PubMed

Related Articles Identification and functional characterization of intermediate-size non-coding RNAs in maize. BMC Genomics. 2018 Oct 04;19(1):730 Authors: Li D, Qiao H, Qiu W, Xu X, Liu T, Jiang Q, Liu R, Jiao Z, Zhang K, Bi L, Chen R, Kan Y Abstract BACKGROUND: The majority of eukaryote genomes can be actively transcribed into non-coding RNAs (ncRNAs), which are functionally important in development and evolution. In the study of maize, an important crop for both humans and animals, aside from microRNAs and long non-coding RNAs, few studies have been conducted on intermediate-size ncRNAs. RESULTS: We constructed a homogenized cDNA library of 50-500 nt RNAs in the maize inbred line Chang 7-2. Sequencing revealed 169 ncRNAs, which contained 58 known and 111 novel ncRNAs (including 70 snoRNAs, 27 snRNAs, 13 unclassified ncRNAs and one tRNA). Forty of the novel ncRNAs were specific to the Panicoideae, and 24% of them are located on sense-strand of the 5' or 3' terminus of protein coding genes on chromosome. Target site analysis found that 22 snoRNAs can guide to 38 2'-O-methylation and pseudouridylation modification sites of ribosomal RNAs and small nuclear RNAs. Expression analysis showed that 43 ncRNAs exhibited significantly altered expression in different tissues or developmental stages of maize seedlings, eight ncRNAs had tissue-specific expression and five ncRNAs were strictly accumulated in the early stage of leaf development. Further analysis showed that 3 of the 5 stage-specific ncRNAs (Zm-3, Zm-18, and Zm-73) can be highly induced under drought and salt stress, while one snoRNA Zm-8 can be repressed under PEG-simulated drought condition. CONCLUSIONS: We provided a genome-wide identification and functional analysis of ncRNAs with a size range of 50-500 nt in maize. 111 novel ncRNAs were cloned and 40 ncRNAs were determined to be specific to Panicoideae. 43 ncRNAs changed significantly during maize development, three ncRNAs can be strongly induced under drought and salt stress, suggesting their roles in maize stress response. This work set a foundation for further study of intermediate-size ncRNAs in maize. PMID: 30286715 [PubMed - in process]

Related Articles Discovery of isatin and 1H-indazol-3-ol derivatives as d-amino acid oxidase (DAAO) inhibitors. Bioorg Med Chem. 2018 05 01;26(8):1579-1587 Authors: Szilágyi B, Kovács P, Ferenczy GG, Rácz A, Németh K, Visy J, Szabó P, Ilas J, Balogh GT, Monostory K, Vincze I, Tábi T, Szökő É, Keserű GM Abstract d-Amino acid oxidase (DAAO) is a potential target in the treatment of schizophrenia as its inhibition increases brain d-serine level and thus contributes to NMDA receptor activation. Inhibitors of DAAO were sought testing [6+5] type heterocycles and identified isatin derivatives as micromolar DAAO inhibitors. A pharmacophore and structure-activity relationship analysis of isatins and reported DAAO inhibitors led us to investigate 1H-indazol-3-ol derivatives and nanomolar inhibitors were identified. The series was further characterized by pKa and isothermal titration calorimetry measurements. Representative compounds exhibited beneficial properties in in vitro metabolic stability and PAMPA assays. 6-fluoro-1H-indazol-3-ol (37) significantly increased plasma d-serine level in an in vivo study on mice. These results show that the 1H-indazol-3-ol series represents a novel class of DAAO inhibitors with the potential to develop drug candidates. PMID: 29472125 [PubMed - indexed for MEDLINE]

