The expression of TNF-α in recurrent aphthous stomatitis: A systematic review and meta-analysis.

OBJECTIVE: The pathogenesis of recurrent aphthous stomatitis (RAS) is related to an increase of pro-inflammatory cytokine, namely tumor necrosis factor α (TNF-α). This cytokine plays an important role in the development of ulcer lesions, both in saliva, tissues and blood. This systematic review analyzed the differences of TNF-α in lesions, salivary and blood and can be used as a reliable method of diagnosis for RAS. METHODS: A comprehensive search of PubMed, Scopus databases, Web of Science, Scielo, Google Scholar and Embase with keywords. The inclusion criteria were studies that assessed the saliva, serum, and RAS lesion, with the outcome reporting the mean of saliva, serum and tissue expression of TNF-α. The risk of bias was also assessed. RESULT: Healthy individuals showed significantly lower TNF-α than RAS (SMD = -1.517, 95% CI [-2.25, -0.78]). Although there is a significant difference between sample (i.e., saliva, serum) and detection type (i.e., cytometry bead array, ELISA), both methods can detect a significant difference in TNF-α between healthy individuals and RAS patients. CONCLUSIONS: The TNF-α is a useful diagnostic marker for RAS. We encourage saliva to detect changes in TNF-α during ulceration as it provides accuracy, reliability, and non-invasive procedure compared to a blood draw.

Combined Hydroxyapatite Scaffold and Stem Cell from Human Exfoliated Deciduous Teeth Modulating Alveolar Bone Regeneration via Regulating Receptor Activator of Nuclear Factor-Κb and Osteoprotegerin System.

BACKGROUND: Tissue engineering using Stem cell from Human Exfoliated Deciduous Teeth (SHED) and a natural biomaterials biomaterial scaffold has become a promising therapy for the alveolar bone defect. The aim of this study was to analyze the Osteoprotegerin (OPG) and Receptor Activator of NF-Κb ligand (RANKL) expression after the application of Hydroxyapatite scaffold and SHED. METHODS: A laboratory experimental research with a post test-only control group. 14 male Wistar rats weighing from 260 to 280 g were used as the animal study. The animals were randomly assigned to an experimental group Hydroxyapatite scaffold (group I) and Hydroxyapatite scaffold combined with SHED (group II). The alveolar bone defect in the animal study model was affected by extracting anterior mandible teeth. Immunostaining was performed after 8 weeks in order to facilitate the examination of OPG and RANKL expression. Data were analyzed by independent t test. The correlation between OPG and RANKL expression were analyzed using Pearson's correlation test (P<0.05). Statistical analysis was performed using R statistical software version 3.4.0. RESULTS: The independent t test showed that the differences were statistically significant. OPG expression in Group I (6.0±1.00) was lower than in Group II (11.6±1.14) (P=0.0004). The independent t test showed that the differences were statistically significant. RANKL expression for Group I (12.67±2.08) and Group II (4.80±1.304) showed a statistically significant difference (P=0.0005). CONCLUSION: Hydroxyapatite scaffold and SHED increase Osteoprotegerin and decrease Receptor Activator of NF-κB Ligand expression with high potential as an effective agent in alveolar bone defect regeneration.

The Effect of Mixed Polymethylmethacrylate and Hydroxyapatite on Viability of Stem Cell from Human Exfoliated Deciduous Teeth and Osteoblast.

OBJECTIVES: Stem cell from human exfoliated deciduous teeth (SHED) has great potential for bone tissue engineering and cell therapy for regenerative medicine. It has been combined with biomaterials such as mixed of polymethylmethacrylate (PMMA) and hydroxyapatite (HA) as candidates for synthetic bone graft biomaterial. The aim of this study was to analyze the toxicity test of mixed PMMA-HA scaffold seeded with SHED and osteoblast in vitro. MATERIALS AND METHODS: SHED was isolated from the pulp of noncarious deciduous teeth and osteoblast cells were cultured, and exposed to PMMA-HA scaffolds with three concentration groups: 20/80, 30/70, and 40/60 for 24 hours. Cytotoxicity test was performed by MTT assay to cell viability. STATISTICAL ANALYSIS: Data were analyzed using IBM SPSS Statistics 25, one-way analysis of variance followed by least significant difference test, considering the level of significance p-value less than 0.05 RESULTS: The percentage of SHED's viability was best in the PMMA-HA group with concentrations of 20/80, followed by 30/70, and 40/60 with 87.03, 75.33, and 65.79%, respectively. The percentage of osteoblast cell's viability was best in the PMMA-HA group with concentrations of 20/80, followed by 30/70, and 40/60 with 123.6, 108.36, and 93.48%, respectively. CONCLUSIONS: Mixed PMMA-HA was not toxic for the SHED and osteoblast. This characteristic is the initial requirement to be proposed as an alternative material for healing alveolar bone defects. In vivo animal research is mandatory to confirm the use of PMMA-HA on the alveolar defect model.

