Effects of slit lamp-delivered retinal laser photobiomodulation in a rat model of choroidal neovascularization.

Neovascular age-related macular degeneration, also known as exudative or wet age-related macular degeneration, is the leading cause of blindness in the developed world. Photobiomodulation has the potential to target the up-stream hypoxic and pro-inflammatory drivers of choroidal neovascularization. This study investigated whether photobiomodulation attenuates characteristic pathological features of choroidal neovascularization in a rodent model. Experimental choroidal neovascularization was induced in Brown Norway rats with laser photocoagulation. A custom-designed, slit-lamp-mounted, 670 nm laser was used to administer retinal photobiomodulation every 3 days, beginning 6 days prior to choroidal neovascularization induction and continuing until the animals were killed 14 days later. The effect of photobiomodulation on the size of choroidal neovascular membranes was determined using isolectin-B4 immunohistochemistry and spectral domain-optical coherence tomography. Vascular leakage was determined with fluorescein angiography. The effect of treatment on levels of vascular endothelial growth factor expression was quantified with enzyme-linked immunosorbent assay. Treatment with photobiomodulation was associated with choroidal neovascular membranes that were smaller, had less fluorescein leakage, and a diminished presence of inflammatory cells as compared to sham eyes. These effects were not associated with a statistically significant difference in the level of vascular endothelial growth factor when compared to sham eyes. The data shown herein indicate that photobiomodulation attenuates pathological features of choroidal neovascularization in a rodent model by mechanisms that may be independent of vascular endothelial growth factor.

Might photobiomodulation therapy interfere with the frequency of severe mucositis and oral candidiasis? A retrospective analysis in patients with head and neck carcinoma.

PURPOSE: Considering the tumor in the oral cavity or the oropharynx and nasopharynx region might be an aggravating factor for oral mucositis (OM) manifestation, the present study aimed to evaluate whether the location of the tumor and the use of photobiomodulation therapy (PBMT) might affect the frequency of oral candidiasis (OC) during radiotherapy (RT) and/or chemotherapy (CT) treatments. METHODS: The medial records of seventy-four patients with head and neck cancer treated in a public service from 2016 to 2019 were evaluated. All these patients were submitted to RT in an accumulated dose of 48 to 70 Gy of radiation. Data about OM and OC were collected and presented according to the application of a therapeutic protocol with laser photobiomodulation (PBMT) to control oral mucositis, or not (No-PBM), and the location of tumor (head and neck or oral cavity). In the PBMT group patients, a low-power laser device composed of InGaAlP diode (maximum output power of 86.7 mW, active tip area of 0.1256 cm2, and continuous wavelength of 660 nm), was applied to the lips (three points each), right and left jugal mucosa (three points each), the limit between hard and soft palate (three points), buccal floor/sublingual gland (one point), lateral edge of the tongue (three points on each side), and back of the tongue (six points), three times weekly, for 5 weeks. The dosimetry used in each application was 2 J for 3 s, thus totaling 56 J. The correlation between clinical characteristics such as age, tumor size (T), metastatic lymph node (N), number of RT and CT sessions, candidiasis, and OM were analyzed. RESULTS: Mucositis grades 1 and 2 were the most common among all patients, especially before the 12th radiotherapy session, regardless of the treatment with PBM (p > 0.05). Additionally, no difference in the grade of OM and OC was significantly observed when comparing the two laser therapy groups. OC was more frequent after the 12th radiotherapy session in all groups. Nonetheless, OM and OC had a different correlation regarding to tumor location (head and neck and oral cavity) being PBMT a positive therapy to delay OM. It was observed a positive and statistically significant correlation between tumors at oral cavity and OM, regardless PBMT (R = 0.84, p < 0.05 to PBMT and R = 0.13, p < 0.05 to No-PBM). Otherwise, OC was positively correlated to local metastasis in patients with oral tumors undergoing PBMT (R = 0.84, p < 0.05). CONCLUSION: Patients with oral cavity tumor presented more OM, especially high grades, then patients with tumors in other regions of the head and neck, which seems to be related to the irradiation parameters of radiotherapy and/or with the limitation of conduction of PBMT in tumor areas. OM and OC were not changed by PBMT, although it helped to reduce the incidence of severe cases of OM.

The effect of photobiomodulation therapy in common maxillofacial injuries: Current status.

