Background: Glutamine and glutamate are known to play important roles in cancer biology. However, no detailed information is available in terms of their levels of involvement in various biological processes across dif...Background: Glutamine and glutamate are known to play important roles in cancer biology. However, no detailed information is available in terms of their levels of involvement in various biological processes across different cancer types, whereas such knowledge could be critical for understanding the distinct characteristics of different cancer types. Our computational study aimed to examine the functional roles of glutamine and glutamate across different cancer types.Methods: We conducted a comparative analysis of gene expression data of cancer tissues versus normal control tissues of 11 cancer types to understand glutamine and glutamate metabolisms in cancer. Specifically, we developed a linear regression model to assess differential contributions by glutamine and/or glutamate to each of seven biological processes in cancer versus control tissues.Results: While our computational predictions were consistent with some of the previous observations, multiple novel predictions were made:(1) glutamine is generally not involved in purine synthesis in cancer except for breast cancer, and is similarly not involved in pyridine synthesis except for kidney cancer;(2) glutamine is generally not involved in ATP production in cancer;(3) glutamine's contribution to nucleotide synthesis is minimal if any in cancer;(4) glutamine is not involved in asparagine synthesis in cancer except for bladder and lung cancers; and(5) glutamate does not contribute to serine synthesis except for bladder cancer.Conclusions: We comprehensively predicted the roles of glutamine and glutamate metabolisms in selected metabolic pathways in cancer tissues versus control tissues, which may lead to novel approaches to therapeutic development targeted at glutamine and/or glutamate metabolism. However, our predictions need further functional validation.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-silking direct photoassimilate deposition, ultimately, leading to grain yield loss.展开更多
Manipulated precipitation patterns can profoundly influence the metabolism of soil microorganisms.However,the responses of soil organic carbon(SOC)and nutrient turnover to microbial metabolic limitation under changing...Manipulated precipitation patterns can profoundly influence the metabolism of soil microorganisms.However,the responses of soil organic carbon(SOC)and nutrient turnover to microbial metabolic limitation under changing precipitation conditions remain unclear in semi-arid ecosystems.This study measured the potential activities of enzymes associated with carbon(C:β-1,4-glucosidase(BG)andβ-D-cellobiosidase(CBH)),nitrogen(N:β-1,4-N-acetylglucosaminidase(NAG)and L-leucine aminopeptidase(LAP))and phosphorus(P:alkaline phosphatase(AP))acquisition,to quantify soil microbial metabolic limitations using enzymatic stoichiometry,and then identify the implications for soil microbial metabolic limitations and carbon use efficiency(CUE)under decreased precipitation by 50%(DP)and increased precipitation by 50%(IP)in a temperate grassland.The results showed that soil C and P were the major elements limiting soil microbial metabolism in temperate grasslands.There was a strong positive dependence between microbial C and P limitations under manipulated precipitation.Microbial metabolism limitation was promoted by DP treatment but reversed by IP treatment.Moreover,CUE was inhibited by DP treatment but promoted by IP treatment.Soil microbial metabolism limitation was mainly regulated by soil moisture and soil C,N,and P stoichiometry,followed by available nutrients(i.e.,NO^(-)_(3),NH^(+)_(4),and dissolved organic C)and microbial biomass(i.e.,MBC and MBN).Overall,these findings highlight the potential role of changing precipitation in regulating ecosystem C turnover by limiting microbial metabolism and CUE in temperate grassland ecosystems.展开更多
Objective:In this study,we focus on the hypoglycemic effects of chlorogenic acid(CGA)in vitro and in vivo and its mechanism base on regulate glucose and lipid metabolism via AMPK activation.Methods:The cytotoxicity,gl...Objective:In this study,we focus on the hypoglycemic effects of chlorogenic acid(CGA)in vitro and in vivo and its mechanism base on regulate glucose and lipid metabolism via AMPK activation.Methods:The cytotoxicity,glucose consumption and intracellular triglyceride assay were been detected by commercial kits.The western blots were used to detection the associated protein levels after CGA treatment,and the inhibiter blocking experiments were also be done.In vivo experiment,the fasting blood-glucose,lipid metabolism,liver function,insulin resistance,glucose tolerance,and pathological change were assessed on streptozocin induced diabetic mice.Results:We found that CGA exhibited no cytotoxicity at concentrations of 100μM,it caused a significant increasing of glucose consumption and reducing of the PA-BSA induced intracellular TG level on HepG2 cells at 50μM and 100μM treatment,CGA exhibited up-regulating the level of p-AMPK(Thr172)and p-ACC(Ser79)in dose-dependent manners in vitro and in vivo.The stimulating activities of CGA on AMPK were completely blocked by compound c(CC)on HepG2 cells.And the efficacies of CGA on glucose consumption and intracellular TG accumulation were also completely blocked by CC pretreatment.The CGA also exhibited potent anti-diabetic effects with hypoglycemic activity,improve insulin resistance and glucose tolerance,regulate glucose and lipid metabolism and protect the liver function in vivo.Conclusion:Our results suggested that CGA can regulate glucose and lipid metabolism by AMPK activation,and exhibit potent anti-hyperglycemic effect in streptozocin induced diabetes mice,and may be used as a potential effective anti-diabetes drug.展开更多
Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diab...Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.展开更多
Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However...Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.展开更多
Stroke is a leading cause of mortality and disability worldwide.Ischemic cell death triggered by the compromised supply of blood oxygen and glucose is one of the major pathophysiology of strokeinduced brain injury.Imp...Stroke is a leading cause of mortality and disability worldwide.Ischemic cell death triggered by the compromised supply of blood oxygen and glucose is one of the major pathophysiology of strokeinduced brain injury.Impaired mitochondrial energy metabolism is observed minutes after stroke and is closely associated with the progression of neuropathology.Recently,a new type of posttranslational modification,known as lysine succinylation,has been recognized to play a significant role in mitochondrial energy metabolism after ischemia.However,the role of succinylation modification in cell metabolism after stroke and its regulation are not well understood.We aimed to review the effects of succinylation on energy metabolism,reactive oxygen species generation,and neuroinflammation,as well as Sirtuin 5 mediated desuccinylation after stroke.We also highlight the potential of targeting succinylation/desuccinylation as a promising strategy for the treatment of stroke.The succinylation level is dynamically regulated by the nonenzymatic or enzymatic transfer of a succinyl group to a protein on lysine residues and the removal of succinyl catalyzed by desuccinylases.Mounting evidence has suggested that succinylation can regulate the metabolic pathway through modulating the activity or stability of metabolic enzymes.Sirtuins,especially Sirtuin 5,are characterized for their desuccinylation activity and have been recognized as a critical regulator of metabolism through desuccinylating numerous metabolic enzymes.Imbalance between succinylation and desuccinylation has been implicated in the pathophysiology of stroke.Pharmacological agents that enhance the activity of Sirtuin 5 have been employed to promote desuccinylation and improve mitochondrial metabolism,and neuroprotective effects of these agents have been observed in experimental stroke studies.However,their therapeutic efficacy in stroke patients should be validated.展开更多
