Publications by authors named "Xuedong Zhou"

379 Publications

The Roles of FOXO1 in Periodontal Homeostasis and Disease.

J Immunol Res 2021 30;2021:5557095. Epub 2021 Mar 30.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.

Periodontitis is an oral chronic inflammatory disease that is initiated by periodontal microbial communities and requires disruption of the homeostatic responses. The prevalence of periodontal disease increases with age; more than 70% of adults 65 years and older have periodontal disease. A pathogenic microbial community is required for initiating periodontal disease. Dysbiotic immune-inflammatory response and bone remodeling are characteristics of periodontitis. The transcription factor forkhead box protein O1 (FOXO1) is a key regulator of a number of cellular processes, including cell survival and differentiation, immune status, reactive oxygen species (ROS) scavenging, and apoptosis. Although accumulating evidence indicates that FOXO1 activity can be induced by periodontal pathogens, the roles of FOXO1 in periodontal homeostasis and disease have not been well documented. The present review summarizes how the FOXO1 signaling axis can regulate periodontal bacteria-epithelial interactions, immune-inflammatory response, bone remodeling, and wound healing.
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http://dx.doi.org/10.1155/2021/5557095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026307PMC
March 2021

Antimicrobial activities of a small molecule compound II-6s against oral streptococci.

J Oral Microbiol 2021 Mar 30;13(1):1909917. Epub 2021 Mar 30.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

: The side effects of present antimicrobials like chlorhexidine (CHX) and the emergence of drug resistance necessitate the development of alternative agents to control dental caries. : This study developed a novel small molecule, namely II-6s, and investigated its antimicrobial activities against common oral streptococci associated with dental caries. : The susceptibility of streptococci to II-6s was evaluated by the microdilution method, time-kill assay and scanning electron microscopy. The exopolysaccharides, dead/live bacteria and bacterial composition of the II-6s-treated // 3-species biofilms were analyzed by confocal laser scanning microscopy, fluorescent hybridization and quantitative PCR. The anti-demineralization effect and cytotoxicity of II-6s were evaluated by transverse microradiography and CCK-8 assay, respectively. Repeated exposure of to II-6s was performed to assess if II-6s could induce drug resistance. : II-6s exhibited antimicrobial activity similar to CHX against and and significantly inhibited exopolysaccharides production, live bacteria and the demineralizing capability of the 3-species streptococcal biofilms. Besides, II-6s showed reduced cytotoxicity relative to CHX and did not induce drug resistance in after 15 passages. : - II-6s may serve as a promising part of a successful caries management plan.
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http://dx.doi.org/10.1080/20002297.2021.1909917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018465PMC
March 2021

Dental Restorative Materials for Elderly Populations.

Polymers (Basel) 2021 Mar 8;13(5). Epub 2021 Mar 8.

State Key Laboratory of Oral Diseases, West China School of Stomatology, National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu 610064, China.

The incidence of dental caries, especially root caries, has risen in elderly populations in recent years. Specialized restorative materials are needed due to the specific site of root caries and the age-related changes in general and oral health in the elderly. Unfortunately, the restorative materials commonly used clinically cannot fully meet the requirements in this population. Specifically, the antibacterial, adhesive, remineralization, mechanical, and anti-aging properties of the materials need to be significantly improved for dental caries in the elderly. This review mainly discusses the strengths and weaknesses of currently available materials, including amalgam, glass ionomer cement, and light-cured composite resin, for root caries. It also reviews the studies on novel anti-caries materials divided into three groups, antimicrobial, remineralization, and self-healing materials, and explores their potential in the clinical use for caries in the elderly. Therefore, specific restorative materials for caries in the elderly, especially for root caries, need to be further developed and applied in clinical practice.
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http://dx.doi.org/10.3390/polym13050828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962827PMC
March 2021

Interactions Between Neutrophils and Periodontal Pathogens in Late-Onset Periodontitis.

Front Cell Infect Microbiol 2021 12;11:627328. Epub 2021 Mar 12.

State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China.

Late-onset periodontitis is associated with a series of inflammatory reactions induced by periodontal pathogens, such as , a keystone pathogen involved in periodontitis. Neutrophils are the most abundant leukocytes in the periodontal pocket/gingival crevice and inflamed periodontal tissues. They form a "wall" between the dental plaque and the junctional epithelium, preventing microbial invasion. The balance between neutrophils and the microbial community is essential to periodontal homeostasis. Excessive activation of neutrophils in response to periodontal pathogens can induce tissue damage and lead to periodontitis persistence. Therefore, illuminating the interactions between neutrophils and periodontal pathogens is critical for progress in the field of periodontitis. The present review aimed to summarize the interactions between neutrophils and periodontal pathogens in late-onset periodontitis, including neutrophil recruitment, neutrophil mechanisms to clear the pathogens, and pathogen strategies to evade neutrophil-mediated elimination of bacteria. The recruitment is a multi-step process, including tethering and rolling, adhesion, crawling, and transmigration. Neutrophils clear the pathogens mainly by phagocytosis, respiratory burst responses, degranulation, and neutrophil extracellular trap (NET) formation. The mechanisms that pathogens activate to evade neutrophil-mediated killing include impairing neutrophil recruitment, preventing phagocytosis, uncoupling killing from inflammation, and resistance to ROS, degranulation products, and NETs.
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http://dx.doi.org/10.3389/fcimb.2021.627328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994856PMC
March 2021

Lipid metabolism in cartilage and its diseases: a concise review of the research progress.

Acta Biochim Biophys Sin (Shanghai) 2021 Apr;53(5):517-527

State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610064, China.

