AAZ2 induces mitochondrial-dependent apoptosis by targeting PDK1 in gastric cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Drastic surges in intracellular reactive oxygen species (ROS) induce cell apoptosis, while most chemotherapy drugs lead to the accumulation of ROS. Here, we constructed an organic compound, arsenical N-‍(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide (AAZ2), which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer (GC). Mechanistically, by targeting pyruvate dehydrogenase kinase 1 (PDK1), AAZ2 caused metabolism alteration and the imbalance of redox homeostasis, followed by the inhibition of phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway and leading to the activation of B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax)/caspase-9 (Cas9)/Cas3 cascades. Importantly, our in vivo data demonstrated that AAZ2 could inhibit the growth of GC xenograft. Overall, our data suggested that AAZ2 could contribute to metabolic abnormalities, leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.

Aspirin effects on MG-63 cell proliferation on different modified titanium surfaces under fluid shear stress / 中国组织工程研究

BACKGROUND:Recent research has shown that the proper concentration of aspirin can increase the proliferation and osteogenic ability of MG-63 cells.OBJECTIVE:To explore the effects of different concentrations of aspirin on osteoblast proliferation on the implant-cell interface under fluid shear stress.METHODS:(1) MG-63 cells were cultured in low-glucose DMEM containing 10％ fetal bovine serum and different concentrations of aspirin (0,0.023,0.046,0.0625,0.125,0.25,0.5,1.0,2.0,4.0 mmol/L) for 1-7 days.Then cell proliferation was detected using MTS method.(2) MG-63 cells were cultured on three different surfaces:glass slide,PT titanium surface and SLA titanium surface.After 3 days of culture with aspirin at a concentration of 0 or 0.5 mmol/L,the cells were subjected to fluid shear stress.MTS test was applied to estimate the proliferation of MG-63 cells at 0,0.5,1,2,4 hours after stress application.RESULTS AND CONCLUSION:(1) After 1-3 days of culture,0.023,0.046,0.5 mmol/L aspirin promoted the proliferation of MG-63 cells,while after 1-7 days of culture,1,2,4 mmol/L aspirin inhibited the proliferation of MG-63 cells.(2) Under the fluid shear stress,aspirin showed significant effects on the cell proliferation as confirmed by one-way analysis of variance (F=8.349,P=0.004),and 0.5 mmol/L aspirin inhibited the cellular proliferation of MG-63 cells.However,surface modification and stress loading time showed no significant effects on the cell proliferation (F=2.826,P=0.064;F=0.893,P=0.406).(3) Under the fluid shear stress,surface modification showed no significant effect on the cell proliferation of MG-63 cells cultured with 0.5 mmol/L aspirin (F=1.803,P=-0.171).Under the fluid shear stress,0.5 mmol/L aspirin significantly inhibited the proliferation of MG-63 cells on the glass slide (P=-0.003),while PT and SLA titanium surfaces showed on inhibitory effect on the cell proliferation (P=0.891,P=0.051).The present results demonstrate that the cell proliferation of MG-63 is related with aspirin in a concentration-dependent manner.In addition,different titanium surfaces may decrease the sensitivity of MG-63 cell proliferation to aspirin.

Effects of cetylpyridinium chloride buccal tablets on halitosis induced by oral conditions / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of cetylpyridinium chloride buccal tablets on halitosis induced by oral conditions.</p><p><b>METHODS</b>With Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum as the testing bacteria, the minimal inhibitory concentration (MIC) of cetylpyridinium chloride buccal tablets was determined using minute amount serial dilution test. The production of volatile sulfur compounds (VSCs) was measured using sulfide detector halimeter in the anaerobic bacteria culture at 4 and 8 h after addition of the tablets. The effect of the tablets in suppressing odor production by mouth-borne halitosis bacteria was assessed using cysteine challenge test in healthy volunteers, and the effectiveness was evaluated by measuring the reduction in VSCs production and the duration of the effect.</p><p><b>RESULTS</b>Cetylpyridinium chloride buccal tablets inhibited the growth of all the 3 bacteria. The tablets obviously inhibited VSCs production by the 3 bacteria with a effect similar to chlorhexidine. Compared with distilled water gargle, the buccal tablets significantly reduced cysteine-induced VSCs production level in the healthy volunteers (P<0.05), and the effect lasted for 230 min.</p><p><b>CONCLUSION</b>Cetylpyridinium chloride tablets can obviously suppress bacteria responsible for oral halitosis and produce good effects in the treatment of halitosis induced by oral conditions.</p>

