Berberine and Cisplatin Exhibit Synergistic Anticancer Effects on Osteosarcoma MG-63 Cells by Inhibiting the MAPK Pathway

Berberine (BBR) has been reported to have potent anticancer activity and can increase the anticancer effects of chemotherapy drugs. The present study aims to investigate whether BBR and cisplatin (DDP) exert synergistic effects on the osteosarcoma (OS) MG-63 cell line. In the present study, MG-63 cells were treated with BBR and DDP alone or in combination. The effects of these therapeutics on cell viability, colony formation, migration, invasion, nuclear morphology, apoptosis, and the cell cycle, as well as their role in regulating the expression of proteins related to apoptosis, the cell cycle, and the mitogen-activated protein kinase (MAPK) pathway, were determined. The results demonstrated that BBR or DDP significantly inhibited the proliferation of MG-63 cells in a dose- and time-dependent manner. The combination treatment of BBR and DDP exerted a prominent inhibitory effect on proliferation and colony formation. Furthermore, the results showed that the combination treatment of BBR and DDP enhanced the inhibition of cell migration and invasion and reversed the changes in nuclear morphology. The results showed that the combination treatment of BBR and DDP induced apoptosis and cell cycle arrest in the G0/G1 phase. Mechanistically, the combination treatment of BBR and DDP inhibited the expression of MMP-2/9, Bcl-2, CyclinD1, and CDK4, enhanced the expression of Bax and regulated the activity of the MAPK pathway. Collectively, our data suggest that the combination therapy of BBR and DDP markedly enhanced OS cell death.     

Synthesis and Characterization of Bismuth-Silver Nanoparticles for Electrochemical Sensor Applications

Silver, bismuth, and bismuth-silver nanoparticles were synthesized and characterized by cyclic voltammetry, electrochemical impedance spectroscopy, ultraviolet-visible spectroscopy, infrared spectroscopy, Raman spectroscopy, and transmission electron microscopy to determine the electrochemical, optical, structural, and morphological properties of the nanomaterials. The silver, bismuth, and bismuth-silver nanoparticles were shown to have an average particle size of 10–30 nanometers by microscopy. The electrochemical results showed that the bismuth-silver nanoparticles exhibited good electrocatalytic activity that can be harnessed for sensor construction and related applications. The ultraviolet-visible, infrared, and Raman spectroscopy results confirmed the structural properties of the bismuth-silver nanoparticles. In addition, the microscopy and electron diffraction morphological characterization confirmed the nature of the bismuth-silver nanoparticles.     

含5-氟尿嘧啶的复合结构纳米颗粒的合成及其光谱研究

合成了包覆有5-氟尿嘧啶的银/二氧化硅复合结构纳米颗粒.用透射电子显微镜、红外光谱和拉曼光谱对合成的化合物进行了表征.讨论了药物分子在银表面的拉曼增强效应以及二氧化硅壳层对它的影响.     

四氨基酞菁锌负载二氧化硅纳米粒子的合成及其对细胞毒性的研究

通过在无极核微乳液中水解乙烯基三乙氧基硅烷(TEVS)和3-氨丙基三乙氧基硅烷(APTES),制备了疏水性光敏剂-2,9,16,23-四氨基酞菁锌负载的表面带有正电荷的二氧化硅纳米粒子(SiO2@ ZnPc( NH2)4).通过透射电镜(TEM)、Zetasizer Nano-ZS粒度仪(DLS)、紫外-可见分光光度计...     

