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Search Results (2,008)

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26 pages, 1229 KiB  
Review
Oral Pathobiont-Derived Outer Membrane Vesicles in the Oral–Gut Axis
by Eduardo A. Catalan, Emilio Seguel-Fuentes, Brandon Fuentes, Felipe Aranguiz-Varela, Daniela P. Castillo-Godoy, Elizabeth Rivera-Asin, Elisa Bocaz, Juan A. Fuentes, Denisse Bravo, Katina Schinnerling and Felipe Melo-Gonzalez
Int. J. Mol. Sci. 2024, 25(20), 11141; https://doi.org/10.3390/ijms252011141 (registering DOI) - 17 Oct 2024
Viewed by 40
Abstract
Oral pathobionts are essential in instigating local inflammation within the oral cavity and contribute to the pathogenesis of diseases in the gastrointestinal tract and other distant organs. Among the Gram-negative pathobionts, Porphyromonas gingivalis and Fusobacterium nucleatum emerge as critical drivers of periodontitis, exerting [...] Read more.
Oral pathobionts are essential in instigating local inflammation within the oral cavity and contribute to the pathogenesis of diseases in the gastrointestinal tract and other distant organs. Among the Gram-negative pathobionts, Porphyromonas gingivalis and Fusobacterium nucleatum emerge as critical drivers of periodontitis, exerting their influence not only locally but also as inducers of gut dysbiosis, intestinal disturbances, and systemic ailments. This dual impact is facilitated by their ectopic colonization of the intestinal mucosa and the subsequent mediation of distal systemic effects by releasing outer membrane vesicles (OMVs) into circulation. This review elucidates the principal components of oral pathobiont-derived OMVs implicated in disease pathogenesis within the oral–gut axis, detailing virulence factors that OMVs carry and their interactions with host epithelial and immune cells, both in vitro and in vivo. Additionally, we shed light on the less acknowledged interplay between oral pathobionts and the gut commensal Akkermansia muciniphila, which can directly impede oral pathobionts’ growth and modulate bacterial gene expression. Notably, OMVs derived from A. muciniphila emerge as promoters of anti-inflammatory effects within the gastrointestinal and distant tissues. Consequently, we explore the potential of A. muciniphila-derived OMVs to interact with oral pathobionts and prevent disease in the oral–gut axis. Full article
(This article belongs to the Special Issue Role of Extracellular Vesicles in Immunology)
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<p>Inflammation and gut dysbiosis induced by oral pathobionts. Outer membrane vesicles (OMVs) of <span class="html-italic">Porphyromonas gingivalis</span> (<span class="html-italic">Pg</span>) and <span class="html-italic">Fusobacterium nucleatum</span> (<span class="html-italic">Fn</span>) transport various virulence factors from the oral cavity to the gut and other distal organs via blood circulation. Subsequently, <span class="html-italic">Pg</span> and <span class="html-italic">Fn</span> could induce inflammation and gut dysbiosis through their OMVs. Created with BioRender (<a href="https://www.biorender.com/" target="_blank">https://www.biorender.com/</a>, accessed on 1 June 2024).</p>
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<p>Proposed model for <span class="html-italic">Akkermansia muciniphila</span>-mediated regulation of oral pathobiont-induced disease at the oral–gut axis. <span class="html-italic">Akkermansia muciniphila</span> (<span class="html-italic">Am</span>) and its OMVs are suggested to exert protective effects, mitigating periodontitis in experimental models and reducing the expression of virulence factors in <span class="html-italic">Porphyromonas gingivalis</span> (<span class="html-italic">Pg</span>) and <span class="html-italic">Fusobacterium nucleatum</span> (<span class="html-italic">Fn</span>). In the gut, <span class="html-italic">Am</span> contributes to maintaining barrier integrity and promoting the expansion of beneficial commensal species, thereby reducing the severity of colitis in mice. Additionally, <span class="html-italic">Am</span> may potentiate the efficacy of cancer immunotherapy. Up and down arrows indicate an increase or decrease in each indicated parameter, respectively. Question marks (shown as “?”) indicate areas where evidence is still inconclusive or remains to be explored. Created with BioRender.</p>
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20 pages, 2552 KiB  
Review
Advances and Functional Integration of Hydrogel Composites as Drug Delivery Systems in Contemporary Dentistry
by Dragos Nicolae Fratila, Dragos Ioan Virvescu, Ionut Luchian, Monica Hancianu, Elena Raluca Baciu, Oana Butnaru and Dana Gabriela Budala
Gels 2024, 10(10), 661; https://doi.org/10.3390/gels10100661 - 16 Oct 2024
Viewed by 463
Abstract
This study explores the recent advances of and functional insights into hydrogel composites, materials that have gained significant attention for their versatile applications across various fields, including contemporary dentistry. Hydrogels, known for their high water content and biocompatibility, are inherently soft but often [...] Read more.
This study explores the recent advances of and functional insights into hydrogel composites, materials that have gained significant attention for their versatile applications across various fields, including contemporary dentistry. Hydrogels, known for their high water content and biocompatibility, are inherently soft but often limited by mechanical fragility. Key areas of focus include the customization of hydrogel composites for biomedical applications, such as drug delivery systems, wound dressings, and tissue engineering scaffolds, where improved mechanical properties and bioactivity are critical. In dentistry, hydrogels are utilized for drug delivery systems targeting oral diseases, dental adhesives, and periodontal therapies due to their ability to adhere to the mucosa, provide localized treatment, and support tissue regeneration. Their unique properties, such as mucoadhesion, controlled drug release, and stimuli responsiveness, make them ideal candidates for treating oral conditions. This review highlights both experimental breakthroughs and theoretical insights into the structure–property relationships within hydrogel composites, aiming to guide future developments in the design and application of these multifunctional materials in dentistry. Ultimately, hydrogel composites represent a promising frontier for advancing materials science with far-reaching implications in healthcare, environmental technology, and beyond. Full article
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<p>Potential uses of hydrogels in the dental field.</p>
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<p>Hydrogel characteristics and classification (with IPN—interpenetrating polymer network).</p>
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<p>The action mechanisms of a smart hydrogel.</p>
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<p>Structures of hydrogels and nanogels.</p>
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<p>The pathway of a drug delivery system to treat periodontal disease.</p>
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17 pages, 1274 KiB  
Protocol
An Innovative One Health Approach: BIOQUALIM, a Transdisciplinary Research Action Protocol—From Cultivated Biodiversity to Human Health Prevention
by Audrey Murat-Ringot, Romain Lan, Laurie Fraticelli, Yohan Fayet, Denis Bourgeois, Rita Nugem, Maëva Piton, Emmie Goetz, Marie Préau, Fabien Dutertre, Nathalie Bernoud-Hubac, Lama Basbous, Anne Lastmann, Marie-Thérèse Charreyre and Florence Carrouel
Nutrients 2024, 16(20), 3495; https://doi.org/10.3390/nu16203495 (registering DOI) - 15 Oct 2024
Viewed by 442
Abstract
Background/Objectives: The “One Health” approach underscores the connection between human, animal, and environmental health, promoting solutions to global challenges like climate change and biodiversity loss. The Planetary Health Diet (PHD) promotes a plant-based diet with organically grown plants to reduce the environmental impact [...] Read more.
