White matter microstructural integrity as a key to effective propagation of gamma entrainment in humans.

Gamma entrainment through sensory stimulation has the potential to reduce the pathology of Alzheimer's disease in mouse models. However, clinical trials in Alzheimer's disease (AD) patients have yielded inconsistent results, necessitating further investigation. This single-center pre-post intervention study aims to explore the influence of white matter microstructural integrity on gamma rhythm propagation from the visual cortex to AD-affected regions in 31 cognitively normal volunteers aged ≥ 65. Gamma rhythm propagation induced by optimal FLS was measured. Diffusion tensor imaging was employed to assess the integrity of white matter tracts of interest. After excluding 5 participants with a deficit in steady-state visually evoked potentials, 26 participants were included in the final analysis. In the linear regression analyses, gamma entrainment was identified as a significant predictor of gamma propagation (p < 0.001). Furthermore, the study identified white matter microstructural integrity as a significant predictor of gamma propagation by flickering light stimulation (p < 0.05), which was specific to tracts that connect occipital and temporal or frontal regions. These findings indicate that, despite robust entrainment of gamma rhythms in the visual cortex, their propagation to other regions may be impaired if the microstructural integrity of the white matter tracts connecting the visual cortex to other areas is compromised. Consequently, our findings have expanded our understanding of the prerequisites for effective gamma entrainment and suggest that future clinical trials utilizing visual stimulation for gamma entrainment should consider white matter tract microstructural integrity for candidate selection and outcome analysis.

Activation of reparative processes of chronic wounds using photobiomodulation therapy (experimental study).

OBJECTIVE: Aim: The aim of the work was to study the ef f ect of photobiomodulation therapy on the regulation of disorders in the healing of chronic wounds at the remodeling stage using indicators of platelet aggregation activity, reactive oxygen species, platelet-derived growth factor, and interleukin-1ß. PATIENTS AND METHODS: Materials and Methods: The study included 3 groups of Wistar rats: intact animals and animals of the control and experimental groups, for which chronic wounds were simulated. Rats in the experimental group received photobiomodulation therapy once a day for 5 days. Wound defects of animals in the control group were fictitiously irradiated. The levels of reactive oxygen species, platelet-derived growth factor, and interleukin-1ß in the blood serum of animals were studied by enzyme immunoassay. The functional activity of platelets was measured on a computerized platelet aggregation analyzer using the turbidimetric method. Histological studies were carried out. RESULTS: Results: Changes in the expression of the studied indicators were found in the blood serum of animals with chronic wounds when using photobiomodulation therapy: an increase in platelet-derived growth factor concentrations, the levels of reactive oxygen species and interleukin-1ß did not have statistically signif i cant differences compared to the corresponding indicators of animals in the control group. There were no significant differences in the indicators of platelet aggregation activity in the control and experimental groups of animals. CONCLUSION: Conclusions: The findings suggest that photobiomodulation therapy may promote wound healing by increasing platelet-derived growth factor levels. Histological studies have shown that using photobiomodulation therapy helps reduce inflammation and better organization of collagen fibers in animals of the experimental group.

The adjunctive use of antimicrobial photodynamic therapy, light-emitting-diode photobiomodulation and ozone therapy in regenerative treatment of stage III/IV grade C periodontitis: a randomized controlled clinical trial.

