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

An NMR based panorama of the heterogeneous biology of acute respiratory distress syndrome (ARDS) from the standpoint of metabolic biomarkers.

Sun, 17/11/2019 - 12:10
An NMR based panorama of the heterogeneous biology of acute respiratory distress syndrome (ARDS) from the standpoint of metabolic biomarkers. NMR Biomed. 2019 Nov 16;:e4192 Authors: Viswan A, Singh C, Kayastha AM, Azim A, Sinha N Abstract Acute respiratory distress syndrome (ARDS), manifested by intricate etiology and pathophysiology, demands careful clinical surveillance due to its high mortality and imminent life support measures. NMR based metabolomics provides an approach for ARDS which culminates from a wide spectrum of illness thereby confounding early manifestation and prognosis predictors. 1 H NMR with its manifold applications in critical disease settings can unravel the biomarker of ARDS thus holding potent implications by providing surrogate endpoints of clinical utility. NMR metabolomics which is the current apogee platform of omics trilogy is contributing towards the possible panacea of ARDS by subsequent validation of biomarker credential on larger datasets. In the present review, the physiological derangements that jeopardize the whole metabolic functioning in ARDS are exploited and the biomarkers involved in progression are addressed and substantiated. The following sections of the review also outline the clinical spectrum of ARDS from the standpoint of NMR based metabolomics which is an emerging element of systems biology. ARDS is the main premise of intensivists textbook, which has been thoroughly reviewed along with its incidence, progressive stages of severity, new proposed diagnostic definition, and the preventive measures and the current pitfalls of clinical management. The advent of new therapies, the need for biomarkers, the methodology and the contemporary promising approaches needed to improve survival and address heterogeneity have also been evaluated. The review has been stepwise illustrated with potent biometrics employed to selectively pool out differential metabolites as diagnostic markers and outcome predictors. The following sections have been drafted with an objective to better understand ARDS mechanisms with predictive and precise biomarkers detected so far on the basis of underlying physiological parameters having close proximity to diseased phenotype. The aim of this review is to stimulate interest in conducting more studies to help resolve the complex heterogeneity of ARDS with biomarkers of clinical utility and relevance. PMID: 31733128 [PubMed - as supplied by publisher]

A pilot investigation of a urinary metabolic biomarker discovery in renal cell carcinoma.

Sun, 17/11/2019 - 12:10
Related Articles A pilot investigation of a urinary metabolic biomarker discovery in renal cell carcinoma. Int Urol Nephrol. 2019 Nov 16;: Authors: Zhang M, Liu X, Liu X, Li H, Sun W, Zhang Y Abstract BACKGROUND: Renal cell carcinoma (RCC) is the most common and lethal malignancy of the kidney. Distinguishing RCC from benign renal tumors and healthy controls is still a clinical challenge. Urine metabolomics has been used to identify biomarkers of clinical diseases. METHODS: In the present study, we explored the urine metabolomes of a cohort of 61 patients with renal tumors (39 RCC and 22 benign renal tumors) and 68 healthy controls using liquid chromatography coupled with high-resolution mass spectrometry (LC-MS). RESULTS: Metabolic profiling of urine could significantly differentiate RCC from healthy controls and benign renal tumors. Metabolic pathways, including lysine metabolism and phenylalanine metabolism, were found to be disturbed in the RCC group. Steroid hormone biosynthesis was significantly different between the benign tumor group and the RCC group. RCC biomarkers were further explored. A metabolite panel consisting of cortolone, testosterone and L-2-aminoadipate adenylate was discovered to have good ability of distinguishing RCC from benign tumors, with an AUC of 0.868 for tenfold cross-validation and 0.873 for the validation group. In addition, the panel of aminoadipic acid, 2-(formamido)-N1-(5-phospho-D-ribosyl) acetamidine and alpha-N-phenylacetyl-L-glutamine could distinguish the RCC group from the healthy control group, with an AUC of 0.841 for tenfold cross-validation and 0.894 for the validation group. CONCLUSIONS: This pilot study suggests that urine metabolomics may be useful in differentiating RCC from healthy controls and benign renal tumors. PMID: 31732842 [PubMed - as supplied by publisher]

Detection and comparison of phenolic compounds in different extracts of black currant leaves by liquid chromatography coupled with high-resolution ESI-LTQ-Orbitrap MS and high-sensitivity ESI-Qtrap MS.

