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Photobiomodulation (PBM) is a procedure that uses light to modulate cellular functions and biological processes. Over the past decades, PBM has gained considerable attention for its potential in various medical applications due to its non-invasive nature and minimal side effects. We conducted a narrative review including articles about photobiomodulation, LED light therapy or low-level laser therapy and their applications on dermatology published over the last 6 years, encompassing research studies, clinical trials, and technological developments. This review highlights the mechanisms of action underlying PBM, including the interaction with cellular chromophores and the activation of intracellular signaling pathways. The evidence from clinical trials and experimental studies to evaluate the efficacy of PBM in clinical practice is summarized with a special emphasis on dermatology. Furthermore, advancements in PBM technology, such as novel light sources and treatment protocols, are discussed in the context of optimizing therapeutic outcomes and improving patient care. This narrative review underscores the promising role of PBM as a non-invasive therapeutic approach with broad clinical applicability. Despite the need for further research to develop standard protocols, PBM holds great potential for addressing a wide range of medical conditions and enhancing patient outcomes in modern healthcare practice.

This study is preliminary to an experiment to be performed onboard the International Space Station (ISS) and on Earth to investigate how low gravity influences the healing of sutured human skin and vein wounds. Its objective was to ascertain whether these tissue explants could be maintained to be viable ex vivo for long periods of time, mimicking the experimental conditions onboard the ISS. We developed an automated tissue culture chamber, reproducing and monitoring the physiological tensile forces over time, and a culture medium enriched with serelaxin (60 ng/mL) and (Zn(PipNONO)Cl) (28 ng/mL), known to extend viability of explanted organs for transplantation. The results show that the human skin and vein specimens remained viable for more than 4 weeks, with no substantial signs of damage in their tissues and cells. As a further clue about cell viability, some typical events associated with wound repair were observed in the tissue areas close to the wound, namely remodeling of collagen fibers in the papillary dermis and of elastic fibers in the vein wall, proliferation of keratinocyte stem cells, and expression of the endothelial functional markers eNOS and FGF-2. These findings validate the suitability of this new ex vivo organ culture system for wound healing studies, not only for the scheduled space experiment but also for applications on Earth, such as drug discovery purposes.

The healing process of superficial skin wounds treated with a blue-LED haemostatic device is studied. Four mechanical abrasions are produced on the back of 10 Sprague Dawley rats: two are treated with the blue-LED device, while the other two are left to naturally recover. Visual observations, non-linear microscopic imaging, as well as histology and immunofluorescence analyses are performed 8 days after the treatment, demonstrating no adverse reactions neither thermal damages in both abraded areas and surrounding tissue. A faster healing process and a better-recovered skin morphology are observed: the treated wounds show a reduced inflammatory response and a higher collagen content. Blue LED induced photothermal effect on superficial abrasions., (© 2016 The Authors. Journal of Biophotonics published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Experimental evidence suggested that Exendin-4 (Exe4), an agonist at glucagon like receptor-1 (GLP-1R), promoted tissue regeneration. We aimed to verify the effect of Exe4, in the absence or in the presence of Exendin-4(9-39), an antagonist at GLP-1R, on the healing of abraded skin. Two wounds (approximately 1.1×1.1 cm(2); namely "upper" and "lower" in respect of the head) were produced by abrasion on the back of 12 mice, which were then randomly assigned to receive an intradermal injection (20 μl) of Group 1: saline (NT) or Exe4 (62 ng) in the upper and lower wound respectively; Group 2: Exendin-4(9-39) (70 ng) in the upper and Exendin-4(9-39) (70 ng) and, after 15 min, Exe4 (62 ng) in the lower wound. Wounds were measured at the time of abrasion (T0) and 144 h (T3) afterward taking pictures with a ruler and by using a software. The inflammatory cell infiltrate, fibroblasts/myofibroblasts, endothelial cells and GLP-1R expression, were each labeled by immunofluorescence in each wound, pERK1/2 was evaluated by Western-blot in wound lysates. At T3, the percentage of healing surface was 53% and 92% for NT and Exe4 wounds respectively and 68% and 79% for those treated with Exendin-4(9-39) and Exendin-4(9-39)+Exe4 respectively. Exe4, but not Exendin-4(9-39) induced quantitative increase in fibroblasts/myofibroblasts and vessel density when compared to NT wounds. This increase was not evident in wounds treated with Exendin-4(9-39)+Exe4. Exe4 promotes wound healing opening to the possible dermatological use of this incretin analogue., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The response to wounds until healing requires the activity of many cell types coordinate in space and time, so that the types of cells in a wound and their localization may be of help to date lesions with respect to death, which would be useful in forensic pathology. Cells reacting to injury include dendritic cells; the early reaction of these cells to skin wounding has not yet been investigated in humans, which was the aim of this study. Samples of wounded and control skin were taken at autopsy and analyzed by affinity histochemistry. Both epidermal and dermal MHC-II+ cells increased transiently in number within the first hour after wounding, then decreased. In the epidermis the increase affected also CD1a+ cells, i.e. well differentiated Langherhans cells, which however increased less, earlier and for a shorter time period than MHC-II+ cells. Dermal MHC-II+ cells became part of a perivascular mononuclear cell infiltrate visible in the subpapillary dermis by 60 min after wounding, which contained also mast cells. The immediately perivascular MHC-II+ cells were DC-SIGN- and CD11c-, while MHC-II+, DC-SIGN+, CD11c+ dendritic cells were predominantly located at the periphery of infiltrates and some were near the epidermis. Mast cells underwent degranulation, besides increase in number, in the first hours after wounding. The results suggest that skin dendritic cells, including Langerhans cells, participate to the early response to wounding in concert with mast cells, and that subpapillary blood vessels are primary sites of cell infiltration during that response in humans. The results show that the ratio between CD1a positive and MHC-II positive cells in the epidermis, the degranulation index of mast cells and the relative volume of MHC-II positive cells in the dermis can be added to the tools useful to distinguish vital from post mortem lesions and, the first two of them, to estimate the interval between a lesion and death., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Mast cell histochemistry has been proposed in addition to classic histological methods to estimate the course of traumatic events before and after death. We have addressed the utility of this approach on nine victims of different types of trauma. Sections of wounded skin were stained with hematoxylin and eosin and with fluorescent avidin to tag mast cells. Mast cell numbers were evaluated by both direct and digitalized counts. Intact skin was used as control. The results on mast cells implemented the findings upon hematoxylin and eosin stain and helped to put the wounds and death in chronological sequence. Digitalized morphometry allowed to reduce intra- and inter-observer variation. We conclude that combined histological and histochemical analyses can be of practical use in forensic pathology, that a preliminary setting of the reference values is needed for each laboratory, and that image analysis can be of help for the quantification of the results., (© 2011 American Academy of Forensic Sciences.)

