IL-10 Promotes CXCL13 Expression in Macrophages Following Foot-and-Mouth Disease Virus Infection.

Foot-and-mouth disease (FMD) is one of the most contagious livestock diseases in the world, posing a constant global threat to the animal trade and national economies. The chemokine C-X-C motif chemokine ligand 13 (CXCL13), a biomarker for predicting disease progression in some diseases, was recently found to be increased in sera from mice infected with FMD virus (FMDV) and to be associated with the progression and severity of the disease. However, it has not yet been determined which cells are involved in producing CXCL13 and the signaling pathways controlling CXCL13 expression in these cells. In this study, the expression of CXCL13 was found in macrophages and T cells from mice infected with FMDV, and CXCL13 was produced in bone-marrow-derived macrophages (BMDMs) by activating the nuclear factor-kappaB (NF-κB) and JAK/STAT pathways following FMDV infection. Interestingly, CXCL13 concentration was decreased in sera from interleukin-10 knock out (IL-10-/-) mice or mice blocked IL-10/IL-10R signaling in vivo after FMDV infection. Furthermore, CXCL13 was also decreased in IL-10-/- BMDMs and BMDMs treated with anti-IL-10R antibody following FMDV infection in vitro. Lastly, it was demonstrated that IL-10 regulated CXCL13 expression via JAK/STAT rather than the NF-κB pathway. In conclusion, the study demonstrated for the first time that macrophages and T cells were the cellular sources of CXCL13 in mice infected with FMDV; CXCL13 was produced in BMDMs via NF-κB and JAK/STAT pathways; and IL-10 promoted CXCL13 expression in BMDMs via the JAK/STAT pathway.

Bioinspired Production of Noniridescent Structural Colors by Adhesive Melanin-like Particles.

Structural color printing of colloidal photonic films with tunable structures or optical properties is of great importance owing to their practical applications. In this article, we present a general method for the fabrication of colloidal particle films with tailored packing geometries by self-assembly of adhesive melanin-like polydopamine (PDA)-coated particles. The adhesion of particles is controlled by varying the thickness of the PDA coating, making it possible for dip coating of colloidal crystals, partly ordered or amorphous colloidal arrays (ACAs) with a tunable degree of order. We further studied the structural color printing of adhesive particles by infiltration-assisted or standard inkjet printing methods. Compared with bare particles, PDA-coated particles not only allow for control over color brightness/angle dependence of the photonic films but also significantly enhance the color quality of ACAs, both of which are useful for display, anticounterfeiting, or sensing applications. Owing to the inherent strong adhesiveness of PDA to virtually all types of surfaces, this PDA-based methodology can be potentially extended to a diverse range of colloidal particles toward the development of photonic devices.

Mesoporous silica nanoparticles in drug delivery and biomedical applications.

In the past decade, mesoporous silica nanoparticles (MSNs) with a large surface area and pore volume have attracted considerable attention for their application in drug delivery and biomedicine. In this review, we highlight the recent advances in silica-assisted drug delivery systems, including (1) MSN-based immediate/sustained drug delivery systems and (2) MSN-based controlled/targeted drug delivery systems. In addition, we summarize the biomedical applications of MSNs, including (1) MSN-based biotherapeutic agent delivery; (2) MSN-assisted bioimaging applications; and (3) MSNs as bioactive materials for tissue regeneration. FROM THE CLINICAL EDITOR: This comprehensive review presents recent advances in mesoporous silica nanoparticles assisted drug delivery systems, including both immediate and sustained delivery systems as well as controlled release and targeted drug delivery systems. In addition to achieving therapeutic agent delivery, imaging applications and potential use of silica NPs in tissue regeneration are also discussed.

Investigation of excipients impact on polysorbate 80 degradation in biopharmaceutical formulation buffers.