Sun, 17/11/2019 - 12:10
Related Articles Detection and comparison of phenolic compounds in different extracts of black currant leaves by liquid chromatography coupled with high-resolution ESI-LTQ-Orbitrap MS and high-sensitivity ESI-Qtrap MS. J Pharm Biomed Anal. 2019 Oct 28;:112926 Authors: D'Urso G, Montoro P, Piacente S Abstract Liquid preparations such as tinctures and infusion derived from Ribes nigrum L. (black currant) leaves are widely used in Europe. Despite the various uses reported for the infusion and hydroalcoholic extracts of the leaves of this species, their chemical profile has not yet been defined. In the present study, the infusion, hydroalcholic and methanolic extracts prepared from R. nigrum leaves were analyzed. LC-MS analyses of these extracts allowed the characterization of 31 phenolic compounds mainly belonging to organic acids, flavonoids, catechins and its oligomers. Quantitative results proved that these preparations are a rich source of polyphenols and flavonoids and among them the infusion presented the highest polyphenol levels. A metabolomics approach was also used for the comparison and evaluation of the chemical composition of the different extracts obtained from R. nigrum leaves. PMID: 31732405 [PubMed - as supplied by publisher]

In vitro cytotoxic activity of six Syzygium leaf extracts as related to their phenolic profiles: An untargeted UHPLC-QTOF-MS approach.

Sun, 17/11/2019 - 12:10
Related Articles In vitro cytotoxic activity of six Syzygium leaf extracts as related to their phenolic profiles: An untargeted UHPLC-QTOF-MS approach. Food Res Int. 2019 Dec;126:108715 Authors: Rocchetti G, Lucini L, Ahmed SR, Saber FR Abstract Untargeted metabolomics was used in this study to discriminate the phenolic fingerprints of six Syzygium species. This approach resulted in the annotation of 441 compounds that belong to different phenolic classes, such as flavonoids, lignans, stilbenes, tyrosols, alkylphenols, and phenolic acids. Multivariate data analysis unraveled the main differences between the studied species. S. paniculatum and S. aqueum were the richest sources in terms of phenolic compounds, cumulatively amounting to 355.3 and 266.4 mg/g dry matter, respectively. Nevertheless, S. jambos showed reduced amounts of phenolics, when compared with other species. The biological activity of Syzygium leaf extracts was assessed on MCF-7 breast adenocarcinoma and MDA-MB-231 breast cancer cell lines. Potent estrogenic activity was detected using the SRB assay on MCF-7. This activity may be ascribable to the presence of phenolic compounds miming phytoestrogens such as lignans, stilbenes, and isoflavonoids in the investigated Syzygium extracts. By examining the biological effect of Syzygium extracts against MDA-MB-231 cell lines, the Syzygium gratum leaf extract exhibited the strongest inhibition, with IC50 = 19.4 µg/mL, followed by S. paniculatum (IC50 = 50.9 µg/mL). However, the Syzygium gratum leaf extract showed a potent cytotoxic effect on normal human skin fibroblasts, HSF (IC50 = 1.24 µg/mL), assuming a nonselective cytotoxic effect. On the other hand, other studied Syzygium leaves proved as safe nutraceuticals (IC50 ≥ 100 µg/mL) on HSF cell lines. Our study suggested a possible implication of Syzygium malaccense and Syzygium aqueum leaves as potential estrogenic candidates in relation to their health-promoting phenolic constituents. PMID: 31732075 [PubMed - in process]

The changes in the release level of polyunsaturated fatty acids (ω-3 and ω-6) and lipids in the untreated and water-soaked chia seed.

Sun, 17/11/2019 - 12:10
Related Articles The changes in the release level of polyunsaturated fatty acids (ω-3 and ω-6) and lipids in the untreated and water-soaked chia seed. Food Res Int. 2019 Dec;126:108665 Authors: Zare T, Rupasinghe TWT, Boughton BA, Roessner U Abstract Despite recent studies on health benefits of chia seed owing to its high content of ω-3 fatty acids, little work has been conducted on extractability of its nutrients. We examined the effect of soaking chia seed in water on the extractability of its omega fatty acids and lipids. State-of-the-art mass spectrometry techniques including GC-MS, LC-MS, and MALDI-MSI were utilized to identify and determine the spatial distribution of omega fatty acids and lipids in chia seed. Results showed that 24 h soaking in water improves the extractability of omega fatty acids and the ω-6:ω-3 ratio. Increase in the release levels of triacylglycerols and diacylglycerols and reduction in the release levels of phosphatidylcholines are envisaged to be the result of cell wall weakening and consequently availability of lipids for extraction. Results of MALDI-MSI show that highly abundant lipid species are mainly localised in the chia seed endosperm rather than its mucilage. PMID: 31732052 [PubMed - in process]

Identification of phenolic markers for saffron authenticity and origin: An untargeted metabolomics approach.

