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.

Window therapeutic of extraoral photobiomodulation for prevention of oral mucositis in HSCT patients: additional arm.

PURPOSE: This study aimed to evaluate the efficacy of 1W extraoral photobiomodulation (EOPBM) and to compare with our previous results of 2W EOPBM and intraoral photobiomodulation (IOPBM) protocols in the management of oral mucositis (OM) related to hematopoietic stem cell transplantation (HSCT). METHODS: A total of 30 patients underwent autologous or allogenic HSCT. Experimental protocol of 1W EOPBM was performed daily beginning in the first day of the conditioning regimen until 5 days after transplantation. The application areas included six points on the face and three points on the cervical area. Additional application of IOPBM was performed if patients had ulcered mucositis. Its severity was assessed daily according to WHO (World Health Organization) and NCI (National Cancer Institute) scales. Oral and oropharynx pains were scored daily by visual analogue scale (VAS). RESULTS: The 1W EOPBM protocol was well tolerated without any complaints. Of total, 13 patients were male and 17 were female and the mean age was 49.3 years old. Most patients (21 patients - 70%) received autologous HSCT, and 24 patients (80%) underwent myeloablative conditioning (MAC) regime and 6 patients (20%) reduced intensive conditioning regime. Nineteen patients (63.3%) developed OM according to WHO criteria, 3 patients grade I, 10 grade II and 6 grade III. NCI mucositis grades were similar to WHO grades. OM outcomes of 1W EOPBM were similar when compared to our previous groups and no significant differences were observed. No differences were found between pain and the protocols (1W EOPBM, IOPBM and 2W EOPBM). CONCLUSION: This 1W EOPBM protocol seemed to be as effective as IOPBM and 2W EOPBM in the prevention of OM in HSCT patients. In addition, we might assume that there is a window of application on EOPBM.

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.

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.

Does photobiomodulation therapy improve the postoperative outcomes of tonsillectomy? A systematic review and meta-analysis.

Introduction: Postoperative management of patients undergoing tonsillectomy is challenging. Photobiomodulation therapy (PBMT) has emerged as a new tool providing therapeutic benefits. However, the contribution of PBMT to the postoperative outcomes of tonsillectomy is still undefined. This systematic review and meta-analysis evaluated the published literature addressing the effects of PBMT on post-tonsillectomy. Methods: Searches in Scopus, PubMed/MEDLINE, Embase, Web of Science, Cochrane Library, and grey literature were carried out for the identification of randomised controlled trials reported up to August/2021. The risk of bias with the Cochrane Collaboration tool and meta-analysis was performed. Outcomes were assessed with the Kaplan-Meier method and the log-rank test. Results: A total of 1183 articles were retrieved, of which only two were included for qualitative and quantitative analysis. The wavelengths were 685 nm and 980 nm with energy density set at 4 J/cm2. The mandibular angle and the surgical wound were the sites of laser irradiation. Individuals who had not undergone PBMT after tonsillectomy were more likely to report pain and odynophagia in the first 24 hours after surgery than individuals who had undergone PBMT after tonsillectomy (P<0.001). Children who received PBMT after tonsillectomy were equally affected by pain and odynophagia in the first seven days after surgery compared to children who had not undergone PBMT after tonsillectomy (P>0.05). However, both studies found a significant association of PBMT with reduced analgesic consumption. Conclusion: Although PBMT seems promising for the management of individuals undergoing tonsillectomy, a limited number of studies are available in the literature.

Comparative study of royal jelly, propolis, and photobiomodulation therapies in 5-fluorouracil-related oral mucositis in rats.

