Pub Date : 2023-08-01DOI: 10.1177/00220345231170538
P Sahrmann, N Naenni, R E Jung, C H F Hämmerle, T Attin, P R Schmidlin
The aim of the study was to compare the clinical and radiographic outcomes of short dental implants (6-mm test group, TG) to longer implants (10-mm control group, CG) with single crown restorations after 10 y of loading. Patients requiring single-tooth replacement in the posterior jaws were randomly assigned to TG or CG. Implants were loaded with screw-retained single crowns after a healing period of 10 wk. Follow-up appointments were scheduled yearly and comprised patient-adapted oral hygiene reinstructions and polishing of all teeth and implants. After 10 y, clinical and radiographical parameters were assessed again. Out of initially 94 patients (47 in TG and CG, each), 70 (36 TG and 34 CG) could be reassessed. Survival rates accounted for 85.7% (TG) and 97.1% (CG), without significant intergroup difference (P = 0.072). All but 1 lost implant had been located in the lower jaw. These implants were not lost due to peri-implantitis but due to a late loss of osseointegration without signs of inflammation and with actually stable marginal bone levels (MBLs) over the investigation period. In general, MBLs were stable with medians (interquartile ranges) of 0.13 (0.78) mm and 0.08 (1.2) mm, for TG and CG, without significant intergroup differences. Crown-to-implant ratio showed a highly significant intergroup difference of 1.06 ± 0.18 mm and 0.73 ± 0.17 mm (P < 0.001). Few technical complications (i.e., screw loosening or chipping) were registered during the investigation period. In conclusion, given stringent professional maintenance, short dental implants with single-crown restorations show a slightly worse but statistically not different survival rate after 10 y, especially in the lower jaw, but can still be considered a valuable alternative, especially when vertical bone dimensions are limited (German Clinical Trials Registry: DRKS00006290).
{"title":"Ten-Year Performance of Posterior 6-mm Implants with Single-Tooth Restorations: A Randomized Controlled Trial.","authors":"P Sahrmann, N Naenni, R E Jung, C H F Hämmerle, T Attin, P R Schmidlin","doi":"10.1177/00220345231170538","DOIUrl":"https://doi.org/10.1177/00220345231170538","url":null,"abstract":"<p><p>The aim of the study was to compare the clinical and radiographic outcomes of short dental implants (6-mm test group, TG) to longer implants (10-mm control group, CG) with single crown restorations after 10 y of loading. Patients requiring single-tooth replacement in the posterior jaws were randomly assigned to TG or CG. Implants were loaded with screw-retained single crowns after a healing period of 10 wk. Follow-up appointments were scheduled yearly and comprised patient-adapted oral hygiene reinstructions and polishing of all teeth and implants. After 10 y, clinical and radiographical parameters were assessed again. Out of initially 94 patients (47 in TG and CG, each), 70 (36 TG and 34 CG) could be reassessed. Survival rates accounted for 85.7% (TG) and 97.1% (CG), without significant intergroup difference (<i>P</i> = 0.072). All but 1 lost implant had been located in the lower jaw. These implants were not lost due to peri-implantitis but due to a late loss of osseointegration without signs of inflammation and with actually stable marginal bone levels (MBLs) over the investigation period. In general, MBLs were stable with medians (interquartile ranges) of 0.13 (0.78) mm and 0.08 (1.2) mm, for TG and CG, without significant intergroup differences. Crown-to-implant ratio showed a highly significant intergroup difference of 1.06 ± 0.18 mm and 0.73 ± 0.17 mm (<i>P</i> < 0.001). Few technical complications (i.e., screw loosening or chipping) were registered during the investigation period. In conclusion, given stringent professional maintenance, short dental implants with single-crown restorations show a slightly worse but statistically not different survival rate after 10 y, especially in the lower jaw, but can still be considered a valuable alternative, especially when vertical bone dimensions are limited (German Clinical Trials Registry: DRKS00006290).</p>","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"102 9","pages":"1015-1021"},"PeriodicalIF":7.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9950710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01DOI: 10.1177/00220345231176522
W D Jiang, P Q Zhu, T Zhang, F C Liao, P P Jiang, N Zhou, X D Wang, X P Huang
