NRSN2 promotes the malignant behavior of HPV-transfected laryngeal carcinoma cells through AMPK/ULK1 pathway mediated autophagy activation.

Neurensin-2 (NRSN2) performs a pro-carcinogenic function in multiple cancers. However, the function of NRSN2 in HPV-infected laryngeal carcinoma (LC) remains unclear. HPV transfection was performed in LC cells. The mRNA and protein levels were monitored using RT-qPCR, immunoblotting, and IF. Cell viability and proliferation were found using the CCK-8 assay and Edu staining. Cell invasion, migration, and apoptosis were probed using the Transwell, wound healing, and flow cytometry, respectively. The autophagosome was observed using TEM. NRSN2 was overexpressed in HPV-transfected LC cells. Inhibition of NRSN2 restrained the autophagy and malignant behavior of HPV-transfected LC cells. Meanwhile, the inhibition of AMPK/ULK1 pathway limited the increased autophagy of HPV-transfected LC cells caused by NRSN2 overexpression. Furthermore, NRSN2 knockdown inhibits autophagy by suppressing AMPK/ULK1 pathway, thereby restraining the malignant behavior of HPV-transfected LC cells. Our research confirmed that HPV transfection increased the autophagy and malignant behavior of LC cells by regulating the NRSN2-mediated activation of the AMPK/ULK1 pathway, offering a new target for cure of LC.

Zinc supplement reduces allergic responses through modulating the p38 MAPK pathway activation in an allergic rhinitis mouse model.

BACKGROUND: Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa mediated by a variety of inflammatory mediators. Zinc (Zn) is one of the main essential trace elements in the human body and plays a variety of biological functions including the inhibition of inflammatory responses. This study aimed to investigate the effects and mechanism of Zn on the ovalbumin (OVA)-induced AR mouse model. METHOD: In this study, we established a model of AR by treating mice with OVA after feeding them with different doses of Zn. ELISA, real-time quantitative PCR, western blot and immunohistochemistry were used to detect the protein expression and mRNA transcription level of IgE, inflammatory cytokines and p38, respectively. RESULTS: The authors identified that immunoglobulin E concentrations were significantly higher in the Zn-deficient mice than in the Zn-normal group; Zn supplementation significantly reversed the increase in IgE concentrations caused by Zn deficiency. The increased concentrations of interleukin-6 and tumor necrosis factor-α in serum caused by Zn deficiency were reduced by Zn supplementation. The study further found that Zn deficiency could significantly increase the expression and activity of the p38 MAPK protein, while its levels were significantly decreased after Zn supplementation. The role of Zn supplement in the inflammatory response induced by Zn deficiency was verified by Zn-deficient mice with a p38 pathway inhibitor (SB203580), and it was observed that the elevated concentrations of IgE and inflammatory cytokines induced by Zn deficiency could be significantly reversed. CONCLUSION: Our data indicated that Zn exerted anti-allergic and anti-inflammatory effects by regulating the p38 MAPK activation in the AR mouse model. The findings provided evidence that Zn might be beneficial in regulating AR.