Traditional Chinese medicine(TCM)has demonstrated unique advantages in the prevention and treatment of chronic diseases such as glycolipid metabolism disorder.However,its widespread application has been hindered by th...Traditional Chinese medicine(TCM)has demonstrated unique advantages in the prevention and treatment of chronic diseases such as glycolipid metabolism disorder.However,its widespread application has been hindered by the unclear biological essence of TCM syndromes and therapeutic mechanisms.As an emerging interdisciplinary field,phenomics integrates multi-dimensional data including genome,transcriptome,proteome,metabolome,and microbiome.When combined with TCM's holistic philosophy,it forms TCM phenomics,providing novel approaches to reveal the biological connotation of TCM syndromes and the mechanisms of herbal medicine.Taking glycolipid metabolism disorder as an example,this paper explores the application of TCM phenomics in glycolipid metabolism disorder.By analyzing molecular characteristics of related syndromes,TCM phenomics identifies differentially expressed genes,metabolites,and gut microbiota biomarkers to elucidate the dynamic evolution patterns of syndromes.Simultaneously,it deciphers the multi-target regulatory networks of herbal formulas,demonstrating their therapeutic effects through mechanisms including modulation of insulin signaling pathways,improvement of gut microbiota imbalance,and suppression of inflammatory responses.Current challenges include the subjective nature of syndrome diagnosis,insufficient standardization of animal models,and lack of integrated multi-omics analysis.Future research should employ machine learning,multimodal data integration,and cross-omics longitudinal studies to establish quantitative diagnostic systems for syndromes,promote the integration of precision medicine in TCM and western medicine,and accelerate the modernization of TCM.展开更多
BACKGROUND The association between ambient air pollution and glycolipid metabolic disorders(GMDs,including diabetes mellitus and dyslipidemia)is still not well understood,especially when it comes to the different effe...BACKGROUND The association between ambient air pollution and glycolipid metabolic disorders(GMDs,including diabetes mellitus and dyslipidemia)is still not well understood,especially when it comes to the different effects of long-term vs short-term exposure and the sources of pollutants(indoor or outdoor).AIM To look at how outdoor particulate matter(PM1,PM_(2.5),PM_(10))and ozone(O3),as well as indoor pollutants from solid fuels,are related to the risk of developing GMDs in a cohort that represents the national population.METHODS We used a longitudinal cohort design to look at how different time periods of air pollution exposure(long-term:5-year averages;short-term:1-year averages)affect the incidence of GMDs in middle-aged and elderly adults.Multivariable logistic regression models,which took into account key factors such as age,sex,and smoking status,were used to calculate odds ratios(ORs)and 95%confidence intervals(CIs).RESULTS Our study found that exposure to air pollution(1μg/m^(3))has different effects on GMDs.Long-term exposure to outdoor pollutants like PM1,PM_(2.5),PM_(10),and O3 consistently increased the risk of diabetes(PM1:OR=1.106,95%CI:1.018-1.205;PM_(2.5):OR=1.038,95%CI:1.007-1.071;PM_(10):OR=1.023,95%CI:1.004-1.043)and dyslipidemia(PM1:OR=1.150,95%CI:1.064-1.249;PM_(2.5):OR=1.053,95%CI:1.023-1.086;PM_(10):OR=1.032,95%CI:1.014-1.052).Short-term exposure showed even stronger associations,particularly for PM1 with dyslipidemia(OR=1.078,95%CI:1.044-1.114)and PM1 with diabetes(OR=1.047,95%CI:1.007-1.089).Notably,certain components of PM_(2.5)-chloride(Cl^(-)),ammonium(NH_(4)^(+)),sulfate(SO_(4)^(2-)),and nitrate(NO3-)-showed a dose-dependent relationship with both conditions(for example,Cl^(-):Diabetes OR=1.797 per 1μg/m^(3),95%CI:1.086-2.991;dyslipidemia OR=2.627,95%CI:1.728-4.012).However,neither long-term nor short-term exposure to indoor solid fuel pollutants was significantly associated with diabetes(long-term OR=1.034,95%CI:0.801-1.333;short-term OR=0.970,95%CI:0.774-1.209)or dyslipidemia(short-term OR=1.159,95%CI:0.967-1.386).CONCLUSION This national cohort study shows that outdoor air pollution-particularly PM1,PM_(2.5),and their chemical components-is an important environmental factor contributing to GMDs,with long-term exposure showing greater metabolic toxicity than short-term exposure.The lack of association between indoor solid fuel pollutants and GMDs underscores the urgent need for targeted interventions to improve outdoor air quality and reduce metabolic risks at the population level.展开更多
BACKGROUND Aloe vera has been used as a traditional herbal therapy for wound management and dermatological conditions worldwide for thousands of years.Scientific evidence has confirmed that acemannan,the bioactive com...BACKGROUND Aloe vera has been used as a traditional herbal therapy for wound management and dermatological conditions worldwide for thousands of years.Scientific evidence has confirmed that acemannan,the bioactive compound in aloe vera gel,exhibits significant anti-inflammatory and immunomodulatory properties that enhance tissue regeneration.This case report describes the successful application of an innovative acemannan-enriched glycolipid sphere dressing derived from aloe vera gel in diabetic foot ulcer(DFU)treatment,which achieved a clinically remarkable outcome.CASE SUMMARY An 80-year-old female patient with a 20-year history of type 2 diabetes mellitus experienced recurrent diabetic foot pain for 15 years.She had multiple hospitalizations due to acute infections and poorly controlled hyperglycemia.Long-term treatments included metformin and gliclazide.Upon presentation,she had a nonhealing wound on her left dorsal foot,diagnosed as a severe DFU(Texas classification:Grade II,stage D).She declined amputation and opted for conservative treatment.The medical team applied an acemannan-enriched glycolipid sphere dressing five times daily to the left calf and foot,avoiding the wound area.Frequency was reduced to three times daily after scab formation.Weight-bearing on the injured foot was avoided.Through in-person and online consultations,the team managed her lifestyle and diet,emphasizing natural foods.After 5 months,the DFU healed without significant scarring or functional loss.No recurrence was observed during the 2-year follow-up.Acemannan-enriched glycolipid sphere dressings promote DFU healing.This suggests the potential of these dressings for treating other refractory wounds.展开更多