A study on the polysorbate 80 stability in various formulation buffers commonly used in biopharmaceuticals was performed, to investigate the excipients influence on polysorbate 80 degradation. Polysorbate 80 is a common excipient in biopharmaceutical products. However, its degradation will potentially impact the drug product quality, and may trigger protein aggregation and particles formation. Due to the heterogeneity of the polysorbates and the mutual effects with other formulation compositions, the study of polysorbate degradation is challenging. Herein, a real-time stability study was designed and performed. The polysorbate 80 degradation trend was monitored by fluorescence micelle-based assay (FMA), reversed-phase-ultra-performance liquid chromatography-evaporative light scattering detector (RP-UPLC-ELSD) assay, and LC-MS assay. These assays provide orthogonal results to reveal both the micelle-forming capability and the compositional changes of polysorbate 80 in different buffer systems. The degradation occurred after a period of storage under 25 °C in different trend, which indicates the excipients could impact the degradation kinetics. Upon comparison, the degradation is prone to happen in histidine buffer than in acetate, phosphate or citrate buffers. LC-MS confirms oxidation as an independent degradation pathway with detection of the oxidative aldehyde. Thus, it is necessary to pay more attention to the excipients selection and their potential impact on polysorbate 80 stability to achieve longer shelf life for the biopharmaceuticals. Besides, the protective roles of several additives were figured out, which could be applied as potential industrial solutions to the polysorbate 80 degradation issues.

Antiviral Effect of Manganese against Foot-and-Mouth Disease Virus Both in PK15 Cells and Mice.

Foot-and-mouth disease (FMD) is an acute contagious disease of cloven-hoofed animals such as cattle, pigs, and sheep. Current emergency FMD vaccines are of limited use for early protection because their protective effect starts 7 days after vaccination. Therefore, antiviral drugs or additives are used to rapidly stop the spread of the virus during FMD outbreaks. Manganese (Mn2+) was recently found to be an important substance necessary for the host to protect against DNA viruses. However, its antiviral effect against RNA viruses remains unknown. In this study, we found that Mn2+ has antiviral effects on the FMD virus (FMDV) both in PK15 cells and mice. The inhibitory effect of Mn2+ on FMDV involves NF-κB activation and up-regulation of interferon-stimulated genes. Animal experiments showed that Mn2+ can be highly effective in protecting C57BL/6N mice from being infected with FMDV. Overall, we suggest Mn2+ as an effective antiviral additive for controlling FMDV infection.

[Determination of crystallinity in Neosinocalamus affinins based on near infrared spectroscopy and PLS methods].

Near infrared spectroscopy technique combined with chemometrics methods was applied to predict crystallinity of Neosinocalamus affinins. Three improved partial least squares (PLS) methods, including interval partial least squares (iPLS), synergy interval partial least squares (siPLS) and backward interval partial least squares (biPLS), were used to find the most informative ranges and build models with better predictive quality based on multiplicative scatter correction spectra. And then the models were compared with PLS model which was developed on the whole wavelength range 350-2 500 nm. The results showed that the models built by the three improved PLS methods had higher predictive ability than that of PLS model, and the optimal model was obtained by siPLS method that separated the whole spectra into 30 intervals and combined three intervals. The siPLS model had correlation coefficient (R) of 0.88 and root mean standard error of prediction (RMSEP) of 0.011 7. Therefore, through selecting the effective wavelength range, siPLS method could accurately and rapidly predict crystallinity in Neosinocalamus affinins.

Improved therapeutic effect of DOX-PLGA-PEG micelles decorated with bivalent fragment HAb18 F(ab')(2) for hepatocellular carcinoma.

Although surgery offers the only hope of cure for hepatocellular carcinoma (HCC), patients with inoperable or metastatic disease have a dismal prognosis. Therefore, there is an urgent need for new and effective treatment strategies. Polymeric micelles composed of drug conjugated to a diblock copolymer have attracted great interest for clinical administration of anticancer drugs. In this work, characteristics and cytotoxicity of doxorubicin-poly(d,l-lactic-co-glycolic acid)-poly(ethylene glycol) (DOX-PLGA-PEG) micelle and its targeted micelle decorated with bivalent fragment HAb18 F(ab')(2) for HCC were studied. These micelles possessed spherical morphology and higher loading efficiency. Cellular uptake and accumulation in tumor tissue of micelles was observed. The accumulation of the targeted micelles depends on dual effects of passive and active targeting. The drug-loading micelles showed cytotoxicity on tumor cells in vitro and in vivo. The targeted micelles resulted in significant improvement in therapeutic response. These results suggest that the novel micelles could be a promising candidate with excellent therapeutic efficacy for targeting the drugs to cancer cells.

