UNASSIGNED: The risk of skin injuries in space is increasing with longer space missions and a growing astronaut population. This highlights the importance of understanding the adverse effects of weightlessness on wound healing. The objective of this research was to examine the therapeutic potential of Low-Level Light Therapy (LLLT) on skin healing processes under simulated microgravity (SMG) conditions and uncover the underlying molecular mechanisms, thus providing innovative solutions and a sound theoretical basis for space skin injuries.
UNASSIGNED: Hindlimb unloading (HU) mice models were used to simulate weightlessness conditions, with or without a complete management of LLLT for 14 days. A systematic testing consisting of HE, Masson and immunohistochemical staining was performed against the standardized mouse tissue specimens. In vitro assessment of cellular biological functions under SMG conditions was carried out in the rotation system of culture (RSOC) using HaCaT and NIH3T3 cell-lines.
UNASSIGNED: Under SMG conditions, LLLT significantly reduced skin wound area in HU mice, especially on Days 10 (p < 0.001), accompanied by increased collagen deposition and elevated levels of Ki67 and CD31. Moreover, LLLT showed impressive anti-inflammatory effects represented by the reduced in pro-inflammatory markers including LY6G, F4/80 and CD86, as well as the decreased levels of IL-1β, IL-6 and TNF-α. Conversely, an elevation in the anti-inflammatory marker CD206 was observed. By employing bioinformatics technology, we further found the PI3K/AKT signaling was prominent in the KEGG pathway analysis and CCR2 acted as a hub gene in the interaction network. Therefore, we demonstrated that LLLT could enhance the phosphorylation of PI3K/AKT and reduce CCR2 expression under SMG conditions, while CCR2 knockdown promoted the phosphorylation of PI3K/AKT, suggesting an important role of CCR2/PI3K/AKT signal axis in LLLT-accelerated wound healing under SMG conditions.
UNASSIGNED: LLLT induced activation of the PI3K/AKT signaling pathway through suppression of CCR2 expression, which significantly enhanced skin wound healing under SMG conditions.s.

Bone repair is faced with obstacles such as slow repair rates and limited bone regeneration capacity. Delayed healing even nonunion could occur in bone defects, influencing the life quality of patients severely. Photobiomodulation (PBM) utilizes different light sources to derive beneficial therapeutic effects with the advantage of being non-invasive and painless, providing a promising strategy for accelerating bone repair. In this review, we summarize the parameters, mechanisms, and effects of PBM regulating bone repair, and further conclude the current clinical application of PBM devices in bone repair. The wavelength of 635-980 nm, the output power of 40-100 mW, and the energy density of less than 100 J/cm2 are the most commonly used parameters. New technologies, including needle systems and biocompatible and implantable optical fibers, offer references to realize an efficient and safe strategy for bone repair. Further research is required to establish the reliability of outcomes from in vivo and in vitro studies and to standardize clinical trial protocols.

UNASSIGNED: Depression is a common mental illness that is widely recognized by its lack of pleasure, fatigue, low mood, and, in severe cases, even suicidal tendencies. Photobiomodulation (PBM) is a non-invasive neuromodulation technique that could treat patients with mood disorders such as depression.
UNASSIGNED: A systematic search of ten databases, including randomized controlled trials (RCTs) for depression, was conducted from the time of library construction to September 25, 2023. The primary outcome was depression. The secondary outcome was sleep. Meta-analysis was performed using RevMan (version 5.4) and Stata (version 14.0). Subgroup analyses were performed to identify sources of heterogeneity. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE).
UNASSIGNED: Three thousand two hundred and sixty-five studies were retrieved from the database and screened for inclusion in eleven trials. The forest plot results demonstrated that PBM alleviated depression (SMD = -0.55, 95% CI [-0.75, -0.35], I2 = 46%). But it is not statistically significant for patients\' sleep outcomes (SMD = -0.82, 95% CI [-2.41, 0.77], I2 = 0%, p > 0.05). Subgroup analysis showed that s-PBM was superior to t-PBM in relieving symptoms of depression. The best improvement for t-PBM was achieved using a wavelength of 823 nm, fluence of 10-100 J/cm2, irradiance of 50-100 mW/cm2, irradiance time of 30 min, treatment frequency < 3/week, and number of treatments >15 times. The best improvement for s-PBM was achieved using a wavelength of 808 nm, fluence ≤1 J/cm2, irradiance of 50-100 mW/cm2, irradiance time ≤ 5 min, treatment frequency ≥ 3/week, number of treatments >15 times. All results had evidence quality that was either moderate or very low, and there was no bias in publication.
UNASSIGNED: We conclude that PBM is effective in reducing depression symptoms in patients. However, the current number of studies is small, and further studies are needed to extend the current analysis results.
UNASSIGNED: https://www.crd.york.ac.uk/PROSPERO/, CRD42023444677.