Objective:To discuss the effect of insulin and metformin on amethylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A(PPARGC1A) of rat offspring with gestational diabetes m...Objective:To discuss the effect of insulin and metformin on amethylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A(PPARGC1A) of rat offspring with gestational diabetes mellitus(GDM).Methods:A total of 45 pregnant rats received the intraperitoneal injection of streptozotocin to establish the pregnant rat model of GDM.A total of 21 pregnant rats with GDM were randomly divided into three groups,with 7ruts in each group,namely the insulin group,metformin group and control group.Rats in the insulin group received the abdominal subcutaneous injection of 1 mL/kg recombinant insulin glargine at 18:00 every day.Rats in the metformin group received the intragastric infusion of metformin hydrochloride at 18:00 every day,with the first dose of 300 mg/kg.The doses of two groups were adjusted every 3 d to maintain the blood glucose level at 2.65-7.62 mmol/L.Rats in the control group received the intragastric infusion of 1 mL normal saline at 18:00 every day.After the natural delivery of pregnant rats.10 offspring rats were randomly selected from each group.At birth,4 wk and 8 wk after the birth of offspring rats,the weight of offspring rats was measured.The blood glucose level of offspring rats was measured at 4wk and 8 wk,while the level of serum insulin,triglyceride and leptin was measured at 8 wk.Results:The weight of offspring rats at birth in the insulin group and metformin group was significantly lower than the one in the control group(P<0.05),and there was no significant difference at 4 wk and 8 wk among three groups(P>0.05).The fasting blood glucose and random blood glucose in the insulin group and metformin group at 4 wk and 8 wk were all significantly lower than ones in the control group(P<0.05);there was no significant difference between the insulin group and metformin group(P>0.05).The expression of PPARGC1 A mRNA in the insulin group and metformin group was significantly higher and the methylation level of PPARGC1 A was significantly lower than the one in the control group(P<0.05),but there was no significant difference between the insulin group and metformin group(P>0.05).Insulin and leptin at 8 wk in the insulin group and metformin group were significantly higher,while triglyceride was significantly lower than the one in the control group(P<0.05);triglyceride level of rats in the insulin group was significantly higher than the one in the metformin group(P<0.05).There was no significant difference in insulin and leptin level of offspring rats between the insulin group and metformin group(P>0.05).Conclusions:GDM can induce the methylation of PPARGC1 A of offspring rats to reduce the expression of PPARGC1 A mRNA and then cause the disorder of glycolipid metabolism when the offspring rats grow up;the insulin or metformin in the treatment of pregnant rats with GDM can reduce the methylation level of PPARGC1 A and thus improve the abnormal glycolipid metabolism of offspring rats.展开更多
OBJECTIVE:To explore the mechanism of Dangua Fang(丹瓜方,DGR)in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics.METHODS:Sprague-Dawley rats with normal glucose levels were ...OBJECTIVE:To explore the mechanism of Dangua Fang(丹瓜方,DGR)in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics.METHODS:Sprague-Dawley rats with normal glucose levels were randomly divided into three groups,including a conventional diet control group(Group A),high-fat-highsugar diet model group(Group B),and DGR group(Group C,high-fat-high-sugar diet containing 20.5 g DGR).After 10 weeks of intervention,the fasting blood glucose(FBG),2 h blood glucose[PBG;using the oral glucose tolerance test(OGTT)],hemoglobin A1c(HbA1c),plasma total cholesterol(TC),and triglycerides(TG)were tested,and the livers of rats were removed to calculate the liver index.Then,hepatic portal TG were tested using the Gross permanent optimization-participatiory action planning enzymatic method and phosphoproteomics was performed using liquid chromatography with tandem mass spectrometry(LC-MS/MS)analysis followed by database search and bioinformatics analysis.Finally,cell experiments were used to verify the results of phosphoproteomics.Phosphorylated mitogen-activated protein kinase kinase kinase kinase 4(MAP4k4)and phosphorylated adducin 1(ADD1)were detected using western blotting.RESULTS:DGR effectively reduced PBG,TG,and the liver index(P<0.05),and significantly decreased HbA1c,TC,and hepatic portal TG(P<0.01),showed significant hematoxylin and eosin(HE)staining,red oil O staining,and Masson staining of liver tissue.The total spectrum was 805334,matched spectrum was 260471,accounting for accounting 32.3%,peptides were 19995,modified peptides were 14671,identified proteins were 4601,quantifiable proteins were 4417,identified sites were 15749,and quantified sites were 14659.Based on the threshold of expression fold change(>1.2),DGR upregulated the modification of 228 phosphorylation sites involving 204 corresponding function proteins,and downregulated the modification of 358 phosphorylation sites involving 358 corresponding function proteins,which included correcting 75 phosphorylation sites involving 64 corresponding function proteins relating to glycolipid metabolism.Therefore,DGR improved biological tissue processes,including information storage and processing,cellular processes and signaling,and metabolism.The metabolic functions regulated by DGR mainly include energy production and conversion,carbohydrate transport and metabolism,lipid transport and metabolism,inorganic ion transport and metabolism,secondary metabolite biosynthesis,transport,and catabolism.In vitro phosphorylation validation based on cell experiments showed that the change trends in the phosphorylation level of MAP4k4 and ADD1 were consistent with that of previous phosphoproteomics studies.CONCLUSION:DGR extensively corrects the modification of phosphorylation sites to improve corresponding glycolipid metabolism-related protein expression in rats with glycolipid metabolism disorders,thereby regulating glycolipid metabolism through a multi-target and multi-method process.展开更多
When cultured in medium limited of nitrogen sources, the phytopathogen Ustilago maydis produces two amphipathic glycolipids: Ustilagic acid (UA) and Mannosylerythritol lipid (MEL), which in addition to the hydrophilic...When cultured in medium limited of nitrogen sources, the phytopathogen Ustilago maydis produces two amphipathic glycolipids: Ustilagic acid (UA) and Mannosylerythritol lipid (MEL), which in addition to the hydrophilic moiety, contain dior tri-hydroxylated C16 fatty acids (UA), or C8 and C16 saturated fatty acids (MEL). We compared the growth and morphology of cells in YPD and in minimum media containing glucose and nitrogen sources such as nitrate or urea and those deprived of nitrogen. Nitrogen-starved cells showed a dramatic accumulation of internal lipids identified as lipid droplets when stained with the hydrophobic probe BODIPY;these lipid droplets were enriched in unsaturated fatty acids. Fatty acids in YPD or medium containing nitrate as nitrogen source showed a combination of saturated/unsaturated lipids, but when urea was the nitrogen source, cells only contained saturated fatty acids. The glycolipid profiles produced in the presence or absence of nitrogen showed preferences towards the production of one kind of glycolipid: cells in media containing nitrate or urea produced different proportions of UA/MEL, but under nitrogen starvation cells contained only UA. The emulsification capacity of the glycolipids produced in media with or without nitrogen was similar (72% - 76%). HPLC of the glycolipids allowed the separation of fractions with different emulsifying characteristics. Our results indicate that U. maydis accumulates lipid droplets when deprived of nitrogen source and confirm that UA is not under nitrogen control, but rather that MEL and lipid droplets are produced and oppositely regulated by nitrogen.展开更多
