Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 33 min 27 sec ago

The metabolome as a biomarker of mortality risk in the common marmoset.

Thu, 27/12/2018 - 12:05
The metabolome as a biomarker of mortality risk in the common marmoset. Am J Primatol. 2018 Dec 26;:e22944 Authors: Hoffman JM, Ross C, Tran V, Promislow DEL, Tardif S, Jones DP Abstract Recently, the common marmoset has been proposed as a non-human primate model of aging. Their short lifespan coupled with pathologies that are similar to humans make them an ideal model to understand the genetic, metabolic, and environmental factors that influence aging and longevity. However, many of the underlying physiological changes that occur with age in the marmoset are unknown. Here, we attempt to determine if individual metabolites are predictive of future death and to recapitulate past metabolomic results after a change in environment (move across the country) was imposed on a colony of marmosets. We first determined that low levels of tryptophan metabolism metabolites were associated with risk of death in a 2-year follow-up in the animals, suggesting these metabolites may be used as future biomarkers of mortality. We also discovered that betaine metabolism and methionine metabolism are associated with aging regardless of environment for the animals, or of metabolomic assay technique. These two metabolic pathways are therefore of particular interest to examine as future targets for health and lifespan extending interventions. Many of the pathways associated with age in our first study of marmoset metabolomics were not found to have significant age effects in our second study, suggesting more work is needed to understand the reproducibility of large scale metabolomic studies in mammalian models. Overall, we were able to show that while several metabolomics markers show promise in understanding health and lifespan relationships with aging, it is possible that choice of technique for assay and reproducibility in these types of studies are still issues that need to be examined further. PMID: 30585652 [PubMed - as supplied by publisher]

Multi-lab EcoFAB study shows highly reproducible physiology and depletion of soil metabolites by a model grass.

Thu, 27/12/2018 - 12:05
Multi-lab EcoFAB study shows highly reproducible physiology and depletion of soil metabolites by a model grass. New Phytol. 2018 Dec 26;: Authors: Sasse J, Kant J, Cole BJ, Klein AP, Arsova B, Schlaepfer P, Gao J, Lewald K, Zhalnina K, Kosina S, Bowen BP, Treen D, Vogel J, Visel A, Watt M, Dangl JL, Northen TR Abstract There is a dynamic reciprocity between plants and their environment: soil physiochemical properties influence plant morphology and metabolism, and root morphology and exudates shape the environment surrounding roots. Here, we investigate the reproducibility of plant trait changes in response to three growth environments. We utilized fabricated ecosystem (EcoFAB) devices to grow the model grass Brachypodium distachyon in three distinct media across four laboratories: phosphate-sufficient and -deficient mineral media allowed to assess the effects of phosphate starvation, and a complex, sterile soil extract represented a more natural environment with yet uncharacterized effects on plant growth and metabolism. Tissue weight and phosphate content, total root length, and root tissue and exudate metabolic profiles were consistent across laboratories and distinct between experimental treatments. Plants grown in soil extract were morphologically and metabolically distinct, with root hairs four times longer compared to other growth conditions. Further, plants depleted half of the investigated metabolites from the soil extract. To interact with their environment, plants not only adapt morphology and release complex metabolite mixtures; they also selectively deplete a range of soil-derived metabolites. The EcoFABs utilized here generated high inter-laboratory reproducibility, demonstrating that their value in standardized investigations of plant traits. This article is protected by copyright. All rights reserved. PMID: 30585637 [PubMed - as supplied by publisher]

Cerebrospinal fluid untargeted metabolomic profiling of aneurysmal subarachnoid hemorrhage: an exploratory study.

