pH-responsive magnetic core-shell nanocomposites for drug delivery.

Polymer-modified nanoparticles, which can load anticancer drugs such as doxorubicin (DOX), showing the release in response to a specific trigger, have been paid much attention in cancer therapy. In our study, a pH-sensitive drug-delivery system consisting of Fe3O4@mSiO2 core-shell nanocomposite (about 65 nm) and a ß-thiopropionate-poly(ethylene glycol) "gatekeeper" (P2) has been successfully synthesized as a drug carrier (Fe3O4@mSiO2@P2). Because of the hydrolysis of the ß-thiopropionate linker under mildly acidic conditions, Fe3O4@mSiO2@P2 shows a pH-sensitive release performance based on the slight difference between a tumor (weakly acid) and normal tissue (weakly alkaline). And before reaching the tumor site, the drug-delivery system shows good drug retention. Notably, the nanocomposites are quickly taken up by HeLa cells due to their small particle size and the poly(ethylene glycol) modification, which is significant for increasing the drug efficiency as well as the cancer therapy of the drug vehicles. The excellent biocompatibility and selective release performance of the nanocomposites combined with the magnetic targeted ability are expected to be promising in the potential application of cancer treatment.

Epstein-Barr Virus Promotes Inflammatory Cytokine Production in Human Gingival Fibroblasts.

BACKGROUND: Periodontitis is one of the most common chronic oral inflammatory diseases. Over the past decade, herpes viruses, particularly Epstein-Barr virus (EBV), have been considered promising pathogenic candidates for periodontitis. However, the specific mechanism by which EBV contributes to the development of periodontitis is still unknown. This study aimed to explore the mechanism of EBV underlying the inflammatory response in human gingival fibroblasts (HGFs). MATERIALS AND METHODS: HGFs were stimulated with different concentrations of EBV (104, 105, 106, 107, and 108 DNA copies/mL) for 0, 8, 24, or 48 hours. The mRNA levels of interleukin (IL)-1ß, tumour necrosis factor-α (TNF-α), IL-8, monocyte chemoattractant protein-1 (MCP-1), and Toll-like receptor 9 (TLR9) were measured using quantitative real-time polymerase chain reaction (PCR). Enzyme-linked immunosorbent assays (ELISAs) were performed for determining the mRNA and protein levels of IL-1ß, TNF-α, IL-8, and MCP-1. Real-time PCR and ELISA were performed to determine the protein levels of IL-1ß, TNF-α, IL-8, and MCP-1. Activation of the TLR9/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) pathway was evaluated using western blotting. RESULTS: The expressions of IL-1ß, TNF-α, IL-8, and MCP-1 were significantly upregulated in HGFs under EBV stimulation in a concentration- and time-dependent manner. EBV promoted TLR9 and MyD88 expression and induced NF-κB transcription. On the contrary, the upregulation of these factors and the activation of NF-κB pathway were drastically inhibited by TLR9 antagonists. CONCLUSIONS: Our findings demonstrate that EBV promotes the production of inflammatory cytokines IL-1ß and TNF-α and chemokines IL-8 and MCP-1 in HGFs through the TLR9/MyD88/NF-κB pathway.

High-performance free-standing microbial fuel cell anode derived from Chinese date for enhanced electron transfer rates.

Traditional anode materials have disadvantages like low specific surface area and poor electrical conductivity. Herein, carbonized Chinese dates (CCD) were synthesized as microbial fuel cells (MFC) anodes. The obtained materials exhibited excellent biocompatibility with fast start-up (within one day) and charge transfer (Rct 4.0 Ω). Their porous structure allows efficient ion transport and microbial community succession, favorable for long-term operation. The biomass analysis shows that CCD anodes can load higher weight of biomass. High-throughput sequencing (16S rRNA) discovered that CCD anode can enrich Geobacter spp., with highest abundance of 73.4%, much higher than carbon felt (CF, 39.2%). Benefit from these properties, the MFC with CCD anodes possess a maximum power density of 12.17 W m-3 (1.62 times of commercial carbon felt). In all, the CCD anode exhibits high performance with low cost and easy fabrication, certificating it a promising candidate for an ideal MFC anode material.

B-Cell Deficiency Exacerbates Inflammation and Bone Loss in Ligature-Induced Experimental Periodontitis in Mice.

