Photobiomodulation on isolated mitochondria at 810 nm: first results on the efficiency of the energy conversion process.

In this paper the photobiomodulation on isolated mitochondria of bovine liver is studied as a thermodynamic process of conversion of energy. This analysis is conducted by considering a particular set-up for the photobiomodulation experiments of interest. It allows, in particular, the computation of the electromagnetic field and the related energetic quantities in the stimulated organelles. The measurements of the excess of biochemical power density produced by the illuminated mitochondria are performed at regular time intervals after the experiments. The calculations and the measurements finally allow us to obtain the first results on the efficiency of the process of conversion of electromagnetic energy into excess of biochemical energy released by the isolated organelles.

Assessing the Effects of Curcumin and 450 nm Photodynamic Therapy on Oxidative Metabolism and Cell Cycle in Head and Neck Squamous Cell Carcinoma: An In Vitro Study.

Oral cancer is the 16th most common malignant tumor worldwide. The risk of recurrence and mortality is high, and the survival rate is low over the following five years. Recent studies have shown that curcumin causes apoptosis in tumor cells by affecting FoF1-ATP synthase (ATP synthase) activity, which, in turn, hinders cell energy production, leading to a loss of cell viability. Additionally, irradiation of curcumin within cells can intensify its detrimental effects on cancer cell viability and proliferation (photodynamic therapy). We treated the OHSU-974 cell line, a model for human head and neck squamous cell carcinoma (HNSCC), and primary human fibroblasts. The treatment involved a 1 h exposure of cells to 0.1, 1.0, and 10 µM curcumin, followed or not by irradiation or the addition of the same concentration of pre-irradiated curcumin. Both instances involved a diode laser with a wavelength of 450 nm (0.25 W, 15 J, 60 s, 1 cm2, continuous wave mode). The treatment with non-irradiated 1 and 10 µM curcumin caused ATP synthase inhibition and a consequent reduction in the oxygen consumption rate (OCR) and the ATP/AMP ratio, which was associated with a decrement in lipid peroxidation accumulation and a slight increase in glutathione reductase and catalase activity. By contrast, 60 s curcumin irradiation with 0.25 W-450 nm caused a further oxidative phosphorylation (OxPhos) metabolism impairment that induced an uncoupling between respiration and energy production, leading to increased oxidative damage, a cellular growth and viability reduction, and a cell cycle block in the G1 phase. These effects appeared to be more evident when the curcumin was irradiated after cell incubation. Since cells belonging to the HNSCC microenvironment support tumor development, curcumin's effects have been analyzed on primary human fibroblasts, and a decrease in cell energy status has been observed with both irradiated and non-irradiated curcumin and an increase in oxidative lipid damage and a slowing of cell growth were observed when the curcumin was irradiated before or after cellular administration. Thus, although curcumin displays an anti-cancer role on OHSU-974 in its native form, photoactivation seems to enhance its effects, making it effective even at low dosages.

Enhancing the quality and safety of Nocellara del Belice green table olives produced using the Castelvetrano method.

The Castelvetrano method is the most widely used among the various table olive processing styles in Sicily. After debittering, the product is stored at low temperatures to prevent the growth of undesirable microorganisms. In an effort to enhance the production process, yeast isolates underwent genotypic characterization and technological screening. The screening process identified two yeast strains Candida norvegica OC10 and Candida boidinii LC1, which can grow at low temperatures and tolerate high pH values (up to 10) and salinity [10% (w/v)]. During the monitoring period, the inoculated trials showed limited presence of spoilage/pathogenic microorganisms. Additionally, the yeasts limited oxidative phenomena and softening of the drupes. The organic compounds detected were higher in the inoculated trials than in the control, and cold storage induced aromatic decay, which was less pronounced in the trial inoculated with C. norvegica. Sensory analysis revealed that the inoculated trials scored higher in sweetness, hardness and crispness.

Evaluation of Sterify Gel as an Adjunctive Treatment to Scaling and Root Planing in Promoting Healing of Periodontal Pockets: A Split-Mouth Randomized Controlled Trial.

