BACKGROUND The progression of diabetic kidney disease(DKD)affects the patient’s kidney glomeruli and tubules,whose normal functioning is essential for maintaining normal calcium(Ca)and phosphorus(P)metabolism in the ...BACKGROUND The progression of diabetic kidney disease(DKD)affects the patient’s kidney glomeruli and tubules,whose normal functioning is essential for maintaining normal calcium(Ca)and phosphorus(P)metabolism in the body.The risk of developing osteoporosis(OP)in patients with DKD increases with the aggravation of the disease,including a higher risk of fractures,which not only affects the quality of life of patients but also increases the risk of death.AIM To analyze the risk factors for the development of OP in patients with DKD and their correlation with Ca-P metabolic indices,fibroblast growth factor 23(FGF23),and Klotho.METHODS One hundred and fifty-eight patients with DKD who were admitted into the Wuhu Second People’s Hospital from September 2019 to May 2021 were selected and divided into an OP group(n=103)and a normal bone mass group(n=55)according to their X-ray bone densitometry results.Baseline data and differences in Ca-P biochemical indices,FGF23,and Klotho were compared.The correlation of Ca-P metabolic indices with FGF23 and Klotho was discussed,and the related factors affecting OP in patients with DKD were examined by multivariate logistic regression analysis.RESULTS The OP group had a higher proportion of females,an older age,and a longer diabetes mellitus duration than the normal group(all P<0.05).Patients in the OP group exhibited significantly higher levels of intact parathyroid hormone(iPTH),blood P,Ca-P product(Ca×P),fractional excretion of phosphate(FeP),and FGF23,as well as lower estimated glomerular filtration rate,blood Ca,24-hour urinary phosphate excretion(24-hour UPE),and Klotho levels(all P<0.05).In the OP group,25-(OH)-D3,blood Ca,and 24-hour UPE were negatively correlated with FGF23 and positively correlated with Klotho.In contrast,iPTH,blood Ca,Ca×P,and FeP exhibited a positive correlation with FGF23 and an inverse association with Klotho(all P<0.05).Moreover,25-(OH)-D3,iPTH,blood Ca,FePO4,FGF23,Klotho,age,and female gender were key factors that affected the lumbar and left femoral neck bone mineral density.CONCLUSION The Ca-P metabolism metabolic indexes,FGF23,and Klotho in patients with DKD are closely related to the occurrence and development of OP.展开更多
Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol ...Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol plays a key role in the establishment and maintenance of the central nervous system.The brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and efflux.Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences.Therefore,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases.Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and morbidity.Historical cholesterol levels are associated with the risk of intracerebral hemorrhage.Moreover,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell death.Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage.In this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell death.We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.展开更多
In the article titled“Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism,”published on pages 650-656,Issue 3,Volum...In the article titled“Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism,”published on pages 650-656,Issue 3,Volume 19 of Neural Regeneration Research(Li et al.,2024),there were two errors that needed to be corrected.展开更多
Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/tissues.Pyrroloquinoline quinone is present in the di...Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/tissues.Pyrroloquinoline quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary administration.Pyrroloquinoline quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many studies.In this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian life.Through the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and death.Pyrroloquinoline quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully elucidated.Here,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological contexts.In addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.展开更多
Surgical intervention is currently the primary treatment for hepatolithiasis;how-ever,some patients still experience residual stones and high recurrence rates after surgery.Cholesterol metabolism seems to play an impo...Surgical intervention is currently the primary treatment for hepatolithiasis;how-ever,some patients still experience residual stones and high recurrence rates after surgery.Cholesterol metabolism seems to play an important role in hepatoli-thiasis pathogenesis.A high cholesterol diet is one of the significant reasons for the increasing incidence of hepatolithiasis.Therefore,regular diet and appropriate medical intervention are crucial measures to prevent hepatolithiasis and reduce recurrence rate after surgery.Reducing dietary cholesterol and drugs that increase cholesterol stone solubility are key therapeutic approaches in treating hepato-lithiasis.This article discusses the cholesterol metabolic pathways related to the pathogenesis of hepatolithiasis,as well as food intake and targeted therapeutic drugs.展开更多
Infection is a public health problem and represents a spectrum of disease that can result in sepsis and septic shock.Sepsis is characterized by a dysregulated immune response to infection.Septic shock is the most seve...Infection is a public health problem and represents a spectrum of disease that can result in sepsis and septic shock.Sepsis is characterized by a dysregulated immune response to infection.Septic shock is the most severe form of sepsis which leads to distributive shock and high mortality rates.There have been significant advances in sepsis management mainly focusing on early identification and therapy.However,complicating matters is the lack of reliable diagnostic tools and the poor specificity and sensitivity of existing scoring tools i.e.,systemic inflammatory response syndrome criteria,sequential organ failure assessment(SOFA),or quick SOFA.These limitations have underscored the modest progress in reducing sepsis-related mortality.This review will focus on novel therapeutics such as oxidative stress targets,cytokine modulation,endothelial cell modulation,etc.,that are being conceptualized for the management of sepsis and septic shock.展开更多
Neuron-derived clone 77 (Nur77) is a member of the NR4A subfamily that plays critical roles in apoptosis, survival, proliferation, autophagy, angiogenesis, inflammatory responses, DNA repair, glycolipid metabolism and...Neuron-derived clone 77 (Nur77) is a member of the NR4A subfamily that plays critical roles in apoptosis, survival, proliferation, autophagy, angiogenesis, inflammatory responses, DNA repair, glycolipid metabolism and energy consumption. The deregulation of Nur77 signalling often relates to various serious diseases, including cancer and non-cancer diseases. A systematic review is necessary for the better understanding of Nur77 in clinical treatment. In this article, we comprehensively conclude the lipid regulation function and expression of Nur77, and its role in COPD. Finally, we prospect that development of drugs and clinical biochemical investigations targeting of Nur77 has considerable potential within healthcare.展开更多
Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primar...Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.展开更多