Glycogen synthase kinase-3: a key kinase in retinal neuron apoptosis in early diabetic retinopathy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Diabetes-related pathogenic factors can cause retinal ganglion cell (RGC) apoptosis, but the specific mechanism is not very clear. The aim of this study is to investigate the correlation between glycogen synthase kinase-3 (GSK-3) activation and retinal neuron apoptosis.</p><p><b>METHODS</b>In an in vitro experiment, the number of apoptotic RGC-5 cells differentiated by staurosporine was evaluated via flow cytometry and nuclei staining using Hoechst 33258. GSK-3 phosphorylation and caspase-3 activation in RGC-5 cells after serum deprivation were determined using Western blotting. Mitochondrial membrane potential was detected using the dye 5, 5', 6, 6'tetrachloro-1, 1', 3, 3'-tetrethyl benzimidalyl carbocyanine iodide, and reactive oxygen species (ROS) levels were measured with dihydroethidium. In an in vivo experiment, the number of apoptotic retinal neurons was evaluated via terminal transferase dUTP nick-end labeling (TUNEL), and GSK-3 phosphorylation was determined using Western blotting, in the retinal nerve epithelial tissue of rats in which diabetes was induced by intravenous tail-vein injection of streptozotocin for 4 weeks.</p><p><b>RESULTS</b>The levels of phosphorylated Ser21/9 in GSK-3α/β and p-T308/S473-AKT were lower and the cleaved caspase-3 levels were higher in the serum-deprived model (P < 0.05). Lithium chloride treatment was associated with a slower rate of apoptosis, increased mitochondrial membrane potential, and decreased ROS levels in differentiated RGC-5 cells (P < 0.05). The level of blood glucose and the number of TUNEL-positive cells in the whole-mounted retinas were higher (P < 0.01), and the levels of phosphorylated Ser21/9 in GSK-3α/β and body weight were lower (P < 0.05). However, the thickness of the retinal nerve epithelial layer was not significantly less in diabetic rats compared with control group. Lithium chloride intravitreal injection increased the levels of phosphorylated Ser21/9 in GSK-3α/β and decreased TUNEL-positive cells in the whole-mounted retinas.</p><p><b>CONCLUSION</b>GSK-3 kinase is closely related to retinal neuron apoptosis, and the application of the GSK-3 inhibitor lithium chloride can reduce retinal neuron apoptosis in early diabetic retinopathy.</p>

RGD peptide-modified chitosan as a gene carrier of implant surface / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study is conducted to explore new methods to perform surface biomodification of titanium implants and improve osteogenic efficiency.</p><p><b>METHODS</b>An RGD peptide and chitosan (CS) were combined by acylation reaction, forming RGD-CS. An RGD-CS/pDNA complex was subsequently prepared using a complex coacervation method and grafted on a pure titanium surface after physical and biochemical treatments were performed. The chemical structural characteristics of RGD-CS were evaluated using an infrared spectrometer and an elemental analyzer. The shape of this complex was then assessed by gel electrophoresis combined with atomic force microscopy. The grafting effect of this complex on the titanium surface was detected by EB staining.</p><p><b>RESULTS</b>CS and RGD peptides were coupled by an amide bond. The RGD-CS/pDNA complex was completely composited at N/P > or = 2. Atomic force microscopy results showed that the morphology of this complex was mainly spherical. EB staining experiments showed that this complex was successfully grafted on the titanium plate.</p><p><b>CONCLUSION</b>RGD peptide-modified CS can be used as a titanium implant surface plasmid package carrier of pDNA.</p>

