Hematological malignancies possess a distinctive immunologic microenvironment compared with solid tumors. Here, using an established computational algorithm (CIBERSORT), we systematically analyzed the overall distribution of 22 tumor-infiltrating leukocyte (TIL) populations in more than 2000 bone marrow (BM) samples from 5 major hematological malignancies and healthy controls. Focusing on significantly altered TILs in acute myeloid leukemia (AML), we found that patients with AML exhibited increased frequencies of M2 macrophages, compared to either healthy controls or the other four malignancies. High infiltration of M2 macrophages was associated with poor outcome in AML. Further analysis revealed that CD206, a M2 marker gene, could faithfully reflect variation in M2 fractions and was more highly expressed in AML than normal controls. High CD206 expression predicted inferior overall survival (OS) and event-free survival (EFS) in two independent AML cohorts. Among 175 patients with intermediate-risk cytogenetics, the survival still differed greatly between low and high CD206 expressers (OS; P < .0001; 3-year rates, 56% v 32%; EFS; P < .001; 3-year rates, 47% v 25%). When analyzed in a metaanalysis, CD206 as a continuous variable showed superior predictive performance than classical prognosticators in AML (BAALC, ERG, EVI1, MN1, and WT1). In summary, M2 macrophages are preferentially enriched in AML. The M2 marker CD206 may serve as a new prognostic marker in AML.
Aiming at further systematically comparing the similarities and differences of the chemical components in ginseng of different ages, especially comparing the younger or the older and mountain-cultivated ginseng (MCG), 4, 5, 6-year-old cultivated ginseng (CG) and 12, 20-year-old MCG were chosen as the analytical samples in the present study. The combination of UPLC-QTOF-MS E , UNIFI platform and multivariate statistical analysis were developed to profile CGs and MCGs. By the screening analysis based on UNIFI, 126 chemical components with various structural types were characterized or tentatively identified from all the CG and MCG samples for the first time. The results showed that all the CG and MCG samples had the similar chemical composition, but there were significant differences in the contents of markers. By the metabolomic analysis based on multivariate statistical analysis, it was shown that CG 4-6 years , MCG 12 years and MCG 20 years samples were obviously divided into three different groups, and a total of 17 potential age-dependent markers enabling differentiation among the three groups of samples were discovered. For differentiation from other two kinds of samples, there were four robust makers such as α-linolenic acid, 9-octadecenoic acid, linoleic acid and panaxydol for CG 4-6 years , five robust makers including ginsenoside Re 1 , -Re 2 , -Rs 1 , malonylginsenoside Rb 2 and isomer of malonylginsenoside Rb 1 for MCG 20 years , and two robust makers, 24-hydroxyoleanolic acid and palmitoleic acid, for MCG 12 years were discovered, respectively. The proposed approach could be applied to directly distinguish MCG root ages, which is an important criterion for evaluating the quality of MCG. The results will provide the data for the further study on the chemical constituents of MCG.Molecules 2019, 24, 33 2 of 24 distinct [4,5], and more aged ginseng is usually of higher economic value. In an investigation of the characteristic components for distinguishing CG (4-7-year of age) and MCG (with 15-years of growth), 12 compounds, including ginsenoside Ra 3 /isomer, gypenoside XVII, quinquenoside R 1 , ginsenoside Ra 7 , notoginsenoside Fe, ginsenoside Ra 2 , ginsenoside Rs 6 /Rs 7 , malonyl ginsenoside Rc, malonyl ginsenoside Rb 1 , malonyl ginsenoside Rb 2 , palmitoleic acid, and ethyl linoleate were regarded as the characteristic chemical markers for the discrimination [6]. Recently, a UPLC/QTOF-MS-based metabolomics approach was applied to the global metabolite profiling of MCG leaf samples aged from 6 to 18 years, and the authors claimed that the approach could also be applied to discriminate MCG root ages indirectly [7]. It is undoubted that the developed method can be used as a standard protocol for discriminating and predicting MCG leaf ages directly, but there might be some inaccuracy and uncertainty when discriminating MCG root ages indirectly.In the past decades, some analytical methods focusing on ginsenosides had been used to distinguish MCG from CG, such as thin layer chromatography (TLC), or high p...
Background and Objective Asthma as a chronic heterogeneous disease seriously affects the quality of life. Incorrect identification for its clinical phenotypes lead to a huge waste of medical resources. Metabolomic technique as a novel approach to explore the pathogenesis of diseases have not been used to study asthma based on their clear defined inflammatory phenotypes. This study is aimed to distinguish the divergent metabolic profile in different asthma phenotypes and clarify the pathogenesis of them. Methods Participants including eosinophilic asthmatics (EA, n=13), noneosinophilic asthmatics (NEA, n=16), and healthy controls (HC, n=15) were enrolled. A global profile of untargeted serum metabolomics was identified with Ultra Performance Liquid Chromatography–Mass Spectrometry technique. Results Multivariate analysis was performed and showed a clear distinction between EA, NEA, and HC. A total of 18 different metabolites were recognized between the three groups based on OPLS-DA model and involved in 10 perturbed metabolic pathways. Glycerophospholipid metabolism, retinol metabolism, and sphingolipid metabolism were identified as the most significant changed three pathways (impact > 0.1 and -log(P) > 4) between the phenotypes. Conclusions We showed that the different inflammatory phenotypes of asthma involve the immune regulation, energy, and nutrients metabolism. The clarified metabolic profile contributes to understanding the pathophysiology of asthma phenotypes and optimizing the therapeutic strategy against asthma heterogeneity.