Circadian rhythm is ubiquitous in nature.Circadian clock genes such as Bmal1 and Clock form a multi-level transcription-translation feedback network,and regulate a variety of physiological and pathological processes,i...Circadian rhythm is ubiquitous in nature.Circadian clock genes such as Bmal1 and Clock form a multi-level transcription-translation feedback network,and regulate a variety of physiological and pathological processes,including bone and cartilage metabolism.Deletion of the core clock gene Bmal1 leads to pathological bone alterations,while the phenotypes are not consistent.Studies have shown that multiple signaling pathways are involved in the process of Bmal1 regulating bone and cartilage metabolism,but the exact regulatory mechanisms remain unclear.This paper reviews the signaling pathways by which Bmal1 regulates bone/cartilage metabolism,the upstream regulatory factors that control Bmal1,and the current Bmal1 knockout mouse models for research.We hope to provide new insights for the prevention and treatment of bone/cartilage diseases related to circadian rhythms.展开更多
Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzhei...Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease development.To do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/PS1)transgenic and control mice at 3,6,9,and 12 months of age.Twelve-month-old APP/PS1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/PS1 mice.Notably,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 mice.These findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies.展开更多
Fucoxanthin,a kind of exclusively algae-derived carotenoids,could reduce lipid content and regulate gut microbiota composition in obese mice,showing potential in preventing hyperlipidemia.This study aimed to illustrat...Fucoxanthin,a kind of exclusively algae-derived carotenoids,could reduce lipid content and regulate gut microbiota composition in obese mice,showing potential in preventing hyperlipidemia.This study aimed to illustrate fucoxanthin efficacy in modulating lipid metabolism in serum and liver of high-fat-induced hyperlipidemia mice,as well as investigate the underlying association with gut microbiota changes.Results showed that fucoxanthin significantly reduced body weight gain and body white fat of the mice.In the serum,total triglycerides(TG),total cholesterol(TC)contents were significantly decreased and high-densitylipoprotein cholesterol levels was significantly upregulated.Moreover,fucoxanthin remarkedly prevented lipid accumulation in the liver.Especially,metabolomics results showed that lipids and lipid-like molecules were significantly downregulated compared with the control,indicating the advance of hepatic lipid metabolism.Bile acids profile in the liver was also greatly changed by fucoxanthin.Meanwhile,fucoxanthin remodeled gut microbiota composition and promoted the relative abundance of Desulfovibrio,Blautia and Clostridia genera.Finally,correlation analysis revealed that these gut microbiota changes were closely related with hepatic metabolites/metabolism and serum lipids.Altogether,this study showed great potential of fucoxanthin in improving serum lipids profile,hepatic lipids and bile acids metabolism of hyperlipidemia mice,which was associated with gut microbiota alteration.展开更多
Background:The emerging incidence of pathogenic liver conditions is turning into a major concern for global health.Induction of pyroptosis in hepatocytes instigates cel-lular disintegration,which in turn liberates sub...Background:The emerging incidence of pathogenic liver conditions is turning into a major concern for global health.Induction of pyroptosis in hepatocytes instigates cel-lular disintegration,which in turn liberates substantial quantities of pro-inflammatory intracellular substances,thereby accelerating the advancement of liver fibrosis.Consequently,directing therapeutic efforts towards inhibiting pyroptosis could po-tentially serve as an innovative approach in managing inflammation related chronic hepatic disorders.Methods:GSDMD-NT^(ki/wt)mice and Alb-cre^(ki/wt)mice were generated using CRISPR/Cas9 technology.After crossing the two strains together,we induced conditional cell death by doxycycline to construct a mouse model of liver fibrosis.We analyzed differ-entially expressed genes by RNA sequencing and explored their biological functions.The efficacy of obeticholic acid(OCA)in the treatment of liver fibrosis was assessed.Results:Doxycycline-treated GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice showed severe liver damage,vacuolation of hepatocytes,increased collagen fibers,and accumulation of lipid droplets.The expression of liver fibrosis related genes was greatly increased in the doxycycline-treated mouse liver compared with untreated mouse liver.RNA-sequencing showed that upregulated differentially expressed genes were involved in inflammatory responses,cell activation,and metabolic processes.Treatment with OCA alleviated the liver fibrosis,with reduced ALT and AST levels seen in the GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice.Conclusions:We successfully constructed a novel mouse model for liver fibrosis.This GSDMD-NT-induced fibrosis may be mediated by abnormal lipid metabolism.Our re-sults demonstrated that we successfully constructed a mouse model of liver fibrosis,and GSDMD-NT induced fibrosis by mediating lipid metabolism.展开更多
Pu-erh tea has been shown to reduce gut inflammation in dextran sulfate sodium(DSS)-induced mice.Also,we found abnormal liver cholesterol metabolism in DSS-induced mice.However,it's not clear how Pu-erh tea improv...Pu-erh tea has been shown to reduce gut inflammation in dextran sulfate sodium(DSS)-induced mice.Also,we found abnormal liver cholesterol metabolism in DSS-induced mice.However,it's not clear how Pu-erh tea improves DSS-induced impaired liver cholesterol metabolism.Here,we established the DSS-induced model and clarified that DSS exacerbated gut inflammation accompanied by disorders of liver cholesterol metabolism.Pu-erh tea reshaped gut microbes,limited gut oxidative stress and inflammation(nicotinamide adenine dinucleotide phosphate oxidase 2/reactive oxygen species/myeloid differentiation primary response protein 88/nuclear factor kappa-B,24.97%-52.89%),reduced gut bile acid reabsorption(up-regulation of farnesoid X receptor(FXR)/fibroblast growth factor 15,24.53%-55.91%),and promoted liver bile acid synthesis(up-regulation of peroxisome proliferator-activated receptor-α/cholesterol 7-alpha hydroxylase,34.65%-79.14%),thereby partly restoring liver cholesterol metabolism(regulated FXR/small heterodimer partner/sterol-regulatory element binding proteins,53.19%-95.40%).Altered bile acid metabolic profiles(increased chenodeoxycholic acid,ursodeoxycholic acid,lithocholic acid,etc.)may also improve liver cholesterol metabolism by altering gut and liver inflammation.Thus,gut microbial reshaping and altered bile acid metabolism may be key targets of Pu-erh tea for improving DSS-induced liver cholesterol metabolism disorders via the gut-gut microbe-bile acid-liver axis.展开更多
