Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Ischemic heart disease is one of the most harmful conditions to cellular structure and function. After reperfusion treatment, a spectrum of adverse effects becomes evident, encompassing altered cell viability, heightened oxidative stress, activated autophagy, and increased apoptosis. Photobiomodulation (PBM) has been utilized in experimental models of cardiac hypoxia to enhance mitochondrial response and ameliorate biochemical changes in injured tissue. However, the effects of PBM on cultured cardiomyocytes subjected to hypoxia/reoxygenation are not yet well established.

H9C2 cardiomyocytes were exposed to hypoxia with concentrations of 300 μM CoCl2 for 24 h, followed by 16 h of reoxygenation through incubation in a normoxic medium. Treatment was conducted using GaAIAs Laser (850 nm) after hypoxia at an intensity of 1 J/cm2. Cells were divided into three groups: Group CT (cells maintained under normoxic conditions), Group HR (cells maintained in hypoxia and reoxygenation conditions without treatment), Group HR + PBM (cells maintained in hypoxia and reoxygenation conditions that underwent PBM treatment). Cell viability was analyzed using MTT, and protein expression was assessed by western blot. One-way ANOVA with the Tukey post hoc test was used for data analysis. Differences were significant when p < 0.05.

PBM at an intensity of 1 J/cm2 mitigated the alterations in cell survival caused by hypoxia/reoxygenation. Additionally, it significantly increased the expression of proteins Nrf2, HSP70, mTOR, LC3II, LC3II/I, and Caspase-9, while reducing the expression of PGC-1α, SOD2, xanthine oxidase, Beclin-1, LC3I, and Bax.

PBM at intensities of 1 J/cm2 reverses the changes related to oxidative stress, mitochondrial biogenesis, autophagy, and apoptosis caused by hypoxia and reoxygenation in a culture of cardiomyocytes.

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 (IL1β) and transforming growth factor beta-1 (TGFβ-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 IL1β and TGFβ-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 IL1β and TGFβ-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.

To assess the incidence, risk factors, and timing of specific causes of reoperations following PVP.

A retrospective analysis of data on men who underwent GreenLight PVP between 2004 and 2019 in a single center and required surgical intervention for bladder neck contracture (BNC), urethral stricture (US), or persistent/recurrent prostate adenoma.

The overall rate of reoperations was 13.8% during a 61-month median follow-up of 377 patients. Reoperations were due to BNC, US, and adenoma in 7.7%, 5.6%, and 4.8% of cases, respectively. The median interval until reoperation for US (11 months) was significantly shorter. None of the risk factors had any relevance to US. In patients who underwent reoperation for BNC, lasing time and energy were significantly lower, and the prostate volume was smaller; however, the multivariate analysis only identified shorter lasing time as a predictor. In patients who had reoperation for persistent/recurrent adenoma, the PSA was increased, while the prostate volume was non-significantly high, and performance by less-experienced surgeons was associated with a higher rate of reoperations (p < 0.05). A longer lasing time predicted an increased risk of reoperation for adenoma in multivariate analysis.

An unselective utilization of PVP may result in a relatively high rate of reoperations. The correlation of BNC with shorter lasing time may imply a higher risk after PVP of smaller prostates. A longer lasing time predicts an increased risk of reoperation due to persistent/recurrent adenoma, which may be related to higher prostate volumes and inefficient PVP by less-experienced surgeons.

Low-level laser therapy (LLLT) is a treatment that is increasingly used in orthopedics practices. In vivo and in vitro studies have shown that low-level laser therapy (LLLT) promotes angiogenesis, fracture healing and osteogenic differentiation of stem cells. However, the underlying mechanisms during bone formation remain largely unknown. Factors such as wavelength, energy density, irradiation and frequency of LLLT can influence the cellular mechanisms. Moreover, the effects of LLLT are different according to cell types treated. This review aims to summarize the current knowledge of the molecular pathways activated by LLLT and its effects on the bone healing process. A better understanding of the cellular mechanisms activated by LLLT can improve its clinical application.

