Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 430
Filter
1.
Article in Chinese | WPRIM | ID: wpr-923021

ABSTRACT

Objective To study the reversal effect of Shenfu decoction(SFD)on adriamycin-induced cardiomyopathy and explore its mechanism by using serum metabolomic technology. Methods The BALB/c mouse model of cardiomyopathy induced by adriamycin was established. The corresponding intervention was given. The serum lactate dehydrogenase(LDH)and creatine phosphatase isoenzyme MB(CK-MB)were measured. The ejection fraction (EF) and shortening fraction (FS) were measured by echocardiography. Mouse serum was collected for gas chromatography-mass spectrometry (GC-MS) analysis. The data obtained was analyzed by multivariate and univariate statistical analysis to compare the changes of endogenous metabolites in the serum of mice in the normal group, model group and Shenfu decoction treatment group, to find the potential biomarkers of Shenfu decoction to reverse the adriamycin-induced cardiomyopathy. Metabolic pathway analysis was used to explore the targeted metabolic pathway of Shenfu decoction. Results The levels of serum LDH and CK-MB in the model group were increased significantly, and the values of EF and FS decreased significantly, indicating that the model was successfully established. The above indicators were significantly improved after treatment with Shenfu decoction. 13 potential biomarkers of adriamycin-induced cardiomyopathy were identified by metabonomic analysis, and Shenfu decoction had significant reversal effect on 11 metabolites. Metabolic pathway analysis showed that the synthesis of phenylalanine, tyrosine and tryptophan, arachidonic acid metabolism, phenylalanine metabolism, tricarboxylic acid cycle and dicarboxylic acid metabolism were the main targeted metabolic pathways of Shenfu decoction. Conclusion Shenfu decoction can reverse adriamycin-induced cardiomyopathy by regulating the unbalanced synthesis of phenylalanine, tyrosine and tryptophan, as well as the metabolism of arachidonic acid, phenylalanine, dicarboxylic acid and tricarboxylic acid cycle.

2.
Acta Pharmaceutica Sinica ; (12): 419-427, 2022.
Article in Chinese | WPRIM | ID: wpr-922924

ABSTRACT

GC-MS metabolomics was used to investigate the effects of fudosteine on lung cancer A549 cells in an inflammatory microenvironment. Eleven metabolites (malic acid, isoleucine, lactose, galactinol, creatinine, gluconic acid, oleic acid, phosphate, S-carboxymethyl-L-cysteine, uridine and tagatose) were identified in the metabolomics results and could be used as biomarkers of fudosteine treatment. Pathway enrichment analysis showed that the metabolic pathways of amino acids including isoleucine, valine, leucine, glycine, serine and threonine were significantly altered, as were the metabolic pathways of carbohydrates such as galactose and pentose phosphate. Fudosteine significantly reduced the level of inflammatory factors in A549 cells and corrected the inflammatory microenvironment by interfering with the effects of amino acid metabolites and amino acid metabolism pathways. This study reveals that fudosteine may be able to inhibit the continuous inflammatory response and prevent the further progression of lung cancer by suppressing the inflammatory microenvironment.

3.
Acta Pharmaceutica Sinica ; (12): 793-801, 2022.
Article in Chinese | WPRIM | ID: wpr-922901

ABSTRACT

Multicellular tumor spheroids (MCTS) can simulate the structure and metabolic characteristics of tumors in vivo, which is of great significance to study the metabolic phenotype of tumor cells and the mechanism of drug intervention. In this study, esophageal cancer MCTS were constructed, and MCTS frozen sections were prepared after treated with different formulations of paclitaxel (PTX) including common PTX injection, PTX liposome and albumin bound PTX. MCTS mass spectrometry imaging analysis method was established by using air flow assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI). The visualization of the permeation and enrichment process of PTX in MCTs after PTX treatment was realized, and the spatially resolved metabolomics of PTX injection group was studied. The results showed that the permeation and enrichment behavior of PTX in MCTs model were related to the formulations. The changes of endogenous metabolites in MCTs of esophageal cancer after treated with PTX injection had temporal and spatial characteristics. The metabolic changes of MCTS during the initial 0-4 hours were dominated by the down-regulation of middle-high polarity metabolites and some lipids in the central region of MCTS, while the metabolic changes of MCTS during 8-72 hours were mainly up-regulated by lipid metabolites in the peripheral region of MCTS. The combination of in vivo tumor-associated MCTs model with label free, highly sensitive and high coverage mass spectrometry imaging technology provided a new method and strategy for the study of pharmacometabolomics.

