Light-emitting Diode Red Light Research Articles

Web Crawling and mRNA Sequencing Analyze Mechanisms of Photobiomodulation.

Background: Photobiomodulation (PBM) is praised as a promising physical therapy, which has many advantages, such as being noninvasive and painless. However, the mechanisms are not fully elucidated. Methods: Using web crawling, mRNA sequence, and bioinformatics analysis, we selected genes, functional annotation, and mechanisms. The expressions of inflammatory cytokines were measured using quantitative real-time PCR (RT-qPCR). Results: A total of 146 human genes and 57 pathways were identified about PBM. The 630 nm light-emitting diode (LED)-stimulated-MH7A cells were sequenced to further analyze the mechanism of PBM. Two thousand nine hundred fifty differentially expressed genes were identified, and the gene ontology term enrichment analysis and Kyoto encyclopedia of genes and genomes pathway analysis were performed to better understand functions and pathways. The 12 pathways were matched with the KEGG results of PBM and MH7A cells. A protein-protein interaction network was performed among genes in 12 pathways, and 10 outstanding proteins were identified. Importantly, the 9 genes were predicted with potential research value. And we also demonstrated that expression of inflammatory factors [interleukin (IL)-6, IL-1β, IL-8, and matrix metalloproteinase-3 (MMP-3)] was reduced; meanwhile, the expression of anti-inflammatory factor IL-10 was promoted after 630 nm LED. Conclusions: Using web crawling, bioinformatics analysis, and mRNA sequence, we obtained 9 key genes and 12 important pathways about PBM. Importantly, we demonstrated the anti-inflammatory effect of 630 nm LED red light by RT-qPCR.

Light emitting diode-red light for reduction of post-surgical scarring: Results from a dose-ranging, split-face, randomized controlled trial.

Scarring has significant esthetic and functional consequences for patients. A need exists for anti-scarring therapeutics. Light emitting diode-red light (LED-RL) has been shown to modulate skin fibrosis. The aim of this study is to evaluate the safety and efficacy of LED-RL to reduce post-operative scarring. Cutaneous Understanding of Red-light Efficacy on Scarring was a randomized, mock-controlled, single-blind, dose-ranging, split-face phase II clinical trial. Starting 1 week post-surgery, patients received LED-RL irradiation and temperature-controlled mock therapy to incision sites at fluences of 160, 320 or 480 J/cm2 , triweekly for 3 weeks. Efficacy was assessed at 1, 3 and 6-12 months. The primary endpoint was difference in scar pliability between LED-RL-treated and control sites. Secondary outcomes included Patient and Observer Scar Assessment Scale, collagen and water concentration, and adverse events. There were no significant differences in scar pliability between treated and control scars. At certain fluences, treated scars showed greater improvements in observer rating and scar pliability, reflected by greater reductions in induration, from baseline to 6months compared to control scars. Treatment-site adverse events included blistering (n=2) and swelling (n=1), which were mild and resolved without sequelae. LED-RL phototherapy is safe in the early postoperative period and may reduce scarring.

Antifibrotic effects of Hypocrellin A combined with LED red light irradiation on keloid fibroblasts by counteracting the TGF-β/Smad/autophagy/apoptosis signalling pathway.

Keloids are characterized by abnormal proliferation of fibroblasts and continuous deposition of extracellular matrix (ECM) components. In the field of dermopathy, photodynamic therapy (PDT) with visible light has been increasingly investigated. The natural photosensitizer Hypocrellin A (HA) was shown to have excellent light induced anticancer, antimicrobial and antiviral activities. In this experiment, we investigated the impacts of HA united light-emitting diode (LED) red light irradiation on human keloid fibroblast cells (KFs). Our results showed that HA combined with red light irradiation treatment (HA-R-PDT) decreased KF viability, reduced KF collagen production and ECM accumulation, inhibited cell proliferation, suppressed cell invasion and induced cell apoptosis. Moreover, our observations demonstrated that the TGF-β/Smad signalling pathway and autophagy were restrained by HA-R-PDT. TGF-β1 could promote autophagy in KFs through both the Smad and ERK pathways, while inhibition of autophagy altered the TGF-β1 levels through negative feedback. Therefore, HA-R-PDT suppressed cell hyperproliferation, collagen synthesis and ECM accumulation of KFs by regulating the TGF-β1-ERK-autophagy-apoptosis signalling pathway. HA-R-PDT deserves systematic investigation as a potential therapeutic strategy for keloids, and autophagy might be a promising candidate in the treatment of KFs.