Sun, 17/11/2019 - 12:10
Related Articles Identification of phenolic markers for saffron authenticity and origin: An untargeted metabolomics approach. Food Res Int. 2019 Dec;126:108584 Authors: Senizza B, Rocchetti G, Ghisoni S, Busconi M, De Los Mozos Pascual M, Fernandez JA, Lucini L, Trevisan M Abstract Saffron is a high-quality and expensive spice being widely subjected to adulteration. An UHPLC-ESI/QTOF-MS metabolomic-based approach was therefore used to investigate the discrimination potential between adulterated (added with different percentage of other parts of the flower) and authentic saffron, as well as to trace its geographical origin. Both unsupervised (hierarchical clustering) and supervised OPLS-DA multivariate statistics allowed discriminating authentic saffron from styles added of other floral components, as well as PDO (Protected Designation of Origin) vs non PDO saffron samples according to their chemical fingerprints. The proposed markers were then validated through ROC curves. Anthocyanins and glycosidic flavonols were the best markers of the styles' adulteration. However, other flavonoids (mainly free flavonols and flavones), together with protocatechuic aldehyde and isomeric forms of hydroxybenzoic acid, were also validated as markers for the discrimination of PDO vs non PDO saffron samples. This work outlines the potential of untargeted metabolomics based on UHPLC-ESI/QTOF mass spectrometry for saffron authenticity and traceability. PMID: 31732022 [PubMed - in process]

Comparative metabolite fingerprinting of legumes using LC-MS-based untargeted metabolomics.

Sun, 17/11/2019 - 12:10
Related Articles Comparative metabolite fingerprinting of legumes using LC-MS-based untargeted metabolomics. Food Res Int. 2019 Dec;126:108666 Authors: Llorach R, Favari C, Alonso D, Garcia-Aloy M, Andres-Lacueva C, Urpi-Sarda M Abstract Legumes are a well-known source of phytochemicals and are commonly believed to have similar composition between different genera. To date, there are no studies evaluating changes in legumes to discover those compounds that help to discriminate for food quality and authenticity. The aim of this work was to characterize and make a comparative analysis of the composition of bioactive compounds between Cicer arietinum L. (chickpea), Lens culinaris L. (lentil) and Phaseolus vulgaris L. (white bean) through an LC-MS-Orbitrap metabolomic approach to establish which compounds discriminate between the three studied legumes. Untargeted metabolomic analysis was carried out by LC-MS-Orbitrap from extracts of freeze-dried legumes prepared from pre-cooked canned legumes. The metabolomic data treatment and statistical analysis were realized by using MAIT R's package, and final identification and characterization was done using MSn experiments. Fold-change evaluation was made through Metaboanalyst 4.0. Results showed 43 identified and characterized compounds displaying differences between the three legumes. Polyphenols, mainly flavonol and flavanol compounds, were the main group with 30 identified compounds, followed by α-galactosides (n = 5). Fatty acyls, prenol lipids, a nucleoside and organic compounds were also characterized. The fold-change analysis showed flavanols as the wider class of discriminative compounds of lentils compared to the other legumes; prenol lipids and eucomic acids were the most discriminative compounds of beans versus other legumes and several phenolic acids (such as primeveroside salycilic), kaempferol derivatives, coumesterol and α-galactosides were the most discriminative compounds of chickpeas. This study highlights the applicability of metabolomics for evaluating which are the characteristic compounds of the different legumes. In addition, it describes the future application of metabolomics as tool for the quality control of foods and authentication of different kinds of legumes. PMID: 31732019 [PubMed - in process]

Plasma Metabolic Profiling Analysis of Gout Party on Acute Gout Arthritis Rats Based on UHPLC-Q-TOF/MS Combined with Multivariate Statistical Analysis.