Aim: To evaluate the sperm motility stimulating activity of a sulfono glycolipid (S-ACT-1) isolated from Gelidiellaacerosa, a Sfi Lankan marine red algae. Methods: S-ACT-I, a white amorphous powder was separated from ...Aim: To evaluate the sperm motility stimulating activity of a sulfono glycolipid (S-ACT-1) isolated from Gelidiellaacerosa, a Sfi Lankan marine red algae. Methods: S-ACT-I, a white amorphous powder was separated from morepolar fractions of the hexane soluble of 1:1 CH_2Cl_2/MeOH extract and subjected to ~1H, ^(13)C NMR and IR Spectroscopyafter reverse phase HPLC for identification. Effects of S-ACT-1 on human sperm motility was assessed in vitro at 10,100 and 1000μg/mL concentrations at 37℃ for 0, 5, 15, 30 and 60 min. Results: S-ACT-1 was identified as aglycolipid sulfate. The lower dose increased the sperm motility slightly, whilst the medium dose significantly increasedthe motility (P < 0.05) from 5 min of incubation reaching a peak at 15 min and the stimulant effect was sustainedthroughout the experimental period. Furthermore, the medium dose rendered 80% of the immotile viable sperm motile.In contrast, the highest dose impaired the sperm motility. The sperm stimulating activity of S-ACT-1 was dose-depen-dent and had a bell-shaped dose response curve for all the 5 incubation periods. Conclusion: S-ACT-1 of Gelidiellaacerosa is a Sulfono glycolipid. S-ACT-1 has a potent sperm motility stimulating activity in vitro and has the potentialto be developed into a sperm stimulant. (Asian J Androl 2001 Mar; 3: 27-31)展开更多
Two single-chain glycolipids, octadecyl-β-D-glucopyranoside(1) and 2-octadecanamido-2-deoxy-D-glucopyranose(2) were synthesized and their dispersing properties in water were studied. Incorporation of 1 into the phosp...Two single-chain glycolipids, octadecyl-β-D-glucopyranoside(1) and 2-octadecanamido-2-deoxy-D-glucopyranose(2) were synthesized and their dispersing properties in water were studied. Incorporation of 1 into the phospholipid liposomes could inhibit the aggregation of liposomes and improve the molecular packing in the bilayer membranes.展开更多
The aim of this experiment was to investigate the ameliorative effect and molecular mechanism of tilapia head glycolipid(TH-GL)on indomethacin(IDM)-induced gastric ulcer in male Sprague Dawley(SD)rats.The gastric ulce...The aim of this experiment was to investigate the ameliorative effect and molecular mechanism of tilapia head glycolipid(TH-GL)on indomethacin(IDM)-induced gastric ulcer in male Sprague Dawley(SD)rats.The gastric ulcer model was established by oral administration of 30mgkg^(-1) IDM after 7 days of TH-GL or omeprazole(OME)administration in rats.Then the macroscopic gastric injury symptoms,gastric mucosa protective factor cyclooxygenase 1(COX-1),cyclooxygenase 2(COX-2),prostaglandin E_(2)(PGE_(2)),the levels of oxidative stress,and inflammatory cytokine expression levels in the rats were analyzed.The experimental results showed that multiple ulcers appeared on the gastric surface of the rats in the model group.Compared to the model group,TH-GL significantly alleviated gastric ulcers and reduced the gastric damage index in rats.In addition,TH-GL significantly promoted the expression of constitutive enzyme COX-1 while inhibited the expression of inducible enzyme COX-2,and make PGE2 maintain at normal levels.TH-GL also inhibited oxidative stress and inflammatory responses,increased superoxide dismutase(SOD)activity and glutathione(GSH)content,decreased the level of malondialdehyde(MDA)and the content of pro-inflammatory factor.In conclusion,these results suggested that TH-GL could maintain the expression levels of COX-1 and PGE2 while inhibit the expression of COX-2 in the gastric of rat and then prevent IDM-induced gastric ulcer,which may be related to the regulation of oxidative stress and inflammatory response.Therefore,TH-GL might be a new option for the prevention of gastric diseases induced by IDM.展开更多
The soaring global prevalence of diabetes makes it urgent to explore new drugs with high efficacy and safety.Nanomaterial-derived bioactive agents are emerging as one of the most promising candidates for biomedical ap...The soaring global prevalence of diabetes makes it urgent to explore new drugs with high efficacy and safety.Nanomaterial-derived bioactive agents are emerging as one of the most promising candidates for biomedical application.In the present study,we investigated the anti-diabetic effects of a functionalized gadofullerene(GF)using obese db/db and non-obese mouse model of type 2 diabete mellitus(MKR)mouse type 2 diabetes mellitus(T2DM)models.In both mouse models,the diabetic phenotypes,including hyperglycemia,impaired glucose tolerance,and insulin sensitivity,were ameliorated after two or four weeks of intraperitoneal administration of GF.GF lowered blood glucose levels in a dose-dependent manner.Importantly,the restored blood glucose levels could persist ten days after withdrawal of GF treatment.The hepatic AKT/GSK3β/FoxO1 pathway is shown to be the main target of GF for rebalancing gluconeogenesis and glycogen synthesis in vivo and in vitro.Furthermore,GF treatment significantly reduced weight gain of db/db mice with reduced hepatic fat storage by the inhibition of de novo lipogenesis through m TOR/S6K/SREBP1 pathway.Our data provide compelling evidence to support the promising application of GF for the treatment of T2DM.展开更多
Glycolipids are lipid compounds,which are a type of amphiphilic molecules containing glycosyl ligands.This experiment studied the efficacy of glycolipids on acne skin care from the aspects of antibacterial,anti-inflam...Glycolipids are lipid compounds,which are a type of amphiphilic molecules containing glycosyl ligands.This experiment studied the efficacy of glycolipids on acne skin care from the aspects of antibacterial,anti-inflammatory,anti-allergic,oil-control,soothing and repair.Research results show that glycolipids have excellent antibacterial properties against P.acnes;when the dosage of glycolipids reaches 10μg/mL,the inhibition rate of glycolipids on lipid synthesis in SZ95 cells can reach 20%;glycolipids can induce LPS induction RAW264.7 cells have the inhibitory effect on the release of inflammatory factors IL-6 and NO;when the glycolipids concentration is 15 mg/mL,the inhibition rate of glycolipids on hyaluronidase reaches 45.8%;when the glycolipids concentration is 25μg/mL,the inhibition rate on calcium ion concentration reaches 45.3%;glycolipids have a significant promoting effect on wound healing.Furthermore,human efficacy evaluation shows that glycolipids products have comprehensive care effects on acne skin.This study will help further promote the application of glycolipids in cosmetic products,especially in skin care products for acne skin.展开更多
