Background:Lung cancer is one of the deadliest cancers worldwide,creating a pressing need to develop novel drugs that inhibit oncogenic signaling pathways.Numerous studies have shown that berberine(BBR)has anti–lung ...Background:Lung cancer is one of the deadliest cancers worldwide,creating a pressing need to develop novel drugs that inhibit oncogenic signaling pathways.Numerous studies have shown that berberine(BBR)has anti–lung cancer potential.We aimed to explore the anti–lung cancer effect of BBR and related mechanisms by targeting the glycogen synthase kinase 3β(GSK3β)/β-catenin pathway.Methods:Lung adenocarcinoma(LUAD)cells A549 and NCI-H1975 were treated with BBR.Results:Our results showed that BBR inhibited cell proliferation by decreasing c-Myc levels and induced cel cycle arrest in the G0/G1 phase by lowering cyclin D1 levels.BBR induced apoptosis by upregulating cleaved caspase 3 levels.BBR inhibited cell migration and invasion by decreasing N-cadherin levels.Furthermore,BBR upregulated the expression of GSK3βprotein and phospho-β-catenin proteins in the cytoplasm,while decreasing the expression ofβ-catenin protein.Next,LUAD cel s were exposed to CHIR-99021(a GSK3βinhibitor).This treatment led to an increase in c-Myc,cyclin D1,andβ-catenin levels at specific concentrations.BBR partially reversed the effects of CHIR-99021.Finally,LUAD cells were treated with CHIR-99021(4μmoL/L)combined with BBR(30 and 60μmoL/L)for 24 h.The expression of programmed death ligand 1(PD-L1)was assessed by Western blot analysis.Jurkat T cells and A549 cel s were cocultured for 24 h to examine the lactate dehydrogenase release rate.Results suggested that BBR suppressed the expression of PD-L1 and heightened the immune lethality of T cells.Conclusions:BBR suppressed the proliferative activity of LUAD cell lines A549 and NCI-H1975 in vitro,induced cell cycle arrest and cancer cel apoptosis in the G0/G1 stage,and repressed the migration and invasion of cancer cells.BBR reduced the PD-L1 protein expression and enhanced T-cell–mediated cytotoxicity.These effects appear to be related to BBR's regulation of the GSK3β/β-catenin pathway.展开更多
Glycogen storage diseases(GSDs)are a group of inherited disorders caused by genetic defects in various enzymes involved in glycogen production or breakdown.Hepatic GSDs often have overlapping clinical features,making ...Glycogen storage diseases(GSDs)are a group of inherited disorders caused by genetic defects in various enzymes involved in glycogen production or breakdown.Hepatic GSDs often have overlapping clinical features,making subtyping or prognostication difficult.With the availability and advancement of next-generation sequencing,definitive molecular diagnosis is now available for most patients,with newer variants being increasingly identified.Molecular diagnosis could help in systematic follow-up,anticipating complications and prognostications.However,the mutations reported in the published literature display wide variations across racial and geographical groups.Hence,natural history,long-term outcome,and genotype-phenotypic correlation studies in patients with various hepatic GSDs are needed for a deeper understanding.Considering the emerging evidence of genetic profiling of patients with hepatic GSDs,including the recent study by Vanduangden et al,this editorial aims to review the various clinical subtypes,the spectrum of genetic mutations,and genotype-phenotype correlations for various hepatic GSDs.展开更多
Peach are a fruit with high nutritional and economic value,but their safety and suitability for diabetic patients have been questioned.This study investigated the effects and potential mechanisms of peach pulp(PP)on t...Peach are a fruit with high nutritional and economic value,but their safety and suitability for diabetic patients have been questioned.This study investigated the effects and potential mechanisms of peach pulp(PP)on type 2 diabetes mellitus(T2DM)in mice induced by a high-fat diet(HFD)combined with streptozotocin(STZ).The results showed that PP alleviated hyperglycemia,hyperlipidemia,hyperuricemia,and tissue dysfunction in T2DM mice through the synergistic effect of nutrients and non-nutrient compounds.Analysis of mRNA expression levels revealed that PP improved glucose metabolism in T2DM mice by promoting glycogen synthesis and inhibiting gluconeogenesis.Furthermore,elevated levels of PP resulted in an increase in acetic acid content following a 4 weeks intervention period.Additionally,it led to the restoration of gut microbiota balance by decreasing the Firmicutes/Bacteroidota(F/B)ratio and enhancing the presence of Romboutsia,Allobaculum,Alloprevotella,and Bacteroides after an 8 weeks intervention.Ultimately,our results suggest that PP may offer advantages for individuals with diabetes.展开更多
