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Olszewska A, Wolny M, Kensy J, Kotela A, Czajka-Jakubowska A, Matys J. Photobiomodulation Therapy for Neurosensory Disturbances in Orthognathic Surgery Patients: A Systematic Review. Life (Basel) 2025; 15:111. [PMID: 39860051 PMCID: PMC11767050 DOI: 10.3390/life15010111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 01/10/2025] [Accepted: 01/14/2025] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND Sensory disturbances and acquired paresthesia constitute a significant proportion of complications following orthognathic surgery. This systematic review examines the application of photobiomodulation (PBM) in managing these complications and its efficacy in promoting sensory recovery. METHODS In November 2024, a comprehensive digital search was performed across reputable databases, including PubMed, Web of Science, and Scopus, using carefully selected search terms: "orthognathic surgery" AND (physiotherapy OR physical therapy OR laser OR LLLT OR PBM OR light OR LED OR acupuncture) AND (nerve OR neurosensory OR paresthesia). The search adhered to the PRISMA guidelines. Of the 424 articles initially identified, 14 met the inclusion criteria and were included in the review. RESULTS The review focused on diode laser therapy for treating inferior alveolar nerve injuries, with most studies targeting this nerve and exploring diverse wavelengths, protocols, and surgical contexts, including orthognathic surgeries. Significant improvements were observed in tactile sensitivity, pain perception, and mechanical responsiveness. Factors such as earlier initiation of therapy, younger patient age, and higher treatment frequency were associated with improved outcomes. CONCLUSIONS Low-level laser therapy emerges as a safe and effective intervention for enhancing neurosensory recovery following orthognathic surgery. However, the development of standardized treatment protocols and the conduct of larger-scale clinical trials are essential to optimize their clinical application.
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Affiliation(s)
- Aneta Olszewska
- Department of Orthodontics and Temporomandibular Disorders, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (A.O.); (M.W.); (A.C.-J.)
| | - Mateusz Wolny
- Department of Orthodontics and Temporomandibular Disorders, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (A.O.); (M.W.); (A.C.-J.)
| | - Julia Kensy
- Faculty of Dentistry, Wroclaw Medical University, 50-425 Wroclaw, Poland;
| | - Agnieszka Kotela
- Medical Center of Innovation, Wroclaw Medical University, Krakowska 26, 50-425 Wroclaw, Poland;
| | - Agata Czajka-Jakubowska
- Department of Orthodontics and Temporomandibular Disorders, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (A.O.); (M.W.); (A.C.-J.)
| | - Jacek Matys
- Department of Dental Surgery, Wroclaw Medical University, 50-425 Wroclaw, Poland
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Rodriguez DA, Song A, Bhatnagar A, Weng CY. Photobiomodulation Therapy for Non-exudative Age-related Macular Degeneration. Int Ophthalmol Clin 2025; 65:47-52. [PMID: 39710905 DOI: 10.1097/iio.0000000000000543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2024]
Abstract
Age-related macular degeneration (AMD) is a chronic condition that causes gradual central vision loss, most commonly in patients 50 years or older. This disease is commonly classified as either dry (non-exudative) or wet (exudative). Most patients with AMD have the non-exudative form, characterized by the presence of drusen in the macula. These patients can be further subclassified based on drusen size into early, intermediate, or late stages. The pathogenesis of this disease is quite complex and has been linked to genetic variations, dysfunction of normal retinal homeostasis, chronic inflammation, and mitochondrial dysfunction. Current treatment options for patients with intermediate dry AMD are limited to lifestyle modifications and vitamin supplementation. Photobiomodulation therapy (PBT) has been proposed as an additional therapy for this disease. Early animal and human studies have shown that PBT can alter many of the pathways implicated in the pathogenesis of AMD including improving mitochondrial function, decreasing inflammation, and promoting wound healing. Clinical trials investigating the use of PBT in patients with non-exudative AMD have shown promising results. Many of these trials showed improvement in both clinical (visual acuity and contrast sensitivity) as well as anatomic (drusen volume and area geographic atrophy) variables. Most, however, are limited by sample size, differences in treatment algorithm, and populations tested. Ongoing clinical trials aim to expand on this work with longer follow-up, larger sample sizes, and studying a global population. Further work is needed to determine ideal treatment algorithms and patient populations that may benefit the most from this technology.
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Affiliation(s)
- Daniel A Rodriguez
- Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas
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Wang K, Zhao H, Zhao X, Zhang X, Zhang W, Cheng Y, Ge J. Photobiomodulation for diabetes and its complications: a review of general presentation, mechanisms and efficacy. Ann Med 2024; 56:2433684. [PMID: 39607829 PMCID: PMC11610354 DOI: 10.1080/07853890.2024.2433684] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 06/12/2024] [Accepted: 08/01/2024] [Indexed: 11/30/2024] Open
Abstract
Diabetes mellitus is a metabolic disease that is marked by persistent hyperglycemia due to inadequate insulin secretion or insulin resistance. Its prevalence is increasing yearly. Diabetes mellitus can lead to serious health complications that are the primary cause of mortality and disability among diabetic patients, including diabetic retinopathy, diabetic foot ulcers, diabetic peripheral neuropathy, and diabetic periodontitis, and so on. Traditional treatments for diabetes and its complications still suffer from limited clinical efficacy and high therapeutic side effects. Photobiomodulation (PBM), which utilizes low levels of red or near-infrared laser to irradiate cells and tissues, has been shown to be efficacious for a wide range of organ damage. In this study, we focus on the application of PBM in diabetes and its complications and mechanisms, as well as the advantages, disadvantages with the aim of developing new ideas for the application of PBM.
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Affiliation(s)
- Keyan Wang
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, China
- Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun, China
- China Japan Union Hospital of Jilin University, Changchun, China
| | - Hongwei Zhao
- Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun, China
| | - Xiaoqing Zhao
- China Japan Union Hospital of Jilin University, Changchun, China
| | - Xiaoyu Zhang
- China Japan Union Hospital of Jilin University, Changchun, China
| | - Wei Zhang
- Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun, China
| | - Yan Cheng
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, China
| | - Jingyan Ge
- Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun, China
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4
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Habib L, Michael-Jubeli R, Abboud M, Lteif R, Tfayli A. Impact of blue light on cutaneous barrier structures and properties: NPLC/HR-MS n and Raman analyses. Analyst 2024; 149:5693-5703. [PMID: 39498767 DOI: 10.1039/d4an01244e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2024]
Abstract
Skin health relies heavily on a well-maintained cutaneous barrier. While the detrimental effects of UV radiation on the epidermis are established, the impact of blue light, a significant component of sunlight and artificial sources, is less clear. This study aims to explore blue light's influence on the reconstructed human epidermis (RHE) using two complementary analytical approaches: Raman microspectroscopy and normal phase liquid chromatography coupled with high-resolution mass spectrometry (NPLC/HR-MSn). RHE samples were exposed to blue light (415 nm and 455 nm) during different stages of their maturation. Raman spectra were acquired for both irradiated and non-irradiated (control) samples. Raman descriptors were analyzed to assess potential alterations in the structural organization of proteins and lipids' conformational changes. Additionally, lipids from RHE samples were extracted and analyzed using NPLC/HR-MSn. Blue light exposure led to changes in the structural organization of RHE lipids and proteins, as well as changes in the lipid composition. These changes varied depending on the wavelength and exposure dose. Exposure to blue light could disrupt the integrity of the skin's protective barrier, leading to increased sensitivity to environmental stressors and potential skin damage.
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Affiliation(s)
- Léa Habib
- Interdisciplinary Unit: Lipids, Analytical and Biological Systems Lip(Sys)2, Faculty of Pharmacy, Université Paris-Saclay, F-91400 Orsay, France.
- Laboratoire d'étude cinétique en milieu hétérogène (LECH), Saint Joseph University, Campus des Sciences et Technologies, Mar Roukos, Mkallès, P.O Box 11-514, Riad El Solh, 1107 2050 Beirut, Lebanon
| | - Rime Michael-Jubeli
- Interdisciplinary Unit: Lipids, Analytical and Biological Systems Lip(Sys)2, Faculty of Pharmacy, Université Paris-Saclay, F-91400 Orsay, France.
| | - Marie Abboud
- Physics department, UR TVA, Faculty of science, Saint Joseph University, B.P. 11-514-Riad El Solh, 1107 2050 Beirut, Lebanon
| | - Roger Lteif
- Laboratoire d'étude cinétique en milieu hétérogène (LECH), Saint Joseph University, Campus des Sciences et Technologies, Mar Roukos, Mkallès, P.O Box 11-514, Riad El Solh, 1107 2050 Beirut, Lebanon
| | - Ali Tfayli
- Interdisciplinary Unit: Lipids, Analytical and Biological Systems Lip(Sys)2, Faculty of Pharmacy, Université Paris-Saclay, F-91400 Orsay, France.
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Selestin Raja I, Kim C, Oh N, Park JH, Hong SW, Kang MS, Mao C, Han DW. Tailoring photobiomodulation to enhance tissue regeneration. Biomaterials 2024; 309:122623. [PMID: 38797121 DOI: 10.1016/j.biomaterials.2024.122623] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 04/25/2024] [Accepted: 05/19/2024] [Indexed: 05/29/2024]
Abstract
Photobiomodulation (PBM), the use of biocompatible tissue-penetrating light to interact with intracellular chromophores to modulate the fates of cells and tissues, has emerged as a promising non-invasive approach to enhancing tissue regeneration. Unlike photodynamic or photothermal therapies that require the use of photothermal agents or photosensitizers, PBM treatment does not need external agents. With its non-harmful nature, PBM has demonstrated efficacy in enhancing molecular secretions and cellular functions relevant to tissue regeneration. The utilization of low-level light from various sources in PBM targets cytochrome c oxidase, leading to increased synthesis of adenosine triphosphate, induction of growth factor secretion, activation of signaling pathways, and promotion of direct or indirect gene expression. When integrated with stem cell populations, bioactive molecules or nanoparticles, or biomaterial scaffolds, PBM proves effective in significantly improving tissue regeneration. This review consolidates findings from in vitro, in vivo, and human clinical outcomes of both PBM alone and PBM-combined therapies in tissue regeneration applications. It encompasses the background of PBM invention, optimization of PBM parameters (such as wavelength, irradiation, and exposure time), and understanding of the mechanisms for PBM to enhance tissue regeneration. The comprehensive exploration concludes with insights into future directions and perspectives for the tissue regeneration applications of PBM.
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Affiliation(s)
| | - Chuntae Kim
- Institute of Nano-Bio Convergence, Pusan National University, Busan, 46241, Republic of Korea; Center for Biomaterials Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea
| | - Nuri Oh
- Department of Chemistry and Biology, Korea Science Academy of KAIST, Busan, 47162, Republic of Korea
| | - Ji-Ho Park
- Department of Bio and Brain Engineering and KAIST Institute for Health Science and Technology, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea
| | - Suck Won Hong
- Department of Cogno-Mechatronics Engineering, College of Nanoscience & Nanotechnology, Pusan National University, Busan, 46241, Republic of Korea
| | - Moon Sung Kang
- Department of Cogno-Mechatronics Engineering, College of Nanoscience & Nanotechnology, Pusan National University, Busan, 46241, Republic of Korea
| | - Chuanbin Mao
- Department of Biomedical Engineering, The Chinese University of Hong Kong, Sha Tin, Hong Kong SAR, China.
| | - Dong-Wook Han
- Institute of Nano-Bio Convergence, Pusan National University, Busan, 46241, Republic of Korea; Department of Cogno-Mechatronics Engineering, College of Nanoscience & Nanotechnology, Pusan National University, Busan, 46241, Republic of Korea.
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6
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da Rocha RB, Araújo DD, Machado FDS, Cardoso VS, Araújo AJ, Marinho-Filho JDB. The role of light emitting diode in wound healing: A systematic review of experimental studies. Cell Biochem Funct 2024; 42:e4086. [PMID: 38956862 DOI: 10.1002/cbf.4086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 05/17/2024] [Accepted: 06/24/2024] [Indexed: 07/04/2024]
Abstract
Wounds represent a growing global issue demanding increased attention. To expedite wound healing, technologies are under development, and light emitting diode (LED) devices of varying wavelengths are being explored for their stimulating influence on the healing process. This article presents a systematic literature review aiming to compile, organize, and analyze the impacts of LED devices on wound healing. This review is registered on the PROSPERO platform [CRD42023403870]. Two blinded authors conducted searches in the Pubmed, Web of Science, Scopus, Embase, and ScienceDirect databases. In vitro and in vivo experimental studies assessing LED utilization in the wound healing process were included. The search yielded 1010 studies, of which 27 were included in the review. It was identified that LED stimulates different healing pathways, promoting enhanced cell proliferation and migration, angiogenesis stimulation, increased collagen deposition, and modulation of the inflammatory response. Thus, it can be concluded that the LED stimulates cellular and molecular processes contingent on the utilized parameters. The effects depend on the standards used. Cell migration and proliferation were better influenced by green and red LED. The extracellular matrix components and angiogenesis were regulated by all wavelengths and the modulation of inflammation was mediated by green, red, and infrared LEDs.
