The effect of RT (8 and 3 × 8 Gy) on Interferon beta (IFNβ), IFN-stimulated genes (ISGs), and HLA-class-I expression in combination with IFN-type-I-response inhibitors (Ruxolitinib, Tofacitinib, Amlexanox) targeting the JAK and TBK1 was studied with Flow cytometry and RT-PCR. The current study supports the theory that baseline autophagy, RT-induced autophagy blockage, and IFN-type-I response enhancement define the HLA-class-I levels in NSCLC cells. This complex interplay emerges as a promising target for the development of radio-vaccination strategies to enhance the efficacy of radio-immunotherapy.

Flow cytometric analysis indicated a significant decrease in M2 macrophages (F4/80+CD206+) in the intervention group, with no substantial change observed in the proportion of M1 macrophages (F4/80+CD86+). Combined administration of amlexanox and anti-MCP-1 mAb inhibited tumor cell proliferation, promoted apoptosis, and reduced infiltration of tumor-associated M2 macrophages, thereby contributing to suppression of tumor progression in the LLC murine model.

The IKBKE-inhibitor Amlexanox, clinically utilized for aphthous ulcers, as well as the MAPK8 inhibitor JNK-IN-8, reinstalled the DCIS-like phenotype of breast cancer cells on high matrix stiffness. This suggests that IKBKE and/or MAPK8 inhibitors could enhance the arsenal of treatments to prevent or treat breast cancer.

Mechanistically, TBK1 deletion or inhibition by amlexanox or GSK8612 reduced the expression of the transcription factor interferon-regulatory factor (IRF)4 and increased the level of IRF5 activation in macrophages stimulated with M-CSF, leading to an M1-like profile with highly proinflammatory factors. IRF5 deletion reversed the effect of TBK1 inhibition on M-CSF-mediated macrophage polarization. Our findings suggest that TBK1 contributes to the regulation of macrophage polarization in response to M-CSF stimulation partly through the IRF5/IRF4 axis.

In conclusion, our study demonstrates that simply inhibiting TBK1 in all immune cells is not effective for the treatment of colitis. Further investigation the anti-inflammatory mechanism of ALX on dendritic cells and macrophages may provide a new strategy for the treatment of IBD.

The importance serpin E2 is clear from its involvement in numerous physiological and pathological processes. In this review, we summarize the structural characteristics of the Serpin E2 gene and protein, as well as its roles physiology and disease.

In vitro studies revealed that SERPINE2 knockdown significantly reduced cell proliferation, migration, and invasion in OSCC cell lines. This study suggests that SERPINE2 may serve as a prognostic biomarker and potential therapeutic target for oral cancer.

P2, N=7, Terminated, University of Michigan | N=15 --> 7 | Suspended --> Terminated; Due to limited funding, trial was suspended, intending to restart with additional funds; then preliminary results were obtained, and research moved on to placebo controlled trial. Results for both have been published.

Overall, the data from this study suggests that targeting the LTB4/Ltb4r1 axis in highly inflammatory and pro-fibrotic conditions of chronic liver disease should be considered with caution.

IKBKE can activate AKT independent of PI3K by directly phosphorylating AKT Ser473 and Thr308, thus increasing the phosphorylation of FOXO3a. Phosphorylated FOXO3a promoted its ubiquitin degradation, and inhibited its transportation into the nucleus, causing radioresistance in glioblastoma. IKBKE inhibitor Amlexanox can pass through the blood-brain barrier and increase the radiosensitivity of intracranial tumor cells.