Sun, 17/11/2019 - 12:10
Related Articles Plasma Metabolic Profiling Analysis of Gout Party on Acute Gout Arthritis Rats Based on UHPLC-Q-TOF/MS Combined with Multivariate Statistical Analysis. Int J Mol Sci. 2019 Nov 15;20(22): Authors: Wang Y, Bi C, Pang W, Liu Y, Yuan Y, Zhao H, Zhang T, Zhao Y, Li Y Abstract Gout Party is a Chinese medicine prescription composed of Aconiti Lateralis Radix Praeparaia, Aconiti Radix Cocta, Cremastrae Pseudobulbus Pleiones Pseudobulbus, Smilacis Glabrae Rhizoma, Rehmanniae Radix, and Glycyrrhizae Radix et Rhizoma, which can relieve joint pain caused by gouty arthritis (GA) and rheumatoid, and has a therapeutic effect on acute gouty arthritis (AGA). However, little information is available on the molecular biological basis and therapeutic mechanism of Gout Party for the treatment of AGA. AGA model was established by injecting sodium urate, and colchicine served as a positive control drug. We established a metabolomic method based on ultra-high-performance liquid chromatography-tandem quadrupole/time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) to analyze the plasma samples of model group rats and blank group rats. Multiple statistical analyses, including principal component analysis (PCA) and partial least square discrimination analysis (PLS-DA), were used to examine metabolite profile changes in plasma samples. Finally, we identified 2-ketobutyric acid, 3-hexenedioic acid, but-2-enoic acid, and so on; 22 endogenous metabolites associated with AGA. After successful molding, we found that 2-ketobutyric acid, 3-hexenedioic acid, but-2-enoic acid, argininic acid, galactonic acid, lactic acid, equol 4'-O-glucuronide, deoxycholic acid glycine conjugate, glycocholic acid, sphinganine 1-phosphate, LPE (0:0/20:3), LPE (0:0/16:0), LPC (15:0) decreased significantly (p < 0.05 or p < 0.01), alanine, erythrulose, 3-dehydrocarnitine, m-methylhippuric acid, 3-hydroxyoctanoic acid, p-cresol sulfate, estriol 3-sulfate 16-glucuronide, 10-hydroxy-9-(phosphonooxy)octadecenoate, docosahexaenoic acid increased significantly (p < 0.05 or p < 0.01). After Gout Party treatment, 14 biomarkers had a tendency to normal conditions. These above biomarkers were mainly involved in fatty acid metabolism, bile acid metabolism, amino acid metabolism, and energy metabolism pathways. These results suggested that Gout Party exerted therapeutic effects of treating AGA by improving energy metabolism disorder and amino acid metabolism dysfunction, and attenuating fatty acid metabolism abnormal and inflammation. The results of this experiment provided a reference for revealing the metabolic mechanism produced by Gout Party in the treatment of AGA, but the subsequent studies need to be further improved and supported by relevant cell experiments and clinical experiments. PMID: 31731809 [PubMed - in process]

White Kidney Bean (Phaseolus Vulgaris L.) Consumption Reduces Fat Accumulation in a Polygenic Mouse Model of Obesity.

Sun, 17/11/2019 - 12:10
Related Articles White Kidney Bean (Phaseolus Vulgaris L.) Consumption Reduces Fat Accumulation in a Polygenic Mouse Model of Obesity. Nutrients. 2019 Nov 15;11(11): Authors: Neil ES, McGinley JN, Fitzgerald VK, Lauck CA, Tabke JA, Streeter-McDonald MR, Yao L, Broeckling CD, Weir TL, Foster MT, Thompson HJ Abstract Clinical studies indicate that eating common bean, Phaseolus vulgaris L., plays a role in body weight regulation but mechanisms have yet to be elucidated. Here, we investigated the anti-obesogenic activity of white kidney bean in a mouse model of dietary-induced obesity. Bean consumption reduced the accumulation of adipose tissue in male and female C57BL6 mice. The anti-obesogenic effect of white kidney bean was not due to alterations in energy intake, energy excreted in the feces, or feed efficiency ratio. While bean consumption increased the mass of the intestine, no marked differences were consistently observed in crypt height, mucin content of goblet cells, proliferation index or zone of proliferation. However, significantly higher concentrations of total bacteria and of Akkermansia muciniphila were detected in cecal content of bean-fed mice, and the ratio of Firmicutes to Bacteroidetes was reduced. Bile acid content was higher in the ileum of bean-fed mice, but transcript levels of farnesoid X receptor were not significantly affected. Whether changes in bile-acid-mediated cell signaling play a role in bean-related differences in fat accumulation and/or overall metabolic health requires further investigation. PMID: 31731665 [PubMed - in process]

Seasonal Changes in the Metabolic Profiles and Biological Activity in Leaves of Diospyros digyna and D. rekoi "Zapote" Trees.

