Effects of the invasive and non-invasive systemic photobiomodulation using low-level laser in experimental models: A systematic review.

Systemic photobiomodulation (PBM) of the blood or over blood vessels has been associated with bio-stimulating, vasodilating, and anti-inflammatory properties. This treatment modality has been used for modulating inflammatory processes, tissue repair, atherosclerosis, and systemic arterial hypertension, and is described more often in clinical studies than experimental models. Therefore, the aim of the present study was to conduct a literature review regarding the effect of systemic PBM involving the intravascular laser irradiation of blood (ILIB) or non-invasive vascular photobiomodulation (VPBM) using low-level laser (LLL) in experimental (animal) models. The PubMed/MEDLINE®, Scopus, SPIE Digital Library, and Web of Science databases were searched for articles on the use of VPBM with LLL in animal models. Nine original articles met the inclusion criteria and were critically evaluated. The variables of interest were the dosimetric laser parameters, different methods for delivering energy, and the main results. The use laser in the red spectrum was more prevalent and VPBM (non-invasive) predominated over ILIB (invasive). No standardization was found in the dosimetric parameters. However, the studies showed the positive effects of VPBM on arterial pressure and blood circulation, the positive effects of ILIB on blood composition and hematological markers, as well as positive effects of both forms of systemic PBM (ILIB and VPBM) on the tissue repair process. In conclusion, the studies evaluated in the present review showed that the use of systemic PBM with ILIB or non-invasive VPBM induced positive effects, modulating metabolic conditions and tissue repair. However, there is a need for standardization in the dosimetric parameters for the different conditions and processes evaluated using experimental models.

Intravascular laser irradiation of blood (ILIB) used to treat lung diseases: a short critical review.

Intravascular laser irradiation of blood (ILIB) was developed to treat cardiovascular diseases due to its rheological effects. In its original form, ILIB was applied by an intravenous optical fiber, restricting its application. However, this technique was modified to non-invasive irradiation through the radial artery, now called vascular photobiomodulation (VPBM). Many studies have used both, ILIB and VPBM, to treat lung diseases. It is well established that lung diseases affect more than 300 million people worldwide with high morbidity and mortality rates. In this short critical review, we discuss the potential benefits of photobiomodulation to treat lung diseases using these two approaches. The search was performed in the electronic database of MEDLINE (Medical Literature Analysis and Retrieval System Online) via PubMed. The data search was carried out from 1991 to 2017. We selected a total of 10 clinical studies using either ILIB or VPBM, in addition to 2 experimental studies in animals. The respiratory diseases treated in these studies included bronchitis, asthma, pneumonia, and tuberculosis. The results showed overall beneficial effects on lung diseases, characterized by a reduction in the inflammatory cascade and antioxidant effects, improvement of hemodynamic parameters, the efficiency of gas exchange, and reduction of hospitalization periods. In conclusion, all studies showed promising effects of ILIB in both animal and human studies. The studies did not discuss any disadvantages or contraindications. However, further studies are needed in order to understand the dosimetry, and the literature is lacking in randomized, controlled clinical trials. Thus, this review highlights the need for additional studies using this approach.

The effectiveness of phototherapy for surface decontamination against SARS-Cov-2. A systematic review.

COVID-19 appeared in December 2019, needing efforts of science. Besides, a range of light therapies (photodynamic therapy, ultraviolet [UV], laser) has shown scientific alternatives to conventional decontamination therapies. Investigating the efficacy of light-based therapies for environment decontamination against SARS-CoV2, a PRISMA systematic review of Phototherapies against SARS-CoV or MERS-CoV species discussing changes in viral RT-PCR was done. After searching MEDLINE/PubMed, EMBASE, and Literatura Latino-Americana e do Caribe em Ciências da Saúde we have found studies about cell cultures irradiation (18), blood components irradiation (10), N95 masks decontamination (03), inanimate surface decontamination (03), aerosols decontamination (03), hospital rooms irradiation (01) with PDT, LED, and UV therapy. The best quality results showed an effective low time and dose UV irradiation for environments and inanimate surfaces without human persons as long as the devices have safety elements dependent on the surfaces, viral charge, humidity, radiant exposure. To interpersonal contamination in humans, PDT or LED therapy seems very promising and are encouraged.