The homeostasis of the vertebrate body depends on anabolic and catabolic activities that are closely linked the inside and outside of the cell. Lipid metabolism plays an essential role in these metabolic activities. Although a large amount of evidence shows that normal lipid metabolism guarantees the conventional physiological activities of organs in the vertebrate body and that abnormal lipid metabolism plays an important role in the occurrence and deterioration of cardiovascular-related diseases, such as obesity, atherosclerosis, and type II diabetes, little is known about the role of lipid metabolism in cartilage and its diseases. This review aims to summarize the latest advances about the function of lipid metabolism in cartilage and its diseases including osteoarthritis, rheumatoid arthritis, and cartilage tumors. With the gradual in-depth understanding of lipid metabolism in cartilage, treatment methods could be explored to focus on this metabolic process in various cartilage diseases.
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http://dx.doi.org/10.1093/abbs/gmab021DOI Listing
April 2021

Candida albicans CHK1 gene from two-component system is essential for its pathogenicity in oral candidiasis.

Appl Microbiol Biotechnol 2021 Mar 26;105(6):2485-2496. Epub 2021 Feb 26.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, Sichuan, China.

The roles of Candida albicans CHK1, a key gene from two-component system, in oral mucosal infection are not clear. This study evaluated the key roles of CHK1 gene in vitro and in vivo. The expression of CHK1 and its regulated virulence factors were tested during the oral epithelial cell infection. The production of lactate dehydrogenase, ROS, and IL-1α combined with the confocal and scanning electron microscope observation was employed to identify the capability of CHK1 in damaging the epithelial cells. Both immunocompetent and immunodeficient mice oropharyngeal infection models were involved to confirm the roles of CHK1 gene in vivo. The expression of CHK1 gene was significantly increased during the oral epithelial cell infection. The chk1Δ/Δ mutant failed to damage the epithelial cells or induce IL-α and ROS production. Interestingly, chk1Δ/Δ can also form the similar hyphae with WT and complementary strains. Accordingly, chk1Δ/Δ did not affect the adhesion and invasion rates of C. albicans to oral epithelial cells. However, chk1Δ/Δ significantly decreased the expression levels of the virulence factors, including ALS2, SAP6, and YWP1. The chk1Δ/Δ also failed to cause oral candidiasis in both immunocompetent and immunodeficient mice indicating that CHK1 gene from the two-component system is essential for the pathogenicity of C. albicans. KEY POINTS: • CHK1gene is essential for C. albicans in oral candidiasis • C. albicans without CHK1 gene can form "non-pathogenic" hyphae. • CHK1 gene regulates the virulence of C. albicans.
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http://dx.doi.org/10.1007/s00253-021-11187-0DOI Listing
March 2021

Reactive Oxygen Species in Pathogen Clearance: The Killing Mechanisms, the Adaption Response, and the Side Effects.

Front Microbiol 2020 4;11:622534. Epub 2021 Feb 4.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Reactive oxygen species (ROS) are attractive weapons in both antibiotic-mediated killing and host-mediated killing. However, the involvement of ROS in antibiotic-mediated killing and complexities in host environments challenge the paradigm. In the case of bacterial pathogens, the examples of some certain pathogens thriving under ROS conditions prompt us to focus on the adaption mechanism that pathogens evolve to cope with ROS. Based on these, we here summarized the mechanisms of ROS-mediated killing of either antibiotics or the host, the examples of bacterial adaption that successful pathogens evolved to defend or thrive under ROS conditions, and the potential side effects of ROS in pathogen clearance. A brief section for new antibacterial strategies centered around ROS was also addressed.
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http://dx.doi.org/10.3389/fmicb.2020.622534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889972PMC
February 2021

Geometric Analysis of the Distolingual Root and Canal in Mandibular First Molars: A Micro-computed Tomographic Study.

J Endod 2021 Feb 18. Epub 2021 Feb 18.

Division of Endodontics, Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada.

Introduction: The purpose of this study was to comprehensively assess by micro-computed tomographic imaging the anatomic features of distolingual (DL) roots and canals in mandibular first molars collected from 1 population.

Methods: One hundred two specimens were examined for the location and initial direction of the DL canal and the relationship between the distance of apical deviation and the angle of root curvature.

Results: All DL roots had only 1 canal. A new 7-category classification system is proposed for the DL roots of mandibular first molars. Most DL roots were type IV (28 teeth), type III (26 teeth), and type V (25 teeth). The average canal curvature in all root types was over 25°. There was a positive correlation between the angles of root and canal curvature for types II, IV, and V (P < .05) but not for types I and III (P > .05). In the buccolingual view, most DL roots were straight, whereas in the mesiodistal view the root curvature was close to the maximum value. The orifice of the DL canal was 4 times further from the line that bisects a line between the mesiobuccal and mesiolingual canal orifices than the distobuccal canal. The angle between the mesiobuccal-mesiolingual line and the horizontal projection of the coronal third of the DL canal on the pulp floor was 8.1° ± 10.0° and 6.1° ± 8.2° for teeth from the left and right side, respectively. The angle between the inserted simulated file and the cementoenamel junction was 57.9° ± 6.3°. Seventy-three percent of the DL canals had no constriction in the apical area. The DL canals were narrow and had a conical frustum-like shape with a 0.04 taper at the apical portion.

Conclusions: The novel classification of the DL roots helps to better understand the clinically challenging anatomy of the root and canal.
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http://dx.doi.org/10.1016/j.joen.2021.02.006DOI Listing
February 2021

Starvation Survival and Biofilm Formation under Subminimum Inhibitory Concentration of QAMs.

