Antiproliferative Activity of N-Acylhydrazone Derivative on Hepatocellular Carcinoma Cells Involves Transcriptional Regulation of Genes Required for G2/M Transition.

Liver cancer is the second leading cause of cancer-related death in males. It is estimated that approximately one million deaths will occur by 2030 due to hepatic cancer. Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer subtype and is commonly diagnosed at an advanced stage. The drug arsenal used in systemic therapy for HCC is very limited. Multikinase inhibitors sorafenib (Nexavar®) and lenvatinib (Lenvima®) have been used as first-line drugs with modest therapeutic effects. In this scenario, it is imperative to search for new therapeutic strategies for HCC. Herein, the antiproliferative activity of N-acylhydrazone derivatives was evaluated on HCC cells (HepG2 and Hep3B), which were chemically planned on the ALL-993 scaffold, a potent inhibitor of vascular endothelial growth factor 2 (VEGFR2). The substances efficiently reduced the viability of HCC cells, and the LASSBio-2052 derivative was the most effective. Further, we demonstrated that LASSBio-2052 treatment induced FOXM1 downregulation, which compromises the transcriptional activation of genes required for G2/M transition, such as AURKA and AURKB, PLK1, and CDK1. In addition, LASSBio-2052 significantly reduced CCNB1 and CCND1 expression in HCC cells. Our findings indicate that LASSBio-2052 is a promising prototype for further in vivo studies.

N-acylhydrazone derivative modulates cell cycle regulators promoting mitosis arrest and apoptosis in estrogen positive MCF-7 breast cancer cells.

Breast cancer is the leading cause of cancer death among women worldwide. About 75% of all diagnosed cases are hormone-positive, which are treated with hormone therapy. However, many patients are refractory or become resistant to the drugs used in therapeutic protocols. In this scenario, it is essential to identify new substances with pharmacological potential against breast cancer. VEGFR2 inhibitors are considered promising antitumor agents not only due to their antiangiogenic activity but also by inhibiting the proliferation of tumor cells. Thus, the present study aimed to evaluate the effects of N-acylhydrazone derivative LASSBio-2029 on the proliferative behavior of MCF-7 cells. We observed a promising antitumor potential of this substance due to its ability to modulate critical cell cycle regulators including mitotic kinases (CDK1, AURKA, AURKB, and PLK1) and CDK inhibitor (CDKN1A). Increased frequencies of abnormal mitosis and apoptotic cells were observed in response to treatment. A molecular docking analysis predicts that LASSBio-2029 could bind to the proto-oncoprotein ABL1, which participates in cell cycle control, interacting with other controller proteins and regulating centrosome-associated tubulins. Finally, we created a gene signature with the downregulated genes, whose reduced expression is associated with a higher relapse-free survival probability in breast cancer patients.

Piperine-Chlorogenic Acid Hybrid Inhibits the Proliferation of the SK-MEL-147 Melanoma Cells by Modulating Mitotic Kinases.

Melanoma is considered the most aggressive form of skin cancer, showing high metastatic potential and persistent high mortality rates despite the introduction of immunotherapy and targeted therapies. Thus, it is important to identify new drug candidates for melanoma. The design of hybrid molecules, with different pharmacophore fragments combined in the same scaffold, is an interesting strategy for obtaining new multi-target and more effective anticancer drugs. We designed nine hybrid compounds bearing piperine and chlorogenic acid pharmacophoric groups and evaluated their antitumoral potential on melanoma cells with distinct mutational profiles SK-MEL-147, CHL-1 and WM1366. We identified the compound named PQM-277 (3a) to be the most cytotoxic one, inhibiting mitosis progression and promoting an accumulation of cells in pro-metaphase and metaphase by altering the expression of genes that govern G2/M transition and mitosis onset. Compound 3a downregulated FOXM1, CCNB1, CDK1, AURKA, AURKB, and PLK1, and upregulated CDKN1A. Molecular docking showed that 3a could interact with the CUL1-RBX1 complex, which activity is necessary to trigger molecular events essential for FOXM1 transactivation and, in turn, G2/M gene expression. In addition, compound 3a effectively induced apoptosis by increasing BAX/BCL2 ratio. Our findings demonstrate that 3a is an important antitumor candidate prototype and support further investigations to evaluate its potential for melanoma treatment, especially for refractory cases to BRAF/MEK inhibitors.