Oysters are of the most economically important bivalves worldwide.It has high nutritional value and is regarded as a good source of proteins,lipids,glycogen,and amino acids.C.gigas and C.angulata are allopatric congen...Oysters are of the most economically important bivalves worldwide.It has high nutritional value and is regarded as a good source of proteins,lipids,glycogen,and amino acids.C.gigas and C.angulata are allopatric congeneric dominant oysters that are widely cultivated in the northern and southern coast of China,and have shown remarkable differentiation in the nutritional content.Interspecific hybridization and backcross of the two species are effective ways to improve the nutritional quality of the oyster.Sixteen progenies were constructed based on a 4×4 diallel crosses among broodstock of C.gigas(G),C.angulata(A)and their hybrids GA(H)and AG(R).The glycogen,fatty acids,and amino acids performance of these progenies were evaluated in 22 months after fertilization.The glycogen content of AA was significantly lower than that of the other 15 progenies(P<0.05),while only the GH progeny was significantly higher than the GG(P<0.05),with a heterosis value of 21.06%.The backcross progenies GR exhibited significantly higher saturated fatty acids,eicosapentaenoic acid(EPA),and polyunsaturated fatty acids(PUFAs)content than those of GG(P<0.05),and did not show significant differences from AA.The AA showed significantly higher content of total amino acids(TAAs)than GG(P<0.05).The AH progeny displayed significantly higher taurine(Tau)content than GG(P<0.05),and the heterosis value was 27.88%.Therefore,the backcross breeding was shown an effective way to improve the glycogen,fatty acids,and TAAs of GG,and the glycogen of AA.This study provided useful information to characterize the benefits of backcrossing in nutritional quality,which will facilitate the production of differentiated products and increase the efficiency of the oyster industry.展开更多
Mitochondria are central organelles in cellular metabolism,orchestrating energy production,biosynthetic pathways,and signaling networks.Nicotinamide adenine dinucleotide(NAD+)and its reduced form(NADH)are essential fo...Mitochondria are central organelles in cellular metabolism,orchestrating energy production,biosynthetic pathways,and signaling networks.Nicotinamide adenine dinucleotide(NAD+)and its reduced form(NADH)are essential for mitochondrial metabolism,functioning both as redox coenzymes and as signaling agents that help regulate cellular balance.Thus,while its major role is in energy production,NAD+is widely recognized as a metabolic cofactor and also serves as a substrate for various enzymes involved in cellular signaling,like sirtuins(SIRTs),poly(ADP-ribosyl)polymerases(PARPs),mono(ADP-ribosyl)transferases,and CD38.Sirtuins,a family of NAD+-dependent deacetylases,are critical in this regulatory network.SIRT3 removes acetyl groups from and enhances the activity of key enzymes that participate in fatty acid breakdown,the tricarboxylic acid(TCA)cycle,and the electron transport chain(etc),thereby enhancing mitochondrial efficiency and energy production.Mitochondrial NAD+biosynthesis involves multiple pathways,including the de novo synthesis from tryptophan via the kynurenine and the salvage pathway,which recycles nicotinamide back to NAD+.Moreover,NAD+concentrations influence mitochondrial dynamics such as fusion,fission,and mitophagy,which are essential for preserving mitochondrial integrity and function.NAD+alsomodulates the balance between glycolysis and oxidative phosphorylation,influencing the metabolic flexibility of cells.During NAD+depletion,mainly in metabolic disorders,cells often shift towards anaerobic glycolysis,reducing ATP production efficiency and increasing lactate production.This metabolic shift is associated with various pathophysiological conditions,including insulin resistance,neurodegeneration,and muscle wasting.This reviewexplores themultifaceted functions of NAD+in regulating mitochondrialmetabolism.It highlights the underlying causes and pathological outcomes of disrupted NAD+metabolism while exploring potential therapeutic targets and treatment strategies.展开更多
We read with great interest the recent article by Valenzuela et al.1titled“Dose-response effect of pre-exercise carbohydrates under muscle glycogen unavailability:Insights from McArdle disease”published in the Journ...We read with great interest the recent article by Valenzuela et al.1titled“Dose-response effect of pre-exercise carbohydrates under muscle glycogen unavailability:Insights from McArdle disease”published in the Journal of Sport and Health Science The study's exploration of the effects of varying carbohydrate(CHO)doses on exercise capacity in Mc Ardle disease,a condition characterized by complete muscle glycogen unavailability,is a significant contribution to the field of sports science and metabolic disorders.展开更多
Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The...Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.展开更多
