The therapeutic potential of SHCZF was evaluated in alpha-naphthylisothiocyanate (ANIT)-induced IC rat model, with ursodeoxycholic acid (UDCA) used as positive control...Importantly, GW6471 altered the regulatory effects of SHCZF on MKK4/JNK pathway and bile acid homeostasis. SHCZF improves IC by regulating PPARα-mediated bile acid homeostasis and MKK4/JNK pathway.

Mechanistic assays revealed that ursodeoxycholic acid (UDCA) upregulated BSEP and reversed resistance via an FXR-independent mechanism: UDCA directly binds cortactin (CTTN), reduces its PRMT1-dependent mono-methylation, and promotes CTTN degradation via chaperone-mediated autophagy, thereby enabling YY1 nuclear translocation and transcriptional activation of BSEP. Clinical specimen analyses corroborated an inverse BSEP-CTTN relationship and UDCA modulation. These findings identify impaired BSEP-mediated BA efflux and GCA accumulation as metabolic features of TKI resistance and support targeting the CTTN/YY1/BSEP axis, including UDCA, to overcome resistance.

These findings suggest that UDCA exerts its anti-tumor effects primarily through direct inhibition of the EGFR-mediated PI3K/Akt/mTOR pathway, accompanied by partial restoration of the intestinal immune-metabolic microenvironment. This study provides new mechanistic insights supporting the therapeutic application of UDCA in CRC.

P4, N=80, Recruiting, Amira Adel Fouly | Not yet recruiting --> Recruiting | Trial completion date: Dec 2024 --> Jun 2026 | Trial primary completion date: Oct 2024 --> Jun 2026

P1, N=14, Completed, Washington University School of Medicine | Recruiting --> Completed

Nearly half of patients developing ir-hepatitis had an inadequate response to steroids and needed MMF as a secondary immunosuppressant. Patients with mixed DILI were more likely to respond to steroids, while alcohol consumption was associated with inadequate steroid response. Immune analyses showed high T cell infiltration in the liver among patients with ir-hepatitis.

P2, N=69, Not yet recruiting, University of Alabama at Birmingham

Eighteen patients with advanced Primary Biliary Cholangitis (stage III and IV) before and after Ursodeoxycholic acid (UDCA) treatment were also studied...It was not significantly increased in HCC, but it was reduced by octreotide and was increased after UDCA. In this retrospective observational study, somatostatin and its analog octreotide have a significant effect on several growth factors involved in HCC pathogenesis.

P1, N=12, Recruiting, Children's Hospital Medical Center, Cincinnati

P2, N=300, Recruiting, Valenta Pharm JSC

P2/3, N=94, Not yet recruiting, Centre Hospitalier Universitaire De Montpellier

Furthermore, they acted together on the p38 mitogen-activated protein kinase (MAPK) signaling pathway, and the addition of the p38 inhibitor SB203580 partially inhibited the expression of p38MAPK. Thus, the combined action of these drugs protected the NVU.