Background/Objectives: The “One Health” approach underscores the connection between human, animal, and environmental health, promoting solutions to global challenges like climate change and biodiversity loss. The Planetary Health Diet (PHD) promotes a plant-based diet with organically grown plants to reduce the environmental impact of meat production and decrease the risk of non-communicable diseases (NCDs). The BIOQUALIM project will evaluate the PHD’s effectiveness in preventing NCDs like periodontal diseases and cancers through four inter-related studies. Methods: The clinical study will involve volunteers reducing their meat consumption and incorporating einkorn into their diet, allow for analysis of their interdental microbiota, oral health, general health, and quality of life. The chemical analysis will study nutrients and anti-cancer compounds in einkorn and common wheat varieties. The behavioral study will explore PHD knowledge, attitudes, and behaviors related to PHD. The psycho-social study will evaluate the impact of peer-support workshops on plant-based dietary cooking among post-therapy cancer patients. Results: The results are expected to demonstrate that einkorn varieties possess nutritional properties that, when incorporated into the PHD enriched with einkorn, can enhance health markers. This study will identify barriers to and facilitators of PHD adoption and highlight how peer-support workshops can improve dietary adherence. Conclusions: BIOQUALIM’s transdisciplinary approach will demonstrate the PHD’s role in preventing NCDs. Full article
(This article belongs to the Section Nutrition and Public Health)
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<p>The studies of the BIOQUALIM project. Made by the authors from a Canva model.</p>
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<p>Summary of BIOQUALIM project.</p>
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<p>A flow chart diagram of the “clinical study”. BOP: Bleeding On Probing, GI: Gingivitis Index, PI: Plaque Index, CAL: Clinical Attachment Level, PPD: Probing Pocket Depth, and BMI: Body Mass Index.</p>
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10 pages, 1724 KiB  
Article
Associations between Systemic and Dental Diseases in Elderly Korean Population
by Se Hoon Kahm and SungEun Yang
Medicina 2024, 60(10), 1693; https://doi.org/10.3390/medicina60101693 (registering DOI) - 15 Oct 2024
Viewed by 438
Abstract
Background and Objectives: Modernization and population aging have increased the prevalence of systemic diseases, such as diabetes and hypertension, which are often accompanied by various dental diseases. Our aim was to investigate associations between common dental conditions and major systemic diseases in an [...] Read more.
Background and Objectives: Modernization and population aging have increased the prevalence of systemic diseases, such as diabetes and hypertension, which are often accompanied by various dental diseases. Our aim was to investigate associations between common dental conditions and major systemic diseases in an elderly Korean population. Materials and Methods: Utilizing electronic medical record data from 43,525 elderly patients, we examined the prevalence of systemic diseases (diabetes, hypertension, rheumatoid arthritis, osteoporosis, dementia) and dental conditions (caries, periodontal disease, pulp necrosis, tooth loss). The analysis focused on the correlations between these diseases. Results: Significant associations were found between systemic diseases and an increased prevalence of dental conditions. Patients with systemic diseases, especially those with multiple conditions, had higher incidences of periodontal disease and tooth loss. The correlation was particularly strong in patients with diabetes and rheumatoid arthritis. Interestingly, temporomandibular joint disorder was less frequent in this cohort. Conclusions: The findings highlight the importance of integrated dental care in managing systemic diseases in elderly populations. Enhanced dental monitoring and proactive treatment are essential due to the strong association between systemic diseases and dental conditions. Collaboration between dental and medical professionals is crucial for comprehensive care that improves health outcomes and quality of life for elderly patients. Full article
(This article belongs to the Special Issue Boundaries Between Oral and General Health)
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<p>Flow diagram for the determination of the study population for assessment.</p>
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<p>Distribution of included patients by sex and age.</p>
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<p>Odds ratios of single systemic diseases for dental disease. The red line represents Odds Ratio = 1.0. Values to the right indicate a higher observation of the dental diseases.</p>
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<p>Odds ratios of complex systemic diseases for dental disease. The red line represents Odds Ratio = 1.0. Values to the right indicate a higher observation of the dental diseases.</p>
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<p>Odds ratios of single and complex systemic diseases for dental diseases. The red line represents Odds Ratio = 1.0. Values to the right indicate a higher observation of the dental diseases.</p>
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13 pages, 1626 KiB  
Case Report
Genetic Testing as a Source of Information Driving Diagnosis and Therapeutic Plan in a Multidisciplinary Case
by Cristina Grippaudo, Concetta Cafiero, Nicola Maria Grande, Leonardo Dassatti, Raffaele Palmirotta, Raffaella Castagnola and Gaetano Isola
Bioengineering 2024, 11(10), 1023; https://doi.org/10.3390/bioengineering11101023 - 14 Oct 2024
Viewed by 346
Abstract
In many cases, the etiopathogenesis of oral cavity diseases depends on the presence of variants in some genes. Being able to identify these variants defines the possibilities and limits of therapies. This multidisciplinary case describes several pathologies of the oral cavity in a [...] Read more.
