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Inflammaging

Id Subject Object Predicate Lexical cue
T1 0-107 Sentence denotes Proteomic analysis of filaggrin deficiency identifies molecular signatures characteristic of atopic eczema.
T2 108-119 Sentence denotes BACKGROUND:
T3 120-195 Sentence denotes Atopic eczema (AE) is characterized by skin barrier and immune dysfunction.
T4 196-386 Sentence denotes Null mutations in filaggrin (FLG), a key epidermal barrier protein, strongly predispose to AE; however, the precise role of FLG deficiency in AE pathogenesis remains incompletely understood.
T5 387-398 Sentence denotes OBJECTIVES:
T6 399-580 Sentence denotes We sought to identify global proteomic changes downstream of FLG deficiency in human epidermal living skin-equivalent (LSE) models and validate findings in skin of patients with AE.
T7 581-589 Sentence denotes METHODS:
T8 590-877 Sentence denotes Differentially expressed proteins from paired control (nontargeting control short hairpin RNA [shNT]) and FLG knockdown (FLG knockdown short hairpin RNA [shFLG]) LSEs were identified by means of proteomic analysis (liquid chromatography-mass spectrometry) and Ingenuity Pathway Analysis.
T9 878-1052 Sentence denotes Expression of key targets was validated in independent LSE samples (quantitative RT-PCR and Western blotting) and in normal and AE skin biopsy specimens (immunofluorescence).
T10 1053-1061 Sentence denotes RESULTS:
T11 1062-1264 Sentence denotes Proteomic analysis identified 17 (P ≤ .05) differentially expressed proteins after FLG knockdown, including kallikrein-7 (KLK7; 2.2-fold), cyclophilin A (PPIA; 0.9-fold), and cofilin-1 (CFL1, 1.3-fold).
T12 1265-1385 Sentence denotes Differential protein expression was confirmed in shNT/shFLG LSEs; however, only KLK7 was transcriptionally dysregulated.
T13 1386-1510 Sentence denotes Molecular pathways overrepresented after FLG knockdown included inflammation, protease activity, cell structure, and stress.
T14 1511-1675 Sentence denotes Furthermore, KLK7 (1.8-fold) and PPIA (0.65-fold) proteins were differentially expressed in lesional biopsy specimens from patients with AE relative to normal skin.
T15 1676-1688 Sentence denotes CONCLUSIONS:
T16 1689-1856 Sentence denotes For the first time, we show that loss of FLG in the absence of inflammation is sufficient to alter the expression level of proteins relevant to the pathogenesis of AE.
T17 1857-1945 Sentence denotes These include proteins regulating inflammatory, proteolytic, and cytoskeletal functions.
T18 1946-2157 Sentence denotes We identify PPIA as a novel protein with levels that are decreased in clinically active AE skin and show that the characteristic upregulation of KLK7 expression in patients with AE occurs downstream of FLG loss.
T19 2158-2297 Sentence denotes Importantly, we highlight disconnect between the epidermal proteome and transcriptome, emphasizing the utility of global proteomic studies.
T1 0-107 Sentence denotes Proteomic analysis of filaggrin deficiency identifies molecular signatures characteristic of atopic eczema.
T2 108-119 Sentence denotes BACKGROUND:
T3 120-195 Sentence denotes Atopic eczema (AE) is characterized by skin barrier and immune dysfunction.
T4 196-386 Sentence denotes Null mutations in filaggrin (FLG), a key epidermal barrier protein, strongly predispose to AE; however, the precise role of FLG deficiency in AE pathogenesis remains incompletely understood.
T5 387-398 Sentence denotes OBJECTIVES:
T6 399-580 Sentence denotes We sought to identify global proteomic changes downstream of FLG deficiency in human epidermal living skin-equivalent (LSE) models and validate findings in skin of patients with AE.
T7 581-589 Sentence denotes METHODS:
T8 590-877 Sentence denotes Differentially expressed proteins from paired control (nontargeting control short hairpin RNA [shNT]) and FLG knockdown (FLG knockdown short hairpin RNA [shFLG]) LSEs were identified by means of proteomic analysis (liquid chromatography-mass spectrometry) and Ingenuity Pathway Analysis.
T9 878-1052 Sentence denotes Expression of key targets was validated in independent LSE samples (quantitative RT-PCR and Western blotting) and in normal and AE skin biopsy specimens (immunofluorescence).
T10 1053-1061 Sentence denotes RESULTS:
T11 1062-1264 Sentence denotes Proteomic analysis identified 17 (P ≤ .05) differentially expressed proteins after FLG knockdown, including kallikrein-7 (KLK7; 2.2-fold), cyclophilin A (PPIA; 0.9-fold), and cofilin-1 (CFL1, 1.3-fold).
T12 1265-1385 Sentence denotes Differential protein expression was confirmed in shNT/shFLG LSEs; however, only KLK7 was transcriptionally dysregulated.
T13 1386-1510 Sentence denotes Molecular pathways overrepresented after FLG knockdown included inflammation, protease activity, cell structure, and stress.
T14 1511-1675 Sentence denotes Furthermore, KLK7 (1.8-fold) and PPIA (0.65-fold) proteins were differentially expressed in lesional biopsy specimens from patients with AE relative to normal skin.
T15 1676-1688 Sentence denotes CONCLUSIONS:
T16 1689-1856 Sentence denotes For the first time, we show that loss of FLG in the absence of inflammation is sufficient to alter the expression level of proteins relevant to the pathogenesis of AE.
T17 1857-1945 Sentence denotes These include proteins regulating inflammatory, proteolytic, and cytoskeletal functions.
T18 1946-2157 Sentence denotes We identify PPIA as a novel protein with levels that are decreased in clinically active AE skin and show that the characteristic upregulation of KLK7 expression in patients with AE occurs downstream of FLG loss.
T19 2158-2297 Sentence denotes Importantly, we highlight disconnect between the epidermal proteome and transcriptome, emphasizing the utility of global proteomic studies.

