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Molecular Insight into Oral Diseases
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Molecular Insight into Oral Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 August 2025 | Viewed by 5539

Special Issue Editor

Dr. Lorenzo Azzi

E-Mail Website
Guest Editor
Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy
Interests: oral medicine; oral surgery; oral pathology; oral diseases; oral cancer; oral autoimmune disorders

Special Issue Information

Dear Colleagues,

Oral diseases represent a global challenge for the medical and dental communities, in terms of both the health and economic burden for affected patients.

Dental caries, periodontal disease, and tooth loss affect billions of individuals worldwide, with inestimable social consequences, especially for children and older adults.

In addition, the 5-year survival rate of oral squamous cell carcinoma has remained at 50% in recent decades, despite recent advances in the field of cancer therapy and the introduction of immunotherapeutic approaches. Furthermore, autoimmune disorders, like oral lichen planus and vesiculobullous diseases, show great variability in terms of response to drug therapy, often representing a real challenge for clinicians.

The aim of this Special Issue is to provide new insights into the field of molecular mechanisms that underlie the pathogenesis, clinical behavior, diagnosis, and response to varying therapies for oral and maxillofacial diseases.

The topics of this Special Issue include, but are not limited to, the following:

  • Dental caries and periodontal disease;
  • Oral potentially malignant disorders and oral squamous cell carcinoma;
  • Salivary gland disorders;
  • Oral lichenoid disorders;
  • Vesiculobullous diseases;
  • HPV-related disease (benign/malignant);
  • Odontogenic cysts and tumors;
  • Jawbone diseases;
  • Orofacial chronic pain disorders;
  • Other relevant conditions relevant for clinical practice.

Dr. Lorenzo Azzi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • dental caries
  • periodontal disease
  • oral cancer
  • oral potentially malignant disorders
  • salivary gland disease
  • oral lichen planus
  • benign mucous membrane pemphigoid
  • bullous dermatoses
  • odontogenic cysts
  • odontogenic tumors
  • orofacial pain
  • human papillomavirus
  • oral diagnosis
  • oral pathology

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Published Papers (4 papers)

