Tailored Sticky Solutions: 3D-Printed Miconazole Buccal Films for Pediatric Oral Candidiasis.

In this research, 3D-printed antifungal buccal films (BFs) were manufactured as a potential alternative to commercially available antifungal oral gels addressing key considerations such as ease of manufacturing, convenience of administration, enhanced drug efficacy and suitability of paediatric patients. The fabrication process involved the use of a semi-solid extrusion method to create BFs from zein-Poly-Vinyl-Pyrrolidone (zein-PVP) polymer blend, which served as a carrier for drug (miconazole) and taste enhancers. After manufacturing, it was determined that the disintegration time for all films was less than 10 min. However, these films are designed to adhere to buccal tissue, ensuring sustained drug release. Approximately 80% of the miconazole was released gradually over 2 h from the zein/PVP matrix of the 3D printed films. Moreover, a detailed physicochemical characterization including spectroscopic and thermal methods was conducted to assess solid state and thermal stability of film constituents. Mucoadhesive properties and mechanical evaluation were also studied, while permeability studies revealed the extent to which film-loaded miconazole permeates through buccal tissue compared to commercially available oral gel formulation. Histological evaluation of the treated tissues was followed. Furthermore, in vitro antifungal activity was assessed for the developed films and the commercial oral gel. Finally, films underwent a two-month drug stability test to ascertain the suitability of the BFs for clinical application. The results demonstrate that 3D-printed films are a promising alternative for local administration of miconazole in the oral cavity.

Minor salivary gland stem cells: a comparative study of the biological properties under clinical-grade culture conditions.

Development of clinical-grade, cell preparations is central to cGMP (good manufacturing practice compliant) conditions. This study aimed to investigate the potential of two serum/xeno-free, cGMP (StemPro, StemMacs) culture media to maintain "stemness" of human minor salivary gland stem cell (mSG-SC) cultures compared to a complete culture medium (CCM). Overall, StemMacs resulted in higher proliferation rates after p.6 compared to the conventional serum-based medium, while StemPro showed substantial delays in cell proliferation after p.9. The mSG-SCs cultures exhibited two distinct cell populations at early passages a mesenchymal subpopulation and an epithelial-like subpopulation. Expression of several markers (CD146, STRO-1, SSEA-4, CD105, CD106, CD34, K 7/8, K14, K18) variably decreased with prolonged passaging (all three media). The percentage of SA-ß-gal positive cells was initially higher for StemMacs compared to StemPro/CCM and increased with prolonged passaging in all cases. The telomere fragment length decreased with prolonged passaging in all three media but more pronouncedly for the CCM. Expansion under serum-free conditions caused pronounced upregulation of ALP and BMP-2, with parallel complete elimination of the baseline expressions of LPL (all three media) and ACAN (serum-free media), therefore, showing a preferential shift of the mSG-SCs towards osteogenic phenotypes. Finally, several markers (Nanog, SOX-2, PDX-1, OTX2, GSC, HCG) decreased with prolonged culture, indicating successive loss of "stemness". Based on the findings, it seems that StemPro preserve stemness of the mSG-SCs after prolonged culture. Nevertheless, there is still a vacant role for the ideal development of clinical-grade culture conditions.

In Situ Gelling Electrospun Ocular Films Sustain the Intraocular Pressure-Lowering Effect of Timolol Maleate: In Vitro, Ex Vivo, and Pharmacodynamic Assessment.

Most common intraocular pressure (IOP) reduction regimens for the management of glaucoma include the topical use of eye drops, a dosage form that is associated with short residence time at the site of action, increased dosing frequency, and reduced patient compliance. In situ gelling nanofiber films comprising poly(vinyl alcohol) and Poloxamer 407 were fabricated via electrospinning for the ocular delivery of timolol maleate (TM), aiming to sustain the IOP-lowering effect of the ß-blocker, compared to conventional eye drops. The electrospinning process was optimized, and the physicochemical properties of the developed formulations were thoroughly investigated. The fiber diameters of the drug-loaded films ranged between 123 and 145 nm and the drug content between 5.85 and 7.83% w/w. Total in vitro drug release from the ocular films was attained within 15 min following first-order kinetics, showing higher apparent permeability (Papp) values across porcine corneas compared to the drug's solution. The fabricated films did not induce any ocular irritation as evidenced by both the hen's egg test on chorioallantoic membrane and the in vivo Draize test. In vivo administration of the ocular films in rabbits induced a faster onset of action and a sustained IOP-lowering effect up to 24 h compared to TM solution, suggesting that the proposed ocular films are promising systems for the sustained topical delivery of TM.