Glycogen serves as the principal energy reserve for metabolic processes in aquatic shellfish and substantially contributes to the flavor and quality of oysters.The Jinjiang oyster(Crassostrea ariakensis)is an economic...Glycogen serves as the principal energy reserve for metabolic processes in aquatic shellfish and substantially contributes to the flavor and quality of oysters.The Jinjiang oyster(Crassostrea ariakensis)is an economically and ecologically important species in China.In the present study,RNA sequencing(RNA-seq)and assay for transposase-accessible chromatin using sequencing(ATAC-seq)were performed to investigate gene expression and chromatin accessibility variations in oysters with different glycogen contents.Analysis identified 9483 differentially expressed genes(DEGs)and 7215 genes with significantly differential chromatin accessibility(DCAGs)were obtained,with an overlap of 2600 genes between them.Notably,a significant proportion of these genes were enriched in pathways related to glycogen metabolism,including“Glycogen metabolic process”and“Starch and sucrose metabolism”.In addition,genome-wide association study(GWAS)identified 526 single nucleotide polymorphism(SNP)loci associated with glycogen content.These loci corresponded to 241 genes,63 of which were categorized as both DEGs and DCAGs.This study enriches basic research data and provides insights into the molecular mechanisms underlying the regulation of glycogen metabolism in C.ariakensis.展开更多
Background:This study aimed to determine the effect of different carbohydrate(CHO)doses on exercise capacity in patients with McArdle disease—the paradigm of“exercise intolerance”,characterized by complete muscle g...Background:This study aimed to determine the effect of different carbohydrate(CHO)doses on exercise capacity in patients with McArdle disease—the paradigm of“exercise intolerance”,characterized by complete muscle glycogen unavailability—and to determine whether higher exogenous glucose levels affect metabolic responses at the McArdle muscle cell(in vitro)level.Methods:Patients with McArdle disease(n=8)and healthy controls(n=9)underwent a 12-min submaximal cycling constant-load bout followed by a maximal ramp test 15 min after ingesting a non-caloric placebo.In a randomized,double-blinded,cross-over design,patients repeated the tests after consuming either 75 g or 150 g of CHO(glucose:fructose=2:1).Cardiorespiratory,biochemical,perceptual,and electromyographic(EMG)variables were assessed.Additionally,glucose uptake and lactate appearance were studied in vitro in wild-type and McArdle mouse myotubes cultured with increasing glucose concentrations(0.35,1.00,4.50,and 10.00 g/L).Results:Compared with controls,patients showed the“classical”second-wind phenomenon(after prior disproportionate tachycardia,myalgia,and excess electromyographic activity during submaximal exercise,all p<0.05)and an impaired endurance exercise capacity(-51%ventilatory threshold and55%peak power output,both p<0.001).Regardless of the CHO dose(p<0.05 for both doses compared with the placebo),CHO intake increased blood glucose and lactate levels,decreased fat oxidation rates,and attenuated the second wind in the patients.However,only the higher dose increased ventilatory threshold(+27%,p=0.010)and peak power output(+18%,p=0.007).In vitro analyses revealed no differences in lactate levels across glucose concentrations in wild-type myotubes,whereas a doseresponse effect was observed in McArdle myotubes.Conclusion:CHO intake exerts beneficial effects on exercise capacity in McArdle disease,a condition associated with total muscle glycogen unavailability.Some of these benefits are dose dependent.展开更多
The effects of ethanol extract of Bidens pilosa L.(EEB)on acute exercise fatigue and its underlying biochemical mechanism were investigated in this study.Sixty adult male ICR mice were divided into control,model,vitam...The effects of ethanol extract of Bidens pilosa L.(EEB)on acute exercise fatigue and its underlying biochemical mechanism were investigated in this study.Sixty adult male ICR mice were divided into control,model,vitamin C(VC)100,EEB40,EEB80,and EEB160 groups,receiving VC(100 mg/kg)or EEB(40,80,160 mg/kg)for 28 days(intragastrically,I.G.).The mice underwent tailsuspension,elevated plus maze(EPM),rotarod,and loaded swimming tasks and biochemical indices were measured.There were no significant differences in body weight,tail suspension time,EPM open arm time/entries and serum cortisone levels among the groups.Compared with the model group,there was an increase in rotarod latency in the VC100/EEB80 groups and an increase in loaded swimming time in the EEB80/EEB160 groups.Furthermore,the haptic and muscle glycogen levels decreased in the model group,while the haptic glycogen levels increased in the all VC/EEB groups.Similarly,the serum lactate and creatinine levels increased in the model group,but decreased in lactate(except for EEB160),creatinine(except for EEB40)and lactate dehydrogenase in the EEB80 group.In the liver,malonaldehyde(MDA)and oxidized glutathione(GSSG)levels increased in the model group;however,glutathione reductase(GR)(except for EEB40),glutathione(GSH)and GSH/GSSG ratios increased,with GSSG levels decreasing in all VC/EEB groups.In the quadriceps,the GR levels increased in the model,whereas it decreased in the VC100,EEB40 and EEB80 groups.These results suggest that EEB has anti-acute fatigue effect,potentially attributed to mitigate metabolite accumulation,enhancing glycogen reserves,and fortifying the antioxidant mechanism.