Targeted Antimicrobial Therapy Against Streptococcus mutans Establishes Protective Non-cariogenic Oral Biofilms and Reduces Subsequent Infection

Aim Dental biofilms are complex communities composed largely of harmless bacteria. Certain pathogenic species including Streptococcus mutans （S. mutans） can become predominant when host factors such as dietary sucrose intake imbalance the biofilm ecology. Current approaches to control S. mutans infection are not pathogen-specific and eliminate the entire oral community along with any protective benefits provided. Here, we tested the hypothesis that removal of S. mutans from the oral community through targeted antimicrobial therapy achieves protection against subsequent S. mutans colonization. Methodology Controlled amounts of S. mutans were mixed with S. mutans-free saliva, grown into biofilms and visualized by antibody staining and cfu quantization. Two specifically-targeted antimicrobial peptides （STAMPs） against S. mutans were tested for their ability to reduce S. mutans biofilm incorporation upon treatment of the inocula. The resulting biofilms were also evaluated for their ability to resist subsequent exogenous S. mutans colonization. Results S. mutans colonization was considerably reduced （9 ± 0.4 fold reduction, P=0.01） when the surface was preoccupied with saliva-derived biofilms. Furthermore, treatment with S. mutans-specific STAMPs yielded S. mutans-deficient biofilms with significant protection against further S. mutans colonization （5 minutes treatment： 38 ± 13 fold reduction P=0.01; 16 hours treatment： 96 ± 28 fold reduction P=0.07）. Conclusion S. mutans infection is reduced by the pre- sence of existing biofilms. Thus maintaining a healthy or ＂normal＂ biofilm through targeted antimicrobial therapy （such as the STAMPs） could represent an effective strategy for the treatment and prevention of S. mutans colonization in the oral cavity and caries progression.

Development and evaluation of a safe and effective sugar-free herbal lollipop that kills cavity-causing bacteria

Dental caries （tooth decay） is caused by a specific group of cariogenic bacteria, like Streptococcus mutans, which convert dietary sugars into acids that dissolve the mineraI in tooth structure. Killing cariogenic bacteria is an effective way to control or prevent tooth decay. In a previous study, we discovered a novel compound （Glycyrrhizol A）, from the extraction of licorice roots, with strong antimicrobial activity against cariogenic bacteria. In the current study, we developed a method to produce these specific herbal extracts in large quantities, and then used these extracts to develop a sugar-free lollipop that effectively kills cariogenic bacteria like Streptococcus mutans. Further studies showed that these sugar-free lollipops are safe and their antimicrobial activity is stable. Two pilot human studies indicate that a brief application of these lollipops （twice a day for ten days） led to a marked reduction of cariogenic bacteria in oral cavity among most human subjects tested. This herbal lollipop could be a novel tool to promote oral health through functional foods.

Soy Isoflavone and Its Effect to Regulate Hypothalamus and Peripheral Orexigenic Gene Expression in Ovariectomized Rats Fed on A High-Fat Diet

Objective To explore the effect of soy isoflavone on obesity in the light of hypothalamus and peripheral orexigenic gene regulation. Methods Fifty-four female rats were randomly assigned to 6 groups： one sham-operated group （SHAM）, one ovariectomized （OVX） control group, three OVX groups fed with 400 ppm （L-SI）, 1 200 ppm （M-SI） and 3 600 ppm （H-SI） isoflavone respectively, and one OVX group receiving 0.45 ppm diethylstilbestrol （EC）. All rats were allowed to take high-fat diet for 4 weeks. Some neuropeptides were measured by RT-PCR. These neuropeptides included NPY, pro-opiomelanocortin （POMC）, cocaine and amphetamine regulated transcript （CART）, orexin, melanin-concentrating hormone （MCH）, ting hormone precursor （P-MCH）, ghrelin, and leptin. Results Compared with the OVX control group, the body weight and food intake in the H-S1 group were reduced significantly and there was a significant dose-dependent manner in the 3 isoflavone groups. The results of RT-PCR showed that the NPY level in the 3 isoflavone groups was significantly increased and the POMC/CART gene expression decreased significantly in rats＇ hypothalamus compared with that in the OVX control group. However, the expression of orexin, MCH and P-MCH had no change. The peripheral grelin mRNA expression was higher in the 3 isoflavone groups, while leptin gene expression in the fat was not consistent. Conclusions This research showed that isoflavone could prevent obesity induced by high-fat diet and ovariectomy through regulating hypothalamus and peripheral orexigenic gene expressions associated with food intake.

