many diseases is accompanied by inflammation,in which inflammasomes play an important role.Inflammasomes are large multimolecular complexes present in the cytosol of stimulated immune cells,which mediate the activation of caspase-1 and the secretion of cytokines,leading to cellular pyroptosis.During this process,metabolic regulation of the inflammasome is gaining increasing attention in this field.This review focuses on a major inflammasome,NOD-,LRR-and pyrin domain-containing protein 3(NLRP3),and discusses the role and significance of its metabolic regulation.展开更多
In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the inte...In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the intestinal barrier and reduced liver fibrosis in a mouse model of ALD.The study also underlines the role of PPARs in intestinal barrier function and lipid homeostasis,which are both affected by ALD.Effective therapies are necessary for ALD because it is a critical health issue that affects people worldwide.This editorial analyzes the possibility of PPAR agonists as treatments for ALD.As key factors of inflammation and metabolism,PPARs offer multiple methods for managing the complex etiology of ALD.We assess the abilities of PPARα,PPARγ,and PPARβ/δagonists to prevent steatosis,inflammation,and fibrosis due to liver diseases.Recent research carried out in preclinical and clinical settings has shown that PPAR agonists can reduce the severity of liver disease.This editorial discusses the data analyzed and the obstacles,advantages,and mechanisms of action of PPAR agonists for ALD.Further research is needed to understand the efficacy,safety,and mechanisms of PPAR agonists for treating ALD.展开更多
The core G protein signaling module,which consists of Gαand extra-large Gα(XLG)subunits coupled with the Gβγdimer,is a master regulator of various stress responses.In this study,we compared the basal and salt stre...The core G protein signaling module,which consists of Gαand extra-large Gα(XLG)subunits coupled with the Gβγdimer,is a master regulator of various stress responses.In this study,we compared the basal and salt stress-induced transcriptomic,metabolomic and phenotypic profiles in Gα,Gβ,and XLG-null mutants of two plant species,Arabidopsis thaliana and Marchantia polymorpha,and showed that G protein mediates the shift of transcriptional and metabolic homeostasis to stress readiness status.We demonstrated that such stress readiness serves as an intrinsic protection mechanism against further stressors through enhancing the phenylpropanoid pathway and abscisic acid responses.Furthermore,WRKY transcription factors were identified as key intermediates of G protein-mediated homeostatic shifts.Statistical and mathematical model comparisons between A.thaliana and M.polymorpha revealed evolutionary conservation of transcriptional and metabolic networks over land plant evolution,whereas divergence has occurred in the function of plant-specific atypical XLG subunit.Taken together,our results indicate that the shifts in transcriptional and metabolic homeostasis at least partially act as the mechanisms of G protein-coupled stress responses that are conserved between two distantly related plants.展开更多
Metabolic-dysfunction-associated fatty liver disease(MAFLD)is a group of highly heterogeneous multi-system diseases,which is closely related to metabolic dysfunction and is one of the most important public health prob...Metabolic-dysfunction-associated fatty liver disease(MAFLD)is a group of highly heterogeneous multi-system diseases,which is closely related to metabolic dysfunction and is one of the most important public health problems in the world.Studies have shown that paracrine fibroblast growth factors(FGFs)play an important role in the occurrence and development of MAFLD by regulating glucose and lipid metabolism,inflammation,and fibrosis.This article reviews the latest progress in understanding of the distribution,function,and metabolic regulation of paracrine FGFs,which paves the way for future FGF-based therapies targeting MAFLD.展开更多
Prodigiosin is a secondary metabolite mainly produced at 30°C in Serratia marcescens,but it can hardly be synthetized at 37°C or higher.In this study,we provide insight into the metabolic regulation of prodi...Prodigiosin is a secondary metabolite mainly produced at 30°C in Serratia marcescens,but it can hardly be synthetized at 37°C or higher.In this study,we provide insight into the metabolic regulation of prodigiosin synthesis in response to temperature through transcriptome sequencing.The analysis of the function of differentially expressed genes suggested that temperature resulted in significant alteration of the metabolic pathways between 30 and 37°C.Specifically,30°C favored transcriptional expression of the pig gene cluster.At the same time,the carbon flux was redistributed to pathways of pyruvate,proline,serine,especially homoserine,cystathionine,homocysteine,methionine,and s-adenosylmethionine metabolism,all involved in prodigiosin biosynthesis,and was finally increased towards the prodigiosin synthesis pathway in S.marcescens at 30°C.Interestingly,results further confirmed increased transcriptional level of five regulators(LuxS,RpoS,Hfq,EepR,CRP),and decreased content of hexS through qPCR.Finally,successful co-overexpression of mmuM and metK,related to homocysteine,methionine,and s-adenosylmethionine metabolism,in the chromosome of JNB5-1(JNB5-1/MK)resulted in increased prodigiosin titer up to 7.57 g/L in JNB5-1/MK at 30°C,which was 41.2%higher than that in JNB5-1.Our transcriptome analysis provides further insight into the strain’s response to temperature changes at the transcription level,which is of great significance for improving the production of prodigiosin.展开更多
