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Molecular Pathogenesis and Therapeutic Innovations in Oral Diseases

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Guest Editor
Periodontal Medicine Center, 3-15-1 Kurosaki, Yahatanishi-ku, Kitakyushu 806-0021, Fukuoka, Japan
Interests: dentistry; molecular biology; functional basic dentistry; dentistry; periodontal dentistry

Special Issue Information

Dear Colleagues,

Advances in molecular biology have brought about major changes in diagnosis, treatment, and preventive measures in the field of dentistry. Furthermore, with the advancement of molecular-based analysis, many scientific papers have been published on the relationship between periodontal disease and lifestyle-related diseases all over the world. In light of this background, appropriate diagnosis of oral diseases at the molecular level and treatment based on that diagnosis are now considered important in current dentistry.

The purpose of this special issue is to provide the latest knowledge on diagnostic methods for various oral diseases, including periodontal disease and peri-implantitis, and the therapeutic effects of drug therapy.

Expected topics:

Molecular biology, oral disease treatment, oral disease diagnosis, drug therapy, regenerative therapy, oral microbiome

Prof. Dr. Tatsuji Nishihara
Guest Editor

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Keywords

  • molecular-based analysis
  • diagnosis of oral disease
  • oral disease treatment
  • regeneration therapy
  • drug therapy
  • periodontitis
  • implantitis

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Published Papers (4 papers)

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Research

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18 pages, 1413 KB  
Article
Time-Dependent Changes in Salivary Antioxidants After 5-ALA Photodynamic Therapy vs. Clobetasol in Oral Lichen Planus: A Randomized Clinical Trial
by Patryk Wiśniewski, Magdalena Sulewska, Jagoda Tomaszuk, Anna Zalewska, Sara Zięba, Aleksandra Pietruska, Emilia Szymańska, Katarzyna Winnicka, Mateusz Maciejczyk, Małgorzata Żendzian-Piotrowska and Małgorzata Pietruska
Int. J. Mol. Sci. 2025, 26(22), 11232; https://doi.org/10.3390/ijms262211232 - 20 Nov 2025
Viewed by 464
Abstract
In this randomized clinical trial, we compared the effects of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and topical clobetasol on the salivary antioxidant profile in patients with oral lichen planus (OLP) and explored their relationships with clinical outcomes. Ninety adults with OLP were randomly [...] Read more.
In this randomized clinical trial, we compared the effects of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and topical clobetasol on the salivary antioxidant profile in patients with oral lichen planus (OLP) and explored their relationships with clinical outcomes. Ninety adults with OLP were randomly allocated to ALA-PDT (five weekly sessions) or clobetasol (twice daily for 14 days). Unstimulated whole saliva was collected at baseline (T0), immediately after treatment (T1), and at 3 (T3) and 6 months (T6). The activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (Px) and reduced glutathione (GSH) were determined, and nonparametric statistics were applied, including Friedman tests with Dunn’s post hoc comparisons and Spearman’s rank correlations. Both therapies induced an early decline in CAT, Px and GSH at T1, followed by partial recovery at later time points. SOD activity changed significantly over time in the clobetasol group, but not in the PDT arm. At T6, Px and GSH remained below baseline in both groups despite improvement from the immediate post-treatment nadir. No significant between-group differences were observed at individual time points, although GSH at T6 showed a non-significant trend favoring PDT. Exploratory analyses revealed modest, treatment-dependent associations between salivary antioxidant activity and lesion size, as well as between the former and pain intensity. Overall, ALA-PDT and topical clobetasol both modulated the salivary redox profile, primarily through short-term depletion of enzymatic and non-enzymatic antioxidants with incomplete recovery over 6 months, and no clear redox superiority of one modality over the other was demonstrated. These findings are hypothesis-generating and underscore the need for larger, longer-term studies with broader redox panels and more advanced between-group analyses. Full article
(This article belongs to the Special Issue Molecular Pathogenesis and Therapeutic Innovations in Oral Diseases)
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Review

