Idiopathic pulmonary fibrosis (IPF) is a fatal disease with high mortality and limited effective therapy. Herein, we reported that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), used in depression and anxiety treatment, also exhibited therapeutic activities in IPF. Fluvoxamine inhibited cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), restrained the activation of their downstream targets, including PERK/ eIF2α/ c-Myc/ miR-9-5p/ TBPL1 and TBK1/ YAP/ JNK1/2/ Bnip3/ CaMKII/ cofilin signaling, thus attenuated the activation and migration of fibroblasts upon TGF-β1 challenge. Fluvoxamine dose-dependently improved pulmonary function, decreased the expression of inflammatory factors, reduced excessive production of extracellular matrix, and thus alleviated bleomycin (BLM)-induced lung fibrosis in mice. Moreover, fluvoxamine at a dose of 10 mg/ kg showed similar efficacy as pirfenidone (PFD) at a dose of 30 mg/kg in a mice model of lung fibrosis. In summary, our results suggest that fluvoxamine is an effective anti-fibrotic agent for IPF.

A novel sextuple interpenetrated copper-naphthalenediimide network based on adamantane-like cages has been constructed and demonstrates outstanding electron transport.

Acute lung injury (ALI), characterized by a severe inflammatory process, is a complex syndrome that can lead to multisystem organ failure. Fatty acid amide hydrolase (FAAH) and N-acylethanolamine acid amidase (NAAA) are two potential therapeutic targets for inflammation-related diseases. Herein, we identified carmofur, a 5-fluorouracil-releasing drug and clinically used as a chemotherapeutic agent, as a dual FAAH and NAAA inhibitor. In Raw264.7 macrophages, carmofur effectively reduced the mRNA expression of pro-inflammatory factors, including IL-1β, IL-6, iNOS, and TNF-α, and down-regulated signaling proteins of the nuclear transcription factor κB (NF-κB) pathway. Furthermore, carmofur significantly ameliorated the inflammatory responses and promoted resolution of pulmonary injury in lipopolysaccharide (LPS)-induced ALI mice. The pharmacological effects of carmofur were partially blocked by peroxisome proliferator-activated receptor-α (PPARα) antagonist MK886 and cannabinoid receptor 2 (CB2) antagonist SR144528, indicating that carmofur attenuated LPS-induced ALI in a PPARα- and CB2-dependent mechanism. Our study suggested that carmofur might be a novel therapeutic agent for ALI, and drug repurposing may provide us effective therapeutic strategies for ALI.

Six new silver-phenylethynide compounds, namely, [(AgCCPh)₄(AgCF₃SO₃)(DMSO)₂] (1), [(AgCCPh)(Ag₃PW₁₂O₄₀)(DMSO)₈] (2), [(AgCCPh)(Ag₃PMo₁₂O₄₀)(DMSO)₈] (3), [(AgCCPh)(Ag₄SiW₁₂O₄₀)(DMSO)₁₀] (4), [(AgCCPh)₈(Ag₄SiW₁₂O₄₀)(DMSO)₁₀] (5), and [(AgCCPh)₁₆(Ag₃PW₁₂O₄₀)(DMSO)₈(H₂O)₂] (6), have been synthesized and structurally characterized by X-ray crystallography. These compounds exhibit a coordinated silver column structure with OTf⁻/POM anions serving as counter-anions (1, 6), an infinite chain structure based on the coordinated Ag₄ aggregates and POM anions (2, 3) and a discrete molecular structure containing coordinated silver aggregates and POM anions (4, 5), respectively. The pure phases of 1–5 are obtained and identified. The antibacterial/antifungal activities of 1–5 are screened by the disk diffusion method against the bacteria strains Bacillus pumilus, Bacillus subtilis, Staphylococcus aureus and Escherichia coli and the fungi strains Aspergillus niger and Canidia albicans, and the MIC/MBC values are also measured. The cytotoxicity and biological toxicity test results showed that these compounds have low toxicity in both cells and animals.