Objective:Psoriasis is associated with lipid metabolism disorders,but the underlying mechanisms remain unclear.This study aims to investigate the role of trimethylamine Noxide(TMAO)in lipid metabolism dysregulation in...Objective:Psoriasis is associated with lipid metabolism disorders,but the underlying mechanisms remain unclear.This study aims to investigate the role of trimethylamine Noxide(TMAO)in lipid metabolism dysregulation in psoriasis.Methods:An imiquimod(IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters,TMAO levels,and liver flavin monooxygenase 3(FMO3)mRNA expression.Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles.To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model,exogenous TMAO,choline,or 3,3-dimethyl-1-butanol(DMB)were administered via intraperitoneal injections or diet in IMQ-treated mice.Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways.Results:IMQ-induced psoriatic mice exhibited abnormal glucose,insulin,and lipid levels.IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2(Glut2)and silence information regulator 1(Sirt1),while upregulating glucose transporter 4(Glut4)and peroxisome proliferator-activated receptor gamma(PPARγ).Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice.Additionally,liver FMO3 mRNA expression was increased in the psoriatic mouse model.In patients,TMAO levels positively correlated with Psoriasis Area and Severity Index(PASI)scores,serum triglyceride(TG),and total cholesterol(TC)levels.The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice.A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice,whereas DMB treatment alleviated these effects.RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122(miR-122),which may suppress the expression of gremlin 2(GREM2),thus contributing to lipid metabolism disorder.Conclusion:TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.展开更多
To investigate the effects of allicin on chickens＇ lipid and antioxidant performance, Hy-laying hens＇ diets were replenished with 0 mg · kg-1, 50 mg · kg-1, 100 mg · kg-1, and 150 mg · kg-1 allic...To investigate the effects of allicin on chickens＇ lipid and antioxidant performance, Hy-laying hens＇ diets were replenished with 0 mg · kg-1, 50 mg · kg-1, 100 mg · kg-1, and 150 mg · kg-1 allicin for 42 days, respectively. The alanine aminotransferase（ALT）, aspartate aminotransferase（AST）, triglyceride（TG）, total cholesterol（TCHO）, high density lipoprotein（HDL）, and low density lipoprotein（LDL） levels were measured in chicken serum. Superoxide dismutase（SOD）, glutathione peroxidase（GSH-Px） activity and malondialdehyde（MDA） levels were measured in chicken serum and liver tissue homogenate. The results showed that the supplement dose of allicin tested did not significantly change the activity of ALT or AST（P〉0.05）; TG and CHOL levels decreased with the increase of allicin additive doses, and the difference between treatment groups and CG was significant（P〈0.05）, and there was the best effect with 100 mg · kg-1; allicin significantly reduced the content of MDA, and increased SOD and GSH-Px activities compared with CG（P〈0.05）, and 100 mg · kg-1 of allicin resulted in the strongest SOD and GSH-Px activity. The antioxidant function test results of liver tissue homogenate were consistant with that of serum. Our findings indicated that allicin could enhance antioxidant capacity and reduce blood lipid level in chickens and 100 mg · kg-1 was the optimal amount of allicin additives.展开更多
OBJECTIVE To investigate the effects of astragaloside IV(which can be extracted from the traditional Chinese medicine Astragalus membranaceus)on lipid and glucose metabolism in acute myocardial infarction(AMI).METHODS...OBJECTIVE To investigate the effects of astragaloside IV(which can be extracted from the traditional Chinese medicine Astragalus membranaceus)on lipid and glucose metabolism in acute myocardial infarction(AMI).METHODS Model of heart failure(HF)after AMI was established with ligation of left anterior descending artery on Sprague-Dawley(SD)rats.The rats were divided into three groups:sham,model and astragaloside IV treatment group.Twenty-eight days after treatment(astragaloside IV,20 mg·kg-1 daily),hematoxylin-eosin(HE)staining was applied to visualize cardiomyocyte morphological changes.High performance liquid chromatography(HPLC)was performed to assess the contents of adenosine phosphates in heart.Positron emission tomography and computed tomography(PET-CT)was conducted to evaluate the cardiac glucose metabolism.Expressions of key molecules such as peroxisome proliferatoractivated receptor γ(PPARγ),sterol carrier protein 2(SCP2)and long chain acyl CoA dehydrogenase(ACADL)were measured by Western blotting and immunohistochemistry.Oxygen-glucose deprivation-reperfusion(OGD/R)-induced H9C2 injury cardiomyocyte model was adopted for potential mechanism research in vitro.RESULTS Treatment with astragaloside Ⅳ rescued hearts from structural and functional damages as well as inflammatory infiltration.Levels of adenosine triphosphate(ATP)and energy charge(EC)in astragaloside IV group were also up-regulated compared to model group.Further results demonstrated that critical enzymes both in lipid metabolism and glucose metabolism compro mised in model group compared to sham group.Intriguingly,astragalosideⅣcould up-regulate critical enzymes including ACADL and SCP2 in lipid metabolism accompanying with promoting effect on molecules in glycolysis simultaneously.Results on upstreaming signaling pathway demonstrated that astragaloside Ⅳ could dramatically increase the expres sions of PPARγ.In vitro study suggested the efficacy of astragalosideⅣcould be blocked by T0070907,a selective PPARγ inhibitor.CONCLUSION Astragaloside IV has cardioprotective effect in improving cardiac function and energy metabolism through regulating lipid and glucose metabolism.The effects may be mediated by PPARγ pathway.展开更多
The energy metabolism structure of microbial community plays an important role in the process of biohydrometallurgy.In this article,an artificial microbial community composed of three strains(Acidithiobacillus ferroox...The energy metabolism structure of microbial community plays an important role in the process of biohydrometallurgy.In this article,an artificial microbial community composed of three strains(Acidithiobacillus ferrooxidans,Leptospirillum ferriphilum and Acidithiobacillus thiooxidans)was used to leach three kinds of chalcopyrites with different iron-sulfur ratios.After 36 d of leaching,the chalcopyrite with iron-sulfur ratio of about 1:1 achieved the highest copper extraction(69.62%).In the early stage,iron oxidizing bacteria predominated,and the expression of rus and rio was 8 times higher than that in the late stage.In the late stage,sulfur oxidizing bacteria predominated,and the expression of tetH and HdrAB was 4 times higher than that in the early stage.Furthermore,the three bioleaching systems above were added with elemental sulfur(3 g/L);the chalcopyrite with iron-sulfur ratio of about 2:1 achieved the highest copper extraction(80.63%).The results suggest that the energy metabolism structure of the microbial community could be changed by changing the iron-sulfur ratio during the leaching process for improving the leaching efficiency of chalcopyrite.展开更多
Background Mepiquat chloride(MC)application and plant population density(PPD)increasing are required for modern cotton production.However,their interactive effects on leaf physiology and carbohydrate metabolism remain...Background Mepiquat chloride(MC)application and plant population density(PPD)increasing are required for modern cotton production.However,their interactive effects on leaf physiology and carbohydrate metabolism remain obscure.This study aimed to examine whether and how MC and PPD affect the leaf morpho-physiological characteristics,and thus final cotton yield.PPD of three levels(D1:2.25 plants·m^(-2),D2:4.5 plants·m^(-2),and D3:6.75 plants·m^(-2))and MC dosage of two levels(MC0:0 g·ha^(-2),MC1:82.5 g·ha^(-2))were combined to create six treatments.The dynamics of nonstructual carbohydrate concentration,carbon metabolism-related enzyme activity,and photosynthetic attributes in cotton leaves were examined during reproductive growth in 2019 and 2020.Results Among six treatments,the high PPD of 6.75 plants·m^(-2)combined with MC application(MC1D3)exhibited the greatest seed cotton yield and biological yield.The sucrose,hexose,starch,and total nonstructural carbohydrate(TNC)concentrations peaked at the first flowering(FF)stage and then declined to a minimum at the first boll opening(FBO)stage.Compared with other treatments,MC1D3 improved starch and TNC concentration by 5.4%~88.4%,7.8%~52.0% in 2019,and by 14.6%~55.9%,13.5%~39.7% in 2020 at the FF stage,respectively.Additionally,MC1D3 produced higher transformation rates of starch and TNC from the FF to FBO stages,indicating greater carbon production and utilization efficiency.MC1D3 displayed the maximal specific leaf weight(SLW)at the FBO stage,and the highest chlorophyll a(Chl a),Chl b,and Chl a+b concentration at the mid-late growth phase in both years.The Rubisco activity with MC1D3 was 2.6%~53.2% higher at the flowering and boll setting stages in both years,and 2.4%~52.7% higher at the FBO stage in 2020 than those in other treatments.These results provided a explanation of higher leaf senescence-resistant ability in MC1D3.Conclusion Increasing PPD coupled with MC application improves cotton yield by enhancing leaf carbohydrate production and utilization efficiency and delaying leaf senescence.展开更多