Effect of periodontal therapy on COPD outcomes: a systematic review.

BACKGROUND: Latest evidence suggests that periodontitis is prevalent among patients with chronic obstructive pulmonary disease (COPD), while recent studies have also reported a potential benefit of periodontal treatment on several COPD outcomes. This systematic review aims to determine the impact of periodontal treatment on exacerbation rate, lung function and quality of life of COPD patients. METHODS: A systematic search of electronic databases of PubMed, Scopus, Virtual Health Library, ScienceDirect, Wiley Online Library, Web of Science, ProQuest Dissertation and Theses Global and Google Scholar was conducted. Search restricted to studies involving human subjects which were published from January 2000 to March 2020 in English language. Distiller Systematic Review software was used for data management. Risk of bias was assessed using Risk of Bias 2 (RoB2) and Risk of Bias for non-randomized studies of intervention (ROBINS-I) tools. Overall quality of evidence was judged based on Grading of Recommendations Assessment, Development and Evaluation working group methodology. RESULTS: Out of 1442 articles retrieved, 7 full text articles were included in the review. Limited evidence suggests that periodontal treatment in patients with COPD and periodontitis is associated with reduced exacerbation frequency and a slower lung function decline rate, while its effects on quality of life remain unclear. In addition, periodontal treatment in COPD is associated with lower hospitalization rates and reduced all-cause mortality. Significant methodological differences were noted amongst included studies, while very low-to-moderate overall quality of evidence was demonstrated. CONCLUSIONS: Although it is reasonable to advise COPD patients not to neglect their dental health, further studies are warranted to determine the role of periodontal therapy on COPD clinical outcomes. TRIAL REGISTRATION: PROSPERO 2020 (CRD42020158481). https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020158481.

Investigation of the relationship between sleep disorders and xerostomia.

OBJECTIVES: To investigate the relationship between sleep disorders, morning hyposalivation, and subjective feeling of dry mouth. MATERIALS AND METHODS: A cross-sectional, observational, clinical study was carried out in a homogenous population sample which consists of Greek male soldiers without any medical history. After the application of oral modified Schirmer test, the sample was divided into a study group (n = 63) (MST < 25 mm/3 min) and a control group (n = 110) (MST ≥ 25 mm/3 min). In order to assess daytime sleepiness, risk of obstructive sleep apnea (OSA), sleep quality, sleep bruxism (SB), and subjective feeling of dry mouth, all the participants filled in the following scales in Greek version: Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Berlin Questionnaire (BQ), a SB questionnaire, and Xerostomia Inventory (XI) respectively. In every subgroup that came of ESS, PSQI, BQ, and SB questionnaire scoring, subjective feeling of dry mouth was evaluated, based on XI values. RESULTS: Statistically significant difference (p < 0.001) through PSQI scores was found between the study and control group. In contrast, a statistically significant difference was not obtained for the scores of ESS (p = 0.293), BQ (p = 0.089), and SB questionnaire (p = 0.730). XI scores introduced statistically significant difference between the subgroups of PSQI (p < 0.001), BQ (p = 0.001), SB questionnaire (p = 0.004)  and statistically weak between the subgroups of ESS (p = 0.049). CONCLUSIONS: This is the first research study so far suggesting that patients with morning hyposalivation exhibit poor sleep quality using an objective method. The present results have, also, shown that subjective feeling of dry mouth is related to excessive daytime sleepiness, poor sleep quality, high risk of obstructive sleep apnea, and sleep bruxism, but larger-scale studies are still needed. CLINICAL RELEVANCE: These findings should keep dentists aware of a possible association between xerostomia and sleep disorders and support larger-scale studies.