Sun, 17/11/2019 - 12:10
Related Articles Seasonal Changes in the Metabolic Profiles and Biological Activity in Leaves of Diospyros digyna and D. rekoi "Zapote" Trees. Plants (Basel). 2019 Oct 25;8(11): Authors: Ramírez-Briones E, Rodríguez-Macías R, Salcedo-Pérez E, Ramírez-Chávez E, Molina-Torres J, Tiessen A, Ordaz-Ortiz J, Martínez-Gallardo N, Délano-Frier JP, Zañudo-Hernández J Abstract Leaves of semi-domesticated Diospyros digyna and wild D. rekoi trees, sampled seasonally in Mexico in 2014, were analyzed. Metabolic fingerprints revealed higher metabolite diversity in D. rekoi leaves. The TLC bands characteristic of glycosylated flavonoids, predominant in this species, matched the detection of quercetin and quercetin 3-O-glucuronides by liquid chromatography (UPLC-MS) of spring leaf extracts (LEs). Further gas chromatography (GC-MS) analysis revealed abundant fatty acids, organic acids, and secondary metabolites including trigonelline, p-coumaric, and ferulic and nicotinic acids. Phenolic-like compounds prevailed in D. digyna LEs, while unidentified triterpenoids and dihydroxylated coumarins were detected by UPLC-MS and GC-MS. A paucity of leaf metabolites in leaves of this species, compared to D. rekoi, was evident. Higher antioxidant capacity (AOC) was detected in D. digyna LEs. The AOC was season-independent in D. digyna but not in D. rekoi. The AOC in both species was concentrated in distinct TLC single bands, although seasonal variation in band intensity was observed among trees sampled. The AOC in D. digyna LEs could be ascribed to the coumarin esculetin. The LEs moderately inhibited phytopathogenic bacteria but not fungi. Leaf chemistry differences in these Mesoamerican Diospyros species substantiated previous variability reported in tree physiology and fruit physical chemistry, postulated to result from domestication and seasonality. PMID: 31731430 [PubMed]

metabolomics; +30 new citations

Sat, 16/11/2019 - 15:03
30 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 2019/11/16PubMed 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.

metabolomics; +30 new citations

Sat, 16/11/2019 - 12:03
30 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 2019/11/16PubMed 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.

The plasma metabolome of women in early pregnancy differs from that of non-pregnant women.

Fri, 15/11/2019 - 14:58
Related Articles The plasma metabolome of women in early pregnancy differs from that of non-pregnant women. PLoS One. 2019;14(11):e0224682 Authors: Handelman SK, Romero R, Tarca AL, Pacora P, Ingram B, Maymon E, Chaiworapongsa T, Hassan SS, Erez O Abstract BACKGROUND: In comparison to the non-pregnant state, the first trimester of pregnancy is characterized by systemic adaptation of the mother. The extent to which these adaptive processes are reflected in the maternal blood metabolome is not well characterized. OBJECTIVE: To determine the differences between the plasma metabolome of non-pregnant and pregnant women before 16 weeks gestation. STUDY DESIGN: This study included plasma samples from 21 non-pregnant women and 50 women with a normal pregnancy (8-16 weeks of gestation). Combined measurements by ultrahigh performance liquid chromatography/tandem mass spectrometry and by gas chromatography/mass spectrometry generated molecular abundance measurements for each sample. Molecular species detected in at least 10 samples were included in the analysis. Differential abundance was inferred based on false discovery adjusted p-values (FDR) from Mann-Whitney-Wilcoxon U tests <0.1 and a minimum median abundance ratio (fold change) of 1.5. Alternatively, metabolic data were quantile normalized to remove sample-to-sample differences in the overall metabolite abundance (adjusted analysis). RESULTS: Overall, 637 small molecules met the inclusion criteria and were tested for association with pregnancy; 44% (281/637) of small molecules had significantly different abundance, of which 81% (229/281) were less abundant in pregnant than in non-pregnant women. Eight percent (14/169) of the metabolites that remained significant in the adjusted analysis also changed as a function of gestational age. A pathway analysis revealed enrichment in steroid metabolites related to sex hormones, caffeine metabolites, lysolipids, dipeptides, and polypeptide bradykinin derivatives (all, FDR < 0.1). CONCLUSIONS: This high-throughput mass spectrometry study identified: 1) differences between pregnant vs. non-pregnant women in the abundance of 44% of the profiled plasma metabolites, including known and novel molecules and pathways; and 2) specific metabolites that changed with gestational age. PMID: 31726468 [PubMed - in process]

Beneficial Effects of n-3 Polyunsaturated Fatty Acids on Offspring's Pancreas of Gestational Diabetes Rats.