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
The agp gene encoding the ADP-glucose pyrophosphorylase involved in cyanobacterial glycogen synthesis was amplified by PCR. The resulting agp fragment was cloned in plasmid pUC118 to generate plasmid pUCA. Part of the...The agp gene encoding the ADP-glucose pyrophosphorylase involved in cyanobacterial glycogen synthesis was amplified by PCR. The resulting agp fragment was cloned in plasmid pUC118 to generate plasmid pUCA. Part of the fragment within the agp DNA was deleted and replaced by an erythromycin resistance cassette to generate plasmid pUCAE, which was used to transform the Synechocystis sp. PCC 6803 wild-type strain and a mutant with resistance to erythromycin was obtained. PCR analysis of the genomic DNA from the resulting mutant indicated that the appropriate deletion and insertion indeed had occurred. The cell growth and Chl a, glycogen content in the mutant showed difference from those in the wild-type strain. The obtained biomass as well as the Chl a content in the mutant strain was higher than that of the wild-type strain, which suggested that the photosynthesis efficiency in the agp(-) strain was higher than that in the wild-type strain. No glycogen was found in the mutant, providing evidence for the correction of the mutant in physiological level.展开更多
The changes and correlations of muscle pH, glycogen, lactic acid and in- tramuscular fat oxidation in Duroc pigs 10 d after their slaughter, and the effects of different storage temperature and time on Duroc muscle pH...The changes and correlations of muscle pH, glycogen, lactic acid and in- tramuscular fat oxidation in Duroc pigs 10 d after their slaughter, and the effects of different storage temperature and time on Duroc muscle pH value, water loss rate, glycogen, lactic acid and 2-thiobarbituric acid （TBA） were studied. The results showed that during the 10 h after the slaughter, the pH value was decreased rapid- ly, the lactic acid content was increased significantly, while the glycogen and TBA contents were remained stable. At the storage temperature of 4 ℃, storage time showed no significant effects on Duroc muscle pH value and glycogen, lactic acid and TBA contents. At the storage temperature of -20 ℃, storage temperature had significant effects on pH value, while no significant effects on other indicators. The correlation analysis demonstrated that during the 10 h after the slaughter, the TBA content was negatively related to glycogen content （P〈0.05）, but positively related to lactic content （P〈0.05）; the pH value was negatively related to lactic acid content （P〈0.05）. At the storage temperature of 4 ℃, the TBA content was negatively relat- ed to water loss rate （P〈0.01） and lactic acid content （P〈0.05）; the water loss rate was positively related to pH value （P〈0.01） and lactic acid content （P〈0.05）. At the storage temperature of -20 ℃, the TBA content was negatively related to pH value （P〈0.01） and positively related to water loss rate （P〈0.05）; the water loss rate was negatively related to pH value （P〈0.01） and lactic acid content （P〈0.05）.展开更多
In this study, molecular interactions of the ligands, quercetin, gallic acid, and metformin with various diabetes mellitus-related protein targets, such as glycogen phosphorylase and peroxisome proliferatoractivated r...In this study, molecular interactions of the ligands, quercetin, gallic acid, and metformin with various diabetes mellitus-related protein targets, such as glycogen phosphorylase and peroxisome proliferatoractivated receptor gamma, were assessed. It was revealed that quercetin possesses good binding affinity to both targets. Quercetin is a major constituent of methanolic extracts of Phyllanthus emblica fruit. The antihyperglycemic effect of quercetin in streptozotocin(STZ)-induced diabetic rats was examined. The isolated quercetin administered at a dose of 75 mg/kg body weight produced a maximum decrease of14.78% in blood glucose levels in the diabetic rats after 7 days of treatment. Furthermore, quercetin doses of 50 and 75 mg/kg were shown to significantly improve the profiles of triglycerides, high-density lipoprotein, very-low-density lipoprotein, low-density lipoprotein, and total cholesterol at the end of the study in STZ-induced diabetic rats. The administration of quercetin(25, 50, and 75 mg/kg body weight)daily for 28 days in STZ-induced diabetic rats resulted in a significant decrease in blood glucose and urine sugar levels, with a considerable rise in plasma insulin and hemoglobin levels. Therefore, quercetin is a potential drug with antidiabetic and antihyperglycemic action mediated by changes in the levels of glucose, cholesterol, and triglycerides as indicated by in silico and in vivo studies.展开更多