Langerhans cells are a dendritic cell type characteristic of the epidermis. Since mast cells secrete molecules potentially influent on dendritic cell differentiation, we have addressed the degree of proximity between these two cell types in biopsies of skin diseases characterized by massive influx of dendritic cell precursors. By fluorescence microscopy, avidin labeled mast cells were found in contact with CD1a+ dendritic cells. By electron microscopy, contacts between mast cells and blunty dendritic cells were found in areas corresponding to those where CD1a+ cells were localized by immunohistochemistry. We propose that mast cells can induce the differentiation of precursors into Langerhans cells through both the release of short range acting soluble factors and contact-mediating plasma membrane molecules.

We have evaluated the numbers and immunohistochemical positivity for tumor necrosis factor (TNF) alpha of the mast cells in (a) 40 skin samples collected at autopsy from subjects who had survived for a few seconds to 1 h, (b) 10 samples of post-mortem skin lesions and (c) 10 surgical biopsies of healthy skin. Sections were treated with fluoresceinated avidin, to tag mast cell granules, followed by indirect immunohistochemistry for TNF-alpha with polyclonal primary and rhodaminated secondary antibodies. We could confirm a progressive increase in mast cell numbers, which became significant 1 h after trauma. More important, the fraction of mast cells positive for TNF-alpha increased progressively in the same time period and became significantly higher than controls in specimens collected more than 15 min after trauma. Samples from post-mortem lesions had significantly fewer mast cells and fewer TNF-alpha-positive cells than any other group of samples. The results suggest that mast cells are quickly recruited to an injured site in response to trauma and upregulate their TNF-alpha content, which can play an early role in directing tissue response to injury. The forensic pathologist can take advantage from this behavior of mast cells for the evaluation of the timing of early vital lesions.

The histamine content in vital wounds is known to increase, with a zenith after 3 h, and then decrease until 24 h after wounding. We addressed whether this biochemical alteration has a morphological counterpart. Since the main source of skin histamine are mast cells, the distribution and number of these cells was assessed upon labeling with fluorescent avidin and with antibodies to the mast cell specific enzymes, chymase and tryptase. Analyses were performed on skin from 15 healthy controls (from surgical biopsies), from 15 post-mortem lesions and 75 vital lesions, obtained at autopsy from subjects who had survived from a few seconds to 24 h. The number of mast cells per unit area of section surface increased progressively with survival time, up to a maximum in subjects who survived 1-3 h ( p<0.01), and decreased thereafter becoming less than in the controls if lesions had occurred earlier than 6 h before death ( p<0.01). Samples from post-mortem lesions had significantly fewer mast cells than those of any other groups of samples ( p<0.01). We suggest that in association to other histological and circumstantial evidence the analysis of mast cells by affinity cytochemistry can help to discriminate vital from post-mortem lesions and to estimate survival time after lesions.

