PubMed

Related Articles A Computational Statistics Approach to Evaluate Blood Biomarkers for Breast Cancer Risk Stratification. Horm Cancer. 2019 Dec 19;: Authors: Oktay K, Santaliz-Casiano A, Patel M, Marino N, Storniolo AMV, Torun H, Acar B, Madak Erdogan Z Abstract Breast cancer is the second leading cause of cancer mortality among women. Mammography and tumor biopsy followed by histopathological analysis are the current methods to diagnose breast cancer. Mammography does not detect all breast tumor subtypes, especially those that arise in younger women or women with dense breast tissue, and are more aggressive. There is an urgent need to find circulating prognostic molecules and liquid biopsy methods for breast cancer diagnosis and reducing the mortality rate. In this study, we systematically evaluated metabolites and proteins in blood to develop a pipeline to identify potential circulating biomarkers for breast cancer risk. Our aim is to identify a group of molecules to be used in the design of portable and low-cost biomarker detection devices. We obtained plasma samples from women who are cancer free (healthy) and women who were cancer free at the time of blood collection but developed breast cancer later (susceptible). We extracted potential prognostic biomarkers for breast cancer risk from plasma metabolomics and proteomics data using statistical and discriminative power analyses. We pre-processed the data to ensure the quality of subsequent analyses, and used two main feature selection methods to determine the importance of each molecule. After further feature elimination based on pairwise dependencies, we measured the performance of logistic regression classifier on the remaining molecules and compared their biological relevance. We identified six signatures that predicted breast cancer risk with different specificity and selectivity. The best performing signature had 13 factors. We validated the difference in level of one of the biomarkers, SCF/KITLG, in plasma from healthy and susceptible individuals. These biomarkers will be used to develop low-cost liquid biopsy methods toward early identification of breast cancer risk and hence decreased mortality. Our findings provide the knowledge basis needed to proceed in this direction. PMID: 31858384 [PubMed - as supplied by publisher]

Related Articles Citrate NMR peak irreproducibility in blood samples after reacquisition of spectra. Metabolomics. 2019 Dec 19;16(1):7 Authors: Hanifa MA, Maltesen RG, Rasmussen BS, Buggeskov KB, Ravn HB, Skott M, Nielsen S, Frøkiær J, Ring T, Wimmer R Abstract BACKGROUND: In our metabolomics studies we have noticed that repeated NMR acquisition on the same sample can result in altered metabolite signal intensities. AIMS: To investigate the reproducibility of repeated NMR acquisition on selected metabolites in serum and plasma from two large human metabolomics studies. METHODS: Two peak regions for each metabolite were integrated and changes occurring after reacquisition were correlated. RESULTS: Integral changes were generally small, but serum citrate signals decreased significantly in some samples. CONCLUSIONS: Several metabolite integrals were not reproducible in some of the repeated spectra. Following established protocols, randomising analysis order and biomarker validation are important. PMID: 31858270 [PubMed - in process]

Related Articles Accumulation of Carboxylate and Aromatic Fluorophores by a Pest-Resistant Sweet Sorghum [Sorghum bicolor (L.) Moench] Genotype. ACS Omega. 2019 Dec 10;4(24):20519-20529 Authors: Uchimiya M, Knoll JE Abstract The sugary juice from sweet sorghum [Sorghum bicolor (L.) Moench] stalks can be used to produce edible syrup, biofuels, or bio-based chemical feedstock. The current cultivars are highly susceptible to damage from sugarcane aphids [Melanaphis sacchari (Zehntner)], but development of new cultivars is hindered by a lack of rapid analytical methods to screen for juice quality traits. The mechanism of aphid resistance/tolerance is also largely unknown, though the importance of defense phytochemicals has been suggested. The purpose of this study was to develop low-cost methods sensitive to fluorescent fingerprints in sweet sorghum juice, which is a complex mixture of saccharides, carboxylates, polyphenols, and metal ions. Of primary juice components, tryptophan and trans-aconitic acid were the highest intensity contributors to the overall fluorescence and UV/visible absorbance, respectively, while tyrosine and polyphenols contributed to a less extent. In a test of 24 sweet sorghum cultivars, tryptophan and tyrosine contents were the highest in the aphid-susceptible hybrid N109A x Chinese, while sucrose, trans-aconitic acid, and polyphenols were the highest in the resistant line No. 5 Gambela. This suggests that the accumulation of carboxylate (trans-aconitic acid) and polyphenolic secondary products in No. 5 Gambela may contribute to its aphid resistance, thus allowing it to maintain sucrose production. Rapid detection of these chemical signatures could be used to prescreen the breeding material for potential resistance and juice quality traits, without analytical separation required for metabolomics. PMID: 31858036 [PubMed]