Anterior knee pain (AKP) is the most common knee pathology in athletes and occurs in 15% of army recruits of elite units during basic training. Of these, 50% are symptomatic 6 years later. Photobiomodulation (PBM) is a nonthermal red-to-near-infrared irradiation used for pain reduction of a variety of etiologies. This study was designed to determine whether addition of PBM to physiotherapy (PT) for AKP in combat soldiers is superior to PT alone.

In this prospective, double-blind, sham-controlled, randomized clinical trial (NCT02845869), 26 combat soldiers/policemen (male:female, 15:11; body mass index [BMI] = 24.2 ± 3.9, n = 46 knees), with AKP due to overuse/load, received 4 weeks of PT + sham (PT + Sham) or active PBM (wavelength = 660 and 850 nm, pulsing = 2.5 Hz, LED power = 50 mW/cm² [local tissue/regional lymph nodes]; 810 nm continuous beam, laser cluster 6 W/cm² [analgesia] and laser pointer 4.75 W/cm² [trigger points]) (PT + PBM). The main outcome measures were subjective pain by visual analog scale (VAS) (0 [none]-100 [intolerable]) and functional disability by Kujala score (0 [worst]-100 [best]). Evaluations were carried out at baseline, end of treatments, and 3-month follow-up.

All participants completed the treatment protocol without any reported adverse device effects. Post-treatment pain was significantly reduced in the PT+PBM group, compared with baseline and sham (Δpain, VAS, mean ± SD: PT + PBM = -19 ± 23, P = 0.002; PT + Sham = -6 ± 21, P = 0.16; between groups, P = 0.032). At 3-month follow-up, pain reduction was similar between groups; however, the Kujala score was significantly improved only in the PBM-treated group (ΔKujala: PT + PBM = 11 ± 10, P = 0.003; PT + Sham = 5 ± 7, P = 0.059).

Addition of PBM to PT for AKP resulted in earlier reduction in pain and improved functionality, compared with PT alone. This noninvasive, nonpharmacologic, adjunctive therapeutic modality can be easily incorporated into team healthcare frameworks or end units and may lead to earlier return to competition or combat-level service. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

To evaluate the safety and efficacy of an at-home photobiomodulation (PBM) device for the treatment of diabetic foot ulcers (DFUs) in a frail population with severe comorbidities.

Prospective, randomized, double-blind, sham-controlled pilot study. Patients (age = 63 ± 11 years, male:female 13:7) with insulin-dependent diabetes type 2, neuropathy, peripheral artery disease, significant co-morbidities, and large osteomyelitis-associated DFUs (University of Texas grade ≥ III) were randomized to receive active (n = 10) or sham (n = 10) at-home daily PBM treatments (pulsed near-infrared 808 nm Ga-Al-As laser, 250 mW, 8.8 J/cm²) for up to 12 weeks in addition to standard care. The primary outcome was the %wound size reduction. The secondary was adverse events.

With the numbers available, PBM-treated group had significantly greater %reduction compared to sham (area [cm²], baseline vs endpoint: PBM 10[20.3] cm² vs 0.2[2.4] cm²; sham, 7.9 [12.0] cm² vs 4.6 [13.8] cm², p = 0.018 by Mann-Whitney U test). Wound closure > 90% occurred in 7 of 10 PBM-treated patients but in only 1 of 10 sham patients (p = 0.006). No adverse device effects were observed.

Photobiomodulation at home, in addition to standard care, may be effective for the treatment of severe DFUs in frail patients with co-morbidities and is particularly relevant at these times of social distancing. Our preliminary results justify the conduction of a larger clinical trial. ClinicalTrials.gov: NCT01493895.

Rupture of Abdominal aortic aneurysm (AAA) is among the 15 leading causes of death after age 65. Using high frequency ultrasound, we showed that photobiomodulation (PBM) prevents formation and progression of AAA in the angiotensin-II (Ang-II)-infused, apolipoprotein-e-deficient mouse model. In the current study we report that while challenge of porcine aortic Smooth Muscle Cells (SMCs) with Ang-II (1 μM) resulted in a marked decay in mitochondrial membrane potential (MitMP) vs non-challenged cells, treatment with PBM (continuous diode laser, 780 nm, 6.7 mW/cm² , 5 minutes, 2 J/cm² ) or pre-incubation with estrogen (50 nM, 1 hour) significantly attenuated this deterioration in MitMP. We also report that PBM and estrogen markedly affected porcine aortic SMC contraction and modified mitochondrial dispersion reflecting important influence on SMC function. These studies provide strong evidence of the important underlying role of mitochondria in the preventive effect of PBM on formation and progression of AAA and its reduced incidence and delayed onset in women.

