Preparation and characterization of a novel molecularly imprinted polymer for the separation of glycyrrhizic acid.

Molecularly imprinted polymers of glycyrrhizic acid were prepared by solution polymerization using glycyrrhizic acid as the template molecule, N-vinypyrrolidone as functional monomer, N,N-methylene bisacrylamide as cross-linker and ascorbic acid and hydrogen peroxide as initiators. Focused on the adsorption capacity and separation degree of the polymer to glycyrrhizic acid, the effects of the monomers, crosslinker and initiators were investigated and optimized. Finally, the structure of the polymer was characterized by using Fourier transform infrared spectroscopy and scanning electron microscopy. To obtain objective results, non-imprinted molecular polymers prepared under the same conditions were also characterized. The adsorption quantity of the polymer was measured by high-performance liquid chromatography. Under the optimum conditions, the maximum adsorption capacity of glycyrrhizic acid approached 15 mg/g, and the separation degree was as high as 2.5. The adsorption kinetics could be well described by a pseudo-first-order model, while the thermodynamics of the adsorption process could be described by the Langmuir model.

An injectable magnesium-loaded hydrogel releases hydrogen to promote osteoporotic bone repair via ROS scavenging and immunomodulation.

Background: The repair of osteoporotic bone defects remains challenging due to excessive reactive oxygen species (ROS), persistent inflammation, and an imbalance between osteogenesis and osteoclastogenesis. Methods: Here, an injectable H2-releasing hydrogel (magnesium@polyethylene glycol-poly(lactic-co-glycolic acid), Mg@PEG-PLGA) was developed to remodel the challenging bone environment and accelerate the repair of osteoporotic bone defects. Results: This Mg@PEG-PLGA gel shows excellent injectability, shape adaptability, and phase-transition ability, can fill irregular bone defect areas via minimally invasive injection, and can transform into a porous scaffold in situ to provide mechanical support. With the appropriate release of H2 and magnesium ions, the 2Mg@PEG-PLGA gel (loaded with 2 mg of Mg) displayed significant immunomodulatory effects through reducing intracellular ROS, guiding macrophage polarization toward the M2 phenotype, and inhibiting the IκB/NF-κB signaling pathway. Moreover, in vitro experiments showed that the 2Mg@PEG-PLGA gel inhibited osteoclastogenesis while promoting osteogenesis. Most notably, in animal experiments, the 2Mg@PEG-PLGA gel significantly promoted the repair of osteoporotic bone defects in vivo by scavenging ROS and inhibiting inflammation and osteoclastogenesis. Conclusions: Overall, our study provides critical insight into the design and development of H2-releasing magnesium-based hydrogels as potential implants for repairing osteoporotic bone defects.

Symmetric and asymmetric Au-AgCdSe hybrid nanorods.

This paper describes a facile method for synthesis of Au-AgCdSe hybrid nanorods with controlled morphologies and spatial distributions. The synthesis involved deposition of Ag tips at the ends of Au nanorod seeds, followed by selenization of the Ag tips and overgrowth of CdSe on these sites. By simply manipulating the pH value of the system, the AgCdSe could selectively grow at one end, at both the ends or on the side surface of a Au nanorod, generating a mike-like, dumbbell-like, or toothbrush-like hybrid nanorod, respectively. These three types of Au-AgCdSe hybrid nanorods displayed distinct localized surface plasmon resonance and photoluminescence properties, demonstrating an effective pathway for maneuvering the optical properties of nanocrystals.

Tribological behavior of a charged atomic force microscope tip on graphene oxide films.