Calycosin,Astragali Radix most prominent ingredient,has drawn more attention as a result of its ability to treat atherosclerosis(AS).However,the mechanism of action has not been fully elucidated.We investigated the ef...Calycosin,Astragali Radix most prominent ingredient,has drawn more attention as a result of its ability to treat atherosclerosis(AS).However,the mechanism of action has not been fully elucidated.We investigated the effects of calycosin on bile acid(BA)metabolism and gut microbiome in ApoE^(-/-)mice fed a high-fat diet(HFD).The data showed that the aorta of ApoE^(-/-)mice treated with HFD showed significant atheromatous plaque formation and lipid accumulation,and the levels of total cholesterol(TC),triglycerides(TG)and low-density lipoprotein cholesterol(LDL-C)were significantly increased,while the levels of high-density lipoprotein cholesterol(HDL-C)were significantly decreased.Calycosin can substantially regulate lipid levels,thereby alleviating liver lipid deposition induced by atherosclerosis.In addition,16S rRNA sequencing showed that calycosin treatment has reshaped the gut microbiota disturbed by HFD,in particular,increasing the ratio of Bacteroidetes/Firmicutes,and improving the relative abundance of Bilophila,Desulfovibrio,Bacteroides,Lactobacillus,etc.Meanwhile,targeted metabolomics analysis showed that calycosin treatment significantly modulated glycodeoxycholic acid(CDCA),taurocholic acids(TCA),lithocholic acid(LCA),deoxycholic acid(DCA),taurodeoxycholic acid(TDCA)and BA pool composition,which were associated with atherosclerotic plaque areas.In addition,calycosin treatment also down-regulated farnesoid X receptor(FXR)protein levels and up-regulated cytochrome P450 family 7 subfamily A member 1(CYP7A1)protein levels in the hepatic.At the same time,calycosin inhibits the ileum FXR/TGR5 signaling pathway,inhibits BA reabsorption,promotes BA excretion,and reduces hepatic cholesterol accumulation by enterohepatic circulation.In addition,we found that calycosin significantly promoted the expression of hepatic ATP-binding cassette transporter A1(ABCA1)and ABCG1 to mediate cholesterol efflux.Meanwhile,calycosin regulates gut microbiota,and Bacteroides,Alistipes,Desulfovibrio,Lactobacillus,Bilophila and Odoribacter are closely related to specific BAs.This enables us to further understand the relationship between BA metabolism and gut microbiota.Calycosin may reduce high-fat diet-induced hepatic cholesterol accumulation in ApoE^(-/-)mice through gut microbiota and BA metabolism,and play a role in treating AS.Finally,we confirmed that calycosin-altered gut microbiota by fecal microbiota transplantation was sufficient to alleviate atherosclerosis.Taken together,our findings provide important insights into the pharmacological mechanisms underlying the efficacy of calycosin on atherosclerosis.展开更多
Objective:Erianin has potential anticancer activities,especially against lung cancer.The specific mechanisms underlying the anticancer effects,including the molecular targets and signaling pathways in lung cancer,rema...Objective:Erianin has potential anticancer activities,especially against lung cancer.The specific mechanisms underlying the anticancer effects,including the molecular targets and signaling pathways in lung cancer,remain poorly understood and necessitate further investigation.Methods:Lung cancer cell viability was evaluated using the CCK-8 assay.Flow cytometry was used to examine the effects of erianin on apoptosis and cell cycle progression.m RNA sequencing and metabolomics analysis were utilized to explore erianin-induced biological changes.Potential targets were identified and validated through molecular docking and Western blot analysis.The roles of mammalian target of rapamycin(m TOR)and carbamoyl-phosphate synthetase/aspartate transcarbamylase/dihydroorotase(CAD)in erianin-induced growth inhibition were studied using gene overexpression/knockdown techniques with uridine and aspartate supplementation confirming pyrimidine metabolism involvement.Additionally,lung cancer-bearing nude mouse models were established to evaluate the anti-lung cancer effects of erianin in vivo.Results:Erianin significantly inhibits the proliferation of lung cancer cells,induces apoptosis,and causes G2/M phase cell cycle arrest.Integrative analysis of m RNA sequencing and metabolomics data demonstrated that erianin disrupts pyrimidine metabolism in lung cancer cells.Notably,uridine supplementation mitigated the inhibitory effects of erianin,establishing a connection between pyrimidine metabolism and anticancer activity.Network pharmacology analyses identified m TOR as a key target of erianin.Erianin inhibited m TOR phosphorylation,thereby blocking downstream effectors(S6K and CAD),which are essential regulators of pyrimidine metabolism.Conclusions:Erianin is a promising therapeutic candidate for lung cancer.Erianin likely inhibits lung cancer cell growth by disrupting pyrimidine metabolism by suppressing m TOR activation.展开更多
Background The objective of this study was to evaluate the effects of dietary fatty acids(FA)saturation and lysophospholipids supplementation on growth,meat quality,oxidative stability,FA profiles,and lipid metabolism...Background The objective of this study was to evaluate the effects of dietary fatty acids(FA)saturation and lysophospholipids supplementation on growth,meat quality,oxidative stability,FA profiles,and lipid metabolism of finishing beef bulls.Thirty-two Angus bulls(initial body weight:623±22.6 kg;21±0.5 months of age)were used.The experiment was a completely randomized block design with a 2×2 factorial arrangement of treatments:2 diets with FA of different degree of unsaturation[high saturated FA diet(HSFA)vs.high unsaturated FA diet(HUFA)]combined with(0.075%,dry matter basis)and without lysophospholipids supplementation.The bulls were fed a high-concentrate diet(forage to concentrate,15:85)for 104 d including a 14-d adaptation period and a 90-d data and sample collection period.Results No interactions were observed between dietary FA and lysophospholipids supplementation for growth and meat quality parameters.A greater dietary ratio of unsaturated FA(UFA)to saturated FA(SFA)from 1:2 to 1:1 led to lower DM intake and backfat thickness,but did not affect growth performance and other carcass traits.Compared with HSFA,bulls fed HUFA had greater shear force in Longissimus thoracis(LT)muscle,but had lower intramuscular fat(IMF)content and SOD content in LT muscle.Compared with HUFA,feeding the HSFA diet up-regulated expression of ACC,FAS,PPARγ,and SCD1,but down-regulated expression of CPT1B.Compared with feeding HSFA,the HUFA diet led to greater concentrations of c9-C18:1 and other monounsaturated FA in LT muscle.Feeding HUFA also led to lower plasma concentrations of cholesterol,but there were no interactions between FA and lysophospholipids detected.Feeding lysophospholipids improved growth and feed conversion ratio and altered meat quality by increasing muscle pH_(24h),redness values(24 h),IMF content,and concentrations of C18:3,C20:5 and total polyunsaturated fatty acids.Furthermore,lysophospholipids supplementation led to lower malondialdehyde content and up-regulated the expression of ACC,FAS,and LPL in LT muscle.Conclusions Results indicated that supplementing a high-concentrate diet with lysophospholipids to beef bulls can enhance growth rate,feed efficiency,meat quality,and beneficial FA.Increasing the dietary ratio of UFA to SFA reduced DM intake and backfat thickness without compromising growth,suggesting potential improvements in feed efficiency.展开更多
Sea cucumber derived sulfated sterols significantly ameliorated insulin resistance and decreased lipid accumulation compared to plant sterols.Interestingly,our recent study found that intervention with sea cucumber su...Sea cucumber derived sulfated sterols significantly ameliorated insulin resistance and decreased lipid accumulation compared to plant sterols.Interestingly,our recent study found that intervention with sea cucumber sulfated sterols could significantly increase blood glucose levels of healthy mice in the presence of glucose,while cholesterol sulfate,as one of sulfated sterols,did not have the same effect.However,the exact mechanism of sulfated sterols on glucose metabolism is still unknown.In the present study,we investigated the potential mechanism by which sulfated sterols influenced blood glucose homeostasis in healthy mice.Results showed that intervention with sea cucumber sulfated sterols did not affect the levels of hormones related to glucose metabolism,while led to a significant decrease in the synthesis of liver glycogen and muscle glycogen.Besides,the expression of proteins associated with the promotion of gluconeogenesis dramatically increased in the mice intervened with sea cucumber sulfated sterols.These findings suggested that sea cucumber sulfated sterols might change blood glucose metabolism in healthy mice by reducing glycogenesis and promoting gluconeogenesis.展开更多