Related Articles Biomarkers in Autism Spectrum Disorders: Current Progress. Clin Chim Acta. 2019 Dec 16;: Authors: Shen L, Liu X, Zhang H, Lin J, Feng C, Iqbal J Abstract Autism spectrum disorder (ASD) refers to a group of complex neurodevelopmental disorders characterized by social interaction and communication deficits and repetitive and stereotyped behaviors. As the etiology and pathogenesis of the disorder have not yet been elucidated, specific treatment and reliable diagnostic biomarkers are not available. Early behavioral interventions have been shown to substantially improve symptoms in children with ASD. Given the rapidly increasing prevalence of ASD, there is an urgent need to identify related diagnostic biomarkers. Although specific diagnostic markers for ASD have not been identified, the related research has made progress in different aspects. This review summarizes recent findings of the use of genes, proteins, peptides, and metabolites as diagnostic markers for ASD. The associated techniques include genetic testing and proteomic and metabolomic analyses. In addition, some studies have focused on single or several proteins and metabolites. Moreover, transcriptomic analysis, immune disturbances and cytokine may also be used for this purpose. The pathogenesis involving genes, proteins, and metabolites is also discussed here. PMID: 31857069 [PubMed - as supplied by publisher]

Related Articles Combining transcriptomics and metabolomics to reveal the underlying molecular mechanism of ergosterol biosynthesis during the fruiting process of Flammulina velutipes. BMC Genomics. 2019 Dec 19;20(1):999 Authors: Wang R, Ma P, Li C, Xiao L, Liang Z, Dong J Abstract BACKGROUND: Flammulina velutipes has been recognized as a useful basidiomycete with nutritional and medicinal values. Ergosterol, one of the main sterols of F. velutipes is an important precursor of novel anticancer and anti-HIV drugs. Therefore, many studies have focused on the biosynthesis of ergosterol and have attempted to upregulate its content in multiple organisms. Great progress has been made in understanding the regulation of ergosterol biosynthesis in Saccharomyces cerevisiae. However, this molecular mechanism in F. velutipes remains largely uncharacterized. RESULTS: In this study, nine cDNA libraries, prepared from mycelia, young fruiting bodies and mature fruiting bodies of F. velutipes (three replicate sets for each stage), were sequenced using the Illumina HiSeq™ 4000 platform, resulting in at least 6.63 Gb of clean reads from each library. We studied the changes in genes and metabolites in the ergosterol biosynthesis pathway of F. velutipes during the development of fruiting bodies. A total of 13 genes (6 upregulated and 7 downregulated) were differentially expressed during the development from mycelia to young fruiting bodies (T1), while only 1 gene (1 downregulated) was differentially expressed during the development from young fruiting bodies to mature fruiting bodies (T2). A total of 7 metabolites (3 increased and 4 reduced) were found to have changed in content during T1, and 4 metabolites (4 increased) were found to be different during T2. A conjoint analysis of the genome-wide connection network revealed that the metabolites that were more likely to be regulated were primarily in the post-squalene pathway. CONCLUSIONS: This study provides useful information for understanding the regulation of ergosterol biosynthesis and the regulatory relationship between metabolites and genes in the ergosterol biosynthesis pathway during the development of fruiting bodies in F. velutipes. PMID: 31856715 [PubMed - in process]

Related Articles Identification of Auxin Metabolites in Brassicaceae by Ultra-Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry. Molecules. 2019 Jul 18;24(14): Authors: Revelou PK, Kokotou MG, Constantinou-Kokotou V Abstract Auxins are signaling molecules involved in multiple stages of plant growth and development. The levels of the most important auxin, indole-3-acetic acid (IAA), are regulated by the formation of amide and ester conjugates with amino acids and sugars. In this work, IAA and IAA amide conjugates with amino acids bearing a free carboxylic group or a methyl ester group, along with some selected IAA metabolites, were studied in positive and negative electrospray ionization (ESI) modes, utilizing high-resolution mass spectrometry (HRMS) as a tool for their structural analysis. HRMS/MS spectra revealed the fragmentation patterns that enable us to identify IAA metabolites in plant extracts from eight vegetables of the Brassicaceae family using a fast and reliable ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QToF-MS) method. The accurate m/z (mass to charge) ratio and abundance of the molecular and fragment ions of the studied compounds in plant extracts matched those obtained from commercially available or synthesized compounds and confirmed the presence of IAA metabolites. PMID: 31323791 [PubMed - indexed for MEDLINE]

