Formation of biofilm is a survival strategy for bacteria and fungi to adapt to their living environment, especially in the hostile environment. Under the protection of biofilm, microbial cells in biofilm become tolerant and resistant to antibiotics and the immune responses, which increases the difficulties for the clinical treatment of biofilm infections. Clinical and laboratory investigations demonstrated a perspicuous correlation between biofilm infection and medical foreign bodies or indwelling devices. Clinical observations and experimental studies indicated clearly that antibiotic treatment alone is in most cases insufficient to eradicate biofilm infections. Therefore, to effectively treat biofilm infections with currently available antibiotics and evaluate the outcomes become important and urgent for clinicians. The review summarizes the latest progress in treatment of clinical biofilm infections and scientific investigations, discusses the diagnosis and treatment of different biofilm infections and introduces the promising laboratory progress, which may contribute to prevention or cure of biofilm infections. We conclude that, an efficient treatment of biofilm infections needs a well-established multidisciplinary collaboration, which includes removal of the infected foreign bodies, selection of biofilm-active, sensitive and well-penetrating antibiotics, systemic or topical antibiotic administration in high dosage and combinations, and administration of anti-quorum sensing or biofilm dispersal agents.
Bacteria survive in nature by forming biofilms on surfaces and probably most, if not all, bacteria （and fungi） are capable of forming biofilms. A biofilm is a structured consortium of bacteria embedded in a self-produced polymer matrix consisting of polysaccharide, protein and extracellular DNA. Bacterial biofilms are resistant to antibiotics, disinfectant chemicals and to phagocytosis and other components of the innate and adaptive inflammatory defense system of the body. It is known, for example, that persistence of staphylococcal infections related to foreign bodies is due to biofilm formation. Likewise, chronic Pseudomonas aeruginosa lung infections in cystic fibrosis patients are caused by biofilm growing mucoid strains. Gradients of nutrients and oxygen exist from the top to the bottom of biofilms and the bacterial cells located in nutrient poor areas have decreased metabolic activity and increased doubling times. These more or less dormant cells are therefore responsible for some of the tolerance to antibiotics. Biofilm growth is associated with an increased level of mutations. Bacteria in biofilms communicate by means of molecules, which activates certain genes responsible for production of virulence factors and, to some extent, biofilm structure. This phenomenon is called quorum sensing and depends upon the concentration of the quorum sensing molecules in a certain niche, which depends on the number of the bacteria. Biofilms can be prevented by antibiotic prophylaxis or early aggressive antibiotic therapy and they can be treated by chronic suppressive antibiotic therapy. Promising strategies may include the use of compounds which can dissolve the biofilm matrix and quorum sensing inhibitors, which increases biofilm susceptibility to antibiotics and phagocytosis.
Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide.Changed bone metabolism is one of the important long-term complications associated with diabetes mellitus.Alveolar bone loss is one of the main outcomes of periodontitis,and diabetes is among the primary risk factors for periodontal disease.In this review,we summarise the adverse effects of diabetes on the periodontium in periodontitis subjects,focusing on alveolar bone loss.Bone remodelling begins with osteoclasts resorbing bone,followed by new bone formation by osteoblasts in the resorption lacunae.Therefore,we discuss the potential mechanism of diabetes-enhanced bone loss in relation to osteoblasts and osteoclasts.
Osteogenesis and angiogenesis are two closely correlated processes during bone growth, development, remodelling and repair. Vascular endothelial growth factor （VEGF） is an essential mediator during the process of angiogenesis. Based on an extensive literature search, which was carried out using the PubMed database and the keywords of osteogenesis, VEGF, endochondral ossification and intramembranous ossification, this manuscript reviews the role of VEGF in ossification, with emphasis on its effect in endochondral and intramembranous ossification. Osteogenesis and angiogenesis are closely correlated processes. VEGF acts as an essential mediator durin~ these processes. It not only functions in bone an~io~enesis but also in various aspects of bone develooment.
‘Bronze teeth＇ reflect the mechanical properties of natural teeth to a certain extent. Their mechanical properties resemble those of a tough metal, and the gradient of these properties lies in the direction from outside to inside. These attributes confer human teeth with effective mastication ability. Understanding the various mechanical properties of human teeth and dental materials is the basis for the development of restorative materials. In this study, the elastic properties, dynamic mechanical properties （visco-elasticity） and fracture mechanical properties of enamel and dentin were reviewed to provide a more thorough understanding of the mechanical properties of human teeth.
Oral cancer has a tendency to be detected at late stage which is detrimental to the patients because of its high mortality and morbidity rates. Early detection of oral cancer is therefore important to reduce the burden of this devastating disease. In this review article, the most common oral precancerous lesions are discussed and the importance of early diagnosis is emphasized. In addition, the most common non-invasive oral cancer devices that can aid the general practitioners in early diagnosis are also discussed.