Responses of melanoma cells to photobiomodulation depend on cell pigmentation and light parameters.

Melanoma is a highly aggressive skin cancer that requires new approaches for its management. Low-level laser therapy, currently named photobiomodulation therapy (PBM), has been used to improve different conditions but its effects and safe use on melanoma remain unexplored. Herein, we investigated the PBM impact on melanoma cells differing by pigmentation using near-infrared (NIR) and red lasers in vitro. In vivo, we evaluated the effects of the red laser on melanoma-bearing mice. Amelanotic (SK-MEL-37) and melanotic (B16F10) cells were exposed in vitro to a NIR (780 nm, 40 mW) or a red laser (660 nm, 40 mW) in 3 different light doses: 30, 90, and 150 J/cm2 and responses were assessed regarding mitochondrial activity, invasiveness, migration, and VEGF production. In vivo, melanoma-bearing mice received the red laser delivering 150 J/cm2 directly to the tumor on 3 consecutive days. Mice were monitored for 15 days regarding tumor progression and mouse survival. We noticed that amelanotic cells were unresponsive to NIR light. In contrast, NIR irradiation at 30 J/cm2 promoted an increase in the invasiveness of pigmented cells, even though all light doses have inhibited cell migration. Regarding the red laser on pigmented cells, the highest light dose (150 J/cm2) decreased the VEGF production and migration. In vivo, melanoma-bearing mice treated with red laser showed smaller tumor volume and longer survival than controls. We conclude that PBM appears to be safe for amelanotic non-pigmented melanoma but triggers different responses in melanotic pigmented cells depending on light parameters. Additionally, a high dose of red laser impairs the invasive behavior of melanoma cells, probably due to the decrease in VEGF synthesis, which may have contributed to tumor arrest and increased mouse survival. These findings suggest that red laser therapy could be a new ally in the supportive care of melanoma patients.

Histological and biochemical effects of preventive and therapeutic vascular photobiomodulation on rat muscle injury.

The intravascular or transcutaneous application of photobiomodulation (PBM) over blood vessels (vascular photobiomodulation, VPBM) has been used for the treatment of inflammatory and chronic conditions with promising systemic results. This study evaluated the VPBM effects on a model of muscle regeneration after acute injury and compared the outcomes of preventive and therapeutic VPBM. Transcutaneous VPBM was administered over the rat's main tail vein. Serum levels of creatine kinase (CK), aspartate aminotransferase (AST), and lactate were evaluated and muscles were processed for macroscopic and microscopic analysis. Preventive and therapeutic VPBM led to decreased inflammatory infiltrate, edema, and myonecrosis but with an increase in immature muscle fibers. CK, AST, and lactate levels were lower in the groups treated with VPBM (lowest concentrations in preventive VPBM application). Preventive and therapeutic VPBM were capable of exerting a positive effect on acute muscle injury repair, with more accentuated results when preventive VPBM was administered.

Effects of photobiomodulation on cellular viability and cancer stem cell phenotype in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy; it has been shown that cancer stem cells (CSC) are present in OSCC and associated with tumor growth, invasion, metastasis, and therapeutic resistance. Photobiomodulation (PBM) is an alternative tool for oncologic treatment adverse effects such as oral mucositis (OM); however, controversy exists regarding the undesirable effects of PBM on tumor or CSC. This study aimed to evaluate in vitro, the effects of PBM, with the same dosimetric parameters as those used in the clinic for OM prevention and treatment, on OSCC cellular viability, as well as PBM's effect on CSC properties and its phenotype. OSCC cell lines were submitted to single or daily PBM with 3 J/cm2 and 6 J/cm2 and then the cellular viability was evaluated by MTT, NRU (neutral red uptake), and CVS (crystal violet staining). The CSC populations were evaluated by clonogenic formation assay, flow cytometry, and RT-qPCR. The single PBM with the 3 J/cm2 group was associated with increased cellular viability. Daily PBM with 3 J/cm2 and 6 J/cm2 was associated with a significant decrease in cellular viability. Additionally, daily PBM was not able to promote CSC self-renewal or the CD44high/ESAlow and CD44high/ESAhigh cellular phenotypes. Moreover, a decrease in the number of spheres and in the expression of the CSC related gene BMI1 was observed after daily PBM with 6 J/cm2. Daily PBM with 3 J/cm2 and 6 J/cm2 showed an inhibitory effect on cellular viability and was not able to promote the CSC self-renewal or phenotype.