Construction of human bone morphogenetic protein 2 and histidine eukaryotic expression plasmid and synthesis of chitosan/pIRES2-EGFP-hBMP2-His nanoparticles / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To clone and construct a eukaryotic expression vector of human bone morphogenetic protein (BMP) 2 and histidine in vitro and synthesize chitosan (CS)/pIRES2-EGFP-hBMP2-His nanoparticles.</p><p><b>METHODS</b>pMD18T-hBMP2-His was digested by EcoR I and BamH I to obtain the hBMP2-His gene, which was inserted into pIRES2-EGFP to form pIRES2-EGFP-hBMP2-His. Afterward, CS, which exhibited five different molecular weights and deacetylation degrees, was complexed with pIRES2-EGFP-hBMP2-His to form CS/pIRES2-EGFP-hBMP2-His nanoparticles; in this procedure, a desolvent method was used at different N/P ratios (amino in CS to phospho in plasmid DNA). The gene-encapsulating ability of CS was evaluated by agarose gel electrophoresis and fluorescence spectrophotometry; size, distribution, and potential were analyzed using a ZetaPALS analyzer. The shape of the nanoparticles was observed under an atomic force microscope.</p><p><b>RESULTS</b>1) pIRES2-EGFP-hBMP2-His was constructed after the cloned hBMP2-His gene was confirmed by sequencing. 2) CS/pIRES2-EGFP-hBMP2-His nanoparticles were synthesized and pIRES2-EGFP-hBMP2-His was packaged by CS. 3) CS/pIRES2-EGFP-hBMP2-His nanoparticles were globular with an average size of 111.7 nm to 3,214.2 nm and an average zeta-potential of 4.93 mV to 16.79 mV.</p><p><b>CONCLUSION</b>CS/pIRES2-EGFP-hBMP2-His nanospheres are successfully synthesized.</p>

Inhibition of Cell Growth of Human Ovarian Cancer by Xiaoaiping Injection via Akt Signal Pathway / 中国中医药信息杂志

Objective To study the effect of Xiaoaiping injection on Caov-3 human ovarian cancer cells and its mechanisms. Methods After treatment with Xiaoaiping injection, viability of Caov-3 cells determined by MTT method. Phase contrast microscopy was used to observed the morphological changes of Caov-3 cells. Cell cycle was assessed by FACS. Cell signaling pathway protein-Akt and pAkt, and cell cycle associated protein-p27 were measured by western blot. Results Xiaoaiping injection inhibited the growth of Caov-3 human ovarian cancer cells in a dose and time dependent manner. Xiaoaiping injection induced G0/G1 phase arrest of Caov-3 cells, accompanied by pAkt down-regulation and p27 up-regulation. Conclusion Xiaoaiping injection can inhibit the proliferation of Caov-3 human ovarian cancer cells by inhibiting PI3K/Akt signaling pathway.

The role of TF-1 cell apoptosis-related gene 19 in systemic lupus erythematosus / 中国病理生理杂志

AIM: To clarify the role of new apoptosis-related gene, TF-1 cell apoptosis-related gene 19(TFAR19), in the pathogenesis of systemic lupus erythematosis (SLE) and the relationship between TFAR19 and SLE. METHODS: DNA Ladder detection, Western blotting, immunological fluorescence method, ELISA and so on were used to test if ultraviolet B(UVB) could induce HaCaT cell apoptosis and TFAR19 expression. RESULTS: HaCaT cell apoptosis could be detected after 24 hours of 30 mj/cm 2 UVB irradiation. Also, we found that in active SLE patients, the TFAR19 antibody was increased, but not significant compared to the normal control. CONCLUSION: TFAR 19 is involved in the process of UVB induced ketatinocyte line HaCaT apoptosis and SLE pathogenesis.