No abstract

FYN, one of the members of the Src family of kinases (SFKs), has been reported to be overexpressed in various types of cancers and correlated with cell motility and proliferation. However, the mechanism is still unclear. In the present study, we found that FYN was overexpressed in breast cancer and overexpression of FYN promoted cell proliferation, migration and invasion in the MCF10A cells, whereas depletion of FYN suppressed cell proliferation, migration and invasion in the MDA-MB-231 cells. Moreover, FYN upregulated the expression of mesenchymal markers and epithelial-mesenchymal transition (EMT)-related transcription factors, and downregulated the expression of epithelial markers, suggesting that FYN induces EMT in breast cancer cells. Furthermore, FYN was transcriptionally regulated by FOXO1 and mediated FGF2-induced EMT through both the PI3K/AKT and ERK/MAPK pathways.

MicroRNAs act as key regulators in carcinogenesis and progression in various cancers. In present study, we explored the role of miR-340 in the breast cancer progression. Our results showed that overexpression of miR-340 inhibits breast cancer cell proliferation and invasion, whereas depletion of miR-340 promotes breast cancer progression. Molecularly, ZEB1 was identified as a target gene of miR-340 and miR-340 suppressed the expression of ZEB1 by directly binding to the 3′-UTR of ZEB1. Furthermore, ZEB1 transcriptionally suppresses miR-340 expression. The negative feedback loop regulated TGF-β-mediated breast cancer progression. In conclusion, our data suggested that miR-340 acted as a tumor suppressor in breast cancer progression.

Abstract. The purpose of the present study was to investigate the effects of bafilomycin A1 (BafA1) on proliferation, apoptosis and autophagy in MG63 osteosarcoma cells. The growth rate of MG63 cells was determined using a Cell Counting Kit-8 assay. The mitochondrial membrane potential (Δψ) was measured using a fluorescent probe, JC-1, and the inhibition of autophagy and apoptosis was monitored by transmission electron microscopy. In addition, the inhibition of autophagy was monitored by western blot analysis of microtubule-associated protein 1 light chain 3 (LC3), and the ratio of LC3-II/LC3-I protein levels was calculated as an indicator of the extent of autophagy. Furthermore, the expression levels of specific proteins associated with autophagy, including p53, Beclin1 and p62, were detected in cultured MG63 cells by western blotting. It was shown that the viability of MG63 cells was inhibited following the use of BafA1, and an induction in the expression levels of the apoptosis-related protein p53 and the autophagic protein Beclin1 was detected. Furthermore, a collapse in Δψ was observed, together with an induction of apoptotic cell death, following treatment with BafA1. Therefore, following BafA1-mediated inhibition of autophagy, the inhibition of MG63 cell proliferation and induction of apoptosis were observed.

It has been well documented that the inhibition of the mammalian target of rapamycin (mTOR) induces autophagy in proliferative cells. Therefore, mTOR inhibitors have been proposed for the treatment of cancer. As autophagy plays significant roles in tumor cell survival, the present study aimed to investigate the contribution of autophagy activation to the antitumor effects of cis-diamminedichloroplatinum (CDDP). An MTT assay was used to determine the cytotoxic effects of rapamycin on MG63 osteosarcoma cells. The cell cycle was assessed using a flow cytometry analysis subsequent to staining the DNA with propidium iodide. The mitochondrial membrane potential (Δψ) was measured using the fluorescent probe, JC-1. Western blot analysis was used to determine the expression of the proteins that are involved in apoptosis and autophagy, including p53, p62, light chain 3 (LC3) and Beclin-1. The viability of the MG63 cells was inhibited following rapamycin or CDDP treatment. The mitochondrial Δψ collapsed following treatment with rapamycin or CDDP. Rapamycin induced cell death and enhanced the effects of the induction of MG63 cell death by CDDP. Western blot analysis detected the induced expression of the p53 and Beclin-1 proteins and the autophagic proteins, LC3 and p62. Rapamycin was observed to induce the death of cancer cells through apoptotic and autophagic mechanisms. Rapamycin may enhance the effects of the activation of autophagy and the induction of apoptosis by CDDP.

