基于UPLC-QTOFMS正、负离子模式对无偿献血者乙型肝炎表面抗原阳性血清代谢组学的研究

目的:基于超高效液相色谱-单四极杆飞行时间质谱(UPLC-QTOFMS)正、负离子模式探讨无偿献血者中乙型肝炎表面抗原阳性和乙型肝炎表面抗原阴性的血清代谢组学的差异,为乙型肝炎的诊断寻找潜在的血清生物标志物。方法:选取2017年10月~2018年1月在青海省血液中心检测的乙型肝炎表面抗原阳性57例(研究组)与同期无偿献血者乙型肝炎表面抗原阴性63例(对照组),利用UPLC-QTOFMS技术建立两组血清代谢指纹图谱,采用主成分分析(PCA)和偏最小二乘法-判别分析(PLS-DA)分析两组间有差异的小分子物质,确定与乙型肝炎相关的生物标志物,并分析相关代谢机制。结果:通过变量重要性投影、质谱鉴定和数据库检索筛选出8个潜在的生物标志物,分别为缬氨酸、胆碱、甘氨鹅去氧胆酸、肉毒碱、高丝氨酸、溶血磷脂酰胆碱、血清溶菌酶和花生四烯酸,涉及胆汁酸代谢、氨基酸代谢、磷脂代谢等。结论:无偿献血者中乙型肝炎表面抗原阳性和乙型肝炎表面抗原阴性的血清代谢物存在显著差异,差异代谢物的发现有助于寻找乙型肝炎的潜在生物标志物,为血液安全提供依据。     

Effects of the Suxiao Jiuxin pill on acute myocardial infarction assessed by comprehensive metabolomics

BackgroundSJP is the commercial Chinese medicine included in the Chinese Pharmacopoeia, with well-established cardiovascular protective effects in the clinic. However, the mechanisms underlying the protective effects of SJP on cardiovascular disease have not yet been clearly elucidated.AimsTo investigate the underlying protective mechanisms of SJP in an acute myocardial infarction (AMI) rat model using comprehensive metabolomics.Materials and methodsThe rat model of AMI was generated by ligating the left anterior descending coronary artery. After 2 weeks treatment with SJP, the entire metabolic changes in the serum, heart, urine and feces of the rat were profiled by HPLC-QTOF-MS/MS.ResultsThe metabolic profiles in different biological samples (heart, serum, urine and feces) were significantly different among groups, in which a total of 112 metabolites were identified. AMI caused comprehensive metabolic changes in amino acid metabolism, galactose metabolism and fatty acid metabolism, while SJP reversed more than half of the differential metabolic changes, mainly affecting amino acid metabolism and fatty acid metabolism. Correlation analysis found that SJP could significantly alter the metabolic activity of 12 key metabolites, regarded as potential biomarkers of SJP treatment. According to the results of network analysis, 6 biomarkers were considered to be hub metabolites, which means that these metabolites may have a major relationship with the SJP therapeutic effects on AMI.ConclusionThe combined comprehensive metabolomics and network analysis, indicated that the protective effect of SJP on cardiovascular disease was associated with systemic metabolic modulation, in particular regulation of amino acid and fatty acid metabolism.     

Untargeted metabolomics: an overview of its usefulness and future potential in prenatal diagnosis

ABSTRACT

Introduction: Metabolomics opens up new avenues for biomarker discovery in different branches of medicine, including perinatology. Chromosomal aberration, preterm delivery (PTD), congenital heart defects, spina bifida, chorioamnionitis, and low birth weight are the main perinatal pathologies. Investigations using untargeted metabolomics have found the candidate metabolites for diagnostic biomarkers.

Areas covered: This review describes areas of prenatal diagnosis in which untargeted metabolomics has been used. Data on the disease, type of sample, techniques used, number of samples used in the study, and metabolites obtained including the sign of their regulation are summarized.

