Glioblastoma (GBM) is the most common primary brain tumor, with poor prognosis and a lack of effective therapeutic options. The aberrant expression transcription factor REST (repressor element 1-silencing factor) had been reported in different kinds tumors. However, function its mechanisms GBM remain elusive. Here, was inhibited by siRNA silencing U-87 U-251 cells. Then CCK-8 assay showed significantly decreased cell proliferation, inhibition migration verified scratch wound healing...

Scaffold proteins play a critical role in controlling the activity of extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. Shoc2 is leucine-rich repeat scaffold protein that acts as positive modulator ERK1/2 signaling. However, precise mechanism by which modulates pathway unclear. Here we report identification E3 ubiquitin ligase HUWE1 binding partner and regulator function. mediates ubiquitination and, consequently, levels Shoc2. Additionally, show both are necessary to control...

Tumor Treating Fields (TTFields) are low-intensity, alternating intermediate-frequency (200 kHz) electrical fields that extend survival of glioblastoma patients receiving maintenance temozolomide (TMZ) chemotherapy. How TTFields exert efficacy on cancer over normal cells or interact with TMZ is unclear. Primary cilia microtubule-based organelles triggered by extracellular ligands, mechanical and field stimulation capable promoting growth chemoresistance. We found in both low- high-grade...

Abstract Holliday junction recognition protein (HJURP) refers to a histone H3 chaperone that has been implicated in different kinds of malignancies. Yet, its character pancreatic cancer remains unclear. The expression HJURP was assessed PDAC tissues by RT-qPCR, immunoblotting, and immunohistochemistry. HJURP-deficient or overexpressed cell lines were constructed, using shRNA plasmids with insert. MTT, sphere formation assay, migration, invasion assays performed evaluate the viability,...

Histone deacetylase 6 (HDAC6) is an emerging therapeutic target that overexpressed in glioblastoma when compared to other HDACs. HDAC6 catalyzes the deacetylation of alpha-tubulin and mediates disassembly primary cilia, a process required for cell cycle progression. inhibition disrupts glioma proliferation, but whether this effect dependent on tumor cilia unknown. We found inhibitors ACY-1215 (1215) ACY-738 (738) inhibited proliferation multiple patient-derived mouse cells. While both...

The scaffold protein Shoc2 accelerates activity of the ERK1/2 pathway. Mutations in result Noonan-like RASopathy, a developmental disorder with wide spectrum symptoms. amplitude signals transduced through complex is fine-tuned by HUWE1-mediated ubiquitination and its signaling partner RAF-1. Here we provide mechanistic basis how RAF-1 controlled. We demonstrate that newly identified binding Shoc2, (AAA+) ATPase PSMC5, triggers translocation to endosomes. At endosomes PSMC5 displaces...

Tolerogenic dendritic cells (tolDCs) have emerged as a potential treatment for rheumatoid arthritis (RA). However, the detailed mechanism requires further investigation. In this study, we aimed to explore effects of tolDCs on T-cell differentiation and NLRP3-mediated pyroptosis in collagen-induced (CIA) rat model. TolDCs were induced using NF-κB ODN decoy. The efficacy intervention alleviating symptoms was evaluated CIA rats. Flow cytometry employed analyze CD4+ subpopulations, while...

Abstract BACKGROUND: Patients with chronic myelogenous leukemia (CML) in blast crisis have a poor response to tyrosine kinase inhibitors designed inhibit the breakpoint cluster region–v‐Abelson murine viral oncogene homolog 1 (BCR‐ABL1) oncogene. Recent work has demonstrated that heme oxygenase (HO‐1) expression is increased BCR‐ABL1–expressing cells and inhibition of HO‐1 CML leads reduced cellular growth, suggesting may be plausible target for therapy. The objective current study was...

Mesenchymal stem cells (MSCs) are emerging as a promising therapeutic approach and genetic modification by non-viral vectors could span their applications. Herein, the capacity of PEI-coated Fe3O4 nanoparticles (NPs) for siRNA delivery to human MSCs derived from different tissues was evaluated. The prepared spherical NPs with charge around +44.0 mV an average diameter 12 nm exhibited proper encapsulation enhanced serum stability. High-purity were isolated bone marrow, adipose tissue amnion...

