Int J Med Sci
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Cartilage destruction in rheumatoid arthritis (RA) occurs primarily in the pannus-cartilage interface. The close contact of the synovium-cartilage interface implicates crosstalk between synovial fibroblasts and chondrocytes. The aim of this study is to explore the differentially expressed genes and novel microRNA regulations potentially implicated in the dysregulated cartilage homeostasis in joint destruction of RA. ⋯ Moreover, fibroblast growth factor 9 (FGF9), kynureninase (KYNU), and regulator of cell cycle (RGCC) were among the top dysregulated genes identified to be potentially affected in the RA joint microenvironment, having similar expression patterns observed in arrays of clinical RA synovial tissues from the Gene Expression Omnibus database. Additionally, among the 31 differentially expressed microRNAs and 10 candidate genes with potential microRNA-mRNA interactions in RA chondrocytes, the novel miR-140-3p-FGF9 interaction was validated in different microRNA prediction databases, and proposed to participate in the pathogenesis of joint destruction through dysregulated cell growth in RA. The findings provide new perspectives for target genes in the management of cartilage destruction in RA.
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Angiogenesis and vascularization are essential for the growth and survival of most tissues. Engineered bone tissue requires an active blood vessel network for survival and integration with mature host tissue. Angiogenesis also has an effect on cell growth and differentiation in vitro. ⋯ Increased expression of angiogenic phenotypes and vascular endothelial growth factor (VEGF) levels were observed over time in both 50:50 DFSC/HUVEC co-cultures and DFSC monocultures during culture period. Our results showed that increased angiogenic activity in DFSC/HUVEC co-cultures may stimulate osteoblast maturation of DFSCs. Therefore, the secretion of angiogenic factors from HUVECs may play a role in the osteogenic differentiation of DFSCs.
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Cardiac glycosides are natural compounds used for the treatment of congestive heart failure and cardiac arrhythmias. Recently, they have been reported to exhibit anticancer activity. Proscillaridin A (PSN-A), a cardiac glycoside constituent of Urginea maritima has been shown to exhibit anticancer activity. ⋯ Of note, LNCaP cells were found to be more sensitive to PSN-A treatment as compared to DU145 cells. Taken together, the data provided first evidence of the anticancer activity and possible molecular mechanism of PSN-A in prostate cancer. Further study is needed to develop PSN-A into a potential lead compound for the treatment of prostate cancer.
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Autophagy is a catabolic process to maintain intracellular homeostasis via removal of cytoplasmic macromolecules and damaged cellular organelles through lysosome-mediated degradation. Trehalose is often regarded as an autophagy inducer, but we reported previously that it could prevent ischemic insults-induced autophagic death in neurons. Thus, we further investigated in this study whether trehalose could protect human dopaminergic SH-SY5Y cells against H2O2-induced lethal autophagy. ⋯ Notably, we found that trehalose inhibited H2O2-induced increase of intracellular ROS and reduction in the activities of CAT and SOD. Consistently, our data revealed as well that mitigation of intracellular ROS levels with antioxidant NAC markedly attenuated H2O2-induced AMPK activation and ER stress. Therefore, we demonstrated in this study that trehalose prevented H2O2-induced autophagic death in SH-SY5Y cells via mitigation of ROS-dependent endoplasmic reticulum stress and AMPK activation.
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Hepatitis A virus (HAV) infection is one of the major causes of acute hepatitis and acute liver failure in developing and developed countries. Although effective vaccines for HAV infection are available, outbreaks of HAV infection still cause deaths, even in developed countries. One approach to control HAV infection is prevention through diet, which can inhibit HAV propagation and replication. ⋯ Japanese miso extracts enhanced GRP78 expression and inhibited HAV replication in human hepatocytes. Together, these results demonstrate that Japanese miso extracts may partly modulate GRP78 expression and additively or synergistically work as antivirals against HAV infection. Japanese miso extracts can be used as effective dietary supplements for severe hepatitis A.