Maackia amurensis seed lectin (MASL) and soluble human podoplanin (shPDPN) sequence analysis and effects on human oral squamous cell carcinoma (OSCC) cell migration and viability.

Maackia amurensis lectins serve as research and botanical agents that bind to sialic residues on proteins. For example, M. amurensis seed lectin (MASL) targets the sialic acid modified podoplanin (PDPN) receptor to suppress arthritic chondrocyte inflammation, and inhibit tumor cell growth and motility. However, M. amurensis lectin nomenclature and composition are not clearly defined. Here, we sought to definitively characterize MASL and its effects on tumor cell behavior. We utilized SDS-PAGE and LC-MS/MS to find that M. amurensis lectins can be divided into two groups. MASL is a member of one group which is composed of subunits that form dimers, evidently mediated by a cysteine residue in the carboxy region of the protein. In contrast to MASL, members of the other group do not dimerize under nonreducing conditions. These data also indicate that MASL is composed of 4 isoforms with an identical amino acid sequence, but unique glycosylation sites. We also produced a novel recombinant soluble human PDPN receptor (shPDPN) with 17 threonine residues glycosylated with sialic acid moieties with potential to act as a ligand trap that inhibits OSCC cell growth and motility. In addition, we report here that MASL targets PDPN with very strong binding kinetics in the nanomolar range. Moreover, we confirm that MASL can inhibit the growth and motility of human oral squamous cell carcinoma (OSCC) cells that express the PDPN receptor. Taken together, these data characterize M. amurensis lectins into two major groups based on their intrinsic properties, clarify the composition of MASL and its subunit isoform sequence and glycosylation sites, define sialic acid modifications on the PDPN receptor and its ability to act as a ligand trap, quantitate MASL binding to PDPN with KD in the nanomolar range, and verify the ability of MASL to serve as a potential anticancer agent.

Identification of common salivary miRNA in oral lichen planus and oral squamous cell carcinoma: systematic review and meta-analysis.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory condition that can impact patients' quality of life. While its exact etiology remains unclear, it is associated with an increased risk of malignant transformation. Currently, the diagnosis of OLP relies on clinical examination and histopathological analysis, which can be invasive. Therefore, there is an urgent need for non-invasive and accurate diagnostic biomarkers. This systematic review and meta-analysis aims to investigate the potential of salivary microRNAs as promising candidates for OLP diagnosis. This meta-analysis seeks to identify specific microRNAs that are differentially expressed and could serve as reliable biomarkers for OLP diagnosis. METHODS: Our strategy involved searching for pertinent keywords in multiple academic databases including Cochrane Library, Embase, LIVIVO, MEDLINE, Ovid, ProQuest, Scopus, Web of Science, Espacenet, and Google Scholar search engine. Upon identification, articles were screened and data extracted from the eligible studies. Split component synthesis method was utilized to assess specificity, sensitivity, likelihood and diagnostic odds ratios. The random-effects meta-analysis approach was used to combine study findings and develop pooled diagnostic performance metrics. Hierarchical summary receiver operating characteristic (ROC) plots were generated to determine area under the curve. Subgroup analyses concerning the type of saliva and control groups were also performed. RESULTS: Among the fourteen studies included in our systematic review, five were eligible for meta-analysis. Salivary microRNAs showed the pooled sensitivity of 0.80 (95% Confidence Interval (95% CI): 0.68-0.88), specificity of 0.89 (95% CI: 0.82-0.94), diagnostic odds ratio of 28.45 (95% CI: 10.40-77.80), and area under the curve (AUC) of 0.93 for OLP diagnosis. Unstimulated saliva had higher sensitivity and specificity than oral swirl samples as the biomarker medium for OLP diagnosis. Meta-analysis uncovered that miR-27a, miR-137, miR-1290, miR-27b, miR-4484, miR-142, and miR-1246 had the highest diagnostic odds ratio for OLP. CONCLUSIONS: Our systematic review and meta-analysis demonstrate that salivary microRNAs can serve as valuable biomarkers for the diagnosis of OLP. The findings highlight the exceptional accuracy of salivary microRNAs in differentiating OLP patients from healthy controls and assessing the risk of malignant transformation.