Background: Periodontal disease is a common infectious disease that leads to the destruction of tooth-supporting structures. Current treatments, such as scaling and root planing (SRP), have limitations in deep and complex pockets, and antibiotic use carries the risk of resistance. Sterify Gel, a medical device composed of polyvinyl polymers, hydroxytyrosol, nisin, and magnesium ascorbyl phosphate, offers a new approach to periodontal care. This study aims to evaluate the safety and efficacy of Sterify Gel as an adjunctive treatment to SRP in promoting the healing of periodontal pockets. Methods: The study includes 34 patients with moderate to advanced chronic periodontal disease. Randomization assigned one site for SRP alone (control) and the other site for SRP with Sterify Gel (treatment). Periodontal parameters were evaluated at baseline, 1, 2, and 3 months after treatment bacterial contamination was assessed through quantitative PCR at baseline and 3 months after treatment. Statistical analysis was conducted using ANOVA and Wilcoxon test. Results: Treatment with Sterify Gel and SRP demonstrated significant improvements in pocket depth, gingival recession, and clinical attachment level compared with SRP alone. Bleeding and plaque indexes, pain perception, tooth mobility, and furcations showed no significant differences between the two groups. The treatment group showed a reduction in bacterial contamination at 3 months. Conclusions: Sterify Gel in combination with SRP shows the potential for improving periodontal health by promoting healing and reducing periodontal pockets. It may offer benefits in preventing bacterial recolonization and reducing reliance on antibiotics.

lifex-ep: a robust and efficient software for cardiac electrophysiology simulations.

BACKGROUND: Simulating the cardiac function requires the numerical solution of multi-physics and multi-scale mathematical models. This underscores the need for streamlined, accurate, and high-performance computational tools. Despite the dedicated endeavors of various research teams, comprehensive and user-friendly software programs for cardiac simulations, capable of accurately replicating both normal and pathological conditions, are still in the process of achieving full maturity within the scientific community. RESULTS: This work introduces [Formula: see text]-ep, a publicly available software for numerical simulations of the electrophysiology activity of the cardiac muscle, under both normal and pathological conditions. [Formula: see text]-ep employs the monodomain equation to model the heart's electrical activity. It incorporates both phenomenological and second-generation ionic models. These models are discretized using the Finite Element method on tetrahedral or hexahedral meshes. Additionally, [Formula: see text]-ep integrates the generation of myocardial fibers based on Laplace-Dirichlet Rule-Based Methods, previously released in Africa et al., 2023, within [Formula: see text]-fiber. As an alternative, users can also choose to import myofibers from a file. This paper provides a concise overview of the mathematical models and numerical methods underlying [Formula: see text]-ep, along with comprehensive implementation details and instructions for users. [Formula: see text]-ep features exceptional parallel speedup, scaling efficiently when using up to thousands of cores, and its implementation has been verified against an established benchmark problem for computational electrophysiology. We showcase the key features of [Formula: see text]-ep through various idealized and realistic simulations conducted in both normal and pathological scenarios. Furthermore, the software offers a user-friendly and flexible interface, simplifying the setup of simulations using self-documenting parameter files. CONCLUSIONS: [Formula: see text]-ep provides easy access to cardiac electrophysiology simulations for a wide user community. It offers a computational tool that integrates models and accurate methods for simulating cardiac electrophysiology within a high-performance framework, while maintaining a user-friendly interface. [Formula: see text]-ep represents a valuable tool for conducting in silico patient-specific simulations.

lifex-fiber: an open tool for myofibers generation in cardiac computational models.

