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

High-Fat Diet, Betaine, and Polydextrose Induce Changes in Adipose Tissue Inflammation and Metabolism in C57BL/6J Mice.

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High-Fat Diet, Betaine, and Polydextrose Induce Changes in Adipose Tissue Inflammation and Metabolism in C57BL/6J Mice. Mol Nutr Food Res. 2018 Oct 05;:e1800455 Authors: Airaksinen K, Jokkala J, Ahonen I, Auriola S, Kolehmainen M, Hanhineva K, Tiihonen K Abstract SCOPE: High-fat diets are a likely cause of low-grade inflammation and obesity-related pathologies. This study measured the effects of a high-fat diet, in combination with two dietary supplements-betaine and polydextrose-on metabolism and inflammation in the adipose tissue of diet-induced obese mice. METHODS AND RESULTS: Forty male C57BL/6J mice were fed a high-fat diet for 8 weeks and compared with low-fat-diet-fed control animals (n = 10). For the last 4 weeks, the high-fat-diet-fed animals were supplemented with 1% betaine, 3.33% polydextrose, their combination, or plain water. Fat depots from subcutaneous and visceral adipose tissue were analyzed for inflammatory markers and nontargeted metabolomics by qPCR and LC-QTOF-MS. This article is protected by copyright. All rights reserved The high-fat diet significantly increased adipose tissue inflammation in both fat depots. By metabolic profiling, we noted clear differences between low-fat-diet and high-fat-diet groups with regard to the levels of several metabolite species-primarily carnitines, lipids, and amino acids. Dietary betaine mitigated the high-fat-diet-induced IL-6 expression and significantly increased betaine and butyrobetaine levels in adipose tissue. CONCLUSIONS: The high-fat diet induced patent changes in carnitine and lipid metabolism in adipose tissue. Betaine supplementation elevated the levels of betaine and its derivatives and certain carnitine species, as reported in muscle and liver, and moderately reduced inflammation. PMID: 30290084 [PubMed - as supplied by publisher]

Application of solid-phase microextraction in current biomedical research.

Sat, 06/10/2018 - 12:12
Application of solid-phase microextraction in current biomedical research. J Sep Sci. 2018 Oct 05;: Authors: Roszkowska A, Miękus N, Bączek T Abstract Extraction of endogenous compounds and drugs and their corresponding metabolites from complex matrices, such as biofluids and solid tissues, requires adequate analytical approach facilitating qualitative and quantitative analysis. To this end, solid-phase microextraction (SPME) has been introduced as modern technology that is capable of efficient and high-throughput extraction of compounds due to its ability to amalgamate sampling, extraction, and pre-concentration steps, while requiring minimal use of organic solvents. SPME's ability to enable analyses on small-volume biological samples and growing availability of biocompatible SPME coatings make it a highly useful technology for variety of applications. For example, SPME is particularly useful for identifying biomarkers in metabolomics studies, and it can be successfully applied in pharmaceutical and toxicological studies requiring the fast and sensitive determination of drug levels, especially those that are present at low levels in biological matrices such as plasma, urine, saliva, and hair. Moreover, SPME can be directly applied in in vivo studies because this extraction technique is non-exhaustive and its biocompatible probes offer minimal invasiveness to the analyzed system. In this article, we review recent progress in well-established SPME technique for in vitro and in vivo analyses of various metabolites and drugs in clinical, pharmaceutical, and toxicological applications. This article is protected by copyright. All rights reserved. PMID: 30289623 [PubMed - as supplied by publisher]

Ethylene signaling regulates natural variation in the abundance of antifungal acetylated diferuloylsucroses and Fusarium graminearum resistance in maize seedling roots.

