PubMed

Related Articles Tryptophan Metabolism via the Kynurenine Pathway: Implications for Graft Optimization during Machine Perfusion. J Clin Med. 2020 Jun 15;9(6): Authors: Zhang A, Carroll C, Raigani S, Karimian N, Huang V, Nagpal S, Beijert I, Porte RJ, Yarmush M, Uygun K, Yeh H Abstract Access to liver transplantation continues to be hindered by the severe organ shortage. Extended-criteria donor livers could be used to expand the donor pool but are prone to ischemia-reperfusion injury (IRI) and post-transplant graft dysfunction. Ex situ machine perfusion may be used as a platform to rehabilitate discarded or extended-criteria livers prior to transplantation, though there is a lack of data guiding the utilization of different perfusion modalities and therapeutics. Since amino acid derivatives involved in inflammatory and antioxidant pathways are critical in IRI, we analyzed differences in amino acid metabolism in seven discarded non-steatotic human livers during normothermic- (NMP) and subnormothermic-machine perfusion (SNMP) using data from untargeted metabolomic profiling. We found notable differences in tryptophan, histamine, and glutathione metabolism. Greater tryptophan metabolism via the kynurenine pathway during NMP was indicated by significantly higher kynurenine and kynurenate tissue concentrations compared to pre-perfusion levels. Livers undergoing SNMP demonstrated impaired glutathione synthesis indicated by depletion of reduced and oxidized glutathione tissue concentrations. Notably, ATP and energy charge ratios were greater in livers during SNMP compared to NMP. Given these findings, several targeted therapeutic interventions are proposed to mitigate IRI during liver machine perfusion and optimize marginal liver grafts during SNMP and NMP. PMID: 32549246 [PubMed]

Related Articles Allelopathic Potential of Rice and Identification of Published Allelochemicals by Cloud-Based Metabolomics Platform. Metabolites. 2020 Jun 15;10(6): Authors: Ho TL, Nguyen TTC, Vu DC, Nguyen NY, Nguyen TTT, Phong TNH, Nguyen CT, Lin CH, Lei Z, Sumner LW, Le VV Abstract The methanol extracts of nine popular cultivated Vietnamese rice cultivars (Oryza sativa L.cv. OM 2395, 5451, 6976, 380, 5930, 4498, 3536, N406, and 7347) were used to explore their allelopathic potential on barnyardgrass (Echinochola crus-galli L.). At 0.1 g mL-1, OM 5930, OM 4498, and OM 6976 correlatively possessed greatest phytotoxicity on barnyardgrass shoot (98.77%, 90.75%, and 87.17%) and root (99.39%, 92.83%, and 86.56%) growth. The following study aimed to detect previously-known allelochemicals in those rice using XCMS online cloud-based metabolomics platform. Twenty allelochemicals were semi-quantified and seven of them were detected predominantly and five was putatively confirmed in OM 5930 (mg/ 100g fresh rice) as salicylic acid (5.0076), vanillic acid (0.1246), p-coumaric acid (0.1590), 2,4-dimethoxybenzoic acid (0.1045), and cinnamic acid (3.3230). These compounds were active at concentrations greater than 0.5 mM and the average EC50 were 1.24 mM. The results indicated that OM 5930 may use as promising candidates in weed biological control for rice production. PMID: 32549240 [PubMed]

Related Articles Panel-Based Nuclear and Mitochondrial Next-Generation Sequencing Outcomes of an Ethnically Diverse Pediatric Patient Cohort with Mitochondrial Disease. J Mol Diagn. 2019 05;21(3):503-513 Authors: Schoonen M, Smuts I, Louw R, Elson JL, van Dyk E, Jonck LM, Rodenburg RJT, van der Westhuizen FH Abstract Mitochondrial disease (MD) is a group of rare inherited disorders with clinical heterogeneous phenotypes. Recent advances in next-generation sequencing (NGS) allow for rapid genetic diagnostics in patients who experience MD, resulting in significant strides in determining its etiology. This, however, has not been the case in many patient populations. We report on a molecular diagnostic study using mitochondrial DNA and targeted nuclear DNA (nDNA) NGS of an extensive cohort of predominantly sub-Saharan African pediatric patients with clinical and biochemically defined MD. Patients in this novel cohort presented mostly with muscle involvement (73%). Of the original 212 patients, a muscle respiratory chain deficiency was identified in 127 cases. Genetic analyses were conducted for these 127 cases based on biochemical deficiencies, for both mitochondrial (n = 123) and nDNA using panel-based NGS (n = 86). As a pilot investigation, whole-exome sequencing was performed in a subset of African patients (n = 8). These analyses resulted in the identification of a previously reported pathogenic mitochondrial DNA variant and seven pathogenic or likely pathogenic nDNA variants (ETFDH, SURF1, COQ6, RYR1, STAC3, ALAS2, and TRIOBP), most of which were identified via whole-exome sequencing. This study contributes to knowledge of MD etiology in an understudied, ethnically diverse population; highlights inconsistencies in genotype-phenotype correlations; and proposes future directions for diagnostic approaches in such patient populations. PMID: 30872186 [PubMed - indexed for MEDLINE]