In many cases, the etiopathogenesis of oral cavity diseases depends on the presence of variants in some genes. Being able to identify these variants defines the possibilities and limits of therapies. This multidisciplinary case describes several pathologies of the oral cavity in a young patient affected by type 1 diabetes. The patient presented with an impacted palatal canine. Further investigation revealed cervical root resorption of the upper right central incisor. Genetic testing was performed for interleukin, VDR receptor genes, and the evaluation of periodontopathogenic bacteria. The mutational analysis carried out for the VDR polymorphisms and the IL1A, IL1B, IL6, and IL10 polymorphisms showed the presence of pathogenetic variants. The results for bacterial load showed the presence of periodontal pathogenes. The first intervention was the intentional replantation of the incisor. The second intervention was the orthodontic recovery of the impacted canine, using light forces and a hybrid anchorage with a miniscrew. At the end of orthodontic treatment, a crack was found in the upper left first premolar, which was extracted. Throughout treatment, non-invasive periodontal interventions were performed periodically to control periodontal inflammation. This case is an example of the integration of genetic analyses into the multidisciplinary diagnostic pathway. Full article
(This article belongs to the Special Issue New Tools for Multidisciplinary Treatment in Dentistry)
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<p>Intraoral photograph of the patient in 2018 at the beginning of treatment.</p>
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<p>This image shows a sagittal view of 1.1 and 1.3 teeth on the cone beam computed tomography (CBCT) scan. ECR, asymptomatic apical periodontitis, and the impacted canine are visible.</p>
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<p>Periapical radiography of the 1.1 tooth after intentional reimplantation and the removal of the splint.</p>
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<p>Orthodontic appliance: the device is anchored on molar bands on the upper first molar and the palatal screw. This device was used to pull the impacted canine into place in the dental arch.</p>
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<p>Intraoral photograph at the end of orthodontic treatment.</p>
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14 pages, 24194 KiB  
Case Report
Antimicrobial Photodynamic Therapy Combined with Photobiomodulation Therapy in Teeth with Asymptomatic Apical Periodontitis: A Case Series
by Francisco Rubio, Josep Arnabat-Domínguez, Eulàlia Sans-Serramitjana, Camila Saa, Kinga Grzech-Leśniak and Pablo Betancourt
Appl. Sci. 2024, 14(20), 9341; https://doi.org/10.3390/app14209341 (registering DOI) - 14 Oct 2024
Viewed by 351
Abstract
Introduction: Apical periodontitis (AP) is an inflammatory disease of the periapical tissues that is often asymptomatic and diagnosed through radiographic examination. A challenge in traditional endodontics is disinfection of the root canal system (RCS), which anatomically presents numerous variations, often leading to persistent [...] Read more.
Introduction: Apical periodontitis (AP) is an inflammatory disease of the periapical tissues that is often asymptomatic and diagnosed through radiographic examination. A challenge in traditional endodontics is disinfection of the root canal system (RCS), which anatomically presents numerous variations, often leading to persistent infections. Antimicrobial photodynamic therapy (aPDT) and photobiomodulation therapy (PBMT) offer promising adjuncts, due to their antimicrobial and tissue-healing properties. Objective: The aim of this article was to report five cases of teeth with pulp necrosis and asymptomatic apical periodontitis (AAP) treated with aPDT and PBMT protocols. Materials and Methods: Five cases of pulp necrosis and AAP were treated with conventional endodontic therapy supplemented with aPDT and PBMT. The treatment protocol included chemomechanical preparation (CMP), aPDT using a 660 nm diode laser (DL) with methylene blue (MB) as a photosensitizer (5 min pre-irradiation time), and PBMT using a 940 nm DL. Treatment results were evaluated through cone-beam computed tomography (CBCT)-based evaluation over 1 year of clinical follow-up. Results: All cases showed significant bone regeneration and tissue healing, demonstrating the efficacy of the combination of aPDT and PBMT. Post-operative pain did not occur in any of the patients, suggesting a possible analgesic effect of PBMT. Conclusions: The combination of aPDT and PBMT in endodontic therapy promoted tissue recovery and improved the prognosis of AAP. Further research and randomized control trials are needed to optimize treatment protocols and evaluate the long-term effects. Full article
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<p>Schematic representation of mechanisms of antimicrobial photodynamic therapy: (<b>A</b>) When light is absorbed, the PS is activated, shifting from its ground state to an excited singlet state. This excited state may undergo inter-system crossing, where the spin quantum number changes, resulting in a lower-energy, longer-lasting triplet state. The triplet state can then react through one or both of the oxygen-dependent mechanisms, known as Type I and Type II photoprocesses; (<b>B</b>) in the type I pathway, electron transfer reactions occur from the triplet PS state, involving a substrate to form radical ions (free radicals), which can then interact with oxygen to generate cytotoxic species such as superoxide, hydroxyl radicals, and lipid radicals. In contrast, in the Type II pathway, energy transfer from the triplet PS state to ground-state molecular oxygen occurs, producing singlet oxygen which can oxidize biological molecules such as proteins, nucleic acids, and lipids, leading to cytotoxic outcomes.</p>
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<p>Schematic of the mechanisms of action and clinical effects of photobiomodulation: (<b>A</b>) Cytochrome C oxidase (CCO), the primary chromophore located in complex IV of the mitochondrial respiratory chain, plays a critical role in PBMT. When CCO absorbs light (particularly in the red and near-infrared wavelengths), it leads to the photodissociation of nitric oxide (NO). This process reduces oxidative stress and subsequently boosts the production of reactive oxygen species (ROS), ATP, and calcium ions (Ca<sup>2+</sup>). As a result of increased ATP and protein synthesis, the growth factor response within cells and tissue occurs. These changes promote the desired biological responses, including anti-inflammatory, analgesic, and healing effects, while also enhancing cellular processes such as differentiation, proliferation, and migration. For these effects to occur, light must be absorbed by chromophores, which are interrelated molecules (e.g., enzymes, cell membranes, and extracellular substances) that have the capacity to absorb light. (<b>B</b>) Extraoral application of laser (red/infrared) directed toward the apical area of the affected tooth. By irradiating this area as a supplement to the endodontic treatment, accelerated bone tissue regeneration can be achieved.</p>