基金Supported by a grant from the National Natural Science Foundation of China(no.82174457)。
文摘Background:Lung cancer is one of the deadliest cancers worldwide,creating a pressing need to develop novel drugs that inhibit oncogenic signaling pathways.Numerous studies have shown that berberine(BBR)has anti–lung cancer potential.We aimed to explore the anti–lung cancer effect of BBR and related mechanisms by targeting the glycogen synthase kinase 3β(GSK3β)/β-catenin pathway.Methods:Lung adenocarcinoma(LUAD)cells A549 and NCI-H1975 were treated with BBR.Results:Our results showed that BBR inhibited cell proliferation by decreasing c-Myc levels and induced cel cycle arrest in the G0/G1 phase by lowering cyclin D1 levels.BBR induced apoptosis by upregulating cleaved caspase 3 levels.BBR inhibited cell migration and invasion by decreasing N-cadherin levels.Furthermore,BBR upregulated the expression of GSK3βprotein and phospho-β-catenin proteins in the cytoplasm,while decreasing the expression ofβ-catenin protein.Next,LUAD cel s were exposed to CHIR-99021(a GSK3βinhibitor).This treatment led to an increase in c-Myc,cyclin D1,andβ-catenin levels at specific concentrations.BBR partially reversed the effects of CHIR-99021.Finally,LUAD cells were treated with CHIR-99021(4μmoL/L)combined with BBR(30 and 60μmoL/L)for 24 h.The expression of programmed death ligand 1(PD-L1)was assessed by Western blot analysis.Jurkat T cells and A549 cel s were cocultured for 24 h to examine the lactate dehydrogenase release rate.Results suggested that BBR suppressed the expression of PD-L1 and heightened the immune lethality of T cells.Conclusions:BBR suppressed the proliferative activity of LUAD cell lines A549 and NCI-H1975 in vitro,induced cell cycle arrest and cancer cel apoptosis in the G0/G1 stage,and repressed the migration and invasion of cancer cells.BBR reduced the PD-L1 protein expression and enhanced T-cell–mediated cytotoxicity.These effects appear to be related to BBR's regulation of the GSK3β/β-catenin pathway.
文摘Glycogen storage diseases(GSDs)are a group of inherited disorders caused by genetic defects in various enzymes involved in glycogen production or breakdown.Hepatic GSDs often have overlapping clinical features,making subtyping or prognostication difficult.With the availability and advancement of next-generation sequencing,definitive molecular diagnosis is now available for most patients,with newer variants being increasingly identified.Molecular diagnosis could help in systematic follow-up,anticipating complications and prognostications.However,the mutations reported in the published literature display wide variations across racial and geographical groups.Hence,natural history,long-term outcome,and genotype-phenotypic correlation studies in patients with various hepatic GSDs are needed for a deeper understanding.Considering the emerging evidence of genetic profiling of patients with hepatic GSDs,including the recent study by Vanduangden et al,this editorial aims to review the various clinical subtypes,the spectrum of genetic mutations,and genotype-phenotype correlations for various hepatic GSDs.
基金supported by the Zhejiang Key R&D Program of China(2020C02037)the Ningbo Agricultural Research Program of China(2022S1542022S138).
文摘Peach are a fruit with high nutritional and economic value,but their safety and suitability for diabetic patients have been questioned.This study investigated the effects and potential mechanisms of peach pulp(PP)on type 2 diabetes mellitus(T2DM)in mice induced by a high-fat diet(HFD)combined with streptozotocin(STZ).The results showed that PP alleviated hyperglycemia,hyperlipidemia,hyperuricemia,and tissue dysfunction in T2DM mice through the synergistic effect of nutrients and non-nutrient compounds.Analysis of mRNA expression levels revealed that PP improved glucose metabolism in T2DM mice by promoting glycogen synthesis and inhibiting gluconeogenesis.Furthermore,elevated levels of PP resulted in an increase in acetic acid content following a 4 weeks intervention period.Additionally,it led to the restoration of gut microbiota balance by decreasing the Firmicutes/Bacteroidota(F/B)ratio and enhancing the presence of Romboutsia,Allobaculum,Alloprevotella,and Bacteroides after an 8 weeks intervention.Ultimately,our results suggest that PP may offer advantages for individuals with diabetes.
