Electrical Activity and Extremes of Individual Suspended ZnO Nanowires for 3D Nanoelectronic Applications.

We explored the electrical activity and extremes inside individual suspended zinc oxide (ZnO) nanowires (NWs) (diameter: 50-550 nm, length: 5-50 µm) subjected to high forward bias-induced Joule heating using two-terminal current-voltage measurements. NWs were isolated using a reproducible nanometrology technique, employing a nanomanipulator inside a scanning electron microscope. Schottky behavior is observed between installed tips and ZnO NW. The suspended ZnO NWs exhibited an average electrical resistivity ρ (approximately 2.3 × 10-2 Ω cm) and a high electron density n (exceeding 1.89 × 1018 cm-3), comparable to that of InP NWs, GaN NWs, and InAs NWs (1018∼1019 cm-3), suggesting the potential to drive advancements in high-performance NW devices. A maximum breakdown current density (JBD) of ∼0.14 MA/cm2 and a maximum breakdown power density (PBD) of 6.93 mW/µm3 were obtained, both of which are higher than substrate-bound ZnO NWs and consistent with previously reported results obtained from probed ZnO NWs grown vertically on the substrate. Moreover, we discovered that NWs experienced thermal breakdown due to Joule heating and exploited this breakdown mechanism to further investigate the temperature distribution along the ZnO NWs, as well as its dependence on the electrical properties and thermal conductance of contact electrodes. Thermal conductance was determined to be ∼0.4 nW K-1 and ∼1.66 pW K-1 at the tungsten(W)-ZnO NW and platinum(Pt)-ZnO NW contacts, respectively. In addition, we measured the elastic modulus (130-171 GPa), which closely approximated bulk values. We also estimated the nanoindentation hardness to be between 5 and 10 GPa. This work provides valuable insights into the electrical activity and extreme mechanisms, thus providing a better understanding of the potentials and limitations associated with utilizing suspended NWs in 3D nanodevices.

Design and Joint Position Control of Bionic Jumping Leg Driven by Pneumatic Artificial Muscles.

Using the skeletal structure and muscle distribution of the hind limbs of a jumping kangaroo as inspiration, a bionic jumping leg was designed with pneumatic artificial muscles (PAMs) as actuators. Referring to the position of biarticular muscles in kangaroos, we constructed a bionic joint using biarticular and monoarticular muscle arrangements. At the same time, the problem of the joint rotation angle limitations caused by PAM shrinkage was solved, and the range of motion of the bionic joint was improved. Based on the output force model of the PAM, we established a dynamic model of the bionic leg using the Lagrange method. In view of the coupling problem caused by the arrangement of the biarticular muscle, an extended state observer was used for decoupling. The system was decoupled into two single-input and single-output systems, and angle tracking control was carried out using active disturbance rejection control (ADRC). The simulation and experimental results showed that the ADRC algorithm had a better decoupling effect and shorter adjustment time than PID control. The jumping experiments showed that the bionic leg could jump with a horizontal displacement of 320 mm and a vertical displacement of 150 mm.

Sea-Surface Target Visual Tracking with a Multi-Camera Cooperation Approach.

Cameras are widely used in the detection and tracking of moving targets. Compared to target visual tracking using a single camera, cooperative tracking based on multiple cameras has advantages including wider visual field, higher tracking reliability, higher precision of target positioning and higher possibility of multiple-target visual tracking. With vast ocean and sea surfaces, it is a challenge using multiple cameras to work together to achieve specific target tracking and detection, and it will have a wide range of application prospects. According to the characteristics of sea-surface moving targets and visual images, this study proposed and designed a sea-surface moving-target visual detection and tracking system with a multi-camera cooperation approach. In the system, the technologies of moving target detection, tracking, and matching are studied, and the strategy to coordinate multi-camera cooperation is proposed. The comprehensive experiments of cooperative sea-surface moving-target visual tracking show that the method used in this study has improved performance compared with contrapositive methods, and the proposed system can meet the needs of multi-camera cooperative visual tracking of moving targets on the sea surface.

