Modulation of gene expression in skin wound healing by photobiomodulation therapy: A systematic review in vivo studies.

BACKGROUND: Wound healing is a multistep process involving coordinated responses of a variety of cell types, cytokines, growth factors, and extracellular matrix (ECM) components leading to the physiological restoration of tissue integrity. Photobiomodulation therapy (PBMT) has been highlighted as an approach to improve the healing process, nonetheless at the molecular level, the effects of PBMT are not entirely understood. AIM: To systematically review publications that investigated gene expression after PBMT during in vivo skin repair. METHODS: An electronic search was undertaken in Medline Ovid (Wolters Kluwer), PubMed (National Library of Medicine), Web of Science (Thomson Reuters), Scopus (Elsevier), Embase, and LILACS databases. The search strategy was conducted from the terms: low-level light therapy, gene expression, and wound healing and their synonyms. The databases were consulted in December 2023 and no publication year limit was used. RESULTS: Eleven studies were included in this review and the expression of 186 genes was evaluated. PBMT modified the expression of several targets genes studied, such as down-regulation of genes related to extracellular matrix proteases (MMP2 and MMP9) and pro-inflammatory cytokines (IL10 and IL6) and up-regulation of DNMT3A and BFGF. CONCLUSION: This review demonstrates that PBMT is capable of regulating gene expression during wound healing. Most evidence showed a positive impact of PBMT in regulating genes linked to inflammatory cytokines improving skin wound healing. Yet, the effects of PBMT in genes involved in other mechanisms still need to be better understood.

Oral and maxillofacial tuberculosis: A systematic review.

OBJECTIVES: This study aimed to analyze the demographic, clinical, histopathological, diagnosis, treatment, and follow-up data on the occurrence of oral and maxillofacial tuberculosis (OMTB). METHODS: Electronic searches without publication date restrictions were undertaken in four databases. Case reports and case series describing the occurrence of OMTB were included. Critical evaluation of studies was done using the Joanna Briggs Institute - University of Adelaide tool for case reports or case series. RESULTS: A total of 217 studies were included in the qualitative synthesis, for a total of 301 cases of OMTB. Of these patients, 192 (63.7%) were male, with an average age of 39.6 ± 19.8 (15 months to 81 years). The tongue (n = 80/26.6%) represented the most common affected site, followed by the mandible (n = 43/14.3%). The clinical presentation consisted mainly of a painful ulcerated lesion (n = 156/56.5%). Histopathological analysis showed a granulomatous inflammation in most cases (n = 156/63.1%). The main diagnostic methods used were sputum test (n = 53/26.8%), culture (n = 49/24.7%) and purified protein derivative (PPD), or Mantoux test (n = 49/24.7%). Antituberculosis therapy was used in 244 cases (100.0%) and 5.2% of patients died. CONCLUSIONS: This systematic review provided clinical, demographic data and information about diagnostic methods of OMTB lesions and served as an important guide to assist health professionals in the early diagnosis of these lesions.

Synchronous odontogenic tumors: A systematic review.

This systematic review aimed to incorporate published information about synchronous odontogenic tumors (SOTs) with an analysis of the demographic and clinical characteristics from the cases published in the literature. Case reports and case series of SOT were searched in PubMed, Web of Science, Scopus, and EMBASE. A descriptive statistical analysis was performed. Twenty-eight studies comprising 30 cases of SOTs were included. Considering all cases published, SOTs mostly occurred simultaneously in the maxilla and mandible (n = 19/63.3%). Lesions were bifocal in 13 (43.3% of all the 30 cases) and multifocal in 17 cases (56.7% of all the 30 cases). All SOTs available in the literature presented the same type of lesion, and two of them also involved another different SOT (n = 2/6.7% of all the 30 cases). Out of all published cases, the most frequent SOTs in the literature were odontomas (n = 10/33.3% of all the 30 cases), squamous odontogenic tumors (OTs) (n = 8/26.7% of all the 30 cases), calcifying epithelial OTs (n = 8/26.7% of all the 30 cases), and adenomatoid OTs (n = 2/6.7% of all the 30 cases). Considering all SOTs cases included, the overall recurrence was 13.3%. Inside a subgroup of the lesion, synchronous calcifying epithelial OT presented the highest (25%). Five cases (16.7% of all the 30 cases) had a previously associated syndrome, with two cases of Schimmelpenning syndrome being reported. Among published SOTs, odontomas were the most common. All SOTs available in the scientific literature showed the same type of OT and mainly affected both jaws simultaneously. Only a few of these cases were associated with a syndrome.