Related Articles NLRP3 inflammasome inhibition attenuates silica-induced epithelial to mesenchymal transition (EMT) in human bronchial epithelial cells. Exp Cell Res. 2018 01 15;362(2):489-497 Authors: Li X, Yan X, Wang Y, Wang J, Zhou F, Wang H, Xie W, Kong H Abstract Silicosis is an incurable and progressive lung disease characterized by chronic inflammation and fibroblasts accumulation. Studies have indicated a vital role for epithelial-mesenchymal transition (EMT) in fibroblasts accumulation. NLRP3 inflammasome is a critical mediator of inflammation in response to a wide range of stimuli (including silica particles), and plays an important role in many respiratory diseases. However, whether NLRP3 inflammasome regulates silica-induced EMT remains unknown. Our results showed that silica induced EMT in human bronchial epithelial cells (16HBE cells) in a dose- and time-dependent manner. Meanwhile, silica persistently activated NLRP3 inflammasome as indicated by continuously elevated extracellular levels of interleukin-1β (IL-1β) and IL-18. NLRP3 inflammasome inhibition by short hairpin RNA (shRNA)-mediated knockdown of NLRP3, selective inhibitor MCC950, and caspase-1 inhibitor Z-YVAD-FMK attenuated silica-induced EMT. Western blot analysis indicated that TAK1-MAPK-Snail/NF-κB pathway involved NLRP3 inflammasome-mediated EMT. Moreover, pirfenidone, a commercially and clinically available drug approved for treating idiopathic pulmonary fibrosis (IPF), effectively suppressed silica-induced EMT of 16HBE cells in line with NLRP3 inflammasome inhibition. Collectively, our results indicate that NLRP3 inflammasome is a promising target for blocking or retarding EMT-mediated fibrosis in pulmonary silicosis. On basis of this mechanism, pirfenidone might be a potential drug for the treatment of silicosis. PMID: 29258746 [PubMed - indexed for MEDLINE]

Related Articles A metabolic mechanism analysis of Fuzheng-Huayu formula for improving liver cirrhosis with traditional Chinese medicine syndromes. Acta Pharmacol Sin. 2018 Jun;39(6):942-951 Authors: Song YN, Chen J, Cai FF, Lu YY, Chen QL, Zhang YY, Liu P, Su SB Abstract Fuzheng-Huayu formula (FZHY), a Chinese herbal mixture prescription, has been proven effective in treating liver fibrosis and cirrhosis in both clinical trials and animal experiments. In this study we assessed the metabolic mechanisms of traditional Chinese medicine (TCM) syndrome-based FZHY treatment in liver cirrhosis (LC). A total of 113 participants, including 50 healthy controls and 63 LC patients, were recruited. According to the diagnosis and differentiation of the TCM syndromes, the LC patients were classified into 5 TCM syndrome groups including the liver stagnation syndrome (LSS), spleen deficiency and damp overabundance syndrome (SDDOS), damp-heat accumulation syndrome (DHAS), liver-kidney Yin deficiency syndrome (LKYDS), and blood stagnation syndrome (BSS), and administered FZHY for 6 months. FZHY treatment significantly decreased serum levels of hyaluronic acid (HA), a biochemical marker for LC, as well as TCM syndrome scores (the TCM syndrome scores were decreased in all the groups with significant decreases in the LSS and LKYDS groups). Furthermore, FZHY treatment gradually shifted the metabolic profiles of LC patients from a pathologic state to a healthy state, especially in LC patients with LSS and LKYDS. Twenty-two differently altered metabolites (DAMs) were identified, including carbohydrates, amino acids, fatty acids, etc with 9 DAMs in LSS patients, 9 in LKYDS patients, and 4 in other patients. The metabolic pathways involved in the conversion of amino acids and the body's detoxification process were regulated first, followed by the pathways involved in the body's energy supply process. In conclusion, the evaluation of the effect of TCM syndrome-based FZHY treatment show that FZHY has a better effect on LKYDS and LSS than on the other TCM syndromes, and the metabolic mechanisms might be involved in the increased detoxification function in LKYDS and the improvement of energy supply in LSS, which provides important evidence for the clinical application of TCM syndrome-based treatment. PMID: 29072258 [PubMed - indexed for MEDLINE]