Arecoline is an alkaloid extracted from the plant betel nut with important pharmacological effects and is an agonist at muscarinic receptors(M receptors).In this study,we investigated the effects of dietary arecoline ...Arecoline is an alkaloid extracted from the plant betel nut with important pharmacological effects and is an agonist at muscarinic receptors(M receptors).In this study,we investigated the effects of dietary arecoline supplementation on hepatopancreatic and muscle glycolipid metabolism in adult grass carp(Ctenopharyngodon idellus).A total of 450 healthy adult grass carp with an initial body weight of 607.87±1.82 g were randomly divided into six experimental groups and fed six levels(0,0.5,1.0,1.5,2.0,and 2.5 mg/kg diet)of arecoline for 60 days.The results showed that feed supplemented with 1.0 mg/kg arecoline up-regulated mRNA levels of M3,and promoted glucose(GLU)and fatty acid metabolism(P<0.05)both in hepatopancreas and muscle.The promotion of glycolipid metabolism by arecoline can be achieved through three pathways.Firstly,arecoline alleviated endoplasmic reticulum(ER)stress in grass carp muscle by suppressing the mRNA levels of ER stress-related genes atf4,chop,ire1,and xbp1 as well as the protein expression of p-PERK and p-IRE1(P<0.05).Secondly,arecoline protected mitochondrial function by promoting the mitochondrial respiratory chain complex IeV-related protein expression and triggering the mitochondrial unfolded protein response(UPRmt)(P<0.05).Finally,arecoline promoted close communication between the ER and mitochondria by increasing the expression of the mitochondria-associated endoplasmic reticulum membrane(MAM)tight junction proteins GRP75 and PACS2 as well as the calcium transporter proteins SERCA1 and IP3R,which in turn promoted lipid metabolism by increasing the protein expression of DGAT2(P<0.05).In conclusion,we found for the first time that dietary arecoline promoted GLU and fatty acid metabolism in hepatopancreas and muscle,which may be related to the regulatory effects of MAM on ER and mitochondria.展开更多
Objective: To investigate the protective effects of modified Linggui Zhugan Decoction(MLZD), a traditional Chinese medicine formula, on obese type 2 diabetes mellitus(T2 DM) rats. Methods:Fifty Sprague-Dawley rats wer...Objective: To investigate the protective effects of modified Linggui Zhugan Decoction(MLZD), a traditional Chinese medicine formula, on obese type 2 diabetes mellitus(T2 DM) rats. Methods:Fifty Sprague-Dawley rats were randomly divided into 5 groups by a random number table, including normal, obese T2 DM(ob-T2 DM), MLZD low-dose [MLDZ-L, 4.625 g/(kg·d)], MLZD middle-dose [MLD-M,9.25 g/(kg·d) ] and MLZD high-dose [MLD-H, 18.5 g/(kg·d)] groups,10 rats in each group. After 4-week intervention, blood samples and liver, pancreas, muscle tissues were collected to assess the insulin resistance(IR), blood lipid, adipokines and inflammation cytokines. The alteration of phosphatidylinositol 3 kinase(PI3 K)-protein kinase B(PKB or Akt)/the mammalian target of rapamycin(mTOR)-ribosome protein subunit 6 kinase 1(S6 K1)/AMP-activated protein kinase(AMPK)-peroxisome proliferator-activated receptor gamma coactivator 1 alpha(PGC-1α) pathways were also studied. Results: MLZD dose-dependently reduced fasting blood glucose,fasting insulin, homeostasis model of assessment for IR index and increased insulin sensitive index compared with ob-T2 DM rats(P<0.05). Similarly, total cholesterol, triglyceride, low-density lipoprotein cholesterol and free fatty acids were also decreased compared with ob-T2 DM rats after 4-week treatment(P<0.05 or P<0.01).Improvements in adipokines and inflammatory cytokines were observed with a raised level of adiponectin and a reduced level of leptin, resistin, tumor necrosis factor-α and interleukin-6(P<0.05 or P<0.01). MLZD regulated the PI3 K-Akt/mTOR-S6 K1/AMPK-PGC-1α pathways and restored the tissue structure of liver and pancreas(P<0.05 or P<0.01). Conclusions: MLZD ameliorated glycolipid metabolism and inflammation, which may be attributed to the regulation of PI3 K-Akt/mTOR-S6 K1/AMPK-PGC-1α pathways.展开更多
Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus(HCV) with unknown mechanism. Here, we showed th...Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus(HCV) with unknown mechanism. Here, we showed that bicyclol significantly inhibited HCV replication in vitro and in hepatitis C patients. Using bicyclol as a probe, we identified glycolipid transfer protein(GLTP) to be a novel restrictive factor for HCV replication. The GLTP preferentially bound host vesicle-associated membrane protein-associated protein-A(VAP-A) in competition with the HCV NS5 A, causing an interruption of the complex formation between VAP-A and HCV NS5 A. As the formation of VAP-A/NS5 A complex is essential for viral RNA replication, up-regulation of GLTP by bicyclol reduced the level of VAP-A/NS5 A complex and thus inhibited HCV replication. Bicyclol also exhibited an inhibition on HCV variants resistant to direct-acting antiviral agents(DAAs) with an efficacy identical to that on wild type HCV. In combination with bicyclol, DAAs inhibited HCV replication in a synergistic fashion. GLTP appears to be a newly discovered host restrictive factor for HCV replication, Up-regulation of GLTP causes spontaneous restriction of HCV replication.展开更多
Objective:To explore the mechanisms of Dangua Recipe(DGR)in improving glycolipid metabolism based on transcriptomics.Methods:Sprague-Dawley rats with normal glucose level were divided into 3 groups according to a rand...Objective:To explore the mechanisms of Dangua Recipe(DGR)in improving glycolipid metabolism based on transcriptomics.Methods:Sprague-Dawley rats with normal glucose level were divided into 3 groups according to a random number table,including a conventional diet group(Group A),a DGR group(Group B,high-calorie diet+20.5 g DGR),and a high-calorie fodder model group(Group C).After 12 weeks of intervention,the liver tissue of rats was taken.Gene sequence and transcriptional analysis were performed to identify the key genes related to glycolipid metabolism reflecting DGR efficacy,and then gene or protein validation of liver tissue were performed.Nicotinamide phosphoribosyl transferase(Nampt)and phosphoenolpyruvate carboxykinase(PEPCK)proteins in liver tissues were detected by enzyme linked immunosorbent assay,fatty acid synthase(FASN)protein was detected by Western blot,and fatty acid binding protein 5(FABP5)-mRNA was detected by quantitative real-time polymerase chain reaction.Furthermore,the functional verification was performed on the diabetic model rats by Nampt blocker(GEN-617)injected in vivo.Hemoglobin A1c(HbA1c),plasma total cholesterol and triglycerides were detected.Results:Totally,257 differentialdominant genes of Group A vs.Group C and 392 differential-dominant genes of Group B vs.Group C were found.Moreover,11 Gene Ontology molecular function terms and 7 Kyoto Encyclopedia of Genes and Genomes enrichment pathways owned by both Group A vs.Group C and Group C vs.Group B were confirmed.The liver tissue target validation showed that Nampt,FASN,PEPCK protein and FABP5-mRNA had the same changes consistent with transcriptome.The in vivo functional tests showed that GEN-617 increased body weight,HbA1c,triglyceride and total cholesterol levels in the diabetic rats(P<0.05 or P<0.01);while all the above-mentioned levels(except triglyceride)were decreased significantly by GEN-617 combined with DGR intervention(P<0.05 or P<0.01).Conclusion:Nampt activation was one of the mechanisms about DGR regulating glycolipid metabolism.展开更多
基金National Natural Science Foundation of China(82474323)High Level Chinese Medical Hospital Promotion Project(HLCMHPP20230CZ40907)China Academy of Chinese Medical Sciences Outstanding Young Scientific and Technological Talents Program(ZZ13-YQ-026).