4.
Acta Pharmaceutica Sinica ; (12): 783-792, 2022.
Article in Chinese | WPRIM | ID: wpr-922891

ABSTRACT

Molecular mass distribution of Astragalus polysaccharides is wide. Astragalus polysaccharides prepared by conventional water extraction and alcohol precipitation are mostly mixture of macromolecules. Although studies have shown that Astragalus polysaccharides have two-sided immunomodulation, the relationship between anti-inflammatory components and molecular mass distribution of Astragalus polysaccharides is not clear. Therefore, Astragalus polysaccharides were extracted by water extraction and alcohol precipitation. The relative molecular weight of them was determined by high performance gel permeation chromatography (HPGPC). Astragalus polysaccharides with different molecular weights were separated and prepared by membrane separation. RAW 264.7 cells were induced by lipopolysaccharide (LPS) to establish an inflammatory cell model in vitro and the anti-inflammatory polysaccharide were screened. The anti-inflammatory regulation mechanism of Astragalus polysaccharides was analyzed by the LC-MS/MS metabonomics technology. The results showed that APS was composed of APS-Ⅰ ( > 2 000 kDa) and APS-Ⅱ (10 kDa). APS-Ⅰ was composed of mannose, rhamnose, galacturonic acid, glucose, galactose, arabinose and the molar ratios of these monosaccharide of APS-I were 0.54∶0.26∶12.24∶17.24∶8.46∶1. APS-II was composed of rhamnose, galacturonic acid, glucose, galactose, arabinose and the molar ratios of these monosaccharide of APS-II were 0.26∶0.14∶24.04∶0.62∶1. APS-Ⅰ and APS-Ⅱ had no cell toxicity to RAW 264.7 macrophage in the range of 0-100 μg·mL-1. Compared with the model group, APS-I at a concentration of 0-100 μg·mL-1could significantly inhibit the secretion of NO and TNF-α by RAW 264.7, and can significantly promote the secretion of IL-10. APS-I had better anti-inflammatory activity than APS-II in vitro. The metabolomics results showed that 32 different metabolites were found between the model group and blank group; APS-I group can significantly callback 18 different metabolites; mainly related to arginine biosynthesis, arginine and proline metabolism, pyrimidine metabolism, citric acid cycle (TCA cycle), cysteine and methionine acid metabolism, tryptophan metabolism. This study found that APS-I had better anti-inflammatory activity than APS-II in vitro, and its mechanism may be closely related to amino acid metabolism and energy metabolism, which indicated the direction for further clarifying the pharmacodynamic material basis of Astragalus polysaccharides.

5.
Article in English | WPRIM | ID: wpr-922754

ABSTRACT

OBJECTIVE@#Numerous studies have demonstrated the close relationship between chronic stress and blood pressure (BP). Hypertensive subjects exhibit exaggerated reactions to stress, especially higher BP. The mechanisms by which stress affects pre-existing hypertension still need to be explored. Danzhi Xiaoyao Powder (DP), a historical traditional Chinese medicine formula, is a promising treatment for BP control in hypertensive patients under stress. The present study investigated the metabolomic disruption caused by chronic stress and the treatment effect and mechanism of DP.@*METHODS@#Spontaneously hypertensive rats (SHRs) were subjected to chronic restraint stress (CRS) for 4 weeks. BP was measured via the tail-cuff method, and anxiety-like behavior was quantified using the elevated-plus-maze test. Meanwhile, DP was administered intragastrically, and its effects were observed. Global metabolomic analysis was performed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, followed by multivariate statistical analysis to detect differential metabolites and pathways.@*RESULTS@#DP alleviated the CRS-induced increase in BP and anxiety-like behavior. Systematic metabolic differences were found among the three study groups. A total of 29 differential plasma metabolites were identified in both positive- and negative-ion modes. These metabolites were involved in triglyceride metabolism, amino acid (phenylalanine, tryptophan, and glycine) metabolism, and steroid hormone pathways.@*CONCLUSION@#These findings expose the metabolomic disturbances induced by chronic stress in SHRs and suggest an innovative treatment for this disorder.