Bone defect (BD) caused by trauma, infection, congenital defects, or neoplasia is a major cause of physical limitation. Distraction osteogenesis (DO) is a highly effective procedure for bone regeneration, while the concrete mechanism remains unknown. In this study, canine DO and BD models of the mandible were established. The results of micro-computed tomography and histological staining revealed that DO led to an increased mineralized volume fraction and robust new bone formation; in contrast, BD demonstrated incomplete bone union. Mesenchymal stem cells (MSCs) from DO and BD calluses were isolated and identified. Compared with BD-MSCs, DO-MSCs were found to have a stronger osteogenic capability. Single-cell RNA sequencing analysis was further performed to comprehensively define cell differences between mandibular DO and BD calluses. Twenty-six clusters of cells representing 6 major cell populations were identified, including paired related homeobox 1-expressing MSCs (PRRX1+MSCs), endothelial cells (ECs), T cells, B cells, neutrophils, and macrophages. Interestingly, 2 subpopulations in PRRX1+MSCs in the DO group were found to express the marker of neural crest cells (NCCs) and were associated with the process of epithelial-mesenchymal transition. The immunofluorescence assay was performed to further corroborate these results in vivo and in vitro, experimentally validating that continuous distraction maintained the PRRX1+MSCs in an embryonic-like state. Finally, we used CRISPR/Cas9 to knock out (KO) PRRX1 in the context of DO, which significantly blunted the capability of jawbone regeneration, resulting in a diminished NCC-like program and reduction of new bone volume. In addition, the ability of osteogenesis, cell migration, and proliferation in cultured PRRX1KO MSCs was inhibited. Taken together, this study provides a novel, comprehensive atlas of the cell fates in the context of DO regeneration, and PRRX1+MSCs act essential roles.
{"title":"<i>PRRX1</i><sup>+</sup>MSCs Enhance Mandibular Regeneration during Distraction Osteogenesis.","authors":"W D Jiang, P Q Zhu, T Zhang, F C Liao, P P Jiang, N Zhou, X D Wang, X P Huang","doi":"10.1177/00220345231176522","DOIUrl":"https://doi.org/10.1177/00220345231176522","url":null,"abstract":"<p><p>Bone defect (BD) caused by trauma, infection, congenital defects, or neoplasia is a major cause of physical limitation. Distraction osteogenesis (DO) is a highly effective procedure for bone regeneration, while the concrete mechanism remains unknown. In this study, canine DO and BD models of the mandible were established. The results of micro-computed tomography and histological staining revealed that DO led to an increased mineralized volume fraction and robust new bone formation; in contrast, BD demonstrated incomplete bone union. Mesenchymal stem cells (MSCs) from DO and BD calluses were isolated and identified. Compared with BD-MSCs, DO-MSCs were found to have a stronger osteogenic capability. Single-cell RNA sequencing analysis was further performed to comprehensively define cell differences between mandibular DO and BD calluses. Twenty-six clusters of cells representing 6 major cell populations were identified, including paired related homeobox 1-expressing MSCs (<i>PRRX1</i><sup>+</sup>MSCs), endothelial cells (ECs), T cells, B cells, neutrophils, and macrophages. Interestingly, 2 subpopulations in <i>PRRX1</i><sup>+</sup>MSCs in the DO group were found to express the marker of neural crest cells (NCCs) and were associated with the process of epithelial-mesenchymal transition. The immunofluorescence assay was performed to further corroborate these results in vivo and in vitro, experimentally validating that continuous distraction maintained the <i>PRRX1</i><sup>+</sup>MSCs in an embryonic-like state. Finally, we used CRISPR/Cas9 to knock out (KO) <i>PRRX1</i> in the context of DO, which significantly blunted the capability of jawbone regeneration, resulting in a diminished NCC-like program and reduction of new bone volume. In addition, the ability of osteogenesis, cell migration, and proliferation in cultured <i>PRRX1</i><sup>KO</sup> MSCs was inhibited. Taken together, this study provides a novel, comprehensive atlas of the cell fates in the context of DO regeneration, and <i>PRRX1</i><sup>+</sup>MSCs act essential roles.</p>","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"102 9","pages":"1058-1068"},"PeriodicalIF":7.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9950714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-01DOI: 10.1177/00220345231174861
M I MacEntee, D M Brunette, A G Hannam
{"title":"George Simpson Beagrie (1923-2023).","authors":"M I MacEntee, D M Brunette, A G Hannam","doi":"10.1177/00220345231174861","DOIUrl":"https://doi.org/10.1177/00220345231174861","url":null,"abstract":"","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"102 7","pages":"705-706"},"PeriodicalIF":7.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10028721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-01DOI: 10.1177/00220345231167769
E-J Kim, H-Y Kim, L Li, Q Tang, K-H Kim, H Ohshima, H-S Jung