The tribological behavior of graphene oxide (GO) films deposited on a mica substrate has been investigated by atomic force microscopy, in which different voltages were applied to a tip. It was found that the frictional forces on the GO films remain unchanged in the presence of negative tip voltages, while the frictional forces increase remarkably with an increase of the voltage when positive voltages are given to the tip, and at a certain positive tip voltage the frictional forces reach a stable value with increasing number of repeated cycles. To study the influence of the tip voltage on the frictional forces of the GO films, the adhesive and electrostatic force gradients between the tip and GO films were measured. The results showed that the adhesive and electrostatic forces increased with increase of the positive tip voltages. This phenomenon is due to the polarization of charges in the GO films induced by the applied tip voltages, which causes intensive electrostatic interactions between the tip and GO films and a corresponding rise in the adhesive forces and the frictional forces.

Comparative in vivo study on the desensitizing efficacy of dentin desensitizers and one-bottle self-etching adhesives.

UNLABELLED: This in vivo study evaluated the desensitizing efficacy of two one-bottle self-etching adhesives, two dentin desensitizers and a placebo (water). METHODS: Thirty-one volunteers with 55 hypersensitive teeth were recruited into this clinical investigation. The sensitive teeth were randomly assigned into five groups and treated with one of the following materials: iBond, Heraeus; Xeno V, Dentsply; Gluma desensitizer, Heraeus; Bifluorid 12, Voco; placebo (water). Mechanical and thermal stimuli were used to assess the tooth sensitivity response. Discomfort interval scale (DIS) scores of the sensitive teeth were recorded at three different investigation times (baseline, immediately and one month after treatment). Impressions were taken from the sensitive teeth at all three different investigation times, and replica models were made for the evaluation of the dentin surfaces by scanning electron microscopy. The Friedman test and the Mann Whitney U-test were used to analyze the data. RESULTS: All dental materials significantly reduced the dentin hypersensitivity immediately (p < 0.05) and one month after treatment (p < 0.05), with the exception of Bifluorid 12 for mechanical tooth sensitivity. The placebo (water) only caused a short-term effect on the thermal dentin hypersensitivity (p < 0.05). Topical application of the dentin adhesives/desensitizers on sensitive dentinal areas resulted in occlusion of the patent tubules. CONCLUSIONS: The one-bottle self-etching adhesives and dentin desensitizers involved in the current clinical investigation could significantly relieve dentin hypersensitivity immediately and over the course of a month after treatment (except for Bifluorid 12 for tooth mechanical sensitivity). The placebo (water) had an immediate effect on thermal dentin hypersensitivity.

Effect of saliva contamination and decontamination on bovine enamel bond strength of four self-etching adhesives.

OBJECTIVE: This study evaluated the effect of saliva contamination on the bovine enamel microtensile bond strengths (microTBS) of four self-etching adhesives. MATERIALS AND METHODS: The labial enamel surfaces of extracted non-carious bovine incisors were serially wet ground. The enamel surfaces were not contaminated (Group A), contaminated with saliva before/after priming (Groups B/C) or they were water-sprayed after salivary contamination occurred before/after priming (Groups D/E). Four self-etching adhesives and the corresponding resin composites from the same manufacturer (Clearfil SE Bond + Clearfil AP-X, Kuraray Co; Xeno III + Ceram X, Densply; Frog + Ice, SDI; FL Bond H + Beautifil II, Shofu Inc) were applied onto the enamel surfaces. The microTBS tests were performed with a micro tester (BISCO, Inc). The enamel surface was analyzed with AFM (Atomic Force Microscopy) before/after salivary contamination occurred or after the saliva-contaminated enamel was water-sprayed. The data were analyzed using one-way ANOVA, factorial design ANOVA and post hoc Tukey's HSD multiple comparisons. RESULTS: Salivary contamination significantly reduced the microTBS of all the adhesives in the current study (p < 0.001). Thorough water-spraying could significantly restore the microTBS of saliva-contaminated enamel to some degree (p < 0.05) or fully restore it for Clearfil SE Bond, but it could not remove some proteins adsorbed on the enamel surface. CONCLUSION: Hydrophilic self-etching adhesives are negatively influenced by salivary contamination. Thorough water-spraying could significantly improve the microTBS of the saliva-contaminated enamel. Proper isolation should be performed before and during application of the adhesives and during placement of the resin composite.