Photobiomodulation enhances the Th1 immune response of human monocytes.

This study aims to evaluate the effects of photobiomodulation (PBM) on human monocytes, assessing the oxidative burst and ultimate fungicidal potential of these cells, as well as the gene expression at the mRNA level of CD68, CD80, CD163, CD204, IL-6, TNF-α and IL-10 in derived macrophages. Primary cultures of human monocytes were irradiated with an InGaAlP (660 nm)/GaAlAs (780 nm) diode laser (parameters: 40 mW, 0.04 cm2, 1 W/cm2; doses: 200, 400 and 600 J/cm2). Cells were submitted to the chemiluminescence assay, and a microbicidal activity assay against Candida albicans was performed. Reactive oxygen species (ROS) and nitric oxide (NO) production were measured, and cell viability was assessed by the exclusion method using 0.2% Trypan blue reagent. Irradiated monocytes were cultured for 72 h towards differentiation into macrophages. Total RNA was extracted, submitted to reverse transcription and real-time PCR. The results were analysed by ANOVA and the Tukey test (α = 0.05). Irradiated monocytes revealed a significant increase in their intracellular and extracellular ROS (P < 0.001). The 660 nm wavelength and 400 J/cm2 dose were the most relevant parameters (P < 0.001). The fungicidal capacity of the monocytes was shown to be greatly increased after PBM (P < 0.001). PBM increased the expression of TNF-α (P = 0.0302) and the production of NO (P < 0.05) and did not impair monocyte viability. PBM induces a pro-inflammatory Th1-driven response in monocytes and macrophages.

Development and Evolution of a Diagnostic and Oral Pathology Service in a Southeast Brazilian State / Desenvolvimento e Evolução de um Serviço de Diagnóstico e de Patologia Bucal em um Estado do Sudeste Brasileiro / Desarrollo y Evolución de un Servicio de Diagnóstico y Patología Oral en un Estado del Sudeste Brasileño

Introduction: Oral squamous cell carcinoma (OSCC) is one of the most frequent cancers whose main causes are preventable because oral cavity is easily accessible for examination. OSCC involves many steps from the diagnosis until treatment which can result in late diagnosis and worst prognosis. Objective: Development and evolution of a Stomatology and Oral Pathology Service at the Federal University of Alfenas addressing early diagnosis and management of oral lesions. Method: Retrospective study developed with the files from 1998 to 2019. Data from all the cases diagnosed as oral malignancies were collected and the demographical, clinical, and microscope diagnosis were included. Results: 270 (84.64%) OSCC were found among 8,952 histopathological diagnoses. The patients age ranged from 24 to 94 years (mean 59.7±13.1 years), and more frequent in the sixth (32.3%) and seventh (26%) decades of life. Men were 2.5 times more affected than women. Most of patients were Caucasian (74.8%), and users of tobacco and alcohol. Over the years, there was an increase in the number of cases diagnosed and expansion of the area covered by the Service. Conclusion: The Dental Clinic (Stomatology) and Oral Pathology Laboratory has been playing an important role for the establishment and improvement of the healthcare system to the local population, mainly in rural áreas

