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
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
Alzheimer’s disease (AD) is the most prevalent cause of dementia worldwide. Because of the progressive neurodegeneration, individual cognitive and behavioral functions are impaired, affecting the quality of life of m...Alzheimer’s disease (AD) is the most prevalent cause of dementia worldwide. Because of the progressive neurodegeneration, individual cognitive and behavioral functions are impaired, affecting the quality of life of millions of people. Although the exact pathogenesis of AD has not been fully elucidated, amyloid plaques, neurofibrillary tangles (NFTs), and sustaining neuroinflammation dominate its characteristics. As one of the major tau kinases leading to hyperphosphorylation and aggregation of tau, glycogen synthase kinase-3β (GSK-3β) has been drawing great attention in various AD studies. Another research focus of AD in recent years is the inflammasome, a multiprotein complex acting as a regulator in immunological reactions to exogenous and endogenous danger signals, of which the Nod-like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome has been studied mostly in AD and proven to play a significant role in AD development by its activation and downstream effects such as caspase-1 maturation and interleukin (IL)-1β release. Studies have shown that the NLRP3 inflammasome is activated in a GSK-3β-dependent way and that inhibition of the NLRP3 inflammasome downregulates GSK-3β, suggesting that these two important proteins are closely related. This article reviews the respective roles of GSK-3β and the NLRP3 inflammasome in AD as well as their relationship and interaction.展开更多
Glycogen storage diseases(GSDs),also referred to as glycogenoses,are inherited metabolic disorders of glycogen metabolism caused by deficiency of enzymes or transporters involved in the synthesis or degradation of gly...Glycogen storage diseases(GSDs),also referred to as glycogenoses,are inherited metabolic disorders of glycogen metabolism caused by deficiency of enzymes or transporters involved in the synthesis or degradation of glycogen leading to aberrant storage and/or utilization.The overall estimated GSD incidence is 1 case per 20000-43000 live births.There are over 20 types of GSD including the subtypes.This heterogeneous group of rare diseases represents inborn errors of carbohydrate metabolism and are classified based on the deficient enzyme and affected tissues.GSDs primarily affect liver or muscle or both as glycogen is particularly abundant in these tissues.However,besides liver and skeletal muscle,depending on the affected enzyme and its expression in various tissues,multiorgan involvement including heart,kidney and/or brain may be seen.Although GSDs share similar clinical features to some extent,there is a wide spectrum of clinical phenotypes.Currently,the goal of treatment is to maintain glucose homeostasis by dietary management and the use of uncooked cornstarch.In addition to nutritional interventions,pharmacological treatment,physical and supportive therapies,enzyme replacement therapy(ERT)and organ transplantation are other treatment approaches for both disease manifestations and longterm complications.The lack of a specific therapy for GSDs has prompted efforts to develop new treatment strategies like gene therapy.Since early diagnosis and aggressive treatment are related to better prognosis,physicians should be aware of these conditions and include GSDs in the differential diagnosis of patients with relevant manifestations including fasting hypoglycemia,hepatomegaly,hypertransaminasemia,hyperlipidemia,exercise intolerance,muscle cramps/pain,rhabdomyolysis,and muscle weakness.Here,we aim to provide a comprehensive review of GSDs.This review provides general characteristics of all types of GSDs with a focus on those with liver involvement.展开更多
Previous studies have shown that fibroblast growth factor 13 is downregulated in the brain of both Alzheimer’s disease mouse models and patients,and that it plays a vital role in the learning and memory.However,the u...Previous studies have shown that fibroblast growth factor 13 is downregulated in the brain of both Alzheimer’s disease mouse models and patients,and that it plays a vital role in the learning and memory.However,the underlying mechanisms of fibroblast growth factor 13 in Alzheimer’s disease remain unclear.In this study,we established rat models of Alzheimer’s disease by stereotaxic injection of amyloid-β(Aβ_(1-42))-induced into bilateral hippocampus.We also injected lentivirus containing fibroblast growth factor 13 into bilateral hippocampus to overexpress fibroblast growth factor 13.The expression of fibroblast growth factor 13 was downregulated in the brain of the Alzheimer’s disease model rats.After overexpression of fibroblast growth factor 13,learning