BackgroundInterleukin-27 (IL-27) is a multifunctional cytokine with both pro-inflammatory and immunoregulatory functions. At present, the role of IL-27 in pulmonary fibrosis remains unknown.MethodsIn this study, we observed the expression of IL-27/IL-27R in a mouse model of bleomycin (BLM)-induced pulmonary fibrosis. We verified the role of IL-27 using hematoxylin and eosin as well as Masson’s staining methods and measuring the content of hydroxyproline as well as collagen I and III. We assessed the differentiation of T lymphocytes in the spleen and measured the concentration of cytokines in bronchoalveolar lavage fluid (BALF) and the expression level of relevant proteins in the JAK/STAT and TGF-ß/Smad signaling pathways in lung tissue.ResultsIncreased IL-27 expression in BLM-induced pulmonary fibrosis was noted. IL-27 treatment may alleviate pulmonary fibrosis and increase the survival of mice. IL-27 inhibited the development of CD4+ IL-17+, CD4+ IL-4+ T, and CD4+ Foxp3+ cells and the secretion of IL-17, IL-4, IL-6, and TGF-ß. IL-27 induced the production of CD4+ IL-10+ and CD4+ INF-γ+ T cells. IL-27 decreased the levels of phosphorylated STAT1, STAT3, STAT5, Smad1, and Smad3 but increased the level of SOCS3.ConclusionsThis study demonstrates that IL-27 potentially attenuates BLM-induced pulmonary fibrosis by regulating Th17 differentiation and cytokine secretion.

This study was approved by the local institutional review board. Written informed consent was obtained from the patient for publication of this study and any accompanying images.

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Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancers worldwide. Transcription factor PTTG1 was seen highly expressed in a variety of tumors and was related to the degree of tumor differentiation, invasion, and metastasis. However, the clinical significance of PTTG1 had yet to be verified, and the mechanism of abnormal PTTG1 expression in ESCC was not clear. In this study, the comprehensive analysis and evaluation of PTTG1 expression in ESCC were completed by synthesizing in-house immunohistochemistry (IHC), clinical sample tissue RNA-seq (in-house RNA-seq), public high-throughput data, and literature data. We also explored the possible signaling pathways and target genes of PTTG1 in ESCC by combining the target genes of PTTG1 (displayed by ChIP-seq), differentially expressed genes (DEGs) of ESCC, and PTTG1-related genes, revealing the potential molecular mechanism of PTTG1 in ESCC. In the present study, PTTG1 protein and mRNA expression levels in ESCC tissues were all significantly higher than in non-cancerous tissues. The pool standard mean difference (SMD) of the overall PTTG1 expression was 1.17 (95% CI: 0.72–1.62, P < 0.01), and the area under curve (AUC) of the summary receiver operating characteristic (SROC) was 0.86 (95% CI: 0.83–0.89). By combining the target genes displayed by ChIP-seq of PTTG1, DEGs of ESCC, and PTTG1-related genes, it was observed that PTTG1 may interact with these genes through chemokines and cytokine signaling pathways. By constructing a protein–protein interaction (PPI) network and combining ChIP-seq data, we obtained four PTTG1 potential target genes, SPTAN1, SLC25A17, IKBKB, and ERH. The gene expression of PTTG1 had a strong positive correlation with SLC25A17 and ERH, which suggested that PTTG1 might positively regulate the expression of these two genes. In summary, the high expression of PTTG1 may play an important role in the formation of ESCC. These roles may be completed by PTTG1 regulating the downstream target genes SLC25A17 and ERH.

These authors contributed equally to this workObjective: The impact of negative lymph nodes (NLNs) count on prognosis in esophageal cancer (EC) was analyzed using two institutions surgical database. Methods: We conducted a retrospective study of 768 EC patients treated by surgical resection between January 2010 and December 2012. The effects of the NLNs count on prognosis was analyzed. Cox regression model was conducted to determine the significant prognostic elements. Results: The number of NLNs was studied as a categorical variable based on the quartiles (Q1: ≤15, Q2: 16-21, Q3: 22-30, Q4: ≥31). And a better overall survival (OS) was observed with increasing number of NLNs (HR= 0.762; 95% CI, 0.596-0.974 for Q2, HR= 0.666; 95% CI, 0.516-0.860 for Q3 and HR= 0.588; 95% CI, 0.450-0.768 for Q4) (all P<0.05).Multivariate regression analysis revealed that the NLNs count was an independent prognostic factor. Besides, for patients in T2 or T3 stage, a high number of NLNs was found to be significantly associated with a favorable OS (log rank P<0.001). Conclusion: A higher number of NLNs is independently related to the better OS in EC patients after surgical resection.