kaiyin_test

Id Subject Object Predicate Lexical cue
T1 120-133 Disease denotes Atopic eczema
T2 196-210 Var denotes Null mutations
T3 225-228 Gene denotes FLG
T4 273-283 Reg denotes predispose
T5 287-289 Disease denotes AE
T6 1386-1404 Pathway denotes Molecular pathways
T9 1405-1420 PosReg denotes overrepresented
T7 1427-1430 Gene denotes FLG
T8 1431-1440 Var denotes knockdown
T10 1722-1726 Var denotes loss
T11 1730-1733 Gene denotes FLG
T12 1782-1787 Reg denotes alter
T13 1792-1820 MPA denotes expression level of proteins
R1 T2 T4 CauseOf Null mutations,predispose
R2 T5 T4 ThemeOf AE,predispose
R3 T3 T2 ThemeOf FLG,Null mutations
R4 T6 T9 ThemeOf Molecular pathways,overrepresented
R5 T7 T8 ThemeOf FLG,knockdown
R6 T8 T9 CauseOf knockdown,overrepresented
R7 T10 T12 CauseOf loss,alter
R8 T13 T12 ThemeOf expression level of proteins,alter
R9 T11 T10 ThemeOf FLG,loss

name_no

Id Subject Object Predicate Lexical cue
T1 120-133 Disease denotes Atopic eczema
T2 196-210 Var denotes Null mutations
T3 225-228 Gene denotes FLG
T4 273-283 Reg denotes predispose
T5 287-289 Disease denotes AE
T6 1386-1404 Pathway denotes Molecular pathways
T9 1405-1420 PosReg denotes overrepresented
T7 1427-1430 Gene denotes FLG
T8 1431-1440 Var denotes knockdown
T10 1722-1726 Var denotes loss
T11 1730-1733 Gene denotes FLG
T12 1782-1787 Reg denotes alter
T13 1792-1820 MPA denotes expression level of proteins
R1 T2 T4 CauseOf Null mutations,predispose
R2 T5 T4 ThemeOf AE,predispose
R3 T3 T2 ThemeOf FLG,Null mutations
R4 T6 T9 ThemeOf Molecular pathways,overrepresented
R5 T7 T8 ThemeOf FLG,knockdown
R6 T8 T9 CauseOf knockdown,overrepresented
R7 T10 T12 CauseOf loss,alter
R8 T13 T12 ThemeOf expression level of proteins,alter
R9 T11 T10 ThemeOf FLG,loss