基金Supported by the Key Research and Development Program of Shandong(No.2022LZGC015)the National Key R&D Program of China(No.2022YFD2400304)+2 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA24030105)the Key Technology Research and Industrialization Demonstration Projects of Qingdao(No.22-3-3-hygg-2-hy)the China Agriculture Research System of MOF and MARA(No.CARS-49)。
文摘Oysters are of the most economically important bivalves worldwide.It has high nutritional value and is regarded as a good source of proteins,lipids,glycogen,and amino acids.C.gigas and C.angulata are allopatric congeneric dominant oysters that are widely cultivated in the northern and southern coast of China,and have shown remarkable differentiation in the nutritional content.Interspecific hybridization and backcross of the two species are effective ways to improve the nutritional quality of the oyster.Sixteen progenies were constructed based on a 4×4 diallel crosses among broodstock of C.gigas(G),C.angulata(A)and their hybrids GA(H)and AG(R).The glycogen,fatty acids,and amino acids performance of these progenies were evaluated in 22 months after fertilization.The glycogen content of AA was significantly lower than that of the other 15 progenies(P<0.05),while only the GH progeny was significantly higher than the GG(P<0.05),with a heterosis value of 21.06%.The backcross progenies GR exhibited significantly higher saturated fatty acids,eicosapentaenoic acid(EPA),and polyunsaturated fatty acids(PUFAs)content than those of GG(P<0.05),and did not show significant differences from AA.The AA showed significantly higher content of total amino acids(TAAs)than GG(P<0.05).The AH progeny displayed significantly higher taurine(Tau)content than GG(P<0.05),and the heterosis value was 27.88%.Therefore,the backcross breeding was shown an effective way to improve the glycogen,fatty acids,and TAAs of GG,and the glycogen of AA.This study provided useful information to characterize the benefits of backcrossing in nutritional quality,which will facilitate the production of differentiated products and increase the efficiency of the oyster industry.
基金A fellowship support from the Golda Meir Fellowship Fund,The Hebrew University of Jerusalem,Israel。
文摘Mitochondria are central organelles in cellular metabolism,orchestrating energy production,biosynthetic pathways,and signaling networks.Nicotinamide adenine dinucleotide(NAD+)and its reduced form(NADH)are essential for mitochondrial metabolism,functioning both as redox coenzymes and as signaling agents that help regulate cellular balance.Thus,while its major role is in energy production,NAD+is widely recognized as a metabolic cofactor and also serves as a substrate for various enzymes involved in cellular signaling,like sirtuins(SIRTs),poly(ADP-ribosyl)polymerases(PARPs),mono(ADP-ribosyl)transferases,and CD38.Sirtuins,a family of NAD+-dependent deacetylases,are critical in this regulatory network.SIRT3 removes acetyl groups from and enhances the activity of key enzymes that participate in fatty acid breakdown,the tricarboxylic acid(TCA)cycle,and the electron transport chain(etc),thereby enhancing mitochondrial efficiency and energy production.Mitochondrial NAD+biosynthesis involves multiple pathways,including the de novo synthesis from tryptophan via the kynurenine and the salvage pathway,which recycles nicotinamide back to NAD+.Moreover,NAD+concentrations influence mitochondrial dynamics such as fusion,fission,and mitophagy,which are essential for preserving mitochondrial integrity and function.NAD+alsomodulates the balance between glycolysis and oxidative phosphorylation,influencing the metabolic flexibility of cells.During NAD+depletion,mainly in metabolic disorders,cells often shift towards anaerobic glycolysis,reducing ATP production efficiency and increasing lactate production.This metabolic shift is associated with various pathophysiological conditions,including insulin resistance,neurodegeneration,and muscle wasting.This reviewexplores themultifaceted functions of NAD+in regulating mitochondrialmetabolism.It highlights the underlying causes and pathological outcomes of disrupted NAD+metabolism while exploring potential therapeutic targets and treatment strategies.
文摘We read with great interest the recent article by Valenzuela et al.1titled“Dose-response effect of pre-exercise carbohydrates under muscle glycogen unavailability:Insights from McArdle disease”published in the Journal of Sport and Health Science The study's exploration of the effects of varying carbohydrate(CHO)doses on exercise capacity in Mc Ardle disease,a condition characterized by complete muscle glycogen unavailability,is a significant contribution to the field of sports science and metabolic disorders.
基金supported by the National Natural Science Foundation of China,Nos. 82173806 and U1803281Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science,Nos. 2021-I2M-1-030 and 2022-I2M-2-002Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences,No. 2022-JKCS-08 (all to RL)。
文摘Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.