Introdução: O carcinoma de células escamosas (CEC) de boca está entre os cânceres mais frequentes. Suas principais causas são evitáveis, pois a cavidade oral é uma área de fácil acesso para exame. No entanto, desde o estabelecimento do diagnóstico até o tratamento final dos pacientes, o CEC envolve muitas etapas e pode resultar em diagnóstico tardio e, portanto, em pior prognóstico para os pacientes. Objetivo: Apresentar o desenvolvimento e a evolução de um Serviço de Estomatologia e Patologia Oral da Universidade Federal de Alfenas, que tem como foco o diagnóstico precoce e o tratamento de lesões bucais. Método: Estudo retrospectivo com os prontuários de 1998 a 2019. Foram coletados dados de todos os casos diagnosticados como malignidades orais e incluídos os diagnósticos demográficos, clínicos e microscópicos. Resultados: Entre 8.952 diagnósticos histopatológicos realizados, 270 (84,64%) eram CCE. A idade dos pacientes variou de 24 a 94 anos (média 59,7±13,1 anos), sendo mais frequente na sexta (32,3%) e sétima (26%) décadas de vida. Os homens foram 2,5 vezes mais afetados do que as mulheres. A maioria dos pacientes era branca (74,8%) e o uso de tabaco e álcool, frequente. Ao longo dos anos, houve um aumento do número de casos diagnosticados, bem como uma ampliação da área de cobertura do Serviço. Conclusão: O Serviço de Estomatologia e Patologia Oral tem desempenhado um papel importante na implantação e melhoria do sistema de saúde da população local, principalmente nas Regiões interioranas e em áreas rurais

Introducción: El carcinoma de células escamosas (CCE) de boca se encuentra entre los cánceres más frecuentes. Sus principales causas se pueden prevenir ya que la cavidad bucal es un área de fácil acceso para su examen. Sin embargo, desde el establecimiento del diagnóstico hasta el tratamiento final de los pacientes, la CEC implica muchos pasos y puede resultar en un diagnóstico tardío y, por lo tanto, un peor pronóstico para los pacientes. Objetivo: Presentar el desarrollo y evolución de un Servicio de Estomatología y Patología Bucal de la Universidad Federal de Alfenas que se enfoca en el diagnóstico y tratamiento precoz de las lesiones bucales. Método: Estudio retrospectivo con historias clínicas de 1998 a 2019. Se recolectaron datos de todos los casos diagnosticados como neoplasias bucales, incluyendo diagnósticos demográficos, clínicos y microscópicos. Resultados: De los 8.952 diagnósticos histopatológicos realizados, 270 (84,64%) fueron CCE. La edad de los pacientes osciló entre 24 y 94 años (media 59,7±13,1 años), siendo más frecuente en la sexta (32,3%) y séptima (26%) décadas de la vida. Los hombres se vieron 2,5 veces más afectados que las mujeres. La mayoría de los pacientes eran de raza blanca (74,8%) y el consumo de tabaco y alcohol era frecuente. A lo largo de los años, ha habido un aumento en el número de casos diagnosticados, así como una expansión del área de cobertura del Servicio. Conclusión: El Servicio de Estomatología y Patología Bucal ha jugado un papel importante en la implementación y mejora del sistema de salud para la población local, especialmente en las Regiones del interior y áreas rurales

Oral Paracoccidioidomycosis affecting women: A systematic review.

Paracoccidioidomycosis (PCM) is an infection caused by fungi of the genus Paracoccidioides and is marked by a strong predilection for men; nevertheless, some women have had developed PCM and have presented oral involvement by the disease. OBJECTIVES: To review all published cases until August 2020 of oral PCM in women, with emphasis on the presence of systemic changes, deleterious habits (tobacco and alcohol) and oral manifestation features through a systematic review. METHODS: Observational studies (both prospective and retrospective) and case reports indexed in the Embase, PubMed, Scopus, Web of Science and LIVIVO databases were selected by two reviewers in a two-phase process following the pre-established PICOS criteria. RESULTS: Twenty-five studies met the eligibility criteria and were selected for qualitative synthesis, of which 72 participants were enrolled. Brazilian White women between 40 and 50 years were the most affected and social history revealed them to be housewives or rural workers. Fifteen women (33.3% of the informed cases) presented any systemic change at the time of PCM diagnosis, namely pregnancy, HIV infection and/or depression. Moriform stomatitis was predominant and affected preferentially the gingivae and alveolar processes in the form of a single painful lesion. Most patients were treated with sulfamethoxazole + trimethoprim or itraconazole. CONCLUSIONS: Oral PCM in women is rare; some cases showed systemic changes at the time of PCM diagnosis, namely HIV infection, pregnancy and depression. New studies should be conducted to elucidate the influence of systemic alterations on the development of oral PCM in women.