Fri, 15/11/2019 - 14:58
Related Articles Beneficial Effects of n-3 Polyunsaturated Fatty Acids on Offspring's Pancreas of Gestational Diabetes Rats. J Agric Food Chem. 2019 Nov 14;: Authors: Gao J, Huang T, Li J, Guo X, Xiao H, Gu J, Tang J, Cai W, Li D Abstract We studied the long-term influence of gestational diabetes mellitus (GDM) on the pancreas of offspring and the effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on offspring's pancreas. GDM offspring were divided into three groups: GDM offspring, n-3 PUFA-adequate-GDM offspring, and n-3 PUFA-deficient GDM offspring. All healthy and GDM offspring were fed up to 11 months old. The pancreas of GDM offspring exhibited fatty infiltration at 11 months old, whereas n-3 PUFA improved the pancreatic fatty infiltration. n-3 PUFA lowered the pancreatic oxidative stress and inflammation. Surprisingly, n-3 PUFA postponed pancreatic telomere shortening of GDM offspring at old age. Nontargeted metabolomics showed that many metabolites were altered in the pancreas of GDM offspring at old age, including l-valine, ceramide, acylcarnitines, tocotrienol, cholesteryl acetate, and biotin. n-3 PUFA modulated some altered metabolites and metabolic pathways. Therefore, GDM caused the long-term effects on offspring's pancreas, whereas n-3 PUFA played a beneficial role. PMID: 31725275 [PubMed - as supplied by publisher]

Understanding osteoarthritis pathogenesis: a multiomics system-based approach.

Fri, 15/11/2019 - 14:58
Related Articles Understanding osteoarthritis pathogenesis: a multiomics system-based approach. Curr Opin Rheumatol. 2019 Nov 12;: Authors: Ratneswaran A, Rockel JS, Kapoor M Abstract PURPOSE OF REVIEW: Osteoarthritis is a heterogenous, multifactorial condition regulated by complex biological interactions at multiple levels. Comprehensive understanding of these regulatory interactions is required to develop feasible advances to improve patient outcomes. Improvements in technology have made extensive genomic, transcriptomic, epigenomic, proteomic, and metabolomic profiling possible. This review summarizes findings over the past 20 months related to omics technologies in osteoarthritis and examines how using a multiomics approach is necessary for advancing our understanding of osteoarthritis as a disease to improve precision osteoarthritis treatments. RECENT FINDINGS: Using the search terms 'genomics' or 'transcriptomics' or 'epigenomics' or 'proteomics' or 'metabolomics' and 'osteoarthritis' from January 1, 2018 to August 31, 2019, we identified advances in omics approaches applied to osteoarthritis. Trends include untargeted whole genome, transcriptome, proteome, and metabolome analyses leading to identification of novel molecular signatures, cell subpopulations and multiomics validation approaches. SUMMARY: To address the complexity of osteoarthritis, integration of multitissue analyses by multiomics approaches with the inclusion of longitudinal clinical data is necessary for a comprehensive understanding of the disease process, and for appropriate development of efficacious diagnostics, prognostics, and biotherapeutics. PMID: 31724972 [PubMed - as supplied by publisher]

Redundancy in regulation of lipid accumulation in skeletal muscle during prolonged fasting in obese men.