The enamel knot (EK), located at the center of cap stage tooth germs, is a transitory cluster of nondividing epithelial cells. The EK acts as a signaling center that provides positional information for tooth morphogenesis and regulates the growth of tooth cusps. To identify species-specific cuspal patterns, this study analyzed the cellular mechanisms in the EK that were related to bone morphogenetic protein (Bmp), which plays a crucial role in cell proliferation and apoptosis. To understand the cellular mechanisms in the EK, the differences between 2 species showing different cuspal patterning, mouse (pointy bunodont cusp) and gerbil (flat lophodont cusp), were analyzed with quantitative reverse transcriptase polymerase chain reaction and immunofluorescent staining. Based on these, we performed protein-soaked bead implantation on tooth germs of the 2 different EK regions and compared the cellular behavior in the EKs of the 2 species. Many genes related with cell cycle, cell apoptosis, and cell proliferation were involved in BMP signaling in the EK during tooth development. A comparison of the cell proliferation and apoptosis associated with Bmp revealed distinctive patterns of the cellular mechanisms. Our findings indicate that the cellular mechanisms, such as cell proliferation and apoptosis, in the EK are related to Bmp4 and play an important role in tooth morphogenesis.
{"title":"Cuspal Shape Alterations by Bmp4 Directing Cell Proliferation and Apoptosis.","authors":"E-J Kim, H-Y Kim, L Li, Q Tang, K-H Kim, H Ohshima, H-S Jung","doi":"10.1177/00220345231167769","DOIUrl":"https://doi.org/10.1177/00220345231167769","url":null,"abstract":"The enamel knot (EK), located at the center of cap stage tooth germs, is a transitory cluster of nondividing epithelial cells. The EK acts as a signaling center that provides positional information for tooth morphogenesis and regulates the growth of tooth cusps. To identify species-specific cuspal patterns, this study analyzed the cellular mechanisms in the EK that were related to bone morphogenetic protein (Bmp), which plays a crucial role in cell proliferation and apoptosis. To understand the cellular mechanisms in the EK, the differences between 2 species showing different cuspal patterning, mouse (pointy bunodont cusp) and gerbil (flat lophodont cusp), were analyzed with quantitative reverse transcriptase polymerase chain reaction and immunofluorescent staining. Based on these, we performed protein-soaked bead implantation on tooth germs of the 2 different EK regions and compared the cellular behavior in the EKs of the 2 species. Many genes related with cell cycle, cell apoptosis, and cell proliferation were involved in BMP signaling in the EK during tooth development. A comparison of the cell proliferation and apoptosis associated with Bmp revealed distinctive patterns of the cellular mechanisms. Our findings indicate that the cellular mechanisms, such as cell proliferation and apoptosis, in the EK are related to Bmp4 and play an important role in tooth morphogenesis.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"102 7","pages":"825-834"},"PeriodicalIF":7.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9737866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-01DOI: 10.1177/00220345231156162
E Schoebrechts, J de Almeida Mello, P Vandenbulcke, E Palmers, A Declercq, D Declerck, J Duyck
Introduction: The oral health (OH) of care-dependent older people is generally poor. Since caregivers are mainly responsible for older people's daily care, they can be considered important intermediaries to improve their OH by performing regular OH assessments. The interRAI instruments are introduced in 37 countries to assess care needs and facilitate care planning across different health care settings. The oral health section (OHS) within the interRAI instrument used in long-term care facilities was optimized for the Belgian context to identify residents who need assistance with daily oral care and/or need to be referred to a dentist. This Delphi study evaluated whether the OHS is also relevant and useful in other countries and modified the OHS accordingly until an international consensus was reached. Participants were experts in OH for older people. During 2 rounds of online questionnaires, experts rated the content, assessment process, triggering of Clinical Assessment Protocols, and accompanying guidelines and instruction videos of the optimized OHS. Based on the experts' comments and suggestions collected during the first round, the OHS was adjusted and presented to the experts in the second round for re-evaluation. The first and second questionnaires were completed by 48 and 42 oral health experts from 29 and 27 countries where the interRAI instruments are introduced, respectively. Five experts from 5 countries where interRAI is not introduced also participated in both rounds. After the second round, a consensus of over 86% was reached on all criteria. International consensus on the OHS was reached, considering national and cultural differences that may affect OH. The next step in this research is to evaluate the assessment process to identify potential barriers and facilitators to achieving reliable OH assessments internationally. Furthermore, the effect of the OHS at the level of the resident and of the caregivers will be evaluated.