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14 pages, 965 KB  
Review
From Oxidised LDL to Potential Novel Applications in Gingival Crevicular Fluid Analysis
by Matsuo Yamamoto, Takayuki Ootani, Hiroko Imai and Hiroyuki Itabe
Int. J. Mol. Sci. 2025, 26(24), 11924; https://doi.org/10.3390/ijms262411924 - 10 Dec 2025
Abstract
Gingival crevicular fluid (GCF) reflects both local periodontal inflammation and systemic conditions. This review highlights the role of oxidative stress, oxidised low-density lipoprotein (oxLDL), and apolipoprotein B (apoB) as molecular links between periodontitis and metabolic disorders. Elevated GCF levels of oxLDL and apoB [...] Read more.
Gingival crevicular fluid (GCF) reflects both local periodontal inflammation and systemic conditions. This review highlights the role of oxidative stress, oxidised low-density lipoprotein (oxLDL), and apolipoprotein B (apoB) as molecular links between periodontitis and metabolic disorders. Elevated GCF levels of oxLDL and apoB indicate enhanced vascular permeability and local oxidative modification, particularly in diabetes. Furthermore, oxLDL promotes the formation of neutrophil extracellular trap (NET) via connecting oxidative stress with immune-mediated tissue injury. These insights establish GCF as a valuable, non-invasive biomarker for understanding the interplay between periodontal and systemic diseases. Full article
(This article belongs to the Special Issue Molecular Pathogenesis and Therapeutic Innovations in Oral Diseases)
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14 pages, 652 KB  
Review
Microbial Coaggregation in the Oral Cavity: Molecular Interactions and Current Insights
by Yuichi Oogai, Yumika Tanaka and Masanobu Nakata
Int. J. Mol. Sci. 2025, 26(21), 10552; https://doi.org/10.3390/ijms262110552 - 30 Oct 2025
Viewed by 659
Abstract
Periodontitis is a chronic inflammatory disease of the periodontal tissues primarily caused by dysbiotic bacterial communities. Accumulating evidence suggests that periodontal pathogens not only drive the initiation and progression of periodontitis but also significantly contribute to systemic disorders, including diabetes mellitus, cardiovascular disease, [...] Read more.
Periodontitis is a chronic inflammatory disease of the periodontal tissues primarily caused by dysbiotic bacterial communities. Accumulating evidence suggests that periodontal pathogens not only drive the initiation and progression of periodontitis but also significantly contribute to systemic disorders, including diabetes mellitus, cardiovascular disease, cancer, and adverse pregnancy outcomes, such as preterm birth. The key periodontal pathogens implicated in disease pathogenesis include Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and Fusobacterium nucleatum. Among the diverse factors governing bacterial colonization and biofilm formation, interspecies interactions, particularly coaggregation, play a critical role in dental plaque maturation and the establishment of pathogenic microbial communities. Coaggregation facilitates the spatial organization of bacteria within biofilms, enhances bacterial survival, and modulates virulence factor expression. This review summarizes current knowledge regarding bacterial interactions involving major periodontal pathogens, with particular emphasis on coaggregation mechanisms, and discusses the implications of this coaggregation for periodontitis pathogenesis and associated systemic diseases. Full article
(This article belongs to the Special Issue Molecular Pathogenesis and Therapeutic Innovations in Oral Diseases)
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20 pages, 819 KB  
Review
Measuring the Invisible: Microbial Diagnostics for Periodontitis—A Narrative Review
by Michihiko Usui, Suzuka Miyagi, Rieko Yamanaka, Yuichiro Oka, Kaoru Kobayashi, Tsuyoshi Sato, Kotaro Sano, Satoru Onizuka, Maki Inoue, Wataru Fujii, Masanori Iwasaki, Wataru Ariyoshi, Keisuke Nakashima and Tatsuji Nishihara
Int. J. Mol. Sci. 2025, 26(20), 10172; https://doi.org/10.3390/ijms262010172 - 19 Oct 2025
Cited by 1 | Viewed by 1054
Abstract
Periodontitis is a biofilm-driven inflammatory disease in which conventional indices (probing depth, clinical attachment level, and radiographs) quantify tissue destruction without capturing the biology of infection. In this review, we synthesized microbiological diagnostics, from chairside tools to omics. We outline sampling strategies and [...] Read more.
Periodontitis is a biofilm-driven inflammatory disease in which conventional indices (probing depth, clinical attachment level, and radiographs) quantify tissue destruction without capturing the biology of infection. In this review, we synthesized microbiological diagnostics, from chairside tools to omics. We outline sampling strategies and emphasize the quantitative monitoring of bacterial load. Enzymatic assays (e.g., N-benzoyl-DL-arginine-2-naphthylamide hydrolysis assay test) measure functional activity at the point of care. Immunological methods include rapid immunochromatography for Porphyromonas gingivalis and enzyme-linked immunosorbent assay for the high-throughput measurement of bacterial antigens. Molecular platforms encompass quantitative polymerase chain reaction (qPCR) (TaqMan, SYBR, multiplex panels; propidium monoazide quantitative-qPCR for viable cells), checkerboard DNA–DNA hybridization for semi-quantitative community profiling, loop-mediated isothermal amplification (LAMP)/molecular beacon-LAMP for portable isothermal detection, and microarrays. Complementary modalities such as fluorescent in situ hybridization, next-generation sequencing, and Fourier transform infrared spectroscopy provide spatial, ecological, and biochemical resolutions. We discuss the limitations of current approaches, including sampling bias, presence–activity discordance, semi-quantitation, method biases, limited strain/function resolution, low-biomass artifacts, and lack of validated cutoffs. To address these challenges, we propose a pragmatic hybrid strategy: site-specific quantitative panels combined with activity and host-response markers interpreted alongside clinical metrics under standardized quality assurance/quality control. Priorities include outcome-linked thresholds, strain-aware/functional panels, robust point-of-care chemistry, and harmonized protocols to enable personalized periodontal care. Full article
(This article belongs to the Special Issue Molecular Pathogenesis and Therapeutic Innovations in Oral Diseases)
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