obeticholic acid oca  (MedChemExpress)

Journal: Journal of Advanced Research

Article Title: Tetramethylpyrazine improves the structure and function of mitochondrial-associated endoplasmic reticulum membrane and liver fibrosis

doi: 10.1016/j.jare.2025.09.003

Figure Lengend Snippet: The anti-fibrotic effect of TMP is closely related to the repair of ER and mitochondria in hepatocytes. (A) The common DEGs between different groups. (B) The KEGG pathway enrichment of common DEGs. (C) GO analysis of DEGs. Representative (D) images and (E) quantitative statistical analysis of liver TEM in different groups of mice. The magnification factor = 2 μM. (F) Expression of Mfn2 , Dnm1l , Ktn1 , and Rtn4 genes in different cell types of mouse liver in the single-cell sequencing database of tabula-muris. Representative images of immunofluorescent result of (G) CKAP4 and RTN4 and (H) Mito-tracker in AML12 cells. Statistical significance: * P < 0.05, ** P < 0.01, *** P < 0.001, compared with vehicle group; # P < 0.05, ## P < 0.01, ### P < 0.001, compared with CCl 4 group. One-way ANOVA with Tukey’s post-hoc tests (n = 8).

Article Snippet: For the chronic carbon tetrachloride (CCl 4 ) (≥95 %, Innochem, A68354) injury experiment, the mice were randomly divided into six groups (n = 8): (1) control group, (2) CCl 4 modeling group, (3–5) CCl 4 + TMP (≥95 %, Innochem, A45751) different-dose groups (40, 80 and 160 mg/kg, respectively) and (6) CCl 4 + obeticholic (OCA, ≥98 %, MCE, HY-12222) group (5 mg/kg).

Techniques: Expressing, Single Cell, Sequencing

Journal: Journal of Advanced Research

Article Title: Tetramethylpyrazine improves the structure and function of mitochondrial-associated endoplasmic reticulum membrane and liver fibrosis

doi: 10.1016/j.jare.2025.09.003

Figure Lengend Snippet: TMP largely improves the abnormal regional contact and quantity of MAM in hepatocytes. Representative (A, left panel) TEM images, (A, right panel) 2D images and (B) quantitative statistical analysis of MAM structures in different liver groups. (C) Representative images of immunofluorescent result of TOM20 and PDI in mice livers. Scale bar = 50 μm. AML12 were pre-treated with TMP at different concentrations for 1 h and then treated with CCl 4 (10 mM) for another 12 h. (D) Representative TEM images and quantitative statistical analysis of MAM changes in different groups of AML12 cells. Representative images of immunofluorescent result of (E) TOM20, PDI, (F) Mitochondria and ER in AML12 cells. Statistical significance: * P < 0.05, ** P < 0.01, *** P < 0.001, compared with vehicle group; # P < 0.05, ## P < 0.01, ### P < 0.001, compared with CCl 4 group. One-way ANOVA with Tukey’s post-hoc tests (n = 8 for animal studies, n = 3 for cell experiments).

Article Snippet: For the chronic carbon tetrachloride (CCl 4 ) (≥95 %, Innochem, A68354) injury experiment, the mice were randomly divided into six groups (n = 8): (1) control group, (2) CCl 4 modeling group, (3–5) CCl 4 + TMP (≥95 %, Innochem, A45751) different-dose groups (40, 80 and 160 mg/kg, respectively) and (6) CCl 4 + obeticholic (OCA, ≥98 %, MCE, HY-12222) group (5 mg/kg).

Techniques:

Journal: Journal of Advanced Research

Article Title: Tetramethylpyrazine improves the structure and function of mitochondrial-associated endoplasmic reticulum membrane and liver fibrosis

doi: 10.1016/j.jare.2025.09.003

Figure Lengend Snippet: The regulatory effect of TMP on the Ca 2+ flow and MFN2-SERCA2 complex within MAM region. Representative images of immunofluorescent result of (A) GRP75, TOM20, (B) GRP75, CALR, (D, upper panel) MFN2, TOM20, (D, lower panel) MFN2, CALR, (E) Rhod-2 (red), Mitochondria (green), (H) PLA staining in livers and AML12 cells. (C) Representative immunoblots against MFN2, VDAC1, ITPR1, GRP75, SERCA2 and β-ACTIN in cytoplastic, mitochondrial and MAM structures of AML12 cells. Representative curves of transient changes in Ca 2+ in different groups of AML12 cells treated with inhibitors and activators of (F) SERCA2 and (G) IP3R. (H) The In situ PLA Blobs in livers and AML12 cells. Statistical significance: * P < 0.05, ** P < 0.01, *** P < 0.001, compared with vehicle group; # P < 0.05, ## P < 0.01, ### P < 0.001, compared with CCl 4 group. One-way ANOVA with Tukey’s post-hoc tests (n = 3).