Neuron-Inspired Self-Healing Composites via Dynamic Construction of Polypyrrole-Decorated Carbon Nanotubes for Smart Physiochemical Sensing.

Mimicking human skin's functions to develop intelligent materials have inspired extensive exploration in the design and synthesis of a novel device. However, how to simulate neuron function and integrate highly sensitive, positive perceptions and self-healing into one single material remains a challenge. Here, we prepared a recycled polyurethane (PU) with high tensile strength values (11.37 ± 0.03 MPa), high maximum elongation (1130 ± 11.59%), and high self-healing property (100% for 6 h at 25 °C) and a smart PU composite of polypyrrole-decorated carbon nanotubes with higher sensitivity. The smart composite can not only actively identify physical change such as strain, moisture, and temperature but also proactively detect various chemical environment changes such as acid, alkali, oxidant, and reductant (T: 25-90 °C, ΔR/R0 values were 0.1-1.6; strain: 10-150%, ΔR/R0 values were 2.5-27; 0.01-0.1 mol L-1 oxidant solutions, ΔR/R0 values were 0.66-0.75; 0.01-0.1 mol L-1 reductant solutions, ΔR/R0 values were 0.51-0.65; 0.1-0.5 mol L-1 acid solutions, ΔR/R0 values were 0.54-0.58; and 0.1-0.5 mol L-1 alkali solutions, ΔR/R0 values were 0.42-0.46). More importantly, the signal values of the smart composite can quickly return to the initial values after eliminating physical and chemical stimuli. The abovementioned features of the smart composite, the high physicochemical response, and significant restorability make it potentially possible to apply it in intelligent chemical manufacturing.

Role of the proportion of cattle manure and biogas residue on the degradation of lignocellulose and humification during composting.

The effects of different proportions of cattle manure (CM) and biogas residue (BR) on the degradation of lignocellulose and humification during composting were investigated. The results showed that increasing the CM content prolonged the thermophilic period duration, thus promoting organic matter degradation and enhancing the humification degree during composting. Compared with the initial compost, the cellulose content decreased 3.90%-22.81%. The addition of CM increased humic acid content by 17.21%-26.02% compared with the control. The excitation-emission matrix (EEM) fluorescence spectroscopy analysis indicated that a higher CM content was conducive to the formation of protein-like substances, but a disadvantage for humic substances. The cell viability decreased as CM content increased. The redundancy analysis (RDA) demonstrated that proportions of CM and BR were positively correlated with cellulose content and negatively correlated with cell viability and the content of lignin. The results suggest that adding 6.7% CM was optimal for BR composting.

Cytotoxicity of paclitaxel incorporated in PLGA nanoparticles on hypoxic human tumor cells.

PURPOSE: The aim of this work was to prepare paclitaxel-loaded PLGA nanoparticles and determine cytotoxicity of released paclitaxel for two hypoxic human tumor cell lines: breast carcinoma (MCF-7) and carcinoma cervicis (HeLa). METHODS: Poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles containing paclitaxel were prepared by o/w emulsification-solvent evaporation method. Physicochemical characteristics of nanoparticles were studied. Cellular uptake of nanoparticles was evaluated by transmission electronic microscopy and fluorescence microscopy. Flow cytometry quantified the number of cells held in G(2)/M phase. Cell viability was determined by the ability of single cell to form colonies. Biodistribution of nanoparticles in mice was evaluated by fluorescence microscopy. RESULTS: The nanoparticles were spherical with average diameter 318 +/- 5.1 nm. The encapsulation efficiency was 88.52%. The drug release profile in vitro exhibited a biphasic pattern. Cellular uptake was observed. Co-culture of tumor cells with paclitaxel-loaded nanoparticles demonstrated that released paclitaxel retained its bioactivity to block cells in G(2)/M phase. Paclitaxel-loaded nanoparticles exhibited cytotoxic effect on both hypoxic MCF-7 and HeLa cells and its cytotoxicity was more significant than that of free paclitaxel. Fluorescent nanoparticles were mainly distributed to liver and spleen of mice. CONCLUSIONS: Paclitaxel-loaded PLGA nanoparticles may be considered a promising drug delivery system to eradicate hypoxic tumor cells.