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Affiliation(s)
- Rebeca Barbosa da Rocha
- Laboratório de Cultura de Células do Delta (LCCDelta), Universidade Federal do Delta do Parnaíba-UFDPar, Parnaíba, Piauí, Brazil
| | - Dakson Douglas Araújo
- Laboratório de Cultura de Células do Delta (LCCDelta), Universidade Federal do Delta do Parnaíba-UFDPar, Parnaíba, Piauí, Brazil
| | - Fabrício Dos Santos Machado
- Laboratório de Cultura de Células do Delta (LCCDelta), Universidade Federal do Delta do Parnaíba-UFDPar, Parnaíba, Piauí, Brazil
| | - Vinicius Saura Cardoso
- Laboratório de Estudos e Pesquisas em Sinais Biológicos (Biosignal), Universidade Federal do Delta do Parnaíba-UFDPar, Parnaíba, Piauí, Brazil
| | - Ana Jérsia Araújo
- Laboratório de Cultura de Células do Delta (LCCDelta), Universidade Federal do Delta do Parnaíba-UFDPar, Parnaíba, Piauí, Brazil
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Pilar EFS, Brochado FT, Schmidt TR, Leite AC, Deluca AA, Mármora BC, Siebert M, Wagner VP, Martins MD. Modulation of gene expression in skin wound healing by photobiomodulation therapy: A systematic review in vivo studies. PHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE 2024; 40:e12990. [PMID: 39031566 DOI: 10.1111/phpp.12990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 05/21/2024] [Accepted: 07/10/2024] [Indexed: 07/22/2024]
Abstract
BACKGROUND Wound healing is a multistep process involving coordinated responses of a variety of cell types, cytokines, growth factors, and extracellular matrix (ECM) components leading to the physiological restoration of tissue integrity. Photobiomodulation therapy (PBMT) has been highlighted as an approach to improve the healing process, nonetheless at the molecular level, the effects of PBMT are not entirely understood. AIM To systematically review publications that investigated gene expression after PBMT during in vivo skin repair. METHODS An electronic search was undertaken in Medline Ovid (Wolters Kluwer), PubMed (National Library of Medicine), Web of Science (Thomson Reuters), Scopus (Elsevier), Embase, and LILACS databases. The search strategy was conducted from the terms: low-level light therapy, gene expression, and wound healing and their synonyms. The databases were consulted in December 2023 and no publication year limit was used. RESULTS Eleven studies were included in this review and the expression of 186 genes was evaluated. PBMT modified the expression of several targets genes studied, such as down-regulation of genes related to extracellular matrix proteases (MMP2 and MMP9) and pro-inflammatory cytokines (IL10 and IL6) and up-regulation of DNMT3A and BFGF. CONCLUSION This review demonstrates that PBMT is capable of regulating gene expression during wound healing. Most evidence showed a positive impact of PBMT in regulating genes linked to inflammatory cytokines improving skin wound healing. Yet, the effects of PBMT in genes involved in other mechanisms still need to be better understood.
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Affiliation(s)
- Emily Ferreira Salles Pilar
- Unit of Laboratorial Research, Experimental Research Center, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil
- Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Fernanda Thomé Brochado
- Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Tuany Rafaeli Schmidt
- Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Amanda Costa Leite
- Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Alexia Antunes Deluca
- Unit of Laboratorial Research, Experimental Research Center, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil
- Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Belkiss Câmara Mármora
- Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Marina Siebert
- Unit of Laboratorial Research, Experimental Research Center, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil
| | - Vivian Petersen Wagner
- Department of Pathology, School of Dentistry, Universidade de São Paulo, São Paulo, Brazil
| | - Manoela Domingues Martins
- Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
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Siqueira RC. Photobiomodulation Using Light-Emitting Diode (LED) for Treatment of Retinal Diseases. Clin Ophthalmol 2024; 18:215-225. [PMID: 38283180 PMCID: PMC10813238 DOI: 10.2147/opth.s441962] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Accepted: 11/30/2023] [Indexed: 01/30/2024] Open
Abstract
Photobiomodulation (PBM) is a type of phototherapy that employs light-emitting diodes (LEDs) or low-power lasers to selectively administer specific wavelengths of visible light, ranging from 500 to 1000 nm, including near-infrared (NIR) wavelengths. LEDs are advantageous compared to lasers due to their ability to treat large areas at a lower cost, lack of tissue damage potential in humans, and reduced risk of eye-related accidents. The ophthalmology community has recently taken interest in PBM as a promising novel approach for managing various retinal conditions such as age-related macular degeneration, retinopathy of prematurity, retinitis pigmentosa, diabetic retinopathy, Leber's hereditary optic neuropathy, amblyopia, methanol-induced retinal damage, and potentially others. This review critically assesses the existing body of research on PBM applications in the retina, focusing on elucidating the underlying mechanisms of action and evaluating the clinical outcomes associated with this therapeutic modality.
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Affiliation(s)
- Rubens Camargo Siqueira
- Department of Retina, Rubens Siqueira Research Center, São José do Rio Preto, São Paulo, Brazil
- Postgraduate Department, Faculty of Medicine of São José do Rio Preto (FAMERP), São José do Rio Preto, São Paulo, Brazil
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He X, Jin S, Dai X, Chen L, Xiang L, Zhang C. The Emerging Role of Visible Light in Melanocyte Biology and Skin Pigmentary Disorders: Friend or Foe? J Clin Med 2023; 12:7488. [PMID: 38068540 PMCID: PMC10707362 DOI: 10.3390/jcm12237488] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 11/22/2023] [Accepted: 12/01/2023] [Indexed: 09/03/2024] Open
Abstract
Electromagnetic radiation, notably visible light (VL), has complicated effects on human skin, particularly pigmentation, which have been largely overlooked. In this review, we discuss the photobiological mechanisms, pathological effects, clinical applications and therapeutic strategies of VL at varying wavelengths on melanocyte biology and skin pigmentary disorders. Different VL wavelengths may impose positive or negative effects, depending on their interactions with specific chromophores, photoaging, ROS production, circadian rhythm and other photon-mediated reactions. Further in vivo and in vitro studies are required to establish the pathologic mechanisms and application principles of VL in pigmentary disorders, as well as optimal photoprotection with coverage against VL wavelengths.
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Affiliation(s)
| | | | | | | | - Leihong Xiang
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China; (X.H.); (S.J.); (X.D.); (L.C.)
| | - Chengfeng Zhang
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China; (X.H.); (S.J.); (X.D.); (L.C.)
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Fantaguzzi F, Tombolini B, Servillo A, Zucchiatti I, Sacconi R, Bandello F, Querques G. Shedding Light on Photobiomodulation Therapy for Age-Related Macular Degeneration: A Narrative Review. Ophthalmol Ther 2023; 12:2903-2915. [PMID: 37768527 PMCID: PMC10640464 DOI: 10.1007/s40123-023-00812-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 08/31/2023] [Indexed: 09/29/2023] Open
Abstract
BACKGROUND Photobiomodulation (PBM) relies on the pathophysiological mechanism whereby red to near-infrared light can target mitochondrial activity and promote ATP synthesis. Preclinical and clinical studies have shown promising results in treating intermediate age-related macular degeneration (AMD), since PBM can produce photochemical reactions in endogenous retinal chromophores. Currently, PBM is approved by the Food and Drug Administration and by the European Medicines Agency for the treatment of intermediate AMD. This narrative review aimed to evaluate the available evidence on the effectiveness and safety of PBM in treating intermediate AMD. METHODS A comprehensive search was conducted using the PubMed database, employing the keywords "photobiomodulation" and "age-related macular degeneration." All English-language studies published up to June 2023 were reviewed, and the search was expanded to include relevant references from selected articles. The included publications were analyzed for this review. RESULTS The available studies on PBM in AMD demonstrated promising but inconsistent results. PBM showed potential in improving best-corrected visual acuity (BCVA) and contrast sensitivity (CS) in patients with AMD. Some studies also suggested a reduction in AMD lesions, such as drusen volume. However, the long-term efficacy and optimal treatment parameters of PBM in AMD remained to be fully determined due to the limitations of the available studies. These included variations in irradiation techniques, wavelengths, exposure times, and treatment sessions, making it challenging to generalize the effectiveness of PBM. Furthermore, the lack of accurate classification of AMD phenotypes in the available studies hindered the understanding of which phenotypes could truly benefit from this treatment. Finally, the strength of evidence varied among studies, with limited sample sizes, unpublished results, and only three randomized sham-controlled trials. CONCLUSIONS Currently, the effectiveness of PBM in promoting drusen resorption or preventing progression to advanced forms of AMD, as observed in the cited studies, remains uncertain.
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Affiliation(s)
- Federico Fantaguzzi
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Division of Head and Neck, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Beatrice Tombolini
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Division of Head and Neck, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Andrea Servillo
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Division of Head and Neck, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Ilaria Zucchiatti
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Division of Head and Neck, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Riccardo Sacconi
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Division of Head and Neck, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Francesco Bandello
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Division of Head and Neck, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Giuseppe Querques
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.
- Division of Head and Neck, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
- Department of Ophthalmology, Vita-Salute San Raffaele University, Via Olgettina 60, 20132, Milan, Italy.
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Fear EJ, Torkelsen FH, Zamboni E, Chen K, Scott M, Jeffery G, Baseler H, Kennerley AJ. Use of 31 P magnetisation transfer magnetic resonance spectroscopy to measure ATP changes after 670 nm transcranial photobiomodulation in older adults. Aging Cell 2023; 22:e14005. [PMID: 37803929 PMCID: PMC10652330 DOI: 10.1111/acel.14005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 09/18/2023] [Accepted: 09/22/2023] [Indexed: 10/08/2023] Open
Abstract
Mitochondrial function declines with age, and many pathological processes in neurodegenerative diseases stem from this dysfunction when mitochondria fail to produce the necessary energy required. Photobiomodulation (PBM), long-wavelength light therapy, has been shown to rescue mitochondrial function in animal models and improve human health, but clinical uptake is limited due to uncertainty around efficacy and the mechanisms responsible. Using 31 P magnetisation transfer magnetic resonance spectroscopy (MT-MRS) we quantify, for the first time, the effects of 670 nm PBM treatment on healthy ageing human brains. We find a significant increase in the rate of ATP synthase flux in the brain after PBM in a cohort of older adults. Our study provides initial evidence of PBM therapeutic efficacy for improving mitochondrial function and restoring ATP flux with age, but recognises that wider studies are now required to confirm any resultant cognitive benefits.
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Affiliation(s)
- Elizabeth J. Fear
- Hull York Medical SchoolUniversity of YorkYorkUK
- Department of Biomolecular SciencesUniversity of Urbino Carlo BoUrbinoItaly
| | | | - Elisa Zamboni
- Department of PsychologyUniversity of YorkYorkUK
- School of PsychologyUniversity of NottinghamNottinghamUK
| | | | - Martin Scott
- Department of PsychologyUniversity of YorkYorkUK
- Department of PsychologyStanford UniversityStanfordCaliforniaUSA
| | - Glenn Jeffery
- Faculty of Brain SciencesInstitute of Ophthalmology, UCLLondonUK
| | - Heidi Baseler
- Hull York Medical SchoolUniversity of YorkYorkUK
- Department of PsychologyUniversity of YorkYorkUK
| | - Aneurin J. Kennerley
- Department of ChemistryUniversity of YorkYorkUK
- Institute of SportManchester Metropolitan UniversityManchesterUK
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Sammons T, Shanks S. Efficacy of red low-level laser for postoperative pain management: A review of literature. J Perioper Pract 2023; 33:350-357. [PMID: 36394302 DOI: 10.1177/17504589221124757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Many patients who undergo surgical procedures experience acute postoperative pain, with less than half receiving adequate pain relief. Recent advancements in postoperative pain management include the market clearance by the US Food and Drug Administration for the utilisation of red low-level laser therapy in providing postoperative pain relief. The Food and Drug Administration market clearance was based on clinical data from randomised controlled trials that supported the safety and effectiveness of visible red laser therapy across various surgical procedures. This review of literature aims to evaluate the mechanisms of action, the dose-response curves and clinical outcomes of red low-level laser for postoperative pain management. A literature search was limited to randomised controlled trials that evaluated the use of red low-level laser therapy on postoperative pain. The results from the literature search found that seven studies met the search qualifications. The literature review findings demonstrated that red low-level laser therapy is a safe and effective treatment alternative for postoperative pain management. In addition to postoperative pain reduction, the findings of the literature revealed that red low-level laser therapy may promote healing and reduce the consumption of postoperative prescription analgesic drugs.