Biomed Res Int 2021 14;2021:8461245. Epub 2021 Jan 14.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Cariology and Endodontics & Department of Oral Pathology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.

Quaternary ammonium methacrylates (QAMs) are useful antimicrobial compounds against oral bacteria. Here, we investigated the effects of two QAMs, dimethylaminododecyl methacrylate (DMADDM) and dimethylaminohexadecyl methacrylate (DMAHDM), on biofilm formation, survival and development of tolerance by biofilm, and survival and development of tolerance against QAMs after prolonged starvation. (. ), (. ), (. ), and (. ) were used. Minimum inhibitory concentration (MIC) of QAMs against multispecies biofilm was determined. Biofilm formed under sub-MIC was observed by crystal violet staining and confocal laser scanning microscopy (CLSM). Metabolic activity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactic acid production measurement. Development of tolerance was determined by MIC values before and after exposure to QAMs or after prolonged starvation. It was found that . and . could survive and form biofilm under sub-MIC of QAMs. Lactic acid production from biofilms formed under sub-MIC was significantly higher than control specimens ( < 0.05). The exposure to sub-MIC of QAMs promoted biofilm formation, and prolonged starvation or prolonged contact with sub-MIC helped bacteria develop tolerance against killing by QAMs.
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http://dx.doi.org/10.1155/2021/8461245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822668PMC
January 2021

Stimuli-responsive drug delivery systems for head and neck cancer therapy.

Drug Deliv 2021 Dec;28(1):272-284

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China.

Head and neck cancer (HNC) is among the most common malignancy that has a profound impact on human health and life quality. The treatment for HNC, especially for the advanced cancer is stage-dependent and in need of combined therapies. Various forms of adjuvant treatments such as chemotherapy, phototherapy, hyperthermia, gene therapy have been included in the HNC therapy. However, there are still restrictions with traditional administration such as limited in situ therapeutic effect, systemic toxicity, drug resistance, etc. In recent years, stimuli-responsive drug delivery systems (DDSs) have attracted the great attention in HNC therapy. These intelligent DDSs could respond to unique tumor microenvironment, external triggers or dual/multi stimulus with more specific drug delivery and release, leading to enhanced treatment efficiency and less reduced side effects. In this article, recent studies on stimuli-responsive DDSs for HNC therapy were summarized, which could respond to endogenous and exogenous triggers including pH, matrix metalloproteinases (MMPs), reactive oxygen species (ROS), redox condition, light, magnetic field and multi stimuli. Their therapeutic remarks, current limits and future prospect for these intelligent DDSs were discussed. Furthermore, multifunctional stimuli-responsive DDSs have also been reviewed. With the modification of drug carriers or co-loading with therapeutic agents. Those intelligent DDSs showed more biofunctions such as combined therapeutic effects or integration of diagnosis and treatment for HNC. It is believed that stimuli-responsive drug delivery systems showed great potential for future clinic translation and application for the treatment of HNC.
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http://dx.doi.org/10.1080/10717544.2021.1876182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850355PMC
December 2021

The alteration of A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) in the knee joints of osteoarthritis mice.

J Histotechnol 2021 Jan 22:1-12. Epub 2021 Jan 22.

State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University , Chengdu, China.

The A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family is gradually being recognized as an important family of mediators that, along with the matrix metalloproteinases (MMPs), control the degradation process in osteoarthritis (OA). The objective of this study was to uncover the detailed alterations of ADAMTS1, ADAMTS2, and ADAMTS5 in the knee joint of OA mice. The OA model was established by anterior cruciate ligament transection (ACLT) on the knee joints of C57BL/6 J mice. The mice showed representative phenotypes of ACLT-induced OA, including obvious deterioration of the cartilage, reductions in the collagen and proteoglycan components in the cartilage matrix of OA mice, and increased inflammation and osteoclast activity. By qPCR, the gene expression levels of were the top-ranked among in cartilage/chondrocytes, osteogenic tissue/osteoblasts, and cortical bone/osteocytes. Moreover, the protein expression levels of ADAMTS1, -2, and -5 were all increased in articular cartilage, the growth plate, and subchondral bone of the knee joint. The results suggest the important roles of ADAMTS1, -2, and -5 in OA disease, which will be helpful in further research on degenerative changes in OA.
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http://dx.doi.org/10.1080/01478885.2020.1861908DOI Listing
January 2021

Biomaterial Stiffness Guides Cross-talk between Chondrocytes: Implications for a Novel Cellular Response in Cartilage Tissue Engineering.

ACS Biomater Sci Eng 2020 08 31;6(8):4476-4489. Epub 2020 Jul 31.

State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.

The exquisite cartilage architecture maintains an orderly dynamic equilibrium as a result of the interplay between chondrocyte functions and the unique extracellular matrix (ECM) microenvironment. Numerous studies have demonstrated that extracellular cues, including topological, mechanical, and biochemical properties of the underlying substrates, dictate the chondrocyte behaviors. Consequently, developing advanced biomaterials with the desired characteristics which could achieve the biointerface between cells and the surrounded matrix close to the physiological conditions becomes a great hotspot in bioengineering. However, how the substrate stiffness influences the intercellular communication among chondrocytes is still poorly reported. We used polydimethylsiloxane with varied stiffnesses as a cell culture substrate to elucidate a novel cell-to-cell communication in a collective of chondrocytes. First, morphological images collected using scanning electron microscopy revealed that the tunable substrate stiffnesses directed the changes in intercellular links among chondrocytes. Next, fibronectin, which played a vital role in the connection of ECM components or linkage of ECM to chondrocytes, was shown to be gathered along cell-cell contact areas and was changed with the tunable substrate stiffnesses. Furthermore, transmembrane junctional proteins including connexin 43 (Cx43) and pannexin 1 (Panx1), which are responsible for gap junction formation in cell-to-cell communication, were mediated by the tunable substrate stiffnesses. Finally, through a scrape loading/dye transfer assay, we revealed cell-to-cell communication changes in a living chondrocyte population in response to the tunable substrate stiffnesses cell-to-cell fluorescent molecule transport. Taken together, this novel cell-to-cell communication regulated by biomaterial stiffness could help us to increase the understanding of cell behaviors under biomechanical control and may ultimately lead to refining cell-based cartilage tissue engineering.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00367DOI Listing
August 2020

