Background: Kawasaki disease (KD) is an immune vasculitis of unknown origin, characterized by transient inflammation. The activation of the cGAS-STING pathway, triggered by mitochondrial DNA (mtDNA) release, has been implicated in the onset of KD. However, its specific role in the progression of inflammation during KD's acute phase remains unclear. Methods: We measured mtDNA and 2’3’-cGAMP expression in KD patient serum using RT-qPCR and ELISA. A murine model of KD was induced by injecting Lactobacillus casei cell wall extract (LCWE), after which cGAS-STING pathway activation and inflammatory markers were assessed via immunohistochemistry, western blot, and RT-qPCR. Human umbilical vein endothelial cells (HUVECs) were treated with KD serum and modulators of the cGAS-STING pathway for comparative analysis. Mitochondrial function was evaluated using Mitosox staining, mPTP opening was quantified by fluorescence microscopy, and mitochondrial membrane potential (MMP) was determined with JC-1 staining. Results: KD patient serum exhibited increased mtDNA and 2’3’-cGAMP expression, with elevated levels of pathway-related proteins and inflammatory markers observed in both in vivo and in vitro models. TEM confirmed mitochondrial damage, and further studies demonstrated that inhibition of mPTP opening reduced mtDNA release, abrogated cGAS-STING pathway activation, and mitigated inflammation. Conclusion: These findings indicate that mtDNA released through the mPTP is a critical activator of the cGAS-STING pathway, contributing significantly to KD-associated inflammation. Targeting mtDNA release or the cGAS-STING pathway may offer novel therapeutic approaches for KD management.

Objectives: Pan-immune-inflammation value (PIV) is defined by the neutrophil, platelet, monocyte, and lymphocyte counts and is associated with immune-checkpoint inhibitor (ICI) therapy outcomes in advanced non-small cell lung cancer (aNSCLC). However, PIV is dynamic under therapy and its longitudinal assessment may help predict efficacy. This study investigated the impact of baseline PIV and its dynamics on ICI efficacy and its immune-related adverse events (irAEs). The study additionally attempted to understand the biological significance of PIV. Patients and methods: This retrospective study analyzed the clinical data of 269 consecutive patients with aNSCLC. PIV was calculated at baseline and at weeks 3–4 to determine its association with overall survival (OS), progression-free survival (PFS), and irAEs. Results: Results revealed that low baseline PIV was positively correlated with the incidence of irAEs. Moreover, a low PIV at baseline was significantly associated with a prolonged PFS (median PFS: 10 vs. 7 months, p = 0.0005) and OS (median OS: 29 vs. 21 months, p < 0.0001). When the PIV at baseline and weeks 3–4 was considered together, its low dynamics correlated with a higher incidence of irAEs (p = 0.001), a longer PFS (median PFS, 9 vs. 6 months, p = 0.012), and a longer OS (median OS; 28 vs. 21 months, p = 0.002). Conclusion: Thus, PIV at baseline and its dynamics are novel and potent predictors of irAEs, PFS, and OS in patients with aNSCLC receiving immunotherapy. Moreover, the PIV dynamics may be an effective, novel surrogate marker to dynamically observe the efficacy of immunotherapy.

Lysophospholipase1 (LYPLA1) also known as acyl‑protein thioesterase1 (APT1) belongs to the superfamily of α/β hydrolase. It has been found to have the properties of a homodimer by manifesting depalmitoylation as well as lysophospholipase activity. LYPLAs are under the control of both microRNAs, miR‑138 and miR‑424. They were observed to be significantly overexpressed in chronic lymphocytic leukemia cells. To date, LYPLAs are the sole enzymes recognized to activate depalmitoylation. In this study, we provide the expression pattern of LYPLA1 in non‑small cell lung cancer (NSCLC) using four different NSCLC cell lines. Western blot analysis and RT‑PCR were performed to detect the protein expression and mRNA expression of LYPLA1 in NSCLC cell lines. We detected the highest LYPLA1 protein expression level in SPC‑A‑1 cells followed by A549 cells, and the highest LYPLA1 mRNA expression level was detected in the SPC‑A‑1 cells followed by the H1299 cell line. We found that suppression of LYPLA1 expression using small‑interfering RNA significantly inhibited proliferation, migration and invasion of the LYPLA1‑transfected NSCLC cells. Furthermore, we explored the involvement of LYPLA1 in the regulation of epithelial‑mesenchymal transition (EMT). The epithelial marker E‑cadherin was significantly increased, while mesenchymal markers N‑cadherin, vimentin and SNAIL were markedly decreased in the LYPLA1‑silenced cells. Collectively the results of the present study suggest that the LYPLA1 gene plays a tumor‑promotor role in NSCLC cells in vitro.