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Calbiague García V, Cadiz B, Herrera P, Díaz A, Schmachtenberg O. Evaluation of Photobiomodulation and Boldine as Alternative Treatment Options in Two Diabetic Retinopathy Models. Int J Mol Sci 2023; 24:ijms24097918. [PMID: 37175628 PMCID: PMC10178531 DOI: 10.3390/ijms24097918] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 04/18/2023] [Accepted: 04/19/2023] [Indexed: 05/15/2023] Open
Abstract
Diabetic retinopathy causes progressive and irreversible damage to the retina through activation of inflammatory processes, overproduction of oxidative species, and glial reactivity, leading to changes in neuronal function and finally ischemia, edema, and hemorrhages. Current treatments are invasive and mostly applied at advanced stages, stressing the need for alternatives. To this end, we tested two unconventional and potentially complementary non-invasive treatment options: Photobiomodulation, the stimulation with near-infrared light, has shown promising results in ameliorating retinal pathologies and insults in several studies but remains controversial. Boldine, on the other hand, is a potent natural antioxidant and potentially useful to prevent free radical-induced oxidative stress. To establish a baseline, we first evaluated the effects of diabetic conditions on the retina with immunofluorescence, histological, and ultrastructural analysis in two diabetes model systems, obese LepRdb/db mice and organotypic retinal explants, and then tested the potential benefits of photobiomodulation and boldine treatment in vitro on retinal explants subjected to high glucose concentrations, mimicking diabetic conditions. Our results suggest that the principal subcellular structures affected by these conditions were mitochondria in the inner segment of photoreceptors, which displayed morphological changes in both model systems. In retinal explants, lactate metabolism, assayed as an indicator of mitochondrial function, was altered, and decreased photoreceptor viability was observed, presumably as a consequence of increased oxidative-nitrosative stress. The latter was reduced by boldine treatment in vitro, while photobiomodulation improved mitochondrial metabolism but was insufficient to prevent retinal structural damage caused by high glucose. These results warrant further research into alternative and complementary treatment options for diabetic retinopathy.
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Affiliation(s)
- Víctor Calbiague García
- Ph. D. Program in Neuroscience, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile
- Centro Interdisciplinario de Neurociencias de Valparaíso (CINV), Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile
| | - Bárbara Cadiz
- Centro Interdisciplinario de Neurociencias de Valparaíso (CINV), Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile
| | - Pablo Herrera
- Instituto de Biología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile
| | - Alejandra Díaz
- Centro Interdisciplinario de Neurociencias de Valparaíso (CINV), Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile
| | - Oliver Schmachtenberg
- Centro Interdisciplinario de Neurociencias de Valparaíso (CINV), Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile
- Instituto de Biología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile
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Candiani M, Ottolina J, Salmeri N, D’Alessandro S, Tandoi I, Bartiromo L, Schimberni M, Ferrari S, Villanacci R. Minimally invasive surgery for ovarian endometriosis as a mean of improving fertility: Cystectomy vs. CO2 fiber laser ablation what do we know so far? Front Surg 2023; 10:1147877. [PMID: 37051570 PMCID: PMC10083313 DOI: 10.3389/fsurg.2023.1147877] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 03/10/2023] [Indexed: 03/29/2023] Open
Abstract
Minimally invasive surgery emerged in the 1980s as a safe and effective technique which requires smaller incisions and, usually, a shorter hospital stay compared to traditional surgery. Since then, minimally invasive surgery has expanded in many surgical specialties. One of its newest application in gynecology stands in the infertility management of young women with unexplained infertility or suspected endometriosis. In these cases, laparoscopy allows to diagnose and treat the disease aiming to increase at best the chances of spontaneous pregnancy or trough assisted reproductive technology. Nowadays, minimally invasive surgical approach of ovarian endometriosis consists of either laparoscopic cystectomy or ablative techniques such as laparoscopic CO2 fiber laser vaporization. Although cystectomy represents the gold standard according to the latest Cochrane review, some endometriosis experts are worried about its detrimental effect on healthy ovarian parenchyma and suggest preferring a less aggressive approach such as CO2 fiber laser vaporization. The aim of this review is to give an overview of the available evidences about the impact of the two surgical procedures on ovarian reserve markers and pregnancy outcome.
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15
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Saloň A, Steuber B, Neshev R, Schmid-Zalaudek K, De Boever P, Bergmann E, Picha R, Fredriksen PM, Nkeh-Chungag BN, Goswami N. Vascular Responses following Light Therapy: A Pilot Study with Healthy Volunteers. J Clin Med 2023; 12:jcm12062229. [PMID: 36983231 PMCID: PMC10054429 DOI: 10.3390/jcm12062229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 02/16/2023] [Accepted: 03/07/2023] [Indexed: 03/16/2023] Open
Abstract
(1) Background: Studies have reported the effectiveness of light therapy in various medical conditions. Our pilot study aimed to assess the effect of Maharishi light therapy (MLT) on physiological parameters, such as the heart rate (HR), HR variability (HRV), blood pressure (BP), BP variability (BPV), and the retinal microvasculature of healthy participants; (2) Methodology: Thirty (14 males and 16 females) healthy, non-smoking participants between 23 and 71 years old (46 ± 18 years) were included in this randomized crossover study. Each participant was tested with a placebo (using LED light) and gem lights, 24 h apart. Hemodynamic parameters were recorded during the session, and 24 h heart rate and BP levels were assessed via mobile devices. Retinal vascular responses were captured with fundus images and the subsequent analysis of retinal vessel widths. A linear model, using repeated measures ANOVA, was used to compare the responses across the sexes and to assess the effect of the MLT; (3) Results: Changes in the central retinal artery equivalent (CRAE) (p < 0.001) and central retinal vein equivalent (CRVE) (p = 0.002) parameters were observed. CRAE and CRVE decreased under MLT and increased under the placebo condition from before to after. However, the baseline values of the participants already differed significantly before the application of any therapy, and the variation in the retinal vessel diameters was already large in the baseline measurements. This suggests that the observed effect results may only reflect naturally occurring fluctuations in the microcirculation and not the effect of MLT. Furthermore, no significant effects were observed in any other investigated parameters; (4) Conclusion: Our study with healthy participants finds significant changes in retinal parameters, but the biological variation in the baseline measurements was large to begin with. This suggests that the observed effect results only reflect naturally occurring fluctuations in the microcirculation and not the effect of MLT. However, in the future, larger studies in which MLT is applied for longer periods and/or in patients with different diseases could discover the physiological impacts of this type of therapy.
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Affiliation(s)
- Adam Saloň
- Gravitational Physiology and Medicine Research Unit, Division of Physiology, Otto Loewi Research Center, Medical University of Graz, 8036 Graz, Austria
- Faculty of Health and Social Sciences, Inland Norway University of Applied Science, 2624 Lillehammer, Norway
| | - Bianca Steuber
- Gravitational Physiology and Medicine Research Unit, Division of Physiology, Otto Loewi Research Center, Medical University of Graz, 8036 Graz, Austria
| | - Ruslan Neshev
- Gravitational Physiology and Medicine Research Unit, Division of Physiology, Otto Loewi Research Center, Medical University of Graz, 8036 Graz, Austria
| | - Karin Schmid-Zalaudek
- Gravitational Physiology and Medicine Research Unit, Division of Physiology, Otto Loewi Research Center, Medical University of Graz, 8036 Graz, Austria
| | - Patrick De Boever
- Centre for Environmental Sciences, Hasselt University, 3500 Hasselt, Belgium
| | - Eva Bergmann
- Meditation Center in Silkeborg, Moerksoevej 71, 8600 Silkeborg, Denmark
| | - Rainer Picha
- Rehabilitation Center for Cardiovascular Disease, 8061 St. Radegund, Austria
| | - Per Morten Fredriksen
- Faculty of Health and Social Sciences, Inland Norway University of Applied Science, 2624 Lillehammer, Norway
| | - Benedicta Ngwechi Nkeh-Chungag
- Department of Biological and Environmental Sciences, Faculty of Health Sciences, Walter Sisulu University PBX1, Mthatha 5117, South Africa
| | - Nandu Goswami
- Gravitational Physiology and Medicine Research Unit, Division of Physiology, Otto Loewi Research Center, Medical University of Graz, 8036 Graz, Austria
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai P.O. Box 505055, United Arab Emirates
- Correspondence: ; Tel.: +43-316-385-73852; Fax: +43-316-385-79005
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Tonolli PN, Vera Palomino CM, Junqueira HC, Baptista MS. The phototoxicity action spectra of visible light in HaCaT keratinocytes. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B: BIOLOGY 2023; 243:112703. [PMID: 37023538 DOI: 10.1016/j.jphotobiol.2023.112703] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 03/16/2023] [Accepted: 03/27/2023] [Indexed: 03/30/2023]
Abstract
Visible light (VL) surely affects human skin in several ways, exerting positive (tissue regeneration, pain relief) and negative (oxidation, inflammation) effects, depending on the radiation dose and wavelength. Nevertheless, VL continues to be largely disregarded in photoprotection strategies, perhaps because the molecular mechanisms occurring during the interaction of VL with endogenous photosensitizers (ePS) and the subsequent biological responses are still poorly understood. Besides, VL encompass photons with different properties and interaction capacities with the ePS, but there are no quantitative comparisons of their effects on humans. Here, we studied the effects of physiologically relevant doses of four wavelengths ranges of VL, i.e. (in nm), 408-violet, 466/478-blue, 522-green, 650-red, in immortalized human skin keratinocytes (HaCaT). The level of cytotoxicity/damage follows the order: violet>blue >green>red. Violet and blue light induced the highest levels of Fpg-sensitive lesions in nuclear DNA, oxidative stress, lysosomal and mitochondrial damage, disruption of the lysosomal-mitochondrial axis of cell homeostasis, blockade of the autophagic flux, as well as lipofuscin accumulation, greatly increasing the toxicity of wideband VL to human skin. We hope this work will stimulate in development of optimized sun protection strategies.
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Efficacy of Low-Level Laser Therapy in a Rabbit Model of Rhinosinusitis. Int J Mol Sci 2023; 24:ijms24010760. [PMID: 36614203 PMCID: PMC9820841 DOI: 10.3390/ijms24010760] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 12/12/2022] [Accepted: 12/16/2022] [Indexed: 01/04/2023] Open
Abstract
Little is known about alternative treatment options for rhinosinusitis (RS). We aimed to evaluate the efficacy of low-level laser therapy (LLLT) for RS in experimentally induced rabbit models of RS. A total of 18 rabbits were divided into four groups: a negative control group (n = 3), an RS group without treatment (n = 5, positive control group), an RS group with natural recovery (n = 5, natural recovery group), and an RS group with laser irradiation (n = 5, laser-treated group). Computed tomography and histopathological staining were performed for each group. mRNA and protein expression levels of local cytokines (IFN-γ, IL-17, and IL-5) were also measured. Tissue inflammation revealed a significant improvement in the laser-treated group compared with the RS and natural recovery groups (p < 0.01). In addition, sinus opacification in the CT scans and cytokine expression was reduced in the laser-treated group, though without statistical significance. LLLT could be an effective option for the management of RS concerning radiological, histological, and molecular parameters.
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18
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The antibacterial activity of photodynamic agents against multidrug resistant bacteria causing wound infection. Photodiagnosis Photodyn Ther 2022; 40:103066. [PMID: 35998880 DOI: 10.1016/j.pdpdt.2022.103066] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 08/04/2022] [Accepted: 08/12/2022] [Indexed: 12/14/2022]
Abstract
Antimicrobial photodynamic inactivation (aPDI) of multidrug-resistant (MDR) wound pathogens was evaluated with cationic porphyrin derivatives (CPDs). MDR bacterial strains including Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, and Klebsiella pneumoniae were used. The CPDs named PM, PE, PN, and PL were synthesized as a photosensitizer (PS). A diode laser with a wavelength of 655 nm was used as a light source. aPDI of the combinations formed with different energy densities (50, 100, and 150 J/cm²) and PS concentrations (ranging from 3.125 to 600 µM) were evaluated on each bacterial strain. Dark toxicity, cytotoxicity, and phototoxicity were determined on fibroblast cells. In the aPDI groups, survival reductions of up to 5.80 log₁₀ for E. coli, 5.90 log₁₀ for P. aeruginosa, 6.11 log₁₀ for K. pneumoniae, and 6.78 log₁₀ for A. baumannii were obtained. The cytotoxic effect of PL and PM on fibroblast cells was very limited. PN was the type of CPD with the highest dark toxicity on fibroblast cells. In terms of providing broad-spectrum aPDI without or with very limited cytotoxic effect, the best result was observed in aPDI application with PL. The other CPDs need some modifications to show bacterial selectivity for use at 50 µM and above.
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Xiao Q, Wang L, Zhang J, Zhong X, Guo Z, Yu J, Ma Y, Wu H. Activation of Wnt/β-Catenin Signaling Involves 660 nm Laser Radiation on Epithelium and Modulates Lipid Metabolism. Biomolecules 2022; 12:1389. [PMID: 36291598 PMCID: PMC9599573 DOI: 10.3390/biom12101389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 09/10/2022] [Accepted: 09/20/2022] [Indexed: 11/17/2022] Open
Abstract
Research has proven that light treatment, specifically red light radiation, can provide more clinical benefits to human health. Our investigation was firstly conducted to characterize the tissue morphology of mouse breast post 660 nm laser radiation with low power and long-term exposure. RNA sequencing results revealed that light exposure with a higher intervention dosage could cause a number of differentially expressed genes compared with a low intervention dosage. Gene ontology analysis, protein-protein interaction network analysis, and gene set enrichment analysis results suggested that 660 nm light exposure can activate more transcription-related pathways in HC11 breast epithelial cells, and these pathways may involve modulating critical gene expression. To consider the critical role of the Wnt/T-catenin pathway in light-induced modulation, we hypothesized that this pathway might play a major role in response to 660 nm light exposure. To validate our hypothesis, we conducted qRT-PCR, immunofluorescence staining, and Western blot assays, and relative results corroborated that laser radiation could promote expression levels of β-catenin and relative phosphorylation. Significant changes in metabolites and pathway analysis revealed that 660 nm laser could affect nucleotide metabolism by regulating purine metabolism. These findings suggest that the Wnt/β-catenin pathway may be the major sensor for 660 nm laser radiation, and it may be helpful to rescue drawbacks or side effects of 660 nm light exposure through relative interventional agents.