BACKGROUND: Modeling the whole cardiac function involves the solution of several complex multi-physics and multi-scale models that are highly computationally demanding, which call for simpler yet accurate, high-performance computational tools. Despite the efforts made by several research groups, no software for whole-heart fully-coupled cardiac simulations in the scientific community has reached full maturity yet. RESULTS: In this work we present [Formula: see text]-fiber, an innovative tool for the generation of myocardial fibers based on Laplace-Dirichlet Rule-Based Methods, which are the essential building blocks for modeling the electrophysiological, mechanical and electromechanical cardiac function, from single-chamber to whole-heart simulations. [Formula: see text]-fiber is the first publicly released module for cardiac simulations based on [Formula: see text], an open-source, high-performance Finite Element solver for multi-physics, multi-scale and multi-domain problems developed in the framework of the iHEART project, which aims at making in silico experiments easily reproducible and accessible to a wide community of users, including those with a background in medicine or bio-engineering. CONCLUSIONS: The tool presented in this document is intended to provide the scientific community with a computational tool that incorporates general state of the art models and solvers for simulating the cardiac function within a high-performance framework that exposes a user- and developer-friendly interface. This report comes with an extensive technical and mathematical documentation to welcome new users to the core structure of [Formula: see text]-fiber and to provide them with a possible approach to include the generated cardiac fibers into more sophisticated computational pipelines. In the near future, more modules will be successively published either as pre-compiled binaries for x86-64 Linux systems or as open source software.

Tackling Inequalities in Oral Health: Bone Augmentation in Dental Surgery through the 3D Printing of Poly(ε-caprolactone) Combined with 20% Tricalcium Phosphate.

The concept of personalized medicine and overcoming healthcare inequalities have become extremely popular in recent decades. Polymers can support cost reductions, the simplicity of customized printing processes, and possible future wide-scale expansion. Polymers with ß-tricalcium phosphate (TCP) are well known for their synergy with oral tissues and their ability to induce osteoconductivity. However, poor information exists concerning their properties after the printing process and whether they can maintain an unaffected biological role. Poly(ε-caprolactone) (PCL) polymer and PCL compounded with TCP 20% composite were printed with a Prusa Mini-LCD-®3D printer. Samples were sterilised by immersion in a 2% peracetic acid solution. Sample analyses were performed using infrared-spectroscopy and statical mechanical tests. Biocompatibility tests, such as cell adhesion on the substrate, evaluations of the metabolic activity of viable cells on substrates, and F-actin labelling, followed by FilaQuant-Software were performed using a MC3T3-E1 pre-osteoblasts line. PCL+ß-TCP-20% composite is satisfactory for commercial 3D printing and appears suitable to sustain an ISO14937:200937 sterilization procedure. In addition, the proper actin cytoskeleton rearrangement clearly shows their biocompatibility as well as their ability to favour osteoblast adhesion, which is a pivotal condition for cell proliferation and differentiation.

Prevention of Dry Socket with Ozone Oil-Based Gel after Inferior Third Molar Extraction: A Double-Blind Split-Mouth Randomized Placebo-Controlled Clinical Trial.

Tooth extraction is followed by a sequence of elaborate local changes affecting hard and soft tissues. Dry socket (DS) can occur as intense pain around and in the extraction site, with an incidence from 1-4% after generic tooth extraction to 45% for mandibular third molars. Ozone therapy has gained attention in the medical field because of its success in the treatment of various diseases, its biocompatible properties and its fewer side effects or discomfort than drugs. To investigate the preventive effect of the sunflower oil-based ozone gel Ozosan® (Sanipan srl, Clivio (VA), Italy) on DS, a double-blind split-mouth randomized placebo-controlled clinical trial was conducted according to the CONSORT guidelines. Ozosan® or the placebo gel were put in the socket, and the gels were washed off 2 min later. In total, 200 patients were included in our study. The patient population comprised 87 Caucasian males and 113 Caucasian females. The mean age of the included patients was 33.1 ± 12.4 years. Ozosan reduced the incidence of DS after inferior third molar extraction from 21.5% of the control to 2% (p < 0.001). Concerning the dry socket epidemiology, the incidence was not significantly correlated with gender, smoking or mesioangular, vertical or distoangular Winter's classification. Post hoc power calculation showed a power of 99.8% for this data, with alpha = 0.001.

Comparison between the Flapless Surgical Approach and a Novel Single Incision Access in Terms of Recovery Time and Comfort after Extraction of Impacted Inferior Third Molars: A Randomised, Blinded, Split-Mouth Controlled Clinical Trial.

