ITGB2-mediated metabolic switch in CAFs promotes OSCC proliferation by oxidation of NADH in mitochondrial oxidative phosphorylation system.

Objectives: Integrins, the coordinator of extracellular and intracellular signaling, are often found to be aberrant in tumors and can reshape the tumor microenvironment. Although previous studies showed that integrin beta 2 (ITGB2) is important for host defense, its expression profile and role in tumors, especially in cancer associated fibroblasts (CAFs) are still unknown. Methods: Immunofluorescence stain and fluorescence activated cell sorting were used to analyze the ITGB2 expression profile in oral squamous cell carcinoma (OSCC). RT-PCR and western blot were used to compare ITGB2 expression in normal fibroblasts (NFs) and cancer associated fibroblasts (CAFs). Clinical data and function-based experiments were used to investigate the promoting tumor growth ability of ITGB2 expressing CAFs. Enhanced glycolysis activity was identified by using bioinformatics analyses and GC/MS assays. MCT1 knockdown OSCC cell lines were constructed to explore the pro-proliferative mechanisms of ITGB2 expressing CAFs in multiple in vitro and in vivo assays. Results: We found that CAFs exhibited significantly higher ITGB2 expression than the matched NFs. In addition, higher ITGB2 expression in CAFs was correlated with higher TNM stages and more Ki67+ tumor cells, indicating its ability to promote OSCC proliferation. Further, co-culture assay demonstrated that ITGB2-mediated lactate release in CAFs promoted OSCC cell proliferation. Mechanically, ITGB2 regulated PI3K/AKT/mTOR pathways to enhance glycolysis activity in CAFs. Accordingly, lactate derived from ITGB2-expressing CAFs was absorbed and metabolized in OSCC to generate NADH, which was then oxidized in the mitochondrial oxidative phosphorylation system (OXPHOS) to produce ATP. Notably, inhibiting the OXPHOS system with metformin delayed the proliferative capacity of OSCC cells cultured in the ITGB2-expressing CAFs medium. Conclusions: Our study uncovered the ITGB2high pro-tumoral CAFs that activated the PI3K/AKT/mTOR axis to promote tumor proliferation in OSCC by NADH oxidation in the mitochondrial oxidative phosphorylation system.

Oral mucosal calcified nodule requiring palatoplasty.

Calcinosis cutis describes a condition of pathologic calcium deposition in the dermis. Several subtypes exist, including the subepidermal calcified nodule. The oral mucosal calcified nodule (OMCN) was posited in 1992 as a specific term for a subepidermal calcified nodule occurring in the oral cavity, and since that time only six such lesions have been described in the literature. This report explores a case of OMCN on the palate of a 3-month-old infant with the goal of supplementing extant literature, providing a consideration of the differentials of palatal lesions in the pediatric population, and describing a unique instance in which OMCN resulted in a full-thickness defect requiring palatoplasty for repair.

Effect of melatonin supplementation in combination with neoadjuvant chemotherapy to miR-210 and CD44 expression and clinical response improvement in locally advanced oral squamous cell carcinoma: a randomized controlled trial.

BACKGROUND: Squamous cell carcinoma of the oral cavity (OSCC) is the sixth most common malignancy. Surgery is mainstay treatment for oral cancers. Surgery in locally advanced OSCC presents many challenges primarily because the head and neck have critical structures that can be damaged by tumor or treatment. It is thought that neoadjuvant chemotherapy (NC) in locally advanced OSCC is able to shrink tumor size. Chemoresistancy is a problem due to hypoxic microenvironment characterized by increased expression of HIF-1α. It is also regulated by miR-210 as well as increased expression of CD44 and CD133. Melatonin has a powerful antioxidant and oncostatic effects that are expected to improve tumor hypoxia and clinical response. Fifty patients with OSCC were included and randomized. miR-210 and CD44 expression were measured before and after intervention using qRT-PCR absolute quantification, and clinical response was evaluated according to RECIST 1.1 criteria. This study aims to determine the effect of melatonin in improving the clinical response of patients with locally advanced oral squamous cell carcinoma (OSCC) after neoadjuvant chemotherapy to miR-210 and CD44 expression. RESULTS: Melatonin administration reduced miR-210 levels but not significant (p = 0.767). CD44 expression also decreased in the melatonin group compared with placebo yet was not significant (p = 0.103). There was a decrease in the expression of miR-210 and CD44 followed by a decrease in the percentage of residual tumor but not significant (p = 0.114). CONCLUSION: In OSCC, the addition of 20-mg melatonin to neoadjuvant chemotherapy (NC) reduced the expression of miR-210 and CD44 and decreased the percentage of tumor residue; however, no statistically significant result was observed. TRIAL REGISTRATION: This study is registered to ClinicalTrials.gov under trial registration number: NCT04137627 with date of registration on October 22, 2019-retrospectively registered, accessible from: https://clinicaltrials.gov/ct2/show/NCT04137627.