BDNF and Krox20 as Indicators of Platelet-rich Plasma-Induced Nerve Regeneration in a Neuropathic Orofacial Pain Model.

OBJECTIVE: Various growth factors contained in PRP can increase angiogenesis and cell proliferation, which plays an essential role in the process of neuroregeneration and peripheral nerve injury recovery. This study analyzed PRP effects in the neuro-regeneration of axonotmesis through brain-derived neurotrophic factor (BDNF) and Krox20 expressions. MATERIALS AND METHODS: Freeze-dried allogeneic platelet-rich plasma (PRP) were prepared from allogeneic sources. Forty-two Rattus norvegicus were divided into three groups: negative control group, positive control group (crushing infraorbital nerve) and treatment group (crushing infraorbital nerve without PRP injection). Each group was observed for fourteen and twenty-one days after injury. Infraorbital nerve tissue is isolated for indirect immunohistochemistry examination with BDNF and Krox20 antibodies. Data analysis was performed using One-Way ANOVA and Mann-Whitney tests with significant value as p < 0.05. RESULTS: The PRP group showed BDNF expression significantly higher than control positive groups, both observation days (p = 0.00). A higher Korx20 expression showed by the PRP group after 21 days than in the control positive groups (p = 0.002). CONCLUSION: PRP can potentially improve neuroregeneration of axonotmesis through increased BDNF and Krox20 expression on the twenty-one days after injury.

Marine Ascomycetes Extract Antifungal Susceptibility against Candida spp. Isolates from Oral Candidiasis HIV/AIDS Patient: An In Vitro Study.

OBJECTIVE: The etiology of oral candidiasis (OC) was Candida albicans, C. krusei, C. dubliniensis, C. tropicalis that are frequently found in human immunodeficiency virus/ acquired immunodeficiency syndrome (HIV/AIDS) patients. Marine ascomycetes (MA) have been widely reported as an important producer of various antibiotic compounds. However, there is limited study of antifungal compounds from MA against Candida species. The aim of this study was to investigate the antifungal susceptibility of MA against Candida spp. isolates from OC HIV/AIDS patient. MATERIALS AND METHODS: Trichoderma sp. is a sponge-associated fungus collected from Karimunjawa National Park, Central Java, Indonesia. The validation of C. albicans, C. krusei, C. dubliniensis, C. tropicalis. was done by ChromAgar. This study was true experimental with post-test only control group design; the sample was four replications for each group. Nystatin administration (K +), the golden standard antifungal drug, was used. The minimum fungicidal concentration (MFC), minimum inhibitory concentration (MIC), and diffusion zone methods were done. Analysis of variance difference test, and post-hoc Tukey's honest significant different were done to analyze the significant different between groups (p ≤ 0.05). RESULTS: The MFC and MIC of MA against C. albicans, C. krusei, C. dubliniensis, and C. tropicalis were found at 12.5%. In addition, the greatest diffusion zone of MA against C. albicans, C. krusei, C. dubliniensis, and C. tropicalis was found at 12.5%. There is no appreciable difference in antifungal activity between K + and 12.5% of MA extract (p ≥ 0.05). CONCLUSION: Concentration of 12.5% MA extract has antifungal susceptibility against Candida spp. isolates from OC HIV/AIDS patient.

Adipose Mesenchymal Stem Cell Metabolites Oral Gel Enhance Pro-Angiogenic Factors Expression, Angiogenesis, and Clinical Outcome of Oral Ulcer Rat Model.