The recent attention to quality of life and oral health care procedures reflects a renewed 'patient-based' approach to dealing with non-life-threatening conditions. In the current study, we proposed a novel surgical approach to the extraction of impacted inferior third molars (iMs3) through a randomised, blinded, split-mouth controlled clinical trial following the CONSORT guidelines. The novel surgical procedure, hereinafter referred to as single incision access (SIA), will be compared with our previously described flapless surgical approach (FSA). The predictor variable was the novel SIA approach, involving access through a single incision without removal of soft tissue, on the impacted iMs3. The primary endpoint was the acceleration of the iMs3 extraction healing time. The secondary endpoints were the incidences of pain and oedema as well as gum health (pocket probing depth and attached gingiva). The study was carried out on 84 teeth of 42 patients with both iMs3 impacted. The cohort was composed of 42% Caucasian males and 58% Caucasian females, aged 23.8 ± 7.9 (17-49) years. We observed faster recovery/wound-healing on the SIA side (33.6 ± 4.3 days) than at the FSA side (42.1 ± 5.4 days; p < 0.05). The FSA approach confirmed the evidence previously detected concerning early post-surgery improvement in terms of attached gingiva and reduced oedema and pain, with respect to the traditional envelope flap. The novel SIA approach follows the early positive post-surgery FSA results.

Iodine Biofortification and Seaweed Extract-Based Biostimulant Supply Interactively Drive the Yield, Quality, and Functional Traits in Strawberry Fruits.

The horticultural sector is seeking innovative and sustainable agronomic practices which could lead to enhanced yield and product quality. Currently, plant biofortification is recognized as a valuable technique to improve microelement concentrations in plant tissues. Among trace elements, iodine (I) is an essential microelement for human nutrition. Concomitantly, the application of biostimulants may improve overall plant production and quality traits. With the above background in mind, an experiment was designed with the aim of assessing the interactive impact of a seaweed extract-based biostimulant (SwE) (0 mL L-1 (served as control) or 3 mL L-1 (optimal dosage)) and 0, 100, 300, or 600 mg L-1 I on the growth parameters, yield, fruit quality, minerals, and functional characteristics of the tunnel-grown "Savana" strawberry. SwE foliar application improved the plant growth-related traits, total and marketable yield, fruit color parameters, soluble solids content, nitrogen (N), potassium (K), and magnesium (Mg) fruit concentrations. Furthermore, an enhancement in the fruit dry matter content, ascorbic acid, and I concentration in fruits was detected when the SwE supply interacted with a mild I dose (100 or 300 mg L-1). The research underlined that combining SwE application and I biofortification increased the strawberry yield and quality and enhanced the plant nutritional status variation, thereby, determining a boosted strawberry I tolerance.

A mathematical model that integrates cardiac electrophysiology, mechanics, and fluid dynamics: Application to the human left heart.

We propose a mathematical and numerical model for the simulation of the heart function that couples cardiac electrophysiology, active and passive mechanics and hemodynamics, and includes reduced models for cardiac valves and the circulatory system. Our model accounts for the major feedback effects among the different processes that characterize the heart function, including electro-mechanical and mechano-electrical feedback as well as force-strain and force-velocity relationships. Moreover, it provides a three-dimensional representation of both the cardiac muscle and the hemodynamics, coupled in a fluid-structure interaction (FSI) model. By leveraging the multiphysics nature of the problem, we discretize it in time with a segregated electrophysiology-force generation-FSI approach, allowing for efficiency and flexibility in the numerical solution. We employ a monolithic approach for the numerical discretization of the FSI problem. We use finite elements for the spatial discretization of partial differential equations. We carry out a numerical simulation on a realistic human left heart model, obtaining results that are qualitatively and quantitatively in agreement with physiological ranges and medical images.

Steering the multipotent mesenchymal cells towards an anti-inflammatory and osteogenic bias via photobiomodulation therapy: How to kill two birds with one stone.