氨基酸5-氟尿嘧啶酯类衍生物的合成及其抗肿瘤活性研究

以N-保护的氨基酸钾盐与1-(ω-溴丙基)-5-氟尿嘧啶和1-(ω-溴丁基)-5-氟尿嘧啶反应,制备了18种氨基酸的ω-(N¹-5-氟尿嘧啶基)-丙醇酯和丁醇酯的盐酸盐,并确定了它们的结构。动物试验的初步结果表明,酪氨酸、苯丙氨酸的3-(N¹-5-氟尿嘧啶基)-丙醇酯盐酸盐对小鼠艾氏腹水癌的抑制率分别为88.1%和86.7%。     

Electrochemical Behavior of MCF‐7 Cells on Carbon Nanotube Modified Electrode and Application in Evaluating the Effect of 5‐Fluorouracil

The electrochemical behavior of human breast cancer cells (MCF‐7) suspension on multiwalled carbon nanotube (MWCNT) modified graphite electrode was studied by using cyclic voltammetry (CV) and potentiometric stripping analysis (PSA). Compared with bare graphite electrode, the MWCNTs‐modified electrode showed electrocatalytic property to the oxidation of electroactive species in the cell suspension. One oxidative peak at about +0.74 V was observed in the cyclic voltammogram. PSA was proved to be more sensitive than CV for investigation of the electrochemical behavior of cells. And it was found that ultrasonication treatment of the cell suspension can significantly enhance the PSA signal. Factors influencing the PSA signal of cells, including deposition time, deposition potential and stripping current, were investigated in detail and the optimum conditions were obtained. The baseline corrected PSA signal was found to be related to the viability of cells and the technique was used for monitoring the growth of MCF‐7 cells. The effect of anticancer drug 5‐fluorouracil (5‐FU) on the growth of MCF‐7 cells was also investigated by PSA.     

1,3-二甲基-5-亚硝基-6-氨基脲嘧啶铂电极电化学加氢机理研究

采用稳态极化法、循环伏安法和恒电位库仑法对1,3-二甲基-5-亚硝基-6-氨基脲嘧啶在铂电极上的电化学加氢机理进行了研究,研究介质为硫酸和硫酸钾水溶液.结果表明,pH=3时,1,3-二甲基-5-亚硝基-6-氨基脲嘧啶在铂电极析氢电位(-600～-800mV,vs.饱和硫酸钾的硫酸亚汞参比电极)前,发生加氢还原反应,氢离子在铂电极表面得到电子生成原子态的氢参与反应.随着pH值降低,加氢反应速度增大,还原电位正移.在铂电极上的电化学加氢过程受扩散控制,增大搅拌速度和提高温度都可提高反应速度.     

Study of Electrooxidation Behavior of Nitrite on Gold Nanoparticles/Graphitizing Carbon Felt Electrode and Its Analytical Application

In this work, a gold nanoparticles/graphitizing carbon felt electrode (AuNPs/GCFE) was fabricated and a disposable sensor was thus fabricated to detect nitrite quickly and conveniently. The kinetic parameters of the electrode were studied in phosphate buffer solution (PBS). Under the optimal conditions, by using cyclic voltammetry, the oxidation peak current was linear with the concentration of nitrite in the range from 1.00 × 10^?6 M to 3.35 × 10^?3 M, with a detection limit of 9.50 × 10^?7 M (3S/k). The influence of various anions on nitrite detection was studied, and the results showed that the fabricated sensor had good specificity toward nitrite.     

Study on Interaction of G-rich Oligonucleotides Modified Gold Nanoparticles with Cells

Herein, two kinds of ssDNA-GNPs (termed as PolyG₁-GNPs and PolyG₂-GNPs, respectively) were synthesized by modification of two different G-rich single-strand oligonucleotides (PolyG₁ and PolyG₂) onto 13-nm citrate-protected gold nanoparticles (GNPs) surface through formation of the sulfur-gold covalent bond, respectively. The as-prepared PolyG₁-GNPs and PolyG₂-GNPs had reasonable colloidal stability in complex dispersing matrixes. The effect of ssDNA sequence on the interaction between ssDNA-GNPs and cells was systematically investigated by UV-visible absorption spectroscopy, cellular transmission electronic microscopy and inductively coupled plasma-mass spectrometry. The experimental results showed that both of the as-prepared PolyG₁-GNPs and PolyG₂-GNPs had low cytotoxicity and exhibited energy related endocytosis. In addition, the cellular internalization amount and dispersibility of ssDNA-GNPs were strongly affected by the sequences of immobilized ssDNAs. PolyG₂ with G-quadruplex (G4) secondary structure could significantly increase the cellular internalization amount and intracellular stability of PolyG₂-GNPs.     

