Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy.

Low-level laser (light) therapy (LLLT) involves absorption of photons being in the mitochondria of cells leading to improvement in electron transport, increased mitochondrial membrane potential (MMP), and greater ATP production. Low levels of reactive oxygen species (ROS) are produced by LLLT in normal cells that are beneficial. We exposed primary cultured murine cortical neurons to oxidative stressors: hydrogen peroxide, cobalt chloride and rotenone in the presence or absence of LLLT (3 J/cm², CW, 810 nm wavelength laser, 20 mW/cm²). Cell viability was determined by Prestoblue™ assay. ROS in mitochondria was detected using Mito-sox, while ROS in cytoplasm was detected with CellRox™. MMP was measured with tetramethylrhodamine. In normal neurons LLLT elevated MMP and increased ROS. In oxidatively-stressed cells LLLT increased MMP but reduced high ROS levels and protected cultured cortical neurons from death. Although LLLT increases ROS in normal neurons, it reduces ROS in oxidatively-stressed neurons. In both cases MMP is increased. These data may explain how LLLT can reduce clinical oxidative stress in various lesions while increasing ROS in cells in vitro.

Consensus Agreement on the Design and Conduct of Clinical Studies with Low-Level Laser Therapy and Light Therapy for Musculoskeletal Pain and Disorders

Stem cells have attracted the researchers interest, due to their applications in regenerative medicine. Their self-renewal capacity for multipotent differentiation, and immunomodulatory properties make them unique to significantly contribute to tissue repair and regeneration applications. Recently, stem cells have shown increased proliferation when irradiated with low-level laser therapy or Photobiomodulation Therapy (PBMT), which induces the activation of intracellular and extracellular chromophores and the initiation of cellular signaling. The purpose of this study was to evaluate this phenomenon in the literature. The literature investigated the articles written in English in four electronic databases of PubMed, Scopus, Google Scholar and Cochrane up to April 2019. Stem cell was searched by combining the search keyword of "low-level laser therapy" OR "low power laser therapy" OR "low-intensity laser therapy" OR "photobiomodulation therapy" OR "photo biostimulation therapy" OR "LED". In total, 46 articles were eligible for evaluation. Studies demonstrated that red to near-infrared light is absorbed by the mitochondrial respiratory chain. Mitochondria are significant sources of reactive oxygen species (ROS). Mitochondria play an important role in metabolism, energy generation, and are also involved in mediating the effects induced by PBMT. PBMT may result in the increased production of (ROS), nitric oxide (NO), adenosine triphosphate (ATP), and cyclic adenosine monophosphate (cAMP). These changes, in turn, initiate cell proliferation and induce the signal cascade effect. The findings of this review suggest that PBMT-based regenerative medicine could be a useful tool for future advances in tissue engineering and cell therapy.

Near-infrared (NIR) light passes readily through the scalp and skull and a small percentage of incident power density can arrive at the cortical surface in humans.1 The primary photoreceptors for red and NIR light are mitochondria, and cortical neurons are exceptionally rich in mitochondria. It is likely that brain cells are ideally set up to respond to light therapy. The basic biochemical pathways activated by NIR light, e.g., increased adenosine-5′-triphosphate (ATP) production, and signaling pathways activated by reactive oxygen species, nitric oxide release, and increased cyclic adenosine monophosphate (AMP) all work together to produce beneficial effects in brains whose function has been compromised by ischemia, traumatic injury, or neurodegeneration. One of the main mechanisms of action of transcranial light therapy (TLT) is to prevent neurons from dying, when they have been subjected to some sort of hypoxic, traumatic, or toxic insult. This is probably because of light-mediated upregulation of cytoprotective gene products such as anti-oxidant enzymes, heat shock proteins, and anti-apoptotic proteins. Light therapy in vitro has been shown to protect neurons from death caused by methanol,2 cyanide or tetrodotoxin,3 and amyloid beta peptide.4 There is also probably a second mechanism operating in TLT; increased neurogenesis. Neurogenesis is the generation of neuronal precursors and birth of new neural cells.5 Two key sites for adult neurogenesis include the subventricular zone (SVZ) of the lateral ventricles, and the subgranular layer (SGL) of the dentate gyrus in the hippocampus.6 Neurogenesis can be stimulated by physiological factors, such as growth factors and environmental enrichment, and by pathological processes, including ischemia and neurodegeneration.7 Adult neurogenesis (in the hippocampus particularly) is now recognized as a major determinant of brain function both in experimental animals and in humans. Neural progenitor cells in their niche in the SGL of the dentate gyrus give birth to newly formed neurons that are thought to play a role in brain function, particularly in olfaction and in hippocampal-dependent learning and memory.8 In small animal models neurogenesis can be readily detected by incorporation of bromodeoxyuridine (BrdU), injected before euthanasia, into proliferating brain cells. Increased neurogenesis after TLT, has been demonstrated in a rat model of stroke,9 and in the Hamblin laboratory after TLT for acute traumatic brain injury (TBI) in mice (W. Xuan, T. Ando, et al., unpublished data). These two mechanisms of action of TLT in ameliorating brain damage (prevention of neuronal death and increased neurogenesis) have motivated studies in both animals and humans for diverse brain disorders and diseases. TLT for acute stroke is the most developed,10 but acute TBI has also been shown to benefit from TLT.11 These areas are reviewed further.