Evaluation of the Effect of Topical Hypericum perforatum Oil on Excisional Palatal Wound Healing in Rabbits.

Aim: The aim of this study was to evaluate the effect of Hypericum perforatum (HP) oil on wound-healing process in rabbit palatal mucosa. Materials and Methods: Thirty-six New Zealand albino rabbits were randomly allocated to following groups; (1) HP oil (test, n = 18) and (2) olive oil (control, n = 18). Palatinal excisional wounds were created and the oils were topically applied (0.1 ml, 30 s, twice a day). Gingival biopsies were excised, and analyzed for re-epithelialization (RE) and granulation tissue maturation (GTM) on days 3, 7, and 14 after surgery. Levels of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) were assessed using the immunohistochemical method. Apoptotic cells (ACs) were evaluated using TUNEL staining. Enzyme-linked immunosorbent assay was used to assess tissue catalase (CAT) and malondialdehyde (MDA) levels. Results: RE and GTM were completed earlier in the HP oil group than in the control group. The number of positively stained cells/vessels was higher in olive oil than in the test group on day 3 for FGF-2 and on days 3 and 7 for VEGF (p < 0.05). In contrast, on day 14, a higher number of vessels was observed in the HP oil group than in the control group. HP oil treatment reduced the number of ACs compared to olive oil (p < 0.05), but the difference during the healing period did not reach significance. Tissue CAT and MDA levels between groups were not different, and also the results were the same when the levels were analyzed by the evaluated time periods (p > 0.05). Conclusions: The results of this study demonstrated that topical HP oil treatment did not provide an additional benefit to its base, olive oil, in the early phase of secondary wound healing.

Avaliação tomográfica da espessura da mucosa palatina em indivíduos com biótipos fino e espesso / Tomographic evaluation of palatine mucosa thickness in individuals with thin and thick biotypes

INTRODUÇÃO: O palato é a principal área doadora de enxerto nas cirurgias periodontais e peri-implantares. O volume de tecido disponível depende da espessura da mucosa palatina e variações intra e interindividuais podem estar relacionadas ao tipo de biótipo do paciente. OBJETIVO: Investigar a diferença da espessura da mucosa palatina em indivíduos com biótipos fino e espesso, avaliada em diferentes regiões. METODOLOGIA: Foram analisadas 30 tomografias de feixe cônico adquiridas no tomógrafo CS8100 3D® e analisadas no software CS 3D Imaging® . O biótipo periodontal foi categorizado em fino (<1,5mm) ou espesso (≥1,5mm) e definido de duas formas: primeiro, o biótipo encontrado nos incisivos centrais foi considerado para os demais dentes. Em seguida, cada dente foi avaliado individualmente. Por fim, a espessura da mucosa palatina foi medida nos caninos, 1º e 2º pré-molares e 1º molares à 3mm, 6mm, 9mm e 12mm a partir da margem gengival. Os testes de Mann-Whitney, Wilcoxon e Friedman foram utilizados para avaliar as diferenças na espessura da mucosa palatina entre os grupos, entre os dentes e nas diferentes regiões, respectivamente. RESULTADOS: Não houve diferença estatística nas espessuras das mucosas palatinas entre os grupos (p> 0,05); em todos os dentes, quanto mais distante da margem gengival, maior a espessura da mucosa palatina (p< 0,0001). Entre os dentes, observou-se menor espessura nas localizações "b" e "c" no primeiro molar (p< 0,05) em todas as avaliações; nessas mesmas localizações, o segundo pré-molar (2PbX1Pb: p<0,0001) e o canino (CcX1Pc: p=0,022 e CcX2Pc: p=0,004) mostraram mucosa mais fina apenas quando categorizados com base no biótipo dos incisivos centrais. CONCLUSÃO: a espessura da mucosa palatina não mostrou relação com o biótipo do paciente, sendo mais fina na região do primeiro molar. Independentemente do dente, áreas mais distantes da margem gengival apresentam maior espessura tecidual (AU).