Keloids are an exuberant response to wound healing, characterized by an exaggerated synthesis of collagen, probably due to the increase of fibroblasts activity and to the reduction of their apoptosis rate: currently no standard treatments or pharmacological therapies are able to prevent keloid recurrence. To reach this goal, in recent years some physical treatments have been proposed, and among them the PhotoBioModulation therapy (PBM). This work analyses the effects of a blue LED light irradiation (410-430 nm, 0.69 W/cm² power density) on human fibroblasts, isolated from both keloids and perilesional tissues. Different light doses (3.43-6.87-13.7-20.6-30.9 and 41.2 J/cm²) were tested. Biochemical assays and specific staining were used to assess cell metabolism, proliferation and viability. Micro-Raman spectroscopy was used to explore direct effects of the blue LED light on the Cytochrome C (Cyt C) oxidase. We also investigated the effects of the irradiation on ionic membrane currents by patch-clamp recordings. Our results showed that the blue LED light can modulate cell metabolism and proliferation, with a dose-dependent behavior and that these effects persist at least till 48 h after treatment. Furthermore, we demonstrated that the highest fluence value can reduce cell viability 24 h after irradiation in keloid-derived fibroblasts, while the same effect is observed 48 h after treatment in perilesional fibroblasts. Electrophysiological recordings showed that the medium dose (20.6 J/cm²) of blue LED light induces an enhancement of voltage-dependent outward currents elicited by a depolarizing ramp protocol. Overall, these data demonstrate the potentials that PBM shows as an innovative and minimally-invasive approach in the management of hypertrophic scars and keloids, in association with current treatments.

Basic dosimetric studies are necessary to support the use of photobiomodulation therapy (PBMT), since the great variety of laser parameters that are reported in the literature have created an obstacle to identifying reproducible results. Thus, the present study evaluates the process of tissue repair after the photobiomodulation therapy, taking into consideration the dose, frequency and the mode of energy delivery used. For this, 6 mm diameter wounds were created on dorsal skin of Wistar rats, and the animals were divided in control and irradiated groups, where L1 and L4 (irradiated with 1 point of 10 J/cm2), L2 and L5 (5 points of 10 J/cm2), L3 and L6 (1 point of 50 J/cm2), respectively for one or multiple days of irradiations. A diode laser, λ 660 nm, 40 mW of power and 0.028 cm2 of spot area was used. Our data showed that the group receiving multiple treatments over the first week post wounding, applied at 10 J/cm2 at each of 5 points on and around the wound (group L5) presented the best improvement of wound closure, higher cytokeratin 10, lower macrophage infiltration, and greater tissue resistance to rupture. We conclude that PBMT improves the skin wound healing process, and the outcomes were directly related to the chosen laser parameters and irradiation mode.

This study investigates the immunomodulatory effects of polychromatic polarized light therapy (PLT) on human monocyte cells. While there is some evidence demonstrating a clinical effect in the treatment of certain conditions, there is little research into its mechanism of action. Herein, U937 monocyte cells were cultured and exposed to PLT. The cells were then analyzed for change in expression of genes and cell surface markers relating to inflammation. It was noted that 6 hours of PLT reduced the expression of the CD14, MHC I and CD11b receptors, and increased the expression of CD86. It was also shown that PLT caused downregulation of the genes IL1B, CCL2, NLRP3 and NOD1, and upregulation of NFKBIA and TLR9. These findings imply that PLT has the capacity for immunomodulation in human immune cells, possibly exerting an anti-inflammatory effect.