The use of photobiomodulation therapy (PBMT) may be used for treating trauma to the maxillofacial region. The effects of PBMT on maxillofacial injuries were discussed in this review article. The electronic databases Pubmed, Scopus, and Web of Science were thoroughly searched. This review included in vitro, in vivo, and clinical studies describing how PBMT can be used in maxillofacial tissue engineering and regenerative medicine. Some studies suggest that PBMT may offer a promising therapy for traumatic maxillofacial injuries because it can stimulate the differentiation and proliferation of various cells, including dental pulp cells and mesenchymal stem cells, enhancing bone regeneration and osseointegration. PBMT reduces pain and swelling after oral surgery and tooth extraction in human and animal models of maxillofacial injuries. Patients with temporomandibular disorders also benefit from PBMT in terms of reduced inflammation and symptoms. PBMT still has some limitations, such as the need for standardizing parameters. PBMT must also be evaluated further in randomized controlled trials in various maxillofacial injuries. As a result, PBMT offers a safe and noninvasive treatment option for patients suffering from traumatic maxillofacial injuries. PBMT still requires further research to establish its efficacy in clinical practice and determine the optimal parameters.

The Effects of Photobiomodulation on Knee Function, Pain, and Exercise Tolerance in Older Adults: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To assess whether photobiomodulation therapy (PBMT) enhances the benefits of exercise in older adults. DATA SOURCES: PubMed, Scopus, Medline, and Web of Science, dated to February 2023. STUDY SELECTION: All included studies were randomized controlled trials of PBMT combined with exercise co-intervention in persons 60 years and older. OUTCOME MEASURES: Western Ontario and McMaster University Osteoarthritis Index (WOMAC-total, pain, stiffness and function), perceived pain intensity, timed Up and Go (TUG) Test, 6-min walk test (6MWT), muscle strength, and knee range of motion were included. DATA EXTRACTION: Two researchers independently performed data extraction. Article data were extracted in Excel and summarized by a third researcher. DATA SYNTHESIS: The meta-analysis included 14 of the 1864 studies searched in the database. No statistical differences were found between the treatment and control groups in terms of WOMAC-stiffness (mean difference [MD]=-0.31, 95% confidence interval [CI] -0.64 to 0.03), TUG (MD=-0.17, 95% CI -0.71 to 0.38), 6MWT (MD=32.2, 95% CI -44.62 to 109.01), or muscle strength (standardized mean difference=0.24, 95% CI -0.02 to 0.50). However, statistically significant differences were found for WOMAC-total (MD=-6.83, 95% CI -12.3 to -1.37), WOMAC-pain (MD=-2.03, 95% CI -4.06 to -0.01), WOMAC-function (MD=-5.03, 95% CI -9.11 to -0.96), visual analog scale/numeric pain rating scale (MD=-1.24, 95% CI -2.43 to -0.06), and knee range of motion (MD=1.47, 95% CI 0.07 to 2.88). CONCLUSIONS: In older adults who exercise regularly, PBMT can potentially provide additional pain relief, improve knee joint function, and increase knee joint range of motion.

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.

A retrospective study of cumulative absolute reduction in axial length after photobiomodulation therapy.

BACKGROUND: To assess the age and timeline distribution of ocular axial length shortening among myopic children treated with photobiomodulation therapy in the real world situations. METHODS: Retrospective study of photobiomodulation therapy in Chinese children aged 4 to 13 years old where axial length measurements were recorded and assessed to determine effectiveness at two age groups (4 ∼ 8 years old group and 9 ∼ 13 years old group). Data was collected from myopic children who received photobiomodulation therapy for 6 ∼ 12 months. Effectiveness of myopia control was defined as any follow-up axial length ≤ baseline axial length, confirming a reduction in axial length. Independent t-test was used to compare the effectiveness of the younger group and the older group with SPSS 22.0. RESULTS: 342 myopic children were included with mean age 8.64 ± 2.20 years and baseline mean axial length of 24.41 ± 1.17 mm. There were 85.40%, 46.30%, 71.20% and 58.30% children with axial length shortening recorded at follow-up for 1 month, 3 months, 6 months and 12 months, respectively. With respect to the axial length shortened eyes, the mean axial length difference (standard deviation) was - 0.039 (0.11) mm, -0.032 (0.11) mm, -0.037 (0.12) mm, -0.028 (0.57) mm at 1, 3, 6, and 12-month follow-up, respectively. Greater AL shortening was observed among the older group who had longer baseline axial lengths than the younger group (P < 0.001). CONCLUSIONS: Overall myopia control effectiveness using photobiomodulation therapy was shown to be age and time related, with the maximum absolute reduction in axial elongation being cumulative.