Thu, 27/12/2018 - 12:05
Cerebrospinal fluid untargeted metabolomic profiling of aneurysmal subarachnoid hemorrhage: an exploratory study. Br J Neurosurg. 2018 Dec 26;:1-5 Authors: Lu AY, Damisah EC, Winkler EA, Grant RA, Eid T, Bulsara KR Abstract INTRODUCTION: Despite advancements in medical and surgical therapies, clinical outcomes of aneurysmal subarachnoid hemorrhage (aSAH) continue to be poor. Currently, aSAH pathophysiology remains poorly understood. No aSAH biomarkers are commonly used in the clinical setting. This exploratory study used metabolomics profiling to identify global metabolic changes and metabolite predictors of long-term outcome using cerebrospinal fluid (CSF) samples of aSAH patients. METHODS AND METHODS: Gas chromatography time-of-flight mass spectrometry was applied to CSF samples collected from 15 consecutive high-grade aSAH patients (modified Fisher grade 3 or 4). Collected CSF samples were analyzed at two time points (admission and the anticipated vasospasm timeframe). Metabolite levels at both time points were compared and correlated with vasospasm status and Glasgow Outcome Scale (GOS) of patients at 1 year post-aSAH. Significance level was defined as p < 0.05 with false discovery rate correction for multiple comparisons. RESULTS: Of 97 metabolites identified, 16 metabolites, primarily free amino acids, significantly changed between the two time points. These changes were magnified in modified Fisher grade 4 compared with grade 3. Six metabolites (2-hydroxyglutarate, tryptophan, glycine, proline, isoleucine, and alanine) correlated with GOS at 1 year post-aSAH independent of vasospasm status. When predicting patients who had low disability (GOS 5 vs. GOS ≤4), 2-hydroxyglutarate had a sensitivity and specificity of 0.89 and 0.83 respectively. CONCLUSIONS: Our preliminary study suggests that specific metabolite changes occur in the brain during the course of aSAH and that quantification of specific CSF metabolites may be used to predict long-term outcome in patients with aSAH. This is the first study to implicate 2-hydroxyglutarate, a known marker of tissue hypoxia, in aSAH pathogenesis. PMID: 30585503 [PubMed - as supplied by publisher]

Systematic metabolic profiling and bioactivity assays for bioconversion of Aceraceae family.

Thu, 27/12/2018 - 12:05
Related Articles Systematic metabolic profiling and bioactivity assays for bioconversion of Aceraceae family. PLoS One. 2018;13(6):e0198739 Authors: Park J, Suh DH, Singh D, Lee S, Lee JS, Lee CH Abstract Plants are an important and inexhaustible source of bioactive molecules in food, medicine, agriculture, and industry. In this study, we performed systematic liquid chromatography-mass spectrometry (LC-MS)-based metabolic profiling coupled with antioxidant assays for indigenous plant family extracts. Partial least-squares discriminant analysis of LC-MS datasets for the extracts of 34 plant species belonging to the families Aceraceae, Asteraceae, and Rosaceae showed that these species were clustered according to their respective phylogenies. In particular, seven Aceraceae species were clearly demarcated with higher average antioxidant activities, rationalizing their application for bioconversion studies. On the basis of further evaluation of the interspecies variability of metabolic profiles and antioxidant activities among Aceraceae family plants, we found that Acer tataricum (TA) extracts were clearly distinguished from those of other species, with a higher relative abundance of tannin derivatives. Further, we detected a strong positive correlation between most tannin derivatives and the observed higher antioxidant activities. Following Aspergillus oryzae-mediated fermentative bioconversion of Acer plant extracts, we observed a time-correlated (0-8 days) linear increase in antioxidant phenotypes for all species, with TA having the highest activity. Temporal analysis of the MS data revealed tannin bioconversion mechanisms with a relatively higher abundance of gallic acid (m/z 169) accumulated at the end of 8 days, particularly in TA. Similarly, quercetin precursor (glycoside) metabolites were also transformed to quercetin aglycones (m/z 301) in most Acer plant extracts. The present study underscores the efficacy of fermentative bioconversion strategies aimed at enhancing the quality and availability of bioactive metabolites from plant extracts. PMID: 29879203 [PubMed - indexed for MEDLINE]

The SnRK1 Kinase as Central Mediator of Energy Signaling between Different Organelles.

Thu, 27/12/2018 - 12:05
Related Articles The SnRK1 Kinase as Central Mediator of Energy Signaling between Different Organelles. Plant Physiol. 2018 02;176(2):1085-1094 Authors: Wurzinger B, Nukarinen E, Nägele T, Weckwerth W, Teige M PMID: 29311271 [PubMed - indexed for MEDLINE]

Draft De Novo Genome Sequence of Agapornis roseicollis for Application in Avian Breeding.