Foreign body reactions related to orofacial esthetic fillers: A systematic review.

The aim of this study was to systematically review the clinicopathological data regarding foreign body reactions (FBR) related to esthetic procedures in the orofacial region. Electronic searches were performed in six databases and in gray literature using PEO acronym for the review question. Case series and case reports describing FBR related to esthetic procedures in the orofacial region were included. The JBI Critical Appraisal Checklist-University of Adelaide tool was used for measuring the risk of bias. Eighty-six studies reporting 139 cases of FBR were identified. The mean age at diagnosis was 54.12 years (14-85 years), with most of the cases reported in America, North America (n = 42/30.70%) and Latin America (n = 33/23.60%), mainly occurring in women (n = 131/94.40%). Asymptomatic (n = 60/43.40%) nodules (n = 71/50.60%) were the main clinical characteristics. The lower lip represented the most affected anatomical location (n = 28/22.20%), followed by the upper lip (n = 27/21.60%). Surgical removal was the treatment of choice (n = 53/35.70%). Twelve different dermal fillers were reported in the study, and the microscopic characteristics of the cases varied according to the material used. The results based on case series and case reports showed that nodule and swelling were the main clinical characteristics of FBR related to orofacial esthetic fillers. The histological characteristics depended on the type of the filler material used.

Impact of photobiomodulation in a patient-derived xenograft model of oral squamous cell carcinoma.

BACKGROUND: Photobiomodulation therapy (PBMT) is an effective method for the prevention of oral mucositis. However, the effects of PBMT on oral squamous cell carcinoma (OSCC) have not yet been fully elucidated. This study aimed to evaluate the impact of PBMT in an OSCC-patient-derived xenograft (OSCC-PDX) model. METHODS: BALB/c nude mice with OSCC-PDX models were divided into Control, without PBMT (n = 8); Immediate irradiation, PBMT since one week after tumor implantation (n = 6); and Late irradiation, PBMT after tumors reached 200 mm3 (n = 6). OSCC-PDX were daily irradiated (660 nm; 100 mW; 6 J/cm2 ; 0,2 J/point) for 12 weeks. The tumors were collected and submitted to volumetric, histological, immunohistochemistry, and cell cycle analysis. RESULTS: No significant differences in the volumetric measurements (p = 0.89) and in the histopathological grade (p > 0.05) were detected between the groups. The immunohistochemical analysis of Ki-67 (p = 0.9661); H3K9ac (p = 0.3794); and BMI1 (p = 0.5182), and the evaluation of the cell cycle phases (p > 0.05) by flow cytometry also did not demonstrate significant differences between the irradiated and non-irradiated groups. CONCLUSION: In this study, PBMT did not impact the behavior of OSCC-PDX models. This is an important preclinical outcome regarding safety concerns of the use of PBMT in cancer patients.

Ewing's sarcoma of the head and neck: A systematic review.

OBJECTIVE: The aim of the present study was to conduct a systematic review of head and neck Ewing sarcoma (ES) concerning patients' demographic and clinical features, histopathological findings, treatment, follow-up, and survival rate. MATERIALS AND METHODS: An electronic search was undertaken in four databases. Articles describing case reports or case series were included. Outcomes were evaluated by the Kaplan-Meier method along with Cox regression. RESULTS: The search yielded 186 studies describing 227 ES cases. The mean age was 22.7 years, and males were slightly more affected. Interestingly, more than half the cases were diagnosed up to 20 years. The respiratory tract was the most reported site, followed by the jawbones. Clinically, symptomatic swelling or nodules were described, with a mean duration of 4 months. Management involved multimodal treatment regimens. Local recurrence, lymph node and distant metastasis were observed in 10.7%, 12.6%, and 20.3% of cases, respectively. Statistical analysis revealed that older patients with distant metastasis had a lower overall survival rate (p < 0.05). CONCLUSION: This study provides an overall view of head and neck ES that can assist oral and maxillofacial pathologists with the diagnosis and extend the knowledge of surgeons and oncologists about this condition.