Introduction: The Mechanism of laser therapy and also its safety are 2 important features of the application of different types of lasers in medicine. This study aims to investigate the critically affected genes after the treatment of squamous cell carcinoma patients. Methods: The gene expression profiles of 4 squamous cell carcinoma patients that were treated via chemoradiotherapy (CRT) plus the laser and 3 similar patients without laser exposure from Gene Expression Omnibus (GEO) were downloaded and were screened to find critical genes via network analysis. The STRING database, Cytoscape software, and the Clue GO plug-in of Cytoscape software were used. Results: The genes HSX70 and NCC27 were determined as neighbors and HSPA1B, CLIC1, RAB13, PPIF, and LCE3D as hub genes. The over-expression of LCE3D was interpreted as the side effect of laser therapy. Apoptosis and the cell cycle were the dominant biological processes regulated by the HSP molecules in the laser-treated patients. Conclusion: The laser affected the main biological processes and simultaneously issued side effects.

It is known that LLLT has beneficial effects on several pathological conditions including wound healing, pain and inflammation. LLLT modulates biological processes, including cell proliferation, apoptosis and angiogenesis. In the present study, we examined the effect of local application of LLLT on follicular dynamics, ovarian reserve, AMH expression, progesterone levels, apoptosis, angiogenesis, and reproductive outcome in adult mice. LLLT (200 J/cm2) increased the percentage of primary and preantral follicles, whilst decreasing the percentage of corpora lutea compared to control ovaries. LLLT-treated ovaries did not exhibit any changes regarding the number of primordial follicles. We observed a higher percentage of AMH-positive follicles (in early stages of development) in LLLT-treated ovaries compared to control ovaries. LLLT reduced the P4 concentration and the apoptosis in early antral follicles compared to control ones. LLLT caused a reduction in the endothelial cell area and an increase in the periendothelial cell area in the ovary. Additionally, LLLT was able to improve oocyte quality. Our findings suggest that local application of LLLT modulates follicular dynamics by regulating apoptosis and the vascular stability in mouse ovary. In conclusion, these data indicate that LLLT might become a novel and useful tool in the treatment of several pathologies, including female reproductive disorders.

Achilles tendinopathy is a common musculoskeletal disorder. Athletes, runners and jumpers, and the sedentary are frequently affected. Numerous are the therapeutic choices to manage these kinds of disorders. The aim of this review is to analyze the available literature to document the up-to-date evidence on conservative management of Achilles tendinopathy. A systematic review of two medical electronic databases was performed by three independent authors, using the following inclusion criteria: conservative treatment consisted of pharmacologic, physical therapy without operative treatment, with more of 6 months symptoms and a minimum average of 6-months follow-up. Studies of any level of evidence, reporting clinical results, and dealing with Achilles tendinopathy and conservative treatment were searched for. A total of n = 1228 articles were found. At the end of the first screening, following the previously described selection criteria, we selected n = 94 articles eligible for full-text reading. Ultimately, after full-text reading and a reference list check, we selected n = 29 articles. Achilles tendinopathy is a frequent musculoskeletal disorder and several conservative treatments have been proposed, but no therapy is universally accepted, except for eccentric exercise training, which is the gold standard and a commonly used protocol.

Objective: The main objective was to verify the modulatory effects of MMP-1, MMP-3, and MMP-13 levels on the partially injured calcaneal tendons of rat exposure to photobiomodulation. Background: Photobiomodulation has been shown to have anti-inflammatory and regenerative effects on tendon injuries. However, there is still uncertainty regarding the beneficial effects in matrix metalloproteinase (MMP) levels, especially MMP-1, -3, and -13. Materials and methods: Sixty-five male Wistar rats were used. Sixty were submitted to a direct trauma on the calcaneal tendons and were randomly distributed into the following six groups: LASER 1, 3, and 7 (10 partially injured calcaneal tendons in each group treated with photobiomodulation for 1, 3, and 7 days, respectively) and Sham 1, 3, and 7 (same injury, with simulated photobiomodulation). The remaining five animals were allocated to the normal group (no injury or treatment procedure). The 780 nm low-level laser was applied with 70 mW of mean power and 17.5 J/cm² of fluency for 10 sec, once a day. The tendons were surgically removed and analyzed for MMP-1, MMP-3, and MMP-13 through immunohistochemistry. Results: MMP-3 levels remained close to normal in all experimental groups (p > 0.05); however, reductions (p < 0.05) in MMP-1 and MMP-13 levels were detected in the groups submitted to one, three, and seven low level laser therapy applications. Conclusions: The photobiomodulation protocol was able to reduce MMP-1 and MMP-13 levels in injured calcaneal tendons.

