Comb Chem High Throughput Screen. 2026 Mar 11. doi: 10.2174/0113862073398293251205055042. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aimed to investigate the protective effects of Siji Kangbingdu Mixture (SKM) against acute lung injury (ALI) in mice and to elucidate its underlying mechanisms.

METHODS: ALI was induced in Kunming mice via intranasal administration of LPS (5 mg/kg), followed by oral SKM treatment for 7 days. Lung wet-to-dry (W/D) ratio, histopathology, multiomics analysis, and network pharmacology were performed. Key targets and pathways were identified through dynamic KEGG analysis and validated by Western blotting.

RESULTS: SKM treatment ameliorated alveolar hemorrhage, alveolar wall disruption, septal thickening, edema, and inflammatory cell infiltration. Integrated multi-omics analysis revealed that SKM primarily modulated the Ras signaling pathway, reducing the protein expression of Phospho- MEK1/2, Raf1, Phospho-ERK1/2, and RASH/RASK/RASN, thereby contributing to the treatment of ALI.

DISCUSSION: SKM alleviated LPS-induced ALI in mice by inhibiting the Ras pathway, highlighting the pathway's role in ALI pathogenesis. However, due to limitations of the animal model and incomplete validation, further studies combining clinical research and in vitro experiments are needed to confirm its efficacy and mechanism.

CONCLUSIONS: SKM shows potential to ameliorate ALI by suppressing inflammatory responses and reducing local tissue fibrosis. The combination of metabolomics, transcriptomics, and network pharmacology elucidated its mechanism, while Western blot analysis suggested that its therapeutic effect is associated with downregulation of the Ras signaling pathway.

PMID:41830142 | DOI:10.2174/0113862073398293251205055042

Comb Chem High Throughput Screen. 2026 Mar 11. doi: 10.2174/0113862073398293251205055042. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aimed to investigate the protective effects of Siji Kangbingdu Mixture (SKM) against acute lung injury (ALI) in mice and to elucidate its underlying mechanisms.

METHODS: ALI was induced in Kunming mice via intranasal administration of LPS (5 mg/kg), followed by oral SKM treatment for 7 days. Lung wet-to-dry (W/D) ratio, histopathology, multiomics analysis, and network pharmacology were performed. Key targets and pathways were identified through dynamic KEGG analysis and validated by Western blotting.

RESULTS: SKM treatment ameliorated alveolar hemorrhage, alveolar wall disruption, septal thickening, edema, and inflammatory cell infiltration. Integrated multi-omics analysis revealed that SKM primarily modulated the Ras signaling pathway, reducing the protein expression of Phospho- MEK1/2, Raf1, Phospho-ERK1/2, and RASH/RASK/RASN, thereby contributing to the treatment of ALI.

DISCUSSION: SKM alleviated LPS-induced ALI in mice by inhibiting the Ras pathway, highlighting the pathway's role in ALI pathogenesis. However, due to limitations of the animal model and incomplete validation, further studies combining clinical research and in vitro experiments are needed to confirm its efficacy and mechanism.

CONCLUSIONS: SKM shows potential to ameliorate ALI by suppressing inflammatory responses and reducing local tissue fibrosis. The combination of metabolomics, transcriptomics, and network pharmacology elucidated its mechanism, while Western blot analysis suggested that its therapeutic effect is associated with downregulation of the Ras signaling pathway.

PMID:41830142 | DOI:10.2174/0113862073398293251205055042

FASEB J. 2026 Mar 31;40(6):e71634. doi: 10.1096/fj.202503587R.

ABSTRACT

Gastric cancer (GC) is a leading cause of cancer-related deaths and has high recurrence rate. Although fibronectin domain-containing protein 1 (FNDC1) is implicated in GC progression, its molecular mechanisms remain unclear. Multi-omics analyses (TCGA, GEO datasets) were used to assess FNDC1 expression and clinical correlation. In vitro (cell proliferation, invasion, EMT markers) and in vivo (xenograft) experiments, combined with molecular assays (Co-IP, WB, ChIP), explored FNDC1's function and mechanism. FNDC1 was significantly upregulated in GC, correlating with advanced clinicopathological features and poor prognosis. Knockdown of FNDC1 suppressed GC cell proliferation, invasion, and metastasis by inhibiting EMT and Wnt/β-catenin signaling. Mechanistically, FNDC1 competitively bound the WD5 domain (residues 224-254) of Gβ2, disrupting Gβγ-Dvl1 interaction. This prevented Dvl1 degradation, promoted Axin1 ubiquitination, and destabilized the β-catenin-destruction complex (GSK3 β-APC-Axin1), leading to β-catenin accumulation and Wnt pathway activation. FNDC1 drives GC malignancy by targeting the Gβ2-Dvl1 axis to activate Wnt/β-catenin signaling, suggesting FNDC1 as a novel prognostic biomarker and therapeutic target.

PMID:41808415 | PMC:PMC12976582 | DOI:10.1096/fj.202503587R