Fluorescent light energy (FLE) has been used to treat various injured tissues in a non-pharmacological and non-thermal fashion. It was applied to stimulate cell proliferation, accelerate healing in chronic and acute wounds, and reduce pain and inflammation. FLE has been shown to reduce pro-inflammatory cytokines while promoting an environment conducive to healing. A possible mechanism of action of FLE is linked to regulation of mitochondrial homeostasis. This work aims to investigate the effect of FLE on mitochondrial homeostasis in an in vitro model of inflammation. Confocal microscopy and gene expression profiling were performed on cultures of inflamed human dermal fibroblasts treated with either direct light from a multi-LED lamp, or FLE from either an amorphous gel or sheet hydrogel matrix. Assessment using confocal microscopy revealed mitochondrial fragmentation in inflamed cells, likely due to exposure to inflammatory cytokines, however, mitochondrial networks were restored to normal 24-h after treatment with FLE. Moreover, gene expression analysis found that treatment with FLE resulted in upregulation of uncoupling protein 1 (UCP1) and carnitine palmitoyltransferase 1B (CPT1B) genes, which encode proteins favoring mitochondrial ATP production through oxidative phosphorylation and lipid β-oxidation, respectively. These observations demonstrate a beneficial effect of FLE on mitochondrial homeostasis in inflamed cells.

Introduction The use of photobiomodulation has been proposed to improve wound healing for the last two decades. Recent development in photobiomodulation has led to the development of a novel biophotonic platform that utilizes fluorescent light energy (FLE) within the visible spectrum of light for healing of skin inflammation and wounds. Materials and Methods In this article, FLE was used in preliminary analysis on 18 case studies of acute second-degree burns and in a pilot study using an ex vivo human skin model. Efficacy of FLE on wound healing and tissue remodeling was evaluated by monitoring improvements in the treated tissues, assessing pain for the patients, and by performing human genome microarray analysis of FLE-treated human skin samples. Results Healing was reported for all 18 patients treated with FLE for acute second-degree burns without reported adverse effects or development of infections. Furthermore, preliminary ex vivo skin model data suggest that FLE impacts different cellular pathways including essential immune-modulatory mechanisms. Conclusions The results presented in this article are encouraging and suggest that FLE balances different stages of wound healing, which opens the door to initiating randomized controlled clinical trials for establishing the efficacy of FLE treatment in different phases of wound healing of second-degree burns.

Fluorescent Light Energy (FLE) is a unique form of photobiomodulation that stimulates healing, reduces inflammation, and alleviates pain. The system works by exciting a chromophore in a topical substrate, which emits FLE with a broad spectral range (~400-700 nm) that is delivered to the target tissue below. Results from in vivo and in vitro studies have shown FLE modulates inflammation via down-regulation of pro-inflammatory cytokines such as IL-6 and TNF-α, and stimulates mitochondria biogenesis 1. A recent study showed FLE-stimulated cells responded more potently compared to cells treated with light from an LED light source ("Mimicking Lamp") designed to generate the same emission spectra and power intensity profile as FLE 2. FLE-treated human dermal fibroblasts (HDF) experienced up-regulated collagen production, while a minor and nonsignificant effect was observed for the Mimicking Lamp-treated HDFs. These results suggest that photons generated by FLE either penetrate tissue differently or are absorbed differently compared to photons from a LED light source. Photonic properties of FLE that could impact tissue penetration or absorption may include polarity or coherency, leading to different cellular responses. To investigate if light polarity may influence cellular responses to FLE stimulation, the present study applied linear and circular-polarizing filters to investigate the influence of FLE's polarity on immune parameters. The data suggest that FLE polarity contributes to its impact on biological systems. Furthermore, the immunemodulatory impact of FLE was investgated in a pilot study on a human ex vivo skin model suggesting that central myeloid immune surface markes are modulated by FLE.

A/J mice are resistant while C57BL/6J are susceptible to casein-induced secondary amyloidosis. One mechanism responsible for this phenotypic expression of resistance/susceptibility was shown to operate at the level of production of the 'amyloid-enhancing factor' (AEF). AEF and processing of the apo-SAA protein appear almost concomitantly during amyloidogenesis. In order to determine if AEF played a role in the processing of the apo-SAA protein, three major parameters (apo-SAA1/apo-SAA2 ratios, level of AEF, and fibril formation) were determined during casein-induced secondary amyloidosis. Kinetics of AEF production and serum levels of the two major apo-SAA isotypes were compared in A/J and C57BL/6J animals. Both strains showed equal relative amounts of the two isotypes after seven, 15 and 21 casein injections, irrespective of the fact that the A/J strain had no detectable level of AEF and no amyloid deposition; while C57BL/6J mice had a high AEF level and were amyloidotic after 15 and 21 injections. An increased apo-SAA1/apo-SAA2 ratio due to a decrease in apo-SAA2 was noted after 38 days of casein injections when both strains had extensive deposits of amyloid fibrils. Involvement of AEF as an effector molecule was determined by following the ratio of the two major serum apo-SAA isotypes and fibril formation during an accelerated protocol of amyloid induction in C57BL/6J animals. AEF had no direct effect on apo-SAA isotype ratios in the serum.

Genetic variations in the development of casein-induced amyloidosis exist among inbred strains of mice: CBA/J and C57BL/6J mice are susceptible, while A/J strain mice are resistant to this disease. Amyloidosis is usually induced by daily injections of an inflammatory stimulus for 2-3 wk. The deposition of amyloid in experimental animals can be accelerated by injection of a material called amyloid-enhancing factor (AEF); when injected concomitantly with an inflammatory stimulus, AEF provokes appearance of amyloidosis as early as 2 days after injection. AEF is extracted from amyloid laden or from normal organs (although in small amount). Our studies were designed to determine if the resistance to amyloidosis seen in A/J mice was either due to a lack of AEF production or to an inability of these mice to respond to AEF. A standard source of CBA/J-derived AEF facilitated the development of amyloidosis in the organs of both the susceptible (CBA/J, C57BL/6J) and the resistant A/J mice. On the contrary, amyloidosis was only induced in susceptible CBA/J hosts when material derived from susceptible (CBA/J, C57BL/6J) animals was injected. CBA/J mice injected with A/J-derived AEF preparation did not develop amyloidosis. These results thus suggest that the determination of resistance or susceptibility to secondary amyloidosis could operate at the level of AEF production.