Article Snippet: For the chronic carbon tetrachloride (CCl 4 ) (≥95 %, Innochem, A68354) injury experiment, the mice were randomly divided into six groups (n = 8): (1) control group, (2) CCl 4 modeling group, (3–5) CCl 4 + TMP (≥95 %, Innochem, A45751) different-dose groups (40, 80 and 160 mg/kg, respectively) and (6) CCl 4 + obeticholic (OCA, ≥98 %, MCE, HY-12222) group (5 mg/kg).

Techniques: Staining, Western Blot, In Situ

Journal: Journal of Advanced Research

Article Title: Tetramethylpyrazine improves the structure and function of mitochondrial-associated endoplasmic reticulum membrane and liver fibrosis

doi: 10.1016/j.jare.2025.09.003

Figure Lengend Snippet: The effects of siRNA-MFN2 and MFN2 activator on CCl 4 -induced MAM impairment and organelle’s dysfunction in hepatocytes. The mRNA levels of (A) Mfn2 , S ercaa2 , (G) Syvn1 and Sel1l in AML12 cells. (B) Representative immunoblots against MFN2, SERCA2 and β-ACTIN in cytoplastic and MAM structures of AML12 cells. Representative TEM images and (C, right panel) their corresponding 2D pictures of MAM changes in different groups of AML12 cells. Representative images of immunofluorescent result of (D, left panel) Mitochondria, ER, (D, right panel) TOM20, PDI, (E) Rhod-2 and Mito-tracker in AML12 cells. (F) The content of ceramide in AML12 cells. (H) Representative immunoblots against HRD1, VCP, SEL1L and β-ACTIN in AML12 cells. (I) The levels of mitochondrial complexes IV and V in AML12 cells. (J) The graphs of real-time OCR using Seahorse XF analyzer. Statistical significance: * P < 0.05, ** P < 0.01, *** P < 0.001, compared with vehicle group; # P < 0.05, ## P < 0.01, ### P < 0.001, compared with CCl 4 group; & P < 0.05, compared with CCl 4 + TMP group. One-way ANOVA with Tukey’s post-hoc tests (n = 3).

Article Snippet: For the chronic carbon tetrachloride (CCl 4 ) (≥95 %, Innochem, A68354) injury experiment, the mice were randomly divided into six groups (n = 8): (1) control group, (2) CCl 4 modeling group, (3–5) CCl 4 + TMP (≥95 %, Innochem, A45751) different-dose groups (40, 80 and 160 mg/kg, respectively) and (6) CCl 4 + obeticholic (OCA, ≥98 %, MCE, HY-12222) group (5 mg/kg).

Techniques: Western Blot

Journal: Journal of Advanced Research

Article Title: Tetramethylpyrazine improves the structure and function of mitochondrial-associated endoplasmic reticulum membrane and liver fibrosis

doi: 10.1016/j.jare.2025.09.003

Figure Lengend Snippet: The knockdown of MFN2 reverses the TMP-remitted liver fibrosis. (A) The levels of ALT, AST and TBA in mice serum and the level of HYP in mice livers. Representative images of (B) H&E, (C) Sirius red and (D) IHC staining of α-SMA of livers in mice. Scale bar = 100 μm. Representative (E, upper panel) TEM images and (E, lower panel) corresponding 2D images and statistical analysis of different mice livers. Immunofluorescent co-staining of (F) TOM20 and PDI and (H) In situ PLA Blobs in mice livers. Scale bar = 50 μm. (G) The mRNA levels of Itpr1 , Vdac1 , Mfn2 and Atp2a2 and in mice livers normalized with Hprt1 . Statistical significance: * P < 0.05, ** P < 0.01, *** P < 0.001, compared with vehicle group; # P < 0.05, ## P < 0.01, ### P < 0.001, compared with CCl 4 group; & P < 0.05, && P < 0.01, &&& P < 0.001, compared with CCl 4 + TMP group (n = 6).

Article Snippet: For the chronic carbon tetrachloride (CCl 4 ) (≥95 %, Innochem, A68354) injury experiment, the mice were randomly divided into six groups (n = 8): (1) control group, (2) CCl 4 modeling group, (3–5) CCl 4 + TMP (≥95 %, Innochem, A45751) different-dose groups (40, 80 and 160 mg/kg, respectively) and (6) CCl 4 + obeticholic (OCA, ≥98 %, MCE, HY-12222) group (5 mg/kg).