OBJECTIVE: Periodontitis, one of the most prevalent chronic oral infectious diseases in humans, is induced by the breakdown in the balance between the biofilm and host immune system. Previous studies have shown the presence of large numbers of B cells in periodontitis lesions, implicating that B lymphocytes play a predominant role during the pathogenesis of periodontitis. This study aimed to investigate the role of all B cells in the initiation of periodontitis. METHODS: Experimental periodontitis was induced in B cell-deficient (CD19Cre) mice and wild-type (WT) control mice by 5-0 silk ligation around the maxillary second molar. Four weeks after ligation, alveolar bone loss was determined by micro-computed tomography. The levels of inflammatory cytokines and receptor activator of NF-κB ligand (RANKL)/osteoprotegerin in periodontal lesions were analyzed using real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry. Lymphocyte populations in the cervical lymph nodes and spleen and among the peripheral blood mononuclear cells were detected by flow cytometry. RESULTS: B-cell deficiency resulted in increased severity of alveolar bone loss in mouse experimental periodontitis, which was associated with increased osteoclast activity and upregulated RANKL expression in the periodontal lesions. In addition, gingiva cytokine expression profiles were shifted to T helper type 1 (Th1) and Th17 in the CD19Cre mice with ligature-induced periodontitis compared with WT mice. In addition, a reduced CD4+/CD8+ T cell ratio was observed in the CD19Cre mice. CONCLUSION: B-cell deficiency exacerbates the inflammation and alveolar bone loss in ligature-induced experimental periodontitis in mice, implicating that B cells may overall play a protective role in the initiation of periodontitis.

Immobilization of RGD peptide on HA coating through a chemical bonding approach.

In this work, Arg-Gly-Asp (RGD) sequence containing peptide was immobilized on hydroxyapatite (HA) coatings through a chemical bonding approach in two steps, surface modification with 3-aminopropyltriethoxysilane (APTES) and RGD immobilization. The results indicate that RGD has been successfully immobilized on HA coatings. Comparing with physical adsorption coatings, the chemically bonded RGD on the coatings shows much better anti-wash-out ability. Since RGD is able to recognize cell-membrane integrins on biointerfaces, the present method will be an effective way to favor interaction of cells with HA coatings.

Surface-engineered vanadium nitride nanosheets for an imaging-guided photothermal/photodynamic platform of cancer treatment.

Of the many strategies for precise tumor treatment, near-infrared (NIR) light-activated "one-for-all" theranostic modality with real-time diagnosis and therapy has attracted extensive attention from researchers. Herein, a brand-new theranostic nanoplatform was established on versatile vanadium nitride (VN) nanosheets, which show significant NIR optical absorption, and resultant photothermal effect and reactive oxygen species activity under NIR excitation, thereby realizing the synergistic action of photothermal/photodynamic co-therapy. As expected, systematic in vitro and in vivo antitumor evaluations demonstrated efficient cancer cell killing and solid tumor removal without recurrence. Meanwhile, the surface modification of VN nanosheets with poly(allylamine hydrochloride) and bovine serum albumin enhanced the biocompatibility of VN and made it more suitable for in vivo delivery. Moreover, VN has been ascertained as a potential photoacoustic imaging contrast for in vivo tumor depiction. Thus, this work highlights the potential of VN nanosheets as a single-component theranostic nanoplatform.

Coinfection with Fusobacterium nucleatum can enhance the attachment and invasion of Porphyromonas gingivalis or Aggregatibacter actinomycetemcomitans to human gingival epithelial cells.

OBJECTIVE: This study was conducted to investigate effects of coinfection of Porphyromonas gingivalis (P. gingivalis) or Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) with Fusobacterium nucleatum (F. nucleatum) on their adhering and invasive capacity to human gingival epithelial cells as well as the expression of interleukin-8 (IL-8) and human beta-defensin-2 (hBD-2) in human gingival epithelial cells. DESIGN: P. gingivalis and A. actinomycetemcomitans were tested for their ability to attach and invade a human gingival epithelial cell line (Ca9-22) alone or coinfecting with F. nucleatum. Also, expression levels of IL-8 and hBD-2 were detected respectively using enzyme linked immunosorbent assay (ELISA) and real-time reverse transcription PCR (RT-PCR) when Ca9-22 cells were infected with P. gingivalis and A. actinomycetemcomitans alone or coinfecting with F. nucleatum. RESULTS: F. nucleatum, P. gingivalis and A. actinomycetemcomitans were allowed to adhere and invade Ca9-22 cells, either each strain alone or under coinfection. The adhering and invasive abilities of P. gingivalis and A. actinomycetemcomitans were significantly greater when they were coincubated with F. nucleatum (P<0.05) than either of them alone. These enhancements were inhibited by galactose. In addition, P. gingivalis and A. actinomycetemcomitans inhibited the activation of IL-8 and hBD-2 by F. nucleatum. Also, galactose disrupted this inhibition on the expression of IL-8 and hBD-2. CONCLUSION: These results suggested coinfection with F. nucleatum can enhance adhesion and invasion of P. gingivalis and A. actinomycetemcomitans to Ca9-22 cells, as well as inhibition on host innate immune response.