PURPOSE: This study aimed to evaluate the effects and mechanisms of action of royal jelly (RJ) and propolis compared to photobiomodulation therapy (PBMT) in an animal model of 5-fluorouracil-related oral mucositis (OM). METHODS: Seventy-two male Wistar rats were randomly allocated to four groups (n = 18 each): control (no treatment), PBMT (intraoral laser, 6 J/cm2), RJ, and propolis. On days 0 and 2, the animals received an injection of 5-fluorouracil (5-FU). The buccal mucosa was scratched (days 3 and 4) and the treatments were initiated on day 5. Six animals of each group were euthanized on days 8, 10, and 14. Phytochemical analysis (thin-layer chromatography, TLC) and clinical, histopathological, and immunohistochemical analysis of pS6, pAKT, and NF-κB were performed, and oxidative stress markers were also investigated. RESULTS: TLC revealed the presence of large amounts of sucrose (Rf 0.34) in RJ and of flavonoids in propolis. Lower clinical OM scores were observed on day 8, and improved morphological data were observed on day 10 in the PBMT, RJ, and propolis groups (p < 0.05). On day 8, immunoexpression of pS6, pAKT, and NF-κB was increased compared to control. On day 14, reduced glutathione (GSH) antioxidant levels were increased in the propolis group compared to control (p < 0.05). CONCLUSIONS: Our results showed that RJ and propolis, as well as PBMT, are effective in the treatment of OM. Considering that some patients who develop OM do not have access to PBMT, the present study demonstrated that topical application of RJ and propolis may be an important alternative for the treatment of OM.

Impact of photobiomodulation therapy on the morphological aspects of submandibular gland submitted to excretory duct ligation and hypothyroidism: an animal study.

The aim of this study was to evaluate the impact of photobiomodulation therapy (PBMT) on histomorphological aspects of submandibular gland (SMG) submitted to salivary gland duct obstruction in hypothyroid rats. Fifty-six male Wistar rats (250 to 300 g) were divided into 4 groups (n = 14): euthyroid (EU), EU + PBMT, hypothyroid (HYPO), and HYPO + PBMT. Duct obstruction of the left submandibular gland (LSMG) was performed in all animals by a ligature procedure. For the induction of hypothyroidism, total thyroidectomy was performed. PBMT groups received irradiation with AlGaInP diode laser (808 nm, 0.04 W, 0.04cm2 spot size, 60 s, 2.4 J per point, 60 J/cm2, 1 W/cm2). Irradiation was performed immediately, 24 h, and 48 h after the obstruction of the salivary gland duct, in one point, extra oral and perpendicular to the gland. Animals were sacrificed after 24 h and 72 h after duct ligature. Our results indicated that salivary duct obstruction and hypothyroidism caused negative modifications on the salivary glands' histomorphology, especially acinar atrophy, after 24 h and 72 h. HYPO + PBMT showed a significant reduction of the inflammatory infiltrate, congested blood vessels, and acinar atrophy in the SMG submandibular salivary gland in 72 h compared to 24 h (p < 0.05). In conclusion, obstruction of the salivary gland excretory duct and hypothyroidism causes severe sialoadenitis with expressive atrophy of the glandular parenchyma. However, PBMT was able to modulate the inflammatory process and delaying acinar atrophy. This study provided insights to better understand the role of the PBMT on the altered salivary gland by duct ligation and associate hypothyroidism.

Intraoral versus extraoral photobiomodulation therapy in the prevention of oral mucositis in HSCT patients: a randomized, single-blind, controlled clinical trial.

To compare the efficacy of intraoral and extraoral photobiomodulation (PBM) protocols for the prevention of oral mucositis (OM) in hematopoietic stem cell transplantation (HSCT) patients. A total of 60 patients was randomized into intraoral PBM (IOPBM) and extraoral PBM (EOPBM) groups. Both PBM protocols were well tolerated and no side effects were observed. EOPBM session times were one fourth of IOPBM durations. Of 60 patients, 35 (58.3%) developed ulcerated OM between day +3 and day +12. No intergroup difference was observed in OM healing times (p = 0.424). The lateral border of the tongue was the most common site affected in both groups. However, the incidence of mucositis on buccal mucosa was significantly reduced in the EOPBM group (p = 0.021). Young patients (OR.5.35, 95%CI 0.94-30.4, p = 0.058) and those who had received myeloablative conditioning (OR.55.1, 95%CI 2.69-1129.3, p = 0.009) were more likely to develop ulcerated OM, whereas autologous HSCT recipients (OR 0.079, 95% CI 0.009-0.67, p = 0.021) had a lower probability of developing ulcerated OM independent of PBM protocol. EOPBM protocol was as effective as IOPBM in the management of OM in HSCT patients, with the advantage of shorter treatment sessions. Trial registration number: RBR-7nww56. Date of trial registration submission: 30th September 2019.