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Affiliation(s)
- Qiyang Xiao
- School of Artificial Intelligence, Henan University, Zhengzhou 450046, China
| | - Lijing Wang
- School of Life Sciences, Henan University, Kaifeng 475000, China
| | - Juling Zhang
- Center for Faculty Development, South China Normal University, Guangzhou 510631, China
| | - Xinyu Zhong
- School of Life Sciences, Henan University, Kaifeng 475000, China
| | - Zhou Guo
- School of Life Sciences, Henan University, Kaifeng 475000, China
| | - Jiahao Yu
- Shandong Zhongbaokang Medical Implements Co., Ltd., Zibo 255000, China
| | - Yuanyuan Ma
- School of Pharmacy, Henan University, Kaifeng 475000, China
| | - Haigang Wu
- School of Artificial Intelligence, Henan University, Zhengzhou 450046, China
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Abstract
Hormetic dose responses are reported here to occur commonly in the dermal wound healing process, with the particular focus on cell viability, proliferation, migration and collagen deposition of human and murine fibroblasts with in vitro studies. Hormetic responses were induced by a wide range of substances, including endogenous agents, pharmaceutical preparations, plant-derived extracts including many well-known dietary supplements, as well as physical stressor agents such as low-level laser treatments. Detailed mechanistic studies have identified common signaling pathways and their cross-pathway communications that mediate the hormetic dose responses. These findings complement and extend a similar comprehensive assessment concerning the occurrence of hormetic dose responses in keratinocytes. These findings demonstrate the generality of the hormetic dose response for key wound healing endpoints, suggesting that the hormesis concept has a fundamental role in wound healing, with respect to guiding strategies for experimental evaluation as well as therapeutic applications.
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Giolo FP, Santos GS, Pacheco VF, Huber SC, Malange KF, Rodrigues BL, Bassora F, Mosaner T, Azzini G, Ribeiro LL, Parada CA, Lana JFSD. Photobiomodulation therapy for osteoarthritis: Mechanisms of action. World J Transl Med 2022; 10:29-42. [DOI: 10.5528/wjtm.v10.i3.29] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 05/23/2022] [Accepted: 08/05/2022] [Indexed: 02/05/2023] Open
Abstract
Photobiomodulation (PBM) is a non-invasive therapeutic modality with demonstrated effects in many fields related to regenerative medicine. In the field of orthopedics, in particular, PBM at various wavelengths has demonstrated the capacity to trigger multiple biological effects associated with protective mechanisms in musculoskeletal tissues. The articles cited in this review show that devices operating close to or within the near infrared range at low intensities can provoke responses which favor the shift in the predominant catabolic microenvironment typically seen in degenerative joint diseases, especially osteoarthritis (OA). These responses include proliferation, differentiation and expression of proteins associated with stable cell cycles. Additionally, PBM can also modulate oxidative stress, inflammation and pain by exerting regulatory effects on immune cells and blocking the transmission of pain through sensory neuron fibers, without adverse events. Collectively, these effects are essential in order to control the progression of OA, which is in part attributed to exacerbated inflammation and degradative enzymatic reactions which gradually contribute to the destruction of joint tissues. PBM may offer medical experts ease of application, financial viability, efficacy and lack of serious adverse events. Therefore, it may prove to be a suitable ally in the management of mild to moderate degrees of OA. This review explores and discusses the principal biological mechanisms of PBM and how the produced effects may contribute to the amelioration of osteoarthritic progression. Literature was reviewed using PubMed and Google Scholar in order to find studies describing the mechanisms of PBM. The investigation included a combination of nomenclature such as: “photobiomodulation”, “phototherapy”, “laser therapy”, “PBM”, “osteoarthritis”, low level light therapy”, “inflammation” and “cartilage”. We considered only articles written in English, with access to the full text.
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Affiliation(s)
- Fábio Pericinoto Giolo
- Department of Physical Therapy, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, Brazil
| | - Gabriel Silva Santos
- Biomedical Science, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, Brazil
| | - Victor Fontes Pacheco
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, Brazil
| | - Stephany Cares Huber
- Biomedical Science, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, Brazil
| | - Kaue Franco Malange
- Neurobiology of Pain and Regenerative Medicine, The University of Campinas, Campinas 13083-862, Brazil
| | - Bruno Lima Rodrigues
- Biomedical Science, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, Brazil
| | - Fernanda Bassora
- Department of Hematology, The University of Campinas, Campinas 13083-878, Brazil
| | - Tomas Mosaner
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, Brazil
| | - Gabriel Azzini
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, Brazil
| | - Lucas Leite Ribeiro
- Department of Orthopedics, Brazilian Institute of Regenerative Medicine, Indaiatuba 13334-170, Brazil
| | - Carlos Amilcar Parada
- Neurobiology of Pain and Regenerative Medicine, The University of Campinas, Campinas 13083-862, Brazil
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Zhang WW, Wang XY, Chu YX, Wang YQ. Light-emitting diode phototherapy: pain relief and underlying mechanisms. Lasers Med Sci 2022; 37:2343-2352. [DOI: 10.1007/s10103-022-03540-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 03/01/2022] [Indexed: 12/15/2022]
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Kheradmand A, Tabeie F, Seif P, Rezaei O, Yasamy MT. Effect of low-level laser therapy (LLLT) on cognitive impairment among patients with chronic schizophrenia: a double-blind randomized placebo-controlled clinical trial. Lasers Med Sci 2022; 37:2717-2725. [PMID: 35314926 DOI: 10.1007/s10103-022-03545-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 03/10/2022] [Indexed: 10/18/2022]
Abstract
Low-level laser therapy (LLLT) is a noninvasive technique used in different medical fields. It has been applied in different medical areas such as wound healing, traumatic brain injuries, neurological disorders, cognitive disorders, Alzheimer's disease, pain, and arthritis, with different results. We studied the effectiveness of LLLT on cognitive impairment in patients with chronic schizophrenia. A randomized controlled double-blind clinical trial was performed in a men's chronic treatment center, in Razi Psychiatric Hospital, in Tehran, Iran. We screened the cognitive impairment by Mini-Mental State Examination (MMSE). Positive And Negative Syndrome Scale (PANSS) was also used to assess the patients' positive and negative symptoms. Seventeen consenting patients were randomly allocated to the treatment arm, and 15 to the sham treatment control arm. The mean age of the control and treated patients was 49.47 ± 6.99 and 50.24 ± 7.69, respectively. No significant difference in PANSS and MMSE test scores was detected in both groups after the 6th session and after 2 months of follow-up after laser therapy. The positive and negative scales and agitation and excitement levels did not change significantly in either group. Nevertheless, the depression/anxiety subscale in the PANSS test showed a significant reduction after 6 sessions but did not persist after 2 months. No improvement in cognitive impairment or the positive and negative symptoms was detected after LLLT in patients with chronic schizophrenia. Trial registration: IRCT 20210520051349N1.
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Affiliation(s)
- Ali Kheradmand
- Department of Psychiatry, Taleghani Hospital Research Development Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Faraj Tabeie
- Department of Basic Sciences, School of Rehabilitation, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Pegah Seif
- Department of Psychiatry, Taleghani Hospital Research Development Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Omid Rezaei
- Department of Psychiatry, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
| | - Mohammad Taghi Yasamy
- Department of Psychiatry, Taleghani Hospital Research Development Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Rosin FCP, de Paula Novaes C, dos Santos AF, Deboni MCZ, Corrêa L. Photobiomodulation Therapy Minimises the DNA Damage in 5FU‐treated Gingival Fibroblasts. Photochem Photobiol 2022; 98:1201-1206. [DOI: 10.1111/php.13609] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 02/16/2022] [Accepted: 02/17/2022] [Indexed: 11/29/2022]
Affiliation(s)
| | | | | | | | - Luciana Corrêa
- Pathology Department School of Dentistry University of São Paulo
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25
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Qi X, Nizamutdinov D, Berman MH, Dougal G, Chazot PL, Wu E, Stevens AB, Yi SS, Huang JH. Gender Differences of Dementia in Response to Intensive Self-Administered Transcranial and Intraocular Near-Infrared Stimulation. Cureus 2021; 13:e16188. [PMID: 34262831 PMCID: PMC8260213 DOI: 10.7759/cureus.16188] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/26/2021] [Indexed: 11/24/2022] Open
Abstract
Background Transcranial near-infrared (tNIR) stimulation was proven to be a safe, reliable, and effective treatment for cognitive and behavioral symptoms of dementia. Dementia patients of different genders differ in terms of gross anatomy, biochemistry, genetic profile, clinical presentations, and socio-psychological status. Studies of the tNIR effect on dementia have thus far been gender-neutral, with dementia subjects being grouped based on diagnoses or dementia severity. This trial hereby investigated how dementia subjects of different sex respond to tNIR treatment. Methods A total of 60 patient-caregiver dyads were enrolled and randomized to this double-blind, sham-controlled clinical trial. The tNIR light has a wavelength of 1,060 nm to 1,080 nm and was delivered via a photobiomodulation (PBM) unit. The active PBM unit emits near-infrared (NIR) light while the sham unit does not. The treatment consists of a six-minute tNIR light stimulation session twice daily for eight weeks. Neuropsychological assessments conducted at baseline (week 0) and endline (week 8) were compared within the female and male group and between different sex, respectively. Results Over the course of treatment, active-arm female subjects had a 20.2% improvement in Mini‐Mental State Exam (MMSE) (mean 4.8 points increase, p < 0.001) and active-arm male cohort had 19.3% improvement (p < 0.001). Control-arm female subjects had a 6.5% improvement in MMSE (mean 1.5 points increase, p < 0.03) and control-arm male subjects had 5.9% improvement (p = 0.35) with no significant differences in the mean MMSE between female and male subjects in both arms respectively. Other comparison of assessments including Clock Copying and Drawing Test, Logical Memory Test - immediate and delayed recall yielded nominal but not statistically significant differences. No significant differences were observed in the mean MMSE between female and male subjects in both arms respectively before treatment implementation (active arm, p = 0.12; control arm, p = 0.50) at week 0, or after treatment completion (active arm, p = 0.11; control arm, p = 0.74) at week 8. Conclusion Despite differences between female and male dementia subjects, the response to tNIR light stimulation does not demonstrate gender-based differences. Further studies are warranted to refine the tNIR treatment protocol for subjects suffering from dementia or dementia-related symptoms.
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Affiliation(s)
- Xiaoming Qi
- Neurosurgery, Baylor Scott & White Health, Temple, USA
| | | | | | - Gordon Dougal
- Chief Executive Officer, Maculume Limited, Spennymoor, GBR
| | | | - Erxi Wu
- Neurosurgery, Baylor Scott & White Health, Temple, USA
| | - Alan B Stevens
- Gerontology, Baylor Scott & White Health Research Institute, Temple, USA
| | - S Stephen Yi
- Oncology, The University of Texas at Austin, Dell Medical School, Austin, USA
| | - Jason H Huang
- Neurosurgery, Baylor Scott & White Medical Center, Temple, USA
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Yoon SR, Hong N, Lee MY, Ahn JC. Photobiomodulation with a 660-Nanometer Light-Emitting Diode Promotes Cell Proliferation in Astrocyte Culture. Cells 2021; 10:1664. [PMID: 34359834 PMCID: PMC8307591 DOI: 10.3390/cells10071664] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 06/24/2021] [Accepted: 06/28/2021] [Indexed: 12/17/2022] Open
Abstract
Astrocytes act as neural stem cells (NSCs) that have the potential to self-renew and differentiate into other neuronal cells. The protein expression of these astrocytes depends on the stage of differentiation, showing sequential expression of multiple proteins such as octamer-binding transcription factor 4 (Oct4), nestin, glial fibrillary acidic protein (GFAP), and aldehyde dehydrogenase 1 family member L1 (aldh1L1). Photobiomodulation (PBM) affects cell apoptosis, proliferation, migration, and adhesion. We hypothesized that astrocyte proliferation and differentiation would be modulated by PBM. We used an optimized astrocyte culture method and a 660-nanometer light-emitting diode (LED) to enhance the biological actions of many kinds of cells. We determined that the 660-nanometer LED promoted the biological actions of cultured astrocytes by increasing the reactive oxygen species levels. The overall viability of the cultured cells, which included various cells other than astrocytes, did not change after LED exposure; however, astrocyte-specific proliferation was observed by the increased co-expression of GFAP and bromodeoxyuridine (BrdU)/Ki67. Furthermore, the 660-nanometer LED provides evidence of differentiation, as shown by the decreased Oct4 and GFAP co-expression and increased nestin and aldh1L1 expression. These results demonstrate that a 660-nanometer LED can modify astrocyte proliferation, which suggests the efficacy of the therapeutic application of LED in various pathological states of the central nervous system.