Post-surgical photobiomodulation therapy improves outcomes following elective gastropexy in dogs.

PURPOSE: To evaluate the effect of post-surgical photobiomodulation therapy in dogs. METHODS: Twenty dogs were selected for elective gastropexy and randomly divided into a control (CG, n = 10) and a PBMT group (PBMTG, n = 10). Pre­medication consisted of medetomidine and butorphanol. Meloxicam was administered before the procedure. Induction was performed with propofol and maintained with sevoflurane. Local blocks with lidocaine were used. Incisional gastropexy was performed in all animals. PBMTG received PBMT immediately after surgery. The need for postoperative rescue analgesia, if the animal had eaten by the evaluation momen, and pain scores were collected using the Glasgow Composite Measure Pain Scale - Short Form (CMPS­SF) at 1, 2, 4, 6, 8, 12, 16, 20, and 24 h post­endotracheal extubation. CMPS­SF scores were compared with the Mann-Whitney Test and proportions of animals that required rescue analgesia and had eaten with a χ2 test. P was set at < 0.05. RESULTS: No rescue analgesia was needed for any animal. Still, significant differences were observed in CMPS-SF scores between CG and PBMTG between 1 and 4 h post-extubation. PBMTG had a significantly higher proportion of animals eating up to the 8 h post-extubation evaluation moment. CONCLUSION: Adding post-surgical photobiomodulation to a standard anesthesia and analgesia protocol reduced CMPS-SF scores and increased the proportion of animals that resumed eating compared to the standard protocol alone.

Low-level laser therapy alleviates periodontal age-related inflammation in diabetic mice via the GLUT1/mTOR pathway.

Diabetes mellitus (DM) is a chronic age-related disease that was recently found as a secondary aging pattern regulated by the senescence associated secretory phenotype (SASP). The purpose of this study is to detect the potential efficacy and the specific mechanisms of low-level laser therapy (LLLT) healing of age-related inflammation (known as inflammaging) in diabetic periodontitis. Diabetic periodontitis (DP) mice were established by intraperitoneal streptozotocin (STZ) injection and oral P. gingivalis inoculation. Low-level laser irradiation (810 nm, 0.1 W, 398 mW/cm2, 4 J/cm2, 10 s) was applied locally around the periodontal lesions every 3 days for 2 consecutive weeks. Micro-CT and hematoxylin-eosin (HE) stain was analyzed for periodontal soft tissue and alveolar bone. Western blots, immunohistochemistry, and immunofluorescence staining were used to evaluate the protein expression changes on SASP and GLUT1/mTOR pathway. The expression of aging-related factors and SASP including tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 were reduced in periodontal tissue of diabetic mice. The inhibitory effect of LLLT on GLUT1/mTOR pathway was observed by detecting the related factors mTOR, p-mTOR, GLUT1, and PKM2. COX, an intracytoplasmic photoreceptor, is a key component of the anti-inflammatory effects of LLLT. After LLLT treatment a significant increase in COX was observed in macrophages in the periodontal lesion. Our findings suggest that LLLT may regulate chronic low-grade inflammation by modulating the GLUT1/mTOR senescence-related pathway, thereby offering a potential treatment for diabetic periodontal diseases.

Expediting the reversal of inferior alveolar nerve block anesthesia in children with photobiomodulation therapy.

In pediatric dentistry, complications arising from extended soft tissue anesthesia can negatively impact patient comfort and trust in dental care. This study evaluates the clinical efficacy of diode laser-based photobiomodulation therapy (PBMT) in expediting the resolution of anesthesia in children aged 6-9 receiving inferior alveolar nerve block (IANB) injections. In this split-mouth double-blind randomized clinical trial, 36 pediatric subjects aged 6-9, requiring pulpotomy procedures on both sides of the mandible, received IANBs (single cartridge of 2% lidocaine/1:100,000 epinephrine). PBMT and sham laser were alternately applied to each side of the mandible, in two separate sessions, with the envelope method determining treatment allocation and intervention side on the first treatment day. During the laser session, laser (808 nm, 250 mW, 23s continuous, 0.5 cm², 11.5 J/cm², direct contact) irradiated two points at the injection site, five intra-oral and five extra-oral points along the infra-alveolar nerve's pathway. Soft tissue anesthesia reversal was quantified through tactile assessment. Soft tissue trauma was also assessed by the researcher and reported by parents 24 h post-dental visit. All data were analyzed using IBM SPSS Statistics v25.0 via Paired T-test, two-way repeated measures ANOVA, and McNemar's test. The laser group exhibited a mean lip anesthesia duration of 122.78 ± 2.26 min, while the sham laser group experienced 134.44 ± 21.8 min, indicating an 11.66-minute reduction in anesthesia duration for the laser group. (P < 0.001) Soft tissue trauma occurred in two sham laser group patients and one laser group patient, with no significant difference. (P = 1) The findings indicate that employing laser with defined parameters can reduce the length of IANB-induced anesthesia.

