Interleukin-36 receptor antagonist alleviates airway inflammation in asthma via inhibiting the activation of Interleukin-36 pathway.

BACKGROUNDS: Asthma is characterized as an inflammatory disorder in the respiratory system with increasing tendency. Most of the asthma patients suffered from the disease since childhood. Thus, developing novel therapeutic targets of pediatric asthma is necessary. Here, we conducted the present study to investigate the effects of IL-36RN (Interleukin-36 receptor antagonist), a newly identified anti-inflammatory factor, on asthma. METHODS: Sixty asthmatic children (30 moderate and 30 mild) were recruited. The levels of IL-36RN in peripheral blood mononuclear cells (PBMCs), serum and induced sputum (IS) samples from asthma patients and healthy controls (HCs) were measured by qPCR and ELISA. The anti-inflammatory effects of IL-36RN were determined in vitro and potential therapeutic effect on asthma was evaluated in the mouse model of asthma. RESULTS: The mRNA and protein levels of IL-36RN were significant down-regulated in asthmatics than HCs. The IL-36RN significantly suppressed the expression of pro-inflammatory factors in PBMCs and sputum cells from asthma patients in vitro. And delivering IL-36RN into the mouse model of asthma showed disease alleviation. Pathway analysis showed that the IL-36RN may alleviate airway inflammation in asthma through suppressing the activation of IL-36 pathway. CONCLUSION: Our data here indicated that IL-36RN may alleviate airway inflammation in asthma through suppressing the activation of IL-36 pathway.

One-stop radiotherapeutic targeting of primary and distant osteosarcoma to inhibit cancer progression and metastasis using 2DG-grafted graphene quantum dots.

The application of radiotherapy (RT) to treat osteosarcoma (OS) has been limited, but this is starting to change as the ability to target radiation energy to niches improves. Furthermore, lung cancer from highly metastatic OS is a major cause of death, so it is critical to explore new strategies to tackle metastasis. In this study, we designed a nanoscale radiosensitizer by grafting 2-deoxy-d-glucose (2DG) onto graphene quantum dots (GQD) to achieve OS targeting and boost RT efficacy. Combining the use of 2DG-grafted GQDs (2DG-g-GQD) with RT produced a significant increase in oxidative stress response and DNA damage in the 143B OS cell line compared with RT alone. Moreover, 2DG-g-GQDs selectively associated with 143B cells, and demonstrated the inhibition of migration in a scratch assay. We also demonstrated remarkable improvement in their ability to inhibit tumour progression and lung metastasis in an OS xenograft mouse model. Our results show that the use of 2DG-g-GQDs as OS-targeting radiosensitizers improves their therapeutic outcome and exhibits potential for use in low-dose precision RT for OS.