Background Dysregulation of lipid metabolism and its consequences on growth performance in young ruminants have attracted attention,especially in the context of alternative feeding strategies.This study aims to elucid...Background Dysregulation of lipid metabolism and its consequences on growth performance in young ruminants have attracted attention,especially in the context of alternative feeding strategies.This study aims to elucidate the effects of milk replacer(MR)feeding on growth,lipid metabolism,colonic epithelial gene expression,colonic microbiota composition and systemic metabolism in goat kids compared to breast milk(BM)feeding,addressing a critical knowledge gap in early life nutrition.Methods Ten female goat kids were divided into 2 groups:those fed breast milk(BM group)and those fed a milk replacer(MR group).Over a period of 28 d,body weight was monitored and blood and tissue samples were collected for biochemical,transcriptomic and metabolomic analyses.Profiling of the colonial microbiota was performed using 16S rRNA gene sequencing.Intestinal microbiota transplantation(IMT)experiments in gnotobiotic mice were per-formed to validate causality.Results MR-fed pups exhibited reduced daily body-weight gain due to impaired lipid metabolism as evidenced by lower serum and liver total cholesterol(TC)and non-esterified fatty acid(NEFA)concentrations.Transcriptomic analysis of the colonic epithelium revealed upregulated genes involved in negative regulation of lipid metabolism,concomitant with microbiota shifts characterized by a decrease in Firmicutes and an increase in Actinobacteria.Specifically,genera such as Bifidobacterium and Prevotella were enriched in the MR group,while Clostridium and Fae-calibacterium were depleted.Metabolomics analyses confirmed alterations in bile acid and fatty acid metabolic path-ways.IMT experiments in mice recapitulated the metabolic phenotype observed in MR-fed goats,confirming the role of the microbiota in modulating host lipid metabolism.Conclusions Milk replacer feeding in goat kids disrupts lipid metabolism and gut microbiota dynamics,result-ing in reduced growth rates and metabolic alterations.These findings highlight the importance of early nutritional intervention on metabolic programming and suggest that modulation of the gut microbiota may be a target for improving growth and metabolic health in ruminants.This study contributes to the understanding of nutritional management strategies in livestock and their impact on animal health and productivity.展开更多
The content of soluble sugars is a vital parameter that indicates the quality of fleshy fruits such as apple(Malus domestica Borkh.).Studying the patterns of accumulation of soluble sugars and regulatory mechanisms as...The content of soluble sugars is a vital parameter that indicates the quality of fleshy fruits such as apple(Malus domestica Borkh.).Studying the patterns of accumulation of soluble sugars and regulatory mechanisms associated with fruit development is crucial for breeding improved fruit varieties.Here,we report that MdCIbHLH1,a low temperature-induced b HLH transcription factor,inhibits the accumulation of soluble sugars by regulating sugar-metabolizing enzyme activities,photosynthetic performance,and the expression of sugar-related genes in developing apple fruits.MdCIbHLH1 inhibits MdFBP and MdPEPCK expression,thus blocking the conversion of acids to sugars in apple fruits.We also discovered that MdCIbHLH1 decreases the photosynthetic rate and carbohydrate accumulation in apple leaves.Our results suggest that soluble sugar accumulation in apple fruits is influenced by multiple factors,including metabolic status,photosynthesis,and carbohydrate allocation.MdCIbHLH1 is critically involved in controlling the accumulation of soluble sugars by coordinating carbohydrate synthesis and allocation,thus influencing sugar transport and its metabolism during the development of apple fruits.展开更多
Constructed wetlands(CWs)are a promising method to treat effluent from wastewater treatment plants(WWTPs).However,low carbon/nitrogen(C/N)ratios of the influent inhibit denitrification in CWs,resulting in poor nitroge...Constructed wetlands(CWs)are a promising method to treat effluent from wastewater treatment plants(WWTPs).However,low carbon/nitrogen(C/N)ratios of the influent inhibit denitrification in CWs,resulting in poor nitrogen removal efficiency.Herein,we compared traditional(control),biochar(BC),and b-cyclodextrin-functionalized biochar(BC@b-CD)CW systems to investigate nitrogen removal from influent with low C/N ratios,and the mechanisms that enhance this process.The highest nitrogen removal rates were observed in the BC@b-CD group,with rates 45.89%and 42.48%higher than those of the control,accompanied by a 70.57%and 85.45%decrease in nitrous oxide release,when the C/N ratio decreased from 4 to 2,respectively.Metagenomic and enzymatic analyses indicated that BC@b-CD enhances nitrogen removal by coordinately promoting carbon metabolism and increasing denitrification enzyme activities,without affecting microbial species diversity in CWs.Structural equation modeling confirmed that the foremost advantages of BC@b-CD were effective electron generation and transportation resulting from increased activities of nicotinamide adenine dinucleotide(NADH)dehydrogenase and the electron transfer system(ETS),thereby strategically reallocating more carbon metabolic flow to support denitrification.Our results show that the application of BC@b-CD in CWs to optimize the reallocation of electrons from carbon metabolism is a feasible strategy to enhance denitrification under low C/N conditions.展开更多
文摘BACKGROUND The progression of diabetic kidney disease(DKD)affects the patient’s kidney glomeruli and tubules,whose normal functioning is essential for maintaining normal calcium(Ca)and phosphorus(P)metabolism in the body.The risk of developing osteoporosis(OP)in patients with DKD increases with the aggravation of the disease,including a higher risk of fractures,which not only affects the quality of life of patients but also increases the risk of death.AIM To analyze the risk factors for the development of OP in patients with DKD and their correlation with Ca-P metabolic indices,fibroblast growth factor 23(FGF23),and Klotho.METHODS One hundred and fifty-eight patients with DKD who were admitted into the Wuhu Second People’s Hospital from September 2019 to May 2021 were selected and divided into an OP group(n=103)and a normal bone mass group(n=55)according to their X-ray bone densitometry results.Baseline data and differences in Ca-P biochemical indices,FGF23,and Klotho were compared.The correlation of Ca-P metabolic indices with FGF23 and Klotho was discussed,and the related factors affecting OP in patients with DKD were examined by multivariate logistic regression analysis.RESULTS The OP group had a higher proportion of females,an older age,and a longer diabetes mellitus duration than the normal group(all P<0.05).Patients in the OP group exhibited significantly higher levels of intact parathyroid hormone(iPTH),blood P,Ca-P product(Ca×P),fractional excretion of phosphate(FeP),and FGF23,as well as lower estimated glomerular filtration rate,blood Ca,24-hour urinary phosphate excretion(24-hour UPE),and Klotho levels(all P<0.05).In the OP group,25-(OH)-D3,blood Ca,and 24-hour UPE were negatively correlated with FGF23 and positively correlated with Klotho.In contrast,iPTH,blood Ca,Ca×P,and FeP exhibited a positive correlation with FGF23 and an inverse association with Klotho(all P<0.05).Moreover,25-(OH)-D3,iPTH,blood Ca,FePO4,FGF23,Klotho,age,and female gender were key factors that affected the lumbar and left femoral neck bone mineral density.CONCLUSION The Ca-P metabolism metabolic indexes,FGF23,and Klotho in patients with DKD are closely related to the occurrence and development of OP.