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Research

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16 pages, 3164 KiB  
Communication
Transcriptomic Profile of Oral Cancer Lesions: A Proof-of-Concept Pilot Study of FFPE Tissue Sections
by Madison E. Richards, Micaela F. Beckman, Ernesto Martinez Duarte, Joel J. Napenas, Michael T. Brennan, Farah Bahrani Mougeot and Jean-Luc C. Mougeot
Int. J. Mol. Sci. 2025, 26(13), 6263; https://doi.org/10.3390/ijms26136263 - 28 Jun 2025
Viewed by 266
Abstract
Oral squamous cell carcinoma (OSCC) is a malignancy that affects the oral mucosa and is characterized by indurated oral lesions. The RNAseq of formalin-fixed, paraffin-embedded (FFPE) samples is readily available in clinical settings. Such samples have long-term preservation and can provide highly accurate [...] Read more.
Oral squamous cell carcinoma (OSCC) is a malignancy that affects the oral mucosa and is characterized by indurated oral lesions. The RNAseq of formalin-fixed, paraffin-embedded (FFPE) samples is readily available in clinical settings. Such samples have long-term preservation and can provide highly accurate transcriptomic information regarding gene fusions, isoforms, and allele-specific expression. We determined differentially expressed genes using the transcriptomic profiles of oral potentially malignant disorder (OPMD) FFPE oral lesion samples of patients who developed OSCC over years. A technical comparison was completed comparing breast cancer (BC) FFPE publicly available data in this proof-of-concept pilot study. OSCC FFPE samples were collected from patients (N = 3) who developed OSCC 3 to 5 years following OPMD diagnosis (n = 3) and were analyzed using RNAseq. RNAseq sequences from the FFPE OSCC samples and publicly available FFPE samples of BC patients (n = 6) (Gene Expression Omnibus Database, GSE58135) aligned to human reference (GRCh38.p13). Genes were counted using the Spliced Transcripts Alignment to a Reference (STARv2.7.9a) software. Differential expression was determined in R using DESeq2v1.40.2 comparing OSCC to BC samples. Principal component analysis (PCA) plots were completed. Differential Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were determined via the Pathviewv.1.40.0 program. STRING v12.0 was used to determine protein–protein interactions between genes represented in more than one KEGG pathway. STARv2.7.9a identified 27,237 and 30,343 genes among the OSCC and BC groups, respectively. DESeq2v1.40.2 determined 9194 differentially expressed genes (DEPs), 4466 being upregulated (OSCC > BC) and 4728 being downregulated (BC > OSCC) (padj < 0.05). Most significant genes included KRT6B, SERPINB5, and DSC3 (5- to 10-fold change range; padj < 10 × 10−100). PCA showed that BC and OSCC samples clustered as separate groups. Pathviewv.1.40.0 identified 17 downregulated KEGG pathways in OSCC compared to the BC group. No upregulated KEGG pathways were identified. STRINGv12.0 determined Gene Ontology Biological Process enrichments for leukocytes and apoptosis in upregulated KEGG genes including multiple PIK3 genes and NIK/NF-kappaB signaling and metabolic responses from lipopolysaccharides in downregulated KEGG genes including CHUK and NFKB1. Using FFPE samples, we determined DEPs characteristic of OSCC and distinct from BC. KRT-family genes and lipopolysaccharide producing periodontal pathogens may be further investigated for their involvement in the OPMD to OSCC transition. Full article
(This article belongs to the Special Issue Molecular Insight into Oral Diseases)
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11 pages, 1957 KiB  
Article
Prediction of Oral Cancer Biomarkers by Salivary Proteomics Data
by Veronica Remori, Manuel Airoldi, Tiziana Alberio, Mauro Fasano and Lorenzo Azzi
Int. J. Mol. Sci. 2024, 25(20), 11120; https://doi.org/10.3390/ijms252011120 - 16 Oct 2024
Viewed by 2004
Abstract
Oral cancer, representing 2–4% of all cancer cases, predominantly consists of Oral Squamous Cell Carcinoma (OSCC), which makes up 90% of oral malignancies. Early detection of OSCC is crucial, and identifying specific proteins in saliva as biomarkers could greatly improve early diagnosis. Here, [...] Read more.
Oral cancer, representing 2–4% of all cancer cases, predominantly consists of Oral Squamous Cell Carcinoma (OSCC), which makes up 90% of oral malignancies. Early detection of OSCC is crucial, and identifying specific proteins in saliva as biomarkers could greatly improve early diagnosis. Here, we proposed a strategy to pinpoint candidate biomarkers. Starting from a list of salivary proteins detected in 10 OSCC patients and 20 healthy controls, we combined a univariate approach and a multivariate approach to select candidates. To reduce the number of proteins selected, a Protein–Protein Interaction network was built to consider only connected proteins. Then, an over-representation analysis (ORA) determined the enriched pathways. The network from 172 differentially abundant proteins highlighted 50 physically connected proteins, selecting relevant candidates for targeted experimental validations. Notably, proteins like Heat shock 70 kDa protein 1A/1B, Pyruvate kinase PKM, and Phosphoglycerate kinase 1 were suggested to be differentially regulated in OSCC patients, with implications for oral carcinogenesis and tumor growth. Additionally, the ORA revealed enrichment in immune system, complement, and coagulation pathways, all known to play roles in tumorigenesis and cancer progression. The employed method has successfully identified potential biomarkers for early diagnosis of OSCC using an accessible body fluid. Full article
(This article belongs to the Special Issue Molecular Insight into Oral Diseases)
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13 pages, 1525 KiB  
Article
MiR-146a Is Mutually Regulated by High Glucose-Induced Oxidative Stress in Human Periodontal Ligament Cells
by Chihiro Fumimoto, Nobuhiro Yamauchi, Emika Minagawa and Makoto Umeda
Int. J. Mol. Sci. 2024, 25(19), 10702; https://doi.org/10.3390/ijms251910702 - 4 Oct 2024
Cited by 3 | Viewed by 1558
Abstract
The high-glucose conditions caused by diabetes mellitus (DM) exert several effects on cells, including inflammation. miR-146a, a kind of miRNA, is involved in inflammation and may be regulated mutually with reactive oxygen species (ROS), which are produced under high-glucose conditions. In the present [...] Read more.
The high-glucose conditions caused by diabetes mellitus (DM) exert several effects on cells, including inflammation. miR-146a, a kind of miRNA, is involved in inflammation and may be regulated mutually with reactive oxygen species (ROS), which are produced under high-glucose conditions. In the present study, we used human periodontal ligament cells (hPDLCs) to determine the effects of the high-glucose conditions of miR-146a and their involvement in the regulation of oxidative stress and inflammatory cytokines using Western blotting, PCR, ELISA and other methods. When hPDLCs were subjected to high glucose (24 mM), cell proliferation was not affected; inflammatory cytokine expression, ROS induction, interleukin-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6) expression increased, but miR-146a expression decreased. Inhibition of ROS induction with the antioxidant N-acetyl-L-cysteine restored miR-146a expression and decreased inflammatory cytokine expression compared to those under high-glucose conditions. In addition, overexpression of miR-146a significantly suppressed the expression of the inflammatory cytokines IRAK1 and TRAF6, regardless of the glucose condition. Our findings suggest that oxidative stress and miR-146a expression are mutually regulated in hPDLCs under high-glucose conditions. Full article
(This article belongs to the Special Issue Molecular Insight into Oral Diseases)
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Review

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22 pages, 1858 KiB  
Review
Relevance of Saliva Analyses in Terms of Etiological Factors, Biomarkers, and Indicators of Disease Course in Patients with Multiple Sclerosis—A Review
by Aleksandra Kapel-Reguła, Irena Duś-Ilnicka and Małgorzata Radwan-Oczko
Int. J. Mol. Sci. 2024, 25(23), 12559; https://doi.org/10.3390/ijms252312559 - 22 Nov 2024
Cited by 1 | Viewed by 1013
Abstract
Multiple sclerosis (MS) is a demyelinating, progressive, and neurodegenerative disease. The cause of this condition remains unknown. Diagnosing and monitoring the course of this disease requires the use of time-consuming, costly, and invasive methods such as magnetic resonance imaging and cerebrospinal fluid analysis. [...] Read more.
Multiple sclerosis (MS) is a demyelinating, progressive, and neurodegenerative disease. The cause of this condition remains unknown. Diagnosing and monitoring the course of this disease requires the use of time-consuming, costly, and invasive methods such as magnetic resonance imaging and cerebrospinal fluid analysis. To date, no specific diagnostic tests for MS are available. The purpose of this publication is to answer the question of whether saliva, as a mirror of oral and general health and easily obtainable test material, can be a significant source of information on etiological factors, biomarkers, and indicators of disease progression and whether analysis of substances in saliva is sensitive enough to replace plasma, urine, or cerebrospinal fluid. For this purpose, a systematic search of databases was conducted: PubMed, Google Scholar, and Embase. Full article
(This article belongs to the Special Issue Molecular Insight into Oral Diseases)
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