Impact of photobiomodulation for prevention of oral mucositis on the quality of life of patients with head and neck cancer: a systematic review.

The aim of this study was to perform a systematic review to evaluate the impact of photobiomodulation therapy (PBMT) for the prevention of oral mucositis (OM) on the quality of life (QoL) of patients with head and neck cancer (HNC) undergoing radiation therapy. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The search strategy was performed in five electronic databases (Cochrane, Embase, PubMed, Scopus, and Web of Science). The included studies assessed the QoL of patients undergoing radiation therapy (RT) for HNC and undergoing PBMT for the management of OM. Seven articles met the eligibility criteria. Data extraction was performed in the selected studies including the PBMT parameters (active medium, application procedure, wavelength, fluence, power, irradiance, irradiation time, spot size, energy per point, schedule of irradiation, and total energy). The included studies were qualitatively analyzed, and descriptive analyses were performed. Also, summary results were evaluated for group comparison analysis. All included studies confirmed a decrease in the QoL of the patients that developed OM throughout the RT progress when compared to baseline. Of the informed cases, most of the patients who received PBMT showed grades 1 and 2 OM, while the control group showed more individuals with severe forms of OM (grades 3 and 4). In this sense, patients submitted to PBMT reported better QoL at the end of the treatment compared with the control group. PBMT used for the management of OM preserves the QoL of patients with head and neck cancer.

Association between perceived self-confidence and abilities to distinguish oral mucosal lesions amongst dental students.

INTRODUCTION: Dentists usually refer to difficulties in performing the diagnosis of oral mucosal lesions. This may be attributed to limited access to theoretical lectures and practical training on this subject along the graduation course. The primary aim of this cross-sectional study was to verify if there is an association between the perception of time dedicated to lectures/training and oral diagnosis abilities in oral medicine. The secondary aim was to evaluate the association between self--confidence to perform oral mucosal lesions diagnosis and performance in a diagnostic abilities test. MATERIALS AND METHODS: The sample comprised 36 final-year dental students of a South-Brazilian dental school. The participants answered a questionnaire on their perception of time dedicated to lectures on oral medicine along the course (sufficient or insufficient) and their self-confidence to diagnose oral mucosal lesions or oral cancer (yes or not). The students were also submitted to a diagnostic abilities test based on 30 clinical photos of oral lesions, which should be classified as benign, potentially malignant or malignant. Moreover, the participants had to inform their clinical impression for each case. Finally, the participants informed their decision making for the case (refer the patient to a specialist or not). RESULTS: Students with higher self-confidence showed a higher percentage of correct answers on classification of the nature of lesions (81.1% vs. 68.5%, p = .03, teste t de Student) and on their clinical impression (66.3% vs. 41.7%, p < .01, Student's t-test). The perception of time dedicated to theoretical lectures on oral medicine as sufficient did not influence the students' diagnostic abilities (p > .05, Student's t-test) CONCLUSION: It may be concluded that self-confidence to diagnose oral lesions is associated with dental students' diagnostic abilities.

Cephaeline is an inductor of histone H3 acetylation and inhibitor of mucoepidermoid carcinoma cancer stem cells.

