Journal: Journal of Advanced Research

Article Title: Perfluorooctane sulfonic acid impairs spermatogenesis via the liver-gut microbiota-testis axis: a central role of chenodeoxycholic acid metabolism

doi: 10.1016/j.jare.2025.06.037

Figure Lengend Snippet: Inhibition of CDCA synthesis contributes to defective spermatogenesis in PFOS-exposed mice. (A) Concentrations of PFOS in mouse serum (μg/mL) and various organs (μg/g) after 35 days of treatment (n = 3 per group). (B) Total cholesterol levels in the livers (n = 5 per group). (C) CDCA levels in the livers (n = 5 per group). (D) Schematic illustration of the pathways involving bile acid synthesis and transport. The hepatic transcriptomes of mice exposed to 10 mg/kg PFOS for 17 days and human hepatocyte spheroids treated with PFOS (20 μM) for 4 days were obtained from the Gene Expression Omnibus (GEO) database. The upward red arrows and downward blue arrows indicate the up- and down-regulated differential genes upon PFOS treatments, respectively. (E) Transcriptomic datasets of human hepatocyte spheroids treated with PFOS for 1, 4, or 10 days were derived from GEO accession GSE144775 . Calculation of the responsiveness of CYP7A1 to PFOS exposure was conducted using benchmark modeling. (F) Representative immunofluorescent staining of CYP7A1 in the mouse livers (Scale bar = 20 μm). (G) Testicular linoleic acid levels (n = 5 per group). (H) Testicular retinol levels (n = 5 per group). (I) Testicular vitamin D3 levels (n = 5 per group). (J) Sperm concentration (control group, n = 9; PFOS group, n = 8; PFOS + CDCA group, n = 8). (K) Hematoxylin and eosin staining of mouse testes (Scale bar = 50 μm). (L) Quantification of spermatogonia, spermatocytes, and round spermatids per seminiferous tubule of mouse testes (n = 5 per group). Values are expressed as mean ± SD. * p < 0.05, ** p < 0.01, *** p < 0.001 versus control group; # p < 0.05, ## p < 0.01, ### p < 0.001 versus PFOS alone-treated group. CYP7A1, cytochrome P450 family 7 subfamily A member 1; CYP8B1, cytochrome P450 family 8 subfamily B member 1; CYP27A1, cytochrome P450 family 27 subfamily A member 1; CYP7B1, cytochrome P450 family 7 subfamily B member 1; BAAT, bile acid-CoA:amino acid N-acyltransferase; BACS, bile acid CoA synthetase; BSEP, bile salt export protein; MRP2/3/4, multidrug resistance-associated protein 2/3/4; OSTα/β, organic solute transporter α/β; CA, cholic acid; CDCA, chenodeoxycholic acid. SPG, spermatogonia; SPC, spermatocyte; SPid, spermatid. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Article Snippet: The antibodies specific for CYP7A1 and TNP1 were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA) and Affinity Biosciences (Cincinnati, OH, USA), respectively.

Techniques: Inhibition, Gene Expression, Derivative Assay, Staining, Concentration Assay, Control

Journal: Journal of Translational Medicine

Article Title: Limonin attenuates hyperlipidemia by regulating the gut microbiota-bile acid-farnesoid X receptor axis

doi: 10.1186/s12967-026-07826-7

Figure Lengend Snippet: Impacts of Limonin upon FXR/FGF15 signaling pathway in hyperlipidemia mice liver. ( A ) mRNA expression levels of fgf15 in liver. ( B ) mRNA expression levels of Fgfr4 in liver. ( C ) mRNA expression levels of Cyp7a1 in liver. ( D ) Representative picture of immunofluorescence expression in mice liver. ( E ) F Immunofluorescence expression of CYP7A1 in liver. ( F ) Immunofluorescence expression of CYP7A1 in liver. ( G ) Immunofluorescence expression of CYP7A1 in liver. ( H ) FGF15 protein expression levels. ( I ) FGFR4 protein expression levels. ( J ) CYP7A1 protein expression levels. ( K ) Representative protein bands detected by WB. Values are denoted by mean ± SD ( n = 3). # P < 0.05, ## P < 0.01 vs. MG and * P < 0.05, ** P < 0.01 vs. NG

Article Snippet: Following blocking in 5% skim milk for 2 h at room temperature, we cultured culture membrane with primary antibody including FXR1 (BOSTER, M03308), FGF15(CUSABIO, O35622 ), ASBT (Cohesion, CQA5895), CYP7A1 (Proteintech, 18054-1-AP), and FGFR4 (BOSTER, BM5163), β-actin (AB_2750915, CPA9121) overnight at 4 °C, followed by reaction of enzyme-labeled secondary antibody for 2 h at room temperature.

Techniques: Expressing, Immunofluorescence

Journal: Journal of Translational Medicine

Article Title: Limonin attenuates hyperlipidemia by regulating the gut microbiota-bile acid-farnesoid X receptor axis

doi: 10.1186/s12967-026-07826-7

Figure Lengend Snippet: Graphical illustration of mechanism mediating anti-hyperlipidemia effects of Limonin. The possible mechanisms by which limonin alleviates dyslipidemia are as follows: (1) Reduced relative abundance of BSH-producing microbes induced by Limonin. (2) Boosted conjugated BAs, particularly TCA, T-αMCA, and T-βMCA acting in antagonistic manner on intestinal FXR, (3) The increased conjugated BAs boosted elimination of BAs via feces, and also as endogenous signaling molecules that inhibited activation of intestinal FXR causing FGF15’s reduced production in the distal ileum. (4) The FGF15 through the enterohepatic circulation to enter mice liver, and regulates liver CYP7A1 expression via negative feedback of FGF15-FGFR4 pathway to promoting the synthesis of TC to BA, thereby reducing TC

Article Snippet: Following blocking in 5% skim milk for 2 h at room temperature, we cultured culture membrane with primary antibody including FXR1 (BOSTER, M03308), FGF15(CUSABIO, O35622 ), ASBT (Cohesion, CQA5895), CYP7A1 (Proteintech, 18054-1-AP), and FGFR4 (BOSTER, BM5163), β-actin (AB_2750915, CPA9121) overnight at 4 °C, followed by reaction of enzyme-labeled secondary antibody for 2 h at room temperature.

Techniques: Activation Assay, Expressing