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Affiliation(s)
- Sung-Ryeong Yoon
- Department of Medical Laser, Graduate School of Medicine, Dankook University, Cheonan 31116, Korea;
- Medical Laser Research Center, College of Medicine, Dankook University, Cheonan 31116, Korea;
| | - Namgue Hong
- Medical Laser Research Center, College of Medicine, Dankook University, Cheonan 31116, Korea;
| | - Min-Young Lee
- Department of Otolaryngology-Head & Neck Surgery, College of Medicine, Dankook University, Cheonan 31116, Korea
- Beckman Laser Institute Korea, College of Medicine, Dankook University, Cheonan 31116, Korea
| | - Jin-Chul Ahn
- Department of Medical Laser, Graduate School of Medicine, Dankook University, Cheonan 31116, Korea;
- Medical Laser Research Center, College of Medicine, Dankook University, Cheonan 31116, Korea;
- Beckman Laser Institute Korea, College of Medicine, Dankook University, Cheonan 31116, Korea
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Nizamutdinov D, Qi X, Berman MH, Dougal G, Dayawansa S, Wu E, Yi SS, Stevens AB, Huang JH. Transcranial Near Infrared Light Stimulations Improve Cognition in Patients with Dementia. Aging Dis 2021; 12:954-963. [PMID: 34221541 PMCID: PMC8219492 DOI: 10.14336/ad.2021.0229] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Accepted: 03/01/2021] [Indexed: 01/13/2023] Open
Abstract
Dementia is a complex syndrome with various presentations depending on the underlying pathologies. Low emission of transcranial near-infrared (tNIR) light can reach human brain parenchyma and be beneficial to a number of neurological and neurodegenerative disorders. We hereby examined the safety and potential therapeutic benefits of tNIR light stimulations in the treatment of dementia. Patients of mild to moderate dementia were randomized into active and sham treatment groups at 2:1 ratio. Active treatment consisted of low power tNIR light stimulations with an active photobiomodulation for 6 min twice daily during 8 consequent weeks. Sham treatment consisted of same treatment routine with a sham device. Neuropsychological battery was obtained before and after treatment. Analysis of variance (ANOVA) was used to analyze outcomes. Sixty subjects were enrolled. Fifty-seven subjects completed the study and had not reported health or adverse side effects during or after the treatment. Three subjects dropped out from trial for health issues unrelated to use of tNIR light treatment. Treatment with active device resulted in improvements of cognitive functions and changes were: an average increase of MMSE by 4.8 points; Logical Memory Tests I and II by ~3.0 points; Trail Making Tests A and B by ~24%; Boston Naming Test by ~9%; improvement of both Auditory Verbal Learning Tests in all subtest categories and overall time of performance. Many patients reported improved sleep after ~7 days of treatment. Caregivers noted that patients had less anxiety, improved mood, energy, and positive daily routine after ~14-21 days of treatment. The tNIR light treatments demonstrated safety and positive cognitive improvements in patients with dementia. Developed treatment protocol can be conveniently used at home. This study suggests that additional dementia treatment trials are warranted with a focus on mitigating caregivers’ burden with tNIR light treatment of dementia patients.
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Affiliation(s)
- Damir Nizamutdinov
- 1Baylor Scott and White Health, Neuroscience Institute, Neurosurgery, Temple, TX, USA.,2Texas A&M University, HSC, College of Medicine, Neurosurgery, Temple, TX, USA
| | - Xiaoming Qi
- 1Baylor Scott and White Health, Neuroscience Institute, Neurosurgery, Temple, TX, USA
| | | | | | - Samantha Dayawansa
- 1Baylor Scott and White Health, Neuroscience Institute, Neurosurgery, Temple, TX, USA.,2Texas A&M University, HSC, College of Medicine, Neurosurgery, Temple, TX, USA
| | - Erxi Wu
- 1Baylor Scott and White Health, Neuroscience Institute, Neurosurgery, Temple, TX, USA.,2Texas A&M University, HSC, College of Medicine, Neurosurgery, Temple, TX, USA.,5Texas A&M University, HSC, College of Pharmacy, Department of Pharmaceutical Sciences, College Station, TX, USA.,6Department of Oncology, Dell Medical School, The University of Texas at Austin, TX, USA
| | - S Stephen Yi
- 6Department of Oncology, Dell Medical School, The University of Texas at Austin, TX, USA
| | - Alan B Stevens
- 1Baylor Scott and White Health, Neuroscience Institute, Neurosurgery, Temple, TX, USA
| | - Jason H Huang
- 1Baylor Scott and White Health, Neuroscience Institute, Neurosurgery, Temple, TX, USA.,2Texas A&M University, HSC, College of Medicine, Neurosurgery, Temple, TX, USA
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28
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Gonçalves de Faria CM, Ciol H, Salvador Bagnato V, Pratavieira S. Effects of photobiomodulation on the redox state of healthy and cancer cells. BIOMEDICAL OPTICS EXPRESS 2021; 12:3902-3916. [PMID: 34457388 PMCID: PMC8367241 DOI: 10.1364/boe.421302] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 04/09/2021] [Accepted: 04/29/2021] [Indexed: 06/13/2023]
Abstract
Photobiomodulation therapy (PBMT) uses light to stimulate cells. The molecular basis of the effects of PBMT is being unveiled, but it is stated that the cytochrome-c oxidase enzyme in mitochondria, a photon acceptor of PBMT, contributes to an increase in ATP production and modulates the reduction and oxidation of electron carriers NADH and FAD. Since its effects are not fully understood, PBMT is not used on tumors. Thus, it is interesting to investigate if its effects correlate to mitochondrial metabolism and if so, how it could be linked to the optical redox ratio (ORR), defined as the ratio of FAD/(NADH + FAD) fluorescences. To that end, fibroblasts (HDFn cell line) and oral squamous cell carcinoma (SCC-25 cell line) were irradiated with a light source of 780 nm and a total dose of 5 J/cm2, and imaged by optical microscopy. PBMT down-regulated the SCC-25 ORR by 10%. Furthermore, PBMT led to an increase in ROS and ATP production in carcinoma cells after 4 h, while fibroblasts only had a modest ATP increase 6 h after irradiation. Cell lines did not show distinct cell cycle profiles, as both had an increase in G2/M cells. This study indicates that PBMT decreases the redox state of oral cancer by possibly increasing glycolysis and affects normal and tumor cells through distinct pathways. To our knowledge, this is the first study that investigated the effects of PBMT on mitochondrial metabolism from the initiation of the cascade to DNA replication. This is an essential step in the investigation of the mechanism of action of PBMT in an effort to avoid misinterpretations of a variety of combined protocols.
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Affiliation(s)
| | - Heloisa Ciol
- São Carlos Institute of Physics - University of São Paulo, São Carlos, SP, Brazil
| | - Vanderlei Salvador Bagnato
- São Carlos Institute of Physics - University of São Paulo, São Carlos, SP, Brazil
- Faculty Fellow at the Hagler Institute for Advanced Study and Visiting Professor at the Department of Biomedical Engineering - Texas A&M University, College Station Texas - USA 77843, USA
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29
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Chen Z, Huang S, Liu M. The review of the light parameters and mechanisms of Photobiomodulation on melanoma cells. PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE 2021; 38:3-11. [PMID: 34181781 DOI: 10.1111/phpp.12715] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 05/27/2021] [Accepted: 06/25/2021] [Indexed: 11/30/2022]
Abstract
Photobiomodulation (PBM) uses low-intensity visible or near-infrared light to produce beneficial effects on cells or tissues, such as brain therapy, wound healing. Still there is no consistent recommendation on the parameters (dose, light mode, wavelength, irradiance) and protocols (repetition, treatment duration) for its clinical application. Herein, we summarize the current PBM parameters for the treatment of melanoma, and we also discuss the potential photoreceptors and downstream signaling mechanisms in the PBM treatment of melanoma cells. It is hypothesized that PBM may inhibit the melanoma cells by activating mitochondria, OPNs, and other receptors. Regardless of the underlying mechanisms, PBM has been shown to be beneficial in treating melanoma. Through further in-depth studies of the underlying potential mechanisms, it can strengthen the applications of PBM for the therapy of melanoma.
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Affiliation(s)
- Zeqing Chen
- Institute of Future Lighting, Academy for Engineering and Technology, Fudan University, Shanghai, China
| | - Shijie Huang
- Zhongshan Fudan Joint Innovation Center, Zhongshan City, China.,Institute for Electric Light Sources, Fudan University, Shanghai, China
| | - Muqing Liu
- Institute of Future Lighting, Academy for Engineering and Technology, Fudan University, Shanghai, China.,Zhongshan Fudan Joint Innovation Center, Zhongshan City, China.,Institute for Electric Light Sources, Fudan University, Shanghai, China
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30
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Keshri GK, Kumar G, Sharma M, Bora K, Kumar B, Gupta A. Photobiomodulation effects of pulsed-NIR laser (810 nm) and LED (808 ± 3 nm) with identical treatment regimen on burn wound healing: A quantitative label-free global proteomic approach. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY 2021. [DOI: 10.1016/j.jpap.2021.100024] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
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31
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Glass GE. Photobiomodulation: The Clinical Applications of Low-Level Light Therapy. Aesthet Surg J 2021; 41:723-738. [PMID: 33471046 DOI: 10.1093/asj/sjab025] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Low-level light therapy (LLLT) is a recent addition to the pantheon of light-based therapeutic interventions. The absorption of red/near-infrared light energy, a process termed "photobiomodulation," enhances mitochondrial ATP production, cell signaling, and growth factor synthesis, and attenuates oxidative stress. Photobiomodulation is now highly commercialized with devices marketed directly to the consumer. In the gray area between the commercial and therapeutic sectors, harnessing the clinical potential in reproducible and scientifically measurable ways remains challenging. OBJECTIVES The aim of this article was to summarize the clinical evidence for photobiomodulation and discuss the regulatory framework for this therapy. METHODS A review of the clinical literature pertaining to the use of LLLT for skin rejuvenation (facial rhytids and dyschromias), acne vulgaris, wound healing, body contouring, and androgenic alopecia was performed. RESULTS A reasonable body of clinical trial evidence exists to support the role of low-energy red/near-infrared light as a safe and effective method of skin rejuvenation, treatment of acne vulgaris and alopecia, and, especially, body contouring. Methodologic flaws, small patient cohorts, and industry funding mean there is ample scope to improve the quality of evidence. It remains unclear if light-emitting diode sources induce physiologic effects of compararable nature and magnitude to those of the laser-based systems used in most of the higher-quality studies. CONCLUSIONS LLLT is here to stay. However, its ubiquity and commercial success have outpaced empirical approaches on which solid clinical evidence is established. Thus, the challenge is to prove its therapeutic utility in retrospect. Well-designed, adequately powered, independent clinical trials will help us answer some of the unresolved questions and enable the potential of this therapy to be realized.
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32
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Oyebode O, Houreld NN, Abrahamse H. Photobiomodulation in diabetic wound healing: A review of red and near-infrared wavelength applications. Cell Biochem Funct 2021; 39:596-612. [PMID: 33870502 DOI: 10.1002/cbf.3629] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 02/13/2021] [Accepted: 02/16/2021] [Indexed: 12/22/2022]
Abstract
The development of a painless, non-invasive, and faster way to diabetic wound healing is at the forefront of research. The complexity associated with diabetic wounds makes it a cause for concern amongst diabetic patients and the world at large. Irradiation of cells generates a photobiomodulatory response on cells and tissues, directly causing alteration of cellular processes and inducing diabetic wound repair. Photobiomodulation therapy (PBMT) using red and near-infrared (NIR) wavelengths is being considered as a promising technique for speeding up the rate of diabetic wound healing, eradication of pain and reduction of inflammation through the alteration of diverse cellular and molecular processes. This review presents the extent to which the potential of red and NIR wavelengths have been harnessed in PBMT for diabetic wound healing. Important research challenges and gaps are identified and discussed, and future directions mapped out. This review thus provides useful insights and strategies into improvement of PBMT, including its acceptance within the global medical research community.