BACKGROUND: This study explores the effectiveness of Photobiomodulation Therapy (PBMT) in enhancing orthodontic tooth movement (OTM), osteogenesis, and angiogenesis through a comprehensive series of in vitro and in vivo investigations. The in vitro experiments involved co-culturing MC3T3-E1 and HUVEC cells to assess PBMT\'s impact on cell proliferation, osteogenesis, angiogenesis, and associated gene expression. Simultaneously, an in vivo experiment utilized an OTM rat model subjected to laser irradiation at specific energy densities.
METHODS: In vitro experiments involved co-culturing MC3T3-E1 and HUVEC cells treated with PBMT, enabling a comprehensive assessment of cell proliferation, osteogenesis, angiogenesis, and gene expression. In vivo, an OTM rat model was subjected to laser irradiation at specified energy densities. Statistical analyses were performed to evaluate the significance of observed differences.
RESULTS: The results revealed a significant increase in blood vessel formation and new bone generation within the PBMT-treated group compared to the control group. In vitro, PBMT demonstrated positive effects on cell proliferation, osteogenesis, angiogenesis, and gene expression in the co-culture model. In vivo, laser irradiation at specific energy densities significantly enhanced OTM, angiogenesis, and osteogenesis.
CONCLUSIONS: This study highlights the substantial potential of PBMT in improving post-orthodontic bone quality. The observed enhancements in angiogenesis and osteogenesis suggest a pivotal role for PBMT in optimizing treatment outcomes in orthodontic practices. The findings position PBMT as a promising therapeutic intervention that could be seamlessly integrated into orthodontic protocols, offering a novel dimension to enhance overall treatment efficacy. Beyond the laboratory, these results suggest practical significance for PBMT in clinical scenarios, emphasizing its potential to contribute to the advancement of orthodontic treatments. Further exploration of PBMT in orthodontic practices is warranted to unlock its full therapeutic potential.

OBJECTIVE: To investigate the effectiveness and safety of combination of 655 nm low level laser helmet device with topical 2 % minoxidil solution at FPHL in Chinese population.
METHODS: Randomized, parallel, controlled, single-blind clinical trial was conducted. FPHL subjects were randomly allocated into 2 % minoxidil group and combination group. The 2 % minoxidil group received 1 ml topical 2 % minoxidil solution twice daily for 24 weeks. The combination group received 1 ml topical 2 % minoxidil solution twice daily together with 20 min 655 nm low-level laser helmet once every other day for 24 weeks. Hair parameters in two scalp areas including midscalp and vertex were evaluated at baseline, 12th week and 24th week.
RESULTS: In midscalp area, the combination group showed a lower increase in intermediate hair percentage than 2 % minoxidil group, which was statistically significant. Besides, the combination group had statistically significant increase than 2 % minoxidil group in mean hair diameter. Reported relative adverse events included slightly hair loss (27.8 %), desquamation (19.0 %), pruritus (15.2 %), seborrhea (2.5 %) and hypertrichosis (2.5 %).
CONCLUSIONS: In our trial, LLLT was demonstrated as a useful supplementary treatment for FPHL and the combination with 2 % minoxidil accomplished better improvement in intermediate hair enlargement and hair diameter of midscalp for FPHL.

Currently, the prevention, assessment, and management of procedural pain in neonates continues to challenge clinicians and researchers. Objective. To investigate the analgesic effect of low-level laser therapy (LLLT) during heel lance compared to breast milk (BM) feeding in healthy term neonates. In this randomized controlled trial, healthy term neonates who underwent heel lance were randomly assigned to an LLLT or a BM group. The LLLT group received laser therapy to the heel lance site for 20 s before heel lance. The BM group received 5 mL expressed BM via a syringe before heel lance. The primary outcomes were behavioral responses. The secondary outcomes were physiological responses and levels of salivary cortisol and α-amylase. A total of 125 neonates were included, of whom 55 in the LLLT group and 59 in the BM group completed the study. There were no significant differences in latency to first cry and cry duration between the two groups. The squeeze time was significantly shorter in the LLLT group than in the BM group (p = 0.047). There were no significant differences in pain scores, heart rate, respiratory rate, oxygen saturation, and blood pressure before and after heel lance between the two groups. There were no significant differences in salivary cortisol and α-amylase levels in the LLLT group before and after heel lance; however, the differences were significant in the BM group. These findings suggest that the analgesic effect of LLLT is similar to that of BM during heel lance in healthy term neonates. LLLT has potential as an analgesic treatment.

OBJECTIVE: To analyse the efficacy of the therapeutic use of low-level laser therapy (LLLT) on the tissue repair process of allogeneic scleral grafts in patients with contracted sockets by analysing the speed of graft vascularisation and fornice depth of contraction percentage.
METHODS: A retrospective chart review was performed from April 2015 to April 2021 including 39patients with socket contraction. Allogeneic scleral grafts were used to repair the sockets in all patients. They were randomly enrolled into two groups. The laser group included 18 patients treated with LLLT after the surgery, whereas the control group included 21 patients without LLLT after the surgery who healed naturally. The LLLT equipment used in the research had a wavelength of 650 nm, 10 mW power, and 3.8 J/cm2 dosimetry, and the procedure was performed once daily for 5 min over 7 days, beginning 1 week postoperatively. All patients were followed up over 6 months to examine the changes in the size of the area of the non-vascularised graft and upper and inferior fornice depth.
RESULTS: The laser group presented a significantly increased speed of conjunctival vascularisation compared with the control group (P = 0.003). The fornice depth of contraction percentage was more apparent in the control group than that in the laser group (P = 0.000).
CONCLUSIONS: LLLT accelerates conjunctival vascularisation, stimulates conjunctival incision healing within a short period, shortens the tissue repair process, reduces the local inflammatory response, and causes no significant shrinkage of the conjunctival sac.