Subject(s)
Animals , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/pharmacology , Humans , Medicine, Chinese Traditional , Powders , Rats , Rats, Inbred SHR
6.
Arq. bras. med. vet. zootec. (Online) ; 73(4): 929-937, Jul.-Aug. 2021. tab, graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1285261

ABSTRACT

The objective of the present study was to investigate the different plasma metabolites between anestrus and estrus postpartum dairy cows and to provide a theoretical basis for prevention of anestrus in dairy farm cows. In the experiment, one hundred and sixty-seven Holstein dairy cows were selected with similar age and parity. According to the concentration of ß-hydroxybutyric acid, non-esterified fatty acids and glucose in plasma during 14 to 21 days in milk, all dairy cows were determined as having a status of energy balance. According to the results of clinical symptom, rectal and B ultrasound examination at 60 to 90 days postpartum, these cows were divided into twenty estrus and twenty-four anestrus group, other dairy cows were removed. 1H nuclear magnetic resonance technology was utilized to detect the plasma metabolites changes and screen different plasma metabolites between anestrus and estrus cows. Ten different metabolites including alanine, glutamic acid, asparagine, creatine, choline, phosphocholine, glycerophosphocholine, low-density lipoprotein, and very-low-density lipoprotein were significantly decreased in anestrous cows compared with estrous cows. Metabolic pathway analyses indicated that differential metabolites were primarily involved in amino acid and glycerophospholipid metabolism. These metabolites and their enrichment pathways indicate that reduced steroid hormone synthesis precursors result in lower levels of estradiol and progesterone and cause anestrus in negative energy balance. These data provide a better understanding of the changes that may affect estrus of postpartum dairy cows at NEB status and lay the ground for further research.(AU)


O objetivo do presente estudo foi investigar os diferentes metabolitos do plasma entre o cio e o cio pós-parto de vacas leiteiras e fornecer uma base teórica para a prevenção do cio de vacas em fazendas de leite. No experimento, foram selecionadas 127 vacas leiteiras Holstein com idade e paridade similares. De acordo com a concentração de ß- ácido hidroxibutírico, ácidos graxos não esterificados e glicose no plasma entre 14 e 21 dias no leite, todas as vacas leiteiras foram determinadas em estado de equilíbrio energético. De acordo com os resultados dos sintomas clínicos, do exame de ultra-som retal e B aos 60 a 90 dias pós-parto, estas vacas foram divididas em vinte cios e vinte e quatro grupos de cio, outras vacas leiteiras foram removidas. A tecnologia de ressonância magnética nuclear 1H foi utilizada para detectar as alterações dos metabólitos plasmáticos e para triar diferentes metabólitos plasmáticos entre as vacas do cio e do cio. Dez diferentes metabólitos incluindo alanina, ácido glutâmico, asparagina, creatina, colina, fosfocholina, glicerofosfocolina, lipoproteína de baixa densidade e lipoproteína de muito baixa densidade foram significativamente diminuídos nas vacas antróficas em comparação com as vacas estro. As análises da via metabólica indicaram que os metabólitos diferenciais estavam principalmente envolvidos no metabolismo de aminoácidos e glicerofosfolipídios. Estes metabólitos e suas vias de enriquecimento indicam que a redução dos precursores da síntese de hormônios esteróides resulta em níveis mais baixos de estradiol e progesterona e causa anestros no balanço energético negativo. Estes dados fornecem uma melhor compreensão das mudanças que podem afetar o cio das vacas leiteiras pós-parto no estado de NEB e preparam o terreno para mais pesquisas.(AU)


Subject(s)
Animals , Female , Cattle , Progesterone/analysis , Anestrus/blood , Estrus/blood , Postpartum Period/blood , Estradiol/analysis , Glycerophospholipids , Fatty Acids, Nonesterified , Amino Acids , Glucose , Hematologic Tests/veterinary
7.
Article in Chinese | WPRIM | ID: wpr-912076

