Effect of nucleolin on adriamycin resistance via the regulation of B-cell lymphoma 2 expression in Burkitt's lymphoma cells.

Nucleolin (NCL, C23) is an important nucleocytoplasmic multifunctional protein. Due to its multifaceted profile and high expression in cancer, NCL is considered to be a marker of drug resistance associated with chemotherapy. However, the biochemical mechanisms in which NCL suppresses drug sensitivity in several cancers have yet to be fully elucidated. This study aims to explore the effect of NCL on drug sensitivity and its potential mechanism in CA46 Burkitt's lymphoma (BL) cells. CA46 BL cells were transfected with lentiviruses carrying the NCL gene (CA46-NCL-overexpression, CA46-NCL-OE), or shRNA sequences that target the endogenous NCL gene (CA46-NCL-knockdown, CA46-NCL-KD). Adriamycin (ADM) IC50 levels for CA46-NCL-overexpressed (OE), CA46-NCL-OE control (OEC), CA46-NCL-knockdown (KD), and CA46-NCL-KD control (KDC) cells were 0.68 ± 0.06 µg/ml, 0.68 ± 0.06 µg/ml, 0.68 ± 0.06 µg/ml, and 0.30 ± 0.04 µg/ml, respectively. Apoptosis rates were significantly increased following NCL KD, whereas the opposite effect was noted in OE cells. A significant reduction of B-cell lymphoma 2 (Bcl-2) mRNA and protein levels in KD cells was observed, while OE cells displayed the opposite effect. The stability of Bcl-2 mRNA was influenced by NCL levels, the half-life of which was extended after NCL-OE, whereas it was reduced in KD cells. Finally, results of RNA-immunoprecipitation assays indicated that NCL could bind to Bcl-2 mRNA in CA46 cells. Taken together, these results suggested that NCL could mediate Bcl-2 expression and stability, and thus enhance ADM resistance in CA46 BL cells.

Design and synthesis of various quinizarin derivatives as potential anticancer agents in acute T lymphoblastic leukemia.

A series of quinizarin derivatives containing quaternary ammonium salts and/or thiourea groups were synthesized and their anticancer activities against leukemia cell lines have been tested. Results showed that most of quinizarin derivatives could inhibit the proliferation of leukemia cells. Among these derivatives, compound 3 showed good inhibition activity against various leukemia cells with IC50 values ranging from 0.90 ±â€¯2.55 µM to 10.90 ±â€¯3.66 µM. At the same time, compound 3 also inhibited the growth of human embryonic kidney-293 cell (HEK-293). Molt-4 and Jurkat cells, acute T lymphoblastic leukemia (T-ALL) cell lines, were selected to reveal potential anticancer mechanism of compound 3. Compound 3 inhibited the proliferation of Molt-4 and Jurkat cells in a dose- and time-dependent manner and led to a marked G0/G1 phase arrest. Analysis of Annexin V-APC and intracellular reactive oxygen species (ROS) level by flow cytometry showed that compound 3 induced significant apoptosis in Molt-4 and Jurkat cells. Western blotting assay showed that compound 3 activated the caspase-dependent apoptosis pathway and induced the degradation of Bcl-2 and c-myc protein.

Synthesis of wheatear-like ZnO nanoarrays decorated with Ag nanoparticles and its improved SERS performance through hydrogenation.

Semiconductor/noble metal composite SERS substrates have been extensively studied due to their unique bifunctionality. In this work, wheatear-like ZnO nanoarrarys have been fabricated via a modified low-temperature solution method. The hierarchical nanostructures that are constructed by stacked nanoflakes and long whiskers of ZnO possess a substantial number of characteristic nano corners and edges, which are proved to be beneficial to deposit more Ag nanoparticles (NPs). Furthermore, hydrogenated wheatear-like ZnO/AgNP composite substrates are achieved via a safe and facile solid hydrogen source (NaBH4). The hydrogenated ZnO/AgNPs (H-ZnO/Ag) substrates exhibit greatly improved SERS activity in detecting R6G molecules with an enhancement factor (EF) up to ∼0.49 × 10(8), over two orders of magnitude higher than that of the substrates before hydrogenation. The outstanding SERS performance of wheatear-like H-ZnO/Ag substrates benefits from the emerging porous structure of ZnO and abundant surface defects introduced by hydrogenation. In addition, the as-prepared substrates also show high detection sensitivity, good repeatability and recyclability, indicating great potential for practical applications.

Biomedical Applications of Advanced Multifunctional Magnetic Nanoparticles.