Expert commentary: Untargeted metabolomics is a powerful tool which can shed a new light on prenatal diagnostics. It helps to discover affected metabolic pathways what may help to reveal disease pathogenesis and propose potential biomarkers. Among others, glycerol and 2- and 3-hydroxybutyrate were proposed as markers of chromosomal aberration. Serum metabolic signature of PTD was characterized by increased lipids and decreased levels of hypoxanthine, tryptophane, and pyroglutamic acid. Lower level lipids and vitamin D3 metabolites together with increased bilirubin level in maternal serum were associated with macrosomia. However, to give a real value to those assays and allow their clinical application multicenter, large cohort validation studies are necessary.     

Metabolic signatures of esophageal cancer: NMR-based metabolomics and UHPLC-based focused metabolomics of blood serum

Focused metabolic profiling is a powerful tool for the determination of biomarkers. Here, a more global proton nuclear magnetic resonance (¹H NMR)-based metabolomic approach coupled with a relative simple ultra high performance liquid chromatography (UHPLC)-based focused metabolomic approach was developed and compared to characterize the systemic metabolic disturbances underlying esophageal cancer (EC) and identify possible early biomarkers for clinical prognosis. Serum metabolic profiling of patients with EC (n = 25) and healthy controls (n = 25) was performed by using both ¹H NMR and UHPLC, and metabolite identification was achieved by multivariate statistical analysis. Using orthogonal projection to least squares discriminant analysis (OPLS-DA), we could distinguish EC patients from healthy controls. The predictive power of the model derived from the UHPLC-based focused metabolomics performed better in both sensitivity and specificity than the results from the NMR-based metabolomics, suggesting that the focused metabolomic technique may be of advantage in the future for the determination of biomarkers. Moreover, focused metabolic profiling is highly simple, accurate and specific, and should prove equally valuable in metabolomic research applications. A total of nineteen significantly altered metabolites were identified as the potential disease associated biomarkers. Significant changes in lipid metabolism, amino acid metabolism, glycolysis, ketogenesis, tricarboxylic acid (TCA) cycle and energy metabolism were observed in EC patients compared with the healthy controls. These results demonstrated that metabolic profiling of serum could be useful as a screening tool for early EC diagnosis and prognosis, and might enhance our understanding of the mechanisms involved in the tumor progression.     

Metabolic profiling of maternal urine can aid clinical management of gestational diabetes mellitus

Introduction

The clinical management of Gestational diabetes mellitus (GDM) would benefit from enhanced metabolic knowledge both at the time of diagnosis and during therapy.

Objectives

This work aimed at unveiling metabolic markers of GDM and of the subjects’ response to therapy.

Methods

Urine NMR metabolomics was used with a variable selection methodology to reduce uninformative variability. The NMR data was analysed by multivariate and univariate analysis methodologies.

Results

The results showed that urine NMR metabolomics enables a metabolic signature of GDM to be identified at the time of diagnosis. This signature comprises relevant changes in 12 NMR metabolites/resonances and qualitative variations in a number of additional metabolites. The metabolite changes characterizing GDM suggest adaptations in a number of different pathways and highlight the relevance of gut microflora disturbances in relation to the disease. The impact of diet and insulin treatments on the excreted metabolome of pregnant GDM women was measured and enabled responsive and resistant metabolic pathways to be identified, as well as side-effects of treatment i.e. metabolic changes induced by treatment and previously unrelated to the disease (including changes in the gut microflora). Furthermore, treatment duration was found to be associated to urine metabolic profile, thus emphasizing the possible future use of urine metabolomics in treatment follow-up and efficacy evaluation. Finally, a possible association of a priori urinary metabolome with future treatment requirements is reported, albeit requiring demonstration in larger cohorts. This result supports the hypothesis of different metabotypes characterizing different subjects and relating to individual response to treatment.

Conclusion

A 12-resonance metabolic signature of GDN at the time of diagnosis was identified and the evaluation of the impact of insulin and/or diet therapies enabled responsive/resistant metabolic pathways and treatment side-effects to be identified.