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<p>Three-dimensional CBCT images of tooth 1.2. (<b>A</b>–<b>C</b>) Coronal, sagittal, and axial pre-treatment sections. The CBCT examination showed an osteolytic lesion of dimensions 14 × 11 × 9 mm, causing expansion and fenestration of the vestibular table. (<b>D</b>–<b>F</b>) Coronal, sagittal, and axial post-laser treatment images show evident bone tissue gain, including recovery of the vestibular bone table.</p>
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<p>Intracanal disinfection with aPDT was conducted utilizing a DL with the following specifications: wavelength 660 ± 10 nm, power 100 mW. (<b>A</b>) MB inside the root canal and pulp chamber; (<b>B</b>) the laser used for all cases was therapy EC; (<b>C</b>) activation of MB using laser light inside the root canal; (<b>D</b>) the PBMT treatment entailed employing a wavelength of 940 ± 10 nm, one spot measuring 0.2 cm<sup>2</sup>, and a power of 0.1 W.</p>
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<p>CBCT images of teeth 1.1 and 2.1: (<b>A</b>–<b>C</b>) Coronal, sagittal, and axial pre-treatment images show an osteolytic lesion measuring 11 × 10 × 8 mm, resulting in expansion and fenestration of the vestibular table and (<b>D</b>–<b>F</b>) coronal, sagittal, and axial post-treatment images, which evidence significant bone regeneration in the affected area.</p>
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<p>CBCT images of tooth 1.2: (<b>A</b>–<b>C</b>) Coronal, Sagittal, and axial pre-treatment images revealed an osteolytic lesion measuring 10 × 10 × 8 mm, resulting in expansion and fenestration of the vestibular table and (<b>D</b>–<b>F</b>) coronal, sagittal, and axial post-treatment images. Notice the gain of bone tissue throughout the affected area.</p>
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<p>CBCT images of tooth 3.3. Coronal, axial, and transverse CBCT views at pre-treatment (<b>A</b>–<b>C</b>) and post-treatment (<b>D</b>–<b>F</b>). The apical lesion initially measured 10 × 9 × 8 mm. A clear recovery of trabecular and buccal cortical bone can be observed, when comparing images C and F, after using conventional endodontic therapy combined with laser therapy in both its aPDT and PBMT modalities.</p>
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<p>CBCT images of tooth 2.7. Coronal, sagittal, and axial CBCT images before (<b>A</b>–<b>C</b>) and after treatment (<b>D</b>–<b>F</b>). The three-dimensional CBCT study reveals an osteolytic lesion measuring 9 × 9 × 6 mm at the apical level, affecting the mesiobuccal and distobuccal roots. Comparing images C and F, it can be observed that, after 1 year of laser therapy, the lesion had satisfactorily resolved.</p>
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<p>Control periapical X-rays of the five cases treated with conventional non-surgical endodontics supplemented with aPDT and PBMT: (<b>A</b>) Case 1, Tooth 1.2. An apical puff can be observed. (<b>B</b>) Case 2, Teeth 1.1 and 2.1. The root canals appear fully obturated. (<b>C</b>) Case 3, Tooth 1.2. A straight root canal is completely sealed. (<b>D</b>) Case 4, Tooth 3.3. The tooth is obturated in the cervical, middle, and apical thirds. (<b>E</b>) Case 5, Tooth 2.7. Endodontic obturation of the mesiobuccal, distobuccal, and palatal canals is visible. In all cases, bone tissue regeneration can be observed at the apical level.</p>
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19 pages, 2073 KiB  
Review
A Natural Approach to the Prevention and Treatment of Gingivitis and Periodontitis: A Review of Pomegranate’s Bioactive Properties
by Georgiana Ioana Potra Cicalău, Laura Grațiela Vicaș, Gabriela Ciavoi, Timea Claudia Ghitea, Nagy Csaba, Roxana Alexandra Cristea, Florina Miere (Groza) and Mariana Ganea
Life 2024, 14(10), 1298; https://doi.org/10.3390/life14101298 - 13 Oct 2024
Viewed by 492
Abstract
(1) Background: This systematic review explores the bioactive properties of Punica granatum (pomegranate) and its potential applications in the prevention and treatment of gingivitis, periodontitis, and other oral diseases. (2) Methods: A comprehensive literature search was conducted using PubMed and Google Scholar, focusing [...] Read more.
(1) Background: This systematic review explores the bioactive properties of Punica granatum (pomegranate) and its potential applications in the prevention and treatment of gingivitis, periodontitis, and other oral diseases. (2) Methods: A comprehensive literature search was conducted using PubMed and Google Scholar, focusing on pomegranate and oral diseases. Inclusion criteria included studies evaluating the effects of pomegranate on oral health, while exclusion criteria eliminated non-peer-reviewed and non-English articles. This review aims to assess the efficacy of pomegranate extracts as a natural alternative to synthetic pharmaceuticals in oral health care. A structured search strategy included key terms such as “pomegranate”, “oral health”, “gingivitis”, and “periodontitis”. A total of 125 relevant references were reviewed to identify the most pertinent findings. (3) Results: The results indicate that pomegranate extracts have demonstrated efficacy in reducing plaque, inhibiting harmful oral microorganisms, and promoting overall oral health. Furthermore, clinical studies highlight the potential of pomegranate-based products, such as mouthwashes and gels, as viable alternatives to conventional pharmaceuticals, particularly in resource-limited settings. However, the review also notes the need for further research, particularly in the form of clinical trials, to establish optimal formulations and long-term safety. (4) Conclusions: Pomegranate presents a promising, natural solution for preventing and treating gingivitis and periodontitis. Further studies should focus on long-term effects and clinical efficacy. Full article
(This article belongs to the Special Issue Advances in the Biomedical Applications of Plants and Plant Extracts)
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<p>PRISMA flowchart of the study selection process.</p>
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<p>The content of polyphenols and tannins of <span class="html-italic">Punica granatum</span>.</p>
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<p>Fatty acid content of <span class="html-italic">Punica granatum</span> seeds.</p>
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<p>Triterpenoid content of <span class="html-italic">Punica granatum</span> flowers.</p>
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<p>Chemical structures of the major active substances in <span class="html-italic">Punica granatum</span>.</p>
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10 pages, 245 KiB  
Article
Screening for Systemic Diseases Associated with Dental Self-Care in Japanese Adolescents
by Masanobu Abe, Akihisa Mitani, Kazuto Hoshi and Shintaro Yanagimoto
J. Clin. Med. 2024, 13(20), 6087; https://doi.org/10.3390/jcm13206087 - 12 Oct 2024
Viewed by 306
Abstract
Background: Toothbrushing is important for maintaining oral health and preventing periodontal disease. However, the association between toothbrushing and systemic diseases remains unclear in adolescence. In this study, the association between dental self-care (frequency and duration of toothbrushing) and systemic diseases/disorders in adolescents was [...] Read more.