INTRODUCTION: The palate is the main donor site in periodontal and periimplant surgeries. The volume of tissue available depends on the thickness of the mucosa and intra and interindividual variations may be related to the patient's biotype. PURPOSE: To investigate the difference of the palatal mucosa thickness in individuals with thin and thick biotypes, evaluated in different regions. METHODS: 30 CBCT scans were acquired in the CS8100 3D® tomograph and analyzed in CS 3D Imaging® software. The periodontal biotype was categorized into thin (<1.5mm) or thick (≥1.5mm) and defined in two ways. First, the biotype found in the central incisors was considered for the remaining teeth. Then, each tooth was categorized individually. Finally, the thickness of the palatal mucosa was measured in the canine, 1st and 2nd premolars and 1st molar at 3mm, 6mm, 9mm and 12mm from the gingival margin. The Mann-Whitney, Wilcoxon and Friedman tests were used to evaluate differences in palatal mucosa between groups, among teeth and in different regions, respectively. RESULTS: There was no statistical difference in the palatal mucosal thickness between the groups (p> 0.05); in all analyzed teeth, the furthest from the gingival margin, the palatal mucosa thickness (p <0.0001) was higher. Among the teeth, the locations "b" and "c" in first molar was thinner (p <0.05) in all evaluations. The second pre-molar (2PbX1Pb: p <0.0001) and the canine (CcX1Pc: p = 0.022 and CcX2Pc: p = 0.004) showed a thinner mucosa only when categorized based on the central incisor biotype. CONCLUSIONS: the palatal mucosa thickness was not related to the patient biotype and was thinner at the first molar region. Regardless of the tooth, areas more distant from the gingival margin had a thicker tissue (AU).

Hard and soft tissue responses to three different implant materials in a dog model.

The aim of this study was to assess hard and soft tissue responses using three dental implants made of different materials. Implants made of titanium (Ti), yttria-stabilized tetragonal zirconia polycrystals (Y-TZP) and ceria partially stabilized zirconia/alumina nanocomposite (Ce-TZP/Al2O3) were used in a dog model. Five male beagles were sacrificed at three months after implantation, and harvested mandible were observed and analyzed. Histological observations were similar in all groups. There were no significant differences in any histomorphometric parameters. Our results suggested the possibility of Ce-TZP/Al2O3 as a dental implant material, similar to Ti and Y-TZP.

Effect of GaAIAs low-level laser therapy on the healing of human palate mucosa after connective tissue graft harvesting: randomized clinical trial.

Among the available techniques to treat gingival recession, connective tissue graft (CTG) presents more foreseeability and better results in the long term. However, this technique causes morbidity and discomfort in the palatine region due to graft removal at that site. The aim of this clinical trial was to evaluate the influence of low-level laser therapy (LLLT) on the healing of the donor palatine area after CTG. Thirty-two patients presenting buccal gingival recession were selected and randomly assigned to receive LLLT irradiation (test group) or LLLT sham (control group) in the palatine area after connective graft removal. A diode laser (AsGaAl, 660 nm) was applied to test the sites immediately after surgery and every other day for 7 days. The evaluated parameters were wound remaining area (WRA), scar and tissue colorimetry (TC), tissue thickness (TT), and postoperative discomfort (D). These parameters were evaluated at baseline and 7, 14, 45, 60, and 90 days after surgery. Two-way repeated measures ANOVA was used for analysis. The test group presented statistically significant smaller wounds at days 14 and 45. None of the patients presented a scar at the operated area, and colorimetry analysis revealed that there was no statistically significant difference between groups (p > 0.05). Patients reported mild to moderate discomfort, with low consumption of analgesic pills. We concluded that LLLT irradiation can accelerate wound healing on palatine mucosa after connective tissue removal for root coverage techniques (ClinicalTrial.org NCT02239042).