Activity of Ligustrum robustum (Roxb.) Blume extract against the biofilm formation and exopolysaccharide synthesis of Streptococcus mutans.

Mol Oral Microbiol 2021 02 31;36(1):67-79. Epub 2020 Dec 31.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, School of Stomatology, Sichuan University, Chengdu, PR China.

Ligustrum robustum (Roxb.) Blume is utilized as a traditional Chinese herbal tea with various health benefits and protective effects. Streptococcus mutans is an important cariogenic oral bacteria species. The present study aimed to assess the influence of Ligustrum robustum extract (LRE) on the biofilm formation of S. mutans and the mechanism of its action, as well as to identify its chemical components. For chemical identification, HPLC-MS and nuclear magnetic resonance were applied and four identified phytochemicals were reported (Ligurobustoside B, Ligurobustoside N, Ligurobustoside J, and Ligurobustoside C). The dose-dependent (0.5 to 2.0 μg/μL) antimicrobial toxicity of LRE against S. mutans biofilm formation and exopolysaccharide (EPS) synthesis was evaluated by confocal laser scanning microscopy (CLSM), Crystal violet stain, and CFU counting. The microstructure of S. mutans biofilm treated with LRE was investigated both on glass coverslips and ex vivo bovine dental enamel by scanning electron microscopy (SEM). Moreover, LRE downregulated the expression of S. mutans glucosyltransferase-encoding genes gtfB, gtfC, and gtfD, and the quorum sensing (QS) factors comD and comE, suggesting its toxic mechanism. In addition, the result of CCK-8 test on human oral cells revealed an acceptable biocompatibility of LRE. These findings indicated the possible application of this daily consumed herbal tea for caries prevention.
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http://dx.doi.org/10.1111/omi.12328DOI Listing
February 2021

Potential implications of SARS-CoV-2 oral infection in the host microbiota.

J Oral Microbiol 2020 Nov 29;13(1):1853451. Epub 2020 Nov 29.

Biofilm Research Labs, Levy Center for Oral Health, Department of Orthodontics, Divisions of Pediatric Dentistry and Community Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

The oral cavity, as the entry point to the body, may play a critical role in the pathogenesis of SARS-CoV-2 infection that has caused a global outbreak of the coronavirus disease 2019 (COVID-19). Available data indicate that the oral cavity may be an active site of infection and an important reservoir of SARS-CoV-2. Considering that the oral surfaces are colonized by a diverse microbial community, it is likely that viruses have interactions with the host microbiota. Patients infected by SARS-CoV-2 may have alterations in the oral and gut microbiota, while oral species have been found in the lung of COVID-19 patients. Furthermore, interactions between the oral, lung, and gut microbiomes appear to occur dynamically whereby a dysbiotic oral microbial community could influence respiratory and gastrointestinal diseases. However, it is unclear whether SARS-CoV-2 infection can alter the local homeostasis of the resident microbiota, actively cause dysbiosis, or influence cross-body sites interactions. Here, we provide a conceptual framework on the potential impact of SARS-CoV-2 oral infection on the local and distant microbiomes across the respiratory and gastrointestinal tracts (''), which remains largely unexplored. Studies in this area could further elucidate the pathogenic mechanism of SARS-CoV-2 and the course of infection as well as the clinical symptoms of COVID-19 across different sites in the human host.
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http://dx.doi.org/10.1080/20002297.2020.1853451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711743PMC
November 2020

Repurposing Napabucasin as an Antimicrobial Agent against Oral Streptococcal Biofilms.

Biomed Res Int 2020 20;2020:8379526. Epub 2020 Nov 20.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Objectives: Disruption of microbial biofilms is an effective way to control dental caries. Drug resistance and side effects of the existing antimicrobials necessitate the development of novel antibacterial agents. The current study was aimed at investigating the antibacterial activities of the repurposed natural compound napabucasin against oral streptococci.

Methods: The minimum inhibitory concentration, minimum bactericidal concentration, minimum biofilm inhibition concentration, and minimum biofilm reduction concentration of , , and were examined by a microdilution method. Cytotoxicity of napabucasin against human oral keratinocytes, human gingival epithelia, and macrophage RAW264.7 was evaluated by CCK8 assays. The dead/live bacterium and exopolysaccharide in the napabucasin-treated multispecies biofilms were evaluated by confocal laser scanning microscopy. Microbial composition within the napabucasin-treated biofilms was further visualized by fluorescent in situ hybridization and qPCR. And the cariogenicity of napabucasin-treated biofilms was evaluated by transverse microradiography.

Results: Napabucasin exhibited good antimicrobial activity against oral streptococcal planktonic cultures and biofilms but with lessened cytotoxicity as compared to chlorhexidine. Napabucasin reduced the cariogenic and increased the proportion of the commensal in the multispecies biofilms. More importantly, napabucasin significantly reduced the demineralization capability of biofilms on tooth enamels.