In order to interpret pathologic mechanism of free radicals and thyroid hormone metabolism in cattle iodine and selenium deficiency, 20 heads of yellow cattle were selected from NiuJia town, Wu Chang City, Heilongjian...In order to interpret pathologic mechanism of free radicals and thyroid hormone metabolism in cattle iodine and selenium deficiency, 20 heads of yellow cattle were selected from NiuJia town, Wu Chang City, Heilongjiang Province, China, and were randomly devided into 4 groups with 5 for each. ① supplemented with 0.7 mg·kg -1 iodine(potassium iodine), ② supplemented with 0.2 mg·kg -1 selenium (sodium selenite), ③ supplemented with 0.7 mg·kg -1 iodine(potassium Iodine) plus 0.2 mg·kg -1 selenium (sodium selenite) per day for 30 days, respectively. ④control group. The whole blood glutathione peroxidase (GSH-px) and catalase (CAT) activities, free radicals (FR) concentration, erythrocyte superoxide dismutase (SOD) activity and molonaldehyde (MDA) concentration, the serum triiodothyronine (T 3)、thyroxine (T 4) and thyrotropin (TSH) were determined on the day of supplementation day-0 and day-30, respectively. It was showed that average iodine concentration in drinking water and diet were 3.82 μg·L -1 and 0.285mg·kg -1 , respectively, Diet selenium was 0.0498mg·kg -1 , Serum protein bound iodine(PBI) was 7.02 μg·100 mL, Blood selenium was 0.14 mg·L -1 , the schoolchildren′s goiter was 21.8%. It indicated that iodine and selenium were deficient in the investigated area. Whole blood GSH-px and CAT activities and serum T 3 concentration were significantly higher (P< 0.01 ), FR concentration and serum TSH were significantly lower(P<0.01) in the first three groups than that of the control, T 4 content in the first group was higher(P<0.05), T 4 was also higher (P>0.05) in the second group. and lower in the third group. The SOD and MDA in erythrocyte were not changed during the experimental period, The results also showed that GSH-px and CAT activities were increased, and FR decreased oberviously in the third group more than the other two groups, In addition, Thyroid hormone metabolism was more coincided with the physiologic status in the third group. the iodine and the selenium played an important role in the pathologic process of free radical metabolic disorder. selenium not only had the function of antioxidation by derectly scavenging free radicals, but also affected through GSH-px and CAT activities. iodine deficiency results in the Goiter, selenium deficiency aggravated iodine deficiency, Iodine and the selenium were dependent and restrained each other in the course of free radicals and thyroid hormone metabolism with a synergistic state.展开更多
Aim To investigate the intra-individual variation in activities of cytochrome P450 enzymes （CYP） in human liver microsomes （HLM）. Methods CYP＇s relative Kin, VmaX and CLi.t （n = 105） expressing as relative meta...Aim To investigate the intra-individual variation in activities of cytochrome P450 enzymes （CYP） in human liver microsomes （HLM）. Methods CYP＇s relative Kin, VmaX and CLi.t （n = 105） expressing as relative metabolic activities （RMAs） and variations of RMAs in 10 CYPs expressing as intra-individual percentage coeffi- cient of variations （ICV） were calculated. Results The ICVs of relative Vmax, K and CLint were 44.03% （16.79% -127.42% ）, 45.88% （18.31% -140. 14% ） and 52.00% （24.20%-134.81% ）. Overall RMAs for 10 CYPs were sorted. The orders, from highest to lowest, were CYP2D6, 1A2, 2C19, C9, 3A4/5, 2B6, 2A6, 2C8 and 2El for K , CYP3A4/5, 2C19, 2D6, 2C8, 2El, 2B6, 1A2, 2A6 and 2C9 for Vmax, CYP2D6, 2B6, 3A4/5, 2C19, 2C9, 1A2, 2El, 2C8 and 2A6 for CLint. CYP2A6＊ 4, CYP2B6 758A 〉 G and 2D6 100C 〉 T contributed to intra-individual variation in activities of CYPs. Conclusion The conception of ＂intra-individual variation＂ in activities of CYPs which means different CYPs presenting different activities of drug metabolism in one person was first put forward. We demonstrated that intra-individual variation in activities of CYPs were very remark- able in normal HLMs for the first time, which built a substantial foundation for the future development of precision medicine.展开更多
Purpose： Fibronectin type III domain-containing protein 5 （FNDC5）, also known as irisin, is a myokine secreted from muscle in response to exercise and improves obesity and glucose homeostasis. However, the molecula...Purpose： Fibronectin type III domain-containing protein 5 （FNDC5）, also known as irisin, is a myokine secreted from muscle in response to exercise and improves obesity and glucose homeostasis. However, the molecular mecha- nisms that regulate FNDC5 expression and the functional significance of FNDC5 in skeletal muscle remain un- known. In this study, we explored the possible pathways that induce FNDC5 expression and delineated its metabol- ic effects on skeletal muscle. Methods： C2C12 myotubes were treated with various concentrations of Sp-cAMP, forskolin, and ionomycin respectively for various durations. FNDC5 and related metabolic genes＇ expressions were measured by quantitative real-time polymerase chain reaction （qRT-PCR）. Cyclic AMP responsive element-binding protein （CREB） phosphorylation was measured by Western blot. Oxidative phosphorylation was quantified by oxy- gen consumption rate （OCR） measurement using XF-96 analyzer （Seahorse Bioscience）. The statistical signifi- cance was calculated by one-way analysis of variance （ANOVA）. Data were considered significant when P 〈 0.05. Results： We found that cAMP and forskolin dose and time dependently increased FNDC5 expression in C2C12 myotubes. A synergistic effect of forskolin and ionomycin on FNDC5 expression was also found. CREB phosphoryl- ation was elevated in myotubes simultaneously upon these treatments. C2C12 myotubes over expressing CREB dis- plays increased FNDC5 expression as well, suggesting CREB was a regulator of FNDC5 expression. Functionally, irisin treatment enhanced mitochondrial biogenesis of C2C12 myotubes through increasing peroxisome proliferator- activated receptor gamma coactivator-1α （PGC-1α）, nuclear respiratory factor 1 （NRF1） and mitochondrial tran-scription factor A （TFAM） expressions, leading to increase myotube mitochondrial respirations and ATP produc- tion. Conclusions Our observation indicates that irisin is a metabolic modulator of skeletal muscle, whose expres- sion is controlled by cAMP pathway and intracellular level of calcium.展开更多
Aim Baicalein is the major flavonoid obtained from the Scutellaria root. Our previous studies have dem- onstrated that baicalein has a clear positive effect on recovery in an experimental model of Parkinsonism. The pu...Aim Baicalein is the major flavonoid obtained from the Scutellaria root. Our previous studies have dem- onstrated that baicalein has a clear positive effect on recovery in an experimental model of Parkinsonism. The put- pose of this study was to investigate the role of baicalein in modulating dopamine （DA） metabolism in PC12 cells and to explore possible mechanisms of its actions. Methods The intracellular content and extracellular release of DA in both rotenone-treated and untreated PC12 cells were examined. Second, PC12 cells were first pretreated with baicalein （ 10 μmol · L^-1 ） for 10 rain, and then incubated with or without ionomycin （5 μmol · L^-1 ） for 10 rain to test whether short-term exposure to baicalein affected calcium-dependent or spontaneous DA release. Third, the intracellular and extracellular contents of DA and its related metabolites were examined. After treatment with baica- lein for 24 h, the The tyrosine hydroxylase （TH）, monoamine oxidase B （MAOB）, catechol-O-methyltransferase （COMT） and dopamine transporter （DAT） were detected by immunoblot analysis. Results The results showed that baicalein prevented rotenone-induced cytotoxicity and significantly increased the DA content in both rotenone- treated and untreated PC12 cells. Furthermore, it had no effect on ionomycin-induced or spontaneous DA release after short-term exposure but significantly increased DA content in a time- and dose-dependent manner after treat- ment for 6 h. Baicalein also significantly decreased the intracellular and extracellular homovanillic acid （HVA） content but increased the intracellular 3,4-dihydroxy phenylacetic acid （DOPAC） content. Finally, baicalein sig- nificantly decreased the expression of COMT and DAT, but it had no effect on the expression of TH and MAOB. Conclusion These data suggest that bacalein has the ability to increase DA content and modulate DA metabolism by inhibiting the expression of COMT and DAT. Our study provides evidence that baicalein may be a potential anti- PD drug that merits further study.展开更多