The bone marrow-derived multipotent mesenchymal cells (MSCs) have captured scientific interest due to their multi-purpose features and clinical applications. The operational dimension of MSCs is not limited to the bone marrow reservoir, which exerts bone-building and niche anabolic tasks; they also meet the needs of quenching inflammation and restoring inflamed tissues. Thus, the range of MSC activities extends to conditions such as neurodegenerative diseases, immune disorders and various forms of osteopenia. Steering these cells towards becoming an effective therapeutic tool has become mandatory. Many laboratories have employed distinct strategies to improve the plasticity and secretome of MSCs. We aimed to present how photobiomodulation therapy (PBM-t) can manipulate MSCs to render them an extraordinary anti-inflammatory and osteogenic instrument. Moreover, we discuss the outcomes of different PBM-t protocols on MSCs, concluding with some perplexities and complexities of PBM-t in vivo but encouraging and feasible in vitro solutions.

Computational electrophysiology of the coronary sinus branches based on electro-anatomical mapping for the prediction of the latest activated region.

This work dealt with the assessment of a computational tool to estimate the electrical activation in the left ventricle focusing on the latest electrically activated segment (LEAS) in patients with left bundle branch block and possible myocardial fibrosis. We considered the Eikonal-diffusion equation and to recover the electrical activation maps in the myocardium. The model was calibrated by using activation times acquired in the coronary sinus (CS) branches or in the CS solely with an electroanatomic mapping system (EAMS) during cardiac resynchronization therapy (CRT). We applied our computational tool to ten patients founding an excellent accordance with EAMS measures; in particular, the error for LEAS location was less than 4 mm. We also calibrated our model using only information in the CS, still obtaining an excellent agreement with the measured LEAS. The proposed tool was able to accurately reproduce the electrical activation maps and in particular LEAS location in the CS branches, with an almost real-time computational effort, regardless of the presence of myocardial fibrosis, even when information only at CS was used to calibrate the model. This could be useful in the clinical practice since LEAS is often used as a target site for the left lead placement during CRT. Overall picture of the computational pipeline for the estimation of LEAS.

Biofortification: Effect of Iodine Fortified Food in the Healthy Population, Double-Arm Nutritional Study.

It is estimated that one-third of the world's population lives in areas where iodine (I) is scarce and its deficiency is responsible for many related disorders, such as goiter, reproductive failure, hearing loss, growth impairment, congenital I deficiency syndrome, and numerous kinds of brain injury. Mineral deficiencies can be overcome via dietary diversification and mineral supplementation. An alternative or even complementary way is represented by the intake of biofortified foods, which can tackle this lack of micronutrients. In this short-term double-arm nutritional intervention study, a cohort of ten people was supplemented with curly endive leaf biofortified with I and ten people with curly endive without biofortification (Intervention Study on Iodine Biofortification Vegetables (Nutri-I-Food - Full-Text View - ClinicalTrials.gov). The effects on whole-body homeostasis and specifically on I, glucose, lipid, and hepatic, iron metabolism was investigated. Blood samples were obtained at baseline and after 12 days of supplementation with curly endive and compared with controls. Hematochemical and urinary parameters were analyzed at baseline and after 12 days. The results showed that short-term I curly endive intervention did not affect the whole body homeostasis in healthy people and revealed an increase in I concentration in urine samples and an increase in vitamin D, calcium, and potassium concentration in blood samples only in the biofortified cohort respect to controls. This study suggests that short-term consumption of I curly endive crops is safe and could positively impact body health.

Impact on Glucose Homeostasis: Is Food Biofortified with Molybdenum a Workable Solution? A Two-Arm Study.

Diabetes is expected to increase up to 700 million people worldwide with type 2 diabetes being the most frequent. The use of nutritional interventions is one of the most natural approaches for managing the disease. Minerals are of paramount importance in order to preserve and obtain good health and among them molybdenum is an essential component. There are no studies about the consumption of biofortified food with molybdenum on glucose homeostasis but recent studies in humans suggest that molybdenum could exert hypoglycemic effects. The present study aims to assess if consumption of lettuce biofortified with molybdenum influences glucose homeostasis and whether the effects would be due to changes in gastrointestinal hormone levels and specifically Peptide YY (PYY), Glucagon-Like Peptide 1 (GLP-1), Glucagon-Like Peptide 2 (GLP-2), and Gastric Inhibitory Polypeptide (GIP). A cohort of 24 people was supplemented with biofortified lettuce for 12 days. Blood and urine samples were obtained at baseline (T0) and after 12 days (T2) of supplementation. Blood was analyzed for glucose, insulin, insulin resistance, ß-cell function, and insulin sensitivity, PYY, GLP-1, GLP-2 and GIP. Urine samples were tested for molybdenum concentration. The results showed that consumption of lettuce biofortified with molybdenum for 12 days did not affect beta cell function but significantly reduced fasting glucose, insulin, insulin resistance and increased insulin sensitivity in healthy people. Consumption of biofortified lettuce did not show any modification in urine concentration of molybdenum among the groups. These data suggest that consumption of lettuce biofortified with molybdenum improves glucose homeostasis and PYY and GIP are involved in the action mechanism.