Radiosensitization of paclitaxel, etanidazole and paclitaxel+etanidazole nanoparticles on hypoxic human tumor cells in vitro.

Paclitaxel and etanidazole are hypoxic radiosensitizers that exhibit cytotoxic action at different mechanisms. The poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles containing paclitaxel, etanidazole and paclitaxel+etanidazole were prepared by o/w and w/o/w emulsification-solvent evaporation method. The morphology of the nanoparticles was investigated by scanning electron microscope (SEM). The drug encapsulation efficiency (EE) and release profile in vitro were measured by high-performance liquid chromatography (HPLC). The cellular uptake of nanoparticles for the human breast carcinoma cells (MCF-7) and the human carcinoma cervicis cells (HeLa) was evaluated by transmission electronic microscopy and fluorescence microscopy. Cell viability was determined by the ability of single cell to form colonies in vitro. The prepared nanoparticles were spherical shape with size between 80 and 150 nm. The EE was higher for paclitaxel and lower for etanidazole. The drug release was controlled over time. The cellular uptake of nanoparticles was observed. Co-culture of the two tumor cell lines with drug-loaded nanoparticles demonstrated that released drug effectively sensitized hypoxic tumor cells to radiation. The radiosensitization of paclitaxel+etanidazole nanoparticles was more significant than that of single drug-loaded nanoparticles.

[Modification of titanium surface with calcium and phosphorus ions using micro-arc oxidation and its effect on osteoblast attachment].

OBJECTIVE: To study the method for modifying titanium surface with calcium and phosphorus ions using micro-arc oxidation technique and observe osteoblast attachment to the modified surface. METHODS: TA(2) titanium discs were treated with micro-arc oxidation in electrolyte solution containing Ca(2+) and PO(4)(3-). The influence of Ca(2+) and PO(4)(3-) concentrations in the solution and the electrical parameters of the micro-arc oxidization on the content of calcium and phosphorus ions incorporated into the surface of titanium was investigated using energy-dispersive X-ray (EDX) analysis. Scanning electron microscopy was employed for morphological observation of the ceramic coating on the metal surface. The binding strength of ceramic coating with titanium was tested by shear bonding experiment. MC-3T3-E1 osteoblast-like cells were then cultured on the treated surface of titanium discs to investigate the influence of the ceramic coating on osteoblast attachment. RESULTS: Micro-arc oxidation treatment produced a layer of porous TiO(2) coating on the surface of titanium discs, with the average pore size of 2 to 10 mum. EDX analysis revealed that the ceramic coating contained Ca and P elements, whose content had close correlation with Ca(2+) and PO(4)(3-) concentrations in the electrolyte solution and voltage, duty cycle and frequency of micro-arc oxidation. The average bonding strength of the ceramic coating with titanium was 22+/-3 MPa, and TiO(2) coating promoted attachment and spread of osteoblast-like cells on the metal surface as demonstrated by cell culture. CONCLUSIONS: Porous TiO(2) coating can be constructed on the surface of titanium using micro-arc oxidation, and Ca(2+) and PO(4)(3-) incorporated into the coating can improve the biocompatibility of titanium. The content of Ca(2+) and PO(4)(3-) in the coating can be modulated by adjusting the concentrations of Ca(2+) and PO(4)(3-) in the electrolyte solution and the electrical parameters of the micro-arc oxidation.