Low-level light/laser therapy versus photobiomodulation therapy.

Laser (and LED) Therapy Is Phototherapy

The use of mitochondrial nutrients to improve the outcome of infertility treatment in older patients

Energy metabolism of two kinds of stromal fibroblasts differently fuel the development of oral squamous cell carcinoma

Photobiomodulation (PBM) therapy has attracted major interest in the field of tissue engineering as it can enhance stem cell differentiation. It has been shown that PBM therapy can stimulate differentiation of cells in culture by exerting biomodulatory effect. Recent evidences show that PBM therapy can positively modulate dental pulp stem cell (DPSC) properties. Combination of PBM therapy with growth factors and biomaterials can possibly accelerate osteogenic differentiation of dental pulp stem cells. To evaluate the biomodulatory effect of low-level laser dose on dental pulp stem cells in the presence of hydroxyapatite-based scaffold particle for osteogenic differentiation. DPSCs were harvested from human premolar teeth and expanded using mesenchymal stem cell medium. Characterization of DPSCs was done using fluorescence-activated cell sorting with CD105, CD44, CD34, and CD45 markers. Cultured DPSCs along with the N-acetylcysteine-labeled hydroxyapatite (NAC-HA) particles and osteogenic differentiation media were exposed to gallium-aluminum-arsenide (Ga-Al-As) diode laser at 810 nm. Cells were divided into 3 groups: L1 (single exposure), L2 (double exposure), and control (no exposure). Osteodifferentiation after PBM therapy was assessed using Alizarin red S staining, Alkaline phosphatase activity (ALP), and by osteopontin expression. Differences between groups at each time point were analyzed using the Mann–Whitney U test. A level of significance of 5% was adopted (p < 0.05). DPSCs grown on NAC-HA polymers show increased cell adhesion and proliferation. Double irradiated groups were consistent with increased calcium (71%) and alkaline phosphatase activity (75%) when compared with single-irradiated groups. mRNA expression of osteopontin was relatively increased in a significant (p < 0.001) manner in L2 when compared with L1 group. Alizarin red S and ALP positive staining confirmed the presence of calcium deposition in the test samples. The osteopontin expression of L2 (216.681) as compared with L1 (123.276) group prove the efficacy of double exposures over a single dose of PBM therapy. The result envisages the enhanced osteogenic potential of PBM therapy on the differentiation of DPSCs in NAC-HA scaffolds. Double exposure of PBM therapy expresses better biomodulatory effect on DPSCs as compared with the single dose.

Background: Hemiplegic shoulder dysfunction is a common and debilitating complication following stroke, often leading to impaired motor function, chronic pain, and reduced quality of life. Photo biomodulation therapy (PBMT), a non-invasive modality using low-level laser or light therapy, has emerged as a potential intervention for neuromuscular rehabilitation. This systematic review aimed to evaluate the effectiveness of PBMT in improving shoulder muscle activation, motor function, pain reduction, and quality of life in hemiplegic patients. Methods and Materials: A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar databases for studies primarily published between 2014 and 2025. Inclusion criteria were clinical trials, cohort studies, or quasi-experimental studies, and review studies that evaluated PBMT effects on post-stroke hemiplegic patients. A total of eighteen studies were included based on predefined inclusion and exclusion criteria. Data extraction focused on study design, sample size, PBMT parameters, and clinical outcomes. Results: The included studies demonstrated consistent evidence that PBMT significantly enhances shoulder muscle activation, improves motor function, reduces pain, and contributes positively to quality of life. Most studies utilized wavelengths between 650–850 nm with positive therapeutic outcomes and minimal adverse effects. Some variability existed in PBMT protocols and patient populations, but overall findings were favourable. Conclusion: PBMT shows promise as an effective adjunct therapy for improving shoulder function and reducing pain in hemiplegic patients. While current evidence is encouraging, further large-scale studies with standardized protocols are needed to confirm its long-term efficacy and optimize clinical application.

