siRNA-based therapy for overcoming drug resistance in human solid tumours; molecular and immunological approaches

Human Immunology, Год журнала: 2024, Номер 86(1), С. 111221 - 111221

Опубликована: Дек. 18, 2024

Язык: Английский

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An amphiregulin reporter mouse enables transcriptional and clonal expansion analysis of reparative lung Treg cells

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 28, 2024

Regulatory T (Treg) cells are known to play critical roles in tissue repair via provision of growth factors such as amphiregulin (Areg). Areg-producing Treg have previously been difficult study because an inability isolate live cells. In this report, we created a novel reporter mouse detect Areg expression (

Язык: Английский

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Salidroside may target PPARα to exert preventive and therapeutic activities on NASH

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Окт. 2, 2024

Background Salidroside (SDS), a phenylpropanoid glycoside, is an antioxidant component isolated from the traditional Chinese medicine Rhodiola rosea and has multifunctional bioactivities, particularly possessing potent hepatoprotective function. Non-alcoholic steatohepatitis (NASH) one of most prevalent chronic liver diseases worldwide, but it still lacks efficient drugs. This study aimed to assess preventive therapeutic effects SDS on NASH its underlying mechanisms in mouse model subjected methionine- choline-deficient (MCD) diet. Methods C57BL/6J mice were fed MCD diet induce NASH. During or after formation MCD-induced model, (24 mg/kg/day) was supplied as form for 4 weeks. The histopathological changes evaluated by H&E staining. Oil Red O staining Sirius used quantitatively determine lipid accumulation collagen fibers liver. Serum enzyme levels measured. morphology autophagic vesicles autophagosomes observed transmission electron microscopy (TEM), qRT-PCR Western blotting detect autophagy-related factor levels. Immunohistochemistry TUNEL evaluate apoptosis tissues. Flow cytometry composition immune cells. ELISA expression serum inflammatory factors. Transcript–proteome sequencing, molecular docking, qRT-PCR, performed explore mechanism target Results oral administration demonstrated comprehensive efficacy showed both promising vivo . could upregulate autophagy, downregulate apoptosis, rebalance immunity, alleviate inflammation exert anti-NASH properties. Finally, results transcript–proteome docking evaluation, experimental validation that might multiple through targeting PPARα. Conclusion Our findings revealed regulate autophagy regulating innate immunity adaptive alleviating prevention therapy via PPAR pathway, suggesting be potential drug future.

Язык: Английский

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A macrophage-smooth muscle cell axis influences vascular remodeling through activation of the EGFR pathway in giant cell arteritis

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 6, 2024

Abstract Background. The role of macrophages and vascular resident cells appears to be predominant in the pathophysiology giant cell arteritis (GCA). We investigated epithelial growth factor receptor (EGFR) signaling pathway, especially through its activation by heparin-binding epidermal (HB-EGF) and/or amphiregulin (AREG) this setting. Materials Methods. Serum samples temporal artery biopsies (TAB) were obtained from patients enrolled a prospective cohort systemic vasculitis. Human THP-1, monocytic line, human aortic smooth muscle (VSMC) used for vitro studies. Results. Using multiplex immunohistochemistry, TAB GCA showed higher expression AREG, HB-EGF, EGFR phospho-EGFR as compared control arteries. HB-EGF predominantly expressed macrophages, whereas phosphor-EGFR αSMA-positive media. Increased levels AREG found culture supernatants M1 M2 produced only HB-EFG. did not increase production pro-inflammatory cytokines THP-1 or but activated p38 MAPK pathway. transcriptomic Western blot analysis VSMC, induced proliferation enhanced interferon alpha gamma responses, Finally, increased both VSMC migration, which completely inhibited AG1478, an inhibitor. Conclusion. show that may play GCA, remodeling phase disease.

Язык: Английский

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Regulation goes awry in the liver

Nature reviews. Immunology, Год журнала: 2024, Номер 24(3), С. 158 - 158

Опубликована: Фев. 13, 2024

Язык: Английский

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