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Producer: Aspose.Pdf for .NET 10.1.0 PDF Creator http://www.pdf-tools.com; modified using iTextSharp™ 5.4.0 ©2000-2012 1T3XT BVBA (AGPL-version) CreationDate: Sat Apr 28 17:29:06 2018 CEST ModDate: Sun May 13 10:39:11 2018 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 599.98 x 799.99 pts Page rot: 0 File size: 1092248 bytes Optimized: no PDF version: 1.4 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- MinionPro-Regular CID Type 0C Identity-H yes no yes 29 0 FNADNH+MinionProIt Type 1C WinAnsi yes yes no 30 0 FNADOI+Minion-Black Type 1C WinAnsi yes yes no 31 0 FNAEDH+MinionProBold Type 1C WinAnsi yes yes no 32 0 FNAELF+MinionProIt+20 Type 1C WinAnsi yes yes no 33 0 FNAEMF+MinionProRegular Type 1C WinAnsi yes yes no 34 0 FNAEMG+MinionProRegular+fb Type 1C Custom yes yes yes 35 0 FNAEMH+MinionMathItalic Type 1C WinAnsi yes yes no 36 0 FNAEMI+MinionMath-Regular Type 1C WinAnsi yes yes no 37 0 HCSDBT+MinionPro-Regular CID TrueType Identity-H yes yes yes 1 0 FNAEOJ+MinionMath-Regular+22 Type 1C Custom yes yes yes 88 0 FNAEPJ+MinionProRegular+20 Type 1C WinAnsi yes yes no 89 0 FNAEPK+MinionMathItalic+03 Type 1C Custom yes yes yes 90 0 FNAFAL+MinionProRegular+21 Type 1C WinAnsi yes yes no 91 0 MinionPro-Regular2 Type 1C WinAnsi yes no no 114 0 FNAHHO+MinionScUnic Type 1C WinAnsi yes yes no 115 0 FNAHLN+MinionProIt+fb Type 1C Custom yes yes yes 149 0 FNAIAN+MinionMath-Regular-Graphic Type 1C WinAnsi yes yes no 150 0 MinionPro-Regular3 Type 1C WinAnsi yes no no 151 0 MinionPro-Regular4 Type 1C WinAnsi yes no no 176 0 MinionPro-Regular5 Type 1C WinAnsi yes no no 187 0 FNAJPG+Minion-Black+20 Type 1C WinAnsi yes yes no 281 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-05-05 02:34:32 CEST RepresentationInformation: pmc_29854824.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2018-06-04 03:40:55 CEST Size: 1092248 Format: PDF Version: 1.4 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 447 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Urinary Proteome Analysis Identified Neprilysin and VCAM as Proteins Involved in Diabetic Nephropathy Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: 1. Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: 2. Subjects and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Children: Item: Title: 2.1. Patients Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@eafc191 Item: Title: 2.2. Blood Pressure, Blood, and Urine Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612fc6eb Item: Title: 2.3. Urine Collection Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1060b431 Item: Title: 2.4. Quantitative Liquid Chromatography Tandem Mass Spectrometry (LC-MSn) Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612679d6 Children: Item: Title: 2.4.1. Sample Preparation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@11758f2a Item: Title: 2.4.2. Protein Digestion and Peptide Labeling Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@e720b71 Item: Title: 2.4.3. Sample Fractionation by Strong Cation Exchange Chromatography Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1b26f7b2 Item: Title: 2.4.4. LC-MSn Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@491cc5c9 Item: Title: 2.4.5. Database Search Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@74ad1f1f Item: Title: 2.5. Bioinformatic Analysis of Proteomic Data Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6a1aab78 Item: Title: 2.6. Urinary Neprilysin and VCAM-1 ELISA Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@462d5aee Item: Title: 2.7. Presentation of Data and Statistical Analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@69b0fd6f Item: Title: 3. Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@757942a1 Children: Item: Title: 3.1. Patients Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4a87761d Item: Title: 3.2. Protein Identification and Relative Quantification Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@66d1af89 Item: Title: 3.3. Proteomic Data Processing and Enrichment Analysis of Differentially Abundant Proteins Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@8646db9 Item: Title: 3.4. Clustering Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@37374a5e Item: Title: 3.5. Key Proteins Involved in DN and RAS Efficacy Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4671e53b Item: Title: 3.6. Urinary Neprilysin and VCAM-1 ELISA Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@2db7a79b Item: Title: 4. Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6950e31 Item: Title: Ethical Approval Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@b7dd107 Item: Title: Consent Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@42eca56e Item: Title: Conflicts of Interest Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@52f759d7 Item: Title: Authors’ Contributions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7cbd213e Item: Title: Acknowledgments Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@192d3247 Item: Title: Supplementary Materials Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3ecd23d9 Info: Title: HDJDR_6165303 1..12 Creator: Aspose Ltd. 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1120, 827 FontFile3: true Encoding: WinAnsiEncoding CIDFontType0: Font: BaseFont: MinionPro-Regular CIDSystemInfo: Registry: Adobe Registry: Identity Supplement: 0 FontDescriptor: FontName: MinionPro-Regular Flags: Nonsymbolic FontBBox: -290, -360, 1684, 989 FontFile3: true CIDFontType2: Font: BaseFont: HCSDBT+MinionPro-Regular CIDSystemInfo: Registry: Adobe Registry: Identity Supplement: 0 FontDescriptor: FontName: HCSDBT+MinionPro-Regular Flags: Nonsymbolic FontBBox: -289, -360, 1684, 917 FontFile2: true XMP: application/pdfUrinary Proteome Analysis Identified Neprilysin and VCAM as Proteins Involved in Diabetic NephropathyGuillén-Gómez, ElenaBardají-de-Quixano, BeatrizFerrer, SílviaBrotons, CarlosKnepper, Mark A.Carrascal, MontserratAbian, JoaquinMas, José M.Calero, FrancescaBallarín, José A.Fernández-Llama, PatriciaUrinary proteome was analyzed and quantified by tandem mass tag (TMT) labeling followed by bioinformatics analysis to study diabetic nephropathy (DN) pathophysiology and to identify biomarkers of a clinical outcome. We included type 2 diabetic normotensive non-obese males with (n=9) and without (n=11) incipient DN (microalbuminuria). Sample collection included blood and urine at baseline (control and DN basal) and, in DN patients, after 3 months of losartan treatment (DN treated). Urinary proteome analysis identified 166 differentially abundant proteins between controls and DN patients, 27 comparing DN-treated and DN-basal patients, and 182 between DN-treated patients and controls. The mathematical modeling analysis predicted 80 key proteins involved in DN pathophysiology and 15 in losartan effect, a total of 95 proteins. Out of these 95, 7 are involved in both processes. VCAM-1 and neprilysin stand out of these 7 for being differentially expressed in the urinary proteome. We observed an increase of VCAM-1 urine levels in DN-basal patients compared to diabetic controls and an increase of urinary neprilysin in DN-treated patients with persistent albuminuria; the latter was confirmed by ELISA. Our results point to neprilysin and VCAM-1 as potential candidates in DN pathology and treatment.Journal of Diabetes ResearchHindawi2018/04/29Research articledoi:10.1155/2018/6165303en Pages: Page: Label: 1 Annotations: Annotation: Subtype: Link Rect: 195, 557, 205, 567 Flags: Print AppearanceDictionary: true Annotation: Subtype: Link Rect: 379, 543, 389, 553 Flags: Print AppearanceDictionary: true Annotation: Subtype: Link Rect: 441, 529, 452, 539 Flags: Print AppearanceDictionary: true Annotation: Subtype: Link Rect: 142, 112, 147, 122 Flags: Print AppearanceDictionary: true Destination: 27 Annotation: Subtype: Link Rect: 280, 55, 285, 65 Flags: Print AppearanceDictionary: true Destination: 27 Annotation: Subtype: Link Rect: 368, 89, 373, 99 Flags: Print AppearanceDictionary: true Destination: 27 Annotation: Subtype: Link Rect: 381, 89, 385, 99 Flags: Print AppearanceDictionary: true Destination: 27 Annotation: Subtype: Link Rect: 440, 66, 444, 76 Flags: Print AppearanceDictionary: 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