The B7/CD28 families of immune checkpoints play vital roles in negatively or positively regulating immune cells in homeostasis and various diseases.Recent basic and clinical studies have revealed novel biology of the ...The B7/CD28 families of immune checkpoints play vital roles in negatively or positively regulating immune cells in homeostasis and various diseases.Recent basic and clinical studies have revealed novel biology of the B7/CD28 families and new therapeutics for cancer therapy.In this review,we discuss the newly discovered KIR3DL3/TMIGD2/HHLA2 pathways,PD-1/PD-L1 and B7-H3 as metabolic regulators,the glycobiology of PD-1/PD-L1,B7x(B7-H4)and B7-H3,and the recently characterized PD-L1/B7-1 cis-interaction.We also cover the tumor-intrinsic and-extrinsic resistance mechanisms to current anti-PD-1/PD-L1 and anti-CTLA-4 immunotherapies in clinical settings.Finally,we review new immunotherapies targeting B7-H3,B7x,PD-1/PD-L1,and CTLA-4 in current clinical trials.展开更多
Microorganisms are important sources of various natural products that have been commercialized for human medicine and animal healthcare.Bacitracin is an important antibacterial natural product predominantly pro-duced ...Microorganisms are important sources of various natural products that have been commercialized for human medicine and animal healthcare.Bacitracin is an important antibacterial natural product predominantly pro-duced by Bacillus licheniformis and Bacillus subtilis,and it is characterized by a broad antimicrobial spectrum,strong activity and low resistance,thus bacitracin is extensively applied in animal feed and veterinary medicine industries.In recent years,various strategies have been proposed to improve bacitracin production.Herein,we systematically describe the regulation of bacitracin biosynthesis in genus Bacillus and its associated mechanism,to provide a theoretical basis for bacitracin overproduction.The metabolic engineering strategies applied for bacitracin production are explored,including improving substrate utilization,using an enlarged precursor amino acid pool,increasing ATP supply and NADPH generation,and engineering transcription regulators.We also present several approaches of fermentation process optimization to facilitate the industrial large-scale production of bacitracin.Finally,the challenges and prospects associated with microbial bacitracin synthesis are discussed to facilitate the establishment of high-yield and low-cost biological factories.展开更多
Ganoderma lucidum is a valuable medical macrofungus with a myriad of diverse secondary metabolites,in which triterpenoids are the major constituents.This paper introduced the germplasm resources of genus Ganoderma fro...Ganoderma lucidum is a valuable medical macrofungus with a myriad of diverse secondary metabolites,in which triterpenoids are the major constituents.This paper introduced the germplasm resources of genus Ganoderma from textual research,its distribution and identification at the molecular level.Also we overviewed G.lucidum in the components,the biological activities and biosynthetic pathways of ganoderic acid,aiming to provide scientific evidence for the development and utilization of G.lucidum germplasm resources and the biosynthesis of ganoderic acid.展开更多
基金supported by the National High Technology Research and Development Program of China (863 Program, 2006AA10Z1A4)the Innovation Team of the Northeast Agricultural University, China (LXT005-1-2)the Talents Foundation of Northeast Agriculture Univesity, China (2010RCB47)
文摘In previous experiment, we isolated a compound dibutyl phthalate (DBP) from Vaccaria segetalis which had galactopoietic function on mammary gland epithelial cells of dairy cow (DCMECs). In this experiment, we ascertained the metabolic regulation function of DBP on DCMECs. Many genes related to lactation including Stat5, AMPK, b-casein, Glut1, SREBP-1, PEPCK, and ACC were detected by real-time PCR. Furthermore, Stat5 and AMPK were detected by Western blot and immunofluorescence co-localization, respectively. The results showed that DBP stimulates the expression of Stat5 and p-Stat5, thus activates Stat5 cell signal transduction pathway and stimulates b-casein synthesis. DBP also raises the activities of Glut1 and AMPK to stimulate glucose uptake and glycometabolism and activates the expression of AMPK downstream target genes PEPCK and ACC and expression of SREBP-1 to stimulate milk fat synthesis. In addition, the activities of HK, G-6-PDH, ICDH, ATPase, and energy charges were stimulated by DBP to increase the energy metabolism level of DCMECs. The results showed DBP stimulates energy metabolism related to galactopoietic function in DCMECs.