Cationic polymer-based micro-emulgel with self-preserving ability for transdermal delivery of diclofenac sodium.

The objective of the present study was to develop a topical preparation with enhanced skin permeation, high safety and self-preserving ability. Microemulsion (ME) and cationic polymer based micro-emulgel (CPBM) were investigated for the transdermal delivery of diclofenac sodium (DS). Medium-chain triglyceride was selected as the oil phase of ME due to its good solubilization of DS and high safety. Orthogonal test was applied to optimize the formula of ME based on the cumulative skin permeation amount in vitro after preliminary formula test. Chitosan (CS) or polylysine was employed as the cationic polymer in the formula of CPBM. The transdermal delivery of DS was evaluated through in vitro skin permeation test. The results showed that the skin permeation rate of DS from the optimized CPBM (126.17 ± 15.82 µg/cm(2)/h) were 1.86-folds and 5.76-folds higher than that of DS commercial Emulgel and DS control hydrogel, respectively. MEs and the cationic polymer were found to have skin penetration co-enhancing effect when they were combined in the CPBM system. Furthermore, the CPBM showed a good growth inhibition of E. coli and S. aureus. The stability test revealed that the CPBM was stable at room temperature and 4 °C for a period of three months.

P(EO-co-LLA) functionalized Fe3O4@mSiO2 nanocomposites for thermo/pH responsive drug controlled release and hyperthermia.

The Fe3O4@mSiO2 nanocarrier that consisted of a magnetic Fe3O4 nanoparticle core and a mesoporous silica (mSiO2) shell was synthesized. It shows a uniform sphere morphology about 65 nm in diameter. Considering the magnetic hyperthermia of Fe3O4 under an alternating magnetic field (AMF), a thermo-sensitive polymer, poly[(ethylene glycol)-co-(L-lactide)] (P(EO-co-LLA)), was used as "gatekeeper" coating outside Fe3O4@mSiO2 to regulate the drug release behavior. The design of the nanocarrier was expected to block off the pores at low temperature and to reopen them at high temperature reversibly. The obtained hybrid nanocomposites were capable of loading the anti-cancer drug doxorubicin (DOX) and controlled drug release behavior trigged by the hyperthermia of Fe3O4 under AMF. Besides, the nanocarriers also show pH-sensitive drug release based on the slight differences between the tumor (weakly acid) and the normal tissue (weakly alkaline). What's more, the chemotherapy of DOX combined with magnetic hyperthermia can improve the cytotoxicity obviously. On the basis of the high stability and excellent controlled release performance, the multifunctional nanocarriers exhibit potential applications in targeted-control drug release and hyperthermia for cancer treatment.

pH-responsive controlled-release system based on mesoporous bioglass materials capped with mineralized hydroxyapatite.

A controlled release system with pH-responsive ability has been presented. Mesoporous bioglass (MBG) was used as the drug carrier and a spontaneous mineralization method was adopted to cap the pores of the carrier with hydroxyapatite (HAp) and to restrict the drug release. It is a simple and green method to realize the ingenious pH-sensitive controlled release. The model drug, metformin hydrochloride (MH), was loaded simultaneously with the mineralization process. Due to the degradation of HAp at acid environments, the system shows well pH-sensitive drug release ability. The release kinetics can be easily adjusted by the mineralization time and the ion concentration of media. The system is recommended as a promising candidate as a pH-sensitive vehicle for drug controlled release to low pH tissues, such as inflammatory sites and tumors.

Pulp mill wastewater sediment reveals novel methanogenic and cellulolytic populations.

Pulp mill wastewater generated from wheat straw is characterized as high alkalinity and very high COD pollution load. A naturally developed microbial community in a pulp mill wastewater storage pool that had been disused were investigated in this study. Owing to natural evaporation and a huge amount of lignocellulose's deposition, the wastewater sediment contains high concentrations of organic matters and sodium ions, but low concentrations of chloride and carbonate. The microbiota inhabiting especially anaerobic community, including methanogenic arhcaea and cellulolytic species, was studied. All archaeal sequences fall into 2 clusters of family Halobacteriaceae and methanogenic archaeon in the phylum Euryarchaeota. In the methanogenic community, phylogenetic analysis of methyl coenzyme M reductase A (mcrA) genes targeted to novel species in genus Methanoculleus or novel genus of order Methanomicrobiales. The predominance of Methanomicrobiales suggests that methanogenesis in this system might be driven by the hydrogenotrophic pathway. As the important primary fermenter for methane production, the cellulolytic community of enzyme GHF48 was found to be dominated by narrower breadth of novel clostridial cellulase genes. Novel anoxic functional members in such extreme sediment provide the possibility of enhancing the efficiency of anoxic treatment of saline and alkaline wastewaters, as well as benefiting to the biomass transformation and biofuel production processes.