Related Articles A shared comparison of diabetes mellitus and neurodegenerative disorders. J Cell Biochem. 2019 09;120(9):14318-14325 Authors: Morsi M, Kobeissy F, Magdeldin S, Maher A, Aboelmagd O, Johar D, Bernstein L Abstract Diabetes mellitus (DM), one of the most prevalent metabolic diseases in the world population, is associated with a number of comorbid conditions including obesity, pancreatic endocrine changes, and renal and cardio-cerebrovascular alterations, coupled with peripheral neuropathy and neurodegenerative disease, some of these disorders are bundled into metabolic syndrome. Type 1 DM (T1DM) is an autoimmune disease that destroys the insulin-secreting islet cells. Type 2 DM (T2DM) is diabetes that is associated with an imbalance in the glucagon/insulin homeostasis that leads to the formation of amyloid deposits in the brain, pancreatic islet cells, and possibly in the kidney glomerulus. There are several layers of molecular pathologic alterations that contribute to the DM metabolic pathophysiology and its associated neuropathic manifestations. In this review, we describe the general signature metabolic features of DM and the cross-talk with neurodegeneration. We will assess the underlying molecular key players associated with DM-induced neuropathic disorders that are associated with both T1DM and T2DM. In this context, we will highlight the role of tau and amyloid protein deposits in the brain as well in the pancreatic islet cells, and possibly in the kidney glomerulus. Furthermore, we will discuss the central role of mitochondria, oxidative stress, and the unfolded protein response in mediating the DM-associated neuropathic degeneration. This study will elucidate the relationship between DM and neurodegeneration which may account for the evolution of other neurodegenerative diseases, particularly Alzheimer's disease and Parkinson's disease as discussed later. PMID: 30565720 [PubMed - indexed for MEDLINE]

Related Articles Serum Metabolites as Diagnostic Biomarkers for Cholangiocarcinoma, Hepatocellular Carcinoma, and Primary Sclerosing Cholangitis. Hepatology. 2019 08;70(2):547-562 Authors: Banales JM, Iñarrairaegui M, Arbelaiz A, Milkiewicz P, Muntané J, Muñoz-Bellvis L, La Casta A, Gonzalez LM, Arretxe E, Alonso C, Martínez-Arranz I, Lapitz A, Santos-Laso A, Avila MA, Martínez-Chantar ML, Bujanda L, Marin JJG, Sangro B, Macias RIR Abstract Early and differential diagnosis of intrahepatic cholangiocarcinoma (iCCA) and hepatocellular carcinoma (HCC) by noninvasive methods represents a current clinical challenge. The analysis of low-molecular-weight metabolites by new high-throughput techniques is a strategy for identifying biomarkers. Here, we have investigated whether serum metabolome can provide useful biomarkers in the diagnosis of iCCA and HCC and could discriminate iCCA from HCC. Because primary sclerosing cholangitis (PSC) is a risk factor for CCA, serum metabolic profiles of PSC and CCA have also been compared. The analysis of the levels of lipids and amino acids in the serum of patients with iCCA, HCC, and PSC and healthy individuals (n = 20/group) showed differential profiles. Several metabolites presented high diagnostic value for iCCA versus control, HCC versus control, and PSC versus control, with areas under the receiver operating characteristic curve (AUC) greater than those found in serum for the nonspecific tumor markers carbohydrate antigen 19-9 (CA 19-9) and alpha-fetoprotein (AFP), commonly used to help in the diagnosis of iCCA and HCC, respectively. The development of an algorithm combining glycine, aspartic acid, SM(42:3), and SM(43:2) permitted to accurately differentiate in the diagnosis of both types of tumors (biopsy-proven). The proposed model yielded 0.890 AUC, 75% sensitivity, and 90% specificity. Another algorithm by combination of PC(34:3) and histidine accurately permitted to differentiate PSC from iCCA, with an AUC of 0.990, 100% sensitivity, and 70% specificity. These results were validated in independent cohorts of 14-15 patients per group and compared with profiles found in patients with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Conclusion: Specific changes in serum concentrations of certain metabolites are useful to differentiate iCCA from HCC or PSC, and could help in the early diagnosis of these diseases. PMID: 30325540 [PubMed - indexed for MEDLINE]

