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Differential plasma expression of candidate protein biomarkers in CTD-ILD and IPF. Expression levels of ( A ) MMP-10, ( B ) <t>FGF-19,</t> ( C ) ADA, and ( D ) TWEAK were compared between CTD-ILD and IPF patients. Statistical comparisons were performed using unpaired two-tailed t-tests. * p < 0.05, ** p < 0.01, *** p < 0.001
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Differential plasma expression of candidate protein biomarkers in CTD-ILD and IPF. Expression levels of ( A ) MMP-10, ( B ) <t>FGF-19,</t> ( C ) ADA, and ( D ) TWEAK were compared between CTD-ILD and IPF patients. Statistical comparisons were performed using unpaired two-tailed t-tests. * p < 0.05, ** p < 0.01, *** p < 0.001
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(A) Biosynthesis, enterohepatic circulation, and negative feedback regulation of BA metabolism. Intestinal BA absorption activates FXR in enterocytes, inducing transcription of fibroblast growth factor 19 <t>(FGF19).</t> Secreted FGF19 reaches the liver via mesenteric blood, where it binds fibroblast growth factor receptor 4 (FGFR4) and its co-receptor β-Klotho, repressing CYP7A1 and thereby inhibiting BA synthesis. , ( B – C ) Distribution of ( B ) primary vs. secondary BAs and ( C ) unconjugated vs. conjugated BAs in serum and liver. The Student’s t -test was used. Data are mean ± SEM. ( D – E ) Relative abundance of individual BAs ( D ) in serum and ( E ) in liver. Unlabeled BAs either comprised <0.1% of the total pool or were undetectable. ( F ) Heatmaps illustrating correlations between serum vs. liver BAs (left), serum BAs vs. serum C4 (middle), and liver BAs vs. serum C4 (right). Crossed cells indicate undetected BAs. ( G – H ) Heatmaps illustrating correlations between ( G ) serum and ( H ) liver BAs and key clinical and histological parameters. * P < 0.05; ** P < 0.01; *** P < 0.001.
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(A) Biosynthesis, enterohepatic circulation, and negative feedback regulation of BA metabolism. Intestinal BA absorption activates FXR in enterocytes, inducing transcription of fibroblast growth factor 19 <t>(FGF19).</t> Secreted FGF19 reaches the liver via mesenteric blood, where it binds fibroblast growth factor receptor 4 (FGFR4) and its co-receptor β-Klotho, repressing CYP7A1 and thereby inhibiting BA synthesis. , ( B – C ) Distribution of ( B ) primary vs. secondary BAs and ( C ) unconjugated vs. conjugated BAs in serum and liver. The Student’s t -test was used. Data are mean ± SEM. ( D – E ) Relative abundance of individual BAs ( D ) in serum and ( E ) in liver. Unlabeled BAs either comprised <0.1% of the total pool or were undetectable. ( F ) Heatmaps illustrating correlations between serum vs. liver BAs (left), serum BAs vs. serum C4 (middle), and liver BAs vs. serum C4 (right). Crossed cells indicate undetected BAs. ( G – H ) Heatmaps illustrating correlations between ( G ) serum and ( H ) liver BAs and key clinical and histological parameters. * P < 0.05; ** P < 0.01; *** P < 0.001.
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(A) Biosynthesis, enterohepatic circulation, and negative feedback regulation of BA metabolism. Intestinal BA absorption activates FXR in enterocytes, inducing transcription of fibroblast growth factor 19 <t>(FGF19).</t> Secreted FGF19 reaches the liver via mesenteric blood, where it binds fibroblast growth factor receptor 4 (FGFR4) and its co-receptor β-Klotho, repressing CYP7A1 and thereby inhibiting BA synthesis. , ( B – C ) Distribution of ( B ) primary vs. secondary BAs and ( C ) unconjugated vs. conjugated BAs in serum and liver. The Student’s t -test was used. Data are mean ± SEM. ( D – E ) Relative abundance of individual BAs ( D ) in serum and ( E ) in liver. Unlabeled BAs either comprised <0.1% of the total pool or were undetectable. ( F ) Heatmaps illustrating correlations between serum vs. liver BAs (left), serum BAs vs. serum C4 (middle), and liver BAs vs. serum C4 (right). Crossed cells indicate undetected BAs. ( G – H ) Heatmaps illustrating correlations between ( G ) serum and ( H ) liver BAs and key clinical and histological parameters. * P < 0.05; ** P < 0.01; *** P < 0.001.
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(A) Biosynthesis, enterohepatic circulation, and negative feedback regulation of BA metabolism. Intestinal BA absorption activates FXR in enterocytes, inducing transcription of fibroblast growth factor 19 <t>(FGF19).</t> Secreted FGF19 reaches the liver via mesenteric blood, where it binds fibroblast growth factor receptor 4 (FGFR4) and its co-receptor β-Klotho, repressing CYP7A1 and thereby inhibiting BA synthesis. , ( B – C ) Distribution of ( B ) primary vs. secondary BAs and ( C ) unconjugated vs. conjugated BAs in serum and liver. The Student’s t -test was used. Data are mean ± SEM. ( D – E ) Relative abundance of individual BAs ( D ) in serum and ( E ) in liver. Unlabeled BAs either comprised <0.1% of the total pool or were undetectable. ( F ) Heatmaps illustrating correlations between serum vs. liver BAs (left), serum BAs vs. serum C4 (middle), and liver BAs vs. serum C4 (right). Crossed cells indicate undetected BAs. ( G – H ) Heatmaps illustrating correlations between ( G ) serum and ( H ) liver BAs and key clinical and histological parameters. * P < 0.05; ** P < 0.01; *** P < 0.001.
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Differential plasma expression of candidate protein biomarkers in CTD-ILD and IPF. Expression levels of ( A ) MMP-10, ( B ) FGF-19, ( C ) ADA, and ( D ) TWEAK were compared between CTD-ILD and IPF patients. Statistical comparisons were performed using unpaired two-tailed t-tests. * p < 0.05, ** p < 0.01, *** p < 0.001