Related Articles Drug monitoring of tamoxifen metabolites predicts vaginal dryness and verifies a low discontinuation rate from the Norwegian Prescription Database. Breast Cancer Res Treat. 2019 Aug;177(1):185-195 Authors: Helland T, Hagen KB, Haugstøyl ME, Kvaløy JT, Lunde S, Lode K, Lind RA, Gripsrud BH, Jonsdottir K, Gjerde J, Bifulco E, Hustad S, Jonassen J, Aas T, Lende TH, Lien EA, Janssen EAM, Søiland H, Mellgren G Abstract PURPOSE: Tamoxifen is an important targeted endocrine therapy in breast cancer. However, side effects and early discontinuation of tamoxifen remains a barrier for obtaining the improved outcome benefits of long-term tamoxifen treatment. Biomarkers predictive of tamoxifen side effects remain unidentified. The objective of this prospective population-based study was to investigate the value of tamoxifen metabolite concentrations as biomarkers for side effects. A second objective was to assess the validity of discontinuation rates obtained through pharmacy records with the use of tamoxifen drug monitoring. METHODS: Longitudinal serum samples, patient-reported outcome measures and pharmacy records from 220 breast cancer patients were obtained over a 6-year period. Serum concentrations of tamoxifen metabolites were measured by LC-MS/MS. Associations between metabolite concentrations and side effects were analyzed by logistic regression and cross table analyses. To determine the validity of pharmacy records we compared longitudinal tamoxifen concentrations to discontinuation rates obtained through the Norwegian Prescription database (NorPD). Multivariable Cox regression models were performed to identify predictors of discontinuation. RESULTS: At the 2nd year of follow-up, a significant association between vaginal dryness and high concentrations of tamoxifen, Z-4'-OHtam and tam-NoX was identified. NorPD showed a tamoxifen-discontinuation rate of 17.9% at 5 years and drug monitoring demonstrated similar rates. Nausea, vaginal dryness and chemotherapy-naive status were significant risk factors for tamoxifen discontinuation. CONCLUSIONS: This real-world data study suggests that measurements of tamoxifen metabolite concentrations may be predictive of vaginal dryness in breast cancer patients and verifies NorPD as a reliable source of adherence data. PMID: 31144152 [PubMed - indexed for MEDLINE]

Related Articles Lipidomic Profiling Links the Fanconi Anemia Pathway to Glycosphingolipid Metabolism in Head and Neck Cancer Cells. Clin Cancer Res. 2018 06 01;24(11):2700-2709 Authors: Zhao X, Brusadelli MG, Sauter S, Butsch Kovacic M, Zhang W, Romick-Rosendale LE, Lambert PF, Setchell KDR, Wells SI Abstract Purpose: Mutations in Fanconi anemia (FA) genes are common in sporadic squamous cell carcinoma of the head and neck (HNSCC), and we have previously demonstrated that FA pathway depletion in HNSCC cell lines stimulates invasion. The goal of our studies was to use a systems approach in order to define FA pathway-dependent lipid metabolism and to extract lipid-based signatures and effectors of invasion in FA-deficient cells.Experimental Design: We subjected FA-isogenic HNSCC keratinocyte cell lines to untargeted and targeted lipidomics analyses to discover novel biomarkers and candidate therapeutic targets in FA-deficient cells. Cellular invasion assays were carried out in the presence and absence of N-butyldeoxynojirimycin (NB-DNJ), a biosynthetic inhibitor of the newly identified class of gangliosides, to investigate the requirement of ganglioside upregulation in FA-deficient HNSCC cells.Results: The most notable element of the lipid profiling results was a consistent elevation of glycosphingolipids, and particularly the accumulation of gangliosides. Conversely, repression of this same class of lipids was observed upon genetic correction of FA patient-derived HNSCC cells. Functional studies demonstrate that ganglioside upregulation is required for HNSCC cell invasion driven by FA pathway loss. The motility of nontransformed keratinocytes in response to FA loss displayed a similar dependence, thus supporting early and late roles for the FA pathway in controlling keratinocyte invasion through lipid regulation.Conclusions: Elevation of glycosphingolipids including the ganglioside GM3 in response to FA loss stimulates invasive characteristics of immortalized and transformed keratinocytes. An inhibitor of glycosphingolipid biosynthesis NB-DNJ attenuates invasive characteristics of FA-deficient HNSCC cells. Clin Cancer Res; 24(11); 2700-9. ©2018 AACR. PMID: 29530934 [PubMed - indexed for MEDLINE]

21 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 2019/12/20PubMed 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.