Lábio duplo bilabial / Bilabial double lip

O lábio duplo é uma entidade rara, com poucos relatos, que geralmente afeta o lábio superior, sendo de fácil diagnóstico clínico. Pode ter origem congênita ou adquirida. O tratamento cirúrgico é indicado por queixa estética ou funcional, de simples execução. Este relato refere-se a um caso de lábio duplo bilabial em paciente do sexo masculino de 14 anos, em que foi realizada correção cirúrgica por motivação estética do paciente, com ótimo resultado dos pontos de vista estético e funcional.

There are few published reports on double lip, a rare entity that usually affects the upper lip, and that is easily diagnosed clinically. It may be congenital or acquired. Surgical treatment is indicated for aesthetic or functional complaints, and is simple to implement. This report describes a case of bilabial double lip in a 14-year-old male patient, in whom surgical correction was carried out for aesthetic reasons, with excellent aesthetic and functional results.

Hyperbaric oxygen therapy accelerates vascularization in keratinized oral mucosal surgical flaps.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) is thought to promote vascular regeneration in wounds. The purpose of this study was to investigate the role of HBOT in advancing vascular regeneration in healing oral mucosal surgical flaps. METHODS: A palatine partial-thickness mucosal flap was raised in 10 male-specific pathogen-free New Zealand White rabbits. Randomized into 2 groups of 5 animals each (control and HBOT), functional capillary density was measured preoperatively (baseline), and immediately postoperatively until day 21 using sidestream dark-field video microscopy. Ten HBOT sessions were administered over the course of 2 weeks at 2.5 atmospheres (2.5 bar O2 /90 minutes). RESULTS: Repeated measures analysis of variance was used to compare the HBOT and control group on the sequential functional capillary density measurements. A significant interaction effect was present between time and group (F [8, 64] = 9.60; p < .0001) resulting from a significant increase in microcirculation in the HBOT group relative to the control group on days 7, 9, and 11. CONCLUSION: Our results suggest that HBOT is capable of advancing wound vascular regeneration in healing keratinized oral mucosal flaps.

Evaluation of antibiotic releasing porous polymethylmethacrylate space maintainers in an infected composite tissue defect model.

This study evaluated the in vitro and in vivo performance of antibiotic-releasing porous polymethylmethacrylate (PMMA)-based space maintainers comprising a gelatin hydrogel porogen and a poly(dl-lactic-co-glycolic acid) (PLGA) particulate carrier for antibiotic delivery. Colistin was released in vitro from either gelatin or PLGA microparticle loaded PMMA constructs, with gelatin-loaded constructs releasing colistin over approximately 7 days and PLGA microparticle-loaded constructs releasing colistin for up to 8 weeks. Three formulations with either burst release or extended release at different doses were tested in a rabbit mandibular defect inoculated with Acinetobacter baumannii (2×10(7) colony forming units ml(-1)). In addition, one material control that released antibiotic but was not inoculated with A. baumannii was tested. A. baumannii was not detectable in any animal after 12 weeks on culture of the defect, saliva, or blood. Defects with high dose extended release implants had greater soft tissue healing compared with defects with burst release implants, with 8 of 10 animals showing healed mucosae compared with 2 of 10 respectively. Extended release of locally delivered colistin via a PLGA microparticle carrier improved soft tissue healing compared with implants with burst release of colistin from a gelatin carrier.

Comparing the 810nm diode laser with conventional surgery in orthodontic soft tissue procedures.

