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An early report: a modified porphyrin-linked metronidazole targeting intracellular Porphyromonas gingivalis in cultured oral epithelial cells

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International Journal of Oral Science 2017年第3期9卷 167-173页

作者： Ping Ye Jiho Chang Lin Feng Foo Benjamin C-M Yap Institute of Dental Research Centre for Oral Health Westmead Hospital Affiliation of Faculty of Dentistry the University of Sydney

Porphyromonas gingivalis （P. gingivalis） has a strong association with the pathogenesis of periodontal disease. Recurrence of periodontal disease following therapy is attributed to numerous factors, and of growing interest is the potential problem of intracellular bacteria that are able to persist and multiply within the host cell, thereby facilitating relapse of infection. The effect of antibiotic therapy in controlling P. gingivalis is questionable. Accordingly, while metronidazole is very effective against anaerobic extracellular P. gingivalis by disrupting the DNA of anaerobic microbial cells, this antibiotic does not effectively penetrate into mammalian cells to inhibit intracellular bacteria. Therefore in the present study, a modified porphyrin-linked metronidazole adducts, developed in our laboratory, was used to kill intracellular P. gingivalis. A series of experiments were performed, including cytotoxicity assays and cellular uptake of adducts by flow cytometry coupled with live cell imaging analysis, P. gingivalis invasion and elimination assays, and the analysis of colocalization of P. gingivalis and porphyrin-linked metronidazole by confocal laser scanning microscopy. Findings indicated that P. gingivalis and porphyrin-linked metronidazole were colocalized in the cytoplasm, and this compound was able to kill P. gingivalis intracellular with a sufficient culture time. This is a novel antimicrobial approach in the elimination of P. gingivalis from the oral cavity.

关键词： porphyrin-linked metronidazole Porphyromonas gingivalis periodontitis oral epithelial cells

Role of Toll-like receptor 2 in inflammation and alveolar bone loss in experimental peri-implantitis ***

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Role of Toll-like receptor 2 in inflammation and alveolar bo...

Comparison of microRNA profiles of human periodontal diseased and healthy gingival tissues

中华口腔医学会全科口腔医学专业委员会第八次学术会议

作者：杨建军于新波 Han Xiaozhe 青岛大学附属医院

Objective and background:Peri-implantitis and periodontitis are different entities in immune characteristics even though they share similar features in clinical and radiologic ***-like receptor 2(TLR2),one of the key pathogen recognition receptors in the innate immune system,plays an important role in the progress of ***,the role of TLR2 in peri-implantitis remains *** objective of this study was to investigate the role of TLR2 in inflammation and alveolar bone loss in a murine model of ligature-induced peri-implantitis and to compare it to ligature-induced ***:Smooth-surface titanium implants were placed in the alveolar bone of the left maxillary molars of Wild Type(WT) and TLR2 knockout(KO) mice 6 weeks after tooth *** ligatures were applied to the left implant fixtures and the right maxillary second molars to induce peri-implantitis and periodontitis 4 weeks after implant *** loss and inflammation around the implants and maxillary second molars were analyzed by micro-computed tomography(micro-CT) and histology and TRAP staining respectively 2 weeks after *** mRNA expressions of pro-inflammatory cytokines(IL-1β,TNF-α),anti-inflammatory cytokine(IL-10)and osteoclastogenesis-related cytokines(RANKL,OPG) were evaluated using real-time quantitative PCR(RT-qPCR).Results:Success Rate(SR) of Implant osseointegration was significantly greater in TLR2 KO mice(85.71%) when compared to WT mice(53.66%)(p=0.0125).Micro-CT revealed significantly decreased bone loss in TLR2 KO mice as compared to WT mice(p= 0.0094) in *** mRNA expressions of IL-1 b(p= 0.0055),TNF-α(p= 0.01) and IL-10(p= 0.0019) was significantly elevated in the peri-implantitis tissues of WT mice,but not in TLR2 KO mice,as compared to ***,the gingival mRNA ratios of RANKL/OPG in peri-implant tissues were significantly up-regulated in both WT(p=0.0488) and TLR2 KO mice(p= 0.0314).Ligature-ind

关键词： TLR2 bone resorption peri-implantitis periodontitis inflammatory cytokine

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International Journal of Oral Science 2011年第3期3卷 125-134页

作者： Yu-feng Xie Rong Shu Shao-yun Jiang Da-li Liu Xiu-li Zhang Department of Periodontology Shanghai Ninth People＇s Hospital Affiliated Shanghai Jiao Tong University School of Medicine Shanghai 200011 China Shanghai Research Institute of Stomatology Shanghai Ninth People＇s Hospital Affiliated Shanghai Jiao Tong University School of Medicine Shanghai 200011 China

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 ***, 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.

