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@#Fatty acid metabolism, including fatty acid oxidation (FAO) and fatty acid synthesis, plays critical roles in signal transduction, energy production and inflammation regulation.Acute kidney injury (AKI), chronic kidney disease (CKD) and renal cell carcinoma (RCC) are typical renal diseases with complex pathogenesis, susceptibility to multiple complications, and still no effective measure for clinical intervention.Current studies reveal that fatty acid metabolism is closely related to the occurrence and development of a variety of kidney diseases.This article reviews the metabolic characteristics of fatty acid in the kidney, the relationship between fatty acid metabolism disorder and renal diseases (i.e., AKI, CKD and RCC), and summarizes traditional Chinese medicines and related active ingredients targeting fatty acid metabolic pathway to alleviate renal diseases, aiming to provide theoretical reference for the in-depth study of mechanisms related to fatty acid metabolism in renal diseases as well as the development of effective interventions.
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@#To investigate the regulatory effects of insulin and oleic acid on serum metabolites in colon cancer, subcutaneous transplantation tumor model of colon carcinoma cell HCT116 was established. Nude mice were randomly divided into 4 groups: control (CON, vehicle); insulin treatment (INS, sc, 2.5 U/kg); oleic acid treatment (OA, ig, 2.0 g/kg); and insulin (sc, 2.5 U/kg) plus oleic acid (ig, 2.0 g/kg) treatment (IO). Non-target metabolomic analysis on the blood samples was performed by GC/MS and LC-IT-TOF/MS. Data pre-processing, including peaking, spectral deconvolution and peak alignment, was performed before data were imported to SIMCA-P for multivariate statistical analysis. Results showed that body weight of individuals in IO group was the lowest, but the tumor weight was the heaviest. Metabolic profiles of IO group were also different compared with the CON group, and the contributing metabolites were urea, arabinose, cholesterol, L-acetylcarnitine and sphingosine. There was no significant difference between OA or INS and CON. This study showed that the combination of insulin and oleic acid promoted colon cancer deterioration and caused metabolic disturbance in blood.Our study may provide theoretical foundation for the discovery of colon cancer biomarker and its early diagnosis.
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Intestinal toxicity induced by chemotherapeutics has become an important reason for the interruption of therapy and withdrawal of approved agents. In this study, we demonstrated that chemotherapeutics-induced intestinal damage were commonly characterized by the sharp upregulation of tryptophan (Trp)-kynurenine (KYN)-kynurenic acid (KA) axis metabolism. Mechanistically, chemotherapy-induced intestinal damage triggered the formation of an interleukin-6 (IL-6)-indoleamine 2,3-dioxygenase 1 (IDO1)-aryl hydrocarbon receptor (AHR) positive feedback loop, which accelerated kynurenine pathway metabolism in gut. Besides, AHR and G protein-coupled receptor 35 (GPR35) negative feedback regulates intestinal damage and inflammation to maintain intestinal integrity and homeostasis through gradually sensing kynurenic acid level in gut and macrophage, respectively. Moreover, based on virtual screening and biological verification, vardenafil and linagliptin as GPR35 and AHR agonists respectively were discovered from 2388 approved drugs. Importantly, the results that vardenafil and linagliptin significantly alleviated chemotherapy-induced intestinal toxicity
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@#The changes of metabolic profile are closely related to external stimulus, and the concentration of the metabolite can directly reflect the physiological or pathological states of organisms. Therefore, the quantitative detection of metabolites is necessary. However, traditional targeted metabolomic methods have such drawbacks as narrow coverage and low sensitivity. In recent years, derivatization techniques have developed rapidly in the field of metabolomics. Derivatization reagents for amine, hydroxyl, carboxyl, carbonyl, hydrosulphonyl and other groups have been used in metabolomics research. This paper introduces various derivatization reactions and their applications according to group classification and reviewes the characteristics of multi-group derivatization techniques, with a propect of their research directions and challenges.
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Pharmacometabolomics has been already successfully used in toxicity prediction for one specific adverse effect. However in clinical practice, two or more different toxicities are always accompanied with each other, which puts forward new challenges for pharmacometabolomics. Gastrointestinal toxicity and myelosuppression are two major adverse effects induced by Irinotecan (CPT-11), and often show large individual differences. In the current study, a pharmacometabolomic study was performed to screen the exclusive biomarkers in predose serums which could predict late-onset diarrhea and myelosuppression of CPT-11 simultaneously. The severity and sensitivity differences in gastrointestinal toxicity and myelosuppression were judged by delayed-onset diarrhea symptoms, histopathology examination, relative cytokines and blood cell counts. Mass spectrometry-based non-targeted and targeted metabolomics were conducted in sequence to dissect metabolite signatures in predose serums. Eventually, two groups of metabolites were screened out as predictors for individual differences in late-onset diarrhea and myelosuppression using binary logistic regression, respectively. This result was compared with existing predictors and validated by another independent external validation set. Our study indicates the prediction of toxicity could be possible upon predose metabolic profile. Pharmacometabolomics can be a potentially useful tool for complicating toxicity prediction. Our findings also provide a new insight into CPT-11 precision medicine.