     

基于PacBio SMRT测序技术评估妊娠期糖尿病人的肠道菌群

[目的]肠道菌群是位于人体肠道内的微生物菌群,其组成与人类多种疾病相关。例如,已有研究表明肠道菌群的变化与妊娠期糖尿病（gestational diabetes mellitus,GDM）的发病密切相关。因此本研究基于PacBio SMRT测序技术评估及比较了不同民族（汉族和蒙古族）及是否患GDM的孕妇的肠道菌群。[方法]本研究利用PacBio SMRT测序技术对97例患有GDM及健康的汉族和蒙古族孕妇粪便样本进行了全长16S rRNA测序及分析。[结果]总体来说,处于相同孕期的4组孕妇肠道菌群的组成相似,不同核心菌群展现出不同强弱的相关性。本研究在种的水平上共鉴定到了44个种。在汉族人中,患有妊娠期糖尿病的孕妇肠道菌群中Akkermansia muciniphila菌的相对丰度要显著低于健康孕妇;而在蒙古族人中,健康孕妇与GDM孕妇间差异并不明显。在健康对照中发现汉族孕妇肠道菌群中Bacteroides uniformis菌的相对丰度显著高于蒙古族孕妇;但在患有GDM组中未找到不同民族分组间的差异。另外,功能预测结果发现四组样本菌群功能组成高度相似,大多数功能基因都与能量代谢有关。汉族GDM患者与健康对照组间没有发现显著差异,但在蒙古族GDM患者中发现无机离子运输等功能相对丰度显著高于与蒙古族正常孕妇。[结论]在相同的孕期,妊娠期孕妇的核心肠道菌群结构与功能是相对稳定的,而民族差异也不会对妊娠期菌群产生显著性影响。但在四组间可以检测到一些低丰度的差异菌群,如Akkermansia muciniphila,其丰度的变化可能导致了肠道中一些与肠道营养吸收等有关的代谢发生变化,而这些变化可能与妊娠期糖尿病的发生密切相关。本研究将有助于探究肠道菌群在GDM发病机制中的作用。     

Serum metabolomics for early diagnosis of esophageal squamous cell carcinoma by UHPLC-QTOF/MS

Introduction

Previous metabolomics studies have revealed perturbed metabolic signatures in esophageal squamous cell carcinoma (ESCC) patients, however, most of these studies included mainly late-staged ESCC patients due to the difficulties of collecting the early-staged samples from asymptotic ESCC subjects.

Objectives

This study aims to explore the early-staged ESCC metabolic signatures and potential of serum metabolomics to diagnose ESCC at early stages.

Methods

Serum samples of 97 ESCC patients (stage 0, 39 cases; stage I, 17 cases; stage II, 11 cases, stage III, 30 cases) and 105 healthy controls (HC) were enrolled and randomly separated into training data (77 ESCCs, 84 HCs) and validation data (20 ESCCs, 21 HCs). Untargeted metabolomics was performed to identify ESCC-related metabolic signatures.

Results

The global metabolomics profiles could clearly distinguish ESCC from HC in training data. 16 ascertained metabolites were found to be disturbed in the metabolic pathways characterized by dysregulated fatty acid biosynthesis, glycerophospholipid metabolism, choline metabolism in cancer and linoleic acid metabolism. The AUC value in validation data was 0.895, with sensitivity 85.0 % and specificity 90.5 %. Good diagnostic performances were also achieved for early stage ESCC, with the values of area under the curve (AUC) 0.881 for the ESCC patients in both stage 0 and I–II. In addition, six metabolites were found to discriminate ESCC stages. Among them, three biomarkers, dodecanoic acid, LysoPA(18:1), and LysoPC(14:0), exhibited clear trend for ESCC progression.

Conclusion

These findings suggest serum metabolomics, performed in a minimally noninvasive and convenient manner, may possess great potential for early diagnosis of ESCC patients.