Related Articles 1H NMR-based dynamic metabolomics delineates the therapeutic effects of Baoyuan decoction on isoproterenol-induced cardiac hypertrophy. J Pharm Biomed Anal. 2018 Sep 29;163:64-77 Authors: Du Z, Wen R, Liu Q, Wang J, Lu Y, Zhao M, Guo X, Tu P, Jiang Y Abstract Cardiac hypertrophy (CH) is a major risk factor for many serious heart diseases. Sustained CH is catastrophic, resulting in cardiac dysfunction that eventually leads to heart failure (HF). Baoyuan decoction (BYD) is a famous traditional Chinese medicine (TCM) formula for supplementing and reinforcing Qi, clinically used for the treatment of cardiovascular diseases (CVDs). However, the therapeutic effects of BYD on CH remain unidentified. We herein investigated the effect of BYD on isoproterenol (ISO)-induced CH in rats and the underlying mechanisms by comprehensive pharmacodynamics and 1H NMR-based dynamic metabolomics analysis of the plasma and urine samples. Results showed that BYD treatment markedly attenuated ISO-induced CH as evidenced by decreasing the left ventricular wall thickness, pathological cardiomyocyte hypertrophy, myocardial collagen fiber deposition and apoptosis, and plasma natriuretic peptide levels. Multivariate trajectory analysis revealed that the BYD treatment could restore the CH-disturbed plasma and urinary metabolite profiles towards the normal metabolic status featuring with a time-dependent tendency. Moreover, the key metabolic alterations in CH rats at different BYD-treated time stages involved energy metabolism, oxidative stress responses, amino acid metabolism, and gut microbiota metabolism. Of particularly, the significant roles of BYD for treating CH lie in the improvement of cardiac energy generation and antioxidant capacity. Our investigation provides a holistic view of BYD for therapeutic intervention of CH through monitoring of the dynamic metabolic changes and the results indicate that BYD may be applied as a potential agent for treating CH. PMID: 30286437 [PubMed - as supplied by publisher]

Related Articles Effect of drought stress on metabolite adjustments in drought tolerant and sensitive thyme. Plant Physiol Biochem. 2018 Sep 29;132:391-399 Authors: Ashrafi M, Azimi-Moqadam MR, Moradi P, MohseniFard E, Shekari F, Kompany-Zareh M Abstract Drought is one of the most important threats to plants and agriculture; therefore, understanding of the mechanism of drought tolerance is crucial for breeding of drought tolerant plants. Here, we assessed effects of four levels of drought (90%, 55%, 40% and 25% FC) on some physiological criteria and metabolite adjustment of two different drought-responsive thyme plants (Thymus vulgaris as drought sensitive and T. Kotschyanus as drought tolerant species), using 1H-NMR. Among three physiological parameters and 18 identified metabolites, species × treatment effects were significant (P ≤ 0.01) for leaf temperature, acetic acid, citric acid, fumaric acid, malic acid, succinic acid, fructose, sucrose and serine. RWC, chlorophyll and carotenoids content, glucose, alanine and choline were affected by simple effects of species and treatment. Correlation analysis revealed that there is a different correlation between physiological parameters and metabolites in both species. This analysis also revealed that, by ignoring the correlation between malic acid and succinic acid in T. vulgaris, there was no significant correlation between TCA intermediate in both species. According to results, sugars, amino acid and energy metabolism were affected by drought and, among them, TCA intermediates had more alternation in two studied species so, this cycle and its intermediates probably have more prominent role than other identified metabolites in the induction of drought tolerance. PMID: 30286404 [PubMed - as supplied by publisher]

Related Articles Co-culture of Bacillus amyloliquefaciens ACCC11060 and Trichoderma asperellum GDFS1009 enhanced pathogen-inhibition and amino acid yield. Microb Cell Fact. 2018 Oct 03;17(1):155 Authors: Wu Q, Ni M, Dou K, Tang J, Ren J, Yu C, Chen J Abstract BACKGROUND: Bacillus spp. are a genus of biocontrol bacteria widely used for antibiosis, while Trichoderma spp. are biocontrol fungi that are abundantly explored. In this study, a liquid co-cultivation of these two organisms was tried firstly. RESULTS AND DISCUSSION: Through liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS), it was discovered that with an inoculation in the ratio of 1.9:1, the antimicrobial effect of the co-cultured fermentation liquor of Bacillus amyloliquefaciens ACCC11060 and Trichoderma asperellum GDFS1009 was found to be significantly higher than that of pure-cultivation. A raise in the synthesis of antimicrobial substances contributed to this significant increase. Additionally, a co-culture with the inoculation of the two organisms in the ratio of 1:1 was found to enhance the production of specific amino acids. This technique could be further explored for either a large scale production of amino acids or could serve as a theoretical base for the generation of certain rare amino acids. CONCLUSIONS: This work clearly demonstrated that co-cultivation of B. amyloliquefaciens ACCC11060 and T. asperellum GDFS1009 could produce more specific biocontrol substances and amino acids. PMID: 30285749 [PubMed - in process]