关键词： microRNA microarray periodontitis gingival tissue

Analysis of differential expression of tight junction proteins in cultured oral epithelial cells altered by Porphyromonas gingivalis,Porphyromonas gingivalis lipopolysaccharide,and extracellular adenosine triphosphate

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International Journal of Oral Science 2017年第4期9卷 238-244页

作者： wei guo peng wang zhong-hao liu ping ye department of endodontics yantai stomatological hospitalbinzhou medical universityYantaiChina department of pediatrics yantai stomatological hospitalbinzhou medical universityYantaiChina department of implant yantai stomatological hospitalbinzhou medical universityYantaiChina institute of dental research centre for oral healthwestmead hospitalWestmeadAustralia faculty of dentistry the university of sydneySydneyAustralia

Tight junctions （TJs） are the most apical intercellular junctions of epithelial cells formed by occludin, claudins, junctional adhesion molecules （JAMs）, and zonula occludens （ZO）. Tight junction proteins can sense the presence of bacteria and regulate the transcription of target genes that encode effectors and regulators of the immune response. The aim of this study was to determine the impact of TJ proteins in response to Porphyromonas gingivalis （P. gingivalis）, P. gingivalis lipopolysaccharide （P. gingivalis LPS）, and extracellular adenosine triphosphate （ATP） in the oral epithelial cell culture model. Quantified real time- polymerase chain reaction （RT-PCR）, immunoblots, and immunostaining were performed to assess the gene and protein expression in TJs. It was found that P. gingivalis infection led to transient upregulation of the genes encoding occludin, claudin- 1, and claudin-4 but not JAM-A, claudin-15, or ZO-1, while P. gingivalis LPS increased claudin-1, claudin-15, and ZO-1 and decreased occludin, JAM-A, and claudin-4. Tight junction proteins showed significant upregulation in the above two groups when cells were pretreated with ATP for 3 h. The findings indicated that P. gingivalis induced the host defence responses at an early stage. P. gingivalis LPS exerted a more powerful stimulatory effect on the disruption of the epithelial barrier than P. gingivalis. ATP stimulation enhanced the reaction of TJ proteins to P. gingivalis invasion and LPS destruction of the epithelium.

关键词： junctional epithelium periodontitis Porphyromonas gingivalis tight junctions

Periodontal disease and risk of benign prostate hyperplasia: a cross-sectional study

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Military Medical Research 2020年第2期7卷 157-165页

作者： Lan Wu Bing-Hui Li Yun-Yun Wang Chao-Yang Wang Hao Zi Hong Weng Qiao Huang You-Jia Zhu Xian-Tao Zeng Center for Evidence-Based and Translational Medicine Zhongnan Hospital of Wuhan UniversityWuhan 430071China department of Stomatology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for Evidence-Based Medicine Institute of Evidence-Based Medicine and Knowledge TranslationHenan UniversityKaifeng 475000China Department of Urology Zhongnan Hospital of Wuhan UniversityWuhan 430071China

