To reveal the underlying mechanism of doxorubicin induced hepatotoxicity, an NMR-based metabolomic approach combined with multivariate statistical analysis was used to observe its metabolic alternations of rat liver. Sixteen differential metabolites between model rats and normal rats were characterized as potential pathological biomarkers related to doxorubicin induced hepatotoxicity. Six pathways, including phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, phenylalanine metabolism, glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, and tyrosine metabolism were regarded as the targeted metabolic pathways according to Metabolic Pathway Analysis (MetPA). The results suggested that the metabolic perturbations in rats with doxorubicin induced hepatotoxicity were mainly involved in amino acid metabolism, lipid pathways, purine metabolism, energy metabolism, dysfunction of biotransformation and oxidative stress. The investigation revealed the effects of doxorubicin on liver in a holistic metabolic way, which laid a foundation for further studies on its toxicity mechanism.
Animals ; Biomarkers ; metabolism ; Doxorubicin ; toxicity ; Energy Metabolism ; Liver ; drug effects ; metabolism ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Metabolic Networks and Pathways ; Metabolomics ; Multivariate Analysis ; Oxidative Stress ; Rats

Objective To study adrenomedullin (AM) mRNA and protein expression level in myocardium of autoimmune myocarditis animal models induced by immunization of mice with lactobacillus casei cell wall element(LCWE). Methods Forty-five Balb/c male mice were randomly divided into experimental group (n = 30) and control group (n = 15), which were intraperitoneally injected with LCWE and phosphate buffered solution(PBS) at day 0,3,5 and 10,respectively. Sera and myocardium samples were gained 14,21 and 28 days after the first immunization. AM expression levels were determined by semiquantitative reverse transcriptase-polymerase chain reaction(RT- PCR) and immunchistochemistry,and mycardial histopathological lesions were observed. The anti- myosin antibodies in different stages were examined by an ELISA. Results There were myocardial necrosis or inflammatory infiltration in the experimental group, but myocardial lesions were not found in the control group. Anti - myosin antibodies were detected in sera of experimental mice,but not in control group. Immunchistochemistry findings demonstrated that AM expression level was higher in the experimental group than in the control group( P

ERF family transcription factor (TF) represented ethylene-responsive protein which harbored a conserved AP2 domain. After searching the plant transcription factor database, a total of 75 unigenes was found which contained AP2 domain from the transcriptome dataset of Panax quinquefolius L. One unique sequence of ERF transcript, named as PqERF1, was cloned with entire open reading frame of 933 base pairs (bp). Protein prediction result indicated that the gene was localized in nucleus and had a conserved AP2 domain. PqERF1 gene could be induced by methyl jasmonate (MeJA) which was consistent to the inducing profile of triterpene ginsenosides. InterproScan prediction indicated that PqERF1 was probably a pathogenesis-related gene. Sequence alignment and phylogenetic analysis demonstrated PqERF1 was with high identity and had relative close relationship to the NtERF4 (Nicotiana tabacum), PhERF12 (Petunia x hybrida) and DcERF1 (Daucus carota) which was related to plant defense, regulation of secondary metabolism and the flower senescence respectively. Therefore, the gene was likely involved in regulation of secondary metabolism, plant defense and physical processes which would provide gene resource for further study on secondary metabolite synthesis and molecular breeding of P. quinquefolius.
Amino Acid Sequence ; Computational Biology ; Daucus carota ; genetics ; metabolism ; Gene Expression Regulation, Plant ; Open Reading Frames ; Panax ; genetics ; metabolism ; Petunia ; genetics ; metabolism ; Phylogeny ; Plant Proteins ; genetics ; metabolism ; Protein Structure, Secondary ; RNA, Plant ; genetics ; Sequence Alignment ; Tobacco ; genetics ; metabolism ; Transcription Factor AP-2 ; genetics ; metabolism