OBJECTIVE: Enhancing wound healing capacity is one of the main principles in oral ulcer management. Efficient oral ulcer management will accelerate clinical symptom amelioration and prevent complications. Adipose mesenchymal stem cell metabolites (AdMSCM), a novel biological product, contains a plethora of bioactive mediators that can induce a series of processes in wound healing. This study will analyze the clinical outcome, angiogenesis, and expression of FGF-2 and VEGFA in the oral ulcer rat model after AdMSCM oral gel application. MATERIALS AND METHODS: Twenty healthy male Wistar rats (Rattus novergicus) were used to create oral ulcer animal models. AdMSCM oral gel treatment was performed three times daily for 3 and 7 days. Clinical outcome was assessed by measuring the major diameter of the ulcer; the angiogenesis was evaluated through histological assessment; the expression of VEGFA and FGF-2 was assessed using the immunohistochemistry method. STATISTICAL ANALYSIS: This study uses parametric comparative analysis using one-way analysis of variance (ANOVA) and post-hoc Tukey's HSD test RESULTS: The application of AdMSCM oral gel in an oral ulcer rat model significantly enhanced the clinical outcome (p < 0.05). In addition, similar results were shown in the histologic assessment of angiogenesis and supported by the significant increase of VEGFA and FGF-2 expression. CONCLUSIONS: AdMSCM oral gel accelerates oral ulcer healing processes, proven by the enhancement of angiogenesis, pro-angiogenic factors expression, and clinical outcomes.

Dentists' knowledge and attitudes regarding PFPT: A single study in East Java, Indonesia.

Objective: Pigmented fungiform papillae of the tongue (PFPT) are infrequently encountered and inadequately documented pigmented lesions that pose challenges in diagnosis and subsequent treatment planning. The study was aimed at analyzing dentists' knowledge and attitudes regarding PFPT morphologies, to determine diagnosis and subsequent treatment planning. Methods: A cross-sectional study was conducted among dentists in East Java through an online questionnaire. Four clinical photographs of PFPT were presented, accompanied by seven questions assessing dentists' knowledge of PFPT, including lesion types, tongue structure involvement, Holzwanger classification, lesion patterns, suspected diagnoses and the nature of the lesion (benign or malignant). Additional questions to evaluate attitudes included prior experience with PFPT in practice, potential malignant transformation, diagnostic investigation and required treatment. Knowledge-associated attitude differences were statistically analyzed with the Mann-Whitney test with a threshold of p < 0.05. Result: A total of 117 dentists participated, most of whom were women (69.23%) and were 26-30 years of age (44.44%). Dentists 41-50 years of age had superior knowledge to those 20-30 years of age (p = 0.005). Practitioners with 1-5 years of experience showed significant differences in knowledge regarding PFPT (p < 0.05). No significant differences in knowledge level and attitudes were observed, particularly regarding PFPT treatment and supporting investigation (p > 0.05). However, prior encounters with PFPT cases were significantly associated with treatment decisions and supporting investigations for diagnosis (p < 0.05). Conclusion: Most participating dentists had substantial knowledge of PFPT cases. Dentists' understanding, as reflected in their attitudes toward investigating and treating PFPT, was notably influenced by prior encounters with PFPT cases.

The effectiveness of essential oil from Citrus limon peel on Candida albicans biofilm formation: An experimental in vivo study.

Objectives: Candida albicans is resistant to commercial antifungal agents. Therefore, it is desirable to use material derived from natural sources as an antifungal agent. Essential oil from Citrus limon peel is able to inhibit the growth of C. albicans in vitro. The purpose of this study was to determine the most effective concentration of essential oil from C. limon peel with regards to the inhibition of C. albicans cyto-morphometric changes and biofilm formation in vivo. Methods: Male Wistar rats weighing 200-300 g were inoculated with C. albicans for 48 h and then given a single dose of oral methylprednisolone as an immunosuppressant. Essential oil from C. limon peel, in a gel form and at three different concentrations (0.39%, 0.78% and 1.56%), was applied twice a day for 2 days. The rats were killed after 48 h and then palatal mucosa tissues were prepared and examined with a scanning electron microscope (SEM) with regards to C. albicans, cyto-morphometric changes and biofilm formation. Results: Essential oil from C. limon peel at a concentration of 1.56% showed the strongest ability to inhibit C. albicans growth when compared to 0.78% and 0.39%. At a concentration of 1.56%, essential oil from C. limon peel disrupted cyto-morphometric changes; cells that were neither in intact nor colonised were evident, the filaments around the cells were smooth, the layer of biofilm had disappeared and there was no evidence of hyphae formation. Conclusion: The effect of essential oil from C. limon peel on cyto-morphometric changes and biofilm formation was concentration-dependent. Essential oil from C. limon peel at a dose of 1.56% showed the strongest ability to inhibit cyto-morphometric changes and biofilm formation. These findings demonstrate that essential oil of C. limon peel is a potential antifungal candidate for the treatment of candidiasis.