and memory abilities of the Alzheimer’s disease model rats were remarkably improved.Fibroblast growth factor 13 overexpression increased brain expression levels of oxidative stress-related markers glutathione,superoxide dismutase,phosphatidylinositol-3-kinase,AKT and glycogen synthase kinase 3β,and anti-apoptotic factor BCL.Furthermore,fibroblast growth factor 13 overexpression decreased the number of apoptotic cells,expression of pro-apoptotic factor BAX,cleaved-caspase 3 and amyloid-βexpression,and levels of tau phosphorylation,malondialdehyde,reactive oxygen species and acetylcholinesterase in the brain of Alzheimer’s disease model rats.The changes were reversed by the phosphatidylinositol-3-kinase inhibitor LY294002.These findings suggest that overexpression of fibroblast growth factor 13 improved neuronal damage in a rat model of Alzheimer’s disease through activation of the phosphatidylinositol-3-kinase/AKT/glycogen synthase kinase 3βsignaling pathway.展开更多
Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in hig...Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.展开更多
A constant increase in dive tourism over the past years in the Revillagigedo National Park, Mexico, could result in a stressful scenario for giant mantas (Mobula birostris). The purpose of this study was to determine ...A constant increase in dive tourism over the past years in the Revillagigedo National Park, Mexico, could result in a stressful scenario for giant mantas (Mobula birostris). The purpose of this study was to determine the degree of oxidative stress in terms of changes in catalase units (CAT) and muscle glycogen concentration in this species during two periods of different tourism intensity in this protected area. A total of 21 muscle biopsies were collected in March (peak tourism) and November (lower tourism), 2019. Stress biomarkers were analysed by commercial kits from the company Cayman Chemical. Oxidative stress (catalase activity) was significantly higher during the period with lower tourism (p = 0.002), compared to the period with more tourism, suggesting the presence of the general adaptation syndrome. In males, there was a significant difference (p = 0.0005) in oxidative stress between periods of different tourism intensity, suggesting that the reproductive season may be a stressor. Morphotypes showed different oxidative stress (p = 0.031);however, the reason is unknown. No statistical differences were detected in glycogen concentrations between the tourism periods (p = 0.123), probably because this polysaccharide is not a proper indicator of chronic stress in giant mantas. Based on these findings, giant mantas may have an adequate response in terms of oxidative stress due to an increase in tourism;however the observed increase in catalase suggests that it is within the tolerance range of these organisms.展开更多
Melatonin is a hormone that regulates several physiological processes,including circadian rhythms,sleep,and immune function.Recent studies have suggested that melatonin may also play a role in exercise performance and...Melatonin is a hormone that regulates several physiological processes,including circadian rhythms,sleep,and immune function.Recent studies have suggested that melatonin may also play a role in exercise performance and recovery.Exercise-induced oxidative stress and inflammation can cause tissue damage and impair recovery.In addition to its intrinsic antioxidant properties,melatonin stimulates several antioxidative enzymes and enhances the efficacy of others.Melatonin also binds to a number of important antioxidant molecules,and indirectly contributes to the maintenance of the redox status in cells.The study suggests that melatonin may have a protective effect against the oxidative stress induced by exercise.Melatonin administration has increased muscle and liver glycogen content in both sedentary and exercised rats.The exercised groups are higher muscle and liver glycogen content compared to the sedentary groups.Melatonin treatment had no significant effect on body weight or food intake.The authors conclude that melatonin may play a role in regulating glycogen storage in skeletal muscle and liver,which could have implications for exercise performance and energy metabolism.Lactic acid is a byproduct of anaerobic metabolism that can accumulate in the muscle during exercise and contribute to muscle fatigue.The relationship between melatonin and lactic acid during exercise is not well understood,but some evidence suggests that melatonin may help to reduce lactic acid levels in the muscle.Zinc is necessary for melatonin synthesis.Melatonin,in turn,increases the absorption of zinc in the digestive system.The decrease observed in zinc levels after pinealectomy can cause muscle exhaustion,and thus,can have a negative impact on performance.It can be concluded that there is a significant relation between melatonin,zinc,and physical performance.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
Polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE) protocol was employed for revealing microbial community structure and succession in a sequential anaerobic and aerobic reactor perform...Polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE) protocol was employed for revealing microbial community structure and succession in a sequential anaerobic and aerobic reactor performing enhanced biological phosphorus removal (EBPR) during start-up period. High phosphorus removal was achieved after 15 d. On day 30, phosphorus removal efficiency reached to 83.2% and the start-up was finished. DGGE profiles of periodical sludge samples showed that dominant microbial species were 19 OTUs (operational taxonomy units). Unweighted pair-group method using arithmetic averages (UPGMA) clustering analysis revealed that rapid community succession correlated to low phosphorus removal rate and high phosphorus removal efficiency reflected on steady community structure. Sequencing results indicated that determined sequences (12 OTUs) belonged to Proteobacterium, Actinobacteria, Gemmatimonadales and unaffiliate group. Proteobacterium, Tetrasphaera elongate and Gemmatimonas aurantiaca may act important roles in phosphorus removal. With little amount as known glycogen accumulating organisms, Candidatus Competibacter phosphatis still at accumulating-phase had limited effect on microbial community structure. When climax community was obtained, dominant microbes were 14 OTUs. Microbes in a large amount were uncultured bacterium Thauera sp., uncultured y-Proteobacterium and Tetrasphaera elongata.展开更多
Objective:To analyze the expression of phosphatidylinositol 3 kinase(PI3-K),protein kinase B(PKB)and glycogen synthase kinase 3 beta(GSK-3β)in skeletal muscle tissue of gestational diabetes mellitus(GDM).Methods:A to...Objective:To analyze the expression of phosphatidylinositol 3 kinase(PI3-K),protein kinase B(PKB)and glycogen synthase kinase 3 beta(GSK-3β)in skeletal muscle tissue of gestational diabetes mellitus(GDM).Methods:A total of 90 cases of pregnant women were divided into observation group and control group according to the occurrence of GDM with 45 cases in either,and the expression of PI3-K,PKB,GSK-3βmRNA expression in skeletal muscle tissue was compared between two groups.Results:The total PI3-K p85 protein was significantly higher in the observation group compared with the control group,the activity of PI3-K was lower than that of the latter;The total PKB,GSK-3βprotein in skeletal tissue had no significant difference between two groups,while the serine phosphorylation levels of PKB and GSK-3βwere significantly lower in observation group compared with the control group.Conclusions:The downregulation of PI3-K,PKB and GSK-3βin skeletal tissue of GDM caused by phosphorylation dysfunction of signaling molecules is the reason for insulin resistance and transporter function decline which lead to GDM.展开更多
AIM: To investigate the regulatory mechanism of glycogen synthase kinase 3β(GSK3β) in epithelialmesenchymal transition(EMT) process after proliferative vitreoretinopathy(PVR) induction. METHODS: Experimenta...AIM: To investigate the regulatory mechanism of glycogen synthase kinase 3β(GSK3β) in epithelialmesenchymal transition(EMT) process after proliferative vitreoretinopathy(PVR) induction. METHODS: Experimental PVR was induced by intravitreal injection of retinal pigment epithelium(RPE) cells in the eyes of rabbits. A PI3 K/Akt inhibitor(wortmannin) and a GSK3β inhibitor(Li Cl) were also injected at different time during PVR progress. Electroretinogram(ERG), ocular fundus photographs, and B-scan ultrasonography were used to observe the PVR progress. Western blot test on the extracted retina were performed at 1, 2, 4 wk. The expression of the mesenchymal marker vimentin was determined by immunohistochemistry. Toxicity of wortmannin and Li Cl were evaluated by ERG and Td Tmediated d UTP nick-end labeling(TUNEL) assay. The vitreous was also collected for metabolomic analysis. RESULTS: Experimental PVR could significantly lead to EMT, along with the suppressed expression of GSK3β and the activation of Wnt/β-catenin and PI3 K/Akt pathways. It was verified that upregulating the expression of GSK3β could effectively inhibit EMT process by suppressing Wnt/β-catenin and PI3 K/Akt pathways. CONCLUSION: GSK3β effectively inhibits EMT via the Wnt/β-catenin and PI3 K/Akt pathways. GSK3β may be regarded as a promising target of experimental PVR inhibition.展开更多
