S100A8/9 modulates perturbation and glycolysis of macrophages in allergic asthma mice.

Background: Allergic asthma is the most prevalent asthma phenotype and is associated with the disorders of immune cells and glycolysis. Macrophages are the most common type of immune cells in the lungs. Calprotectin (S100A8 and S100A9) are two pro-inflammatory molecules that target the Toll-like receptor 4 (TLR4) and are substantially increased in the serum of patients with severe asthma. This study aimed to determine the effects of S100A8/A9 on macrophage polarization and glycolysis associated with allergic asthma. Methods: To better understand the roles of S100A8 and S100A9 in the pathogenesis of allergic asthma, we used ovalbumin (OVA)-induced MH-S cells, and OVA-sensitized and challenged mouse models (wild-type male BALB/c mice). Enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, flow cytometry, hematoxylin-eosin staining, and western blotting were performed. The glycolysis inhibitor 3-bromopyruvate (3-BP) was used to observe changes in glycolysis in mice. Results: We found knockdown of S100A8 or S100A9 in OVA-induced MH-S cells inhibited inflammatory cytokines, macrophage polarization biomarker expression, and pyroptosis cell proportion, but increased anti-inflammatory cytokine interleukin (IL)-10 mRNA; also, glycolysis was inhibited, as evidenced by decreased lactate and key enzyme expression; especially, knockdown of S100A8 or S100A9 inhibited the activity of TLR4/myeloid differentiation primary response gene 88 (MyD88)/Nuclear factor kappa-B (NF-κB) signaling pathway. Intervention with lipopolysaccharides (LPS) abolished the beneficial effects of S100A8 and S100A9 knockdown. The observation of OVA-sensitized and challenged mice showed that S100A8 or S100A9 knockdown promoted respiratory function, improved lung injury, and inhibited inflammation; knockdown of S100A8 or S100A9 also suppressed macrophage polarization, glycolysis levels, and activation of the TLR4/MyD88/NF-κB signaling pathway in the lung. Conversely, S100A9 overexpression exacerbated lung injury and inflammation, promoting macrophage polarization and glycolysis, which were antagonized by the glycolysis inhibitor 3-BP. Conclusion: S100A8 and S100A9 play critical roles in allergic asthma pathogenesis by promoting macrophage perturbation and glycolysis through the TLR4/MyD88/NF-κB signaling pathway. Inhibition of S100A8 and S100A9 may be a potential therapeutic strategy for allergic asthma.

CD147 promotes epithelial-mesenchymal transition of prostate cancer cells via the Wnt/ß-catenin pathway.

The majority of deaths among patients with prostate cancer (PCa) occur following metastasis; therefore, there is a critical need for effective treatment of metastatic PCa. Epithelial-mesenchymal transition (EMT) is vital in the early stage of cancer cell metastasis and CD147 has been reported to be associated with various types of cancer. The goal of this study was to investigate the role of CD147 in the EMT of PCa cells via short hairpin (sh)RNA-mediated knockdown of CD147 in lymph node carcinoma of the prostate (LNCaP) cells. Reverse transcription-quantitative PCR and western blotting were performed to examine gene and protein expression. Cell migration and invasion were detected using a Transwell assay. Cell Counting Kit-8 assay was performed to investigate cell viability. The knockdown of CD147 in LNCaP cells (LNCaP/shCD147 cells) resulted in an increase in the expression of E-cadherin (an epithelial marker), and a decrease in the expression of N-cadherin and vimentin (mesenchymal markers). Importantly, the downregulation of CD147 in LNCaP cells inhibited the expression levels of nuclear ß-catenin and Snail, and phosphorylation of glycogen synthase kinase (GSK)-3ß on Ser 9, and increased the expression of phosphorylated (p)-ß-catenin (Ser33/37/Thr41). Treatment with lithium chloride (LiCl), a Wnt/ß-catenin pathway agonist or a GSK-3ß inhibitor, attenuated CD147 downregulation-induced p-ß-catenin (Ser33/37/Thr41) expression, which resulted in the upregulation of ß-catenin in the nucleus. LiCl treatment prompted ß-catenin-mediated expression of target proteins such as Snail and vimentin in LNCaP/shCD147 cells, and prevented E-cadherin expression, a molecule downstream to Snail. In conclusion, these findings revealed an important role of CD147 in the regulation of the invasive and metastatic potential of PCa cells. CD147, via modulation of the Wnt/ß-catenin pathway, may be implicated in the regulation of EMT of PCa cells and could be a potential therapeutic target for PCa.

The impact of resilience on psychological outcomes in women with threatened premature labor and spouses: a cross-sectional study in Southwest China.

BACKGROUND: Threatened premature labor (TPL) is a severe obstetric complication which affects the mental and physical health of both the mother and fetus. Family resilience may have protective role against psychological distress in women experiencing these pregnancy complications. There may be resilience related risk factors in TPL women, and interplays may exist among psychological variables and within couples. This study aims to examine psychological outcomes influenced by different levels of resilience, and explore psychological interactions in TPL women, spouses, and between women and spouses. METHODS: Six validated questionnaires were used to measure the psychological outcomes (Connor-Davidson resilience scale CD-RISC, Edinburgh postnatal depression scale EPDS, positive and negative affect scale PANAS, pregnancy pressure scale PPS, simplified coping style questionnaire SCSQ, social support rating scale SSRS) in 126 TPL women hospitalized in three tertiary hospitals and 104 spouses in Southwest China. RESULTS: Low resilient women had significantly more complicated placenta praevia, longer pediatric observation, more pressure than high resilient women. They also had significantly less active coping and positive affect, more negative affect and depression compared to high resilient women and their spouses. Although the socio-demographic characteristics of both TPL women and spouses and psychometric parameters of spouses had no significant differences, the prevalence rates of depression in spouses were notable. Compared with spouses, TPL women had a more complex interaction among these psychometric factors, with women's resilience negatively associated with their partners' negative affect, and their pressure positively correlated with pressure and negative affect of spouses. CONCLUSIONS: Pregnancy complicated with placenta praevia and pediatric observation may be risk factors for resilience of women with TPL. Maternal resilience has an important impact on the psychological outcomes in TPL women. A screening for resilience, depression and other psychological outcomes in couples with TPL and early psychological intervention of low resilient couples may be appropriate to promote resilience and well-being of these families.