An unusual case of oral phleboliths without evidence of associated vascular anomalies.

Phleboliths are calcified thrombi found within a dilated blood vessel. When located in the maxillofacial region, they are commonly associated with hemangiomas or vascular malformations. This article reports an unusual case of a 59-year-old woman presenting with noncalcified phleboliths without evidence of associated vascular anomalies. Therefore, although a radiographic finding of phleboliths in the soft tissues of the head and neck represents evidence that a vascular malformation may be present, these lesions can occur without associated vascular anomalies. The association between the estimated age and elemental composition of the phleboliths in the present case suggests that the calcification process is relatively slow.

Pyogenic granuloma in the tongue of a patient with Down syndrome.

Down syndrome (DS), a genetic disorder caused by chromosome 21 trisomy, is characterized by intellectual disability, congenital malformations, craniofacial alterations, and dentofacial anomalies. Although some oral lesions have been reported in patients with DS, this is the first reported case of a pyogenic granuloma affecting the tongue of a patient with DS. A 20-year-old man presented with a well-demarcated nodular lesion on the right lateral border of the tongue. The 2-cm lesion had a pedunculated base, flaccid consistency, and a superficial ulceration covered by a serofibrinous pseudomembrane. The patient's mother reported that the patient had a recurring habit of traumatizing the lateral border of the tongue. A similar lesion had been surgically removed from the site 1 month earlier, but the excised tissue had not been sent for pathologic analysis. Surgical excision of the new lesion was performed under local anesthesia, and microscopic analysis confirmed the diagnostic hypothesis of pyogenic granuloma, a nonneoplastic vascular hyperplasia of a reactive nature. There was another recurrence at the same site 2 months after the second surgical excision. The patient was given a mandibular silicone mouthguard for 1 month of nightly use to prevent further trauma to the site. Complete healing of the site was observed at the 18-month follow-up examination, and there was no sign of recurrence. Considering the high prevalence of oral alterations in patients with DS, dentists should be able to recognize, diagnose, and correctly manage oral pyogenic granuloma.

Erythema multiforme induced by fluconazole in an immunocompetent patient: a case report and review of the literature.

Erythema multiforme (EM) is an acute hypersensitivity reaction that affects the skin and/or mucosa. EM induced by fluconazole is extremely rare, with only 2 previously published case reports. The aims of this article are to report a rare case of severe EM induced by fluconazole in an immunocompetent patient and to review all similar published cases. A 35-year-old man presented with multiple painful superficial ulcerated lesions on the lips, superficial ulcers on the right and left ocular mucosa, and erythematous macules on the right cervical region. Moreover, multiple painful superficial ulcers covered by a serofibrinous pseudomembrane were located on the oral mucosa. The lesions appeared after the initial oral use of fluconazole (100 mg) 3 weeks previously for the treatment of onychomycosis. The clinical diagnosis was EM associated with fluconazole. The antifungal medication was discontinued, and a single dose of intramuscular Diprospan (5 mg of betamethasone dipropionate/2 mg of betamethasone disodium phosphate) was prescribed. Complete healing of all lesions at the 7-day follow-up was observed.

New WHO odontogenic tumor classification: impact on prevalence in a population.