Effect of photobiomodulation therapy on the morphology, intracellular calcium concentration, free radical generation, apoptosis and necrosis of human mesenchymal stem cells-an in vitro study.

The aim of the study was to investigate the impact of multiwave locked system (MLS M1) emitting synchronized laser radiation at 2 wavelength simultaneous (λ = 808 nm, λ = 905 nm) on the mesenchymal stem cells (MSCs). Human MSCs were exposed to MLS M1 system laser radiation with the power density 195-318 mW/cm2 and doses of energy 3-20 J, in continuous wave emission (CW) or pulsed emission (PE). After irradiation exposure in doses of energy 3 J, 10 J (CW, ƒ = 1000 Hz), and 20 J (ƒ = 2000 Hz), increased proliferation of MSCs was observed. Significant reduction of Fluo-4 Direct™ Ca2+ indicator fluorescence over controls after CW and PE with 3 J, 10 J, and 20 J was noticed. A decrease in fluorescence intensity after the application of radiation with a frequency of 2000 Hz in doses of 3 J, 10 J, and 20 J was observed. In contrary, an increase in DCF fluorescence intensity after irradiation with laser radiation of 3 J, 10 J, and 20 J (CW, ƒ = 1000 Hz and ƒ = 2000 Hz) was also shown. Laser irradiation at a dose of 20 J, emitted at 1000 Hz and 2000 Hz, and 3 J emitted at a frequency of 2000 Hz caused a statistically significant loss of MSC viability. The applied photobiomodulation therapy induced a strong pro-apoptotic effect dependent on the laser irradiation exposure time, while the application of a sufficiently high-energy dose and frequency with a sufficiently long exposure time significantly increased intracellular calcium ion concentration and free radical production by MSCs.

The adjunctive use of antimicrobial photodynamic therapy, light-emitting-diode photobiomodulation and ozone therapy in regenerative treatment of stage III/IV grade C periodontitis: a randomized controlled clinical trial.

OBJECTIVES: To assess the short-term efficacy of multiple sessions of antimicrobial photodynamic therapy (aPDT), light-emitting-diode (LED) photobiomodulation, and topical ozone therapy applications following surgical regenerative treatments on clinical parameters, patient-centered outcomes, and mRNA expression levels of VEGF, IL-6, RunX2, Nell-1, and osterix in gingival crevicular fluid samples in patients with stage III/IV, grade C periodontitis. MATERIALS AND METHODS: Forty-eight systemically healthy patients were assigned into four groups to receive adjunctive modalities with regenerative periodontal surgical treatment. A 970 ± 15 nm diode laser plus indocyanine-green for aPDT group, a 626 nm LED for photobiomodulation group, and topical gaseous ozone were applied at 0, 1, 3, and 7 postoperative days and compared to control group. The clinical periodontal parameters, early wound healing index (EHI), and postoperative patients' morbidity were evaluated. The mRNA levels of biomarkers were assessed by real-time polymerase chain reaction. RESULTS: No significant difference in the clinical parameters except gingival recession (GR) was identified among the groups. For group-by-time interactions, plaque index (PI) and probing pocket depths (PD) showed significant differences (p = 0.034; p = 0.022). In sites with initial PD > 7 mm, significant differences were observed between control and photobiomodulation groups in PD (p = 0.011), between control and aPDT, and control and photobiomodulation groups in CAL at 6-month follow-up (p = 0.007; p = 0.022). The relative osterix mRNA levels showed a statistically significant difference among the treatment groups (p = 0.014). CONCLUSIONS: The additional applications of aPDT and LED after regenerative treatment of stage III/IV grade C periodontitis exhibited a more pronounced beneficial effect on clinical outcomes in deep periodontal pockets.