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Affiliation(s)
- Olajumoke Oyebode
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein, South Africa
| | - Nicolette Nadene Houreld
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein, South Africa
| | - Heidi Abrahamse
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein, South Africa
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33
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Cios A, Ciepielak M, Szymański Ł, Lewicka A, Cierniak S, Stankiewicz W, Mendrycka M, Lewicki S. Effect of Different Wavelengths of Laser Irradiation on the Skin Cells. Int J Mol Sci 2021; 22:ijms22052437. [PMID: 33670977 PMCID: PMC7957604 DOI: 10.3390/ijms22052437] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 02/19/2021] [Accepted: 02/25/2021] [Indexed: 12/22/2022] Open
Abstract
The invention of systems enabling the emission of waves of a certain length and intensity has revolutionized many areas of life, including medicine. Currently, the use of devices emitting laser light is not only an indispensable but also a necessary element of many diagnostic procedures. It also contributed to the development of new techniques for the treatment of diseases that are difficult to heal. The use of lasers in industry and medicine may be associated with a higher incidence of excessive radiation exposure, which can lead to injury to the body. The most exposed to laser irradiation is the skin tissue. The low dose laser irradiation is currently used for the treatment of various skin diseases. Therefore appropriate knowledge of the effects of lasers irradiation on the dermal cells’ metabolism is necessary. Here we present current knowledge on the clinical and molecular effects of irradiation of different wavelengths of light (ultraviolet (UV), blue, green, red, and infrared (IR) on the dermal cells.
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Affiliation(s)
- Aleksandra Cios
- Department of Microwave Safety, Military Institute of Hygiene and Epidemiology, 04-141 Warsaw, Poland; (A.C.); (M.C.); (W.S.)
| | - Martyna Ciepielak
- Department of Microwave Safety, Military Institute of Hygiene and Epidemiology, 04-141 Warsaw, Poland; (A.C.); (M.C.); (W.S.)
| | - Łukasz Szymański
- Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Science, Postępu 36A, 05-552 Magdalenka, Poland
- Correspondence:
| | - Aneta Lewicka
- Laboratory of Food and Nutrition Hygiene, Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, Poland;
| | - Szczepan Cierniak
- Department of Patomorphology, Military Institute of Medicine, Szaserów 128, 04-141 Warsaw, Poland;
| | - Wanda Stankiewicz
- Department of Microwave Safety, Military Institute of Hygiene and Epidemiology, 04-141 Warsaw, Poland; (A.C.); (M.C.); (W.S.)
| | - Mariola Mendrycka
- Faculty of Medical Sciences and Health Sciences, Kazimierz Pulaski University of Technology and Humanities, 26-600 Radom, Poland;
| | - Sławomir Lewicki
- Department of Regenerative Medicine and Cell Biology, Military Institute of Hygiene and Epidemiology, 04-141 Warsaw, Poland;
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34
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Chen Q, Yang X, You D, Luo J, Hu X, Xu Z, Xiao W. Dim Red Light During Scotophase Enhances Mating of a Moth Through Increased Male Antennal Sensitivity Against the Female Sex Pheromone. Front Genet 2021; 12:611476. [PMID: 33719334 PMCID: PMC7943464 DOI: 10.3389/fgene.2021.611476] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 01/07/2021] [Indexed: 11/13/2022] Open
Abstract
Insects are behaviorally and physiologically affected by different light conditions, including photoperiod, light intensity, and spectrum. Light at night has important influences on nocturnal insects, including most moth species. Moth copulation and mating usually occur at night. Although a few studies examine changes in insect mating under artificial light at night, detailed influences of light, such as that of monochromatic light, on moth mating remain largely unknown. In this study, on the basis of long-term insects rearing experience, dim red light (spectrum range: 610-710nm, with a peak at 660nm; 2.0 Lux) during scotophase was hypothesized to enhance mating in the yellow peach moth, Conogethes punctiferalis. To test the hypothesis, the mating of moths under dim red, blue, and white lights during scotophase was observed. Under the dim red light, the enhancement of mating in C. punctiferalis was observed. In addition, the electroantennografic response of males against the female sex pheromone increased with red light treatment during scotophase. In an analysis of the differentially expressed genes in the antennae of males under red light and dark conditions, the expression levels of two odorant-binding protein (OBP) genes, CpunOBP2 and CpunPBP5, were up-regulated. Two genes were then expressed in Escherichia coli, and the recombinant proteins showed strong binding to female pheromone components in fluorescence-binding assays. Thus, the results of this study indicated that dim red light at night enhanced the mating of C. punctiferalis. One of the mechanisms for the enhancement was probably an increase in the antennal sensitivity of males to the female sex pheromone under red light that was caused by increases in the expression levels of pheromone-binding protein genes in male antennae.
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Affiliation(s)
- Qiuying Chen
- Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing, China.,Academy of Agricultural Sciences, Southwest University, Chongqing, China.,State Cultivation Base of Crop Stress Biology for Southern Mountainous Land of Southwest University, Southwest University, Chongqing, China
| | - Xi Yang
- Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing, China.,Academy of Agricultural Sciences, Southwest University, Chongqing, China.,State Cultivation Base of Crop Stress Biology for Southern Mountainous Land of Southwest University, Southwest University, Chongqing, China
| | - Dongrui You
- Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing, China.,Academy of Agricultural Sciences, Southwest University, Chongqing, China.,State Cultivation Base of Crop Stress Biology for Southern Mountainous Land of Southwest University, Southwest University, Chongqing, China
| | - Jiaojiao Luo
- Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing, China.,Academy of Agricultural Sciences, Southwest University, Chongqing, China.,State Cultivation Base of Crop Stress Biology for Southern Mountainous Land of Southwest University, Southwest University, Chongqing, China
| | - Xiaojing Hu
- Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing, China.,Academy of Agricultural Sciences, Southwest University, Chongqing, China.,State Cultivation Base of Crop Stress Biology for Southern Mountainous Land of Southwest University, Southwest University, Chongqing, China
| | - Zhifeng Xu
- Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing, China.,Academy of Agricultural Sciences, Southwest University, Chongqing, China.,State Cultivation Base of Crop Stress Biology for Southern Mountainous Land of Southwest University, Southwest University, Chongqing, China
| | - Wei Xiao
- Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing, China.,Academy of Agricultural Sciences, Southwest University, Chongqing, China.,State Cultivation Base of Crop Stress Biology for Southern Mountainous Land of Southwest University, Southwest University, Chongqing, China
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35
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The effects of photobiomodulation on human dermal fibroblasts in vitro: A systematic review. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY 2021; 214:112100. [DOI: 10.1016/j.jphotobiol.2020.112100] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 10/28/2020] [Accepted: 11/30/2020] [Indexed: 12/16/2022]
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36
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Ng WSV, Trigano M, Freeman T, Varrichio C, Kandaswamy DK, Newland B, Brancale A, Rozanowska M, Votruba M. New avenues for therapy in mitochondrial optic neuropathies. THERAPEUTIC ADVANCES IN RARE DISEASE 2021; 2:26330040211029037. [PMID: 37181108 PMCID: PMC10032437 DOI: 10.1177/26330040211029037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Accepted: 06/10/2021] [Indexed: 05/16/2023]
Abstract
Mitochondrial optic neuropathies are a group of optic nerve atrophies exemplified by the two commonest conditions in this group, autosomal dominant optic atrophy (ADOA) and Leber's hereditary optic neuropathy (LHON). Their clinical features comprise reduced visual acuity, colour vision deficits, centro-caecal scotomas and optic disc pallor with thinning of the retinal nerve fibre layer. The primary aetiology is genetic, with underlying nuclear or mitochondrial gene mutations. The primary pathology is owing to retinal ganglion cell dysfunction and degeneration. There is currently only one approved treatment and no curative therapy is available. In this review we summarise the genetic and clinical features of ADOA and LHON and then examine what new avenues there may be for therapeutic intervention. The therapeutic strategies to manage LHON and ADOA can be split into four categories: prevention, compensation, replacement and repair. Prevention is technically an option by modifying risk factors such as smoking cessation, or by utilising pre-implantation genetic diagnosis, although this is unlikely to be applied in mitochondrial optic neuropathies due to the non-life threatening and variable nature of these conditions. Compensation involves pharmacological interventions that ameliorate the mitochondrial dysfunction at a cellular and tissue level. Replacement and repair are exciting new emerging areas. Clinical trials, both published and underway, in this area are likely to reveal future potential benefits, since new therapies are desperately needed. Plain language summary Optic nerve damage leading to loss of vision can be caused by a variety of insults. One group of conditions leading to optic nerve damage is caused by defects in genes that are essential for cells to make energy in small organelles called mitochondria. These conditions are known as mitochondrial optic neuropathies and two predominant examples are called autosomal dominant optic atrophy and Leber's hereditary optic neuropathy. Both conditions are caused by problems with the energy powerhouse of cells: mitochondria. The cells that are most vulnerable to this mitochondrial malfunction are called retinal ganglion cells, otherwise collectively known as the optic nerve, and they take the electrical impulse from the retina in the eye to the brain. The malfunction leads to death of some of the optic nerve cells, the degree of vision loss being linked to the number of those cells which are impacted in this way. Patients will lose visual acuity and colour vision and develop a central blind spot in their field of vision. There is currently no cure and very few treatment options. New treatments are desperately needed for patients affected by these devastating diseases. New treatments can potentially arise in four ways: prevention, compensation, replacement and repair of the defects. Here we explore how present and possible future treatments might provide hope for those suffering from these conditions.
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Affiliation(s)
| | - Matthieu Trigano
- Mitochondria and Vision Lab, School of
Optometry and Vision Sciences, Cardiff University, Cardiff, UK
| | - Thomas Freeman
- Mitochondria and Vision Lab, School of
Optometry and Vision Sciences, Cardiff University, Cardiff, UK
| | - Carmine Varrichio
- School of Pharmacy and Pharmaceutical Sciences,
Cardiff University, Cardiff, UK
| | - Dinesh Kumar Kandaswamy
- Mitochondria and Vision Lab, School of
Optometry and Vision Sciences, Cardiff University, Cardiff, UK
| | - Ben Newland
- School of Pharmacy and Pharmaceutical Sciences,
Cardiff University, Cardiff, UK
| | - Andrea Brancale
- School of Pharmacy and Pharmaceutical Sciences,
Cardiff University, Cardiff, UK
| | - Malgorzata Rozanowska
- Mitochondria and Vision Lab, School of
Optometry and Vision Sciences, Cardiff University, Cardiff, UK
| | - Marcela Votruba
- School of Optometry and Vision Sciences,
Cardiff University, Maindy Road, Cardiff, CF24 4HQ, Wales, UK; Cardiff Eye
Unit, University Hospital of Wales, Cardiff, UK
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37
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Zhu Q, Xiao S, Hua Z, Yang D, Hu M, Zhu YT, Zhong H. Near Infrared (NIR) Light Therapy of Eye Diseases: A Review. Int J Med Sci 2021; 18:109-119. [PMID: 33390779 PMCID: PMC7738953 DOI: 10.7150/ijms.52980] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Accepted: 10/15/2020] [Indexed: 12/18/2022] Open
Abstract
Near infrared (NIR) light therapy, or photobiomodulation therapy (PBMT), has gained persistent worldwide attention in recent years as a new novel scientific approach for therapeutic applications in ophthalmology. This ongoing therapeutic adoption of NIR therapy is largely propelled by significant advances in the fields of photobiology and bioenergetics, such as the discovery of photoneuromodulation by cytochrome c oxidase and the elucidation of therapeutic biochemical processes. Upon transcranial delivery, NIR light has been shown to significantly increase cytochrome oxidase and superoxide dismutase activities which suggests its role in inducing metabolic and antioxidant beneficial effects. Furthermore, NIR light may also boost cerebral blood flow and cognitive functions in humans without adverse effects. In this review, we highlight the value of NIR therapy as a novel paradigm for treatment of visual and neurological conditions, and provide scientific evidence to support the use of NIR therapy with emphasis on molecular and cellular mechanisms in eye diseases.
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Affiliation(s)
- Qin Zhu
- Department of Ophthalmology, the First Affiliated Hospital of Kunming Medical University, Kunming 650031, China
| | - Shuyuan Xiao
- Department of Ophthalmology, the First Affiliated Hospital of Kunming Medical University, Kunming 650031, China
| | - Zhijuan Hua
- Department of Ophthalmology, the First Affiliated Hospital of Kunming Medical University, Kunming 650031, China
| | - Dongmei Yang
- Department of Ophthalmology, the Second People's Hospital of Yunnan Province, Kunming 650021, China
| | - Min Hu
- Department of Ophthalmology, the Second People's Hospital of Yunnan Province, Kunming 650021, China
| | | | - Hua Zhong
- Department of Ophthalmology, the First Affiliated Hospital of Kunming Medical University, Kunming 650031, China
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38
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Glass GE. Photobiomodulation: A review of the molecular evidence for low level light therapy. J Plast Reconstr Aesthet Surg 2020; 74:1050-1060. [PMID: 33436333 DOI: 10.1016/j.bjps.2020.12.059] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Revised: 11/18/2020] [Accepted: 12/19/2020] [Indexed: 12/22/2022]
Abstract
Light energy is harnessed for therapeutic use in a number of ways, most recently by way of photobiomodulation (PBM). This phenomenon is a cascade of physiological events induced by the nonthermal exposure of tissue to light at the near infrared end of the visible spectrum. Therapeutic PBM has become a highly commercialized interest, marketed for everything from facial rejuvenation to fat loss, and diode-based devices are popular in both the clinic setting and for use at home. The lack of regulatory standards makes it difficult to draw clear conclusions about efficacy and safety but it is crucial that we understand the theoretical basis for PBM, so that we can engage in an honest dialogue with our patients and design better clinical studies to put claims of efficacy to the test. This article presents a summary of the science of PBM and examines the differences between laser light, on which much of the preclinical evidence is based and light from diodes, which are typically used in a clinical setting.
