Crystallization Behavior and Mechanical Property of Biodegradable Poly(butylene succinate-co-2-methyl succinate)/Cellulose Nanocrystals Composites.

Biodegradable poly(butylene succinate-co-2-methyl succinate) (PBSMS)/cellulose nanocrystals (CNC) composites were successfully prepared at low CNC loadings with the aims of improving crystallization and mechanical properties and extending the practical application of PBSMS. CNC is finely dispersed in the PBSMS matrix without obvious aggregations. The low content of CNC obviously promoted the crystallization behavior of PBSMS under different conditions. The spherulitic morphology study revealed that CNC, as an effective heterogeneous nucleating agent, provided more nucleation sites during the melt crystallization process. In addition, the nucleation effect of CNC was quantitatively evaluated by the following two parameters, i.e., nucleation activity and nucleation efficiency. The crystal structure and crystallization mechanism of PBSMS remained unchanged in the composites. In addition, as a reinforcing nanofiller, CNC significantly increased Young's modulus and the yield strength of PBSMS. The crystallization behavior and mechanical properties of PBSMS were significantly improved by the low content of CNC, which should be interesting and essential from the perspective of biodegradable polymer composites.

20 abnormal metabolites of Stage IV Grade C periodontitis was discovered by CPSI-MS.

Saliva is a noninvasive biofluid that contains the metabolic signature of severe periodontitis (SP, Stage IV and Grade C). Conductive polymer spray ionization mass spectrometry (CPSI-MS) was used to record a wide range of metabolites within a few seconds, making this technique a promising point-of-care method for the early detection of SP (Stage IV and Grade C). Saliva samples from 31 volunteers, consisting of 16 healthy controls (HC) and 15 patients with SP (Stage IV and Grade C), were collected to identify dysregulated metabolites. Twenty metabolites were screened out, including seven amino acids. Moreover, the results showed that amino acid metabolism is closely related to the development of periodontitis. The present study further confirmed that salivary metabolites in the oral cavity were significantly altered after plaque removal. These results suggest that the combination of CPSI-MS is a feasible tool for preclinical screening of SP (Stage IV and Grade C).

Imaging and Monitoring the Hydrogen Peroxide Level in Heart Failure by a Fluorescent Probe with a Large Stokes Shift.

Heart failure is the terminal stage of many cardiovascular diseases and is considered to be closely related to oxidative stress. Early understanding of pathogenesis can greatly improve the treatment and reduce the mortality of heart disease. In this work, based on the analysis of coumarin derivates by theoretical calculations, we designed and synthesized a fluorescent probe BCO with a large Stokes shift (107 nm) and excellent selectivity toward H2O2 in a living system. The distribution of H2O2 in the heart and thoracic aorta tissues was imaged with the aid of the probe BCO, which demonstrated that the cellular H2O2 level is upregulated in heart failure. This work provides a useful tool, BCO, for the evaluation of cellular oxidative stress and to further understand the pathophysiology process of heart disease.

An ICT-based fluorescent probe guided by theoretical calculation for selectively mapping endogenous GSH in living cells.

Glutathione (GSH) is one of the most essential bio-thiols to maintain the redox balance of organisms which is strongly associated with many physiological processes. Detecting the concentration and mapping the distribution of GSH in the living system is significant to study many related diseases. In this work, we have successfully constructed an ICT-based model to guide the design and synthesis of GSH specific fluorescent probe CF1. A serials spectroscopy test demonstrated that the response of CF1 towards GSH owned large stokes shift (~167 nm) and an excellent linear relationship (0-120 µM, R2 = 0.9961). Furthermore, CF1 was successfully applied to image endogenous GSH in different cell lines with high sensitivity. This work is instructive for the oriented synthesis of ICT-based functional fluorescent probe and the further visualization of intracellular targets in the living system.

RGD functionalized polymeric nanoparticles targeting periodontitis epithelial cells for the enhanced treatment of periodontitis in dogs.

