Journal: International Journal of Molecular Sciences

Article Title: Resmetirom Ameliorates NASH-Model Mice by Suppressing STAT3 and NF-κB Signaling Pathways in an RGS5-Dependent Manner

doi: 10.3390/ijms24065843

Figure Lengend Snippet: Resmetirom effectively improved NASH in cell models generated using oleic acid. ( A ), HepG2 and NCTC 1469 cells were treated with the indicated doses of oleic acid for 48 h, and Oil red O staining experiment was performed to determine the intracellular lipid accumulation. ( B ), ELISA assay was performed to detect the intracellular TG levels in cells treated as in ( A ). ( C ), HepG2 and NCTC 1469 cells were treated with the indicated concentrations of resmetirom for 48 h, MTT assay was used to assess the cytotoxicity of the drug. ( D ), HepG2 and NCTC 1469 cells were pre-incubated with the indicated concentrations of resmetirom for 48 h, followed by another 48 h treatment with the indicated doses of oleic acid to establish the NASH cell model, and Oil red O staining experiment was performed to determine the intracellular lipid accumulation. ( E ), ELISA assay was performed to detect the intracellular TG levels in cells treated as in ( D ). Data are presented by mean ± SD for three independent experiments. * p < 0.05; ** p < 0.01 vs. control.

Article Snippet: Then, cells were treated with different doses of resmetirom (0 mM, 100 mM, 200 mM, 300 mM, 400 mM, and 500 mM, obtained from Selleck) for 48 h. After that, the medium was removed, and 50 μL of MTT solution (1mg/mL in PBS) was added to each well to incubate for 2–4 h at 37 °C.

Techniques: Generated, Staining, Enzyme-linked Immunosorbent Assay, MTT Assay, Incubation, Control

Journal: International Journal of Molecular Sciences

Article Title: Resmetirom Ameliorates NASH-Model Mice by Suppressing STAT3 and NF-κB Signaling Pathways in an RGS5-Dependent Manner

doi: 10.3390/ijms24065843

Figure Lengend Snippet: mRNA sequencing was performed to elucidate the mRNA expression profile in the resmetirom-treated NASH cell model. ( A ), HepG2 cells were pre-incubated with 0 or 100 μM resmetirom for 48 h, followed by treatment with 0- or 1.2-mM oleic acid for another 48 h, and Oil red O staining experiment was performed to determine the intervention effect of the drug. ( B ), Total RNA was extracted for mRNA-sequencing assay, differentially expressed genes (DEGs, fold change > 2, p < 0.05) were obtained, and volcano plots were generated using DEGs between NASH (NASH cell model) vs. control (left panel), and NASH_R (NASH cell model treated with 100 μM resmetirom) vs. NASH (right panel). ( C ), Heat maps were produced for DEGs between NASH vs. control (upper panel), and NASH_R vs. NASH (lower panel). ( D ), GO enrichment analysis was performed in DEGs between NASH vs. control (upper panel), and NASH_R vs. NASH (lower panel). ( E ), KEGG enrichment analysis was performed in DEGs between NASH vs. control (upper panel), and NASH_R vs. NASH (lower panel).

Article Snippet: Then, cells were treated with different doses of resmetirom (0 mM, 100 mM, 200 mM, 300 mM, 400 mM, and 500 mM, obtained from Selleck) for 48 h. After that, the medium was removed, and 50 μL of MTT solution (1mg/mL in PBS) was added to each well to incubate for 2–4 h at 37 °C.