     

Metabolomics study of type 2 diabetes using ultra-performance LC-ESI/quadrupole-TOF high-definition MS coupled with pattern recognition methods

Type 2 diabetes (T2D), called the burden of the twenty-first century, is growing with an epidemic rate. Here, we explored the differences in metabolite concentrations between T2D patients and healthy volunteers. Metabolomics represents an emerging discipline concerned with comprehensive analysis of small molecule metabolites and provides a powerful approach to discover biomarkers in biological systems. The acquired data were analyzed by ultra-performance liquid chromatography–electrospray ionization/quadrupole time-of-flight high-definition mass spectrometry coupled with pattern recognition approach [principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA)] to identify potential disease-specific biomarkers. PCA showed satisfactory clustering between patients and healthy volunteers. Biomarkers reflected the biochemical events associated with early stages of T2D which were observed in PLS-DA loading plots. These urinary differential metabolites, such as adiponectin, acylcarnitines, citric acid, kynurenic acid, 3-indoxyl sulfate, urate, and glucose, were identified involving several key metabolic pathways such as taurine and hypotaurine metabolism; cysteine and methionine metabolism; valine, leucine, and isoleucine biosynthesis metabolism, etc. Our data suggest that robust metabolomics has the potential as a noninvasive strategy to evaluate the early diagnosis of T2D patients and provides new insight into pathophysiologic mechanisms and may enhance the understanding of its cause of disease.     

Influence of gestational diabetes on the activity of δ-aminolevulinate dehydratase and oxidative stress biomarkers

Objective: This study aimed to evaluate the activity of delta-aminolevulinate dehydratase (δ-ALA-D) and oxidative stress biomarkers in pregnant women with gestational diabetes mellitus (GDM), in order to demonstrate the involvement of oxidative stress in this condition, which presents pathophysiology still undetermined.

Methods: δ-ALA-D activity, lipid peroxidation estimated as the levels of thiobarbituric acid reactive substances (TBARS), protein (P-SH) and non-protein thiol (NP-SH) content, catalase (CAT) activity and concentration of vitamin C (VIT C) in samples of pregnant women with GDM (n?=?48) and in healthy pregnant women (n?=?30), who constituted the control group.

Results: The δ-ALA-D activity was significantly lower in pregnant women with GDM compared to controls, as well as levels of thiols, VIT C and CAT activity. Lipid peroxidation was higher in GDM group.

Discussion: The results suggest that the main factor for the increase in oxidative stress and reduced δ-ALA-D activity in diabetic pregnant women is gestational hyperglycemic environment, which changed the redox balance and interfered on mechanism of the δ-ALA-D activity in relation to normoglycemic pregnant women.     

Metabolomics reveals metabolite changes of patients with pulmonary arterial hypertension in China

The specific mechanism of pulmonary arterial hypertension (PAH) remains elusive. The present study aimed to explore the underlying mechanism of PAH through the identity of novel biomarkers for PAH using metabolomics approach. Serum samples from 40 patients with idiopathic PAH (IPAH), 20 patients with congenital heart disease‐associated PAH (CHD‐PAH) and 20 healthy controls were collected and analysed by ultra‐high‐performance liquid chromatography coupled with high‐resolution mass spectrometry (UPLC‐HRMS). Orthogonal partial least square‐discriminate analysis (OPLS‐DA) was applied to screen potential biomarkers. These results were validated in monocrotaline (MCT)‐induced PAH rat model. The OPLS‐DA model was successful in screening distinct metabolite signatures which distinguished IPAH and CHD‐PAH patients from healthy controls, respectively (26 and 15 metabolites). Unbiased analysis from OPLS‐DA identified 31 metabolites from PAH patients which were differentially regulated compared to the healthy controls. Our analysis showed dysregulation of the different metabolic pathways, including lipid metabolism, glucose metabolism, amino acid metabolism and phospholipid metabolism pathways in PAH patients compared to their healthy counterpart. Among these metabolites from dysregulated metabolic pathways, a panel of metabolites from lipid metabolism and fatty acid oxidation (lysophosphatidylcholine, phosphatidylcholine, perillic acid, palmitoleic acid, N‐acetylcholine‐d ‐sphingomyelin, oleic acid, palmitic acid and 2‐Octenoylcarnitine metabolites) were found to have a close association with PAH. The results from the analysis of both real‐time quantitative PCR and Western blot showed that expression of LDHA, CD36, FASN, PDK1 GLUT1 and CPT‐1 in right heart/lung were significantly up‐regulated in MCT group than the control group.     