Diabetes mellitus affects virtually every organ system in the body and the degree of organ involvement depends on the duration and severity of the disease,and other co-morbidities.Gastrointestinal(GI) involvement can ...Diabetes mellitus affects virtually every organ system in the body and the degree of organ involvement depends on the duration and severity of the disease,and other co-morbidities.Gastrointestinal(GI) involvement can present with esophageal dysmotility,gastro-esophageal reflux disease(GERD),gastroparesis,enteropathy,non alcoholic fatty liver disease(NAFLD) and glycogenic hepatopathy.Severity of GERD is inversely related to glycemic control and management is with prokinetics and proton pump inhibitors.Diabetic gastroparesis manifests as early satiety,bloating,vomiting,abdominal pain and erratic glycemic control.Gastric emptying scintigraphy is considered the gold standard test for diagnosis.Management includes dietary modifications,maintaining euglycemia,prokinetics,endoscopic and surgical treatments.Diabetic enteropathy is also common and management involves glycemic control and symptomatic measures.NAFLD is considered a hepatic manifestation of metabolic syndrome and treatment ismainly lifestyle measures,with diabetes and dyslipidemia management when coexistent.Glycogenic hepatopathy is a manifestation of poorly controlled type 1 diabetes and is managed by prompt insulin treatment.Though GI complications of diabetes are relatively common,awareness about its manifestations and treatment options are low among physicians.Optimal management of GI complications is important for appropriate metabolic control of diabetes and improvement in quality of life of the patient.This review is an update on the GI complications of diabetes,their pathophysiology,diagnostic evaluation and management.展开更多
As a major microtubule-associated protein, tau plays an important role in promoting microtubule assembly and stabilizing microtubules. In Alzheimer’s disease(AD) and other tauopathies, the abnormally hyperphosphoryla...As a major microtubule-associated protein, tau plays an important role in promoting microtubule assembly and stabilizing microtubules. In Alzheimer’s disease(AD) and other tauopathies, the abnormally hyperphosphorylated tau proteins are aggregated into paired helical filaments and accumulated in the neurons with the form of neurofibrillary tangles. An imbalanced regulation in protein kinases and protein phosphatases is the direct cause of tau hyperphosphorylation. Among various kinases and phosphatases, glycogen synthase kinase-3β(GSK-3β) and protein phosphatase 2A(PP2A) are the most implicated. Accumulation of the hyperphosphorylated tau induces synaptic toxicity and cognitive impairments. Here, we review the upstream factors or pathways that can regulate GSK-3β or PP2A activity mainly based on our recent findings. We will also discuss the mechanisms that may underlie tau-induced synaptic toxicity.展开更多
Isoflurane and sevoflurane are both inhalation anesthetics,but in clinical application,sevoflurane has been considered to be less suitable for long-term anesthesia because of its catabolic compounds and potential neph...Isoflurane and sevoflurane are both inhalation anesthetics,but in clinical application,sevoflurane has been considered to be less suitable for long-term anesthesia because of its catabolic compounds and potential nephrotoxicity.Nevertheless,recent studies have shown that these two inhalation anesthetics are similar in hepatorenal toxicity,cost,and long-term anesthetic effect.Moreover,sevoflurane possibly has less cognitive impact on young mice.In this study,C57BL/6 mice aged 8–10 weeks were exposed to 1.2%isoflurane or 2.4%sevoflurane for 6 hours.Cognitive function and memory were examined in young mice using the novel object recognition,contextual fear conditioning,and cued-fear extinction tests.Western blot assay was performed to detect expression levels of D1 dopamine receptor,catechol-O-methyltransferase,phospho-glycogen synthase kinase-3β,and total glycogen synthase kinase-3βin the hippocampus.Our results show that impaired performance was not detected in mice exposed to sevoflurane during the novel object recognition test.Contextual memory impairment in the fear conditioning test was shorter in the sevoflurane group than the isoflurane group.Long-term sevoflurane exposure did not affect memory consolidation,while isoflurane led to memory consolidation and reduced retention.Downregulation of hippocampal D1 dopamine receptors and phosphorylated glycogen synthase kinase-3β/total glycogen synthase kinase-3βand upregulation of catechol-O-methyltransferase may be associated with differing memory performance after exposure to isoflurane or sevoflurane.These results confirm that sevoflurane has less effect on cognitive impairment than isoflurane,which may be related to expression of D1 dopamine receptors and catechol-O-methyltransferase and phosphorylation of glycogen synthase kinase-3βin the hippocampus.This study was approved by the Institutional Animal Care and Use Committee,Nanjing University,China on November 20,2017(approval No.20171102).展开更多
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.