27 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/06/18PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

27 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/06/18PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

48 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/06/17PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

48 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/06/17PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Bariatric surgery decreases oxidative stress and protein glycosylation in patients with morbid obesity. Eur J Clin Invest. 2020 Jun 14;:e13320 Authors: Carmona-Maurici J, Amigó N, Cuello E, Bermúdez M, Baena-Fustegueras JA, Peinado-Onsurbe J, Pardina E, Vascular and Renal Translational Research Group, IRBLleida, Spain and Spanish Research Network for Renal Diseases (RedInRen. ISCIII) Abstract BACKGROUND: There is growing evidence that oxidative stress (OS) is a critical factor linking obesity with its associated comorbidities, such as cardiovascular diseases. AIM: To evaluate the degree of OS in people with morbid obesity and its relationship with glycoproteins, determined using 1H-NMR spectroscopy, before and after bariatric surgery (BS). METHODS: In this observational cohort study, plasma from 24 patients with BMI ≥ 40 kg/m2 (age: 21-65 years) was used to measure metabolites implicated in OS. We measured glycoprotein (GlycA, GlycB and GlycF) areas and shape factors (H/W = height/width). RESULTS: One year after BS, oxidized low-density lipoprotein had decreased by 49% (p < 0.0001), malondialdehyde by 32% (p = 0.0019) and lipoprotein (a) by 21% (p = 0.0039). The antioxidant enzymes paraoxonase-1 and catalase increased after BS (43%, p < 0.0001 and 54%, p = 0.0002, respectively). Superoxide dismutase-2 had fallen one year after BS (32%, p = 0.0052). After BS, both the glycoprotein areas and shape factors decreased by 20%-26%. These glycoproteins were significantly correlated with OS parameters. The plasma atherogenic index was 63% higher in obese individuals than one year after BS and correlated positively with glycoproteins. For the first time, we here demonstrate the relationship between OS parameters and glycoproteins in people with morbid obesity. So glycoproteins could therefore be a good indicator, together with the oxidative state to assess patient prognosis after BS. PMID: 32535887 [PubMed - as supplied by publisher]

Minimally Invasive Biospecimen Collection for Exposome Research in Children's Health. Curr Environ Health Rep. 2020 Jun 13;: Authors: Petrick LM, Arora M, Niedzwiecki MM Abstract PURPOSE OF REVIEW: The advent of low-volume biosampling and novel biomarker matrices offers non- or minimally invasive approaches to sampling in children. These new technologies, combined with advancements in mass spectrometry that provide high sensitivity, robust measurements of low-concentration exposures, facilitate the application of untargeted metabolomics in children's exposome research. Here, we review emerging sampling technologies for alternative biomatrices-dried capillary blood, interstitial fluid, saliva, teeth, and hair-and highlight recent applications of these samplers to drive discovery in population-based exposure research. RECENT FINDINGS: Biosampling and biomarker technologies demonstrate potential to directly measure exposures during key developmental time periods. While saliva is the most traditional of the reported biomatrices, each technology has key advantages and disadvantages. For example, hair and teeth provide retrospective analysis of past exposures, and dried capillary blood provides quantitative measurements of systemic exposures that can be more readily compared with traditional venous blood measurements. Importantly, all technologies can or have the potential to be used at home, increasing the convenience and parental support for children's biosampling. This review describes emerging sample collection technologies that hold promise for children's exposome studies. While applications in metabolomics are still limited, these novel matrices are poised to facilitate longitudinal exposome studies to discover key exposures and windows of susceptibility affecting children's health. PMID: 32535858 [PubMed - as supplied by publisher]

