Journal of Lasers in Medical Sciences

Introduction: Diabetes is a highly prevalent disease worldwide. Despite routine treatments, there is no effective treatment approach for patients with diabetic foot ulcers (DFUs). A new approach to reduce complications and control DFU is low-level laser therapy (LLLT). In the present study, we evaluated the therapeutic effects of LLLT on the symptoms of DFU patients.
Methods: Sixty diabetic patients with DFU were included in this randomized clinical trial and were randomly allocated into two groups of laser (n=30) and control (n=30) with signed written consent. The LLLT group underwent visible and infrared laser therapy and conventional medical treatment, while the control group received only conventional medical treatment. The total laser irradiation sessions of the patients were 20 sessions, (three sessions a week) and each session lasted for 30 minutes over the entire surface of the wound. The power density per session for each laser was calculated to be 35.65 mW/cm2 with an energy density of 64.17 J/cm2.
Results: The mean area of ulcers in the LLLT group reduced significantly (P<0.001) from 441.7±365.5 mm2 before LLLT to 163.9±213.9 mm2 from the baseline up to the last session of LLLT, indicating a 62.99% reduction in mean ulcer area. In the control group, the mean ulcer area did not change significantly. Wagner’s classification of the patients in the LLLT group reduced to lower grades significantly (P<0.01), while the classification moved towards higher grades in the control group (P<0.08).
Conclusion: In this study, we showed the effectiveness of LLLT in the reduction of the surface and depth of DFUs. The results documented that patients experienced significant improvements in the healing of their foot ulcers after laser therapy. It is recommended that the LLLT be considered as a non-invasive method for the treatment of DFU patients.

Introduction: One of the clinical problems following orthodontic treatment is white spot lesions around orthodontic brackets due to enamel demineralization. Confronting enamel demineralization during fixed treatments has long been a challenge for orthodontists. The aim of this in vitro study was to evaluate the effect of CO2 laser and Titanium Tetra-fluoride (TiF4) application on the prevention of enamel demineralization around orthodontic brackets.
Methods: Eighty permanent premolars were selected and bonded with brackets. They were randomly divided into four groups (n=20): topical titanium tetra-fluoride gel 4% (TiF4), CO2 laser (10.6 μm wavelength for 10 seconds, peak power=291 W), fluoride+laser (F+L), and control (C). All specimens were demineralized for 10 days in a 0.2 M acetate buffer solution. The mean lesion depths were determined by using polarized light microscopy.
Results: The mean depth of lesion was the highest in the C group and then decreased in the TiF4, CO2
laser, and F+L groups, respectively. The difference between all groups was significant (P<0.05), except for the CO2 laser and F+L groups.
Conclusion: The lowest amount of demineralization around the orthodontic brackets was observed in the L+F group, followed by the CO2 laser, TiF4, and control groups, respectively

Introduction: Polycystic ovary syndrome (PCOS) is a complex condition that can have various symptoms and complications, one of which is infertility. Dysregulation of miRNA has been associated with the pathogenesis of numerous illnesses such as PCOS. In this study, we evaluated the effect of photobiomodulation therapy (PBMT) and exosome therapy (EXO) on the regulation of miRNA and nucleus acetylation in a PCOS oocyte.
Methods: In this research, 36 oocytes were divided into three groups: control, EXO, and PBM (Wavelength of 640 nm). Subsequently, in-vitro maturation (IVM) was evaluated. Real-time PCR was used to evaluate miRNA-21,16,19,24,30,106,155 and GAPDH. Afterward, oocyte glutathione (GSH) and nucleus acetylation were measured by H4K12.
Results: The expression of the miR-16, miRNA-19, miRNA-24, miRNA-106 and miRNA-155 genes in the EXO and PBMT groups was significantly down-regulated in comparison to the control group, but the expression of miRNA-21 and miR-30 significantly increased in the EXO and PBMT groups in comparison to the control group. The EXO and PBMT significantly increased GSH and nucleus acetylation (P<0.0001).
Conclusion: The results of this study showed that the use of EXO and PBMT can improve GSH and nucleus acetylation in the PCOS oocyte and also change the expression of miRNAs.