Discovery of highly potent tubulin polymerization inhibitors: Design, synthesis, and structure-activity relationships of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidines.

By removing 5-methyl and 6-acetyl groups in our previously reported compound 3, we designed a series of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine derivatives as potential tubulin polymerization inhibitors. Among them, compound 5e displayed low nanomolar antiproliferative efficacy on HeLa cells which was 166-fold higher than the lead analogue 3. Interestingly, 5e displayed significant selectivity in inhibiting cancer cells over HEK-293 (normal human embryonic kidney cells). In addition, 5e dose-dependently arrested HeLa in G2/M phase through the alterations of the expression levels of p-cdc2 and cyclin B1, and caused HeLa cells apoptosis by regulation of expressions of cleaved PARP. Further evidence demonstrated that 5e effectively inhibited tubulin polymerization and was 3-fold more powerful than positive control CA-4. Moreover, molecular docking analysis indicated that 5e overlapped well with CA-4 in the colchicine-binding site. These studies demonstrated that 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine skeleton might be used as the leading unit to develop novel tubulin polymerization inhibitors as potential anticancer agents.

Mechanical/Electrical Characterization of ZnO Nanomaterial Based on AFM/Nanomanipulator Embedded in SEM.

ZnO nanomaterials have been widely used in micro/nano devices and structure due to special mechanical/electrical properties, and its characterization is still deficient and challenging. In this paper, ZnO nanomaterials, including nanorod and nanowire are characterized by atomic force microscope (AFM) and nanomanipulator embedded in scanning electron microscope (SEM) respectively, which can manipulate and observe simultaneously, and is efficient and cost effective. Surface morphology and mechanical properties were observed by AFM. Results showed that the average Young's modulus of ZnO nanorods is 1.40 MPa and the average spring rate is 0.08 N/m. Electrical properties were characterized with nanomanipulator, which showed that the ZnO nanomaterial have cut-off characteristics and good schottky contact with the tungsten probes. A two-probe strategy was proposed for piezoelectric property measurement, which is easy to operate and adaptable to multiple nanomaterials. Experiments showed maximum voltage of a single ZnO nanowire is around 0.74 mV. Experiment criteria for ZnO manipulation and characterization were also studied, such as acceleration voltage, operation duration, sample preparation. Our work provides useful references for nanomaterial characterization and also theoretical basis for nanomaterials application.

Synthesis and biological evaluation of benzofuran-based 3,4,5-trimethoxybenzamide derivatives as novel tubulin polymerization inhibitors.

A new series of derivatives characterized by the presence of the 3,4,5-trimethoxylbenzamide substituted benzofurans were synthesized and evaluated for antiproliferative activity against four cancer cell lines and one normal human cell line. Among them, derivative 6g with greatest cytotoxicity significantly inhibited the growth of MDA-MB-231, HCT-116, HT-29 and HeLa cell lines with IC50 values of 3.01, 5.20, 9.13, and 11.09 µM, respectively. Importantly, 6g possessed excellent selectivity over non-tumoral cell lines HEK-293 (IC50 > 30 µM). Moreover, mechanistic studies revealed that 6g induced HeLa cells arrested in G2/M phase in a concentration-dependent manner, and inhibited polymerization of tubulin via a consistent way with CA-4. In general, these observations suggest that 6g is a promising anti-cancer lead and is worth further investigation to generate potential antitumor agents.

Frying Oil Evaluation by a Portable Sensor Based on Dielectric Constant Measurement.

A portable capacitive sensor was designed to assess frying oil degradation by measuring the changes in electrical capacitance. An interdigital electrode (IDE) was designed to be implemented as the testing probe (as IDEs are resistive to parasitic capacitance), together with an adjacent capacitive chip Pcap01 and a further microprocessor STM32, which were used as the data-processing elements. Experimental results demonstrated that viscosity could be a useful frying oil quality indicator, and also proved a preliminary correlation between IDE capacitance and oils' total polar materials. This implies that IDE capacitance could be a suitable metric for conveniently assessing frying oil degradation. The designed capacitance sensor is light in weight, cost effective, and has excellent potential for simple, inexpensive, on-the-spot testing of the current quality of frying oil.