Expression of VEGF and CD-31 in traumatic ulcer of diabetic Wistar rats after application of Citrus limon peel essential oil.

Objective: Diabetes mellitus (DM) is a metabolic disease that delays the healing process, including the interruption of the processes of angiogenesis and vasculogenesis. The etiology of most angiogenic-related diseases, such as diabetes complications, includes the presence of hypoxia caused by declined vascular endothelium growth factor (VEGF) and CD-31. d-limonene, one of the main constituents of Citrus limon, is considered to have angiogenic, antioxidant, hypoglycemic, and anti-inflammatory activities. However, the exact mechanism of this process remains unclear. This study aimed to determine the potential of C. limon as a medication for diabetic ulceration. Methods: A total of 30 Wistar rats (Rattus novergicus) induced with DM and traumatic ulcers on the lower lip mucosa were divided into six groups-three each for control and treatment groups. Control groups were treated with CMC 5% gel, and treatment groups were administered with C. limon peel essential oil gel. The expression of VEGF and CD-31 was observed on days 5, 7, and 9. Immunohistochemical examinations were performed with the monoclonal antibodies anti-VEGF and anti-CD-31. ANOVA was conducted to analyze the differences between the groups (p < 0.05). Result: An increase in VEGF and CD-31 expression in the treatment group was observed compared with that of the control group (p < 0.05). Conclusion: Citrus limon peel essential oil gel increased VEGF and CD-31 expression during the healing process of traumatic ulcers in diabetes-afflicted Wistar rats.

RANK-RANKL-OPG expression after gingival mesenchymal stem cell hypoxia preconditioned application in an orthodontic tooth movement animal model.

Background: The expression of receptor activator of Nuclear Factor Kappa Beta (RANK) and its ligand (RANKL), as well as osteoprotegrin (OPG), in the alveolar bone (AB), may improve bone remodeling during orthodontic tooth movement (OTM). It is hypothesized that hypoxia-preconditioned gingival mesenchymal stem cells (GMSC) may be more effective than normoxia-preconditioned GMSC in this regard. This study aims to investigate the expression of RANK, RANKL, and OPG in the compression and tension sides of AB after allogeneic administration of GMSC that were normoxia or hypoxia-preconditioned in rabbits (Oryctolagus cuniculus) undergoing OTM. Methods: Twenty-four healthy young male rabbits were divided into two groups: T1, which underwent OTM and received normoxia-preconditioned GMSC, and T2, which underwent OTM and received hypoxia-preconditioned GMSC. A ligature wire was attached to the mandibular first molar and connected to a 50 g/mm2 closed coil spring, exerting force on the central incisor and left mandibular molar of the experimental animals. After 24 h of OTM, either normoxia- or hypoxia-preconditioned GMSC were injected into the gingiva of the samples in a single dose of 20 µl of phosphate-buffered saline (PBS). All samples were sacrificed on days 7, 14, and 28, and immunohistochemistry was performed to analyze the expression of RANK, RANKL, and OPG on the tension and compression sides. Results: The expressions of RANK-RANKL-OPG in the alveolar bone of the compression and tension sides were significantly different during the 14-day period of OTM following allogeneic administration of GMSC that were normoxia or hypoxia-preconditioned (p < 0.05). Conclusion: The expression of RANK-RANKL was significantly increased on the compression side of the alveolar bone during OTM after the administration of hypoxia-preconditioned allogeneic GMSC but not on the tension side. Conversely, RANKL-OPG expression was enhanced on the tension side but not on the compression side, as observed through immunohistochemical analysis in vivo.