OBJECTIVES: To assess the short-term efficacy of multiple sessions of antimicrobial photodynamic therapy (aPDT), light-emitting-diode (LED) photobiomodulation, and topical ozone therapy applications following surgical regenerative treatments on clinical parameters, patient-centered outcomes, and mRNA expression levels of VEGF, IL-6, RunX2, Nell-1, and osterix in gingival crevicular fluid samples in patients with stage III/IV, grade C periodontitis. MATERIALS AND METHODS: Forty-eight systemically healthy patients were assigned into four groups to receive adjunctive modalities with regenerative periodontal surgical treatment. A 970 ± 15 nm diode laser plus indocyanine-green for aPDT group, a 626 nm LED for photobiomodulation group, and topical gaseous ozone were applied at 0, 1, 3, and 7 postoperative days and compared to control group. The clinical periodontal parameters, early wound healing index (EHI), and postoperative patients' morbidity were evaluated. The mRNA levels of biomarkers were assessed by real-time polymerase chain reaction. RESULTS: No significant difference in the clinical parameters except gingival recession (GR) was identified among the groups. For group-by-time interactions, plaque index (PI) and probing pocket depths (PD) showed significant differences (p = 0.034; p = 0.022). In sites with initial PD > 7 mm, significant differences were observed between control and photobiomodulation groups in PD (p = 0.011), between control and aPDT, and control and photobiomodulation groups in CAL at 6-month follow-up (p = 0.007; p = 0.022). The relative osterix mRNA levels showed a statistically significant difference among the treatment groups (p = 0.014). CONCLUSIONS: The additional applications of aPDT and LED after regenerative treatment of stage III/IV grade C periodontitis exhibited a more pronounced beneficial effect on clinical outcomes in deep periodontal pockets.

Might photobiomodulation therapy interfere with the frequency of severe mucositis and oral candidiasis? A retrospective analysis in patients with head and neck carcinoma.

PURPOSE: Considering the tumor in the oral cavity or the oropharynx and nasopharynx region might be an aggravating factor for oral mucositis (OM) manifestation, the present study aimed to evaluate whether the location of the tumor and the use of photobiomodulation therapy (PBMT) might affect the frequency of oral candidiasis (OC) during radiotherapy (RT) and/or chemotherapy (CT) treatments. METHODS: The medial records of seventy-four patients with head and neck cancer treated in a public service from 2016 to 2019 were evaluated. All these patients were submitted to RT in an accumulated dose of 48 to 70 Gy of radiation. Data about OM and OC were collected and presented according to the application of a therapeutic protocol with laser photobiomodulation (PBMT) to control oral mucositis, or not (No-PBM), and the location of tumor (head and neck or oral cavity). In the PBMT group patients, a low-power laser device composed of InGaAlP diode (maximum output power of 86.7 mW, active tip area of 0.1256 cm2, and continuous wavelength of 660 nm), was applied to the lips (three points each), right and left jugal mucosa (three points each), the limit between hard and soft palate (three points), buccal floor/sublingual gland (one point), lateral edge of the tongue (three points on each side), and back of the tongue (six points), three times weekly, for 5 weeks. The dosimetry used in each application was 2 J for 3 s, thus totaling 56 J. The correlation between clinical characteristics such as age, tumor size (T), metastatic lymph node (N), number of RT and CT sessions, candidiasis, and OM were analyzed. RESULTS: Mucositis grades 1 and 2 were the most common among all patients, especially before the 12th radiotherapy session, regardless of the treatment with PBM (p > 0.05). Additionally, no difference in the grade of OM and OC was significantly observed when comparing the two laser therapy groups. OC was more frequent after the 12th radiotherapy session in all groups. Nonetheless, OM and OC had a different correlation regarding to tumor location (head and neck and oral cavity) being PBMT a positive therapy to delay OM. It was observed a positive and statistically significant correlation between tumors at oral cavity and OM, regardless PBMT (R = 0.84, p < 0.05 to PBMT and R = 0.13, p < 0.05 to No-PBM). Otherwise, OC was positively correlated to local metastasis in patients with oral tumors undergoing PBMT (R = 0.84, p < 0.05). CONCLUSION: Patients with oral cavity tumor presented more OM, especially high grades, then patients with tumors in other regions of the head and neck, which seems to be related to the irradiation parameters of radiotherapy and/or with the limitation of conduction of PBMT in tumor areas. OM and OC were not changed by PBMT, although it helped to reduce the incidence of severe cases of OM.

Direct Photobiomodulation Therapy on the Sciatic Nerve Significantly Attenuates Acute Nociceptive Sensitivity Without Affecting Motor Output.