基金supported by grants from the National Natural Science Foundation of China(No.92049107 and No.31929002)the Innovative Research Groups of the National Natural Science Foundation of China(No.81721005)the Academic Frontier Youth Team Project to Xiaochuan Wang from Huazhong University of Science and Technology.
文摘Alzheimer’s disease (AD) is the most prevalent cause of dementia worldwide. Because of the progressive neurodegeneration, individual cognitive and behavioral functions are impaired, affecting the quality of life of millions of people. Although the exact pathogenesis of AD has not been fully elucidated, amyloid plaques, neurofibrillary tangles (NFTs), and sustaining neuroinflammation dominate its characteristics. As one of the major tau kinases leading to hyperphosphorylation and aggregation of tau, glycogen synthase kinase-3β (GSK-3β) has been drawing great attention in various AD studies. Another research focus of AD in recent years is the inflammasome, a multiprotein complex acting as a regulator in immunological reactions to exogenous and endogenous danger signals, of which the Nod-like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome has been studied mostly in AD and proven to play a significant role in AD development by its activation and downstream effects such as caspase-1 maturation and interleukin (IL)-1β release. Studies have shown that the NLRP3 inflammasome is activated in a GSK-3β-dependent way and that inhibition of the NLRP3 inflammasome downregulates GSK-3β, suggesting that these two important proteins are closely related. This article reviews the respective roles of GSK-3β and the NLRP3 inflammasome in AD as well as their relationship and interaction.
文摘Glycogen storage diseases(GSDs),also referred to as glycogenoses,are inherited metabolic disorders of glycogen metabolism caused by deficiency of enzymes or transporters involved in the synthesis or degradation of glycogen leading to aberrant storage and/or utilization.The overall estimated GSD incidence is 1 case per 20000-43000 live births.There are over 20 types of GSD including the subtypes.This heterogeneous group of rare diseases represents inborn errors of carbohydrate metabolism and are classified based on the deficient enzyme and affected tissues.GSDs primarily affect liver or muscle or both as glycogen is particularly abundant in these tissues.However,besides liver and skeletal muscle,depending on the affected enzyme and its expression in various tissues,multiorgan involvement including heart,kidney and/or brain may be seen.Although GSDs share similar clinical features to some extent,there is a wide spectrum of clinical phenotypes.Currently,the goal of treatment is to maintain glucose homeostasis by dietary management and the use of uncooked cornstarch.In addition to nutritional interventions,pharmacological treatment,physical and supportive therapies,enzyme replacement therapy(ERT)and organ transplantation are other treatment approaches for both disease manifestations and longterm complications.The lack of a specific therapy for GSDs has prompted efforts to develop new treatment strategies like gene therapy.Since early diagnosis and aggressive treatment are related to better prognosis,physicians should be aware of these conditions and include GSDs in the differential diagnosis of patients with relevant manifestations including fasting hypoglycemia,hepatomegaly,hypertransaminasemia,hyperlipidemia,exercise intolerance,muscle cramps/pain,rhabdomyolysis,and muscle weakness.Here,we aim to provide a comprehensive review of GSDs.This review provides general characteristics of all types of GSDs with a focus on those with liver involvement.
