Search Results (228)

This study aimed to evaluate the effects of laser photobiomodulation (PBM) therapy in SaOs-2 osteosarcoma cells treated with zoledronic acid (ZA), a bisphosphonate, in vitro, mimicking a bisphosphonate-related osteonecrosis of the jaw (BRONJ) situation. Cells were treated with 100 μM ZA for 24 h and subjected to PBM using wavelengths of 660 nm and 808 nm at energy delivered of 1, 5, 10, and 20 J. After 24 h, metabolic activity, apoptosis, and BAX and BCL-2 gene expression were analyzed. Data were compared using one-way ANOVA followed by Tukey’s post hoc test (p < 0.05). ZA significantly reduced metabolic activity (p < 0.05), an effect attenuated by PBM at 808 nm with 1 J, while BCL-2 expression increased with 1 J at 660 nm and with 1 J and 20 J at 808 nm. However, PBM did not reverse ZA-induced apoptosis. In conclusion, PBM modulated the response of SaOs-2 osteoblastic cells treated with ZA in a wavelength- and dose-dependent manner. PBM at 808 nm and 1 J stimulated cell metabolic activity and upregulated BCL-2 expression, suggesting a potential protective effect against ZA-induced cytotoxicity. Full article

Down Syndrome Regression Disorder (DSRD) is a rare but severe neuropsychiatric condition characterized by abrupt loss of speech, autonomy, and cognitive abilities in individuals with Down syndrome, often associated with immune dysregulation and gut–brain axis dysfunction. We report the case of an 11-year-old girl with Down syndrome who developed developmental regression at age five, in temporal proximity to a family transition (the birth of a younger sibling), with loss of continence, language, and comprehension, alongside persistent behavioral agitation and gastrointestinal symptoms. Laboratory assessment revealed Giardia duodenalis infection, elevated fecal calprotectin and secretory IgA, and microbial imbalance with overgrowth of Streptococcus anginosus and S. sobrinus. The patient received a single oral dose of tinidazole (2 g), daily folinic acid (1 mg/kg), and a 90-day course of transcranial and abdominal photobiomodulation (PBM) (1064 nm, 10 min per site). Post-treatment, stool analysis showed normalized inflammation markers and restoration of beneficial bacterial genera (Bacteroides, Bifidobacterium, Lactobacillus) with absence of Enterococcus growth. Behaviorally, she exhibited marked recovery: CARS-2-QPC decreased from 106 to 91, ABC from 63 to 31, and ATEC from 62 to 57, alongside regained continence, speech, and fine-motor coordination. These outcomes suggest that abdominal and transcranial PBM, by modulating mitochondrial metabolism, mucosal immunity, and microbiota composition, may facilitate systemic and neurobehavioral recovery in DSRD. This translational case supports further investigation of PBM as a non-invasive, multimodal therapy for neuroimmune regression in genetic and developmental disorders including validation through future randomized controlled clinical trials. Full article

Photobiomodulation (PBM) therapy has been effectively used to relieve pain and inflammation and promote tissue healing and regeneration in a broad range of ailments. Prior work has focused on intracellular mitochondrial cytochrome c oxidase, while extracellular latent TGF-β1 activation had been noted. This work investigated the role of PBM-generated redox signaling and integration in normal oral keratinocytes, using Western blots and pathway-specific small molecule inhibitors. We observed that PBM primarily generates ROS intracellularly within mitochondria, which then diffuse extracellularly to activate latent TGF-β1. This activation triggers ATF-4 expression through both canonical (Smad3) and non-canonical (p38, ERK) TGF-β signaling pathways. We observed a critical role for NFκB as an essential integrator, coordinating these responses as evidenced by the loss of ATF-4 expression following NFκB inhibition (BAY II) after both PBM and TGF-β1 treatments. Proteomic pathway analysis revealed that PBM downregulates inflammatory and apoptotic pathways while activating stress-adaptive responses in the NFκB pathway. A core set of PBM-induced redox, NFκB, and TGF-β signaling targets was identified. These findings suggest that optimal PBM treatment responses require a coordinated action of multiple signaling pathways that optimize cellular adaptation to stress and promote tissue repair rather than protracted inflammation and cell death. Full article