Facial rejuvenation using photodynamic therapy with a novel preparation of ALA and hyaluronic acid in young adults

Photodynamic therapy (PDT) is a well-established, non-invasive treatment modality that has shown desirable effects such as improvement of fine lines, dyspigmentation, and other signs of photodamage. Many patients seek to decrease, or reverse, effects of sun damage on the skin. Hyaluronic acid (HA), a naturally occurring glycosaminoglycan found in the body, has enormous potential to bind water which allows the skin to retain moisture and maintain elasticity. Topical application of HA has been found to produce anti-wrinkle effects. We conducted a pilot case series evaluating the safety and efficacy of a commercially available 2% 5-aminolevulinic acid (ALA) gel with hyaluronic acid (ALA-HA) and light-emitting diode-red light (LED-RL) for facial rejuvenation as determined by clinical assessments and digital skin analysis of rhytides, pore size, and erythema. All patients noted improvement of their skin and experienced minimal pain during PDT. Evaluation by dermatologists demonstrated significant improvement in overall skin appearance. Digital analysis of photographs revealed improvement of skin spots, wrinkles, pores, texture, UV spots, brown spots, red areas, and porphyrins. Our findings demonstrated safety and efficacy of this novel preparation of photodynamic gel with HA and subsequent activation with LED-RL.

Safety of light emitting diode-red light on human skin: Two randomized controlled trials.

Therapeutic applications of light emitting diode-red light (LED-RL) are expanding, yet data on its clinical effects are lacking. Our goal was to evaluate the safety of high fluence LED-RL (≥160 J/cm2 ). In two phase I, single-blind, dose escalation, randomized controlled trials, healthy subjects received LED-RL or mock irradiation to the forearm thrice weekly for 3 weeks at fluences of 160-640 J/cm2 for all skin types (STARS 1, n = 60) and at 480-640 J/cm2 for non-Hispanic Caucasians (STARS 2, n = 55). The primary outcome was the incidence of adverse events (AEs). The maximum tolerated dose was the highest fluence that did not elicit predefined AEs. Dose-limiting AEs, including blistering and prolonged erythema, occurred at 480 J/cm2 in STARS 1 (n = 1) and 640 J/cm2 in STARS 2 (n = 2). AEs of transient erythema and hyperpigmentation were mild. No serious AEs occurred. We determined that LED-RL is safe up to 320 J/cm2 for skin of color and 480 J/cm2 for non-Hispanic Caucasian individuals. LED-RL may exert differential cutaneous effects depending on race and ethnicity, with darker skin being more photosensitive. These findings may guide future studies to evaluate the efficacy of LED-RL for the treatment of various diseases.

A dose-ranging, parallel group, split-face, single-blind phase II study of light emitting diode-red light (LED-RL) for skin scarring prevention: study protocol for a randomized controlled trial

BackgroundSkin fibrosis is a significant global health problem that affects over 100 million people annually and has a profoundly negative impact on quality of life. Characterized by excessive fibroblast proliferation and collagen deposition, skin fibrosis underlies a wide spectrum of dermatologic conditions ranging from pathologic scars secondary to injury (e.g., burns, surgery, trauma) to immune-mediated diseases. Effective anti-scarring therapeutics remain an unmet need, underscoring the importance of developing novel approaches to treat and prevent skin fibrosis. Our in vitro data show that light emitting diode-red light (LED-RL) can modulate key cellular and molecular processes involved in skin fibrosis. In two phase I clinical trials (STARS 1 and STARS 2), we demonstrated the safety and tolerability of LED-RL at fluences of 160 J/cm2 up to 480 J/cm2 on normal human skin.Methods/designCURES (Cutaneous Understanding of Red-light Efficacy on Scarring) is a dose-ranging, randomized, parallel group, split-face, single-blind, mock-controlled phase II study to evaluate the efficacy of LED-RL to limit post-surgical skin fibrosis in subjects undergoing elective mini-facelift surgery. Thirty subjects will be randomly allocated to three treatment groups to receive LED-RL phototherapy or temperature-matched mock irradiation (control) to either periauricular incision site at fluences of 160 J/cm2, 320 J/cm2, or 480 J/cm2. Starting one week post-surgery (postoperative days 4–8), treatments will be administered three times weekly for three consecutive weeks, followed by efficacy assessments at 30 days, 3 months, and 6 months. The primary endpoint is the difference in scar pliability between LED-RL-treated and control sites as determined by skin elasticity and induration measurements. Secondary outcomes include clinical and photographic evaluations of scars, 3D skin imaging analysis, histological and molecular analyses, and adverse events.DiscussionLED-RL is a therapeutic modality of increasing importance in dermatology, and has the potential to limit skin fibrosis clinically by decreasing dermal fibroblast activity and collagen production. The administration of LED-RL phototherapy in the early postoperative period may optimize wound healing and prevent excessive scarring. The results from this study may change the current treatment paradigm for fibrotic skin diseases and help to pioneer LED-RL as a safe, non-invasive, cost-effective, portable, at-home therapy for scars.Trial registrationClinicalTrials.gov, NCT03795116. Registered on 20 December 2018.