Voltammetry and Spectroscopy Study of In Vitro Interaction of Fenitrothion with DNA

The interaction of Fenitrothion with DNA has been studied using the voltammetric and spectroscopic methods. An irreversible reduction was concluded from the CV data of Fenitrothion. The values of (αn)_f=1.91 and (αn)_b=2.06 were measured and the reduction process of Fenitrothion was performed with 4 electrons. By using non‐linear regression analysis of CV data, the binding constant, binding site size, and diffusion coefficient for free Fenitrothion (D_f) and DNA‐Fenitrothion (D_b) were calculated as: 1.03×10⁴, 1.204, 5.2×10^?4 and 1.72×10^?5, respectively. Also the voltammetric, spectroscopic, thermodynamic and activation energy of DNA‐Fenitrothion complex revealed that the mode of interaction might be partial‐intercalative and complex formation is entropy favored.     

Electrochemical and ESR study of 5-nitrofuryl-containing thiosemicarbazones antiprotozoal drugs

Cyclic voltammetry and electron spin resonance (ESR) techniques were used in the investigation of several potential antiprotozoal thiosemicarbazones nitrofurane derivatives. A self-protonation process involving the protonation of the nitro group due to the presence of an acidic proton in the thiosemicarbazone moiety was observed in the first step of a CEE(rev) reduction mechanism of these derivatives. ESR spectra of the free radicals obtained by electrolytic reduction were characterized and analyzed. AM1 methodology was used to obtain the optimized geometries and UB3LYP calculations were performed to obtain the theoretical hyperfine coupling constants. The theoretical study exhibited an unusual assignment of the spin densities showing a free radical centered in the thiosemicarbazone moiety rather than the nitro which are in agreement with the experimental hyperfine pattern.     

Electrochemical Determination of Nanoparticle Size: Combined Theoretical and Experimental Study for Matrixless Silver Nanoparticles

A chronoamperometric procedure for the preparation of silver nanoparticles (AgNPs) in aqueous systems with no extra added stabilizing agents is presented. The uniqueness of the prepared nanoparticle systems was explored by theoretical considerations. The proposed theoretical model predicts the structural parameters of the obtained nanoparticle system. The parameters required for the calculations (the zeta potential, conductivity, and effective diffusion coefficient of ionic silver) are available from independently performed measurements. Chronoamperometry at a microelectrode was employed for the evaluation of the effective diffusion coefficient of ionic silver present in the AgNP solution. The values of AgNP radii predicted by the theoretical model for the selected samples were compared to those obtained by Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS) methods. Because of the high polydispersity of the prepared nanoparticle samples, DLS results were overestimated in comparison to both: the TEM results and some theoretical predictions. By correcting the theoretical predictions by the Debye length, the calculated nanoparticle sizes become comparable (within their expanded uncertainties) to those measured in TEM images, especially for the nanosystems at early stages of their formation via the electrosynthesis process.     

Parallel G-quadruplex Structures Increase Cellular Uptake and Cytotoxicity of 5-Fluoro-2′-deoxyuridine Oligomers in 5-Fluorouracil Resistant Cells