Background: Parkinson’s disease (PD) involves progressive neurodegeneration with clinical or subclinical disturbance of the gut–brain axis, including altered gastrointestinal motility and enteric nervous system involvement. Clinical studies have reported gut microbiome alterations in PD, with shifts in taxa associated with inflammatory signalling and short-chain fatty acid (SCFA) metabolism. Photobiomodulation (PBM), a non-invasive light therapy, has been investigated as a potential adjunctive treatment for PD, with proposed effects on neural, metabolic, and immune pathways. We previously reported the five-year clinical outcomes in a PBM-treated Parkinson’s disease case series. Here we report the five-year gut microbiome outcomes based on longitudinal samples collected from the same participants. This was an exploratory, open-label longitudinal study without a control group. Objective: Our objective was to assess whether long-term PBM was associated with changes in gut microbiome diversity and composition in the same Parkinson’s disease cohort as previously assessed for changes in Parkinson’s symptoms. Methods: Six participants from the earlier PBM proof-of-concept study who had been diagnosed with idiopathic PD and who had continued treatment (transcranial light emitting diode [LED] plus abdominal and neck laser) for five years had their faecal samples analysed by 16S rDNA sequencing to assess microbiome diversity and taxonomic composition. Results: Microbiome analysis revealed significantly reduced evenness (α-diversity) and significant shifts in β-diversity over five years, as assessed by Permutational Multivariate Analysis of Variance (PERMANOVA). At the phylum level, Pseudomonadota and Methanobacteriota decreased in four of the six participants. Both of these phyla are often increased in the Parkinson’s microbiome compared with the microbiomes of healthy controls. Family-level changes included increased acetate-producing Bifidobacteriaceae (five of the six participants); decreased pro-inflammatory, lipopolysaccharide (LPS)-producing Enterobacteriaceae (two of the three participants who have this bacterial family present); and decreased LPS- and H₂S-producing Desulfovibrionaceae (five of six). At the genus level, Faecalibacterium, a key butyrate producer, increased in four of the six participants, potentially leading to more SCFA availability, although other SCFA-producing bacteria were decreased. This was accompanied by reductions in pro-inflammatory LPS and H₂S-producing genera that are often increased in the Parkinson’s microbiome. Conclusions: This five-year case series represents the longest follow-up of microbiome changes in Parkinson’s disease, although the interpretation of results is limited by very small numbers, the lack of a control group, and the inability to control for lifestyle influences such as dietary changes. While causal relationships cannot be inferred, the parallel changes in improvements in mobility and non-motor Parkinson’s symptoms observed in this cohort, raises the hypothesis that PBM may interact with the gut–brain axis via the microbiome. Controlled studies incorporating functional multi-omics are needed to clarify potential mechanistic links between microbial function, host metabolism, and clinical outcomes. Full article

Myopia is a major global public health concern, with a particularly high and increasing prevalence in East Asia. Although significant progress has been made in regard to developing strategies to slow the progression of myopia, the precise biological mechanisms underlying the onset and progression of myopia remain unclear. Repeated low-level red light (RLRL) therapy, a novel non-invasive photobiomodulation (PBM) technique, has demonstrated promising efficacy for controlling axial elongation and refractive error progression. This review first outlines the clinical definition, epidemiology, and global health impact of myopia, followed by the etiology-based pathogenesis and corresponding intervention strategies. Special attention has been given to emerging mechanistic evidence supporting RLRL, particularly its role in activating mitochondrial cytochrome c oxidase (CCO), enhancing retinal metabolism, influencing choroidal changes in blood perfusion and thickness, and in scleral remodeling. Finally, the feasibility and potential mechanism of the RLRL therapy for slowing myopia progression have been discussed from the perspective of safety. Full article