Salivary noncoding RNA in the diagnosis of pancreatic cancer: Systematic review and meta-analysis.

BACKGROUND: Pancreatic cancer is considered one of the most deadly malignancies, primarily because of its diagnostic challenges. We performed a systematic review and diagnostic meta-analysis to evaluate the diagnostic value of noncoding salivary RNAs in pancreatic cancer diagnosis. METHODS: Our investigation involved pertinent studies published in PubMed, Scopus, Web of Science, LIVIVO, Ovid and also the Google Scholar search engine. Specificity and sensitivity were calculated, as were positive and negative likelihood ratios (PLR and NLR), and the diagnostic odds ratio (DOR). The summary receiver-operating characteristics and area under the curve were plotted and assessed. RESULTS: This meta-analysis and systematic review involved and examined five studies that contained 145 study units with a total of 2731 subjects (1465 pancreatic cancer patients versus 1266 noncancer controls). The pooled specificity, sensitivity, NLR, PLR and DOR were 0.783 (95% CI: 0.759-0.805), 0.829 (95% CI: 0.809-0.848), 0.309 (95% CI: 0.279-0.343), 3.386 (95% CI: 2.956-3.879) and 18.403 (95% CI: 14.753-22.954), respectively, with the area under the curve (AUC) equal to 0.882. Subgroup analyses were conducted based on the saliva type (unstimulated and stimulated), mean age of patients, sample size, type of control, serum carbohydrate antigen 19-9 (CA19-9) level and type of salivary noncoding RNA (microRNA (miRNA) and long noncoding RNA (lncRNA)). CONCLUSIONS: The results of our systematic review and meta-analysis suggest that noncoding RNA biomarkers in the stimulated saliva could be a promising approach for accurate pancreatic cancer diagnosis in the early stages.

Monckeberg's Medial Sclerosis as a Cause for Headache and Facial Pain.

PURPOSE OF REVIEW: Mönckeberg's medial sclerosis (MMS) is a chronic, non-inflammatory degenerative condition affecting primarily the tunica media of muscular arteries resulting in their calcification. The purpose of this comprehensive review is to describe MMS as it appears in the literature, in the context of headache and facial pain. Understanding the etiopathology, the associated conditions, and the differential diagnoses is important in managing MMS. RECENT FINDINGS: Management of MMS primarily depends upon identification of its associated conditions and their treatment. Due to the rare incidence and inadequate literature on MMS presenting with headaches, the diagnosis of the pain and the entity itself is challenging. MMS is characterized by associated systemic conditions and absence of inflammatory markers. It can mimic giant cell arteritis (GCA) and other pain entities. An interdisciplinary approach involving appropriate specialties is recommended.

HIV Modifies the Effect of Tobacco Smoking on Oral Human Papillomavirus Infection.

BACKGROUND: People living with HIV (PLWH) are more likely to smoke and harbor oral human papillomavirus (HPV) infections, putting them at higher risk for head and neck cancer. We investigated effects of HIV and smoking on oral HPV risk. METHODS: Consecutive PLWH (n = 169) and at-risk HIV-negative individuals (n = 126) were recruited from 2 US health centers. Smoking history was collected using questionnaires. Participants provided oral rinse samples for HPV genotyping. We used multivariable logistic regression models with interaction terms for HIV to test for smoking effect on oral HPV. RESULTS: PLWH were more likely to harbor oral HPV than HIV-negative individuals, including α (39% vs 28%), ß (73% vs 63%), and γ-types (33% vs 20%). HIV infection positively modified the association between smoking and high-risk oral HPV: odds ratios for smoking 3.46 (95% confidence interval [CI], 1.01-11.94) and 1.59 (95% CI, .32-8.73) among PLWH and HIV-negative individuals, respectively, and relative excess risk due to interaction (RERI) 3.34 (95% CI, -1.51 to 8.18). RERI for HPV 16 was 1.79 (95% CI, -2.57 to 6.16) and 2.78 for ß1-HPV (95% CI, -.08 to 5.65). CONCLUSION: Results show tobacco smoking as a risk factor for oral HPV among PLWH.