文摘Traditional Chinese medicine(TCM)has demonstrated unique advantages in the prevention and treatment of chronic diseases such as glycolipid metabolism disorder.However,its widespread application has been hindered by the unclear biological essence of TCM syndromes and therapeutic mechanisms.As an emerging interdisciplinary field,phenomics integrates multi-dimensional data including genome,transcriptome,proteome,metabolome,and microbiome.When combined with TCM's holistic philosophy,it forms TCM phenomics,providing novel approaches to reveal the biological connotation of TCM syndromes and the mechanisms of herbal medicine.Taking glycolipid metabolism disorder as an example,this paper explores the application of TCM phenomics in glycolipid metabolism disorder.By analyzing molecular characteristics of related syndromes,TCM phenomics identifies differentially expressed genes,metabolites,and gut microbiota biomarkers to elucidate the dynamic evolution patterns of syndromes.Simultaneously,it deciphers the multi-target regulatory networks of herbal formulas,demonstrating their therapeutic effects through mechanisms including modulation of insulin signaling pathways,improvement of gut microbiota imbalance,and suppression of inflammatory responses.Current challenges include the subjective nature of syndrome diagnosis,insufficient standardization of animal models,and lack of integrated multi-omics analysis.Future research should employ machine learning,multimodal data integration,and cross-omics longitudinal studies to establish quantitative diagnostic systems for syndromes,promote the integration of precision medicine in TCM and western medicine,and accelerate the modernization of TCM.
基金Supported by the Teaching Research and Reform Fund Project of Central South University,No.2024jy178.
文摘BACKGROUND The association between ambient air pollution and glycolipid metabolic disorders(GMDs,including diabetes mellitus and dyslipidemia)is still not well understood,especially when it comes to the different effects of long-term vs short-term exposure and the sources of pollutants(indoor or outdoor).AIM To look at how outdoor particulate matter(PM1,PM_(2.5),PM_(10))and ozone(O3),as well as indoor pollutants from solid fuels,are related to the risk of developing GMDs in a cohort that represents the national population.METHODS We used a longitudinal cohort design to look at how different time periods of air pollution exposure(long-term:5-year averages;short-term:1-year averages)affect the incidence of GMDs in middle-aged and elderly adults.Multivariable logistic regression models,which took into account key factors such as age,sex,and smoking status,were used to calculate odds ratios(ORs)and 95%confidence intervals(CIs).RESULTS Our study found that exposure to air pollution(1μg/m^(3))has different effects on GMDs.Long-term exposure to outdoor pollutants like PM1,PM_(2.5),PM_(10),and O3 consistently increased the risk of diabetes(PM1:OR=1.106,95%CI:1.018-1.205;PM_(2.5):OR=1.038,95%CI:1.007-1.071;PM_(10):OR=1.023,95%CI:1.004-1.043)and dyslipidemia(PM1:OR=1.150,95%CI:1.064-1.249;PM_(2.5):OR=1.053,95%CI:1.023-1.086;PM_(10):OR=1.032,95%CI:1.014-1.052).Short-term exposure showed even stronger associations,particularly for PM1 with dyslipidemia(OR=1.078,95%CI:1.044-1.114)and PM1 with diabetes(OR=1.047,95%CI:1.007-1.089).Notably,certain components of PM_(2.5)-chloride(Cl^(-)),ammonium(NH_(4)^(+)),sulfate(SO_(4)^(2-)),and nitrate(NO3-)-showed a dose-dependent relationship with both conditions(for example,Cl^(-):Diabetes OR=1.797 per 1μg/m^(3),95%CI:1.086-2.991;dyslipidemia OR=2.627,95%CI:1.728-4.012).However,neither long-term nor short-term exposure to indoor solid fuel pollutants was significantly associated with diabetes(long-term OR=1.034,95%CI:0.801-1.333;short-term OR=0.970,95%CI:0.774-1.209)or dyslipidemia(short-term OR=1.159,95%CI:0.967-1.386).CONCLUSION This national cohort study shows that outdoor air pollution-particularly PM1,PM_(2.5),and their chemical components-is an important environmental factor contributing to GMDs,with long-term exposure showing greater metabolic toxicity than short-term exposure.The lack of association between indoor solid fuel pollutants and GMDs underscores the urgent need for targeted interventions to improve outdoor air quality and reduce metabolic risks at the population level.
文摘BACKGROUND Aloe vera has been used as a traditional herbal therapy for wound management and dermatological conditions worldwide for thousands of years.Scientific evidence has confirmed that acemannan,the bioactive compound in aloe vera gel,exhibits significant anti-inflammatory and immunomodulatory properties that enhance tissue regeneration.This case report describes the successful application of an innovative acemannan-enriched glycolipid sphere dressing derived from aloe vera gel in diabetic foot ulcer(DFU)treatment,which achieved a clinically remarkable outcome.CASE SUMMARY An 80-year-old female patient with a 20-year history of type 2 diabetes mellitus experienced recurrent diabetic foot pain for 15 years.She had multiple hospitalizations due to acute infections and poorly controlled hyperglycemia.Long-term treatments included metformin and gliclazide.Upon presentation,she had a nonhealing wound on her left dorsal foot,diagnosed as a severe DFU(Texas classification:Grade II,stage D).She declined amputation and opted for conservative treatment.The medical team applied an acemannan-enriched glycolipid sphere dressing five times daily to the left calf and foot,avoiding the wound area.Frequency was reduced to three times daily after scab formation.Weight-bearing on the injured foot was avoided.Through in-person and online consultations,the team managed her lifestyle and diet,emphasizing natural foods.After 5 months,the DFU healed without significant scarring or functional loss.No recurrence was observed during the 2-year follow-up.Acemannan-enriched glycolipid sphere dressings promote DFU healing.This suggests the potential of these dressings for treating other refractory wounds.