Multifunctional bone cement for synergistic magnetic hyperthermia ablation and chemotherapy of osteosarcoma.

Myelosuppression, gastrointestinal toxicity and hypersensitivities always accompany chemotherapy of osteosarcoma (OS). In addition, the intricate karyotype of OS, the lack of targeted antitumor drugs and the bone microenvironment that provides a protective alcove for tumor cells reduce the therapeutic efficacy of chemotherapy. Here, we developed a multifunctional bone cement loaded with Fe3O4 nanoparticles and the antitumor drug doxorubicin (DOX/Fe3O4@PMMA) for synergistic MH ablation and chemotherapy of OS. The localized intratumorally administered DOX/Fe3O4@PMMA can change from liquid into solid at the tumor site via a polyreaction. The designed multifunctional bone cement was constructed with Fe3O4 nanoparticles, PMMA, and an antitumor drug approved by the U.S. Food and Drug administration (FDA). The injectability, magnetic hyperthermia (MH) performance, controlled drug release profile, and synergistic therapeutic effect of DOX/Fe3O4@PMMA in vitro were investigated in detail. Furthermore, the designed DOX/Fe3O4@PMMA controlled the release of DOX, enhanced the apoptosis of OS tissue, and inhibited the proliferation of tumor cells, demonstrating synergistic MH ablation and chemotherapy of OS in vivo. The biosafety of DOX/Fe3O4@PMMA was also evaluated in detail. This strategy significantly reduced surgical time, avoided operative wounds and prevented patient pain, showing a great clinical translational potential for OS treatment.

An artificially engineered "tumor bio-magnet" for collecting blood-circulating nanoparticles and magnetic hyperthermia.

It is a great challenge to directly endow a tumor with specific functions for theranostic treatment. In this study, we report on a novel approach to transform a tumor into a "bio-magnet", to be magnetized on demand, in order to create an intrinsic tumor magnetic field that would collect magnetic nanoparticles (MNPs) circulating in the blood and achieve simultaneous magnetic hyperthermia. This was achieved by the localized intratumoral injection of liquid Nd2Fe14B/Fe3O4-PLGA, followed by solvent exchange that induces a liquid-to-solid transformation. After the magnetism charging process, the solid Nd2Fe14B/Fe3O4-PLGA implant was endowed with permanent magnetic properties and in situ created the magnetic field within the tumor tissue, making the tumor a "bio-magnet". After the creation of the bio-magnet, intravenously injected MNPs accumulated into the tumor tissue due to the tumor magnetic field. Importantly, both the in vitro and ex vivo results demonstrated the high efficiency of the implanted bio-magnet for magnetic hyperthermia. This new approach achieves magnetic targeting by creating a tumor "bio-magnet", which generates a strong magnetic field within the tumor, paving a new way for the development of an efficient targeting strategy for tumor therapy.

PMMA-Fe3O4 for internal mechanical support and magnetic thermal ablation of bone tumors.