Effects of photobiomodulation in salivary glands of chronic kidney disease patients on hemodialysis.

This randomized placebo-controlled trial evaluates the impact of photobiomodulation (PBMT) on the salivary flow and biochemistry of patients with chronic kidney disease (CKD) on hemodialysis. Forty-four patients on hemodialysis self-responded two questionnaires for oral health and salivary gland function perception. The subjects were evaluated for function of salivary glands and randomly allocated to two groups: PBMT group (three irradiations at 808 nm, 100 mW, 142 J/cm2, and 4 J per site); and placebo group. Patients were submitted to non-stimulated and stimulated sialometry and after the treatment at baseline and 14 days. Salivary volume and biochemical of the saliva were analyzed. At baseline, most subjects had self-perception of poor oral health (52.6%) and salivary dysfunction (63.1%). Clinical exam revealed that 47.3% of subjects presented dry mucosa. PBMT promoted increase of the non-stimulated (p = 0.027) and stimulated saliva (p = 0.014) and decrease of urea levels in both non-stimulated (p = 0.0001) and stimulated saliva (p = 0.0001). No alteration was detected in total proteins and calcium analysis. Patients with kidney disease can present alteration in flow, concentrations, and composition of saliva, affecting oral health, but our findings suggest that PBMT is effective to improve hyposalivation and urea levels in saliva of patients with CKD.

Effectiveness of phytotherapeutics in the prevention and treatment of 5-fluorouracil-induced oral mucositis in animal models: A systematic review.

OBJECTIVES: This systematic review evaluated the effect of phytotherapeutics in the treatment and prevention of 5-fluorouracil (5-FU)-induced oral mucositis (OM) in animal models. DESIGN: A search was performed in PubMed/Medline, CENTRAL (The Cochrane Library), EMBASE, and Web of Science, including studies published up to January 2020. Only articles investigating the chemoinduction of OM by 5-FU in animal models were included. Eligibility was evaluated and data were extracted from the eligible studies following the predefined PICO questions. The Cochrane Collaboration Risk of Bias Assessment tool was used to evaluate the quality of the included studies. RESULT: A total of 503 articles were retrieved and 13 were included. The hamster was the animal model used in all included studies. The treatment method ranged from the topical application of ointment (n = 3), gel (n = 5) and extract (n = 3) to the oral ingestion of the phytotherapeutics (n = 3). Chamomilla recutita L. (n = 3) and Pistacia atlantica (n = 3) were the most used therapeutic agents. Although all studies were classified as high risk of bias, all of them reported promising results regarding the use of phytotherapeutics in the management of OM, including lower clinical and histopathological scores as well as healing, anti-inflammatory, antimicrobial, and antioxidant activities. CONCLUSION: Despite the high risk of bias of the studies, phytotherapy is a promising alternative for the treatment of 5-FU-induced OM, showing interesting results in terms of tissue healing and anti-inflammatory, antimicrobial and antioxidant activity.

The impact of photobiomodulation therapy on the biology and behavior of head and neck squamous cell carcinomas cell lines.