OBJECTIVES: Pharmacologic pain treatments lack specific targeting and often produce unwanted side effects (eg, addiction, additional hyperalgesia). We previously established that the direct application of laser irradiation (direct photobiomodulation [PBM]) of the sural nerve reduces thermal hypersensitivity in a rodent model of chronic pain, but not mechanical hypersensitivity. These observations were consistent with a selective reduction in the small-diameter fiber contribution to electrophysiologically measured evoked response after direct PBM of a sensory nerve (saphenous). However, to our knowledge, direct application of laser irradiation has never been performed in an animal model of acute nociceptive pain or on a mixed nerve in which sensory and motor outcomes can be observed. MATERIALS AND METHODS: In this study, we describe the effects of direct application of laser irradiation (808 nm, 60 mW, 4 minutes) on a mixed nerve (sciatic nerve) in an acute nociceptive pain model (intradermal capsaicin injection) in rats over the course of two weeks. To investigate whether laser irradiation of a mixed nerve alters motor function, in separate experiments, we applied laser irradiation to the sciatic nerve (using the same parameters as in the chronic pain experiments), and force generation of the gastrocnemius was measured. RESULTS: Capsaicin-induced hypersensitivities to mechanical (pin prick) and thermal (Hargreaves) noxious stimuli, associated with Aδ- and C-fibers, showed a maximal reduction of 70% and 56.2%, respectively, by direct PBM, when compared with a control group (vehicle injection, no PBM) on the same day. This reduction was determined to be significant using a mixed-design analysis of variance with a p value < 0.05. Force generation remained unchanged for up to 120 minutes after laser irradiation. In summary, direct PBM selectively inhibits C- and Aδ-fiber transmission while leaving Aɑ-, Aß-, and motor-fiber activity intact. CONCLUSIONS: These results, in conjunction with our previous analyses of laser irradiation effects on the sural nerve in a chronic spared nerve injury pain model, suggest that direct PBM is a promising candidate for treating pain induced by small-diameter fiber activity.

Effects of photobiomodulation on colon cancer cell line HT29 according to mitochondria.

BACKGROUND/AIM: Although photobiomodulation therapy (PBMt) is available to alleviate post-operative side effects of malignant diseases, its application is still controversial due to some potential of cancer recurrence and occurrence of a secondary malignancy. We investigated effect of PBMt on mitochondrial function in HT29 colon cancer cells. METHODS: HT29 cell proliferation was determined with MTT assay after PBMt. Immunofluorescent staining was performed to determine mitochondrial biogenesis and reactive oxygen species (ROS). Mitochondrial membrane potential was measured with Mitotracker. Western blotting was executed to determine expression of fission, fusion, UCP2, and cyclin B1 and D1 proteins. In vivo study was performed by subcutaneously inoculating cancer cells into nude mice and immunohistochemistry was done to determine expression of FIS1, MFN2, UCP2, and p-AKT. RESULTS: The proliferation and migration of HT29 cells reached maximum with PBMt (670 nm, light emitting diode, LED) at 2.0 J/cm2 compared to control (P < 0.05) with more expression of cyclin B1 and cyclin D1 (P < 0.05). Immunofluorescent staining showed that ROS and mitochondrial membrane potential were enhanced after PBMt compared to control. ATP synthesis of mitochondria was also higher in the PBMt group than in the control (P < 0.05). Expression levels of fission and fusion proteins were significantly increased in the PBMt group than in the control (P < 0.05). Electron microscopy revealed that the percentage of mitochondria showing fission was not significantly different between the two groups. Oncometabolites including D-2-hydoxyglutamate in the supernatant of cell culture were higher in the PBMt group than in the control with increased UCP2 expression (P < 0.05). Both tumor size and weight of xenograft in nude mice model were bigger and heavier in the PBMt group than in the control (P < 0.05). Immunohistologically, mitochondrial biogenesis proteins UCP2 and p-AKT in xenograft of nude mice were expressed more in the PBMt group than in the control (P < 0.05). CONCLUSIONS: Treatment with PBM using red light LED may induce proliferation and progression of HT29 cancer cells by increasing mitochondrial activity and fission.

Can transcranial photobiomodulation improve cognitive function in TBI patients? A systematic review.