Thu, 27/12/2018 - 12:05
Related Articles Draft De Novo Genome Sequence of Agapornis roseicollis for Application in Avian Breeding. Anim Biotechnol. 2018;29(4):241-246 Authors: van der Zwan H, van der Westhuizen F, Visser C, van der Sluis R Abstract In aviculture, lovebirds are considered one of the most popular birds to keep. This African parakeet is known for its range of plumage colors and ease to tame. Plumage variation is the most important price-determining trait of these birds, and also the main selection criterion for breeders. Currently, no genetic screening tests for traits of economic importance or to confirm pedigree data are available for any of the nine lovebird species. As a starting point to develop these tests, the de novo genome of Agapornis roseicollis (rosy-faced lovebird) was sequenced, assembled, and annotated. Sequencing was done on the Illumina HiSeq 2000 platform and the assembly was performed using SOAPdenovo v2.04. The genome was found to be 1.1 Gb in size and 16,044 genes were identified and annotated. This compared well with other previously sequenced avian genomes, such as the chicken, zebra finch, and budgerigar. To assess genome completeness, the number of benchmarking universal single-copy orthologs were identified in the genome. This was compared to other previously assembled avian genomes and the results indicated that the genome will be useful in the development of genetic screening tests to aid lovebird breeders in selecting breeding pairs. PMID: 29035135 [PubMed - indexed for MEDLINE]

metabolomics; +22 new citations

Thu, 27/12/2018 - 00:01
22 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 2018/12/26PubMed 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.

Chronic exposure of bumblebees to neonicotinoid imidacloprid suppresses the entire mevalonate pathway and fatty acid synthesis.

Tue, 25/12/2018 - 20:39
Related Articles Chronic exposure of bumblebees to neonicotinoid imidacloprid suppresses the entire mevalonate pathway and fatty acid synthesis. J Proteomics. 2018 Dec 21;: Authors: Erban T, Sopko B, Talacko P, Harant K, Kadlikova K, Halesova T, Riddellova K, Pekas A Abstract Determining the side effects of pesticides on pollinators is an important topic due to the increasing loss of pollinators. We aimed to determine the effects of chronic sublethal exposure of the neonicotinoid pesticide imidacloprid on the bumblebee Bombus terrestris under laboratory conditions. The analytical standard of imidacloprid in sugar solution was used for the treatment. Verification of pesticides using UHPLC-QqQ-MS/MS in the experimental bumblebees showed the presence of only two compounds, imidacloprid and imidacloprid-olefin, which were found in quantities of 0.57 ± 0.22 and 1.95 ± 0.43 ng/g, respectively. Thus, the level of the dangerous metabolite imidacloprid-olefin was 3.4-fold higher than that of imidacloprid. Label-free nanoLC-MS/MS quantitative proteomics of bumblebee heads enabled quantitative comparison of 2883 proteins, and 206 proteins were significantly influenced by the imidacloprid treatment. The next analysis revealed that the highly downregulated markers are members of the terpenoid backbone biosynthesis pathway (KEGG: bter00900) and that imidacloprid treatment suppressed the entire mevalonate pathway, fatty acid synthesis and associated markers. The proteomics results indicate that the consequences of imidacloprid treatment are complex, and the marker changes are associated with metabolic and neurological diseases and olfaction disruption. This study provides important markers and can help to explain the widely held assumptions from biological observations. PMID: 30583045 [PubMed - as supplied by publisher]

Involvement of non melanocytic skin cells in vitiligo.

