92120fecaf149684ba98fc370a5c7d59 biomedicines_a2022v10n3p674.pdf daee82b5cf59d50acad8c9bb806763a8f9b3d13f biomedicines_a2022v10n3p674.pdf fad7b92e211762d3a90eaa887752c7d0e0b236cd706bad7bf93e716ce6cf2967 biomedicines_a2022v10n3p674.pdf Title: HPLC-MS/MS Oxylipin Analysis of Plasma from Amyotrophic Lateral Sclerosis Patients Subject: Oxylipins play a critical role in regulating the onset and resolution phase of inflammation. Despite inflammation is a pathological hallmark in amyotrophic lateral sclerosis (ALS), the plasma oxylipin profile of ALS patients has not been assessed yet. Herein, we develop an oxylipin profile-targeted analysis of plasma from 74 ALS patients and controls. We found a significant decrease in linoleic acid-derived oxylipins in ALS patients, including 9-hydroxy-octadecadienoic acid (9-HODE) and 13-HODE. These derivatives have been reported as important regulators of inflammation on different cell systems. In addition, some 5-lipoxygenase metabolites, such as 5-hydroxy- eicosatetraenoic acid also showed a significant decrease in ALS plasma samples. Isoprostanes of the F2 family were detected only in ALS patients but not in control samples, while the hydroxylated metabolite 11-HETE significantly decreased. Despite our effort to analyze specialized pro-resolving mediators, they were not detected in plasma samples. However, we found the levels of 14-hydroxy-docosahexaenoic acid, a marker pathway of the Maresin biosynthesis, were also reduced in ALS patients, suggesting a defective activation in the resolution programs of inflammation in ALS. We further analyze oxylipin concentration levels in plasma from ALS patients to detect correlations between these metabolites and some clinical parameters. Interestingly, we found that plasmatic levels of 13-HODE and 9-HODE positively correlate with disease duration, expressed as days since onset. In summary, we developed a method to analyze “(oxy)lipidomics” in ALS human plasma and found new profiles of metabolites and novel lipid derivatives with unknown biological activities as potential footprints of disease onset. Keywords: amyotrophic lateral sclerosis; lipidomics; oxylipin; specialized pro-resolving mediators; mass spectrometry Author: Mauricio Mastrogiovanni, Andrés Trostchansky, Hugo Naya, Raúl Dominguez, Carla Marco, Mònica Povedano, Rubèn López-Vales and Homero Rubbo Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Mar 15 05:46:13 2022 CET ModDate: Tue Mar 15 05:48:51 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 927801 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- NFMTJI+VnURWPalladioL Type 1 Custom yes yes no 10 0 LEVXPH+EURM10 Type 1 Builtin yes yes no 15 0 IHLBXE+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 YSCNIN+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 ITPQAX+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 BVLWOG+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 40 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 44 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 48 0 EBFBTV+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 60 0 QMDDXF+CMSY10 Type 1 Builtin yes yes no 85 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes no 95 0 WABLSD+SFRM1000 Type 1 Custom yes yes no 99 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 118 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 122 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 126 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 130 0 Arial,Bold TrueType WinAnsi no no no 138 0 Arial,BoldItalic TrueType WinAnsi no no no 141 0 Arial TrueType WinAnsi no no no 153 0 Arial,Bold CID TrueType Identity-H yes no yes 157 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 173 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 177 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 181 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 185 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-06-10 02:39:53 CEST RepresentationInformation: biomedicines_a2022v10n3p674.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-03-23 11:27:42 CET Size: 927801 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 366 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Materials Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Sample Preparation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Oxylipin Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Quantitation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: General LOD and LOQ Determination Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Specilized Pro-Resolving Lipid Mediators LOD and LOQ Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Children: Item: Title: Oxylipin Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Individual Oxylipin Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Multivariate Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Correlation Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Info: Title: HPLC-MS/MS Oxylipin Analysis of Plasma from Amyotrophic Lateral Sclerosis Patients Author: Mauricio Mastrogiovanni, Andrés Trostchansky, Hugo Naya, Raúl Dominguez, Carla Marco, Mònica Povedano, Rubèn López-Vales and Homero Rubbo Subject: Oxylipins play a critical role in regulating the onset and resolution phase of inflammation. Despite inflammation is a pathological hallmark in amyotrophic lateral sclerosis (ALS), the plasma oxylipin profile of ALS patients has not been assessed yet. Herein, we develop an oxylipin profile-targeted analysis of plasma from 74 ALS patients and controls. We found a significant decrease in linoleic acid-derived oxylipins in ALS patients, including 9-hydroxy-octadecadienoic acid (9-HODE) and 13-HODE. These derivatives have been reported as important regulators of inflammation on different cell systems. In addition, some 5-lipoxygenase metabolites, such as 5-hydroxy- eicosatetraenoic acid also showed a significant decrease in ALS plasma samples. Isoprostanes of the F2 family were detected only in ALS patients but not in control samples, while the hydroxylated metabolite 11-HETE significantly decreased. Despite our effort to analyze specialized pro-resolving mediators, they were not detected in plasma samples. However, we found the levels of 14-hydroxy-docosahexaenoic acid, a marker pathway of the Maresin biosynthesis, were also reduced in ALS patients, suggesting a defective activation in the resolution programs of inflammation in ALS. We further analyze oxylipin concentration levels in plasma from ALS patients to detect correlations between these metabolites and some clinical parameters. Interestingly, we found that plasmatic levels of 13-HODE and 9-HODE positively correlate with disease duration, expressed as days since onset. In summary, we developed a method to analyze “(oxy)lipidomics” in ALS human plasma and found new profiles of metabolites and novel lipid derivatives with unknown biological activities as potential footprints of disease onset. 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