The cross-linking and protective effect of artemisinin and its derivatives on collagen fibers of demineralized dentin surface.

OBJECTIVE: To investigate the cross-linking and protective effect of artemisinin (ART), dihydroartemisinin (DHA), and artesunate (AST) on collagen fibers of demineralized dentin surface. METHODS: Molecular docking was used to predict potential interactions of ART, DHA, and AST with dentin type I collagen. Human third molars without caries were completely demineralized and treated with different solutions for 1 min. The molecular interactions and cross-linking degree of ART and its derivatives with dentin collagen were evaluated by FTIR spectroscopy, total extractable protein content, and a ninhydrin assay. Scanning electron microscopy, hydroxyproline release, and ultimate microtensile strength tests (µUTS) were employed to confirm the mechanical properties and anti-collagenase degradation properties of dentin collagen fibers. RESULTS: ART, DHA, and AST combined with dentin type I collagen mainly through hydrogen bonding and hydrophobic interactions, and the cross-linking reaction sites were mainly C=O and CN functional groups. Compared to the control group, ART and its derivatives significantly increased the degree of cross-linking. Additionally, significant increases were observed in resistance to enzymatic digestion and mechanical properties of the artemisinin and its derivatives group. CONCLUSION: ART, DHA, and AST could cross-link with demineralized dentin collagen, through improving the mechanical properties and anti-collagenase degradation properties. CLINICAL SIGNIFICANCE: The study endorses the potential use of ART and its derivatives as a prospective collagen cross-linking agent for degradation-resistant and long-period dentin bonding in composite resin restorations.

Effect of La2 O3 and CeO2 on anaerobic methanogenesis process: Kinetics analysis and process mechanism study.

La2 O3 and CeO2 , as main rare earth oxides, with unique physical and chemical properties have been widely used in catalyst and grinding industry. In this study, the effects of La2 O3 and CeO2 on the anaerobic process were investigated. The biological methane production tests showed that 0-0.05 g/L La2 O3 and 0-0.05 g/L CeO2 enhanced anaerobic methanogenesis process. The result showed maximum specific methanogenic rates of La2 O3 and CeO2 were 56.26 mL/(h·gVSS) and 49.43 mL/(h·gVSS) and, compared with the control, increased 4% and 3%, respectively. La2 O3 significantly reduced the accumulation of volatile fatty acids (VFAs), whereas CeO2 had no similar effect. Dissolution experiments demonstrated that the content of extracellular La in the anaerobic granular sludge reached 404 µg-La/g volatile suspended solid (VSS), which was 134 times higher than that of extracellular Ce (3 µg-Ce/gVSS). The content of intracellular La reached 206 µg-La/gVSS, which was 19 times higher than that of intracellular Ce (11 µg-Ce/gVSS). The different stimulation between La3+ and Ce3+ could be attributed to the different dissolution of La2 O3 and CeO2 . The result of this work is helpful to optimize anaerobic processes and to develop novel additives. PRACTITIONER POINTS: Novel anaerobic additives were developed. La2O3 and CeO2 in 0-0.05 g/L enhanced organics degradation and methane production. The addition of La2O3 significantly reduced the accumulation of volatile fatty acids. The solubilization of La2O3 was stronger than CeO2. The promoting effects of low concentrations of La2O3 and CeO2 were derived from dissolved La and Ce.

Mechanism of vanadium(IV) resistance of the strains isolated from a vanadium titanomagnetite mining region.

Microbial treatment for vanadium contamination of soils is a favorable and environment-friendly method. However, information of the resistant mechanism of the strains in soils to vanadium, especially to tetravalent vanadium [vanadium(IV)], is still limited. Herein, potential of the vanadium(IV) biosorption and biotransformation of the strains (4K1, 4K2, 4K3 and 4K4) which were capable of tolerating vanadium(IV) was determined. For biosorption, the bioadsorption and the bioabsorption of vanadium(IV) occur on the bacterial cell wall and within the cell, respectively, were taken into consideration. Comparison of the vanadium(IV) adsorbed on the bacterial cell walls and remained in the cells after sorption indicated the major bacterial vanadium(IV) sorption role of the bioadsorption which was at least one order of magnitude higher than the bioabsorption amount. Isotherm study using various isotherm models revealed a monolayer and a multilayer vanadium(IV) biosorption by 4K2 and the others (4K1, 4K3 and 4K4), respectively. Higher biosorption was observed in acidic conditions than in alkaline conditions, and the maximum biosorption was 2.41, 9.35, 7.76 and 8.44 mg g-1 observed at pH 6 for 4K1, at pH 3 for 4K2, and at pH 4 for 4K3 and 4K4, respectively. At the present experimental range of the initial vanadium(IV) concentration, optimal biosorption capacity of the bacteria was observed at the vanadium(IV) level of 100-250 mg L-1. Different biotransformation level of vanadium(IV) in soils by the stains was observed during a 28-d pot incubation of the soils mixed with the strains, which can be attributed to the discrepancy of both soil properties and bacterial species. Present study can help to fill up the gaps of the insufficient knowledge of the vanadium(IV) resistant mechanism of the strains in soils.