Tue, 25/12/2018 - 20:39
Related Articles Involvement of non melanocytic skin cells in vitiligo. Exp Dermatol. 2018 Dec 24;: Authors: Bastonini E, Bellei B, Filoni A, Kovacs D, Iacovelli P, Picardo M Abstract Despite melanocytes are the key players in vitiligo, a continuous cross-talk between epidermal and dermal cells may strictly affect their functionality, in both lesional and non-lesional skin. Focusing on this interplay, we have reviewed existing literature supporting evidence on cellular and functional alterations of surrounding epidermal keratinocytes, extracellular matrix (ECM) proteins and fibroblasts in the underlying dermal compartment that may contribute to melanocyte disappearance in vitiligo. We have also examined some clinical and therapeutic aspects of the disease to sustain the non-exclusive involvement of melanocytes within vitiligo. As a result, a different and more complex scenario has appeared that may enable to provide better understanding about origins and progress of vitiligo and that should be considered in the evaluation of new treatment approaches. This article is protected by copyright. All rights reserved. PMID: 30582762 [PubMed - as supplied by publisher]

Omics in traditional vegetable fermented foods and beverages.

Tue, 25/12/2018 - 20:39
Related Articles Omics in traditional vegetable fermented foods and beverages. Crit Rev Food Sci Nutr. 2018 Dec 22;:1-19 Authors: Rizo J, Guillén D, Farrés A, Díaz-Ruiz G, Sánchez S, Wacher C, Rodríguez-Sanoja R Abstract For a long time, food microbiota has been studied using traditional microbiological techniques. With the arrival of molecular or culture-independent techniques, a strong understanding of microbiota dynamics has been achieved. However, analyzing the functional role of microbial communities is not an easy task. The application of omics sciences to the study of fermented foods would provide the metabolic and functional understanding of the microbial communities and their impact on the fermented product, including the molecules that define its aroma and flavor, as well as its nutritional properties. Until now, most omics studies have focused on commercial fermented products, such as cheese, wine, bread and beer, but traditional fermented foods have been neglected. Therefore, the information that allows to relate the present microbiota in the food and its properties remains limited. In this review, reports on the applications of omics in the study of traditional fermented foods and beverages are reviewed to propose new ways to analyze the fermentation phenomena. PMID: 30582346 [PubMed - as supplied by publisher]

Phytochemical characterization of Tabernanthe iboga root bark and its effects on dysfunctional metabolism and cognitive performance in high-fat-fed C57BL/6J mice.

Tue, 25/12/2018 - 20:39
Related Articles Phytochemical characterization of Tabernanthe iboga root bark and its effects on dysfunctional metabolism and cognitive performance in high-fat-fed C57BL/6J mice. J Food Bioact. 2018 Sep;3:111-123 Authors: Bading-Taika B, Akinyeke T, Magana AA, Choi J, Ouanesisouk M, Torres ERS, Lione LA, Maier CS, Bobe G, Raber J, Miranda CL, Stevens JF Abstract Preparations of the root bark of Tabernanthe iboga have long been used in Central and West African traditional medicine to combat fatigue, as a neuro-stimulant in rituals, and for treatment of diabetes. The principal alkaloid of T. iboga, ibogaine, has attracted attention in many countries around the world for providing relief for opioid craving in drug addicts. Using a plant metabolomics approach, we detected five phenolic compounds, including 3-O-caffeoylquinic acid, and 30 alkaloids, seven of which were previously reported from T. iboga root bark. Following a report that iboga extracts contain insulinotropic agents, we aimed to determine the potential alleviating effects of the water extract of iboga root bark on high-fat diet (HFD)-induced hyperglycemia as well as its effects on cognitive function in male C57BL/6J mice. Feeding a HFD to mice for 10 weeks produced manifestations of metabolic syndrome such as increased body weight and increased plasma levels of glucose, triacylglycerols, total cholesterol, LDL-cholesterol, insulin, leptin, and pro-inflammatory mediators (IL-6, MCP-1, ICAM-1), as compared to mice fed a low-fat diet (LFD). Supplementation of HFD with iboga extract at ibogaine doses of 0.83 (low) and 2.07 (high) mg/kg/day did not improve these HFD-induced metabolic effects except for a reduction of plasma MCP-1 in the low dose group, indicative of an anti-inflammatory effect. When the HFD mice were tested in the water maze, the high-dose iboga extract caused hippocampus-dependent impairments in spatial learning and memory, as compared to mice receiving only a HFD. PMID: 30582133 [PubMed]

Zinc oxide nanoparticles impose metabolic toxicity by de-regulating proteome and metabolome in Saccharomyces cerevisiae.