ABSTRACT

Objective:To research the metabolomic alterations of human lung bronchial epithelial cells infected with human rhinovirus 1B (HRV1B).Methods:Untargeted metabolomics was used to determine the metabolomic alterations in human lung bronchial epithelial cells (BEAS-2B) 6 h, 12 h and during the dynamic process (6 h∶12 h) after HRV1B infection.Results:A total of 93 differentially significant metabolites (DSMs) (47 DSMs were up-regulated and 46 DSMs were down-regulated) and 88 DSMs (37 DSMs were up-regulated and 51 DSMs were down-regulated) at post infection of HRV1B in BEAS-2B at 6 h or 12 h, respectively. A total of 30 DSMs (12 DSMs were up-regulated and 18 DSMs were down-regulated) in a dynamic process (6 h∶12 h) after HRV1B infection. Unknown metabolites took up most proportions. The trends of fatty acid, lipid, amino acid, nucleotide and carbohydrate were increased along with the prolonging of HRV1B infection. DSMs such as Diisononyl phthalate was co-detected DSMs among three groups.Conclusions:Metabolites such as fatty acid, lipid, amino acid, nucleotide and carbohydrate of BEAS-2B cells are changed induced by HRV1B infection.

8.
Article in Chinese | WPRIM | ID: wpr-910358

ABSTRACT

Objective:To study the effect of fasting on 137Cs γ-ray radiation-induced intestinal injury in mice, and to explore the effect of fasting on fecal metabolites of mice through non-targeted metabolomics. Methods:C57BL/6 mice were divided into healthy control group, 9 Gy γ-ray whole body irradiation (WBI)/ 15 Gy γ-ray whole abdominal irradiation (WAI) group, fasting (24 h, 48 h, 72 h)+ 9 Gy WBI/ 15 Gy WAI group. After irradiation, the survival rate, spleen index and thymus index were calculated. C57BL/6 mice in non-target metabolism experiment were randomly divided into four groups: control group, fasting 24 h group, 15 Gy γ-ray WAI group, fasting 24 h + 15 Gy γ-ray WAI group, 6 mice in each group. After 15 Gy WAI, the feces of mice in each group were collected at 3.5 days for non-targeted metabolomics detection.Results:The median survival time of mice with 48 h and 24 h fasting before 9 Gy γ-ray irradiation was increased by 1 day and 4 days, and the survival rates of mice treated with 48 h and 24 h fasting before 15 Gy WAI were 16.67% and 25%, respectively. 15 Gy γ-ray WAI on mice with fasting for 24 h before irradiation could increase the body weight ( t=2.338, P=0.042) and spleen index ( t=2.289, P=0.045) at 3.5 days after irradiation. Through non-targeted metabonomic analysis, it was found that there were 30 differentially expressed metabolites in fecal samples of fasting and non-fasting mice subjected to WAI, and metabolic pathway enrichment analysis showed that there was an imbalance in the metabolic pathway of steroid biosynthesis. Conclusions:Fasting before irradiation can improve the survival rate of mice with intestinal radiation injury and change their intestinal metabolites, suggesting that pre-irradiation fasting or short-term dietary nutrition changes are involved in the regulation of intestinal radiation damage.

9.
Article in Chinese | WPRIM | ID: wpr-910329

ABSTRACT

Objective:To investigate the metabolite changes in rat plasma after total body irradiation (TBI) and to explore dose classification based on radiation sensitive metabolites.Methods:The differential metabolites induced by radiation were screened and verified by metabolomics. In the discovery stage, 50 SD rats were irradiated with 0, 1, 2, 3, 5 and 8 Gy of 60Co γ-rays. In the verification stage, 25 rats were irradiated with 0, 0.5, 2.5, 4 and 6 Gy. Peripheral blood samples were collected 4 h after irradiation, and plasma was separated. Radiation-induced differential metabolites were identified and their concentrations were determined. Receiver operating characteristic (ROC) curve of the differential metabolites was used to classify dose range. Results:In the discovery stage, 8 radiation-induced differential metabolites in rat plasma were identified and four of them (cytosine, L-hexylcarnitine, Linoelaidylcarnitine and L-palmitylcarnitine) were upregulated, which was confirmed in the verification stage. The area under the curve (AUC) for the specific dose was >0.75. After combining these four metabolites, the AUC value to classify the radiation dose of 0 Gy versus >0 Gy, <2 Gy versus ≥2 Gy, <5 Gy versus ≥5 Gy were 0.96, 1 and 0.94, respectively.Conclusions:The metabolites in rat plasma changed significantly at 4 h after TBI, where 8 differential metabolites were identified. Cytosine, L-hexylcarnitine, linoelaidylcarnitine and L-palmiylcarnitine were stably over-expressed in the plasma after irradiation. The combination of these four compounds had high classification accuracy and thus may applicable as radiation sensitive biomarkers for dose classification.