Pleomorphic Adenoma of the Upper Lip: A Rare Case.

Salivary gland tumors account for a small fraction of head and neck tumors. Pleomorphic adenoma, the most common salivary gland neoplasm, frequently arises in major salivary glands; its localization to minor salivary glands is uncommon and typically involves the palate. We describe a patient with an asymptomatic, long-standing mass of the upper lip, which was found to be a pleomorphic adenoma.

Oral Psoriasis: An Overlooked Enigma.

Although cutaneous psoriasis is common, the existence of its manifestations in the oral cavity has been questioned. The definitive diagnosis of oral psoriasis can be challenging due to the variability of presentations, and overlapping clinical and histological features with a number of other conditions as well as the lack of consensus. We review oral psoriasis, noting its variable clinical appearance, delineate the differential diagnosis, and discuss management strategies.

Oral Human Papillomavirus Infection and Oral Lesions in HIV-Positive and HIV-Negative Dental Patients.

We evaluated the risk factors associated with oral human papillomavirus (HPV) infection and oral lesions in 161 human immunodeficiency virus (HIV)-positive patients and 128 HIV-negative patients presenting for oral examination at 2 urban healthcare centers. Patients were interviewed on risk factors and provided oral-rinse samples for HPV DNA typing by polymerase chain reaction. Statistical associations were assessed by logistic regression. Oral HPV was prevalent in 32% and 16% of HIV-positive patients and HIV-negative patients, respectively, including high-risk HPV type 16 (8% and 2%, respectively; P = .049) and uncommon HPV types 32/42 (6% and 5%, respectively; P = .715). Among HIV-negative patients, significant risk factors for oral HPV included multiple sex partners (≥21 vs ≤5; odds ratio [OR], 9.1; 95% confidence interval [CI], 1.7-49.3), heavy tobacco smoking (>20 pack-years vs none; OR, 9.2; 95% CI, 1.4-59.4), and marijuana use (OR, 4.0; 95% CI, 1.3-12.4). Among HIV-positive patients, lower CD4(+) T-cell count only was associated with oral HPV detection (≤200 vs ≥500 cells/mm(3); OR, 4.5; 95% CI, 1.3-15.5). Detection of high-risk HPV was also associated with concurrent detection of potentially cancerous oral lesions among HIV-negative patients but not among HIV-positive patients. The observed risk factor associations with oral HPV in HIV-negative patients are consistent with sexual transmission and local immunity, whereas in HIV-positive patients, oral HPV detection is strongly associated with low CD4(+) T-cell counts.

Activity of potent and selective host defense peptide mimetics in mouse models of oral candidiasis.

There is a strong need for new broadly active antifungal agents for the treatment of oral candidiasis that not only are active against many species of Candida, including drug-resistant strains, but also evade microbial countermeasures which may lead to resistance. Host defense peptides (HDPs) can provide a foundation for the development of such agents. Toward this end, we have developed fully synthetic, small-molecule, nonpeptide mimetics of the HDPs that improve safety and other pharmaceutical properties. Here we describe the identification of several HDP mimetics that are broadly active against C. albicans and other species of Candida, rapidly fungicidal, and active against yeast and hyphal cultures and that exhibit low cytotoxicity for mammalian cells. Importantly, specificity for Candida over commensal bacteria was also evident, thereby minimizing potential damage to the endogenous microbiome which otherwise could favor fungal overgrowth. Three compounds were tested as topical agents in two different mouse models of oral candidiasis and were found to be highly active. Following single-dose administrations, total Candida burdens in tongues of infected animals were reduced up to three logs. These studies highlight the potential of HDP mimetics as a new tool in the antifungal arsenal for the treatment of oral candidiasis.

