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High fluence light emitting diode-generated red light modulates characteristics associated with skin fibrosis.

ABSTRACT: Skin fibrosis, often referred to as skin scarring, is a significant international health problem with limited treatment options. The hallmarks of skin fibrosis are increased fibroblast proliferation, collagen production, and migration speed. Recently published clinical observations indicate that visible red light may improve skin fibrosis. In this study we hypothesize that high-fluence light-emitting diode-generated red light (HF-LED-RL) modulates the key cellular features of skin fibrosis by decreasing cellular proliferation, collagen production, and migration speed of human skin fibroblasts. Herein, we demonstrate that HF-LED-RL increases reactive oxygen species (ROS) generation for up to 4 hours, inhibits fibroblast proliferation without increasing apoptosis, inhibits collagen production, and inhibits migration speed through modulation of the phosphoinositide 3-kinase (PI3K)/Akt pathway. We demonstrate that HF-LED-RL is capable of inhibiting the unifying cellular processes involved in skin fibrosis including fibroblast proliferation, collagen production, and migration speed. These findings suggest that HF-LED-RL may represent a new approach to treat skin fibrosis. LED advantages include low cost, portability, and ease of use. Further characterizing the photobiomodulatory effects of HF-LED-RL on fibroblasts and investigating the anti-fibrotic effects of HF-LED-RL in human subjects may provide new insight into the utility of this therapeutic approach for skin fibrosis.

SUBMITTER: Mamalis A

PROVIDER: S-EPMC5107354 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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High fluence light emitting diode-generated red light modulates characteristics associated with skin fibrosis.

Mamalis Andrew A Koo Eugene E Garcha Manveer M Murphy William J WJ Isseroff R Rivkah RR Jagdeo Jared J

Journal of biophotonics 20160513 11-12

Skin fibrosis, often referred to as skin scarring, is a significant international health problem with limited treatment options. The hallmarks of skin fibrosis are increased fibroblast proliferation, collagen production, and migration speed. Recently published clinical observations indicate that visible red light may improve skin fibrosis. In this study we hypothesize that high-fluence light-emitting diode-generated red light (HF-LED-RL) modulates the key cellular features of skin fibrosis by de ...[more]

PMID: 27174640

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Project description:Skin fibrosis is involved in a variety of pathologic conditions ranging from scar formation secondary to surgery or trauma to immune-mediated processes. Skin fibrosis is a significant international health problem with an estimated incidence of greater than 100 million people affected per year worldwide with few effective treatment options available. Preliminary in vitro data generated by our research group suggests that red light can function as a stand-alone treatment for skin fibrosis. To our knowledge, no prior clinical trials have been performed to determine the safety of high-fluence (dose) light-emitting diode-red light (LED-RL) phototherapy. The goal of this study is to evaluate the safety of LED-RL fluences from 160 J/cm(2) up to 640 J/cm(2) in healthy subjects.This is a single-blind, dose escalation, randomized controlled, phase I study to evaluate the safety of high-fluence LED-RL on human skin. The protocol for dose escalation requires subjects be enrolled sequentially in groups of five. Within each group, three subjects will be randomized to LED-RL phototherapy and two subjects randomized to mock therapy. Subjects in group 1 randomized to LED-RL phototherapy will receive the maximum recommended starting dose (160 J/cm(2)). LED-RL dose will be escalated in subsequent groups (320 J/cm(2), 480 J/cm(2) and 640 J/cm(2)). The maximally tolerated dose (MTD) is defined as the dose level below the dose producing unacceptable but reversible toxicity and is considered to be the upper limit of subject tolerance. After either a MTD has been established, or the study endpoint of 640 J/cm(2) has been achieved, an additional 27 LED-RL phototherapy subjects (for a total of 30) and 18 mock therapy subjects (for a total of 20) (determined randomly) will be enrolled. Each subject will receive a total of nine procedures, three times per week for three consecutive weeks.This study may provide important safety information on the effects of high-fluence LED-RL phototherapy on human skin and help facilitate future phase II studies to evaluate the efficacy of high-fluence LED-RL as a potential noninvasive, safe, portable, at-home therapy for treatment of skin fibrosis.ClinicalTrials.gov NCT02630303 . Registered on 9 December 2015.

Project description: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.

Project description:Supplemental interlighting is commonly used in modern greenhouses to improve light deficiency, but the light spectrum affects fruit quality and color change. This study aimed to analyze the effect of interlighting with red, blue, and additional far-red light on the fruit qualities and carotenoid contents of red and yellow sweet peppers (Capsicum annuum L.). Three light treatments were applied: natural light (NL), NL with red + blue LED interlighting (71 μmol m-2 s-1) (RB), and RB with far-red light (55 μmol m-2 s-1) (RBFR). Ascorbic acid, free sugars, and individual carotenoid content were quantified with HPLC analysis. Fruits were sampled on 2020.11.14 (Group 1) and 2021.01.03 (Group 2) from the plants grown under average light intensities of 335.9 and 105.6 μmol m-2 s-1, respectively. In the overall period, total yields in RB and RBFR were 22 and 33% higher than those in NL in red fruits and 2 and 21% higher in yellow fruits, respectively. In both colored fruits, ascorbic acid, total soluble sugar, and carotenoid content were higher in RB and RBFR than NL. In Group 1, ascorbic acid and total soluble sugar were significantly different between RB and RBFR only in red fruits. In Group 2, ascorbic acids in red and yellow fruits were 9 and 3% higher in RBFR than RB but total soluble sugars were 4 and 2% lower, respectively. Carotenoid contents in red and yellow fruits were 3.0- and 2.1-fold higher in RB and 2.0- and 1.4-fold higher in RBFR than those in NL, respectively. In this study, interlighting had a significant impact on fruit quality in Group 2, mainly due to the increase in the ratio of interlighting to total light by seasonal changes. In particular, red and yellow fruit yields were 9% and 19% higher in RBFR than RB, but carotenoid contents were 26 to 9% lower, respectively. This result exhibited that additional far-red lighting has a trade-off relationship between fruit yield and carotenoid content. Thus, it is necessary to provide an adequate light spectrum according to a specific cultivation purpose, such as improving yield or accumulating plastids in fruits.

Dataset Information

High fluence light emitting diode-generated red light modulates characteristics associated with skin fibrosis.

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High fluence light emitting diode-generated red light modulates characteristics associated with skin fibrosis.

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