Techniques: Knockdown, Immunohistochemistry, Staining, In Situ

Journal: Cell Death Discovery

Article Title: Spermidine suppresses liver fibrosis by remodeling the communication signal between liver sinusoidal endothelial cells and hepatic stellate cells

doi: 10.1038/s41420-026-03129-4

Figure Lengend Snippet: A Schematic diagram of the SPD treatment protocol. 8-week-old C57BL/6 J mice ( n = 6) received intraperitoneal injections of CCl₄ for 8 consecutive weeks to induce liver fibrosis. From the second week onward, SPD (3 mM) was added to the drinking water, and obeticholic acid (OCA, 5 mg/kg) was administered daily via oral gavage for the remaining 7 weeks. B Representative images of H&E and Sirius Red staining, as well as immunohistochemical staining for α-SMA, CD34, and LYVE1 in liver sections (bar = 100 µm). C Analysis of protein levels of COL1A1, α-SMA, CD34, and LYVE1 in liver tissues by western blot ( n = 3, performed in biological replicates). D , E Analysis of mRNA levels of COL1A1, α-SMA, TIMP-1, TNF-α, IL-1, LYVE1, STAB1, STAB2, CD209B, EHD3, CD34, EDN1, LAMB1 and PECAM1 in liver tissues by RT-qPCR ( n = 6, performed in biological replicates). F Representative TEM and SEM images of liver tissues from CCl₄ and CCl₄ +SPD group. G Schematic of the co-culture model. LX-2 cells were co-cultured with SPD-treated (or untreated) HUVEC. H Analysis of protein levels of CD34 and LYVE1 in HUVEC. I Analysis of protein levels of COL1A1 and α-SMA expression in co-cultured LX-2 cells. J Matrigel tube-formation assay in HUVEC ( n = 3, performed in biological replicates). Cells were pretreated with SPD (20 μM) for 24 h, then seeded on matrigel-coated 48-well plates and stimulated with VEGFA (25 ng/mL) for 24 h. Images were captured 24 h after seeding. Data are represented as mean ± SD, * P < 0.05, ** P < 0.01, *** P < 0.001.

Article Snippet: After a 2-week acclimatization period, the mice were randomly assigned to four groups ( n = 6 per group): Control (Con), CCl4, CCl4 + Spermidine (SPD, Sigma-Aldrich, S0266), and CCl4 + Obeticholic Acid (OCA; MedChemExpress, HY-12222).

Techniques: Staining, Immunohistochemical staining, Western Blot, Quantitative RT-PCR, Co-Culture Assay, Cell Culture, Expressing, Tube Formation Assay

Journal: Cell Death Discovery

Article Title: Spermidine suppresses liver fibrosis by remodeling the communication signal between liver sinusoidal endothelial cells and hepatic stellate cells

doi: 10.1038/s41420-026-03129-4

Figure Lengend Snippet: A Schematic Diagram of mice treatment. Briefly, mice ( n = 6) received intraperitoneal injections of CCl₄ and were administered with AAV vectors (AAV-control or AAV- Bgn ) via the tail vein at 10 weeks of age, followed by an 8-week SPD treatment. B Body weight, liver weight, liver/body weight ratio, serum ALT and AST levels in each group. C Representative images of H&E staining of liver sections (bar = 100 μM). D – G Effects of AAV- Bgn on LSECs dysfunction. D Analysis of BGN ubiquitination, BGN, UBE2G2, ERK/p-ERK, p38/p-p38, CD34, LYVE1 expression in the liver tissues by western blot. The arrow indicates the IgG heavy chain band. E Analysis of mRNA levels of LSECs markers and capillary endothelial markers in liver tissues ( n = 6, performed in biological replicates). F Immunofluorescence staining of LYVE1 and CD34 (bar = 100 μM). G Representative TEM and SEM images of liver tissues. Effects of AAV- Bgn on HSCs activation. H Representative images of Sirius Red staining and immunohistochemical staining for COL1A1 and α-SMA in liver sections (bar = 100 μM). I Analysis of related protein levels in the livers tissues ( n = 3, performed in biological replicates). J Analysis of mRNA levels of fibrotic markers in liver tissues ( n = 6, performed in biological replicates). Data are represented as mean ± SD, * P < 0.05, ** P < 0.01, *** P < 0.001.

Article Snippet: After a 2-week acclimatization period, the mice were randomly assigned to four groups ( n = 6 per group): Control (Con), CCl4, CCl4 + Spermidine (SPD, Sigma-Aldrich, S0266), and CCl4 + Obeticholic Acid (OCA; MedChemExpress, HY-12222).

Techniques: Control, Staining, Ubiquitin Proteomics, Expressing, Western Blot, Immunofluorescence, Activation Assay, Immunohistochemical staining