Inkjet printing of a thermolabile model drug onto FDM-printed substrates: formulation and evaluation.

OBJECTIVE: The inkjet printing (IP) and fused deposition modeling (FDM) technologies have emerged in the pharmaceutical field as novel and personalized formulation approaches. Specific manufacturing factors must be considered in each adopted methodology, i.e. the development of suitable substrates for IP and the incorporation of highly thermostable active pharmaceutical compounds (APIs) for FDM. In this study, IP and FDM printing technologies were investigated for the fabrication of hydroxypropyl methylcellulose-based mucoadhesive films for the buccal delivery of a thermolabile model drug. Significance: This proof-of-concept approach was expected to provide an alternative formulation methodology for personalized mucoadhesive buccal films. METHODS: Mucoadhesive substrates were prepared by FDM and were subjected to sequential IP of an ibuprofen-loaded liquid ink. The interactions between these processes and the performance of the films were evaluated by various analytical and spectroscopic techniques, as well as by in vitro and ex vivo studies. RESULTS: The model drug was efficiently deposited by sequential IP passes onto the FDM-printed substrates. Significant variations were revealed on the morphological, physicochemical and mechanical properties of the prepared films, and linked to the number of IP passes. The mechanism of drug release, the mucoadhesion and the permeation of the drug through the buccal epithelium were evaluated, in view of the extent of ink deposition onto the buccal films, as well as the distribution of the API. CONCLUSIONS: The presented methodology provided a proof-of-concept formulation approach for the development of personalized mucoadhesive films.

Synergistic Antitumor Potency of a Self-Assembling Peptide Hydrogel for the Local Co-delivery of Doxorubicin and Curcumin in the Treatment of Head and Neck Cancer.

Combination therapy has been conferred with manifold assets leveraging the synergy of different agents to achieve a sufficient therapeutic outcome with lower administered drug doses and reduced side effects. The therapeutic potency of a self-assembling peptide hydrogel for the co-delivery of doxorubicin and curcumin was assessed against head and neck cancer cells. The dual loaded peptide hydrogel enabled control over the rate of drug release based on drug's aqueous solubility. A significantly enhanced cell growth inhibitory effect was observed after treatment with the combination drug-loaded hydrogel formulations compared to the respective combination drug solution. The synergistic pharmacological effect of selected hydrogel formulations was further confirmed with enhanced apoptotic cell response, interference in cell cycle progression, and significantly altered apoptotic/anti-apoptotic gene expression profiles obtained in dose levels well below the half-maximal inhibitory concentrations of both drugs. The in vivo antitumor efficacy of the drug-loaded peptide hydrogel formulation was confirmed in HSC-3 cell-xenografted severe combined immunodeficient mice and visualized with µCT imaging. Histological and terminal deoxynucleotidyl transferase dUTP nick end labeling assay analyses of major organs were implemented to assess the safety of the topically administered hydrogel formulation. Overall, results demonstrated the therapeutic utility of the dual drug-loaded peptide hydrogel as a pertinent approach for the local treatment of head and neck cancer.

Salivary Gland Stem Cells and Tissue Regeneration: An Update on Possible Therapeutic Application.

The aim of this review is to combine literature and experimental data concerning the impact of salivary gland (SG) stem cells (SCs) and their therapeutic prospects in tissue regeneration. So far, SCs were isolated from human and rodent major and minor SGs that enabled their regeneration. Several scaffolds were also combined with "SCs" and different "proteins" to achieve guided differentiation, although none have been proven as ideal. A new aspect of SC therapy aims to establish a vice versa relationship between SG and other ecto- or endodermal organs such as the pancreas, liver, kidneys, and thyroid. SC therapy could be a cheap and simple, non-traumatic, and individualized therapy for medically challenging cases like xerostomia and major organ failures. Functional improvement has been achieved in these organs, but till date, the whole organ in vivo regeneration was not achieved. Concerns about malignant formations and possible failures are yet to be resolved. In this review article, we highlight the basic embryology of SGs, existence of SG SCs with a detailed exploration of various cellular markers, scaffolds for tissue engineering, and, in the later part, cover potential therapeutic applications with a special focus on the pancreas and liver. Keywords: Salivary gland stem cells, Stem cell therapy, Tissue regeneration.