Tue, 25/12/2018 - 20:39
Related Articles Zinc oxide nanoparticles impose metabolic toxicity by de-regulating proteome and metabolome in Saccharomyces cerevisiae. Toxicol Rep. 2019;6:64-73 Authors: Kumar Babele P Abstract As zinc oxide nanoparticles are being increasingly used in various applications, it is important to assess their potential toxic implications. Stress responses and adaptations are primarily controlled by modulation in cellular proteins (enzyme) and concentration of metabolites. To date proteomics or metabolomics applications in nanotoxicity assessment have been applied to a restricted extent. Here we utilized 2DE and 1H NMR based proteomics and metabolomics respectively to delineate the toxicity mechanism of zinc oxide nanoparticles (ZnO-NPs) in budding yeast S. cerevisiae. We found that the physiological and metabolic processes were altered in the S. cerevisiae upon ZnO-NPs exposure. Almost 40% proteins were down-regulated in ZnO-NPs (10 mg L-1) exposed cell as compared to control. Metabolomics and system biology based pathway analysis, revealed that ZnO-NPs repressed a wide range of key metabolites involved in central carbon metabolism, cofactors synthesis, amino acid and fatty acid biosynthesis, purines and pyrimidines, nucleoside and nucleotide biosynthetic pathways. These metabolic changes may be associated with the energy metabolism, antioxidation, DNA and protein damage and membrane stability. We concluded that untargeted proteomic and metabolic approaches provide more complete measurements and suggest probable molecular mechanisms of nanomaterials toxicity. PMID: 30581761 [PubMed]

Study of Methanol Extracts from Different Parts of Peganum harmala L. Using 1H-NMR Plant Metabolomics.

Tue, 25/12/2018 - 20:39
Related Articles Study of Methanol Extracts from Different Parts of Peganum harmala L. Using 1H-NMR Plant Metabolomics. J Anal Methods Chem. 2018;2018:6532789 Authors: Li Y, He Q, Du S, Guo S, Geng Z, Deng Z Abstract A nuclear magnetic resonance- (NMR-) based metabolomics method was used to identify differential metabolites of methanol extracts obtained from six parts of Peganum harmala L. (P. harmala), namely, the root, stem, leaf, flower, testa, and seed. Two multivariate statistical analysis methods, principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), were combined to clearly distinguish among the P. harmala samples from the six different parts. Eleven differential components were screened by the PLS-DA loading plot, and the relative contents were calculated by univariate analysis of variance. Chemometric results showed significant differences in the metabolites of the different parts of P. harmala. The seeds contained large amounts of harmaline, harmine, and vasicine compared to other organs. The acetic acid, proline, lysine, and sucrose contents of the roots were significantly higher than those of the other parts. In the testa, the vasicine, asparagine, choline, and 4-hydroxyisoleucine contents were clearly dominant. The obtained data revealed the distribution characteristics of the metabolomes of the different P. harmala parts and provided fundamental knowledge for the rational development of its medicinal parts. PMID: 30581649 [PubMed]

Independent or integrative processing approach of metabolite datasets from different biospecimens potentially affects metabolic pathway recognition in metabolomics.