Angiotensin II (Ang II) infusion promotes the development of aortic aneurysms and accelerates atherosclerosis in ApoE^-/- mice. In order to elucidate the role of hematopoietic cells in these pathologies, irradiation and bone marrow transplantation (BMT) are commonly utilized. The aim of this study was to investigate the effects of irradiation and BMT on abdominal and thoracic aortic aneurysm formation and acute leukocyte recruitment in the aortic root and descending aorta, in an experimental mouse model of aortic aneurysm formation.

ApoE^-/- mice were either lethally irradiated and reconstituted with ApoE^-/- bone marrow or non-irradiated. Following engraftment, mice were treated with Ang II to induce aortic inflammation and accelerate atherosclerosis.

Ang II infusion (0.8 mg/kg/day) in BMT mice resulted in reduced aortic aneurysms and atherosclerosis with decreased leukocyte infiltration in the aorta compared to non-BMT mice, when receiving the same dose of Ang II. Furthermore, the reduced aortic infiltration in BMT mice was accompanied by increased levels of monocytes in the spleen and bone marrow. A dose of 3 mg/kg/day Ang II was required to achieve a similar incidence of aneurysm formation as achieved with 0.8 mg/kg/day in non-BMT mice.

This study provides evidence that BMT can alter inflammatory cell recruitment in experimental mouse models of aortic aneurysm formation and atherosclerosis and suggests that irradiation and BMT have a considerably more complex effect on vascular inflammation, which should be evaluated.

Breast cancer related lymphedema (BCRL) is a prevalent complication secondary to cancer treatments which significantly impacts the physical and psychological health of breast cancer survivors. Previous research shows increasing use of low level laser therapy (LLLT), now commonly referred to as photobiomodulation (PBM) therapy, for BCRL. This systematic review evaluated the effectiveness of LLLT (PBM) in the management of BCRL.

Clinical trials were searched in PubMed, AMED, Web of Science, and China National Knowledge Infrastructure up to November 2016. Two reviewers independently assessed the methodological quality and adequacy of LLLT (PBM) in these clinical trials. Primary outcome measures were limb circumference/volume, and secondary outcomes included pain intensity and range of motion. Because data were clinically heterogeneous, best evidence synthesis was performed.

Eleven clinical trials were identified, of which seven randomized controlled trials (RCTs) were chosen for analysis. Overall, the methodological quality of included RCTs was high, whereas the reporting of treatment parameters was poor. Results indicated that there is strong evidence (three high quality trials) showing LLLT (PBM) was more effective than sham treatment for limb circumference/volume reduction at a short-term follow-up. There is moderate evidence (one high quality trial) indicating that LLLT (PBM) was more effective than sham laser for short-term pain relief, and limited evidence (one low quality trial) that LLLT (PBM) was more effective than no treatment for decreasing limb swelling at short-term follow-up.

Based upon the current systematic review, LLLT (PBM) may be considered an effective treatment approach for women with BCRL. Due to the limited numbers of published trials available, there is a clear need for well-designed high-quality trials in this area. The optimal treatment parameters for clinical application have yet to be elucidated.