10.
Article in Chinese | WPRIM | ID: wpr-909608

ABSTRACT

OBJECTIVE To explore the pathogenesis of depression according to the LC-MS/MS-based metabolo?mics in the mouse model which exhibits social avoidance state induced by the chronic social defeat stress model (CSDS). METHODS Twenty male C57BL/6N mice were randomly divided into control group and model group suffering CSDS, and the ICR retired breeder mice were used to attack the model group for 14 d of chronic social defeated stress. The open field test and source preference test were both used to observe depression-like behavior. Besides, the social inter?action test is used to observe the social interaction state, especially. After the stress, the serum samples of mice were collected, and the changes of endogenous metabolites were analyzed by LC-MS metabolomics technology, and the pathway analysis of the differential metabolites was performed to explore the pathogenesis of the CSDS induced depres?sive-like mouse model. RESULTS After the stress of CSDS was completed, the mice in the model group showed a significant slowdown in body weight growth, a reduction in the source preference rate, and a significant reduction in the total distance and the number of rearing in the open field test. Distinctively, the social interaction rate is remarkably decreasing. There are 24 differential metabolites found in the serum of CSDS model mice. CONCLUSION The mouse who suffered CSDS stress would show depressive-like behavior. Based on the LC-MS/MS metabolomics, 24 differential metabolites were found in the serum of CSDS model mice. The amino acid metabolism might be significant to the patho?genesis of the CSDS induced depressive-like mouse model.

11.
Article in Chinese | WPRIM | ID: wpr-909571

ABSTRACT

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 candi?date drug for the prevention of PAH, but the underlying modulatory mechanism is still unclear. Our study aims at investi?gating the metabolic modulatory mechanism of osthole against PAH employing functional metabolomics strategy. METH?ODS PAH model rats were successfully established with MCT, following osthole administration, then functional metabo?lomics 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 biosyn?thesize 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.

12.
Chinese Journal of Endemiology ; (12): 524-529, 2021.
Article in Chinese | WPRIM | ID: wpr-909045

ABSTRACT

Objective:To screen differential metabolites and metabolic pathways which are related to knee osteoarthritis in rats, and to provide clues for further study of biomarkers of osteoarthritis.Methods:Sixty SPF male SD rats were divided into model and control groups according to their body weight (300 - 350 g) by random number table method, with 30 rats in each group. The experimental periods were 4, 8 and 12 weeks, each period included 10 rats in each group. The left knee joints of rats in the model group were operated by the modified Hulth method. After 5 d, rats in the model group were driven to move for 30 min every day. All rats were fed ordinary solid fodder and drank tap water. At the end of the experimental period, the knee joints and blood samples of rats were collected. Hematoxylin-eosin (HE) staining was used to observe histopathological changes of knee joint, ultra-performance liquid chromatography quadrupole time-flight mass spectrometry (UPLC-Q-TOF-MS) was used to detect small molecule metabolites in serum, and multivariate statistical analysis and database comparison were used to screen the differential metabolites and related metabolic pathways associated with osteoarthritis.Results:In the model group, the articular cartilage of knee was thinned, the surface was roughness, defect or peeling, chondrocytes were degeneration, necrosis and deletion, and the lesions were aggravated with prolonged experimental period. A total of 11 serum differential metabolites related to osteoarthritis were screened out, including selenocysteine, 6-hydroxymelatonin, γ-glutamylcysteine, arachidonic acid, sphinganine, leukotriene A4, leukotriene B4, 11,12-epoxy-eicostrienoic acid (11,12-EpETrE), lysopc, ceramide and N-arachidonoyl glycine. Among them, 9 metabolites were screened out at 4 weeks, compared with the control group, 5 metabolites were increased and 4 metabolites were decreased in the model group; 8 metabolites were screened out at 8 weeks, compared with the control group, 2 metabolites were increased and 6 metabolites were decreased in the model group; 8 metabolites were screened out at 12 weeks, compared with the control group, 5 metabolites were increased and 3 metabolites were decreased in the model group. The most relevant metabolic pathways related to osteoarthritis were sphingolipid metabolic pathway and arachidonic acid metabolic pathway. Sphinganine and ceramide were belonged to sphingolipid metabolic pathway, whereas arachidonic acid, leukotriene A4 and leukotriene B4 were belonged to arachidonic acid metabolic pathway.Conclusions:The progression of osteoarthritis can affect the composition and level of serum metabolite profile. Eleven serum differential metabolites are involved in sphingolipid metabolic pathway and arachidonic acid metabolic pathway, which are related to the occurrence and development of osteoarthritis.