Mixed PEGylated surfactant modifying system decrease the accelerated blood clearance phenomenon of nanoemulsions in rats.

The accelerated blood clearance (ABC) phenomenon which is induced by repeated injection of poly (ethylene glycol) (PEG)-coated colloidal carriers gives clinical challenge to the promising drug delivery system. It is necessary to decrease this unexpected immunological response. A novel 4-arm poly (ethylene glycol-5000)4-cholesteryl methyl amide (4-arm PEG5000-CHMA) has been synthesized. The structure of 4-arm PEG5000-CHMA was confirmed by IR and 1H-NMR spectrum. The pharmacokinetics of the tocopheryl nicotinate (TN)-loaded nanoemulsions modified with 4-arm PEG5000-CHMA or/and 1, 2-distearoyl-Sn-glycero-3-phosphoethanolamine-n-[methoxy(poly-ethyleneglycol)-2000] (mPEG2000-DSPE) have been studied. Furthermore, the ABC phenomenon has been detailed investigated in rats by TN-loaded nanoemulsions modified with 4-arm PEG5000-CHMA and mPEG2000-DSPE (CPNE). The plasma levels of TN and anti-PEG IgM antibody were determined by HPLC and ELISA, respectively. The circulation time of the CPNEs were comparable to the mPEG2000-DSPE coated nanoemulsions. Moreover, the ABC phenomenon can be decreased by CPNEs. This study designs a method to decrease the ABC phenomenon and develops a clinical promising nanoemulsion for therapeutic or imaging purpose.

Effects of complement inhibition on the ABC phenomenon in rats.

Researchers reported that intravenously injected PEGylated colloidal drug carriers lose their long-circulating characteristic and accumulated extensively in liver when they are administrated twice in the same animal with certain intervals. This phenomenon was referred to as the "accelerated blood clearance (ABC) phenomenon". Some former studies had found that complement-mediated phagocytosis, activated by antigen-antibody complex, was responsible for inducing the phenomenon. According to the theory, we have used cobra venom factor to deplete complement in vivo and to investigate the effect of complement inhibition on the ABC phenomenon. Rats were administered by injection of cobra venom factor solution to build up the model of complement exhaustion/inhibition, and the effect of the inhibition of complement on ABC phenomenon was carried out. It seemed that inhibition of complement didn't affect the pharmacokinetic of the first infection. By contrast, in rats of which complement had been depleted, the second dose of PEGylated nanoemulsions showed enhanced circulation time compared with normal rats in a complement inhibition-independent manner, but the ABC phenomenon was not completely eliminated. It indicated that complement inhibition could certainly weaken the accelerated clearance; meanwhile, there were other factors causing the ABC effect. These findings provide novel insights into the attenuating of ABC phenomenon and lay foundation for further study of immune mechanism.

A frustrating problem: accelerated blood clearance of PEGylated solid lipid nanoparticles following subcutaneous injection in rats.

Colloidal particles have preferential access to the lymphatic system following subcutaneous administration, achieving lymphatic targeting by drug accumulation in the regional lymph nodes. Moreover, the surface PEGylated colloidal particles have shown enhanced drainage into lymphatics and uptake by macrophages of the regional lymph nodes after subcutaneous injection. Nevertheless, it is reported that upon repeated intravenous injection, the PEG-specific IgM produced by the administration of the PEGylated colloidal particles markedly accelerates the clearance of subsequent doses of PEGylated particles. In this article, we report that the first subcutaneous injection of PEGylated solid lipid nanoparticles also induces the intravenously administered PEGylated particles to be cleared very rapidly from the circulation, and the "ABC index," a parameter for the intensity of accelerated blood clearance, for subcutaneous injection was equivalent to or even lower than that following the first intravenous injection. Moreover, the small quantities of distributed particles in the spleen after the first s.c. dose but the significantly higher elimination rate of the second i.v. dose, strongly suggest that, in addition to the spleen, the regional lymph nodes also play a promotive role in this phenomenon, although the exact lymphocytes causing this phenomenon remain unclear. Our observations may thus have important implications for considering combination therapy with PEGylated productions requiring different administration routes such as intravenous and subcutaneous injection, and great care is needed.