Ex vivo buccal drug delivery of ropinirole hydrochloride in the presence of permeation enhancers: the effect of charge.

In the current study, the ex vivo permeation of ropinirole hydrochloride (RH) across porcine buccal mucosa in the presence of three permeation enhancers, namely N-trimethyl chitosan (TMC) (positively charged) a chitosan derivative, sulfobutyl ether-ß-cyclodextrin (SBE-ß-CD) (negatively charged) and hydroxypropyl-ß-cyclodextrin (HP-ß-CD) (neutral), was investigated. Buccal permeation studies were conducted using Franz diffusion cells. Cumulative amounts of RH were plotted versus time. The presence of the permeation enhancers significantly increased the transport of the drug across the porcine buccal epithelium compared to its plain congener (RH solution). The rank order effect of the permeation enhancers for the transport of RH across buccal epithelium was TMC ≥ SBE-ß-CD > HP-ß-CD > RH solution. The presence of TMC increased 1.34-fold the transport of RH across buccal epithelium, whereas an increase of 1.23- and 1.28-fold was reported in the presence of HP-ß-CD and SBE-ß-CD, respectively. Infrared spectroscopy (IR) was employed to investigate the interaction of permeation enhancers with the epithelial lipids of porcine buccal mucosa corroborating the permeation results. Finally, light microscopy was performed to assess the histological changes in the porcine epithelium. Formation of vacuoles, spongiosis and acantholysis linear detachment and destruction of the epithelium resulted from the presence of the permeation enhancers. The data suggest that all enhancers tested, and particularly TMC, increase the transport of RH across buccal epithelium.

Desmoglein-3/γ-catenin and E-cadherin/ß-catenin differential expression in oral leukoplakia and squamous cell carcinoma.

OBJECTIVE: The purpose of this study was to investigate gene/protein expression alterations of intercellular connections' components in oral leukoplakia (OLs) and squamous-cell carcinoma (OSCCs). MATERIALS AND METHODS: Expression of desmogleins-2,3 (Dsg2/Dsg3), E-cadherin, and their cytoplasmic ligand, ß/γ-catenins were quantitatively assessed in HSC-3 cells growing as monolayer cultures (ML)/multicellular aggregates (MCAs), using RT-PCR/Western blot, whereas their localization was detected by immunofluorescence. Furthermore, their expression was semi-quantitatively investigated in tissues from 25 OLs/25 OSCCs, using automated immunohistochemistry. RESULTS: The steady-state levels of Dsg3 RNA transcripts increased as HSC-3 cells enter their exponential phase of growth, before a dramatic decrease to be observed as cells reached their plateau phase especially in MCAs. Upon the same period of time, Dsg2 levels have been increased. The expression of γ-catenin but not that of ß-catenin was increased after 48 h in both MLs and MCAs. In clinical samples, Dsg3, Ε-cadherin, ß/γ-catenin down-regulation was observed to be associated with the grade of OLs-dysplasia and OSCCs. Importantly, a membrane-to-cytoplasmic switch of expression and strong perinuclear aggregation of Dsg3/γ-catenin was seen in both HSC-3 cells and OLs/OSCCs. CONCLUSIONS: The altered expression of Dsg3/γ-catenin and E-cadherin/ß-catenin, in vitro and in ODs/OSCC imply their involvement in growth regulation and phenotype of dysplastic/malignant oral epithelial cells, contributing to the better understanding of epithelial dysplasia and OSCCs. CLINICAL RELEVANCE: The observed alterations of their expression suggest a role of Dsg3 and γ-catenin (additionally to E-cadherin/ß-catenin) as biomarkers of malignant transformation risk of oral dysplasia and the biological behavior (aggressiveness) of oral cancer, respectively.

Bilateral masseter and internal pterygoid muscle hypertrophy: a diagnostic challenge.

