interferon alfa-2a (Proquiferon)

Correction: Postoperative adding-on phenomenon in Lenke 1A/B and 2A/B adolescent idiopathic scoliosis: risk factors and predictive index.

Zhang Hongqi H, Li Tao T, Zhang Gengming G, Deng Ang A et al.

Clean Synthesis of N-4-Alkylamino-7-chloroquinoline Cyclic Imides: Influence of Lipophilicity on Antibacterial and Ecotoxicological Properties.

Luz-Filho Agenor P AP, Silva Thais C TC, Silva Matheus B MB, Sousa Abraão P AP et al.

Motivated by the promising antimicrobial and ecotoxicological effects of 4-alkylamino-7-chloroquinoline and N-alkylphthalimide derivatives, these privileged nuclei were linked to investigate how lipophilicity influences antibacterial activity and ecotoxicity. For this purpose, seven 4-alkylamino-7-chloroquinolines (2a-g) were prepared, of which four were used as precursors (2a-d) and reacted with different anhydrides. Using a clean synthetic approach, 4-alkylamino-7-chloroquinoline-succinimides (3a-d) and -phthalimides (5a-d) were obtained in yields of 60%-99% after only filtration with distilled water. In vitro assays were performed to determine the minimum inhibitory/bactericidal concentration (MIC/MBC) against Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus mutans. Lipophilicity (log P) and toxicity were predicted using the pkCSM program. In vitro toxicity tests on Artemia salina larvae were used as an indicator of ecotoxicity. 4-Alkylamino-7-chloroquinolines (2b, 2f, 2g) revealed a moderate MIC of 156.25 µg·mL-1 against Gram-(-) and Gram-(+) bacteria, whose predicted toxicity does not pose a potential risk to human health. Results indicate a correlation between increased lipophilicity and higher ecotoxicity, where less lipophilic compounds were less toxic to A. salina (LC50 133.01-777.50 µg·mL-1) than 4-alkylamino-7-chloroquinoline-phthalimides, suggesting further investigation of their cytotoxicity.

IRF8 Suppresses Hepatocellular Carcinoma Progression Through LIAS-Dependent IFN Production and Cuproptosis Activation.

Zhu Li L, Hu Zhaoxia Z, Wu Bei B, Duan Meng M et al.

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. Cuproptosis is a novel form of regulated cell death closely linked to tumor progression. Although interferon regulatory factors (IRFs) exert tumor-suppressive effects in various cancers, its precise regulatory mechanisms concerning cuproptosis in HCC remain largely elusive. IRF8 expression was evaluated in clinical HCC specimens and cell lines. Gain- and loss-of-function assays were conducted. Underlying transcriptional mechanisms were elucidated using ChIP-qPCR and dual-luciferase reporter assays. Subcutaneous nude mouse xenograft models were utilized to validate in vivo phenotypes. IRF8 was significantly downregulated in HCC. IRF8 overexpression induced oxidative stress and cuproptosis, as evidenced by excessive intracellular copper accumulation, elevated reactive oxygen species (ROS), and lipid peroxidation. Mechanistically, IRF8 directly bound to the promoter region of lipoyl synthase (LIAS) to activate its transcription. Phenotypic rescue assays confirmed that LIAS is indispensable for IRF8-induced interferon (IFN-α/β) production, copper engorgement, and cuproptosis. Furthermore, in vivo xenograft models demonstrated that IRF8 profoundly impeded tumor growth, an effect that was effectively abrogated by LIAS silencing. IRF8 inhibits HCC progression by directly upregulating LIAS to instigate lethal cuproptosis and interferon responses. The IRF8/LIAS axis may serve as a potential mechanistic basis and candidate axis for developing HCC therapeutic strategies.

Cathepsin L potentiates autoimmunity by inhibiting lysosome-mediated STING degradation.

Xing Jia-Qing JQ, Zhang Zhi-Hao ZH, Guo Zeng-Lin ZL, Cai Hong H et al.

The stimulator of interferon genes (STING) orchestrates type I interferon (IFN) production in response to cytosolic DNA and plays essential roles in antiviral defense and autoimmune pathogenesis. The stability of STING determines the activation intensity of the pathway. Therefore, identifying proteins that govern its homeostatic regulation is needed. Here, we uncover the lysosomal protease cathepsin L (CTSL) as a critical stabilizer of STING in cells. CTSL deficiency selectively impairs STING-induced IFN responses without compromising overall lysosomal digestive function. Mechanistically, CTSL interacts with AP1B1 to prevent AP1B1-mediated lysosomal degradation of STING, thereby enhancing IFN signaling. Furthermore, CTSL expression is elevated in cells from systemic lupus erythematosus (SLE) patients and positively correlates with disease activity. Together, our findings establish an important role of CTSL in innate immunity by regulating STING homeostasis.