Techniques: Sequencing, Expressing, Incubation, Staining, Generated, Control, Produced

Journal: International Journal of Molecular Sciences

Article Title: Resmetirom Ameliorates NASH-Model Mice by Suppressing STAT3 and NF-κB Signaling Pathways in an RGS5-Dependent Manner

doi: 10.3390/ijms24065843

Figure Lengend Snippet: Resmetirom might ameliorate NASH in an RGS5-dependent manner. ( A ) The expressions of the top five DEGs were further validated by qPCR. ( B ), HepG2 cells were treated with indicated concentrations of oleic acid for 48 h, Western blot assay was used to determine the expression of RGS5 protein. The protein level was analyzed and is presented in the histogram in the right panel. ( C ), HepG2 cells were pre-incubated with 0 or 100 μM resmetirom for 48 h, followed by treatment with 0- or 1.2-mM oleic acid for another 48 h, and the indicated protein expressions were determined by Western blot assays. The protein level was analyzed and is presented in the histogram in the right panel. ( D ), HepG2 cells were transfected with RGS5 siRNA or NC siRNA for 24 h, and qPCR experiment was performed to examine the silence efficiency. ( E ), Total proteins were extracted in cells treated as in ( D ), and Western blot assay was performed to detect the RGS5 expression. The protein level was analyzed and is presented in the histogram in the right panel. ( F ), HepG2 cells were pre-incubated with 0 or 100 μM resmetirom for 48 h and transfected with RGS5 siRNA-2 or NC for 24 h, followed by treatment with 0- or 1.2-mM oleic acid for another 48 h, and Oil red O staining experiment was performed to determine the cellular lipid accumulation. ( G ), Total proteins were extracted in cells treated as in ( F ), and Western blot assay was performed to detect the expressions of the indicated proteins. The protein level was analyzed and is presented in the histogram in the right panel. Data are presented by mean ± SD for three independent experiments. * p < 0.05; ** p < 0.01 vs. control.

Article Snippet: Then, cells were treated with different doses of resmetirom (0 mM, 100 mM, 200 mM, 300 mM, 400 mM, and 500 mM, obtained from Selleck) for 48 h. After that, the medium was removed, and 50 μL of MTT solution (1mg/mL in PBS) was added to each well to incubate for 2–4 h at 37 °C.

Techniques: Western Blot, Expressing, Incubation, Transfection, Staining, Control

Journal: International Journal of Molecular Sciences

Article Title: Resmetirom Ameliorates NASH-Model Mice by Suppressing STAT3 and NF-κB Signaling Pathways in an RGS5-Dependent Manner

doi: 10.3390/ijms24065843

Figure Lengend Snippet: Resmetirom significantly suppressed NASH in mouse model generated by AMLN diet. After finishing the establishment of the NASH mouse models, all mice were continually feeding as previously, while sixteen mice of NASH group were treated with either a low dose (3 mg/kg, eight mice) or high dose (5 mg/kg, eight mice) of resmetirom every day. ( A ), Body weights were measured every four days. ( B ), After 48 days of treatment, mice were sacrificed and the presented mouse for each group is shown. The arrows indicate the positions of the liver. ( C ), Livers were removed and presented. ( D ), The ratios of livers to body weights were calculated and presented. ( E ), IHC assay was performed to confirm the pan-macrophage marker F4/80 in livers, and the infiltration of macrophages is quantified and statistically analyzed in right panel. ( F ), qPCR analysis of genes associated with liver fibrosis. ( G ), qPCR analysis of genes associated with inflammation. Data are presented by mean ± SEM for three independent experiments. * p < 0.05; ** p < 0.01 vs. control.

Article Snippet: Then, cells were treated with different doses of resmetirom (0 mM, 100 mM, 200 mM, 300 mM, 400 mM, and 500 mM, obtained from Selleck) for 48 h. After that, the medium was removed, and 50 μL of MTT solution (1mg/mL in PBS) was added to each well to incubate for 2–4 h at 37 °C.

Techniques: Generated, Marker, Control

Journal: International Journal of Molecular Sciences

Article Title: Resmetirom Ameliorates NASH-Model Mice by Suppressing STAT3 and NF-κB Signaling Pathways in an RGS5-Dependent Manner

doi: 10.3390/ijms24065843

Figure Lengend Snippet: Resmetirom effectively inhibited lipid accumulation in NASH mouse model. ( A ), Sections of livers from mice in were used to perform the Oil red O staining assay to determine the lipid accumulation in liver tissue. ( B ), HE staining assay was used to confirm the pathological change in livers. ( C ), TUNEL assays were used to evaluate the cell apoptosis in liver tissues. ( D ), Masson staining assays were used to evaluate the fibrosis status in liver tissues. For all experiments, representative pictures are shown.