Introduction: This study was carried out to assess and compare the efficacies of transcutaneous electrical nerve stimulation (TENS) and low-level laser therapy (LLLT) applied to sciatic Valleix points to reduce sciatica in patients with chronic lumbar radiculopathy.
Methods: The study population consisted of 164 patients with chronic radicular pain caused by LDH. The remaining 75 patients were studied in three groups. TENS and hotpack were applied to the lower back region of all patients. In addition, group 1 (n=24), group 2 (n=25), and group 3 (n=26) received LLLT (4 J/cm2 for each point), TENS, and sham LLLT, respectively, on sciatic Valleix points five days a week, for three weeks (15 sessions). Outcomes were assessed at the beginning of the treatment, after completion of 3 weeks of treatment, and after three months (follow-up).
Results: Post-treatment assessments indicated that all parameters investigated within the scope of the study improved in all three groups, except for the VAS leg pain (VASLP) score in group 3. Post-treatment VASLP and DN4 scores of group 1 were significantly superior to those of group 2 (P˂0.001). Follow-up assessments revealed an improvement only in the VASLP score and in group 1. The VASLP, DN-4, and ODI scores of groups 1 and 2 were significantly superior to those of group 3. There was no significant difference between the groups in the PSQI score and lumbar ROM value.
Conclusion: LLLT and TENS were effective in treating the sciatic nerve associated with lumbar disk herniation with radiculopathy. LLLT was found to be more effective than TENS in reducing leg and neuropathic pains. Follow-up assessments revealed that the only lasting effect of the treatments, which continued into the third month, was the improvement in leg pain.

Introduction: Fiber-reinforced composite posts (FRCP) have become popular due to their multiple advantages in teeth with extensive crown destruction. Proper disinfection is essential for the successful bonding of these posts. Commonly used solutions for cleaning and disinfecting the root canals adversely affect the bond strength (BS). Photodynamic therapy is an alternative method for irrigating the root canal and disinfecting the post space. This study was designed to evaluate the impact of photodynamic therapy on the BS of fiber posts to root canal dentin.
Methods: Human maxillary canines were recruited for this study. The tooth crowns were removed at the cervical line and endodontically treated. After fiber post spaces were prepared, the teeth were assigned to five groups based on the light-sensitive material: deionized water, indocyanine green and 810-nm laser, methylene blue and 660-nm laser, toluidine blue and 635-nm laser, curcumin and LED. The posts were cemented after photodynamic therapy. Cervical, middle, and apical samples were prepared by transverse sectioning. Push-out bond strength (PBS) values were measured in a universal testing machine. Finally, the data underwent statistical analyses with ANOVA and Howell-Games tests.
Results: One-way ANOVA revealed no significant differences between the groups (P<0.001). The Games-Howell test showed that curcumin (7.23±3.75) and the control group (5.92±4.04) had a similar BS (P>0.005). The BS was lower in the methylene blue (3.34±2.15), indocyanine green (2.59±3.16), and toluidine blue (2.45±1.73) groups than in the control group (P<0.005).
Conclusion: Unlike other light-sensitive materials, curcumin did not adversely affect the BS.

Introduction: Photothermal therapy (PTT) by using a near-infrared (NIR) laser, as a successful treatment of cancer, has attracted extensive attention of researchers. Its advantages as a noninvasive and suitable method have been confirmed. Discovery of the NIR laser molecular mechanism at the cellular level via system biology assessment to identify the crucial targeted genes is the aim of this study.
Methods: RNA-seq series of six samples were retrieved from Gene Expression Omnibus (GEO) and pre-evaluated by the GEO2R program for more analysis. The significant differentially expressed genes (DEGs) were determined and studied via gene expression analysis, proteinprotein interaction (PPI) network assessment, action map evaluation, and gene ontology enrichment.
Results: HSPA5, DDIT3, TRIB3, PTGS2, HMOX1, ASNS, GDF15, SLC7A11, and SQSTM1 were identified as central genes. Comparing the central genes and the determined crucial genes via gene expression analysis, actin map results, and gene ontology enrichment led to the introduction of HSPA5, DDIT3, PTGS2, HMOX1, and GDF15 as critical genes in response to the NIR laser.
Conclusion: The results indicated that the principle biological process “Endoplasmic reticulum unfolded protein response” and HSPA5, DDIT3, PTGS2, HMOX1, and GDF15 are the crucial
targets of the NIR laser. The results also showed that the NIR laser induces stress conditions in the irradiated cells.