Tue, 25/12/2018 - 20:39
Related Articles Independent or integrative processing approach of metabolite datasets from different biospecimens potentially affects metabolic pathway recognition in metabolomics. J Chromatogr A. 2018 Dec 14;: Authors: Zhou L, Xu JD, Zhou SS, Zhu H, Kong M, Shen H, Zou YT, Cong LJ, Xu J, Li SL Abstract In metabolomics studies, metabolic pathway recognition (MPR) is performed by software tools to screen out the significant pathways disturbed by diseases or reinstated by drugs. To achieve MPR, the significantly changed metabolites determined in different biospecimens (e.g. plasma and urine) are analyzed either independently (metabolites from each biospecimen as a dataset) or integratively (metabolites from all biospecimens as a dataset). However, whether the choice of these two processing approaches affects the results of MPR remains unknown. In this study, this issue was addressed by selecting evaluation of the effects of the herbal medicine Rehmanniae Radix (RR) on anemia and adrenal fatigue by UPLC-QTOF-MS/MS-based metabolomics as an example. The significant pathways disturbed by the modeling of anemia and adrenal fatigue and those reinstated by treatments with raw and processed RR were recognized using MetPA software tool (MetaboAnalyst 3.0), and compared by independent and integrative processing of the significantly changed metabolites determined in plasma and urine. The results showed that the two processing approaches could yield different impact values of pathways and thereby recognize different significant pathways. The differences appear to happen more easily when metabolites from different biospecimens shared the same metabolic pathway. Such pathway could be recognized as a significant pathway by integrative processing but could be excluded by independent processing due to the converged and dispersed importance contributions of the involved metabolites to MPR in the two processing approaches. This issue should concern researchers because MPR is crucial not only to understanding metabolomics data but also to guiding subsequent mechanistic research. PMID: 30580960 [PubMed - as supplied by publisher]

Metabolomic profiling and anti-infective potential of Zinnia elegans and Gazania rigens (Family Asteraceae).

Tue, 25/12/2018 - 20:39
Related Articles Metabolomic profiling and anti-infective potential of Zinnia elegans and Gazania rigens (Family Asteraceae). Nat Prod Res. 2018 Dec 22;:1-4 Authors: Gomaa AA, Samy MN, Abdelmohsen UR, Krischke M, Mueller MJ, Wanas AS, Desoukey SY, Kamel MS Abstract The present study evaluates the chemical composition of Zinnia elegans and Gazania rigens based on their metabolomic profiles using liquid chromatography coupled with high-resolution mass spectrometry (LC-HR-MS), alongside with the anti-infective activities of their ethanol extracts, as well as, different fractions. A significant difference was observed between the LC-MS profiles of the two plants such as, coumarins, sesquiterpene lactones and phenylethanoids which were characteristic for Z. elegans, while amides and phenolic acid derivatives were characteristic for G. rigens. These results highlight the chemical potential of Z. elegans and G. rigens. Furthermore, the ethyl acetate fraction of Z. elegans showed a significant antimalarial activity with IC50 values of 21.03 and 13.72 µg/mL against Plasmodium falciparum D6 and P. falciparum W2, respectively. PMID: 30580583 [PubMed - as supplied by publisher]

Development of A Correlative Strategy to Discover Colorectal Tumor Tissue Derived Metabolite Biomarkers in Plasma Using Untargeted Metabolomics.

Tue, 25/12/2018 - 20:39
Related Articles Development of A Correlative Strategy to Discover Colorectal Tumor Tissue Derived Metabolite Biomarkers in Plasma Using Untargeted Metabolomics. Anal Chem. 2018 Dec 23;: Authors: Wang Z, Cui B, Zhang F, Yang Y, Shen X, Li Z, Zhao W, Zhang Y, Deng K, Rong Z, Yang K, Yu X, Li K, Han P, Zhu ZJ Abstract The metabolic profiling of biofluids using untargeted metabolomics provides a promising choice to discover metabolite biomarkers for clinical cancer diagnosis. However, metabolite biomarkers discovered in biofluids may not necessarily reflect the pathological status of tumor tissue, which makes these biomarkers difficult to reproduce. In this study, we developed a new analysis strategy by integrating the univariate and multivariate correlation analysis approach to discover tumor tissue derived (TTD) metabolites in plasma samples. Specifically, untargeted metabolomics was first used to profile a set of paired tissue and plasma samples from 34 colorectal cancer (CRC) patients. Then, univariate correlation analysis was used to select correlative metabolite pairs between tissue and plasma, and a random forest regression model was utilized to define 243 TTD metabolites in plasma samples. The TTD metabolites in CRC plasma were demonstrated to accurately reflect the pathological status of tumor tissue, and have great potentials for metabolite biomarker discovery. Accordingly, we conducted a clinical study using a set of 146 plasma samples from CRC patients and gender-matched polyp controls to discover metabolite biomarkers from TTD metabolites. As a result, eight metabolites were selected as potential biomarkers for CRC diagnosis with high sensitivity and specificity. For CRC patients after surgery, the survival risk score defined by metabolite biomarkers also performed well in predicting overall survival time (p = 0.022) and progression free survival time (p = 0.002). In conclusion, we developed a new analysis strategy which effectively discovers tumor tissue related metabolite biomarkers in plasma for cancer diagnosis and prognosis. PMID: 30580524 [PubMed - as supplied by publisher]