Journal: Respiratory Research

Article Title: Plasma proteomic and machine learning models for differentiating idiopathic pulmonary fibrosis and connective tissue disease–associated interstitial lung disease: findings from a prospective cohort

doi: 10.1186/s12931-026-03596-4

Figure Lengend Snippet: Differential plasma expression of candidate protein biomarkers in CTD-ILD and IPF. Expression levels of ( A ) MMP-10, ( B ) FGF-19, ( C ) ADA, and ( D ) TWEAK were compared between CTD-ILD and IPF patients. Statistical comparisons were performed using unpaired two-tailed t-tests. * p < 0.05, ** p < 0.01, *** p < 0.001

Article Snippet: FGF-19 concentrations were determined using the Human FGF-19 ELISA kit (DY969, R&D Systems), and TWEAK levels were quantified using the Human TWEAK ELISA kit (DY1090, R&D Systems).

Techniques: Clinical Proteomics, Expressing, Two Tailed Test

Gene expression of candidate biomarkers in control, COPD, and ILD samples ( GSE47460 dataset). Transcriptomic data ( n = 582) were analyzed for ( A ) MMP-10, ( B ) FGF-19, ( C ) ADA, and ( D ) TNFSF12 (TWEAK). Groups included control (Ctrl), chronic obstructive pulmonary disease (COPD), and ILD. Each dot represents one sample; bars show mean ± SD. Statistical significance was assessed by one-way ANOVA with Tukey’s post hoc test. * p < 0.05, *** p < 0.001

Journal: Respiratory Research

Article Title: Plasma proteomic and machine learning models for differentiating idiopathic pulmonary fibrosis and connective tissue disease–associated interstitial lung disease: findings from a prospective cohort

doi: 10.1186/s12931-026-03596-4

Figure Lengend Snippet: Gene expression of candidate biomarkers in control, COPD, and ILD samples ( GSE47460 dataset). Transcriptomic data ( n = 582) were analyzed for ( A ) MMP-10, ( B ) FGF-19, ( C ) ADA, and ( D ) TNFSF12 (TWEAK). Groups included control (Ctrl), chronic obstructive pulmonary disease (COPD), and ILD. Each dot represents one sample; bars show mean ± SD. Statistical significance was assessed by one-way ANOVA with Tukey’s post hoc test. * p < 0.05, *** p < 0.001

Article Snippet: FGF-19 concentrations were determined using the Human FGF-19 ELISA kit (DY969, R&D Systems), and TWEAK levels were quantified using the Human TWEAK ELISA kit (DY1090, R&D Systems).