Accurate Measurements of the Rotational Velocities of Brushless Direct Current-Motors by Using an Ultrasensitive Magnetoimpedance Sensing System.

Reports on measurements of the rotational velocity by using giant magnetoimpedance sensors are rarely seen. In this study, a rotational-velocity sensing system based on giant magnetoimpedance (GMI) effect was established to measure rotational velocities of brushless direct-current motors. Square waves and sawtooth waves were observed due to the rotation of the shaft. We also found that the square waves gradually became sawtooth waves with increasing the measurement distance and rotational velocity. The GMI-based rotational-velocity measurement results (1000-4300 r/min) were further confirmed using the Hall sensor. This GMI sensor is capable of measuring ultrahigh rotational velocity of 84,000 r/min with a large voltage response of 5 V, even when setting a large measurement distance of 9 cm. Accordingly, the GMI sensor is very useful for sensitive measurements of high rotational velocity.

Interactive Manipulation of Nonconductive Microparticles in Scanning Electron Microscope by a Virtual Nano-hand Strategy.

Micro/nano-manipulation is the fabrication of particular constructs on devices at the micro/nano-scale. Precise manipulation of microparticles is one of the key technological difficulties in manufacturing micro/nano-scale components. Based on scanning electron microscopy and nanomanipulator, this paper adopts a direct push method to operate randomly distributed microparticles into ordered structures. A two-probe interaction strategy is proposed to enable microparticle movements in all directions efficiently and avoid scratching the substrate surface. To overcome the uncertainties in micromanipulation, a virtual nano-hand strategy was also implemented: long-range advance of each microparticle is realized by multiple single-step pushes, whose trajectory is theoretically analyzed. The pushes are well programmed to imitate effects of a more powerful and determined hand. Experimental results show that the theoretical single-step motion trajectory is in line with actual operation, and the proposed strategy can ensure precise operation of the microparticles in all directions and improve reliability and effectiveness of operation.

Tumor Microenvironment Characterization in Gastric Cancer Identifies Prognostic and Immunotherapeutically Relevant Gene Signatures.

Tumor microenvironment (TME) cells constitute a vital element of tumor tissue. Increasing evidence has elucidated their clinicopathologic significance in predicting outcomes and therapeutic efficacy. Nonetheless, no studies have reported a systematic analysis of cellular interactions in the TME. In this study, we comprehensively estimated the TME infiltration patterns of 1,524 gastric cancer patients and systematically correlated the TME phenotypes with genomic characteristics and clinicopathologic features of gastric cancer using two proposed computational algorithms. Three TME phenotypes were defined, and the TMEscore was constructed using principal component analysis algorithms. The high TMEscore subtype was characterized by immune activation and response to virus and IFNγ. Activation of transforming growth factor ß, epithelial-mesenchymal transition, and angiogenesis pathways were observed in the low TMEscore subtype, which are considered T-cell suppressive and may be responsible for significantly worse prognosis in gastric cancer [hazard ratio (HR), 0.42; 95% confidence interval (CI), 0.33-0.54; P < 0.001]. Multivariate analysis revealed that the TMEscore was an independent prognostic biomarker, and its value in predicting immunotherapeutic outcomes was also confirmed (IMvigor210 cohort: HR, 0.63; 95% CI, 0.46-0.89; P = 0.008; GSE78220 cohort: HR, 0.25; 95% CI, 0.07-0.89; P = 0.021). Depicting a comprehensive landscape of the TME characteristics of gastric cancer may, therefore, help to interpret the responses of gastric tumors to immunotherapies and provide new strategies for the treatment of cancers.

Discovery and optimization of 3,4,5-trimethoxyphenyl substituted triazolylthioacetamides as potent tubulin polymerization inhibitors.