Plasma Cell Mucositis: A Clinical Conundrum.

Plasma cell mucositis (PCM) is an unusual disorder most evident in the accessible mucosa and usually reported in the upper aerodigestive tract, although it is named according to its specific anatomical site of involvement such as plasma cell cheilitis, plasma cell gingivitis, plasma cell vulvitis, and Zoon's balanitis. PCM reflects a dense polyclonal rather than a monoclonal plasma cell proliferation of unclear and unknown etiology. This perplexing disorder tends to be treated by avoiding possible triggers and intralesional and/or systemic steroids. In this work, we provide a review and update on PCM, which often represents a clinical conundrum.

Secretory carcinoma of minor salivary glands.

Secretory carcinoma is a malignant salivary gland tumor, which typically presents as an indolent painless mass within the parotid gland. Involvement of the minor gland is reported but less common. Secretory carcinoma was often misclassified as other salivary gland mimics, particularly acinic cell carcinoma, prior to 2010. It was first recognized as a molecularly distinct salivary gland tumor harboring the same fusion gene as well as histologic and cytogenetic features seen in juvenile breast cancer. Secretory carcinoma is generally managed in the same way as other low-grade salivary gland neoplasms and has a favorable prognosis; however, high-grade transformation requiring aggressive therapeutic interventions have been documented. Recent studies of biologic agents targeting products of this fusion gene offer the promise of a novel therapeutic option for treatment of this malignancy. Due to the limited number of reported cases, the spectrum of clinical behavior, best practices for management, and long-term treatment outcomes for secretory carcinoma remain unclear. A long-standing secretory carcinoma involving minor salivary glands of the mucobuccal fold, which was detected years after it was first noted by the patient, is reported. This case brings to light the importance of a thorough clinical exam during dental visits and reviews diagnostic differentiation of this malignancy from other mimics and discusses decision making for its management.

Systemic Factors Affecting Healing in Dentistry.

Healing process in the oral cavity is influenced by a range of systemic factors. More specifically, patient health status, medications, habits, and nutritional state play crucial roles in dental healing. Additionally, the body's immune response, inflammation, and overall well-being are key determinants in wound repair. Understanding these systemic factors is essential for dental professionals to optimize patient care, minimize complications, and achieve successful healing.

A novel oral medicine-centered interprofessional curricular initiative to promote collaboration and build oral health capacity.

INTRODUCTION: Oral physicians should possess knowledge, skills, and attitudes required for functioning in the evolving integrated care systems. Paramount for addressing the existing oral health disparities is also adequate training of non-dental health professionals in the foundations of oral health. We conducted interprofessional oral medicine-centered case conferences to prepare dental students for collaborative care and to increase awareness of non-dental students about the mouth-body connection. Herein, we share our perspective and the students' feedback about this educational program. METHODS: Students from seven health profession and social work programs attended an interactive, online oral medicine-centered case conference facilitated by an oral medicine faculty and at least one faculty from another profession. Faculty facilitators guided students to identify key points and encouraged team-based care. Anonymous, voluntary online surveys were distributed to participants immediately after each session. Descriptive data tabulated and analyzed. RESULTS: A total of 151 students participated in conferences between 11/11/2022 and 3/24/2023 and 132 (87%) submitted postexperience surveys. Students agreed that the case conference was applicable to their profession (95%) and meaningful (94%), they learned new information about other professions (94%), they could contribute to discussions (90%), interactions were respectful (99%), and discussions emphasized interprofessional collaboration (96%). Non-dental respondents learned more about oral-systemic link (95%), recognized a broader role for dentists (90%), and agreed with inclusion of more oral health content in their curricula (79%). CONCLUSION: Oral medicine-centered case conferences provided an effective curricular path for demonstrating oral-systemic connection, promoting meaningful interprofessional collaboration, and building oral health capacity among students of non-dental health professions.

A dramatic case of oral epitheliolysis.