Related Articles Cheesomics: the future pathway to understanding cheese flavour and quality. Crit Rev Food Sci Nutr. 2018 Oct 04;:1-15 Authors: Afshari R, Pillidge CJ, Dias DA, Osborn AM, Gill H Abstract Cheese is a fermented dairy product, harboring diverse microbial communities (microbiota) that change over time and vary depending on the type of cheese and their respective starter and adjunct cultures. These microorganisms play a crucial role in determining the flavor, quality and safety of the final product. Exploring the composition of cheese microbiota and the underlying molecular mechanisms involved in cheese ripening has been the subject of many studies. Recent advances in next generation sequencing (NGS) methods and the development of sophisticated bioinformatics tools have provided deeper insights into the composition and potential functionality of cheese microbiota far beyond the information provided by culture-dependent methods. These advances, which include rRNA gene amplicon sequencing and metagenomics, have been complemented and expanded in recent years by the application of metatranscriptomics, metaproteomics and metabolomics. This paper reviews studies in which application of these meta-omics technologies has led to a better understanding of the microbial composition and functionality of cheese and highlights opportunities by which the integration of outputs from diverse multi-omics analytical platforms (cheesomics) could be used in the future to advance our knowledge of the cheese ripening process and identify biomarkers for predicting cheese flavor, quality, texture and safety, and bioactive metabolites with potential to influence human health. PMID: 30285475 [PubMed - as supplied by publisher]

Related Articles Self-assembly of a Si-based cage by the formation of 24 equivalent covalent bonds. Chem Commun (Camb). 2018 Oct 04;: Authors: Holmes JL, Abrahams BF, Ahveninen A, Boughton BA, Hudson TA, Robson R, Thinagaran D Abstract A robust, nano-sized covalent cage, of composition, [(PhSi)6(ctc)4]6- (H6ctc = cyclotricatechylene) has been prepared in a simple reaction in good yield. The tetrahedral anionic cage is stable in both the solid and solution state and exhibits an affinity for Cs+ ions which bind to the internal surface of the cage. PMID: 30283934 [PubMed - as supplied by publisher]

Related Articles Chinese Black Truffle (Tuber indicum) Alters the Ectomycorrhizosphere and Endoectomycosphere Microbiome and Metabolic Profiles of the Host Tree Quercus aliena. Front Microbiol. 2018;9:2202 Authors: Li Q, Yan L, Ye L, Zhou J, Zhang B, Peng W, Zhang X, Li X Abstract Truffles are one group of the most famous ectomycorrhizal fungi in the world. There is little information on the ecological mechanisms of truffle ectomycorrhizal synthesis in vitro. In this study, we investigated the ecological effects of Tuber indicum - Quercus aliena ectomycorrhizal synthesis on microbial communities in the host plant roots and the surrounding soil using high-throughput sequencing and on the metabolic profiles of host plant roots using metabolomics approaches. We observed an increase in the diversity and richness of prokaryotic communities and a decrease in richness of fungal communities in the presence of T. indicum. The microbial community structures in the host roots and the surrounding soil were altered by ectomycorrhizal synthesis in the greenhouse. Bacterial genera Pedomicrobium, Variibacter, and Woodsholea and fungal genera Aspergillus, Phaeoacremonium, and Pochonia were significantly more abundant in ectomycorhizae and the ectomycorrhizosphere soil compared with the corresponding T. indicum-free controls (P < 0.05). Truffle-colonization reduced the abundance of some fungal genera surrounding the host tree, such as Acremonium, Aspergillus, and Penicillium. Putative prokaryotic metabolic functions and fungal functional groups (guilds) were also differentiated by ectomycorrhizal synthesis. The ectomycorrhizal synthesis had great impact on the measured soil physicochemical properties. Metabolic profiling analysis uncovered 55 named differentially abundant metabolites between the ectomycorhizae and the control roots, including 44 upregulated and 11 downregulated metabolites. Organic acids and carbohydrates were two major upregulated metabolites in ectomycorhizae, which were found formed dense interactions with other metabolites, suggesting their crucial roles in sustaining the metabolic functions in the truffle ectomycorrhization system. This study revealed the effects of truffle-colonization on the metabolites of ectomycorrhiza and illustrates an interactive network between truffles, the host plant, soil and associated microbial communities, shedding light on understanding the ecological effects of truffles. PMID: 30283422 [PubMed]