OBJECTIVE To map a comprehensive metabolic pathway of herbacetin in rats,specifically,to elucidate the biotransformation of herbacetin in vivo and to simultaneously monitor the pharmacokinetic process of both parent d...OBJECTIVE To map a comprehensive metabolic pathway of herbacetin in rats,specifically,to elucidate the biotransformation of herbacetin in vivo and to simultaneously monitor the pharmacokinetic process of both parent drug and its major metabolites.METHODS liquid chromatography/ion trap mass spectrometry(LC/MS n) and ultra-liquid chromatography coupled with mass spectrometry(UPLC/MS) were combined in the current study for qualitative and quantitative determinations of herbacetin and its metabolites in bile,urine and feces after both oral and intravenous administration of herbacetin to rats.Enzyme kinetic studies on the intestinal and hepatic metabolism of herbacetin were further conducted to elucidate metabolic profiles of herbacetin in rat tissues and organs.Additionally,plasma concentration profiles of herbacetin and its metabolites in rats were obtained to characterize the overall pharmacokinetic behavior of herbacetin.RESULTS It was found that herbacetin was excreted primarily from rat urine in the form of glucuronide-conjugations.Subsequent in vitro enzyme kinetic studies and in vivo pharmacokinetic investigations suggested an extensive hepatic metabolism of herbacetin and the high exposure of herbacetin-glucuronides in systemic circulation.The clearance,half-life and bioavailability of herbacetin in rats were determined as(16.4±1.92)mL·kg^(-1)·min^(-1),(11.9±2.7)min,and 1.32%,respectively.On basis of these findings,a comprehensive metabolic pathway of herbacetin in rats was composed.In addition,a physiology based pharmacokinetic(PBPK) model was successfully developed with the aid of the Gastro Plus to simulate the pharmacokinetic process of herbacetin in rats.Application of the PBPK modeling can provide a useful starting point to understand and extrapolate pharmacokinetic parameters among different species,populations,and disease states.CONCLUSION After oral administration,herbacetin was subjected to colonic degradation and extensive first pass metabolism,with glucuronidation as its dominating in vivo metabolic pathway.展开更多
Objective To elucidate the transformation of energy metabolism patterns in the process of myocardial remodeling induced by volumeoverload and to explore a novel intervention target for the prevention,delay or even rev...Objective To elucidate the transformation of energy metabolism patterns in the process of myocardial remodeling induced by volumeoverload and to explore a novel intervention target for the prevention,delay or even reversal of structural heart dysfunction.Methods Thirty C57/BL6 mice,20-30 g,half male and half female,were randomly divided into model group(n=15)and sham operation group(n=15).Each group was divided into subacute phase(2 weeks after surgery,n=5),cardiac functional compensation phase(5 weeks after surgery,n=5)and decompensation phase(15 weeks after surgery,n=5).展开更多
OBJECTIVE Forsythiae Fructus(Lianqiao)is a typical heat-clearing and detoxicating traditional Chinese medicine(TCM)herb,which has been traditionally used for treating cancer according to TCM theory.However,the underly...OBJECTIVE Forsythiae Fructus(Lianqiao)is a typical heat-clearing and detoxicating traditional Chinese medicine(TCM)herb,which has been traditionally used for treating cancer according to TCM theory.However,the underlying mechanism has not been fully explained.METHODS In this study,we investigated the antitumor effect of Forsythiae Fructus aqueous extract(FAE)on B16-F10 melanoma.RESULTS FAE strongly inhibited the tumor growth and metastasis formation in B16-F10 melanoma transplanted mice.The survival time of tumor-bearing mice was also significantly prolonged by FAE.The levels of ROS,MDA,TNF-αand IL-6 decreased,while GSH increased in the FAE treatment group,indicating FAE possesses strong anti-oxidative and anti-inflammatory activity.Western blotting analysis demonstrated that antioxidant proteins Nrf2 and HO-1,tumor suppressors P53 and p-PTEN,and the MAPK pathways in tumor tissues were upregulated by FAE treatment.Serum metabolomics analysis further uncovered that 17 metabolites mostly involving in glycerophospholipid metabolism were correlated with the antitumor effect of FAE.Notably,several lysophosphatidylcholines(LysoPCs)significantly decreased in tumor model group,while FAE treatment restored the changes of these phospholipids to about normal condition.LysoPC acyltransferase 1(LPCAT1)and autotaxin(ATX)highly expressed in melanoma and markedly downregulated by FAE were believed to be responsible for this modulation.CONCLUSION FAE exhibites strong antitumor activity against B16-F10 melanoma through activating MAPKs/Nrf2/HO-1 mediated anti-oxidation and anti-inflammation and modulating glycerophospholipid metabolism via downregulating LPCAT1 and ATX.Besides,it is suggested that serum LysoPCs could be potential biomarkers for the diagnosis and prognosis of melanoma.展开更多
The aim of this study was to determine the effects of supplementing organic forms of zinc(zinc acetate,ZnA)and inorganic zinc(zinc sulfate,Zn S)on performance,the gain to feed ratio(G:F)and skeletal characters in broi...The aim of this study was to determine the effects of supplementing organic forms of zinc(zinc acetate,ZnA)and inorganic zinc(zinc sulfate,Zn S)on performance,the gain to feed ratio(G:F)and skeletal characters in broilers from the first day to the 42th day.A total of 240-day-old broilers(Arbor Acres)were randomly distributed in four groups.A corn-soybean meal-based control diet containing recommended concentrations of inorganic trace minerals and other nutrients was prepared.On the basal diets,the control goup(CG)was supplemented with Zn S and the treatment group(TG)feeding diets were with different ZnA supplemental levels(80,100 and 150 mg·kg^-1)of ZnA.Each group was allotted randomly to five replicates and 12 broilers in each replicate and fed ad libitum from the first day to the 42th day.The results showed that supplementation of ZnA significantly increased(p<0.05)energy and phosphorus(P)compared to that fed Zn S on the 21th day.Calcium(Ca),tibia weight,ash weight,tibia Ca and tibia P in TG(80 mg·kg^-1 of ZnA)were the highest(p<0.05).The pancreas Zn content of TG was higher than that in CG and increased with the supplementation of ZnA.On the 42th day,the content of energy,crude protein(CP),Ca and tibia Ca in TG(80 mg·kg^-1 of ZnA)were the highest(p<0.05),the change of pancreas Zn was the same as the results on the 21th day,but enter extract(EE),tibia weight,tibia length,tibia width and ash weight were not affected(p>0.05)by ZnA.The results of this study showed that ZnA was better than Zn S in improving the early growth performance,nutrient utilization rate in broilers,the length and weight of broiler tibia,it promoted the calcium,phosphorus deposition and normal growth of tibia,and the optimum dietary ZnA level to feed was 80 mg·kg^-1.ZnA affected body Zn stores and the apparent metabolic rate of nutrients.展开更多