13.
Article in Chinese | WPRIM | ID: wpr-908788

ABSTRACT

Solid phase microextraction(SPME)in combination with high-resolution mass spectrometry was employed for the determination of metabolomic profile of mouse melanoma growth within in vitro 2D,in vitro 3D,and in vivo models.Such multi-model approach had never been investigated before.Due to the low-invasiveness of SPME,it was possible to perform time-course analysis,which allowed building time profile of biochemical reactions in the studied material.Such approach does not require the multiplication of samples as subsequent analyses are performed from the very same cell culture or from the same individual.SPME already reduces the number of animals required for experiment;therefore,it is with good concordance with the 3Rs rule(replacement,reduction,and refinement).Among tested models,the largest number of compounds was found within the in vitro 2D cell culture model,while in vivo and in vitro 3D models had the lowest number of detected compounds.These results may be connected with a higher metabolic rate,as well as lower integrity of the in vitro 2D model compared to the in vitro 3D model resulting in a lower number of compounds released into medium in the latter model.In terms of in vitro-in vivo extrapolation,the in vitro 2D model performed more similar to in vivo model compared to in vitro 3D model;however,it might have been due to the fact that only compounds secreted to medium were investigated.Thus,in further experiments to obtain full metabolome infor-mation,the intraspheroidal assessment or spheroid dissociation would be necessary.

14.
Article in Chinese | WPRIM | ID: wpr-908781

ABSTRACT

Astragali radix(AR,the dried root of Astragalus)is a popular herbal remedy in both China and the United States.The commercially available AR is commonly classified into premium graded(PG)and ungraded(UG)ones only according to the appearance.To uncover novel sensitive and specific markers for AR grading,we took the integrated mass spectrometry-based untargeted and targeted metabolomics ap-proaches to characterize chemical features of PG and UG samples in a discovery set(n=16 batches).A series of five differential compounds were screened out by univariate statistical analysis,including arginine,calycosin,ononin,formononetin,and astragaloside Ⅳ,most of which were observed to be accumulated in PG samples except for astragaloside Ⅳ.Then,we performed machine learning on the quantification data of five compounds and constructed a logistic regression prediction model.Finally,the external validation in an independent validation set of AR(n=20 batches)verified that the five com-pounds,as well as the model,had strong capability to distinguish the two grades of AR,with the pre-diction accuracy>90%.Our findings present a panel of meaningful candidate markers that would significantly catalyze the innovation in AR grading.

15.
Article in Chinese | WPRIM | ID: wpr-908770

ABSTRACT

The aim of this study was to develop a diagnostic strategy for esophageal squamous cell carcinoma(ESCC) that combines plasma metabolomics with machine learning algorithms.Plasma-based untargeted metabolomics analysis was performed with samples derived from 88 ESCC patients and 52 healthy controls.The dataset was split into a training set and a test set.After identification of differential me-tabolites in training set,single-metabolite-based receiver operating characteristic (ROC) curves and multiple-metabolite-based machine learning models were used to distinguish between ESCC patients and healthy controls.Kaplan-Meier survival analysis and Cox proportional hazards regression analysis were performed to investigate the prognostic significance of the plasma metabolites.Finally,twelve differential plasma metabolites (six up-regulated and six down-regulated) were annotated.The pre-dictive performance of the six most prevalent diagnostic metabolites through the diagnostic models in the test set were as follows:arachidonic acid (accuracy:0.887),sebacic acid (accuracy:0.867),indoxyl sulfate (accuracy:0.850),phosphatidylcholine (PC) (14:0/0:0) (accuracy:0.825),deoxycholic acid(accuracy:0.773),and trimethylamine N-oxide (accuracy:0.653).The prediction accuracies of the ma-chine learning models in the test set were partial least-square (accuracy:0.947),random forest (accu-racy:0.947),gradient boosting machine (accuracy:0.960),and support vector machine (accuracy:0.980).Additionally,survival analysis demonstrated that acetoacetic acid was an unfavorable prognostic factor(hazard ratio (HR):1.752),while PC (14:0/0:0) (HR:0.577) was a favorable prognostic factor for ESCC.This study devised an innovative strategy for ESCC diagnosis by combining plasma metabolomics with machine learning algorithms and revealed its potential to become a novel screening test for ESCC.