Evaluation of Resin-Based Material Containing Copaiba Oleoresin (Copaifera Reticulata Ducke): Biological Effects on the Human Dental Pulp Stem Cells.

The purpose of this study was to analyze in vitro the biological effects on human dental pulp stem cells triggered in response to substances leached or dissolved from two experimental cements for dental pulp capping. The experimental materials, based on extracts from Copaifera reticulata Ducke (COP), were compared to calcium hydroxide [Ca(OH)2] and mineral trioxide aggregate (MTA), materials commonly used for direct dental pulp capping in restorative dentistry. For this, human dental pulp stem cells were exposed to COP associated or not with Ca(OH)2 or MTA. Cell cytocompatibility, migration, and differentiation (mineralized nodule formation (Alizarin red assay) and gene expression (RT-qPCR) of OCN, DSPP, and HSP-27 (genes regulated in biomineralization events)) were evaluated. The results showed that the association of COP reduced the cytotoxicity of Ca(OH)2. Upregulations of the OCN, DSPP, and HSP-27 genes were observed in response to the association of COP to MTA, and the DSPP and HSP-27 genes were upregulated in the Ca(OH)2 + COP group. In up to 24 h, cell migration was significantly enhanced in the MTA + COP and Ca(OH)2 + COP groups. In conclusion, the combination of COP with the currently used materials for dental pulp capping [Ca(OH)2 and MTA] improved the cell activities related to pulp repair (i.e., cytocompatibility, differentiation, mineralization, and migration) including a protective effect against the cytotoxicity of Ca(OH)2.

Photobiomodulation in oral mucositis in patients with head and neck cancer: a systematic review and meta-analysis followed by a cost-effectiveness analysis.

BACKGROUND: Oral mucositis (OM) is an oral toxicity caused by cancer treatment, found often in patients with head and neck cancer. Low-intensity laser therapy for OM has anti-inflammatory, analgesic, and tissue reparative properties. OBJECTIVE: The objective of this work is to perform a systematic review and meta-analysis of the randomized clinical trials of OM laser therapy in patients undergoing treatment for head and neck cancers, followed by a cost-effectiveness analysis of the therapy. METHOD: The search terms, mucositis and phototherapy, laser therapy and mucositis, photobiomodulation and mucositis, and low-level laser therapy and mucositis, were used to search the databases of PubMed, Web of Science, and MEDLINE. Randomized clinical trials were divided into two groups: one treated with laser therapy and the other given a placebo. Only 13 studies were included in the systematic review, and 6 studies in the meta-analysis. RESULTS: The results of the systematic review and meta-analysis show that the laser therapy presented good results in clinical improvement and pain reduction, decreasing the patients' likelihood of developing OM, with degrees of debilitating lesions, to 64% (RR = 0.36 [95% CI = 0.29-0.44]). The cost-effectiveness analysis revealed an incremental cost of R$ 3687.53 for the laser group, with an incremental effectiveness of 132.2. The incremental cost-effectiveness ratio (ICER) was 27.89, for the severe OM cases that were avoided. CONCLUSION: It was concluded, therefore, that photobiomodulation for OM in patients receiving head and neck cancer treatment was clinically effective and cost-effective.

Differential expression of inflammatory and anti-inflammatory mediators by M1 and M2 macrophages after photobiomodulation with red or infrared lasers.