Introduction: Transcranial photobiomodulation (tPBM) is a non-invasive neuromodulation technology which has become a promising therapy for treating many brain diseases. Although it has been confirmed in studies targeting neurological diseases including Alzheimer's and Parkinson's that tPBM can improve cognitive function, the effectiveness of interventions targeting TBI patients remains to be determined. This systematic review examines the cognitive outcomes of clinical trials concerning tPBM in the treatment of traumatic brain injury (TBI). Methods: We conducted a systematic literature review, following the PRISMA guidelines. The PubMed, Web of Science, Scopus, EMBASE, and Cochrane Library databases were searched before October 31, 2023. Results: The initial search retrieved 131 articles, and a total of 6 studies were finally included for full text-analysis after applying inclusion and exclusion criteria. Conclusion: Results showed improvements in cognition for patients with chronic TBI after tPBM intervention. The mechanism may be that tPBM increases the volume of total cortical gray matter (GM), subcortical GM, and thalamic, improves cerebral blood flow (CBF), functional connectivity (FC), and cerebral oxygenation, improving brain function. However, due to the significant heterogeneity in application, we cannot summarize the optimal parameters for tPBM treatment of TBI. In addition, there is currently a lack of RCT studies in this field. Therefore, given this encouraging but uncertain finding, it is necessary to conduct randomized controlled clinical trials to further determine the role of tPBM in cognitive rehabilitation of TBI patients.

Effect of combined red and infrared wavelengths on inflammation, hemorrhage, and muscle damage caused by Bothrops leucurus snake venom.

To evaluate the effects of red and infrared wavelengths, separately and combined, on the inflammatory process and collagen deposition in muscle damage caused by B. leucurus venom. 112 mice were inoculated with diluted venom (0.6mg/kg) in the gastrocnemius muscle. The animals were divided into four groups: one control (CG) and three treatments, namely: 1) red laser (λ=660 nm) (RG), 2) infrared laser (λ=808 nm) (IG) and 3) red laser (λ=660 nm) + infrared (λ=808 nm) (RIG). Each group was subdivided into four subgroups, according to the duration of treatment application (applications every 24 hours over evaluation times of up to 144 hours). A diode laser was used (0.1 W, CW, 1J/point, ED: 10 J/cm2). Both wavelengths reduced the intensity of inflammation and the combination between them significantly intensified the anti-inflammatory response. Photobiomodulation also changed the type of inflammatory infiltrate observed and RIG had the highest percentage of mononuclear cells in relation to the other groups. Hemorrhage intensity was significantly lower in treated animals and RIG had the highest number of individuals in which this variable was classified as mild. As for collagen deposition, there was a significant increase in RG in relation to CG, in RIG in relation to CG and in RIG in relation to IG. Photobiomodulation proved to be effective in the treatment of inflammation and hemorrhage caused by B. leucurus venom and stimulated collagen deposition. Better results were obtained with the combined wavelengths.

High-frequency low-intensity semiconductor laser irradiation enhances osteogenic differentiation of human cementoblast lineage cells.

PURPOSE: Laser irradiation activates a range of cellular processes in the periodontal components and promotes tissue repair. However, its effect on osteogenic differentiation of human cementoblast lineage cells remains unclear. This study aimed to examine the effects of high-frequency semiconductor laser irradiation on the osteogenic differentiation of human cementoblast lineage (HCEM) cells. METHODS: HCEM cells were cultured to reach 80% confluence and irradiated with a gallium-aluminum-arsenide (Ga-Al-As) semiconductor laser with a pulse width of 200 ns and wavelength of 910 at a dose of 0-2.0 J/cm2. The outcomes were assessed by analyzing the mRNA levels of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and type I collagen (COLL1) using real-time polymerase chain reaction (PCR) analysis 24 h after laser irradiation. Cell mineralization was evaluated using ALP activity, calcium deposition, and Alizarin Red staining. RESULTS: The laser-irradiated HCEM cells showed significantly enhanced gene expression levels of ALP, RUNX2, and COLL1 as well as ALP activity and calcium concentration in the culture medium compared with the non-irradiated cells. In addition, enhanced calcification deposits were confirmed in the laser-irradiated group compared with the non-irradiated group at 21 and 28 days after the induction of osteogenic differentiation. CONCLUSION: High-frequency semiconductor laser irradiation enhances the osteogenic differentiation potential of cultured HCEM cells, underscoring its potential utility for periodontal tissue regeneration.

Photobiomodulation transiently increases the spontaneous firing in the superficial layer of the rat spinal dorsal horn.