Based on our previous research, three series of new triazolylthioacetamides possessing 3,4,5-trimethoxyphenyl moiety were synthesized, and evaluated for antiproliferative activities and inhibition of tubulin polymerization. The most promising compounds 8b and 8j demonstrated more significant antiproliferative activities against MCF-7, HeLa, and HT-29 cell lines than our lead compound 6. Moreover, analogues 8f, 8j, and 8o manifested more potent antiproliferative activities against HeLa cell line with IC50 values of 0.04, 0.05 and 0.16 µM, respectively, representing 100-, 82-, and 25-fold improvements of the activity compared to compound 6. Furthermore, the representative compound, 8j, was found to induce significant cell cycle arrest at the G2/M phase in HeLa cell lines via a concentration-dependent manner. Meanwhile, compound 8b exhibited the most potent tubulin polymerization inhibitory activity with an IC50 value of 5.9 µM, which was almost as active as that of CA-4 (IC50 = 4.2 µM). Additionally, molecular docking analysis suggested that 8b formed stable interactions in the colchicine-binding site of tubulin.

Polymer Self-Assembled BMSCs with Cancer Tropism and Programmed Homing.

Targeted therapy can improve the accuracy of diagnosis and treatment in the field of cancer management. Cellular surface engineering can enhance cell functions via mounting functional molecules onto cellular membranes. A novel amphiphilic hyperbranched polymer (AHP) conjugated with oleic acid (OA) and tumor-targeted ligand folic acid (FA) is employed. The lipophilic chain can self-assemble and infuse with the cytomembrane of bone marrow mesenchymal stem cells (BMSCs) with the end of FA left on the outside for targeting. The polymer tailored BMSCs can enhance tumor tropism in gastric cancer. BMSCs are characterized by the low immunogenicity and tumor tropism, which makes them promising targeting carriers. Regarding the integrated advantages of these two vectors, it is demonstrated that the functional amphiphilic AHP-OA-FA enhances the tumor tropism of BMSCs. Flow cytometry, standard MTT assay, and wound-healing assay show that AHP-OA-FA has no influence on CD expression, proliferative capacity, and cell motility of BMSCs, respectively. Furthermore, in vitro transwell assay and ex vivo fluorescence image verify that AHP-OA-FA enhances tumor tropism of BMSCs compared to BMSCs and AHP-OA-Rhodamine B-BMSCs. Finally, histological analysis demonstrates that AHP-OA-FA causes no damage to major organs. The results of this study suggest that living BMSCs self-assembled with a polymer might be a promising vehicle for targeted delivery to cancer cells.

Combined neutrophil/platelet/lymphocyte/differentiation score predicts chemosensitivity in advanced gastric cancer.

BACKGROUND: Gastric cancer is common in developing regions, and we hope to find out an economical but practical prognostic indicator. It was reported that pre-treatment peripheral neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as well as differentiation status, were associated with cancer progression. Hence, we introduced a novel combined Neutrophil/platelet/lymphocyte/differentiation Score (cNPLDS) to improve the prediction value of palliative chemotherapeutic response in advanced gastric cancer. METHODS: According to statistical sample size estimation, 136 primary diagnosed unresectable advanced ptaients were included for a retrospective study. The follow-up end-point was progression free survival (PFS) during the first-line palliative chemotherapy. Differentiation stratified patients into well, medium and poor groups by score 1 to 3, while patients with neither elevated NLR and PLR, only one elevated, or both elevated were of the combined NLR-PLR score (cNPS) 1 to 3, respectively. The cNPLDS was calculated by multiplying the tumor differentiation score and cNPS. RESULTS: Determined by the receiver operating characteristic (ROC) curve, the optimal cut-off points for NLR and PLR were 3.04 and 223. Through univariate analysis and survival analysis, poor differentiation, high NLR, high PLR, high cNPS, and high cNPLDS respectively indicated inferior PFS during the first-line palliative chemotherapy. Patients were furhter classified into low to high risk groups by cNPLDS. Groups of elevated NLR, PLR, cNPS, and cNPLDS showed lower disease control rate. Compared to other parameters, cNPLDS significantly improved the accuracy in predicing the first-progression. CONCLUSIONS: This study indicates that the novel parameter cNPLDS is superior to NLR or PLR alone, or even cNPS, in predicting the first-line chemosensitivity in advanced gastric cancer.