Article Snippet: Then, cells were treated with different doses of resmetirom (0 mM, 100 mM, 200 mM, 300 mM, 400 mM, and 500 mM, obtained from Selleck) for 48 h. After that, the medium was removed, and 50 μL of MTT solution (1mg/mL in PBS) was added to each well to incubate for 2–4 h at 37 °C.

Techniques: Staining, TUNEL Assay

Journal: International Journal of Molecular Sciences

Article Title: Resmetirom Ameliorates NASH-Model Mice by Suppressing STAT3 and NF-κB Signaling Pathways in an RGS5-Dependent Manner

doi: 10.3390/ijms24065843

Figure Lengend Snippet: Resmetirom restored RGS5 expression and repressed the activation of STAT3 signaling pathway in NASH mouse model. ( A ), Sections of livers from mice in were used to perform the IHC assay to determine the RGS5 expression in liver tissue. Representative data are shown. ( B ), Total protein was extracted from livers in , Western blot assay was performed to detect the expression of the indicated proteins. The protein level was analyzed and is presented in the histogram in the lower panel. ( C ), The potential underlying mechanism of how resmetirom improves NASH in a mouse model. Data are presented by mean ± SEM for three independent experiments. * p < 0.05; ** p < 0.01 vs. control.

Article Snippet: Then, cells were treated with different doses of resmetirom (0 mM, 100 mM, 200 mM, 300 mM, 400 mM, and 500 mM, obtained from Selleck) for 48 h. After that, the medium was removed, and 50 μL of MTT solution (1mg/mL in PBS) was added to each well to incubate for 2–4 h at 37 °C.

Techniques: Expressing, Activation Assay, Western Blot, Control

Journal: Hepatology Communications

Article Title: Early experience with resmetirom to treat metabolic dysfunction–associated steatohepatitis with fibrosis in a real-world setting

doi: 10.1097/HC9.0000000000000670

Figure Lengend Snippet: Stakeholders in the resmetirom prescription process at Indiana University Health Academic Health Center

Article Snippet: Specialty Pharmacy , Limited network of 7 pharmacies approved to distribute resmetirom (Accredo, Alliance WAG, Centerwell, CVS Specialty Pharmacy, Optum, Acaria, and Amber).

Techniques:

Journal: Hepatology Communications

Article Title: Early experience with resmetirom to treat metabolic dysfunction–associated steatohepatitis with fibrosis in a real-world setting

doi: 10.1097/HC9.0000000000000670

Figure Lengend Snippet: Approach to appeal the denial by payors and a description of Madrigal’s Patient Assistance Program. This figure outlines the steps needed for a patient to receive resmetirom if prior authorizations have been denied by the payor. The manufacturer evaluates on a case-by-case basis to provide the medication at a low or free cost to patients. The manufacturer requires 2 appeal denials for the long-term bridge. *Long-term bridge requires 2 appeal denials.

Article Snippet: Specialty Pharmacy , Limited network of 7 pharmacies approved to distribute resmetirom (Accredo, Alliance WAG, Centerwell, CVS Specialty Pharmacy, Optum, Acaria, and Amber).

Techniques:

Journal: Hepatology Communications

Article Title: Early experience with resmetirom to treat metabolic dysfunction–associated steatohepatitis with fibrosis in a real-world setting

doi: 10.1097/HC9.0000000000000670

Figure Lengend Snippet: Disposition of 113 patients who were prescribed resmetirom between April 2024 and November 2024. This flowchart describes the number of patients who were initially referred and approved for resmetirom. Of 110 patients receiving approval, 83 reported starting resmetirom while 25 did not. Of 83 who started resmetirom, 70 remained on the regimen while 13 discontinued. *Approved by Payor or Madrigal Patient Assistance Program.

