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.

Alteration of salivary LPO, MDA, LDH, glutathione, GPx, SOD and vitamins in oral submucous fibrosis: A three-level meta-analysis study.

This study aims to investigate the alteration of salivary biomarker profiling in the development of oral submucous fibrosis (OSMF) and to explore the influence of saliva in the diagnosis of OSMF. A systematic search of published articles using the PRISMA guidelines was conducted to identify relevant studies on OSMF and saliva. All eligible studies, including case-control, cross-sectional studies, cohort, and pilot studies, contained the evaluation of salivary biomarker profiling in patients with OSMF. Salivary biomarker data from 28 selected articles were categorized into nine groups, and their mean values were determined. A three-step meta-analysis was performed by grouping salivary biomarker profiling into more heterogeneous categories based on OSMF classification, considering functional, histological, and clinical grading. The salivary biomarker profiling analysis revealed significant alterations in all markers, indicating their efficacy in OSMF diagnosis. Subgroup analyses highlighted significant associations in oxidative stress and protein with increased mean values, particularly emphasizing lipid peroxidase (LPO), malondialdehyde (MDA), and lactate dehydrogenase (LDH). Conversely, decreased mean values were observed in glutathione, glutathione peroxidase (GPx), superoxide dismutase (SOD), and vitamins. Notably, OSMF grading analysis demonstrated a significant difference in weighted effect sizes for histological grading, particularly in stage IV. The study underscores the alteration of specific salivary biomarkers, particularly those associated with LPO, MDA, LDH, glutathione, GPx, SOD, and vitamins, in diagnosing and grading OSMF.

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.

Oral hyperpigmentation as an adverse effect of highly active antiretroviral therapy in HIV patients: A systematic review and pooled prevalence.

Background: Human Immunodeficiency Virus (HIV) infects patients via CD4+ cells which are later be destroyed subsequently causing the deteriotation of immune system. HIV generally manifests in the oral cavity as the first indicating sign and a marker of disease progression. HAART medications are used to reduce the incidence of oral manifestations, however it can also generate adverse effects in the oral cavity including oral hyperpigmentation. This review aimed to estimate the prevalence of oral hyperpigmentation which affect individual quality of life as a side effect of HAART. Material and Methods: This systematic review applied Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2020. Literature search was performed in ScienceDirect, PubMed, and Scopus by combining terms such as highly active antiretroviral therapy, oral manifestation, epidemiology or prevalence published between January 1998 to March 2022. Results: Of 108 articles, eleven articles were included for systematic review and meta-analysis. The pooled prevalence of oral hyperpigmentation in HAART patients was 25% (95% CI: 11%, 38%; I2: 99%). Subgroup analysis based on geographical location showed varied result may be due to the type and duration of HAART used in study population. The most widely used type of ARV was from the NRTI group (n=7) and the study with the shortest duration showed the lowest oral hyperpigmentation prevalence (n=7). Conclusions: There is an increased prevalence of oral hyperpigmentation by the use of HAART. Future study should investigate the correlation between HAART duration and the degree of oral hyperpigmentation. Key words:HAART, oral hyperpigmentation; pooled prevalence.

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.

Bovine Lactoferrin Suppresses Tumor Angiogenesis through NF-κB Pathway Inhibition by Binding to TRAF6.

Tumor angiogenesis is essential for tumor progression. The inhibition of tumor angiogenesis is a promising therapy for tumors. Bovine lactoferrin (bLF) has been reported as an anti-tumor agent. However, bLF effects on tumor angiogenesis are not well demonstrated. This study evaluated the inhibitory effects of bLF on tumor angiogenesis in vivo and in vitro. Herein, tumor endothelial cells (TECs) and normal endothelial cells (NECs) were used. Proliferation, migration, tube formation assays, RT-PCR, flow cytometry, Western blotting, siRNA experiments and immunoprecipitation were conducted to clarify the mechanisms of bLF-induced effects. CD-31 immunoexpression was examined in tumor tissues of oral squamous cell carcinoma mouse models with or without Liposomal bLF (LbLF)-administration. We confirmed that bLF inhibited proliferation/migration/tube formation and increased apoptosis in TECs but not NECs. TNF receptor-associated factor 6 (TRAF6), p-p65, hypoxia inducible factor-α (HIF-1α) and vascular endothelial growth factor (VEGF) were highly expressed in TECs. In TECs, bLF markedly downregulated VEGF-A, VEGF receptor (VEGFR) and HIF-1α via the inhibition of p-p65 through binding with TRAF6. Since NECs slightly expressed p-p65, bLF-TRAF-6 binding could not induce detectable changes. Moreover, orally administrated LbLF decreased CD31-positive microvascular density only in TECs. Hence, bLF specifically suppressed tumor angiogenesis through p-p65 inhibition by binding to TRAF6 and suppressing HIF-1α activation followed by VEGF/VEGFR down-regulation. Collectively, bLF can be an anti-angiogenic agent for tumors.