Related Articles Photosystem-II D1 protein mutants of Chlamydomonas reinhardtii in relation to metabolic rewiring and remodelling of H-bond network at QB site. Sci Rep. 2018 Oct 03;8(1):14745 Authors: Antonacci A, Lambreva MD, Margonelli A, Sobolev AP, Pastorelli S, Bertalan I, Johanningmeier U, Sobolev V, Samish I, Edelman M, Havurinne V, Tyystjärvi E, Giardi MT, Mattoo AK, Rea G Abstract Photosystem II (PSII) reaction centre D1 protein of oxygenic phototrophs is pivotal for sustaining photosynthesis. Also, it is targeted by herbicides and herbicide-resistant weeds harbour single amino acid substitutions in D1. Conservation of D1 primary structure is seminal in the photosynthetic performance in many diverse species. In this study, we analysed built-in and environmentally-induced (high temperature and high photon fluency - HT/HL) phenotypes of two D1 mutants of Chlamydomonas reinhardtii with Ala250Arg (A250R) and Ser264Lys (S264K) substitutions. Both mutations differentially affected efficiency of electron transport and oxygen production. In addition, targeted metabolomics revealed that the mutants undergo specific differences in primary and secondary metabolism, namely, amino acids, organic acids, pigments, NAD, xanthophylls and carotenes. Levels of lutein, β-carotene and zeaxanthin were in sync with their corresponding gene transcripts in response to HT/HL stress treatment in the parental (IL) and A250R strains. D1 structure analysis indicated that, among other effects, remodelling of H-bond network at the QB site might underpin the observed phenotypes. Thus, the D1 protein, in addition to being pivotal for efficient photosynthesis, may have a moonlighting role in rewiring of specific metabolic pathways, possibly involving retrograde signalling. PMID: 30283151 [PubMed - in process]

Related Articles Glycerophosphatidylcholine PC(36:1) absence and 3'-phosphoadenylate (pAp) accumulation are hallmarks of the human glioma metabolome. Sci Rep. 2018 Oct 03;8(1):14783 Authors: Li W, Jia H, Li Q, Cui J, Li R, Zou Z, Hong X Abstract Glioma is the most prevalent malignant brain tumor. A comprehensive analysis of the glioma metabolome is still lacking. This study aims to explore new special metabolites in glioma tissues. A non-targeted human glioma metabolomics was performed by UPLC-Q-TOF/MS. The gene expressions of 18 enzymes associated with 3'-phosphoadenylate (pAp) metabolism was examined by qRT-PCR. Those enzymes cover the primary metabolic pathway of pAp. We identified 15 new metabolites (13 lipids and 2 nucleotides) that were significantly different between the glioma and control tissues. Glycerophosphatidylcholine [PC(36:1)] content was high and pAp content was significantly low in the control brain (p  < 0.01). In glioma tissues, PC(36:1) was not detected and pAp content was significantly increased. The gene expressions of 3'-nucleotidases (Inositol monophosphatase (IMPAD-1) and 3'(2'),5'-bisphosphate nucleotidase 1(BPNT-1)) were dramatically down-regulated. Meanwhile, the gene expression of 8 sulfotransferases (SULT), 2 phosphoadenosine phosphosulfate synthases (PAPSS-1 and PAPSS-2) and L-aminoadipate-semialdehyde dehydrogenase-phosphopante-theinyl transferase (AASDHPPT) were up-regulated. PC(36:1) absence and pAp accumulation are the most noticeable metabolic aberration in glioma. The dramatic down-regulation of IMPAD-1 and BPNT-1 are the primary cause for pAp dramatic accumulation. Our findings suggest that differential metabolites discovered in glioma could be used as potentially novel therapeutic targets or diagnostic biomarkers and that abnormal metabolism of lipids and nucleotides play roles in the pathogenesis of glioma. PMID: 30283018 [PubMed - in process]