基金supported by the National Key R&D Program of China(2022YFD2400105,2018YFD0900104)Central Publicinterest Scientific Institution Basal Research Fund,CAFS(2021XT0102,2023TD30)+2 种基金Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology(Qingdao)(2021QNLM050103)Key Research and Development Project of Shandong Province(2021LZGC028)National Marine Genetic Resource Center。
文摘Glycogen serves as the principal energy reserve for metabolic processes in aquatic shellfish and substantially contributes to the flavor and quality of oysters.The Jinjiang oyster(Crassostrea ariakensis)is an economically and ecologically important species in China.In the present study,RNA sequencing(RNA-seq)and assay for transposase-accessible chromatin using sequencing(ATAC-seq)were performed to investigate gene expression and chromatin accessibility variations in oysters with different glycogen contents.Analysis identified 9483 differentially expressed genes(DEGs)and 7215 genes with significantly differential chromatin accessibility(DCAGs)were obtained,with an overlap of 2600 genes between them.Notably,a significant proportion of these genes were enriched in pathways related to glycogen metabolism,including“Glycogen metabolic process”and“Starch and sucrose metabolism”.In addition,genome-wide association study(GWAS)identified 526 single nucleotide polymorphism(SNP)loci associated with glycogen content.These loci corresponded to 241 genes,63 of which were categorized as both DEGs and DCAGs.This study enriches basic research data and provides insights into the molecular mechanisms underlying the regulation of glycogen metabolism in C.ariakensis.
基金supported by a Sara Borrell postdoctoral contract granted by Instituto de Salud Carlos III(CD21/00138).PLV,DB-G and AL are funded by the Spanish Ministry of Economy and Competitiveness and Fondos Feder(Alejandro Lucia,Grant No.PI18/00139)TP is funded by the Spanish Ministry of Economy and Competitiveness and Fondos Feder(Tomas Pinos,Grant No.PI22/00201).
文摘Background:This study aimed to determine the effect of different carbohydrate(CHO)doses on exercise capacity in patients with McArdle disease—the paradigm of“exercise intolerance”,characterized by complete muscle glycogen unavailability—and to determine whether higher exogenous glucose levels affect metabolic responses at the McArdle muscle cell(in vitro)level.Methods:Patients with McArdle disease(n=8)and healthy controls(n=9)underwent a 12-min submaximal cycling constant-load bout followed by a maximal ramp test 15 min after ingesting a non-caloric placebo.In a randomized,double-blinded,cross-over design,patients repeated the tests after consuming either 75 g or 150 g of CHO(glucose:fructose=2:1).Cardiorespiratory,biochemical,perceptual,and electromyographic(EMG)variables were assessed.Additionally,glucose uptake and lactate appearance were studied in vitro in wild-type and McArdle mouse myotubes cultured with increasing glucose concentrations(0.35,1.00,4.50,and 10.00 g/L).Results:Compared with controls,patients showed the“classical”second-wind phenomenon(after prior disproportionate tachycardia,myalgia,and excess electromyographic activity during submaximal exercise,all p<0.05)and an impaired endurance exercise capacity(-51%ventilatory threshold and55%peak power output,both p<0.001).Regardless of the CHO dose(p<0.05 for both doses compared with the placebo),CHO intake increased blood glucose and lactate levels,decreased fat oxidation rates,and attenuated the second wind in the patients.However,only the higher dose increased ventilatory threshold(+27%,p=0.010)and peak power output(+18%,p=0.007).In vitro analyses revealed no differences in lactate levels across glucose concentrations in wild-type myotubes,whereas a doseresponse effect was observed in McArdle myotubes.Conclusion:CHO intake exerts beneficial effects on exercise capacity in McArdle disease,a condition associated with total muscle glycogen unavailability.Some of these benefits are dose dependent.
基金Supported by the National Natural Science Foundation of China(31760278)。
文摘The effects of ethanol extract of Bidens pilosa L.(EEB)on acute exercise fatigue and its underlying biochemical mechanism were investigated in this study.Sixty adult male ICR mice were divided into control,model,vitamin C(VC)100,EEB40,EEB80,and EEB160 groups,receiving VC(100 mg/kg)or EEB(40,80,160 mg/kg)for 28 days(intragastrically,I.G.).The mice underwent tailsuspension,elevated plus maze(EPM),rotarod,and loaded swimming tasks and biochemical indices were measured.There were no significant differences in body weight,tail suspension time,EPM open arm time/entries and serum cortisone levels among the groups.Compared with the model group,there was an increase in rotarod latency in the VC100/EEB80 groups and an increase in loaded swimming time in the EEB80/EEB160 groups.Furthermore,the haptic and muscle glycogen levels decreased in the model group,while the haptic glycogen levels increased in the all VC/EEB groups.Similarly,the serum lactate and creatinine levels increased in the model group,but decreased in lactate(except for EEB160),creatinine(except for EEB40)and lactate dehydrogenase in the EEB80 group.In the liver,malonaldehyde(MDA)and oxidized glutathione(GSSG)levels increased in the model group;however,glutathione reductase(GR)(except for EEB40),glutathione(GSH)and GSH/GSSG ratios increased,with GSSG levels decreasing in all VC/EEB groups.In the quadriceps,the GR levels increased in the model,whereas it decreased in the VC100,EEB40 and EEB80 groups.These results suggest that EEB has anti-acute fatigue effect,potentially attributed to mitigate metabolite accumulation,enhancing glycogen reserves,and fortifying the antioxidant mechanism.