基金This work was financially supported by the National Natural Science Foundation of China(Grant Nos.21811530003,21861132017,U1663227,21706006)。
文摘The use of traditional chemical catalysis to produce chemicals has a series of drawbacks,such as high dependence on fossil resources,high energy consumption,and environmental pollution.With the development of synthetic biology and metabolic engineering,the use of renewable biomass raw materials for chemicals synthesis by constructing efficient microbial cell factories is a green way to replace traditional chemical catalysis and traditional microbial fermentation.This review mainly summarizes several types of bulk chemicals and high value-added chemicals using metabolic engineering and synthetic biology strategies to achieve efficient microbial production.In addition,this review also summarizes several strategies for effectively regulating microbial cell metabolism.These strategies can achieve the coupling balance of material and energy by regulating intracellular material metabolism or energy metabolism,and promote the efficient production of target chemicals by microorganisms.
文摘The metabolic cycle firstly considered here is composed of a unique initial substrate, six enzymes, and five empty boxes to accommodate the substrates derived from the transformation of the initial substrate. This cycle was considered as a pre-Closed Metabolic Cycle (CMC). Using this model, the influence of changing the kinetic constant values of any enzyme on the substrate concentration was explored. This model was transformed into an open metabolic cycle (OMC) by the input and output of two metabolites catalyzed by two external enzymes. In this case, the relative rates of input and output of metabolites were also examined;it can be concluded that the OMC cycles form delicate and fragile structures which can be theoretically disrupted, making them metabolically unfeasible.
基金Supported by National Natural Science Foundation of China,No. 82000511 and 82170558Scientific and Technological Projects of Tianjin,No. 21JCQNJC01120+3 种基金Health Science and Technology Project of Tianjin,No. TJWJ2021QN006Scientific Research Project of Tianjin Education Commission,No. 2019KJ197Natural Science Foundation of Zhejiang Province,No. LQ23H050005Scientific Research Project of Zhejiang Provincial Education Department,No. Y202250731
文摘The relevance of constipation to the development and progression of colorectal cancer(CRC)is currently a controversial issue.Studies have shown that changes in the composition of the gut microbiota,a condition known as ecological imbalance,are correlated with an increasing number of common human diseases,including CRC and constipation.CRC is the second leading cause of cancerrelated deaths worldwide,and constipation has been receiving widespread attention as a risk factor for CRC.Early colonoscopy screening of constipated patients,with regular follow-ups and timely intervention,can help detect early intestinal lesions and reduce the risks of developing colorectal polyps and CRC.As an important regulator of the intestinal microenvironment,the gut microbiota plays a critical role in the onset and progression of CRC.An increasing amount of evidence supports the thought that gut microbial composition and function are key determinants of CRC development and progression,with alterations inducing changes in the expression of host genes,metabolic regulation,and local and systemic immunological responses.Furthermore,constipation greatly affects the composition of the gut microbiota,which in turn influences the susceptibility to intestinal diseases such as CRC.However,the crosstalk between the gut microbiota,constipation,and CRC is still unclear.
基金supported by the National Key R&D Program of China(grant 2018YFA0800400 to Q.Q.T.)the National Natural Science Foundation of China(NSFC)(grants 82370881,82170884,and 81970744 to Y.L.)Shanghai Rising-Star Program(grant 22QA1402100 to Y.L.).