Objectives: The aim of this systematic review was to evaluate the effectiveness of photobiomodulation (PBM) on pain and function in individuals with Patellofemoral Pain Syndrome (PFPS). Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Search was performed across PubMed/Midline, Scopus, Web of Science, EBSCO, ScienceDirect, Wiley Online Library, Springer, Cochrane CENTRAL, PEDro, ResearchGate, and Google Scholar from inception to January 2025. Randomized controlled trials (RCT) examining PBM in individuals with PFPS were included. Data extraction, risk-of-bias assessment (RoB 2), and quality of evidence evaluation (GRADE) were performed independently by multiple reviewers. Primary and secondary outcomes were pain and function, respectively. A random effect meta-analysis was performed to estimate the standardized mean difference (SMD) at 95% confidence interval (CI) and overall effect size. Results: Eight trials (340 participants) met the inclusion criteria. PBM significantly reduced pain compared with the control (SMD = −0.83; 95% CI −1.40 to −0.27). Functional outcomes demonstrated a significant improvement favoring PBM (SMD = 0.68; 95% CI 0.08 to 1.27), although substantial heterogeneity was present (I² = 83%). RoB2 showed five high-risk studies. GRADE showed a very low quality of evidence due to study limitations, imprecision, and inconsistency which limit the confidence to the effect estimate. Conclusions: PBM, combined with exercise, provides improvements in pain and knee function in individuals with PFPS. While findings support PBM as an effective adjunct modality, standardized dosing protocols and larger, high-quality RCTs are needed to strengthen future clinical recommendations. Full article

Background/Objectives: The zebrafish is a widely used research model due to its characteristics, such as being transparent during development, sharing 70% of its genes with humans, and having conserved features of vertebrate aging, including deterioration of mitochondrial and cognitive functions. While affecting approximately 15% of the world population, neurodegenerative diseases, such as Alzheimer’s disease (AD), are currently incurable, requiring testing of alternative treatment strategies. Hence, this study was conducted to test the hypothesis that an optimized photobiomodulation (PBM) therapy improves AD pathology through its multifaceted beneficial effects, including enhancing mitochondrial function and reducing oxidative stress and neuroinflammation. Methods: A pharmacological zebrafish model of AD was developed by adding small amounts (100 nM) of okadaic acid (OKA) directly to fish tanks for nine days. Next, some of OKA-treated and control zebrafish were subjected to an optimized near-infrared PBM therapy while others remain untreated. Results: When examined after OKA treatment, zebrafish brains displayed histological hallmarks of AD including, neurofibrillary tangles, vacuoles, and neuroinflammation. Behavioral tests using a T-maze revealed that OKA-treated zebrafish spent significantly less time in the reward arm than untreated controls (15.2% vs. 50%). In contrast, a sequential PBM therapy significantly reduced formation of neurofibrillary tangles, vacuoles, neuroinflammation, and improved mitochondrial biogenesis in brains of OKA-treated zebrafish while also improving their cognitive function as evidenced by being able to recall the reward arm and spending more time there similar to controls (55 and 57%, respectively). Conclusions: These findings suggest that (1) a fast, cost-effective zebrafish AD model can be developed using OKA treatment and (2) PBM therapy holds promise to ameliorate AD pathology. Full article

Tendon healing is limited by hypocellularity and low metabolic activity, resulting in poor regeneration. Mesenchymal stem cells (MSCs) offer potential for tendon repair, but reliable tenogenic differentiation protocols remain undefined. Photobiomodulation (PBM) has been proposed as an adjunct to assist differentiation, yet standardized parameters are lacking, particularly in 3D systems. This study evaluated the effects of PBM at 525 nm, 825 nm, and combined wavelengths, delivered at 5 J/cm² and 10 J/cm², on immortalized adipose-derived MSCs (iADMSCs) encapsulated in TrueGel3D hydrogels, with the goal of optimizing parameters to support tenogenic differentiation. Immortalized ADMSCs were characterized by immunofluorescence (CD44, CD90, and CD166) and encapsulated in hydrogels. Following a single PBM exposure, differentiation was induced with transforming growth factor-β1 and ascorbic acid for 3 days, followed by the addition of connective tissue growth factor for an additional 7 days. Morphology, membrane permeability, proliferation, and gene expression were assessed at days 1, 4, and 10. The cells adopted a spindle-shaped fibroblastic morphology, forming dense cellular networks throughout the hydrogel, although without alignment due to random RGD distribution. LDH release remained low across groups, confirming biocompatibility. Proliferation rates were not significantly different on day 1. By day 4, green and consecutive PBM at 10 J/cm² and day 10 green PBM at 5 J/cm² showed increased proliferation rates, respectively. PCR analysis showed co-expression of Scleraxis and Tenomodulin in all groups by day 10, confirming tenogenic differentiation. NIR and consecutive (10 J/cm²) PBM maintained Scleraxis expression over time, with NIR PBM enhancing Collagen I, III, Biglycan and Tenascin-C on day 1 and 4. However, consecutive PBM (10 J/cm²) maintained higher expression patterns more consistently compared to NIR on day 10. Thus, consecutive (525/825 nm) wavelengths at 10 J/cm² proved effective in enhancing tenogenic marker expression for a single-dose PBM protocol. Full article

