Background: Alveolar epithelial cell death plays a critical role in the pathogenesis of lipopolysaccharide (LPS)-induced acute lung injury. Increased autophagy has a dual effect on cell survival. However, it is not known whether autophagy promotes death or survival in human alveolar epithelial cells exposed to LPS. Methods: Genetic and pharmacological approaches were used to evaluate the effect of autophagy on A549 cell viability upon LPS exposure. The endoplasmic reticulum (ER) stress and unfolded protein response (UPR) pathways were examined with immunoblotting studies to further explore underlying mechanisms. Results: Treatment with LPS (50 µg/ml) led to autophagy activation and decreased cell viability in A549 cells. Blocking autophagy via short interfering RNA or inhibitor significantly decreased, whereas rapamycin increased, the LPS-induced effect on viability. ER stress was activated in LPS-stimulated A549 cells, and ER stress inhibitor reduced LPS-induced autophagy. LPS activated only the PERK pathway and had rarely effect on the ATF6 and IRE1 branches of the UPR in A549 cells. Moreover, the knockdown of PERK and ATF4 attenuated LPS-induced autophagy and promoted cell survival. Conclusion: In human alveolar epithelial A549 cells, LPS induces autophagic cell death that depends on the activation of the PERK branch of the UPR upon ER stress.

BACKGROUND CD4 + T helper 17 (Th17) cells play critical roles in inflammation and tumor development. The involvement of Th17 cells in chronic obstructive pulmonary disease (COPD)‐type inflammation‐associated lung cancer has also been confirmed in animal models. However, to the authors' knowledge, it is unknown whether the role of Th17 cells is different in patients with lung cancer complicated with COPD compared with those without COPD. In the current study, the authors attempted to determine the association between the circulating levels of Th17‐related cytokines and the clinical characteristics of non–small cell lung cancer (NSCLC) in patients with or without COPD. METHODS The authors designed a matched case‐control study that included 70 patients with NSCLC with COPD, 148 patients with NSCLC without COPD, and 148 healthy controls. The data regarding the clinicopathological features of these participants were collected. Circulating levels of Th17‐related cytokines, including interleukin (IL) 23 (IL‐23), IL‐17A, IL‐17F, IL‐22, and tumor necrosis factor‐α, were measured. RESULTS The circulating levels of IL‐23, IL‐17A, IL‐17F, IL‐22, and tumor necrosis factor‐α were found to be significantly higher in the patients with NSCLC compared with the healthy controls (P<.05). The elevated levels were found to be significantly associated with lung cancer risk (P<.05). However, no significant differences were found between patients with NSCLC with COPD and patients without COPD. It is interesting to note that, among patients with NSCLC without COPD, the levels of these cytokines were consistently higher among patients with stage I to stage IIIA disease compared with those with stage IIIB to stage IV disease (P<.05). In addition, the 5 Th17‐related cytokines demonstrated pairwise correlations, with Spearman rank correlation coefficients of 0.646 to 0.888 (P<.05). CONCLUSIONS The results of the current study indicate a clear association between the Th17‐related cytokine profile and the risk of NSCLC complicated by the presence or absence of COPD. Cancer 2015;121:3122‐9. © 2015 American Cancer Society.

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This study was to evaluate the impacts of micronutrients added to low-fishmeal diet on the flesh quality and immune response of largemouth bass, Micropterus salmoides. Two diets (FM48 and FM32) were formulated with 48% and 32% fishmeal, respectively, micronutrients (Zn, Mn, Se, VB12 and niacin) were added in FM32 to formulated the LFM diet. Largemouth bass with an initial weight of 12.65 ± 0.04 g were fed with three diets for eight weeks. The results showed that the feed coefficient rate of the shrimp in LFM group was significantly lower than that of the other two groups. There were no significant differences in muscle moisture, crude protein and crude lipids content among the three groups. The activity of muscle superoxide dismutase in the LFM group and FM48 group was significantly higher than that in the FM32 group. Zn content was highest in the muscles of FM48 group, and Se was higher in the muscles of the LFM group than that in the FM48 and FM32 groups. The results of histological analysis showed that the density of muscle fibers was improved after the addition of micronutrients. RT-qPCR results suggested that the expression of ribosomal protein, mammalian target of rapamycin, and eukaryotic translation initiation factor 4E-binding protein1 in the FM48 group were significantly higher than those in the FM32 group and LFM group. The expression of myogenic differentiation 1 was significantly upregulated in the LFM group, which was significantly higher than that in the FM48 and FM32 groups. The expression of tumor necrosis factorαwas significantly upregulated in the shrimp of LFM group compared with those in other groups. These results showed that the addition of micro-nutrients in low fishmeal diet did not affect the growth of largemouth bass, while increase the contents of Mn and Se in the muscle, enhanced the antioxidant capacity, promoted the proliferation of muscle fibers of largemouth bass.