Background: Toothbrushing is important for maintaining oral health and preventing periodontal disease. However, the association between toothbrushing and systemic diseases remains unclear in adolescence. In this study, the association between dental self-care (frequency and duration of toothbrushing) and systemic diseases/disorders in adolescents was examined. Methods: We conducted a retrospective review of mandatory medical questionnaires administered during legally mandated freshman medical checkups between 2017 and 2019 at the University of Tokyo, Japan. Out of 9376 total responses, 9098 cases involving individuals under the age of 20 were included in the analysis. Respondents were classified into three groups based on their daily toothbrushing frequency: “1 time or less”, “twice”, and “3 times or more”. For the duration of each toothbrushing session, they were classified into three groups: “1 min or less”, “2–3 min”, and “4 min or more”. A statistical analysis was performed by Pearson’s χ2 test and multinomial logistic regression analysis. Results: Regarding frequency of daily toothbrushing: The χ2 test showed no significant relationship between frequency of toothbrushing and 17 systemic diseases/disorders. A multivariate analysis found that gingival bleeding and sex were independent factors. The risk of gingival bleeding decreased dramatically with increased frequency of toothbrushing (odds ratio (OR): 0.428; 95% confidence interval (CI), 0.366–0.501; p < 0.001). Regarding the amount of time spent on toothbrushing: The χ2 test showed atopic dermatitis and arrhythmia were significantly associated with the duration of toothbrushing (p = 0.032 and p = 0.016, respectively). In the multivariate analysis, atopic dermatitis, gingival bleeding, and sex were independent factors regarding the duration of toothbrushing; longer brushing time was associated with a lower risk of atopic dermatitis (OR: 0.731, 95% CI: 0.578–0.924, p = 0.009) and a lower risk of gingival bleeding (OR: 0.643, 95% CI: 0.567–0.729, p < 0.001). Conclusions: Dental self-care was most strongly associated with gingival bleeding, while the risk of atopic dermatitis was found to increase with shorter toothbrushing times. The results suggest that dental self-care during adolescence is important not only for oral health but also for general health. Full article
(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)
12 pages, 4398 KiB  
Article
Impacts of Hyperglycemia on Epigenetic Modifications in Human Gingival Fibroblasts and Gingiva in Diabetic Rats
by Kento Kojima, Nobuhisa Nakamura, Airi Hayashi, Shun Kondo, Megumi Miyabe, Takeshi Kikuchi, Noritaka Sawada, Tomokazu Saiki, Tomomi Minato, Reina Ozaki, Sachiko Sasajima, Akio Mitani and Keiko Naruse
Int. J. Mol. Sci. 2024, 25(20), 10979; https://doi.org/10.3390/ijms252010979 - 12 Oct 2024
Viewed by 321
Abstract
Periodontal disease is considered one of the diabetic complications with high morbidity and severity. Recent studies demonstrated the involvement of the epigenome on diabetic complications. Histone modifications change chromatin architecture and gene activation. Histone modifications have been reported to alter chromatin structure and [...] Read more.
Periodontal disease is considered one of the diabetic complications with high morbidity and severity. Recent studies demonstrated the involvement of the epigenome on diabetic complications. Histone modifications change chromatin architecture and gene activation. Histone modifications have been reported to alter chromatin structure and regulate gene transcription. In this study, we investigated the impacts of H3 lysine 4 trimethylation (H3K4me3) and specific histone methyltransferases of H3K4 methylation, su(var)3-9, enhancer-of-zeste, and trithorax domain 1A (SETD1A) on periodontal tissue affected by the diabetic condition. We observed the increase in H3K4me3 and SETD1A in gingival tissue of diabetic rats compared with the normal rats. Cultured human fibroblasts (hGFs) confirmed a high glucose-induced increase in H3K4me3 and SETD1A. We further demonstrated that high glucose increased the gene expression of matrix metalloproteinase (MMP) 1 and MMP13, which were canceled by sinefungin, an SETD1A inhibitor. Our investigation suggests that diabetes triggers histone modifications in the gingival tissue, resulting in gingival inflammation. Histone modifications may play crucial roles in the development of periodontal disease in diabetes. Full article
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<p>Comparison of alveolar bone between control group and diabetic group. (<b>A</b>) Three-dimensional reconstructed image of alveolar bone using microcomputed tomography (µCT). Scale = 3000 µm. (<b>B</b>) Alveolar bone was assessed by µCT of the distance from the cement–enamel junction (CEJ) to the alveolar bone crest (ABC). The results are presented as the mean ± S.E.M. (<span class="html-italic">n</span> = 6).</p>
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<p>Expression of H3K4me3 and SETD1A in periodontal tissue in the control and diabetes groups. The expression of local H3K4me3 and SETD1A in gingival tissues was visualized by immunohistochemical staining. The immunofluorescence staining of nuclei stained with 4′,6-diamidino-2-phenylindole (DAPI, blue) and H3K4me3 (red), SETD1A (red) was performed. (<b>A</b>) Low-power images of H3K4me3 in the periapical maxillary second molar gingiva of control and diabetic rats. Scale bar = 50 µm (×20). (<b>B</b>) High-magnification images of H3K4me3. Scale bar = 50 µm (×40). (<b>C</b>) Quantitative measurement of H3K4me3 expression per cell was performed using Image J (<span class="html-italic">n</span> = 4). (<b>D</b>) Low-power image of SETD1A in the periapical maxillary second molar gingiva of normal and diabetes rats. Scale bar = 50 µm (×20). (<b>E</b>) High-magnification images of SETD1A. Scale bar = 50 µm (×40). (<b>F</b>) Quantitative measurement of SETD1A expression per cell was performed using Image J. * <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Immunohistochemical staining revealed changes in the expression of histone-methylated proteins (H3K4me3) and histone methyltransferases (SETD1A) owing to high glucose levels. The immunofluorescence staining of the nuclei with DAPI (blue), H3K4me3 (red), and SETD1A (red) was performed. (<b>A</b>) H3K4me3 stained images of control, high glucose, and high glucose with sinefungin. Scale bar = 50 µm (×40). (<b>B</b>) ImageJ software (<span class="html-italic">n</span> = 6) was used to quantitatively measure the H3K4me3 expression per cell. (<b>C</b>) SETD1A stained images of control, high glucose, and high glucose with sinefungin. Scale bar = 50 µm (×40). (<b>D</b>) ImageJ software (<span class="html-italic">n</span> = 6) was used to quantitatively measure the SETD1A expression per cell. ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>The expression of MMPs and TIMPs in cells cultured with D-glucose (27.5 mM) was inhibited by sinefungin. The hGFs were cultured with D-glucose (27.5 mM) and inhibited by sinefungin. The mRNA expression levels of MMP1, MMP13, and TIMP1 were analyzed using real-time polymerase chain reaction. Results are presented as the mean ± S.E.M. (<span class="html-italic">n</span> = 6). * <span class="html-italic">p</span> &lt; 0.05. The ratio was calculated and analyzed using comparative quantitative values of MMP and TIMP (<span class="html-italic">n</span> = 6). * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>Schematic of mechanisms of increasing susceptibility to periodontal disease in diabetes. Hyperglycemia-induced upregulation of SETD1A increases H3K4me3 levels, which in turn leads to elevated expression of MMPs.</p>
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12 pages, 2984 KiB  
Article
Response of a Blood Clot Adherent to Bone, Oral Mucosa and Hard Dental Tissues to a Uniaxial Tensile Test: An In Vitro Study
by Gaia Pellegrini, Roberto Fedele, Daniela Carmagnola, Claudia Dellavia, Giorgio Pagni, Dolaji Henin, Gianguido Cossellu, Sabrine Fessi and Giulio Rasperini
Medicina 2024, 60(10), 1673; https://doi.org/10.3390/medicina60101673 - 12 Oct 2024
Viewed by 317
Abstract
Background and Objectives: Periodontal therapy aims to arrest the progression of periodontal diseases and possibly to regenerate the periodontal apparatus. To shift healing from repair to regeneration, the blood clot that fills the periodontal defect and remains in contact with structures such [...] Read more.