The therapeutic benefits of photobiomodulation (PBM) in pain management, although well documented, are accompanied by concerns about potential risks, including pain, particularly at higher laser intensities. This study investigated the effects of laser intensity on pain perception using behavioral and electrophysiological evaluations in rats. Our results show that direct laser irradiation of 1000 mW/cm2 to the sciatic nerve transiently increases the frequency of spontaneous firing in the superficial layer without affecting the deep layer of the spinal dorsal horn, and this effect reverses to pre-irradiation levels after irradiation. Interestingly, laser irradiation at 1000 mW/cm2, which led to an increase in spontaneous firing, did not prompt escape behavior. Furthermore, a significant reduction in the time to initiate escape behavior was observed only at 9500 mW/cm2 compared to 15, 510, 1000, and 4300 mW/cm2. This suggests that 1000 mW/cm2, the laser intensity at which an increase in spontaneous firing was observed, corresponds to a stimulus that did not cause pain. It is expected that a detailed understanding of the risks and mechanisms of PBM from a neurophysiological perspective will lead to safer and more effective use of PBM.

Impact of Photobiomodulation on IL1ß and TGFß-1 concentrations in patients with aphthous stomatitis.

Laser therapy has shown effectiveness in promoting wound healing by influencing various physiological factors such as blood flow, cytokines, histamine, nerve signals, lymphocyte function, tissue oxygenation, and cell growth. This study aims to evaluate the therapeutic efficacy of Photobiomodulation (PBM) treatment, by using diode laser, in modifying the levels of interleukin-1 beta (IL1ß) and transforming growth factor beta-1 (TGFß-1) in patients diagnosed with aphthous stomatitis. A before-after interventional design was conducted over 10 months with 20 subjects. Data on demographic details and serum concentrations of IL1ß and TGFß-1 were collected pre-treatment and on Days 3 and 7 post-treatments. The intervention involved a single session of four 30-second applications of a QuickLase dual-wavelength laser operating at 980 nm. Results show significant reductions in IL1ß and TGFß-1 levels after 7 days of treatment, indicating a time-dependent effect of PBM therapy on these inflammatory markers. The findings suggest that PBM therapy holds promise as an intervention for reducing inflammation associated with aphthous stomatitis.

Regenerative Potential of Dental Pulp Stem Cells in Response to a Bioceramic Dental Sealer and Photobiomodulation: An In Vitro Study.

AIMS: This study aims to assess the synergistic effect of utilizing a bioceramic sealer, NeoPutty, with photobiomodulation (PBM) on dental pulp stem cells (DPSCs) for odontogenesis. MATERIALS AND METHODS: Dental pulp stem cells were collected from 10 premolars extracted from healthy individuals. Dental pulp stem cells were characterized using an inverted-phase microscope to detect cell shape and flow cytometry to detect stem cell-specific surface antigens. Three experimental groups were examined: the NP group, the PBM group, and the combined NP and PBM group. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) experiment was conducted to assess the viability of DPSCs. The odontogenic differentiation potential was analyzed using Alizarin red staining, RT-qPCR analysis of odontogenic genes DMP-1, DSPP, and alkaline phosphatase (ALP), and western blot analysis for detecting BMP-2 and RUNX-2 protein expression. An analysis of variance (ANOVA) followed by a post hoc t-test was employed to examine and compare the mean values of the results. RESULTS: The study showed a notable rise in cell viability when NP and PBM were used together. Odontogenic gene expression and the protein expression of BMP-2 and RUNX-2 were notably increased in the combined group. The combined effect of NeoPutty and PBM was significant in enhancing the odontogenic differentiation capability of DPSCs. CONCLUSION: The synergistic effect of NeoPutty and PBM produced the most positive effect on the cytocompatibility and odontogenic differentiation potential of DPSCs. CLINICAL SIGNIFICANCE: Creating innovative regenerative treatments to efficiently and durably repair injured dental tissues. How to cite this article: Alshawkani HA, Mansy M, Al Ankily M, et al. Regenerative Potential of Dental Pulp Stem Cells in Response to a Bioceramic Dental Sealer and Photobiomodulation: An In Vitro Study. J Contemp Dent Pract 2024;25(4):313-319.