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Affiliation(s)
- Graeme E Glass
- Department of Surgery, Sidra Medicine, Doha, Qatar; Chair, laser safety committee, Sidra Medicine, Doha, Qatar; Weill Cornell Medical College, New York and Qatar.
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Locke RC, Lemmon EA, Dudzinski E, Kopa SC, Wayne JM, Soulas JM, De Taboada L, Killian ML. Photobiomodulation does not influence maturation and mildly improves functional healing of mouse achilles tendons. J Orthop Res 2020; 38:1866-1875. [PMID: 31965620 PMCID: PMC8637462 DOI: 10.1002/jor.24592] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Accepted: 01/13/2020] [Indexed: 02/04/2023]
Abstract
Tendon rupture can occur at any age and is commonly treated nonoperatively, yet can result in persisting symptoms. Thus, a need exists to improve nonoperative treatments of injured tendons. Photobiomodulation (PBM) therapy has shown promise in the clinic and is hypothesized to stimulate mitochondrial-related metabolism and improve healing. However, the effect of PBM therapy on mitochondrial function during tendon maturation and healing are unknown, and its effect on tendon structure and function remain unclear. In this study, near-infrared light (980:810 nm blend, 2.5 J/cm2 ) was applied at low (30 mW/cm2 ) or high (300 mW/cm2 ) irradiance to unilateral Achilles tendons of CD-1 mice during postnatal growth (maturation) as well as adult mice with bilateral Achilles tenotomy (healing). The chronic effect of PBM therapy on tendon structure and function was determined using histology and mechanics, and the acute effect of PBM therapy on mitochondrial-related gene expression was assessed. During maturation and healing, collagen alignment, cell number, and nuclear shape were unaffected by chronic PBM therapy. We found a sex-dependent effect of PBM therapy during healing on mechanical outcomes (eg, increased stiffness and Young's modulus for PBM-treated females, and increased strain at ultimate stress for PBM-treated males). Mitochondria-related gene expression was marginally influenced by PBM therapy for both maturation and healing studies. This study was the first to implement PBM therapy during both growth and healing of the murine tendon. PBM therapy resulted in marginal and sex-dependent effects on the murine tendon. Clinical significance: PBM may be beneficial for tendon healing because functional remodeling improves without adverse effects.
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Affiliation(s)
- Ryan C. Locke
- Department of Biomedical Engineering, University of Delaware, Newark, Delaware
| | - Elisabeth A. Lemmon
- Department of Biomedical Engineering, University of Delaware, Newark, Delaware
| | - Ellen Dudzinski
- Department of Biomedical Engineering, University of Delaware, Newark, Delaware
| | - Sarah C. Kopa
- Department of Biomedical Engineering, University of Delaware, Newark, Delaware
| | - Julianna M. Wayne
- Department of Biomedical Engineering, University of Delaware, Newark, Delaware
| | - Jaclyn M. Soulas
- Department of Biomedical Engineering, University of Delaware, Newark, Delaware
| | | | - Megan L. Killian
- Department of Biomedical Engineering, University of Delaware, Newark, Delaware
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Van Wijk R, Van Wijk EP, Pang J, Yang M, Yan Y, Han J. Integrating Ultra-Weak Photon Emission Analysis in Mitochondrial Research. Front Physiol 2020; 11:717. [PMID: 32733265 PMCID: PMC7360823 DOI: 10.3389/fphys.2020.00717] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 05/29/2020] [Indexed: 12/11/2022] Open
Abstract
Once regarded solely as the energy source of the cell, nowadays mitochondria are recognized to perform multiple essential functions in addition to energy production. Since the discovery of pathogenic mitochondrial DNA defects in the 1980s, research advances have revealed an increasing number of common human diseases, which share an underlying pathogenesis involving mitochondrial dysfunction. A major factor in this dysfunction is reactive oxygen species (ROS), which influence the mitochondrial-nuclear crosstalk and the link with the epigenome, an influence that provides explanations for pathogenic mechanisms. Regarding these mechanisms, we should take into account that mitochondria produce the majority of ultra-weak photon emission (UPE), an aspect that is often ignored - this type of emission may serve as assay for ROS, thus providing new opportunities for a non-invasive diagnosis of mitochondrial dysfunction. In this article, we overviewed three relevant areas of mitochondria-related research over the period 1960-2020: (a) respiration and energy production, (b) respiration-related production of free radicals and other ROS species, and (c) ultra-weak photon emission in relation to ROS and stress. First, we have outlined how these research areas initially developed independently of each other - following that, our review aims to show their stepwise integration during later stages of development. It is suggested that a further stimulation of research on UPE may have the potential to enhance the progress of modern mitochondrial research and its integration in medicine.
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Affiliation(s)
- Roeland Van Wijk
- Meluna Research, Department of Biophotonics, Geldermalsen, Netherlands
| | | | - Jingxiang Pang
- Key Laboratory for Biotech-Drugs of National Health Commission, Shandong Medicinal Biotechnology Center, Jinan, China
- Shandong First Medical University, Jinan, China
- Shandong Academy of Medical Sciences, Jinan, China
| | - Meina Yang
- Key Laboratory for Biotech-Drugs of National Health Commission, Shandong Medicinal Biotechnology Center, Jinan, China
- Shandong First Medical University, Jinan, China
- Shandong Academy of Medical Sciences, Jinan, China
| | - Yu Yan
- Meluna Research, Department of Biophotonics, Geldermalsen, Netherlands
| | - Jinxiang Han
- Key Laboratory for Biotech-Drugs of National Health Commission, Shandong Medicinal Biotechnology Center, Jinan, China
- Shandong First Medical University, Jinan, China
- Shandong Academy of Medical Sciences, Jinan, China
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Rosenberg N, Gendelman R, Noofi N. Photobiomodulation of human osteoblast-like cells in vitro by low-intensity-pulsed LED light. FEBS Open Bio 2020; 10:1276-1287. [PMID: 32392363 PMCID: PMC7327916 DOI: 10.1002/2211-5463.12877] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 05/01/2020] [Accepted: 05/07/2020] [Indexed: 12/12/2022] Open
Abstract
Visible light irradiation is an emerging area in regenerative medicine research. We hypothesized that low‐intensity‐pulsed LED light irradiance may exert photobiomodulatory effects on cultured osteoblast‐like cells. To test this hypothesis, we investigated cell proliferation and markers of cell maturation and metabolic activity following pulsed LED irradiance. Monolayer explant cultures of human osteoblast‐like cells were exposed four times in 24‐h intervals to 2 min of pulsed white LED irradiance of 2.4–2.5 mW·cm−2 and its different spectra of 0.2–0.5 mW·cm−2 (frequency range of 10–40 Hz). Cell proliferation was estimated from microscopic cell counting and cell death by lactate dehydrogenase activity in culture media (measured by a colorimetric method). The early markers of osteoblast maturation and metabolic activity, that is, cellular alkaline phosphatase activity and osteocalcin content, were measured using a colorimetric method and ELISA, respectively. Irradiance of 40 Hz caused the highest increase in cell number (P < 0.01). Osteocalcin content in cells decreased following 40 Hz and 10 Hz irradiance (P < 0.05). The 40 Hz blue range irradiance (diffuse transmittance 420–580 nm, maximal cell irradiance 0.5 mW·cm−2) caused a decrease in alkaline phosphatase cellular activity (P < 0.001) and an increase in media osteocalcin content (P < 0.05). The 40 Hz green range (diffuse transmittance 560–650 nm, maximal cell irradiance 0.4 mW·cm−2) irradiance caused an increase in the number of cells and in cell death. In summary, pulsed (40 Hz) white light irradiance has photomodulatory effects, with its green range spectrum affecting cell proliferation and cell death, and its blue range spectrum affecting cellular maturation and metabolism. The results indicate a low‐intensity threshold of photobiomodulation of osteoblast‐like cells in vitro.
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Affiliation(s)
- Nahum Rosenberg
- Laboratory of Musculoskeletal Research, Rambam Health Care Campus and Ruth & Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel
| | - Raya Gendelman
- Laboratory of Musculoskeletal Research, Rambam Health Care Campus and Ruth & Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel
| | - Nesreen Noofi
- Laboratory of Musculoskeletal Research, Rambam Health Care Campus and Ruth & Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel
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Tripodi N, Feehan J, Husaric M, Kiatos D, Sidiroglou F, Fraser S, Apostolopoulos V. Good, better, best? The effects of polarization on photobiomodulation therapy. JOURNAL OF BIOPHOTONICS 2020; 13:e201960230. [PMID: 32077232 DOI: 10.1002/jbio.201960230] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 02/17/2020] [Accepted: 02/17/2020] [Indexed: 06/10/2023]
Abstract
Photobiomodulation therapy (PBMT) is a widely adopted form of phototherapy used to treat many chronic conditions that effect the population at large. The exact physiological mechanisms of PBMT remain unsolved; however, the prevailing theory centres on changes in mitochondrial function. There are many irradiation parameters to consider when investigating PBMT, one of which is the state of polarization. There is some evidence to show that polarization of red and near-infrared light may promote different and/or increased biological activity when compared to otherwise identical non-polarized light. These enhanced cellular effects may also be present when the polarized light is applied linear to the tissue direction. Herein, we synthesize the current experimental and clinical evidence pertaining to polarized photobiomodulation therapy; ultimately, to better inform future research into this area of phototherapy.
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Affiliation(s)
- Nicholas Tripodi
- Institute for Health and Sport, Victoria University, Melbourne, Australia
- First Year College, Victoria University, Melbourne, Australia
| | - Jack Feehan
- Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, St. Albans, Australia
- Department of Medicine-Western Health, Melbourne Medical School, The University of Melbourne, St. Albans, Australia
| | - Maja Husaric
- Institute for Health and Sport, Victoria University, Melbourne, Australia
- First Year College, Victoria University, Melbourne, Australia
| | - Dimitrios Kiatos
- Institute for Health and Sport, Victoria University, Melbourne, Australia
- Department of Medicine-Western Health, Melbourne Medical School, The University of Melbourne, St. Albans, Australia
- College of Health and Biomedicine, Victoria University, Melbourne, Australia
| | - Fotios Sidiroglou
- First Year College, Victoria University, Melbourne, Australia
- Institute for Sustainable Industries and Liveable Cities, Victoria University, Melbourne, Australia
| | - Sarah Fraser
- Institute for Health and Sport, Victoria University, Melbourne, Australia
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Michanek P, Toth T, Bergström E, Treffenberg-Pettersson H, Bergh A. Effect of infrared and red monochromatic light on equine wound healing. Equine Vet J 2020; 53:143-148. [PMID: 32285517 DOI: 10.1111/evj.13266] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Revised: 04/02/2020] [Accepted: 04/04/2020] [Indexed: 11/29/2022]
Abstract
BACKGROUND Light-emitting diodes (LEDs) are commonly used for treating a variety of disorders in horses, including wounds. Despite its claim to shorten healing times, there is a lack of scientific documentation regarding its effects. OBJECTIVES To investigate if treatment with pulsating visible red light (λ ≈ 637 nm) and near-infrared (NIR) light (λ ≈ 956 nm) affects wound healing. STUDY DESIGN Randomised blinded controlled experimental study. METHODS A circular skin wound (Ø = 2 cm) was created on each side of the neck in eight healthy horses. One randomly chosen wound received light treatment and the other served as an untreated control. Treatment duration was 4 minutes and 40 seconds (red light 95 seconds, 2.3 mW/cm2 ; NIR light 185 seconds, 6.4 mW/cm2 ) and was performed once daily on day 0-4, 7-11, 14-18 and 21-25. The wounds were photographed and evaluated using digital photoplanimetry on day 0, 1, 2, 3, 4, 7, 14, 21, 28 and 35. The degree of swelling was assessed with diagnostic ultrasound on the same days except the last recording was performed on day 36 instead of 35. Days to total healing was recorded. ANOVA was used for statistical analysis (P < .05). RESULTS The wound area (P = .2-.9) and degree of swelling (P = .2-1.0) did not differ between treated and control groups on any day. There was a significant difference (P = .03) in healing time between control (49.0, 95% CI = 35.4-62.6 days) and treated wounds (51.8, 95% CI = 38.7-64.8 days). MAIN LIMITATIONS The wounds were treated until day 25 and this study does not investigate the effect of a longer treatment period than 25 days. CONCLUSIONS The results of this study do not indicate any clinically relevant positive effect of pulsating visible red light and NIR light on the healing of experimental skin wounds in horses, compared with no treatment.