Controlling intracranial pressure,nerve cell regeneration,and microenvironment regulation are the key issues in reducing mortality and disability in acute brain injury.There is currently a lack of effective treatment ...Controlling intracranial pressure,nerve cell regeneration,and microenvironment regulation are the key issues in reducing mortality and disability in acute brain injury.There is currently a lack of effective treatment methods.Hibernation has the characteristics of low temperature,low metabolism,and hibernation rhythm,as well as protective effects on the nervous,cardiovascular,and motor systems.Artificial hibernation technology is a new technology that can effectively treat acute brain injury by altering the body’s metabolism,lowering the body’s core temperature,and allowing the body to enter a state similar to hibernation.This review introduces artificial hibernation technology,including mild hypothermia treatment technology,central nervous system regulation technology,and artificial hibernation-inducer technology.Upon summarizing the relevant research on artificial hibernation technology in acute brain injury,the research results show that artificial hibernation technology has neuroprotective,anti-inflammatory,and oxidative stress-resistance effects,indicating that it has therapeutic significance in acute brain injury.Furthermore,artificial hibernation technology can alleviate the damage of ischemic stroke,traumatic brain injury,cerebral hemorrhage,cerebral infarction,and other diseases,providing new strategies for treating acute brain injury.However,artificial hibernation technology is currently in its infancy and has some complications,such as electrolyte imbalance and coagulation disorders,which limit its use.Further research is needed for its clinical application.展开更多
Copper is an essential trace element,and plays a vital role in numerous physiological processes within the human body.During normal metabolism,the human body maintains copper homeostasis.Copper deficiency or excess ca...Copper is an essential trace element,and plays a vital role in numerous physiological processes within the human body.During normal metabolism,the human body maintains copper homeostasis.Copper deficiency or excess can adversely affect cellular function.Therefore,copper homeostasis is stringently regulated.Recent studies suggest that copper can trigger a specific form of cell death,namely,cuproptosis,which is triggered by excessive levels of intracellular copper.Cuproptosis induces the aggregation of mitochondrial lipoylated proteins,and the loss of iron-sulfur cluster proteins.In neurodegenerative diseases,the pathogenesis and progression of neurological disorders are linked to copper homeostasis.This review summarizes the advances in copper homeostasis and cuproptosis in the nervous system and neurodegenerative diseases.This offers research perspectives that provide new insights into the targeted treatment of neurodegenerative diseases based on cuproptosis.展开更多
Popular fermented golden pomfret(Trachinotus ovatus)is prepared via spontaneous fermentation;however,the mechanisms underlying the regulation of its flavor development remain unclear.This study shows the roles of the ...Popular fermented golden pomfret(Trachinotus ovatus)is prepared via spontaneous fermentation;however,the mechanisms underlying the regulation of its flavor development remain unclear.This study shows the roles of the complex microbiota and the dynamic changes in microbial community and flavor compounds during fish fermentation.Single-molecule real-time sequencing and molecular networking analysis revealed the correlations among different microbial genera and the relationships between microbial taxa and volatile compounds.Mechanisms underlying flavor development were also elucidated via KEGG based functional annotations.Clostridium,Shewanella,and Staphylococcus were the dominant microbial genera.Forty-nine volatile compounds were detected in the fermented fish samples,with thirteen identified as characteristic volatile compounds(ROAV>1).Volatile profiles resulted from the interactions among the microorganisms and derived enzymes,with the main metabolic pathways being amino acid biosynthesis/metabolism,carbon metabolism,and glycolysis/gluconeogenesis.This study demonstrated the approaches for distinguishing key microbiota associated with volatile compounds and monitoring the industrial production of high-quality fermented fish products.展开更多
Adult neural stem cells are neurogenesis progenitor cells that play an important role in neurogenesis.Therefore,neural regeneration may be a promising target for treatment of many neurological illnesses.The regenerati...Adult neural stem cells are neurogenesis progenitor cells that play an important role in neurogenesis.Therefore,neural regeneration may be a promising target for treatment of many neurological illnesses.The regenerative capacity of adult neural stem cells can be chara cterized by two states:quiescent and active.Quiescent adult neural stem cells are more stable and guarantee the quantity and quality of the adult neural stem cell pool.Active adult neural stem cells are chara cterized by rapid proliferation and differentiation into neurons which allow for integration into neural circuits.This review focuses on diffe rences between quiescent and active adult neural stem cells in nutrition metabolism and protein homeostasis.Furthermore,we discuss the physiological significance and underlying advantages of these diffe rences.Due to the limited number of adult neural stem cells studies,we refe rred to studies of embryonic adult neural stem cells or non-mammalian adult neural stem cells to evaluate specific mechanisms.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common liver disease worldwide,with an estimated prevalence of 31%in Latin America.The presence of metabolic comorbidities coexisting with liv...Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common liver disease worldwide,with an estimated prevalence of 31%in Latin America.The presence of metabolic comorbidities coexisting with liver disease varies substantially among populations.It is acknowledged that obesity is boosting the type 2 diabetes mellitus“epidemic,”and both conditions are significant contributors to the increasing number of patients with MASLD.Nonalcoholic steatohepatitis represents a condition of chronic liver inflammation and is considered the most severe form of MASLD.MASLD diagnosis is based on the presence of steatosis,noninvasive scores and altered liver tests.Noninvasive scores of liver fibrosis,such as serum biomarkers,which should be used in primary care to rule out advanced fibrosis,are simple,inexpensive,and widely available.Currently,guidelines from international hepatology societies recommend using noninvasive strategies to simplify case finding and management of high-risk patients with MASLD in clinical practice.Unfortunately,there is no definite pharmacological treatment for the condition.Creating public health policies to treat patients with risk factors for MASLD prevention is essential.展开更多
Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2...Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin.TGP(5.1×10^(3) Da)was composed of mannose,glucosamine,rhamnose,glucuronic acid,galactosamine,glucose,galactose,xylose,and fucose.It could significantly alleviate weight loss,reduce fasting blood glucose levels,reverse dyslipidemia,reduce liver damage from oxidative stress,and improve insulin sensitivity.RT-PCR and Western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance.TGP increased the abundance of Allobaculum,Akkermansia,and Bifidobacterium,restored the microbiota abundance in the intestinal tracts of mice with T2DM,and promoted short-chain fatty acid production.This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical.展开更多
Background The red macroalgae Asparagopsis is an effective methanogenesis inhibitor due to the presence of halogenated methane(CH_(4))analogues,primarily bromoform(CHBr_(3)).This study aimed to investigate the degrada...Background The red macroalgae Asparagopsis is an effective methanogenesis inhibitor due to the presence of halogenated methane(CH_(4))analogues,primarily bromoform(CHBr_(3)).This study aimed to investigate the degradation process of CHBr3 from A taxiformis in the rumen and whether this process is diet-dependent.An in vitro batch culture system was used according to a 2×2 factorial design,assessing two A taxiformis inclusion rates[0(CTL)and 2%DM diet(AT)]and two diets[high-concentrate(HC)and high-forage diet(HF)].Incubations lasted for 72 h and samples of headspace and fermentation liquid were taken at 0,0.5,1,3,6,8,12,16,24,48 and 72 h to assess the pattern of degradation of CHBr_(3) into dibromomethane(CH_(2)Br_(2))and fermentation parameters.Additionally,an in vitro experiment with pure cultures of seven methanogens strains(Methanobrevibacter smithii,Methanobrevibacter ruminantium,Methanosphaera stadtmanae,Methanosarcina barkeri,Methanobrevibacter millerae,Methanorhermobacter wolfei and Methanobacterium mobile)was conducted to test the effects of increasing concentrations of CHBr3(0.4,2,10and 50μmol/L).Results The addition of AT significantly decreased CH_(4) production(P=0.002)and the acetate:propionate ratio(P=0.003)during a 72-h incubation.The concentrations of CHBr_(3) showed a rapid decrease with nearly 90%degraded within the first 3 h of incubation.On the contrary,CH_(2)Br_(2) concentration quickly increased during the first 6 h and then gradually decreased towards the end of the incubation.Neither CHBr_(3) degradation nor CH_(2)Br_(2) synthesis were affected by the type of diet used as substrate,suggesting that the fermentation rate is not a driving factor involved in CHBr_(3)degradation.The in vitro culture of methanogens showed a dose-response effect of CHBr3 by inhibiting the growth of M.smithii,M.ruminantium,M.stadtmanae,M.barkeri,M.millerae,M.wolfei,and M.mobile.Conclusions The present work demonstrated that CHBr_(3) from A.taxiformis is quickly degraded to CH_(2)Br_(2)in the rumen and that the fermentation rate promoted by different diets is not a driving factor involved in CHBr_(3)degradation.展开更多
Spinal cord injuries impose a notably economic burden on society,mainly because of the severe after-effects they cause.Despite the ongoing development of various therapies for spinal cord injuries,their effectiveness ...Spinal cord injuries impose a notably economic burden on society,mainly because of the severe after-effects they cause.Despite the ongoing development of various therapies for spinal cord injuries,their effectiveness remains unsatisfactory.However,a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic reprogramming.In this review,we explore the metabolic changes that occur during spinal cord injuries,their consequences,and the therapeutic tools available for metabolic reprogramming.Normal spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic coupling.However,spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism,lipid metabolism,and mitochondrial dysfunction.These metabolic disturbances lead to corresponding pathological changes,including the failure of axonal regeneration,the accumulation of scarring,and the activation of microglia.To rescue spinal cord injury at the metabolic level,potential metabolic reprogramming approaches have emerged,including replenishing metabolic substrates,reconstituting metabolic couplings,and targeting mitochondrial therapies to alter cell fate.The available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord injury.To further advance the metabolic treatment of the spinal cord injury,future efforts should focus on a deeper understanding of neurometabolism,the development of more advanced metabolomics technologies,and the design of highly effective metabolic interventions.展开更多
Fructose and glucose are often widely used in food processing and may contribute to many metabolic diseases.To observe the effects of different doses of glucose and fructose on human metabolism and cellular communicat...Fructose and glucose are often widely used in food processing and may contribute to many metabolic diseases.To observe the effects of different doses of glucose and fructose on human metabolism and cellular communication,volunteers were given low,medium,and high doses of glucose and fructose.Serum cytokines,glucose,lactate,nicotinamide adenine dinucleotide(NADH)and metabolic enzymes were assayed,and central carbon metabolic pathway networks and cytokine communication networks were constructed.The results showed that the glucose and fructose groups basically maintained the trend of decreasing catabolism and increasing anabolism with increasing dose.Compared with glucose,low-dose fructose decreased catabolism and increased anabolism,significantly enhanced the expression of the inflammatory cytokine interferon-γ(IFN-γ),macrophage-derived chemokine(MDC),induced protein-10(IP-10),and eotaxin,and significantly reduced the activity of isocitrate dehydrogenase(ICDH)and pyruvate dehydrogenase complexes(PDHC).Both medium and high doses of fructose increase catabolism and anabolism,and there are more cytokines and enzymes with significant changes.Furthermore,multiple cytokines and enzymes show strong relevance to metabolic regulation by altering the transcription and expression of enzymes in central carbon metabolic pathways.Therefore,excessive intake of fructose should be reduced to avoid excessive inflammatory responses,allergic reactions and autoimmune diseases.展开更多
Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most count...Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries.MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma.Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis.The mechanisms involved in maintaining gut-liver axis homeostasis are complex.One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gutliver axis functionality.An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis.Moreover,alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis.Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)are a class of drugs developed for the treatment of type 2 diabetes mellitus.They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis.The mechanisms reported to be involved in this effect include an improved regulation of glycemia,reduced lipid synthesis,β-oxidation of free fatty acids,and induction of autophagy in hepatic cells.Recently,multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment.A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD.This review presents the current understanding of the role of the gutliver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.展开更多
BACKGROUND An increasing number of studies have focused on the role of cellular metabolism in the development of colorectal cancer(CRC).However,no work is currently available to synthesize the field through bibliometr...BACKGROUND An increasing number of studies have focused on the role of cellular metabolism in the development of colorectal cancer(CRC).However,no work is currently available to synthesize the field through bibliometrics.AIM To analyze the development in the field of“glucose metabolism”(GM),“amino acid metabolism”(AM),“lipid metabolism”(LM),and“nucleotide metabolism”(NM)in CRC by visualization.METHODS Articles within the abovementioned areas of GM,AM,LM and NM in CRC,which were published from January 1,1991,to December 31,2022,are retrieved from the Web of Science Core Collection and analyzed by CiteSpace 6.2.R4 and VOSviewer 1.6.19.RESULTS The field of LM in CRC presented the largest number of annual publications and the fastest increase in the last decade compared with the other three fields.Meanwhile,China and the United States were two of the most prominent contri-butors in these four areas.In addition,Gang Wang,Wei Jia,Maria Notar-nicola,and Cornelia Ulrich ranked first in publication numbers,while Jing-Yuan Fang,Senji Hirasawa,Wei Jia,and Charles Fuchs were the most cited authors on average in these four fields,respectively.“Gut microbiota”and“epithelial-mesenchymal transition”emerged as the newest burst words in GM,“gut microbiota”was the latest outburst word in AM,“metastasis”,“tumor microenvironment”,“fatty acid metabolism”,and“metabolic reprogramming”were the up-to-date outbreaking words in LM,while“epithelial-mesenchymal transition”and“apoptosis”were the most recently occurring words in NM.CONCLUSION Research in“cellular metabolism in CRC”is all the rage at the moment,and researchers are particularly interested in exploring the mechanism to explain the metabolic alterations in CRC.Targeting metabolic vulnerability appears to be a promising direction in CRC therapy.展开更多
Breast cancer brain metastasis(BCBrM)is a crucial and hard area of research which guarantees an urgent need to understand the underlying molecular mechanisms.A recent study by Li et al.[1]published in Military Medical...Breast cancer brain metastasis(BCBrM)is a crucial and hard area of research which guarantees an urgent need to understand the underlying molecular mechanisms.A recent study by Li et al.[1]published in Military Medical Research investigated the role of retinoic acid receptor responder 2(RARRES2)in regulating lipid metabolism in BCBrM,highlighting the clinical relevance of alterations in lipid metabolites,such as phosphatidylcholine(PC)and triacylglycerols(TAGs),by RARRES2 through the modulation of phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway.This commentary aims to elaborate on the key findings and their relevance to the field.展开更多
Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq dat...Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells and 65 glycogen metabolism genes were analyzed bya nonnegative matrix factorization(NMF).The prognosis and immune response of new glycogen TME cell dusters were predicted by using HCC and immunotherapy cohorts from public databases.HOC single cell analysis was divided into fibroblasts,NT T cells,macrophages,endothelial clls,and B cells,which were separately divided into new cell clusters by glycogen metabolism gene annotation.Pseudo temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell dusters.Cellular communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME cell.related subtypes and diferent glycogen subtype cell clusters.SCENIC analysis of transcription factors upstream of TME cell clusters with different glycogen metabolism.In addition,TME cell dusters of glycogen metabolism were found to be enriched in expression in CAF subtypes,CD8 depleted,M1,and M2 types.Bulk seq analysis showed the prognostic signifcance of glycogen metabolism.mediated TME cell dusters in HCC,while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade(ICB),especially for CAFs,T cells,and macrophages In summary,our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell dusters.展开更多
基金supported by Georgia Research Alliance and the National Natural Science Foundation of China(Grant Nos.81320108025,61402194,61572227)the Science-Technology Development Project from Jilin Province(Nos.20160101259JC,20160204022GX,20170520063JH)
文摘Background: Glutamine and glutamate are known to play important roles in cancer biology. However, no detailed information is available in terms of their levels of involvement in various biological processes across different cancer types, whereas such knowledge could be critical for understanding the distinct characteristics of different cancer types. Our computational study aimed to examine the functional roles of glutamine and glutamate across different cancer types.Methods: We conducted a comparative analysis of gene expression data of cancer tissues versus normal control tissues of 11 cancer types to understand glutamine and glutamate metabolisms in cancer. Specifically, we developed a linear regression model to assess differential contributions by glutamine and/or glutamate to each of seven biological processes in cancer versus control tissues.Results: While our computational predictions were consistent with some of the previous observations, multiple novel predictions were made:(1) glutamine is generally not involved in purine synthesis in cancer except for breast cancer, and is similarly not involved in pyridine synthesis except for kidney cancer;(2) glutamine is generally not involved in ATP production in cancer;(3) glutamine's contribution to nucleotide synthesis is minimal if any in cancer;(4) glutamine is not involved in asparagine synthesis in cancer except for bladder and lung cancers; and(5) glutamate does not contribute to serine synthesis except for bladder cancer.Conclusions: We comprehensively predicted the roles of glutamine and glutamate metabolisms in selected metabolic pathways in cancer tissues versus control tissues, which may lead to novel approaches to therapeutic development targeted at glutamine and/or glutamate metabolism. However, our predictions need further functional validation.