A single-blind, dose-escalation, phase I study of high-fluence light-emitting diode-red light on Caucasian non-Hispanic skin: study protocol for a randomized controlled trial

BackgroundVisible light (400 to 700 nm) is common in our environment, comprising 44% of total solar radiation and a large component of environmental light exposure. The effects of visible light on skin remain undefined. The red light portion of the visible spectrum (600 to 700 nm) may be used to treat skin diseases as a monotherapeutic modality or in combination with other agents. Light-emitting diode-red light (LED-RL) phototherapy may represent an important advance in light-based treatment modalities because it is non-invasive, inexpensive, portable, and easily combinable with other therapies. We previously determined the maximum tolerated dose (MTD) of high-fluence LED-RL (HF-LED-RL) in skin of color individuals to be 320 J/cm2. To the best of our knowledge, no clinical trials have been performed to determine the safety of higher doses of HF-LED-RL in Caucasian non-Hispanic individuals. The aim of this study is to investigate the safety of HF-LED-RL at doses of 480 and 640 J/cm2 in healthy Caucasian non-Hispanic individuals.MethodsThis is a single-blind, dose-escalation, randomized, controlled, phase I trial titled Safety Trial Assessing Red-light on Skin (STARS) 2. Healthy subjects will be randomly assigned to groups of five (three subjects randomly assigned to HF-LED-RL phototherapy and two subjects randomly assigned to mock therapy). Subjects in group 1 will receive HF-LED-RL or mock irradiation at the starting dose of 480 J/cm2, and the dose will be escalated in the subsequent group (group 2) to 640 J/cm2. The MTD is defined as the dose level below the dose at which two or more subjects (>20% of the cohort) experience a dose-limiting toxicity (DLT). After either the MTD is established or the study endpoint of 640 J/cm2 is achieved, additional HF-LED-RL phototherapy subjects and mock therapy subjects will be enrolled at that fluence (group 3) for a total number of up to 60 subjects. Each subject will receive a total of nine irradiation sessions, three times per week for three consecutive weeks.DiscussionThis follow-up study aims to provide important knowledge about safety and cutaneous effects of HF-LED-RL phototherapy of 480 and 640 J/cm2 in Caucasian non-Hispanic subjects. The importance of this clinical trial is that it may establish new treatment paradigms and a safety profile for LED-RL based on race and ethnicity.Trial registrationClinicalTrials.gov Identifier: NCT03433222. Registered on February 1, 2018 - Retrospectively registered.Protocol date and version: January 12, 2018; version 1.

MicroRNA expression analysis of human skin fibroblasts treated with high-fluence light-emitting diode-red light.

Skin fibrosis is a chronic debilitating feature of several skin diseases that lead to characteristic increases in dermal fibroblast proliferation and collagen deposition through upregulation in components of the transforming growth factor beta (TGF-B)/SMAD pathway. In contrast to ultraviolet phototherapy, high-fluence light-emitting diode-generated red light (HF-LED-RL, 633 ± 15 nm) is a safe, economic and non-invasive therapy with in vitro evidence that supports modulation of the key cellular characteristics involved in the pathogenesis of skin fibrosis. Limited data exists pertaining to the effects of HF-LED-RL on human skin fibroblast microRNA (miRNA). Herein, we explored the effects of HF-LED-RL on fibroblast miRNA levels using RNA-seq and miRNA expression analysis. Using RNA-seq analysis we found that HF-LED-RL at 320 and 640 J/cm2 increased transcription of key miRNA that are involved in skin fibrosis including miRNA-29, miRNA-196a and Let-7a, and decreased transcription of miRNA-21, miRNA-23b and miRNA-31. These microRNA findings provide insight into the molecular underpinnings of HF-LED-RL and highlight potential therapeutic targets of interest for the treatment of skin fibrosis. Additional research on the specific molecular mechanisms underlying HF-LED-RL effects on fibroblasts may provide further mechanistic insight into this therapy and may reveal additional future therapeutic targets for skin fibrosis.