Serum metabolomics identifies metabolite panels that differentiate lame dairy cows from healthy ones. Metabolomics. 2020 Jun 13;16(6):73 Authors: Zhang G, Zwierzchowski G, Mandal R, Wishart DS, Ametaj BN Abstract INTRODUCTION: Although much is known about lameness application of metabolomics technologies to better understanding its etiology and pathogenesis is of utmost interest. OBJECTIVES: The objective of this study was to investigate serum metabolite alterations in pre-lame, lame and post-lame dairy cows in order to identify potential screening serum metabolite biomarkers for lameness and better understand its pathobiology. METHODS: A combination of direct injection and tandem mass spectrometry (DI-MS/MS) with a reverse-phase liquid chromatography and tandem mass spectrometry (LC-MS/MS) analysis was performed in the serum of six cases of lameness and 20 healthy control cows (CON) at - 8 and - 4 weeks prepartum, at lameness diagnosis week, and at + 4 and + 8 weeks postpartum. RESULTS: Data indicated that pre-lame, lame, and post-lame cows experienced altered concentrations of multiple metabolites. It is interesting to note that throughout the 16-weeks of the study, 7 serum metabolites [e.g., diacyl-phosphatidylcholine (PC aa) C30:0, phosphatidylcholine acyl-alkyl (PC ae) C40:2, sphingomyelin (SM) (OH) C14:1, SM C18:0, isoleucine (Ile), leucine (Leu), and lysine (Lys)] differentiated CON cows from the lame ones. Furthermore, 4 metabolic pathways (i.e., Lys degradation, biotin metabolism, tryptophan (Trp) metabolism, and valine [(Val)-Leu-Ile degradation) were altered in cows with lameness during the onset and progression of the disease. CONCLUSION: Multiple metabolite and pathway alterations were identified in the serum of pre-lame, lame, and post-lame cows that through light into the pathobiology of the disease and that can be used as potential biomarker sets that can predict the risk of lameness in dairy cows. PMID: 32535675 [PubMed - as supplied by publisher]

Early-life exposure to widespread environmental toxicants and maternal-fetal health risk: A focus on metabolomic biomarkers. Sci Total Environ. 2020 Jun 03;739:139626 Authors: Dai Y, Huo X, Cheng Z, Faas MM, Xu X Abstract Prenatal exposure to widespread environmental toxicants is detrimental to maternal health and fetal development. The effects of environmental toxicants on maternal and fetal metabolic profile changes have not yet been summarized. This systematic review aims to summarize the current studies exploring the association between prenatal exposure to environmental toxicants and metabolic profile alterations in mother and fetus. We searched the MEDLINE (PubMed) electronic database for relevant literature conducted up to September 18, 2019 with some key terms. From the initial 155 articles, 15 articles met the inclusion and exclusion criteria, and consist of highly heterogeneous research methods. Seven studies assessed the effects of multiple environmental pollutants (metals, organic pollutants, nicotine, air pollutants) on the maternal urine and blood metabolomic profile; five studies evaluated the effects of arsenic, polychlorinated biphenyls (PCBs), nicotine, and ambient fine particulate matter (PM2.5) on the cord blood metabolomic profile; and one study assessed the effects of smoking exposure on the amniotic fluid metabolomic profile. The alteration of metabolic pathways in these studies mainly involve energy metabolism, hormone metabolism, oxidative stress and inflammation. No population study investigated the association between environmental toxicants and placental metabolomics. This systematic review provides evidence that prenatal exposure to a variety of environmental pollutants can affect maternal and fetal metabolomic characteristics. Integration of environmental toxicant exposure and metabolomics data in maternal-fetal samples is helpful to understand the interaction between toxicants and metabolites, so as to reveal the pathogenesis of fetal disease or diseases of fetal origin. PMID: 32535459 [PubMed - as supplied by publisher]