Sat, 06/10/2018 - 12:12
Ethylene signaling regulates natural variation in the abundance of antifungal acetylated diferuloylsucroses and Fusarium graminearum resistance in maize seedling roots. New Phytol. 2018 Oct 05;: Authors: Zhou S, Zhang YK, Kremling KA, Ding Y, Bennett JS, Bae JS, Kim DK, Ackerman HH, Kolomiets MV, Schmelz EA, Schroeder FC, Buckler ES, Jander G Abstract The production and regulation of defensive specialized metabolites play a central role in pathogen resistance in maize (Zea mays) and other plants. Therefore, identification of genes involved in plant specialized metabolism can contribute to improved disease resistance. We used comparative metabolomics to identify previously unknown antifungal metabolites in maize seedling roots, and investigated the genetic and physiological mechanisms underlying their natural variation using quantitative trait locus (QTL) mapping and comparative transcriptomics approaches. Two maize metabolites, smilaside A (3,6-diferuloyl-3',6'-diacetylsucrose) and smiglaside C (3,6-diferuloyl-2',3',6'-triacetylsucrose), that could contribute to maize resistance against Fusarium graminearum and other fungal pathogens were identified. Elevated expression of an ethylene signaling gene, ETHYLENE INSENSITIVE 2 (ZmEIN2), co-segregated with a decreased smilaside A/smiglaside C ratio. Pharmacological and genetic manipulation of ethylene availability and sensitivity in vivo indicated that, whereas ethylene was required for the production of both metabolites, the smilaside A/smiglaside C ratio was negatively regulated by ethylene sensitivity. This ratio, rather than the absolute abundance of these two metabolites, was important for maize seedling root defense against F. graminearum. Ethylene signaling regulates the relative abundance of the two F. graminearum-resistance-related metabolites and affects resistance against F. graminearum in maize seedling roots. This article is protected by copyright. All rights reserved. PMID: 30289553 [PubMed - as supplied by publisher]

Natural Variation in Freezing Tolerance and Cold Acclimation Response in Arabidopsis thaliana and Related Species.

Sat, 06/10/2018 - 12:12
Related Articles Natural Variation in Freezing Tolerance and Cold Acclimation Response in Arabidopsis thaliana and Related Species. Adv Exp Med Biol. 2018;1081:81-98 Authors: Zuther E, Lee YP, Erban A, Kopka J, Hincha DK Abstract During low-temperature exposure, temperate plant species increase their freezing tolerance in a process termed cold acclimation. The molecular mechanisms involved in cold acclimation have been mostly investigated in Arabidopsis thaliana. In addition, other Brassicaceae species related to A. thaliana have been employed in recent years to study plant stress responses on a phylogenetically broader basis and in some cases with extremophile species with a much higher stress tolerance. In this paper, we briefly summarize cold acclimation responses in A. thaliana and current knowledge about cold acclimation in A. thaliana relatives with special emphasis on Eutrema salsugineum and two closely related Thellungiella species. We then present a transcriptomic and metabolomic analysis of cold acclimation in five A. thaliana and two E. salsugineum accessions that differ widely in their freezing tolerance. Differences in the cold responses of the two species are discussed. PMID: 30288705 [PubMed - in process]

Serum kidney injury molecule 1 and β2-microglobulin perform as well as larger biomarker panels for prediction of rapid decline in renal function in type 2 diabetes.