Myocardial ischemia reperfusion injury is a negative pathophysiological event that may result in cardiac cell apoptosis and is a result of coronary revascularization and cardiac intervention procedures. The resulting loss of cardiomyocyte cells and the formation of scar tissue, leads to impaired heart function, a major prognostic determinant of long-term cardiac outcomes. Photobiomodulation is a novel cardiac intervention that has displayed therapeutic effects in reducing myocardial ischemia reperfusion related myocardial injury in animal models. A growing body of evidence supporting the use of photobiomodulation in myocardial infarct models has implicated multiple molecular interactions. A systematic review was conducted to identify the strength of the evidence for the therapeutic effect of photobiomodulation and to summarise the current evidence as to its mechanisms. Photobiomodulation in animal models showed consistently positive effects over a range of wavelengths and application parameters, with reductions in total infarct size (up to 76%), decreases in inflammation and scarring, and increases in tissue repair. Multiple molecular pathways were identified, including modulation of inflammatory cytokines, signalling molecules, transcription factors, enzymes and antioxidants. Current evidence regarding the use of photobiomodulation in acute and planned cardiac intervention is at an early stage but is sufficient to inform on clinical trials.

In this study, clinical, biochemical and histological analysis were used to compare different phototherapies, including LED, low and high-power laser (HPL) for the treatment of chemotherapy (CT)-induced oral mucositis (OM). One-hundred-fifty hamsters were divided into five groups: C: control; CH: CT/OM induction; L: CT/OM induction and treatment with LED (635 nm, 1.2 J), HL: CT/OM induction and treatment with HPL (808 nm, 10 J), LL: CT/OM induction and treatment with low-level laser therapy (LLLT) (660 nm, 1.2 J). OM was induced by scratches performed on check pouch mucosa after two injections of 5-Fluorouracil. The experiment lasted 10 days and OM was analyzed by specific clinical scales on days 5, 7 and 10. The animals were euthanized and the cheek pouch mucosa removed for biochemical (TNF-α concentration) and histological (light microscopy) analysis. After statistical analysis, the authors' results showed LED and LLLT therapies were efficient treatments for OM, decreasing TNF-α concentration on day 7 (p < 0.05) and completely healing the mucosa on day 10. HPL showed no interference in final healing of OM. According to the methodology used and the results obtained in the present study, LLLT and LED therapies were the best choices to decrease the severity of OM, accelerating tissue repair and decreasing the inflammatory process. Clinical evaluation of OM in Groups CH, LL, L and HL and their respective arrangement of phototherapy treatments at different time intervals (5, 7 and 10 days).

The purpose of this article was to review the molecular mechanisms of low-level laser irradiation (LLLI) preconditioning for heart cell therapy.

Stem cell transplantation appears to offer a better alternative to cardiac regenerative therapy. Previous studies have confirmed that the application of LLLI plays a positive role in regulating stem cell proliferation and in remodeling the hostile milieu of infarcted myocardium. Greater understanding of LLLI's underlying mechanisms would be helpful in translating cell transplantation therapy into the clinic.

Studies investigating LLLI preconditioning for cardiac regenerative therapy published up to 2015 were retrieved from library sources and Pubmed databases.

LLLI preconditioning stimulates proliferation and differentiation of stem cells through activation of cell proliferation signaling pathways and alteration of microRNA expression. It also could stimulate paracrine secretion of stem cells and alter cardiac cytokine expression in infarcted myocardium.

LLLI preconditioning provides a promising approach to maximize the efficacy of cardiac cell-based therapy. Although many studies have reported possible molecular mechanisms involved in LLLI preconditioning, the exact mechanisms are still not clearly understood.

This study was conducted to investigate the effect of combining extremely low frequency-pulsed electromagnetic field (ELF-PEMF) and low-level laser therapy (LLLT) on alkali-burned rabbit corneas. Fifty alkali-burned corneas of 50 rabbits were categorized into five groups: ELF-PEMF therapy with 2 mT intensity (ELF 2) for 2 h daily; LLLT for 30 min twice daily; combined ELF-PEMF and LLLT (ELF + LLLT); medical therapy (MT); and control (i.e., no treatment). Clinical examination and digital photography of the corneas were performed on days 0, 2, 7, and 14. After euthanizing the rabbits, the affected eyes were evaluated by histopathology. The clinical and histopathologic results were compared between the groups. On days 7 and 14, no significant difference in the corneal defect area was evident between the ELF, LLLT, ELF + LLLT, and MT groups. Excluding the controls, none of the study groups demonstrated a significant corneal neovascularization in both routine histopathology and immunohistochemistry for CD31. Keratocyte loss was significantly higher in the MT group than in the ELF, LLLT, and ELF + LLLT groups. Moderate to severe stromal inflammation in the LLLT group was comparable with that in the MT group and was significantly lower than that in the other groups. In conclusion, combining LLLT and ELF was not superior to ELF alone or LLLT alone in healing corneal alkali burns. However, given the lower intensity of corneal inflammation and the lower rate of keratocytes loss with LLLT, this treatment may be superior to other proposed treatment modalities for healing alkali-burned corneas.