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-silking direct photoassimilate deposition, ultimately, leading to grain yield loss.
基金the National Natural Science Foundation of China(41730638)the Key Research and Development Program of Shaanxi Province,China(2021ZDLSF05-02)+2 种基金the Scientific and Technological Innovation Project of Shaanxi Forestry Academy of Sciences,China(SXLK2021-0206)the Funding of Special Support Plan of Young Talents Project in China(2021)the National Forestry and Grassland Administration in China(20201326015).
文摘Manipulated precipitation patterns can profoundly influence the metabolism of soil microorganisms.However,the responses of soil organic carbon(SOC)and nutrient turnover to microbial metabolic limitation under changing precipitation conditions remain unclear in semi-arid ecosystems.This study measured the potential activities of enzymes associated with carbon(C:β-1,4-glucosidase(BG)andβ-D-cellobiosidase(CBH)),nitrogen(N:β-1,4-N-acetylglucosaminidase(NAG)and L-leucine aminopeptidase(LAP))and phosphorus(P:alkaline phosphatase(AP))acquisition,to quantify soil microbial metabolic limitations using enzymatic stoichiometry,and then identify the implications for soil microbial metabolic limitations and carbon use efficiency(CUE)under decreased precipitation by 50%(DP)and increased precipitation by 50%(IP)in a temperate grassland.The results showed that soil C and P were the major elements limiting soil microbial metabolism in temperate grasslands.There was a strong positive dependence between microbial C and P limitations under manipulated precipitation.Microbial metabolism limitation was promoted by DP treatment but reversed by IP treatment.Moreover,CUE was inhibited by DP treatment but promoted by IP treatment.Soil microbial metabolism limitation was mainly regulated by soil moisture and soil C,N,and P stoichiometry,followed by available nutrients(i.e.,NO^(-)_(3),NH^(+)_(4),and dissolved organic C)and microbial biomass(i.e.,MBC and MBN).Overall,these findings highlight the potential role of changing precipitation in regulating ecosystem C turnover by limiting microbial metabolism and CUE in temperate grassland ecosystems.
基金Fund Project:Natural Science Foundation for Youth of Hainan Province(No.819QN226)Scientific Research Project of Hainan Colleges and Universities(No.Hnky2019ZD-32)Innovation and Entrepreneurship Training Planning Project for College Students(No.202011810010,X20201181058)。
文摘Objective:In this study,we focus on the hypoglycemic effects of chlorogenic acid(CGA)in vitro and in vivo and its mechanism base on regulate glucose and lipid metabolism via AMPK activation.Methods:The cytotoxicity,glucose consumption and intracellular triglyceride assay were been detected by commercial kits.The western blots were used to detection the associated protein levels after CGA treatment,and the inhibiter blocking experiments were also be done.In vivo experiment,the fasting blood-glucose,lipid metabolism,liver function,insulin resistance,glucose tolerance,and pathological change were assessed on streptozocin induced diabetic mice.Results:We found that CGA exhibited no cytotoxicity at concentrations of 100μM,it caused a significant increasing of glucose consumption and reducing of the PA-BSA induced intracellular TG level on HepG2 cells at 50μM and 100μM treatment,CGA exhibited up-regulating the level of p-AMPK(Thr172)and p-ACC(Ser79)in dose-dependent manners in vitro and in vivo.The stimulating activities of CGA on AMPK were completely blocked by compound c(CC)on HepG2 cells.And the efficacies of CGA on glucose consumption and intracellular TG accumulation were also completely blocked by CC pretreatment.The CGA also exhibited potent anti-diabetic effects with hypoglycemic activity,improve insulin resistance and glucose tolerance,regulate glucose and lipid metabolism and protect the liver function in vivo.Conclusion:Our results suggested that CGA can regulate glucose and lipid metabolism by AMPK activation,and exhibit potent anti-hyperglycemic effect in streptozocin induced diabetes mice,and may be used as a potential effective anti-diabetes drug.
基金supported by the Projects of the National Key R&D Program of China,Nos.2021YFC2400803(to YO),2021YFC2400801(to YQ)the National Natural Science Foundation of China,Nos.82002290(to YQ),82072452(to YO),82272475(to YO)+5 种基金the Young Elite Scientist Sponsorship Program by Cast,No.YESS20200153(to YQ)the Sino-German Mobility Programme,No.M-0699(to YQ)the Excellent Youth Cultivation Program of Shanghai Sixth People’s Hospital,No.ynyq202201(to YQ)the Shanghai Sailing Program,No.20YF1436000(to YQ)the Medical Engineering Co-Project of University of Shanghai for Science and Technology,10-22-310-520(to YO)a grant from Shanghai Municipal Health Commission,No.202040399(to YO).
文摘Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.
基金financially supported by the National Natural Science Foundation of China,No.81303115,81774042 (both to XC)the Pearl River S&T Nova Program of Guangzhou,No.201806010025 (to XC)+3 种基金the Specialty Program of Guangdong Province Hospital of Chinese Medicine of China,No.YN2018ZD07 (to XC)the Natural Science Foundatior of Guangdong Province of China,No.2023A1515012174 (to JL)the Science and Technology Program of Guangzhou of China,No.20210201 0268 (to XC),20210201 0339 (to JS)Guangdong Provincial Key Laboratory of Research on Emergency in TCM,Nos.2018-75,2019-140 (to JS)
文摘Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.