Background:Both periodontal disease and benign prostatic hyperplasia are age-related diseases that affect millions of people ***,this study aimed to investigate the association between periodontal disease and the risk of benign prostatic ***:A total of 4930 participants were selected from an available health examination that was carried out in 2017,only males were considered for further *** eligible males were divided into benign prostatic hyperplasia and normal groups,the benign prostatic hyperplasia group was then divided into prostate volume≤60 g and>60 g subgroups;all their periodontal status was extracted and then into normal(CPI score of 0),periodontal disease(CPI score between 1 and 4),and periodontitis(CPI score between 3 and 4)*** correlation between periodontal disease and benign prostatic hyperplasia was investigated using logistic regression analyses and greedy matching case-control *** analysis based on prostate volume was also *** analyses were conducted with SAS 9.4 ***:A total of 2171 males were selected for this *** presence of periodontal disease significantly increased the risk of benign prostatic hyperplasia by 1.68 times(OR=1.68,95%CI:1.26–2.24),and individuals with periodontitis showed a higher risk(OR=4.18,95%CI:2.75–6.35).In addition,among matched cases and controls,this association remained robust(periodontal disease:OR=1.85,95%CI:1.30–2.64;periodontitis:OR=4.83,95%CI:2.57–9.07).Subgroup analysis revealed that periodontal disease significantly increased benign prostate hyperplasia risk as well(for prostate volume≤60 g:OR=1.64,95%CI:1.22–2.20;for volume>60 g:OR=2.17,95%CI:1.04–4.53),and there was a higher risk in the group with a prostate volume greater than 60 ***:Periodontal disease is significantly and positively associated with an increased risk of benign prostatic *** validation studies should be performed to explore the re

关键词： Benign prostate hyperplasia Periodontal disease periodontitis Risk factor Inflammatory disease

Influence of local anesthesia on the outcomes of non-surgical periodontal treatment

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Chinese Medical Journal 2020年第16期133卷 1908-1914页

作者： Shu-Wen Shi Jian Jiao Li Zhang Rui-Fang Lu Huan-Xin Meng Zhan-Qiang Cao Dong Shi Yi Song Department of Periodontology Peking University School and Hospital of StomatologyBeijing 100081China Department of Periodontology Peking University Hospital of Stomatology First Clinic DivisionBeijing 100034China Information Center Peking University School and Hospital of StomatologyBeijing 100081China Institute of Child and Adolescent Health School of Public HealthPeking UniversityBeijing 100191China Department of Clinical Sciences Social Medicine and Global HealthLund UniversityMalmö20213Sweden

Background:There is limited evidence of the effects of local anesthesia(LA)on outcomes of non-surgical periodontal treatment(NSPT),in particular among the *** retrospective cohort study aimed to evaluate the effects of LA on short-term treatment outcomes of NSPT and to determine under what circumstances LA should be prescribed to improve these ***:Data from periodontal examinations of 3980 patients were *** data were from 3-month re-evaluation records of an electronic periodontal charting record system in the Department of Periodontology of Peking University School and Hospital of Stomatology from June 2008 to January *** analyses included changes in probing depth(PD)and the Mazza bleeding index(BI).Two-level(patient and tooth)logistic regression models and three-level(patient,tooth,and site)linear regression models were constructed to analyze the influence of LA on PD for all teeth/sites and teeth/sites with an initial PD≥5 *** in PD and BI at sites under LA using the initial PD were also ***:A significantly higher mean decrease in PD after NSPT was found in the LA group than in the no local anesthesia(NLA)group(0.98 vs.0.54 mm,t=24.12,P1 and BI>2)for all teeth(16.7%vs.13.8%,t=3.75,P<0.001;34.7%vs.28.1%,t=6.73,P<0.001)and PD for teeth with PD≥5mm(32.3%vs.17.3%,t=28.48,P<0.001).The difference in PD between the LA and NLA groups increased as the initial PD *** difference between the two groups was 0.12 to 0.22 mm for sites with a baseline PD<7 mm;however,it increased to 0.41 to 1.37 mm for sites with a baseline PD≥7 ***:LA improved the decrease in PD after *** debridement at sites with initial PD≥7 mm should be performed under routine LA.

关键词： Local anesthesia periodontitis Periodontal debridement

Relationship between microorganisms in coronary atheromatous plaques and periodontal pathogenic bacteria

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Chinese Medical Journal 2008年第16期121卷 1595-1597页

作者： ZHANG Yuan-ming ZHONG Liang-jun LIANG Ping LIU Hua MU La-ti AI Si-ka-er Centre of Cardiology First Affiliated Hospital of Xinjiang Medical University Urumqi Xinjiang 830054 China Department of Stomatology First Affiliated Hospital of Xinjiang Medical University Urumqi Xinjiang 830054 China

Inflammation plays an important role in the pathogenesis .of atherosclerosis, and low-grade chronic systemicinflammation is thought to be related to adverse cardiovascular outcomes,In the past decade, epidemiological studies have repeatedly shown an association between coronary heart disease and periodontal disease. Observational studies have shown that periodontitis is associated with an increased risk of myocardial infarction and stroke, although a causal link has not yet been proven.