文摘Previous studies have shown that fibroblast growth factor 13 is downregulated in the brain of both Alzheimer’s disease mouse models and patients,and that it plays a vital role in the learning and memory.However,the underlying mechanisms of fibroblast growth factor 13 in Alzheimer’s disease remain unclear.In this study,we established rat models of Alzheimer’s disease by stereotaxic injection of amyloid-β(Aβ_(1-42))-induced into bilateral hippocampus.We also injected lentivirus containing fibroblast growth factor 13 into bilateral hippocampus to overexpress fibroblast growth factor 13.The expression of fibroblast growth factor 13 was downregulated in the brain of the Alzheimer’s disease model rats.After overexpression of fibroblast growth factor 13,learning and memory abilities of the Alzheimer’s disease model rats were remarkably improved.Fibroblast growth factor 13 overexpression increased brain expression levels of oxidative stress-related markers glutathione,superoxide dismutase,phosphatidylinositol-3-kinase,AKT and glycogen synthase kinase 3β,and anti-apoptotic factor BCL.Furthermore,fibroblast growth factor 13 overexpression decreased the number of apoptotic cells,expression of pro-apoptotic factor BAX,cleaved-caspase 3 and amyloid-βexpression,and levels of tau phosphorylation,malondialdehyde,reactive oxygen species and acetylcholinesterase in the brain of Alzheimer’s disease model rats.The changes were reversed by the phosphatidylinositol-3-kinase inhibitor LY294002.These findings suggest that overexpression of fibroblast growth factor 13 improved neuronal damage in a rat model of Alzheimer’s disease through activation of the phosphatidylinositol-3-kinase/AKT/glycogen synthase kinase 3βsignaling pathway.
基金supported by National Natural Science Foundation of China(32072212)Multi-Year Research Grant of University of Macao(MYRG2018-00169-ICMS)+5 种基金Science and Technology Development Fund of Macao(FDCT)(0098/2020/A)MICINN supporting the Ramón y Cajal grant for M.A.Prieto(RYC-201722891)Jianbo Xiao(RYC2020-030365-I)Xunta de Galicia supporting the Axudas Conecta Peme,the IN852A 2018/58 Neuro Food Project,the program EXCELENCIA-ED431F 2020/12the pre-doctoral grants of P.García-Oliveira(ED481A-2019/295)to Ibero-American Program on Science and Technology(CYTED-AQUA-CIBUS,P317RT0003).
文摘Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.
文摘A constant increase in dive tourism over the past years in the Revillagigedo National Park, Mexico, could result in a stressful scenario for giant mantas (Mobula birostris). The purpose of this study was to determine the degree of oxidative stress in terms of changes in catalase units (CAT) and muscle glycogen concentration in this species during two periods of different tourism intensity in this protected area. A total of 21 muscle biopsies were collected in March (peak tourism) and November (lower tourism), 2019. Stress biomarkers were analysed by commercial kits from the company Cayman Chemical. Oxidative stress (catalase activity) was significantly higher during the period with lower tourism (p = 0.002), compared to the period with more tourism, suggesting the presence of the general adaptation syndrome. In males, there was a significant difference (p = 0.0005) in oxidative stress between periods of different tourism intensity, suggesting that the reproductive season may be a stressor. Morphotypes showed different oxidative stress (p = 0.031);however, the reason is unknown. No statistical differences were detected in glycogen concentrations between the tourism periods (p = 0.123), probably because this polysaccharide is not a proper indicator of chronic stress in giant mantas. Based on these findings, giant mantas may have an adequate response in terms of oxidative stress due to an increase in tourism;however the observed increase in catalase suggests that it is within the tolerance range of these organisms.
文摘Melatonin is a hormone that regulates several physiological processes,including circadian rhythms,sleep,and immune function.Recent studies have suggested that melatonin may also play a role in exercise performance and recovery.Exercise-induced oxidative stress and inflammation can cause tissue damage and impair recovery.In addition to its intrinsic antioxidant properties,melatonin stimulates several antioxidative enzymes and enhances the efficacy of others.Melatonin also binds to a number of important antioxidant molecules,and indirectly contributes to the maintenance of the redox status in cells.The study suggests that melatonin may have a protective effect against the oxidative stress induced by exercise.Melatonin administration has increased muscle and liver glycogen content in both sedentary and exercised rats.The exercised groups are higher muscle and liver glycogen content compared to the sedentary groups.Melatonin treatment had no significant effect on body weight or food intake.The authors conclude that melatonin may play a role in regulating glycogen storage in skeletal muscle and liver,which could have implications for exercise performance and energy metabolism.Lactic acid is a byproduct of anaerobic metabolism that can accumulate in the muscle during exercise and contribute to muscle fatigue.The relationship between melatonin and lactic acid during exercise is not well understood,but some evidence suggests that melatonin may help to reduce lactic acid levels in the muscle.Zinc is necessary for melatonin synthesis.Melatonin,in turn,increases the absorption of zinc in the digestive system.The decrease observed in zinc levels after pinealectomy can cause muscle exhaustion,and thus,can have a negative impact on performance.It can be concluded that there is a significant relation between melatonin,zinc,and physical performance.