基金supported by the National Natural Science Foundation of China,No.82071283(to QH)the Natural Science Foundation of Shanghai,No.22ZR1437700(to QH)。
文摘Stroke is a leading cause of mortality and disability worldwide.Ischemic cell death triggered by the compromised supply of blood oxygen and glucose is one of the major pathophysiology of strokeinduced brain injury.Impaired mitochondrial energy metabolism is observed minutes after stroke and is closely associated with the progression of neuropathology.Recently,a new type of posttranslational modification,known as lysine succinylation,has been recognized to play a significant role in mitochondrial energy metabolism after ischemia.However,the role of succinylation modification in cell metabolism after stroke and its regulation are not well understood.We aimed to review the effects of succinylation on energy metabolism,reactive oxygen species generation,and neuroinflammation,as well as Sirtuin 5 mediated desuccinylation after stroke.We also highlight the potential of targeting succinylation/desuccinylation as a promising strategy for the treatment of stroke.The succinylation level is dynamically regulated by the nonenzymatic or enzymatic transfer of a succinyl group to a protein on lysine residues and the removal of succinyl catalyzed by desuccinylases.Mounting evidence has suggested that succinylation can regulate the metabolic pathway through modulating the activity or stability of metabolic enzymes.Sirtuins,especially Sirtuin 5,are characterized for their desuccinylation activity and have been recognized as a critical regulator of metabolism through desuccinylating numerous metabolic enzymes.Imbalance between succinylation and desuccinylation has been implicated in the pathophysiology of stroke.Pharmacological agents that enhance the activity of Sirtuin 5 have been employed to promote desuccinylation and improve mitochondrial metabolism,and neuroprotective effects of these agents have been observed in experimental stroke studies.However,their therapeutic efficacy in stroke patients should be validated.
基金supported by the National Defense Science and Technology Outstanding Youth Science Fund Project,No.2021-JCJQ-ZQ-035National Defense Innovation Special Zone Project,No.21-163-12-ZT-006-002-13Key Program of the National Natural Science Foundation of China,No.11932013(all to XuC).
文摘Controlling intracranial pressure,nerve cell regeneration,and microenvironment regulation are the key issues in reducing mortality and disability in acute brain injury.There is currently a lack of effective treatment methods.Hibernation has the characteristics of low temperature,low metabolism,and hibernation rhythm,as well as protective effects on the nervous,cardiovascular,and motor systems.Artificial hibernation technology is a new technology that can effectively treat acute brain injury by altering the body’s metabolism,lowering the body’s core temperature,and allowing the body to enter a state similar to hibernation.This review introduces artificial hibernation technology,including mild hypothermia treatment technology,central nervous system regulation technology,and artificial hibernation-inducer technology.Upon summarizing the relevant research on artificial hibernation technology in acute brain injury,the research results show that artificial hibernation technology has neuroprotective,anti-inflammatory,and oxidative stress-resistance effects,indicating that it has therapeutic significance in acute brain injury.Furthermore,artificial hibernation technology can alleviate the damage of ischemic stroke,traumatic brain injury,cerebral hemorrhage,cerebral infarction,and other diseases,providing new strategies for treating acute brain injury.However,artificial hibernation technology is currently in its infancy and has some complications,such as electrolyte imbalance and coagulation disorders,which limit its use.Further research is needed for its clinical application.
基金supported by grants from the National Natural Science Foundation of China(No.81971891,No.82172196 and No.82372507)the Natural Science Foundation of Hunan Province(No.2023JJ40804)the Key Laboratory of Emergency and Trauma of Ministry of Education(Hainan Medical University,No.KLET-202210).
文摘Copper is an essential trace element,and plays a vital role in numerous physiological processes within the human body.During normal metabolism,the human body maintains copper homeostasis.Copper deficiency or excess can adversely affect cellular function.Therefore,copper homeostasis is stringently regulated.Recent studies suggest that copper can trigger a specific form of cell death,namely,cuproptosis,which is triggered by excessive levels of intracellular copper.Cuproptosis induces the aggregation of mitochondrial lipoylated proteins,and the loss of iron-sulfur cluster proteins.In neurodegenerative diseases,the pathogenesis and progression of neurological disorders are linked to copper homeostasis.This review summarizes the advances in copper homeostasis and cuproptosis in the nervous system and neurodegenerative diseases.This offers research perspectives that provide new insights into the targeted treatment of neurodegenerative diseases based on cuproptosis.
基金supported by the National Natural Science Foundation of China(32001733)the Earmarked fund for CARS(CARS-47)+3 种基金Guangxi Natural Science Foundation Program(2021GXNSFAA196023)Guangdong Basic and Applied Basic Research Foundation(2021A1515010833)Young Talent Support Project of Guangzhou Association for Science and Technology(QT20220101142)the Special Scientific Research Funds for Central Non-profit Institutes,Chinese Academy of Fishery Sciences(2020TD69)。
文摘Popular fermented golden pomfret(Trachinotus ovatus)is prepared via spontaneous fermentation;however,the mechanisms underlying the regulation of its flavor development remain unclear.This study shows the roles of the complex microbiota and the dynamic changes in microbial community and flavor compounds during fish fermentation.Single-molecule real-time sequencing and molecular networking analysis revealed the correlations among different microbial genera and the relationships between microbial taxa and volatile compounds.Mechanisms underlying flavor development were also elucidated via KEGG based functional annotations.Clostridium,Shewanella,and Staphylococcus were the dominant microbial genera.Forty-nine volatile compounds were detected in the fermented fish samples,with thirteen identified as characteristic volatile compounds(ROAV>1).Volatile profiles resulted from the interactions among the microorganisms and derived enzymes,with the main metabolic pathways being amino acid biosynthesis/metabolism,carbon metabolism,and glycolysis/gluconeogenesis.This study demonstrated the approaches for distinguishing key microbiota associated with volatile compounds and monitoring the industrial production of high-quality fermented fish products.