Related Articles Metabolomic Analyses Reveal Extensive Progenitor Cell Deficiencies in a Mouse Model of Duchenne Muscular Dystrophy. Metabolites. 2018 Oct 03;8(4): Authors: Joseph J, Cho DS, Doles JD Abstract Duchenne muscular dystrophy (DMD) is a musculoskeletal disorder that causes severe morbidity and reduced lifespan. Individuals with DMD have an X-linked mutation that impairs their ability to produce functional dystrophin protein in muscle. No cure exists for this disease and the few therapies that are available do not dramatically delay disease progression. Thus, there is a need to better understand the mechanisms underlying DMD which may ultimately lead to improved treatment options. The muscular dystrophy (MDX) mouse model is frequently used to explore DMD disease traits. Though some studies of metabolism in dystrophic mice exist, few have characterized metabolic profiles of supporting cells in the diseased environment. Using nontargeted metabolomics we characterized metabolic alterations in muscle satellite cells (SCs) and serum of MDX mice. Additionally, live-cell imaging revealed MDX-derived adipose progenitor cell (APC) defects. Finally, metabolomic studies revealed a striking elevation of acylcarnitines in MDX APCs, which we show can inhibit APC proliferation. Together, these studies highlight widespread metabolic alterations in multiple progenitor cell types and serum from MDX mice and implicate dystrophy-associated metabolite imbalances in APCs as a potential contributor to adipose tissue disequilibrium in DMD. PMID: 30282911 [PubMed]

Related Articles Exploring a Novel Screening Method for Patients with Oral Squamous Cell Carcinoma: A plasma Metabolomics Analysis. Kobe J Med Sci. 2018 Sep 11;64(1):E26-E35 Authors: Enomoto Y, Kimoto A, Suzuki H, Nishiumi S, Yoshida M, Komori T Abstract AIM: This study aimed to explore novel metabolite biomarker candidates for screening oral squamous cell carcinoma (OSCC). PATIENTS & METHODS: We collected plasma samples from 48 patients with OSCC and 29 with an oral disease and conducted a plasma metabolomics analysis of patients with OSCC using gas chromatography mass spectrometry. Then, we used the cross-validation procedure to ensure the accuracy of biomarker candidates. RESULTS: We selected four biomarker candidates against OSCC. Their sensitivity was more than 90%, and the AUC was over 0.9 according to the receiver operating characteristic curve analysis. CONCLUSIONS: The findings of this study suggest four potential metabolites as biomarkers for OSCC screening. PMID: 30282895 [PubMed - in process]

Related Articles Metabolic Profiling of the hippocampus of rats experiencing nicotine-withdrawal symptoms. Biol Pharm Bull. 2018 Oct 02;: Authors: Akimoto H, Oshima S, Michiyama Y, Negishi A, Nemoto T, Kobayashi D Abstract Nicotine-withdrawal symptoms have been indicated as a possible risk factor for neuropsychiatric events, such as depression and suicide, during use of smoking-cessation drugs. We aimed to investigate whether the results of the metabolomic analysis of the rat brain reflect nicotine-withdrawal symptoms. We also aimed to investigate the relative changes in each metabolite in the brains of rats with nicotine-withdrawal symptoms. We created rats experiencing nicotine-withdrawal symptoms through repeat administration of nicotine followed by a 12-h withdrawal period, and rats recovered from nicotine-withdrawal symptoms followed by an 18-h withdrawal period. We then implemented brain metabolic profiling by combining high-resolution magic-angle spinning 1H nuclear magnetic resonance (NMR) spectroscopy with partial least square discriminant analysis (PLS-DA). We found that metabolic profiling of the brain reflects the state during nicotine-withdrawal symptoms and the state after recovery from nicotine-withdrawal symptoms. Additionally, N-acetylaspartate and glutamate increased and aspartate, GABA, and creatine decreased in the hippocampus of rats experiencing nicotine-withdrawal symptoms. Therefore, it is suggested that neurogenesis and neuronal differentiation could be changed and abnormal energy metabolism could occur in the hippocampus during nicotine-withdrawal symptoms. PMID: 30282850 [PubMed - as supplied by publisher]