Blue light irradiation suppresses oral squamous cell carcinoma through induction of endoplasmic reticulum stress and mitochondrial dysfunction.

The therapeutic potential of blue light photobiomodulation in cancer treatment, particularly in inhibiting cell proliferation and promoting cell death, has attracted significant interest. Oral squamous cell carcinoma (OSCC) is a prevalent form of oral cancer, necessitating innovative treatment approaches to improve patient outcomes. In this study, we investigated the effects of 420 nm blue LED light on OSCC and explored the underlying mechanisms. Our results demonstrated that 420 nm blue light effectively reduced OSCC cell viability and migration, and induced G2/M arrest. Moreover, we observed that 420 nm blue light triggered endoplasmic reticulum (ER) stress and mitochondrial dysfunction in OSCC cells, leading to activation of the CHOP signal pathway and alterations in the levels of Bcl-2 and Bax proteins, ultimately promoting cell apoptosis. Additionally, blue light suppressed mitochondrial gene expression, likely due to its damage to mitochondrial DNA. This study highlights the distinct impact of 420 nm blue light on OSCC cells, providing valuable insights into its potential application as a clinical treatment for oral cancer.

The Effect of Delayed Photobiomodulation Therapy on Inferior Alveolar Nerve Recovery After Third Molar Removal: A Triple-Blinded Randomized Clinical Trial.

Background: Third molar removal is the primary reason for inferior alveolar nerve (IAN) damage, with 2% causing persistent neurosensory deficits. This study aimed to investigate how delayed photobiomodulation therapy affects long-lasting neurosensory disturbances. Methods: This study was conducted on patients with neurosensory disturbances lasting longer than 6 months. Patients were randomly allocated to the study and control groups, with the study group receiving a low-power diode laser (continuous wavelength of 810 nm, power of 200 mW) on 16 points (30 sec at each) for 12 sessions (2 sessions/week), while the control group received a placebo treatment by switched-off laser probe. Visual analog scale (VAS; ranging from 1 to 5), static light touch, two-point discrimination, direction discrimination, pinprick, and thermal discrimination tests were performed on each visit up to 9 months post-therapy to evaluate the recovery status. Results: Each group comprised 18 participants. The mean time since injury was 8.26 ± 2.05 and 8.38 ± 1.98 months for the control and intervention groups, respectively (p = 0.81). There was a significant improvement in the intervention group on the static light touch (p = 0.041), two-point discrimination (p = 0.028), VAS (p = 0.031), and pinprick (p = 0.014) tests on the 11th session and subsequent visits and also on direction discrimination test on the 12th session (p = 0.044) and after that. There was no significant difference in the thermal discrimination tests between the two groups (p > 0.05). Conclusion: Photobiomodulation demonstrated potential benefits in resolving persistent neurosensory deficits of the IAN, with noticeable improvements typically observed after around 35 days of treatment initiation (10 sessions).

Effect of photobiomodulation in the balance between effector and regulatory T cells in an experimental model of COPD.

Introduction: Currently, Chronic Obstructive Pulmonary Disease (COPD) has a high impact on morbidity and mortality worldwide. The increase of CD4+, CD8+ cells expressing NF-κB, STAT4, IFN-γ and perforin are related to smoking habit, smoking history, airflow rate, obstruction and pulmonary emphysema. Furthermore, a deficiency in CD4+CD25+Foxp3+ regulatory T cells (Tregs) may impair the normal function of the immune system and lead to respiratory immune disease. On the other hand, the anti-inflammatory cytokine IL-10, produced by Treg cells and macrophages, inhibits the synthesis of several pro-inflammatory cytokines that are expressed in COPD. Therefore, immunotherapeutic strategies, such as Photobiomodulation (PBM), aim to regulate the levels of cytokines, chemokines and transcription factors in COPD. Consequently, the objective of this study was to evaluate CD4+STAT4 and CD4+CD25+Foxp3+ cells as well as the production of CD4+IFN- γ and CD4+CD25+IL-10 in the lung after PBM therapy in a COPD mice model. Methods: We induced COPD in C57BL/6 mice through an orotracheal application of cigarette smoke extract. PMB treatment was applied for the entire 7 weeks and Bronchoalveolar lavage (BAL) and lungs were collected to study production of IFN- γ and IL-10 in the lung. After the last administration with cigarette smoke extract (end of 7 weeks), 24 h later, the animals were euthanized. One-way ANOVA followed by NewmanKeuls test were used for statistical analysis with significance levels adjusted to 5% (p < 0.05). Results: This result showed that PBM improves COPD symptomatology, reducing the number of inflammatory cells (macrophages, neutrophils and lymphocytes), the levels of IFN-γ among others, and increased IL-10. We also observed a decrease of collagen, mucus, bronchoconstriction index, alveolar enlargement, CD4+, CD8+, CD4+STAT4+, and CD4+IFN-γ+ cells. In addition, in the treated group, we found an increase in CD4+CD25+Foxp3+ and CD4+IL-10+ T cells. Conclusion: This study suggests that PBM treatment could be applied as an immunotherapeutic strategy for COPD.