Exploration of chemical markers using a metabolomics strategy and machine learning to study the different origins of Ixeris denticulata (Houtt.) Stebb. Food Chem. 2020 Jun 04;330:127232 Authors: Li Y, Wang X, Li C, Huang W, Gu K, Wang Y, Yang B, Li Y Abstract As a generally edible plant, Ixeris denticulata (Houtt.) Stebb is widely distributed in China. Its medicinal value has attracted much attention in recent years. However, the chemical markers that cause quality and taste differences in I. denticulata from different regions are currently unclear. In this study, samples from 8 different origins were collected and analysed by UPLC-Q-TOF/MS. A metabolomics data processing strategy and machine learning method were established to explore the reasons for the difference in quality and taste of different origins from the perspective of chemical composition. With the established strategy, 10 characteristic chemical markers were identified that could be used to distinguish the origins of I. denticulata. The strategy proposed in this study could provide a certain basis for quality control and reasonable consumption of I. denticulata and additional food and medicinal homologous species. PMID: 32535318 [PubMed - as supplied by publisher]

Metabotyping of different soybean genotypes and distinct metabolism in their seeds and leaves. Food Chem. 2020 Jun 04;330:127198 Authors: Yun DY, Kang YG, Kim M, Kim D, Kim EH, Hong YS Abstract The metabolome of three soybean genotypes, Glycine max Hwangkeum (elite or domesticated cultivar), Glycine max Napjakong (landrace or semi-wild cultivar) and Glycine soja Dolkong (wild cultivar), were characterized in seeds and leaves using a 1H NMR-based metabolomics approach. Expression of primary and secondary metabolites were different in seeds and leaves as well as amongst soybean genotypes. Different kaempferol glycosides were observed in the leaves but not in the seeds, and quercetin derivatives were found only in G. max Napjakong and G. soja Dolkong. Moreover, epicatechin was found only in the seeds of G. max Napjakong and G. soja Dolkong. These results demonstrate distinct adaptations of different soybean genotypes to given environmental conditions. The current study, therefore, provides useful information on global metabolic compositions that might be used to develop soybean-based products through better understanding of the metabolic phenotypes of existing soybean genotypes. PMID: 32535313 [PubMed - as supplied by publisher]

`Untargeted metabolomics study and pro-apoptotic properties of B-norcholesteryl benzimidazole compounds in ovarian cancer SKOV3 cells. J Steroid Biochem Mol Biol. 2020 Jun 11;:105709 Authors: Gan C, Huang X, Wu Y, Zhan J, Zhang X, Liu Q, Huang Y Abstract The current study aims to evaluate the antiproliferative activity of B-norcholesteryl benzimidazole compounds in human ovarian cancer cells (SKOV3). Our experimental data indicates that the tested compounds can induce apoptosis in SKOV3 cells, block S-phase growth, and decrease mitochondrial membrane potential. Western blot results showed that B-norcholesteryl benzimidazole compounds (1 and 2) induced apoptosis in SKOV3 cells via activation of the mitochondrial signaling pathway. Following SKOV3 cells treatment with compounds 1 and 2, the cell metabolism was assessed using the UHPLC-QE-MS (Ultra High Performance Liquid Chromatography-Q Exactive Orbitrap- Mass Spectrometry) non-target metabolomics analysis method. The results showed 10 metabolic pathways that mediated the effects of compound 1, including arginine and proline metabolism; alanine, aspartate, and glutamate metabolism; histidine metabolism; D-glutamine and D-glutamate metabolism; cysteine and methionine metabolism; aminoacyl-tRNA biosynthesis; purine metabolism; Glutathione metabolism; D-Arginine and D-ornithine metabolism; and Nitrogen metabolism. From the perspective of metabolomics, compound 1 inhibits intracellular metabolism, protein synthesis, and slows down energy metabolism in SKOV3 cells. These changes result in the inhibition of proliferation and signal transduction, abrogate invasive and metastatic properties, and induce apoptosis, thus, exerting anti-tumor effects. Application of compound 2 altered activation of metabolic pathways in SKOV3 cells. The main metabolic pathways involved were glycerophospholipid metabolism; arginine and proline metabolism; purine metabolism; glycine, serine, and threonine metabolism; and ether lipid metabolism. The metabolic pathway with the greatest impact and the deepest enrichment was the glycerophospholipid metabolism. In conclusion, compound 2 inhibits proliferation of SKOV3 cells by interfering with glycerate metabolism, which plays a major role in regulation of cell membrane structure and function. Additionally, compound 2 can inhibit the invasion and metastasis of SKOV3 cells and induce apoptosis via interfering with the metabolism of arginine and proline. PMID: 32535031 [PubMed - as supplied by publisher]