{"title":"International Delphi Study to Optimize the Oral Health Section in interRAI.","authors":"E Schoebrechts, J de Almeida Mello, P Vandenbulcke, E Palmers, A Declercq, D Declerck, J Duyck","doi":"10.1177/00220345231156162","DOIUrl":"https://doi.org/10.1177/00220345231156162","url":null,"abstract":"<p><p><b>Introduction:</b> The oral health (OH) of care-dependent older people is generally poor. Since caregivers are mainly responsible for older people's daily care, they can be considered important intermediaries to improve their OH by performing regular OH assessments. The interRAI instruments are introduced in 37 countries to assess care needs and facilitate care planning across different health care settings. The oral health section (OHS) within the interRAI instrument used in long-term care facilities was optimized for the Belgian context to identify residents who need assistance with daily oral care and/or need to be referred to a dentist. This Delphi study evaluated whether the OHS is also relevant and useful in other countries and modified the OHS accordingly until an international consensus was reached. Participants were experts in OH for older people. During 2 rounds of online questionnaires, experts rated the content, assessment process, triggering of Clinical Assessment Protocols, and accompanying guidelines and instruction videos of the optimized OHS. Based on the experts' comments and suggestions collected during the first round, the OHS was adjusted and presented to the experts in the second round for re-evaluation. The first and second questionnaires were completed by 48 and 42 oral health experts from 29 and 27 countries where the interRAI instruments are introduced, respectively. Five experts from 5 countries where interRAI is not introduced also participated in both rounds. After the second round, a consensus of over 86% was reached on all criteria. International consensus on the OHS was reached, considering national and cultural differences that may affect OH. The next step in this research is to evaluate the assessment process to identify potential barriers and facilitators to achieving reliable OH assessments internationally. Furthermore, the effect of the OHS at the level of the resident and of the caregivers will be evaluated.</p>","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"102 8","pages":"901-908"},"PeriodicalIF":7.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9785996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-01DOI: 10.1177/00220345231160747
S Kageyama, S Sakata, J Ma, M Asakawa, T Takeshita, M Furuta, T Ninomiya, Y Yamashita
Ectopic enrichment of oral microbes in the gut is a notable alteration in gut microbial balance. These microbes are likely delivered from the oral cavity with saliva and food; however, evidence of oral-gut microbial transmission is insufficient and needs further investigation. In this observational study, we examined 144 pairs of saliva and stool samples collected from community-dwelling adults to verify the oral-gut microbial link and identify the relevant influencing factors on the increased abundance of oral microbes within the gut. The bacterial composition of each sample was determined using PacBio single-molecule long-read sequencing of the full-length 16S ribosomal RNA gene and amplicon sequence variant (ASV) analysis. Although the bacterial compositions of salivary and gut microbiota were distinctly different, at least 1 ASV was shared between salivary and gut microbiota in 72.9% of subjects. Shared ASVs accounted for 0.0% to 63.1% (median 0.14%) of the gut microbiota in each subject and frequently included abundant Streptococcus salivarius and Streptococcus parasanguinis. Their total relative abundance in the gut was significantly higher in older subjects or those with dental plaque accumulation. The gut microbiota with ≥5% of shared ASVs displayed a higher abundance of Streptococcus, Lactobacillus, and Klebsiella and a lower abundance of Faecalibacterium, Blautia, Megamonas, and Parabacteroides. Our study presents evidence for the translocation of oral bacteria to the gut in community-dwelling adults and suggests that aging and dental plaque accumulation contribute to an increased abundance of oral microbes in the gut, which might be relevant to the compositional shift in the gut commensals.