Background and Objectives: Periodontal therapy aims to arrest the progression of periodontal diseases and possibly to regenerate the periodontal apparatus. To shift healing from repair to regeneration, the blood clot that fills the periodontal defect and remains in contact with structures such as tooth root, mucosa and bone needs to be stable, which is a reason why the treatment of non-containing periodontal bone defects, in which the clot may undergo displacement, is challenging. The gingival soft tissue, properly sutured, may act as a wall for blood clot stabilization. Knowledge on the response of the blood clot to stress and how it might vary according to the characteristics of the tissues it gets in contact with might be deepened. The aim of this study was to investigate in vitro, by means of a micro-loading device, the response of the complex formed by a blood clot and diverse tissues, simulating those involved in periodontal regeneration, to a displacing tensile test. Materials and Methods: Experimental samples made of two layers of either hard dental tissues, cancellous bone or oral mucosa, between which fresh blood was interposed, underwent a debonding experiment by means of a micro-loading device that measured their response to uniaxial tensile stress. Results: The peak of tensile stress and the overall work needed for the complete rupture of the clot’s fibrin filaments were significantly higher for hard dental tissues than for other tissues. However, mucosa sustained the highest maximal strain in terms of relative displacement between the plates of the micro-loading device to accomplish the complete rupture of the fibrin filaments compared to the other tissues, suggesting that the mucosa might act as a stable interface with the clot and be able to sustain tensile stresses. Conclusions: This in vitro study seems to support the use of mucosa to act as a wall for regenerative procedures of suprabony periodontal defects given its capability to form a stable interface with the clot. Full article
(This article belongs to the Section Dentistry and Oral Health)
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<p>The micro-loading device.</p>
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<p>(<b>A</b>) The first slice was glued by a drop of acrylic resin to the lower flat plate connected to the load cell of the machine; (<b>B</b>) The second slice was positioned on the top of the first one and vertically aligned; (<b>C</b>) The second slice was glued to the upper plate of the machine fixed to the actuator and was then moved up to create space between the slices; (<b>D</b>) The upper surface of the lower (first) slice was completely covered by 1 microliter of blood; (<b>E</b>) The upper (second) slice was moved down to reach 40 μm from the lower slice and left in this position for 45 min (BCT). (<b>F</b>) After coagulation, the vertical displacement of the actuator was started. TS: tensile stress measured at the end of the coagulation time (TS1) and at its peak during the debonding experiment (TS2); AC: area under the curve. The red arrow indicates the direction of the movement.</p>
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<p>Blood clot filaments have formed between two bone samples. The fibrin filaments become thinner while the distance between the facing surfaces increases, until rupture occurs.</p>
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<p>Mechanical response of the blood clot–tissue complexes in terms of relative TS versus normal separation (i.e., vertical relative displacement (w) for hard dental tissues (I), bone (II) and mucosa (III)). TS is represented at the 45th minute, immediately before the vertical displacement (TS1), at the peak force (TS2) and at RP.</p>
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15 pages, 1665 KiB  
Article
Multifunctional Nanoemulsified Clinacanthus nutans Extract: Synergistic Anti-Pathogenic, Anti-Biofilm, Anti-Inflammatory, and Metabolic Modulation Effects against Periodontitis
by Sirintip Pechroj, Thida Kaewkod, Pachara Sattayawat, Angkhana Inta, Sureeporn Suriyaprom, Teerapong Yata, Yingmanee Tragoolpua and Itthayakorn Promputtha
Biology 2024, 13(10), 815; https://doi.org/10.3390/biology13100815 - 11 Oct 2024
Viewed by 402
Abstract
This study investigates the therapeutic potential of Clinacanthus nutans extracts, focusing on the 95% ethanol (95E) extract and its nanoemulsified form, against oral pathogens and their bioactive effects. The findings demonstrate potent antibacterial activity against Streptococcus mutans and Staphylococcus aureus, essential for [...] Read more.
This study investigates the therapeutic potential of Clinacanthus nutans extracts, focusing on the 95% ethanol (95E) extract and its nanoemulsified form, against oral pathogens and their bioactive effects. The findings demonstrate potent antibacterial activity against Streptococcus mutans and Staphylococcus aureus, essential for combating periodontal diseases, and significant anti-biofilm properties crucial for plaque management. Additionally, the extracts exhibit promising inhibitory effects on α-glucosidase enzymes, indicating potential for diabetes management through glucose metabolism regulation. Their anti-inflammatory properties, evidenced by reduced nitric oxide production, underscore their potential for treating oral infections and inflammation. Notably, the nanoemulsified 95E extract shows higher efficiency than the conventional extract, suggesting a multifunctional treatment approach for periodontal issues and metabolic disorders. These results highlight the enhanced efficacy of the nanoemulsified extract, proposing it as an effective treatment modality for periodontal disease in diabetic patients. This research offers valuable insights into the development of innovative drug delivery systems using natural remedies for improved periodontal care in diabetic populations. Full article
(This article belongs to the Section Medical Biology)
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<p>Antibacterial activity of <span class="html-italic">C. nutans</span> extracts assessed by the agar-well diffusion method. (<b>A</b>) <span class="html-italic">S. mutans</span>, (<b>B</b>) <span class="html-italic">S. pyogenes</span>, (<b>C</b>) <span class="html-italic">K. pneumoniae</span>, and (<b>D</b>) <span class="html-italic">S. aureus</span>, with G = gentamicin as the positive control. Each test was performed using different extracts: 95% methanol (95M), 95% ethanol (95E), 70% ethanol (70E), and water (W).</p>
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<p>Particle size distribution of nanoemulsified 95E extract of <span class="html-italic">C. nutans</span> measured using NanoSizer.</p>
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<p>Comparative analysis of biofilm inhibition: (<b>A</b>) biofilm formation and (<b>B</b>) biofilm degradation by 95E extract of <span class="html-italic">C. nutans</span> and its nanoemulsified form. Data are presented as mean ± SD from three independent experiments. Statistical significance is denoted by * <span class="html-italic">p</span> &lt; 0.001, indicating significant differences between extract and nanoemulsion formulations.</p>
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<p>Comparison of α-glucosidase inhibition activity between 95E <span class="html-italic">C. nutans</span> extract and its nanoemulsified formulation. * <span class="html-italic">p</span> &lt; 0.001 indicates a significant difference between the 95E extract and the nanoemulsified 95E.</p>
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18 pages, 294 KiB  
Review
Exploring the Link between Xerostomia and Oral Health in Mental Illness: Insights from Autism Spectrum Disorder, Depression, Bipolar Disorder, and Schizophrenia
by Rou-Jun Chen, Kuei-Hung Lai, Chun-Hung Lee, Hao-Ying Lin, Cheng-Chieh Lin, Chi-Hsiu Chen, Wei Chen, Wei-Yu Chen, Thi Thuy Tien Vo and I-Ta Lee
Healthcare 2024, 12(20), 2018; https://doi.org/10.3390/healthcare12202018 - 11 Oct 2024
Viewed by 309
Abstract
Background: The relationship between mental disorders and oral health is complex, involving behavioral, biological, and psychosocial factors. This review aims to investigate the impact of mental disorders, including autism spectrum disorder (ASD), depression, bipolar disorder, and schizophrenia, on oral health outcomes. Methods: A [...] Read more.