Long term retention of antimicrobials with effective drug concentration in gingival crevicular fluid (GCF) is of vital importance for the treatment of chronic periodontitis. In this study, a novel epithelial cell-targeting nanoparticle drug delivery system by conjugating minocycline-loaded poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) nanoparticles (NP-MIN) with RGD peptide were developed and administrated locally for targeting periodontitis epithelial cells and enhancing the treatment of periodontitis in dogs. Biodegradable NP-MIN was made with an emulsion/solvent evaporation technique. RGD peptide was conjugated to the surface of nanoparticles via Maleimide group reaction with hydrosulfide in RGD peptide (RGD-NP-MIN). Transmission electron microscopy examination and dynamic light scattering results revealed that RGD-NP-MIN had a sphere shape, with a mean diameter around 106nm. In vitro release of minocycline from RGD-NP-MIN showed that RGD modification did not change the remarkable sustained releasing characteristic of NP-MIN. To elucidate the interaction of RGD-NP and epithelial cells, RGD-NP binding, uptake and cellular internalization mechanisms by calu-3 cells were investigated. It was shown RGD modification significantly enhanced nanoparticles binding and uptake by Calu-3 cells, and RGD-NP uptake was an energy-dependent process through receptor-mediated endocytosis. Both clathrin-associated endocytosis and caveolae-dependent endocytosis pathway were involved in the RGD-NP uptake, and the intracellular transport of RGD-NP was related to lysosome and Golgi apparatus. Finally, in vivo pharmacokinetics of minocycline in the periodontal pockets and anti-periodontitis effects of RGD-NP-MIN on periodontitis-bearing dogs were evaluated. After local administration of RGD-NP-MIN, minocycline concentration in gingival crevicular fluid decreased slowly and maintained an effective drug concentration for a longer time than that of NP-MIN. Anti-periodontitis effects demonstrated that RGD-NP-MIN could significantly decrease symptoms of periodontitis, which was better than any other control group. These findings suggested that these epithelial cell-targeting nanoparticles offered a novel and effective local delivery system for the treatment of periodontitis.

Local delivery of minocycline-loaded PEG-PLA nanoparticles for the enhanced treatment of periodontitis in dogs.

BACKGROUND: Rapid local drug clearance of antimicrobials is a major drawback for the treatment of chronic periodontitis. In the study reported here, minocycline-loaded poly(ethylene glycol)-poly(lactic acid) nanoparticles were prepared and administered locally for long drug retention and enhanced treatment of periodontitis in dogs. METHODS: Biodegradable poly(ethylene glycol)-poly(lactic acid) was synthesized to prepare nanoparticles using an emulsion/solvent evaporation technique. The particle size and zeta potential of the minocycline-loaded nanoparticles (MIN-NPs) were determined by dynamic light scattering and the morphology of the nanoparticles was observed by transmission electron microscopy. The in vitro release of minocycline from MIN-NPs and in vivo pharmacokinetics of minocycline in gingival crevice fluid, after local administration of MIN-NPs in the periodontal pockets of beagle dogs with periodontitis, were investigated. The anti-periodontitis effects of MIN-NPs on periodontitis-bearing dogs were finally evaluated. RESULTS: Transmission electron microscopy examination and dynamic light scattering results revealed that the MIN-NPs had a round shape, with a mean diameter around 100 nm. The in vitro release of minocycline from MIN-NPs showed a remarkably sustained releasing characteristic. After local administration of the MIN-NPs, minocycline concentration in gingival crevice fluid decreased slowly and retained an effective drug concentration for a longer time (12 days) than Periocline(®). Anti-periodontitis effects demonstrated that MIN-NPs could significantly decrease symptoms of periodontitis compared with Periocline and minocycline solution. These findings suggest that MIN-NPs might have great potential in the treatment of periodontitis.

Qualitative and quantitative analysis of anthraquinones in rhubarbs by high performance liquid chromatography with diode array detector and mass spectrometry.

Rhubarb is well known in traditional Chinese medicines (TCMs) mainly due to its effective purgative activity. Anthraquinones, including anthraquinone derivatives and their glycosides, are thought to be the major active components in rhubarb. To improve the quality control method of rhubarb, we studied on the extraction method, and did qualitative and quantitative analysis of widely used rhubarbs, Rheum tanguticum Maxim. ex Balf. and Rheum palmatum L., by HPLC-photodiode array detection (HPLC-DAD) and HPLC-mass spectrum (HPLC-MS) on a Waters SymmetryShield RP18 column (250 mm × 4.6 mm i.d., 5 µm). Amount of five anthraquinones was viewed as the evaluating standard. A standardized characteristic fingerprint of rhubarb was provided. From the quantitative analysis, the rationality was demonstrated for ancestors to use these two species of rhubarb equally. Under modern extraction methods, the amount of five anthraquinones in Rheum tanguticum Maxim. ex Balf. is higher than that in Rheum palmatum L. Among various extraction methods, ultrasonication with 70% methanol for 30 min is a promising one. For HPLC analysis, mobile phase consisted of methanol and 0.1% phosphoric acid in water with a gradient program, the detection wavelength at 280nm for fingerprinting analysis and 254 nm for quantitative analysis are good choices.