Platycodonis radix is extensively used for treating cough, excessive phlegm, sore throat, bronchitis and asthma in the clinic. Meanwhile, the stems, leaves and seeds of Platycodon grandiflorum (PG) have some pharmaceutical activities such as anti-inflammation and anti-oxidation effects, etc. These effects must be caused by the different metabolites in various parts of herb. In order to profile the different parts of PG, the ultra-high performance liquid chromatography combined with quadrupole time-of- flight mass spectrometry (UPLC-QTOF-MSE) coupled with UNIFI platform and multivariate statistical analyses was used in this study. Consequently, for the constituent screening, 73, 42, 35, 44 compounds were characterized from the root, stem, leaf and seed, respectively. The stem, leaf and seed contain more flavonoids but few saponins that can be easily discriminated in the root. For the metabolomic analysis, 15, 5, 7, 11 robust biomarkers enabling the differentiation among root, stem, leaf and seed, were discovered. These biomarkers can be used for rapid identification of four different parts of PG grown in northeast China.
Hedyotis diffuse Willd. (HD) and Hedyotis corymbosa (L.) Lam. (HC), two closely related species of the same genus, are both used for health benefits and disease prevention in China. HC is also indiscriminately sold as HD in the wholesale chain and food markets. This confusion has led to a growing concern about their identification and quality evaluation. In order to further understand the molecular diversification between them, we focus on the screening of chemical components and the analysis of non-targeted metabolites. In this study, UPLC-QTOF-MSE, UNIFI platform and multivariate statistical analyses were used to profile them. Firstly, a total of 113 compounds, including 80 shared chemical constituents of the two plants, were identified from HC and HD by using the UNIFI platform. Secondly, the differences between two herbs were highlighted with the comparative analysis. As a result, a total of 33 robust biomarkers enabling the differentiation were discovered by using multivariate statistical analyses. For HC, there were 18 potential biomarkers (either the contents were much greater than in HD or being detected only in HC) including three iridoids, eight flavonoids, two tannins, two ketones, one alcohol and two monoterpenes. For HD, there were15 potential biomarkers (either the contents were much greater than in HC or being detected only in HD) including two iridoids, eight flavonoids, one tannin, one ketone, and three anthraquinones. With a comprehensive consideration of the contents or the MS responses of the chemical composition, Hedycoryside A and B, detected only in HC, could be used for rapid identification of HC. The compounds 1,3-dihydroxy-2-methylanthraquinone and 2-hydroxy-3-methylanthraquinone, detected only in HD, could be used for rapid identification of that plant. The systematic comparison of similarities and differences between two confusing Chinese herbs will provide reliable characterization profiles to clarify the pharmacological fundamental substances. HC should not be used as the substitute of HD.
Platycodon grandiflorum (PG) is extensively used for treating cough, excessive phlegm, sore throat, bronchitis and asthma, whereas Adenophora stricta (AS) is commonly used to reduce phlegm, clear lung and tonify stomach. Due to similar appearances, PG is sometimes adulterated with cheap AS so as to gain profits. And this will inevitably result in different pharmacological property. In order to further clarify the differences in the chemical composition of these two Chinese herbs, the ultra-high performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry coupled with UNIFI platform was used to establish a reliable, simple, sensitive and rapid analytical method. Seventy-five compounds, including triterpenoid saponins, organic acids, flavonoids, steroids, phenols, etc., were identified from PG based on MS data and retention time under the optimized conditions. Meanwhile, 57 compounds including triterpenoid saponins, organic acids, steroids, phenols, alkaloids, etc. were identified from AS. Among all the identified compounds, there were only 14 common components (mainly organic acids) existing in two herbs, and most of the other chemical compositions are totally different between the two herbs. Based on the results, AS cannot substitute for PG. In addition, PG adulterated with AS will lead a poor efficacy in clinical application. In addition, the systematic comparison of similarities and differences between two Chinese herbs will provide reliable characterization profiles to clarify the pharmacological fundamental substances.
Aiming to evaluate the similarities and differences of the phytochemicals in different morphological regions of wild-simulated American ginseng (WsAG) root, the comprehensive metabolite profiling of main root (MR), branch root (BR), rhizome (RH), adventitious root (AR), and fibrous root (FR) was performed on the basis of ultra-high-performance liquid chromatography−quadrupole time-of-flight mass spectrometry for the first time. First, in the screening analysis, a total of 128 shared compounds were identified or tentatively characterized. The results showed that these five parts were all rich in phytochemicals and contained similar structure types. Second, in the untargeted metabolomic study, it was found that there indeed existed differences between the MR&BR group, RH&AR group, and FR part when considering the contents of every ingredient. A total of 31 (12, 7, and 12 for MR&BR, RH&AR, and FR, respectively) potential chemical markers enabling the differentiation were discovered. This comprehensive phytochemical profile study revealed the structural diversity of secondary metabolites and the similar/different patterns in five morphological regions of WsAG root. It could provide chemical evidence for the rational application of different parts of WsAG root.
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