基金supported by the National Natural Science Foundation of China,No.82072110Suzhou Municipal Science and Technology Bureau,No.SKJY2021046+1 种基金Shanghai Key Lab of Forensic Medicine&Key Lab of Forensic Science,Ministry of Justice,China(Academy of Forensic Science),No.KF202201a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)(all to TW).
文摘Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol plays a key role in the establishment and maintenance of the central nervous system.The brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and efflux.Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences.Therefore,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases.Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and morbidity.Historical cholesterol levels are associated with the risk of intracerebral hemorrhage.Moreover,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell death.Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage.In this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell death.We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.
文摘In the article titled“Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism,”published on pages 650-656,Issue 3,Volume 19 of Neural Regeneration Research(Li et al.,2024),there were two errors that needed to be corrected.
基金supported by Karolinska Institutet in the form of a Board of Research Faculty Funded Career Positionby St.Erik Eye Hospital philanthropic donationsVetenskapsrådet 2022-00799.
文摘Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/tissues.Pyrroloquinoline quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary administration.Pyrroloquinoline quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many studies.In this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian life.Through the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and death.Pyrroloquinoline quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully elucidated.Here,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological contexts.In addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.
基金Supported by Hebei Natural Science Foundation,No.H2022206539Hebei Provincial Government Funded Clinical Talents Training Project,No.ZF2023143.
文摘Surgical intervention is currently the primary treatment for hepatolithiasis;how-ever,some patients still experience residual stones and high recurrence rates after surgery.Cholesterol metabolism seems to play an important role in hepatoli-thiasis pathogenesis.A high cholesterol diet is one of the significant reasons for the increasing incidence of hepatolithiasis.Therefore,regular diet and appropriate medical intervention are crucial measures to prevent hepatolithiasis and reduce recurrence rate after surgery.Reducing dietary cholesterol and drugs that increase cholesterol stone solubility are key therapeutic approaches in treating hepato-lithiasis.This article discusses the cholesterol metabolic pathways related to the pathogenesis of hepatolithiasis,as well as food intake and targeted therapeutic drugs.
文摘Infection is a public health problem and represents a spectrum of disease that can result in sepsis and septic shock.Sepsis is characterized by a dysregulated immune response to infection.Septic shock is the most severe form of sepsis which leads to distributive shock and high mortality rates.There have been significant advances in sepsis management mainly focusing on early identification and therapy.However,complicating matters is the lack of reliable diagnostic tools and the poor specificity and sensitivity of existing scoring tools i.e.,systemic inflammatory response syndrome criteria,sequential organ failure assessment(SOFA),or quick SOFA.These limitations have underscored the modest progress in reducing sepsis-related mortality.This review will focus on novel therapeutics such as oxidative stress targets,cytokine modulation,endothelial cell modulation,etc.,that are being conceptualized for the management of sepsis and septic shock.
文摘Neuron-derived clone 77 (Nur77) is a member of the NR4A subfamily that plays critical roles in apoptosis, survival, proliferation, autophagy, angiogenesis, inflammatory responses, DNA repair, glycolipid metabolism and energy consumption. The deregulation of Nur77 signalling often relates to various serious diseases, including cancer and non-cancer diseases. A systematic review is necessary for the better understanding of Nur77 in clinical treatment. In this article, we comprehensively conclude the lipid regulation function and expression of Nur77, and its role in COPD. Finally, we prospect that development of drugs and clinical biochemical investigations targeting of Nur77 has considerable potential within healthcare.
基金financially supported by the Science and Technology Innovation Program of Hunan Province,No.2022RC1220(to WP)China Postdoctoral Science Foundation,No.2022M711733(to ZZ)+2 种基金the National Natural Science Foundation of China,No.82160920(to ZZ)Hebei Postdoctoral Scientific Research Project,No.B2022003040(to ZZ)Hunan Flagship Department of Integrated Traditional Chinese and Western Medicine(to WP)。
文摘Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.
基金National Natural Science Foundation of China(82171003 and 82171002)Research and Develop Program of West China Hospital of Stomatology Sichuan University(NO.LCYJ-2022-YY-1)。
文摘Circadian rhythm is ubiquitous in nature.Circadian clock genes such as Bmal1 and Clock form a multi-level transcription-translation feedback network,and regulate a variety of physiological and pathological processes,including bone and cartilage metabolism.Deletion of the core clock gene Bmal1 leads to pathological bone alterations,while the phenotypes are not consistent.Studies have shown that multiple signaling pathways are involved in the process of Bmal1 regulating bone and cartilage metabolism,but the exact regulatory mechanisms remain unclear.This paper reviews the signaling pathways by which Bmal1 regulates bone/cartilage metabolism,the upstream regulatory factors that control Bmal1,and the current Bmal1 knockout mouse models for research.We hope to provide new insights for the prevention and treatment of bone/cartilage diseases related to circadian rhythms.