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.

Role of Candida albicans in Oral Carcinogenesis.

Oral carcinogenesis is also dependent on the balance of the oral microbiota. Candida albicans is a member oral microbiota that acts as an opportunistic pathogen along with changes in the epithelium that can predispose to premalignancy and/or malignancy. This systematic review uses the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to analyze the role of Candida albicans in the process of oral carcinogenesis. Eleven articles qualified inclusion criteria, matched keywords, and provided adequate information about the carcinogenesis parameters of Candida albicans in oral cancer. Candida albicans in oral carcinogenesis can be seen as significant virulent factors for patients with oral squamous cell carcinoma (OSCC) or potentially malignant disorder (OPMD) with normal adjacent mucosa. Candida albicans have a role in the process of oral carcinogenesis concerning morphological phenotype changes in cell structure and genotype and contribute to the formation of carcinogenic substances that can affect cell development towards malignancy.

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

Abstract 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.

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.

Oral administration of bovine lactoferrin suppresses the progression of rheumatoid arthritis in an SKG mouse model.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammatory bone destruction in which tumor necrosis factor alpha (TNF-α) plays a key role. Bovine lactoferrin (bLF) is a multifunctional protein with anti-inflammatory and immunomodulatory properties. This study aimed to clarify the inhibitory effects of bLF on the pathological progression of RA. The mannan-induced arthritis model in SKG mice (genetic RA model) was used. Orally applied liposomal bLF (LbLF) markedly reduced ankle joint swelling and bone destruction. Histologically, pannus formation and osteoclastic bone destruction were prevented in the LbLF-treated animals. Moreover, orally administered LbLF improved the balance between Th17 cells and regulatory T cells isolated from the spleen of mannan-treated SKG mice. In an in vitro study, the anti-inflammatory effects of bLF on TNF-α-induced TNF-α production and downstream signaling pathways were analyzed in human synovial fibroblasts from RA patients (RASFs). bLF suppressed TNF-α production from RASFs by inhibiting the nuclear factor kappa B and mitogen-activated protein kinase pathways. The intracellular accumulation of bLF in RASFs increased in an applied bLF dose-dependent manner. Knockdown of the lipoprotein receptor-related protein-1 (LRP1) siRNA gene reduced bLF expression in RASFs, indicating that exogenously applied bLF was mainly internalized through LRP-1. Immunoprecipitated proteins with anti-TNF receptor-associated factor 2 (TRAF2; an adapter protein/ubiquitin ligase) included bLF, indicating that bLF binds directly to the TRAF2-TRADD-RIP complex. This indicates that LbLF may effectively prevent the pathological progression of RA by suppressing TNF-α production by binding to the TRAF2-TRADD-RIP complex from the RASFs in the pannus. Therefore, supplemental administration of LbLF may have a beneficial effect on preventive/therapeutic reagents for RA.

The Response of the Tongue Epithelial on Cigarette Smoke Exposure as a Risk Factor for Oral Cancer Development.