Fluoropyrimidines, such as 5-fluorouracil (5-FU) and related prodrugs have been considered first-line chemotherapy agents for the treatment of colorectal cancer. However, poor specificity and tumor cell resistance remain major limiting bottlenecks. G-quadruplexes, have been suggested as preferred nanostructures for enhancing cellular uptake mediated by G-quadruplex binding proteins which are abundant at the membranes of some tumor cells. In the current study, we propose a new strategy to deliver 5-fluoro-2′-deoxyuridine (5-FdU) monophosphate, the main active drug from 5-FU derivatives that may circumvent the cellular mechanisms of FU-resistant cancer cells. Two G-quadruplexes delivery systems containing four and six G-tetrads ((TG₄T) and (TG₆T)) linked to a FdU oligonucleotide were synthesized. Biophysical studies show that the G-quadruplex parallel structures are not affected by the incorporation of the 5 units of FdU at the 5’-end. Internalization studies confirmed the ability of such G-quadruplex nanostructures to facilitate the transport of the FdU pentamer and increase its cytotoxic effect relative to conventional FU drug in FU-resistant colorectal cancer cells. These results suggest that FdU oligomers linked to G-quadruplex parallel sequences may be a promising strategy to deliver fluoropyrimidines to cancer cells.     

Cu2+离子掺杂钙锰矿的合成及电化学性质研究

采用不同方法制备出单一或掺杂Cu2+离子的钙锰矿, 分析了其隧道或者骨架结构中掺杂Cu2+离子的合成条件, 并应用粉末微电极考察了其电化学活性和稳定性. 单一或骨架中掺杂Cu2+离子的钙锰矿可在常压回流条件下制备; 隧道中掺杂Cu2+离子的钙锰矿须经高温高压热液反应合成, 且反应温度是影响产物纯度的主导因素. 钙锰矿在高pH值溶液中电化学稳定性较好; 骨架中掺杂Cu2+离子可提高钙锰矿的电化学活性和稳定性, 而隧道中掺杂Cu2+离子的钙锰矿电化学活性较低; 结合循环伏安法进一步证明了后者掺杂的Cu2+离子主要位于钙锰矿的隧道中.     

A No-washing Point-of-Care Electrochemical Biosensor Based on CuS Nanoparticles for Rapid and Sensitive Detection of Neuron-specific Enolase

Electrochemical biosensors have made outstanding achievements in recent years. However, the single pursuit of sensitivity and accuracy sometimes cannot meet the detection requirements and achieve high-efficiency measurements. Therefore, no-washing biosensors have more practical advantages. In this work, a disposable point-of-care (POC) electrochemical biosensor was designed for the sensitive and fast detection of neuron-specific enolase (NSE). Fe₃O₄ and CuS nanoparticles were used as the substrate material for capturing Ab₁ and the signal probe for labeling Ab₂ respectively. The disposable syringe filter was introduced into the determination procedure for simple sample separation, which easily realized no-washing detection. Due to the syringe filters with 200 nm pore diameter could only allow the small nanoparticles of CuS−Ab₂ pass through, the large-sized immunocomplex of Fe₃O₄−Ab₁/NSE/CuS−Ab₂ were blocked on the membrane. The uncombined CuS−Ab₂ particles were pushed out from the syringe and would occur electron transfer between Cu²⁺ and Cu⁺ to generate a current signal detected by the Au electrode. Under optimal conditions, the no-washing biosensor shows a wide linear concentration range (100 fg mL⁻¹∼50 ng mL⁻¹) with the limit of detection of 33 fg mL⁻¹ (S/N=3). Additionally, the biosensor exhibited excellent selectivity, storage stability and reproducibility. The outstanding advantages of the no-washing biosensor make it more suitable for POC testing.     

Electrochemical Behaviours and Detection of Adenosine‐5¢‐triphosphate on an Ionic Liquid Modified Carbon Paste Electrode