Sat, 06/10/2018 - 12:12
Related Articles Serum kidney injury molecule 1 and β2-microglobulin perform as well as larger biomarker panels for prediction of rapid decline in renal function in type 2 diabetes. Diabetologia. 2018 Oct 05;: Authors: Colombo M, Looker HC, Farran B, Hess S, Groop L, Palmer CNA, Brosnan MJ, Dalton RN, Wong M, Turner C, Ahlqvist E, Dunger D, Agakov F, Durrington P, Livingstone S, Betteridge J, McKeigue PM, Colhoun HM, SUMMIT Investigators Abstract AIMS/HYPOTHESIS: As part of the Surrogate Markers for Micro- and Macrovascular Hard Endpoints for Innovative Diabetes Tools (SUMMIT) programme we previously reported that large panels of biomarkers derived from three analytical platforms maximised prediction of progression of renal decline in type 2 diabetes. Here, we hypothesised that smaller (n ≤ 5), platform-specific combinations of biomarkers selected from these larger panels might achieve similar prediction performance when tested in three additional type 2 diabetes cohorts. METHODS: We used 657 serum samples, held under differing storage conditions, from the Scania Diabetes Registry (SDR) and Genetics of Diabetes Audit and Research Tayside (GoDARTS), and a further 183 nested case-control sample set from the Collaborative Atorvastatin in Diabetes Study (CARDS). We analysed 42 biomarkers measured on the SDR and GoDARTS samples by a variety of methods including standard ELISA, multiplexed ELISA (Luminex) and mass spectrometry. The subset of 21 Luminex biomarkers was also measured on the CARDS samples. We used the event definition of loss of >20% of baseline eGFR during follow-up from a baseline eGFR of 30-75 ml min-1 [1.73 m]-2. A total of 403 individuals experienced an event during a median follow-up of 7 years. We used discrete-time logistic regression models with tenfold cross-validation to assess association of biomarker panels with loss of kidney function. RESULTS: Twelve biomarkers showed significant association with eGFR decline adjusted for covariates in one or more of the sample sets when evaluated singly. Kidney injury molecule 1 (KIM-1) and β2-microglobulin (B2M) showed the most consistent effects, with standardised odds ratios for progression of at least 1.4 (p < 0.0003) in all cohorts. A combination of B2M and KIM-1 added to clinical covariates, including baseline eGFR and albuminuria, modestly improved prediction, increasing the area under the curve in the SDR, Go-DARTS and CARDS by 0.079, 0.073 and 0.239, respectively. Neither the inclusion of additional Luminex biomarkers on top of B2M and KIM-1 nor a sparse mass spectrometry panel, nor the larger multiplatform panels previously identified, consistently improved prediction further across all validation sets. CONCLUSIONS/INTERPRETATION: Serum KIM-1 and B2M independently improve prediction of renal decline from an eGFR of 30-75 ml min-1 [1.73 m]-2 in type 2 diabetes beyond clinical factors and prior eGFR and are robust to varying sample storage conditions. Larger panels of biomarkers did not improve prediction beyond these two biomarkers. PMID: 30288572 [PubMed - as supplied by publisher]

Impact of chemotactic factors and receptors on the cancer immune infiltrate: a bioinformatics study revealing homogeneity and heterogeneity among patient cohorts.

Sat, 06/10/2018 - 12:12
Related Articles Impact of chemotactic factors and receptors on the cancer immune infiltrate: a bioinformatics study revealing homogeneity and heterogeneity among patient cohorts. Oncoimmunology. 2018;7(10):e1484980 Authors: Stoll G, Pol J, Soumelis V, Zitvogel L, Kroemer G Abstract Multiple soluble factors including proteins (in particular chemokines), non-proteinaceous factors released by dead cells, as well as receptors for such factors (in particular chemokine receptors, formyl peptide receptors and purinergic receptors), influence the recruitment of distinct cell subsets into the tumor microenvironment. We performed an extensive bioinformatic analysis on tumor specimens from 5953 cancer patients to correlate the mRNA expression levels of chemotactic factors/receptors with the density of immune cell types infiltrating the malignant lesions. This meta-analysis, which included specimens from breast, colorectal, lung, ovary and head and neck carcinomas as well as melanomas, revealed that a subset of chemotactic factors/receptors exhibited a positive and reproducible correlation with several infiltrating cell types across various solid cancers, revealing a universal pattern of association. Hence, this meta-analysis distinguishes between homogeneous associations that occur across different cancer types and heterogeneous correlations, that are specific of one organ. Importantly, in four out of five breast cancer cohorts for which clinical data were available, the levels of expression of chemotactic factors/receptors that exhibited universal (rather than organ-specific) positive correlations with the immune infiltrate had a positive impact on the response to neoadjuvant chemotherapy. These results support the notion that general (rather than organ-specific) rules governing the recruitment of immune cells into the tumor bed are particularly important in determining local immunosurveillance and response to therapy. PMID: 30288345 [PubMed]

The metabolomic quest for a biomarker in chronic kidney disease.

Sat, 06/10/2018 - 12:12
Related Articles The metabolomic quest for a biomarker in chronic kidney disease. Clin Kidney J. 2018 Oct;11(5):694-703 Authors: Davies R Abstract Chronic kidney disease (CKD) is a growing burden on people and on healthcare for which the diagnostics are niether disease-specific nor indicative of progression. Biomarkers are sought to enable clinicians to offer more appropriate patient-centred treatments, which could come to fruition by using a metabolomics approach. This mini-review highlights the current literature of metabolomics and CKD, and suggests additional factors that need to be considered in this quest for a biomarker, namely the diet and the gut microbiome, for more meaningful advances to be made. PMID: 30288265 [PubMed]

A Novel Antithrombotic Protease from Marine Worm Sipunculus Nudus.