In this review, we have presented the latest results and highlights on biomedical applications of a class of noble metal nanoparticles, such as gold, silver and platinum, and a class of magnetic nanoparticles, such as cobalt, nickel and iron. Their most important related compounds are also discussed for biomedical applications for treating various diseases, typically as cancers. At present, both physical and chemical methods have been proved very successful to synthesize, shape, control, and produce metal- and oxide-based homogeneous particle systems, e.g., nanoparticles and microparticles. Therefore, we have mainly focused on functional magnetic nanoparticles for nanomedicine because of their high bioadaptability to the organs inside human body. Here, bioconjugation techniques are very crucial to link nanoparticles with conventional drugs, nanodrugs, biomolecules or polymers for biomedical applications. Biofunctionalization of engineered nanoparticles for biomedicine is shown respective to in vitro and in vivo analysis protocols that typically include drug delivery, hyperthermia therapy, magnetic resonance imaging (MRI), and recent outstanding progress in sweep imaging technique with Fourier transformation (SWIFT) MRI. The latter can be especially applied using magnetic nanoparticles, such as Co-, Fe-, Ni-based nanoparticles, α-Fe2O3, and Fe3O4 oxide nanoparticles for analysis and treatment of malignancies. Therefore, this review focuses on recent results of scientists, and related research on diagnosis and treatment methods of common and dangerous diseases by biomedical engineered nanoparticles. Importantly, nanosysems (nanoparticles) or microsystems (microparticles) or hybrid micronano systems are shortly introduced into nanomedicine. Here, Fe oxide nanoparticles ultimately enable potential and applicable technologies for tumor-targeted imaging and therapy. Finally, we have shown the latest aspects of the most important Fe-based particle systems, such as Fe, α-Fe2O3, Fe3O4, Fe-Fe(x)O(y) oxide core-shell nanoparticles, and CoFe2O4-MnFe2O4 core-shell nanoparticles for nanomedicine in the efficient treatment of large tumors at low cost in near future.

Controlled synthesis of porous platinum nanostructures for catalytic applications.

Porous platinum, that has outstanding catalytic and electrical properties and superior resistant characteristics to corrosion, has been widely applied in chemical, petrochemical, pharmaceutical, electronic, and automotive industries. As the catalytic activity and selectivity depend on the size, shape and structure of nanomaterials, the strategies for controlling these factors of platinum nanomaterials to get excellent catalytic properties are discussed. Here, recent advances in the design and preparation of various porous platinum nanostructures are reviewed, including wet-chemical synthesis, electro-deposition, galvanic replacement reaction and de-alloying technology. The applications of various platinum nanostructures are also discussed, especially in fuel cells.

Synthesis of Pt-Pd Bimetallic Porous Nanostructures as Electrocatalysts for the Methanol Oxidation Reaction.

Pt-based bimetallic nanostructures have attracted a great deal of attention due to their unique nanostructures and excellent catalytic properties. In this study, we prepared porous Pt-Pd nanoparticles using an efficient, one-pot co-reduction process without using any templates or toxic reactants. In this process, Pt-Pd nanoparticles with different nanostructures were obtained by adjusting the temperature and ratio of the two precursors; and their catalytic properties for the oxidation of methanol were studied. The porous Pt-Pd nanostructures showed better electrocatalytic activity for the oxidation of methanol with a higher current density (0.67 mA/cm²), compared with the commercial Pt/C catalyst (0.31 mA/cm²). This method provides one easy pathway to economically prepare different alloy nanostructures for various applications.

Integration of bioinformatics and experiments to identify TP53 as a potential target in Emodin inhibiting diffuse large B cell lymphoma.

Non-Hodgkin's Lymphoma (NHL) is a group of lymphoid malignancies with unsatisfactory treatment effect in some aggressive subtypes, including diffuse large B cell lymphoma (DLBCL). Emodin is an anthraquinone with potent anti-cancer activities. However, the molecular mechanism of Emodin repressing aggressive NHL remains to be revealed in detail. This study delineated the active mechanism of Emodin action in aggressive NHL by using bioinformatics analysis and in vitro assay. 4 Emodin's primary direct protein targets (DPT) were identified and the DPTs-associated proteins/genes were predicted. Those Emodin-related proteins/genes were subject to enrich Emodin-associated pathways, from which 3 significantly NHL-related signal pathways were refined identified. Advanced integrated analysis exhibited TP53 and PI3K as the significant molecule and pathway by which Emodin may function in NHL. To verify those bioinformatics findings, effects of Emodin and E35, a novel derivative of emodin were investigated on DLBCL cell lines SU-DHL4. Emodin and E35 suppressed proliferation and induced apoptosis of SU-DHL4 cells in a time- and dose-dependent manner. Emodin and E35 declined TP53 protein expression and decreased phosphorylation of PI3K/AKT protein in a dose-dependent manner. All of above showed that combined bioinformatics analysis with experiments offered a novel approach for outlining the mechanisms of Emodin action in DLBCL with convenience and integrity.