Gonioscopy and Ultrasound Biomicroscopy in the Detection of Angle Closure in Patients with Shallow Anterior Chamber

Objective To assess the agreement between gonioscopy and ultrasound biomicroscopy(UBM) in detecting angle closure in Chinese patients with shallow anterior chamber. Methods An observational comparative study of the two different examination methods was conducted. Patients with normal intraocular pressure and temporal peripheral anterior chamber depth less than a quarter of corneal thickness based on slit lamp examination were included in this study from December 2007 to May 2009 in the outpatient clinic of First Hospital of Tsinghua University. Gonioscopy was performed with a Goldman goniolens in dark room first and followed by full beam light and indentation. If the filtering trabecular meshwork was invisible or any peripheral anterior synechia was found, that quadrant of the angle was considered closed. UBM was first undertaken in a darkened room then repeated with normal room lighting. If iridotrabecular apposition was showed, that quadrant of the angle was considered closed. The status of angle closure of each quadrant with different methods was recorded. Results 85 eyes of 46 patients were included in this study. The agreement between gonioscopy and UBM was poor(κ<0.4) with Kappa analysis in both dark and light conditions in each quadrant. The accordance of agreement between gonioscopy and UBM was hardly affected by age or sex, while in dark condition, eyes with deeper anterior chamber(P=0.005) or plateau iris configuration tended to produce different results(P=0.075) in the 2 methods. Conclusion Gonioscopy and UBM are both indispensable methods for detecting angle closure, neither can completely replace the other.

Fe_(3)O_(4)@Angelica sinensis polysaccharide nanoparticles as an ultralow-toxicity contrast agent for magnetic resonance imaging

Although iron oxide(Fe_(3)O_(4)) nanoparticles have broad application prospects as magnetic resonance imaging(MRI) contrast agent, their biocompatibility and biotoxicity still need to be improved. In this study, we prepared Fe_(3)O_(4)@Angelica sinensis polysaccharide nanoparticles(Fe_(3)O_(4)@ASP NPs) with a 9 nm Fe_(3)O_(4) core and ASP as the coating material. The Fe_(3)O_(4)@ASP NPs are superparamagnetic, can be taken up by liver and spleen macrophages in the circulatory system in vivo, and are a good-biocompatibility and low-toxicity transverse relaxation time(T_(2)) and T_(2)-star(T_(2)^(*)) magnetic resonance imaging(MRI) contrast agent for the liver. The cytotoxicity assessment using HeLa cells and the pathological tests in mice validate that Fe_(3)O_(4)@ASP NPs have low toxicity and good biocompatibility in vivo, which can be attributed to the ASP as a natural polysaccharide with good biocompatibility and its function of protecting the liver. Fe_(3)O_(4)@ASP NPs are a potential new MRI contrast agent with high signal intensity in vivo.

基于X射线吸收谱的重金属电化学催化检测机制研究

电化学方法现场检测重金属离子(HMI)独具优势,对于控制与消除重金属污染意义重大.相关研究大多依赖于经验测试或侧重于报道检测性能,对催化检测机制缺乏科学认识,导致功能敏感材料的设计缺乏指导性策略,严重影响检测的准确性和可靠性.本文综述了近几年来本课题组利用X射线吸收精细结构谱(XAFS)研究HMI催化检测机制的研究工作.主要介绍了六种不同的传感策略增强HMI检测的原理和特点,指出了各类敏感材料在电分析应用中所面临的机遇与挑战,提出了从催化的角度探究电化学检测机制的研究新思路.最后,展望了利用原位XAFS技术、数值模拟计算和机器学习等探究电化学反应动态过程的重要性和必要性.本文对开发功能型传感界面具有重要的指导意义.