[Coupling anaerobic baffled reactor and membrane-aerated biofilm reactor].

Based on the consistent anaerobic status of outer layer of membrane-aerated biofilm reactor (MABR) and internal anaerobic baffled reactor (ABR), MABR and ABR were started up separately. The aerating membrane module was installed into a compartment of anaerobic baffled bioreactor to form the Hybrid MAB-ABR (HMABR). After the installation of membrane module, total COD and VFA concentrations in the HMABR effluent were deceased by 59.5% and 68.1% respectively, with increased nitrogenous pollutant remove efficiency by 83.5%, at influent COD concentration of 1600 mg/L and NH4+ -N concentration of 80 mg/L. When organic loading rate was increased by 50%, the effluent COD concentration was still below the level of 60 mg/L, indicating its good capability of counteracting influent organic loading fluctuation. Due to the decreased COD concentration and increased nitrate concentration in the third compartment after installing the membrane module, the biogas volume and methane contents in the third compartment were decreased, resulting in the steady and excellent effluent quality. In this hybrid process, the improved simultaneous removal of carbon and nitrogen for high-strength nitrogenous organic pollutants was realized in a single reactor.

OTS-modified HA and its toughening effect on PLLA/HA porous composite.

In this paper, hydroxyapatite (HA) particles was modified with long-chain organic silane-Octadecyltrichlorosilane (OTS), and the modified particles were further used for preparing Poly(L-lactic acid) PLLA/HA porous composite. The modified particles were characterized by means of XRD, FTIR, and XPS techniques. Both XPS and FTIR results showed that OTS had been combined with HA, and the formation of P-O-Si bond, a covalent bond, on the HA particle surface was confirmed by XPS. OTS-modified HA particles were used to prepare porous composites by thermally induced phase separation method. The results showed that the composite had an interconnected pore structure with 100-300 mum macropores. With OTS dosage increasing during modification, the mechanical properties of PLLA/OTS-modified HA porous composites increased obviously. These results showed that OTS modification can effectively improve the interface compatibility between HA surface and PLLA.

A constructed alkaline consortium and its dynamics in treating alkaline black liquor with very high pollution load.

BACKGROUND: Paper pulp wastewater resulting from alkaline extraction of wheat straw, known as black liquor, is very difficult to be treated and causes serious environmental problems due to its high pH value and chemical oxygen demand (COD) pollution load. Lignin, semicellulose and cellulose are the main contributors to the high COD values in black liquor. Very few microorganisms can survive in such harsh environments of the alkaline wheat straw black liquor. A naturally developed microbial community was found accidentally in a black liquor storing pool in a paper pulp mill of China. The community was effective in pH decreasing, color and COD removing from the high alkaline and high COD black liquor. FINDINGS: Thirty-eight strains of bacteria were isolated from the black liquor storing pool, and were grouped as eleven operational taxonomy units (OTUs) using random amplified polymorphic DNA-PCR profiles (RAPD). Eleven representative strains of each OTU, which were identified as genera of Halomonas and Bacillus, were used to construct a consortium to treat black liquor with a high pH value of 11.0 and very high COD pollution load of 142,600 mg l(-1). After treatment by the constructed consortium, about 35.4% of color and 39,000 mg l(-1) (27.3%) COD(cr) were removed and the pH decreased to 7.8. 16S rRNA gene polymerase chain reaction denaturant gradient gel electrophoresis (PCR-DGGE) and gas chromatography/mass spectrometry (GC/MS) analysis suggested a two-stage treatment mechanism to elucidate the interspecies collaboration: Halomonas isolates were important in the first stage to produce organic acids that contributed to the pH decline, while Bacillus isolates were involved in the degradation of lignin derivatives in the second stage under lower pH conditions. CONCLUSIONS/SIGNIFICANCE: Tolerance to the high alkaline environment and good controllability of the simple consortium suggested that the constructed consortium has good potential for black liquor treatment. Facilitating the treatment process by the constructed consortium would provide a promising opportunity to reduce the pollution, as well as to save forest resources and add value to a waste product.