One-Pot and Facile Fabrication of Hierarchical Branched Pt-Cu Nanoparticles as Excellent Electrocatalysts for Direct Methanol Fuel Cells.

Hierarchical branched nanoparticles are one promising nanostructure with three-dimensional open porous structure composed of integrated branches for superior catalysis. We have successfully synthesized Pt-Cu hierarchical branched nanoparticles (HBNDs) with small size of about 30 nm and composed of integrated ultrathin branches by using a modified polyol process with introduction of poly(vinylpyrrolidone) and HCl. This strategy is expected to be a general strategy to prepare various metallic nanostructures for catalysis. Because of the special open porous structure, the as-prepared Pt-Cu HBNDs exhibit greatly enhanced specific activity toward the methanol oxidation reaction as much as 2.5 and 1.7 times compared with that of the commercial Pt-Ru and Pt-Ru/C catalysts, respectively. Therefore, they are potentially applicable as electrocatalysts for direct methanol fuel cells.

Decreased expression of nucleophosmin/B23 increases drug sensitivity of adriamycin-resistant Molt-4 leukemia cells through mdr-1 regulation and Akt/mTOR signaling.

Nucleophosmin/B23 (NPM) is a nuclear protein with prosurvival and ribosomal RNA processing functions. However, the potential role of NPM involved in drug-resistance in leukemia has not been investigated clearly. In this study, we generated an adriamycin (ADM)-resistant lymphoblastic cell line Molt-4/ADR (MAR) by stepwise induction. Cell proliferation, sensitivity to chemotherapy agents and expressions of drug resistance related molecules were assessed. The IC50 of Molt-4 cells were 0.58±0.11µmol/L and MAR cells were 22.56±1.94µmol/L, meaning MAR cells were 38.63 fold resistant to Molt-4 cells. Furthermore, MAR cells gained an expression of mdr-1 (P-gp) and a higher expression of NPM compared to Molt-4 cells. Knockdown of NPM by RNA interference (RNAi) suppressed the viability of both Molt-4 and MAR cells. After NPM RNAi, the IC50 of MAR and Molt-4 cells were 3.83±0.38µmol/L and 0.19±0.02µmol/L respectively. Both of them revealed an increase of drug sensitivity with down-regulation of mdr-1 and Akt/mTOR signaling. Knockdown of mdr-1 could also reverse the drug resistance, with no change in NPM expression. It could be concluded that knockdown of NPM reversed the drug resistance by down-regulating P-gp and Akt/mTOR signal pathway, indicating that NPM may serve as a potential modulator in drug resistance.

Large-scale template-free synthesis of ordered mesoporous platinum nanocubes and their electrocatalytic properties.

Here we report a facile, one-pot and template-free approach to synthesize mesoporous monocrystalline Pt nanocubes with uniform shapes and sizes, in which small Pt particles with a size of ∼5 nm are three-dimensionally and periodically built up into cubes with a size of ∼50 nm. The forming process is illustrated through a novel meso-crystal self-assembly mechanism. Very interestingly, the mesoporous structures are ordered, which are thought to be beneficial to increase their catalytic activity. Compared with nonporous Pt nanoparticles and porous Pt nanoparticles without order, the ordered mesoporous Pt nanocubes exhibit a highly improved electrocatalytic ability for methanol and formic acid oxidation, and are potentially applicable as electrocatalysts for direct methanol and formic acid fuel cells. Furthermore, this approach can be used to synthesize other Pt-series metallic mesoporous nanoparticles, such as Pd.

Synthesis and characterization of Fe-based metal and oxide based nanoparticles: discoveries and research highlights of potential applications in biology and medicine.

In this review, we have presented the controlled synthesis of Fe-based metal and oxide nanoparticles with large size by chemical methods. The issues of the size, shape and morphology of Fe nanoparticles are discussed in the certain ranges of practical applications in biology and medicine. The homogeneous nanosystems of Fe-based metal and oxide nanoparticles with various sizes and shapes from the nano-to-micro ranges can be used in order to meet the demands of the treatments of dangerous tumors and cancers through magnetic hyperthermia and magnetic resonance imaging (MRI). In this context, the polyhedral Fe-based metal and oxide nanoparticles having large size in the ranges from 1000 nm to 5000 nm can be potentially used in magnetic hyperthermia and MRI in the innovative drug delivery, diagnosis, treatment, and therapy of tumor and cancer diseases because of their very high bio-adaptability. We have suggested that high stability and durability of Fe-based metal and oxide nanoparticles are very crucial to recent magnetic hyperthermia and MRI technology. The roles of various Fe-based nanostructures are focused in biomedical applications of tumors and cancers diagnostics, targeted drug delivery, and magnetic hyperthermia. Finally, Fe-based, α-, ß- and γ-Fe2O3, and Fe3O4-based nanoparticles are shortly discussed in various potential applications in catalysis, biology, and medicine.