Photobiomodulation versus fractional carbon dioxide laser for stria alba in phototype III-IV: a randomized controlled study.

Striae distensae are common dermatological complaint. Cold laser using low-level light/laser therapy (LLLT) offers healing and analgesic effects and was not yet compared to 'hot lasers' efficacy. Study objective: to assess the efficacy and safety of LLLT in the management of stria alba compared to fractional carbon dioxide (FCO2) laser alone and to the combined use of both devices. Thirty patients with stria alba were randomized to receive either LLLT using diode 808 nm; 8-12 sessions, 2-3 sessions weekly (Group A) or FCO2 laser; 2 monthly sessions (Group B) or combined both devices simultaneously (Group C). Follow up was at 1 month and 3 months after last session. The efficacy of LLLT was statistically comparable to FCO2, despite numerical superiority of the latter. The combined group had the least numerical values in all efficacy outcomes. Patients in LLLT group did not experience any downtime. LLLT is effective in the management of stria alba comparable to the FCO2 laser. The lack of downtime with LLLT is reflected positively on patient's satisfaction. However, this is counterbalanced by the frequent weekly visits. Although adding LLLT to FCO2 laser palliates the laser side effects but it offers the least efficacy. Trial registration number NCT04165226 (clinicaltrials.gov).

Transcranial photobiomodulation therapy improves cognitive test scores in dogs with presumptive canine cognitive dysfunction: A case series of five dogs.

Background: Canine cognitive dysfunction (CCD) is considered the canine version of human Alzheimer's disease (AD). As with AD, CCD is a multifactorial and progressive neurodegenerative disorder for which effective treatment options are continuously being sought. Transcranial photobiomodulation (tPBMT) or transcranial laser therapy has shown promise as a treatment for cognitive impairment in rodent AD investigations and several human AD clinical trials. Aim: The purpose of this prospective case series was to evaluate the effect of tPBMT on cognitive scores when applied to senior dogs with CCD over a 60-day period. Methods: Five senior (>9-year-old) dogs with moderate (16-33) to severe (>33) cognitive scores were enrolled. Owners were instructed on the use of a Class IM laser device and administered a specific dose of laser energy transcranially to both sides of the patient's head, three times per week for one month and two times per week for a second month. No additional therapeutic measures aimed at enhancing cognitive ability were permitted during the 60-day evaluation time. Baseline cognitive scores were compared with scores obtained at 30- and 60-days post-treatment. Results: Cognitive scores showed improvement in 4/5 dogs at 30 days (27.6% reduction) and all dogs at 60 days (43.4% reduction). There were no adverse effects attributable to tPBMT. Conclusion: Results of our small case series suggest that tPBMT may improve cognitive scores in dogs with moderate to severe CCD by 30 days of application and the improvement is sustained at 60 days. Further studies are needed to ascertain optimal tPBMT protocols for CCD.

Study and optimization of the photobiomodulation effects induced on mitochondrial metabolic activity of human cardiomyocytes for different radiometric and spectral conditions.