OBJECTIVE: To describe an unusual case of bilateral masseter and pterygoid muscle hypertrophy. CLINICAL PRESENTATION AND INTERVENTION: A 53-year-old female patient presented with a bilateral, painless swelling at the parotid areas without improvement after using antibiotics/systemic corticosteroids/nonsteroidal anti-inflammatory agents. Her medical history included thyroid nodules, but no dental/occlusal disorders were observed. The initial differential diagnosis included salivary gland/jaw bone/masseter pathology, but the CT/MRI revealed only an increase in the size of the masseter and pterygoid muscles. The patient was informed of the benign nature of the swelling and was advised to discontinue the use of nonsteroidal anti-inflammatory agents. CONCLUSION: The bilateral hypertrophy of masseter muscles should be considered in differential diagnosis in cases of unilateral or bilateral swelling of the parotid or lateral mandible area.

Immune-mediated oral mucosal pathology: a comprehensive review and update for clinicians - part II.

The oral mucosa can be involved in a wide variety of mucocutaneous conditions that may present primarily in the mouth or affect other cutaneous or mucosal sites. Many of these conditions are immune mediated and typically present as inflammatory mucosal pathology. Patients experiencing such conditions usually seek medical evaluation and treatment due to the associated pain and discomfort, and occasionally taste disturbance or dysphagia and the overall deterioration in the oral health-related quality of life. These conditions share some common features and there could be some overlap in their clinical presentation, which can lead to delays in diagnosis and proper management of patients. Clinicians dealing with such disorders, including dermatologists, need to be aware of the oral manifestations of mucocutaneous conditions, their clinical features, underlying mechanisms, diagnostic approaches, and treatment options, as well as the recent advances in the research on these conditions. This review provides a comprehensive, evidence-based reference for clinicians, with updated insights into a group of immune mediated conditions known to cause oral mucosal pathology. Part one will cover oral lichen planus, erythema multiforme and systemic lupus erythematosus, while part two will cover recurrent aphthous stomatitis, pemphigus vulgaris and mucous membrane pemphigoid, in addition to the less common disorders linear IgA disease, dermatitis herpetiformis and epidermolysis bullosa.

Multidisciplinary Therapeutic Approach of a Patient With Sjogren's Syndrome: A Three-Year Follow-Up Study.

Sjögren's syndrome is a chronic, inflammatory autoimmune disorder characterized by lymphocyte infiltration of the exocrine glands. Notably, the rehabilitation of partially edentulous patients with Sjögren's syndrome is limited by the scarce availability of studies that could inform therapeutic modalities and potential challenges during clinical procedures. This case report aimed to present the oral rehabilitation of a patient with Sjögren's syndrome who received fixed partial dentures (FPDs). A 28-year-old female patient sought treatment to restore her missing teeth. She was diagnosed with Sjögren's syndrome by a rheumatologist adhering to the revised version of the European criteria proposed by the American-European Consensus Group and was on a medication regimen including prednisolone, hydroxychloroquine, pantoprazole, pilocarpine, and tear substitutes to manage her condition. The final treatment plan consisted of extractions, management of gingivitis, post-and-core restorations, and a 2 mm vertical dimension increase with the placement of 15 porcelain-fused-to-metal (PFM) crowns and 4 short-span bridges. The patient underwent regular clinical and radiographic evaluations every 3 months since June 2020. Throughout this period, the fixed prostheses, teeth, and periodontal tissues demonstrated remarkable stability and exhibited no complications. This three-year case study provides evidence that meticulous planning and clinical execution can facilitate successful oral rehabilitation in young edentulous patients with Sjögren's syndrome. Tooth-supported fixed prostheses can effectively restore oral function and aesthetic appeal in these individuals, provided they undergo more frequent dental examinations than the general population and maintain a cooperative attitude throughout the treatment process.

Implant Treatment in Patients With Autoimmune Diseases: A Systematic Review and Analysis of Studies.