In this paper a new electrochemical method based on the ionic liquid modified carbon paste electrode (IL‐CPE) was proposed for the determination of adenosine‐5′‐triphosphate (ATP) in a pH 4.5 Britton‐Robinson (B‐R) buffer solution. IL‐CPE was prepared by using 1‐butyl‐3‐methylimidazolium trifluoroacetate (BMIMCF₃COO) as the modifier. Cyclic voltammetry was used to investigate the electrochemical behaviors of ATP on the IL‐CPE, and the results indicated that IL‐CPE exhibited strong electrocatalytic ability to promote the oxidation of ATP with a single well‐defined irreversible adsorption‐controlled oxidation peak appeared. The electrochemical reaction parameters of ATP were calculated with the results of the electron transfer coefficient (α) as 0.40, the electron transfer number (n) as 1.17, the apparent heterogeneous electron transfer rate constant (ks) as 3.66 × 10^‐6 s^‐1 and the surface coverage (Γ_τ) as 2.48 × 10^‐9 mol cm^‐2. Under the selected conditions the proposed IL‐CPE showed good performances to the ATP detection in the concentration range from 0.1 to 1000.0 μmol L^‐1 with the detection limit as 3.65 × 10^‐8 mol L^‐1 (3σ) by differential pulse voltammetry. The method showed good selectivity to the ATP detection without the interferences of coexisting substances and was successfully applied to the ATP injection samples detection with satisfactory results.     

Therapeutic Effect of Green Synthesized Silver Nanoparticles Using Erodium glaucophyllum Extract against Oral Candidiasis: In Vitro and In Vivo Study

Oral candidiasis (OC) is a fungal infection caused by an opportunistic fungi Candida albicans, which is found in the normal flora of healthy people. In this study, we examined the anti-candidal effect of green synthesized silver nanoparticles using leaf extract of Erodium glaucophyllum (EG-AgNPs) against C. albicans in vitro and in vivo. EG-AgNPs were synthesized for the first time using E. glaucophyllum extract and characterized by imaging (transmission electron microscopy (TEM), UV-VIS spectroscopy, zeta potential, X-ray diffraction (XRD), Energy dispersive x-ray analysis (EDX), and Fourier transform infrared spectroscopy (FTIR). A mouse model of OC was used for in vivo study. The agar well diffusion method showed the anti-candidal activity of EG-AgNPs against C. albicans with MIC 50 µg/mL. EG-AgNPs inhibited the dimorphic transition of C. albicans and suppressed the formation of biofilm by 56.36% and 52%, respectively. Additionally, EG-AgNPs significantly inhibited the production of phospholipases and proteinases by 30% and 45%, respectively. EG-AgNPs cause cytoplasm disintegration and deterioration of cell wall as imaged by SEM and TEM. Interestingly, EG-AgNPs did not display any cytotoxicity on the human gingival fibroblast-1 HGF-1 cell line at MIC concentrations. Topical treatment of the tongue of the OC mouse model with EG-AgNPs showed significant reduction in candidal tissue invasion, less inflammatory changes, and no tissue modification, in association with marked low scare and hyphal counts as compared to control group. In conclusion, our data demonstrated the potent inhibitory action of EG-AgNPs on the growth and morphogenesis of C. albicans in vitro and in vivo. Thus, EG-AgNPs represent a novel plausible therapeutic approach for treatment of OC.     

界面可控硫醇SAMs纳米金修饰金电极的电化学行为研究

在裸金电极上自组装不同比例的4,4’-二甲基联苯硫醇(MTP)和硫辛酸(TA)混合液,形成自组装膜(MTP+TA/Au SAMs),再修饰纳米金,制得纳米金混合巯基修饰金电极(AuNPs/MTP+TA/Au)。研究了纳米金混合巯基修饰金电极的电化学行为和阻抗行为,结果表明电极表面pH值的改变对电极表面的电子转移有重要影响。对葡萄糖传感器的制备条件、测定条件、抗干扰能力等进行了讨论,结果表明修饰电极的微结构和微环境有必要进一步研究。     

Scaffold Effects on Osteogenic Differentiation of Equine Mesenchymal Stem Cells: An In Vitro Comparative Study

The in vitro viability, osteogenic differentiation, and mineralization of four different equine mesenchymal stem cells (MSCs) from bone marrow, periosteum, muscle, and adipose tissue are compared, when they are cultured with different collagen‐based scaffolds or with fibrin glue. The results indicate that bone marrow cells are the best source of MSCs for osteogenic differentiation, and that an electrochemically aggregated collagen gives the highest cell viability and best osteogenic differentiation among the four kinds of scaffolds studied.