In response to stimuli in the microenvironment, macrophages adopt either the M1 or M2 phenotype to coordinate the tissue repair process. Photobiomodulation (PBM) plays an important role in the modulation of acute inflammation, including cellular influx, macrophage polarization, and the release of inflammatory mediators. The aim of the present study was to evaluate the effects of red and infrared PBM on the mRNA expression of cytokines and chemokines in macrophages polarized to the M1 and M2 phenotypes. J774 macrophages activated to induce M1 (lipopolysaccharide + interferon gamma) or M2 (interleukin-4) phenotypes were irradiated with red or infrared PBM (1 J). After 4 and 24 h, gene expression was analyzed by qPCR. PBM at 660 nm decreased the mRNA expression of CCL3, CXCL2, and TNF-α in M1 macrophages and CXCL2 in M2 macrophages 4 h after irradiation. Similarly, PBM at 780 nm decreased mRNA expression levels of CCL3 and IL-6 by M1 macrophages 24 h after irradiation. Moreover, PBM at 780 nm increased the mRNA expression of TGFß1 4 h after irradiation and decreased the expression of this gene after 24 h in M2 macrophages. Although red and infrared PBM were able to modulate and reduce M1/M2a-related markers, infrared laser irradiation promoted a temporal increase in the expression of TGFß1 in M2 macrophages. Thus, depending on the time PBM is used on injured tissue, different parameters can promote optimal results by modulating specific macrophage phenotypes.

The Effects of Photobiomodulation on Inflammatory Infiltrate During Muscle Repair in Advanced-Age Rats.

Photobiomodulation (PBM) enhances muscle repair in aged animals, but its effect on the modulation of the phenotype of immune cells has not yet been determined. Rats (20-month-old) were submitted to cryoinjury of the tibialis anterior muscle and were treated with PBM. After 1, 3, and 7 days, the muscles were submitted to immunohistochemical analysis for the determination of neutrophils and macrophage phenotypes. The muscles treated with PBM exhibited a smaller number of neutrophils after 1 day of treatment and a greater number of both M1 and M2 macrophages after 3 days of treatment. The irradiated tissues exhibited a smaller amount of both macrophage phenotypes after 7 days of treatment. PBM produced temporal alterations in the phenotype of the inflammatory cells during muscle repair process in advanced-age animals, indicating that these mechanisms may contribute to the beneficial effects of this therapy in the treatment of muscle injuries.

Effect of irradiation with intravascular laser on the hemodynamic variables of hypertensive patients: Study protocol for prospective blinded randomized clinical trial.

BACKGROUND: High blood pressure (HBP) is a multifactorial clinical condition, with a high morbidity and mortality rate and low rates of control. Due to its high prevalence, it is necessary to search for methods which aim to improve the quality of life of hypertensive patients. Studies have shown that low level laser therapy (LLLT) is capable of inducing a photobiological response within the cells which modifies the micro and macrovascular response; this accompanies evidence showing the systemic effects of intravascular laser irradiation of blood (ILIB). In the hypothesis that the use of LLLT can influence blood pressure levels, and perhaps facilitate adherence to treatment, this study aims to present a clinical research protocol with the goal of determining the effect of photobiomodulation in relation to changes in the hemodynamic parameters of hypertensive and normotensive patients. METHOD: Forty-four participants, frequent attendees of an ambulatory university clinic, will be subdivided into 4 groups, and then submitted to protocol sessions of ILIB. The technique is noninvasive and consists of a laser which is attached to a bracelet which has been specifically developed for the light beam to be transcutaneously carried over the radial artery. Before the procedure, at the end of the photobiomodulation cycles, and 1 month after the end of therapy, blood samples will be collected for the evaluation of C-reactive protein, interleukin 6, and nitric oxide, to be analyzed by immunoturbidimetric, ELISA, and Griess reactions, respectively. ANALYSIS OF RESULTS: Results will be analyzed using descriptive and inferential statistics and will be compiled into tables and/or graphs, with the help of SPSS version 24.0 with the adopted significance level for all tests being α = 0.05. DISCUSSION: The treatment of HBP involves both pharmacological and nonpharmacological therapy. Animal studies with photobiomodulation have previously shown hypotensive effects. Gaps in the literature exist regarding the applicability of this nonpharmacological therapy in humans. This study aims to consider the possibility of offering nonpharmacological therapy to hypertensive patients with the goal of increasing adherence to the treatment as well as minimizing morbidity and mortality caused by hypertension.

The role of photobiomodulation when associated with microneedling in female pattern hair loss: A randomized, double blind, parallel group, three arm, clinical study protocol.