基金supported by the National Natural Science Foundation of China,No.82171336(to XX)。
文摘Adult neural stem cells are neurogenesis progenitor cells that play an important role in neurogenesis.Therefore,neural regeneration may be a promising target for treatment of many neurological illnesses.The regenerative capacity of adult neural stem cells can be chara cterized by two states:quiescent and active.Quiescent adult neural stem cells are more stable and guarantee the quantity and quality of the adult neural stem cell pool.Active adult neural stem cells are chara cterized by rapid proliferation and differentiation into neurons which allow for integration into neural circuits.This review focuses on diffe rences between quiescent and active adult neural stem cells in nutrition metabolism and protein homeostasis.Furthermore,we discuss the physiological significance and underlying advantages of these diffe rences.Due to the limited number of adult neural stem cells studies,we refe rred to studies of embryonic adult neural stem cells or non-mammalian adult neural stem cells to evaluate specific mechanisms.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common liver disease worldwide,with an estimated prevalence of 31%in Latin America.The presence of metabolic comorbidities coexisting with liver disease varies substantially among populations.It is acknowledged that obesity is boosting the type 2 diabetes mellitus“epidemic,”and both conditions are significant contributors to the increasing number of patients with MASLD.Nonalcoholic steatohepatitis represents a condition of chronic liver inflammation and is considered the most severe form of MASLD.MASLD diagnosis is based on the presence of steatosis,noninvasive scores and altered liver tests.Noninvasive scores of liver fibrosis,such as serum biomarkers,which should be used in primary care to rule out advanced fibrosis,are simple,inexpensive,and widely available.Currently,guidelines from international hepatology societies recommend using noninvasive strategies to simplify case finding and management of high-risk patients with MASLD in clinical practice.Unfortunately,there is no definite pharmacological treatment for the condition.Creating public health policies to treat patients with risk factors for MASLD prevention is essential.
基金funded by the National Key Research and Development Program of China(2020YFD0900902)Zhejiang Province Public Welfare Technology Application Research Project(LGJ21C20001)Zhejiang Provincial Key Research and Development Project of China(2019C02076 and 2019C02075)。
文摘Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin.TGP(5.1×10^(3) Da)was composed of mannose,glucosamine,rhamnose,glucuronic acid,galactosamine,glucose,galactose,xylose,and fucose.It could significantly alleviate weight loss,reduce fasting blood glucose levels,reverse dyslipidemia,reduce liver damage from oxidative stress,and improve insulin sensitivity.RT-PCR and Western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance.TGP increased the abundance of Allobaculum,Akkermansia,and Bifidobacterium,restored the microbiota abundance in the intestinal tracts of mice with T2DM,and promoted short-chain fatty acid production.This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical.
基金funded by Blue Ocean Barns.AB has a Ramón y Cajal research contract(RYC2019-027764-I)funded by the Spanish State Research Agency(AEI)。
文摘Background The red macroalgae Asparagopsis is an effective methanogenesis inhibitor due to the presence of halogenated methane(CH_(4))analogues,primarily bromoform(CHBr_(3)).This study aimed to investigate the degradation process of CHBr3 from A taxiformis in the rumen and whether this process is diet-dependent.An in vitro batch culture system was used according to a 2×2 factorial design,assessing two A taxiformis inclusion rates[0(CTL)and 2%DM diet(AT)]and two diets[high-concentrate(HC)and high-forage diet(HF)].Incubations lasted for 72 h and samples of headspace and fermentation liquid were taken at 0,0.5,1,3,6,8,12,16,24,48 and 72 h to assess the pattern of degradation of CHBr_(3) into dibromomethane(CH_(2)Br_(2))and fermentation parameters.Additionally,an in vitro experiment with pure cultures of seven methanogens strains(Methanobrevibacter smithii,Methanobrevibacter ruminantium,Methanosphaera stadtmanae,Methanosarcina barkeri,Methanobrevibacter millerae,Methanorhermobacter wolfei and Methanobacterium mobile)was conducted to test the effects of increasing concentrations of CHBr3(0.4,2,10and 50μmol/L).Results The addition of AT significantly decreased CH_(4) production(P=0.002)and the acetate:propionate ratio(P=0.003)during a 72-h incubation.The concentrations of CHBr_(3) showed a rapid decrease with nearly 90%degraded within the first 3 h of incubation.On the contrary,CH_(2)Br_(2) concentration quickly increased during the first 6 h and then gradually decreased towards the end of the incubation.Neither CHBr_(3) degradation nor CH_(2)Br_(2) synthesis were affected by the type of diet used as substrate,suggesting that the fermentation rate is not a driving factor involved in CHBr_(3)degradation.The in vitro culture of methanogens showed a dose-response effect of CHBr3 by inhibiting the growth of M.smithii,M.ruminantium,M.stadtmanae,M.barkeri,M.millerae,M.wolfei,and M.mobile.Conclusions The present work demonstrated that CHBr_(3) from A.taxiformis is quickly degraded to CH_(2)Br_(2)in the rumen and that the fermentation rate promoted by different diets is not a driving factor involved in CHBr_(3)degradation.
基金supported by the National Natural Science Foundation of China,No.82202681(to JW)the Natural Science Foundation of Zhejiang Province,Nos.LZ22H090003(to QC),LR23H060001(to CL).
文摘Spinal cord injuries impose a notably economic burden on society,mainly because of the severe after-effects they cause.Despite the ongoing development of various therapies for spinal cord injuries,their effectiveness remains unsatisfactory.However,a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic reprogramming.In this review,we explore the metabolic changes that occur during spinal cord injuries,their consequences,and the therapeutic tools available for metabolic reprogramming.Normal spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic coupling.However,spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism,lipid metabolism,and mitochondrial dysfunction.These metabolic disturbances lead to corresponding pathological changes,including the failure of axonal regeneration,the accumulation of scarring,and the activation of microglia.To rescue spinal cord injury at the metabolic level,potential metabolic reprogramming approaches have emerged,including replenishing metabolic substrates,reconstituting metabolic couplings,and targeting mitochondrial therapies to alter cell fate.The available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord injury.To further advance the metabolic treatment of the spinal cord injury,future efforts should focus on a deeper understanding of neurometabolism,the development of more advanced metabolomics technologies,and the design of highly effective metabolic interventions.