16.
Article in Chinese | WPRIM | ID: wpr-906473

ABSTRACT

Objective:To investigate the effect of Huayu Jiedu prescription (HYJDP) on gut microbiota and fecal metabolites in mice with endometriosis. Method:Normal female C57BL/6J mice were divided into normal control group (CO), endometriosis group (EM) and Chinese medicine Huayu Jiedu decocotion group (CM). CO and EM groups received normal saline and CM group received HYJDP by intragastric administration. Untargeted metabolomics method was used to detect metabolites in fecal supernatant of mice, and receiver operating characteristic (ROC) analysis was used to screen the differential metabolites, 16S rRNA high-throughput sequencing was used to detect the gut microbiota, and Spearman correlation coefficient was used to represent the degree of correlation between differential metabolites and intestinal flora. Lipopolysaccharides (LPSs) in intestinal wall tissue, serum and peritoneal lavage fluid were detected by enzyme-linked immunosorbent assay (ELISA). The expression of Vimentin and E-cadherin in ectopic lesions was detected by immunohistochemistry. Result:HYJDP alleviated the disorders of fecal metabolites and gut microbiota in EMS mice, especially with the recovered levels of homoveratric acid, melilotoside C and physapubescin in fecal supernatant. In the comparison of these three factors between EM group and CO group as well as between EM group and CM group, the variable important in projection (VIP) value was both above 2, and AUC in ROC analysis was both >0.9. As compared with EM group, HYJDP restored the abundance of species such as <italic>Lachnospiraceae_NK4A136_group</italic>, <italic>Lactobacillus</italic> and <italic>Blautia </italic>(<italic>P</italic><0.05). In addition, the level of LPS in peritoneal fluid supernatant of EM group was significantly higher than that of CO group (<italic>P</italic><0.05) and CM group (<italic>P</italic><0.05). The protein expression of vimentin and E-cadherin in endometriosis decreased significantly (<italic>P</italic><0.05). Conclusion:HYJDP which can improve the intestinal environment and reduce the level of LPS in mice with endometriosis, is an effective drug for the treatment of endometriosis.

17.
Article in Chinese | WPRIM | ID: wpr-906412

ABSTRACT

Liver, as a critical organ of metabolism and detoxification, can be damaged by viral infection, drug abuse, and heavy drinking. Liver diseases pose a serious threat to people's health and life in China.At present, drug therapy has been primarily adopted clinically in the treatment of the liver injury.In-depth investigation of the mechanism of liver-protective drugs is of great significance to the prevention and treatment of clinical liver diseases.In recent years, with the development of the medical industry in China, an increasing number of studies have focused on the treatment of liver injury with Chinese medicine.Compared with western medicine, Chinese medicine is advantageous in few side effects and overall regulation, which plays a pivotal role in liver protection.However, its underlying mechanism in liver protection still needs to be further studied due to its complex compositions and diverse targets.Metabolomics, a new approach to studying the metabolic pathway of biological systems, provides integral and systematic views in the investigation of liver protection with Chinese medicine. By virtue of metabolomics, the mechanism of Chinese medicine in multi-target and multi-pathway liver protection can be analyzed comprehensively, and the corresponding biomarkers can also be screened out. The authors analyzed the studies of the treatment of chemical liver injury models induced by carbon tetrachloride (CCl4), dimethylnitrosamine (DMN), α-naphthyl isothiocyanate (ANIT), and alcohol by Chinese medicinal compounds, single herbal medicines, and monomers of Chinese medicine based on metabolomics, and summarized the biomarkers and related metabolic pathways of Chinese medicine in the intervention of each type of liver injury, aiming at providing a reference for the further research and clinical application in the treatment of different types of liver injuries by Chinese medicine.