Conclusion: Napabucasin shows lessened cytotoxicity and comparable antimicrobial effects to chlorhexidine. Repurposing napabucasin may represent a promising adjuvant for the management of dental caries.
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http://dx.doi.org/10.1155/2020/8379526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700029PMC
November 2020

Comparative analysis of oral microbiome from Zang and Han populations living at different altitudes.

Arch Oral Biol 2021 Jan 12;121:104986. Epub 2020 Nov 12.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Cariology and Endodontics West China School of Stomatology, Sichuan University, Chengdu 610041, China. Electronic address:

Objectives: The aim of this study was to obtain greater insight into the environmental and genetic factors affecting the oral microbiome.

Design: To this end, we investigated the oral microbiome composition in Han and Zang populations living at different altitudes. The saliva microbiome in 115 individuals from Zang and Han populations living at different altitudes was analyzed using the 16 s rRNA gene sequencing method on the Illumina MiSeq platform. The dominant species in the oral microbiome were verified by quantitative real-time polymerase chain reaction (qPCR) analysis.

Results: The Han population, living at an altitude of 500 m, had higher microbiome diversity than the Zang population living at altitudes of 3000-4000 m. People living at 3000 m had a higher relative abundance of Leptothrix genus, but people living at 500 m had a higher relative abundance of Capnocytophaga genus according to Lefse difference analysis (P < 0.05). Compared to the Zang population, the Han population had higher relative abundances of Porphyromonas and Treponema genus organisms, especially Porphyromonas (P < 0.001). qPCR analysis confirmed that people living at high altitudes had the highest relative abundance of Porphyromonas gingivalis (P < 0.01).

Conclusions: This study showed that both genetics and the environment had significant influences on the oral microbiome composition. The study proposed a meaningful research direction to explore the relationship between different ethnic and altitude groups and oral diseases, such as periodontal diseases.
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http://dx.doi.org/10.1016/j.archoralbio.2020.104986DOI Listing
January 2021

Role of the fibroblast growth factor 19 in the skeletal system.

Life Sci 2021 Jan 24;265:118804. Epub 2020 Nov 24.

State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China. Electronic address:

Fibroblast growth factor family (FGFs) is a kind of cytokine that plays an important role in growth, development, metabolism and disease. During bone development, multiple FGFs and fibroblast growth factor receptors (FGFRs) play important roles. Previous reports have elucidated the great importance of FGF1, 2, 4, 6, 7, 8, 9, 10, and 18 in bone development, and FGF21 and 23 in bone homeostasis and bone regulation. FGF19 was initially found in the human foetal brain, and its gene location is related to osteoporosis pseudoglioma syndrome. Presently, gene chip detection has repeatedly found that FGF19 shows spatiotemporal specificity of gene expression in bone development and bone-related diseases, as well as differences in the protein level, indicating that FGF19 affects the skeletal system. Considering the current insufficient understanding of FGF19 and its potential function in the skeletal system, this review aims to introduce the background of FGF19 in bone, summarise the research progress of FGF19 in the skeletal system, and discuss the role and therapeutic potential of FGF19 in bone development and bone-related diseases.
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http://dx.doi.org/10.1016/j.lfs.2020.118804DOI Listing
January 2021

Rechargeable adhesive with calcium phosphate nanoparticles inhibited long-term dentin demineralization in a biofilm-challenged environment.

J Dent 2021 01 12;104:103529. Epub 2020 Nov 12.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China. Electronic address:

Objectives: This study aims to investigate the long-term demineralization-inhibition capability of a rechargeable adhesive with nanoparticles of amorphous calcium phosphate (NACP) on dentin in a biofilm-challenged environment.

Methods: The NACP adhesive was immersed in a pH 4 solution to exhaust calcium (Ca) and phosphate (P) ions and then recharged with Ca and P ions. Dentin samples were demineralized underStreptococcus mutans biofilms for 24 h and randomly divided into two groups: (1) dentin control, (2) dentin with recharged NACP adhesives. Each day, all the samples were immersed in brain heart infusion broth with 1% sucrose (BHIS) for 4 h, and then in artificial saliva (AS) for 20 h. This cycle was repeated for 10 days. The pH of BHIS, the Ca and P ions content of the BHIS and AS were measured daily. After 10 days, the lactic acid production and colony-forming units of the biofilms were tested. The changes of remineralization/demineralization were also analyzed.

Results: Dentin in the control group showed further demineralization. The recharged NACP adhesive neutralized acids, increasing the pH to above 5, and released large amounts of Ca and P ions each day. The recharged NACP adhesive decreased the production of lactic acid (P < 0.05), inhibited dentin demineralization and sustained the dentin hardness in the biofilm-challenged environment, showing an excellent long-term demineralization-inhibition capability.

Conclusions: The NACP adhesive could continuously inhibit dentin demineralization in a biofilm-challenged environment by recharging with Ca and P ions.

Significance: The rechargeable NACP adhesive could provide long-term dentin bond protection.
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http://dx.doi.org/10.1016/j.jdent.2020.103529DOI Listing
January 2021

Biochanin A alleviates gingival inflammation and alveolar bone loss in rats with experimental periodontitis.

Exp Ther Med 2020 Dec 23;20(6):251. Epub 2020 Oct 23.

Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, P.R. China.