{"title":"High-Resolution Detection of Translocation of Oral Bacteria to the Gut.","authors":"S Kageyama, S Sakata, J Ma, M Asakawa, T Takeshita, M Furuta, T Ninomiya, Y Yamashita","doi":"10.1177/00220345231160747","DOIUrl":"https://doi.org/10.1177/00220345231160747","url":null,"abstract":"<p><p>Ectopic enrichment of oral microbes in the gut is a notable alteration in gut microbial balance. These microbes are likely delivered from the oral cavity with saliva and food; however, evidence of oral-gut microbial transmission is insufficient and needs further investigation. In this observational study, we examined 144 pairs of saliva and stool samples collected from community-dwelling adults to verify the oral-gut microbial link and identify the relevant influencing factors on the increased abundance of oral microbes within the gut. The bacterial composition of each sample was determined using PacBio single-molecule long-read sequencing of the full-length 16S ribosomal RNA gene and amplicon sequence variant (ASV) analysis. Although the bacterial compositions of salivary and gut microbiota were distinctly different, at least 1 ASV was shared between salivary and gut microbiota in 72.9% of subjects. Shared ASVs accounted for 0.0% to 63.1% (median 0.14%) of the gut microbiota in each subject and frequently included abundant <i>Streptococcus salivarius</i> and <i>Streptococcus parasanguinis</i>. Their total relative abundance in the gut was significantly higher in older subjects or those with dental plaque accumulation. The gut microbiota with ≥5% of shared ASVs displayed a higher abundance of <i>Streptococcus</i>, <i>Lactobacillus</i>, and <i>Klebsiella</i> and a lower abundance of <i>Faecalibacterium</i>, <i>Blautia</i>, <i>Megamonas</i>, and <i>Parabacteroides</i>. Our study presents evidence for the translocation of oral bacteria to the gut in community-dwelling adults and suggests that aging and dental plaque accumulation contribute to an increased abundance of oral microbes in the gut, which might be relevant to the compositional shift in the gut commensals.</p>","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"102 7","pages":"752-758"},"PeriodicalIF":7.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/11/23/10.1177_00220345231160747.PMC10288163.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9706514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-01DOI: 10.1177/00220345231165209
L-Z Zhang, J-G Yang, H-F Xia, J Huang, H-M Liu, M Wu, B Liu, W-M Wang, G Chen
Immune checkpoint molecule PD-1, expressed on the cell surface, impairs antigen-driven activation of T cells and thus plays a critical role in tumorigenesis, progression, and the poor prognosis of oral squamous cell carcinoma (OSCC). In addition, increasing evidence indicates that PD-1 carried on small extracellular vesicles (sEVs) also mediates tumor immunity, although their contributions to OSCC are yet unclear. Here, we investigated the biological functions of sEV PD-1 in patients with OSCC. The cell cycle, proliferation, apoptosis, migration, and invasion of CAL27 cell lines treated with or without sEV PD-1 were examined in vitro. We performed mass spectrometry to investigate the underlying biological process, combined with an immunohistochemical study of SCC7-bearing mice models and OSCC patient samples. In vitro data demonstrated that sEV PD-1 induced senescence and subsequent epithelial-mesenchymal transition (EMT) in CAL27 cells by ligating with tumor cell surface PD-L1 and activating the p38 mitogen-activated protein kinase (MAPK) pathway. Comprehensive immunohistochemical analysis of the xenograft mice models and OSCC patient samples revealed a very close correlation between the level of circulating sEV PD-1 and lymph node metastasis. These results demonstrate that circulating sEV PD-1 triggers senescence-initiated EMT in a PD-L1-p38 MAPK-dependent manner, contributing to tumor metastasis. It also suggests that the inhibition of sEV PD-1 may be a promising therapeutic target for the treatment of OSCC.