Photobiomodulation (PBM) represents a promising and powerful approach for non-invasive therapeutic interventions. This emerging field of research has gained a considerable attention due to its potential for multiple disciplines, including medicine, neuroscience, and sports medicine. While PBM has shown the ability to stimulate various cellular processes in numerous medical applications, the fine-tuning of treatment parameters, such as wavelength, irradiance, treatment duration, and illumination geometry, remains an ongoing challenge. Furthermore, additional research is necessary to unveil the specific mechanisms of action and establish standardized protocols for diverse clinical applications. Given the widely accepted understanding that mitochondria play a pivotal role in the PBM mechanisms, our study delves into a multitude of PBM illumination parameters while assessing the PBM's effects on the basis of endpoints reflecting the mitochondrial metabolism of human cardiac myocytes (HCM), that are known for their high mitochondrial density. These endpoints include: i) the endogenous production of protoporphyrin IX (PpIX), ii) changes in mitochondrial potential monitored by Rhodamine 123 (Rhod 123), iii) changes in the HCM's oxygen consumption, iv) the fluorescence lifetime of Rhod 123 in mitochondria, and v) alterations of the mitochondrial morphology. The good correlation observed between these different methods to assess PBM effects underscores that monitoring the endogenous PpIX production offers interesting indirect insights into the mitochondrial metabolic activity. This conclusion is important since many approved therapeutics and cancer detection approaches are based on the use of PpIX. Finally, this correlation strongly suggests that the PBM effects mentioned above have a common "fundamental" mechanistic origin.

Photobiomodulation Inhibits Ischemia-Induced Brain Endothelial Senescence via Endothelial Nitric Oxide Synthase.

Recent research suggests that photobiomodulation therapy (PBMT) positively impacts the vascular function associated with various cerebrovascular diseases. Nevertheless, the specific mechanisms by which PBMT improves vascular function remain ambiguous. Since endothelial nitric oxide synthase (eNOS) is crucial in regulating vascular function following cerebral ischemia, we investigated whether eNOS is a key element controlling cerebrovascular function and the senescence of vascular endothelial cells following PBMT treatment. Both rat photothrombotic (PT) stroke and in vitro oxygen-glucose deprivation (OGD)-induced vascular endothelial injury models were utilized. We demonstrated that treatment with PBMT (808 nm, 350 mW/cm2, 2 min/day) for 7 days significantly reduced PT-stroke-induced vascular permeability. Additionally, PBMT inhibited the levels of endothelial senescence markers (senescence green and p21) and antiangiogenic factor (endostatin), while increasing the phospho-eNOS (Ser1177) in the peri-infarct region following PT stroke. In vitro study further indicated that OGD increased p21, endostatin, and DNA damage (γH2AX) levels in the brain endothelial cell line, but they were reversed by PBMT. Intriguingly, the beneficial effects of PBMT were attenuated by a NOS inhibitor. In summary, these findings provide novel insights into the role of eNOS in PBMT-mediated protection against cerebrovascular senescence and endothelial dysfunction following ischemia. The use of PBMT as a therapeutic is a promising strategy to improve endothelial function in cerebrovascular disease.

Vitamin E Attenuates Red-Light-Mediated Vasodilation: The Benefits of a Mild Oxidative Stress.

Red light (670 nm) energy controls vasodilation via the formation of a transferable endothelium-derived nitric oxide (NO)-precursor-containing substance, its intracellular traffic, and exocytosis. Here we investigated the underlying mechanistic effect of oxidative stress on light-mediated vasodilation by using pressure myography on dissected murine arteries and immunofluorescence on endothelial cells. Treatment with antioxidants Trolox and catalase decreased vessel dilation. In the presence of catalase, a lower number of exosomes were detected in the vessel bath. Light exposure resulted in increased cellular free radical levels. Mitochondrial reactive oxygen species were also more abundant but did not alter cellular ATP production. Red light enhanced the co-localization of late exosome marker CD63 and cellular S-nitrosoprotein to a greater extent than high glucose, suggesting that a mild oxidative stress favors the localization of NO precursor in late exosomes. Exocytosis regulating protein Rab11 was more abundant after irradiation. Our findings conclude that red-light-induced gentle oxidative stress facilitates the dilation of blood vessels, most likely through empowering the traffic of vasodilatory substances. Application of antioxidants disfavors this mechanism.