Background: Minimally invasive modalities are of great interest in the field of treating bone tumors. However, providing reliable mechanical support and fast killing of tumor cells to achieve rapid recovery of physical function is still challenging in clinical works. Methods: A material with two functions, mechanical support and magnetic thermal ablation, was developed from Fe3O4 nanoparticles (NPs) distributed in a polymethylmethacrylate (PMMA) bone cement. The mechanical properties and efficiency of magnetic field-induced thermal ablation were systematically and successfully evaluated in vitro and ex vivo. CT images and pathological examination were successfully applied to evaluate therapeutic efficacy with a rabbit bone tumor model. Biosafety evaluation was performed with a rabbit in vivo, and a cytotoxicity test was performed in vitro. Results: An NP content of 6% Fe3O4 (PMMA-6% Fe3O4, mFe: 0.01 g) gave the most suitable performance for in vivo study. At the 56-day follow-up after treatment, bone tumors were ablated without obvious side effects. The pathological examination and new bone formation in CT images clearly illustrate that the bone tumors were completely eliminated. Correspondingly, after treatment, the tendency of bone tumors toward metastasis significantly decreased. Moreover, with well-designed mechanical properties, PMMA-6%Fe3O4 implantation endowed tumor-bearing rabbit legs with excellent bio-mimic bone structure and internal support. Biosafety evaluation did not induce an increase or decrease in the immune response, and major functional parameters were all at normal levels. Conclusion: We have presented a novel, highly efficient and minimally invasive approach for complete bone tumor regression and bone defect repair by magnetic thermal ablation based on PMMA containing Fe3O4 NPs; this approach shows excellent heating ability for rabbit VX2 tibial plateau tumor ablation upon exposure to an alternating magnetic field (AMF) and provides mechanical support for bone repair. The new and powerful dual-function implant is a promising minimally invasive agent for the treatment of bone tumors and has good clinical translation potential.

Synthesis and characterization of folate-PEG-grafted-hyperbranched-PEI for tumor-targeted gene delivery.

A great challenge for gene therapy is to develop a high efficient gene delivery system with low toxicity. Nonviral vectors are still attractive although the current agents displayed some disadvantages (i.e., low transfection efficiency, high toxicity). To overcome the high toxicity of poly(ethylene imine) (PEI) and low transfection efficiency of PEGylated PEI (PEG-PEI), we linked a cell specific target molecule folate (FA) on poly(ethylene glycol) (PEG) and then grafted the FA-PEG onto hyperbranched PEI 25kDa. The FA-PEG- grafted-hyperbranched-PEI (FA-PEG-PEI) effectively condensed plasmid DNA (pDNA) into nanoparticles with positive surface charge under a suitable N/P ratio. Tested in deferent cell lines (i.e., HEK 293T, glioma C6 and hepatoma HepG2 cells), no significant cytotoxicity of FA-PEG-PEI was added to PEG-PEI. More importantly, significant transfection efficiency was exhibited in FA-targeted cells. Reporter assay showed that FA-PEG-PEI/pDNA complexes had significantly higher transgene activity than that of PEI/pDNA in folate-receptor (FR) positive (HEK 293T and C6) cells but not FR-negative (HepG2) cells. These results indicated that FA-PEG-PEI might be a promising candidate for gene delivery with the characteristics of good biocompatibility, potential biodegradability, and relatively high gene transfection efficiency.

Injectable and thermally contractible hydroxypropyl methyl cellulose/Fe3O4 for magnetic hyperthermia ablation of tumors.

The development of efficient strategies for the magnetic hyperthermia ablation of tumors remains challenging. To overcome the significant safety limitations, we developed a thermally contractible, injectable and biodegradable material for the minimally invasive and highly efficient magnetic hyperthermia ablation of tumors. This material was composed of hydroxypropyl methyl cellulose (HPMC), polyvinyl alcohol (PVA) and Fe3O4. The thermal contractibility of HPMC/Fe3O4 was designed to avoid damaging the surrounding normal tissue upon heating, which was confirmed by visual inspection, ultrasound imaging and computed tomography (CT). The efficient injectability of HPMC/Fe3O4 was proven using a very small needle. The biosafety of HPMC/Fe3O4 was evaluated by MTT and biochemical assays as well as flow cytometry (FCM). All the aforementioned data demonstrated the safety of HPMC/Fe3O4. The results of in vitro and ex vivo experiments showed that the temperature and necrotic volume of excised bovine liver were positively correlated with the HPMC/Fe3O4 weight, iron content and heating duration. The in vivo experimental results showed that the tumors could be completely ablated using 0.06 ml of HPMC/60%Fe3O4 after 180 s of induction heating. We believe that this novel, safe and biodegradable material will promote the rapid bench-to-bed translation of magnetic hyperthermia technology, and it is also expected to bring a new concept for the biomaterial research field.