Exploring the protective effects of Danqi Tongmai tablet on acute myocardial ischemia rats by comprehensive metabolomics profiling

BackgroundDanqi Tongmai tablet (DQTM), a combination of salvianolic acids (SA) and panax notoginsenosides (PNS), is now in phase II clinical trial developed for the treatment of cardiovascular diseases. However, the mechanisms of its protective effects through regulating endogenous metabolites remain unclear.PurposeThe purpose of this study was to explore the protective effects of DQTM on acute myocardial ischemia rats by comprehensive metabolomics profiling.Study designThe rats were divided into three groups: sham-operating, acute myocardial ischemia (AMI) and DQTM groups. The plasma and heart were collected and profiled by LC-MS based metabolomics and lipidomics. Based on the identified differential metabolites, the pathway analysis results were obtained and further validated using the network pharmacology approach.MethodsThe AMI model was induced by ligating the left anterior descending coronary artery. The metabolomics and lipidomics profiling were based on two established LC–QTOF/MS analysis methods. The raw data were processed using XCMS Online, then the differential metabolites with nonparametric t-test p value less than 0.05 were selected and identified using HMDB and METLIN. The pathway analysis was conducted using MetaboAnalyst and validated with the predicted network results obtained by BATMAN-TCM.ResultsThe metabolomics and lipidomics profiles of plasma and heart in response to AMI and DQTM were significantly different. The AMI operation had a serious influence on metabolites in heart ischemia region, while DQTM had a greater impact on lipids in heart non-ischemia region. A total of 151 differential metabolites were identified, including mainly amino acids and fatty acids. Multiple metabolic pathways were disturbed after AMI and could be restored by DQTM, of which arachidonic acid metabolism was further validated with the predicted results of network pharmacology.ConclusionThe protective effects of DQTM on acute myocardial ischemia rats could be achieved through the regulation of multiple metabolic pathways.     

5-Hydroxy-4-methoxycanthin-6-one alleviates dextran sodium sulfate-induced colitis in rats via regulation of metabolic profiling and suppression of NF-κB/p65 signaling pathway

Background5-Hydroxy-4-methoxycanthin-6-one (PQ-A) is the main active compound in Ramulus et Folium Picrasmae, a Chinese herbal medicine commonly used in colitis treatment.PurposeTo clarify PQ-A's role and mechanism in colitis treatment based on a non-targeted metabolomics study.MethodsRats with ulcerative colitis (UC) established with 4% dextran sulfate sodium (DSS) were orally treated with PQ-A. Body weight, disease activity index (DAI), colon length, biochemical parameters (MDA and SOD), and histopathological score in colon tissue were measured. A UPLC-Q-TOF-MS/MS approach-based metabolomics analysis was conducted to explore the underlying mechanisms of PQ-A in colitis treatment. Inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10) concentrations in serum and their protein levels in the colon were determined. CD3 and NF-κB/p65 immunohistochemistry in the colon was semi-quantified. The related protein or mRNA in IKK-NF-κB/p65 signaling pathway was measured by Western blotting or RT-PCR, respectively. Potential molecular interactions between PQ-A and NF-κB/p65 was predicted using DS 2.5 software.ResultsPQ-A significantly prevented body weight loss and colonic shortening in colitic rats, and reduced the DAI and histopathologic score as well. PQ-A decreased MDA levels in the UC rat serum and increased those of SOD. Metabolomics results revealed forty-nine differential metabolites as biomarkers of DSS-induced colitis, demonstrating that the path-mechanism of colitis involved the perturbation of eight metabolic pathways, including alpha-linolenic acid and linoleic acid metabolism, sphingolipid metabolism, retinol metabolism, bile acid metabolism, et al. Thirty-six biomarkers were especially reversed to normal-like levels by PQ-A via regulation of alpha-linolenic acid and linoleic acid metabolism, sphingolipid metabolism, and retinol metabolism, which effectively hinted the potential pharmacological mechanism of PQ-A related to NF-κB/p65 inflammatory signaling. Molecular docking results predicted high affinity interaction between PQ-A and NF-κB/p65, involving hydrogen-bond interactions at five amino acid residues, suggesting NF-κB/p65 as a target. PQ-A decreased TNF-α, IL-1β, and IL-6 concentrations in serum and their protein levels in colon tissue in colitic rats. CD3, MYD88, p-IκBα, NF-κB/p65, and p-NF-κB/p65 expression levels decreased, whereas those of IKKβ and IκBα increased in colitic tissue following PQ-A treatment. PQ-A strongly inhibited nuclear translocation of NF-κB/p65.ConclusionsWe provide an overview of PQ-A's possible mechanism of action in colitis treatment based on serum non-targeted metabolomics. PQ-A treatment can protect rats against DSS-induced colitis by suppressing the NF-κB/p65 signaling pathway.     