Efficacy of photobiomodulation therapy in recurrent herpes labialis management: a randomized controlled trial.

OBJECTIVES: This study is aimed at assessing the therapeutic efficacy of photobiomodulation therapy (PBMT) for the management of recurrent herpes labialis (RHL) by evaluating both pain and clinical recovery. MATERIAL AND METHODS: A randomized, double-blind, controlled trial was conducted on 40 patients with RHL, and they were randomly divided into two groups, where 20 patients received treatment with PBMT (650 nm, 100 mW, 4.7 J/cm2), continuous mode, for 120 s, and placebo cream, while another 20 patients (control group) were treated with acyclovir cream 5% (5 times/5 days) and passive laser. Pain was assessed at five different times. The day when the complete disappearance of the pain was observed and the day when the crust fell off spontaneously were also recorded. RESULTS: The pain level in the control group was significantly higher than that in the PBMT group after the second application of the laser, while the differences were not significant between the two groups at other times. The pain in the PBMT group disappeared faster than that in the control group, but the difference was not significant in terms of clinical recovery. CONCLUSIONS: Photobiomodulation therapy of herpes labialis reduced pain significantly faster than acyclovir, but there was no difference in healing time between the groups in light of the parameters used in this study. CLINICAL RELEVANCE: PBMT is a promising treatment that may be an effective alternative to acyclovir in the management of recurrent herpes labialis. TRIAL REGISTRATION ISRCTN: com ID: ISRCTN87606522.

Activation of reparative processes of chronic wounds using photobiomodulation therapy (experimental study).

OBJECTIVE: Aim: The aim of the work was to study the ef f ect of photobiomodulation therapy on the regulation of disorders in the healing of chronic wounds at the remodeling stage using indicators of platelet aggregation activity, reactive oxygen species, platelet-derived growth factor, and interleukin-1ß. PATIENTS AND METHODS: Materials and Methods: The study included 3 groups of Wistar rats: intact animals and animals of the control and experimental groups, for which chronic wounds were simulated. Rats in the experimental group received photobiomodulation therapy once a day for 5 days. Wound defects of animals in the control group were fictitiously irradiated. The levels of reactive oxygen species, platelet-derived growth factor, and interleukin-1ß in the blood serum of animals were studied by enzyme immunoassay. The functional activity of platelets was measured on a computerized platelet aggregation analyzer using the turbidimetric method. Histological studies were carried out. RESULTS: Results: Changes in the expression of the studied indicators were found in the blood serum of animals with chronic wounds when using photobiomodulation therapy: an increase in platelet-derived growth factor concentrations, the levels of reactive oxygen species and interleukin-1ß did not have statistically signif i cant differences compared to the corresponding indicators of animals in the control group. There were no significant differences in the indicators of platelet aggregation activity in the control and experimental groups of animals. CONCLUSION: Conclusions: The findings suggest that photobiomodulation therapy may promote wound healing by increasing platelet-derived growth factor levels. Histological studies have shown that using photobiomodulation therapy helps reduce inflammation and better organization of collagen fibers in animals of the experimental group.

IS THE PHOTOBIOMODULATION THERAPY EFFECTIVE IN CONTROLLING POST-SURGICAL SIDE EFFECTS AFTER THE EXTRACTION OF MANDIBULAR THIRD MOLARS? A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVES: The extraction of third molars is one of the most performed surgical procedures in oral and maxillofacial surgery. Pain, oedema, and trismus are the most frequently complications related in the surgical postoperative period. The literature has indicated PBM as a potential adjuvant method to reduce these complications. The aim of this review and meta-analysis is evaluate the PBM, as an optimal method to improve patient experience and minimize postoperative morbidity. Additionally, we seek to determine which wavelength, site, and frequency of application are most effective. METHODS: This review was registered in PROSPERO (CRD42023429966) and followed PRISMA guidelines. The search was carried out in the main databases, PubMed/MEDLINE, Cochrane Library, Embase, Scopus, and Lilacs, including reviews in the most important journals in the area of oral surgery and laser applied to oral surgery. In addition, all article references and also gray literature were reviewed. After the studies selection, the relevant data was collected. All the studies were randomized controlled trials and the patients were allocated into two groups: active PBM and inactive PBM. The statistical analysis was carried out using Stata v.16, and the methodological quality and risk of bias were assessed by the Jadad scale and RoB 2.0, respectively. RESULTS: Where included 22 studies and 989 subjects, to all with a minimum follow-up of 7 days. Pain and oedema showed statistically significant results in favor to the active PBM group. Especially when laser applied in infrared mode, for pain and oedema at 48 h, MD = -1.80 (CI95% -2.88, -0.72) I²â€¯= 92.13% and MD = -1.45 (CI95% -2.42, -0.48) I²â€¯= 65.01%, respectively. The same is not true for trismus at 48 h, MD = 0.07 (CI95% -0.06, 0.21) I²â€¯= 3.26%. The meta-analysis also presented results in respect of laser site of application and number of PBM sessions. CONCLUSIONS: PBM with infrared laser, in a combination intraoral and extraoral application, in one session in the immediate postoperative period, has been shown to be effective to achieve the objectives of reducing pain and oedema after third molar extraction.