Combination of a 2940 nm Er:YAG laser with recombinant bovine basic fibroblast growth factor (rb-bFGF) and light-emitting diode-red light (LED-RL) for the treatment of striae alba: A pilot study.

Striae distensae (SD) are a common dermatologic problem that plagues many people. Although there are many therapeutic modalities have been used to treat SD, effective method has been disappointing for striae Alba. To evaluate the clinical and histopathologic efficacy and safety of the 2940-nm erbium yttrium aluminum garnet (Er:YAG) ablative fractional laser (AFL) with recombinant bovine basic fibroblast growth factor (rb-bFGF) and light-emitting diode-red light (LED-RL) for the treatment of striae alba. Thirty volunteers with striae distensae alba were enrolled. The subjects completed treatments with the 2940-nm Er:YAG AFL 6 times at 4-week intervals. Following this treatment, the subjects were required to spray rb-BFGF for 1week at home. They then received LED-RL once every 7days for three sessions between the two laser treatments. Two independent investigators evaluated clinical improvement at pretreatment and 1, 3, 6, and 12months post-treatment, patients also provided self-assessments of clinical improvement. Two biopsies were obtained from two subjects, both of the same sites of striae alba, one before the first treatment and one 6months after the last session. All 30 subjects demonstrated clinical improvement after treatment. Skin biopsies after treatment showed an increase in epidermal thickness, dermal thickness, and collagen and elastin density when compared to that at the baseline. The combination of the 2940-nm Er:YAG laser with rb-bFGF and LED-RL for the treatment of striae alba was a safe and effective approach for improving the appearance of striae alba.

Light-emitting diode red light therapy: evidence base for aesthetic indications

Non-invasive approaches to skin rejuvenation, such light-emitting diode (LED) red light therapy, are increasing in popularity owing to their affordability, effective treatment outcomes and minimal downtime. In contrast to traumatic ablative (e.g. laser resurfacing) and non-ablative (e.g. intense pulsed light) skin rejuvenation modalities, which induce secondary tissue repair by causing controlled damage to the epidermis or dermis, LED red light therapy is atraumatic and bypasses the initial destructive step by directly stimulating regenerative processes in the skin. Its mechanisms of action encompass increased cellular proliferation, as well as stimulation of tissue regeneration, through targeting fibroblasts, keratinocytes and immune cells (mast cells, neutrophils and macrophages), which can be stimulated using specific wavelengths with significant tissue penetration properties. A growing body of literature supports the safe use of this treatment modality in aesthetic medicine.

Neuroglobin – A potential biological marker of retinal damage induced by LED light

Neuroglobin (NGB), a protein highly expressed in the retina, has been shown to be up-regulated to protect neurons from hypoxic and ischemic injuries. It exhibits neuroprotective functions and plays an important role in the survival of neurons. Recent studies show that light-emitting diode (LED) white light emitted significant amounts of blue light (short-wavelength), which may be harmful to retinal cells, but the studies about biomarkers for evaluating the damage from LED white light are still insufficient. In our study, we found that NGB levels in the retina showed a twofold increase and peaked at 1h after a 1-h exposure to blue light (453nm) which did not cause damage to the retina. However, retinal damage was observed after 2h of blue-light irradiation, which induced an approximate sevenfold increase of NGB levels as confirmed by Western blot and RT-PCR analysis. Immunofluorescence study demonstrated that NGB was predominantly up-regulated in the ganglion cell layer (GCL), plexiform layer (PL) and photoreceptor layer (PRL). We also examined Ngb mRNA and protein expression in the damaged retina induced by light of other wavelengths given equal photon fluxes. The LED red light (625nm), green light (527nm) and blue light (453nm) increased the expression of NGB and caused TdT-mediated dUTP nick-end labeling-positive cells, especially in the blue-light group. In addition, a negative correlation between NGB and rhodopsin was observed. These findings suggested that there was a correlation between NGB expression and the severity of the retinal damage, indicating NGB’s potential function as a biological marker of retinal damage induced by LED light.