Article Snippet: Specialty Pharmacy , Limited network of 7 pharmacies approved to distribute resmetirom (Accredo, Alliance WAG, Centerwell, CVS Specialty Pharmacy, Optum, Acaria, and Amber).

Techniques:

Journal: Hepatology Communications

Article Title: Early experience with resmetirom to treat metabolic dysfunction–associated steatohepatitis with fibrosis in a real-world setting

doi: 10.1097/HC9.0000000000000670

Figure Lengend Snippet: Baseline characteristics of patients with MASH who were approved for resmetirom between April 1, 2024, and November 8, 2024

Article Snippet: Specialty Pharmacy , Limited network of 7 pharmacies approved to distribute resmetirom (Accredo, Alliance WAG, Centerwell, CVS Specialty Pharmacy, Optum, Acaria, and Amber).

Techniques:

Journal: Hepatology Communications

Article Title: Early experience with resmetirom to treat metabolic dysfunction–associated steatohepatitis with fibrosis in a real-world setting

doi: 10.1097/HC9.0000000000000670

Figure Lengend Snippet: Baseline characteristics of patients who discontinued resmetirom between April 1, 2024, and November 8, 2024

Article Snippet: Specialty Pharmacy , Limited network of 7 pharmacies approved to distribute resmetirom (Accredo, Alliance WAG, Centerwell, CVS Specialty Pharmacy, Optum, Acaria, and Amber).

Techniques: Medications

Journal: Hepatology Communications

Article Title: Early experience with resmetirom to treat metabolic dysfunction–associated steatohepatitis with fibrosis in a real-world setting

doi: 10.1097/HC9.0000000000000670

Figure Lengend Snippet: Changes in liver biochemistries among patients who continued resmetirom therapy. (A) Changes in ALT after starting resmetirom. (B) Changes in ALP after starting resmetirom. (C) Changes in serum total bilirubin after starting resmetirom.

Article Snippet: Specialty Pharmacy , Limited network of 7 pharmacies approved to distribute resmetirom (Accredo, Alliance WAG, Centerwell, CVS Specialty Pharmacy, Optum, Acaria, and Amber).

Techniques:

Journal: JHEP Reports

Article Title: A thioacrylamide-based compound directly counteracts hepatic fibrosis with profound anti-obesity action

doi: 10.1016/j.jhepr.2026.101792

Figure Lengend Snippet: HK1 and HK3 counteract upregulation of pro-fibrotic and inflammation-related proteins in LX2 cell model. LX2 cells were exposed to HK1 or HK3 (10 μM) prior to stimulation with TGF-β1 (5 ng/ml, 24 h) or the corresponding treatments alone. Relative protein levels of (A) FN1 and (B, C) COL1A1 were quantified by normalizing to the total protein amounts of vinculin, β-tubulin and GAPDH, respectively. (C) In addition, LX cells were exposed to semaglutide, lanifibranor and resmetirom (all 10 μM). mRNA levels of (D) ACTA2 , (E) EGR2 , and (F) SMAD4 were normalized to the endogenous control gene GAPDH . Secreted protein levels of (G) LIF and (H) VEGFA were measured by OLINK, and the fold change was calculated by conversion of NPX values to a linear scale (2 NPX ). Plasma concentrations of (I) IL-6 were determined by ELISA. Data are presented as the mean ± SEM; n = 3-5; one-way ANOVA with Tukey’s (A-D, G-I) or Dunnett’s post hoc test (E, F); ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001 vs . corresponding vehicle normalized in control (A, B, D-F) or vs . untreated cells (C, G-I); # p < 0.05, ## p < 0.01, ### p < 0.001 vs . TGF-β1 alone. NPX, normalized protein expression.

Article Snippet: Although numerous compounds are currently being tested in clinical trials, only two drugs, resmetirom (Rezdiffra; Madrigal Pharmaceuticals) and semaglutide (Wegovy; Novo Nordisk) have been approved for the treatment of metabolic dysfunction-associated steatohepatitis (MASH).

Techniques: Control, Clinical Proteomics, Enzyme-linked Immunosorbent Assay, Expressing