Saliva is secreted from the salivary glands and has multiple functions, including mouth cleaning and protection, antibacterial effects and digestion. With the rapid advancement in salivaomics, saliva is well recognized as a pool of biological markers. Saliva, as a non-invasive and safe source, could be a substitute for blood in the diagnosis and prognosis of diseases. This review summarizes the latest advancements in saliva-related studies and addresses the potential value of saliva in the early diagnosis of oral diseases, such as dental caries and periodontal disease, as well as cancer, diabetes and other systemic disorders. Saliva biomarkers range from changes in the biochemical indices of DNA, RNA and proteins to the diversification of microbiota structures. This study integrates data reported in the recent literature and discusses the clinical significance and prospects for the application of saliva in the early diagnosis of diseases, translational medicine and precision medicine.
The Hedgehog（Hh） signalling pathway plays many important roles in development,homeostasis and tumorigenesis.The critical function of Hh signalling in bone formation has been identified in the past two decades.Here,we review the evolutionariiy conserved Hh signalling mechanisms with an emphasis on the functions of the Hh signalling pathway in bone development,homeostasis and diseases.In the early stages of embryonic limb development,Sonic Hedgehog（Shh） acts as a major morphogen in patterning the limb buds.Indian Hedgehog（Ihh） has an essential function in endochondral ossification and induces osteoblast differentiation in the perichondrium.Hh signalling is also involved intramembrane ossification.Interactions between Hh and Wnt signalling regulate cartilage development,endochondral bone formation and synovial joint formation.Hh also plays an important role in bone homeostasis,and reducing Hh signalling protects against age-related bone loss.Disruption of Hh signalling regulation leads to multiple bone diseases,such as progressive osseous heteroplasia.Therefore,understanding the signalling mechanisms and functions of Hh signalling in bone development,homeostasis and diseases will provide important insights into bone disease prevention,diagnoses and therapeutics.
Halitosis, bad breath or oral malodour are all synonyms for the same pathology. Halitosis has a large social and economic impact. For the majority of patients suffering from bad breath, it causes embarrassment and affects their social communication and life. Moreover, halitosis can be indicative of underlying diseases. Only a limited number of scientific publications were presented in this field until 1995. Ever since, a large amount of research is published, often with lack of evidence. In general, intraoral conditions, like insufficient dental hygiene, periodontitis or tongue coating are considered to be the most important cause （85%） for halitosis. Therefore, dentists and periodontologists are the first-line professionals to be confronted with this problem. They should be well aware of the origin, the detection and especially of the treatment of this pathology. In addition, ear-nose-throat-associated （10%） or gastrointestinal/ endocrinological （5%） disorders may contribute to the problem. In the case of halitophobia, psychiatrical or psychological problems may be present. Bad breath needs a multidisciplinary team approach： dentists, periodontologists, specialists in family medicine, ear- nose-throat surgeons, internal medicine and psychiatry need to be updated in this field, which still is surrounded by a large taboo. Multidisciplinary bad breath clinics offer the best environment to examine and treat this pathology that affects around 25% of the whole population. This article describes the origin, detection and treatment of halitosis, regarded from the different etiological origins.
Bone remodeling is balanced by bone formation and bone resorption as well as by alterations in the quantities and functions of seed cells, leading to either the maintenance or deterioration of bone status. The existing evidence indicates that micro RNAs（mi RNAs）, known as a family of short non-coding RNAs, are the key post-transcriptional repressors of gene expression,and growing numbers of novel mi RNAs have been verified to play vital roles in the regulation of osteogenesis, osteoclastogenesis,and adipogenesis, revealing how they interact with signaling molecules to control these processes. This review summarizes the current knowledge of the roles of mi RNAs in regulating bone remodeling as well as novel applications for mi RNAs in biomaterials for therapeutic purposes.
Bacterial biofilms can be viewed as a specific type of persistent bacterial infection. After initial invasion, microbes can attach to living and non-living surfaces, such as prosthetics and indwelling medical devices, and form a biofilm composed of extracellular polysaccharides, proteins, and other components. In hosts, bioffim formation may trigger drug resistance and inflammation, resulting in persistent infections. The clinical aspects of biofilm formation and leading strategies for hiofilm inhihitors will be discussed in this mini-review.
This review highlights the recent advances in X-ray microcomputed tomography （Micro-CT） applied in dental research. It summarizes Micro-CT applications in mea- surement of enamel thickness, root canal morphology, evaluation of root canal preparation, craniofacial skeletalstructure, micro finite element modeling, dental tissue engineering, mineral density of dental hard tissues and about dental implants. Details of studies in each of these areas are highlighted along with the advantages of Micro-CT, and finally a summary of the future applications of Micro-CT in dental research is given.
