In CTD-ILD patients, serum CEA and CA 19-9 are elevated and can be indicators of disease severity. Moreover, serum CEA is a significant and independent predictor of survival.

Objective: Our aim was to investigate the effect of emodin on intestinal and lung injury induced by acute intestinal injury in rats and explore potential molecular mechanisms. Methods: Healthy male Sprague-Dawley (SD) rats were randomly divided into five groups (n=10, each group): normal group; saline group; acute intestinal injury model group; model + emodin group; model + NF-kB inhibitor pynolidine dithiocarbamate (PDTC) group. Histopathological changes of intestine/lung tissues were observed by H&E and TUNEL staining. Serum IKBα, p-IKBα, SP-A and TLR4 levels were examined using ELISA. RT-qPCR was performed to detect the mRNA expression levels of IKBα, SP-A and TLR4 in intestine/lung tissues. Furthermore, the protein expression levels of IKBα, p-IKBα, SP-A and TLR4 were detected by western blot. Results: The pathological injury of intestinal/lung tissues was remarkedly ameliorated in models treated with emodin and PDTC. Furthermore, the intestinal/lung injury scores were significantly decreased after emodin or PDTC treatment. TUNEL results showed that both emodin and PDTC treatment distinctly attenuated the apoptosis of intestine/lung tissues induced by acute intestinal injury. At the mRNA level, emodin significantly increased the expression levels of SP-A and decreased the expression levels of IKBα and TLR4 in intestine/lung tissues. According to ELISA and western blot, emodin remarkedly inhibited the expression of p-IKBα protein and elevated the expression of SP-A and TLR4 in serum and intestine/lung tissues induced by acute intestinal injury. Conclusion: Our findings suggested that emodin could protect against intestinal and lung injury induced by acute intestinal injury by modulating SP-A and TLR4/NF-κB pathway.

Ubiquitin C‐terminal hydrolase‐L3 (UCH‐L3) is a deubiquitinase that has a crucial role in oncogenesis. This study was aimed to explore the biological function of UCH‐L3 in non‐small cell lung cancer (NSCLC). Bioinformatics analysis was used to detect UCH‐L3 expression in NSCLC tissues and normal lung tissues, and to analyze the relationship between UCH‐L3 expression and survival of patients. qRT‐PCR and western blotting assays were used to detect UCH‐L3 expression in NSCLC tumor tissues and adjacent normal tissues. CCK‐8 assay was performed to examine the effect of UCH‐L3 on NSCLC cell proliferation. Flow cytometry assay was conducted to examine the effect of UCH‐L3 on NSCLC cell cycle and apoptosis. The expression of UCH‐L3 in NSCLC tissues was markedly higher than in normal lung tissues, and high expression of UCH‐L3 was positively associated with the poor survival of patients. UCH‐L3 knockdown significantly inhibited the proliferation of NSCLC cells, whereas UCH‐L3 overexpression had the opposite effect. Moreover, UCH‐L3 promoted NSCLC cells proliferation via accelerating cell cycle and inhibiting cell apoptosis. UCH‐L3 is upregulated in NSCLC and positively associated with the poor survival, and its expression contributes to NSCLC cell proliferation by accelerating cell cycle and inhibiting cell apoptosis.

Background. Acquired resistance occurred in the majority of nonsmall cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) therapy, and this may be related to the activation of the HIF-1 pathway. Therefore, we examined the influence of the hypoxia-inducible factor-1 (HIF-1) pathway inhibition on the sensitivity of HCC827 gefitinib-resistant (HCC827 GR) cells with MET amplification to gefitinib. Methods. We established HCC827 GR cell line with MET amplification and set four groups with different treatment. An MTT assay, a colony formation analysis, and a wound healing assay were performed to determine the sensitivity change of HCC827 GR cells after different treatments. HIF-1α, p-EGFR, and p-Met levels were detected with western blot. Correlations among HIF-1α, p-EGFR, and p-Met levels of HCC827 GR cells with different treatments were analyzed with Pearson’s correlation analysis. Results. HIF-1 inhibitor YC-1 enhanced the sensitivity of HCC827 GR cells to gefitinib. p-Met level was correlated with HIF-1α level, while there was no correlation between p-Met level and p-EGFR level. Conclusion. HIF-1 inhibitor YC-1 is able to reverse the acquired resistance of HCC827 GR to gefitinib, and the regulation of the HIF-1 pathway on MET may be one of the mechanisms.

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