Possible metabolic switch between environmental and pathogenic Pseudomonas aeruginosa strains: 1H NMR based metabolomics study. J Pharm Biomed Anal. 2020 May 25;188:113369 Authors: Mielko KA, Jabłoński SJ, Wojtowicz W, Milczewska J, Sands D, Łukaszewicz M, Młynarz P Abstract The study aimed to assess whether Pseudomonas aeruginosa strains from different sources can be distinguished by the metabolomic fingerprint and to check whether antibiotic susceptibility distinctions are available through metabolomic analysis. 1H NMR spectroscopy analysis of the bacteria metabolites was performed. Twenty-nine strains were tested (18 isolated form cystic fibrosis patients and 11 environmental). Thirty-one metabolites were identified, 12 were up-regulated in strains from CF patients, while 2 were higher level in strains from the environment. Changed carbohydrate catabolic metabolism and the metabolic shift toward the utilization of amino acids is suggested in strains from CF patients. PMID: 32534405 [PubMed - as supplied by publisher]

TiO2 nanoparticles induced sugar impairments and metabolic pathway shift towards amino acid metabolism in wheat. J Hazard Mater. 2020 May 28;399:122982 Authors: Silva S, Ribeiro TP, Santos C, Pinto DCGA, Silva AMS Abstract TiO2-nanoparticles (TiO2-NP) have the potential to impair plant development. Nevertheless, the metabolic processes behind the physiological responses to TiO2-NP are still far from being fully understood. In this study, Triticum aestivum plants were exposed for 21 days to different concentrations (0; 5; 50; 150 mg L-1) of TiO2-NP (P25). After treatment, the metabolite profiles of roots and leaves were analysed. The content of >70 % of the identified metabolites changed in response to P25 and the impact on metabolic pathways increased with TiO2-NP dose, with leaves showing higher alterations. Roots up-regulated monosaccharides, azelaic acid, and γ-aminobutanoic acid and triggered the tyrosine metabolism, whereas leaves up-regulated the metabolisms of reserve sugars and tocopherol, and the phenylalanine and tryptophan pathways. Both organs (mainly leaves) up-regulated the aspartate family pathway together with serine, alanine and valine metabolisms and the glycerolipids' biosynthesis. In addition, the citrate and glyoxylate metabolisms were down-regulated in both organs (highest dose). Sugar biosynthesis breakdown, due to photosynthetic disturbances, shifted the cell metabolism to use amino acids as an alternative energy source, and both ROS and sugars worked as signalling molecules activating organ dependent antioxidant responses. Concluding, these NP-pollutants severely impact multiple crop metabolic pathways and may ultimately compromise plant performance. PMID: 32534391 [PubMed - as supplied by publisher]