OBJECTIVE To investigate berberine(BBR)attenuates arthritis in adjuvant-induced arthritic(AA)rats associated with regulating the energy metabolism and correcting the polarization of macrophages through activation of A...OBJECTIVE To investigate berberine(BBR)attenuates arthritis in adjuvant-induced arthritic(AA)rats associated with regulating the energy metabolism and correcting the polarization of macrophages through activation of AMP-activated protein kinase(AMPK)and inhibition of hypoxia inducible factor 1α(HIF-1α).METHODS AA rats were treated with BBR(40,80,or 160 mg·kg-1)from days 15 to 29 after immunization.The histopathology of ankle joint was examined through hematoxylin-eosin(HE)staining.The concentrations of tumour necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β,IL-2,IL-17A,interferon-gamma(IFN-γ),monocyte chemotactic protein 1(MCP-1),IL-4,IL-10,transforming growth factor-β1(TGF-β1),ATP,and lactic acid were measured by using ELISA kits.The percentage of M1 and M2 macro⁃phage cells in joint tissues were evaluated by immune-fluorescence.The expressions of p-AMPK and HIF-1αin joint of AA rats were determined according to immunohistochemistry analysis.The migration of macrophage was detected by Transwell assays.The expression of inducible nitric oxide synthase(iNOS),Arginase-1(Arg1),p-AMPK,AMPK and HIF-1αwere examined by Western blotting.The labeled macrophages were observed with laser confocal microscopy.RESULTS BBR relieved signs and symptoms of AA rats and reversed pathological changes.BBR treatment group exhibited decreases in pro-inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-2,IL-17A,IFN-γ,and MCP-1)coupled with increases anti-inflammatory cytokines(IL-4,IL-10,TGF-β1)in the serum.The number of M1 macrophage was reduced,while the number of M2 macrophage was increased in BBR group joint tissues.Moreover,BBR showed marked up-regu⁃lation the expression of p-AMPK and down-regulation the expression of HIF-1αin joint of AA rats.Next in vitro study,we found BBR up-regulated the expression of p-AMPK,Arg1(M2 marker)and down-regulated the expression of HIF-1α,iNOS(M1 marker)induced by LPS in peritoneal macrophages from normal SD rat.Furthermore,BBR treatment inhibited the migration of macrophages stimulated by LPS.The level of ATP was elevated and lactic acid was reduced in LPSinduced macrophages after treated by BBR.However,Compound C significantly attenuated the effects of BBR on acti⁃vated macrophages.CONCLUSION BBR alleviates inflammation by regulating energy metabolism and correcting the polarization of macrophage through AMPK-HIF-1αpathway.BBR might have great therapeutic value for RA.展开更多
The nitrogen (N) metabolic experiments were made to estimate separately amino acid requirements of 4348 weeks old layers for maintenance, for protein accretion to estabolish models to estimate digestible amino acid re...The nitrogen (N) metabolic experiments were made to estimate separately amino acid requirements of 4348 weeks old layers for maintenance, for protein accretion to estabolish models to estimate digestible amino acid requirements. The regression relationship of nitrogen retention vs amino acid intake was estimated for each amino acid by giving, at rate of N intake of 091, 052, 015 and 0007gkg-1 body-weight (W075) per d, the semi-synthetic diets was made specially deficient in one amino acid. From the regression coefficients, it was calculated that, for the accretion of 1 g protein, the dietary digestible amino acid requirements were (mg) Thr 631, Val 1004, Met 399, Ile 886, Leu 1143, Phe 632, Lys 870, His 205, Arg 879, Trp 214, Met+Cys 776, and Phe+Tyr 1143. Daily amino acid requirements for N equilibrium were estimated to be (mgkg-1W075 per day) Thr 506, Val 747, Met 303, ILe 667 Leu 814, Phe 448, Lys 605 His 147, Arg 739 ,Trp 173, Met+Cys 586, and Phe+Tyr 839 The dietary degestible amino acid patterns for protein accretion and N equilibrium were also proposed. The models of estimating digestible amino acid requirements for the different productions were developed.展开更多
OBJECTIVE Pulmonary arterial hypertension(PAH)is a malignant pulmonary vascular disease lacking efficacy therapeutics.Therefore,it urgently needs to develop safe and effective drugs for PAH treatment.Osthole derived f...OBJECTIVE Pulmonary arterial hypertension(PAH)is a malignant pulmonary vascular disease lacking efficacy therapeutics.Therefore,it urgently needs to develop safe and effective drugs for PAH treatment.Osthole derived from Cnidium monnieri(L.)Cusson(Shechuangzi)or Angelica pubescens Maxim(Duhuo)has the capacity to alleviate PAH by decreasing pulmonary arterial pressure and alleviating pulmonary vascular remodeling in rats,which is a candidate drug for the prevention of PAH,but the underlying modulatory mechanism is still unclear.Our study aims at investigating the metabolic modulatory mechanism of osthole against PAH employing functional metabolomics strategy.METHODS PAH model rats were successfully established with MCT,following osthole administration,then functional metabolomics based on untargeted metabolomics assay,targeted lipidomics analysis,qRT-PCR,Western blotting and ELISA were performed to investigate the modulatory mechanism of osthole against pulmonary arterial pressure and pulmonary vascular remodeling in PAH.RESULTS Untargeted metabolomics results found that sphingosine 1-phosphate(S1P)was the differential metabolites characterized PAH and reversed by osthole treatment.S1P is a crucial sphingolipid metabolite catalyzed by sphingosine kinases1(Sphk1)and functions as promoting PASMCs proliferation contributing to pulmonary vascular remodeling and pulmonary arterial pressure increase.We revealed that osthole reversed high level of S1P by modulating metabolic enzyme Sphk1 via inactivating microRNA-21-PI3K/Akt/mTOR signal pathway to decrease pulmonary arterial pressure in rats with PAH.Then,targeted phospholipid metabolomics results uncovered that decadienyl-L-carnitine(C10:2)was the differential metabolite characterized PAH and corrected by osthole treatment in rat with PAH.C10:2 is the intermediate metabolite of fatty acid oxidation(FAO),and C10:2 accumulation indicated mitochondrial dysfunction and FAO increase.CONCLUSION Osthole could block lipid metabolic reprogramming through functional modulating the expression of fatty acid translocase,fatty acid synthase,phospholipase A2,carnitine palmitoyltransferase 1A to inhibit C10:2,thus to improve mitochondrial dysfunction and inhibit utilizing lipid to biosynthesize necessary essence for pulmonary artery smooth muscle cells(PASMCs)proliferation.Moreover,we delineated that C10:2 and metabolic reprogramming enzymes were modulated by miRNA-22-3p which was involved in PASMCs proliferation and pulmonary vascular remodeling.Therefore,osthole inhibited miRNA-22-3p mediated lipid metabolic reprogramming to ameliorate pulmonary vascular remodeling.展开更多
To investigate the effects and mechanisms of the benzimidazole carbamate and benmidine drugs on Cysticerci cellulosae and choose effective drugs on Cysticerci cellulosae, the membrane metabolism of Cysticerci cellulos...To investigate the effects and mechanisms of the benzimidazole carbamate and benmidine drugs on Cysticerci cellulosae and choose effective drugs on Cysticerci cellulosae, the membrane metabolism of Cysticerci cellulosae in vitro was tested after three kinds of drugs which were used respectively. The indexes included the contents of lipids, the contents of SA and the changes of the membrane fluidity. The results showed that oxfendazole could inhibit the membrane metabolism of immature and mature Cysticerci cellulosae in vitro, and albendazole only inhibited the mature one, while thibendimidine neither acted on the immature nor mature one.展开更多
The nuclear receptor peroxisome proliferator-activated receptor γ（PPAR-γ） is a key transcriptional regulator of adipocyte differentiation.It also modulates the synthesis of adipocytokines in the adipose tissue.Its...The nuclear receptor peroxisome proliferator-activated receptor γ（PPAR-γ） is a key transcriptional regulator of adipocyte differentiation.It also modulates the synthesis of adipocytokines in the adipose tissue.Its polymorphisms are associated with the risk of type Ⅱ diabetes,obesity,cardiovascular diseases and cancer.In the present study,to investigate the regulatory mechanism of PPAR-γ gene on lipid metabolism,the computational prediction of peroxisome proliferator response elements（PPREs） was pursued with a genome-wide scale by using MEME/MAST method based on the information of TRANSFAC database,then GO and KEGG analyses were carried out.The results showed that a huge number of predicted target genes of PPAR-γ were significantly enriched in 36 GO terms（P〈0.05） and 10 KEGG pathways（P〈0.05） which were related closely to the lipid metabolism.The results should be a valuable resource for elucidation of the regulatory mechanism of PPAR-γ influence on lipid metabolism,also of the major importance to the diagnosis,prevention and treatment of the complex diseases such as obesity and diabete.展开更多