The female hair loss pattern was originally described as a synonym for androgenetic alopecia. It has been defined as progressive miniaturizations of the hair follicles, with a great impact on the quality of life of affected patients, causing significant psychosocial limitations. It was recently proven that photobiomodulation is a safe and effective way to treat the different types of hair loss. It was also known that microneedling is a minimally invasive dermatological procedure that is applied to a wide range of dermatological conditions, including androgenic alopecia, telogen effluvium, as well as other facial and bodily conditions. GOAL: The aim of this study is to verify if there is an increase in the capillary density of strands of hair, when combining 660 nm red laser photobiomodulation and microneedling in addressing female pattern hair loss (FPHL). METHODS: There will be 66 patients divided into 3 treatment groups. G1: microneedling and 660 nm red laser photobiomodulation sham; G2: 660 nm red laser photobiomodulation and microneedling sham; G3: microneedling and 660 nm red laser photobiomodulation. The treatment will consist in 36 sessions, 3 times a week for 3 consecutive months, with an insertion of microneedling every 30 days. The patients and the researchers will be blinded. The patients will be evaluated before, during, and after the treatments, by digital photography and the trichoscopy method (dermoscopic imaging of the scalp and hair). EXPECTED RESULTS: It is expected that differences will be found in the growth rates of a strand of hair in mm/d, in the density of a strand of hair in n/cm, in the diameter of a strand of hair, as well as in the anagen/telogen ratio. ETHICS AND DISSEMINATION: This protocol was approved by the Research Ethics Committee of the Nove de Julho University, São Paulo, Brazil, on the date of November 28, 2018 (CAAE: 01381718.0.0000.5511 - Acceptance Number: 3044061). This trial has been registered with the Brazilian Registry of Clinical Trials (REBEC TRIAL RBR-76VCCV). This study is not yet recruiting. Issue date: February 20, 2019.

Efficacy of photobiomodulation on oral lichen planus: a protocol study for a double-blind, randomised controlled clinical trial.

INTRODUCTION: Oral lichen planus (OLP) is an idiopathic chronic mucocutaneous disease with a wide range of clinical manifestations, including white reticular patches, erosive/ulcerative and atrophic lesions, both associated with intense symptomatology. Topical corticosteroids are commonly used as standard therapy. However, patients frequently present relapses after the discontinuation of treatment as well as developing resistance to corticosteroid therapy. Photobiomodulation (PBM) has been shown to be a potential therapeutic tool to treat inflammatory disorders, including OLP. The aim of this study was to compare the efficacy of PBM (660 nm) with corticosteroid therapy with clobetasol propionate 0.05% for the treatment of OLP. METHODS AND ANALYSIS: Forty-four patients with symptomatic and histopathological diagnosis of OLP will be randomised into two experimental groups in a double-blind manner: control group (n=22): clobetasol propionate 0.05%+placebo PBM, and experimental group (n=22): PBM (λ=660 nm, power 100 mW, radiant exposure: 177 J/cm2 and 0.5J per point)+placebo gel. Laser will be applied 2×/week for 1 month and clobetasol propionate three times a day for 30 days and the same for placebo treatments. The primary variable (pain) and the secondary variables (clinical score, evaluation of functional scores, clinical resolution, OLP recurrence, quality of life and anxiety and depression) will be evaluated at the baseline, once a week during treatment (depending on the variables) and after 30 days and 60 days of follow-up. Pain will be evaluated using visual analogue scale and clinical characteristics will be scored using the Thongprasom Index. The quality of life and anxiety and depression will be evaluated by Oral Health Impact Profile-14 questionnaire and by Hospital Anxiety and Depression Scale for anxiety scale, respectively. The serum and salivary levels of interleukin (IL)-6, IL-10, IL-1ß, INF-γ and tumour necrosis factor-α will be evaluated by ELISA at baseline and at the end of treatment. ETHICS AND DISSEMINATION: This protocol was approved (#2.375.410) by the Nove de Julho University (UNINOVE) Research Ethics Committee. The data gathered using this protocol will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT03320460.

Evaluation of in-office tooth whitening treatment with violet LED: protocol for a randomised controlled clinical trial.