基金financially supported by the National Natural Science Foundation of China,No.823 74552 (to WP)the Science and Technology Innovation Program of Hunan Province,No.2022RC1220 (to WP)+1 种基金the Natural Science Foundation of Hunan Province of China,Nos.2020JJ4803 (to WP),2022JJ40723 (to MY)the Scientific Research Launch Project for New Employees of the Second Xiangya Hospital of Central South University (to MY)
文摘Alzheimer’s disease not only affects the brain,but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota.The aim of this study was to investigate systemic changes that occur in Alzheimer’s disease,in particular the association between changes in peripheral organ metabolism,changes in gut microbial composition,and Alzheimer’s disease development.To do this,we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1(APP/PS1)transgenic and control mice at 3,6,9,and 12 months of age.Twelve-month-old APP/PS1 mice exhibited cognitive impairment,Alzheimer’s disease-related brain changes,distinctive metabolic disturbances in peripheral organs and fecal samples(as detected by untargeted metabolomics sequencing),and substantial changes in gut microbial composition compared with younger APP/PS1 mice.Notably,a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 mice.These findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development,indicating potential new directions for therapeutic strategies.
基金funded by the National Natural Science Foundation of China(31901624)the Key-Area Research and Development Program of Guangdong Province(2018B020206001)+2 种基金Guangdong Province Zhujiang Talent Program(2019ZT08H476)Shenzhen Science and Technology Program(KQTD20180412181334790)the Innovation Team Project of Universities in Guangdong Province(2020KCXTD023)。
文摘Fucoxanthin,a kind of exclusively algae-derived carotenoids,could reduce lipid content and regulate gut microbiota composition in obese mice,showing potential in preventing hyperlipidemia.This study aimed to illustrate fucoxanthin efficacy in modulating lipid metabolism in serum and liver of high-fat-induced hyperlipidemia mice,as well as investigate the underlying association with gut microbiota changes.Results showed that fucoxanthin significantly reduced body weight gain and body white fat of the mice.In the serum,total triglycerides(TG),total cholesterol(TC)contents were significantly decreased and high-densitylipoprotein cholesterol levels was significantly upregulated.Moreover,fucoxanthin remarkedly prevented lipid accumulation in the liver.Especially,metabolomics results showed that lipids and lipid-like molecules were significantly downregulated compared with the control,indicating the advance of hepatic lipid metabolism.Bile acids profile in the liver was also greatly changed by fucoxanthin.Meanwhile,fucoxanthin remodeled gut microbiota composition and promoted the relative abundance of Desulfovibrio,Blautia and Clostridia genera.Finally,correlation analysis revealed that these gut microbiota changes were closely related with hepatic metabolites/metabolism and serum lipids.Altogether,this study showed great potential of fucoxanthin in improving serum lipids profile,hepatic lipids and bile acids metabolism of hyperlipidemia mice,which was associated with gut microbiota alteration.
基金National Natural Science Foundation of China,Grant/Award Number:82174292Key Project of Jiangsu Provincial Administration of Traditional Chinese Medicine,Grant/Award Number:ZD202312+2 种基金Natural Science Foundation of Laboratory Medicine School in Chengdu Medical College,Grant/Award Number:JYZK202203Sichuan Province Science and Technology Program,Grant/Award Number:2024NSFSC0577 and 2021YFG0316Technology innovation group project of Foshan 2019,Grant/Award Number:FS0AA-KJ919-4402-0027。
文摘Background:The emerging incidence of pathogenic liver conditions is turning into a major concern for global health.Induction of pyroptosis in hepatocytes instigates cel-lular disintegration,which in turn liberates substantial quantities of pro-inflammatory intracellular substances,thereby accelerating the advancement of liver fibrosis.Consequently,directing therapeutic efforts towards inhibiting pyroptosis could po-tentially serve as an innovative approach in managing inflammation related chronic hepatic disorders.Methods:GSDMD-NT^(ki/wt)mice and Alb-cre^(ki/wt)mice were generated using CRISPR/Cas9 technology.After crossing the two strains together,we induced conditional cell death by doxycycline to construct a mouse model of liver fibrosis.We analyzed differ-entially expressed genes by RNA sequencing and explored their biological functions.The efficacy of obeticholic acid(OCA)in the treatment of liver fibrosis was assessed.Results:Doxycycline-treated GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice showed severe liver damage,vacuolation of hepatocytes,increased collagen fibers,and accumulation of lipid droplets.The expression of liver fibrosis related genes was greatly increased in the doxycycline-treated mouse liver compared with untreated mouse liver.RNA-sequencing showed that upregulated differentially expressed genes were involved in inflammatory responses,cell activation,and metabolic processes.Treatment with OCA alleviated the liver fibrosis,with reduced ALT and AST levels seen in the GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice.Conclusions:We successfully constructed a novel mouse model for liver fibrosis.This GSDMD-NT-induced fibrosis may be mediated by abnormal lipid metabolism.Our re-sults demonstrated that we successfully constructed a mouse model of liver fibrosis,and GSDMD-NT induced fibrosis by mediating lipid metabolism.
基金supported by the National Natural Science Foundation of China funded project(32172627)Chongqing Modern Tea Technology System for Efficient Agriculture in Mountainous Areas 2022[8]the Germplasm Creation Research Program of Southwest University。
文摘Pu-erh tea has been shown to reduce gut inflammation in dextran sulfate sodium(DSS)-induced mice.Also,we found abnormal liver cholesterol metabolism in DSS-induced mice.However,it's not clear how Pu-erh tea improves DSS-induced impaired liver cholesterol metabolism.Here,we established the DSS-induced model and clarified that DSS exacerbated gut inflammation accompanied by disorders of liver cholesterol metabolism.Pu-erh tea reshaped gut microbes,limited gut oxidative stress and inflammation(nicotinamide adenine dinucleotide phosphate oxidase 2/reactive oxygen species/myeloid differentiation primary response protein 88/nuclear factor kappa-B,24.97%-52.89%),reduced gut bile acid reabsorption(up-regulation of farnesoid X receptor(FXR)/fibroblast growth factor 15,24.53%-55.91%),and promoted liver bile acid synthesis(up-regulation of peroxisome proliferator-activated receptor-α/cholesterol 7-alpha hydroxylase,34.65%-79.14%),thereby partly restoring liver cholesterol metabolism(regulated FXR/small heterodimer partner/sterol-regulatory element binding proteins,53.19%-95.40%).Altered bile acid metabolic profiles(increased chenodeoxycholic acid,ursodeoxycholic acid,lithocholic acid,etc.)may also improve liver cholesterol metabolism by altering gut and liver inflammation.Thus,gut microbial reshaping and altered bile acid metabolism may be key targets of Pu-erh tea for improving DSS-induced liver cholesterol metabolism disorders via the gut-gut microbe-bile acid-liver axis.