Comments on: Red light of 647 nm enhances osteogenic differentiation in mesenchymal stem cells

Dear Editors, We read the article “Red light of 647 nm enhances osteogenic differentiation in mesenchymal stem cells.” by Kim et al. [1]. The authors reported that they irradiated the cells in 96-well microplates to assay the cell proliferation with methyl-tetra-zolium (MTT). They showed that compared with the control group, the irradiated cells did not proliferate significantly. However, the authors did not explain this clearly in their article. From our point of view, there may be two flaws in the experimental design. Firstly, the distribution of the light energy density from the light-emitting diode (LED) is not uniform (Fig. 1). Therefore it is very possible that the energy dosages absorbed by different wells were significantly different. From this point of view, the result of MTT assay should not be able to reflect the real proliferation effect of cells irradiated by LED red light. In order to confirm our concern, we designed a simple experiment. We used a light power meter (Model SGN-2, Gangdong Co., Ltd, Tianjin, China) to measure the power density of a red light LED (632.8 nm, 45° viewing angle). The distance between the LED and the light power meter was 3 cm, as reported in Ref. [1]. At the central point of the light spot, the power density was 2.46mW/cm. At the points 0.5 cm, 1.0 cm, and 1.5 cm away from the central point, the corresponding power densities were 1.06±0.55 mW/cm, 0.34±0.20 mW/cm, and 0.06±0.02 mW/cm, respectively. The differences were significant(P<0.05, n=4). According to our experiment, a single LED is unsuitable to be used as a light source to irradiate the wells in microplates at the same time. The LED array may even not be an ideal light source for such an experiment even though it is possible to generate interference by monochromatic lights emitted by LED array. How did the authors guarantee that all wells received the same energy? More details are necessary about their experiment. Secondly, the authors reported that MTT assay was applied 48 h after the cells were irradiated [1]. According to the report of Ozawa et al. [2], significant proliferation should occur on the sixth day after irradiation. It does not make any sense to assay cell proliferation only 48 h after

Successful treatment of an extensive verrucous carcinoma with topical 5‐aminolevulinic acid‐mediated photodynamic therapy

Our recent study found that a new topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) protocol composed of multiple 3-min fractionated irradiations with a light emitting diode (LED) red light at 635 +/- 5 nm for a total of 1000 s (fluence rate: 100 mW/cm(2); light exposure dose: 100 J/cm(2)) after topical application of 20% ALA for 1.5 or 2 h can be used successfully for the treatment of oral verrucous hyperplasia. In this case report, we tested the efficacy of this new treatment protocol of ALA-PDT for an extraoral verrucous carcinoma (VC) lesion at the right mouth angle and an intraoral VC lesion at the right buccal mucosa of a 56-year-old male areca quid chewer and smoker. The extraoral tumor was cleared after six treatments of topical ALA-PDT and the intraoral tumor showed complete regression after 22 treatments of topical ALA-PDT. No recurrence of the VC lesion was found after a follow-up period of 6 months. We suggest that PDT using a topical application of 20% ALA followed by multiple 3-min fractionated irradiations with an LED red light is also an effective and successful treatment modality for VC.

Successful treatment of oral verrucous hyperplasia with topical 5-aminolevulinic acid-mediated photodynamic therapy

Previous studies have shown a selective accumulation of 5-aminolevulinic acid (ALA)-derived protoporphrin IX (PpIX) in oral premalignant and malignant tissues. This provides a biologic rationale for the clinical use of ALA-mediated PDT (ALA-PDT) for oral premalignant and malignant lesions. In this study, five patients with oral verrucous hyperplasia (OVH) were treated with a new protocol of ALA-PDT composed of multiple 3-min irradiations with a light emitting diode (LED) red light at 635 ± 5 nm separated with several 3-min rests for a total of 1000 s (fluence rate, 100 mW/cm 2; light exposure dose, 100 J/cm 2) after topical application of 20% ALA for 1.5 or 2 h. Topical ALA-PDT was repeated once a week until the complete regression of the lesion. Complete regression of all OVH lesions was observed after 1–3 treatments (average, 2 treatments) of topical ALA-PDT. At an average follow-up of 5.6 months (range, 3–11 months), all the five OVH patients were free of tumor recurrence. We conclude that topical ALA-PDT with fractionated irradiations by an LED red light at 635 ± 5 nm is an effective and successful treatment modality for OVH.