• Valentine Thorsen posted an update 6 months, 3 weeks ago

    The deregulation of exosomal microRNAs (miRNAs) plays an important role in the progression of hepatocarcinogenesis. In this study, we highlight exosomes as mediators involved in modulating miRNA profiles in liver cancer cells after induction of the epithelial-mesenchymal transition (EMT) and metastasis. Initially, we induced EMT in a hepatocellular carcinoma cell (HCC) line (Hep3B) by stimulation with transforming growth factor-β (TGF-β) and confirmed by western blot detection of EMT markers such as vimentin and E-cadherin. Exosomes were then isolated from the cells and identified by nanoparticle tracking analysis (NTA). The isolated exosomal particles from unstimulated Hep3B cells (Hep3B exo) or TGF-β-stimulated EMT Hep3B cells (EMT-Hep3B exo) contained higher levels of exosome marker proteins, CD63 and TSG101. After incubation with EMT-Hep3B exo, Hep3B cell proliferation increased. EMT-Hep3B exo promoted the migration and invasion of Hep3B and 7721 cells. High-throughput sequencing of miRNAs and mRNA within the exosomes showed 119 upregulated and 186 downregulated miRNAs and 156 upregulated and 166 downregulated mRNA sequences in the EMT-Hep3B exo compared with the control Hep3B exo. The most differentially expressed miRNAs and target mRNA sequences were validated by RT-qPCR. Based on the known miRNA targets for specific mRNA sequences, we hypothesized that GADD45A was regulated by miR-374a-5p. Inhibition of miR-374a-5p in Hep3B cells resulted in exosomes that inhibited the proliferation, migration, and invasion of HCC cells. These results enhance our understanding of metastatic progression of liver cancer and provide a foundation for the future development of potential biomarkers for diagnosis and prognosis of hepatic cancer. AJTR Copyright © 2020.Osteonecrosis of the femoral head (ONFH) is a common disorder that may be idiopathic, caused by trauma, or associated with alcohol or glucocorticoid use. The goals of early treatment include delaying or avoiding hip replacement, but there are no effective treatments for early-stage disease. The aim of the present study was to evaluate the effects of treatment with 3D-printed porous titanium alloy scaffold combined with daily intraperitoneal trans-cinnamaldehyde (TCA) in a dog model of ONFH. Four weeks after creation of the ONFH model, MRI examination of the femoral head showed the characteristic “double line sign” of ONFH, verifying the validity of our model. After another 12 weeks, femoral head specimens were harvested and examined by gross inspection; micro-computed tomography; histologic staining (hematoxylin and eosin; Masson); immunohistochemical analysis and quantitative real-time polymerase chain reaction analysis. Gross inspection of the femoral head in untreated ONFH animals at 16 weeks after model creation showed pale, exfoliating articular cartilage and disordered trabecular bone. Treatment with 3D-printed titanium alloy porous scaffold combined with TCA ameliorated the pathologic ONFH changes and significantly reduced inmature bone tissue as well as imature collagen in the femoral head, as shown by Masson staining. This treatment also increased VEGF, BMP2, β-catenin, b-FGF, and RUNX2 expression and decreased PPARγ expression, compared with untreated ONFH. In conclusion, 3D-printed titanium alloy porous scaffold combined with TCA can effectively improve ONFH, which may be related to local repair. This provides the theoretical basis for a new treatment strategy for ONFH. selleck products AJTR Copyright © 2020.Sox9 is the master transcription factor essential for cartilage development and homeostasis. To investigate the specific role of Sox9 during chondrocyte hypertrophy, we generated a novel Col10a1-Sox9 transgenic mouse model, in which Sox9 is specifically expressed in hypertrophic chondrocytes driven by a well-characterized 10-kb Col10a1 promoter. These mice were viable and fertile, and appeared normal at birth. However, they developed dwarfism by ten weeks of age. The histological analysis of the growth plates from these transgenic mice demonstrated an abnormal growth plate architecture and a significantly reduced amount of trabecular bone and mineral content in the primary spongiosa. Real-time qPCR analysis revealed the reduced expression of Col10a1, and increased expressions of adipogenic differentiation markers in primary hypertrophic chondrocytes isolated from transgenic mice. Concomitantly, the transgenic mouse chondrocyte cultures had increased lipid droplet accumulation. Unexpectedly, we also observed an increased incidence of spontaneous osteoarthritis (OA) development in the transgenic mice by X-ray analysis, micro-computed tomography scanning, and histological examination of knee joints. The manifestation of OA in Col10a1-Sox9 transgenic mice began by six-months of age, and worsened by eleven-months of age. In conclusion, we provide strong evidence that the proper spatiotemporal expression of Sox9 is necessary for normal adult hypertrophic cartilage homeostasis, and that the aberrant expression of Sox9 might lead to spontaneous OA development. AJTR Copyright © 2020.Tumor biopsy is the standard method for cancer diagnosis and provides an important sample for pathological assessment. With the development of precision medicine, liquid biopsies are now an important tool to detect molecular changes and tumor heterogeneity. In recent years, research related to circulating tumor DNA (ctDNA) has intensified due to its non-invasive, convenient, comprehensive, and safety characteristics. Herein, we provide a review describing the clinical applications and prospects of ctDNA in colorectal cancer (CRC) diagnosis, monitoring and prognosis. AJTR Copyright © 2020.Dinaciclib is a small molecule cyclin-dependent kinase inhibitor with the potential to treat multiple cancers. To better understand its cytotoxic action in pancreatic ductal adenocarcinoma (PDAC), we evaluated dinaciclib therapeutic effects in the transgenic mouse model (LSL-KrasG12D/+ ; LSL-Trp53R172H/+ ; Pdx-1-Cre mice; KPC mice). Tumor growth and microenvironment were dynamically monitored by magnetic resonance imaging (MRI). Dinaciclib therapy significantly delayed tumor progression (P less then 0.001) and prolonged survival (P = 0.007) in KPC mice. In vitro assays showed that dinaciclib exerted antiproliferative effects on PDAC cells by increasing surface calreticulin expression and release of ATP. Dinaciclib treatment inhibited proliferation and induced apoptosis in KPC tumor as assessed by Ki67 and cleaved caspase 3, respectively. Particularly, the tumor infiltrating CD8+ T cells were increased after dinaciclib treatment in KPC mice. Additionally, the mean apparent diffusion coefficient values of KPC tumor calculated from diffusion weighted MR images were significantly lower after dinaciclib treatment (P = 0.

All content contained on CatsWannaBeCats.Com, unless otherwise acknowledged,is the property of CatsWannaBeCats.Com and subject to copyright.

CONTACT US

We're not around right now. But you can send us an email and we'll get back to you, asap.

Sending

Log in with your credentials

or    

Forgot your details?

Create Account