文摘In addition to their pivotal roles in energy storage and expenditure,adipose tissues play a crucial part in the secretion of bioactive molecules,including peptides,lipids,metabolites,and extracellular vesicles,in response to physiological stimulation and met-abolic stress.These secretory factors,through autocrine and paracrine mechanisms,regulate various processes within adipose tissues.These processes include adipogenesis,glucose and lipid metabolism,inflammation,and adaptive thermogenesis,all of which are essential for the maintenance of the balance and functionality of the adipose tissue micro-environment.A subset of these adipose-derived secretory factors can enter the circulation and target the distant tissues to regulate appetite,cognitive function,energy expenditure,insulin secretion and sensitivity,gluconeogenesis,cardiovascular remodeling,and exercise capac-ity.In this review,we highlight the role of adipose-derived secretory factors and their signaling pathways in modulating meta-bolic homeostasis.Furthermore,we delve into the alterations in both the content and secretion processes of these factors under various physiological and pathological conditions,shedding light on potential pharmacological treatment strategies for related diseases.
基金supported by grants from National Natural Sciences Foundation of China (No.39970307)Hubei Provincial Natural Sciences Foundation of China (No.2005ABA092)
文摘This study examined the effect of insulin on the expression of very low density lipoprotein receptor (VLDLR) subtypes of SGC7901 cells and discussed its biological implication.In vitro, moderately or poorly-differentiated human gastric adenocarcinoma cell line SGC7901 was incubated with insulin for different lengths of time, and then the expression of protein and RNA level in VLDLR subtypes were detected by Western blotting and real-time PCR, respectively.The results showed that, at certain time interval, insulin could down-regulate expression of type Ⅰ VLDLR and up-regulate the expression of type Ⅱ VLDLR in SGC7901 cells, at both protein and RNA level.We are led to conclude that insulin serves as a regulator in maintaining the balance between glucose and lipid metabolism in vivo, possibly through its effect on the differential expression of VLDLR subtypes.
基金supported by grants from the National Key R&D Program of China(2021YFA1100600 to S.S.)the Guangdong Financial Fund for High-Caliber Hospital Construction(174-2018-XMZC-0001-03-0125,D-07 to S.S.,D-11 to X.K.)+5 种基金the Pearl River Talent Recruitment Program(2019ZT08Y485)the National Science and Technology Major Project of the Ministry of Science and Technology of China(2018ZX10302207-001-002)the Sun Yat-sen University Young Teacher Key Cultivation Project(18ykzd05 to X.K.)the Natural Science Foundation of Guangdong(2016A030313262 to X.M.)the National Natural Science Foundation of China(82170924 to X.K.,81700928 to L.M.)the Youth Teacher Training Project of Sun Yat-sen University(17ykpy71 to L.M.).
文摘Over 300 billion of cells die every day in the human body,producing a large number of endogenous apoptotic extracellular vesicles(apoEVs).Also,allogenic stem cell transplantation,a commonly used therapeutic approach in current clinical practice,generates exogenous apoEVs.It is well known that phagocytic cells engulf and digest apoEVs to maintain the body’s homeostasis.In this study,we show that a fraction of exogenous apoEVs is metabolized in the integumentary skin and hair follicles.Mechanistically,apoEVs activate the Wnt/β-catenin pathway to facilitate their metabolism in a wave-like pattern.The migration of apoEVs is enhanced by treadmill exercise and inhibited by tail suspension,which is associated with the mechanical force-regulated expression of DKK1 in circulation.Furthermore,we show that exogenous apoEVs promote wound healing and hair growth via activation of Wnt/β-catenin pathway in skin and hair follicle mesenchymal stem cells.This study reveals a previously unrecognized metabolic pathway of apoEVs and opens a new avenue for exploring apoEV-based therapy for skin and hair disorders.
基金supported by the National Natural Science Foundation of China(81973837)Scientific and technological innovation project of China Academy of Chinese Medical Sciences(CI2021A016)National Key projects for international cooperation on science,technology and innovation(2021YFE0201100).
文摘Interactions between diet and the intestinal microbiome play an important role in human health and disease development.It is well known that such interactions,whether direct or indirect,trigger a series of metabolic reactions in the body.Evidence suggests that intestinal stem cells(ISCs),which are phenotypic precursors of various intestinal epithelial cells,play a significant role in the regulation of intestinal barrier function and homeostasis.The advent and evolution of intestinal organoid culture techniques have presented a key opportunity to study the association between the intestinal microenvironment and ISCs.As a result,the effects exerted by dietary factors,intestinal microbiomes,and their metabolites on the metabolic regulation of ISCs and the potential mechanisms underlying such effects are being gradually revealed.This review summarises the effects of different dietary patterns on the behaviour and functioning of ISCs and focuses on the crosstalk between intestinal microbiota,related metabolites,and ISCs,with the aim of fully understanding the relationship between these three factors and providing further insights into the complex mechanisms associated with ISCs in the human body.Gaining an understanding of these mechanisms may lead to the development of novel dietary interventions or drugs conducive to intestinal health.