An Innovative Malaxer Equipped with SCADA Platform for Improving Extra Virgin Olive Oil Quality.

Agriculture 4.0 is gaining more attention, and all companies are thinking about innovating machines to increase income and improve the quality of the final products. In the agro-food sector, there is space for innovation, as it is far behind the industrial sector. This paper reports an industrial-scale study on the application of an innovative system for the extraction of Sicilian EVOO (extra virgin olive oil) to improve both process management and the quality of the product. Based on previous studies, the authors suggested an innovative machine equipped with a SCADA (supervisory control and data acquisition system) for oxygen and process duration monitoring and control. The objective of the research was thus to discuss the development of a SCADA platform applied to the malaxer and the establishment of an optimized approach to control the main process parameters for obtaining high-quality EVOO. The SCADA system application in the EVOO extraction process allowed a qualitative improvement of the Sicilian EVOO of Nocellara del Belice and Cerasuola cultivars. The use of the innovative system made it possible to increase the values of tocopherols (by about 25%) in Cerasuola cultivar and total phenol content (by about 30%) in Nocellara del Belice cultivar EVOOs.

A Narrative Review on Oral and Periodontal Bacteria Microbiota Photobiomodulation, through Visible and Near-Infrared Light: From the Origins to Modern Therapies.

Photobiomodulation (PBM) consists of a photon energy transfer to the cell, employing non-ionizing light sources belonging to the visible and infrared spectrum. PBM acts on some intrinsic properties of molecules, energizing them through specific light wavelengths. During the evolution of life, semiconducting minerals were energized by sun radiation. The molecules that followed became photoacceptors and were expressed into the first proto-cells and prokaryote membranes. Afterward, the components of the mitochondria electron transport chain influenced the eukaryotic cell physiology. Therefore, although many organisms have not utilized light as an energy source, many of the molecules involved in their physiology have retained their primordial photoacceptive properties. Thus, in this review, we discuss how PBM can affect the oral microbiota through photo-energization and the non-thermal effect of light on photoacceptors (i.e., cytochromes, flavins, and iron-proteins). Sometimes, the interaction of photons with pigments of an endogenous nature is followed by thermal or photodynamic-like effects. However, the preliminary data do not allow determining reliable therapies but stress the need for further knowledge on light-bacteria interactions and microbiota management in the health and illness of patients through PBM.

Near-Infrared 810 nm Light Affects Porifera Chondrosia reniformis (Nardo, 1847) Regeneration: Molecular Implications and Evolutionary Considerations of Photobiomodulation-Animal Cell Interaction.

Chemotrophic choice as a metabolic source of energy has characterised animal cell evolution. However, light interactions with animal cell photoacceptors that are able to increase energetic metabolism (photo-biomodulation (PBM)) have been previously described. In the present study, we cut three specimens of Chondrosia reniformis into four equal parts (12 fragments), and we irradiated the regenerating edge of six fragments with the previously characterised 810 nm near-infrared light, delivered at 1 W, 60 J/cm2, 1 W/cm2, and 60 J in a continuous-wave mode for 60 s through a flat-top hand-piece with a rounded spot-size area of 1 cm2. Six fragments were irradiated with 0 W for 60 s as the controls. We performed irradiation at the time 0 h and every 24 h for a total of five administrations. We monitored the regeneration process for five days (120 h) in aquaria by examining the macroscopic and histological changes. We analysed the gene expression profile of the inflammatory processes, apoptosis, heat stress, growth factors, and collagen production and determined oxidative stress enzyme activity and the total prokaryotic symbiont content. PBM sped up C. reniformis regeneration when compared to the controls. Particularly, transforming growth factor TGF3 and TGF6 upregulation during the early phase of regeneration and TGF5 upregulation 120 h postinjury in the irradiated samples supports the positive effect of PBM in sponge tissue recovery. Conversely, the expression of TGF4, a sponge fibroblast growth factor homologue, was not affected by irradiation, indicating that multiple, independent pathways regulate the TGF genes. The results are consistent with our previous data on a wide range of organisms and humans, suggesting that PBM interaction with primary and secondary cell targets has been conserved through the evolution of life forms.