Related Articles The airway epithelium undergoes metabolic reprogramming in individuals at high risk for lung cancer. JCI Insight. 2016 11 17;1(19):e88814 Authors: Rahman SM, Ji X, Zimmerman LJ, Li M, Harris BK, Hoeksema MD, Trenary IA, Zou Y, Qian J, Slebos RJ, Beane J, Spira A, Shyr Y, Eisenberg R, Liebler DC, Young JD, Massion PP Abstract The molecular determinants of lung cancer risk remain largely unknown. Airway epithelial cells are prone to assault by risk factors and are considered to be the primary cell type involved in the field of cancerization. To investigate risk-associated changes in the bronchial epithelium proteome that may offer new insights into the molecular pathogenesis of lung cancer, proteins were identified in the airway epithelial cells of bronchial brushing specimens from risk-stratified individuals by shotgun proteomics. Differential expression of selected proteins was validated by parallel reaction monitoring mass spectrometry in an independent set of individual bronchial brushings. We identified 2,869 proteins, of which 312 proteins demonstrated a trend in expression. Pathway analysis revealed enrichment of carbohydrate metabolic enzymes in high-risk individuals. Glucose consumption and lactate production were increased in human bronchial epithelial BEAS2B cells treated with cigarette smoke condensate for 7 months. Increased lipid biosynthetic capacity and net reductive carboxylation were revealed by metabolic flux analyses of [U-13C5] glutamine in this in vitro model, suggesting profound metabolic reprogramming in the airway epithelium of high-risk individuals. These results provide a rationale for the development of potentially new chemopreventive strategies and selection of patients for surveillance programs. PMID: 27882349 [PubMed - indexed for MEDLINE]

Related Articles Temporal clustering analysis of endothelial cell gene expression following exposure to a conventional radiotherapy dose fraction using Gaussian process clustering. PLoS One. 2018;13(10):e0204960 Authors: Heinonen M, Milliat F, Benadjaoud MA, François A, Buard V, Tarlet G, d'Alché-Buc F, Guipaud O Abstract The vascular endothelium is considered as a key cell compartment for the response to ionizing radiation of normal tissues and tumors, and as a promising target to improve the differential effect of radiotherapy in the future. Following radiation exposure, the global endothelial cell response covers a wide range of gene, miRNA, protein and metabolite expression modifications. Changes occur at the transcriptional, translational and post-translational levels and impact cell phenotype as well as the microenvironment by the production and secretion of soluble factors such as reactive oxygen species, chemokines, cytokines and growth factors. These radiation-induced dynamic modifications of molecular networks may control the endothelial cell phenotype and govern recruitment of immune cells, stressing the importance of clearly understanding the mechanisms which underlie these temporal processes. A wide variety of time series data is commonly used in bioinformatics studies, including gene expression, protein concentrations and metabolomics data. The use of clustering of these data is still an unclear problem. Here, we introduce kernels between Gaussian processes modeling time series, and subsequently introduce a spectral clustering algorithm. We apply the methods to the study of human primary endothelial cells (HUVECs) exposed to a radiotherapy dose fraction (2 Gy). Time windows of differential expressions of 301 genes involved in key cellular processes such as angiogenesis, inflammation, apoptosis, immune response and protein kinase were determined from 12 hours to 3 weeks post-irradiation. Then, 43 temporal clusters corresponding to profiles of similar expressions, including 49 genes out of 301 initially measured, were generated according to the proposed method. Forty-seven transcription factors (TFs) responsible for the expression of clusters of genes were predicted from sequence regulatory elements using the MotifMap system. Their temporal profiles of occurrences were established and clustered. Dynamic network interactions and molecular pathways of TFs and differential genes were finally explored, revealing key node genes and putative important cellular processes involved in tissue infiltration by immune cells following exposure to a radiotherapy dose fraction. PMID: 30281653 [PubMed - in process]

Related Articles From Food for Survival to Food for Personalized Optimal Health: A Historical Perspective of How Food and Nutrition Gave Rise to Nutrigenomics. J Am Coll Nutr. 2018 Oct 03;:1-12 Authors: Sikalidis AK Abstract Human nutrition has progressed impressively from the hunter-gatherer mode to that of promising personalized nutrition for health optimization through advanced and sophisticated omics technologies. The contemporary major diseases, while having strong genetic components, do not conform to Mendelian genetics; hence, their expression/manifestation is not controlled by a single gene. Noncommunicable diseases such as obesity, cancer, type 2 diabetes mellitus, and cardiovascular disease are attributed to a series of chronic anomalies closely related to dietary, among other, environmental factors, and consistent deregulation of one or more groups of genes (polygenic). Collectively, these diseases constitute the main cause of death globally and pose tremendous financial burden on healthcare systems. Dietary interventions offer significant possibilities for cost-effective strategies to reduce risk of a series of metabolic diseases and/or improve the outcome of prognosis. In recent decades, the ability of particular nutrients to influence certain cellular functions as well as the regulation of several metabolic pathways via genomic interplay has been demonstrated. Nutrients can influence cellular responses and hence exert an effect on health parameters and outcomes. Several nutrients have been documented to extend their regulatory capacity at various levels including gene expression profile signatures' modulation. In addition, specific nutrients can modulate expression/activation of genes that encode regulatory hormones, which in turn are signaling agents strongly affecting metabolism and subsequently risk levels for certain metabolic diseases. The field of nutrigenomics attempts to revolutionize modern thinking on diet, food, and health; whether it will deliver is still an open matter of debate Key teaching points: A brief, yet comprehensive account on how food and nutrition evolved to give rise to nutrigenomics. Discusses potential of nutrigenomics for public health contribution in noncommunicable diseases. Debates credibility of nutrigenomics' commercial products versus the bio-hype in the field. Presents experts' and stakeholders' opinions for future directions of nutrigenomics. PMID: 30280996 [PubMed - as supplied by publisher]