[Correlations of plasma concentrations of ß-amyloid peptide and S-100ß with postoperative cognitive dysfunction in patients undergoing oral and maxillofacial cancer surgery].

PURPOSE: To evaluate the changes of perioperative plasma concentrations of Aß1-40 and S-100ß to determine the relationship with postoperative cognitive dysfunction in elderly patients undergoing oral and maxillofacial cancer surgeries. METHODS: One hundred and fifteen patients aged at least 60 years undergoing oral and maxillofacial tumor resection were investigated between May 2014 to December 2014.Neuropsychological tests for detecting postoperative cognitive dysfunction(POCD) were performed one day before surgery and 7 days postoperatively. According to the results of neuropsychological tests on day 7, patients were divided into POCD group and non-POCD group.Plasma values of Aß1-40 and S-100ß were determined with enzyme linked immunosorbent assay (ELISA) before anesthesia induction, 24 h and 7 days after surgery. The data were analyzed using SPSS 19.0 software package. RESULTS: According to the definition, POCD was present in 37 of 115 (32.3%) patients 1 week after surgery. Compared with pre-anesthesia, S-100ß levels in POCD group were significantly increased (P<0.05); the level of Aß1-40 was significantly higher 24 h after surgery (P<0.05). Compared with non-POCD group, S-100ß levels were significantly increased 24 h postoperatively (P<0.05); Aß1-40 levels were significantly higher 24 h and 7 days postoperatively (P<0.05). CONCLUSIONS: POCD was present in 32.2% of patients on day 7 after oral and maxillofacial surgeries with general anesthesia. The increasing levels of Aß1-40, S-100ß may be associated with the occurence of POCD. Patients with long-lasting operation and high concentrations of Aß1-40 and S-100ß after surgeries were at a higher risk of POCD. The clinical values of Aß1-40 and S-100 as predictive measurements of POCD after oral and maxillofacial cancer surgery appear to be reasonable.

Water soluble cationic dextran derivatives containing poly(amidoamine) dendrons for efficient gene delivery.

To develop new dextran derivatives for efficient gene delivery, the conjugation of poly(amidoamine) dendrons onto biocompatible dextran was carried out by a Cu(I)-catalyzed azide-alkyne cycloaddition, as confirmed by FTIR and (1)H NMR analyses. For resultant dextran conjugates with various generations of poly(amidoamine) dendrons, their buffering capacity and in vitro cytotoxicity were evaluated by acid-base titration and MTT tests, respectively. In particular, their physicochemical characteristics for the complexation with plasmid DNA were investigated by the combined analyses from agarose gel electrophoresis, zeta potential, particle size, transmission electron microscopy and fluorescence emission spectra. Moreover, their complexes with plasmid DNA were studied with respect to their transfection efficiency in human embryonic kidney (HEK293) cell lines. In the case of a higher generation of poly(amidoamine) dendrons, such a dextran conjugate was found to have much lower cytotoxicity and better gene delivery capability when compared to branched polyethylenimine (bPEI, 25kDa), a commonly used gene vector.

The contribution of chemical bonding to the short- and long-term enamel bond strengths.