Incompatibility assessment of Genkwa Flos and Glycyrrhizae Radix et Rhizoma with biochemical, histopathological and metabonomic approach.

Tue, 25/12/2018 - 20:39
Related Articles Incompatibility assessment of Genkwa Flos and Glycyrrhizae Radix et Rhizoma with biochemical, histopathological and metabonomic approach. J Ethnopharmacol. 2019 Jan 30;229:222-232 Authors: Chen YY, Tang YP, Shang EX, Zhu ZH, Tao WW, Yu JG, Feng LM, Yang J, Wang J, Su SL, Zhou H, Duan JA Abstract ETHNOPHARMACOLOGICAL RELEVANCE: As recorded in traditional Chinese medicine (TCM) theory, Genkwa Flos (YH) and Glycyrrhizae Radix et Rhizoma (GC) compose one herbal pair of the so-called "eighteen incompatible medicaments", which indicate pairs of herbs that are mutually incompatible and that theoretically should not be applied simultaneously. However, the theory has been called into question due to a lack of evidence. AIMS OF STUDY: In this study, the incompatibility of YH and GC was investigated based on an assessment of the toxic effects of their combination by traditional safety methods and a modern metabonomic approach. MATERIALS AND METHODS: Sprague-Dawley rats were used to evaluate the subacute toxicity of YH and YH-GC. The serum, urine, and several tissues were collected for biochemical analysis, histopathological examination, and metabonomic analysis. RESULTS: Rats exposed to a dose of 1.0 g/kg YH (3 times of the Chinese Pharmacopoeia maximum dose) exhibited toxicity of the heart, liver, kidney and testes, and rats exposed to a YH-GC combination (1.0 g/kg YH + 1.0 g/kg GC) exhibited similar hepatotoxicity, which aggravated renal and reproductive toxicity. Following this, a metabonomic study tentatively identified 14 potential biomarkers in the YH group and 10 potential biomarkers in the YH-GC group, and metabolic pathways were then constructed. YH disturbed the pathways of glycerophospholipid metabolism, primary bile acid biosynthesis, and sphingolipid metabolism, while YH-GC combination induced disruptions in phenylalanine, tyrosine and tryptophan biosynthesis, tyrosine metabolism, and glycerophospholipid metabolism. CONCLUSION: The toxicities of YH and YH-GC combination above the Chinese Pharmacopoeia dose were obvious but different. Metabonomics combined with biochemical and histopathological methods can be applied to elucidate the toxicity mechanism of the YH-GC combination that caused liver, kidney and reproductive injuries in rats. PMID: 30339979 [PubMed - indexed for MEDLINE]

Transcriptomics and metabonomics of the anti-aging properties of total flavones of Epimedium in relation to lipid metabolism.

Tue, 25/12/2018 - 20:39
Related Articles Transcriptomics and metabonomics of the anti-aging properties of total flavones of Epimedium in relation to lipid metabolism. J Ethnopharmacol. 2019 Jan 30;229:73-80 Authors: Wu B, Xiao X, Li S, Zuo G Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Total flavones of Epimedium (TFE) is the main active ingredient in Herba Epimedii, which is a well-known Chinese herbal medicine that is widely used to treat certain age-related diseases in oriental countries. AIM OF THE STUDY: The aim of this work was to investigate the anti-aging properties of TFE related to lipid metabolism. MATERIALS AND METHODS: Both transcriptomics and metabonomics were applied in this work to investigate the anti-aging properties of TFE. Microarray and LC-MS analysis were conducted on liver samples of three groups of rats, including young (4 months), old (24 months), and old rats administrated TFE. RESULTS: Transcriptomics analysis highlighted 287 transcripts related to the anti-aging effect of TFE, in which the expression ratio of 18 genes regulating lipid metabolism, including HMGCS1 and NR1H3, returned to normal levels after TFE treatment. In addition, 24 aging-related metabolites were discovered in a metabonomics study, and 15 of these were structurally identified, including palmitic amide, linoleamide, and oleamide. Bioinformatics and integral data analysis on the results of the transcriptomics and metabonomics suggest the involvement of 12 key metabolic pathways, half of which are highly related to lipid metabolism. CONCLUSIONS: This study demonstrates that the role played by TFE in the lipid metabolism of aging rats is multifaceted and multi-layered. PMID: 30278205 [PubMed - indexed for MEDLINE]