关键词： cardiovascular diseases periodontitis polymerase chain reaction DNA sequencing

What Is Dentists’ Role in Modulating Environmental and Epigenetic Determinant in Oral Health of Diabetic Patients?

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Journal of Biosciences and Medicines 2023年第2期11卷 152-168页

作者： Zhengzhang Guo Department of Nutritional Science University of Toronto Toronto ON Canada Department of Human Biology University of Toronto Toronto ON Canada

Background and Purpose: With the unexpectedly rapid increase in the prevalence of types of diabetes worldwide, this chronic disease is no longer being viewed as a systemic health issue, but also treated as the start of the deadly disease. As the sixth complication of diabetes, periodontitis is a chronic inflammatory condition that leads directly and indirectly to a severer condition of diabetes via its underlying mechanisms. Interestingly, both diseases are not been fully identified in their bidirectional relationships by researchers. Thus, healthcare agencies must pay appropriate attention. This literature review paper aims to investigate and discuss dentists’ role in modulating environmental and epigenetic determinants in the oral health of diabetic patients based on the bidirectional relationship between these diseases, their prevalence and how treatment of one disease affects the other. Methods: The authors conducted electronic searches in PubMed, Google Scholar, One Search UofT, ScienceDirect, and the National Library of Medicine. The paper also included gray literature from government resources related to the topic. The paper will review the epidemiology, pathogenesis, and epigenetics of both diabetes and periodontal disease and their functions with each other. Results: The literature has consistently shown that diabetes and periodontal disease have responded to the formation and severity of each other. Patients with pre- and diabetes have potentially higher risks of causing periodontal disease and other complications if adequate diagnosis and treatment are not involved timely. The combination of risk factors, including individual, social, environmental, and genetic, play a crucial role in the development of diabetes and the severity of periodontitis. Conclusions: Based on the results, the collaboration between dentists and other healthcare practitioners is inevitable in the overall development of treatment for both diseases. With the proper and updated knowle

关键词： periodontitis Diabetes Mellitus Epigenetic Pathogenesis Epidemiology

Histopathological and Immunohistochemical Study of Peri-Implant Epithelium

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Open Journal of Stomatology 2023年第9期13卷 309-321页

作者： Yoshikazu Nakayama Chieko Taguchi Mitsuko Nakayama Masaaki Suemitsu Kayo Kuyama Department of Oral Pathology Nihon University Graduate School Dentistry at Matsudo Chiba Japan Department of Community Oral Health Nihon University School of Dentistry at Matsudo Chiba Japan Department of Pathology Nihon University School of Dentistry at Matsudo Chiba Japan

Background: Human beta-defensins (HBDs), epithelial-derived antimicrobial peptides, contribute to gingival health and periodontal disease. Particularly, the upregulation of HBD-3 expression in periodontal tissues is described to contribute to periodontal tissue regeneration. Specifically, the upregulation of HBD-3 expression in periodontal tissues is described to contribute to periodontal tissue regeneration. But there has been insufficient investigation of the inner epithelium in peri-implantitis, especially the HBD expression patterns as protection against oral infection. Objectives: The purpose of this study was to investigate the histopathological characteristics of the inner implant epithelium in peri-implantitis using histopathological and immunohistochemical methods and to compare it with the inner marginal epithelium in periodontitis. Materials and Methods: The biopsied cases consisted of 10 peri-implantitis, 11 periodontitis, and 10 controls. HE observation, measurement of the thickness of the inner epithelium, and immunohistochemical analysis for Ki-67 and HBD-3 were conducted. Results: Concerning the thickness of the inner epithelium, it was significantly higher in periodontitis (156.2 [138.0, 186.4] μm) than in peri-implantitis and control, 70.7 [67.5, 97.5] μm and 80.7 [76.6, 89.4] μm, respectively (p Conclusion: Decreased production of HBD-3 in keratinocytes composing the inner implant epithelium may be one of the factors affecting tissue repair in peri-implantitis.

关键词： Peri-Implantitis periodontitis Ki-67 HBD-3 Inner Epithelium