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.
基金supported by the National Natural Science Foundation of China (No. 50508011).
文摘Polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE) protocol was employed for revealing microbial community structure and succession in a sequential anaerobic and aerobic reactor performing enhanced biological phosphorus removal (EBPR) during start-up period. High phosphorus removal was achieved after 15 d. On day 30, phosphorus removal efficiency reached to 83.2% and the start-up was finished. DGGE profiles of periodical sludge samples showed that dominant microbial species were 19 OTUs (operational taxonomy units). Unweighted pair-group method using arithmetic averages (UPGMA) clustering analysis revealed that rapid community succession correlated to low phosphorus removal rate and high phosphorus removal efficiency reflected on steady community structure. Sequencing results indicated that determined sequences (12 OTUs) belonged to Proteobacterium, Actinobacteria, Gemmatimonadales and unaffiliate group. Proteobacterium, Tetrasphaera elongate and Gemmatimonas aurantiaca may act important roles in phosphorus removal. With little amount as known glycogen accumulating organisms, Candidatus Competibacter phosphatis still at accumulating-phase had limited effect on microbial community structure. When climax community was obtained, dominant microbes were 14 OTUs. Microbes in a large amount were uncultured bacterium Thauera sp., uncultured y-Proteobacterium and Tetrasphaera elongata.
基金supported by Medical Fund of Zhejiang Province(No.2013KYA207)Shaoxing Science and Technology Bureau Program(No.2011A23013 and No.2013B70079)
文摘Objective:To analyze the expression of phosphatidylinositol 3 kinase(PI3-K),protein kinase B(PKB)and glycogen synthase kinase 3 beta(GSK-3β)in skeletal muscle tissue of gestational diabetes mellitus(GDM).Methods:A total of 90 cases of pregnant women were divided into observation group and control group according to the occurrence of GDM with 45 cases in either,and the expression of PI3-K,PKB,GSK-3βmRNA expression in skeletal muscle tissue was compared between two groups.Results:The total PI3-K p85 protein was significantly higher in the observation group compared with the control group,the activity of PI3-K was lower than that of the latter;The total PKB,GSK-3βprotein in skeletal tissue had no significant difference between two groups,while the serine phosphorylation levels of PKB and GSK-3βwere significantly lower in observation group compared with the control group.Conclusions:The downregulation of PI3-K,PKB and GSK-3βin skeletal tissue of GDM caused by phosphorylation dysfunction of signaling molecules is the reason for insulin resistance and transporter function decline which lead to GDM.
基金Supported by the National Natural Science Foundation of China(No.81371039)Shanghai Natural Science Foundation(No.18ZR1440200)
文摘AIM: To investigate the regulatory mechanism of glycogen synthase kinase 3β(GSK3β) in epithelialmesenchymal transition(EMT) process after proliferative vitreoretinopathy(PVR) induction. METHODS: Experimental PVR was induced by intravitreal injection of retinal pigment epithelium(RPE) cells in the eyes of rabbits. A PI3 K/Akt inhibitor(wortmannin) and a GSK3β inhibitor(Li Cl) were also injected at different time during PVR progress. Electroretinogram(ERG), ocular fundus photographs, and B-scan ultrasonography were used to observe the PVR progress. Western blot test on the extracted retina were performed at 1, 2, 4 wk. The expression of the mesenchymal marker vimentin was determined by immunohistochemistry. Toxicity of wortmannin and Li Cl were evaluated by ERG and Td Tmediated d UTP nick-end labeling(TUNEL) assay. The vitreous was also collected for metabolomic analysis. RESULTS: Experimental PVR could significantly lead to EMT, along with the suppressed expression of GSK3β and the activation of Wnt/β-catenin and PI3 K/Akt pathways. It was verified that upregulating the expression of GSK3β could effectively inhibit EMT process by suppressing Wnt/β-catenin and PI3 K/Akt pathways. CONCLUSION: GSK3β effectively inhibits EMT via the Wnt/β-catenin and PI3 K/Akt pathways. GSK3β may be regarded as a promising target of experimental PVR inhibition.