Anti-Periodontopathogenic Ability of Mangrove Leaves (Aegiceras corniculatum) Ethanol Extract: In silico and in vitro study.

OBJECTIVE: Mangrove (Aegiceras corniculatum) is an abundant natural marine resource of Indonesia, which can be explored for treating periodontal disease due to its potential as immunoregulatory, antibacterial, and antioxidant properties. The objective of this study was to investigate the active compound from Indonesian mangrove leaf extract (A. corniculatum) (MLE) for developing a herbal-based mouthwash through in silico and in vitro studies. MATERIALS AND METHODS: Phytochemistry and liquid chromatography-high resolution mass spectrometry (LC-HRMS) were done to explore the active compounds in MLE. Chemistry screening and interaction, absorption, distribution, metabolism, and excretion (ADME), molecular docking simulation, and visualization of MLE active compounds as anti-inflammatory, antioxidant, and antibacterial were investigated in silico The inhibition zone of MLE against Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), and Fusobacterium nucleatum (Fn) as periodontopathogenic bacterias was performed by diffusion method. Doxycycline 100 mg was used as a positive control, as a treatment group, there were five groups, namely 0%, 25%, 50%, 75%, and 100% MLE. RESULTS: Alkaloid, saponin, flavonoid, triterpenoid, steroid, tannin, and quinone were detected in MLE. A high concentration of (-)epicatechin and coumaric acid (CA) were found in MLE. MLE in 100% concentration has the most effective ability to inhibit Fn, Pg, Aa growth in vitro. (-)-Epicatechin has a higher negative binding affinity than CA that can enhance heat shock protein (HSP)-30, HSP-70, HSP-90, interleukin-10, and FOXP3 and also inhibit interleukin-6, peptidoglycan, flagellin, and dectin in silico. CONCLUSION: MLE of A. corniculatum has antioxidant, anti-inflammatory, and antibacterial activities that can be a potential raw material for developing a herbal-based mouthwash.

Malondialdehyde Level and Tissue Apoptosis Count as an Early-Detection Marker of Oral Potentially Malignant Disorders.

OBJECTIVES: The malondialdehyde (MDA) level and TA count represent the progression of oral potentially malignant disorders (OPMD) to malignancy and thus may be used as an indicator of oral epithelial dysplasia (OED). This study aimed to determine the MDA level and tissue apoptosis (TA) count in oropharyngeal tissue of Wistar rats exposed to sidestream cigarette smoke. MATERIALS AND METHODS: Wistar rats were divided into three groups: T4 group (4-week cigarette smoke exposure), T8 group (8-week cigarette smoke exposure), and control group, which was not exposed to cigarette smoke. The oropharyngeal tissue of the rats from each group was examined histopathologically to count the number of apoptotic cells, and then the blood serum was made to measure the MDA level. STATISTICAL ANALYSIS: Bonferroni test was performed to see the differences in each group for MDA level. While the data from tissue apoptosis were analyzed using Mann-Whitney U test for the significance. All data were considered significant if p < 0.05. RESULTS: The MDA level and TA count increased as the duration of cigarette smoke exposure increased. In the T8 group, the MDA level and TA count were significantly higher compared with the T4 and control groups with a p-value < 0.05. CONCLUSIONS: Exposure to sidestream cigarette smoke increased the TA count and MDA level in the oropharyngeal tissue of Wistar rats. The TA count and MDA level may be used as markers of OPMD.

Gingival Mesenchymal Stem Cells Metabolite Decreasing TRAP, NFATc1, and Sclerostin Expression in LPS-Associated Inflammatory Osteolysis In Vivo.