AIM: To evaluate the potential use of Cephaeline as a therapeutic strategy to manage mucoepidermoid carcinomas (MEC) of the salivary glands. MATERIAL AND METHODS: UM-HMC-1, UM-HMC-2, and UM-HMC-3A MEC cell lines were used to establish the effects of Cephaeline over tumor viability determined by MTT assay. In vitro wound healing scratch assays were performed to address cellular migration while immunofluorescence staining for histone H3 lysine 9 (H3k9ac) was used to identify the acetylation status of tumor cells upon Cephaeline administration. The presence of cancer stem cells was evaluated by the identification of ALDH enzymatic activity by flow cytometry and through functional assays using in vitro tumorsphere formation. RESULTS: A single administration of Cephaeline resulted in reduced viability of MEC cells along with the halt on tumor growth and cellular migration potential. Administration of Cephaeline resulted in chromatin histone acetylation as judged by the increased levels of H3K9ac and disruption of tumorspheres formation. Interestingly, ALDH levels were increased in UM-HMC-1 and UM-HMC-3A cell lines, while UM-HMC-2 showed a reduced enzymatic activity. CONCLUSION: Cephaeline has shown anti-cancer properties in all MEC cell lines tested by regulating tumor cells' viability, migration, proliferation, and disrupting the ability of cancer cells to generate tumorspheres.

Risk factors associated with the development of oral mucositis in pediatric oncology patients: Systematic review and meta-analysis.

OBJECTIVES: Oral mucositis (OM) is an acute toxicity related to cancer treatment. This systematic review aimed to identify potential risk factors associated with the development of OM in pediatric cancer patients. METHODS: A search was performed in four electronic databases to identify studies that analyzed risk factors for OM in pediatric cancer patients. RESULTS: Nineteen articles were included. The incidence of OM ranged from 20% to 80.4%. Chemotherapeutic agents were potential risk factors for OM in eight (42%) studies. Hematological, hepatic, and renal parameters were also considered in eight (42%) studies, while specific individual factors were reported in five (26.3%) studies. Baseline disease, oral microbiota, genetic profile, and biomarkers were reported in four (21.5%) studies each. Meta-analysis showed that groups submitted to high-risk chemotherapy for OM had a 2.79-fold increased risk of OM. CONCLUSIONS: Identifying risk factors for OM is essential in order to allow individualized and early prevention treatment.

Malignant peripheral nerve sheath tumour of the oral and maxillofacial region-A systematic review.

To integrate the available data published on malignant peripheral nerve sheath tumours (MPNST) of the oral and maxillofacial region. Searches in Embase, PubMed, Web of Science and Scopus were conducted for the identification of case reports/case series in English language. The risk of bias was assessed using the Joanna Briggs Institute tool. Outcomes were evaluated by Cox regression and Kaplan-Meier methods. A total of 306 articles were retrieved, 50 of which reporting 57 MPNST were included. The lesion showed a predilection for the mandible (n = 18/31.57%) of middle-aged adults (~40.5 years) with a male/female ratio of 1.1:1. The individuals were mostly symptomatic with a mean evolution time of 9.6 months. Surgical removal plus adjuvant therapy (especially radiotherapy) was the main approach (51.86%). Recurrence was reported in 39.62% of cases. Nodal and distant metastases were identified in 28.26% and 26.66% of cases, respectively. The 2-year cumulative survival rate was 55%. Independent predictors of poor survival were the presence of neurofibromatosis type 1 (p = 0.04) and distant metastases (p = 0.004). The diagnosis of MPNST is challenging due to the variety of its clinical and histopathological presentations. Local aggressiveness and the potential for metastases are common outcomes of this neoplasm.

Effects of different protocols of defocused high-power laser on the viability and migration of myoblasts-a comparative in vitro study.

The aim of the present study was to analyze for the first time the effect of photobiomodulation therapy (PBMT) using defocused high-power laser (DHPL) in myoblast cell line C2C12 viability and migration and compare them with low-power laser therapy. Cells were divided into 9 groups: Sham irradiation 10% fetal bovine serum (FBS); Sham irradiation 5%FBS; low-power laser 0.1 W; DHPL 810 1 W; DHPL 810 2 W; DHPL 980 1 W; DHPL 980 2 W; DHPL dual 1 W; DHPL dual 2 W. To simulate stress conditions, all groups exposed to irradiation were maintained in DMEM 5% FBS. The impact of therapies on cell viability was assessed through sulforhodamine B assay and on cells migration through scratch assays and time-lapse. Myoblast viability was not modified by PBMT protocols. All PBMT protocols were able to accelerate the scratch closure after 6 and 18 h of the first irradiation (p < 0.001). Also, an increase in migration speed, with a more pronounced effect of DHPL laser using dual-wavelength protocol with 2 W was observed (p < 0.001). In conclusion, the diverse PBMT protocols used in this study accelerated the C2C12 myoblasts migration, with 2-W dual-wavelength outstanding as the most effective protocol tested. Benefits from treating muscle injuries with PBMT appear to be related to its capacity to induce cell migration without notable impact on cell viability.