Photobiomodulation therapy (PBMT) is an emerging therapeutic modality designed to prevent and treat chemotherapy-driven oral mucositis (OM). However, the response of tumor cells to the effects of PBMT remains poorly understood. Our study explores the effects of PBMT in head and neck squamous cell carcinoma (HNSCC) based on cellular proliferation, migration, and survival of tumor cells and its population of cancer stem cells (CSC). We explored the behavior of two HNSCC cell lines (HN6 and HN13) under two distinct conditions, a physiological growing condition (10% FBS), and under stress growing condition (2% FBS) prior to irradiation using diode laser (InGaAlP; MM Optics, São Carlos, SP, Brazil). Diode laser (660 nm) was applied with a power of 100 mW delivering a total energy per point of 0.24 J. MTT and wound healing test (scratch assay) were performed to evaluate, respectively, proliferation and migration of tumor cells. Clonogenic and spheres formation assays were also performed to evaluate the survival and percentage of CSC upon irradiation. Overall, we observed that PBMT does not exacerbate the behavior of HNSCC. We could only observe a decrease in cellular proliferation of one cell line (HN6) when cultured under nutritional stress conditions (p < .05). There were no significant differences between the control and the PBMT groups regarding cell migration, survival and the percentage of CSC. Collectively, our results suggest that in vitro administration of PBMT to HNSCC does not modify the behavior of tumor cells.

Safety and Effectiveness of Copaiba Oleoresin (C. reticulata Ducke) on Inflammation and Tissue Repair of Oral Wounds in Rats.

In traditional communities of the Brazilian Amazon, the copaiba oleoresin (C. reticulata Ducke) is widely known for its therapeutic activity, especially its wound healing and anti-inflammatory actions. Our study aimed to evaluate these effects in oral lesions and the safety of the dosage proposed. A punch biopsy wound was induced on the ventral surface of the tongue of forty-five male Wistar rats under anesthesia. Animals were randomly allocated to one of three groups based on the treatment: control, corticoid and copaiba. A daily dose of each treatment and vehicle was administrated by oral gavage for three consecutive days. Sample collections took place on the third, seventh and 15th days post-wounding for clinical and histopathological analyses. Blood was collected on the third and seventh days for kidneys and liver function tests. Semi-quantitative analyses were performed based on scores of inflammation and reepithelization. Tissue collagen deposition was detected by PicroSirius red staining. Copaiba-treated wounds revealed a smaller wound area, decreased of acute inflammatory reaction and enhanced reepithelization. The levels of kidney and liver function tests did not reveal presence of damage post-treatments. Our findings suggest that copaiba oleoresin is a safe and effective alternative therapy for inflammation and tissue repair of oral wounds in this animal model.

Comparison of photobiomodulation using either an intraoral or an extraoral laser on oral mucositis induced by chemotherapy in rats.

PURPOSE: The aim of the present study was to compare the effect of intraoral (IO) and extraoral (EO) diode laser irradiation on oral mucositis (OM) induced by 5-fluorouracil (5-FU) in rats. METHODS: Animals (n = 78) were divided into the following groups: negative control (NC), positive control (PC), IO 6 J/cm2, EO with 6 J/cm2 (EO 6 J/cm2), and 12 J/cm2 (EO 12 J/cm2). OM was induced with an intraperitoneal injection of 5-FU and scarification of the buccal mucosa. Over the following 14 days, animals received photobiomodulation (PBM) daily. Clinical and histological evaluation was done by scores at days 8, 10, and 14. The redox state was evaluated by reactive species levels, antioxidant network, and immunohistochemistry analysis. RESULTS: Clinically, on day 8, PBM groups showed lower scores of OM with EO 6 J/cm2 presenting a significantly lower degree compared to PC (p < 0.05). On days 10 and 14, all PBM groups exhibited improvement of OM compared to PC (p < 0.01). On day 8, all PBM groups exhibited an accelerated healing process compared to PC (p < 0.01) and reduction of reactive species (p < 0.001). Also, all PBM groups demonstrated higher levels of antioxidant GPx compared to PC (p < 0.001). Analysis of nitrotyrosine revealed that on day 14, this protein damage marker was significantly reduced in the EO 6 J/cm2 group (p > 0.05). CONCLUSIONS: An EO diode laser protocol promoted positive effects in the clinical, histopathological, and redox state in OM induced by 5-FU in rats. Among the EO protocols, EO 6 J/cm2 showed the most encouraging results.