Introduction: Numerous strategies have been investigated for addressing recurrent implantation failure (RIF) and enhancing endometrial receptivity, yet agreement on the optimal intervention remains elusive. Our investigation endeavors to assess the effect of low-level laser therapy (LLLT) on pregnancy outcomes in individuals who have undergone a minimum of three unsuccessful embryo transfer cycles (ET).
Methods: In our randomized single-blinded clinical trial, we enrolled thirty females with a medical history of RIF who were eligible for frozen-thawed embryo transfer (FET). Through a random allocation sequence, the participants were divided into two groups. The LLLT was performed one cycle before blastocyst transfer in 15 cases using a New Age BIOLASER device (New Age Co., Italy) with a 900-milliwatt power output and an 850-nm wavelength. The irradiation sessions were conducted transabdominal on the hypogastric area. The considered outcomes were biochemical pregnancy, identified by a positive blood pregnancy test, and clinical pregnancy, confirmed through visualization of the gestational sac using ultrasonography.
Results: The mean age of the subjects was 34.17 years, and they had undergone three to seven previous embryo transfers. There was no significant difference in basic characteristics between the group undergoing laser treatment and the control group. However, the laser-treated group exhibited elevated rates of both biochemical and clinical pregnancies compared to the control group (46.7% vs. 33.3%; P==0.710 and 33.3% vs. 20.0%; P=0.682 respectively).
Conclusion: To our knowledge, this study represents the first single-blinded randomized clinical trial to assess the effectiveness of LLLT pretreatment in individuals with RIF. The findings propose that LLLT may potentially enhance biochemical and clinical pregnancy rates among RIF patients

Introduction: Studies on head and neck cancer (HNC) patients undergoing radiotherapy have revealed increased numbers of Candida spp., leading to oral candidiasis and oral mucositis. The effects of laser therapy on Candida spp. have been studied with varied results. This study aimed to investigate the effect of low-level laser therapy (LLLT) on C. albicans colonies isolated from HNC patients undergoing radiotherapy.
Methods: This study included a treated group, wherein 11 C. albicans isolates were obtained from the saliva of HNC patients undergoing radiotherapy at a dose exceeding 30 Gy. The control groups consisted of an untreated negative control and a positive control treated with nystatin. The treatment groups were subjected to LLLT in continuous mode for 50 seconds at a wavelength of 976 nm, 0.1 W at a dose of 5 J/cm2 for Laser 1 (L1) group and 0.2 W at a dose of 10 J/cm2 for Laser 2 (L2) group. The tests were conducted using C. albicans inoculum equivalent to a 0.5-McFarland suspension on 96-well plates. All test group inoculums were then cultured on Sabouraud dextrose agar (SDA), and the colony count was assessed at 104 CFU/mL.
Results: LLLT at 5 and 10 J/ cm2 reduced C. albicans colonies by 7.01% and 10.94%, respectively, but the reductions were not statistically significant (P>0.05). Nystatin eliminated all the colonies.
Conclusion: LLLT shows potential for reducing C. albicans colonies in HNC patients undergoing radiotherapy. However, further studies with varied parameters and methods are necessary.

Introduction: The adhesion ability of mesenchymal stem cells can significantly affect their viability and is considered a prerequisite for cell therapy. The current study sought to evaluate the effect of fibroblast growth factor 2 (FGF2) and low-level laser therapy (LLLT), either individually or in conjunction, on the adhesion and proliferation of periodontal ligament stem cells (PDLSCs) when applied on the first day of cell seeding.
Methods: The experimental groups of this study comprised a control group and different combinations of adjunctive FGF2 (50 ng/mL) and LLLT with an 808 nm diode laser in one (LLLT1) or two sessions (LLLT-2) of irradiation. The proliferation and adhesion of cells were evaluated by using the methylthiazolyl tetrazolium (MTT) assay and 4′,6-diamidino-2-phenylindole (DAPI) staining. All experiments were done in triplicates on the first, third, and fifth days after cell seeding. Two-way ANOVA and post hoc Tukey tests were used to analyze the data of the MTT assay. P<0.05 was considered statistically significant.
Results: One-day post-culture, only significant differences were found between the control group and the FGF2 (P=0.04) and FGF2+LLLT-2 application (P=0.04) groups. After three days post-cell culture, only a significantly higher proliferation rate was found in the control group than in the FGF2 group (P=0.01). After five days, the control group and LLLT-2 groups showed significantly higher amounts of proliferation compared to the other groups (P<0.05). DAPI staining qualitatively confirmed the results of the MTT assay.
Conclusion: The LLLT can be applied to PDLSCs on the day of seeding without causing a notable decrease in their viability and adhesion. Conversely, the administration of FGF2 should be restricted on the seeding day and postponed to subsequent days as it may have adverse effects on their adhesion and proliferation.