Objective: To investigate the effects of photobiomodulation therapy (PBMT) on hard tissue healing in rat maxillary first molar extraction sockets. Methods: A total of 20 male Wistar rats were used in the study. The right extraction sockets were irradiated with a Ga-Al-As laser (500 mW, 980 nm) for 51.7 J/cm2 every 24 h for 7 days, while the left sockets served as controls. Rats were sacrificed on days 3, 7, 14, and 28 after tooth extraction, and microcomputed tomography (CT) analysis, histopathological evaluation, and enzyme-linked immunosorbent assay (ELISA) were conducted at different time points. Results: Micro-CT analysis showed that the percentage of bone volume/tissue volume (TV) and bone mineral density were significantly higher in the experimental group compared to the control group on day 28 (p < 0.05). Histopathological evaluation revealed that PBMT promoted new bone formation and accelerated bone remodeling. ELISA demonstrated a significant increase in alkaline phosphatase expression in the laser sides on days 7 and 14 (p < 0.05). Conclusions: One application postextraction followed by seven consecutive daily applications of PBMT can effectively promote hard tissue healing in rat maxillary first molar extraction sockets.

Low-level Laser Therapy (LLLT) was widely used in clinical practice for tendon disorders. However, the underlying mechanisms and effectiveness of LLLT in treating tendon injury remain unclear. Therefore, the present study was conducted aiming to summarize the evidence regarding the histological, physiological, and biomechanical effects of LLLT on tendon healing in animal and human models. Four databases were searched for relevant literature. Four independent reviewers screened abstracts and full-text articles, extracted relevant data, evaluated the risk of bias, and quantified the quality of evidence. Database searches yielded 1400 non-duplicated citations. Fifty-five studies were included (50 animal and five human studies). Animal studies revealed that LT had stimulating effects on collagen organization, collagen I and collagen II formation, matrix metalloproteinase (MMP)-8, transforming growth factor β1, vascular endothelial growth factor, hydroxyproline, maximum load, maximum elongation before breaking, and tendon stiffness. However, LLLT had inhibitory effects on the number of inflammatory cells, histological scores, relative amount of collagen III, cyclooxygenase-2, prostaglandin E2 (PGE2), interleukin-6, tumor necrosis factor-α, MMP-1, and MMP-3. Although one human study found that LLLT reduced the concentration of PGE2 in peritendinous tissue of the Achilles tendon, other human studies revealed that the effects of LLLT on the physiology and biomechanics of human tendons remained uncertain. LLLT facilitates tendon healing through various histological, physiological, and biomechanical effects in animal models. Only post-LLLT anti-inflammatory effects were found in human studies.

Burning mouth syndrome (BMS) is a complex chronic pain disorder that significantly impairs patients\' quality of life. Low-level laser therapy (LLLT) uses infrared or near-infrared light to produce analgesic, anti-inflammatory, and biological stimulation effects. The aim of this systematic review is to evaluate the effect of LLLT on burning pain, quality of life, and negative emotions in patients with BMS.
The PubMed, Embase, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Cochrane Library, Web of Science, and Scopus databases were searched up January 2023 to identify relevant articles. All randomized controlled trials that were published in English and examined the use of LLLT treatment for BMS were included. The methodological quality of the included trials was assessed using the Cochrane risk of bias tool for randomized controlled trials (RCTs). A meta-analysis was performed to evaluate burning pain, quality of life, and negative emotions. Sensitivity, subgroup, and funnel plot analyses were also carried out.
Fourteen RCTs involving a total of 550 patients with BMS met the inclusion criteria. The results showed that LLLT (measured by the Visual Analog Scale; SMD: -0.87, 95% CI: -1.29 to -0.45, P < 0.001) was more effective for reducing burning pain than placebo LLLT or clonazepam. LLLT improved quality of life (evaluated by the Oral Health Impact Profile-14; SMD: 0.01, 95% CI: -0.58 to 0.60, P = 0.97) and negative emotions (evaluated by the Hospital Anxiety and Depression Scale; SMD: -0.12, 95% CI: -0.54 to 0.30, P = 0.59), but these effects were not statistically significant.
The meta-analysis revealed that LLLT may be an effective therapy for improving burning pain in patients with BMS, and producing a positive influence on quality of life and negative emotions. A long-term course of intervention, a larger sample size, and a multidisciplinary intervention design are urgently needed in future research.
PROSPERO registration number: CRD42022308770.