Biochanin A (BA) is an organic compound produced by and with anti-inflammatory and antioxidative effects. The aim of the current study was to evaluate the effects of BA on gingival inflammation and alveolar bone destruction in rats with experimental periodontitis. Experimental rats (n=25) were distributed equally into five groups: i) Healthy control (control) group; ii) experimental periodontitis (ligation) group; and iii) and ligation plus low, medium and high dose of BA (12.5, 25 and 50 mg/kg/day, respectively) groups. A nylon ligature was inserted around rats' maxillary molars for 14 days to trigger the experimental periodontitis. BA was intravenous injected once daily for 4 weeks. After that, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS) and osteocalcin (OCN) levels were determined in gingival and/or serum samples using ELISA or reverse transcription-quantitative PCR. Alveolar bone volume was assessed via hematoxylin and eosin staining and micro-computed tomography. Osteoclasts were identified by tartrate-resistant acid phosphatase staining, and the level of the nuclear factor erythroid-2 related factor 2 (Nrf2) was also detected by immunohistochemical staining. BA treatment groups showed alleviated alveolar bone resorption compared with the ligation group. Moreover, BA treatment significantly inhibited IL-1β, TNF-α, ROS levels, and reduced leukocyte acid phosphatase-positive cells, as well as increased OCN and Nrf2 levels compared with the ligation group. BA had beneficial effects on experimental periodontitis of rats. BA treatment inhibited inflammation, regulated unbalanced oxidative stress response and ameliorated the alveolar bone loss.
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http://dx.doi.org/10.3892/etm.2020.9381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654219PMC
December 2020

Epigenetic Regulation of Dental Pulp Stem Cell Fate.

Stem Cells Int 2020 13;2020:8876265. Epub 2020 Oct 13.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.

Epigenetic regulation, mainly involving DNA methylation, histone modification, and noncoding RNAs, affects gene expression without modifying the primary DNA sequence and modulates cell fate. Mesenchymal stem cells derived from dental pulp, also called dental pulp stem cells (DPSCs), exhibit multipotent differentiation capacity and can promote various biological processes, including odontogenesis, osteogenesis, angiogenesis, myogenesis, and chondrogenesis. Over the past decades, increased attention has been attracted by the use of DPSCs in the field of regenerative medicine. According to a series of studies, epigenetic regulation is essential for DPSCs to differentiate into specialized cells. In this review, we summarize the mechanisms involved in the epigenetic regulation of the fate of DPSCs.
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http://dx.doi.org/10.1155/2020/8876265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603635PMC
October 2020

Candida albicans promotes tooth decay by inducing oral microbial dysbiosis.

ISME J 2021 03 4;15(3):894-908. Epub 2020 Nov 4.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, 610041, Chengdu, China.

Candida albicans has been detected in root carious lesions. The current study aimed to explore the action of this fungal species on the microbial ecology and the pathogenesis of root caries. Here, by analyzing C. albicans in supragingival dental plaque collected from root carious lesions and sound root surfaces of root-caries subjects as well as caries-free individuals, we observed significantly increased colonization of C. albicans in root carious lesions. Further in vitro and animal studies showed that C. albicans colonization increased the cariogenicity of oral biofilm by altering its microbial ecology, leading to a polymicrobial biofilm with enhanced acidogenicity, and consequently exacerbated tooth demineralization and carious lesion severity. More importantly, we demonstrated that the cariogenicity-promoting activity of C. albicans was dependent on PHR2. Deletion of PHR2 restored microbial equilibrium and led to a less cariogenic biofilm as demonstrated by in vitro artificial caries model or in vivo root-caries rat model. Our data indicate the critical role of C. albicans infection in the occurrence of root caries. PHR2 is the major factor that determines the ecological impact and caries-promoting activity of C. albicans in a mixed microbial consortium.
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http://dx.doi.org/10.1038/s41396-020-00823-8DOI Listing
March 2021

Advances of Anti-Caries Nanomaterials.

Molecules 2020 Oct 30;25(21). Epub 2020 Oct 30.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu 610041, China.

Caries is the most common and extensive oral chronic disease. Due to the lack of anti-caries properties, traditional caries filling materials can easily cause secondary caries and lead to treatment failure. Nanomaterials can interfere with the bacteria metabolism, inhibit the formation of biofilm, reduce demineralization, and promote remineralization, which is expected to be an effective strategy for caries management. The nanotechnology in anti-caries materials, especially nano-adhesive and nano-composite resin, has developed fast in recent years. In this review, the antibacterial nanomaterials, remineralization nanomaterials, and nano-drug delivery systems are reviewed. We are aimed to provide a theoretical basis for the future development of anti-caries nanomaterials.
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http://dx.doi.org/10.3390/molecules25215047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662703PMC
October 2020

Potential Roles of Bone Morphogenetic Protein 9 in the Odontogenic Differentiation of Dental Pulp Cells.

J Endod 2021 Mar 28;47(3):436-443. Epub 2020 Oct 28.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address:

Introduction: The differentiation of dental pulp cells (DPCs) plays an important role in the repair of dental pulp injury. Bone morphogenetic protein 9 (BMP9) is one of the most effective BMPs to induce the differentiation of stem cells. However, the role of BMP9 in promoting the odontogenic differentiation of DPCs and dentinogenesis is worth knowing.

Methods: Fluorescence in situ hybridization and immunohistochemistry staining were performed to detect the BMP9 expression in human dental pulp. BMP9 was overexpressed in human DPCs (hDPCs), and the mineralization of hDPCs was tested by alkaline phosphatase staining and alizarin red staining. The expression of odontogenic differentiation-related genes was examined by quantitative real-time polymerase chain reaction and western blotting. The subcutaneous transplantation experiment was performed to test the odonto-induction ability of BMP9 in vivo. The rat direct pulp-capping experiment was performed to test the function of BMP9 in promoting dentin formation.