基金supported by Shandong Natural Science Fund(Y2008c170)
文摘Objective:To discuss the effect of insulin and metformin on amethylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A(PPARGC1A) of rat offspring with gestational diabetes mellitus(GDM).Methods:A total of 45 pregnant rats received the intraperitoneal injection of streptozotocin to establish the pregnant rat model of GDM.A total of 21 pregnant rats with GDM were randomly divided into three groups,with 7ruts in each group,namely the insulin group,metformin group and control group.Rats in the insulin group received the abdominal subcutaneous injection of 1 mL/kg recombinant insulin glargine at 18:00 every day.Rats in the metformin group received the intragastric infusion of metformin hydrochloride at 18:00 every day,with the first dose of 300 mg/kg.The doses of two groups were adjusted every 3 d to maintain the blood glucose level at 2.65-7.62 mmol/L.Rats in the control group received the intragastric infusion of 1 mL normal saline at 18:00 every day.After the natural delivery of pregnant rats.10 offspring rats were randomly selected from each group.At birth,4 wk and 8 wk after the birth of offspring rats,the weight of offspring rats was measured.The blood glucose level of offspring rats was measured at 4wk and 8 wk,while the level of serum insulin,triglyceride and leptin was measured at 8 wk.Results:The weight of offspring rats at birth in the insulin group and metformin group was significantly lower than the one in the control group(P<0.05),and there was no significant difference at 4 wk and 8 wk among three groups(P>0.05).The fasting blood glucose and random blood glucose in the insulin group and metformin group at 4 wk and 8 wk were all significantly lower than ones in the control group(P<0.05);there was no significant difference between the insulin group and metformin group(P>0.05).The expression of PPARGC1 A mRNA in the insulin group and metformin group was significantly higher and the methylation level of PPARGC1 A was significantly lower than the one in the control group(P<0.05),but there was no significant difference between the insulin group and metformin group(P>0.05).Insulin and leptin at 8 wk in the insulin group and metformin group were significantly higher,while triglyceride was significantly lower than the one in the control group(P<0.05);triglyceride level of rats in the insulin group was significantly higher than the one in the metformin group(P<0.05).There was no significant difference in insulin and leptin level of offspring rats between the insulin group and metformin group(P>0.05).Conclusions:GDM can induce the methylation of PPARGC1 A of offspring rats to reduce the expression of PPARGC1 A mRNA and then cause the disorder of glycolipid metabolism when the offspring rats grow up;the insulin or metformin in the treatment of pregnant rats with GDM can reduce the methylation level of PPARGC1 A and thus improve the abnormal glycolipid metabolism of offspring rats.
基金the National Natural Science Foundation of China:Based on the"miR34a/Nampt-NAD+-TAC"Pathway to Study the Mechanism of Simultaneously Treating the Phlegm and Blood Stasis in the Regulation of Glycolipid(No.81873213)Study on the Mechanism of Simultaneously Treating the Phlegm and Blood Stasis on Glycolipid Metabolism Based on Intestinal Fat Absorption Regulated by miR-34a/Stat3-Nfil3 Pathway(82074308)+1 种基金a New Mechanism of Regulating the Amino Acid Metabolism of Type 2 Diabetes Mellitus with Dissipating Phlegm-Stasis:Based on the TCA Cycle-Mediated Transformation of"α-KG→Glutamate"(82274389)by Industry-University Cooperation Project for University in Fujian Province:Preparation of Monomeric Traditional Chinese Medicine Complexes Based on Nampt's Activation of Tricarboxylic Acid Cycle and Respiratory Chain to Interfere with Glycolipid Metabolism(2022Y41010015)。
文摘OBJECTIVE:To explore the mechanism of Dangua Fang(丹瓜方,DGR)in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics.METHODS:Sprague-Dawley rats with normal glucose levels were randomly divided into three groups,including a conventional diet control group(Group A),high-fat-highsugar diet model group(Group B),and DGR group(Group C,high-fat-high-sugar diet containing 20.5 g DGR).After 10 weeks of intervention,the fasting blood glucose(FBG),2 h blood glucose[PBG;using the oral glucose tolerance test(OGTT)],hemoglobin A1c(HbA1c),plasma total cholesterol(TC),and triglycerides(TG)were tested,and the livers of rats were removed to calculate the liver index.Then,hepatic portal TG were tested using the Gross permanent optimization-participatiory action planning enzymatic method and phosphoproteomics was performed using liquid chromatography with tandem mass spectrometry(LC-MS/MS)analysis followed by database search and bioinformatics analysis.Finally,cell experiments were used to verify the results of phosphoproteomics.Phosphorylated mitogen-activated protein kinase kinase kinase kinase 4(MAP4k4)and phosphorylated adducin 1(ADD1)were detected using western blotting.RESULTS:DGR effectively reduced PBG,TG,and the liver index(P<0.05),and significantly decreased HbA1c,TC,and hepatic portal TG(P<0.01),showed significant hematoxylin and eosin(HE)staining,red oil O staining,and Masson staining of liver tissue.The total spectrum was 805334,matched spectrum was 260471,accounting for accounting 32.3%,peptides were 19995,modified peptides were 14671,identified proteins were 4601,quantifiable proteins were 4417,identified sites were 15749,and quantified sites were 14659.Based on the threshold of expression fold change(>1.2),DGR upregulated the modification of 228 phosphorylation sites involving 204 corresponding function proteins,and downregulated the modification of 358 phosphorylation sites involving 358 corresponding function proteins,which included correcting 75 phosphorylation sites involving 64 corresponding function proteins relating to glycolipid metabolism.Therefore,DGR improved biological tissue processes,including information storage and processing,cellular processes and signaling,and metabolism.The metabolic functions regulated by DGR mainly include energy production and conversion,carbohydrate transport and metabolism,lipid transport and metabolism,inorganic ion transport and metabolism,secondary metabolite biosynthesis,transport,and catabolism.In vitro phosphorylation validation based on cell experiments showed that the change trends in the phosphorylation level of MAP4k4 and ADD1 were consistent with that of previous phosphoproteomics studies.CONCLUSION:DGR extensively corrects the modification of phosphorylation sites to improve corresponding glycolipid metabolism-related protein expression in rats with glycolipid metabolism disorders,thereby regulating glycolipid metabolism through a multi-target and multi-method process.
文摘When cultured in medium limited of nitrogen sources, the phytopathogen Ustilago maydis produces two amphipathic glycolipids: Ustilagic acid (UA) and Mannosylerythritol lipid (MEL), which in addition to the hydrophilic moiety, contain dior tri-hydroxylated C16 fatty acids (UA), or C8 and C16 saturated fatty acids (MEL). We compared the growth and morphology of cells in YPD and in minimum media containing glucose and nitrogen sources such as nitrate or urea and those deprived of nitrogen. Nitrogen-starved cells showed a dramatic accumulation of internal lipids identified as lipid droplets when stained with the hydrophobic probe BODIPY;these lipid droplets were enriched in unsaturated fatty acids. Fatty acids in YPD or medium containing nitrate as nitrogen source showed a combination of saturated/unsaturated lipids, but when urea was the nitrogen source, cells only contained saturated fatty acids. The glycolipid profiles produced in the presence or absence of nitrogen showed preferences towards the production of one kind of glycolipid: cells in media containing nitrate or urea produced different proportions of UA/MEL, but under nitrogen starvation cells contained only UA. The emulsification capacity of the glycolipids produced in media with or without nitrogen was similar (72% - 76%). HPLC of the glycolipids allowed the separation of fractions with different emulsifying characteristics. Our results indicate that U. maydis accumulates lipid droplets when deprived of nitrogen source and confirm that UA is not under nitrogen control, but rather that MEL and lipid droplets are produced and oppositely regulated by nitrogen.