This study compared the results of the minimally invasive coracoclavicular (CC) fixation with a single TightRope (MITR) procedure and the hook plate (HP) procedure for acute acromioclavicular (AC) joint dislocation treatment. Sixteen patients with a mean age of 44.9 ± 11 years were treated with the MITR procedure. Nineteen patients with a mean age of 40.2 ± 8.7 years were treated using the HP procedure. Clinical outcomes were evaluated with the Visual Analog Scale (VAS) for pain, Constant–Murley Score (CMS), and University of California at Los Angeles (UCLA) Shoulder score. Vertical displacement of the clavicle with reference to the height of the acromion was measured in standard anteroposterior radiographs. The mean follow-up was 27 months in the MITR group and 30 months in the HP group. No statistically significant differences were found between the MITR group and the HR group in terms of VAS score (0.4 ± 0.6 vs 0.7 ± 0.6, P = 0.138), UCLA Shoulder score (33.9 ± 2.5 vs 33.7 ± 1.5, P = 0.843), or CMS (95.7 ± 7.3 vs 93.7 ± 6.6, P = 0.400). No redislocation was identified in the HP group, while redislocation occurred in 1 of 16 (6.3%) patients in the MITR group. One patient in the HP group (5.3%) had acromial osteolysis, while no acromial osteolysis was found in the MITR group. No other adverse events, such as infections, tunnel widening, fractures, or implant-related complications, were observed. Both procedures provided satisfactory results. The HP procedure provided better reduction, while the MITR procedure provided a slightly lower tendency of pain. Long-term follow-up is needed to investigate the clinical outcomes and radiological outcomes of both groups.

Cost-effective treatment strategies for liver fibrosis or cirrhosis are limited. Many clinical trials of stem cells for liver disease shown that stem cells might be a potential therapeutic approach. This review will summarize the published clinical trials of stem cells for the treatment of liver fibrosis/cirrhosis and provide the latest overview of various cell sources, cell doses, and delivery methods. We also describe the limitations and strengths of various stem cells in clinical applications. Furthermore, to clarify how stem cells play a therapeutic role in liver fibrosis, we discuss the molecular mechanisms of stem cells for treatment of liver fibrosis, including liver regeneration, immunoregulation, resistance to injury, myofibroblast repression, and extracellular matrix degradation. We provide a perspective for the prospects of future clinical implementation of stem cells.

Abnormal destruction of the components of the articular extracellular matrix (ECM) such as type II collagen and aggrecan caused by advanced glycation end products (AGEs) has been considered as one of the pathological characteristics of osteoarthritis (OA). Receptor-interacting protein 1 (RIP1), an important serine/threonine kinase, possesses a variety of biological functions including cell proliferation, survival and death. The physiological roles of RIP1 in OA have not been reported before. Here, we found that AGEs increased the expression of RIP1 in human chondrosarcoma cell line SW1353 cells. Importantly, we found that antagonism of RIP1 using its specific inhibitor necrostatin-1 (Nec-1) ameliorated AGE-induced degradation of type II collagen and aggrecan in SW1353 cells. We also found that treatment with Nec-1 reduced the expression of MMP-3 and MMP-13 but restored the expression of Tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. Also, our results indicate that Nec-1 inhibited AGE-induced expression of ADAMTS-4 and ADAMTS-5. Mechanistically, we found that Nec-1 treatment inhibited the activation of JNK and the transcriptional factor AP-1 by reducing the expressions of c-Fos and c-Jun, the two main components of AP-1. Additionally, we found that Nec-1 treatment abolished AGE-induced activation of the transcriptional factor NF-jB by suppressing the nuclear translocation of p65. These findings suggest that RIP1 might be an important therapeutic target of OA.