Background/Objectives: Bidirectional communication between the gut and brain is central to neurological and psychiatric health, and abdominal photobiomodulation (PBM) has emerged as a promising non-invasive way to modulate this axis by targeting intestinal mitochondria, epithelial integrity, and the microbiota. We systematically reviewed preclinical and clinical evidence on abdominal PBM, alone or in combined protocols, reporting microbiome, metabolic, or neurobehavioral outcomes. Methods: Following PRISMA 2020 recommendations, we searched MEDLINE, Scopus, Web of Science, and ScienceDirect through May 2025 for animal and human studies applying PBM to the abdomen and reporting gut-related, metabolic, or brain-related outcomes. Results: Nine studies met the eligibility criteria (five human, four animal). Human trials, mainly in Parkinson’s and Alzheimer’s disease, used 630–904 nm light and reported gains in mobility, balance, cognition, and olfaction; one trial also showed microbiota modulation with a decreased Firmicutes:Bacteroidetes ratio. Animal models revealed cognitive improvement, reduced neuroinflammation, dopaminergic neuroprotection, and microbial rebalancing. Mechanistic findings converged on enhanced mitochondrial bioenergetics, redox and anti-inflammatory signaling, vagal activation, and short-chain fatty acid-mediated effects. Conclusions: Current evidence, though limited by small samples, heterogeneous dosimetry, combined treatment sites, and few sham-controlled human trials, suggests that abdominal PBM can influence the gut–brain axis through converging mitochondrial, immune, and microbial mechanisms. Adequately powered randomized trials with standardized dosimetry, validated mechanistic biomarkers, and integrative multi-omics analyses are needed to clarify causal pathways and optimize translational applications. Full article

Background/Objectives: Cerebral palsy (CP) is a non-progressive, permanent syndrome of childhood, with approximately 80% of patients exhibiting spasticity. Untreated spasticity can cause pain, structural changes in bones, muscles, and nerves negatively impacting quality of life and functionality. Photobiomodulation (PBM) has demonstrated biological effects such as tissue regeneration, muscle relaxation, inflammation reduction, and pain relief. The objective of this pilot study is to evaluate the action of PBM on the spasticity of the medial and lateral right gastrocnemius muscles of children and adolescents with spastic cerebral palsy. Methods: This single-blinded, randomized, controlled trial evaluated PBM’s effect on gastrocnemius spasticity in children and adolescents with CP. The study presents pilot preliminary results from twelve children and adolescents (7–16 years) with spastic CP who were randomized into two groups: active PBM (850 nm, 100 mW, 1.5 J/point, 2 points, weekly for 8 weeks) or placebo (same protocol, device off). Both groups received standard rehabilitation exercises. Outcomes were assessed using the Modified Ashworth Scale (MAS), Pediatric Evaluation of Disability Inventory (PEDI), Gross Motor Function Classification System (GMFCS), and ankle range of motion before and after the intervention (8 weeks). Results: MAS and all outcomes improved significantly over time in both groups. No significant differences were found between groups for all outcomes. The PBM effect size on MAS improvement (ANOVA, Analysis of Vari, η² = 0.171) suggests modest but positive benefits. PBM did not worsen spasticity, and no adverse effects were reported. Conclusion: This study represents a pioneering effort in evaluating a safe PBM protocol for the spastics gastrocnemius in children and adolescents with CP. This protocol, used as an adjunct to physiotherapy, demonstrated no short-term adverse effects and no participant dropouts. Future studies should explore this PBM protocol in patients with less severe GMFCS levels, those with minimally preserved functionality, or those with contraindications to physiotherapeutic exercises. Full article