AIM: To compare the use of the 810nm diode laser with conventional surgery in the management of soft tissue mucogingival problems associated with orthodontic treatment. METHODS: Orthodontic patients requiring different soft tissue surgical procedures were randomly assigned to receive conventional surgery or soft tissue diode laser, (wavelength 810 nm). MAIN OUTCOME MEASURES: Parameters documented include the type of anaesthesia used, intra and post operative pain, bleeding, the use of scalpel and sutures. The chi-squared test was used to test for significance at 95% confidence level. Probability values (p-values) less than 0.05 were regarded as significant. RESULTS: Only 2(16.7%) of the procedures carried out with the soft tissue laser required infiltration anaesthesia compared to 10 (90.9%) with conventional surgery and this was significant (P<0.001). Post operative pain was significantly reduced in all cases treated with the diode laser (P<0.001). There was also a significant difference (P<0.05) in post operative bleeding in all cases treated with the diode laser. No sutures were used in all soft tissue cases managed with the diode laser and this was significant (P<0.001). There was no statistically significant difference in treatment time in the use of the laser compared with conventional surgery. CONCLUSION: Orthodontic patients treated with the diode laser required less infiltration anaesthesia, had reduced bleeding during and after surgery, rapid postoperative haemostasis, elimination of the need for sutures and an improved postoperative comfort and healing.

Social exclusion and myiasis of the upper lip in a Brazilian rural resident.

CONTEXT: People living in rural or remote Brazil, as in other sub-tropical or tropical nations, are vulnerable to infections that would not normally occur in urban areas or wealthier nations. Brazil is a geographically extensive nation, historically marked by vast socioeconomic inequalities. Approximately 16% of the population live in rural areas. ISSUE: This clinical case report demonstrates the vulnerability of rural residents who are underserved by Brazil's 'universal' public healthcare system, despite social and economic challenges that increase their risk for disease. Myiasis (especially oral myiasis) is a rare health condition in humans caused by fly larvae. Oral myiasis usually appears in periodontal pockets and open wounds, such as after dental extractions. It is associated with poverty, lack of access to health care, and very poor overall health status. While myiasis has a worldwide distribution, it is particularly associated with the tropical and sub-tropical regions of North and South America. LESSONS LEARNED: This article describes a rare case of myiasis in the upper lip of a rural male patient. The case report demonstrate that rural and remote residents can be socially excluded from the benefits of technology and biomedicine, making them vulnerable to rare infections.

Healing process and laser therapy in the superficial periodontium: a histological study.

AIM: To evaluate the efficiency of laser therapy in healing, regeneration and repair processes located in the superficial periodontium after gingivectomy procedures. MATERIALS AND METHODS: The study group consisted of 38 patients without any systemic diseases presenting with gingival hypertrophy developed exclusively within the clinical context of gingivitis and/or periodontitis. All patients were included in the study based on their informed consent. All patients required several surgical interventions at the level of the superficial periodontium. Subgroup 1 (17 patients) was treated only through gingivectomy procedures. For subgroup 2 (21 patients), the gingivectomy was associated with laser therapy, applied every day for seven days. Gingival mucosa fragments were taken on day 1 (curative gingivectomy) and on day 21 (clinical control and corrective gingivectomy), and routinely processed for the microscopic exam, using Hematoxylin-Eosin and special stains (trichrome Szekely and Periodic Acid-Schiff). RESULTS AND DISCUSSION: The comparison between the morphological pictures characterizing the healing process associated or not with laser therapy, allowed the identification of some features supporting the benefits of laser therapy. We believe that the decrease in the inflammatory infiltrate located in the lamina propria is the critical morphological trait for the control of a healing process as near to restitutio ad integrum as possible. The diminished number of lymphocytes and macrophages will implicitly determine a lower production of chemical mediators interfering with the sequences of the healing process. CONCLUSIONS: The morphological differences identified at the gingival epithelium level and subjacent lamina propria support the value of laser therapy, stimulating an improved healing of the damaged tissues.

Evaluation of neodymium-doped yttrium aluminium garnet laser, scalpel incision wounds, and low-level laser therapy for wound healing in rabbit oral mucosa: a pilot study.