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An acute myocardial infarction rat model was established by ligation of the left ventricular coronary artery.Plasma samples of rats were collected and analyzed by ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) to study the myocardial protection mechanism of compound Danshen dropping pill (CDDP).After principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), 22 metabolites were identified as potential biomarker of AMI.Furthermore, CDDP had remarkable effect on AMI rats.p-Tolyl sulfate, hippuric acid, equol 7-O-glucuronide, lysoPC(16∶0), cholic acid, oleamide, palmitic amide and SM(d18∶1/16∶0) were significantly changed in treatment group.The results showed that CDDP had a very good myocardial protection effect on AMI rats, and might influence the pathways of phenylalanine metabolism, glycerophospholipid metabolism, fatty acid metabolism, primary bile acid biosynthesis and Sphingolipid metabolism.
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Huangqin Decoction is a classic recipe for treatment of diarrhea from Treatise on Exogenous Febrile Disease,and consists of Scutellaria baicalensis,Paeonia lactiflora,Glycyrrhiza uralensis and Ziziphus jujuba.Huangqin Decoction has been used for nearly 1800 years for the treatment of gastrointestinal ailments,including dysentery,diarrhea and so on.Treatment of gastrointestinal disease by traditional Chinese medicine is considered to be safer than western medicine.This paper presented a review ofpharmacodynamic material basis of Huangqin Decoction,its advances in treating ulcerative colitis and reduction of the gastrointestinal side effects arising from chemotherapy drugs according to related literature.It also reviewed the deficiencies in present research,outlined the future direction and provided reference for further study.
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A colorimetric self-indicating probe for glucose was constructed by self-assembly of MnO2 nanosheets (MnO2 NSs) and glucose oxidase(GOD) in this paper.Under the weak acidic medium,glucose oxidase specifically catalyzes glucose into gluconic acid and hydrogen peroxide.The by-product of hydrogen peroxide could efficiently dissolve the MnO2 nanosheets,resulting into a significant decrease of the characteristic absorbance at 374 nm assigned to MnO2 NSs.Furthermore,the absorbance difference was linearly proportional to the concentration of glucose ranging from 1 to 20 μmol/L The fitted curve could be used for quantification of glucose with a correlation coefficient of 0.990 1.And the detection limit as low as 0.1 μmol/L could be reached based on the definition of three times of the deviation of the blank signal (3σ) and there was negligible interference with other co-existing amino acids,anions,cations and protein,which indicated high sensitivity and selectivity of the hybrid probe.The construction strategy of designated probe is readily generalized in principle for detection of numerous analytes in view of reactive property of MnO2 and the diversity of enzymes.
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Aim:To develop a rapid high-performance liquid chromatography-mass spectrometry (HPLC-MS) method for the quantification of tiopronin in human plasma.Methods:Cysteine was chosen as antioxidant and firstly added into the whole blood firstly.After adding mycophenolic acid as internal standard (IS) and 1 mol/L HCl into the plasma,the samples were extracted with acetic ether and then determined by HPLC-MS.The chromatographic separation was performed on a Shim-pack VP-ODS C18 column (250 mm×2.0 mm,5 μm) using methanol-0.1% acetic acid (70∶30) as mobile phase with a flow rate of 0.2 mL/min.Results:The assay exhibited a linear range of tiopronin between 30～4 000 ng/mL.The precisions for intra- and inter-batch were all within 8.5%.The extraction recoveries were more than 70%.The total HPLC-MS analysis time was within 7.5 min per a run.The fully validated method was successfully applied to quantify tiopronin in human plasma for a bioavailability study.Conclusion:The assay proved to be accurate,sensitive,selective and convenient.The fully validated method can be applied to study the pharmacokinetics and bioavailability of tiopronin and tiopronin formulations in human.
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Objective: To establish the fingerprint of Danshen Glucose Injection by HPLC. Methods: Separation was performed on an Alltima C18(4.6mm?250mm,5?m) analytical column, with mobile phase consisting of 1 %acetic-water and 1 %acetic acid-methanol and with gradient elute at the flow rate of 1mL/min-1. The UV detection was set at 281nm. Results: Six peaks of Danshen Glucose Injection wre indicated, and the chief ingredients were determined by HPLC. Conclusion: This method is accurate and with good reproducibility and can be used for the quality control of Danshen Glucose Injection.