Low-level laser or light therapy (LLLT) or photobiomodulation therapy has been widely investigated for hair growth and recovery in alopecia.This review investigates the documented effects of LLLT on androgenetic alopecia (AGA) by evaluating articles on the treatment of AGA using LLLT published in the past 10 years in the PubMed database.A total of 11 clinical studies were included in the said online database.Despite various parameters and conditions, the clinical trials reported that compared to the control group, applying LLLT to alopecia significantly increases the density, thickness, and number of hairs.In a recent study, the combination of using existing drugs and other treatments with LLTT significantly improved hair loss.

Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit with polymorphic manifestations. The four key elements leading to the formation of acne lesions are alteration of follicular keratinization that leads to comedones, increased and altered sebum production under androgen control, follicular colonization by&nbsp; Propionibacterium acnes , and complex inflammatory mechanisms that involve both innate and acquired immunity. Phototherapy (light, lasers, and photodynamic therapy) has been proposed as an alternative therapeutic modality to treat acne vulgaris and is proposed to have less side effects compared to other treatment options. Recently, low-level laser (light) therapy (LLLT) which refers to the use of red-beam or near-infrared laser with a wave-length between 600 and 1000 nanometers and power from 5 to 500 milliwatts, starts to be used in the treatment of acne. Mechanism of action of LLLT for acne is through photochemical reaction that produces reactive free radicals and singlet oxygen species which in turn lead to bacterial destruction by blue light. Meanwhile, red light can affect the sebum secretion of sebaceous glands, change keratinocytes behavior, and modulate cytokines from macrophages and other cells that reduce inflammation. LLLT is proposed to be effective as an alternative modality for inflammatory type lesions in acne vulgaris. &nbsp; Keywords : acne vulgaris, blue light, low level laser therapy, red light. Normal 0 false false false EN-US X-NONE X-NONE

