ABSTRACT
BACKGROUND: The unfolded protein response (UPR) is one of the cytoprotective mechanisms against various stresses and essential for the normal function of skin. Skin injury caused by ionizing radiation (IR) is a common side effect of radiotherapy and it is unclear how UPR affects IR-induced skin injury. OBJECTIVES: To verify the effect of UPR on IR-induced DNA damage in keratinocytes and the relation between an endoplasmic reticulum (ER) protein KTN1 and UPR. METHODS: All experiments were performed on keratinocytes models: HaCaT and HEK-A. ER lumen and the expression levels of KTN1 and UPR pathway proteins (PERK, IRE1α and ATF6) were examined by transmission electron microscopy and immunoblotting, respectively. 4-PBA, an UPR inhibitor, was used to detected its effects on DNA damage and cell proliferation. Subsequently, the effects of KTN1 deletion on UPR, DNA damage and cell proliferation after IR were detected. Tunicamycin was used to reactivate UPR and then we examined its effects on DNA damage. RESULTS: UPR was activated by IR in keratinocytes. Inhibition of UPR aggravated DNA damage and suppressed cell proliferation after IR. KTN1 expression was upregulated by IR and KTN1 depletion reduced ER expansion and the expression of UPR-related proteins. Moreover, KTN1 depletion aggravated DNA damage and suppressed cell proliferation after IR could reversed by reactivation of UPR. CONCLUSION: KTN1 deletion aggravates IR-induced keratinocyte DNA damage via inhibiting UPR. Our findings provide new insights into the mechanisms of keratinocytes in response to IR-induced damage.
Subject(s)
Cell Proliferation , DNA Damage , HaCaT Cells , Keratinocytes , Radiation, Ionizing , Unfolded Protein Response , Humans , Cell Line , Cell Proliferation/radiation effects , Cell Proliferation/drug effects , DNA Damage/radiation effects , Endoplasmic Reticulum/metabolism , Endoplasmic Reticulum/radiation effects , Endoplasmic Reticulum/drug effects , Endoplasmic Reticulum Stress/radiation effects , Endoplasmic Reticulum Stress/drug effects , Keratinocytes/radiation effects , Keratinocytes/metabolism , Membrane Proteins/metabolism , Membrane Proteins/genetics , Skin/radiation effects , Skin/pathology , Skin/cytology , Skin/drug effects , Skin/metabolism , Unfolded Protein Response/radiation effects , Unfolded Protein Response/drug effectsABSTRACT
Background: Indocyanine green (ICG) is a nontoxic, albumin-bound, liver-metabolized fluorescent iodide dye that has been widely utilized in clinical applications since the mid-1950s. However, after the 1970s, in-depth research on the fluorescence properties of ICG greatly expanded its application in the medical field. Methods: In our mini-review, we searched the relevant literature on common oncology surgeries from PubMed, including lung cancer, breast cancer, gastric cancer, colorectal cancer, liver cancer, and pituitary tumors, using keywords such as indocyanine green, fluorescence imaging technology, and near-infrared fluorescence imaging. In addition, the application of targeted ICG photothermal technology in tumor therapy is briefly mentioned. Results: In this mini-review, we analyzed studies on ICG fluorescence imaging in common surgical oncology and offered a thorough analysis of each form of cancer or tumor. Conclusion: ICG has demonstrated significant potential in the detection and treatment of tumors in current clinical practice, although many applications are still in the preliminary stages, and multicenter studies are still required to more precisely define its indications, effectiveness, and safety.
ABSTRACT
BACKGROUND: The aim of this study is to investigate role of Visfatin, one of the pro-inflammatory adipokines, in sepsis-induced intestinal injury and to clarify the potential mechanism. METHODS: C57BL/6 mice underwent cecal ligation and puncture (CLP) surgery to establish sepsis model in vivo. Intestinal epithelial cells were stimulated with LPS to mimic sepsis-induced intestinal injury in vitro. FK866 (the inhibitor of Visfatin) with or without XMU-MP-1 (the inhibitor of Hippo signaling) was applied for treatment. The expression levels of Visfatin, NF-κB and Hippo signaling pathways-related proteins were detected by western blot or immunohistochemistry. The intestinal cell apoptosis and intestinal injury were investigated by TUNEL staining and H&E staining, respectively. ELISA was used to determine the production of inflammatory cytokines. RESULTS: The expression of Visfatin increased in CLP mice. FK866 reduced intestinal pathological injury, inflammatory cytokines production, and intestinal cell apoptosis in sepsis mice. Meanwhile, FK866 affected NF-κB and Hippo signaling pathways. Additionally, the effects of FK866 on inflammatory response, apoptosis, Hippo signaling and NF-κB signaling were partly abolished by XMU-MP-1, the inhibitor of Hippo signaling. In vitro experiments also revealed that FK866 exhibited a protective role against LPS-induced inflammatory response and apoptosis in intestinal cells, as well as regulating NF-κB and Hippo signaling, whereas addition of XMU-MP-1 weakened the protective effects of FK866. CONCLUSION: In short, this study demonstrated that inhibition of Visfatin might alleviate sepsis-induced intestinal injury through Hippo signaling pathway, supporting a further research on Visfatin as a therapeutic target.