Effects of a mucoadhesive formulation containing Curcuma longa L. on oral wound healing

Introduction: The aim of this study was to investigate the effects of a topical mucoadhesive formulation with Curcuma longa L. extract (MFC) on oral wound healing. Methods: Seventy-two Wistar rats were randomly assigned to 3 groups: Control, Vehicle, and MFC. Traumatic ulcers were made on the dorsum of the tongue with a 3-mm diameter punch. Vehicle and MFC groups received application of the products twice a day, while animals in the control group were cared for in identical conditions but received no product application. Six rats in each group were euthanized at days 3, 5, 10, and 14. Percentage of repair was calculated based on wound area. HE-stained histological sections were obtained for semi-quantitative analysis of re-epithelization and inflammation. Results: Clinical findings revealed that at days 3 and 5, animals from the MFC group exhibited a significantly higher percentage of wound repair. At day 5, animals from this group also demonstrated a significant increase in the degree of re-epithelization and inflammation. Conclusions: MFC is capable of accelerating oral wound repair in an in vivo model by modulating the inflammatory process and stimulating epithelial proliferation. (AU)

Influence of photobiomodulation therapy on root development of rat molars with open apex and pulp necrosis.

This study aimed to evaluate the role of photobiomodulation (PBM) in apexification and apexogenesis of necrotic rat molars with an open apex. Rat molars were exposed to the oral environment for 3 weeks. Canals were rinsed with 2.5% NaOCl and 17% EDTA, filled with antibiotic paste and sealed. After 7 days, canals were rinsed and divided into six groups (n=6): mineral trioxide aggregate (MTA); blood clot (BC); human dental pulp stem cells (hDPSC); MTA+PBM; BC+PBM; and hDPSC+PBM. In hDPSC groups, a 1% agarose gel scaffold was used. Two groups were not exposed: healthy tooth+PBM (n = 6), healthy tooth (n = 3); and one was exposed throughout the experiment: necrotic tooth (n = 3). In PBM groups, irradiation was performed with aluminum gallium indium phosphide (InGaAlP) diode laser for 30 days within 24-h intervals. After that, the specimens were processed for histological and immunohistochemical analyses. Necrotic tooth showed greater neutrophil infiltrate (p < 0.05). Necrotic tooth, healthy tooth, and healthy tooth+PBM groups showed absence of a thin layer of fibrous condensation in the periapical area. All the other groups stimulated the formation of a thicker layer of fibers (p < 0.05). All groups formed more mineralized tissue than necrotic tooth (p < 0.05). PBM associated with MTA, BC, or hDPSC formed more mineralized tissue (p < 0.05). MTA+PBM induced apexification (p < 0.05). Rabbit polyclonal anti-bone sialoprotein (BSP) antibody confirmed the histological findings of mineralized tissue formation, and hDPSC groups exhibited higher percentage of BSP-positive cells. It can be concluded that PBM improved apexification and favored apexogenesis in necrotic rat molars with an open apex.

Examining tumor modulating effects of photobiomodulation therapy on head and neck squamous cell carcinomas.