OBJECTIVE: Bone is a dynamic tissue that undergoes remodeling. During bone remodeling, there are transcription factors such as nuclear factor-activated T cells-1 (NFATc1), sclerostin, and tartrate-resistant acid phosphatase (TRAP) that are released for bone resorption. Metabolite from gingival mesenchymal stem cells (GMSCs) has the ability to activate proliferation, migration, immunomodulation, and tissue regeneration of bone cells and tissues. Furthermore, the aim of this study is to investigate the metabolite of GMSCs' effect on expression of NFATc1, TRAP, and sclerostin in calvaria bone resorption of Wistar rats. MATERIALS AND METHODS: Twenty male healthy Wistar rats (Rattus norvegicus), 1 to 2 months old, 250 to 300 g body were divided into four groups, namely group 1 (G1): 100 µg phosphate-buffered saline day 1 to 7; group 2 (G2): 100 µg lipopolysaccharide (LPS) day 1 to 7; group 3 (G3): 100 µg LPS + 100 µg GMSCs metabolite day 1 to 7; and group 4 (G4): 100 µg GMSCs metabolite day 1 to 7. Escherichia coli LPS was used to induce inflammatory osteolysis on the calvaria with subcutaneous injection. GMSCs metabolite was collected after passage 4 to 5, then injected subcutaneously on the calvaria. All samples were sacrificed on the day 8 through cervical dislocation. The expression of TRAP, NFATc1, and sclerostin of osteoclast in the calvaria was observed with 1,000× magnification. STATISTICAL ANALYSIS: One-way analysis of variance and Tukey honest significant different were conducted to analyze differences between groups (p < 0.05). RESULTS: The administration of GMSCs metabolite can significantly decrease TRAP, NFATc1, and sclerostin expression (p < 0.05) in LPS-associated inflammatory osteolysis calvaria in Wistar rats (R. norvegicus). There were significantly different TRAP, NFATc1, and sclerostin expressions between groups (p < 0.05). CONCLUSION: GMSCs metabolite decrease TRAP, NFATc1, and sclerostin expression in LPS-associated osteolysis calvaria in Wistar rats (R. norvegicus) as documented immunohistochemically.

Study of Alveolar Bone Remodeling Using Deciduous Tooth Stem Cells and Hydroxyapatite by Vascular Endothelial Growth Factor Enhancement and Inhibition of Matrix Metalloproteinase-8 Expression in vivo.

Background: Periodontitis progression is characterized by alveolar bone loss, and its prevention is a major clinical problem in periodontal disease management. Matrix metalloproteinase-8 (MMP-8) has been shown to adequately monitor the treatment of chronic periodontitis patients as gingival crevicular fluid MMP-8s were positively associated with the severity of periodontal disease. Moreover, modulating the vascular endothelial growth factor (VEGF) levels in bones could be a good way to improve bone regeneration and cure periodontitis as VEGF promotes endothelial cell proliferation, proteolytic enzyme release, chemotaxis, and migration; all of which are required for angiogenesis. Purpose: The aim of this study was to determine the effect of hydroxyapatite incorporated with stem cells from exfoliated deciduous teeth (SHED) in Wistar rats' initial alveolar bone remodeling based on the findings of MMP-8 and VEGF expressions. Methods: A hydroxyapatite scaffold (HAS) in conjunction with SHED was transplanted into animal models with alveolar mandibular defects. A total of 10 Wistar rats (Rattus norvegicus) were divided into two groups: HAS and HAS + SHED. Immunohistochemistry staining was performed after 7 days to facilitate the examination of MMP-8 and VEGF expressions. Results: The independent t-test found significant downregulation of MMP-8 and upregulation VEGF expressions in groups transplanted with HAS in conjunction with SHED compared with the HAS group (p < 0.05). Conclusion: The combination of SHED with HAS on alveolar bone defects may contribute to initial alveolar bone remodeling as evident through the assessments of MMP-8 and VEGF expressions.

Prevalence of Oral Normal Variance in Healthy Elderly Patients: A Descriptive Study on Oral Pseudo-Lesions.

Introduction The aging process in the elderly can change the condition of the oral cavity, regarding both clinical appearance and function. The oral mucosa becomes more susceptible to mechanical damage and irritant agents. Any changes in the oral mucosa, including normal variance, should be examined. This is especially true for the elderly, to improve oral health and prevent any abnormalities. Objective To describe the prevalence of oral normal variance in healthy elderly patients. Methods An observational descriptive study with a cross-sectional design with total sampling conducted from March to April 2020. Results Among the 117 elderly patients who participated in this study, 58 were described as healthy without any comorbidities. From those subjects, there were 117 cases of normal variance in the oral mucosa. The three most prevalent issues were fissured tongue (93.1%), coated tongue (58.62%), and crenated tongue (27.59%). Conclusion Fissured tongue is a normal variance of the oral mucosa that is commonly found in healthy elderly patients.