文摘Aim: To evaluate the sperm motility stimulating activity of a sulfono glycolipid (S-ACT-1) isolated from Gelidiellaacerosa, a Sfi Lankan marine red algae. Methods: S-ACT-I, a white amorphous powder was separated from morepolar fractions of the hexane soluble of 1:1 CH_2Cl_2/MeOH extract and subjected to ~1H, ^(13)C NMR and IR Spectroscopyafter reverse phase HPLC for identification. Effects of S-ACT-1 on human sperm motility was assessed in vitro at 10,100 and 1000μg/mL concentrations at 37℃ for 0, 5, 15, 30 and 60 min. Results: S-ACT-1 was identified as aglycolipid sulfate. The lower dose increased the sperm motility slightly, whilst the medium dose significantly increasedthe motility (P < 0.05) from 5 min of incubation reaching a peak at 15 min and the stimulant effect was sustainedthroughout the experimental period. Furthermore, the medium dose rendered 80% of the immotile viable sperm motile.In contrast, the highest dose impaired the sperm motility. The sperm stimulating activity of S-ACT-1 was dose-depen-dent and had a bell-shaped dose response curve for all the 5 incubation periods. Conclusion: S-ACT-1 of Gelidiellaacerosa is a Sulfono glycolipid. S-ACT-1 has a potent sperm motility stimulating activity in vitro and has the potentialto be developed into a sperm stimulant. (Asian J Androl 2001 Mar; 3: 27-31)
文摘Two single-chain glycolipids, octadecyl-β-D-glucopyranoside(1) and 2-octadecanamido-2-deoxy-D-glucopyranose(2) were synthesized and their dispersing properties in water were studied. Incorporation of 1 into the phospholipid liposomes could inhibit the aggregation of liposomes and improve the molecular packing in the bilayer membranes.
基金supported by the National Key R&D Pro-grams of China(No.2018YFD0901103)the Hainan Provincial Natural Science Foundation of China(No.2019 RC093).
文摘The aim of this experiment was to investigate the ameliorative effect and molecular mechanism of tilapia head glycolipid(TH-GL)on indomethacin(IDM)-induced gastric ulcer in male Sprague Dawley(SD)rats.The gastric ulcer model was established by oral administration of 30mgkg^(-1) IDM after 7 days of TH-GL or omeprazole(OME)administration in rats.Then the macroscopic gastric injury symptoms,gastric mucosa protective factor cyclooxygenase 1(COX-1),cyclooxygenase 2(COX-2),prostaglandin E_(2)(PGE_(2)),the levels of oxidative stress,and inflammatory cytokine expression levels in the rats were analyzed.The experimental results showed that multiple ulcers appeared on the gastric surface of the rats in the model group.Compared to the model group,TH-GL significantly alleviated gastric ulcers and reduced the gastric damage index in rats.In addition,TH-GL significantly promoted the expression of constitutive enzyme COX-1 while inhibited the expression of inducible enzyme COX-2,and make PGE2 maintain at normal levels.TH-GL also inhibited oxidative stress and inflammatory responses,increased superoxide dismutase(SOD)activity and glutathione(GSH)content,decreased the level of malondialdehyde(MDA)and the content of pro-inflammatory factor.In conclusion,these results suggested that TH-GL could maintain the expression levels of COX-1 and PGE2 while inhibit the expression of COX-2 in the gastric of rat and then prevent IDM-induced gastric ulcer,which may be related to the regulation of oxidative stress and inflammatory response.Therefore,TH-GL might be a new option for the prevention of gastric diseases induced by IDM.
基金supported by the National Natural Science Foundation of China (31871163, 81471000)the Ministry of Science and Technology of China (2014DFA32120)
文摘The soaring global prevalence of diabetes makes it urgent to explore new drugs with high efficacy and safety.Nanomaterial-derived bioactive agents are emerging as one of the most promising candidates for biomedical application.In the present study,we investigated the anti-diabetic effects of a functionalized gadofullerene(GF)using obese db/db and non-obese mouse model of type 2 diabete mellitus(MKR)mouse type 2 diabetes mellitus(T2DM)models.In both mouse models,the diabetic phenotypes,including hyperglycemia,impaired glucose tolerance,and insulin sensitivity,were ameliorated after two or four weeks of intraperitoneal administration of GF.GF lowered blood glucose levels in a dose-dependent manner.Importantly,the restored blood glucose levels could persist ten days after withdrawal of GF treatment.The hepatic AKT/GSK3β/FoxO1 pathway is shown to be the main target of GF for rebalancing gluconeogenesis and glycogen synthesis in vivo and in vitro.Furthermore,GF treatment significantly reduced weight gain of db/db mice with reduced hepatic fat storage by the inhibition of de novo lipogenesis through m TOR/S6K/SREBP1 pathway.Our data provide compelling evidence to support the promising application of GF for the treatment of T2DM.
文摘Glycolipids are lipid compounds,which are a type of amphiphilic molecules containing glycosyl ligands.This experiment studied the efficacy of glycolipids on acne skin care from the aspects of antibacterial,anti-inflammatory,anti-allergic,oil-control,soothing and repair.Research results show that glycolipids have excellent antibacterial properties against P.acnes;when the dosage of glycolipids reaches 10μg/mL,the inhibition rate of glycolipids on lipid synthesis in SZ95 cells can reach 20%;glycolipids can induce LPS induction RAW264.7 cells have the inhibitory effect on the release of inflammatory factors IL-6 and NO;when the glycolipids concentration is 15 mg/mL,the inhibition rate of glycolipids on hyaluronidase reaches 45.8%;when the glycolipids concentration is 25μg/mL,the inhibition rate on calcium ion concentration reaches 45.3%;glycolipids have a significant promoting effect on wound healing.Furthermore,human efficacy evaluation shows that glycolipids products have comprehensive care effects on acne skin.This study will help further promote the application of glycolipids in cosmetic products,especially in skin care products for acne skin.
基金supported by the National Science Fund for Distinguished Young Scholars of China(32425056)the National Key R&D Program of China(2023YFD2400600)+1 种基金National Natural Science Foundation of China(U23A20250)the earmarked fund for CARS(CARS-45).
文摘Arecoline is an alkaloid extracted from the plant betel nut with important pharmacological effects and is an agonist at muscarinic receptors(M receptors).In this study,we investigated the effects of dietary arecoline supplementation on hepatopancreatic and muscle glycolipid metabolism in adult grass carp(Ctenopharyngodon idellus).A total of 450 healthy adult grass carp with an initial body weight of 607.87±1.82 g were randomly divided into six experimental groups and fed six levels(0,0.5,1.0,1.5,2.0,and 2.5 mg/kg diet)of arecoline for 60 days.The results showed that feed supplemented with 1.0 mg/kg arecoline up-regulated mRNA levels of M3,and promoted glucose(GLU)and fatty acid metabolism(P<0.05)both in hepatopancreas and muscle.The promotion of glycolipid metabolism by arecoline can be achieved through three pathways.Firstly,arecoline alleviated endoplasmic reticulum(ER)stress in grass carp muscle by suppressing the mRNA levels of ER stress-related genes atf4,chop,ire1,and xbp1 as well as the protein expression of p-PERK and p-IRE1(P<0.05).Secondly,arecoline protected mitochondrial function by promoting the mitochondrial respiratory chain complex IeV-related protein expression and triggering the mitochondrial unfolded protein response(UPRmt)(P<0.05).Finally,arecoline promoted close communication between the ER and mitochondria by increasing the expression of the mitochondria-associated endoplasmic reticulum membrane(MAM)tight junction proteins GRP75 and PACS2 as well as the calcium transporter proteins SERCA1 and IP3R,which in turn promoted lipid metabolism by increasing the protein expression of DGAT2(P<0.05).In conclusion,we found for the first time that dietary arecoline promoted GLU and fatty acid metabolism in hepatopancreas and muscle,which may be related to the regulatory effects of MAM on ER and mitochondria.