Oral epitheliolysis or mucosal shedding is an infrequently described phenomenon characterized by epithelial desquamation, revealing mucosa of normal color and texture underneath. The condition has a predilection for middle-aged females and primarily affects nonkeratinized oral tissues. Although some cases are idiopathic, certain oral hygiene products have been implicated as the culprit, and resolution of the condition documented with their discontinuation. Severity of desquamation and symptoms vary with frequency and duration of contact with the irritant and its concentration. A case is presented of a dramatic case of shedding oral mucosa in an elderly female, which appeared to be caused by habitual chewing of an aspirin-containing over-the-counter analgesic.

Novel treatment approach of localized juvenile spongiotic gingival hyperplasia with use of Nd:YAG laser.

INTRODUCTION: This article describes the management of two patients who presented with localized juvenile spongiotic gingival hyperplasia. This disease entity is poorly understood, and literature regarding successful treatment is scant. However, there are common themes to management including proper diagnosis and treatment via removal of the affected tissue. The biopsy demonstrates intercellular edema and neutrophil infiltrate with epithelial and connective tissue disease components, so surgical deepithelialization may not be adequate to definitively treat the disease. METHODS AND RESULTS: This article presents two cases of the disease and suggests the use of the Nd:YAG laser as an alternative management modality. CONCLUSION: To our knowledge, we present the first cases of localized juvenile spongiotic gingival hyperplasia treated with the Nd:YAG laser. KEY POINTS: Why are these cases new information? To our knowledge, this case series illustrates the first use of an Nd:YAG laser to treat the rare pathology localized juvenile spongiotic gingival hyperplasia. What are the keys to successful management of these cases? To properly manage this rare presentation, proper diagnosis is paramount. Following diagnosis with microscopic evaluation, deepithelialization and treatment of underlying connective tissue infiltrate via the Nd:YAG laser offers an elegant option to treat the pathology and maintain esthetic outcomes. What are the primary limitations to success in these cases? The primary limitations of these cases include the small sample size, which is attributable to the rarity of the disease.

Plasma Cell Mucositis: A Clinical Conundrum.

Plasma cell mucositis (PCM) is an unusual disorder most evident in the accessible mucosa and usually reported in the upper aerodigestive tract, although it is named according to its specific anatomical site of involvement, such as plasma cell cheilitis, plasma cell gingivitis, plasma cell vulvitis, and Zoon's balanitis. PCM reflects a dense polyclonal, rather than a monoclonal, plasma cell proliferation of unclear and unknown etiology. This perplexing disorder tends to be treated by avoiding possible triggers and intralesional and/or systemic steroids. Herein we review and provide an update on PCM, which often represents a clinical conundrum.

Systemic Factors in Temporomandibular Disorder Pain.

The science of temporomandibular disorder (TMD) pain and its management has gone through significant changes during the last several decades. The authors strongly feel that the effect of systemic factors influencing TMD pain has been largely overlooked and poorly accounted for, even in established pain-management programs and protocols. The hope is that this article will act as a wake-up call for the pain management community to consider the importance of adequate knowledge of the systemic factors that affect the experience of TMD pain by the patient.

The oral cavity contains abundant known and novel human papillomaviruses from the Betapapillomavirus and Gammapapillomavirus genera.

BACKGROUND: Human papillomaviruses (HPVs) primarily sort into 3 genera: Alphapapillomavirus (α-HPV), predominantly isolated from mucosa, and Betapapillomavirus (ß-HPV) and Gammapapillomavirus (γ-HPV), predominantly isolated from skin. HPV types might infect body sites that are different from those from which they were originally isolated. METHODS: We investigated the spectrum of HPV type distribution in oral rinse samples from 2 populations: 52 human immunodeficiency virus (HIV)-positive men and women and 317 men who provided a sample for genomic DNA for a prostate cancer study. HPV types were detected with the MY09/MY11 and FAP59/64 primer systems and identified by dot blot hybridization and/or direct sequencing. RESULTS: Oral rinse specimens from 35 (67%) of 52 HIV-positive individuals and 117 (37%) of 317 older male participants tested positive for HPV DNA. We found 117 type-specific HPV infections from the HIV-positive individuals, including 73 α-HPV, 33 ß-HPV, and 11 γ-HPV infections; whereas, the distribution was 46 α-HPV, 108 ß-HPV, and 14 γ-HPV infections from 168 type-specific infections from the 317 male participants. CONCLUSIONS: The oral cavity contains a wide spectrum of HPV types predominantly from the ß-HPV and γ-HPV genera, which were previously considered to be cutaneous types. These results could have significant implications for understanding the biology of HPV and the epidemiological associations of HPV with oral and skin neoplasia.

