Nat Commun. 2026 Aug 7;17(1):9491. doi: 10.1038/s41467-026-76495-3.

ABSTRACT

Cancer-associated fibroblasts comprise diverse functionally distinct cellular subsets, with certain subpopulations exerting pivotal influence in shaping the pancreatic cancer immune microenvironment. Here we show that Lin28b⁺ cancer-associated fibroblasts contribute to establishing an immunologically cold tumor microenvironment in pancreatic ductal adenocarcinoma. Mechanistically, Lin28b directly binds to STING mRNA and promotes its degradation, thereby suppressing STING expression and downstream type I interferon signaling. Loss of Lin28b in cancer-associated fibroblasts activates the cGAS-STING-interferon signaling cascade, enhancing dendritic cell antigen presentation and CD8⁺ T cell cytotoxic function. Importantly, genetic inhibition of Lin28b in cancer-associated fibroblasts enhances sensitivity to anti-PD-L1 immune checkpoint blockade therapy. These findings reveal that targeting the Lin28b-STING axis represents a promising therapeutic strategy for overcoming the intrinsic resistance of pancreatic ductal adenocarcinoma to immunotherapy.

PMID:42693143 | PMC:PMC13542369 | DOI:10.1038/s41467-026-76495-3

J Ethnopharmacol. 2026 Apr 4:121650. doi: 10.1016/j.jep.2026.121650. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Madeng'ai (MDA) is a traditional medicinal plant of the Dong ethnic group. Its roots have been widely used in folk medicine for clearing heat and removing toxins, alleviating swelling and relieving pain, dispersing blood stasis and arresting bleeding, as well as promoting wound healing. It is taxonomically classified as a variety of Potentilla freyniana Bornm.

AIM OF THE STUDY: Acute lung injury (ALI) is a life-threatening pulmonary disorder associated with high mortality, underscoring the urgent need to explore novel therapeutic strategies. This study aimed to evaluate the protective effects of the ethyl acetate fraction of MDA (MEA) against LPS-induced ALI in mice and to investigate its underlying mechanisms.

MATERIALS AND METHODS: LC-MS/MS was employed to tentatively identify the bioactive components of MEA. A mouse model of ALI was established by LPS induction. The protective effects of MEA were evaluated through assessments of lung histopathology, inflammatory cytokine levels, and oxidative stress markers. The underlying mechanisms were systematically investigated by integrating transcriptomics, metabolomics, network pharmacology, molecular docking, and Western blotting.

RESULTS: MEA significantly attenuated LPS-induced pulmonary pathological lesions, pulmonary edema, and excessive inflammatory responses in ALI mice. Comprehensive bioinformatics analyses predicted potential mechanisms involving oxidative stress and the regulation of metabolic pathways. Experimental validation via Western blotting confirmed that MEA inhibited TLR4-mediated inflammatory signaling and modulated the PI3K/AKT pathway, thereby exerting multi-pathway protective effects against ALI.

CONCLUSIONS: Collectively, this study confirms that MEA, as a traditional herbal extract, holds potential as an adjuvant therapeutic agent for ALI, providing experimental evidence for the modernization and development of ethnic medicines.

PMID:41941987 | DOI:10.1016/j.jep.2026.121650

J Ethnopharmacol. 2026 Apr 4:121650. doi: 10.1016/j.jep.2026.121650. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Madeng'ai (MDA) is a traditional medicinal plant of the Dong ethnic group. Its roots have been widely used in folk medicine for clearing heat and removing toxins, alleviating swelling and relieving pain, dispersing blood stasis and arresting bleeding, as well as promoting wound healing. It is taxonomically classified as a variety of Potentilla freyniana Bornm.

AIM OF THE STUDY: Acute lung injury (ALI) is a life-threatening pulmonary disorder associated with high mortality, underscoring the urgent need to explore novel therapeutic strategies. This study aimed to evaluate the protective effects of the ethyl acetate fraction of MDA (MEA) against LPS-induced ALI in mice and to investigate its underlying mechanisms.

MATERIALS AND METHODS: LC-MS/MS was employed to tentatively identify the bioactive components of MEA. A mouse model of ALI was established by LPS induction. The protective effects of MEA were evaluated through assessments of lung histopathology, inflammatory cytokine levels, and oxidative stress markers. The underlying mechanisms were systematically investigated by integrating transcriptomics, metabolomics, network pharmacology, molecular docking, and Western blotting.

RESULTS: MEA significantly attenuated LPS-induced pulmonary pathological lesions, pulmonary edema, and excessive inflammatory responses in ALI mice. Comprehensive bioinformatics analyses predicted potential mechanisms involving oxidative stress and the regulation of metabolic pathways. Experimental validation via Western blotting confirmed that MEA inhibited TLR4-mediated inflammatory signaling and modulated the PI3K/AKT pathway, thereby exerting multi-pathway protective effects against ALI.

CONCLUSIONS: Collectively, this study confirms that MEA, as a traditional herbal extract, holds potential as an adjuvant therapeutic agent for ALI, providing experimental evidence for the modernization and development of ethnic medicines.

PMID:41941987 | DOI:10.1016/j.jep.2026.121650