23 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 2019/12/19PubMed 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.

78 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 2019/12/18PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Macrophage inflammatory and metabolic responses to graphene-based nanomaterials differing in size and functionalization. Colloids Surf B Biointerfaces. 2019 Dec 05;186:110709 Authors: Cicuéndez M, Fernandes M, Ayán-Varela M, Oliveira H, Feito MJ, Diez-Orejas R, Paredes JI, Villar-Rodil S, Vila M, Portolés MT, Duarte IF Abstract The preparation of graphene-based nanomaterials (GBNs) with appropriate stability and biocompatibility is crucial for their use in biomedical applications. In this work, three GBNs differing in size and/or functionalization have been synthetized and characterized, and their in vitro biological effects were compared. Pegylated graphene oxide (GO-PEG, 200-500 nm) and flavin mononucleotide-stabilized pristine graphene with two different sizes (PG-FMN, 200-400 nm and 100-200 nm) were administered to macrophages, chosen as cellular model due to their key role in the processing of foreign materials and the regulation of inflammatory responses. The results showed that cellular uptake of GBNs was mainly influenced by their lateral size, while the inflammatory potential depended also on the type of functionalization. PG-FMN nanomaterials (both sizes) triggered significantly higher nitric oxide (NO) release, together with some intracellular metabolic changes, similar to those induced by the prototypical inflammatory stimulus LPS. NMR metabolomics revealed that macrophages incubated with smaller PG-FMN displayed increased levels of succinate, itaconate, phosphocholine and phosphocreatine, together with decreased creatine content. The latter two variations were also detected in cells incubated with larger PG-FMN nanosheets. On the other hand, GO-PEG induced a decrease in the inflammatory metabolite succinate and a few other changes distinct from those seen in LPS-stimulated macrophages. Assessment of TNF-α secretion and macrophage surface markers (CD80 and CD206) further corroborated the low inflammatory potential of GO-PEG. Overall, these findings revealed distinct phenotypic and metabolic responses of macrophages to different GBNs, which inform on their immunomodulatory activity and may contribute to guide their therapeutic applications. PMID: 31841776 [PubMed - as supplied by publisher]

Alterations in plasma concentrations of energy-balance-related metabolites in patients with lung, or head & neck, cancers: Effects of radiotherapy. J Proteomics. 2019 Dec 10;:103605 Authors: Rodríguez-Tomàs E, Arguís M, Arenas M, Fernández-Arroyo S, Murcia M, Sabater S, Torres L, Baiges-Gayà G, Hernández-Aguilera A, Camps J, Joven J Abstract We investigated the alterations in the plasma concentrations of energy-balance-related metabolites in patients with lung (LC) or head & neck (HNC) cancer and the changes on these parameters induced by radiotherapy. The study was conducted in 33 patients with non-small cell LC and 28 patients with HNC. We analyzed the concentrations of 17 metabolites involved in glycolysis, citric acid cycle and amino acid metabolism using targeted gas chromatography coupled to quadrupole time-of-flight mass spectrometry. For comparison, a control group of 50 healthy individuals was included in the present study. Patients with LC or HNC had significant alterations in the plasma levels of several energy-balance-related metabolites. Radiotherapy partially normalized these alterations in patients with LC, but not in those with HNC. The measurement of plasma glutamate concentration was an excellent predictor of the presence of LC or HNC, with sensitivity >90% and specificity >80%. Also, associations with disease prognosis were observed with plasma glutamate, amino acids and β-hydroxybutyrate concentrations. SIGNIFICANCE: This study analyzed the changes produced in the plasma concentrations of energy-balance-related metabolites in patients with lung cancer or head and neck cancer. The results obtained identified glutamate as the parameter with the highest discrimination capacity between patients and the control group. The relationships between various metabolites and clinical outcomes were also analyzed. These results extend the knowledge of metabolic alterations in cancer, thus facilitating the search for biomarkers and therapeutic targets. PMID: 31841666 [PubMed - as supplied by publisher]