Recurrent Aphthous Stomatitis: An Enigmatic Entity and Sign of Systemic Disease.

Recurrent aphthous stomatitis (RAS) is a common oral disease characterized by intermittent eruptions of painful oral ulcerations. Hippocrates first described aphthous stomatitis with the Greek word aphthi meaning "to inflame." RAS affects 10-20% of the population with the incidence being the highest among young adults. The peak age of onset is between 10 and 19 years of age. It has three main forms of presentation. The most common being minor RAS, along with the major and herpetiform types. Many local and systemic factors are associated with RAS pathogenesis. The main concern with oral aphthae in many cases is local pain, which can be severe enough to interfere with eating, speaking, and swallowing. It is important to differentiate RAS from systemic diseases with aphthae-such as Behçet's syndrome and the newly-delineated, autoinflammatory PFAPA (periodic fever with aphthous stomatitis, pharyngitis, and adenitis) syndrome-as well as from other aphthous-like ulcerations like herpes simplex virus (HSV) or Coxsackie oral lesions. The management depends upon the clinical presentation and symptomatology-focusing on analgesic, antimicrobial, and immunomodulatory drugs.

Salivary biomarkers in breast cancer diagnosis: A systematic review and diagnostic meta-analysis.

BACKGROUND: Salivary diagnostics and their utility as a nonaggressive approach for breast cancer diagnosis have been extensively studied in recent years. This meta-analysis assesses the diagnostic value of salivary biomarkers in differentiating between patients with breast cancer and controls. METHODS: We conducted a meta-analysis and systematic review of studies related to salivary diagnostics published in PubMed, EMBASE, Scopus, Ovid, Science Direct, Web of Science (WOS), and Google Scholar. The articles were chosen utilizing inclusion and exclusion criteria, as well as assessing their quality. Specificity and sensitivity, along with negative and positive likelihood ratios (NLR and PLR) and diagnostic odds ratio (DOR), were calculated based on random- or fixed-effects model. Area under the curve (AUC) and summary receiver-operating characteristic (SROC) were plotted and evaluated, and Fagan's Nomogram was evaluated for clinical utility. RESULTS: Our systematic review and meta-analysis included 14 papers containing 121 study units with 8639 adult subjects (4149 breast cancer patients and 4490 controls without cancer). The pooled specificity and sensitivity were 0.727 (95% CI: 0.713-0.740) and 0.717 (95% CI: 0.703-0.730), respectively. The pooled NLR and PLR were 0.396 (95% CI: 0.364-0.432) and 2.597 (95% CI: 2.389-2.824), respectively. The pooled DOR was 7.837 (95% CI: 6.624-9.277), with the AUC equal to 0.801. The Fagan's nomogram showed post-test probabilities of 28% and 72% for negative and positive outcomes, respectively. We also conducted subgroup analyses to determine specificity, sensitivity, DOR, PLR, and NLR based on the mean age of patients (≤52 or >52 years old), saliva type (stimulated and unstimulated saliva), biomarker measurement method (mass spectrometry [MS] and non-MS measurement methods), sample size (≤55 or >55), biomarker type (proteomics, metabolomics, transcriptomics and proteomics, and reagent-free biophotonic), and nations. CONCLUSION: Saliva, as a noninvasive biomarker, has the potential to accurately differentiate breast cancer patients from healthy controls.