Introduction: The purpose of this study is to achieve a significant increase in the proliferative activity of mesenchymal stem cells (MSCs) of the bone marrow (BM) at early passages after laser exposure to a suspension of these cells and to estimate the effect of light and heat components of laser radiation on the proliferation of BM MSCs.
Methods: The studies were performed on rats with BM MSCs. MSC suspension was placed into the wells and heated by using laser radiation (980 nm wavelength) or a water bath at 70 °C providing similar temperature dynamics. The studies were carried out in 3 comparison groups: (1) control suspension of MSCs, which was not subjected to heating in a water bath or laser exposure; (2) MSC suspension, which was heated in a water bath; and (3) suspension of MSCs, which was subjected to laser exposure. The exposure times for the 2nd and 3rd experimental groups were 10- 50 seconds.
Results: Under optimal parameters of laser action on the suspension of BM MSCs, a six-fold increase in the number of BM MSCs colonies was registered compared to the control. The role of the light and heat components of laser exposure to MSCs was determined by comparable heating of a suspension of BM MSCs in a water bath, at which only a twofold increase in the number of colonies was maximally obtained.
Conclusion: The increase in the MSC proliferation activity occurs due to their ThermoPhotobiomodulation. The result obtained is important for practical use in cell transplantation in the treatment of traumatic injuries of bone, cartilage, and tendon tissues when a rapid and multiple increase in the initial number of autologous BM MSCs is required.

Introduction: This in vitro study was conducted to assess the phototoxic effects of curcumin, nanocurcumin, and erythrosine on the viability of Streptococcus mutans (S. mutans) in suspension and biofilm forms.
Methods: Various concentrations of curcumin (1.5 g/L, 3 g/L), nano-curcumin (3 g/L), and erythrosine (100 μM/L, 250 μM/L) were examined for their impact on planktonic and biofilm cultures of S. mutans, either individually or in conjunction with light irradiation (photodynamic therapy or PDT). A blue light-emitting diode (LED) with a central wavelength of 450 nm served as the light source. The results were compared to 0.12% chlorhexidine digluconate (CHX) as the positive control, and a solution containing neither a photosensitizer (PS) nor a light source as the negative control group. The dependent variable was the number of viable microorganisms per experiment (CFU/mL).
Results: Antimicrobial PDT caused a significant reduction in the viability of S. mutans in both
planktonic and biofilm forms, compared to the negative control group (P<0.05). The highest cell
killing was observed in PDT groups with curcumin 3 g/L or erythrosine 250 μmol/L, although the
difference with PDT groups using curcumin 1.5 g/L or erythrosine 100 μmol/L was not significant
(P>0.05). Antimicrobial treatments were more effective against planktonic S. mutans than the
biofilm form.
Conclusion: PDT with either curcumin 1.5 g/L or erythrosine 100 μmol/L may be suggested as an alternative to CHX to inactivate the bacteria in dental plaque or deep cavities. Nanocurcumin, at the selected concentration, exhibited lower efficacy in killing S. mutans compared to Curcumin or erythrosine.

