Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by aberrant fibroblast activation and excessive extracellular matrix accumulation, predominantly collagen, leading to irreversible lung remodeling. Sinigrin (SNG), a naturally occurring glucosinolate with reported anti-inflammatory and antioxidant activities, has not been investigated in the context of pulmonary fibrosis. In the present study, we evaluated the therapeutic activity of SNG using complementary in vitro and in vivo models of IPF. In the current investigation, inflammatory responses were induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages and precision-cut lung slices (PCLS), whereas fibrotic activation was elicited by TGF-β in LL29, DHLF cells, and PCLS. Treatment with sinigrin and dexamethasone significantly suppressed LPS-induced inflammatory mediators (IL-6, TNF-α, IL-1β, CCL2, MMP-9, and COX-2). In TGF-β-stimulated fibroblasts/PCLS, SNG and pirfenidone markedly attenuated collagen accumulation and downregulated the expression of key fibrotic markers (FN-1, α-SMA, TIMP-1, TIMP-3, COL1α1, and COL3α1). SNG administration in a bleomycin-induced pulmonary fibrosis mouse model significantly improved body weight, survival rate, and pulmonary index. Histopathological analyses revealed reduced collagen deposition and lowered Ashcroft scores, accompanied by decreased oxidative stress and improved lung function in SNG treatment compared to BLM and PFD groups. Consistently, gene and protein expression analyses demonstrated that SNG dose-dependently attenuated the bleomycin-induced inflammatory and fibrotic marker expression. Further mechanistic investigations, including an AMPK siRNA-based approach, demonstrated that SNG exerts its anti-inflammatory and antifibrotic effects partly through activation of AMPK signaling. Collectively, these findings suggest that SNG may represent a therapeutic candidate for the treatment of IPF.

Sepsis is marked by dysregulated inflammation and coagulopathy, with macrophages playing a central role. However, the molecular mechanisms linking macrophage dysfunction to sepsis-associated coagulopathy remain unclear. This study investigated the role of the E3 ubiquitin ligase Peli1 in sepsis progression and its downstream mechanism. Public scRNA-seq data from sepsis patients were analyzed to identify Peli1-associated immune signatures. Peli1 expression was validated in monocytes from sepsis patients and in CLP-induced septic mice. Peli1-deficient iBMDMs and myeloid cell-specific Peli1-deficient mice were used to assess its functional role. Transcriptomic profiling (RNA-seq), RT-qPCR, Western blotting, cycloheximide (CHX) chase assays, and co-immunoprecipitation (Co-IP) assays were performed to investigate the downstream molecular mechanisms and post-translational modifications. Peli1 was highly enriched in monocytes from fatal sepsis cases and markedly upregulated in monocytes from septic patients and CLP-induced septic mice. Peli1 deficiency attenuated macrophage inflammatory activation, improved platelet aggregation abnormalities, and enhanced survival in septic mice. Mechanistically, Lipg was identified as a crucial downstream target of Peli1 from transcriptomic analysis. Western blot and RT-qPCR validation confirmed that Peli1 predominantly regulated Lipg protein abundance through a post-transcriptional or post-translational mechanism, particularly under LPS-stimulated conditions. Peli1 was detected in the Lipg-immunoprecipitated complex, suggesting an association between Peli1 and Lipg. Further biochemical mapping revealed that Peli1 facilitated polyubiquitination specifically at the critical KR2 residue of Lipg to maintain its stability and shield it from proteasomal degradation. Ectopic restoration of Lipg successfully reversed the anti-inflammatory phenotypes and blunted cytokine production caused by Peli1 deficiency. Peli1 promoted sepsis-induced hyper-inflammation and coagulopathy by post-translationally maintaining Lipg stability in macrophages via site-specific ubiquitination. Target disruption of the Peli1-Lipg axis represents a promising therapeutic avenue to attenuate detrimental inflammation and immunothrombotic responses during sepsis.

Peri-extubation dexamethasone is used to prevent post-extubation upper airway obstruction in critically ill children, but pediatric randomized trials differ substantially in population selection, dosing, timing, and outcome definitions. We systematically reviewed randomized controlled trials evaluating peri-extubation dexamethasone in mechanically ventilated children. PubMed/MEDLINE, Scopus, and Web of Science were searched from inception to June 22, 2026. Nine trials randomized 1,063 children, with 949 included in reported analyses. Because comparator architecture, dexamethasone exposure, extubation context, outcome constructs, and follow-up windows were not clinically comparable, findings were synthesized narratively rather than pooled. Among placebo-controlled trials with interpretable pairwise binary airway outcomes, no trial provided statistically significant evidence of a reduction in the principal airway obstruction outcome. A 24-hour versus 6-hour regimen comparison reported less clinically significant airway obstruction with the 24-hour regimen, but the groups also differed in pre-extubation dose count and cumulative exposure, preventing attribution to timing alone. A low-dose versus high-dose trial did not establish non-inferiority of the lower-dose regimen. Reintubation outcomes showed no consistent treatment effect and were limited by imprecision and variable attribution. Adverse event ascertainment was limited. Seven trials raised some concerns, and two were at high overall risk of bias. Current randomized evidence does not define a single optimal peri-extubation dexamethasone regimen. Standardized eligibility criteria, explicit reporting of actual pre-extubation exposure, consistent airway outcome definitions, and prospective attribution of reintubation are needed before an optimal prophylactic strategy can be established.

A phytochemical investigation of Artemisia nujianensis resulted in the isolation of fifteen compounds, comprising two eudesmane-type (1 and 5), two germacrene-type (2 and 3), and five guaiane-type (4 and 6-9) sesquiterpene lactones, together with four polyacetylenes (10-13) and two thiophene-containing acetylenes (14 and 15). Among these, four sesquiterpene lactones, artenujianenolides A-D (1-4), and one linear polyacetylene, artenujianenol A (10), are previously undescribed. Their structures were established through extensive spectroscopic analysis (1D and 2D NMR, HRESIMS) combined with quantum chemical calculations. In anti-inflammatory activity assays, compounds 1, 2, 5, 8, and 13 significantly inhibited nitric oxide (NO) production in LPS-stimulated RAW264.7 macrophages, with IC50 values in the range of 2.49-7.52 μM, compared with the positive control dexamethasone (IC50 = 0.21 ± 0.01 μM). These results not only enrich the structural diversity of the genus Artemisia and broaden the chemical space of sesquiterpene lactones and acetylenes, but also offer promising lead scaffolds for the development of anti-inflammatory agents.