Objective At present no deep investigation has been done on the relationship between handgrip strength and appendicular lean mass (ALM) in patients with chronic obstructive pulmonary disease (COPD). The study aimed to explore the present situation of handgrip strength in patients with stable COPD and relationship between handgrip strength and ALM.Methods A total of 93 patients with stable COPD who hospitalized in our department from August 2016 to July 2017 were selected for the study. All the patients underwent handgrip strength test, body composition analysis, as well as the analysis of the relationship between handgrip strength and ALM.Results Multivariate linear regression analysis showed age(X1), education(X2), smoking(X3), course of disease(X4) and lower limb lean mass(X5) could be taken as predictive factors for the variation degree of handgrip strength (R2=50.5%), and multiple linear regression equation was Y=9.959-4.315X1+1.397X2+2.679X3-1.526X4+1.538X5. The variation degree decreased to 48.1% when the course of disease was removed from the model, 28.3% when the limb lean mass was removed, 26.5% when two variables were removed. The correlation coefficients of ALM, upper limb, lower limb and torso lean mass (\[22.32±3.25\]kg, \[6.48±1.05\]kg, \[15.83±2.26\]kg, \[22.27±3.22\]kg) with handgrip strength (\[32.27±7.27\]kgf) were respectively 0.484, 0.436, 0.496 and 0.496 (P＜0.01).Conclusion The handgrip strength in patients with stable COPD is closely associated with ALM, and the course of disease and the lower limb lean mass greatly affect the handgrip strength. Clinical workers should pay extra attention to the relationship in order to give timely clinical intervention.

Objective To investigate the predictive value of preoperative viable myocardium and postoperative left ventricular mechanical dyssynchrony (LVMD) for adverse cardiovascular events(ACE) after coronary artery bypass graft (CABG) in patients with coronary artery disease (CAD) using myocardial perfusion imaging (MPI).Methods From September 2012 to March 2016,49 patients (44 males,5 females,average age:(64±8) years) with CAD were prospectively recruited.All patients underwent 99Tcmmethoxyisobutylisonitrile (MIBI) SPECT gated MPI (GMPI) and 18F-fluorodeoxyglucose (FDG) PET myocardial metabolic imaging to assess myocardial viability preoperatively.GMPI was repeated 4-6 months after CABG to record postoperative LVMD.Phase analysis was used to measure bandwidth (BW) and standard deviation (SD).Regular follow-up was performed,and ACE were taken as the end point.Cox proportional hazard model,Kaplan-Meier method and log-rank test were used to analyze the data.Results The mean duration of follow-up was (3.82±0.80) years,and ACE were present after CABG in 17 CAD patients (34.7％,17/49).Cox multi-analysis revealed that the number of preoperative viable segments (hazard ratio (HR)=0.208,95％ CI:0.068-0.642) and postoperative BW (HR=1.245,95％ CI:1.099-1.411)were independent influencing factors of ACE in CAD patients after CABG (both P＜0.01).Kaplan-Meier survival analysis showed that the incidence of ACE in patients with ＜ 3 viable segments was significantly higher than those with ≥ 3 viable segments (57.1％ (12/21) vs 17.9％ (5/28);x2 =21.023,P＜0.01).The incidence of ACE was significantly higher in the postoperative BW≥98° group than that in the postoperative BW＜98° group (14/19 vs 10％ (3/30);x2 =38.395,P＜0.01).Conclusions Less preoperative viable segments and severe postoperative LVMD are independent risk factors of ACE after CABG in CAD patients.Postoperative LVMD in CAD patients undergoing CABG may have important clinical value in the riskrestratification and prognosis evaluation.