Applications of laser technology in the manipulation of human spermatozoa.

The application of laser technology in the field of assisted reproductive technology (ART) has experienced rapid growth over the past decades owing to revolutionary techniques such as intracytoplasmic sperm injection (ICSI), preimplantation genetic testing (PGT), and in vitro manipulation of gametes and embryos. For male gametes, in vitro manipulation techniques include spermatozoa selection, sorting, immobilization, and quality assessment. A number of studies have been conducted to investigate the application of different laser technologies in the manipulation of human spermatozoa. However, there is a lack of a unified understanding of laser application in the in vitro manipulation of sperm and safety considerations in ART and, subsequently, the inability to make clear and accurate decisions on the clinical value of these laser technologies. This review summarizes the advancements and improvements of laser technologies in the manipulation of human spermatozoa, such as photobiomodulation therapy, laser trap systems for sperm analysis and sorting, laser-assisted selection of immotile sperm and laser-assisted immobilization of sperm prior to ICSI. The safety of those technologies used in ART is also discussed. This review will provide helpful and comprehensive insight into the applications of laser technology in the manipulation of human spermatozoa.

Evaluation of photobiomodulation therapy (117 and 90s) on pain, regeneration, and epigenetic factors (HDAC 2, DNMT3a) expression following spinal cord injury in a rat model.

BACKGROUND: Photobiomodulation therapy (PBMT), due to its anti-inflammatory, analgesic effects, and most importantly as a non-invasive procedure, has currently gained a special setting in pain relief and the treatment of Spinal cord injuries (SCI). However, the mechanism of action of the PBM is not yet completely understood. METHODS: In this study, SCI is induced by an aneurysm clip, and PBM therapy was applied by a continuous-wave (CW) laser with a wavelength of 660 nm. Adult male rats were divided into four groups: Control, SCI, SCI + PBMT 90s, and SCI + PBMT 117s. After 7 weeks, hyperalgesia, allodynia, and functional recovery were assessed. Fibroblasts infiltrating the spinal cord were counted after H&E staining. The expression of epigenetic factors (HDAC2, DNMT3a), protein relevant for pain (GAD65), and astrocytes marker (GFAP) after 4 weeks of daily PBMT (90 and 117s) was probed by western blotting. RESULTS: Both PBMTs (90 and 117s) significantly improved the pain and ability to move and fibroblast invasion was reduced. SCI + PBMT 90s, increased GAD65, HDAC2, and DNMT3a expression. However, PBMT 117s decreased GFAP, HDAC2, and DNMT3a. CONCLUSION: PBMT 90 and 117s improved the pain, and functional recovery equally. The regulation of epigenetic mechanisms appears to be a significant effect of PBMT117s, which emphasizes on impact of radiation duration and accumulative energy.

Effects of a mucoadhesive phytomedicine (Curcuma longa L. and Bidens pilosa L.) on radiotherapy-induced oral mucositis and quality of life of patients undergoing head and neck cancer treatment: randomized clinical trial.