The lncRNA MACC1-AS1 promotes gastric cancer cell metabolic plasticity via AMPK/Lin28 mediated mRNA stability of MACC1.

BACKGROUND: Metabolic plasticity has been increasingly thought to be a determinant of tumor growth and metastasis. MACC1, a transcriptional regulator of MET, was recognized as an oncogene in gastric cancer (GC); however, its transcriptional or post-translational regulation was not clear. We previously reported the metabolic role of MACC1 in glycolysis to promote GC progression. MACC1-AS1 is the antisense lncRNA of MACC1, yet its function was previously unknown. METHODS: We profiled and analyzed the expression of MACC1-AS1 utilizing the TCGA database as well as in situ hybridization using 123 pairs of GC tissues and matched adjacent normal gastric mucosa tissues (ANTs). The biological role of MACC1-AS1 in cell growth and metastasis was determined by performing in vitro and in vivo functional experiments. Glycolysis and antioxidant capabilities were assayed to examine its metabolic function. Further, the specific regulatory effect of MACC1-AS1 on MACC1 was explored transcriptionally and post-transcriptionally. RESULTS: MACC1-AS1 was shown to be expressed significantly higher in GC tissues than in ANTs, which predicted poor prognosis in GC patients. MACC1-AS1 promoted GC cell proliferation and inhibited cell apoptosis under metabolic stress. Mechanistically, MACC1-AS1 stabilized MACC1 mRNA and post-transcriptionally augmented MACC1 expression. Further, MACC1-AS1 was shown to mediate metabolic plasticity through MACC1 upregulation and subsequent enhanced glycolysis and anti-oxidative capabilities, and this was suggested to be coordinated by the AMPK/Lin28 pathway. CONCLUSIONS: Elevated expression of MACC1-AS1 in gastric cancer tissues is linked to poor prognosis and promotes malignant phenotype upon cancer cells. MACC1-AS1 is elevated under metabolic stress and facilitates metabolic plasticity by promoting MACC1 expression through mRNA stabilization. Our study implicates lncRNA MACC1-AS1 as a valuable biomarker for GC diagnosis and prognosis.

Inhibition of SLC1A5 sensitizes colorectal cancer to cetuximab.

Cetuximab resistance is a key barrier in treating metastatic colorectal cancer (mCRC). Targeting of metabolic resources import could resensitize drug-resistant cancer cells to anticancer treatments. Here we showed that the expression of the glutamine transporter solute carrier 1 family member 5 (SLC1A5) in clinical CRC samples of patients resisted to cetuximab was significantly higher than in those of patients responded to cetuximab. Inhibition of SLC1A5 by shRNA-mediated gene silencing or pharmacological inhibitor significantly suppressed the growth of CRC. Moreover, inhibition of SLC1A5 significantly enhanced the inhibitory efficacy of cetuximab on CRC proliferation both in vitro and in vivo. Mechanistically, SLC1A5 inhibition facilitated EGFR degradation through the ubiquitin-proteasome pathway, and decreased the expression of nuclear EGFR, both of which might have contribution to the improved response to cetuximab. This study provides the metabolic molecule SLC1A5 as a potential therapeutic target to increase the efficacy of cetuximab on CRC.

Cysteine Dioxygenase 1 Mediates Erastin-Induced Ferroptosis in Human Gastric Cancer Cells.

