Moraleslorentsen2594

2018.3464].Previous studies have confirmed that astragaloside (AST) exerts a positive effect on alleviating synovial and joint injury in rheumatoid arthritis (RA). However, the precise mechanisms through which AST acts in the treatment of RA remain unclear. Long non‑coding RNA (lncRNA) LOC100912373 was identified as a key gene related to RA and has been proven to interact with miR‑17‑5p, in order to regulate the pyruvate dehydrogenase kinase 1 and protein kinase B axis (PDK1/AKT axis). The present study aimed to determine whether AST may treat RA through the interaction between lncRNA LOC100912373 and the miR‑17‑5p/PDK1 axis. MTT assays and flow cytometry were used to detect the proliferation and cell cycle progression of AST‑treated fibroblast‑like synoviocytes (FLSs). The expression of lncRNA LOC100912373 and miR‑17‑5p, as well as relative the mRNA expression of the PDK1 and AKT genes following AST intervention was detected by reverse transcription‑quantitative PCR (RT‑qPCR), immunofluorescence and western blot analysis. The results revealed that AST inhibited FLS proliferation, reduced lncRNA LOC100912373 expression levels, increased miR‑17‑5p expression levels, and decreased the PDK1 and p‑AKT expression levels. Additionally, consecutive rescue experiments revealed that AST counteracted the effects of lncRNA LOC100912373 overexpression on FLS proliferation and cell cycle progression. On the whole, the present study demonstrates that AST inhibits FLS proliferation by regulating the expression of lncRNA LOC100912373 and the miR‑17‑5p/PDK1 axis.Liver cancer is one of the most common types of malignant tumor, and is characterized by high malignancy, rapid progression, high morbidity and mortality. Oxaliplatin (OXA) has been reported to have marked efficiency against advanced liver cancer with tolerable toxicity. In solid tumors, the hypoxic microenvironment promotes epithelial‑mesenchymal transition (EMT), which can also induce drug resistance of liver cancer to platinum drugs. Herba Cistanche (Cistanche tubulosa) has been frequently used in traditional Chinese medicine and the phenylethanol glycosides from Herba Cistanche (CPhGs) are the major active components. The present study aimed to investigate the effects of CPhGs on viability, apoptosis, migration and invasion of liver cancer cells. HepG2 liver cancer cells were divided into the control, DMSO, CoCl2, OXA, OXA + CoCl2 and CPhGs + OXA + CoCl2 groups. Subsequently, reverse transcription‑quantitative PCR and western blot analysis were performed to determine the expression levels of hypoxia‑inducible factor 1α (HIF‑1α), lysyl oxidase‑like 2 (LOXL2) and EMT‑related genes and proteins (i.e., E‑cadherin and Twist), in order to investigate the effects of CPhGs on liver cancer. The results demonstrated that CPhGs could enhance the effects of OXA on liver cancer, and inhibit the migration, invasion and apoptotic rate of liver cancer cells. Additionally, CPhGs treatment effectively induced downregulation of HIF‑1α, LOXL2 and Twist, and upregulation of E‑cadherin. The present findings indicated that CPhGs triggered a significant increase in sensitivity to OXA and suppression of hypoxia‑induced EMT in liver cancer by inhibiting the HIF‑1α signaling pathway. Therefore, CPhGs may be considered an effective platinum drug sensitizer, which could improve chemotherapeutic efficacy in patients with liver cancer.Glioblastoma multiforme (GBM) is a primary brain tumor with a high mortality rate and a median survival time of ~14 months from the initial diagnosis. Although progress has been made in the currently available therapies, the treatment of GBM remains palliative. GBM contains subsets of GBM stem cells (GSCs) that share numerous neural stem/progenitor cell characteristics, such as expression of stem cell markers, self‑renewal and multi‑lineage differentiation capacity, thus contributing to the heterogeneity and complexity of these tumors. GSCs are potentially associated with tumor initiation and they are considered as the driving force behind tumor formation, as they possess tumor‑propagating potential and exhibit preferential resistance to radiotherapy and chemotherapy. Targeting self‑renewal signaling pathways in cancer stem cells may effectively reduce tumor recurrence and significantly improve prognosis. The aim of the present review was to summarize the current knowledge on the self‑renewal signaling pathways of GSCs and discuss potential future targeting strategies for the design of differentiation therapies.Localization of phosphorylated (p)‑JNK to the mitochondria can lead to functional mitochondrial disorder, resulting in a decrease in energy supply and membrane potential, as well as an increase in reactive oxygen species production and apoptosis. 4SC-202 clinical trial JNK is involved in the occurrence of acute lung injury (ALI), and activation of the JNK pathway is one of the crucial factors resulting in injury. The aim of the present study was to investigate whether the JNK‑mitochondria (mitoJNK) location participated in the occurrence of ALI and acute respiratory distress syndrome (ALI/ARDS). The present study examined the activation of the JNK pathway, the content of JNK located on the mitochondria and the treatment effects of a cell‑permeable peptide Tat‑SabKIM1, which can selectively inhibit the location of JNK on mitochondria. The expression levels of proteins were detected by western blot analysis. Lung injuries were evaluated by histological examination, wet‑to‑dry weight ratios, and H2O2 and malondialdehyde concentrations in the lung tissues. Lung cells apoptosis was evaluated using TUNEL assay. The results demonstrated that JNK was phosphorylated and activated during seawater inhalation‑induced ALI/ARDS, not only in the routine JNK pathway but also in the mitoJNK pathway. It was also found that Tat‑SabKIM1 could specifically inhibit JNK localization to mitochondria and the activation of mitoJNK signaling. Furthermore, Tat‑SabKIM1 could inhibit Bcl‑2‑regulated autophagy and mitochondria‑mediated apoptosis. In conclusion, mitoJNK localization disrupted the normal physiological functions of the mitochondria during ALI/ARDS, and selective inhibition of JNK and mitochondrial SH3BP5 (also known as Sab) binding with Tat‑SabKIM1 can block deterioration from ALI/ARDS.