Pigmented Fungiform Papillae (PFP) of the Tongue: A Systematic Review of Current Aetiopathogenesis and Pathophysiology.

The pigmentation of the fungiform papillae of the tongue is a rare idiopathic condition in which only the fungiform papillae appear hyperpigmented. In the absence of any reviews on the subject, we conducted a systematic review of the aetiopathogenesis and pathophysiology of pigmented fungiform papillae (PFP) of the tongue, including its demographic and histopathological features, trying to outline a possible aetiology. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) was performed using PubMed, Scopus, EMBASE databases and manual searches, for publications between January 1974 and July 2022. Inclusion criteria were case reports defining patients' characteristics, their general medical and dental conditions, histopathological and/or immunohistochemical findings, all with a final definitive diagnosis of PFP. Overall, 51 studies comprising 69 cases of PFP which included histopathological descriptions were reviewed. Prominent features consisted of hyperpigmentation of melanocytes, melanophages, chromatophores, and a lymphocytic infiltrate in the subepidermal area of the fungiform papillae. On special staining, PFP contained melanin, not iron or hemosiderin. On immunohistochemistry, immune-reactive CD3+ T lymphocytes, S-100 and Sox10, but non-immune-reactive melan-A intraepithelial melanocytes were noted in some studies. The presence of hyperpigmented melanocytes and melanophages, with non-immune-reactive melan-A, suggests that PFP are a benign and physiological form of pigmentation. The inflammatory infiltrates described in some papillary lesions could possibly be due to traumatic events during mastication. Nevertheless, the true reasons for the hyperpigmentation of the fungiform papillae are as of yet elusive, and remain to be determined.

Role of Inflammatory Cell Responses in Stimulating Fibroblasts in Diabetic Oral Ulcer after Treatment with Liquid Smoke of Coconut Endocarp: A Histological Assessment.

OBJECTIVE: The liquid smoke of coconut endocarp (LS-CE) contains high antioxidants that promote oral ulcer healing in diabetics. This study reveals the profile of inflammatory cell responses to oral ulcer healing in diabetics under treatment with LS-CE. MATERIALS AND METHODS: A diabetic model was induced with alloxan. Treatment with LS-CE was performed on oral ulcer at a dose of 1 µL/g weight for 3, 5, and 7 days. The anti-inflammatory effect was tested on animal's oral ulcer model by measuring the inflammatory cell responses of the neutrophils, macrophages, lymphocytes, and fibroblasts through histological assessment. RESULTS: The LS-CE stimulated the healing by simultaneously increasing the inflammatory cell responses. The numbers of neutrophils, macrophages, and fibroblasts after treatment for 7 days are higher than that after 3 days and 5 days (p < 0.01), but not for neutrophils. The LS-CE shows increase in the fibroblasts by hastening responses of macrophage recruitment by five times, but not neutrophil and lymphocyte recruitment. The higher phenolic compounds in LS-CE are responsible for increase in the proliferation of fibroblasts, as it hastens cellular responses of macrophages. CONCLUSIONS: The application of LS-CE enables hastening of the healing of diabetic oral ulcer by stimulating the macrophages.

The differences in the number of fibroblasts and blood vessels after the topical and systemic administration of Lactobacillus casei Shirota probiotics for the treatment of traumatic ulcers in Wistar rats (Rattus norvegicus).

BACKGROUND AND AIM: The use of drugs as a therapy for traumatic ulcers may lead to drug resistance and other side effects. Lactobacillus casei Shirota can affect the number of fibroblasts and blood vessels in wound healing. The aim of this study was to investigate the difference in the number of fibroblast cells and blood vessels after the topical and systemic administration of L. casei Shirota probiotics in Wistar rats with traumatic ulcer. MATERIALS AND METHODS: Overall, 36 healthy male Wistar rats aged 2-3 months old and weighing 175-250 g in body weight were used as a sample. Traumatic ulcer was made on the labial fornix incisive inferior. The subject rats were divided into groups: (1) A control group over 3 days, (2) a group that used distilled water over 7 days, (3) a group that underwent topical treatment over 3 days, (4) a group that used probiotics administered topically over 7 days, (5) a group that underwent systemic treatment over 3 days, and (6) a group that took oral probiotics for the traumatic ulcers over 7 days. The number of fibroblasts and blood vessels was observed through a hematoxylin-eosin examination. RESULTS: Based on the results of the study, a significant difference was observed in the number of fibroblasts (p=0.00) and blood vessels (p=0.018) in the 3-day topical group that underwent a 3-day systemic administration of probiotics compared with the number of fibroblast cells in the 7-day topical group and 7-day systemic group (p=0.00). CONCLUSION: Overall, significant differences were observed in the number of fibroblasts and blood vessels in Wistar rats with traumatic ulcer after undergoing the topical and systemic administration of L. casei Shirota probiotics.