Dental implants provide a reliable solution for edentulous patients with autoimmune diseases improving quality of life. The present systematic review aimed to determine whether autoimmune diseases with oral manifestations could affect the survival rate of dental implants. A systematic search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA), using Google Scholar and PubMed electronic databases, between the year 2000 and February 2024. The eligibility criteria included human studies, in English language reporting on patients with autoimmune diseases treated with dental implants. Nineteen studies were included: nine on oral lichen planus (OLP), four on Sjögren's syndrome (SS), five on epidermolysis bullosa (EB), and one on lupus erythematosus (LE). A total of 389 implants in 142 patients with OLP showed a survival rate (SR) of 94.6%, while 316 implants in 111 patients with SS had a survival rate of 95.8%. In 31 patients with EB, 181 implants were placed with a survival rate of 99.5%, and 12 implants were placed in five patients with LE with a survival rate of 100% after one year of function. Despite the heterogeneity and methodological limitations of most of the studies, the results showed that dental implant survival rates were comparable to those reported in the general population. This review suggested that dental implants are a viable treatment option for patients with autoimmune diseases. Nevertheless, proper daily oral hygiene and long-term follow-up are decisive factors for the long-term maintenance of dental implants.

An Unusual Case of Psoriatic Arthritis With Secondary Lingual Lesions, Resembling Geographic Tongue.

Psoriatic arthritis (PsA) is a chronic inflammatory condition that impacts a significant proportion of individuals diagnosed with psoriasis. This report presents a rare case of a patient diagnosed with PsA who never had active psoriatic skin lesions but only a family history of psoriasis, with secondary lingual lesions, resembling geographic tongue (GT). A male patient, 24 years old, was referred with two painless erythematous areas resembling (without whitish borders, as in GT) rounded atrophic lesions on the dorsal surface of the tongue, resistant to any kind of antimicrobial/antifungal treatment for more than six months. The patient was diagnosed with PsA two years ago fulfilling the CASPAR (ClASsification for Psoriatic ARthritis) criteria. The patient never had active psoriatic skin lesions, but his father had psoriasis. The biopsy of lingual lesions showed moderate hyperkeratosis, spongiosis, and diffuse inflammatory infiltration of lymphocytes and neutrophils in the lamina propria as well as in the stratified squamous epithelium forming Munro's microabscesses at the superficial layers. The manifestation of the atypical psoriasiform, GT-like lingual lesions was considered as part of psoriasis manifestations and the patient was advised to follow regular checkups so that any major exacerbation of the systematic symptoms could be preemptively avoided. Not only GT but also atypical lingual GT-like reddish oral lesions may be considered as transient forms of psoriasis supporting an early diagnosis and monitoring of psoriasis/PsA.

Investigation of the Vascular-Endothelial Pattern of Expression of DAPK-1 in Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders Through Immunohistochemistry.

Introduction Potentially malignant disorders, like oral lichen planus (OLP) and oral leukoplakia (OL) of several degrees of dysplasia, manifest a significant potential of malignant transformation being a precursor of oral squamous cell carcinoma (OSCC). The role of microvascularization in carcinogenesis is critical; therefore, microvascularization constitutes a major therapeutic target. DAPK-1 constitutes a possible cancer marker, with proven implications in other human cancers, and there isn't any study on its vascular endothelial expression in the oral cavity, particularly in oral cancer and oral potentially malignant diseases. The present study aims to investigate the vascular endothelial expression of the DAPK-1 in paraffin-embedded tissue samples of oral leukoplakia, oral squamous cell carcinoma, and oral lichen planus. Materials and methods The study focuses on the immunohistochemical, vascular-endothelial, expression pattern of biomarker DAPK-1 (NBP2-38468, Novus Biologicals, Centennial, CO, US). Tissue samples were obtained from six cases of oral lichen planus (OLP) (3 of reticular and 3 of erosive form), 30 cases of oral leukoplakia (OL) (10 with no dysplasia, 10 with mild dysplasia, and 10 with moderate/severe dysplasia), 22 cases of OSCC (2 well-differentiated, 17 moderately differentiated, and 3 poorly differentiated), as well as 5 cases of normal oral epithelium. The tissue samples were retrieved from the archives of the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, as well as from St Lukas Hospital of Thessaloniki, Greece, from 2004-2019. In accordance with the Research and Ethics Committee guidelines of the Aristotle University, School of Dentistry, and the Helsinki II declaration, the study was conducted. The primary inclusion criteria for the study focused on the presence of sufficient precancerous or cancerous tissue. Conversely, inadequate tissue served as the exclusion criteria. The staining was evaluated exclusively in a quantitative manner. The vascular endothelial staining was evaluated as either positive or negative. If at least one endothelial cell exhibited positive staining, the section was classified as positive. Statistical analysis was carried out using SPSS Statistics v25.0 (IBM Corp., Armonk, NY, US) utilizing Pearson's chi-square or Fisher's exact test, depending on the sample size, to compare OLP to OL, OLP to OSCC, OLP to normal, OL to OSCC, OL to normal, and OSCC to normal. The significance level was established at 0.05 (p=0.05). Results A prevalence of positive OL cases may be noticed. The comparison between OLP and OL yielded Fisher's exact test of p>0.999, OLP and OSCC p=0.389, OLP and normal oral epithelium p>0.999, OL and OSCC p=0.226, OL and normal oral epithelium p>0.999, as well as OSCC and normal oral epithelium p=0.342. Conclusions The role of DAPK in tumorigenesis is already supported by limited literature. However, its implication in the development of OSCC and oral potentially malignant disorders (OPMDs) has yet to be elucidated. Its elevated expression in OL suggests a role in affecting the microenvironment, the vessels, in particular, surrounding oral potentially malignant lesions, possibly assisting their transition into cancer. The evaluation of the vascular-endothelial immunohistochemical profile of DAPK-1 in OL, OLP, and OSCC requires further studies in more tissue samples to illustrate its possible implications.