OBJECTIVE: The aim of the present randomized controlled clinical trial was to assess the clinical and histopathological effects of laser and low-level laser therapy (LLLT) on healing of the oral mucosa after vestibuloplasty surgery. METHODS: The alterations at the end of healing in scalpel- and laser-incised and LLLT-applied oral mucosa were studied in eight healthy adult New Zealand white rabbits by taking specimens for light microscopic inspection. For the evaluation of wound healing, the surgical areas were stained using a solution (Mira-2-tones), and the stained surfaces were measured horizontally immediately after the surgery and on postoperative days 4, 7, and 10. RESULTS: Although the stained surface areas of the groups were similar immediately after the surgical procedures, the LLLT-applied sites had significantly fewer stained surface areas than the other groups on postoperative days 4, 7, and 10. Areas of hyperkeratosis and parakeratinization were observed in the epithelia of the laser surgery groups. A significant increase in epithelial thickness was found, suggesting increased scar tissue after wound repair; long and irregular connective tissue protrusions projecting into the undersurface of the epithelium were noted in these groups. CONCLUSION: LLLT used for soft tissue operations provides better and faster wound healing, and LLLT enhances epithelization.

Removal of an irritation fibroma using an Er,Cr:YSGG laser: a case report.

The irritation fibroma is a benign proliferation that occurs as a response to local irritation. It is an elevated pedunculated or sessile lesion that ranges in size from a few millimeters to a few centimeters and is normal in color, although it may appear to be more pale than the normal mucosa. This article describes the case of a 39-year-old woman with an asymptomatic nodular lesion that involved the left buccal mucosa. The lesion was removed using an Er,Cr:YSGG laser. Only topical anesthesia was applied to the fibroma and adjacent mucosa and no infiltration was required. No pain medication or antibiotics were required after surgery and wound healing was excellent and achieved rapidly. The oral pathology report confirmed the presurgical clinical diagnosis. Laser excision is a modern approach for treating oral soft tissue lesions and should be considered as an alternative to conventional scalpel surgery.

Harvesting buccal mucosa graft under local infiltration analgesia--mitigating need for general anesthesia.

For buccal mucosal graft urethroplasty, nasal or oral endotracheal intubation anesthesia is used for harvesting the graft from the oral cavity. A technique of graft harvesting under local anesthesia using 2% lidocaine solution with adrenaline (1:200,000) is described. This method requires a cooperative patient but saves the morbidity of general anesthesia.

Fibrolipoma em mucosa jugal: relato de um caso / Fibrolipoma in the cheek: a case report

O lipoma é uma neoplasia benigna de tecido adiposo, pouco frequente na mucosa bucal, de desenvolvimento lento e assintomático. O fibrolipoma é a variante mais comum desta neoplasia, caracterizado pela presença de tecido adiposo e fibroconjuntivo. O presente artigo tem como objetivo relatar um caso clínico de fibrolipoma, ressaltando seus aspectos clínico e histopatológico

Papiloma bucal: relato de um caso clínico / Oral papilloma: a clinical case report

Os autores apresentam um caso clínico de papiloma bucal na mucosa labial inferior, de um paciente infantil, ressaltando suas características clínicas, histopatológicas e importância do correto diagnóstico para uma adequada abordagem cirúrgica.

Patients' pain experience following oral mucosal biopsy under local anaesthesia.

OBJECTIVE: To examine the incidence and severity of post-operative pain and use of analgesics following biopsy of oral mucosal lesions. DESIGN: A patient survey using a self-completed pain diary. SUBJECTS AND METHODS: Seventy-six patients attending an oral medicine clinic for investigation of oral mucosal disease recorded overall and worst pain experiences and analgesic usage over 7 post-operative days following biopsy using visual analogue scales in patient completed diaries. RESULTS: One third of patients reported no post-operative pain on any day. Most patients recorded no pain or mild pain. The percentage experiencing pain dropped from the first day (61%) to the seventh day (21%). Most patients did not use any analgesics. Analgesic use was not related to the presence of pain. Only a small minority of patients recorded severe pain. CONCLUSION: Biopsy of oral mucosal lesions does not cause undue pain in most patients.