Deep learning for the precise peak detection in high-resolution LC-MS data. Anal Chem. 2019 Dec 16;: Authors: Melnikov A, Tsentalovich YP, Yanshole VV Abstract This article is devoted to the application of machine learning, namely convolutional neural networks to solve problems in the initial steps of the common pipeline for data analysis in metabolomics. These steps are the peak detection and the peak integration in raw liquid chromatography - mass spectrometry (LC-MS) data. Widely used algorithms suffer from rather poor precision for these tasks, yielding many false positive signals. In the present work, we developed an algorithm named peakonly, which has high flexibility for the detection or exclusion of low-intensity noisy peaks, and shows excellent quality in the detection of true positive peaks, approaching the highest possible precision. The current approach was developed for the analysis of high-resolution LC-MS data for the purposes of metabolomics, but potentially it can be applied with several adaptations in other fields, which utilize high-resolution GC- or LC-MS techniques. Peakonly is freely available on GitHub (https://github.com/arseha/peakonly) under MIT license. PMID: 31841624 [PubMed - as supplied by publisher]

Effects of carbon sources on 17 beta-estradiol degradation by Sphingomonas sp. and the analysis of the involved intracellular metabolomics. Environ Sci Process Impacts. 2019 Dec 16;: Authors: Li C, Kong X, Lan L, Tadda MA, Liu D Abstract 17β-estradiol (E2) ubiquitously exists in various water bodies with long-term endocrine-disrupting and carcinogenic impacts on wildlife even at the trace level of ng L-1. However, it remains unclear how easy-to-degrade carbon sources alter E2 biodegradation patterns. In this study, E2 biodegradation by Sphingomonas sp. MCCC 1A06484 was investigated with regard to alternative carbon sources. Results showed that the bacterium preferentially utilized glucose, sodium succinate and sodium acetate over E2. Interestingly, the presence of these preferred nutrients increased the E2 removal efficiency by 20.1%. Furthermore, a positive relation (p < 0.05) between the utilization of total organic carbon (TOC) and E2 was found. Using intracellular metabolomics by UHPLC-QTOF-MS, 11 up-regulated and 35 down-regulated metabolites (variable importance > 1, p < 0.05) were identified in the bacterium when cultivated with E2 under various carbon and nitrogen backgrounds. The E2 exposure contributed to metabolism changes of lipid, nucleotide, carbohydrate, amino acid and membrane transport, which were considered to play roles in the E2 metabolism. The up-regulated phosphatidylcholine might act as an indicator during the bacterial degradation of E2. Generally, this study contributes to an in-depth understanding of E2 biodegradation in complex environments with multiple carbon and nitrogen sources. PMID: 31841122 [PubMed - as supplied by publisher]

Re: Metabolomics Analysis of Blood Identifies Potential Biomarkers and Possible Treatment Targets for Nocturia. J Urol. 2019 Dec 16;:101097JU000000000000066202 Authors: Kaplan SA PMID: 31841074 [PubMed - as supplied by publisher]

'Omics': The new language in medicine that we all must learn. Respirology. 2019 Dec 16;: Authors: Moodley Y, Yang IA PMID: 31840902 [PubMed - as supplied by publisher]

Metabolic changes in mice cardiac tissue after low-dose irradiation revealed by 1H NMR spectroscopy. J Radiat Res. 2019 Dec 16;: Authors: Gramatyka M, Boguszewicz ᴌ, Ciszek M, Gabryś D, Kulik R, Sokół M Abstract Ionizing radiation may cause cardiotoxicity not only at high, but even at low (considered as harmless) doses, yet the molecular mechanisms of the heart's response to low doses are not clear. In this work, we used high-resolution nuclear magnetic resonance (NMR) spectroscopy to detect the early and late effects of radiation on the metabolism of murine hearts. The hearts of C57Bl/6NCrl female mice were irradiated in vivo with single 0.2 Gy or 2 Gy doses using 6 MV photons, then tissues were collected 48 h and 20 weeks after exposure. The most distinct changes in the profile of polar metabolites were detected 48 h after irradiation with 2 Gy, and included increased levels of pantothenate and glutamate as well as decreased levels of alanine, malonate, acetylcarnitine, glycine and adenosine. Significant effects of the 2 Gy dose were also observed 20 weeks after irradiation and included decreased levels of glutamine and acetylcarnitine when compared with age-matched controls. Moreover, several differences were observed between hearts irradiated with 2 Gy and analyzed either 48 h or 20 weeks after the exposure, which included changes in levels of acetylcarnitine, alanine, glycine, glutamate, glutamine, formate, myo-inositol and trimethylamine. No statistically significant effects induced by the 0.2 Gy dose were observed 20 weeks after irradiation. In general, radiation-affected compounds were associated with energy metabolism, fatty acid beta-oxidation, oxidative stress and damage to cell structures. At the same time, radiation-related effects were not detected at the level of tissue histology, which indicated a higher sensitivity of metabolomics-based tests for cardiac tissue response to radiation. PMID: 31840756 [PubMed - as supplied by publisher]