OBJECTIVE: The aim of this study is to analyze the tongue epithelial response to cigarette smoke exposure on a number of macrophages, lymphocytes, plasma cells, and matrix metalloproteinase 9 (MMP-9) expression to determine the risk factor of oral cancer development. MATERIALS AND METHODS: Thirty Rattus norvegicus will be exposed to two kinds of cigarette smoke by a smoking pump for 4 and 8 weeks. The tongues were collected to analyze the number of macrophages, lymphocytes, and plasma cells with hematoxylin-eosin. The MMP-9 expression was similarly analyzed with immunohistochemical staining and then compared with the control group. RESULTS: The number of macrophages, lymphocytes, and MMP-9 expression was higher in the 8-week cigarette smoke exposure compared to the 4-week cigarette smoke exposure and the control group (p < 0.000). The number of plasma cell did not differ in the 8-week cigarette smoke exposure from that of the control group (p > 0.05). The number of plasma cells in the tongue tissue during the 4-week cigarette smoke exposure was not determined. CONCLUSION: Cigarette smoke exposure induces the risk of oral cancer development as a result of an increase in the number of macrophages, lymphocytes, and MMP-9 expression in the tongue epithelial.

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.

Oral Candidiasis in Immunosuppressed Wistar Rats (Rattus norvegicus) Post Dexamethasone Injection at 7. 2 mg/kg and 16 mg/kg Doses / Candidíase oral em ratos Wistar imunossuprimidos (Rattus norvegicus) pós-injeção de dexametasona com doses de 7, 2 mg / kg e 16 mg / kg

Objective: Oral candidiasis is an infection that occurs in the oral cavity and is caused by candida species, often Candida albicans. This infection commonly occurs in a condition of immunosuppression caused by dexamethasone. Due to the side effects of antifungal therapy, developing a standardized immunosuppressed animal model to induce oral candidiasis for new therapies is required. The aim of this study is to observe oral candidiasis in immunosuppressed Wistar rats post dexamethasone injection at 7.2 mg/kg and 16 mg/kg doses. Material and Methods: Twenty-one Wistar rats were divided into three groups: control group, treatment group 1 (injected with dexamethasone at a concentration of 7.2 mg/kg), and treatment group 2 (at a concentration of 16 mg/kg) for five days. Immunosuppression status was observed by leukocyte count and all the subjects' palates were inoculated with C. albicans 0.1 ml of 15x108 UFC/ml 24 hours later. The subjects' tongues were observed and confirmed by laboratory examination on day 10. A statistical analysis was performed using one way ANOVA, Kruskal­Wallis, Tukey HSD, and Mann-Whitney U tests. Results: A significant clinical appearance of the subjects' tongues was observed only between C and T1 (p=0.023; p<0.05). Significant hyphal formation was observed between C and T1 (p= 0.037; p<0.05) and between C and T2 (p=0.007; p<0.05), and no significant difference was observed between T1 and T2. A significant increase in the colony count was also observed in similar results. Conclusion: Dexamethasone injection at doses of 7.2 mg/kg and 16 mg/kg is effective in triggering immunosuppression to induce oral candidiasis in immunosuppressed Wistar rats. (AU)

Candidíase oral é uma infecção que ocorre na cavidade oral e é causada por espécies de Candida, freqüentemente Candida albicans. Esta infecção geralmente ocorre em uma condição de imunossupressão causada por dexametasona. Devido aos efeitos colaterais de terapia antifúngica, o desenvolvimento de um padrão de modelo animal imunossuprimido para induzir candidíase oral para testar novas terapias se faz necessário. O objetivo deste estudo é observar candidíase oral em ratos Wistar imunossuprimidos pós-injeção de dexametasona utilizando doses de 7,2 mg /kg e 16 mg / kg. Material e métodos: Vinte e um ratos Wistar foram divididos em três grupos: grupo controle, tratamento grupo 1 (injetado com dexametasona na concentração de 7,2 mg / kg), e tratamento grupo 2 (concentração de 16 mg / kg) por cinco dias. A imunossupressão foi observada pela contagem de leucócitos e todos os palatos dos animais foram inoculados com C. albicans 0,1 ml de 15x108 UFC / ml após 24horas. As línguas dos animais foram observadas e confirmadas por exame laboratorial após 10 dias. A análise estatística foi realizada usando os testes de ANOVA um fator, kruskal ­ Wallis, Tukey HSD e de Mann-Whitney. Resultados: Significante diferença na aparência clínica da língua dos animais foi observada apenas entre C e T1 (p = 0,023; p <0,05). Significativa diferença na formação de hifas foi observada entre C e T1(p = 0,037; p <0,05) e entre C e T2 (p = 0,007; p <0,05), e nenhuma diferença significativa foi observada entre T1 e T2. Um aumento significativo na contagem de colônias foi também observado com resultados semelhantes. Conclusão: Injeção de dexametasona utilizando doses de 7,2 mg / kg e 16 mg / kg é eficaz no desencadeamento da imunossupressão para induzir candidíase oral em ratos Wistar imunossuprimidos. (AU)