Background: The relationship between mental disorders and oral health is complex, involving behavioral, biological, and psychosocial factors. This review aims to investigate the impact of mental disorders, including autism spectrum disorder (ASD), depression, bipolar disorder, and schizophrenia, on oral health outcomes. Methods: A comprehensive review of existing literature was conducted to analyze the oral health outcomes associated with each mental disorder. The focus was on examining dietary habits, oral hygiene behaviors, physiological changes, and medication side effects that contribute to oral health issues. Results: The findings indicate that individuals with ASD often exhibit unique dietary habits and reduced oral hygiene capabilities due to sensory sensitivities, leading to a higher prevalence of dental caries and periodontal diseases. Depression and bipolar disorder are associated with physiological changes such as reduced saliva production and poor oral hygiene behaviors, increasing the risk of oral health problems. Medications used for these conditions exacerbate issues like xerostomia, further elevating the risk of dental diseases. Schizophrenia poses additional challenges, including cognitive impairments and medication side effects that hinder effective oral care, heightening susceptibility to oral diseases. Conclusions: This review highlights the specific oral health challenges associated with different mental disorders and emphasizes the need for tailored dental care strategies that integrate mental health considerations. The study contributes to the literature by demonstrating the unique oral health impacts of these disorders. However, the findings are limited by the scope of available cross-sectional data and the absence of longitudinal studies. Future research should focus on longitudinal and intervention-based studies to explore causal relationships and develop effective treatments. Full article
(This article belongs to the Special Issue Mental Health at a Personal, Communal, and Social Level)
13 pages, 1000 KiB  
Article
The Impact of Type 2 Diabetes Mellitus on Non-Surgical Periodontal Treatment: A Non-Randomized Clinical Trial
by Lícia Clara Garcia Belizário, Carlos Marcelo S. Figueredo, João Victor Soares Rodrigues, Thamiris Cirelli, Rafael Scaf de Molon, Valdir Gouveia Garcia and Letícia Helena Theodoro
J. Clin. Med. 2024, 13(19), 5978; https://doi.org/10.3390/jcm13195978 - 8 Oct 2024
Viewed by 531
Abstract
Background/Objectives: Periodontitis (P), a chronic inflammatory condition that affects the supportive tissues around the teeth, is three to four times more prevalent in individuals with diabetes mellitus (DM), with a direct correlation between its severity and the levels of glycosylated hemoglobin (HbA1c). This [...] Read more.
Background/Objectives: Periodontitis (P), a chronic inflammatory condition that affects the supportive tissues around the teeth, is three to four times more prevalent in individuals with diabetes mellitus (DM), with a direct correlation between its severity and the levels of glycosylated hemoglobin (HbA1c). This study aimed to evaluate the periodontal clinical parameters following non-surgical periodontal treatment (NSPT) in P patients with or without type 2 DM. Methods: Forty patients with P were divided into two groups: Group DM/P and Group P. All the patients were assessed at baseline and at 90 and 180 days after receiving NSPT. The parameters evaluated included the HbA1c level, plaque index (PI), probing pocket depth (PPD), clinical attachment level (CAL), and bleeding on probing (BoP). A statistical analysis was performed with a significance level set at α = 5%. Results: There were significant differences in the HbA1c levels between the DM/P and P groups at baseline, 90, and 180 days, as expected. Importantly, the HbA1c levels did not change after NSPT. Group P showed a significant reduction in both the PI and the BoP values at 90 and 180 days (p < 0.05). In contrast, Group DM/P demonstrated a significant increase in the percentage of sites with a PPD ≥ 5 mm at 180 days (p < 0.05). Additionally, Group P exhibited an increase in sites with a PPD ≤ 4 mm and a decrease in sites with a PPD ≥ 5 mm at both 90 and 180 days (p < 0.05). Conclusions: Our findings suggest that DM may compromise the effectiveness of NSPT, potentially hindering favorable outcomes during the follow-up period. Full article
(This article belongs to the Special Issue Innovative Research in Periodontology and Implantology)
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<p>Flowchart of the study.</p>
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<p>The Pearson correlation matrix between the predictor variables and the clinical endpoint. The Pearson correlation matrix between the variables, namely group, the number of teeth, the plaque index (PI), the bleeding on probing (BoP), and the clinical endpoint. The correlation values are accompanied by their respective <span class="html-italic">p</span>-values, indicated in parentheses. The intensity of the colors in the matrix reflects the strength and direction of the correlations, where colors closer to blue indicate negative correlations, and colors closer to red indicate positive correlations. Statistically significant correlations (<span class="html-italic">p</span> &lt; 0.05) indicate important associations between the analyzed variables.</p>
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11 pages, 526 KiB  
Article
Association between Periodontal Disease and Oral Benign, Potentially Malignant, Malignant, and Chronic Immune-Mediated Disorders: A Clinical Study
by Antonio Barbarisi, Francesca Cremonini, Dorina Lauritano, Valeria Visconti, Gianluigi Caccianiga and Saverio Ceraulo
Healthcare 2024, 12(19), 1999; https://doi.org/10.3390/healthcare12191999 - 7 Oct 2024
Viewed by 450
Abstract
Background: Periodontal disease is an inflammatory, chronic, and multifactorial disease. The objective of this study is to analyze the association between periodontal disease and some disorders such as papillomas (benign lesions), lichen planus (a chronic immune-mediated disorder), leukoplakia (potentially malignant lesions), and [...] Read more.