Resveratrol (RES) can inhibit the growth and proliferation of liver cancer cells. However, its role in the precancerous stage is still unclear. This paper aims to study the effect and mechanism of RES on the precancerous stage of liver cancer in rats induced by diethylinitrosamine (DEN). SD rats were divided into normal control group, RES treatment group, DEN treatment group and RES-DEN treatment group. The results showed that after the rats were treated with DEN for 8 weeks, the total expression level of proliferating cell nuclear antigen (PCNA) of hepatocytes increased to 2-fold (P<0.05), and the expression level of PCNA protein in the nucleus increased to 3-fold (P<0.001). However, the expression levels of total PCNA (P<0.05) and nuclear PCNA protein (P<0.001) in hepatocytes of rats treated with RES-DEN decreased, suggesting that RES could significantly inhibit the liver malignant proliferation of cells. Through non-targeted metabolomics and KEGG metabolic pathway enrichment analysis, the results showed that the level of glycolysis did not increase significantly in the hepatocytes of RES-DEN-treated rats, although the transition from the pentose phosphate pathway to the glycolysis pathway was enhanced when compared with the DEN group rats. This finding suggested that the metabolic pathway of phosphoenolpyruvate-pyruvate-lactate was inhibited. Further verification found that the protein expression levels of key enzymes M2-type pyruvate kinase (PKM2) and lactate dehydrogenase (LDHA) in this metabolic pathway were inhibited (P<0.05). RES can reprogram glucose metabolism and inhibit DEN-induced excessive proliferation of rat hepatocytes in the precancerous stage of liver cancer, providing an experimental basis for RES to prevent liver cancer.

OBJECTIVE: To observe the impact of energy saving light,incandescent light and circadian light on the ethology of depressive rats and explore its possible mechanism on affecting the secretion of melatonin. METHODS: Thirty rats aged 6weeks were randomly selected from 40 specific pathogen free health female SD rats after they adapted to the living environment,depressive rat models were established in the rats by bilateral ovariectomy combined with isolated living and chronic unpredictable mild stress stimulation at the age of 11-14 weeks. Then these 30 ovariectomized rats were randomly divided into 3 intervention groups,including an energy saving light group,an incandescent light group and a circadian light group,with 10 rats in each group. The rats in these 3 groups were given specific experimental light intervention for 3 weeks respectively at the age of 17 weeks. The other 10 rats were raised in conventional environment as the control group. Their body weights were measured at the age of 17,19,20 and 21 weeks. The ethology tests were carried out by sucrose preference test and the open-field test at the age of 7,14 and 20 weeks respectively. The melatonin levels in peripheral blood of 7 time points from 19: 30 to 8: 30 were measured in the rats at age of 21 weeks. One rat in each group at every time point was randomly selected for examination. RESULTS: At the age of 17 weeks before light-intervention,the body weights of rats in 4 groups showed no significant difference( P > 0. 05). After light-intervention,at the age of 17-20 weeks,the body weights of rats in 3 intervention groups were gradually increased with the increase of age( P < 0. 05).There was no significant difference between body weights of rats at the age of 21 weeks and those at the age of 20 weeks in each group( P > 0. 05). At age of 7 weeks,no significant differences were found in sucrose consumption and standing scores among these 4 groups( P > 0. 05). After the depressive models were established,at the age of 14 weeks before light-intervention,in rats of these 3 intervention groups,the sucrose consumption and standing scores were lower than those of the control group( P < 0. 05),and there was no significant difference found in the above 2 indexes among these 3intervention groups( P > 0. 05). At the age of 20 weeks after light-intervention,the sucrose consumption and standing scores were not significantly different from each other among the 4 groups( P > 0. 05). The peak levels of melatonin in the peripheral blood of rats in these 3 intervention groups were higher than that in the control group. The peak levels onsets of melatonin in peripheral blood of rats in the circadian light group and the energy saving light group were earlier or 2 hours delayed compared to that of control group,while it was similar between the incandescent light group and control group.CONCLUSION: The circadian light,the energy saving light and the incandescent light are similarly effective in improving the behaviors of depressive rats. The circadian light can delay the onset of peak level of melatonin in peripheral blood.