Photobiomodulation (PBM) therapy is an effective method for preventing and managing oral mucositis (OM) in head and neck squamous cell carcinoma (HNSCC) patients undergoing radiotherapy alone or in combination with chemotherapy. However, the potential effects of PBM therapy on premalignant and malignant cells eventually present in the treatment site are yet unknown. The aim of this systematic review was to analyze the effects of PBM therapy on HNSCC. A literature search was conducted in four indexed databases as follows: MEDLINE/PubMed, EMBASE, Web of Science, and Scopus. The databases were reviewed for papers published up to and including in October 2018. In vitro and in vivo studies that investigated the effects of PBM therapy on HNSCC were selected. From the 852 initially gathered studies, 15 met the inclusion criteria (13 in vitro and 2 in vivo). Only three in vitro studies were noted to have a low risk of bias. The included data demonstrated wide variations of study designs, PBM therapy protocols, and study outcomes. Cell proliferation and viability were the primary evaluation outcome in the in vitro studies. Of the 13 in vitro studies, seven noted a positive effect of PBM therapy on inhibiting or preventing an effect on HNSCC tumor cells, while six studies saw increased proliferation. One in vivo study reported increased oral SCC (OSCC) progression, while the other observed reduced tumor progression. Overall, the data from the studies included in the present systematic review do not support a clear conclusion about the effects of PBM therapy on HNSCC cells.

Tumor safety and side effects of photobiomodulation therapy used for prevention and management of cancer treatment toxicities. A systematic review.

Photobiomodulation therapy (PBMT), also known as low-level laser therapy (LLLT), has been increasingly used for the treatment of toxicities related to cancer treatment. One of the challenges for the universal acceptance of PBMT use in cancer patients is whether or not there is a potential for the light to stimulate the growth of residual malignant cells that evaded oncologic treatment, increasing the risk for tumor recurrences and development of a second primary tumor. Current science suggests promising effects of PBMT in the prevention and treatment of breast cancer-related lymphedema and oral mucositis, among other cancer treatment toxicities. Nevertheless, this seems to be the first systematic review to analyze the safety of the use of PBMT for the management of cancer-related toxicities. Scopus, MEDLINE/PubMed, and Embase were searched electronically. A total of 27 articles met the search criteria. Selected studies included the use of PBMT for prevention and treatment of oral mucositis, lymphedema, radiodermatitis, and peripheral neuropathy. Most studies showed that no side effects were observed with the use of PBMT. The results of this systematic review, based on current literature, suggest that the use of PBMT in the prevention and management of cancer treatment toxicities does not lead to the development of tumor safety issues.

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.

Histologic Evaluation of Early Bone Regeneration Treated with Simvastatin Associated with Low-Level Laser Therapy.

PURPOSE: This histologic study aimed at assessing bone healing after treatment with simvastatin in association with low-level laser therapy (LLLT). METHODS: Twenty-four male rats (Wistar) were submitted to surgery to create a bone defect of 5 mm in diameter in the parietal bone. These rats were randomly and equally divided into four treatment groups (n = 6): control (C), in which no treatment was performed; simvastatin (SIM), in which rats received daily subcutaneous doses of 2.5 mg/kg of simvastatin; LLLT, which was daily applied to the bone defect; and SIM-LLLT, in which both SIM and LLLT were daily applied. All laser irradiations were carried out with a 830-nm infrared diode laser (GaAlAs) with maximum output of 100 mW and a dose of 4 J, totaling 16 J per session. Rats were euthanized on the 12th postoperative day. Formalin-fixed paraffin-embedded bone samples were obtained and stained with hematoxylin-eosin (HE) and toluidine blue for optical microscope analysis. Degree of inflammation, new vascular formation, tissue repair, and osteoblastic activity were assessed. RESULTS: Categorical analysis of the histologic slides revealed newly formed bone reaching the center of the surgical wound in two animals from the SIM group, two from the LLLT group, and three from the SIM-LLLT group. Greater new bone formation and a lower degree of inflammation were observed in the animals that had bone neoformation at the center of the defect, especially in the LLLT and SIM-LLLT groups. SIM and C groups presented greater angiogenesis than LLLT and SIM-LLLT. SIMLLLT therapy showed a statistically significant reduction in the degree of inflammation when compared to the control group (P < .05). CONCLUSION: Within the limitations of this study, the present results suggest that a combination of simvastatin and low-level laser therapy may stimulate better bone formation.

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.