OBJECTIVES: This study approaches the history of reclassifications and redefinitions around the odontogenic keratocyst (OK), as proposed by the World Health Organization (WHO), and aims to understand the impact of those changes on the prevalence and epidemiology of odontogenic tumors (OTs). METHODOLOGY: Cases of OTs diagnosed in an Oral Pathology service between January 1996 and December 2016 were reviewed. Demographic data of patients such as age, gender and site of lesions were retrieved from their respective records. RESULTS: Within the studied period, 7,805 microscopic reports were elaborated and 200 (2.56%) of these were diagnosed as OTs. Out of these 200, between 1996 and 2005, prior to the 2005 WHO classification, there were 41 (20.5%) OTs cases, being odontoma the most frequent (23; 56.09%), followed by ameloblastoma (8; 19.51%) and myxoma (03; 7.31%). Between 2006 and 2016, after the previous 2005 WHO classification there were 159 (79.5%) OTs, being odontogenic keratocystic tumor (KCOT) the most frequent (68; 42.76%), followed by odontoma (39; 24.52%) and ameloblastoma (21; 13.20%). CONCLUSIONS: As of today, the most recent WHO classification to be followed brings KCOT back to the cyst category, which will impact on the prevalence and epidemiology of OTs; thus, this study was able to identify a considerable increase (287.80%) in the prevalence of OTs when the 2005 WHO classification was utilized. Despite being an important academic exercise, classifying odontogenic lesions and determining whether to place the odontogenic keratocyst in a cyst or tumor category is crucial to establish the correct diagnosis and treatment to follow, whether by oral medicine or oral surgery specialist, or by the general practitioner.

New WHO odontogenic tumor classification: impact on prevalence in a population

Abstract Objectives: This study approaches the history of reclassifications and redefinitions around the odontogenic keratocyst (OK), as proposed by the World Health Organization (WHO), and aims to understand the impact of those changes on the prevalence and epidemiology of odontogenic tumors (OTs). Methodology: Cases of OTs diagnosed in an Oral Pathology service between January 1996 and December 2016 were reviewed. Demographic data of patients such as age, gender and site of lesions were retrieved from their respective records. Results: Within the studied period, 7,805 microscopic reports were elaborated and 200 (2.56%) of these were diagnosed as OTs. Out of these 200, between 1996 and 2005, prior to the 2005 WHO classification, there were 41 (20.5%) OTs cases, being odontoma the most frequent (23; 56.09%), followed by ameloblastoma (8; 19.51%) and myxoma (03; 7.31%). Between 2006 and 2016, after the previous 2005 WHO classification there were 159 (79.5%) OTs, being odontogenic keratocystic tumor (KCOT) the most frequent (68; 42.76%), followed by odontoma (39; 24.52%) and ameloblastoma (21; 13.20%). Conclusions: As of today, the most recent WHO classification to be followed brings KCOT back to the cyst category, which will impact on the prevalence and epidemiology of OTs; thus, this study was able to identify a considerable increase (287.80%) in the prevalence of OTs when the 2005 WHO classification was utilized. Despite being an important academic exercise, classifying odontogenic lesions and determining whether to place the odontogenic keratocyst in a cyst or tumor category is crucial to establish the correct diagnosis and treatment to follow, whether by oral medicine or oral surgery specialist, or by the general practitioner.

Odontomas are associated with impacted permanent teeth in orthodontic patients.