INTRODUCTION: In-office tooth whitening treatment using violet light emited diode (LED) (405 nm) is a novel bleaching method that causes less sensitivity while offering the same effectiveness as the gold standard (35% hydrogen peroxide, H2O2). This study describes a protocol for the first randomised controlled clinical trial to compare the effects of the two methods. METHODS AND ANALYSIS: Eighty patients will be divided into four groups: G1 violet LED; G2 violet LED +35% carbamide peroxide; G3 35% H2O2 and G4 violet LED +gingivoplasty. Colour will be measured at baseline, immediately after the first session and at the 15 and 180 days follow-up using the Vita Classical and the digital Easyshade V spectrophotometer (Vita, Zahnfabrik, Germany). Sensitivity after whitening will be measured using the Visual Analogue Scale at baseline and at each session in all groups and in all follow-ups. The tissue removed during gingivoplasty (G4) will be submitted to immunohistochemical analysis for the determination of inflammatory changes caused by violet LED. The Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ) will be evaluated before, as well as at established time point controls. The results will be expressed as mean and SD values. After determining the normality of the data, a one-way repeated-measures analysis of variance will be used for the comparison of data with normal distribution and the Kruskal-Wallis test will be used for data with non-normal distribution. A p<0.05 will be considered indicative of statistical significance. After determining the normality of the data, the Kruskal-Wallis test will be used for non-parametric data. Multivariate analysis of variance (MANOVA) and the Wilcoxon test will be used for comparing data from the PIDAQ. ETHICS AND DISSEMINATION: This protocol has been approved by the Human Research Ethics Committee of UniversidadeNove de Julho (certificate: 2.034.518). The findings will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT03192852; Pre-results.

Effect of photobiomodulation treatment in the sublingual, radial artery region, and along the spinal column in individuals with multiple sclerosis: Protocol for a randomized, controlled, double-blind, clinical trial.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease, for which the forms of treatment are medication and rehabilitation. However, in vitro and in vivo studies have demonstrated that photobiomodulation can be an effective treatment modality for inflammatory diseases, including MS. Photobiomodulation has a broad range of benefits, such as the avoidance of cell and tissue death, the stimulation of healing and injury repair, reductions in pain, edema and inflammation, cell proliferation, and even apoptosis. The outcomes of photobiomodulation include the regeneration of cells, the stimulation of the growth of Schwann cells, a reduction in spasticity, functional improvements, a reduction in nitric oxide levels, and the upregulation of the cytokine IL10, demonstrating that this therapeutic modality can offer neuroprotection. METHODS: A randomized, controlled, double-blind, clinical trial is proposed. The patients will be divided into 6 groups. Groups 1 and 2 will receive sham and active photobiomodulation in the sublingual region, respectively. Groups 3 and 4 will receive sham and active photobiomodulation along the spinal cord, respectively. Group 5 will receive placebo treatment with photobiomodulation on the skin in the region of the radial artery with a specific bracelet. Group 6 will be treated with photobiomodulation on the skin in the region of the radial artery. DISCUSSION: Treatment for MS is directed at the immune response and slowing the progression of the disease. This is one of the first clinical trials involving photobiomodulation in the sublingual region and along the spinal cord, which could help establish a promising new form of nonpharmacological treatment for autoimmune diseases. This is one of the first clinical trials with sublingual photobiomodulation and along the spinal cord that could help establish a new form of promising treatment of the disease associated with pharmacological treatment.

Use of low-level laser therapy on children aged 1 to 5 years with energy-protein malnutrition: A clinical trial.

BACKGROUND: Episodes of malnutrition in early childhood can produces alterations in the salivary glands. The investigation of mechanisms that can reduce the impact of malnutrition on the defenses of the organism is of the utmost important and interest to public health. The aim of this study is to evaluate the effect of low-level laser on the saliva of children aged 1 to 5 years with energy-protein malnutrition. METHODS: Mandatory inclusion criteria are diagnosis of malnutrition. The sample will consist of 50 men and women malnourished children aged 12 to 71 months. Saliva will be collected and the volume of saliva will be measured and the salivary flow rate will be determined (mL/min). Concentrations of salivary IgA in all samples will be measured using a commercial Enzyme-Linked Immunosorbent Assay (ELISA) kit. Low-level laser (laser diode) will be administered in the region of the parotid glands bilaterally as well as in the regions of the submandibular and sublingual glands. DISCUSSION: This study will be the first that investigate the effects of local laser therapy on the salivary glands of malnourished children. TRIAL REGISTRATION: Clinical.trials.gov as NCT03355313, first received in 21 November 2017.