基金supported by Heilongjiang Postdoctoral Program(ZHY2022-114)General program of Heilongjiang Province(LBHZ22251)Young Elite Scientists Sponsorship Program(2022-QNRC1-27)。
文摘Calycosin,Astragali Radix most prominent ingredient,has drawn more attention as a result of its ability to treat atherosclerosis(AS).However,the mechanism of action has not been fully elucidated.We investigated the effects of calycosin on bile acid(BA)metabolism and gut microbiome in ApoE^(-/-)mice fed a high-fat diet(HFD).The data showed that the aorta of ApoE^(-/-)mice treated with HFD showed significant atheromatous plaque formation and lipid accumulation,and the levels of total cholesterol(TC),triglycerides(TG)and low-density lipoprotein cholesterol(LDL-C)were significantly increased,while the levels of high-density lipoprotein cholesterol(HDL-C)were significantly decreased.Calycosin can substantially regulate lipid levels,thereby alleviating liver lipid deposition induced by atherosclerosis.In addition,16S rRNA sequencing showed that calycosin treatment has reshaped the gut microbiota disturbed by HFD,in particular,increasing the ratio of Bacteroidetes/Firmicutes,and improving the relative abundance of Bilophila,Desulfovibrio,Bacteroides,Lactobacillus,etc.Meanwhile,targeted metabolomics analysis showed that calycosin treatment significantly modulated glycodeoxycholic acid(CDCA),taurocholic acids(TCA),lithocholic acid(LCA),deoxycholic acid(DCA),taurodeoxycholic acid(TDCA)and BA pool composition,which were associated with atherosclerotic plaque areas.In addition,calycosin treatment also down-regulated farnesoid X receptor(FXR)protein levels and up-regulated cytochrome P450 family 7 subfamily A member 1(CYP7A1)protein levels in the hepatic.At the same time,calycosin inhibits the ileum FXR/TGR5 signaling pathway,inhibits BA reabsorption,promotes BA excretion,and reduces hepatic cholesterol accumulation by enterohepatic circulation.In addition,we found that calycosin significantly promoted the expression of hepatic ATP-binding cassette transporter A1(ABCA1)and ABCG1 to mediate cholesterol efflux.Meanwhile,calycosin regulates gut microbiota,and Bacteroides,Alistipes,Desulfovibrio,Lactobacillus,Bilophila and Odoribacter are closely related to specific BAs.This enables us to further understand the relationship between BA metabolism and gut microbiota.Calycosin may reduce high-fat diet-induced hepatic cholesterol accumulation in ApoE^(-/-)mice through gut microbiota and BA metabolism,and play a role in treating AS.Finally,we confirmed that calycosin-altered gut microbiota by fecal microbiota transplantation was sufficient to alleviate atherosclerosis.Taken together,our findings provide important insights into the pharmacological mechanisms underlying the efficacy of calycosin on atherosclerosis.
基金supported by the National Natural Science Foundation of China(82104207)Natural Science Foundation of Zhejiang Province(LQ22H280001)。
文摘Objective:Erianin has potential anticancer activities,especially against lung cancer.The specific mechanisms underlying the anticancer effects,including the molecular targets and signaling pathways in lung cancer,remain poorly understood and necessitate further investigation.Methods:Lung cancer cell viability was evaluated using the CCK-8 assay.Flow cytometry was used to examine the effects of erianin on apoptosis and cell cycle progression.m RNA sequencing and metabolomics analysis were utilized to explore erianin-induced biological changes.Potential targets were identified and validated through molecular docking and Western blot analysis.The roles of mammalian target of rapamycin(m TOR)and carbamoyl-phosphate synthetase/aspartate transcarbamylase/dihydroorotase(CAD)in erianin-induced growth inhibition were studied using gene overexpression/knockdown techniques with uridine and aspartate supplementation confirming pyrimidine metabolism involvement.Additionally,lung cancer-bearing nude mouse models were established to evaluate the anti-lung cancer effects of erianin in vivo.Results:Erianin significantly inhibits the proliferation of lung cancer cells,induces apoptosis,and causes G2/M phase cell cycle arrest.Integrative analysis of m RNA sequencing and metabolomics data demonstrated that erianin disrupts pyrimidine metabolism in lung cancer cells.Notably,uridine supplementation mitigated the inhibitory effects of erianin,establishing a connection between pyrimidine metabolism and anticancer activity.Network pharmacology analyses identified m TOR as a key target of erianin.Erianin inhibited m TOR phosphorylation,thereby blocking downstream effectors(S6K and CAD),which are essential regulators of pyrimidine metabolism.Conclusions:Erianin is a promising therapeutic candidate for lung cancer.Erianin likely inhibits lung cancer cell growth by disrupting pyrimidine metabolism by suppressing m TOR activation.
基金financially supported by the National Key Research and Development Program of China(2022YFD1301105)the earmarked fund for CARS(CARS-36)。
文摘Background The objective of this study was to evaluate the effects of dietary fatty acids(FA)saturation and lysophospholipids supplementation on growth,meat quality,oxidative stability,FA profiles,and lipid metabolism of finishing beef bulls.Thirty-two Angus bulls(initial body weight:623±22.6 kg;21±0.5 months of age)were used.The experiment was a completely randomized block design with a 2×2 factorial arrangement of treatments:2 diets with FA of different degree of unsaturation[high saturated FA diet(HSFA)vs.high unsaturated FA diet(HUFA)]combined with(0.075%,dry matter basis)and without lysophospholipids supplementation.The bulls were fed a high-concentrate diet(forage to concentrate,15:85)for 104 d including a 14-d adaptation period and a 90-d data and sample collection period.Results No interactions were observed between dietary FA and lysophospholipids supplementation for growth and meat quality parameters.A greater dietary ratio of unsaturated FA(UFA)to saturated FA(SFA)from 1:2 to 1:1 led to lower DM intake and backfat thickness,but did not affect growth performance and other carcass traits.Compared with HSFA,bulls fed HUFA had greater shear force in Longissimus thoracis(LT)muscle,but had lower intramuscular fat(IMF)content and SOD content in LT muscle.Compared with HUFA,feeding the HSFA diet up-regulated expression of ACC,FAS,PPARγ,and SCD1,but down-regulated expression of CPT1B.Compared with feeding HSFA,the HUFA diet led to greater concentrations of c9-C18:1 and other monounsaturated FA in LT muscle.Feeding HUFA also led to lower plasma concentrations of cholesterol,but there were no interactions between FA and lysophospholipids detected.Feeding lysophospholipids improved growth and feed conversion ratio and altered meat quality by increasing muscle pH_(24h),redness values(24 h),IMF content,and concentrations of C18:3,C20:5 and total polyunsaturated fatty acids.Furthermore,lysophospholipids supplementation led to lower malondialdehyde content and up-regulated the expression of ACC,FAS,and LPL in LT muscle.Conclusions Results indicated that supplementing a high-concentrate diet with lysophospholipids to beef bulls can enhance growth rate,feed efficiency,meat quality,and beneficial FA.Increasing the dietary ratio of UFA to SFA reduced DM intake and backfat thickness without compromising growth,suggesting potential improvements in feed efficiency.