Sat, 06/10/2018 - 12:12
Related Articles A Novel Antithrombotic Protease from Marine Worm Sipunculus Nudus. Int J Mol Sci. 2018 Oct 04;19(10): Authors: Ge YH, Chen YY, Zhou GS, Liu X, Tang YP, Liu R, Liu P, Li N, Yang J, Wang J, Yue SJ, Zhou H, Duan JA Abstract Sipunculus nudus, an old marine species, has great potential for use as functional seafood due to its various bioactivities. Its potential antithrombotic activity pushed us to isolate the bio-active components bio-guided by tracking fibrinolytic activity. As a result, a novel protease named as SK (the kinase obtained from S. nudus) was obtained, which possessed a molecular weight of 28,003.67 Da and 15 N-terminal amino acid sequences of PFPVPDPFVWDTSFQ. SK exerted inhibitory effects on thrombus formation through improving the coagulation system with dose-effect relationship within a certain range. Furthermore, in most cases SK got obviously better effect than that of urokinase. With the help of untargeted mass spectrometry-based metabolomics profiling, arachidonic acid, sphingolipid, and nicotinate and nicotinamide mechanism pathways were found to be important pathways. They revealed that the effect mechanism of SK on common carotid arterial thrombosis induced by FeCl₃ was achieved by inhibiting vessel contraction, platelet aggregation, adhesion, and release, correcting endothelial cell dysfunction and retarding process of thrombus formation. This study demonstrated SK was a promising thrombolytic agent on the basis of its comprehensive activities on thrombosis, and it should get further exploitation and utilization. PMID: 30287737 [PubMed - in process]

A systematic review of the small molecule studies of Osteoarthritis using Nuclear Magnetic Resonance and Mass Spectroscopy.

Sat, 06/10/2018 - 12:12
Related Articles A systematic review of the small molecule studies of Osteoarthritis using Nuclear Magnetic Resonance and Mass Spectroscopy. Osteoarthritis Cartilage. 2018 Oct 01;: Authors: Jaggard MKJ, Boulangé CL, Akhbari P, Vaghela U, Bhattacharya R, Williams HRT, Lindon JC, Gupte CM Abstract OBJECTIVE: To perform a systematic review of the small molecule metabolism studies of osteoarthritis utilising nuclear magnetic resonance or mass spectroscopy analysis (viz., metabolomics or metabonomics), thereby providing coherent conclusions and reference material for future study. METHOD: We applied PRISMA guidelines (PROSPERO 95068) with the following MESH terms: 1. "osteoarthritis" AND ("metabolic" OR "metabonomic" OR "metabolomic" OR "metabolism") 2. ("synovial fluid" OR "cartilage" OR "synovium" OR "serum" OR "plasma" OR "urine") AND ("NMR" or "Mass Spectroscopy"). Databases searched were "Medline" and "Embase". Studies were searched in English and excluded review articles not containing original research. Study outcomes were significant or notable metabolites, species (human or animal) and the Newcastle-Ottawa Score. RESULTS: In the 27 studies meeting the inclusion criteria, there was a shift towards anaerobic and fatty acid metabolism in OA disease, although whether this represents the inflammatory state remains unclear. Lipid structure and composition was altered within disease subclasses including phosphatidyl choline (PC) and the sphingomyelins. Macromolecular proteoglycan destruction was described, but the correlation to disease factors was not demonstrated. Collated results suggested arachidonate signalling pathways and androgen sex hormones as future metabolic pathways for investigation. CONCLUSION: Our meta-analysis demonstrates significant small molecule differences between sample types, between species (such as human and bovine), with potential OA biomarkers and targets for local or systemic therapies. Studies were limited by numbers and a lack of disease correlation. Future studies should use NMR and MS analysis to further investigate large population subgroups including inflammatory arthropathy, OA subclasses, age and joint differences. PMID: 30287397 [PubMed - as supplied by publisher]

Rice stripe virus-derived siRNAs play different regulatory roles in rice and in the insect vector Laodelphax striatellus.