Langerhans cells (LC) play a critical role in the induction of contact hypersensitivity (CH), and ultraviolet B radiation (UVR) impairs CH induction in UVB-susceptible (UVB-S) mice via a TNF-alpha-dependent mechanism. A possible explanation of this effect is that UVR impairs CH in UVB-S mice by immobilizing LC transiently in the epidermis and upper dermis, thereby preventing their timely migration to draining lymph nodes. To test this hypothesis we examined in vitro and in vivo the effects of in vivo UVR on migration of Ia(+) cells from skin of UVB-S and UVB-resistant (UVB-R) mice. Dorsal surfaces of ears of mice were irradiated with 400 J/cm(2) UVB and either explanted in vitro or transplanted orthotopically to the thoracic wall of syngeneic recipients. After 24, 48, and 72 h the epidermis was recovered from these explants/grafts and the number of Ia(+) cells determined by immunohistochemistry. Culture medium obtained after explants were removed was also evaluated for content of Ia(+) cells. The density of Ia(+)-bearing cells in the epidermis of cultured untreated skin explants and of grafted skin fell progressively for both UVB-S and UVB-R skin during the observation period. The rate of decline in Ia(+) cells density during this interval was greatly impaired if the skin was exposed to UVR prior to excision; this effect was seen equally in UVB-S and UVB-R skin. Recovery of Ia(+) cells in the medium after removal of cultured untreated skin explants was maximum after 24 h and comparable in UVB-S and UVB-R skin. However, the number of Ia(+) cells recovered in the medium from UVB-exposed skin was significantly reduced only if the skin donor was UVB-S. We conclude that the ability of UVR to impede LC migration from epidermis is significantly greater for UVB-S mice, accounting in part for the failure of these mice after UVR to acquire CH.

In the induction of contact hypersensitivity (CH) to an epicutaneously applied hapten, we have previously proposed that low doses of hapten sensitize primarily through epidermal Langerhans' cells (LC), whereas high doses rely largely on dermal antigen-presenting cells (APC). To examine this issue further, we applied either high or low doses of dinitrofluorobenzene (DNFB) epicutaneously to mice. We observed reduced LC density at the site after 12 h (nadir), which returned to normal levels at 24 h only after a low dose of hapten. When a low dose of an unrelated hapten, oxazolone, was painted on skin that had been painted 12 h previously with high dose of DNFB, oxazolone-specific CH was impaired. When grafts of whole skin, dermis alone, and epidermis alone prepared from skin painted 2 h previously with low or high doses of DNFB were placed onto naive, syngeneic mice, CH was induced by whole skin after both types of doses, by epidermis only after a low dose, and by dermis only after high dose. When epidermal cell suspensions were derivatized in vitro with low or high doses of DNFB, only cells exposed to a low dose induced proliferation of hapten-specific Tcells. Thus, only a low dose of hapten reveals the APC functions of LC without the participation of dermal APC.

Background: Progressive pigmented purpura (Schamberg's disease), a form of purpura pigmentosa chronica, is a lymphocytic capillaritis of unknown etiology and obscure pathogenesis. Our purpose was to assess the expression of cell membrane antigens (CD3, CD4, CD1a, CD36), of adhesion receptors (leukocyte function adhesion 1, LFA-1, endothelial leukocyte adhesion molecule 1, ELAM-1) intercellular adhesion molecule 1, ICAM-1), and the intercellular relationships in the early phase of the disease., Methods: Quantitative immunohistochemistry and electron-microscopy were performed on specimens of five subjects, aged 45 to 63 years. These studies were repeated in two patients after treatment with topical corticosteroid (betamethasone valerate cream 0.1%) and psoralen-ultraviolet A (PUVA)., Results: The infiltrate consisted mainly of CD4+ lymphocytes and CD1a+ dendritic cells. Electron-microscopic investigation showed typical lymphocytes and two distinct types of dendritic cells. In the very early phase of the disease the adhesion receptors LFA-1 and ICAM-1 were expressed intensely by all infiltrating cells; the adhesion receptors ICAM-1 and ELAM-1 were expressed by endothelial cells. Close contact occurred between lymphocytes and dendritic cells. After PUVA (120 J per cm2) and topical steroid therapy the infiltrate disappeared completely., Conclusions: These data suggest that a cell-mediated immune mechanism may be important in progressive pigmented purpura and that the early endothelial expression of adhesion receptors may determine the pattern of organization of the pericapillary infiltrate.