Potentially carcinogenic effects of hydrogen peroxide for tooth bleaching on the oral mucosa: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: Little is known about the extent to which hydrogen peroxide as used for tooth bleaching could be carcinogenic to the oral mucosa. PURPOSE: The purpose of this systematic review and meta-analysis was to evaluate whether hydrogen peroxide as used for tooth bleaching has carcinogenic effects on the oral mucosa. MATERIAL AND METHODS: PubMed, Web of Science, Scopus, and Embase electronic databases were searched. Studies evaluating different outcomes potentially related to the carcinogenic effects of hydrogen peroxide for tooth bleaching on the oral mucosa were included. Risk of bias was assessed by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE), Risk Of Bias in Non-randomized Studies of Interventions (ROBINS-I), or Risk of Bias 2 (RoB 2) tools. The strength of the evidence was assessed by using the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) protocol. The quantitative analysis was performed with means, standard deviations, and 95% confidence intervals (CIs). Heterogeneity was analyzed by using I-squared statistics. RESULTS: Thirteen articles comprising 5 animal and 8 clinical studies met the inclusion criteria. Three of the 5 animal studies associated the bleaching agents with a carcinogen and demonstrated an enhancement of the carcinogenic effect, but probably with the bleaching agent acting only as a promoter. Five clinical studies concluded that the bleaching agents did not cause mutagenic stress on the oral mucosa by using the micronucleus test. The meta-analysis demonstrated that the frequency of micronuclei did not differ significantly between baseline and 30 days after bleaching (mean difference: 0.48; 95% CI, -1.49, 2.46; P=.63). CONCLUSIONS: This systematic review indicated that hydrogen peroxide does not appear to have carcinogenic effects on the oral mucosa.

Clinicopathological analysis of oral and maxillofacial acinic cell carcinoma: A systematic review.

BACKGROUND: The aim of the present systematic review was to analyze the available data regarding acinic cell carcinoma of the oral and maxillofacial region. METHODS: A search strategy was performed using PubMed, Web of Science, Scopus, and Embase electronic databases. RESULTS: Available data revealed a slight female preference (54.73%) and a mean age at diagnosis of 47.51 ± 19.85 years. The parotid glands (67.72%) were most frequently affected, and most cases were asymptomatic (69.54%). A microcystic histopathological pattern was reported in 21.56% of the cases, and the Periodic acid-Schiff was the staining method most frequently used, after the hematoxylin and eosin staining, in the tumors analyzed. The lesions were mainly treated by surgical removal (72.32%). Recurrence was reported in 81 cases (27.83%) and metastasis in 100 (42.91%). Statistical data analysis revealed that tumors located in major salivary glands and exhibiting high-grade histology were associated with local recurrence (P = .01). In addition, the patients older than 57 years, lesions with bone involvement, the high-grade tumors and the cases with a history of recurrence and metastasis were associated with a lower overall survival (P < .05). CONCLUSION: By assembling all eligible cases in the literature, the present systematic review determined the most common clinicopathological profile of acinic cell carcinoma and the most relevant prognostic factors in a distinctly representative sample. The survey demonstrated the importance of considering the histopathological grading in order to better define the treatment for each case.

Mantle cell lymphoma, malt lymphoma, small lymphocytic lymphoma, and follicular lymphoma of the oral cavity: An update.