{"title":"PD-1 Carried on Small Extracellular Vesicles Leads to OSCC Metastasis.","authors":"L-Z Zhang, J-G Yang, H-F Xia, J Huang, H-M Liu, M Wu, B Liu, W-M Wang, G Chen","doi":"10.1177/00220345231165209","DOIUrl":"https://doi.org/10.1177/00220345231165209","url":null,"abstract":"<p><p>Immune checkpoint molecule PD-1, expressed on the cell surface, impairs antigen-driven activation of T cells and thus plays a critical role in tumorigenesis, progression, and the poor prognosis of oral squamous cell carcinoma (OSCC). In addition, increasing evidence indicates that PD-1 carried on small extracellular vesicles (sEVs) also mediates tumor immunity, although their contributions to OSCC are yet unclear. Here, we investigated the biological functions of sEV PD-1 in patients with OSCC. The cell cycle, proliferation, apoptosis, migration, and invasion of CAL27 cell lines treated with or without sEV PD-1 were examined <i>in vitro</i>. We performed mass spectrometry to investigate the underlying biological process, combined with an immunohistochemical study of SCC7-bearing mice models and OSCC patient samples. <i>In vitro</i> data demonstrated that sEV PD-1 induced senescence and subsequent epithelial-mesenchymal transition (EMT) in CAL27 cells by ligating with tumor cell surface PD-L1 and activating the p38 mitogen-activated protein kinase (MAPK) pathway. Comprehensive immunohistochemical analysis of the xenograft mice models and OSCC patient samples revealed a very close correlation between the level of circulating sEV PD-1 and lymph node metastasis. These results demonstrate that circulating sEV PD-1 triggers senescence-initiated EMT in a PD-L1-p38 MAPK-dependent manner, contributing to tumor metastasis. It also suggests that the inhibition of sEV PD-1 may be a promising therapeutic target for the treatment of OSCC.</p>","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"102 7","pages":"795-805"},"PeriodicalIF":7.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9737865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-01DOI: 10.1177/00220345231162336
D G Moussa, R W Kung, J S Tse, W L Siqueira
Dental caries remains the most widespread chronic disease worldwide. Basically, caries originates within biofilms accumulated on dental enamel. Despite the nonrenewable nature of the enamel tissue, targeted preventive strategies are still very limited. We previously introduced customized multifunctional proteinaceous pellicles (coatings) for controlling bacterial attachment and subsequent biofilm succession. Stemmed from our whole proteome/peptidome analysis of the in vivo acquired enamel pellicle, we designed these pellicles using hybrid mixtures of the most abundant and complementary-acting antimicrobial and antifouling proteins/peptides for synergetic suppression of early biofilms. In conjugating these domains synthetically, their bioinhibitory efficacy was remarkably boosted. Herein, we sought to explore the key structure-function relationship of these potent de novo hybridized conjugates in comparison with their individual domains, solely or in physical mixtures. Specifically, we interrelated the following facets: physicochemical and 3-dimensional folding characteristics via molecular dynamics simulations, adopted secondary structure by circular dichroism, immobilization capacity on enamel through high-spatial resolution multiphoton microscopy, and biofilm suppression potency. Our data showed consistent associations among the increased preference for protein folding structures, α-helix content, and enamel-immobilization capacity; all were inversely correlated with the attached bioburden. The expressed phenotypes could be explained by the adopted strongly amphipathic helical conformation upon conjugation, mediated by the highly anionic and acidic N-terminal pentapeptide shared region/motif for enhanced immobilization on enamel. In conclusion, conjugating bioactive proteins/peptides is a novel translational approach to engineer robust antibiofilm pellicles for caries prevention. The adopted α-helical conformation is key to enhance the antibiofilm efficacy and immobilization capacity on enamel that are promoted by certain physicochemical properties of the constituent domains. These data are valuable for bioengineering versatile therapeutics to prevent/arrest dental caries, a condition that otherwise requires invasive treatments with substantial health care expenditures.
