Int J Med Sci
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Background and aim: The molecular signatures of lung adenocarcinoma (LUAD) are not well understood. Centromere protein F (CENPF) has been shown to promote oncogenesis in many cancers; however, its role in LUAD has not been illustrated. We explored the role of CENPF in LUAD. ⋯ Besides, CENPF knockdown greatly suppressed A549 cell proliferation, induced S phase arrest, promoted apoptosis and decreased colony numbers of LUAD cells. Furthermore, knockdown of CENPF significantly inhibited the tumor growth of the LUAD cells in an experimental xenograft lung cancer model of nude mice armpit of right forelimb. Conclusion: Taken together, these results demonstrated that CENPF may serve as a potential biomarker of prognostic relevance and a potential therapeutic target for LUAD.
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Salinomycin (Sal) is a recently identified anti-tumor drug for treating several types of solid tumor; however, its effects on the migratory and invasive properties of non-small cell lung cancer (NSCLC) remain unclear. This study investigated the inhibitory effect underlying mechanisms of Salon transforming growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) and cell migration. Sal solidly blocked cell migration and invasion enhancement by TGF-β1-induced EMT, through recovering E-cadherin loss and suppressing mesenchymal markers induction, as well as TGF-β1-mediated AMPK/SIRT signaling activity upregulation. ⋯ Next we demonstrated that the MMP-2 and MMP-9 knockdown can act synergistically with Sal to inhibit TGF-β1-induced EMT. Moreover, treatment of PMA of MMP activator increased TGF-β1-induced MMP-2 and MMP-9, even with Sal. Our results demonstrate that Sal suppresses TGF-β1-induced EMT by downregulating MMP-2 and MMP-9 through the AMPK/SIRT pathway, thereby inhibiting lung cancer cell migration and invasion.
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Rationale: Postoperative ileus (POI) is a frequent complication arising after gastrointestinal surgery but pathogenesis of POI is still not fully understood. While Th1 immune cells are implicated in POI, the involvement of Th2 cells has not yet been clarified. Given the impact of reactive oxygen species (ROS) in the regulation of Th1 and Th2 balance, we hypothesized that not only Th1 but also Th2 immune response can be involved in the development of experimental POI. ⋯ We found that POI-induced accumulation of ROS was associated with an increased expression of the transcriptional factors HMBGI, NF-κB, and p38. This increased expression seemed to be associated with a Th2 response. Conclusion: Th2 immune response can be involved in the activation of mast cells in POI, which was associated with ROS mediated activation of NF-κB and p38 MAPK signaling pathway.
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Fluid resuscitation after hemorrhagic shock is a model of systemic ischemia/reperfusion injury (SI/RI), and the liver is one of the main target organs. Ischemic preconditioning (IPC) can reduce hepatic ischemia-reperfusion injury (I/RI) via autophagy. However, whether remote ischemic preconditioning (RIPC) can alleviate the liver injury that is secondary to hemorrhagic shock and the role of autophagy in this process remain unclear. ⋯ Levels of inflammatory factors TNF-α, IL-1β and apoptosis were attenuated, autophagosomes was increased in the RIPC group compared with controls. IHC and WB both revealed increased LC3 and Beclin-1 but decreased p62 protein expression levels in the RIPC group. Together, our data suggest that RIPC-activated autophagy could play a protective role against secondary liver injury following hemorrhagic shock.
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Background: Regulating the polarization of macrophages to antitumor M1 macrophages is a promising strategy for overcoming the immunosuppression of the tumor microenvironment for cancer therapy. Ferumoxytol (FMT) can not only serve as a drug deliver agent but also exerts anti-tumor activity. β-glucan has immuno-modulating properties to prevent tumor growth. Thus, a nanocomposite of FMT surface-coated with β-glucan (FMT-β-glucan) was prepared to explore its effect on tumor suppression. ⋯ Moreover, FMT-β-glucan boosted the expression of M1 type markers, and increased phagocytic activity and ROS in RAW 264.7 cells. Further research indicated that FMT-β-glucan treatment promoted the level of Dectin-1 on the surface of RAW 264.7 cells and that knockdown of Dectin-1 abrogated the phosphorylation levels of several components in MAPK and NF-κB signaling. Conclusion: The nanocomposite FMT-β-glucan suppressed melanoma growth by inducing the M1 macrophage-activated tumor microenvironment.