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Aim To explore the effeet of riboflavin on the establishment of pressure overload-induced heart failure model in mice by thoracic aortie constrietion (TAC ) and its preventive mechanism.Methods Eight-week-old SPF C57BL/6J mice were seleeted and divided into four groups; Sham group.Sham + ribofla¬vin group, TAC group and TAC + riboflavin group.A mouse heart failure model was constructed in the TAC group.The miee in the TAC + riboflavin group were given riboflavin by gavage one week before and eight weeks after the operation.The cardiac ultrasound inde¬xes, the changes of cardiac morphology and mitochon¬drial function indexes, the expression of apoptosis pro¬teins, ATP content, SCAD mRNA and protein expres¬sion, enzyme activity and flavin adenine dinucleotide (FAD) content in myocardial tissues were detected.Hie free fatty acid content in serum and myocardial tis¬sues were also detected.Results Compared with the sham group, the cardiac function indexes of the mice in the TAC group decreased, anrl typical heart failure occurred.Moreover, the expression of SCAD, enzyme activity, ATP and FAD content in the myocardium sig-nificantly decreased, and the free fatty acid content in myocardium and serum significantly increased.Com¬pared with the TAC group, after riboflavin treatment, the cardiac function of mice in TAC + Riboflavin group was significantly improved.In addition, ATP content, SCAD expression, enzyme activity and FAD content in myocardium all significantly increased, and free fatty acid content in myocardium and serum markedly de¬creased.Conclusions Riboflavin may improve myo-cardial energy metabolism by increasing FAD content and activating SCAD, thereby inhibiting pressure over¬load-induced heart failure in mice.
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OBJECTIVE@#To observe the effect of protein kinase D1 (PKD1) on the growth and metabolism of oral squamous cell carcinoma HSC-4 cells and related molecular mechanisms in the tumor microenvironment.@*METHODS@#HSC-4 cell lines were transfected with shRNA plasmids. Three groups (Wild, control-shRNA, and PKD1-shRNA) were cultured under acidic or hypoxic environment for a certain time. Western blot was used to detect the expression of autophagy-related and glycolytic-related proteins. The proliferation changes were detected by CCK-8 kits.@*RESULTS@#The PKD1-knockdown HSC-4 cell line was established. PKD1 silencing increased autophagy activity. Under hypoxic and acidic conditions, the PKD1-knockdown HSC-4 cells showed lower proliferation than the parental cells. PKD1-knockdown also decreased the expression of hypoxia induciblefactor 1α (HIF-1α) and pyruvate kinase M2 (PKM2).@*CONCLUSIONS@#Under hypoxic and acidic conditions, PKD1 gene silencing can increase apoptotic autophagy activity. Downregulated PKD1 gene expression can reduce the glycolysis of oral squamous cell carcinoma cells and inhibit tumor cell proliferation. This study revealed the important role of PKD1 in the metabolism and growth of oral squamous cell carcinoma, making it a possible target for the treatment of oral squamous cell carcinoma.
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Humanos , Carcinoma de Células Escamosas , Línea Celular Tumoral , Proliferación Celular , Subunidad alfa del Factor 1 Inducible por Hipoxia , Neoplasias de la Boca , Proteínas Quinasas , Microambiente TumoralRESUMEN
Aim Modelorganismzebrafishwasusedto study metabolites and metabolite profile of the gallic acid and protocatechuic acid of effective fractions of Polygonum capitatum,and discuss the feasibility and rationality of the model organism zebrafish in the study ofdrugmetabolism.Methods Thetwocomponents were exposed to model organism zebrafish after 24 h of solution treatment by using ultra-high performance liq-uid chromatography-quadrupole-time-of-flight tandem mass spectrometry technology (UHPLC-Q-TOF MS ) method with mass defect filter (MDF ),and the data was treated with data mining software(Metabolite Tool-sTM).Results Afterzebrafishmetabolism,themain reactions of gallic acid and protocatechuic were methyl-ation sulfated. In addition to the two parent com-pounds,six phase II metabolites were identified,in-cluding four methyl sulfate products and two sulfation products.Conclusions Themetabolismofthegallic acid and protocatechuic acid of effective fractions of Polygonum capitatum by zebrafish presents phase Ⅱmetabolites,which is highly consistent with the meta-bolic mechanism of rats.Thus it indicates the rationali-ty of the methods.At the same time,it also provides the experimental basis for clarifying the substance basis of the drug.