BACKGROUND: Although uncommon, mature small B-cell lymphomas may arise in the oral/maxillofacial area and oral pathologists must be aware of the key characteristics of these neoplasms to perform an accurate diagnosis. In this manuscript, we attempted to integrate the currently available data on the clinicopathological features of follicular lymphoma (FL), mantle cell lymphoma (MCL), extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT-L), and chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL) affecting these anatomical regions. METHODS: An updated descriptive literature review was carried out and a detailed electronic search was done in multiple databases to gather all cases affecting the oral/maxillofacial region and palatine tonsils. RESULTS: We observed that MALT-L was the most frequently reported subtype, followed by FL, MCL, and CLL/SLL. The palate was affected in a high proportion of cases and the most usual clinical presentation was an asymptomatic swelling. MALT-L and CLL/SLL neoplastic cells were strongly associated with small salivary glands. FL showed no gender preference, while MCL and CLL/SLL were more prevalent in males and MALT-L in females. Overall, cases were more common in elderly individuals. Patients' treatment and outcome varied, with MCL being the most aggressive neoplasm with a dismal prognosis in comparison to FL and MALT-L. CONCLUSION: Despite the poor documentation in many of the cases available, especially regarding the microscopic and molecular features of tumors, this review demonstrated that the oral mature small B-cell lymphomas investigated share similar clinical presentation, but carry different prognostic significance, demanding an accurate diagnosis.

Activation of BDNF/TrkB/Akt pathway is associated with aggressiveness and unfavorable survival in oral squamous cell carcinoma.

OBJECTIVES: To evaluate the expression of brain-derived neurotrophic factor (BDNF), its tyrosine kinase receptor B (TrkB), and two downstream targets of this pathway, Akt and ribosomal protein S6 (RPS6), in normal oral mucosa (NOM), oral leukoplakia (OL), and oral squamous cell carcinoma (OSCC) and correlate this expression with OSCC patients' outcomes, cell senescence, and "stemness" profile. MATERIALS AND METHODS: Ten cases of NOM, 32 OL, and 72 primary OSCC were included. Immunohistochemical analysis for BDNF, TrkB, p-TrkB, p-Akt, and p-RPS6 was performed. Cell senescence and stemness profile of OSCC were evaluated through p16 and BMI-1 immunohistochemical expression, respectively. The slides were scanned into high-resolution images and quantified through digital analysis. RESULTS: Oral squamous cell carcinoma presented increased expression of BDNF/TrkB/Akt pathway compared to NOM and OL. OSCC diagnosed in advanced clinical stages presented an upregulation of BDNF and p-TrkB. BDNF and p-Akt were identified as predictors of poor disease-specific survival. The increase in stemness profile was correlated with a decrease in p-TrkB and p-Akt expression. CONCLUSIONS: BDNF/TrkB/Akt pathway is significantly increased in malignant cells from OSCC. Moreover, BDNF and Akt represent biomarkers capable to predict a poor prognosis of OSCC patients.

Mucoadhesive formulation containing Curcuma longa L. reduces oral mucositis induced by 5-fluorouracil in hamsters.

We explored the effects of a mucoadhesive formulation containing curcuminoid (MFC) from Curcuma longa L. extract on oral mucositis (OM) induced by 5-fluorouracil (5-FU) in hamsters. Seventy-two golden Syrian hamsters were randomly allocated into four groups: control, placebo, chamomilla, and MFC. Animals received an intraperitoneal injection of 5-FU at Days 0 and 2. On Days 3 and 4, the buccal mucosa was scratched. Therapy was initiated on Day 5. Animals received two applications of the substances per day according to the experimental group. Six animals were euthanized on Days 8, 10, and 14. Clinical analysis were performed using photography and histopathological sections of 3 µm were stained by hematoxylin-eosin for semiquantitative analysis of re-epithelization and inflammation. Immunohistochemistry was used for angiogenesis (CD31) and transforming growth factor beta 1 (TGF-ß1) analysis. On Day 5, all groups exhibited OM. Clinical and histopathological findings revealed that on Day 8, both MFC and chamomilla groups exhibited better wound healing. In addition, the MFC group demonstrated lower angiogenesis and TGF-ß1 levels on Day 8 compared with placebo and control groups. Collectively, these findings suggest that MFC has a therapeutic effect on OM, accelerating wound healing through re-epithelization and anti-inflammatory action as modulation of angiogenesis and TGF-ß1 expression.

