Nestin is widely expressed in numerous tumors and has become a diagnostic and prognostic indicator. However, the exact mechanism by which nestin contributes to tumor malignancy remains poorly understood. Here, we found marked upregulation of nestin expression in highly proliferative and invasive gastrointestinal stromal tumor (GIST) specimens. Nestin knockdown in GIST cells reduced the proliferative and invasive activity owing to a decrease of mitochondrial intracellular reactive oxygen species (ROS) generation. Furthermore, nestin was co-localized with mitochondria, and knockdown of nestin increased mitochondrial elongation and influenced the mitochondrial function, including oxygen consumption rates, ATP generation and mitochondrial membrane potential and so on. In exploring the underlying mechanism, we demonstrated nestin knockdown inhibited the mitochondrial recruitment of Dynamin-related protein1 and induced the change of mitochondrial dynamics. Thus, nestin may have an important role in GIST malignancy by regulating mitochondrial dynamics and altering intracellular ROS levels. The findings provide new clues to reveal mechanisms by which nestin mediates the proliferation and invasion of GISTs.
ABSTRACT. Silica (SiO 2 ) nanoparticles are being progressively applied in various applications, including cosmetics, food technology, and medical diagnostics. Although crystalline SiO 2 is a known carcinogen, the carcinogenicity of SiO 2 nanoparticles remains unclear. Here, we assessed the cytotoxic effects and DNA injury induced by exposure to various dosages of SiO 2 nanoparticles at 0-2400 mg/mL (0-3200 mg/mL microscale SiO 2 as positive control) for 24 h using RAW264.7 cells, followed by methyl tetrazolium (MTT) assay. Cells were also treated by 31.25, 125, and 500 mg/mL SiO 2 nanoparticles (500 mg/mL microscale SiO 2 as positive control) for 24 h and examined by single cell gel electrophoresis assay (SCEG) and flow cytometry. Outstanding dose-related decline in cell viability was observed with enhancing dosages of SiO 2 nanoparticles by MTT assay. The inhibitory concentration 50% of SiO 2 nanoparticles and microscale SiO 2 was 16690 and 5080 mg/mL, respectively. The comet rate (comet%), length of tail, the percentage in DNA tail (TDNA%) and olive tail moment (OTM) induced by SiO 2 nanoparticles were significantly increased in comparison with control and microscale SiO 2 at 500 mg/mL. 500 mg/mL SiO 2 nanoparticles and microscale SiO 2 caused a significant increase in apoptosis rate, decreased proliferation index and increased cell proportions in G 0 /G 1 phases by contrast to the negative control (P < 0.05). This indicates that SiO 2 nanoparticles are more cytotoxic than microscale SiO 2 particles; they induce DNA injury, increase apoptosis, and decrease the proliferation index in RAW264.7 cells. DNA injury and apoptosis may be involved in reducing cell proliferation.
A synthesized benzothiazole containing mono-methacrylate monomer BTTMA was incorporated into Bis-GMA/TEGDMA dental resin system with a series of mass concentration from 5 to 30 wt.% as an antibacterial agent. The influence of BTTMA on physicochemical properties of dental resin system, such as double bond conversion (DC), volumetric shrinkage (VS), flexural strength (FS) and modulus (FM), water sorption (WS) and solubility (SL) were investigated. Direct contact testing and agar diffusion testing were used to evaluate the antibacterial activity of BTTMA containing dental resin. The results showed that BTTMA could endow dental resin with significant antibacterial activity when its concentration reached a certain amount (20 wt.%), and the antibacterial activity of BTTMA containing dental resin was mainly attributed to the immobilized BTTMA instead of the unreacted leachable BTTMA. BTTMA had no negative effect on physicochemical properties of dental resin, and even some BTTMA containing dental resins had advantages like higher DC, lower VS and WS when compared with control resin. Therefore, BTTMA could be considered as a suitable antibacterial agent in dental material, but much more researches concerned about biocompatibility should be done in future to prove whether it could be applied in clinic.
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