Redox-responsive mesoporous silica as carriers for controlled drug delivery: a comparative study based on silica and PEG gatekeepers.

Hybrid mesoporous silica nanoparticles (MSNs) modified with polymer polyethylene glycol (PEG) through the biodegradable disulfide bonds were prepared to achieve 'on demand' drug release. In this system, PEG chains were chosen as the representative gatekeepers that can block drugs within the mesopores of MSNs. After the addition of glutathione (GSH), the gatekeepers were removed from the pore outlets of MSNs, followed by the release of encapsulated drugs. In this research, the effects of grafting density of gatekeepers on the drug release and biocompatibility of silica carriers were also investigated. First, PEG modified MSNs were prepared by the condensation reaction between the carboxyl groups of MSN and the hydroxyl of PEG. The structure of the resultant MSN-SS-PEG was characterized by transmission electron microscopy (TEM), nitrogen adsorption/desorption isotherms analysis and Fourier transform infrared spectroscopy (FTIR). Rhodamine B (RhB) as the model drug was loaded into MSNs. The in vitro assay results indicated that RhB was released rapidly after the addition of 10 mM GSH; M1-SS-PEG had the best capping efficiency compared with M0.5 and M1.5 groups. Moreover, hemolysis assay, serum protein adsorption and cell viability test indicated that with the increase of PEG grafting density, the biocompatibility of silica carriers increased.

Different influence of Ti, PMMA, UHMWPE, and Co-Cr particles on peripheral blood monocytes during periprosthetic inflammation.

This study investigated cellular trafficking and inflammatory markers in orthopedic biomaterial particle-challenged human peripheral blood monocytes (PBMCs) using a murine immunodeficiency (SCID) model. Periprosthetic tissues from aseptic loosening patients were transplanted into muscles of SCID mice. PBMCs from the same patients were stimulated in vitro with Ti-6Al-4V, PMMA, UHMWPE, or Co-Cr particles for 3 days before administered intraperitoneally to the periprosthetic tissue-implanted mice. The xenografts were harvested 2 weeks later for histological and molecular analyses. Significant cell infiltration was obvious in the transplanted tissues from mice transfused with Ti-alloy, PMMA and UHMWPE-provoked PBMCs compared to controls, and UHMWPE-provoked PBMCs group accumulated significantly more cells among all groups. There were ubiquitous TRAP+ stained cells in all xenografts from particle-stimulated PBMCs mice. Immunohistochemical staining indicated that significantly more IL-1ß and TNF positive cells occurred in Ti and PMMA groups; while the UHMWPE group resulted in stronger positive MCP-1 and IL-6 stains. Polymerase chain reaction (PCR) confirmed overexpression of both IL-1ß and TNF in Ti and PMMA-stimulated groups; and more MIP-1α gene expression developed in the UHMWPE group. Overall, different type of orthopedic materials influenced the trafficking ability of particle-activated PBMCs which may depend on upregulation of various proinflammatory cytokines and chemokines.

Electroactive species-doped poly(3,4-ethylenedioxythiophene) films: enhanced sensitivity for electrochemical simultaneous determination of vitamins B2, B6 and C.

Herein, functionalized PEDOT films were prepared by incorporation of two electroactive species, ferrocenecarboxylic acid (Fc(-)) and ferricyanide (Fe(CN)6(4-)) as doping anions during the electropolymerization of PEDOT at glassy carbon electrodes (GCEs) from aqueous solution. The electrochemically synthesized electroactive species-doped PEDOT films have been carefully characterized by scanning electron microscopy (SEM), FTIR and UV/Vis spectra and various electrochemical techniques. Such nanostructured films combined the advantages of PEDOT (high conductivity and stability) together with electroactive species (good electrochemical activity) and were applied as electrochemical sensors for simultaneous determination of vitamin B2 (VB2), vitamin B6 (VB6) and vitamin C (VC). The results showed that the oxidation peak currents of vitamins obtained at the GCEs modified with electroactive species-doped PEDOT films were much higher than those at the ClO4(-)-doped PEDOT films and bare GCEs. The experiment results also illustrated that the sensors possessed high selectivity with no interference from other potential competing species. Moreover, the proposed sensors were successfully employed for the determination of vitamins in orange juice samples with satisfactory results.