PURPOSE: To assess the effect of a mucoadhesive herbal medicine containing curcuminoids and a glycerinated extract of Bidens pilosa L. (FITOPROT) in association with photobiomodulation (PBM) therapy and a Preventive Oral Care Program (POCP) compared to PBM and POCP in the treatment of radiotherapy (RT)-induced oral mucositis (ROM) and in the quality of life of these patients. METHODS: A double-blind clinical trial was performed with head and neck cancer patients undergoing RT or chemoradiotherapy. Participants were randomized into two groups: Group 1 (n=27): PBM and POCP; and Group 2 (n=25): PBM, POCP and FITOPROT. The PBM protocol was daily irradiation, 660 nm, 25mW, 0.25 J/point from the first until the last day of RT. The FITOPROT was used as mouthwash twice a day. ROM was evaluated based on the scales of the World Health Organization and National Cancer Institute. The quality of life was evaluated using the University of Washington Questionnaire, OHIP-14 and Patient-Reported Oral Mucositis Symptom Scale. The MMAS-8 questionnaire was used to evaluated the adherence to POCP and FITOPROT. Data were collected at baseline, 7th, 14th, 21st, and 30th RT sessions. RESULTS: No statistical differences were found between the groups for the ROM evaluation. Both groups experienced worsening of the quality of life during the RT. No statistically significant differences between groups were observed for any of the instruments evaluated. CONCLUSION: The results suggest that PBM associated with FITOPROT and POCP control the severity of ROM and stabilize the QoL of patients with head and neck cancer. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (ReBEC-RBR-9vddmr; UTN code: U1111-1193-2066), registered in August 8th, 2017.

Photobiomodulation therapy for the prevention of acute radiation dermatitis: a systematic review and meta-analysis.

PURPOSE: Approximately 95% of patients undergoing radiotherapy (RT) experience radiation dermatitis (RD). Evidence has suggested that photobiomodulation therapy (PBMT) can stimulate skin renewal and minimize RD. The aim of the present paper was to investigate the efficacy of PBMT in RD prevention through a comprehensive literature review. METHODS: A literature search of Ovid MEDLINE, Embase, and Cochrane databases was conducted from 1980 to March 2021 to identify RCT on the use of PBMT for RD prevention. Forest plots were developed using RevMan software to quantitatively compare data between studies. RESULTS: Five papers were identified: four in breast and one in head and neck cancer patients. Patients receiving PBMT experienced less severe RD than the control groups after 40 Gray (Gy) of RT (grade 3 toxicity: Odds Ratio (OR): 0.57, 95% CI 0.14-2.22, p = 0.42) and at the end of RT (grade 0 + 1 vs. 2 + 3 toxicity: OR: 0.28, 95% CI 0.15-0.53, p < 0.0001). RT interruptions due to RD severity were more frequent in the control group (OR: 0.81, 95% CI 0.10-6.58, p = 0.85). CONCLUSION: Preventive PBMT may be protective against the development of severe grades of RD and reduce the frequency of RT interruptions. Larger sample sizes and other cancer sites at-risk of RD should be evaluated in future studies to confirm the true efficacy of PBMT, also in preventing the onset of RD and to finalize a standardized protocol to optimize the technique. At present, starting PBMT when RT starts is recommendable, as well as performing 2 to 3 laser sessions weekly.

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.

Expression and degranulation of mast cells in laser photobiomodulated mucositis chemo-induced: pilot study in hamsters.

This study aimed to evaluate the influence of laser photobiomodulation on the expression and degranulation of mast cells in chemo-induced oral mucositis (OM) lesions in hamsters. Twelve adult male Syrian hamsters (Mesocricetus auratus), golden lineage, were submitted to OM induction. They were divided into three groups: control-OM without treatment (C), OM treated with red laser (RL), OM treated with infrared laser (IL) and analyzed in the experimental time of 7 days. Three and 4 days after the intraperitoneal injection of the chemotherapy drug fluorouracil, the OM lesions were induced by making grooves in the right cheek pouch. Immediately after chemoinduction, the hamsters were submitted to photobiomodulation every 48 h for 7 days. The specimens were processed and stained using the hematoxylin-eosin and toluidine blue techniques. There was a predominance of mild chronic inflammation in the experimental groups and a greater persistence of neutrophils in the control group (C), although not statistically significant. The group irradiated with red laser (RL) had the highest mean mast cell expression (38.28 ± 19.05) (p < 0.001). As for the degranulation activity in mast cells, the control group (C) showed a greater number of fields with more than 50% of degranulated cells, presenting statistical significance when comparing it with the RL (p < 0.009) and IL (p = 0.036) group. It can be concluded that photobiomodulation, at both wavelengths, decreased mast cell degranulation, accelerating the inflammatory process. The use of infrared laser provided, in addition to less degranulation, the quantitative reduction of mast cells.