BACKGROUND: Ferroptosis is a recently discovered form of iron-dependent nonapoptotic cell death. It is characterized by loss of the activity of the lipid repair enzyme, glutathione peroxidase 4 (GPX4), and accumulation of lethal reactive lipid oxygen species. However, we still know relatively little about ferroptosis and its molecular mechanism in gastric cancer (GC) cells. Here, we demonstrate that erastin, a classic inducer of ferroptosis, induces this form of cell death in GC cells and that cysteine dioxygenase 1 (CDO1) plays an important role in this process. METHODS: We performed quantitative real-time polymerase chain reaction, Western blotting, cell viability assay, reactive oxygen species (ROS) assay, glutathione assay, lipid peroxidation assay, RNAi and gene transfection, immunofluorescent staining, dual-luciferase reporter assay, transmission electron microscopy, and chromatin immunoprecipitation assay to study the regulation of ferroptosis in GC cells. Mouse xenograft assay was used to figure out the mechanism in vivo. RESULTS: Silencing CDO1 inhibited erastin-induced ferroptosis in GC cells both in vitro and in vivo. Suppression of CDO1 restored cellular GSH levels, prevented ROS generation, and reduced malondialdehyde, one of the end products of lipid peroxidation. In addition, silencing COO1 maintained mitochondrial morphologic stability in erastin-treated cells. Mechanistically, c-Myb transcriptionally regulated CDO1, and inhibition of CDO1 expression upregulated GPX4 expression. CONCLUSIONS: Our findings give a better understanding of ferroptosis and its molecular mechanism in GC cells, gaining insight into ferroptosis-mediated cancer treatment.

Ameliorative effects of Xue-Fu-Zhu-Yu decoction, Tian-Ma-Gou-Teng-Yin and Wen-Dan decoction on myocardial fibrosis in a hypertensive rat mode.

BACKGROUND: Xue-Fu-Zhu-Yu decoction (XFZYD), Tian-Ma-Gou-Teng-Yin (TMGTY) and Wen-Dan decoction (WDD) are Chinese herbal formulas used to treat hypertension and cardiovascular diseases in traditional Chinese medicine (TCM). The goal of our study is to determine if XFZYD, TMGTY or WDD treatment ameliorated myocardial fibrosis in spontaneously hypertensive rats (SHRs) and to identify the mechanisms underlying any beneficial effects observed during the courses of the investigation. METHODS: Forty-five 12-week-old male spontaneously hypertensive rats and five age-matched male Wistar-Kyoto control rats were studied for 16 weeks. Each day 6 g∙kg(-1) or 12 g∙kg(-1) of XFZYD, TMGTY or WDD was orally administered at the indicated dose, and the systolic blood pressure (SBP) of all rats was measured using the tail-cuff method. Collagen levels were measured via hydroxyproline content assays and histological examination. Transforming growth factor beta-1 (TGF-ß1) protein levels were determined via immunhistochemical and Western blot analysis. TGF-ß1 mRNA levels were assessed using real-time reverse transcription polymerase chain reaction. RESULTS: Systolic blood pressure was unaffected, but collagen and TGF-ß1 levels in SHRs treated with captopril and XFZYD (12 g∙kg(-1)) were significantly reduced when compared with untreated control SHRs. Administration of 12 g∙kg(-1) XFZYD increased myocardial cell protection and decreased TGF-ß1 mRNA and protein expression when compared with the other SHR treatment groups. CONCLUSIONS: XFZYD treatment demonstrated a superior ability to reverse myocardial fibrosis when compared with WDD or TMGTY treatment in SHRs. XFZYD also decreased TGF-ß1 mRNA and protein expression, suggesting that the TGF-ß1 signaling pathway plays a role in the therapeutic effects of XFZYD treatment.

[Effect of RbAp48 knockdown on migration and invasion of human cervical cancer cell line MS751 in vitro].