Mesenchymal stem cells （MSCs） are characterized by their self-renewing capacity and differentiation potential into multiple tissues. Thus, management of the differentiation capacities of MSCs is important for MSC-based regenerative medicine, such as craniofacial bone regeneration, and in new treatments for metabolic bone diseases, such as osteoporosis. In recent years, histone modification has been a growing topic in the field of MSC lineage specification, in which the Su（var）3-9, enhancer-of-zeste, trithorax （SET） domain-containing family and the Jumonji C （JmjC） domain-containing family represent the major histone lysine methyltransferases （KMTs） and histone lysine demethylases （KDMs）, respectively. In this review, we summarize the current understanding of the epigenetic mechanisms by which SET domain-containine KMTs and JmiC domain-containinlz KDMs balance the osteogenic and adipogenic differentiation of MSCs.
Herpes simplex virus （HSV）, a member of the Herpesviridae family, is a significant human pathogen that results in mucocutaneous lesions in the oral cavity or genital infections. Acyclovir （ACV） and related nucleoside analogues can successfully treat HSV infections, but the emergence of drug resistance to ACV has created a barrier for the treatment of HSV infections, especially in immunocompromised patients. There is an urgent need to explore new and effective tactics to circumvent drug resistance to HSV. This review summarises the current strategies in the development of new targets （the DNA helicase/primase （H/P） complex）, new types of molecules （nature products） and new antiviral mechanisms （lethal mutagenesis of Janus-type nucleosides） to fight the drug resistance of HSV.
Alkali production by oral bacteria is believed to have a major impact on oral microbial ecology and to be inibitory to the initiation and progression of dental caries. A substantial body of evidence is beginning to accumulate that indicates the modulation of the alkalinogenic potential of dental biofilms may be a promising strategy for caries control. This brief review highlights recent progress toward understanding molecular genetic and physiologic aspects of important alkali-generating pathways in oral bacteria, and the role of alkali production in the ecology of dental biofilms in health and disease. International Journal of Oral Science (2012) 4, 135-140; doi:10.1038/ijos.2012.54; published online 21 September 2012
Dental composites are commonly used restorative materials; however, secondary caries due to biofilm acids remains a major problem. The objectives of this study were （1） to develop a composite containing quaternary ammonium dimethacrylate （QADM）, nanoparticles of silver （NAg）, and nanoparticles of amorphous calcium phosphate （NACP）, and （2） to conduct the first investigation of the mechanical properties, biofilm response and acid production vs water-ageing time from 1 day to 12 months. A 4 x 5 design was utilized, with four composites （NACP-QADM composite, NACP-NAg composite, NACP-QADM-NAg composite, and a commercial control composite）, and five water-ageing time periods （1 day, and 3, 6, 9, and 12 months）. After each water- ageing period, the mechanical properties of the resins were measured in a three-point flexure, and antibacterial properties were tested via a dental plaque biofilm model using human saliva as an inoculum. After 12 months of water-ageing, NACP-QADM- NAg had a flexural strength and elastic modulus matching those of the commercial control （P〉 0.1）. Incorporation of QADM or NAg into the NACP composite greatly reduced biofilm viability, metabolic activity and acid production. A composite containing both QADM and NAg possessed a stronger antibacterial capability than one with QADM or NAg alone （P〈0.05）. The anti-biofilm activity was maintained after 12 months of water-ageing and showed no significant decrease with increasing time （P〉0.1）. In conclusion, the NACP-QADM-NAg composite decreased biofilm viability and lactic acid production, while matching the load- bearing capability of a commercial composite. There was no decrease in its antibacterial properties after 1 year of water-ageing. The durable antibacterial and mechanical properties indicate that NACP-QADM-NAg composites may be useful in dental restorations to combat caries.