{"title":"Mechanistic Insights into Bioengineered Antibiofilm Enamel Pellicles.","authors":"D G Moussa, R W Kung, J S Tse, W L Siqueira","doi":"10.1177/00220345231162336","DOIUrl":"https://doi.org/10.1177/00220345231162336","url":null,"abstract":"<p><p>Dental caries remains the most widespread chronic disease worldwide. Basically, caries originates within biofilms accumulated on dental enamel. Despite the nonrenewable nature of the enamel tissue, targeted preventive strategies are still very limited. We previously introduced customized multifunctional proteinaceous pellicles (coatings) for controlling bacterial attachment and subsequent biofilm succession. Stemmed from our whole proteome/peptidome analysis of the <i>in vivo</i> acquired enamel pellicle, we designed these pellicles using hybrid mixtures of the most abundant and complementary-acting antimicrobial and antifouling proteins/peptides for synergetic suppression of early biofilms. In conjugating these domains synthetically, their bioinhibitory efficacy was remarkably boosted. Herein, we sought to explore the key structure-function relationship of these potent <i>de novo</i> hybridized conjugates in comparison with their individual domains, solely or in physical mixtures. Specifically, we interrelated the following facets: physicochemical and 3-dimensional folding characteristics via molecular dynamics simulations, adopted secondary structure by circular dichroism, immobilization capacity on enamel through high-spatial resolution multiphoton microscopy, and biofilm suppression potency. Our data showed consistent associations among the increased preference for protein folding structures, α-helix content, and enamel-immobilization capacity; all were inversely correlated with the attached bioburden. The expressed phenotypes could be explained by the adopted strongly amphipathic helical conformation upon conjugation, mediated by the highly anionic and acidic N-terminal pentapeptide shared region/motif for enhanced immobilization on enamel. In conclusion, conjugating bioactive proteins/peptides is a novel translational approach to engineer robust antibiofilm pellicles for caries prevention. The adopted α-helical conformation is key to enhance the antibiofilm efficacy and immobilization capacity on enamel that are promoted by certain physicochemical properties of the constituent domains. These data are valuable for bioengineering versatile therapeutics to prevent/arrest dental caries, a condition that otherwise requires invasive treatments with substantial health care expenditures.</p>","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"102 7","pages":"743-751"},"PeriodicalIF":7.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10288165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9760126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-01DOI: 10.1177/00220345231164111
K Mokabari, M Iriti, E M Varoni
Vaccine technology has evolved continuously since its beginning, and mucosal vaccination, including intranasal, sublingual, and oral administrations, has recently gained great scientific interest. The oral mucosa represents a promising minimally invasive route for antigen delivery, mainly at sublingual and buccal mucosal sites, and it is easily accessible, immunologically rich, and able to promote an effective systemic and local immune response. The aim of this review is to provide an updated overview on the technologies for oral mucosal vaccination, with emphasis on mucoadhesive biomaterial-based delivery systems. Polymeric-based nanoparticles, multilayer films and wafers, liposomes, microneedles, and thermoresponsive gels are the most investigated strategies to deliver antigens locally, showing mucoadhesive properties, controlled release of the antigen, and the ability to enhance immunological responses. These formulations have achieved adequate properties in terms of vaccine stability, are minimally invasive, and are easy to produce and manage. To date, oral mucosa vaccine delivery systems represent a promising and open field of research. Future directions should focus on the role of these systems to induce sustained innate and adaptive immune responses, by integrating the recent advances achieved in mucoadhesion with those related to vaccine technology. Being painless, easy to administer, highly stable, safe, and effective, the antigen delivery systems via the oral mucosa may represent a useful and promising strategy for fast mass vaccination, especially during pandemic outbreaks.
{"title":"Mucoadhesive Vaccine Delivery Systems for the Oral Mucosa.","authors":"K Mokabari, M Iriti, E M Varoni","doi":"10.1177/00220345231164111","DOIUrl":"https://doi.org/10.1177/00220345231164111","url":null,"abstract":"<p><p>Vaccine technology has evolved continuously since its beginning, and mucosal vaccination, including intranasal, sublingual, and oral administrations, has recently gained great scientific interest. The oral mucosa represents a promising minimally invasive route for antigen delivery, mainly at sublingual and buccal mucosal sites, and it is easily accessible, immunologically rich, and able to promote an effective systemic and local immune response. The aim of this review is to provide an updated overview on the technologies for oral mucosal vaccination, with emphasis on mucoadhesive biomaterial-based delivery systems. Polymeric-based nanoparticles, multilayer films and wafers, liposomes, microneedles, and thermoresponsive gels are the most investigated strategies