interferon alpha 2b

Correction: Deubiquitinase USP35 restrains STING-mediated interferon signaling in ovarian cancer.

Zhang Jiawen J, Chen Yunfei Y, Chen Xianfei X, Zhang Wen W et al.

Rosavin alleviates COPD via inhibition of IL-17-enriched NET formation and NF-κB signaling.

Xiao Guanhua G, Li Jing J, Yuan Lu L, Huang Wenqi W et al.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and is characterized by persistent inflammation, microbiota dysbiosis, and excessive neutrophil extracellular trap (NET) formation. Rosavin, a natural phenylpropanoid glycoside, exhibits anti-inflammatory and immunomodulatory activities, but its therapeutic potential in COPD remains unclear. A COPD rat model was induced by intratracheal lipopolysaccharide instillation combined with chronic passive cigarette smoke exposure. Rosavin (50 or 100 mg/kg) or the NF-κB inhibitor BAY 11-7082 (3 mg/kg) was administered for treatment. Pulmonary function tests (FEV1/FVC, PEF, and airway resistance), histopathological evaluation (HE and PAS staining), bronchoalveolar lavage fluid (BALF) inflammatory cell counts, ELISA-based cytokine assays, and oxidative stress markers (MDA, MPO, and SOD) were systematically assessed. NET formation was evaluated using MPO-DNA ELISA, Western blotting, and immunofluorescence for CitH3 and MPO/IL-17 colocalization. In addition, lung microbiota composition was analyzed by 16 S rRNA gene sequencing. Cigarette smoke extract (CSE)-stimulated BEAS-2B cells were used to assess the direct effects of Rosavin on NF-κB activation in vitro. Rosavin significantly inhibited NF-κB activation, improved lung function, and reduced structural damage, oxidative stress, and inflammatory cytokines in COPD rats. It also suppressed NET formation, including IL-17-enriched NETs, by downregulating MPO, NE, and CitH3. In BEAS-2B cells, Rosavin similarly reduced CSE-induced NF-κB activation and cytokine release. Microbiota profiling showed decreased diversity and enrichment of Fusobacterium nucleatum in COPD rats, whereas Rosavin restored beneficial taxa such as Lactobacillus spp. BAY 11-7082 produced comparable effects, supporting NF-κB inhibition as a key mechanism. Rosavin ameliorates COPD-associated pathology through integrated mechanisms involving NF-κB inhibition, reduction of IL-17-enriched NET formation, and modulation of lung microbiota composition. These findings identify Rosavin as a promising multi-target therapeutic candidate for COPD.

Lost and found in translation: the value of the human imiquimod model.

Meijs Anouk C AC, van den Noort Juliette A JA, Assil Salma S, Klarenbeek Naomi B NB et al.

Topical imiquimod (IMQ), a Toll-like receptor (TLR) 7 agonist, induces transient cutaneous inflammation and is widely used in preclinical research as a 'psoriasis-like' mouse model. However, accumulating evidence indicates substantial divergence between IMQ-driven biology and human plaque psoriasis pathogenesis. To bridge this translational gap, we compare here the experimental conduct, readouts and mechanistic insights engaged by IMQ challenge in mice vs. healthy human participants. Importantly, molecular and cellular analyses indicate that IMQ predominantly activates interferon regulatory factor (IRF) signalling in humans, rather than NF-κB pathways as observed in animals. Moreover, differences in neutrophil response and complement activation were also identified. These discrepancies may reflect interspecies variation in TLR7 expression as well as methodological differences between the animal and human IMQ model. Despite certain limitations related to psoriasis translatability, the human IMQ model has demonstrated translational relevance in several early phase clinical trials. It represents a valuable tool for evaluating target engagement and characterizing downstream pharmacodynamic effects of novel compounds, particularly those targeting the TLR7-IRF-type I interferon axis. In conclusion, the human IMQ model can serve as valuable mechanistic model driving disease-related pathways, rather than as a proxy for plaque psoriasis disease biology. Fit-for-purpose benchmarking and method standardization are essential to maximize translational utility of the IMQ model.

Structural insights into histone mimicry by the small hepatitis delta antigen.

Hu Haiyun H, Lv Mengjiao M, Wang Xiaohui X, Shang Xinci X et al.

Hepatitis delta virus (HDV) is a satellite RNA virus that requires hepatitis B virus (HBV) for propagation but replicates its genome independently in the nucleus. The small form of the hepatitis delta antigen (S-HDAg) is essential for replication and is regulated by post-translational modifications. Acetylation at lysine 72 (K72ac) enables S-HDAg to interact with the bromodomain (BRD) of the host chromatin remodeler bromodomain adjacent to zinc finger domain protein 2B (BAZ2B) to promote viral replication. However, the structural basis for this interaction has remained elusive. Here, we provide structural and biophysical insights into this interaction through quantitative binding assays and X-ray crystallography. Isothermal titration calorimetry revealed that BRDs of BAZ2B and its close homolog BAZ2A bind to the viral peptide weakly, with BAZ2A-BRD exhibiting a modestly higher affinity. The crystal structure of BAZ2A-BRD in complex with the S-HDAg-K72ac peptide demonstrates an inverted binding orientation relative to canonical histone ligands, rationalizing the weak interaction. Mutagenesis studies confirmed the critical binding interface both in vitro and in cells. These findings elucidate the molecular mechanism by which HDV co-opts host BAZ2 bromodomains via a unique, weak-affinity interaction, providing a structural framework for understanding viral replication.