Techniques: Gene Expression, Control

(A) Biosynthesis, enterohepatic circulation, and negative feedback regulation of BA metabolism. Intestinal BA absorption activates FXR in enterocytes, inducing transcription of fibroblast growth factor 19 (FGF19). Secreted FGF19 reaches the liver via mesenteric blood, where it binds fibroblast growth factor receptor 4 (FGFR4) and its co-receptor β-Klotho, repressing CYP7A1 and thereby inhibiting BA synthesis. , ( B – C ) Distribution of ( B ) primary vs. secondary BAs and ( C ) unconjugated vs. conjugated BAs in serum and liver. The Student’s t -test was used. Data are mean ± SEM. ( D – E ) Relative abundance of individual BAs ( D ) in serum and ( E ) in liver. Unlabeled BAs either comprised <0.1% of the total pool or were undetectable. ( F ) Heatmaps illustrating correlations between serum vs. liver BAs (left), serum BAs vs. serum C4 (middle), and liver BAs vs. serum C4 (right). Crossed cells indicate undetected BAs. ( G – H ) Heatmaps illustrating correlations between ( G ) serum and ( H ) liver BAs and key clinical and histological parameters. * P < 0.05; ** P < 0.01; *** P < 0.001.

Journal: medRxiv

Article Title: Hepatic insulin resistance is the basis of bile acid dysmetabolism in metabolic dysfunction-associated steatotic liver disease

doi: 10.1101/2025.11.18.25340381

Figure Lengend Snippet: (A) Biosynthesis, enterohepatic circulation, and negative feedback regulation of BA metabolism. Intestinal BA absorption activates FXR in enterocytes, inducing transcription of fibroblast growth factor 19 (FGF19). Secreted FGF19 reaches the liver via mesenteric blood, where it binds fibroblast growth factor receptor 4 (FGFR4) and its co-receptor β-Klotho, repressing CYP7A1 and thereby inhibiting BA synthesis. , ( B – C ) Distribution of ( B ) primary vs. secondary BAs and ( C ) unconjugated vs. conjugated BAs in serum and liver. The Student’s t -test was used. Data are mean ± SEM. ( D – E ) Relative abundance of individual BAs ( D ) in serum and ( E ) in liver. Unlabeled BAs either comprised <0.1% of the total pool or were undetectable. ( F ) Heatmaps illustrating correlations between serum vs. liver BAs (left), serum BAs vs. serum C4 (middle), and liver BAs vs. serum C4 (right). Crossed cells indicate undetected BAs. ( G – H ) Heatmaps illustrating correlations between ( G ) serum and ( H ) liver BAs and key clinical and histological parameters. * P < 0.05; ** P < 0.01; *** P < 0.001.

Article Snippet: Technicians blinded to clinical data used ELISAs to measure concentrations of serum adiponectin (Human Adiponectin ELISA; B-Bridge International Inc., San Jose, CA), serum PRO-C3 (Nordic Bioscience A/S, Herlev, Denmark), serum CK-18 fragments using the M65 antibody (M65 ELISA; VLVbio AB, Nacka, Sweden), and plasma FGF19 (Human FGF-19 Quantikine ELISA, DF1900; R&D Systems, Minneapolis, MN), with all analyses performed in duplicate.

Techniques:

( A – H ) Comparisons of serum ( A ) total BAs, ( B ) primary BAs, ( C ) secondary BAs, ( D ) glycine-conjugated BAs, ( E ) taurine-conjugated BAs, ( F ) unconjugated BAs, ( G ) ratio of 12α-hydroxylated to non-12α-hydroxylated BAs, and ( H ) BA hydrophobicity index between the low and high HOMA-IR groups. ( I ) Heatmap illustrating standardized Z-scores of relative BA abundances across quartiles of HOMA-IR. Data are shown only for BAs with significantly ( P < 0.05) altered relative abundances as a function of HOMA-IR. Blue color denotes lower and orange color higher Z-scores. ( J ) Variable importance in projection (VIP) scores for serum BAs derived from a multivariate PLS-DA model for the high vs. low HOMA-IR comparison. The horizontal dotted line marks the threshold (VIP > 1) above which BAs are considered to have a significant influence on HOMA-IR. ( K ) Relationship between log 10 -transformed concentrations of plasma FGF19 and serum C4. The line fit was obtained by linear regression. ( L – M ) Comparison of ( L ) serum C4 and ( M ) plasma FGF19 concentrations between the low and high HOMA-IR groups. Mann-Whitney U test: * P < 0.05; ** P < 0.01; *** P < 0.001.