Results: BMP9 showed an increased expression in odontoblast layer at both the mRNA and protein levels. BMP9 enhanced the mineralization and induced the expression of odontogenic differentiation-related genes in hDPCs. More mineralized nodules, and increased expression of dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP1) were detected in the beta-tricalcium phosphate scaffold/cells composites of BMP9 group compared with the control group. Meanwhile, there was thicker reparative dentin formation in the BMP9 group in the rat pulp exposure experiment.

Conclusions: BMP9 participates in the process of DPC differentiation and promotes DPC mineralization and dentinogenesis. BMP9 might be a potential therapeutic target in the repair of dental pulp injury.
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http://dx.doi.org/10.1016/j.joen.2020.10.018DOI Listing
March 2021

The positive rate of saliva for the detection of 2019-nCoV and possible factors related to the sensitivity results.

J Med Virol 2020 Oct 27. Epub 2020 Oct 27.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1002/jmv.26627DOI Listing
October 2020

IL-1α Regulates Osteogenesis and Osteoclastic Activity of Dental Follicle Cells Through JNK and p38 MAPK Pathways.

Stem Cells Dev 2020 12 1;29(24):1552-1566. Epub 2020 Dec 1.

State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Inflammatory cytokines such as interleukin-1α (IL-1α) are increased in teeth with periapical lesions. Primary teeth with periapical lesions have a propensity for accelerated eruption of the successors. In this study, we asked whether increased levels of IL-1α in the dental follicle (DF) occurring as the result of periapical lesions promote tooth eruption, possibly due to enhanced osteoclastic remodeling of DF cells (DFCs). To this end, we studied the effect and possible mechanism of IL-1α on osteogenic differentiation, osteoclastogenic activity, and matrix remodeling of DFCs. Results demonstrated that DFCs cultured with IL-1α exhibited reduced osteogenic capacity, higher osteoclastogenic activity, and stronger invasive ability. Phosphorylation of JNK and p38 was upregulated, and pretreatment with SB203580 and SP600125 reversed the effect of IL-1α on DFCs. Neonatal rats subjected to subcutaneous injection of an IL-1 receptor antagonist exhibited a reduced number in activated osteoclasts, increased expression of alkaline phosphatase and osteopontin, and delayed tooth eruption. These data support our hypothesis that increased IL-1α cytokine levels as they occur during periodontal and periapical inflammation cause osteoclastic remodeling of the alveolar socket as a requirement for tooth eruption and thus may indirectly promote the vertical eruption of teeth toward the occlusal plane.
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http://dx.doi.org/10.1089/scd.2020.0118DOI Listing
December 2020

Role of Oral Bacteria in the Development of Oral Squamous Cell Carcinoma.

Cancers (Basel) 2020 Sep 29;12(10). Epub 2020 Sep 29.

State Key Laboratory of Oral Diseases & West China School of Stomatology & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu 610041, China.

Oral squamous cell carcinoma (OSCC) is an invasive epithelial neoplasm that is influenced by various risk factors, with a low survival rate and an increasing death rate. In the past few years, with the verification of the close relationship between different types of cancers and the microbiome, research has focused on the compositional changes of oral bacteria and their role in OSCC. Generally, oral bacteria can participate in OSCC development by promoting cell proliferation and angiogenesis, influencing normal apoptosis, facilitating invasion and metastasis, and assisting cancer stem cells. The study findings on the association between oral bacteria and OSCC may provide new insight into methods for early diagnosis and treatment development.
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http://dx.doi.org/10.3390/cancers12102797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600411PMC
September 2020

Salivary microbiome in patients undergoing hemodialysis and its associations with the duration of the dialysis.

BMC Nephrol 2020 09 29;21(1):414. Epub 2020 Sep 29.

State Key Laboratory of Oral Diseases & National Clinical Research Centre for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, Section 3, Renmin South Road, Chengdu, 610041, Sichuan, China.

Background: Chronic kidney disease (CKD) patients, especially those with end stage renal disease (ESRD) undergoing hemodialysis (HD), exhibit high prevalence of periodontitis. This cross-sectional study aimed to investigate the periodontal status of HD patients and its relationship with salivary microbiome.

Methods: One hundred eight HD patients and one hundred healthy control individuals were recruited. They were subjected to periodontal examination followed by saliva samples collection for 16S rRNA gene sequencing.

Results: The HD patients were with worse periodontal health status, and exhibited higher salivary microbial diversity and lower richness. The periodontal pathogens were significantly enriched in the HD patients. The inferred functional analyze showed microbes enriched in the HD patients were mainly related to metabolism. Despite the periodontal status and overall structure of the microbiome were not significantly altered as the HD duration prolonged, the abundance of Lachnospiraceae [G-2] sp. |HMT_096| is positively correlated with the duration of HD and the community periodontal index (CPI). Five OTUs (operational taxonomic units) belonging to the phyla Firmicutes were enriched as the duration prolonged, and four OTUs originated from the phyla Proteobacteria were negatively related with the CPI index. ESRD patients undergoing HD exhibited microbiota structural, compositional and functional differences compared with the healthy controls. And the species changed as the duration of hemodialysis prolonged.

Conclusions: End stage renal disease changes salivary microbiome and is a risk factor for oral dysbiosis.
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http://dx.doi.org/10.1186/s12882-020-02009-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523083PMC
September 2020

Identification and characterization of a novel adiponectin receptor agonist adipo anti-inflammation agonist and its anti-inflammatory effects in vitro and in vivo.