A UPLC-Q-TOF/MS-based plasma metabolomics approach reveals the mechanism of Compound Kushen Injection-based intervention against non-small cell lung cancer in Lewis tumor-bearing mice. Phytomedicine. 2020 Jun 02;76:153259 Authors: Wu H, Wang L, Zhan X, Wang B, Wu J, Zhou A Abstract BACKGROUND: Compound Kushen Injection (CKI), a well-known Chinese Medicine preparation, has been used to treat non-small cell lung cancer (NSCLC) for more than 15 years, and its clinical curative effect is considered to be beneficial. HYPOTHESIS/PURPOSE: This study was designed to evaluate the effects and underlying mechanisms of CKI against NSCLC using an ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based plasma metabolomics approach. METHODS: 4',6-diamidino-2-phenylindole (DAPI) staining and 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) dye reduction assay were employed to assess apoptosis and the viability of A549 cells with and without CKI treatment. The weight/volume of Lewis lung carcinoma (LLC) sarcomas and histopathological examinations were used to evaluate the anti-tumor effects of CKI against NSCLC. A UPLC-Q-TOF/MS method combined with multivariate data analysis was developed to characterize metabolomic fingerprinting and to screen functional biomarkers that are linked to the CKI treatment of LLC mice, and then metabolic pathway analysis was used to investigate the therapeutic mechanism of CKI. RESULTS: DAPI staining and MTT dye reduction assays indicated that CKI-induced apoptosis and inhibited the proliferation of A549 cells, respectively, in a concentration-dependent manner. The sarcoma volumes and weights in LLC tumor-bearing mice in CKI-dosed groups were significantly lower than those in a model group, which was treated with physiological saline. Histopathological analysis of sections of sarcomas and left pulmonary lobes indicated that CKI exerts an ameliorative effect against LLC. Fourteen functional biomarkers that are related to the therapeutic effects of CKI on LLC were screened and identified using a metabolomics study. Analysis of metabolic pathways revealed that the therapeutic effects of CKI on LLC mainly involved glycerophospholipid metabolism, amino acid metabolism and sphingolipid metabolism. As glycerophospholipid metabolism is a crucial feature of cancer-specific metabolism, the enzymes that are involved in 1-acyl-sn-glycero-3-phosphoinositol biosynthesis were further evaluated. Western blotting results indicated that CKI modulated the abnormal biosynthesis pathway of 1-acyl-sn-glycero-3-phosphoinositol by activation of cytidine diphosphate-diacylglycerol-inositol 3-phosphatidyltransferase (CDIPT) and cytosolic phospholipase A2 (cPLA2), and by inhibition of lysophosphatidic acid acyltransferase gamma (AGPAT3). CONCLUSION: This study demonstrated that CKI has a favorable anti-tumor effect and that a UPLC-Q-TOF/MS-based metabolomics method in conjunction with further verifications at the biochemical level is a promising approach for investigating its underlying mechanisms. PMID: 32534358 [PubMed - as supplied by publisher]

Anoectochilus roxburghii polysaccharide prevents carbon tetrachloride-induced liver injury in mice by metabolomic analysis. J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Jun 02;1152:122202 Authors: Zeng B, Su M, Chen Q, Chang Q, Wang W, Li H Abstract Anoectochilus roxburghii (Wall.) Lindl, a traditional Chinese medicine, is used for the effective treatment of liver disease in China. Anoectochilus roxburghii polysaccharide (ARPT) is an important constituent of Anoectochilus roxburghii. ARPT exerts a hepatoprotective effect and contributes directly to the therapeutic benefit of Anoectochilus roxburghii. However, the hepatoprotective mechanism of ARPT requires further elucidation. The present study was designed to assess the effects and underlying mechanism of ARPT when used to pretreat carbon tetrachloride (CCl4)-induced liver injury in mice. Mice were randomly divided into three groups: control group (no ARPT treatment or liver injury), model group (liver injury induced with CCl4), and the ARPT group (ARPT pretreatment followed by liver injury). A metabolomic method, based on liquid chromatography combined with mass spectrometry (LC-MS) and pattern recognition analysis, was applied. The data were analyzed with principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), to determine differentiating metabolites in the serum and liver tissue between the experimental groups. The PCA and OPLS-DA scores plots of the serum and liver tissue samples based on the LC-MS data showed a clear separation between the control and liver injury model group, while the ARPT-treated group showed a trend of close with the control. There were eleven metabolites [PS(O-18:0/0:0), phosphocholine, phenylalanine, hippuric acid, α-ketoisovaleric acid, metyrosine, leucinic acid, ketoleucine, Cer(d18:1/19:0), α-kamlolenic acid, and 4-formyl indole] were identified as candidate biomarkers in the serum samples, eight such metabolites (valine, phosphohydroxypyruvic acid, phosphocholine, ornithine, indole, xanthine, uridine, and glucose 6-phosphate) were found in the liver tissue samples, and one metabolite (phosphocholine) was observed in both the serum and liver tissue samples. These endogenous metabolites are considered to be in response to the hepatoprotective effects of ARPT and are involved in amino acid metabolism, lipid metabolism, gut bacteria metabolism, energy metabolism, and the methylation pathway. These findings suggest that ARPT mitigates the metabolic effect of CCl4-induced hepatotoxicity in mice by affecting at least five different pathways. LC-MS-based metabolomics provides a powerful approach for identifying potential biomarkers and for elucidating the protective mechanisms of traditional Chinese medicines against disease. PMID: 32534261 [PubMed - as supplied by publisher]