The integration of several cellular responses initiates the process of wound healing. Matrix Metalloproteinases (MMPs) play an integral role in wound healing. Their main function is degradation, by removal of damaged extracellular matrix (ECM) during the inflammatory phase, breakdown of the capillary basement membrane for angiogenesis and cell migration during the proliferation phase, and contraction and remodelling of tissue in the remodelling phase. For effective healing to occur, all wounds require a certain amount of these enzymes, which on the contrary could be very damaging at high concentrations causing excessive degradation and impaired wound healing. The imbalance in MMPs may increase the chronicity of a wound, a familiar problem seen in diabetic patients. The association of diabetes with impaired wound healing and other vascular complications is a serious public health issue. These may eventually lead to chronic foot ulcers and amputation. Low intensity laser irradiation (LILI) or photobiomodulation (PBM) is known to stimulate several wound healing processes; however, its role in matrix proteins and diabetic wound healing has not been fully investigated. This review focuses on the role of MMPs in diabetic wound healing and their interaction in PBM.

To investigate combined effect of photobiomodulation with a matrix metalloproteinase (MMP) inhibitor on the relapse rate in relation to MMP expression in rats.

Fifty-two rats were divided into four groups according to the treatment modality: control group, irradiation group, doxycycline group, and irradiation with doxycycline group. During a relapse period of 5 days after orthodontic movement, maxillary central incisors were treated by low-level laser therapy (LLLT) as a photobiomodulation and/or doxycycline as a synthetic MMP inhibitor. Relapse rate was evaluated in association with MMP expression at the gene and protein levels.

Relapse rates were increased by LLLT (1.57-fold) and decreased by doxycycline (0.83-fold) compared with the control, showing positive correlation with the levels of expression for all MMPs in the periodontal ligament (PDL). LLLT concomitant with doxycycline administration resulted in no significant differences of relapse rate and MMP expression from the control.

The combined effect of photobiomodulation with an MMP inhibitor around the relapsing teeth proved to be antagonistic to PDL remodeling activity during relapse. This study suggests a basis for developing a novel biologic procedure targeting the MMP-dependent PDL remodeling to control the relapse rate.

Plantar fasciitis affects nearly 1 million persons in the United States at any one time. Conservative therapies have been reported to successfully treat 90% of plantar fasciitis cases; however, for the remaining cases, only invasive therapeutic solutions remain. This investigation studied newly emerging technology, low-level laser therapy. From September 2011 to June 2013, 69 subjects were enrolled in a placebo-controlled, randomized, double-blind, multicenter study that evaluated the clinical utility of low-level laser therapy for the treatment of unilateral chronic fasciitis. The volunteer participants were treated twice a week for 3 weeks for a total of 6 treatments and were evaluated at 5 separate time points: before the procedure and at weeks 1, 2, 3, 6, and 8. The pain rating was recorded using a visual analog scale, with 0 representing "no pain" and 100 representing "worst pain." Additionally, Doppler ultrasonography was performed on the plantar fascia to measure the fascial thickness before and after treatment. Study participants also completed the Foot Function Index. At the final follow-up visit, the group participants demonstrated a mean improvement in heel pain with a visual analog scale score of 29.6 ± 24.9 compared with the placebo subjects, who reported a mean improvement of 5.4 ± 16.0, a statistically significant difference (p < .001). Although additional studies are warranted, these data have demonstrated that low-level laser therapy is a promising treatment of plantar fasciitis.

