A Review of Antimicrobial Activity of Dental Mesenchymal Stromal Cells: Is There Any Potential?

Antimicrobial defense is an essential component of host-microbial homeostasis and contributes substantially to oral health maintenance. Dental mesenchymal stromal cells (MSCs) possess multilineage differentiation potential, immunomodulatory properties and play an important role in various processes like regeneration and disease progression. Recent studies show that dental MSCs might also be involved in antibacterial defense. This occurs by producing antimicrobial peptides or attracting professional phagocytic immune cells and modulating their activity. The production of antimicrobial peptides and immunomodulatory abilities of dental MSCs are enhanced by an inflammatory environment and influenced by vitamin D3. Antimicrobial peptides also have anti-inflammatory effects in dental MSCs and improve their differentiation potential. Augmentation of antibacterial efficiency of dental MSCs could broaden their clinical application in dentistry.

Surgical Margins After Computer-Assisted Mandibular Reconstruction: A Retrospective Study

Purpose: The use of virtual surgical planning in head and neck surgery is growing strongly. In the literature, its validity, accuracy and clinical utility for mandibular reconstruction are widely documented. Virtual planning of surgical bone resection and reconstruction takes place several days before surgery and its very sensitive nature can negatively affect an intervention aimed at maximum precision in term of oncological safety.Methods: The study focuses on a retrospective evaluation of the surgical margins in 26 consecutive cases with oral cavity malignancy and who underwent computer-assisted mandibular resection/reconstruction guided by the different types of bone, periosteal and peri-mandibular tissue involvement. The goal was to analyze the strategic and technical aspects useful to minimize the risk of positive or close margins and to vary the reconstructive strategy in the case of intraoperative findings of a non-radical planned resection.Results: No intraoperative or perioperative complications occurred. In 20 patients, virtual surgical planning permitted mandibular reconstruction to be performed using composite fibular free flaps, characterized by high accuracy and negative bone margins. In the remaining 6 patients, also virtually planned but otherwise reconstructed due to poor general condition (advanced age, severe comorbidity), negative bone margins were obtained. Intraoperative enlargement of the resection was carried out in one case and positive soft tissue margins were observed in another case.Conclusion: The results were satisfactory in terms of oncological radicality and precision. The functional benefits and reduction in operating times, previously demonstrated in other articles also by the authors, seem to justify the side effects related to the risk of modifying the planned surgery. During virtual planning, the surgeons must bear in mind that an unexpected progression of the tumor or a limited planned resection will entail modifying the extent of the resection intraoperatively and nullifying the virtual planning on which the reconstruction was based. Further investigations are necessary to clarify all aspects of virtual surgical planning in this setting.

Deep Machine Learning for Oral Cancer: From Precise Diagnosis to Precision Medicine

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide and its incidence is on the rise in many populations. The high incidence rate, late diagnosis, and improper treatment planning still form a significant concern. Diagnosis at an early-stage is important for better prognosis, treatment, and survival. Despite the recent improvement in the understanding of the molecular mechanisms, late diagnosis and approach toward precision medicine for OSCC patients remain a challenge. To enhance precision medicine, deep machine learning technique has been touted to enhance early detection, and consequently to reduce cancer-specific mortality and morbidity. This technique has been reported to have made a significant progress in data extraction and analysis of vital information in medical imaging in recent years. Therefore, it has the potential to assist in the early-stage detection of oral squamous cell carcinoma. Furthermore, automated image analysis can assist pathologists and clinicians to make an informed decision regarding cancer patients. This article discusses the technical knowledge and algorithms of deep learning for OSCC. It examines the application of deep learning technology in cancer detection, image classification, segmentation and synthesis, and treatment planning. Finally, we discuss how this technique can assist in precision medicine and the future perspective of deep learning technology in oral squamous cell carcinoma.

Therapeutic Perspectives for the Perioperative Period in Oral Squamous Cell Carcinoma (OSCC)

The perioperative period is the relatively short window of time, usually measured in days or weeks, around the surgical procedure. Despite its short duration, this time period is of great importance for cancer patients. From a biological point of view, the perioperative period is complex. Synchronous with primary tumor removal, surgery has local and distant consequences, including systemic and local inflammation, coagulation and sympathetic activation. Furthermore, the patients often present comorbidities and receive several medical prescriptions (hypnotics, pain killers, anti-emetics, hemostatics, inotropes, antibiotics). Because of the complex nature of the perioperative period, it is often difficult to predict the oncological outcome of tumor resection. Here, we review the biological consequences of surgery of Oral Squamous Cell Carcinoma (OSCC), the most frequent form of primary head and neck tumors. We briefly address the specificities and the challenges of the surgical care of these tumors and highlight the biological and clinical studies that offer insight into the perioperative period. The recent trials examining neoadjuvant immunotherapy for OSCC illustrate the therapeutic opportunities offered by the perioperative period.