妊娠糖尿病患者血清HbA1c与CRP水平的相关性分析

目的:为明确妊娠期糖尿病(gestational diabetes mellitus,GDM)患者血清糖化血红蛋白(glycosylated hemoglobin,Hb A1c)与C反应蛋白(C-reactive protein,CRP)的关系,本研究检测了GDM患者血糖、血清Hb A1c与CRP水平,并对Hb A1c与CRP的相关性进行了分析。方法:以68例2015年4月至2017年4月于我院诊治的GDM孕妇为研究对象,所有患者均符合《妇产科学》中关于GDM的诊断标准,另选取68例正常孕妇为对照组。采用葡萄糖氧化酶法检测血糖水平(空腹血糖及餐后2 h血糖水平),采用免疫凝集法检测和比较两组血清糖化血红蛋白(HbA1c)水平,采用免疫透射比浊法检测血清C反应蛋白(CRP)水平,并分析HbA1c与CRP的相关性。结果:GDM组患者空腹血糖(fasting plasma glucose,FPG)、2 h血糖(plasma glucose,PG)、血清HbA1c和CRP水平均显著高于正常组(P0.05),GDM患者血清Hb A1c和CRP水平呈显著正相关关系(r=0.654,P0.05)。结论:GDM患者血清HbAlC和CRP水平相较于正常孕妇有显著提高,且二者呈显著的正相关关系,二者联合检测可能作为GDM早期诊断的筛查的重要参考指标。     

钩藤散改善APP/PS1双转基因小鼠学习记忆功能的代谢组学研究

目的:采用非靶向的高通量尿液代谢组学技术对钩藤散改善淀粉样前体蛋白/早老素蛋白1基因,即APP/PS1双转基因小鼠的作用机制进行研究。方法:5月龄APP/PSI小鼠采用Morris水迷宫实验检测双转基因小鼠的空间学习能力,在确定出现空间记忆能力功能损伤地条件下采用基于非靶向的尿液代谢组学技术研究APP/PSI小鼠的代谢网络,聚焦关键通路,同时观察钩藤散在水迷宫和代谢水平上的治疗作用。结果:Morris水迷宫对比发现APP/PSI小鼠的空间记忆能力明显长于同窝野生小鼠,给予钩藤散后呈现一定程度的回调趋势,经非靶向的代谢轮廓分析和核心代谢通路聚焦后,成功发现正常小鼠(同窝野生小鼠)和APP/PSI双转基因小鼠代谢轮廓间差异最大的信号,经质谱解析和权威数据库检索后鉴定6个与学习记忆相关的潜在生物标记物,分别是牛磺酸(taurine)、叶酸(pteroylglutamic acid)、新蝶呤(neopterin)、磺乙谷酰胺(glutaurine)、戊邻酮二酸盐(2-oxoglutarate)、二氢新蝶呤(dihydroneopterin),他们主要涉及牛磺酸代谢及叶酸代谢等,经钩藤散治疗后能有效回调。结论:钩藤散对APP/PSI双转基因小鼠的学习记忆能力具有一定治疗作用,本次发现的6个生物标记物可能是APP/PSI双转基因小鼠发病的潜在靶点,为钩藤散的相关药效学研究提供实验依据。     