Fri, 15/11/2019 - 14:58
Related Articles Redundancy in regulation of lipid accumulation in skeletal muscle during prolonged fasting in obese men. Physiol Rep. 2019 Nov;7(21):e14285 Authors: Høgild ML, Gudiksen A, Pilegaard H, Stødkilde-Jørgensen H, Pedersen SB, Møller N, Jørgensen JOL, Jessen N Abstract Fasting in human subjects shifts skeletal muscle metabolism toward lipid utilization and accumulation, including intramyocellular lipid (IMCL) deposition. Growth hormone (GH) secretion amplifies during fasting and promotes lipolysis and lipid oxidation, but it is unknown to which degree lipid deposition and metabolism in skeletal muscle during fasting depends on GH action. To test this, we studied nine obese but otherwise healthy men thrice: (a) in the postabsorptive state ("CTRL"), (b) during 72-hr fasting ("FAST"), and (c) during 72-hr fasting and treatment with a GH antagonist (GHA) ("FAST + GHA"). IMCL was assessed by magnetic resonance spectroscopy (MRS) and blood samples were drawn for plasma metabolomics assessment while muscle biopsies were obtained for measurements of regulators of substrate metabolism. Prolonged fasting was associated with elevated GH levels and a pronounced GHA-independent increase in circulating medium- and long-chain fatty acids, glycerol, and ketone bodies indicating increased supply of lipid intermediates to skeletal muscle. Additionally, fasting was associated with a release of short-, medium-, and long-chain acylcarnitines to the circulation from an increased β-oxidation. This was consistent with a ≈55%-60% decrease in pyruvate dehydrogenase (PDHa) activity. Opposite, IMCL content increased ≈75% with prolonged fasting without an effect of GHA. We suggest that prolonged fasting increases lipid uptake in skeletal muscle and saturates lipid oxidation, both favoring IMCL deposition. This occurs without a detectable effect of GHA on skeletal muscle lipid metabolism. PMID: 31724339 [PubMed - in process]

The Advent of Salivary Breast Cancer Biomarker Detection Using Affinity Sensors.

Fri, 15/11/2019 - 14:58
Related Articles The Advent of Salivary Breast Cancer Biomarker Detection Using Affinity Sensors. Sensors (Basel). 2019 May 23;19(10): Authors: Abrao Nemeir I, Saab J, Hleihel W, Errachid A, Jafferzic-Renault N, Zine N Abstract Breast Cancer is one of the world's most notorious diseases affecting two million women in 2018 worldwide. It is a highly heterogeneous disease, making it difficult to treat. However, its linear progression makes it a candidate for early screening programs, and the earlier its detection the higher the chance of recovery. However, one key hurdle for breast cancer screening is the fact that most screening techniques are expensive, time-consuming, and cumbersome, making them impractical for use in several parts of the world. One current trend in breast cancer detection has pointed to a possible solution, the use of salivary breast cancer biomarkers. Saliva is an attractive medium for diagnosis because it is readily available in large quantities, easy to obtain at low cost, and contains all the biomarkers present in blood, albeit in lower quantities. Affinity sensors are devices that detect molecules through their interactions with biological recognition molecules. Their low cost, high sensitivity, and selectivity, as well as rapid detection time make them an attractive alternative to traditional means of detection. In this review article, we discuss the current status of breast cancer diagnosis, its salivary biomarkers, as well as the current trends in the development of affinity sensors for their detection. PMID: 31126047 [PubMed - indexed for MEDLINE]

Transcriptome and Proteome Profiling of Different Colored Rice Reveals Physiological Dynamics Involved in the Flavonoid Pathway.

Fri, 15/11/2019 - 14:58
Related Articles Transcriptome and Proteome Profiling of Different Colored Rice Reveals Physiological Dynamics Involved in the Flavonoid Pathway. Int J Mol Sci. 2019 May 18;20(10): Authors: Chen X, Tao Y, Ali A, Zhuang Z, Guo D, Guo Q, Riaz A, Zhang H, Xu P, Liao Y, Wang J, Sun C, Xiang Q, Wu X Abstract Black and red rice are rich in both anthocyanin and proanthocyanin content, which belong to a large class of flavonoids derived from a group of phenolic secondary metabolites. However, the molecular pathways and mechanisms underlying the flavonoid biosynthetic pathway are far from clear. Therefore, this study was undertaken to gain insight into physiological factors that are involved in the flavonoid biosynthetic pathway in rice cultivars with red, black, and white colors. RNA sequencing of caryopsis and isobaric tags for relative and absolute quantification (iTRAQ) analyses have generated a nearly complete catalog of mRNA and expressed proteins in different colored rice cultivars. A total of 31,700 genes were identified, of which 3417, 329, and 227 genes were found specific for red, white, and black rice, respectively. A total of 13,996 unique peptides corresponding to 3916 proteins were detected in the proteomes of black, white, and red rice. Coexpression network analyses of differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) among the different rice cultivars showed significant differences in photosynthesis and flavonoid biosynthesis pathways. Based on a differential enrichment analysis, 32 genes involved in the flavonoid biosynthesis pathway were detected, out of which only CHI, F3H, ANS, and FLS were detected by iTRAQ. Taken together, the results point to differences in flavonoid biosynthesis pathways among different colored rice cultivars, which may reflect differences in physiological functions. The differences in contents and types of flavonoids among the different colored rice cultivars are related to changes in base sequences of Os06G0162500, Os09G0455500, Os09G0455500, and Os10G0536400. Current findings expand and deepen our understanding of flavonoid biosynthesis and concurrently provides potential candidate genes for improving the nutritional qualities of rice. PMID: 31109052 [PubMed - indexed for MEDLINE]

Lack of the brain-specific isoform of apoptosis-inducing factor aggravates cerebral damage in a model of neonatal hypoxia-ischemia.