Related Articles Arginine reprogramming in ADPKD results in arginine-dependent cystogenesis. Am J Physiol Renal Physiol. 2018 Oct 03;: Authors: Trott JF, Hwang VJ, Ishimaru T, Chmiel K, Zhou X, Shim K, Stewart B, Mahjoub MR, Jen KY, Barupal D, Li X, Weiss RH Abstract Research into metabolic reprogramming in cancer has become commonplace, yet this area of research has only recently come of age in nephrology. In light of the parallels between cancer and ADPKD, the latter is currently being studied as a metabolic disease. In clear cell renal cell carcinoma (RCC), which is now considered a metabolic disease, we and others have shown derangements in the enzyme arginosuccinate synthase (ASS1) resulting in RCC cells becoming auxotrophic for arginine and leading to a new therapeutic paradigm involving reducing extracellular arginine. Based on our earlier finding that glutamine pathways are reprogrammed in ARPKD, and given the connection between arginine and glutamine synthetic pathways via citrulline, we investigated the possibility of arginine reprogramming in ADPKD. We now show that, in a remarkable parallel to RCC, ASS1 expression is reduced in murine and human ADPKD, and arginine depletion results in a dose dependent compensatory increase in ASS1 levels as well as decreased cystogenesis in vitro and ex vivo with minimal toxicity to normal cells. Non-targeted metabolomics analysis of mouse kidney cell lines grown in arginine-deficient vs. arginine-replete media suggests arginine-dependent alterations in the glutamine and proline pathways. Thus, depletion of this conditionally-essential amino acid by dietary or pharmacological means, such as with arginine-degrading enzymes, may be a novel treatment for this disease. PMID: 30280600 [PubMed - as supplied by publisher]

Related Articles Combination Metabolomics Approach for Identifying Endogenous Substrates of Carnitine/Organic Cation Transporter OCTN1. Pharm Res. 2018 Oct 02;35(11):224 Authors: Masuo Y, Ohba Y, Yamada K, Al-Shammari AH, Seba N, Nakamichi N, Ogihara T, Kunishima M, Kato Y Abstract PURPOSE: Solute carrier SLC22A4 encodes the carnitine/organic cation transporter OCTN1 and is associated with inflammatory bowel disease, although little is known about how this gene is linked to pathogenesis. The aim of the present study was to identify endogenous substrates that are associated with gastrointestinal inflammation. METHODS: HEK293/OCTN1 and mock cells were incubated with colon extracts isolated from dextran sodium sulfate-induced colitis mice; the subsequent cell lysates were mixed with the amino group selective reagent 3-aminopyridyl-N-hydroxysuccinimidyl carbamate (APDS), to selectively label OCTN1 substrates. Precursor ion scanning against the fragment ion of APDS was then used to identify candidate OCTN1 substrates. RESULTS: Over 10,000 peaks were detected by precursor ion scanning; m/z 342 had a higher signal in HEK293/OCTN1 compared to mock cells. This peak was detected as a divalent ion that contained four APDS-derived fragments and was identified as spermine. Spermine concentration in peripheral blood mononuclear cells from octn1 gene knockout mice (octn1-/-) was significantly lower than in wild-type mice. Lipopolysaccharide-induced gene expression of inflammatory cytokines in peritoneal macrophages from octn1-/- mice was lower than in wild-type mice. CONCLUSIONS: The combination metabolomics approach can provide a novel tool to identify endogenous substrates of OCTN1. PMID: 30280275 [PubMed - in process]