Introduction: This study aimed to assess the photobiomodulation effects of blue and red lasers on the proliferation and osteogenic differentiation of periodontal ligament mesenchymal stem cells (PDLMSCs).
Methods: PDLMSCs were cultured and tested in 4 groups. The first two groups were exposed to 445 nm diode laser irradiation (200 mW, 6 and 12 J/cm2), and the third group was exposed to
660 nm diode laser irradiation (50 mW, 4 J/cm2). The fourth group was also considered as the
control group without irradiation. Cell viability/proliferation was assessed by MTT assay. RUNX2, alkaline phosphatase (ALP), collagen type 1 (col1), and osteocalcin (OCN) were evaluated by RTPCR, and Alizarin red was used to evaluate the colonization. The data were analyzed by means of one-way analysis of variance.
Results: The results of our study showed that cell survival/proliferation in the second group was significantly lower than that in the control group on days 1 and 7 (P<0.05). RT-PCR showed a significant increase in osteogenic genes in all three laser groups compared to the control group (P<0.05). All groups showed a significant increase in calcium content compared to the control group (P<0.05). ALP activity also confirmed the osteoblastic differentiation of cells in laser groups.
Conclusion: 445 nm and 660 nm lasers with the studied parameters showed positive effects on the proliferation and osteoblastic differentiation of PDLMSCs.

Introduction: Radiotherapy-induced xerostomia is an important side effect of head and neck cancer (HNC) treatment. Photobiomodulation (PBM) is one of the new emerging methods for preventing or reducing this problem. The aim of this study is to evaluate the effect of PBM on radiation-induced xerostomia in HNC patients.
Methods: Thirty-seven patients with HNC were referred for radiotherapy to Mashhad Cancer Center. In the case group, an infrared diode laser was used in contact mode on 16 points (covering minor and major salivary glands). The device emitted a wavelength of 810 nm and operated at the power of 200 mW and continuous wave mode. Each area was irradiated for 4 seconds in contact mode with gentle pressure, and the laser energy was 0.8 J with an energy density of 2.85 J/cm2 at the surface of the probe (spot size, 0.28 cm2). The total dose was 45.6 J/cm2. The power density was 714.2 w/cm2. In the control group, the sham laser device was used. Subjective xerostomia was evaluated through the LENT SOMA scale (LSS). Stimulated and unstimulated saliva was also assessed. Data were analyzed with SPSS 22 statistical software.
Results: The study included 26 men and 11 women with a mean age of 55.6±15.3 years. In the sixth week, the case group produced more stimulated saliva than the control group (P=0.006). They also had less subjective xerostomia than the control group in weeks four to six.
Conclusion: In the present study, PBM had a preventive effect on stimulated saliva and subjective
xerostomia and can be recommended as an adjunctive treatment. Further studies with a higher
sample size and the use of a low-level laser in more sessions are needed for definitive comment.

Introduction: In men, several factors cause infertility, among which we can mention damage to sperm due to high temperature. So far, various treatments have been proposed for it, but they have not been highly effective. The current study aimed to evaluate the effect of exosome therapy (EXO) and photobiomodulation therapy (PBMT) on spermatogenesis arrest in male mice after scrotum hyperthermia.
Methods: In this experimental study, the animals were divided into four groups: control, scrotal hyperthermia, scrotal hyperthermia+EXO (100 μL/d) (mice were treated for 30 days), scrotal hyperthermia+PBMT (laser of 0.03 J/cm2 for 30 seconds/for 30 days). Hyperthermia was induced
by exposure to the temperature of 43 °C for 20 minutes every day 5 times. After 6 weeks, the animals were sacrificed.
Results: The treated groups showed a significant increase in sperm parameters compared to the hyperthermic groups. Moreover, these favorable effects were observed in relation to the volume of testicular tissue, the number of germ cells, Leydig cells, and Sertoli cells, and the level of testosterone. Research on antioxidants showed a significant reduction in oxidized glutathione (GSSG) and reactive oxygen species (ROS) in the treatment groups in comparison to the hyperthermia group (P<0.001). Also, there has been a significant increase in the amount of hydrogen peroxide enzyme observed in the hyperthermia group as opposed to the treatment group (P<0.001).
Conclusion: These findings show that EXO and PBMT can improve spermatogenesis caused by hyperthermia, reduce ROS and GSSG, and increase glutathione (GSH) and sperm quality.