Background: Periodontal disease is an inflammatory, chronic, and multifactorial disease. The objective of this study is to analyze the association between periodontal disease and some disorders such as papillomas (benign lesions), lichen planus (a chronic immune-mediated disorder), leukoplakia (potentially malignant lesions), and oral cancer (malignant lesions). Methods: For this study, 42 patients were recruited whose supragingival and subgingival plaque was qualitatively analyzed using a phase-contrast microscope, which allowed for the detection of compatible bacterial flora (immobile and composed mainly of cocci) indicative of periodontal health and incompatible bacterial flora (mobile and composed mainly of spirochetes) indicative of periodontal pathology. Patients with incompatible bacterial flora were then subjected to a laser-assisted periodontal treatment with irrigation with hydrogen peroxide within the periodontal pockets (a non-surgical laser-assisted periodontal protocol which is referred to as dye-free photodynamic therapy). Results: Based on the 42 patients recruited, there was no association between oral cavity lesions and periodontal pathogenic bacteria. Four of them were found to have incompatible bacterial flora. Indeed, it was found that almost all the patients had been previously instructed in the proper techniques of home oral hygiene, and more than half of them reported that they carried out periodic check-ups by a dental hygienist. Of the four patients with signs and symptoms of periodontitis, two stated a willingness to undergo the non-surgical laser-assisted periodontal protocol and showed improvements in periodontal indices such as CAL, PPD, and BoP. Conclusions: hygienists and dentists are determining factors in the prevention of periodontal disease and for the maintenance of good oral health. Full article
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<p>Diagnostic and therapeutic process.</p>
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12 pages, 4143 KiB  
Article
Apelin Counteracts the Effects of Fusobacterium nucleatum on the Migration of Periodontal Ligament Cells In Vitro
by Pablo Cores Ziskoven, Andressa V. B. Nogueira, Sigrun Eick and James Deschner
Int. J. Mol. Sci. 2024, 25(19), 10729; https://doi.org/10.3390/ijms251910729 - 5 Oct 2024
Viewed by 396
Abstract
To better understand the link between periodontitis and metabolic diseases, our in vitro study aimed to assess the influence of the adipokine apelin and/or the periodontal pathogen Fusobacterium nucleatum on periodontal cells. Periodontal ligament (PDL) cells were exposed to F. nucleatum in the [...] Read more.
To better understand the link between periodontitis and metabolic diseases, our in vitro study aimed to assess the influence of the adipokine apelin and/or the periodontal pathogen Fusobacterium nucleatum on periodontal cells. Periodontal ligament (PDL) cells were exposed to F. nucleatum in the presence and absence of apelin. Scratch assays were used to analyze the in vitro wound healing and velocity of cell migration. To investigate if F. nucleatum and/or apelin have a regulatory effect on cell proliferation and apoptosis, proliferation and viability assays were performed as well as an analysis of caspase 9 expression. Both the in vitro wound closure and the cell migration rate were significantly reduced by F. nucleatum. Simultaneous incubation with apelin counteracted the adverse effects of F. nucleatum. The proliferation assay demonstrated that neither apelin nor F. nucleatum significantly affected PDL cell proliferation. Furthermore, neither apelin nor F. nucleatum was cytotoxic or affected apoptosis after 48 h. Apelin could play a modulatory role in the pathogenesis of periodontitis, as it was able to compensate for the inhibitory effects of the periodontal pathogen F. nucleatum on PDL cell migration in vitro. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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<p>(<b>A</b>) In vitro wound closure of the cell-free area (%) by PDL cells under different conditions (blue: control; red: <span class="html-italic">F. nucleatum</span> (OD<sub>660</sub>: 0.025); green: apelin (1 ng/ml); yellow: <span class="html-italic">F. nucleatum</span> + apelin) over 48 h. (<b>B</b>) Average in vitro wound closure of the cell-free area (%) by PDL cells exposed to <span class="html-italic">F. nucleatum</span> (OD<sub>660</sub>: 0.025) and/or apelin (1 ng/ml), as shown in (A). A minus sign indicates the absence of <span class="html-italic">F. nucleatum</span> or apelin, whereas a plus sign indicates the presence of <span class="html-italic">F. nucleatum</span> or apelin. (<b>C</b>) Representative light microscope images of in vitro wound closure of PDL cell monolayers in the presence and absence of <span class="html-italic">F. nucleatum</span> (OD<sub>660</sub>: 0.025) and/or apelin (1 ng/ml) at 0 h and 48 h. Untreated cells served as control. * significantly (<span class="html-italic">p</span> &lt; 0.05) different.</p>
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<p>(<b>A</b>) Velocity of PDL cell migration (μm/h) under different conditions (blue: control; red: <span class="html-italic">F. nucleatum</span> (OD<sub>660</sub>: 0.025); green: apelin (1 ng/ml); yellow: <span class="html-italic">F. nucleatum</span> + apelin) over 48 h. (<b>B</b>) Average migration velocity (μm/h) of PDL cells exposed to <span class="html-italic">F. nucleatum</span> (OD<sub>660</sub>: 0.025) and/or apelin (1 ng/ml), as shown in (<b>A</b>). A minus sign indicates the absence of <span class="html-italic">F. nucleatum</span> or apelin, whereas a plus sign indicates the presence of <span class="html-italic">F. nucleatum</span> or apelin. Untreated cells served as control. * significantly (<span class="html-italic">p</span> &lt; 0.05) different.</p>
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<p>Analysis of the average number of PDL cells in vitro in the presence and absence of <span class="html-italic">F. nucleatum</span> (OD<sub>660</sub>: 0.025) and/or apelin (1 ng/ml) at 24 h (<b>A</b>) and 48 h (<b>B</b>). A minus sign indicates the absence of <span class="html-italic">F. nucleatum</span> or apelin, whereas a plus sign indicates the presence of <span class="html-italic">F. nucleatum</span> or apelin. Untreated cells served as control.</p>
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<p>Viability of PDL cells in the presence and absence of <span class="html-italic">F. nucleatum</span> (OD<sub>660</sub>: 0.025) and/or apelin (1 ng/ml) in vitro at 48 h, as analyzed by live and dead assay and light microscopy. Unfiltered image (brightfield) and positive control for dead cells (70 % ethanol).</p>
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<p>Effects of <span class="html-italic">F. nucleatum</span> (OD<sub>660</sub>: 0.025) and/or apelin (1 ng/ml) on the expression of caspase 9 at 24 h (<b>A</b>) and 48 h (<b>B</b>). A minus sign indicates the absence of <span class="html-italic">F. nucleatum</span> or apelin, whereas a plus sign indicates the presence of <span class="html-italic">F. nucleatum</span> or apelin. Untreated cells served as control. * significant (<span class="html-italic">p</span> &lt; 0.05) difference between groups.</p>
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