We encourage submission of fundamental discoveries or technological advancement in areas of plant main metabolism,discovering of medicinal plant and natural products,elucidating of metabolism pathways and their biolog...We encourage submission of fundamental discoveries or technological advancement in areas of plant main metabolism,discovering of medicinal plant and natural products,elucidating of metabolism pathways and their biological functions,application of metabolic engineering for synthesis of bioactive natural products,and study on metabolic networks and their functions.展开更多
In order to research effects of the nitrogen top-dressing levels on carbon-nitrogen metabolism and yield of Desmodium styracifolium, a field experiment was conducted on the research farm of Guangxi University in 2007....In order to research effects of the nitrogen top-dressing levels on carbon-nitrogen metabolism and yield of Desmodium styracifolium, a field experiment was conducted on the research farm of Guangxi University in 2007. Some physiological indexes and yield ofD. styracifolium were compared among five nitrogen top-dressing levels （0, 37.5, 75.0, 112.5 and 150.0 kg N. hm-2）. Results showed that the nitrogen top-dressing could significantly increase the contents of chlorophyll, soluble protein, sucrose and nitrogen as well as nitrate reducase activity. However, there were no significant differences in most of these indexes under high nitrogen levels. Consistently, there was no significant difference in yield among nitrogen top-dressing levels of 75 kg N.hm-2, 112.5 kg N. hm-2 and 150 kg N-hm-2. Therefore, the optimum nitrogen top-dressing level ofD. styracifolium was 75 kg N. hm-2.展开更多
基金supported by the National Natural Science Foundation(82173426)the Natural Science Foundation of Hunan Province(2023JJ30984),China。
文摘Objective:Psoriasis is associated with lipid metabolism disorders,but the underlying mechanisms remain unclear.This study aims to investigate the role of trimethylamine Noxide(TMAO)in lipid metabolism dysregulation in psoriasis.Methods:An imiquimod(IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters,TMAO levels,and liver flavin monooxygenase 3(FMO3)mRNA expression.Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles.To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model,exogenous TMAO,choline,or 3,3-dimethyl-1-butanol(DMB)were administered via intraperitoneal injections or diet in IMQ-treated mice.Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways.Results:IMQ-induced psoriatic mice exhibited abnormal glucose,insulin,and lipid levels.IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2(Glut2)and silence information regulator 1(Sirt1),while upregulating glucose transporter 4(Glut4)and peroxisome proliferator-activated receptor gamma(PPARγ).Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice.Additionally,liver FMO3 mRNA expression was increased in the psoriatic mouse model.In patients,TMAO levels positively correlated with Psoriasis Area and Severity Index(PASI)scores,serum triglyceride(TG),and total cholesterol(TC)levels.The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice.A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice,whereas DMB treatment alleviated these effects.RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122(miR-122),which may suppress the expression of gremlin 2(GREM2),thus contributing to lipid metabolism disorder.Conclusion:TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.
文摘To investigate the effects of allicin on chickens＇ lipid and antioxidant performance, Hy-laying hens＇ diets were replenished with 0 mg · kg-1, 50 mg · kg-1, 100 mg · kg-1, and 150 mg · kg-1 allicin for 42 days, respectively. The alanine aminotransferase（ALT）, aspartate aminotransferase（AST）, triglyceride（TG）, total cholesterol（TCHO）, high density lipoprotein（HDL）, and low density lipoprotein（LDL） levels were measured in chicken serum. Superoxide dismutase（SOD）, glutathione peroxidase（GSH-Px） activity and malondialdehyde（MDA） levels were measured in chicken serum and liver tissue homogenate. The results showed that the supplement dose of allicin tested did not significantly change the activity of ALT or AST（P〉0.05）; TG and CHOL levels decreased with the increase of allicin additive doses, and the difference between treatment groups and CG was significant（P〈0.05）, and there was the best effect with 100 mg · kg-1; allicin significantly reduced the content of MDA, and increased SOD and GSH-Px activities compared with CG（P〈0.05）, and 100 mg · kg-1 of allicin resulted in the strongest SOD and GSH-Px activity. The antioxidant function test results of liver tissue homogenate were consistant with that of serum. Our findings indicated that allicin could enhance antioxidant capacity and reduce blood lipid level in chickens and 100 mg · kg-1 was the optimal amount of allicin additives.
基金National Natural Science Foundation of China(81530100,81673802,81673712,81822049)。
文摘OBJECTIVE To investigate the effects of astragaloside IV(which can be extracted from the traditional Chinese medicine Astragalus membranaceus)on lipid and glucose metabolism in acute myocardial infarction(AMI).METHODS Model of heart failure(HF)after AMI was established with ligation of left anterior descending artery on Sprague-Dawley(SD)rats.The rats were divided into three groups:sham,model and astragaloside IV treatment group.Twenty-eight days after treatment(astragaloside IV,20 mg·kg-1 daily),hematoxylin-eosin(HE)staining was applied to visualize cardiomyocyte morphological changes.High performance liquid chromatography(HPLC)was performed to assess the contents of adenosine phosphates in heart.Positron emission tomography and computed tomography(PET-CT)was conducted to evaluate the cardiac glucose metabolism.Expressions of key molecules such as peroxisome proliferatoractivated receptor γ(PPARγ),sterol carrier protein 2(SCP2)and long chain acyl CoA dehydrogenase(ACADL)were measured by Western blotting and immunohistochemistry.Oxygen-glucose deprivation-reperfusion(OGD/R)-induced H9C2 injury cardiomyocyte model was adopted for potential mechanism research in vitro.RESULTS Treatment with astragaloside Ⅳ rescued hearts from structural and functional damages as well as inflammatory infiltration.Levels of adenosine triphosphate(ATP)and energy charge(EC)in astragaloside IV group were also up-regulated compared to model group.Further results demonstrated that critical enzymes both in lipid metabolism and glucose metabolism compro mised in model group compared to sham group.Intriguingly,astragalosideⅣcould up-regulate critical enzymes including ACADL and SCP2 in lipid metabolism accompanying with promoting effect on molecules in glycolysis simultaneously.Results on upstreaming signaling pathway demonstrated that astragaloside Ⅳ could dramatically increase the expres sions of PPARγ.In vitro study suggested the efficacy of astragalosideⅣcould be blocked by T0070907,a selective PPARγ inhibitor.CONCLUSION Astragaloside IV has cardioprotective effect in improving cardiac function and energy metabolism through regulating lipid and glucose metabolism.The effects may be mediated by PPARγ pathway.
基金Project(2017zzts382)supported by Central South University Postgraduate Independent Exploration and Innovation,ChinaProject(2014jpkc003)supported by Central South University Graduate Excellent Course,China+1 种基金Project(2015JJ2165)supported by Hunan Provincial Natural Science Foundation of ChinaProject(165611031)supported by Central South University Fundamental Research Funds Special Funding,China。
文摘The energy metabolism structure of microbial community plays an important role in the process of biohydrometallurgy.In this article,an artificial microbial community composed of three strains(Acidithiobacillus ferrooxidans,Leptospirillum ferriphilum and Acidithiobacillus thiooxidans)was used to leach three kinds of chalcopyrites with different iron-sulfur ratios.After 36 d of leaching,the chalcopyrite with iron-sulfur ratio of about 1:1 achieved the highest copper extraction(69.62%).In the early stage,iron oxidizing bacteria predominated,and the expression of rus and rio was 8 times higher than that in the late stage.In the late stage,sulfur oxidizing bacteria predominated,and the expression of tetH and HdrAB was 4 times higher than that in the early stage.Furthermore,the three bioleaching systems above were added with elemental sulfur(3 g/L);the chalcopyrite with iron-sulfur ratio of about 2:1 achieved the highest copper extraction(80.63%).The results suggest that the energy metabolism structure of the microbial community could be changed by changing the iron-sulfur ratio during the leaching process for improving the leaching efficiency of chalcopyrite.