BACKGROUND: Odontomas are the most frequent odontogenic tumors in the oral cavity and can result in failure of eruption of permanent teeth or be associated with impacted teeth. MATERIAL AND METHODS: The present study evaluated the prevalence of complex and compound odontomas in non-syndromic patients prior to the onset of orthodontic treatment. Panoramic radiographs of 4,267 non-syndromic patients were evaluated; 22 cases were included being 54.5% complex and 45.4% compound odontomas. RESULTS: The sample was composed predominantly by White males with mean age of 14.5 years. Complex odontomas were commonly found in the maxilla (83.3%) while compound type was mostly located on mandible (60%), presenting a significant association (P=0.027). Moreover, odontomas were significantly associated with impacted teeth (P<0.0001). The most frequently odontoma-associated impacted teeth were lower canines, followed by upper central incisors and upper canines, while impacted teeth with no odontoma were predominantly upper canines, lower second premolars and upper second premolars. Compound and complex odontomas showed mean size of 10.5 and 7.25 mm, respectively, presenting significant association between lesion size and odontoma type (P=0.021). CONCLUSIONS: Odontomas affected mainly White male patients with mean age of 14.5 years, being the complex type commonly found in the maxilla and the compound type mostly located on mandible. Furthermore, odontomas were significantly associated with impacted teeth, affecting mainly lower canines. Early diagnosis and correct treatment are essential to avoid any complications, such as prolonged retention of primary teeth and delayed eruption of permanent teeth. Key words:Odontoma, odontogenic tumors, dental anomalies.

Different DNA methylation profile is demonstrated in paracoccidioidomycosis patients without oral lesions.

BACKGROUND: Paracoccidioidomycosis (PCM) is a neglected fungal infection with a high impact on the quality of life of the affected patients. The disease presents primary pulmonary involvement and systemic dissemination may occur. About 50% of the cases show oral involvement, and the factors that lead to this manifestation are not clear. OBJECTIVES: The aim of this study was to evaluate the DNA methylation profile in PCM patients with oral lesions. MATERIAL AND METHODS: Genomic DNA was extracted from whole blood of eighteen PCM patients, being ten with oral lesions and eight with no oral lesion. Analysis of methylation profile was performed using the technique of methylation-sensitive arbitrarily primed PCR (MS-AP-PCR). The sequences of recombinant plasmids obtained were evaluated according to parameters that define a CpG island, as well as their relative position in the known human genome genes and/or CpG islands. RESULTS: After DNA amplification, three different expressed bands were observed between the two groups, being found in the samples of patients with no oral manifestations. The cloned fragment in the plasmid showed similarity with a DNA sequence present in chromosome 20, next to the YTHDF1 gene. Other bands showed homology with intronic region in the genes RBPMS2 and DPH6 and no CpG island was identified. CONCLUSIONS: DNA methylation was found in PCM patients with no oral lesion affecting the YTHDF1 gene. Further studies are necessary to elucidate to role of YTHDF1 gene in the oral PCM manifestations.

Giant Peripheral Ossifying Fibroma Treated With Piezosurgery and Platelet-Rich Fibrin: A Rare Case Report.

INTRODUCTION: The peripheral ossifying fibroma (POF) is a benign reactive lesion that exclusively arises from gingiva. The lesion may gain considerably large sizes and present peculiar clinical and radiographic features that would then allow it to be called a giant POF; in that case, its otherwise simple surgical extraction could create a challenge. Thus, we elect here, for the very first time, a plausible alternative for treating giant POF: piezosurgery followed by placement of platelet-rich fibrin (PRF). CASE PRESENTATION: A 31-year-old black male presented a large asymptomatic nodule on the lower gingiva; the lesion had caused vestibular displacement of teeth and had been present for 18 years. Following the diagnostic hypothesis of a giant POF, an excisional biopsy was performed under local anesthesia using piezosurgery (microvibration of 36,000 times/sec was used in a bone cortical working mode), which confirmed the diagnosis. The surgical procedure was facilitated with the use of piezosurgery followed by placement of PRF, being the trans- and postoperative periods occurred with no complications. One year after the treatment, the patient shows no signs of disease recurrence and remains under follow-up. CONCLUSIONS: Giant POF is a rare gingival reactive lesion that can reach large dimensions, causing teeth displacement, functional, and esthetic impairments. The lesion can be successfully managed with piezosurgery and PRF, as illustrated herein, avoiding extensive bone loss and damage to the surrounding soft tissues.