DNA methylation analysis reveals the effect of arsenic on gestational diabetes mellitus

BackgroundArsenic (As) exposure is one of the risk factors for gestational diabetes mellitus (GDM). This study aimed to explore the effect of As-exposure on DNA methylation in GDM and to establish a risk assessment model of GDM in As exposed pregnant women.MethodWe collected elbow vein blood of pregnant women before delivery to measure As concentration and DNA methylation data. Then compared the DNA methylation data and established a nomogram.ResultWe identified a total of 10 key differentially methylated CpGs (DMCs) and found 6 corresponding genes. Functions were enriched in Hippo signaling pathway, cell tight junction, prophetic acid metabolism, ketone body metabolic process, and antigen processing and presentation. A nomogram was established that can predict GDM risks (c-index = 0.595, s:p = 0.973).ConclusionWe found 6 genes associated with GDM with high As exposure. The prediction of the nomograms has been proven to be effective.     

Quantitative Detection of 15 Serum Bile Acid Metabolic Products by LC/MS/MS in the Diagnosis of Primary Biliary Cholangitis

To determine 15 bile acid metabolic products in human serum by liquid chromatography-tandem mass spectrometry (LC/MS/MS) and value their diagnostic outcome in primary biliary cholangitis (PBC). Serum from 20 healthy controls and 26 patients with PBC were collected and went LC/MS/MS analysis of 15 bile acid metabolic products. The test results were analyzed by bile acid metabolomics, and the potential biomarkers were screened and their diagnostic performance was judged by statistical methods such as principal component and partial least squares discriminant analysis and area under curve (AUC). 8 differential metabolites can be screened out: Deoxycholic acid (DCA), Glycine deoxycholic acid (GDCA), Lithocholic acid (LCA), Glycine ursodeoxycholic acid (GUDCA), Taurolithocholic acid (TLCA), Tauroursodeoxycholic acid (TUDCA), Taurodeoxycholic acid (TDCA), Glycine chenodeoxycholic acid (GCDCA). The performance of the biomarkers was evaluated by the AUC, specificity and sensitivity. In conclusion, DCA, GDCA, LCA, GUDCA, TLCA, TUDCA, TDCA and GCDCA were identified as eight potential biomarkers to distinguish between healthy people and PBC patients by multivariate statistical analysis, which provided reliable experimental basis for clinical practice.     

Metabonomic studies on potential plasma biomarkers in rats exposed to ionizing radiation and the protective effects of Hong Shan Capsule

An ultra performance liquid chromatography coupled to mass spectrometry-based metabonomic approach, combined with pattern recognition methods including PCA, PLS-DA, RF and heatmap, has been developed to characterize the global serum metabolic profile associated with ionizing radiation (IR). As the VIP-value threshold cutoff of the metabolites was set to 2, metabolites above this threshold were filtered out as potential target biomarkers. Nineteen distinct potential biomarkers in rat plasma were identified. To further elucidate the pathophysiology of IR, related metabolic pathways have been studied. It was found that IR was closely related to disturbed fatty acid metabolism, taurine and hypotaurine metabolism, sphingolipid metabolism, purine metabolism, pyrimidine metabolism, phospholipid catabolism, tryptophan metabolism, phenylalanine metabolism, and bile acid metabolism. With the presented metabonomic method, we systematically analyzed the protective effects of Traditional Chinese Medicine Hong Shan Capsule (HSC). The results demonstrated that HSC administration could provide satisfactory effects on IR through partially regulating the perturbed metabolic pathways.