808-nm Photobiomodulation Affects the Viability of a Head and Neck Squamous Carcinoma Cellular Model, Acting on Energy Metabolism and Oxidative Stress Production.

Photobiomodulation (PBM) is a form of low-dose light therapy that acts through energy delivery from non-ionizing sources. During the recent two decades, there has been tremendous progress with PBM acceptance in medicine. However, PBM effects on potential stimulation of existing malignant or pre-malignant cells remain unknown. Thus, the primary endpoint was to assess the safety of PBM treatment parameters on head and neck squamous cell carcinoma (HNSCC) proliferation or survival. The secondary endpoint was to assess any putative anti-cancer effects of PBM treatments. Cell viability, energy metabolism, oxidative stress, and pro- and anti-apoptotic markers expression were investigated on a Human Head and Neck Squamous Cell Carcinoma cellular model (OHSU-974 FAcorr cell line). PBM therapy was administered through the 810 nm diode laser (GaAlAs) device (Garda Laser, 7024 Negrar, Verona, Italy) at the powers of 0, 0.25, 0.50, 0.75, 1.00, or 1.25 W in continuous wave (CW) mode for an exposure time of 60 s with a spot-size of 1 cm2 and with a distance of 1.86 cm from the cells. Results showed that 810-nm PBM affected oxidative phosphorylation in OHSU-971 FAcorr, causing a metabolic switch to anaerobic glycolysis. In addition, PBM reduced the catalase activity, determining an unbalance between oxidative stress production and the antioxidant defenses, which could stimulate the pro-apoptotic cellular pathways. Our data, at the parameters investigated, suggest the safeness of PBM as a supportive cancer therapy. Pre-clinical and clinical studies are necessary to confirm the in vitro evidence.

Improving Consistency of Photobiomodulation Therapy: A Novel Flat-Top Beam Hand-Piece versus Standard Gaussian Probes on Mitochondrial Activity.

The tremendous therapeutic potential of photobiomodulation therapy in different branches of medicine has been described in the literature. One of the molecular mechanisms for this treatment implicates the mitochondrial enzyme, cytochrome C oxidase. However, the efficacy and consistency of clinical outcomes with photobiomodulation treatments has been fiercely debated. This work was motivated by this need to improve photobiomodulation devices and delivery approaches. We designed a novel hand-piece with a flat-top beam profile of irradiation. We compared the beam profile versus a standard hand-piece and a fibre probe. We utilized isolated mitochondria and performed treatments at various spots within the beam, namely, the centre, left and right edge. We examined mitochondrial activity by assessing ATP synthesis with the luciferin/luciferase chemiluminescent method as a primary endpoint, while mitochondrial damage was assessed as the secondary endpoint. We observed a uniform distribution of the power density with the flat-top prototype compared to a wide Gaussian beam profile with the standard fibre and standard hand-piece. We noted increased production of ATP in the centre of all three beams with respect to the non-treated controls (p < 0.05). Both the fibre and standard hand-piece demonstrated less increase in ATP synthesis at the edges than the centre (p < 0.05). In contrast, ATP synthesis was increased homogenously in the flat-top handpiece, both in the centre and the edges of the beam. Fibre, standard hand-piece and the flat-top hand-piece prototype have discrete beam distribution characteristics. This significantly affected the mitochondrial activity with respect to their position within the treated areas. Flat-top hand-piece enhances the uniformity of photobiomodulation treatments and can improve the rigour and reproducibility of PBM clinical outcomes.