MicroRNAs （miRNAs） have been clemonstrated to play an important role in regulation of the immunoinflammatory response; however, the function of miRNAs in periodontal inflammation has not been investigated. The objective of this study was to explore the properties of miRNAs in periodontal inflammation by comparing miRNA profiles of inflamed and healthy gingival tissues. Gingival tissues were obtained from 10 periodontitis patients and 10 healthy subjects. After RNA extraction, miRNA profiles were analyzed by microarray, and expression levels of selected miRNAs were confirmed by real-time quantitative reverse transcription polymerase chain reaction （RT-PCR）. Analyses using two computational methods, Targetscan and MicroRNA.org, were combined to identify common targets of these miRNAs. Finally, the individual miRNA expression levels of three toll-like receptor （TLR）-related miRNAs from inflamed and healthy gingival tissues were evaluated by RT-PCR. Ninety-one miRNAs were found to be upregulated and thirty-four downregulated over two-fold in inflamed gingival tissue compared with those in healthy gingival tissue. Twelve selected inflammatory-related miRNAs, hsa-miR-126＊, hsa-miR-20a, hsa-miR-142-3p, hsa-miR-19a, hsa-let-7f, hsa-miR-203, hsa-miR-17, hsa-miR-223, hsa-miR-146b, hsa-miR-146a, hsa-miR-155, and hsa-miR-205 showed comparable expression levels by microarray and real-time quantitative RT-PCR analyses. In addition, the putative inflammation targets of these miRNAs were predicted, and three that were tested （hsa-miRNA-146a, hsa-miRNA-146b, and hsa-miRNA-155）, showed significant differences between inflamed and healthy gingiva. This remarkable difference in miRNA profiles between periodontal diseased and healthy gingiva implicates a probable close relationship between miRNAs and periodontal inflammation. The data also suggest that the regulation of TLRs in periodontal inflammation may involve miRNA pathways.
Altered bowel flora is currently thought to play a role in a variety of disease conditions, and the use of Bifidobacterium spp. and Lactobacillus spp. as probiotics has been demonstrated to be health-promoting, even if the success of their administration depends on the applied bacterial strain（s） and the targeted disease. In the last few decades, specific probiotics have been shown to be effective in the treatment or the prevention of acute viral gastroenteritis, pediatric post-antibiotic-associated diarrhea, some pediatric allergic disorders, necrotizing enterocolitis in preterm infants, inflammatory bowel diseases and postsurgical pouchitis. The potential application of probiotics is continuously widening, with new evidence accumulating to support their effect on the prevention and treatment of other disease conditions, including several oral diseases, such as dental caries, periodontal diseases and oral malodor, as well as genitourinary and wound infections. Considering the increasingly widespread ability of pathogens to generate persistent biofilm-related infections, an even more attractive proposal is to administer probiotics to prevent or counteract biofilm development.The response of biofilm-based oral, intestinal, vaginal and wound infections to probiotics treatment will be reviewed here in light of the most recent results obtained in this field.
Recently,gingival margin-derived stem/progenitor cells isolated via STRO-1/magnetic activated cell sorting（MACS） showed remarkable periodontal regenerative potential in vivo.As a second-stage investigation,the present study＇s aim was to perform in vitro characterisation and comparison of the stem/progenitor cell characteristics of sorted STRO-1-positive（MACS~＋） and STRO-1-negative（MACS~-） cell populations from the human free gingival margin.Cells were isolated from the free gingiva using a minimally invasive technique and were magnetically sorted using anti-STRO-1 antibodies.Subsequently,the MACS~＋ and MACS~- cell fractions were characterized by flow cytometry for expression of CD14,CD34,CD45,CD73,CD90,CD105,CD146/MUC18 and STRO-1.Colony-forming unit（CFU） and multilineage differentiation potential were assayed for both cell fractions.Mineralisation marker expression was examined using real-time polymerase chain reaction（PCR）.MACS~＋ and MACS- cell fractions showed plastic adherence.MACS~＋ cells,in contrast to MACS- cells,showed all of the predefined mesenchymal stem/progenitor cell characteristics and a significantly higher number of CFUs（P〈0.01）.More than 95%of MACS~＋ cells expressed CD105,CD90 and CD73;lacked the haematopoietic markers CD45,CD34 and CD14,and expressed STRO-1 and CD146/MUC18.MACS- cells showed a different surface marker expression profile,with almost no expression of CD14 or STRO-1,and more than 95%of these cells expressed CD73,CD90 and CD146/MUC18,as well as the haematopoietic markers CD34 and CD45 and CD105.MACS~＋ cells could be differentiated along osteoblastic,adipocytic and chondroblastic lineages.In contrast,MACS- cells demonstrated slight osteogenic potential.Unstimulated MACS~＋ cells showed significantly higher expression of collagen I（P〈0.05） and collagen III（P〈0.01）,whereas MACS~- cells demonstrated higher expression of osteonectin（P〈0.05;MannWhitney）.The present study is the first to compare gingival MACS~＋ and MACS- cell populations demonstrating that MACS~＋ cells,in contrast to MACS- cells,harbour stem/progenitor cell characteristics.This study also validates the effectiveness of the STRO-l/MACS~＋technique for the isolation of gingival stem/progenitor cells.Human free gingival margin-derived STRO-1/MACS~＋ cells are a unique renewable source of multipotent stem/progenitor cells.