Tetramic Acids Mutanocyclin and Reutericyclin A, Produced by Streptococcus mutans Strain B04Sm5 Modulate the Ecology of an in vitro Oral Biofilm

The human oral microbiome consists of diverse microbes actively communicating and interacting through a variety of biochemical mechanisms. Dental caries is a major public health issue caused by fermentable carbohydrate consumption that leads to dysbiosis of the oral microbiome. Streptococcus mutans is a known major contributor to caries pathogenesis, due to its exceptional ability to form biofilms in the presence of sucrose, as well as to its acidophilic lifestyle. S. mutans can also kill competing bacteria, which are typically health associated, through the production of bacteriocins and other small molecules. A subset of S. mutans strains encode the muc biosynthetic gene cluster (BGC), which was recently shown to produce the tetramic acids, mutanocyclin and reutericyclins A, B, and C. Reutericyclin A displayed strong antimicrobial activity and mutanocyclin appeared to be anti-inflammatory; however the effect of these compounds, and the carriage of muc by S. mutans, on the ecology of the oral microbiota is not known, and was examined here using a previously developed in vitro biofilm model derived from human saliva. While reutericyclin significantly inhibited in vitro biofilm formation and acid production at sub-nanomolar concentrations, mutanocyclin did not present any activity until the high micromolar range. 16S rRNA gene sequencing revealed that reutericyclin drastically altered the biofilm community composition, while mutanocyclin showed a more specific effect, reducing the relative abundance of cariogenic Limosilactobacillus fermentum. Mutanocyclin or reutericyclin produced by the S. mutans strains amended to the community did not appear to affect the community in the same way as the purified compounds, although the results were somewhat confounded by the differing growth rates of the S. mutans strains. Regardless of the strain added, the addition of S. mutans to the in vitro community significantly increased the abundance of S. mutans and Veillonella infantium, only. Overall, this study illustrates that reutericyclin A and mutanocyclin do impact the ecology of a complex in vitro oral biofilm; however, further research is needed to determine the extent to which the production of these compounds affects the virulence of S. mutans.

Effects of Saliva From Periodontally Healthy and Diseased Subjects on Barrier Function and the Inflammatory Response in in vitro Models of the Oral Epithelium

Background: Periodontitis is a multifactorial, bacteria-mediated chronic inflammatory disease that results in the progressive destruction of the tooth-supporting tissues. It is well-known that saliva from subjects suffering from this disease generally contains higher levels of pro-inflammatory mediators, matrix metalloproteinases (MMP), and bacteria-derived toxic products. The aim of this study was to investigate and compare the effects of saliva from periodontally healthy and diseased subjects on the barrier function and inflammatory response in in vitro models of the oral epithelium.Methods: Unstimulated saliva samples from two groups of subjects, one with a healthy periodontium (n = 12) and one with severe generalized periodontitis (n = 11), were filter-sterilized. All the saliva samples were analyzed using an immunological multiplex assay to determine the levels of various cytokines and MMPs relevant to periodontitis. The impact of saliva on epithelial barrier integrity was assessed by monitoring transepithelial electrical resistance (TER) in an oral epithelium model using the B11 keratinocyte cell line. GMSM-K oral epithelial cells were treated with saliva from both groups to determine their ability to induce the secretion of interleukin-6 (IL-6) and interleukin-8 (IL-8), as determined by an enzyme-linked immunosorbent assay (ELISA).Results: Saliva from the periodontitis subjects contained significantly higher concentrations of matrix metalloproteinase-8 (MMP-8), matrix metalloproteinase-9 (MMP-9), IL-8, and C-X-C motif chemokine ligand 1 (CXCL1) compared to saliva from the healthy subjects. Saliva from the healthy and periodontitis subjects affected cytokine secretion and TER in a similar manner. More specifically, saliva from both groups increased TER and induced IL-6 and IL-8 secretion in the in vitro oral epithelium models used.Conclusion: Independently of the presence or absence of periodontitis, saliva can increase the relative TER and the secretion of IL-6 and IL-8 in in vitro models of the oral epithelium.

Frontiers in Oral Mucosal Immunity and the Microbiome

The 2nd International Conference on Oral Mucosal Immunity and the Microbiome (OMIM) took place at the Grecotel Kos Imperial Hotel, Kos, Greece, between 25th and 30th September 2021, under the auspices of the Aegean Conferences. This has only been the second Aegean Conference of this thematic, the first one having taken place in 2018 in Crete, during the same period of the year. Given the hardships in travel and heightened infection transmission risks amid the COVID-19 pandemic, the Conference was well attended by 29 international speakers across the world. For many of the participants, this was the first conference travel in the post-pandemic era, and quite significant that it has taken place on the island of Hippocrates. Stringent regional health and safety regulations had to be followed to accomplish for this in-person Conference to take place. Frontiers in Oral Health has hosted papers from presentations of the Conference, whereas the present article serves as the proceedings of the Conference with summaries of the presentations.

A Literature Review and Framework Proposal for Halitosis Assessment in Cigarette Smokers and Alternative Nicotine-Delivery Products Users

Halitosis is a health condition which counts cigarette smoking (CS) among its major risk factors. Cigarette smoke can cause an imbalance in the oral bacterial community, leading to several oral diseases and conditions, including intraoral halitosis. Although the best approach to decrease smoking-related health risks is quitting smoking, this is not feasible for many smokers. Switching to potentially reduced-risk products, like electronic vapor products (EVP) or heated tobacco products (HTP), may help improve the conditions associated with CS. To date, there have been few systematic studies on the effects of CS on halitosis and none have assessed the effects of EVP and HTP use. Self-assessment studies have shown large limitations owing to the lack of reliability in the participants' judgment. This has compelled the scientific community to develop a strategy for meaningful assessment of these new products in comparison with cigarettes. Here, we compiled a review of the existing literature on CS and halitosis and propose a 3-layer approach that combines the use of the most advanced breath analysis techniques and multi-omics analysis to define the interactions between oral bacterial species and their role in halitosis both in vitro and in vivo. Such an approach will allow us to compare the effects of different nicotine-delivery products on oral bacteria and quantify their impact on halitosis. Defining the impact of alternative nicotine-delivery products on intraoral halitosis and its associated bacteria will help the scientific community advance a step further toward understanding the safety of these products and their potentiall risks for consumers.