基金Supported by the National Natural Science Foundation of China (No. 81302877)Science and Technology Project of Guangdong Province of China (No. 2014A020212056)。
文摘Objective: To investigate the protective effects of modified Linggui Zhugan Decoction(MLZD), a traditional Chinese medicine formula, on obese type 2 diabetes mellitus(T2 DM) rats. Methods:Fifty Sprague-Dawley rats were randomly divided into 5 groups by a random number table, including normal, obese T2 DM(ob-T2 DM), MLZD low-dose [MLDZ-L, 4.625 g/(kg·d)], MLZD middle-dose [MLD-M,9.25 g/(kg·d) ] and MLZD high-dose [MLD-H, 18.5 g/(kg·d)] groups,10 rats in each group. After 4-week intervention, blood samples and liver, pancreas, muscle tissues were collected to assess the insulin resistance(IR), blood lipid, adipokines and inflammation cytokines. The alteration of phosphatidylinositol 3 kinase(PI3 K)-protein kinase B(PKB or Akt)/the mammalian target of rapamycin(mTOR)-ribosome protein subunit 6 kinase 1(S6 K1)/AMP-activated protein kinase(AMPK)-peroxisome proliferator-activated receptor gamma coactivator 1 alpha(PGC-1α) pathways were also studied. Results: MLZD dose-dependently reduced fasting blood glucose,fasting insulin, homeostasis model of assessment for IR index and increased insulin sensitive index compared with ob-T2 DM rats(P<0.05). Similarly, total cholesterol, triglyceride, low-density lipoprotein cholesterol and free fatty acids were also decreased compared with ob-T2 DM rats after 4-week treatment(P<0.05 or P<0.01).Improvements in adipokines and inflammatory cytokines were observed with a raised level of adiponectin and a reduced level of leptin, resistin, tumor necrosis factor-α and interleukin-6(P<0.05 or P<0.01). MLZD regulated the PI3 K-Akt/mTOR-S6 K1/AMPK-PGC-1α pathways and restored the tissue structure of liver and pancreas(P<0.05 or P<0.01). Conclusions: MLZD ameliorated glycolipid metabolism and inflammation, which may be attributed to the regulation of PI3 K-Akt/mTOR-S6 K1/AMPK-PGC-1α pathways.
基金supported by the National Natural Science Foundation of China(81321004,81621064,Jiandong Jiang81322050,Zonggen Peng)+2 种基金National Mega-Project for “R&D for Innovative drugs”,Ministry of Science and Technology,China(2012ZX09301-002-001,Jiandong Jiang,2018ZX09711001-003-010,Zonggen Peng)Ministry of Education,China(NCET-12-0072,Zonggen Peng)CAMS Innovation Fund for Medical Sciences,China(CIFMS)(2017-I2M-3-012,Zonggen Peng)
文摘Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus(HCV) with unknown mechanism. Here, we showed that bicyclol significantly inhibited HCV replication in vitro and in hepatitis C patients. Using bicyclol as a probe, we identified glycolipid transfer protein(GLTP) to be a novel restrictive factor for HCV replication. The GLTP preferentially bound host vesicle-associated membrane protein-associated protein-A(VAP-A) in competition with the HCV NS5 A, causing an interruption of the complex formation between VAP-A and HCV NS5 A. As the formation of VAP-A/NS5 A complex is essential for viral RNA replication, up-regulation of GLTP by bicyclol reduced the level of VAP-A/NS5 A complex and thus inhibited HCV replication. Bicyclol also exhibited an inhibition on HCV variants resistant to direct-acting antiviral agents(DAAs) with an efficacy identical to that on wild type HCV. In combination with bicyclol, DAAs inhibited HCV replication in a synergistic fashion. GLTP appears to be a newly discovered host restrictive factor for HCV replication, Up-regulation of GLTP causes spontaneous restriction of HCV replication.
基金the National Natural Science Foundation of China(No.81873213,81473550)the Natural Science Foundation of Fujian Province(No.2017J01213,2016J0146)the Inn ovation Fund of Medical Science of Fujian Provi nee(No.2017-CX-42),China。
文摘Objective:To explore the mechanisms of Dangua Recipe(DGR)in improving glycolipid metabolism based on transcriptomics.Methods:Sprague-Dawley rats with normal glucose level were divided into 3 groups according to a random number table,including a conventional diet group(Group A),a DGR group(Group B,high-calorie diet+20.5 g DGR),and a high-calorie fodder model group(Group C).After 12 weeks of intervention,the liver tissue of rats was taken.Gene sequence and transcriptional analysis were performed to identify the key genes related to glycolipid metabolism reflecting DGR efficacy,and then gene or protein validation of liver tissue were performed.Nicotinamide phosphoribosyl transferase(Nampt)and phosphoenolpyruvate carboxykinase(PEPCK)proteins in liver tissues were detected by enzyme linked immunosorbent assay,fatty acid synthase(FASN)protein was detected by Western blot,and fatty acid binding protein 5(FABP5)-mRNA was detected by quantitative real-time polymerase chain reaction.Furthermore,the functional verification was performed on the diabetic model rats by Nampt blocker(GEN-617)injected in vivo.Hemoglobin A1c(HbA1c),plasma total cholesterol and triglycerides were detected.Results:Totally,257 differentialdominant genes of Group A vs.Group C and 392 differential-dominant genes of Group B vs.Group C were found.Moreover,11 Gene Ontology molecular function terms and 7 Kyoto Encyclopedia of Genes and Genomes enrichment pathways owned by both Group A vs.Group C and Group C vs.Group B were confirmed.The liver tissue target validation showed that Nampt,FASN,PEPCK protein and FABP5-mRNA had the same changes consistent with transcriptome.The in vivo functional tests showed that GEN-617 increased body weight,HbA1c,triglyceride and total cholesterol levels in the diabetic rats(P<0.05 or P<0.01);while all the above-mentioned levels(except triglyceride)were decreased significantly by GEN-617 combined with DGR intervention(P<0.05 or P<0.01).Conclusion:Nampt activation was one of the mechanisms about DGR regulating glycolipid metabolism.