文摘In plants, vitamin B6 biosynthesis requires the activity of PDX1 and PDX2 proteins. Arabidopsis thaliana encodes for three PDX1 proteins, named PDXI.1, 1.2, and 1.3, but only one PDX2. Here, we show in planta complex assembly of PDX proteins, based on split-YFP and FPLC assays, and can demonstrate their presence in higher complexes of around 750 kDa. Metabolic profiling of plants ectopically expressing the different PDX proteins indicates a negative influence of PDX1.2 on vitamin Be biosynthesis and a correlation between aberrant vitamin B6 content, PDX1 gene expression, and light sensitivity specifically for PDX1.3. These findings provide first insights into in planta vitamin B6 synthase complex assembly and new information on how the different PDX proteins affect plant metabolism.
基金supported by grants from the One Hundred Talents Program of the Chinese Academy of Sciencesthe National Basic Research Program(973 Program)(Grant Nos.2009CB919000 and 2010CB912500)+1 种基金the National Natural Science Foundation of China(Grant Nos.30970587 and 31070679)the Science and Technology Commission of Shanghai Municipality(10ZR1435000).
文摘Thyroid hormone plays pivotal roles in growth,differentiation,development and metabolic homeostasis via thyroid hormone receptors(TRs)by controlling the expression of TR target genes.The transcriptional activity of TRs is modulated by multiple factors including various TR isoforms,diverse thyroid hormone response elements,different heterodimeric partners,coregulators,and the cellular location of TRs.In the present review,we summarize recent advance in understanding the molecular mechanisms of thyroid hormone action obtained from human subject research,thyroid hormone mimetics application,TR isoform-specific knock-in mouse models,and mitochondrion study with highlights in metabolic regulations.Finally,as future perspectives,we share our thoughts about current challenges and possible approaches to promote our knowledge of thyroid hormone action in metabolism.
文摘Although a considerable increase in our knowledge concerning the importance of metabolic adjustments to unfavorable growth conditions has been recently provided, relatively little is known about the adjustments which occur in response to fluctuation in environmental factors. Evaluating the metabolic adjustments occurring under changing environmental conditions thus offers a good opportunity to increase our current understanding of the crosstalk between the major pathways which are affected by such conditions. To this end, plants growing under normal conditions were transferred to different light and temperature conditions which were anticipated to affect (amongst other processes) the rates of photosynthesis and photorespiration and characterized at the physiological, molecular, and metabolic levels following this transition. Our results revealed similar behavior in response to both treatments and imply a tight connec- tivity of photorespiration with the major pathways of plant metabolism. They further highlight that the majority of the regulation of these pathways is not mediated at the level of transcription but that leaf metabolism is rather pre-poised to adapt to changes in these input parameters.
基金supported by the National Natural Science Foundation of China(No.81773993)
文摘Diterpenoid lactones(DLs),a group of furan-containing compounds found in Dioscorea bulbifera L.(DB),have been reported to be associated with hepatotoxicity.Different hepatotoxicities of these DLs have been observed in vitro,but reasonable explanations for the differential hepatotoxicity have not been provided.Herein,the present study aimed to confirm the potential factors that contribute to varied hepatotoxicity of four representative DLs(diosbulbins A,B,C,F).In vitro toxic effects were evaluated in various cell models and the interactions between DLs and CYP3 A4 at the atomic level were simulated by molecular docking.Results showed that DLs exhibited varied cytotoxicities,and that CYP3 A4 played a modulatory role in this process.Moreover,structural variation may cause different affinities between DLs and CYP3 A4,which was positively correlated with the observation of cytotoxicity.In addition,analysis of the glutathione(GSH)conjugates indicated that reactive intermediates were formed by metabolic oxidation that occurred on the furan moiety of DLs,whereas,GSH consumption analysis reflected the consistency between the reactive metabolites and the hepatotoxicity.Collectively,our findings illustrated that the metabolic regulation played a crucial role in generating the varied hepatotoxicity of DLs.
