ABSTRACT
Knee osteoarthritis (OA), an age-related degenerative disease characterized by severe pain and disability, is treated using polynucleotides (PNs) and hyaluronic acid (HA). The intra-articular (IA) injection of HA has been studied extensively in both animal models and in humans; however, the efficacy and mechanisms of action remain unclear. In addition, there has been a paucity of research regarding the use of PN alone or in combination with HA in OA. To investigate the effect of the combined injection of PN and HA in vivo, pathological and behavioral changes were assessed in an OA model. Anterior cruciate ligament transection and medial meniscectomy were performed in Sprague-Dawley rats to create the OA animal model. The locomotor activity improved following PNHA injection, while the OARSI grade improved in the medial tibia and femur. In mild OA, TNFα levels decreased histologically in the PN, HA, and PNHA groups but only the PNHA group showed behavioral improvement in terms of distance. In conclusion, PNHA exhibited anti-inflammatory effects during OA progression and improved locomotor activity regardless of the OARSI grade.
Subject(s)
Hyaluronic Acid , Osteoarthritis, Knee , Rats , Humans , Animals , Hyaluronic Acid/pharmacology , Polynucleotides/pharmacology , Polynucleotides/therapeutic use , Rats, Sprague-Dawley , Osteoarthritis, Knee/drug therapy , Anterior Cruciate Ligament/surgery , Injections, Intra-ArticularABSTRACT
Fas-associated factor 1 (FAF1) has gained a reputation as a member of the FAS death-inducing signalling complex. However, the role of FAF1 in the immunity response is not fully understood. Here, we report that, in the human retinal pigment epithelial (RPE) cell line ARPE-19 cells, FAF1 expression level was downregulated by Toxoplasma gondii infection, and PI3K/AKT inhibitors reversed T. gondii-induced FAF1 downregulation. In silico analysis for the FAF1 promoter sequence showed the presence of a FOXO response element (FRE), which is a conserved binding site for FOXO1 transcription factor. In accordance with the finding, FOXO1 overexpression potentiated, whereas FOXO1 depletion inhibited intracellular FAF1 expression level. We also found that FAF1 downregulation by T. gondii is correlated with enhanced IRF3 transcription activity. Inhibition of PI3K/AKT pathway with specific inhibitors had no effect on the level of T. gondii-induced IRF3 phosphorylation but blocked IRF3 nuclear import and ISGs transcription. These results suggest that T. gondii can downregulate host FAF1 in PI3K/AKT/FOXO1-dependent manner, and the event is essential for IRF3 nuclear translocation to active the transcription of ISGs and thereby T. gondii proliferation.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Apoptosis Regulatory Proteins/genetics , Gene Expression Regulation , Host-Parasite Interactions/genetics , Interferon Regulatory Factor-3/metabolism , Toxoplasma/physiology , Adaptor Proteins, Signal Transducing/metabolism , Apoptosis Regulatory Proteins/metabolism , Cell Line , Cells, Cultured , Fluorescent Antibody Technique , Forkhead Box Protein O1/metabolism , Humans , Interferon Regulatory Factor-3/genetics , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Toxoplasmosis/genetics , Toxoplasmosis/metabolism , Toxoplasmosis/parasitologyABSTRACT
Red Ginseng is well-known functional food in Asia which is produced by steaming and drying fresh ginseng (Panax ginseng). In the production of red ginseng extract, around 65% of the original material is left over as by-product and discarded. Most studies on ginseng are focused on ginsenosides. Many functional substances other than ginsenoside are found in red ginseng, but they have not been studied and are usually discarded. Acidic polysaccharides, which are functional polysaccharides found in the by-product of red ginseng, can be utilized as excellent high-value-added material. In this study, we developed red ginseng by-product polysaccharides (RGBPs) by applying an enzyme-linked high-pressure process (ELHPP). We have demonstrated the antioxidant, anti-aging, and anti-atopic dermatitis efficacy of ELHPP-RGBPs in this study. In acute oral toxicity and skin irritation tests, ELHPP-RGBPs were found to be very low in toxicity. ELHPP-RGBPs inhibited solar ultraviolet-induced matrix metalloproteinase-1 (MMP-1) protein through activator protein-1 (AP-1), a major transcription factor for MMP-1. ELHPP-RGBP attenuated DFE-induced AD-like symptoms as assessed by skin lesion analyses, dermatitis score, and skin thickness. Taken together, these results suggest that ELHPP-RGBP may have potential as a nutraceutical ingredient for skin health. PRACTICAL APPLICATIONS: This paper presents a new method of using ginseng by-product that has not been used and discarded. The use of polysaccharides in ginseng by-product has been shown to prevent skin wrinkles and atopic dermatitis. This is an economical new functional food material.