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OBJECTIVE:To explore the effects of acadesine on myocardial energy metabolism of model dogs with myocardial ischemia-reperfusion injury (MIRI) after cardiopulmonary bypass (CPB). METHODS:Dogs were randomly divided into control group,model group,acadesine low-dose,high-dose groups(0.8,3.2 mg/kg),6 in each group. All dogs received CPB. Except for control group,dogs in other groups were reduced for MIRI model,and perfused St.Thomas cardiac cardioplegia lipid containing rel-evant drugs 60 min after main artery block. The uptake rates of myocardial glucose and free fatty acid(FFA),creatine kinase isoen-zyme(CK-MB)concent in venous sinus plasma and adenosine triphosphate(ATP)content in mitochondria were detected and calcu-lated before bypass and after 15,60,90 min of reperfusion. Left ventricular systolic pressure(LVSP)and left ventricular end dia-stolic pressure(LVEDP)were analyzed,and mRNA expression of adenylate-activated protein kinase(AMPK)and protein expres-sion of phosphorylated AMPK(p-AMPK)in myocardial tissue were detected. RESULTS:Before bypass,all indexes in each group had no statistic significances(P>0.05). After bypass,compared with control group,uptake rates of myocardial glucose and FAA, ATP content,mRNA expression of AMPK and protein expression of p-AMPK and LVSP in 3 time points in model group and each administration group were obviously decreased(P<0.05);LVEDP and CK-MB concent in plasma were obviously increased(P<0.05). Compared with model group,uptake rates of myocardial glucose and FAA,ATP content,mRNA expression of AMPK and protein expression of p-AMPK and LVSP in 3 time points in each administration group were obviously increased (P<0.05);LVEDP and CK-MB concent in plasma were obviously decreased (P<0.05);and high-dose group showed more obvious change than that of low-dose group (P<0.05). CONCLUSIONS:Acadesine can promote the AMPK phosphorylation,contribute to the myocardial glucose and FFA uptake to promote the increase of ATP in myocardial mitochondria and relieve MIRI after CPB.
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OBJECTIVE:To explore the effects of acadesine on myocardial energy metabolism of model dogs with myocardial ischemia-reperfusion injury (MIRI) after cardiopulmonary bypass (CPB). METHODS:Dogs were randomly divided into control group,model group,acadesine low-dose,high-dose groups(0.8,3.2 mg/kg),6 in each group. All dogs received CPB. Except for control group,dogs in other groups were reduced for MIRI model,and perfused St.Thomas cardiac cardioplegia lipid containing rel-evant drugs 60 min after main artery block. The uptake rates of myocardial glucose and free fatty acid(FFA),creatine kinase isoen-zyme(CK-MB)concent in venous sinus plasma and adenosine triphosphate(ATP)content in mitochondria were detected and calcu-lated before bypass and after 15,60,90 min of reperfusion. Left ventricular systolic pressure(LVSP)and left ventricular end dia-stolic pressure(LVEDP)were analyzed,and mRNA expression of adenylate-activated protein kinase(AMPK)and protein expres-sion of phosphorylated AMPK(p-AMPK)in myocardial tissue were detected. RESULTS:Before bypass,all indexes in each group had no statistic significances(P>0.05). After bypass,compared with control group,uptake rates of myocardial glucose and FAA, ATP content,mRNA expression of AMPK and protein expression of p-AMPK and LVSP in 3 time points in model group and each administration group were obviously decreased(P<0.05);LVEDP and CK-MB concent in plasma were obviously increased(P<0.05). Compared with model group,uptake rates of myocardial glucose and FAA,ATP content,mRNA expression of AMPK and protein expression of p-AMPK and LVSP in 3 time points in each administration group were obviously increased (P<0.05);LVEDP and CK-MB concent in plasma were obviously decreased (P<0.05);and high-dose group showed more obvious change than that of low-dose group (P<0.05). CONCLUSIONS:Acadesine can promote the AMPK phosphorylation,contribute to the myocardial glucose and FFA uptake to promote the increase of ATP in myocardial mitochondria and relieve MIRI after CPB.
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Aim To further study the molecular mecha-nism of the herbs with hot nature on the regulational action on TRPV1 channel based on the 7900 Real-time PCR instrument. Methods 7900 PCR instrument was applied to detect the intracellular flurescence of TRPV1 channel in the dorsal root ganglions ( DRG ) neurons and the effect on the TRPV1 ’ s thermo-sensational functions of the selected 11 ingredients from hot herbs was explored. Results TRPV1 channels could be ac-tivated by gradually elevated temperature; the activa-tion process could be blocked by the TRPV1 specific blocking agent capsaizepine. Most of the ingredients from hot-nature herbs had the potential to up-regualate TRPV1 channel function. Conclusions The estab-lished TRPV1 channel detection system based on PCR instrument is suitable for the analysis of regulational functions of drugs on the heat-activated TRPV1 chan-nel;the functions of hot herbs may be related to the up-regualtional effects of its active ingredients on the TRPV1 channel which will further up-regulate energy metabolism.