基金This work was supported by the National Natural Science Foundation of China(81930042,81730047,31670926,and 31800759)the National Key Research and Development Program of China(2018YFC1105203 and 2016YFC1100204).
文摘The progression of many diseases is accompanied by inflammation,in which inflammasomes play an important role.Inflammasomes are large multimolecular complexes present in the cytosol of stimulated immune cells,which mediate the activation of caspase-1 and the secretion of cytokines,leading to cellular pyroptosis.During this process,metabolic regulation of the inflammasome is gaining increasing attention in this field.This review focuses on a major inflammasome,NOD-,LRR-and pyrin domain-containing protein 3(NLRP3),and discusses the role and significance of its metabolic regulation.
文摘In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the intestinal barrier and reduced liver fibrosis in a mouse model of ALD.The study also underlines the role of PPARs in intestinal barrier function and lipid homeostasis,which are both affected by ALD.Effective therapies are necessary for ALD because it is a critical health issue that affects people worldwide.This editorial analyzes the possibility of PPAR agonists as treatments for ALD.As key factors of inflammation and metabolism,PPARs offer multiple methods for managing the complex etiology of ALD.We assess the abilities of PPARα,PPARγ,and PPARβ/δagonists to prevent steatosis,inflammation,and fibrosis due to liver diseases.Recent research carried out in preclinical and clinical settings has shown that PPAR agonists can reduce the severity of liver disease.This editorial discusses the data analyzed and the obstacles,advantages,and mechanisms of action of PPAR agonists for ALD.Further research is needed to understand the efficacy,safety,and mechanisms of PPAR agonists for treating ALD.
基金This study was supported by the Agency for Science,Technology and Research(A*STAR)Singapore under the Industry Alignment Fund Pre-positioning Program,the High Performance Precision Agriculture(HiPPA)system(A19E4a0101)the Singapore-MIT Aliance for Research and Technology,and Disruptive&Sustainable Technologies for Agricul-tural Precision(DISTAP)(to D.U.)a discovery grant from the Natural Sciences and Engineering Research Council of Canada(ARGPIN-2020-07097)(to K-LL)。
文摘The core G protein signaling module,which consists of Gαand extra-large Gα(XLG)subunits coupled with the Gβγdimer,is a master regulator of various stress responses.In this study,we compared the basal and salt stress-induced transcriptomic,metabolomic and phenotypic profiles in Gα,Gβ,and XLG-null mutants of two plant species,Arabidopsis thaliana and Marchantia polymorpha,and showed that G protein mediates the shift of transcriptional and metabolic homeostasis to stress readiness status.We demonstrated that such stress readiness serves as an intrinsic protection mechanism against further stressors through enhancing the phenylpropanoid pathway and abscisic acid responses.Furthermore,WRKY transcription factors were identified as key intermediates of G protein-mediated homeostatic shifts.Statistical and mathematical model comparisons between A.thaliana and M.polymorpha revealed evolutionary conservation of transcriptional and metabolic networks over land plant evolution,whereas divergence has occurred in the function of plant-specific atypical XLG subunit.Taken together,our results indicate that the shifts in transcriptional and metabolic homeostasis at least partially act as the mechanisms of G protein-coupled stress responses that are conserved between two distantly related plants.
基金This work was supported by the National Natural Science Foundation of China(Grant number 82070593)。
文摘Metabolic-dysfunction-associated fatty liver disease(MAFLD)is a group of highly heterogeneous multi-system diseases,which is closely related to metabolic dysfunction and is one of the most important public health problems in the world.Studies have shown that paracrine fibroblast growth factors(FGFs)play an important role in the occurrence and development of MAFLD by regulating glucose and lipid metabolism,inflammation,and fibrosis.This article reviews the latest progress in understanding of the distribution,function,and metabolic regulation of paracrine FGFs,which paves the way for future FGF-based therapies targeting MAFLD.
基金This work was supported by the National Key Research and Development Program of China(2018YFA0900300)the National Natural Science Foundation of China(31870066,21778024)+1 种基金National First-Class Discipline Program of Light Industry Technology and Engineering(LITE2018-06)the Program of Introducing Talents of Discipline to Universities(111-2-06).