Photobiomodulation therapy modulates epigenetic events and NF-κB expression in oral epithelial wound healing.

The aim of this study was to evaluate the effect of photobiomodulation therapy (PBMT) on histone 3 acetylation (acH3) and NF-κB expression during oral ulcer healing. A total of 48 male Wistar rats were divided into control group (CG) and PBMT group (n = 24 each). Traumatic ulcers were created in the dorsum of the rats' tongue with a punch tool. Irradiation with InGaAlP laser, 660 nm, 40 mW, 0.04 cm2 spot size, 4 J/cm2, 4 s, and 0.16 J per spot was performed once a day in close contact for 10 consecutive days. CG received only daily handling. Rats were euthanized on days 3, 5, and 10 (n = 8) and were monitored daily to assess wound status. Immunohistochemical analysis for acH3 and NF-κB detection was performed. One thousand epithelial cells were counted, and mean acH3- and NF-κB-positive cells were calculated and compared between the groups. PBMT accelerated the repair of oral ulcers. On day 3, PBMT showed significantly higher means for acH3- and NF-κB-positive cells than CG. On day 5, no difference was observed between the groups concerning both markers. On day 10, PBMT presented lower acH3 and NF-κB means than the control group. We concluded that PBMT stimulates keratinocyte migration in the early stage of oral wound healing and keratinocyte differentiation at the final stage by modulating histone acetylation and NF-κB expression.

Uncovering the role of brain-derived neurotrophic factor/tyrosine kinase receptor B signaling in head and neck malignancies.

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors that was first known as responsible for sustain the growth, function, and plasticity of neural cells. BDNF exerts its effects by binding to the tyrosine kinase receptor B (TrkB). The BDNF/TrkB axis has been reported to be overexpressed in several neurogenic and non-neurogenic tumors. Its higher expression was associated with a poor prognosis to patients affected by different human malignancies, tumor growth, invasion, and metastasis; epithelial-mesenchymal transition and resistance to chemotherapy. BDNF/TrkB represent promising targets to the development of novel anticancer therapies. Some clinical trials are currently evaluating the efficacy of Trk protein-target drugs in different types of solid tumors. To date, few groups have evaluated the DNF/TrkB pathway in head and neck malignancies. The aims of this study were to review the literature concerning the role of BDNF/TrkB activation in head and neck squamous cell carcinoma and malignant salivary gland tumors and to discuss future perspectives of BDNF/TrkB-target therapy.

Reduced chromatin acetylation of malignant salivary gland tumors correlates with enhanced proliferation.

BACKGROUND: Epigenetic changes refer to any heritable modification in gene expression independent of alterations in the DNA sequence. Currently, it is well established that epigenetics represents a crucial player for tumor development. Nevertheless, the epigenetic mechanisms involved in the development and progression of salivary gland tumors (SGTs) remain poorly understood. METHODS: In this study, we analyzed the pattern of acetyl-histone H3 (lys9) expression in benign and malignant SGTs and further correlate our results with tumors' proliferative activity and clinical outcomes. We assembled tissue microarrays (TMAs) of 84 cases of SGTs and analyzed for acetyl-histone H3 (lys9) and Ki-67 using immunohistochemistry. The study comprised 42 benign and 42 malignant SGTs. RESULTS: All cases included in this study were positive to acetyl-H3 (lys9). We observed that malignant SGTs were hypoacetylated compared with benign (P = 0.04). Moreover, acetyl-H3 (lys9) expression was inversely correlated with Ki67 (**P = 0.02). CONCLUSION: This study provides the first insight regarding histone modifications in SGTs. Our results suggest that epigenetic mechanism, particularly hypoacetylation of histone H3 (lys9), might play a role in the behavior of salivary gland tumors. Also, our findings suggest that interfering with the acetylation pattern of tumor histones represents a potential novel therapeutic strategy for the treatment of SGTs.