Insights & Research

Why is the world focusing on the PDE4B inhibitor (BI 1015550) as the next-generation IPF treatment following Ofev/Esbriet? We explain why "PDE4B"? its precise selectivity mechanism, the Phase 3 trial FIBRONEER-IPF results, and the path to approval.

With the weapons of Resmetirom and Semaglutide in hand, where is humanity heading next? We explore next-generation drugs like FGF21 analogs (Pegozafermin), game-changing NITs (Non-Invasive Tests), and concrete strategies for "Combination Therapy".

Semaglutide demonstrated remarkable results in the ESSENCE trial. This article explores its mechanism (direct vs. indirect), efficacy on non-invasive markers like ELF score, and the debate surrounding its application for "Lean MASH".

Resmetirom becomes the first approved treatment for MASH. A deep dive into its THR-β selectivity mechanism and the full Phase 3 MAESTRO-NASH results, including secondary endpoints like LDL-C and liver enzymes.

Assessment methods determine the quality of fibrosis research. We explain the principles and tips of histological assessment (Sirius Red, Masson's Trichrome) and biochemical quantification (Hydroxyproline), as well as objective quantification using the latest AI image analysis.

The Wnt/β-catenin pathway is crucial for development and tissue repair. How is this pathway reactivated in chronic diseases to promote fibrosis? We explain the crosstalk with TGF-β and the latest trends in inhibitor development.

TGF-β1 is the central promoter in fibrosis of all organs. We explain the molecular mechanisms of its signaling pathways (canonical Smad pathway, non-Smad pathways), negative feedback, and the current status of anti-fibrotic drug development.

NF-κB is the central transcription factor of the inflammatory response. We explain the activation mechanisms of canonical and non-canonical pathways, regulation by IκB, its role in the transition from chronic inflammation to fibrosis, and therapeutic strategies.

YAP/TAZ are mechanosensors that sense tissue "stiffness." We explain the control mechanism by the Hippo pathway, the "vicious cycle of stiffness (positive feedback)" in fibrotic tissue, and their potential as novel therapeutic targets.

Explaining the duality of macrophages in fibrosis (M1: Inflammation, M2: Fibrosis/Repair). We introduce the roles of M2 subtypes (M2a/b/c), the switch mechanism in fibrosis progression/resolution, and their potential as therapeutic targets.

Why does chronic inflammation lead to fibrosis? We detail the cellular and molecular mechanisms driving this pathological transition, including macrophage polarization from M1 to M2, the duality of TGF-β, and Epithelial-Mesenchymal Transition (EMT).

Inflammation is not just a defense response but a crucial step towards tissue repair. We explain the initiation of acute inflammation, the active "resolution" via SPMs (Specialized Pro-resolving Mediators) and Efferocytosis, and the mechanisms of transition to chronicity.

"Fibrosis" is a runaway tissue repair process. We explain the central players—myofibroblasts, their origins, TGF-β signaling, and mechanotransduction, where tissue stiffness exacerbates pathology—based on the latest research findings.

Myofibroblasts are the executioners of fibrosis. We explain their diverse origins (resident fibroblasts, pericytes, EMT), activation mechanisms by TGF-β and mechanotransduction, and markers like α-SMA.

We explain the mechanisms of Pirfenidone and Nintedanib, approved for Idiopathic Pulmonary Fibrosis (IPF), and the latest development trends of novel anti-fibrotic candidates for MASH and renal fibrosis currently in Phase 2/3 clinical trials.

Explaining the technical challenges of the UUO (Unilateral Ureteral Obstruction) model used in CKD research and the utility of the IRI (Ischemia-Reperfusion Injury) model for assessing renal function. Reducing variability through skilled microsurgery is key.

The Bleomycin pulmonary fibrosis model is the gold standard for IPF drug discovery. We explain solutions to its biggest challenges—"spontaneous resolution" and "variability"—using Micro-Sprayer technology for uniform administration and optimal study design.

Explaining the paradigm shift in research models following the nomenclature change from NASH to MASH. We discuss the limitations of traditional diet-induced models (duration, mild fibrosis) and introduce "Accelerated MASH Models" and objective fibrosis quantification methods based on the latest findings.

DSS and TNBS models are widely used in Ulcerative Colitis (UC) and Crohn's Disease (CD) research. We explain how to resolve challenges such as lot variability, technical inconsistency, and subjective evaluation through pre-validation and endoscopic (MEICS) assessment.

Biomarkers are essential for non-invasive evaluation of fibrosis. We explain the diagnostic value, prognostic ability, and limitations of major markers for lung (KL-6, SP-D), liver (Hyaluronic Acid, ELF Score), heart, and kidney.