Alzheimer’s disease (AD) is a major neurodegenerative disorder with limited effective and affordable therapies. Photobiomodulation (PBM) offers a safe, non-invasive treatment strategy, yet conventional transcranial PBM (tc-PBM) is restricted by low skull penetration. To overcome this limitation, gut microbiota-targeted PBM (gm-PBM) has been proposed to modulate the gut–brain axis, though its efficacy and mechanisms remain unclear. Here, six-month-old APPswe/PS1dE9 mice received gm-PBM or tc-PBM (810 nm, 25 mW/cm², 20 min/day for 4 weeks). Behavioral testing revealed that both treatments improved spatial learning and memory, while histological analyses showed reduced amyloid-β deposition and microglial shift toward an anti-inflammatory phenotype. Notably, gm-PBM specifically enriched short-chain fatty acid-producing bacteria, elevated propionate, butyrate, and secondary bile acids, and restored intestinal barrier integrity, whereas tc-PBM induced minimal microbiota changes. These findings suggest that gm-PBM confers neuroprotective effects comparable to or exceeding tc-PBM through modulation of the gut microbiota–metabolism–immune axis, highlighting its potential as a non-invasive and cost-effective therapeutic approach for AD. Full article

Background/Objectives: Tinnitus lateralization, a perceptual characteristic often neglected in clinical assessment, may reflect underlying auditory plasticity. This study aimed to investigate whether changes in tinnitus lateralization following a multimodal neuromodulation protocol are associated with improved clinical outcomes, particularly regarding tinnitus severity and discomfort. Methods: A retrospective interventional study was conducted with 104 adults diagnosed with chronic tinnitus. All participants underwent a combined protocol involving transcutaneous auricular vagus nerve stimulation (taVNS), cervical transcutaneous electrical nerve stimulation (TENS), and photobiomodulation (PBM) targeting auditory pathways. Clinical assessments included the Tinnitus Handicap Inventory (THI), Visual Analog Scales (VAS) for loudness and discomfort, and lateralization reports before and after treatment. Lateralization patterns were categorized and compared using ANOVA and Kruskal–Wallis tests. Linear models explored demographic and clinical predictors of symptom change. Results: Substantial changes in lateralization were observed post-treatment. Participants who shifted from bilateral to unilateral tinnitus or from unilateral to non-perception showed the greatest symptom reductions (p < 0.001). The Bilateral → Unilateral group presented the most marked THI reduction (−20.82 ± 7.12), while minimal changes were observed in the Bilateral → Bilateral group. Loudness and discomfort improvements followed similar trends. No significant influence of age or sex on clinical response was identified, whereas longer tinnitus duration showed a modest positive association with symptom improvement. Conclusions: Perceptual reorganization of tinnitus lateralization may serve as a clinical marker of response to neuromodulation. Tracking lateralization could provide a simple, cost-effective adjunct to outcome monitoring in tinnitus management. Full article

