Fournierhald1265

miR-142-5p and Sema3C were co-regulators of epithelial-mesenchymal transition. Clinically, miR-142-5p expression was conversely related with Sema3C expression in glioma samples. Together, we identified that Sema3C could promote the progression of glioma and its expression was negatively regulated by miR-142-5p in vitro. Thus, the miR-142-5p-Sema3C axis plays importantly in glioma and holds potential to be therapeutic targets as well.Non-alcoholic fatty liver disease (NAFLD) or non-alcoholic seatohepatitis (NASH) is one of the major health problems world wide, because of increased abdominal obesity. To date, specific and effective medications to treat or prevent NAFLD/NASH have not been established. To identify appropriate molecular targets for that purpose, suitable animal models of NAFLD/NASH have been explored. A choline-deficient amino acid-defined high fat diet (CDAHFD)-induced mouse model of NASH has been developed. However, its relevance to human NASH, including serum lipid profiles, have not been clearly defined. In this study, we have revealed that mice fed CDAHFD showed significantly lowerd serum total cholesterol and triglyceride (TG) levels, in addition to reduced body weight (BW). Furthermore, hepatic microsomal triglyceride transfer protein (MTP) expression was significantly downregulated in CDAHFD-fed mice. Thus, the current CDAHFD-fed mouse model has points that are distinct from human NAFLD/NASH, in general, which is based upon abdominal obesity.Liver transplantation and hepatocyte transplantation are effective treatments for severe liver injuries, but the donor shortage is a serious problem. Therefore, hepatocyte-like cells generated from human induced pluripotent stem (iPS) cells with unlimited proliferative ability are expected to be a promising new transplantation resource. The technology for hepatic differentiation from human iPS cells has made great progress in this decade. The efficiency of hepatic differentiation now exceeds 90%, making it possible to produce nearly homogeneous hepatocyte-like cells from human iPS cells. Because there is little contamination of undifferentiated cells, there is a lower risk of teratoma formation. To date, the transplantation of human iPS cell-derived hepatocyte-like cells has been shown to have therapeutic effects using various liver injury model mice. Currently, studies are underway using model animals larger than mice. The day when human iPS cell-derived hepatocyte-like cells can be used as cellular medicine is surely approaching. In this review, we introduce the forefront of regenerative medicine applications using human iPS cell-derived hepatocyte-like cells.Lipoproteins are naturally occurring nanoparticles and their main physiological function is the promotion of lipid metabolism. They can be prepared in vitro for use as drug carriers, and these reconstituted lipoproteins show similar biological activity to their natural counterparts. Some lipoproteins can cross the blood-retinal barrier and are involved in intraocular lipid metabolism. Drug-loaded lipoproteins can be delivered to the retina for the treatment of posterior eye diseases. In this review, we have discussed the therapeutic applications of lipoproteins for eye diseases and introduced the emerging animal models used for the evaluation of their therapeutic effects.The last few years have witnessed a great advance in the development of nonviral systems for in vivo targeted delivery of nucleic acids. Lipid nanoparticles (LNPs) are the most promising carriers for producing clinically approved products in the future. Compared with other systems used for nonviral gene delivery, LNPs provide several advantages including higher stability, low toxicity, and greater efficiency. Additionally, systems based on LNPs can be modified with ligands and devices for controlled biodistribution and internalization into specific cells. Efforts are ongoing to improve the efficiency of lipid-based gene vectors. These efforts depend on the appropriate design of nanocarriers as well as the development of new lipids with improved gene delivery ability. Several ionizable lipids have recently been developed and have shown dramatically improved efficiency. However, enhancing the ability of nanocarriers to target specific cells in the body remains the most difficult challenge. Systemically administered LNPs can access organs in which the capillaries are characterized by the presence of fenestrations, such as the liver and spleen. The liver has received the most attention to date, although targeted delivery to the spleen has recently emerged as a promising tool for modulating the immune system. In this review, we discuss recent advances in the use of LNPs for cell-specific targeted delivery of nucleic acids. We focus mainly on targeting liver hepatocytes and spleen immune cells as excellent targets for gene therapy. We also discuss the potential of endothelial cells as an alternate approach for targeting organs with a continuous endothelium.Small extracellular vesicles (sEVs), including exosomes as typical example, are cell-derived vesicles comprising lipid bilayer with a diameter approximately 100 nm. sEVs are endogenous delivery vehicles that deliver their contents such as nucleic acids and proteins to recipient cells. Because of their potential nature as endogenous delivery vehicles, therapeutic applications of sEVs as delivery systems of various drugs are expected. To develop sEV-based therapeutics, a variety of challenges should be overcome. In this review, we summarize the current status and future perspectives of therapeutic applications of sEVs. Several pharmaceutical and pharmacokinetic challenges will be discussed.Blood coagulation and the fibrinolytic system contribute to vascular lesions. Fibrinolysis in normal circulating blood strongly depends on the balance between tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) secreted from vascular endothelial cells; however, the mechanisms by which endothelial fibrinolysis is regulated remain to be fully understood. GKT137831 mouse In the present study, human vascular endothelial EA.hy926 cells were transfected with small interfering RNA for nuclear factor erythroid 2-related factor 2 (NRF2) and the expression of t-PA and PAI-1 and fibrinolytic activity in the conditioned medium were examined. EA.hy926 cells were also treated with sulforaphane, an NRF2 activator, and fibrinolytic activity was examined to confirm the NRF2 signaling pathway's effect. Enhanced fibrinolytic activity in the conditioned medium was observed in association with increased expression and secretion levels of t-PA in NRF2 knockdown EA.hy926 cells. However, sulforaphane inhibited fibrinolytic activity and t-PA synthesis in EA.