Chem Biodivers. 2026 Oct;23(10):e71778. doi: 10.1002/cbdv.71778.

ABSTRACT

Pancreatic cancer has a dismal prognosis and limited therapeutic options, highlighting an urgent need for effective treatments. Sophoricoside (SOP), a natural isoflavone glycoside, has exhibited anticancer activities in multiple malignancies, including lung cancer, glioblastoma, and hepatocellular carcinoma. We combined cellular assays, network pharmacology, machine learning, and multi-omics to investigate SOP's effects. SOP-inhibited proliferation of MIA PaCa-2, SW1990, and PANC-1 cells dose-dependently. Network pharmacology revealed 85 overlapping targets enriched in MAPK, apoptosis, and PD-L1/PD-1 pathways. Machine learning and differential expression identified PTPN1 as the core target. PTPN1 was markedly upregulated in pancreatic adenocarcinoma, and its high expression correlated with poor survival and immune infiltration. Functional enrichment linked PTPN1 to TGF-β, VEGF, and metabolic reprogramming. Molecular docking suggested a possible binding mode between SOP and PTPN1, involving four predicted hydrogen bonds. SOP reduced PTPN1 mRNA, and PTPN1 knockdown phenocopied SOP's antiproliferative effect with no additivity upon combination. Collectively, this first report demonstrates that SOP restrains pancreatic cancer cell proliferation, with PTPN1 identified as a key functionally required downstream mediator based on integrative computational and functional evidence. This work offers an integrated strategy for mechanistic exploration and highlights PTPN1 as a promising therapeutic biomarker and target for pancreatic cancer.

PMID:42814531 | PMC:PMC13626263 | DOI:10.1002/cbdv.71778

Chem Biodivers. 2026 Oct;23(10):e71778. doi: 10.1002/cbdv.71778.

ABSTRACT

Pancreatic cancer has a dismal prognosis and limited therapeutic options, highlighting an urgent need for effective treatments. Sophoricoside (SOP), a natural isoflavone glycoside, has exhibited anticancer activities in multiple malignancies, including lung cancer, glioblastoma, and hepatocellular carcinoma. We combined cellular assays, network pharmacology, machine learning, and multi-omics to investigate SOP's effects. SOP-inhibited proliferation of MIA PaCa-2, SW1990, and PANC-1 cells dose-dependently. Network pharmacology revealed 85 overlapping targets enriched in MAPK, apoptosis, and PD-L1/PD-1 pathways. Machine learning and differential expression identified PTPN1 as the core target. PTPN1 was markedly upregulated in pancreatic adenocarcinoma, and its high expression correlated with poor survival and immune infiltration. Functional enrichment linked PTPN1 to TGF-β, VEGF, and metabolic reprogramming. Molecular docking suggested a possible binding mode between SOP and PTPN1, involving four predicted hydrogen bonds. SOP reduced PTPN1 mRNA, and PTPN1 knockdown phenocopied SOP's antiproliferative effect with no additivity upon combination. Collectively, this first report demonstrates that SOP restrains pancreatic cancer cell proliferation, with PTPN1 identified as a key functionally required downstream mediator based on integrative computational and functional evidence. This work offers an integrated strategy for mechanistic exploration and highlights PTPN1 as a promising therapeutic biomarker and target for pancreatic cancer.

PMID:42814531 | PMC:PMC13626263 | DOI:10.1002/cbdv.71778

Gut. 2026 Feb 9;75(3):576-587. doi: 10.1136/gutjnl-2025-337506.

ABSTRACT

BACKGROUND: Current guidelines recommend a two-step approach for risk stratification of metabolic dysfunction-associated steatotic liver disease (MASLD), starting with Fibrosis-4 index (FIB-4) followed by liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE).

OBJECTIVE: To evaluate this approach for predicting advanced fibrosis and liver-related events (LREs) in patients with type 2 diabetes (T2D).

DESIGN: A prospective liver biopsy cohort of T2D patients with histologically confirmed MASLD from seven centres in China was used to assess diagnostic performance for advanced fibrosis. The international VCTE-Prognosis cohort, including T2D patients with MASLD who underwent VCTE at 16 centres in the USA, Europe and Asia, with longitudinal follow-up, was used to assess LREs, defined as hepatic decompensation or hepatocellular carcinoma.

RESULTS: 4781 participants were included. In the liver biopsy cohort (n=352; 22.2% with advanced fibrosis), applying LSM thresholds of <8 kPa and >12 kPa after FIB-4 classified patients into 63.4% low-risk, 9.4% intermediate-risk and 27.3% high-risk, with a correct classification rate of 71%. In the VCTE-Prognosis cohort (n=4429; median follow-up 51.3 (IQR 27.4-70.7) months), 140 (3.2%) patients developed LREs (110 (2.5%) with hepatic decompensation and 59 (1.3%) with hepatocellular carcinoma). The two-step approach classified 72.6%, 6.8% and 20.6% of patients into low-risk, intermediate-risk and high-risk groups, with corresponding 5-year cumulative LRE incidences of 0.7%, 0.9% and 11.8%. Refining classification of intermediate FIB-4 patients using LSM <10 kPa (low-risk) and >15 kPa (high-risk) reduced the intermediate-risk group to 5.6% while preserving predictive accuracy.

CONCLUSION: The non-invasive two-step approach of FIB-4 followed by LSM effectively stratifies MASLD-related advanced fibrosis and LREs risk in T2D. Applying LSM cut-offs of 10 and 15 kPa further optimises risk stratification for future LREs.

PMID:41911049 | DOI:10.1136/gutjnl-2025-337506