Background/Objectives: Photobiomodulation (PBM) is a non-invasive, low-level laser treatment shown to improve insulin resistance, glucose metabolism, and obesity-related inflammation. This study examined whether PBM could acutely enhance mitochondrial efficiency and energy metabolism in women with obesity. Methods: In a randomized, crossover within-subject design, 16 women with obesity (43 ± 5 years; BMI: 36 ± 4 kg/m²) and 16 sedentary normal-weight women (43 ± 5 years; BMI: 22.7 ± 2 kg/m²) underwent PBM (front and back exposure; red light, 633–660 nm; NIR, 850–940 nm) and a sham stimulation (SHAM), as a control, for 12 min. Resting energy expenditure (REE) was assessed via indirect calorimetry before and after exposure. Secondary measures included skin autofluorescence, heart rate, blood pressure, profile of mood states, rate of perceived exertion (RPE), and flexibility. Diet and physical activity were controlled. Results: A 2 × 2 × 2 ANOVA revealed a significant group × time interaction (F_3,60 = 3.054, p = 0.03) and a main effect of time (F_1,60 = 10.88, p = 0.001). Women with obesity showed a significant increase in REE post-PBM compared to pre-PBM (+9.3%, 1624 ± 314 vs. 1486 ± 327 kcal/day; p < 0.001), with no change in the respiratory exchange ratio. Additionally, RPE decreased and flexibility improved in both groups following PBM. Front and back skin temperatures increased significantly post-PBM, with greater changes observed in the back versus the front. Conclusions: These preliminary findings indicate that PBM acutely enhances energy utilization efficiency in women with obesity, increasing resting energy expenditure without modifying substrate oxidation. PBM may represent a promising non-invasive adjunctive strategy for improving the metabolic health of obese individuals. Full article

Female infertility from polycystic ovarian syndrome (PCOS) and endometriosis poses a challenge for both clinicians and women who are trying to conceive. The present clinical single case report aimed to evaluate the efficacy of multiple wavelengths of red and near-infrared (NIR) laser photobiomodulation (PBM) for increasing the potential of fertility in a woman with PCOS, endometriosis and low ovarian reserve. The observations helped to inform and establish the following: (1) any adverse effects; (2) the possibility of producing an effective PBM protocol; and (3) a healthy live birth. The case report concerns a female who failed to conceive naturally beyond five years and had experienced one unsuccessful IVF cycle. Methods: Case report of one female subject with infertility issues, which included failure to conceive naturally beyond five years. Previous conditions were recorded and then compared with outcomes from after the patient received a course of PBM treatments. PBM treatments were given at weekly and/or at two-week intervals over a 5-month period during the follicular stage of the menstrual cycle, using IR and NIR wavelengths between 600 and 1000 nm. Results: After five months a spontaneous conception was achieved. The case resulted in a full-term pregnancy and the birth of a healthy baby. Improvements in reproductive health outcomes in this case give reason to suggest that PBM helped to alleviate PCOS and endometriosis which could have been associated with a low ovarian reserve. Conclusions: The case report indicates that a multiwavelength of red and NIR-PBM laser therapy could have positively contributed to a healthy live birth in a female diagnosed with PCOS, endometriosis and a low ovarian reserve. Extensive studies with large data are warranted to validate our PBM dosimetry and treatment protocols to assess the potential impact of PBM for treating endometriosis and PCOS. Subsequently, to understand the genetic and phenotype biomarkers would be an important step further to standardise a range of PBM light dosimetry. Full article

Orthodontic tooth movement (OTM) arises from force-induced mechanotransduction within the periodontal ligament (PDL), which coordinates osteoblast and osteoclast activity with immune responses to remodel the PDL and alveolar bone. This review integrates contemporary biological insights on OTM and assesses photobiomodulation (PBM) as an adjunctive therapy. We propose that mechanical and photonic inputs may interact and potentiate signaling through the Ca²⁺-NFAT, MAPK (ERK, p38, JNK), PI3K–Akt–mTOR, NF-kB, TGF-β/Smad, and Wnt/β-catenin pathways. Such interaction could influence processes such as cell proliferation, differentiation, specific cellular functions, apoptosis, autophagy, and communication between stromal and immune cells. This convergence establishes a solid foundation for understanding the context-dependent effects of PBM in OTM. In principle, PBM appears most effective as a phase-tuned adjunct, promoting early inflammatory recruitment of osteoclasts and subsequently facilitating late-phase remodeling through immunomodulatory and reparative mechanisms. However, inconsistent irradiation parameters, small sample sizes, trial heterogeneity, and the absence of mechanistic endpoints undermine current conclusions. Furthermore, the lack of integrated PBM–OTM models limits mechanistic understanding, as much of the available evidence is derived from non-OTM contexts. Overall, PBM remains a promising adjunct in orthodontics, with the potential to integrate mechanical and photonic signals in a phase-dependent manner, though its application is not yet standardized. Full article