Introduction: The preference for endovascular techniques in treating varicose veins, particularly in the great saphenous vein (GSV), has increased due to their minimally invasive nature and reduced complications. Post-operative care, especially involving compression therapy, remains crucial to improve outcomes, prevent varicose vein recurrence, and enhance overall recovery. This study aimed to evaluate the efficacy of eccentric compression therapy compared to alternative post-operative care methods following endovenous laser treatment (EVLT) for GSV insufficiency.
Methods: This prospective randomized clinical trial encompassed 88 EVLT procedures for GSV insufficiency. The participants were divided into two groups, each receiving different postoperative compression methods, and were evaluated over a specified period. The primary outcome was the pain scale after EVLT; meanwhile, the secondary outcome measured in the present study was the rate of GSV occlusion after EVLT.
Results: Both groups underwent all EVLT procedures successfully without any complications. At the one-month duplex ultrasound (DUS) follow-up, the sapheno-femoral junction occlusion rates were 97% (43 out of 44) for group A (eccentric compression plus gradual compression stocking) and 95% (42 out of 44) for group B (only gradual compression stocking). Ecchymosis was observed in only 12 patients across both groups, accounting for an overall occurrence of 13.6%. Group A patients reported significantly lower analgesic usage (10%) compared to group B (18%), although this difference did not reach statistical significance. Analysis of postoperative pain data utilizing the visual analog scale (VAS) showed a median value of 5.5 in group B patients, which decreased to 3.1 with the application of eccentric compression. Moreover, there was less ecchymosis in group A observed by one week.
Conclusion: This study contributes to the ongoing discourse on the efficacy of postoperative compression in varicose vein treatment. It underscores the necessity for more comprehensive, well-designed studies to yield clearer conclusions and provide better guidance for postprocedure care.

Introduction: Endodontic treatment of teeth with periapical lesions presents more clinical difficulty. Various lasers in several methods are used in endodontics, and most of them are utilized as an adjunctive protocol in order to reduce the bacterial load of the root canal system. Improved disinfection plays a crucial role in enhanced and accelerated healing of periapical lesions. This review aims to summarize studies assessing the effect of lasers on periapical lesion healing.
Methods: PubMed/MEDLINE, Scopus, Embase, and Web of Science (ISI) online databases were searched, with no publication year or status restriction, for relevant articles on April 2023. Clinical studies evaluating the effect of laser application on the periapical lesion of patients using radiographic assessment were considered eligible for inclusion.
Results: Eight studies were included after carefully screening the obtained articles, first by their title and abstract and then by their full texts. Diode (4), Er, Cr: YSGG (3), and Nd: YAG (1) lasers were used with output powers that varied from 0.75 to 2 watts. Photodynamic therapy was employed in two studies, and in other studies, the root canal system was directly irradiated. Irradiation of the root canal system was adjunctive to standard preparation in all studies. The healing of the teeth treated with lasers was not inferior to those conventionally treated. In all of the included studies, laser application outperformed the standard cleaning and shaping protocol; however, this improved or faster healing was not statistically significant in most studies.
Conclusion: Lasers might expedite and improve the healing process of periapical lesions. Since lasers enhance the quality of cleaning of the root canal system, it is hard to point out the exact mechanism of it. Further investigations are needed to realize the effectiveness of this treatment modality and to discover the underlying biological concepts.

Introduction: Developing regenerative endodontic treatment (RET) is an exciting approach to managing immature permanent teeth with pulp necrosis. RET is usually performed in two clinical steps: disinfection (first step) and tissue engineering (second step). Recently, laser therapy has entered the field of RET. This study aimed to provide an overview of the literature that employed laser therapy for root regeneration.
Methods: A comprehensive search was performed on four databases, including PubMed, Web of Science, Scopus, and Google Scholar. The searched keywords were laser, regenerative endodontics, immature permanent teeth, and dental pulp necrosis, and related English-published articles were included up to October 2023.
Results: Thirteen studies utilized a laser for RET. In the first step of RET, both high-power and low level lasers (through photodynamic therapy [PDT]) may be applied for canal disinfection. In contrast, regenerative procedures in the second step of RET are just accelerated by low-power lasers (biostimulation). The literature does not support the benefit of laser-assisted irrigation in improving the clinical success of RET. There is some evidence that laser-assisted disinfection with a diode laser may provide comparable results to triple antibiotic paste in reducing bacterial counts in root canals while providing slightly better clinical and radiographic outcomes. PDT may be an effective and suitable adjunct to conventional disinfection methods in immature, necrotic teeth.
Conclusion: Low-power lasers may be beneficial tools for improving the results of regenerative endodontics through chemical disinfection in the first step (PDT) or by biostimulation in the second step of RET.