Decreased expression of folate transport proteins in oral cancer.

OBJECTIVES: The purpose of this study was to assess the expression of the 3 major folate transporters-folate receptors (FRs), reduced folate carrier (RFC), and proton-coupled folate transporter (PCFT)-in oral squamous cell carcinoma (OSCC). We hypothesized that patterns of expression of folate transporters would be different in OSCC compared with normal oral epithelium. STUDY DESIGN: We used immunohistochemistry to examine the expression of FR, RFC, and PCFT in 15 primary specimens collected from patients with OSCC, 2 human cadaveric samples of OSCC, and 12 normal human cadaveric oral tissues from a medical gross anatomy laboratory. Possible correlations between the expression of each folate transporter and patients' clinical data were determined. RESULTS: All 3 folate transporters were highly expressed in normal oral epithelium. In contrast, OSCC samples generally demonstrated low expression of FR, RFC, and PCFT, with wide distribution in the invading cancer cells. There were no differences in folate transporter expression between OSCC samples collected from patients and from human cadavers. The lowest expression of FR and PCFT characterized less-differentiated tumors, and the lowest expression of RFC correlated with higher lymph node involvement. CONCLUSIONS: Human oral cancer samples expressed decreased amounts of all 3 major folate transport proteins compared with controls from normal cadaveric oral tissues.

Piezoelectric Surgery in the Inferior Alveolar Nerve Lateralization With Simultaneous Implant Placement: A Case Report.

The aim of this case report was to describe the inferior alveolar nerve (IAN) lateralization technique using the piezoelectric device for the posterior rehabilitation of an atrophic mandible with implants. The patient presented the absence of elements 35 and 36 associated with a vertical defect impairing the adequate dental implant placement without IAN damage. A full-thickness mucoperiosteal flap was raised, and a bone window was made with a piezoelectric device centralized on the IAN canal position. After dissection, the IAN was moved buccally with a sterile elastic strip. Morse cone 4.0 × 1.5-mm implants were inserted while the IAN remained retracted. At the 4-month follow-up, the screw-retained prosthesis was installed guaranteeing the recovering masticatory function. In conclusion, the case report showed that the IAN lateralization performed with an adequate surgical technique can be successfully indicated for longer implant placement in edentulous atrophic posterior mandible with no permanent neural damage.

A preliminary comparison between the effects of red and infrared laser irradiation on viability and proliferation of SHED.

The aim of this preliminary study was to compare the effects of different energy densities from red and infrared low-level laser (LLL) on viability and proliferation of stem cells from human exfoliated deciduous teeth (SHED). SHED were irradiated with red laser (R) or infrared laser (IR) set with the following dosimetry: 1.2 J/cm2 (0.05 J), 2.5 J/cm2 (0.1 J), 5.0 J/cm2 (0.2 J), and 7.5 J/cm2 (0.3 J). Positive (C+) and negative (C-) control groups comprised non-irradiated cells. Data were analyzed by two-way ANOVA followed by Tukey's test (P < 0.05). At 24- and 48-h period, group R5.0 showed significantly higher cell viability rates than R1.2 and R2.5. At 48 h, R2.5 also revealed lower proliferation than R5.0. Comparing to the C+ group, R2.5 exhibited lower viability at 72 h, and proliferation at 24 and 48 h. Groups R1.2, IR1.2, and IR5.0 were less viable at 24 h, while R1.2, IR2.5, and IR5.0 revealed lower proliferative capacity at 48 h. Overall, our results showed that LLL can favor viability and proliferation of SHED, especially when cells receive red laser irradiation at 5.0 J/cm2. Therefore, according to this preliminary investigation, 5 J/cm2 applied by red LLL induced high rates of cell viability and proliferation, while the same irradiation dose using infrared laser led to negative effects. LLL irradiation with 1.2 and 2.5 J/cm2 was deleterious to metabolic activity and proliferation of SHED regardless of the type of laser. Further studies are necessary to gain in-depth knowledge about the effects of different wavelengths of LLL on SHED viability and proliferation.