OBJECTIVES: MDP (10-methacryloyloxydecyl dihydrogenphosphate) has been proven to possess chemical bonding ability to tooth hard tissues, but its contribution to the enamel bond strength has not been recognized. The aim of this study was to investigate the contribution of chemical bonding to the short- and long-term bovine enamel micro-tensile bond strengths (µTBS). METHODS: The acid-etched enamel surfaces were treated without any primer (control) or with one of three MDP-containing primers (containing different ratio of MDP/HEMA/Bis-GMA, Kuraray Co.) for 5s, water-sprayed and air-dried. Subsequently, the pretreated enamel surfaces were applied with an etch-and-rinse adhesive Durafill Bond (Heraeus Kulzer) and placed with composite resin Durafill VS (Heraeus Kulzer). The specimens were prepared for µTBS tests after 24-h or 1-yr water storage. The etched enamel surfaces treated with or without MDP-containing primers were analyzed by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). RESULTS: The acid-etched enamel treated with the MDP-primers for a very short time could produce the greater enamel µTBS than the control did (p<0.05), and change enamel micromorphology. No significant different µTBS were found between 24-h and 1-yr water storage (p>0.05). The chemical bonding of MDP on the enamel surfaces was re-confirmed by XPS. SIGNIFICANCE: The additional chemical bonding of MDP around the enamel crystallites of the etched enamel substrate could significantly increase the short- and long-term enamel µTBS, and their µTBS surpass those of the etch-and-rinse adhesive alone.

Improvement of enamel bond strengths for conventional and resin-modified glass ionomers: acid-etching vs. conditioning.

OBJECTIVE: This study deals with the effect of phosphoric acid etching and conditioning on enamel micro-tensile bond strengths (µTBSs) of conventional and resin-modified glass ionomer cements (GICs/RMGICs). METHODS: Forty-eight bovine incisors were prepared into rectangular blocks. Highly-polished labial enamel surfaces were either acid-etched, conditioned with liquids of cements, or not further treated (control). Subsequently, two matching pre-treated enamel surfaces were cemented together with one of four cements [two GICs: Fuji I (GC), Ketac Cem Easymix (3M ESPE); two RMGICs: Fuji Plus (GC), RelyX Luting (3M ESPE)] in preparation for µTBS tests. Pre-treated enamel surfaces and cement-enamel interfaces were analyzed by scanning electron microscopy (SEM). RESULTS: Phosphoric acid etching significantly increased the enamel µTBS of GICs/RMGICs. Conditioning with the liquids of the cements produced significantly weaker or equivalent enamel µTBS compared to the control. Regardless of etching, RMGICs yielded stronger enamel µTBS than GICs. A visible hybrid layer was found at certain enamel-cement interfaces of the etched enamels. CONCLUSIONS: Phosphoric acid etching significantly increased the enamel µTBSs of GICs/RMGICs. Phosphoric acid etching should be recommended to etch the enamel margins before the cementation of the prostheses such as inlays and onlays, using GICs/RMGICs to improve the bond strengths. RMGICs provided stronger enamel bond strength than GICs and conditioning did not increase enamel bond strength.

The use of folate-PEG-grafted-hybranched-PEI nonviral vector for the inhibition of glioma growth in the rat.

Combined treatment using nonviral agent-mediated enzyme/prodrug therapy and immunotherapy had been proposed as a powerful alternative method of cancer therapy. The present study was aimed to evaluate the cytotoxicity in vitro and the therapeutic efficacy in vivo when the cytosine deaminase/5-fluorocytosine (CD/5-FC) and TNF-related apoptosis-inducing ligand (TRAIL) genes were jointly used against rat C6 glioma cells. The potency of the FA-PEG-PEI used as a nonviral vector was tested in the FR-expressed C6 glioma cells and Wistar rats. The C6 glioma cells and animal model were treated by the combined application of FA-PEG-PEI/pCD/5-FC and FA-PEG-PEI/pTRAIL. The antitumor effect was evaluated by survival assays and tumor volume. This study revealed a significant increase of cytotoxicity in vitro following the combined application of FA-PEG-PEI/pCD/5-FC and FA-PEG-PEI/pTRAIL treatments in C6 glioma cells. Animal studies showed a significant growth inhibition of the C6 glioma xenografts using the combined treatment. These results demonstrated that the combined treatment generated additive cytotoxic effect in C6 glioma cells in both in vitro and in vivo conditions, and indicated that such treatment method using both enzyme/prodrug therapy and TRAIL immunotherapy might be a promising therapeutic strategy in treating glioma.