基金supported by the National Natural Science Foundation of China(grant no.31960385)the Natural Science Foundation of Jiangxi,China(grant no.20212BAB215009)。
文摘Background Mepiquat chloride(MC)application and plant population density(PPD)increasing are required for modern cotton production.However,their interactive effects on leaf physiology and carbohydrate metabolism remain obscure.This study aimed to examine whether and how MC and PPD affect the leaf morpho-physiological characteristics,and thus final cotton yield.PPD of three levels(D1:2.25 plants·m^(-2),D2:4.5 plants·m^(-2),and D3:6.75 plants·m^(-2))and MC dosage of two levels(MC0:0 g·ha^(-2),MC1:82.5 g·ha^(-2))were combined to create six treatments.The dynamics of nonstructual carbohydrate concentration,carbon metabolism-related enzyme activity,and photosynthetic attributes in cotton leaves were examined during reproductive growth in 2019 and 2020.Results Among six treatments,the high PPD of 6.75 plants·m^(-2)combined with MC application(MC1D3)exhibited the greatest seed cotton yield and biological yield.The sucrose,hexose,starch,and total nonstructural carbohydrate(TNC)concentrations peaked at the first flowering(FF)stage and then declined to a minimum at the first boll opening(FBO)stage.Compared with other treatments,MC1D3 improved starch and TNC concentration by 5.4%~88.4%,7.8%~52.0% in 2019,and by 14.6%~55.9%,13.5%~39.7% in 2020 at the FF stage,respectively.Additionally,MC1D3 produced higher transformation rates of starch and TNC from the FF to FBO stages,indicating greater carbon production and utilization efficiency.MC1D3 displayed the maximal specific leaf weight(SLW)at the FBO stage,and the highest chlorophyll a(Chl a),Chl b,and Chl a+b concentration at the mid-late growth phase in both years.The Rubisco activity with MC1D3 was 2.6%~53.2% higher at the flowering and boll setting stages in both years,and 2.4%~52.7% higher at the FBO stage in 2020 than those in other treatments.These results provided a explanation of higher leaf senescence-resistant ability in MC1D3.Conclusion Increasing PPD coupled with MC application improves cotton yield by enhancing leaf carbohydrate production and utilization efficiency and delaying leaf senescence.
文摘In order to interpret pathologic mechanism of free radicals and thyroid hormone metabolism in cattle iodine and selenium deficiency, 20 heads of yellow cattle were selected from NiuJia town, Wu Chang City, Heilongjiang Province, China, and were randomly devided into 4 groups with 5 for each. ① supplemented with 0.7 mg·kg -1 iodine(potassium iodine), ② supplemented with 0.2 mg·kg -1 selenium (sodium selenite), ③ supplemented with 0.7 mg·kg -1 iodine(potassium Iodine) plus 0.2 mg·kg -1 selenium (sodium selenite) per day for 30 days, respectively. ④control group. The whole blood glutathione peroxidase (GSH-px) and catalase (CAT) activities, free radicals (FR) concentration, erythrocyte superoxide dismutase (SOD) activity and molonaldehyde (MDA) concentration, the serum triiodothyronine (T 3)、thyroxine (T 4) and thyrotropin (TSH) were determined on the day of supplementation day-0 and day-30, respectively. It was showed that average iodine concentration in drinking water and diet were 3.82 μg·L -1 and 0.285mg·kg -1 , respectively, Diet selenium was 0.0498mg·kg -1 , Serum protein bound iodine(PBI) was 7.02 μg·100 mL, Blood selenium was 0.14 mg·L -1 , the schoolchildren′s goiter was 21.8%. It indicated that iodine and selenium were deficient in the investigated area. Whole blood GSH-px and CAT activities and serum T 3 concentration were significantly higher (P< 0.01 ), FR concentration and serum TSH were significantly lower(P<0.01) in the first three groups than that of the control, T 4 content in the first group was higher(P<0.05), T 4 was also higher (P>0.05) in the second group. and lower in the third group. The SOD and MDA in erythrocyte were not changed during the experimental period, The results also showed that GSH-px and CAT activities were increased, and FR decreased oberviously in the third group more than the other two groups, In addition, Thyroid hormone metabolism was more coincided with the physiologic status in the third group. the iodine and the selenium played an important role in the pathologic process of free radical metabolic disorder. selenium not only had the function of antioxidation by derectly scavenging free radicals, but also affected through GSH-px and CAT activities. iodine deficiency results in the Goiter, selenium deficiency aggravated iodine deficiency, Iodine and the selenium were dependent and restrained each other in the course of free radicals and thyroid hormone metabolism with a synergistic state.
文摘Aim To investigate the intra-individual variation in activities of cytochrome P450 enzymes （CYP） in human liver microsomes （HLM）. Methods CYP＇s relative Kin, VmaX and CLi.t （n = 105） expressing as relative metabolic activities （RMAs） and variations of RMAs in 10 CYPs expressing as intra-individual percentage coeffi- cient of variations （ICV） were calculated. Results The ICVs of relative Vmax, K and CLint were 44.03% （16.79% -127.42% ）, 45.88% （18.31% -140. 14% ） and 52.00% （24.20%-134.81% ）. Overall RMAs for 10 CYPs were sorted. The orders, from highest to lowest, were CYP2D6, 1A2, 2C19, C9, 3A4/5, 2B6, 2A6, 2C8 and 2El for K , CYP3A4/5, 2C19, 2D6, 2C8, 2El, 2B6, 1A2, 2A6 and 2C9 for Vmax, CYP2D6, 2B6, 3A4/5, 2C19, 2C9, 1A2, 2El, 2C8 and 2A6 for CLint. CYP2A6＊ 4, CYP2B6 758A 〉 G and 2D6 100C 〉 T contributed to intra-individual variation in activities of CYPs. Conclusion The conception of ＂intra-individual variation＂ in activities of CYPs which means different CYPs presenting different activities of drug metabolism in one person was first put forward. We demonstrated that intra-individual variation in activities of CYPs were very remark- able in normal HLMs for the first time, which built a substantial foundation for the future development of precision medicine.
文摘Purpose： Fibronectin type III domain-containing protein 5 （FNDC5）, also known as irisin, is a myokine secreted from muscle in response to exercise and improves obesity and glucose homeostasis. However, the molecular mecha- nisms that regulate FNDC5 expression and the functional significance of FNDC5 in skeletal muscle remain un- known. In this study, we explored the possible pathways that induce FNDC5 expression and delineated its metabol- ic effects on skeletal muscle. Methods： C2C12 myotubes were treated with various concentrations of Sp-cAMP, forskolin, and ionomycin respectively for various durations. FNDC5 and related metabolic genes＇ expressions were measured by quantitative real-time polymerase chain reaction （qRT-PCR）. Cyclic AMP responsive element-binding protein （CREB） phosphorylation was measured by Western blot. Oxidative phosphorylation was quantified by oxy- gen consumption rate （OCR） measurement using XF-96 analyzer （Seahorse Bioscience）. The statistical signifi- cance was calculated by one-way analysis of variance （ANOVA）. Data were considered significant when P 〈 0.05. Results： We found that cAMP and forskolin dose and time dependently increased FNDC5 expression in C2C12 myotubes. A synergistic effect of forskolin and ionomycin on FNDC5 expression was also found. CREB phosphoryl- ation was elevated in myotubes simultaneously upon these treatments. C2C12 myotubes over expressing CREB dis- plays increased FNDC5 expression as well, suggesting CREB was a regulator of FNDC5 expression. Functionally, irisin treatment enhanced mitochondrial biogenesis of C2C12 myotubes through increasing peroxisome proliferator- activated receptor gamma coactivator-1α （PGC-1α）, nuclear respiratory factor 1 （NRF1） and mitochondrial tran-scription factor A （TFAM） expressions, leading to increase myotube mitochondrial respirations and ATP produc- tion. Conclusions Our observation indicates that irisin is a metabolic modulator of skeletal muscle, whose expres- sion is controlled by cAMP pathway and intracellular level of calcium.