基金supported by National Natural Science Foundation of China(32072145)。
文摘Sea cucumber derived sulfated sterols significantly ameliorated insulin resistance and decreased lipid accumulation compared to plant sterols.Interestingly,our recent study found that intervention with sea cucumber sulfated sterols could significantly increase blood glucose levels of healthy mice in the presence of glucose,while cholesterol sulfate,as one of sulfated sterols,did not have the same effect.However,the exact mechanism of sulfated sterols on glucose metabolism is still unknown.In the present study,we investigated the potential mechanism by which sulfated sterols influenced blood glucose homeostasis in healthy mice.Results showed that intervention with sea cucumber sulfated sterols did not affect the levels of hormones related to glucose metabolism,while led to a significant decrease in the synthesis of liver glycogen and muscle glycogen.Besides,the expression of proteins associated with the promotion of gluconeogenesis dramatically increased in the mice intervened with sea cucumber sulfated sterols.These findings suggested that sea cucumber sulfated sterols might change blood glucose metabolism in healthy mice by reducing glycogenesis and promoting gluconeogenesis.
基金financially supported by National Natural Science Foundation of China (32160801)China Agriculture Research System (CARS-39-12)+1 种基金Young Talent Fund of Association for Science and Technology in Shaanxi, China (2023-6-2-1)“Double-chain” project on livestock breeding (2022GDTSLD-46)
文摘Background Dysregulation of lipid metabolism and its consequences on growth performance in young ruminants have attracted attention,especially in the context of alternative feeding strategies.This study aims to elucidate the effects of milk replacer(MR)feeding on growth,lipid metabolism,colonic epithelial gene expression,colonic microbiota composition and systemic metabolism in goat kids compared to breast milk(BM)feeding,addressing a critical knowledge gap in early life nutrition.Methods Ten female goat kids were divided into 2 groups:those fed breast milk(BM group)and those fed a milk replacer(MR group).Over a period of 28 d,body weight was monitored and blood and tissue samples were collected for biochemical,transcriptomic and metabolomic analyses.Profiling of the colonial microbiota was performed using 16S rRNA gene sequencing.Intestinal microbiota transplantation(IMT)experiments in gnotobiotic mice were per-formed to validate causality.Results MR-fed pups exhibited reduced daily body-weight gain due to impaired lipid metabolism as evidenced by lower serum and liver total cholesterol(TC)and non-esterified fatty acid(NEFA)concentrations.Transcriptomic analysis of the colonic epithelium revealed upregulated genes involved in negative regulation of lipid metabolism,concomitant with microbiota shifts characterized by a decrease in Firmicutes and an increase in Actinobacteria.Specifically,genera such as Bifidobacterium and Prevotella were enriched in the MR group,while Clostridium and Fae-calibacterium were depleted.Metabolomics analyses confirmed alterations in bile acid and fatty acid metabolic path-ways.IMT experiments in mice recapitulated the metabolic phenotype observed in MR-fed goats,confirming the role of the microbiota in modulating host lipid metabolism.Conclusions Milk replacer feeding in goat kids disrupts lipid metabolism and gut microbiota dynamics,result-ing in reduced growth rates and metabolic alterations.These findings highlight the importance of early nutritional intervention on metabolic programming and suggest that modulation of the gut microbiota may be a target for improving growth and metabolic health in ruminants.This study contributes to the understanding of nutritional management strategies in livestock and their impact on animal health and productivity.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.32122080,31972375)Shandong Province(Grant No.ZR2020YQ25)。
文摘The content of soluble sugars is a vital parameter that indicates the quality of fleshy fruits such as apple(Malus domestica Borkh.).Studying the patterns of accumulation of soluble sugars and regulatory mechanisms associated with fruit development is crucial for breeding improved fruit varieties.Here,we report that MdCIbHLH1,a low temperature-induced b HLH transcription factor,inhibits the accumulation of soluble sugars by regulating sugar-metabolizing enzyme activities,photosynthetic performance,and the expression of sugar-related genes in developing apple fruits.MdCIbHLH1 inhibits MdFBP and MdPEPCK expression,thus blocking the conversion of acids to sugars in apple fruits.We also discovered that MdCIbHLH1 decreases the photosynthetic rate and carbohydrate accumulation in apple leaves.Our results suggest that soluble sugar accumulation in apple fruits is influenced by multiple factors,including metabolic status,photosynthesis,and carbohydrate allocation.MdCIbHLH1 is critically involved in controlling the accumulation of soluble sugars by coordinating carbohydrate synthesis and allocation,thus influencing sugar transport and its metabolism during the development of apple fruits.
基金supported by the National Natural Science Foundation of China(52321005)the Guangdong Basic and Applied Basic Research Foundation(2023A1515012383 and 2024A1515030138)+1 种基金the State Key Laboratory of Urban Water Resource and Environment(Harbin Institute of Technology,2021TS30)the Shenzhen Science and Technology Program(KQTD20190929172630447 and KCXFZ20211020163404007).
文摘Constructed wetlands(CWs)are a promising method to treat effluent from wastewater treatment plants(WWTPs).However,low carbon/nitrogen(C/N)ratios of the influent inhibit denitrification in CWs,resulting in poor nitrogen removal efficiency.Herein,we compared traditional(control),biochar(BC),and b-cyclodextrin-functionalized biochar(BC@b-CD)CW systems to investigate nitrogen removal from influent with low C/N ratios,and the mechanisms that enhance this process.The highest nitrogen removal rates were observed in the BC@b-CD group,with rates 45.89%and 42.48%higher than those of the control,accompanied by a 70.57%and 85.45%decrease in nitrous oxide release,when the C/N ratio decreased from 4 to 2,respectively.Metagenomic and enzymatic analyses indicated that BC@b-CD enhances nitrogen removal by coordinately promoting carbon metabolism and increasing denitrification enzyme activities,without affecting microbial species diversity in CWs.Structural equation modeling confirmed that the foremost advantages of BC@b-CD were effective electron generation and transportation resulting from increased activities of nicotinamide adenine dinucleotide(NADH)dehydrogenase and the electron transfer system(ETS),thereby strategically reallocating more carbon metabolic flow to support denitrification.Our results show that the application of BC@b-CD in CWs to optimize the reallocation of electrons from carbon metabolism is a feasible strategy to enhance denitrification under low C/N conditions.