Photobiomodulation has been found to increase gene expression and release of various growth factors and cytokines involved in wound healing. Photobiomodulation has been used to treat a wide variety of disorders, and has been found to be beneficial in the treatment of chronic wounds, however the exact underlying mechanism is not well understood. This study aimed to profile 84genes in response to irradiation at 660nm. WS1 human skin fibroblasts were used in gene expression profiling studies in response to irradiation with a 660nm diode laser at a fluence of 5J/cm(2) and power density of 11mW/cm(2). Forty-eight hours post-irradiation, 1μg RNA was reverse transcribed and used in real-time qualitative polymerase chain reaction (qPCR). Genes involved in the extracellular matrix and cell adhesion, inflammatory cytokines and chemokines, growth factors and signal transduction were evaluated. A total of 76genes were regulated by laser irradiation, 43genes were up-regulated while 33genes were down-regulated. Irradiation of WS1 cells at 660nm modulates the expression of genes involved in collagen production, cellular adhesion, remodelling and spreading, the cytoskeleton, inflammatory cytokines and chemokines, growth factors and molecules involved in signal transduction.

Light amplification by stimulated emission of radiation (LASER) diode irradiation (LDI) has some beneficial effects on the wound healing. However, little is known about the biochemical effect of LDI on wound healing. We have performed animal study to clarify the effect of LDI on wound healing based on microscopic findings.

Eight-month-old male rats (NTacSam:SD, SamtakoBioKorea), weighting 250-300 g, were used. Round blade, of 1 cm diameter, was penetrated through the skin and subcutaneous level after elevating the skin just above the thoracic spine of the rats. Laser diode of 655, 785, and 850 nm wavelengths were irradiated to the skin wound for 9 days, 20 min a day. Eight rats were used in each four groups including non-irradiated group. Immunochemical staining was carried out to evaluate pan-cytokeratin and actin, and Masson's trichrome staining was carried to evaluate the cellular and protein components relating to wound healing. Wound size was measured on 9th postoperative day with computer system.

Collagen formation was graded as 2+, 3+, and 4 + in the order of non-radiation group, 655, 785, and 850 nm irradiation groups, respectively. Myofibroblast was formed more abundantly in LDI group than in non-irradiated group. The mean values of proliferating cell nuclear antigen (PCNA) were 67.8 ± 5.0, 84.0 ± 4.6, 78.0 ± 6.8, and 74.2 ± 4.0 nm in the order of non-radiation group, 655, 785, and 850 nm irradiation groups, respectively. Mean values of defect size were 2,840 ± 124 um, 1,689 ± 125 um, 1,254 ± 94 um, and 1,423 ± 113 in the order of non-radiation group, 65, 785, and 850 nm groups, respectively.

LDI has beneficial effects on the formation of fibroblast and collagen, and results in better wound healing.

A simple, easy, and safe procedure aiming to improve liver regeneration could be of great clinical benefit in critical situations such as major hepatectomy, trauma, or hemorrhage. Low-power laser irradiation (LPLI) has come into a wide range of use in clinical practice by inducing regeneration in healthy and injured tissues. However, the effect of LPLI on the process of liver regeneration, especially those related to the molecular mechanisms, is not fully understood. Thus, the aim of the present study was to investigate the main molecular mechanisms involved in liver regeneration of partially hepatectomized rats exposed to LPLI. We used Wistar male rats, which had their remaining liver irradiated or not with LPLI (wavelength of 632.8 nm and fluence of 65 mW/cm(2)) for 15 min after a 70% hepatectomy. We subsequently investigated hepatocyte growth factor (HGF), Met, Akt, and Erk 1/2 signaling pathways through protein expression and phosphorylation analyses along with cell proliferation (proliferating cell nuclear antigen (PCNA) and Ki-67) using immunoblotting and histological studies. Our results show that LPLI can improve liver regeneration as shown by increased HGF protein expression and the phosphorylation levels of Met, Akt, and Erk 1/2 accompanied by higher levels of the PCNA and Ki-67 protein in the remnant livers. In summary, our results suggest that LPLI may play a clinical role as a simple, fast, and easy-to-perform strategy in order to enhance the liver regenerative capacity of a small liver remnant after hepatectomy.