文摘Aim Baicalein is the major flavonoid obtained from the Scutellaria root. Our previous studies have dem- onstrated that baicalein has a clear positive effect on recovery in an experimental model of Parkinsonism. The put- pose of this study was to investigate the role of baicalein in modulating dopamine （DA） metabolism in PC12 cells and to explore possible mechanisms of its actions. Methods The intracellular content and extracellular release of DA in both rotenone-treated and untreated PC12 cells were examined. Second, PC12 cells were first pretreated with baicalein （ 10 μmol · L^-1 ） for 10 rain, and then incubated with or without ionomycin （5 μmol · L^-1 ） for 10 rain to test whether short-term exposure to baicalein affected calcium-dependent or spontaneous DA release. Third, the intracellular and extracellular contents of DA and its related metabolites were examined. After treatment with baica- lein for 24 h, the The tyrosine hydroxylase （TH）, monoamine oxidase B （MAOB）, catechol-O-methyltransferase （COMT） and dopamine transporter （DAT） were detected by immunoblot analysis. Results The results showed that baicalein prevented rotenone-induced cytotoxicity and significantly increased the DA content in both rotenone- treated and untreated PC12 cells. Furthermore, it had no effect on ionomycin-induced or spontaneous DA release after short-term exposure but significantly increased DA content in a time- and dose-dependent manner after treat- ment for 6 h. Baicalein also significantly decreased the intracellular and extracellular homovanillic acid （HVA） content but increased the intracellular 3,4-dihydroxy phenylacetic acid （DOPAC） content. Finally, baicalein sig- nificantly decreased the expression of COMT and DAT, but it had no effect on the expression of TH and MAOB. Conclusion These data suggest that bacalein has the ability to increase DA content and modulate DA metabolism by inhibiting the expression of COMT and DAT. Our study provides evidence that baicalein may be a potential anti- PD drug that merits further study.
基金supported by National Foundation of Natural Sciences of China(81573683 and 81173121)
文摘OBJECTIVE To map a comprehensive metabolic pathway of herbacetin in rats,specifically,to elucidate the biotransformation of herbacetin in vivo and to simultaneously monitor the pharmacokinetic process of both parent drug and its major metabolites.METHODS liquid chromatography/ion trap mass spectrometry(LC/MS n) and ultra-liquid chromatography coupled with mass spectrometry(UPLC/MS) were combined in the current study for qualitative and quantitative determinations of herbacetin and its metabolites in bile,urine and feces after both oral and intravenous administration of herbacetin to rats.Enzyme kinetic studies on the intestinal and hepatic metabolism of herbacetin were further conducted to elucidate metabolic profiles of herbacetin in rat tissues and organs.Additionally,plasma concentration profiles of herbacetin and its metabolites in rats were obtained to characterize the overall pharmacokinetic behavior of herbacetin.RESULTS It was found that herbacetin was excreted primarily from rat urine in the form of glucuronide-conjugations.Subsequent in vitro enzyme kinetic studies and in vivo pharmacokinetic investigations suggested an extensive hepatic metabolism of herbacetin and the high exposure of herbacetin-glucuronides in systemic circulation.The clearance,half-life and bioavailability of herbacetin in rats were determined as(16.4±1.92)mL·kg^(-1)·min^(-1),(11.9±2.7)min,and 1.32%,respectively.On basis of these findings,a comprehensive metabolic pathway of herbacetin in rats was composed.In addition,a physiology based pharmacokinetic(PBPK) model was successfully developed with the aid of the Gastro Plus to simulate the pharmacokinetic process of herbacetin in rats.Application of the PBPK modeling can provide a useful starting point to understand and extrapolate pharmacokinetic parameters among different species,populations,and disease states.CONCLUSION After oral administration,herbacetin was subjected to colonic degradation and extensive first pass metabolism,with glucuronidation as its dominating in vivo metabolic pathway.
文摘Objective To elucidate the transformation of energy metabolism patterns in the process of myocardial remodeling induced by volumeoverload and to explore a novel intervention target for the prevention,delay or even reversal of structural heart dysfunction.Methods Thirty C57/BL6 mice,20-30 g,half male and half female,were randomly divided into model group(n=15)and sham operation group(n=15).Each group was divided into subacute phase(2 weeks after surgery,n=5),cardiac functional compensation phase(5 weeks after surgery,n=5)and decompensation phase(15 weeks after surgery,n=5).
文摘OBJECTIVE Forsythiae Fructus(Lianqiao)is a typical heat-clearing and detoxicating traditional Chinese medicine(TCM)herb,which has been traditionally used for treating cancer according to TCM theory.However,the underlying mechanism has not been fully explained.METHODS In this study,we investigated the antitumor effect of Forsythiae Fructus aqueous extract(FAE)on B16-F10 melanoma.RESULTS FAE strongly inhibited the tumor growth and metastasis formation in B16-F10 melanoma transplanted mice.The survival time of tumor-bearing mice was also significantly prolonged by FAE.The levels of ROS,MDA,TNF-αand IL-6 decreased,while GSH increased in the FAE treatment group,indicating FAE possesses strong anti-oxidative and anti-inflammatory activity.Western blotting analysis demonstrated that antioxidant proteins Nrf2 and HO-1,tumor suppressors P53 and p-PTEN,and the MAPK pathways in tumor tissues were upregulated by FAE treatment.Serum metabolomics analysis further uncovered that 17 metabolites mostly involving in glycerophospholipid metabolism were correlated with the antitumor effect of FAE.Notably,several lysophosphatidylcholines(LysoPCs)significantly decreased in tumor model group,while FAE treatment restored the changes of these phospholipids to about normal condition.LysoPC acyltransferase 1(LPCAT1)and autotaxin(ATX)highly expressed in melanoma and markedly downregulated by FAE were believed to be responsible for this modulation.CONCLUSION FAE exhibites strong antitumor activity against B16-F10 melanoma through activating MAPKs/Nrf2/HO-1 mediated anti-oxidation and anti-inflammation and modulating glycerophospholipid metabolism via downregulating LPCAT1 and ATX.Besides,it is suggested that serum LysoPCs could be potential biomarkers for the diagnosis and prognosis of melanoma.
文摘The aim of this study was to determine the effects of supplementing organic forms of zinc(zinc acetate,ZnA)and inorganic zinc(zinc sulfate,Zn S)on performance,the gain to feed ratio(G:F)and skeletal characters in broilers from the first day to the 42th day.A total of 240-day-old broilers(Arbor Acres)were randomly distributed in four groups.A corn-soybean meal-based control diet containing recommended concentrations of inorganic trace minerals and other nutrients was prepared.On the basal diets,the control goup(CG)was supplemented with Zn S and the treatment group(TG)feeding diets were with different ZnA supplemental levels(80,100 and 150 mg·kg^-1)of ZnA.Each group was allotted randomly to five replicates and 12 broilers in each replicate and fed ad libitum from the first day to the 42th day.The results showed that supplementation of ZnA significantly increased(p<0.05)energy and phosphorus(P)compared to that fed Zn S on the 21th day.Calcium(Ca),tibia weight,ash weight,tibia Ca and tibia P in TG(80 mg·kg^-1 of ZnA)were the highest(p<0.05).The pancreas Zn content of TG was higher than that in CG and increased with the supplementation of ZnA.On the 42th day,the content of energy,crude protein(CP),Ca and tibia Ca in TG(80 mg·kg^-1 of ZnA)were the highest(p<0.05),the change of pancreas Zn was the same as the results on the 21th day,but enter extract(EE),tibia weight,tibia length,tibia width and ash weight were not affected(p>0.05)by ZnA.The results of this study showed that ZnA was better than Zn S in improving the early growth performance,nutrient utilization rate in broilers,the length and weight of broiler tibia,it promoted the calcium,phosphorus deposition and normal growth of tibia,and the optimum dietary ZnA level to feed was 80 mg·kg^-1.ZnA affected body Zn stores and the apparent metabolic rate of nutrients.