A novel 3D breast-cancer-on-chip platform for therapeutic evaluation of drug delivery systems.

Tue, 25/12/2018 - 20:39
Related Articles A novel 3D breast-cancer-on-chip platform for therapeutic evaluation of drug delivery systems. Anal Chim Acta. 2018 Dec 07;1036:97-106 Authors: Chen Y, Gao D, Wang Y, Lin S, Jiang Y Abstract The ability to rapidly screen drugs and drug delivery systems with a more accurate tumor model to better predict their in vivo performance is of great importance in drug development, because there have been some limitations in currently used tumor models. To address this problem, we developed an in vitro breast tumor model on a chip, composed of a microvessel wall, the extracellular matrix (ECM) and uniformly sized multicellular tumor spheroids (MCTS), for the evaluation of nanoparticle-based drug delivery systems. A carbon dots (CDs)-based drug delivery system was synthesized as a model to evaluate the real-time monitoring ability of the system transport through the endothelium and the penetrability into MCTS with a high spatio-temporal resolution on the established platform. Moreover, a modified 96-well plate was used to hold the microfluidic devices for in situ cytotoxicity assays of the MCTS by a microplate reader. Our findings revealed that the synthesized drug delivery system could be transported across an endothelial monolayer within 3 h and was nontoxic to the cells throughout the experiment. In addition, we demonstrated the capabilities of this model by assessing the delivery and efficacy of the drug delivery system in BT549 and T47D spheroids, two cell lines representative of triple negative breast cancer (TNBC) and non-TNBC, respectively. This microfluidic platform enables evaluation of dynamic transport behavior and in situ cytotoxicity evaluation in one system. The established platform provides a more accurate and low-cost in vitro model for rapid drug screening in pre-clinical studies. PMID: 30253842 [PubMed - indexed for MEDLINE]

Metabolomic changes induced by nicotine in adult zebrafish skeletal muscle.

Tue, 25/12/2018 - 20:39
Related Articles Metabolomic changes induced by nicotine in adult zebrafish skeletal muscle. Ecotoxicol Environ Saf. 2018 Nov 30;164:388-397 Authors: Gómez-Canela C, Prats E, Lacorte S, Raldúa D, Piña B, Tauler R Abstract Acute exposure to nicotinic agonists induces myotoxicity in zebrafish embryos. The main goal of this work was to evaluate the potential myotoxicity of nicotine acetylcholine receptor agonists on adult zebrafish muscle tissue by using nicotine as a model compound. Liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) datasets were processed with different chemometric tools based on the selection of Regions of Interest (ROI) and Multivariate Curve-Resolution (ROI-MCR procedure) Alternating Least Squares (ALS) for the analysis of different exposure experiments. Analysis of Variance Simultaneous Component Analysis (ASCA) of changes on metabolite peak profile areas showed significant nicotine concentration and exposure time-dependent changes, clearly differentiating between exposed and non-exposed samples and between short (2 h) and long exposure times (6 h or 24 h). Most of the changes observed in the concentrations of different metabolites are probably secondary to the observed hyperlocomotion, as they have been also observed in humans after strenuous muscular exercise. The absence of myotoxicity might be related with the reduced calcium permeability of adult muscle-type nicotinic acetylcholine receptors (nAChRs). PMID: 30142605 [PubMed - indexed for MEDLINE]

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