18.
Article in Chinese | WPRIM | ID: wpr-905907

ABSTRACT

Objective:To investigate the biological essence of the content variation of differential primary and secondary metabolites in fresh<italic> </italic>roots of <italic>Scutellaria baicalensis </italic>under drought stress. Method:The changes of metabolites were analyzed by ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass/mass (UHPLC-ESI-Q-TOF-MS/MS). Result:A total of 11 differential compounds were identified from the roots of <italic>S. baicalensis</italic> (VIP≥2). Under drought stress, citric acid content increased and shikimic acid content decreased, indicating that the drought stress weakened the primary metabolism but strengthened secondary metabolism. Drought stress raised the content and regulated the proportion of various secondary metabolites by modulating the biosynthesis and biotransformation of them. To be specific, the content of free flavonoids with many phenolic hydroxyl groups and high biological activity and pharmacological activity, such as baicalin, wogonoside, baicalein, wogonin, chrysin, eriodictyol, 5,2',6'-trihydroxy-7,8-dimethoxyflavone, 5,8-dihydroxy-6,7-dimethoxyflavone, and 3,5,7,2',6'-pentahydroxyflavanone, was significantly increased. The massive compounds, like an intricate buffer, maintain metabolism stable as quickly and accurately as possible through biosynthesis and biotransformation, thus responding to the changing environment, which reveals how the quality of genuine regional drugs is influenced and why compounds in herbal medicine are complex. Conclusion:Secondary metabolites with low content but high activity are important influencing factors of medicinal material quality and metabolites with high content and high activity are evaluation indicators of genuine regional drug quality.

19.
Article in English | WPRIM | ID: wpr-922775

ABSTRACT

Oral mucositis (OM) caused by cancer therapy is the most common adverse reaction in the radiotherapy of head and neck tumors. In severe cases, it can lead to the interruption of treatment, which affects the control of the disease and the quality of life. Shuanghua Baihe Tablet (SBT) is a traditional Chinese medicine (TCM) formula, which is administerd to treat OM in China. It has been clinically effective for more than 30 years, but the underlying mechanism is not completely understood. With the development of multiple omics, it is possible to explore the mechanism of Chinese herbal compound prescriptions. Based on transcriptomics and metabolomics, we explored the underlying mechanism of SBT in the treatment of OM. An OM model of rats was established by 5-FU induction, and SBT was orally administered at dosages of 0.75 and 3 g·kg


Subject(s)
Animals , Drugs, Chinese Herbal , Metabolome , Quality of Life , Rats , Stomatitis , Tablets , Transcriptome
20.
Acta Pharmaceutica Sinica B ; (6): 3665-3677, 2021.
Article in English | WPRIM | ID: wpr-922433

ABSTRACT

Detailed knowledge on tissue-specific metabolic reprogramming in diabetic nephropathy (DN) is vital for more accurate understanding the molecular pathological signature and developing novel therapeutic strategies. In the present study, a spatial-resolved metabolomics approach based on air flow-assisted desorption electrospray ionization (AFADESI) and matrix-assisted laser desorption ionization (MALDI) integrated mass spectrometry imaging (MSI) was proposed to investigate tissue-specific metabolic alterations in the kidneys of high-fat diet-fed and streptozotocin (STZ)-treated DN rats and the therapeutic effect of astragaloside IV, a potential anti-diabetic drug, against DN. As a result, a wide range of functional metabolites including sugars, amino acids, nucleotides and their derivatives, fatty acids, phospholipids, sphingolipids, glycerides, carnitine and its derivatives, vitamins, peptides, and metal ions associated with DN were identified and their unique distribution patterns in the rat kidney were visualized with high chemical specificity and high spatial resolution. These region-specific metabolic disturbances were ameliorated by repeated oral administration of astragaloside IV (100 mg/kg) for 12 weeks. This study provided more comprehensive and detailed information about the tissue-specific metabolic reprogramming and molecular pathological signature in the kidney of diabetic rats. These findings highlighted the promising potential of AFADESI and MALDI integrated MSI based metabolomics approach for application in metabolic kidney diseases.

SELECTION OF CITATIONS
SEARCH DETAIL