Oral Manifestation of Lymphomatoid Granulomatosis.

Lymphomatoid granulomatosis (LYG) is a rare B-cell lymphoproliferative disorder driven by Esptein-Barr virus (EBV) that most commonly affects the lungs, although extra pulmonary sites like the central nervous system, skin, liver and kidney can also be involved. It is microscopically characterized by an angiocentric and angiodestructive growth pattern, predominantly composed by small T-cells, although a smaller population of atypical large B-cells is considered the true neoplastic component. Oral cavity involvement of LYG has rarely been described and the diagnosis of this neoplasm is very difficult. The aim of this report is to present a rare case of LYG affecting an 86-year-old female patient that was diagnosed due to an extensive, ulcerated and painful oral lesion affecting the hard palate. Detailed microscopic evaluation together with a large immunohistochemical study were necessary to achieve the correct diagnosis of LYG.

DC-SIGN and VDR polymorphisms are associated with chronic form of paracoccidioidomycosis with oral manifestations.

Paracoccidioidomycosis (PCM) is a granulomatous disease caused by fungi of the species complex of the Paracoccidioides genus. One of the main clinical manifestations of PCM is the presence of oral lesions with the presence of epithelioid granulomas. In this work, we aimed to evaluate the frequency of SNPs in the TNF-α, JAK1, VDR, DC-SIGN and FcγRIIa genes in patients with chronic PCM and verify possible association of these SNPs with the organisation pattern of the granulomas in the oral lesions. A total of 66 samples of DNA were obtained from oral lesions biopsies and 106 DNA samples were obtained from healthy individuals. The individuals were genotyped for SNPs in DC-SIGN (rs4804803), FcγRIIa (rs1801274), JAK1 (rs11208534), TNF-α (rs1800629) and VDR (rs7975232) by real-time PCR and allele discrimination method. Granulomas were classified as loose or dense according to the histological pattern. In the VDR (rs7975232), the CC genotype (P < 0.001, OR = 5.94, 95% CI = 2.07-17.05), and the C allele (P = 0.027, OR = 2.71, 95% CI = 1.07-6.86), as well as the GG genotype in DC-SIGN (rs4804803) (P = 0.032, OR: 3.76, 95%, I = 1.06-13.38) are associated with an increased risk of oral PCM. Our data indicate that VDR and DC-SIGN genetics variations are related to the susceptibility of oral PCM in the group of patients analysed.

Bell's palsy treated with photobiomodulation in an adolescent: Rare case report and review of the published literature.

BACKGROUND: Bell's palsy represents a peripheral unilateral facial nerve paralysis, being an acute, idiopathic disorder, which can affect children and adolescents. Some therapeutic approaches have been proposed including facial exercises, biofeedback, photobiomodulation, electrotherapy, massage, and thermotherapy. The present report documents a rare case of Bell's palsy in an adolescent successfully treated with a new protocol of photobiomodulation, consisting of a short-term treatment. CASE REPORT: A 13-year-old girl presented absence of facial movement on the right side when smiling, inability to close the right eye and to raise the right eyebrow, intense painful symptoms on the right side of the face, difficult in chewing and talking, and sialorrhea. She was diagnosed with an idiopathic facial paralysis or Bell's palsy associated with right masseter myalgia, and treated with three sessions of photobiomodulation using infrared laser, 100 mW output power, 100 J/cm2 of energy density, 28 seconds per point, applied at the origin and insertion of the right superficial masseter muscle. The patient presented complete regression of paralysis, improvement of speech and chewing, and absence of muscular pain. CONCLUSION: Photobiomodulation was effective to treat Bell's palsy in a pediatric patient, being a true noninvasive approach and with no side effects, although there is still no established definitive protocol.