Citalopram-Induced Oral Melanotic Macules in a Female Patient and a Review of the Literature.

Pigmented lesions in the oral cavity can arise from the accumulation of external substances or internal pigments, resulting in black or brown discoloration. The etiology can be categorized as physiologic, reactive, neoplastic, idiopathic, or indicative of systemic illness. Several systemic drugs have been linked to the development of oral and/or cutaneous pigmentation, either by stimulating the production of melanin or by the accumulation of the drug or its byproducts. The medications most commonly associated with this condition include antimalarials, hormones, oral contraceptives, phenothiazines, chemotherapeutics, amiodarone, minocycline, zidovudine, clofazimine, and ketoconazole. The aim of this case report is to illustrate the drug-induced appearance of multiple melanotic macules in an 89-year-old female patient. The patient was referred to the Department of Oral Medicine and Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece, complaining of the recent and constant appearance of black spots in her oral cavity. Her medical history revealed a multitude of prescribed drugs, with citalopram being the most recently prescribed one, approximately one year prior to the examination. The clinical examination revealed multiple melanotic macules, on the upper and lower lip as well as on the hard and soft palate. Based on these findings, a biopsy of a melanotic macule of the lip was carried out. The histopathological examination showed that the basal layer of the stratified squamous epithelium exhibited hyperpigmentation (melanin-pigmented basal cells). In addition, scattered melaninophages were noted in lamina propria. Psychotropic drugs associated with cutaneous hyperpigmentation include citalopram. Therefore, our case constitutes an exception since citalopram induced intraoral and perioral, instead of cutaneous, hyperpigmentation.

Pancreatic Differentiation of Oral Minor Salivary Gland Stem Cells.

INTRODUCTION: Stem cells from various sources including major salivary glands have been used to establish pancreatic differentiation in an attempt to provide new treatment options for patients with diabetes mellitus. In contrast, the potential of using the more easily accessible intraoral minor salivary glands has not been evaluated so far. MATERIALS AND METHODS: Salivary stem cells were isolated from normal labial minor salivary glands that were removed during the excision of a mucocele and were attempted to differentiate into pancreatic cell lines using a culture medium enriched with activin A, retinoic acid and GLP-1.Real time RT-PCR was used to evaluate the expression of the genes of pancreatic transcription factors MafA, Ptf1a, Hb9 and Arx. Complementary, 22 labial minor salivary gland paraffin-embedded specimens were examined using immunohistochemistry for the presence of the relevant gene products of the pancreatic transcription factors Arx, MafA, Ptf1a and Pdx1. RESULTS: The differentiated salivary stem cells(cells of passage 3) expressed the genes of the pancreatic transcription factors MafA, Ptf1a, Hb9 and Arx even on the first day of the experiment while immunohistochemistry also confirmed the presence of the protein products of Arx, MafA, Ptf1a as well as Pdx1[> 50% of the specimens for Arx(5/8) and MafA(7/8), < 50% for Ptf1a(5/11) and Pdx1(5/11)] in ducts, mesenchymal connective tissue and acinar cells. CONCLUSIONS: Labial minor salivary glands may share gene and protein characteristics with pancreas suggesting a possible usefulness for pancreatic regeneration or substitution in cases of deficiency.