基金National Natural Science Foundation of China(81703529)
文摘OBJECTIVE To investigate berberine(BBR)attenuates arthritis in adjuvant-induced arthritic(AA)rats associated with regulating the energy metabolism and correcting the polarization of macrophages through activation of AMP-activated protein kinase(AMPK)and inhibition of hypoxia inducible factor 1α(HIF-1α).METHODS AA rats were treated with BBR(40,80,or 160 mg·kg-1)from days 15 to 29 after immunization.The histopathology of ankle joint was examined through hematoxylin-eosin(HE)staining.The concentrations of tumour necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β,IL-2,IL-17A,interferon-gamma(IFN-γ),monocyte chemotactic protein 1(MCP-1),IL-4,IL-10,transforming growth factor-β1(TGF-β1),ATP,and lactic acid were measured by using ELISA kits.The percentage of M1 and M2 macro⁃phage cells in joint tissues were evaluated by immune-fluorescence.The expressions of p-AMPK and HIF-1αin joint of AA rats were determined according to immunohistochemistry analysis.The migration of macrophage was detected by Transwell assays.The expression of inducible nitric oxide synthase(iNOS),Arginase-1(Arg1),p-AMPK,AMPK and HIF-1αwere examined by Western blotting.The labeled macrophages were observed with laser confocal microscopy.RESULTS BBR relieved signs and symptoms of AA rats and reversed pathological changes.BBR treatment group exhibited decreases in pro-inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-2,IL-17A,IFN-γ,and MCP-1)coupled with increases anti-inflammatory cytokines(IL-4,IL-10,TGF-β1)in the serum.The number of M1 macrophage was reduced,while the number of M2 macrophage was increased in BBR group joint tissues.Moreover,BBR showed marked up-regu⁃lation the expression of p-AMPK and down-regulation the expression of HIF-1αin joint of AA rats.Next in vitro study,we found BBR up-regulated the expression of p-AMPK,Arg1(M2 marker)and down-regulated the expression of HIF-1α,iNOS(M1 marker)induced by LPS in peritoneal macrophages from normal SD rat.Furthermore,BBR treatment inhibited the migration of macrophages stimulated by LPS.The level of ATP was elevated and lactic acid was reduced in LPSinduced macrophages after treated by BBR.However,Compound C significantly attenuated the effects of BBR on acti⁃vated macrophages.CONCLUSION BBR alleviates inflammation by regulating energy metabolism and correcting the polarization of macrophage through AMPK-HIF-1αpathway.BBR might have great therapeutic value for RA.
文摘The nitrogen (N) metabolic experiments were made to estimate separately amino acid requirements of 4348 weeks old layers for maintenance, for protein accretion to estabolish models to estimate digestible amino acid requirements. The regression relationship of nitrogen retention vs amino acid intake was estimated for each amino acid by giving, at rate of N intake of 091, 052, 015 and 0007gkg-1 body-weight (W075) per d, the semi-synthetic diets was made specially deficient in one amino acid. From the regression coefficients, it was calculated that, for the accretion of 1 g protein, the dietary digestible amino acid requirements were (mg) Thr 631, Val 1004, Met 399, Ile 886, Leu 1143, Phe 632, Lys 870, His 205, Arg 879, Trp 214, Met+Cys 776, and Phe+Tyr 1143. Daily amino acid requirements for N equilibrium were estimated to be (mgkg-1W075 per day) Thr 506, Val 747, Met 303, ILe 667 Leu 814, Phe 448, Lys 605 His 147, Arg 739 ,Trp 173, Met+Cys 586, and Phe+Tyr 839 The dietary degestible amino acid patterns for protein accretion and N equilibrium were also proposed. The models of estimating digestible amino acid requirements for the different productions were developed.
文摘OBJECTIVE Pulmonary arterial hypertension(PAH)is a malignant pulmonary vascular disease lacking efficacy therapeutics.Therefore,it urgently needs to develop safe and effective drugs for PAH treatment.Osthole derived from Cnidium monnieri(L.)Cusson(Shechuangzi)or Angelica pubescens Maxim(Duhuo)has the capacity to alleviate PAH by decreasing pulmonary arterial pressure and alleviating pulmonary vascular remodeling in rats,which is a candidate drug for the prevention of PAH,but the underlying modulatory mechanism is still unclear.Our study aims at investigating the metabolic modulatory mechanism of osthole against PAH employing functional metabolomics strategy.METHODS PAH model rats were successfully established with MCT,following osthole administration,then functional metabolomics based on untargeted metabolomics assay,targeted lipidomics analysis,qRT-PCR,Western blotting and ELISA were performed to investigate the modulatory mechanism of osthole against pulmonary arterial pressure and pulmonary vascular remodeling in PAH.RESULTS Untargeted metabolomics results found that sphingosine 1-phosphate(S1P)was the differential metabolites characterized PAH and reversed by osthole treatment.S1P is a crucial sphingolipid metabolite catalyzed by sphingosine kinases1(Sphk1)and functions as promoting PASMCs proliferation contributing to pulmonary vascular remodeling and pulmonary arterial pressure increase.We revealed that osthole reversed high level of S1P by modulating metabolic enzyme Sphk1 via inactivating microRNA-21-PI3K/Akt/mTOR signal pathway to decrease pulmonary arterial pressure in rats with PAH.Then,targeted phospholipid metabolomics results uncovered that decadienyl-L-carnitine(C10:2)was the differential metabolite characterized PAH and corrected by osthole treatment in rat with PAH.C10:2 is the intermediate metabolite of fatty acid oxidation(FAO),and C10:2 accumulation indicated mitochondrial dysfunction and FAO increase.CONCLUSION Osthole could block lipid metabolic reprogramming through functional modulating the expression of fatty acid translocase,fatty acid synthase,phospholipase A2,carnitine palmitoyltransferase 1A to inhibit C10:2,thus to improve mitochondrial dysfunction and inhibit utilizing lipid to biosynthesize necessary essence for pulmonary artery smooth muscle cells(PASMCs)proliferation.Moreover,we delineated that C10:2 and metabolic reprogramming enzymes were modulated by miRNA-22-3p which was involved in PASMCs proliferation and pulmonary vascular remodeling.Therefore,osthole inhibited miRNA-22-3p mediated lipid metabolic reprogramming to ameliorate pulmonary vascular remodeling.
基金Supported by the Key Teacher Foundation of Education Offi ce of Heilongjiang Province(2000)
文摘To investigate the effects and mechanisms of the benzimidazole carbamate and benmidine drugs on Cysticerci cellulosae and choose effective drugs on Cysticerci cellulosae, the membrane metabolism of Cysticerci cellulosae in vitro was tested after three kinds of drugs which were used respectively. The indexes included the contents of lipids, the contents of SA and the changes of the membrane fluidity. The results showed that oxfendazole could inhibit the membrane metabolism of immature and mature Cysticerci cellulosae in vitro, and albendazole only inhibited the mature one, while thibendimidine neither acted on the immature nor mature one.
基金Supported by National 973 Project of China (2006CB102105)Natural Science Foundation Key Project of Heilongjiang Province (ZJN0604-01)National 863 Project of China (2006AA10A120)
文摘The nuclear receptor peroxisome proliferator-activated receptor γ（PPAR-γ） is a key transcriptional regulator of adipocyte differentiation.It also modulates the synthesis of adipocytokines in the adipose tissue.Its polymorphisms are associated with the risk of type Ⅱ diabetes,obesity,cardiovascular diseases and cancer.In the present study,to investigate the regulatory mechanism of PPAR-γ gene on lipid metabolism,the computational prediction of peroxisome proliferator response elements（PPREs） was pursued with a genome-wide scale by using MEME/MAST method based on the information of TRANSFAC database,then GO and KEGG analyses were carried out.The results showed that a huge number of predicted target genes of PPAR-γ were significantly enriched in 36 GO terms（P〈0.05） and 10 KEGG pathways（P〈0.05） which were related closely to the lipid metabolism.The results should be a valuable resource for elucidation of the regulatory mechanism of PPAR-γ influence on lipid metabolism,also of the major importance to the diagnosis,prevention and treatment of the complex diseases such as obesity and diabete.
文摘We encourage submission of fundamental discoveries or technological advancement in areas of plant main metabolism,discovering of medicinal plant and natural products,elucidating of metabolism pathways and their biological functions,application of metabolic engineering for synthesis of bioactive natural products,and study on metabolic networks and their functions.
基金Supported by Scientifi c Research Foundation of Guangxi University (x061106)
文摘In order to research effects of the nitrogen top-dressing levels on carbon-nitrogen metabolism and yield of Desmodium styracifolium, a field experiment was conducted on the research farm of Guangxi University in 2007. Some physiological indexes and yield ofD. styracifolium were compared among five nitrogen top-dressing levels （0, 37.5, 75.0, 112.5 and 150.0 kg N. hm-2）. Results showed that the nitrogen top-dressing could significantly increase the contents of chlorophyll, soluble protein, sucrose and nitrogen as well as nitrate reducase activity. However, there were no significant differences in most of these indexes under high nitrogen levels. Consistently, there was no significant difference in yield among nitrogen top-dressing levels of 75 kg N.hm-2, 112.5 kg N. hm-2 and 150 kg N-hm-2. Therefore, the optimum nitrogen top-dressing level ofD. styracifolium was 75 kg N. hm-2.