Sat, 06/10/2018 - 12:12
Related Articles Rice stripe virus-derived siRNAs play different regulatory roles in rice and in the insect vector Laodelphax striatellus. BMC Plant Biol. 2018 Oct 04;18(1):219 Authors: Yang M, Xu Z, Zhao W, Liu Q, Li Q, Lu L, Liu R, Zhang X, Cui F Abstract BACKGROUND: Most plant viruses depend on vector insects for transmission. Upon viral infection, virus-derived small interfering RNAs (vsiRNAs) can target both viral and host transcripts. Rice stripe virus (RSV) is a persistent-propagative virus transmitted by the small brown planthopper (Laodelphax striatellus, Fallen) and can cause a severe disease on rice. RESULTS: To investigate how vsiRNAs regulate gene expressions in the host plant and the insect vector, we analyzed the expression profiles of small RNAs (sRNAs) and mRNAs in RSV-infected rice and RSV-infected planthopper. We obtained 88,247 vsiRNAs in rice that were predominantly derived from the terminal regions of the RSV RNA segments, and 351,655 vsiRNAs in planthopper that displayed relatively even distributions on RSV RNA segments. 38,112 and 80,698 unique vsiRNAs were found only in rice and planthopper, respectively, while 14,006 unique vsiRNAs were found in both of them. Compared to mock-inoculated rice, 273 genes were significantly down-regulated genes (DRGs) in RSV-infected rice, among which 192 (70.3%) were potential targets of vsiRNAs based on sequence complementarity. Gene ontology (GO) analysis revealed that these 192 DRGs were enriched in genes involved in kinase activity, carbohydrate binding and protein binding. Similarly, 265 DRGs were identified in RSV-infected planthoppers, among which 126 (47.5%) were potential targets of vsiRNAs. These planthopper target genes were enriched in genes that are involved in structural constituent of cuticle, serine-type endopeptidase activity, and oxidoreductase activity. CONCLUSIONS: Taken together, our results reveal that infection by the same virus can generate distinct vsiRNAs in different hosts to potentially regulate different biological processes, thus reflecting distinct virus-host interactions. PMID: 30286719 [PubMed - in process]

Identification and functional characterization of intermediate-size non-coding RNAs in maize.

Sat, 06/10/2018 - 12:12
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]

Discovery of isatin and 1H-indazol-3-ol derivatives as d-amino acid oxidase (DAAO) inhibitors.

Sat, 06/10/2018 - 12:12
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]

NLRP3 inflammasome inhibition attenuates silica-induced epithelial to mesenchymal transition (EMT) in human bronchial epithelial cells.

Sat, 06/10/2018 - 12:12
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]

A metabolic mechanism analysis of Fuzheng-Huayu formula for improving liver cirrhosis with traditional Chinese medicine syndromes.

Sat, 06/10/2018 - 12:12
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]

1H NMR-based dynamic metabolomics delineates the therapeutic effects of Baoyuan decoction on isoproterenol-induced cardiac hypertrophy.

Fri, 05/10/2018 - 14:52
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]

Effect of drought stress on metabolite adjustments in drought tolerant and sensitive thyme.

Fri, 05/10/2018 - 14:52
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]

Co-culture of Bacillus amyloliquefaciens ACCC11060 and Trichoderma asperellum GDFS1009 enhanced pathogen-inhibition and amino acid yield.

Fri, 05/10/2018 - 14:52
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]

Cheesomics: the future pathway to understanding cheese flavour and quality.

Fri, 05/10/2018 - 14:52
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]

Self-assembly of a Si-based cage by the formation of 24 equivalent covalent bonds.

Fri, 05/10/2018 - 14:52
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]

Chinese Black Truffle (Tuber indicum) Alters the Ectomycorrhizosphere and Endoectomycosphere Microbiome and Metabolic Profiles of the Host Tree Quercus aliena.

Fri, 05/10/2018 - 14:52
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]

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