Polymethylmethacrylate and titanium alloy particles activate peripheral monocytes during periprosthetic inflammation and osteolysis.

We investigated the interactions of particulate PMMA or titanium alloy, patient blood monocytes, and periprosthetic tissues using a SCID-hu model of aseptic loosening. Periprosthetic tissues and bone chips obtained at revision surgery for loosening were transplanted into muscles of SCID mice. Peripheral blood monocytes (PBMCs) isolated from the same donors were fluorescently labeled and co-cultured with PMMA or Ti-6Al-4V particles before intraperitoneal injection. Control mice with periprosthetic tissue or non-inflammatory ligament xenografts received naive PBMCs transfusion. Mice were euthanized 2 weeks after PBMC transfusion. The human tissues were well accepted in SCID mice. Transfused fluorescent-labeled PBMCs were markedly accumulated in transplanted periprosthetic tissues. Multinucleated osteoclast-like cells were commonly seen within retrieved xenograft tissue, and focal bone erosions were ubiquitous. Total cell densities and CD68+ cells within the xenograft were significantly increased in mice transfused with PMMA and Ti-provoked PBMCs compared to the naïve PBMC animals (p < 0.05). Immunohistochemical staining identified much stronger positive IL-1 and TNF stains in xenografts from either PMMA or Ti-stimulated monocytes transfusion groups (p < 0.05). TRAP+ cells were found around bone chips in both activated-PBMCs groups, although markedly more aggregated TRAP+ cells in the PMMA-challenged group than in the titanium group (p < 0.05). MicroCT assessment confirmed the significant decrease of bone mineral density in chips interacted with activated-monocytes/osteoclasts. In conclusion, PMMA or titanium particles readily activate peripheral monocytes and promote the cell trafficking to the debris-containing prosthetic tissues. Particles-provoked PBMCs participated in and promoted the local inflammatory process, osteoclastogenesis, and bone resorption.

Paclitaxel-loaded poly(D,L-lactide-co-glycolide) nanoparticles for radiotherapy in hypoxic human tumor cells in vitro.

Radioresistant hypoxic cells may contribute to the failure of radiation therapy in controlling certain tumors. Some studies have suggested the radiosensitizing effect of paclitaxel. The poly (D,L-lactide-co-glycolide)(PLGA) nanoparticles containing paclitaxel were prepared by o/w emulsification-solvent evaporation method. The physicochemical characteristics of the nanoparticles (i.e., encapsulation efficiency, particle size distribution, morphology, in vitro release) were studied. The morphology of the two human tumor cell lines: a carcinoma cervicis (HeLa) and a hepatoma (HepG(2)), treated with paclitaxel-loaded nanoparticles was photomicrographed. Flow cytometry was used to quantify the number of the tumor cells held in the G(2)/M phase of the cell cycle. The cellular uptake of nanoparticles was evaluated by transmission electronic microscopy. Cell viability was determined by the ability of single cell to form colonies in vitro. The prepared nanoparticles were spherical in shape with size between 200 nm and 800 nm. The encapsulation efficiency was 85.5%. The release behaviour of paclitaxel from the nanoparticles exhibited a biphasic pattern characterised by a fast initial release during the first 24 h, followed by a slower and continuous release. Co-culture of the two tumor cell lines with paclitaxel-loaded nanoparticles demonstrated that the cell morphology was changed and the released paclitaxel retained its bioactivity to block cells in the G(2)/M phase. The cellular uptake of nanoparticles was observed. The free paclitaxel and paclitaxel-loaded nanoparticles effectively sensitized hypoxic HeLa and HepG(2) cells to radiation. Under this experimental condition, the radiosensitization of paclitaxel-loaded nanoparticles was more significant than that of free paclitaxel.