Objective: To investigate the mechanism by which an 810-nm diode low-level laser (LLL) promotes angiogenesis through activation of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (NRF2-HO-1) signaling pathway, and to provide a theoretical basis for the repair of acute soft-tissue injury. Methods: 1. In vitro experiments, oxidative stress injury in human umbilical vein endothelial cells (HUVECs)was induced by treatment with 100 μmol/L H2O2 for 12 h. The cells were divided into a control group, an H2O2 group, and low-level laser intervention groups. The intervention groups received 810-nm diode laser irradiation at energy densities of 2 J/cm2 (E1 group), 4 J/cm2 (E2 group), and 8 J/cm2 (E3 group). Cell proliferation was assessed using the CCK-8 assay. Cell migration was evaluated using wound-healing and Transwell assays. Tube formation on Matrigel was performed to assess in vitro capillary-like structure formation. Intracellular reactive oxygen species (ROS) levels were measured using the 2', 7'-dichlorodihydrofluorescein diacetate (DCFH-DA) probe, and mitochondrial membrane potential was detected using the JC-1 probe. Immunofluorescence staining was performed to detect NRF2 nuclear translocation and HO-1 expression. 2. In vivo experiments, SPF male Sprague-Dawley rats (200-250 g) were used to establish a full-thickness skin wound model. The rats were randomly divided into a control group and a LLL therapy (LLLT) group. The LLLT group received 810-nm laser irradiation at an energy density of 40 J/cm2 on the wound area, whereas the control group received no laser treatment. Wound area and healing rate were measured using ImageJ software. Histological changes were observed by HE and Masson staining, and angiogenesis was evaluated by CD31 immunofluorescence staining. Results: Compared with the control group, H2O2 treatment significantly decreased the proliferative activity of HUVECs, increased intracellular ROS levels, and reduced mitochondrial membrane potential. After LLL irradiation, cell proliferation increased in all treatment groups compared with the H2O2 group. In particular, the E2 group (4 J/cm2) showed optical density values of 1.24±0.11, 1.43±0.06, and 1.83±0.14 at 24, 48, and 72 h, respectively, which were higher than those in the H2O2 group (P<0.05). The wound-healing assay showed significant differences in migration rates among groups (P<0.001), with the E2 group showing a migration rate of (%56.07±5.61%), compared with (24.83%±4.31%) in the H2O2 group. Transwell assay results also showed significant differences in the number of migrated cells among groups (P<0.001); the E2 group had 74.62±5.98 migrated cells, which was higher than the 20.21±6.55 cells observed in the H2O2 group. Tube formation analysis showed significant differences in the number of tubes among groups (P<0.05), with the E2 group exhibiting 43.95±3.47 tubes compared with 26.74±4.65 in the H2O2 group. ROS levels decreased and mitochondrial membrane potential increased after LLL treatment. Immunofluorescence analysis showed that the NRF2 nuclear/cytoplasmic fluorescence intensity ratio increased to 2.07±0.46 in the LLL group, compared with 1.39±0.26 in the H2O2 group (P<0.05), accompanied by increased HO-1 expression. In the animal experiment, wound healing rates in the LLL group at days 3, 7, and 14 were (37.98±1.14)%, (54.15±6.39)%, and (90.25±2.25)%, respectively, which were higher than those in the control group [(23.16±2.86)%, (34.95±0.39)%, and (77.22±6.01)%] (P<0.05). Histological observation showed increased collagen deposition and more capillary-like structures in the LLL group. Conclusions: 810 nm low-level laser may attenuate H2O2-induced oxidative stress damage in HUVECs by activating the NRF2-HO-1 signaling pathway, thereby improving cell proliferation, migration, and in vitro tube formation capability, as well as promoting acute wound healing in rats.

Pre-conditioning by ischemia, hyperthermia, hypothermia, hyperbaric oxygen (and numerous other modalities) is a rapidly growing area of investigation that is used in pathological conditions where tissue damage may be expected. The damage caused by surgery, heart attack, or stroke can be mitigated by pre-treating the local or distant tissue with low levels of a stress-inducing stimulus, that can induce a protective response against subsequent major damage. Low-level laser (light) therapy (LLLT) has been used for nearly 50 years to enhance tissue healing and to relieve pain, inflammation and swelling. The photons are absorbed in cytochrome(c) oxidase (unit four in the mitochondrial respiratory chain), and this enzyme activation increases electron transport, respiration, oxygen consumption and ATP production. A complex signaling cascade is initiated leading to activation of transcription factors and up- and down-regulation of numerous genes. Recently it has become apparent that LLLT can also be effective if delivered to normal cells or tissue before the actual insult or trauma, in a pre-conditioning mode. Muscles are protected, nerves feel less pain, and LLLT can protect against a subsequent heart attack. These examples point the way to wider use of LLLT as a pre-conditioning modality to prevent pain and increase healing after surgical/medical procedures and possibly to increase athletic performance.

Low-level laser (light) therapy has been used before exercise to increase muscle performance in both experimental animals and in humans. However, uncertainty exists concerning the optimum time to apply the light before exercise. The mechanism of action is thought to be stimulation of mitochondrial respiration in muscles, and to increase adenosine triphosphate (ATP) needed to perform exercise. The goal of this study was to investigate the time course of the increases in mitochondrial membrane potential (MMP) and ATP in myotubes formed from C2C12 mouse muscle cells and exposed to light-emitting diode therapy (LEDT). LEDT employed a cluster of LEDs with 20 red (630 ± 10 nm, 25 mW) and 20 near-infrared (850 ± 10 nm, 50 mW) delivering 28 mW cm(2) for 90 s (2.5 J cm(2)) with analysis at 5 min, 3 h, 6 h and 24 h post-LEDT. LEDT-6 h had the highest MMP, followed by LEDT-3 h, LEDT-24 h, LEDT-5 min and Control with significant differences. The same order (6 h > 3 h > 24 h > 5 min > Control) was found for ATP with significant differences. A good correlation was found (r = 0.89) between MMP and ATP. These data suggest an optimum time window of 3-6 h for LEDT stimulate muscle cells.