Gingival-Derived Mesenchymal Stem Cell from Rabbit (Oryctolagus cuniculus): Isolation, Culture, and Characterization.

OBJECTIVE: This study aims to confirm whether the GDMSCs isolated from rabbit's (Oryctolagus cuniculus) gingiva are mesenchymal stem cells (MSCs). MATERIALS AND METHODS: This study design was partly quasi-experimental with an observational design. GDMSCs were isolated from the gingiva of healthy male rabbits (O. cuniculus) (n = 2), 6 months old, and 3 to 5 kg of body weight. The specific cell surface markers of MSCs; clusters of differentiation (CD), namely, CD44, CD73, CD90, CD105, and CD200 expressions; and hematopoietic stem cell surface markers CD34 and CD45 were examined using flow cytometry and immunohistochemistry with immunofluorescence. The osteogenic differentiation of isolated GDMSCs was examined using alizarin red staining. RESULTS: GDMSCs in the fourth passage showed a spindle-like formation and fibroblast-like cells that attached to the base of the culture plate. GDMSCs were MSCs that positively expressed CD44, CD73, CD90, CD105, and CD200 but did not express CD34 and CD45 when examined using flow cytometry and immunohistochemical analysis. GDMSCs had osteogenic differentiation confirmed by calcified deposits in vitro with a red-violet and brownish color after alizarin red staining. CONCLUSION: GDMSCs isolated from the rabbits (O. cuniculus) were confirmed as MSCs in vitro documented using immunohistochemistry and flow cytometry. GDMSCs can differentiate into osteogenic lineage in vitro that may be suitable for regenerative dentistry.

Molecular docking of anthocyanins and ternatin in Clitoria ternatea as coronavirus disease oral manifestation therapy.

Herbal active compound with immunoregulator ability is considered a potential therapy for COVID-19 oral manifestation by downregulating pro-inflammatory cytokine storm. Meanwhile, anthocyanin and ternatin are the active compounds in Clitoria ternatea, which may act as a potential immunoregulator for COVID-19 therapy. The intention of this investigation was to investigate anthocyanin and ternatin as active compounds in C. ternatea that may be able to increase anti-inflammatory cytokine and inhibit pro-inflammatory cytokine and key proteins of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This study implemented bioinformatic approach to analyze anthocyanin and ternatin as active compounds in C. ternatea with anti- and pro-inflammatory cytokines and antiviral examination history through blind molecular docking study (in silico). Moreover, anthocyanins and ternatin were obtained from PubChem database by minimizing ligand structure in PyRx software to increase the flexibility. RCSB database was employed for preparing the protein samples consisting of interleukin (IL)-6, SARS-CoV-2-ACE2 glycoprotein complex, tumor necrosis factor-α receptor (TNF-αR), matrix metalloproteinase-9 (MMP-9), IL-6, IL-10, and human beta defensin-2 (HBD-2). In addition, The PyMol sofware was used to sterilize the protein samples to obtain the molecular docking optimization. This investigation found that, in the molecular docking simulation, the anthocyanin and ternatin showed producing the negative binding affinity to the ACE2 domain which interacted with RBD glycoprotein SARS-CoV-2. Anthocyanin and ternatin were then predicted to be able to influence any inhibitory activity of TNF-αR, MMP-9, and IL-6; increase IL-10; and increase HBD2 binding affinity values negatively. It can be predicted through molecular docking that anthocyanin and ternatin as the active compounds in C. ternatea contribute as a potential agent for COVID-19 oral manifestation therapy.