In this study, we identified wound healing-related proteins secreted by human amniotic epithelial cells (hAECs) and mesenchymal stem (hAMSCs). We observed increased migration reduced proliferation differentiation when keratinocytes were co-cultured in media conditioned hAECs (hAECs-CM) hAMSCs (hAMSCs-CM). Label-free mass spectrometry bioinformatic analyses of the hAECs-CM hAMSCs-CM proteome revealed several associated with healing, angiogenesis, cellular differentiation, immune response cell...

ADP-ribosylation factor-like protein 13B (ARL13B), a regulatory GTPase and guanine exchange factor (GEF), enriches in primary cilia promotes tumorigenesis part by regulating Smoothened (SMO), GLI, Sonic Hedgehog (SHH) signaling. Gliomas with increased

Tumor Treating Fields (TTFields) extend the survival of glioblastoma (GBM) patients by interfering with a broad range tumor cellular processes. Among these, TTFields disrupt primary cilia stability on GBM cells. Here we asked if concomitant treatment other agents that interfere ciliogenesis further suppress cell proliferation in vitro. Aurora kinase A (AURKA) promotes both disassembly and growth. Inhibitors AURKA, such as Alisertib, inhibit increase ciliary frequency various types. However,...

Abstract Background: To investigate the effect and mechanism of exosomes derived from human amniotic mesenchymal stem cells (hAMSC-Exos) promoting angiogenesis. Methods: HAMSC-Exos were isolated using ultracentrifugation characterized by transmission electron microscopy, NTA, Western blot. The uptake hAMSC-Exos hUVECs was analyzed PKH-26 labeling, on angiogenesis in umbilical vein endothelial cell viability assay, Transwell migration Matrigel tube formation plug assays nude mice....

Abstract Tonsillar marginal zone hyperplasia may mimic mucosa-associated lymphoid tissue lymphoma, a rare diagnosis in children. Histologically, both entities can demonstrate expansion of the with disruption follicular architecture. However, appear polyclonal by flow cytometry. We present two pediatric tonsillectomy cases tonsillar and discuss diagnostic challenges this poses population. Both tonsillectomies demonstrated zones partial architectural effacement, cytometric analysis detected...

This study aimed to detect the roles of miRNA-203a in fetal cutaneous regeneration.The levels miR-203a eight mid-gestational and ten late-gestational epidermis tissues were detected by real-time qRT-PCR.The expressions α-SMA, TGF-β2 TGF-β3 qRT-PCR Western blot.Moreover, proliferation migration abilities keratinocytes (KCs) fibroblasts (FBs) examined using MTS transwell cell assays.Bioinformatics analyses, luciferase reporter ELISA assays used examine potential target genes.The results showed...

Objective: To explore the clinical efficacy of damage control orthopaedics in treatment patients with severe traumatic brain injury combined limb fracture. Methods: Total 149 sTBI fracture treated Emergency Surgery Department Shandong University Qilu Hospital from January, 2011 to December, 2018 were collected. Patients that immediate definitive fixation before March 31st, 2013 included into routine group (group A, 47 cases), and (DCO) after April 1st, DCO B, 102 cases). The data during...

Abstract Tumor Treating Fields (TTFields) are low intensity, alternating intermediate frequency (200kHz) electrical fields that extend survival of glioblastoma patients receiving maintenance temozolomide (TMZ) chemotherapy. How TTFields exert efficacy on cancer over normal cells, or interact with TMZ is unclear. Primary cilia microtubule-based organelles triggered by extracellular ligands, mechanical and field stimulation, capable promoting growth chemoresistance. We found in both high grade...

Abstract Tumor Treating Fields (TTFields) can prolong survival of patients with glioblastoma (GBM), but GBM cells still escape this therapy requiring an urgent need for new or adjunct treatments. Recently we reported that TTFields disrupt primary cilia on which lowers resistance to standard care temozolomide chemotherapy. Here asked if concomitant sequential treatment other agents interfere ciliogenesis enhance efficacy. Aurora Kinase A (AURKA) plays both a role in promoting disassembly and...

Abstract Tumor Treating Fields (TTFields) have been shown to extend the survival of glioblastoma (GBM) patients. TTFields interfere with a broad range cellular processes which may contribute their efficacy. Among these, disrupt primary cilia stability on GBM cells. Here we asked if concomitant treatment other agents that ciliogenesis can further suppress cell proliferation in vitro. Aurora Kinase A (AURKA) promotes both disassembly and growth vitro xenograft models. Inhibitors AURKA such as...