A Preliminary Study of the Role of Endothelial-Mesenchymal Transitory Factor SOX 2 and CD147 in the Microvascularization of Oral Squamous Cell Carcinoma.

INTRODUCTION: The aim of this study was to detect the possible endothelial expression of embryonic-type cancer stem cells (CSC) marker SOX2 and the stemness-type CSC marker CD147 in oral potential malignant disorders (OPMDs), oral leukoplakia (OL) in particular, and oral squamous cell carcinoma (OSCC). METHODS: This study focuses on the immunohistochemical pattern of expression of CSC protein-biomarkers SOX2 and CD147 in paraffin-embedded samples of 21 OSCCs of different grades of differentiation and 30 cases of OLs with different grades of dysplasia, compared to normal oral mucosa. RESULTS: The protein biomarker SOX2 was expressed in the endothelial cells, but without establishing any statistically significant correlation among OSCC, OL, and normal tissue specimens. However, SOX endothelial staining was noticed in 7/30 (23.3%) cases of OL (one non-dysplastic, one mildly dysplastic, one moderately dysplastic, and four severely dysplastic cases) and 5/21 (23.8%) cases of OSCC (two well-differentiated, one moderately differentiated, and two poorly differentiated cases). Although CD147 is expressed in normal oral epithelium, OL, and OSCC neoplastic cells, its vascular-endothelial expression was noticed in only 2/5 (40%) cases of normal oral epithelium, 1/30 (3.3%) cases of OL (one severely dysplastic case), and 4/21 (19%) cases of OSCC (two well-differentiated, one moderately differentiated, and one poorly differentiated case). Therefore, no statistically significant correlation among OSCC, OL, and normal tissue specimens was established. CONCLUSION: The endothelial presence of SOX2 both in oral potentially malignant and malignant lesions suggests that SOX2 may be implicated in the microvascularization process and associated with the degree of dysplasia in OL. The expression of CD147 may be attributed both to local inflammation and tumorigenesis. The implementation of CD147 in larger groups of tissue samples will shed some light on its role in cancer and inflammation. The evidence so far supports the need for more studies, which may support the clinical significance of these novel cancer stem cell biomarkers.

Evaluation of 3D-Printed Solid Microneedles Coated with Electrosprayed Polymeric Nanoparticles for Simultaneous Delivery of Rivastigmine and N-Acetyl Cysteine.

In the current study, coated microneedle arrays were fabricated by means of digital light processing (DLP) printing. Three different shapes were designed, printed, and coated with PLGA particles containing two different actives. Rivastigmine (RIV) and N-acetyl-cysteine (NAC) were coformulated via electrohydrodynamic atomization (EHDA), and they were incorporated into the PLGA particles. The two actives are administered as a combined therapy for Alzheimer's disease. The printed arrays were evaluated regarding their ability to penetrate skin and their mechanical properties. Optical microscopy and scanning electron microscopy (SEM) were employed to further characterize the microneedle structure. Confocal laser microscopy studies were conducted to construct 3D imaging of the coating and to simulate the diffusion of the particles through artificial skin samples. Permeation studies were performed to investigate the transport of the drugs across human skin ex vivo. Subsequently, a series of tape strippings were performed in an attempt to examine the deposition of the APIs on and within the skin. Light microscopy and histological studies revealed no drastic effects on the membrane integrity of the stratum corneum. Finally, the cytocompatibility of the microneedles and their precursors was evaluated by measuring cell viability (MTT assay and live/dead staining) and membrane damages followed by LDH release.