Br J Pharmacol 2021 Jan 18;178(2):280-297. Epub 2020 Dec 18.

Division of Oral Biology, Tufts University School of Dental Medicine, Boston, Massachusetts, USA.

Background And Purpose: Adiponectin (APN) is an adipokine secreted from adipocytes that binds to APN receptors AdipoR1 and AdipoR2 and exerts an anti-inflammatory response through mechanisms not fully understood. There is a need to develop small molecules that activate AdipoR1 and AdipoR2 and to be used to inhibit the inflammatory response in lipopolysaccharide (LPS)-induced endotoxemia and other inflammatory disorders.

Experimental Approach: We designed 10 new structural analogues of an AdipoR agonist, AdipoRon (APR), and assessed their anti-inflammatory properties. Bone marrow-derived macrophages (BMMs) and peritoneal macrophages (PEMs) were isolated from mice. Levels of pro-inflammatory cytokines were measured by reverse transcription and real-time quantitative polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and microarray in LPS-induced endotoxemia mice and diet-induced obesity (DIO) mice in which systemic inflammation prevails. Western blotting, immunohistochemistry (IHC), siRNA interference and immunoprecipitation were used to detect signalling pathways.

Key Results: A novel APN receptor agonist named adipo anti-inflammation agonist (AdipoAI) strongly suppresses inflammation in DIO and endotoxemia mice, as well as in cultured macrophages. We also found that AdipoAI attenuated the association of AdipoR1 and APPL1 via myeloid differentiation marker 88 (MyD88) signalling, thus inhibiting activation of nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK) and c-Maf pathways and limiting the production of pro-inflammatory cytokines in LPS-induced macrophages.

Conclusion And Implications: AdipoAI is a promising alternative therapeutic approach to APN and APR to suppress inflammation in LPS-induced endotoxemia and other inflammatory disorders via distinct signalling pathways.
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http://dx.doi.org/10.1111/bph.15277DOI Listing
January 2021

The combined use of salivary biomarkers and clinical parameters to predict the outcome of scaling and root planing: A cohort study.

J Clin Periodontol 2020 11 13;47(11):1379-1390. Epub 2020 Oct 13.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Aim: To explore the application of the combined use of baseline salivary biomarkers and clinical parameters in predicting the outcome of scaling and root planing (SRP).

Materials And Methods: Forty patients with advanced periodontitis were included. Baseline saliva samples were analysed for interleukin-1β (IL-1β), matrix metalloproteinase-8 and the loads of Porphyromonas gingivalis, Prevotella intermedia, Aggregatibacter actinomycetemcomitans and Tannerella forsythia. After SRP, pocket closure and further attachment loss at 6 months post-treatment were chosen as outcome variables. Models to predict the outcomes were established by generalized estimating equations.

Results: The combined use of baseline clinical attachment level (CAL), site location and IL-1β (area under the curve [AUC] = 0.764) better predicted pocket closure than probing depth (AUC = 0.672), CAL (AUC = 0.679), site location (AUC = 0.654) or IL-1β (AUC = 0.579) alone. The combination of site location, tooth loss, percentage of deep pockets, detection of A. actinomycetemcomitans and T. forsythia load (AUC = 0.842) better predicted further clinical attachment loss than site location (AUC = 0.715), tooth loss (AUC = 0.530), percentage of deep pockets (AUC = 0.659) or T. forsythia load (AUC = 0.647) alone.

Conclusion: The combination of baseline salivary biomarkers and clinical parameters better predicted SRP outcomes than each alone. The current study indicates the possible usefulness of salivary biomarkers in addition to tooth-related parameters in predicting SRP outcomes.
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http://dx.doi.org/10.1111/jcpe.13367DOI Listing
November 2020

Novel Nanocomposite Inhibiting Caries at the Enamel Restoration Margins in an In Vitro Saliva-Derived Biofilm Secondary Caries Model.

Int J Mol Sci 2020 Sep 2;21(17). Epub 2020 Sep 2.

Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School, Baltimore, MD 21201, USA.

Secondary caries often occurs at the tooth-composite margins. This study developed a novel bioactive composite containing DMAHDM (dimethylaminohexadecyl methacrylate) and NACP (nanoparticles of amorphous calcium phosphate), inhibiting caries at the enamel restoration margins in an in vitro saliva-derived biofilm secondary caries model for the first time. Four composites were tested: (1) Heliomolar nanocomposite, (2) 0% DMAHDM + 0% NACP, (3) 3% DMAHDM + 0% NACP, (D) 3% DMAHDM + 30% NACP. Saliva-derived biofilms were tested for antibacterial effects of the composites. Bovine enamel restorations were cultured with biofilms, Ca and P ion release of nanocomposite and enamel hardness at the enamel restoration margins was measured. Incorporation of DMAHDM and NACP into composite did not affect the mechanical properties ( > 0.05). The biofilms' CFU (colony-forming units) were reduced by 2 logs via DMAHDM ( < 0.05). Ca and P ion release of the nanocomposite was increased at cariogenic low pH. Enamel hardness at the margins for DMAHDM group was 25% higher than control ( < 0.05). With DMAHDM + NACP, the enamel hardness was the greatest and about 50% higher than control ( < 0.05). Therefore, the novel composite containing DMAHDM and NACP was strongly antibacterial and inhibited enamel demineralization, resulting in enamel hardness at the margins under biofilms that approached the hardness of healthy enamel.
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http://dx.doi.org/10.3390/ijms21176369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503730PMC
September 2020