to deliver antigens locally, showing mucoadhesive properties, controlled release of the antigen, and the ability to enhance immunological responses. These formulations have achieved adequate properties in terms of vaccine stability, are minimally invasive, and are easy to produce and manage. To date, oral mucosa vaccine delivery systems represent a promising and open field of research. Future directions should focus on the role of these systems to induce sustained innate and adaptive immune responses, by integrating the recent advances achieved in mucoadhesion with those related to vaccine technology. Being painless, easy to administer, highly stable, safe, and effective, the antigen delivery systems via the oral mucosa may represent a useful and promising strategy for fast mass vaccination, especially during pandemic outbreaks.</p>","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"102 7","pages":"709-718"},"PeriodicalIF":7.6,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9674509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-01Epub Date: 2023-05-19DOI: 10.1177/00220345231167771
T Yamamoto, M Hanazato, H Hikichi, K Kondo, K Osaka, I Kawachi, J Aida
Access to dental clinics is a feature of the neighborhood service environment that may influence oral health care utilization. However, residential selection poses a challenge to causal inference. By studying the involuntary relocation of survivors of the 2011 Great East Japan Earthquake and Tsunami (GEJE), we examined the association between changes in geographic distance to dental clinics and dental visits. Longitudinal data from a cohort of older residents in Iwanuma City directly impacted by the GEJE were analyzed in this study. The baseline survey was conducted in 2010, 7 mo before the occurrence of GEJE, and a follow-up was conducted in 2016. Using Poisson regression models, we estimated the incidence rate ratios (IRR) and 95% confidence intervals (CIs) for the uptake of denture use (as a proxy for dental visits) according to changes in distance from the nearest dental clinic to their house. Age at baseline, housing damage by the disaster, deteriorating economic conditions, and worsened physical activity were used as confounders. Among the 1,098 participants who had not worn dentures before the GEJE, 495 were men (45.1%), with a mean ± SD age at baseline of 74.0 ± 6.9 y. During the 6-year follow-up, 372 (33.9%) participants initiated denture use. Compared to those who experienced a large increase in distance to dental clinics (>370.0-6,299.1 m), a large decrease in distance to dental clinics (>429.0-5,382.6 m) was associated with a marginally significantly higher initiation of denture use among disaster survivors (IRR = 1.28; 95% CI, 0.99-1.66). The experience of major housing damage was independently associated with higher initiation of denture use (IRR = 1.77; 95% CI, 1.47-2.14). Improved geographic access to dental clinics may increase dental visits of disaster survivors. Further studies in non-disaster-affected areas are needed to generalize these findings.
{"title":"Change in Geographic Accessibility to Dental Clinics Affects Access to Care.","authors":"T Yamamoto, M Hanazato, H Hikichi, K Kondo, K Osaka, I Kawachi, J Aida","doi":"10.1177/00220345231167771","DOIUrl":"10.1177/00220345231167771","url":null,"abstract":"<p><p>Access to dental clinics is a feature of the neighborhood service environment that may influence oral health care utilization. However, residential selection poses a challenge to causal inference. By studying the involuntary relocation of survivors of the 2011 Great East Japan Earthquake and Tsunami (GEJE), we examined the association between changes in geographic distance to dental clinics and dental visits. Longitudinal data from a cohort of older residents in Iwanuma City directly impacted by the GEJE were analyzed in this study. The baseline survey was conducted in 2010, 7 mo before the occurrence of GEJE, and a follow-up was conducted in 2016. Using Poisson regression models, we estimated the incidence rate ratios (IRR) and 95% confidence intervals (CIs) for the uptake of denture use (as a proxy for dental visits) according to changes in distance from the nearest dental clinic to their house. Age at baseline, housing damage by the disaster, deteriorating economic conditions, and worsened physical activity were used as confounders. Among the 1,098 participants who had not worn dentures before the GEJE, 495 were men (45.1%), with a mean ± SD age at baseline of 74.0 ± 6.9 y. During the 6-year follow-up, 372 (33.9%) participants initiated denture use. Compared to those who experienced a large increase in distance to dental clinics (>370.0-6,299.1 m), a large decrease in distance to dental clinics (>429.0-5,382.6 m) was associated with a marginally significantly higher initiation of denture use among disaster survivors (IRR = 1.28; 95% CI, 0.99-1.66). The experience of major housing damage was independently associated with higher initiation of denture use (IRR = 1.77; 95% CI, 1.47-2.14). Improved geographic access to dental clinics may increase dental visits of disaster survivors. Further studies in non-disaster-affected areas are needed to generalize these findings.</p>","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"102 7","pages":"719-726"},"PeriodicalIF":5.7,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10286177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9706513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}