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Affiliation(s)
- Peter Michanek
- Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden
| | - Tamás Toth
- University Animal Hospital, Swedish University of Agricultural Sciences, Uppsala, Sweden
| | - Evelina Bergström
- Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
| | | | - Anna Bergh
- Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
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Protective Effect of the Aqueous Extract of Deschampsia antarctica (EDAFENCE ®) on Skin Cells against Blue Light Emitted from Digital Devices. Int J Mol Sci 2020; 21:ijms21030988. [PMID: 32024276 PMCID: PMC7038134 DOI: 10.3390/ijms21030988] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 01/31/2020] [Indexed: 01/04/2023] Open
Abstract
Skin is being increasingly exposed to artificial blue light due to the extensive use of electronic devices. This, together with recent observations reporting that blue light—also known as high-energy visible light—can exert cytotoxic effects associated with oxidative stress and promote hyperpigmentation, has sparked interest in blue light and its potential harmful effects on skin. The photoprotective properties of new extracts of different botanicals with antioxidant activity are therefore being studied. Deschampsia antarctica (Edafence®, EDA), a natural aqueous extract, has shown keratinocyte and fibroblast cell protection effects against ultraviolet radiation and dioxin toxicity. In this regard, we studied the protective capacity of EDA against the deleterious effects of artificial blue light irradiation in human dermal fibroblasts (HDF) and melanocytes. We analyzed the impact of EDA on viability, cell morphology, oxidative stress, melanogenic signaling pathway activation and hyperpigmentation in HDF and melanocytes subjected to artificial blue light irradiation. Our results show that EDA protects against cell damage caused by artificial blue light, decreasing oxidative stress, melanogenic signaling pathway activation and hyperpigmentation caused by blue light irradiation. All these findings suggest that EDA might help prevent skin damage produced by artificial blue light exposure from screen of electronic devices.
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Choi SH, Chang SY, Biswas R, Chung PS, Mo S, Lee MY, Ahn JC. Light-emitting diode irradiation using 660 nm promotes human fibroblast HSP90 expression and changes cellular activity and morphology. JOURNAL OF BIOPHOTONICS 2019; 12:e201900063. [PMID: 31066512 DOI: 10.1002/jbio.201900063] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/16/2019] [Revised: 04/27/2019] [Accepted: 05/07/2019] [Indexed: 06/09/2023]
Abstract
We evaluated changes in cell viability and morphology in response to low-level light irradiation and underlying variations in the levels of heat shock proteins (HSPs). Human fibroblasts were irradiated with a light-emitting diode (LED) array at 660 nm (50 mW for 15, 30, and 60 minutes). Cell viability and morphological changes were evaluated via epifluorescence analysis; we also assessed cell viability and length changes. The expression levels of adenosine triphosphate (ATP) and various HSPs (HSP27, 60, 70, and 90) were analyzed by immunohistochemical staining, Western blotting and microarray analysis. After LED irradiation, cellular viability and morphology changed. Of the several HSPs analyzed, the HSP90 level increased significantly, suggesting that this protein played roles in the morphological and cellular changes. Thus, low-level irradiation triggered cellular changes mediated by increased HSP90 expression; this may explain why skin irradiation enhances wound-healing.
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Affiliation(s)
- Sun-Hyang Choi
- Medical Laser Research Center, Dankook University, Cheonan, Republic of Korea
| | - So-Young Chang
- Beckman Laser Institute Korea, College of Medicine, Dankook University, Cheonan, Republic of Korea
| | - Raktim Biswas
- Medical Laser Research Center, Dankook University, Cheonan, Republic of Korea
| | - Phil-Sang Chung
- Beckman Laser Institute Korea, College of Medicine, Dankook University, Cheonan, Republic of Korea
- Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Dankook University, Cheonan, Republic of Korea
| | - Sangjoon Mo
- Medical Laser Research Center, Dankook University, Cheonan, Republic of Korea
| | - Min Young Lee
- Beckman Laser Institute Korea, College of Medicine, Dankook University, Cheonan, Republic of Korea
- Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Dankook University, Cheonan, Republic of Korea
| | - Jin Chul Ahn
- Medical Laser Research Center, Dankook University, Cheonan, Republic of Korea
- Department of Biomedical Science, College of Medicine, Dankook University, Cheonan, Republic of Korea
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Kim HS, Kim YJ, Kim SJ, Kang DS, Lee TR, Shin DW, Kim HJ, Seo YR. Transcriptomic analysis of human dermal fibroblast cells reveals potential mechanisms underlying the protective effects of visible red light against damage from ultraviolet B light. J Dermatol Sci 2019; 94:276-283. [PMID: 30956030 DOI: 10.1016/j.jdermsci.2019.03.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Revised: 03/19/2019] [Accepted: 03/20/2019] [Indexed: 10/27/2022]
Abstract
BACKGROUND Ultraviolet B (UVB) radiation is a major cause of skin photodamage, including the damage associated with photodermatoses, aging, and cancer. Although many studies have shown that red light has photoprotective effects on skin, the mechanisms underlying these effects are still poorly understood. OBJECTIVE The aim of this study was to identify the photoprotective effects of visible red light against UVB-induced skin damage in normal human dermal fibroblast cells using a transcriptomic approach. METHODS Next-generation sequencing-based transcriptomic analyses were used to profile transcriptomic alterations and identify genes that are differentially expressed by visible red light and by UVB exposure. To understand the biological networks among identified genes, a literature-based biological pathway analysis was performed. Quantitative real-time polymerase chain reaction assays were used for mRNA-level validation of selected key genes. RESULTS We observed that visible red light contributes to skin cell protection against UVB by modulating gene expression that enhances the adaptive response to redox and inflammatory balancing and by upregulating genes involved in DNA excision repair processes. We also identified that several key genes in the red light-induced biological network were differentially regulated. CONCLUSIONS Visible red light enhanced the UVB-protective effects in normal human skin cells via the transcriptomic modulation of genes involved in cell-protective processes. Our findings from this next-generation sequencing analysis may lead to a better understanding of the cytoprotective effects of visible red light and provide direction for further molecular or mechanistic studies.
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Affiliation(s)
- Hyun Soo Kim
- Department of Life Science, Institute of Environmental Medicine, Dongguk University Biomedi Campus, 32, Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10326, Republic of Korea
| | - Yeo Jin Kim
- Department of Life Science, Institute of Environmental Medicine, Dongguk University Biomedi Campus, 32, Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10326, Republic of Korea
| | - Su Ji Kim
- Department of Life Science, Institute of Environmental Medicine, Dongguk University Biomedi Campus, 32, Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10326, Republic of Korea
| | - Doo Seok Kang
- Department of Life Science, Institute of Environmental Medicine, Dongguk University Biomedi Campus, 32, Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10326, Republic of Korea
| | - Tae Ryong Lee
- Bioscience Research Institute, Amorepacific Corporation R&D Center, 1920, Yonggu-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 17074, Republic of Korea
| | - Dong Wook Shin
- College of Biomedical & Health Science, Konkuk University, Chungju, 27478, Korea.
| | - Hyoung-June Kim
- Bioscience Research Institute, Amorepacific Corporation R&D Center, 1920, Yonggu-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 17074, Republic of Korea
| | - Young Rok Seo
- Department of Life Science, Institute of Environmental Medicine, Dongguk University Biomedi Campus, 32, Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10326, Republic of Korea
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Panchaprateep R, Pisitkun T, Kalpongnukul N. Quantitative proteomic analysis of dermal papilla from male androgenetic alopecia comparing before and after treatment with low-level laser therapy. Lasers Surg Med 2019; 51:600-608. [PMID: 30843235 DOI: 10.1002/lsm.23074] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/27/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Currently, low-level laser therapy (LLLT) has been approved as a new treatment for androgenetic alopecia (AGA). However, it has not been elucidated how LLLT promotes hair growth in vivo. OBJECTIVES To investigate the change in protein expression from dermal papilla (DP) tissues in male AGA patients after LLLT treatment using liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. METHODS This is an open-label, prospective, single-arm study obtained punch scalp biopsy specimens from patients with AGA before and after LLLT treatment. Each subject was self-treated with helmet type of LLLT (655 nm, 5 mW) device at home for 25 minutes per treatment every other day for 24 weeks. LC-MS/MS analysis based on the dimethyl labeling strategy for protein quantification was used to identify proteins expressed in DP tissues from AGA patients. RESULTS Proteomic analysis revealed 11 statistically significant up-regulated and 2 down-regulated proteins in LLLT treated DP compared with baseline (P < 0.05). A bioinformatic analysis signifies that these proteins are involved in several biological processes such as regulation of cellular transcription, protein biosynthesis, cell energy, lipid homeostasis, extracellular matrix (ECM), ECM structural constituent, cell-cell/cell-matrix adhesion as well as angiogenesis. ATP-binding cassette sub-family G member, a transporter involved in cellular lipid homeostasis, was the most up-regulated protein. Additionally, LLLT increased the main ECM proteins in DP which results in a bigger volume of DP and a clinical improvement of hair diameter in AGA patients. CONCLUSION We identified the proteome set of DP proteins of male patients with AGA treated with LLLT which implicates the role of LLLT in promoting hair growth and reversing of miniaturization process of AGA by enhancing DP cell function. Our results strongly support the benefit of LLLT in the treatment of AGA. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
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Affiliation(s)
- Ratchathorn Panchaprateep
- Faculty of Medicine, Division of Dermatology, Department of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Trairak Pisitkun
- Center of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Nuttiya Kalpongnukul
- Center of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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da Silva PAV, Dos Anjos LMJ, Abduch TF, Pereira R, da Fonseca ADS, de Paoli F. Photobiomodulation can alter mRNA levels cell death-related. Lasers Med Sci 2019; 34:1373-1380. [DOI: 10.1007/s10103-019-02732-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2018] [Accepted: 01/21/2019] [Indexed: 11/27/2022]
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Mussttaf RA, Jenkins DFL, Jha AN. Assessing the impact of low level laser therapy (LLLT) on biological systems: a review. Int J Radiat Biol 2019; 95:120-143. [DOI: 10.1080/09553002.2019.1524944] [Citation(s) in RCA: 117] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Affiliation(s)
- Ruwaidah A. Mussttaf
- School of Computing, Electronics and Mathematics, University of Plymouth, Plymouth, UK
| | - David F. L. Jenkins
- School of Computing, Electronics and Mathematics, University of Plymouth, Plymouth, UK
| | - Awadhesh N. Jha
- School of Biological and Marine Sciences, University of Plymouth, Plymouth, UK
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Simonian M, Shirasaki D, Lee VS, Bervini D, Grace M, Loo RRO, Loo JA, Molloy MP, Stoodley MA. Proteomics identification of radiation-induced changes of membrane proteins in the rat model of arteriovenous malformation in pursuit of targets for brain AVM molecular therapy. Clin Proteomics 2018; 15:43. [PMID: 30602943 PMCID: PMC6305998 DOI: 10.1186/s12014-018-9217-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Accepted: 12/12/2018] [Indexed: 12/27/2022] Open
Abstract
Background Rapid identification of novel targets and advancement of a vascular targeting strategy requires a comprehensive assessment of AVM endothelial membrane protein changes in response to irradiation. The aim of this study is to provide additional potential target protein molecules for evaluation in animal trials to promote intravascular thrombosis in AVM vessels post radiosurgery. Methods We employed in vivo biotinylation methodology that we developed, to label membrane proteins in the rat model of AVM post radiosurgery. Mass spectrometry expression (MSE) analysis was used to identify and quantify surface protein expression between irradiated and non irradiated rats, which mimics a radiosurgical treatment approach. Results Our proteomics data revealed differentially expressed membrane proteins between irradiated and non irradiated rats, e.g. profilin-1, ESM-1, ion channel proteins, annexin A2 and lumican. Conclusion This work provides additional potential target protein molecules for evaluation in animal trials to promote intravascular thrombosis in AVM vessels post radiosurgery. Electronic supplementary material The online version of this article (10.1186/s12014-018-9217-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Margaret Simonian
- 1Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW Australia.,2Department of Biological Chemistry, David Geffen School of Medicine, University of California Los Angeles (UCLA), 611 Charles E. Young Drive East, Los Angeles, CA 90095 USA
| | - Dyna Shirasaki
- 2Department of Biological Chemistry, David Geffen School of Medicine, University of California Los Angeles (UCLA), 611 Charles E. Young Drive East, Los Angeles, CA 90095 USA
| | - Vivienne S Lee
- 1Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW Australia
| | - David Bervini
- 1Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW Australia.,3Neurosurgery Department, Bern University Hospital, Bern, Switzerland
| | - Michael Grace
- 4Genesis Cancer Care, Macquarie University Hospital, Sydney, NSW Australia
| | - Rachel R Ogorzalek Loo
- 2Department of Biological Chemistry, David Geffen School of Medicine, University of California Los Angeles (UCLA), 611 Charles E. Young Drive East, Los Angeles, CA 90095 USA
| | - Joseph A Loo
- 2Department of Biological Chemistry, David Geffen School of Medicine, University of California Los Angeles (UCLA), 611 Charles E. Young Drive East, Los Angeles, CA 90095 USA
| | - Mark P Molloy
- 5Department of Chemistry and Bimolecular Sciences, Australian Proteome Analysis Facility (APAF), Macquarie University, Sydney, NSW Australia.,Lawrence Penn Chair of Bowel Cancer Research, Faculty of Medicine and Health, Northern Clinical School, Sydney, Australia
| | - Marcus A Stoodley
- 1Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW Australia
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