基金financially supported by National Natural Science Foundation of China(31901782)。
文摘Fructose and glucose are often widely used in food processing and may contribute to many metabolic diseases.To observe the effects of different doses of glucose and fructose on human metabolism and cellular communication,volunteers were given low,medium,and high doses of glucose and fructose.Serum cytokines,glucose,lactate,nicotinamide adenine dinucleotide(NADH)and metabolic enzymes were assayed,and central carbon metabolic pathway networks and cytokine communication networks were constructed.The results showed that the glucose and fructose groups basically maintained the trend of decreasing catabolism and increasing anabolism with increasing dose.Compared with glucose,low-dose fructose decreased catabolism and increased anabolism,significantly enhanced the expression of the inflammatory cytokine interferon-γ(IFN-γ),macrophage-derived chemokine(MDC),induced protein-10(IP-10),and eotaxin,and significantly reduced the activity of isocitrate dehydrogenase(ICDH)and pyruvate dehydrogenase complexes(PDHC).Both medium and high doses of fructose increase catabolism and anabolism,and there are more cytokines and enzymes with significant changes.Furthermore,multiple cytokines and enzymes show strong relevance to metabolic regulation by altering the transcription and expression of enzymes in central carbon metabolic pathways.Therefore,excessive intake of fructose should be reduced to avoid excessive inflammatory responses,allergic reactions and autoimmune diseases.
文摘Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries.MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma.Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis.The mechanisms involved in maintaining gut-liver axis homeostasis are complex.One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gutliver axis functionality.An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis.Moreover,alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis.Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)are a class of drugs developed for the treatment of type 2 diabetes mellitus.They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis.The mechanisms reported to be involved in this effect include an improved regulation of glycemia,reduced lipid synthesis,β-oxidation of free fatty acids,and induction of autophagy in hepatic cells.Recently,multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment.A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD.This review presents the current understanding of the role of the gutliver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.
基金National Natural Science Foundation of China,No.82173063 and No.81972220Wuxi Taihu Lake Talent Plan Supporting for Leading Talents in Medical and Health Profession+2 种基金Wuxi Medical Key Discipline,No.ZDXK2021002China Postdoctoral Science Foundation,No.2022M711370Postgraduate Research&Practice Innovation Program of Jiangsu Province,No.KYCX23_2573.
文摘BACKGROUND An increasing number of studies have focused on the role of cellular metabolism in the development of colorectal cancer(CRC).However,no work is currently available to synthesize the field through bibliometrics.AIM To analyze the development in the field of“glucose metabolism”(GM),“amino acid metabolism”(AM),“lipid metabolism”(LM),and“nucleotide metabolism”(NM)in CRC by visualization.METHODS Articles within the abovementioned areas of GM,AM,LM and NM in CRC,which were published from January 1,1991,to December 31,2022,are retrieved from the Web of Science Core Collection and analyzed by CiteSpace 6.2.R4 and VOSviewer 1.6.19.RESULTS The field of LM in CRC presented the largest number of annual publications and the fastest increase in the last decade compared with the other three fields.Meanwhile,China and the United States were two of the most prominent contri-butors in these four areas.In addition,Gang Wang,Wei Jia,Maria Notar-nicola,and Cornelia Ulrich ranked first in publication numbers,while Jing-Yuan Fang,Senji Hirasawa,Wei Jia,and Charles Fuchs were the most cited authors on average in these four fields,respectively.“Gut microbiota”and“epithelial-mesenchymal transition”emerged as the newest burst words in GM,“gut microbiota”was the latest outburst word in AM,“metastasis”,“tumor microenvironment”,“fatty acid metabolism”,and“metabolic reprogramming”were the up-to-date outbreaking words in LM,while“epithelial-mesenchymal transition”and“apoptosis”were the most recently occurring words in NM.CONCLUSION Research in“cellular metabolism in CRC”is all the rage at the moment,and researchers are particularly interested in exploring the mechanism to explain the metabolic alterations in CRC.Targeting metabolic vulnerability appears to be a promising direction in CRC therapy.
文摘Breast cancer brain metastasis(BCBrM)is a crucial and hard area of research which guarantees an urgent need to understand the underlying molecular mechanisms.A recent study by Li et al.[1]published in Military Medical Research investigated the role of retinoic acid receptor responder 2(RARRES2)in regulating lipid metabolism in BCBrM,highlighting the clinical relevance of alterations in lipid metabolites,such as phosphatidylcholine(PC)and triacylglycerols(TAGs),by RARRES2 through the modulation of phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway.This commentary aims to elaborate on the key findings and their relevance to the field.
基金Liuzhou City's Top Ten Hundred Talents Project,Liuzhou Science and Technology Project(Grant Nos.2021CBC0126 and 2021CBC0123)Guangxi Zhuang Autonomous Region Health and Family Planning Commission Projects(Z20210561,Z20210903)+1 种基金liuzhou Scienceand Technology Plan Projects(2021CBC0121,2021CBC0128).
文摘Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells and 65 glycogen metabolism genes were analyzed bya nonnegative matrix factorization(NMF).The prognosis and immune response of new glycogen TME cell dusters were predicted by using HCC and immunotherapy cohorts from public databases.HOC single cell analysis was divided into fibroblasts,NT T cells,macrophages,endothelial clls,and B cells,which were separately divided into new cell clusters by glycogen metabolism gene annotation.Pseudo temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell dusters.Cellular communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME cell.related subtypes and diferent glycogen subtype cell clusters.SCENIC analysis of transcription factors upstream of TME cell clusters with different glycogen metabolism.In addition,TME cell dusters of glycogen metabolism were found to be enriched in expression in CAF subtypes,CD8 depleted,M1,and M2 types.Bulk seq analysis showed the prognostic signifcance of glycogen metabolism.mediated TME cell dusters in HCC,while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade(ICB),especially for CAFs,T cells,and macrophages In summary,our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell dusters.