Journal: medRxiv

Article Title: Hepatic insulin resistance is the basis of bile acid dysmetabolism in metabolic dysfunction-associated steatotic liver disease

doi: 10.1101/2025.11.18.25340381

Figure Lengend Snippet: ( A – H ) Comparisons of serum ( A ) total BAs, ( B ) primary BAs, ( C ) secondary BAs, ( D ) glycine-conjugated BAs, ( E ) taurine-conjugated BAs, ( F ) unconjugated BAs, ( G ) ratio of 12α-hydroxylated to non-12α-hydroxylated BAs, and ( H ) BA hydrophobicity index between the low and high HOMA-IR groups. ( I ) Heatmap illustrating standardized Z-scores of relative BA abundances across quartiles of HOMA-IR. Data are shown only for BAs with significantly ( P < 0.05) altered relative abundances as a function of HOMA-IR. Blue color denotes lower and orange color higher Z-scores. ( J ) Variable importance in projection (VIP) scores for serum BAs derived from a multivariate PLS-DA model for the high vs. low HOMA-IR comparison. The horizontal dotted line marks the threshold (VIP > 1) above which BAs are considered to have a significant influence on HOMA-IR. ( K ) Relationship between log 10 -transformed concentrations of plasma FGF19 and serum C4. The line fit was obtained by linear regression. ( L – M ) Comparison of ( L ) serum C4 and ( M ) plasma FGF19 concentrations between the low and high HOMA-IR groups. Mann-Whitney U test: * P < 0.05; ** P < 0.01; *** P < 0.001.

Article Snippet: Technicians blinded to clinical data used ELISAs to measure concentrations of serum adiponectin (Human Adiponectin ELISA; B-Bridge International Inc., San Jose, CA), serum PRO-C3 (Nordic Bioscience A/S, Herlev, Denmark), serum CK-18 fragments using the M65 antibody (M65 ELISA; VLVbio AB, Nacka, Sweden), and plasma FGF19 (Human FGF-19 Quantikine ELISA, DF1900; R&D Systems, Minneapolis, MN), with all analyses performed in duplicate.

Techniques: Derivative Assay, Comparison, Transformation Assay, Clinical Proteomics, MANN-WHITNEY

(A) Simulated 24-hour BA concentrations within plasma and liver compartments, showing the effects of stepwise reduced hepatic clearance of conjugated BAs from the sinusoidal space: 100% (left), 75% (middle), and 50% (right). Meals were administered at 08:30, 12:00, 18:00, and 20:30 in the simulations (arrows). (B–G) Model outputs for plasma concentrations of (B) total BAs, (C) conjugated BAs, (D) unconjugated BAs, (E) FGF19, and (F) C4, as well as (G) hepatic de novo BA synthesis rate, simulated at 100%, 75%, and 50% clearance. All parameters were evaluated at t = 08:00, corresponding to the overnight-fasted state.

Journal: medRxiv

Article Title: Hepatic insulin resistance is the basis of bile acid dysmetabolism in metabolic dysfunction-associated steatotic liver disease

doi: 10.1101/2025.11.18.25340381

Figure Lengend Snippet: (A) Simulated 24-hour BA concentrations within plasma and liver compartments, showing the effects of stepwise reduced hepatic clearance of conjugated BAs from the sinusoidal space: 100% (left), 75% (middle), and 50% (right). Meals were administered at 08:30, 12:00, 18:00, and 20:30 in the simulations (arrows). (B–G) Model outputs for plasma concentrations of (B) total BAs, (C) conjugated BAs, (D) unconjugated BAs, (E) FGF19, and (F) C4, as well as (G) hepatic de novo BA synthesis rate, simulated at 100%, 75%, and 50% clearance. All parameters were evaluated at t = 08:00, corresponding to the overnight-fasted state.

Article Snippet: Technicians blinded to clinical data used ELISAs to measure concentrations of serum adiponectin (Human Adiponectin ELISA; B-Bridge International Inc., San Jose, CA), serum PRO-C3 (Nordic Bioscience A/S, Herlev, Denmark), serum CK-18 fragments using the M65 antibody (M65 ELISA; VLVbio AB, Nacka, Sweden), and plasma FGF19 (Human FGF-19 Quantikine ELISA, DF1900; R&D Systems, Minneapolis, MN), with all analyses performed in duplicate.

Techniques: Clinical Proteomics