Fri, 15/11/2019 - 14:58
Related Articles Lack of the brain-specific isoform of apoptosis-inducing factor aggravates cerebral damage in a model of neonatal hypoxia-ischemia. Cell Death Dis. 2018 12 18;10(1):3 Authors: Rodriguez J, Zhang Y, Li T, Xie C, Sun Y, Xu Y, Zhou K, Huo K, Wang Y, Wang X, Andersson D, Ståhlberg A, Xing Q, Mallard C, Hagberg H, Modjtahedi N, Kroemer G, Blomgren K, Zhu C Abstract Apoptosis-inducing factor (AIF) may contribute to neuronal cell death, and its influence is particularly prominent in the immature brain after hypoxia-ischemia (HI). A brain-specific AIF splice-isoform (AIF2) has recently been discovered, but has not yet been characterized at the genetic level. The aim of this study was to determine the functional and regulatory profile of AIF2 under physiological conditions and after HI in mice. We generated AIF2 knockout (KO) mice by removing the AIF2-specific exon and found that the relative expression of Aif1 mRNA increased in Aif2 KO mice and that this increase became even more pronounced as Aif2 KO mice aged compared to their wild-type (WT) littermates. Mitochondrial morphology and function, reproductive function, and behavior showed no differences between WT and Aif2 KO mice. However, lack of AIF2 enhanced brain injury in neonatal mice after HI compared to WT controls, and this effect was linked to increased oxidative stress but not to caspase-dependent or -independent apoptosis pathways. These results indicate that AIF2 deficiency exacerbates free radical production and HI-induced neonatal brain injury. PMID: 30584234 [PubMed - indexed for MEDLINE]

Endoscopic Hemostasis in Porcine Gastrointestinal Tract Using CO2 Low-Temperature Plasma Jet.

Fri, 15/11/2019 - 14:58
Related Articles Endoscopic Hemostasis in Porcine Gastrointestinal Tract Using CO2 Low-Temperature Plasma Jet. J Surg Res. 2019 02;234:334-342 Authors: Kurosawa M, Takamatsu T, Kawano H, Hayashi Y, Miyahara H, Ota S, Okino A, Yoshida M Abstract BACKGROUND: Recently, atmospheric low-temperature plasma (LTP) has attracted attention as a novel medical tool that might be useful for achieving hemostasis. However, conventional plasma sources are too big for use with endoscopes, and the efficacy of LTP for achieving hemostasis in cases of gastrointestinal bleeding is difficult to investigate. In this study, to solve the problem, we developed a 3D-printed LTP jet that has a diameter of 2.8 mm and metal body for endoscopic use. The characteristics, hemostasis efficacy, and safety were investigated. MATERIALS AND METHODS: On investigating the basic characteristics of the developed plasma jet, the electron densities, gas temperatures, and reactive species were measured by emission spectroscopy and thermocouple. To evaluate the efficacy of such hemostatic treatment, porcine gastrointestinal bleeding was treated with the device. In addition, to investigate the safety of such treatment, the CO2 LTP-treated tissue was compared with tissue that was treated with clipping-based or argon plasma coagulation-based hemostasis for 5 d, and hematoxylin and eosin staining was used to evaluate tissue damage in the treated regions. RESULTS: The measurement of emission spectroscopy, power, and electron density of various gas plasmas suggested that a high-density (1014 cm-3) LTP of CO2 was generated by the LTP jet, and the gas temperature was 41.5°C at 3 mm from the outlet of the LTP jet. The CO2 LTP achieved hemostasis of oozing blood by 70 ± 20 s. In addition, the CO2 LTP resulted in earlier recovery than clipping-based or argon plasma coagulation-based hemostases, and the treated regions had no damage by the CO2 LTP treatment. CONCLUSIONS: These results indicated that the developed LTP plasma jet has the potential to be used for endoscopic hemostasis. PMID: 30527494 [PubMed - indexed for MEDLINE]

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