文摘Prodigiosin is a secondary metabolite mainly produced at 30°C in Serratia marcescens,but it can hardly be synthetized at 37°C or higher.In this study,we provide insight into the metabolic regulation of prodigiosin synthesis in response to temperature through transcriptome sequencing.The analysis of the function of differentially expressed genes suggested that temperature resulted in significant alteration of the metabolic pathways between 30 and 37°C.Specifically,30°C favored transcriptional expression of the pig gene cluster.At the same time,the carbon flux was redistributed to pathways of pyruvate,proline,serine,especially homoserine,cystathionine,homocysteine,methionine,and s-adenosylmethionine metabolism,all involved in prodigiosin biosynthesis,and was finally increased towards the prodigiosin synthesis pathway in S.marcescens at 30°C.Interestingly,results further confirmed increased transcriptional level of five regulators(LuxS,RpoS,Hfq,EepR,CRP),and decreased content of hexS through qPCR.Finally,successful co-overexpression of mmuM and metK,related to homocysteine,methionine,and s-adenosylmethionine metabolism,in the chromosome of JNB5-1(JNB5-1/MK)resulted in increased prodigiosin titer up to 7.57 g/L in JNB5-1/MK at 30°C,which was 41.2%higher than that in JNB5-1.Our transcriptome analysis provides further insight into the strain’s response to temperature changes at the transcription level,which is of great significance for improving the production of prodigiosin.
基金NIH R01CA175495 and R01CA262132the Department of Defense(PC210331 and BC190403)the Price Family Foundation.M.C.P.is supported by NIH 5TL1TR002557.A.T.M.is supported by Scandinavia/Borge.
文摘The B7/CD28 families of immune checkpoints play vital roles in negatively or positively regulating immune cells in homeostasis and various diseases.Recent basic and clinical studies have revealed novel biology of the B7/CD28 families and new therapeutics for cancer therapy.In this review,we discuss the newly discovered KIR3DL3/TMIGD2/HHLA2 pathways,PD-1/PD-L1 and B7-H3 as metabolic regulators,the glycobiology of PD-1/PD-L1,B7x(B7-H4)and B7-H3,and the recently characterized PD-L1/B7-1 cis-interaction.We also cover the tumor-intrinsic and-extrinsic resistance mechanisms to current anti-PD-1/PD-L1 and anti-CTLA-4 immunotherapies in clinical settings.Finally,we review new immunotherapies targeting B7-H3,B7x,PD-1/PD-L1,and CTLA-4 in current clinical trials.
基金supported by National Key Research and Development Program of China(2022YFA0911800)Knowledge Innovation Program of Wuhan-Shuguang Project(2022020801020334)Science and Technology Project of Hubei Tobacco Company(027Y2021-023,027Y2020-013).
文摘Microorganisms are important sources of various natural products that have been commercialized for human medicine and animal healthcare.Bacitracin is an important antibacterial natural product predominantly pro-duced by Bacillus licheniformis and Bacillus subtilis,and it is characterized by a broad antimicrobial spectrum,strong activity and low resistance,thus bacitracin is extensively applied in animal feed and veterinary medicine industries.In recent years,various strategies have been proposed to improve bacitracin production.Herein,we systematically describe the regulation of bacitracin biosynthesis in genus Bacillus and its associated mechanism,to provide a theoretical basis for bacitracin overproduction.The metabolic engineering strategies applied for bacitracin production are explored,including improving substrate utilization,using an enlarged precursor amino acid pool,increasing ATP supply and NADPH generation,and engineering transcription regulators.We also present several approaches of fermentation process optimization to facilitate the industrial large-scale production of bacitracin.Finally,the challenges and prospects associated with microbial bacitracin synthesis are discussed to facilitate the establishment of high-yield and low-cost biological factories.
基金supported by the Key Scientific and Technological Grant of Zhejiang for Breeding New Agricultural Varieties(No.2021C02074 and 2021C02073)Zhejiang Provincial Natural Science Foundation of China(No.LR21H280002)Zhejiang Key Agricultural Enterprise Institute(No.2017Y20001)。
文摘Ganoderma lucidum is a valuable medical macrofungus with a myriad of diverse secondary metabolites,in which triterpenoids are the major constituents.This paper introduced the germplasm resources of genus Ganoderma from textual research,its distribution and identification at the molecular level.Also we overviewed G.lucidum in the components,the biological activities and biosynthetic pathways of ganoderic acid,aiming to provide scientific evidence for the development and utilization of G.lucidum germplasm resources and the biosynthesis of ganoderic acid.