文摘Diabetes mellitus affects virtually every organ system in the body and the degree of organ involvement depends on the duration and severity of the disease,and other co-morbidities.Gastrointestinal(GI) involvement can present with esophageal dysmotility,gastro-esophageal reflux disease(GERD),gastroparesis,enteropathy,non alcoholic fatty liver disease(NAFLD) and glycogenic hepatopathy.Severity of GERD is inversely related to glycemic control and management is with prokinetics and proton pump inhibitors.Diabetic gastroparesis manifests as early satiety,bloating,vomiting,abdominal pain and erratic glycemic control.Gastric emptying scintigraphy is considered the gold standard test for diagnosis.Management includes dietary modifications,maintaining euglycemia,prokinetics,endoscopic and surgical treatments.Diabetic enteropathy is also common and management involves glycemic control and symptomatic measures.NAFLD is considered a hepatic manifestation of metabolic syndrome and treatment ismainly lifestyle measures,with diabetes and dyslipidemia management when coexistent.Glycogenic hepatopathy is a manifestation of poorly controlled type 1 diabetes and is managed by prompt insulin treatment.Though GI complications of diabetes are relatively common,awareness about its manifestations and treatment options are low among physicians.Optimal management of GI complications is important for appropriate metabolic control of diabetes and improvement in quality of life of the patient.This review is an update on the GI complications of diabetes,their pathophysiology,diagnostic evaluation and management.
文摘As a major microtubule-associated protein, tau plays an important role in promoting microtubule assembly and stabilizing microtubules. In Alzheimer’s disease(AD) and other tauopathies, the abnormally hyperphosphorylated tau proteins are aggregated into paired helical filaments and accumulated in the neurons with the form of neurofibrillary tangles. An imbalanced regulation in protein kinases and protein phosphatases is the direct cause of tau hyperphosphorylation. Among various kinases and phosphatases, glycogen synthase kinase-3β(GSK-3β) and protein phosphatase 2A(PP2A) are the most implicated. Accumulation of the hyperphosphorylated tau induces synaptic toxicity and cognitive impairments. Here, we review the upstream factors or pathways that can regulate GSK-3β or PP2A activity mainly based on our recent findings. We will also discuss the mechanisms that may underlie tau-induced synaptic toxicity.
基金supported by the National Natural Science Foundation of China,No.81730033(to XPG),No.81701371(to TJX)
文摘Isoflurane and sevoflurane are both inhalation anesthetics,but in clinical application,sevoflurane has been considered to be less suitable for long-term anesthesia because of its catabolic compounds and potential nephrotoxicity.Nevertheless,recent studies have shown that these two inhalation anesthetics are similar in hepatorenal toxicity,cost,and long-term anesthetic effect.Moreover,sevoflurane possibly has less cognitive impact on young mice.In this study,C57BL/6 mice aged 8–10 weeks were exposed to 1.2%isoflurane or 2.4%sevoflurane for 6 hours.Cognitive function and memory were examined in young mice using the novel object recognition,contextual fear conditioning,and cued-fear extinction tests.Western blot assay was performed to detect expression levels of D1 dopamine receptor,catechol-O-methyltransferase,phospho-glycogen synthase kinase-3β,and total glycogen synthase kinase-3βin the hippocampus.Our results show that impaired performance was not detected in mice exposed to sevoflurane during the novel object recognition test.Contextual memory impairment in the fear conditioning test was shorter in the sevoflurane group than the isoflurane group.Long-term sevoflurane exposure did not affect memory consolidation,while isoflurane led to memory consolidation and reduced retention.Downregulation of hippocampal D1 dopamine receptors and phosphorylated glycogen synthase kinase-3β/total glycogen synthase kinase-3βand upregulation of catechol-O-methyltransferase may be associated with differing memory performance after exposure to isoflurane or sevoflurane.These results confirm that sevoflurane has less effect on cognitive impairment than isoflurane,which may be related to expression of D1 dopamine receptors and catechol-O-methyltransferase and phosphorylation of glycogen synthase kinase-3βin the hippocampus.This study was approved by the Institutional Animal Care and Use Committee,Nanjing University,China on November 20,2017(approval No.20171102).