ABSTRACT
Inflammatory bowel disease (IBD) is one of the main factors leading to colitis-associated colorectal cancer (CAC). Therefore, it is critical to develop an effective treatment for IBD to prevent secondary colorectal carcinogenesis. M2 macrophages play crucial roles in the resolution phase of intestinal inflammation. However, traditional drugs rarely target intestinal M2 macrophages, and they are not easily cleared. Gold nanoclusters are known for their in vivo safety and intrinsic biomedical activities. In this study, a glutathione-protected gold nanocluster is synthesized and evaluated, namely, GA. Interestingly, GA specifically accumulates in the colon during IBD. Furthermore, GA not only promotes M2 differentiation of IL-4-treated peritoneal macrophages but also reprograms macrophage polarization from M1 to M2 in a pro-inflammatory environment. Mechanistically, this regulatory effect is exerted through activating the antioxidant Nrf2 signaling pathway, but not traditional STAT6. When applied in IBD mice, we found that GA elevates M2 macrophages and alleviates IBD in an Nrf2-dependent manner, evidenced by the abolished therapeutic effect upon Nrf2 inhibitor treatment. Most importantly, GA administration significantly suppresses AOM/DSS-induced CAC, without causing obvious tissue damage, providing critical evidence for the potential application of gold nanoclusters as nanomedicine for the treatment of IBD and CAC.
Subject(s)
Colorectal Neoplasms , Inflammatory Bowel Diseases , Animals , Mice , NF-E2-Related Factor 2 , Macrophages , Carcinogenesis , Gold/pharmacology , Inflammatory Bowel Diseases/drug therapy , Inflammation , Colorectal Neoplasms/drug therapyABSTRACT
Propofol has been previously demonstrated to relieve hepatocellular carcinoma (HCC). However, the specific molecular mechanisms mediated by propofol remain to be explored. mRNA or miRNA expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Protein expression was determined by Western blot. The interaction between microRNA (miR)-556-3p and long coding RNA non-coding RNA activated by DNA damage (NORAD) or migration and invasion enhancer 1 (MIEN1) was verified by luciferase reporter gene and RNA pull-down assays. Cellular functions were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetra-zolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), and Transwell assays. Propofol notably suppressed the proliferation and EMT of Hep3B and SNU449 cell lines. NORAD was overexpressed in the HCC tissues and cells, while propofol decreased NORAD levels in the HCC cells. Conversely, overexpression of NORAD partially restored malignant behaviors of the HCC cells and abolished the effects of propofol. Additionally, NORAD sponged miR-556-3p to upregulate MIEN1. However, the knockdown of MIEN1 suppressed the proliferation and EMT of HCC cells. Propofol inhibited HCC cell proliferation and EMT progress via NORAD/miR-556-3p/MIEN1 axis. These data provided a potent prognosis and diagnostic marker for HCC and supplemented the underlying mechanism of propofol-induced anti-tumor effects.
Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Hepatocellular/drug therapy , Cell Proliferation/drug effects , Epithelial-Mesenchymal Transition/drug effects , Liver Neoplasms/drug therapy , Propofol/pharmacology , DNA Damage/drug effects , Humans , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolismABSTRACT
Purpose: To evaluate retinal and choroidal microvascular features of VKH patients in acute and convalescent phases after treatment using OCTA.Methods: A prospective, observational study was conducted in patients with initial VKH at the acute stage (n = 15) and healthy participants (n = 15) served as controls. After 3-month systemic corticosteroid treatment, patients' vascular parameters were recorded by OCTA before and after treatment and compared with results observed in healthy participants.Results: Our findings first uncovered that there are two types of abnormalities in the choriocapillary layer of patients with VKH in the acute stage: one is characterized as multiple dark spots of choriocapillary flow void and the other involves highly reflective areas surrounded by light spots with an increased flow area. During the convalescent stage, all eyes showed multifocal dark spots in the choriocapillary layer, leading to a reduced choroidal flow area.Conclusions: OCTA provides a better display of the microvascular appearance of the choroid to noninvasively evaluate choriocapillaris abnormalities in VKH disease.