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.
文摘The agp gene encoding the ADP-glucose pyrophosphorylase involved in cyanobacterial glycogen synthesis was amplified by PCR. The resulting agp fragment was cloned in plasmid pUC118 to generate plasmid pUCA. Part of the fragment within the agp DNA was deleted and replaced by an erythromycin resistance cassette to generate plasmid pUCAE, which was used to transform the Synechocystis sp. PCC 6803 wild-type strain and a mutant with resistance to erythromycin was obtained. PCR analysis of the genomic DNA from the resulting mutant indicated that the appropriate deletion and insertion indeed had occurred. The cell growth and Chl a, glycogen content in the mutant showed difference from those in the wild-type strain. The obtained biomass as well as the Chl a content in the mutant strain was higher than that of the wild-type strain, which suggested that the photosynthesis efficiency in the agp(-) strain was higher than that in the wild-type strain. No glycogen was found in the mutant, providing evidence for the correction of the mutant in physiological level.
基金Supported by Funds for Swine Innovation Team Construction of Shandong Provincial Modern Agriculture Industry Technology System(SDAIT-06-011-03)Fine Breeds Engineering Project of Shandong Province(2011LZ013-01)China Swine Industry Technology System(CARS-36)~~
文摘The changes and correlations of muscle pH, glycogen, lactic acid and in- tramuscular fat oxidation in Duroc pigs 10 d after their slaughter, and the effects of different storage temperature and time on Duroc muscle pH value, water loss rate, glycogen, lactic acid and 2-thiobarbituric acid （TBA） were studied. The results showed that during the 10 h after the slaughter, the pH value was decreased rapid- ly, the lactic acid content was increased significantly, while the glycogen and TBA contents were remained stable. At the storage temperature of 4 ℃, storage time showed no significant effects on Duroc muscle pH value and glycogen, lactic acid and TBA contents. At the storage temperature of -20 ℃, storage temperature had significant effects on pH value, while no significant effects on other indicators. The correlation analysis demonstrated that during the 10 h after the slaughter, the TBA content was negatively related to glycogen content （P〈0.05）, but positively related to lactic content （P〈0.05）; the pH value was negatively related to lactic acid content （P〈0.05）. At the storage temperature of 4 ℃, the TBA content was negatively relat- ed to water loss rate （P〈0.01） and lactic acid content （P〈0.05）; the water loss rate was positively related to pH value （P〈0.01） and lactic acid content （P〈0.05）. At the storage temperature of -20 ℃, the TBA content was negatively related to pH value （P〈0.01） and positively related to water loss rate （P〈0.05）; the water loss rate was negatively related to pH value （P〈0.01） and lactic acid content （P〈0.05）.
基金the DST-SERB Major Research Project,New Delhi,India[Project File No.SB/YS/LS-109/2014]for funding this projectthe Management of A.V.V.M.Sri Pushpam College(Autonomous)+1 种基金Poondi,and Sharmila Institute of Medicinal Products Research Academy(SIMPRA)Thanjavur,India,for providing necessary facilities and support in carrying out this work
文摘In this study, molecular interactions of the ligands, quercetin, gallic acid, and metformin with various diabetes mellitus-related protein targets, such as glycogen phosphorylase and peroxisome proliferatoractivated receptor gamma, were assessed. It was revealed that quercetin possesses good binding affinity to both targets. Quercetin is a major constituent of methanolic extracts of Phyllanthus emblica fruit. The antihyperglycemic effect of quercetin in streptozotocin(STZ)-induced diabetic rats was examined. The isolated quercetin administered at a dose of 75 mg/kg body weight produced a maximum decrease of14.78% in blood glucose levels in the diabetic rats after 7 days of treatment. Furthermore, quercetin doses of 50 and 75 mg/kg were shown to significantly improve the profiles of triglycerides, high-density lipoprotein, very-low-density lipoprotein, low-density lipoprotein, and total cholesterol at the end of the study in STZ-induced diabetic rats. The administration of quercetin(25, 50, and 75 mg/kg body weight)daily for 28 days in STZ-induced diabetic rats resulted in a significant decrease in blood glucose and urine sugar levels, with a considerable rise in plasma insulin and hemoglobin levels. Therefore, quercetin is a potential drug with antidiabetic and antihyperglycemic action mediated by changes in the levels of glucose, cholesterol, and triglycerides as indicated by in silico and in vivo studies.