Related Articles Metabolic compounds within the porcine uterine environment are unique to the type of conceptus present during the early stages of blastocyst elongation. Mol Reprod Dev. 2019 Dec 16;: Authors: Walsh SC, Miles JR, Yao L, Broeckling CD, Rempel LA, Wright-Johnson EC, Pannier AK Abstract The objective of this study was to identify metabolites within the porcine uterine milieu during the early stages of blastocyst elongation. At Days 9, 10, or 11 of gestation, reproductive tracts of White cross-bred gilts (n = 38) were collected immediately following harvest and flushed with Roswell Park Memorial Institute-1640 medium. Conceptus morphologies were assessed from each pregnancy and corresponding uterine flushings were assigned to one of five treatment groups based on these morphologies: (a) uniform spherical (n = 8); (b) heterogeneous spherical and ovoid (n = 8); (c) uniform ovoid (n = 8); (d) heterogeneous ovoid and tubular (n = 8); and (e) uniform tubular (n = 6). Uterine flushings from these pregnancies were submitted for nontargeted profiling by gas chromatography-mass spectrometry (GC-MS) and ultra performance liquid chromatography (UPLC)-MS techniques. Unsupervised multivariate principal component analysis (PCA) was performed using pcaMethods and univariate analysis of variance was performed in R with false discovery rate (FDR) adjustment. PCA analysis of the GC-MS and UPLC-MS data identified 153 and 104 metabolites, respectively. After FDR adjustment of the GC-MS and UPLC-MS data, 38 and 59 metabolites, respectively, differed (p < .05) in uterine flushings from pregnancies across the five conceptus stages. Some metabolites were greater (p  < .05) in abundance for uterine flushings containing earlier stage conceptuses (i.e., spherical), such as uric acid, tryptophan, and tyrosine. In contrast, some metabolites were greater (p < .05) in abundance for uterine flushings containing later stage conceptuses (i.e., tubular), such as creatinine, serine, and urea. These data illustrate several putative metabolites that change within the uterine milieu during early porcine blastocyst elongation. PMID: 31840336 [PubMed - as supplied by publisher]

Related Articles Matrix-assisted laser desorption/ionization mass spectrometry imaging to uncover protein alterations associated with the progression of IgA nephropathy. Virchows Arch. 2019 Dec 14;: Authors: Ivanova M, Dyadyk O, Ivanov D, Clerici F, Smith A, Magni F Abstract IgA nephropathy (IgAN) is one of the most diffuse glomerulonephrites worldwide, and many issues still remain regarding our understanding of its pathogenesis. The disease is diagnosed by renal biopsy examination, but potential pitfalls still persist with regard to discriminating its primary origin and, as a result, determining patient outcome remains challenging. In this pilot study, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) was performed on renal biopsies obtained from patients with IgAN (n = 11) and other mesangioproliferative glomerulonephrites (MesPGN, n = 6) in order to enlighten proteomic alterations that may be associated with the progression of IgAN. Differences in the proteomic profiles of IgAN and MesPGN tissue could clearly be detected using this approach and, furthermore, 14 signals (AUC ≥ 0.8) were observed to have an altered intensity among the different CKD stages within the IgAN group. In particular, large increases in the intensity of these signals could be observed at CKD stages II and above. These signals primarily corresponded to proteins involved in either inflammatory and healing pathways and their increased intensity was localized within regions of tissue with large amounts of inflammatory cells or sclerosis. Despite much work in recent years, our molecular understanding of IgAN progression remains incomplete. This pilot study represents a promising starting point in the search for novel protein markers that can assist clinicians in better understanding the pathogenesis of IgAN and highlighting those patients who may progress to end-stage renal disease. PMID: 31838587 [PubMed - as supplied by publisher]