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AIM:To investigate the effect of short-chain acyl-CoA dehydrogenase ( SCAD) on collagen expres-sion and proliferation of rat cardiac fibroblasts and to explore the relationship between SCAD and cardiac fibrosis . METHODS:The model of proliferation and collagen expression of rat cardiac fibroblasts induced by angiotensin II was es -tablished.After treatment with siRNA-1186, the expression of SCAD at mRNA and protein levels , fatty acids beta oxida-tion rate, ATP, the enzyme activity of SCAD and free fatty acids in the rat cardiac fibroblasts were determined . RESULTS:The mRNA and protein expression of SCAD was decreased in the rat cardiac fibroblasts induced by angiotensin II compared with the control cells , and the expression of collagen I and collagen III was significantly upregulated .Com-pared with negative control group , SCAD expression and activity , fatty acid beta-oxidation rate and ATP significantly de-creased in siRNA-1186 group, but the content of free fatty acids were obviously increased in the rat cardiac fibroblasts , and the expression of collagen I and collagen III was significantly up-regulated.CONCLUSION:The expression and synthesis disorder of collagen may be triggered by down-regulation of SCAD .SCAD may be a promising therapeutic target for myocar-dial fibrosis .
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[ ABSTRACT] AIM:To investigate the effects of Chaihu Shugan powder ( CSP) on lipid metabolism and the pro-teins involved in adenosine 5’-monophosphate-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway in the liver tissues of the rats with non-alcoholic fatty liver disease (NAFLD).METHODS: Sprague-Dawley rats were randomly di-vided into normal control ( NC) group, with HFD ( HFD) group and CSP group.The NAFLD models were established by feeding with HFD for 16 weeks in the rats.The rats in CSP group were intragastrically administered with CSP extracts (9.6 g· kg-1 · d-1 ) , and blood and liver samples were collected 16 weeks later.Serum and liver levels of total cholesterol ( TC) and triglyceride ( TG) , and serum levels of alanine aminotransferase ( ALT) and aspartate aminotransferase ( AST) were measured using an automatic biochemical analyzer.The histological changes of liver tissues were observed with HE staining, while the lipid deposition was observed with Oil Red O staining.The ultrastructural changes of the liver tissues were observed under transmission electron microscope.Moreover, the protein levels of AMPK, phosphorylated AMPK (pAMPK), SIRT1 and uncoupling protein 2 (UCP2) in the liver were detected by Western blot.RESULTS:The results of HE staining, Oil Red O staining and electron microscopy demonstrated that NAFLD rat model was successfully estab-lished.Compared with NC group, the serum and liver levels of TC and TG, and serum level of AST in model group were markedly elevated ( P<0.01) .Moreover, the protein levels of pAMPK and SIRT1 in HFD group were markedly reduced (P<0.01), whereas UCP2 level was elevated (P<0.01).Furthermore, liver levels of TC and TG, and serum level of AST in GSP group were markedly reduced as compared with HFD group ( P<0.05 ) .The protein levels of pAMPK and SIRT1 were elevated ( P<0.05 ) , whereas the UCP2 level was reduced as compared with HFD group ( P<0.01 ) .The protein level of AMPK between the 3 groups had no significant difference.CONCLUSION: CSP attenuates hepatic lipid disorder and hepatic lipid deposition in NAFLD rats induced by feeding with HFD for 16 weeks, which is associated with the activation of AMPK/SIRT1 pathway.
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Fructus Ligustri Lucidi ( FLL) is a traditional Chinese medicine commonly used in clinic. This paper reviews the phar-macological action of FLL and its compounds, especially demon-strates the regulation and mechanism in calcium homeostasis and bone metabolism.
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AIM:To investigate the change of short-chain acyl-CoA dehydrogenase (SCAD) expression during cardiomyocyte apoptosis and to explore the relationship between SCAD and cardiomyocyte apoptosis .METHODS: The neonatal rat cardiomyocytes treated by tert-butyl hydroperoxide (tBHP) were used as the model of cardiomyocyte apoptosis . The cell viability , the expression of SCAD at mRNA and protein levels , the activity of SCAD and the content of free fatty acids were determined .RESULTS:The mRNA and protein expression of SCAD decreased in the cardiomyocyte apoptosis model.Compared with negative control group , SCAD expression and activity were both significantly decreased in siRNA-1186 group, but the content of free fatty acids were obviously increased in the cardiomyocytes .Meanwhile, SCAD siRNA treatment triggered the same apoptosis as cardiomyocytes treated with tBHP .CONCLUSION: Down-regulation of SCAD may play an important role in primary cardiomyocyte apoptosis .Increase in the expression of SCAD may become an impor-tant part in intervening cardiomyocyte apoptosis .