OBJECTIVE: To investigate the effect of RbAp48 knockdown on the migration and invasion of human cervical cancer cells and explore the mechanism. METHODS: A small interference RNA (siRNA) was used to knock down the expression of RbAp48 in MS751 cells. The changes in cell migration and invasion were evaluated using wound healing assay and Transwell assay, respectively, and the expressions of RbAp48, vimentin, N-cadherin, E-cadherin, Snail, Twist, MMP-2 and TIMP-2 were determined with Western blotting. RESULTS: After siRNA-mediated RbAp48 knockdown, MS751 cells showed a significantly reduced expression of RbAp48 with significantly suppressed cell migration and invasion (P<0.01). RbAp48 knockdown induced obvious down-regulation of the expressions of interstitial cell phenotype proteins vimentin, N-cadherin, and MMP-2 and up-regulation of epithelial cell phenotype proteins E-cadherin and TIMP-2, suggesting the inhibition of epithelial- mesenchymal transition of the cells. The expressions of Snail and Twist were significantly down-regulated in the cells following RbAp48 knockdown. CONCLUSION: Knockdown of RbAp48 can significantly inhibit epithelial-mesenchymal transition and suppress the migration and invasion of cervical cancer cell line MS751, the mechanism of which may involve the down-regulation of Snail and Twist expressions.

[Effect of silencing Bmi-1 expression in reversing cisplatin resistance in lung cancer cells and its mechanism].

OBJECTIVE: To investigate the effect of silencing Bmi-1 expression in reversing cisplatin resistance in human lung cancer cells and explore the possible mechanisms. METHODS: Cisplatin-resistant A549/DDP cells with small interference RNA (siRNA)-mediated Bmi-1 expression silencing were examined for cisplatin sensitivity using MTT assay and alterations in cell cycle distribution and apoptosis with flow cytometry, and the changes in cell senescence was assessed using ß-galactosidase staining. The protein expressions of Bmi-1, P14(ARF), P16(INK4a), P53, P21, Rb and ubi-H2AK119 in the cells were determined with Western blotting. RESULTS: A549/DDP cells showed significantly higher Bmi-1 expression than A549 cells. After siRNA-mediated Bmi-1 silencing, A549/DDP cells showed significantly enhanced cisplatin sensitivity with an increased IC50 from 40.3±4.1 µmol/L to 18.3±2.8 µmol/L (P<0.01) and increased cell percentage in G0/G1 phase from (48.9±2.3)% to (78.7±7.6)% (P<0.01). Silencing Bmi-1 did not cause significant changes in the cell apoptosis rate but induced obvious senescence phenotype in A549/DDP cells with down-regulated expression of ubi-H2AK119 and up-regulated expressions of P14(ARF), P16(INK4a), P53, P21 and Rb. CONCLUSION: Silencing Bmi-1 by RNA interference can induce cell senescence and resensitize A549/DDP cells to cisplatin possibly by regulating INK4a/ARF/Rb senescence pathway.

1,3,4-tri-O-galloyl-6-O-caffeoyl-ß-D-glucopyranose, a new anti-proliferative ellagitannin, regulates the expression of microRNAs in HepG(2) cancer cells.

OBJECTIVE: MicroRNAs (miRNAs) play important roles in cell proliferation, differentiation and apoptosis. 1, 3, 4-tri-O-galloyl-6-O-caffeoyl-ß-D-glucopyranose (BJA32515) is a new natural ellagitannin compound extracted from Balanophora Japonica MAKINO. The effect of BJA32515 on the expression of miRNAs in cancer cells has not yet been explored. Objective The present study was carried out to examine the changes in miRNA expression profiles in human HepG(2) hepatocarcinoma cells following BJA32515 exposure. METHODS: The proliferation of BJA32515-exposed HepG(2) cells was assessed using a colorimetric assay (cell counting kit-8). The miRNA expression profile of the cancer cells was analyzed using a miRNA array and quantitative real-time PCR. Apoptosis was assessed by annexin V and propidium iodide staining. RESULTS: BJA32515 inhibited the cell proliferation and increased apoptosis in HepG(2) cancer cells. The exposure to BJA32515 also caused alterations in the miRNA expression profile in the cells, with 33 miRNAs upregulated and 59 down-regulated. The up-regulation of let-7a and miR-29a and the down-regulation of miR-373 and miR-197 were verified by quantitative real-time PCR. CONCLSION: BJA32515-modifed miRNA expression may mediate the antiproliferative effect of this compound in HepG(2) cancer cells.