Roles of VEGF-Flt-1 signaling in malignant behaviors of oral squamous cell carcinoma.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a highly specific signaling protein for vascular endothelial cells that plays a critical role in tumor growth and invasion through angiogenesis, and may contribute to cell migration and activation of pre-osteoclasts, osteoclasts and some tumor cells. OBJECTIVES: We aimed to clarify the detailed roles of VEGF-Flt-1 signaling in bone invasion of oral squamous cell carcinoma (OSCC) cells. RESULTS: Forty-two (42) of 54 cases with gingival SCC (77.8%) strongly expressed VEGF, and had a significantly increased number of Flt-1+ osteoclasts (p<0.01) and more aggressive bone invasion (p<0.05). PlGF, a ligand of Flt-1, induced osteoclastogenesis in single culture of bone marrow cells (BMCs), and inhibition of Flt-1-signaling by VEGF tyrosine kinase inhibitor and It's down stream (Akt and ERK1/2) inhibitos reduced osteoclastogenesis in PlGF-stimulated BMCs (p<0.01). In molecular level, PlGF stimulation significantly upregulated RANKL expression in Flt-1-expressing HSC2 cells via phosphorylation of Akt and ERK1/2. In the co-culture of VEGF-producing HSC2 cells and BMCs, number of TRAP-positive osteoclasts markedly increased (p<0.01). The osteoclastogenesis was significantly inhibited by RANKL-neutralizing antibody (p<0.01) as well as by VEGF tyrosine kinase inhibitor (p<0.01) and it's downstream (Akt and ERK1/2) inhibitors (p<0.01, p<0.05, respectively). CONCLUSION: VEGF-Flt-1 signaling induces osteoclastogenesis in OSCC through two possible ways: 1) VEGF produced from OSCC cells can directly stimulate the Flt-1 pathway in preosteoclasts to induce migration to future bone resorbing area and differentiation into osteoclasts, and 2) VEGF-Flt-1 signaling upregulates RANKL expression in OSCC cells, which indirectly leads to osteoclast differentiation. Therefore, blocking of the VEGF-Flt-1 signaling may help inhibit bone invasion of OSCC.

Infection with Porphyromonas gingivalis exacerbates endothelial injury in obese mice.

BACKGROUND: A number of studies have revealed a link between chronic periodontitis and cardiovascular disease in obese patients. However, there is little information about the influence of periodontitis-associated bacteria, Porphyromonas gingivalis (Pg), on pathogenesis of atherosclerosis in obesity. METHODS: In vivo experiment: C57BL/6J mice were fed with a high-fat diet (HFD) or normal chow diet (CD), as a control. Pg was infected from the pulp chamber. At 6 weeks post-infection, histological and immunohistochemical analysis of aortal tissues was performed. In vitro experiment: hTERT-immortalized human umbilical vein endothelial cells (HuhT1) were used to assess the effect of Pg/Pg-LPS on free fatty acid (FFA) induced endothelial cells apoptosis and regulation of cytokine gene expression. RESULTS: Weaker staining of CD31 and increased numbers of TUNEL positive cells in aortal tissue of HFD mice indicated endothelial injury. Pg infection exacerbated the endothelial injury. Immunohistochemically, Pg was detected deep in the smooth muscle of the aorta, and the number of Pg cells in the aortal wall was higher in HFD mice than in CD mice. Moreover, in vitro, FFA treatment induced apoptosis in HuhT1 cells and exposure to Pg-LPS increased this effect. In addition, Pg and Pg-LPS both attenuated cytokine production in HuhT1 cells stimulated by palmitate. CONCLUSIONS: Dental infection of Pg may contribute to pathogenesis of atherosclerosis by accelerating FFA-induced endothelial injury.