Mitochondrial folate metabolism-mediated α-linolenic acid exhaustion masks liver fibrosis resolution.

Sustainable TGF-β1 signaling drives organ fibrogenesis. However, the cellular adaptation to maintain TGF-β1 signaling remains unclear. In this study, we revealed that dietary folate restriction promoted the resolution of liver fibrosis in mice with nonalcoholic steatohepatitis.

Rational design, synthesis and biological evaluation of dual PARP-1/2 and TNKS1/2 inhibitors for cancer therapy.

Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors are the first and most successful drugs designed to exploit the concept of synthetic lethality (SL) between PARP-1 and BRCA1/2, which provides a novel strategy for tumor treatment. However, narrowed indications and resistance to PARP-1 inhibitors have hampered their further clinical application. Inducing "BRCAness" by targeting other targets, which will directly or indirectly disturb the homologous recombination (HR) repair pathway of double-strand DNA breaks (DSBs), is a promising strategy for expanding the clinical application of PARP-1 inhibitors and overcoming resistance to these inhibitors.

Small molecule targeting CELF1 RNA-binding activity to control HSC activation and liver fibrosis.

CUGBP Elav-like family member 1 (CELF1), an RNA-binding protein (RBP), plays important roles in the pathogenesis of diseases such as myotonic dystrophy, liver fibrosis and cancers. However, targeting CELF1 is still a challenge, as RBPs are considered largely undruggable. Here, we discovered that compound 27 disrupted CELF1-RNA binding via structure-based virtual screening and biochemical assays.