PMID: 

Mediators Inflamm. 2020 ;2020:9025705. Epub 2020 Feb 20. PMID: 32148443

Abstract Title: 

Effects of Shikonin on the Functions of Myeloid Dendritic Cells in a Mouse Model of Severe Aplastic Anemia.

Abstract: 

This study is aimed at investigating the effects of shikonin, a pyruvate kinase M2 (PKM2) inhibitor, on the functions of myeloid dendritic cells (mDCs) in a mouse model of severe aplastic anemia (AA) generated by total body irradiation and lymphocyte infusion. Flow cytometry and qPCR were used to determine the proportions of PKM2+ mDCs and other immune indicators in the AA mice. Glucose consumption level, pyruvate generation level, and ATP content were used to determine the level of glycolytic metabolism in the mDCs. The survival rates of AA mice were evaluated after the administration of shikonin or the immunosuppressive agent cyclosporin A. The AA mice displayed pancytopenia, decreased CD4+/CD8+ cell ratio, increased perforin and granzyme levels in CD8+ cells, increased costimulatory CD80 and CD86 expressions, and inadequate regulatory T cell number.animal experiments showed that the shikonin-mediated inhibition of the PKM2 expression in mice was associated with high survival rates. In addition, the administration of cyclosporin A or shikonin decreased the expression of cytotoxic molecules and costimulatory CD80 and CD86 on CD8+ cells. Taken together, the results of this study indicated that shikonin could inhibit the activation and proliferation of mDCs as well as the activation of downstream cytotoxic T cells by reducing the PKM2 level in mDCs.

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PMID: 

Chin Med. 2020 ;15:23. Epub 2020 Mar 10. PMID: 32175001

Abstract Title: 

Shikonin and 4-hydroxytamoxifen synergistically inhibit the proliferation of breast cancer cells through activating apoptosis signaling pathway in vitro and in vivo.

Abstract: 

Background: Tamoxifen (TAM) is a cell type-specific anti-estrogen and is applied to improve the survival of patients with estrogen receptor positive (ER +) breast cancer. However, long-term TAM use can induce serious drug resistance, leading to breast cancer recurrence and death in patients. Further, it is almost useless among patients with estrogen receptor negative (ER -) breast cancer. Shikonin (SK) is a natural product broadly explored in cancer therapy. Some studies have demonstrated the combined treatment of SK and clinical anticancer drugs including TAM on various tumors. However, the combined effect of SK and 4-hydroxytamoxifen (4-OHT) on ER- breast cancer is not known. The current study aimed to assess the combination effects ofSK and 4-OHT on human breast cancer cells, MCF-7 (ER +) and MDA-MB-435S (ER -), in vitro and in vivo and to investigate the underlying mechanisms.Methods: CCK-8 assays and flow cytometry were conducted to determine the cell viability and apoptotic profiles of human breast cancer cell lines (MCF-7 and MDA-MB-435S) treated with SK, 4-OHT, and the combination. ROS and JC-1 assays were used to determine ROS level and mitochondrial membrane potential. Western blot analysis was performed to investigate proteins that are associated with apoptosis. Haematoxylin&Eosin (HE) staining was used to detect the tumor and kidney morphology of mice. TUNEL and immunohistochemical staining were performed to detect Ki67 expression level and cell apoptotic profile in tumor tissues.Results: SK and 4-OHT synergistically inhibited MCF-7 and MDA-MB-435S cell proliferation and promoted apoptosis by reducing mitochondrial membrane potential and increasing the intracellular ROS level. The combination of SK and 4-OHT activated the mitochondrial-dependent apoptosis and the death receptor pathways, significantly regulating the PI3K/AKT/Caspase 9 signaling pathway. Compared with SK and 4-OHT alone, the combination of SK and 4-OHT could better inhibit tumor growth in mice.Conclusion: The combination of SK and 4-OHT shows highly efficient anticancer effects on breast cancer therapy. SK may be a promising candidate as an adjuvant to 4-OHT for breast cancer treatments, especially for ER- breast cancer.

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PMID: 

Neuropsychiatr Dis Treat. 2019 ;15:3255-3272. Epub 2019 Nov 22. PMID: 31819453

Abstract Title: 

Transcranial Photobiomodulation For The Management Of Depression: Current Perspectives.

Abstract: 

Major depressive disorder (MDD) is a prevalent condition associated with high rates of disability, as well as suicidal ideation and behavior. Current treatments for MDD have significant limitations in efficacy and side effect burden. FDA-approved devices for MDD are burdensome (due to repeated in-office procedures) and are most suitable for severely ill subjects. There is a critical need for device-based treatments in MDD that are efficacious, well-tolerated, and easy to use. In this paper, we review a novel neuromodulation strategy, transcranial photobiomodulation (t-PBM) with near-infrared light (NIR). The scope of our review includes the known biological mechanisms of t-PBM, as well as its efficacy in animal models of depression and in patients with MDD. Theoretically, t-PBM penetrates into the cerebral cortex, stimulating the mitochondrial respiratory chain, and also significantly increases cerebral blood flow. Animal and human studies, using a variety of t-PBM settings and experimental models, suggest that t-PBM may have significant efficacy and good tolerability in MDD. In aggregate, these data support the need for large confirmatory studies for t-PBM as a novel, likely safe, and easy-to-administer antidepressant treatment.

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PMID: 

Lasers Med Sci. 2020 Jan 4. Epub 2020 Jan 4. PMID: 31900692

Abstract Title: 

Blue light therapy to treat candida vaginitis with comparisons of three wavelengths: an in vitro study.

Abstract: 

Anti-fungal blue light (ABL) therapies have been widely studied to treat various microbial infections in the literature. The blue light with wavelengths ranging from 400 to 470 nm has been reported to be effective to inhibit various kinds of bacteria and fungi. The existing studies usually report the viability rates of the pathogens under the irradiation of the blue light with different dosage parameters. However, to the best of our knowledge, there is still no work especially focusing on studying the effect of ABL therapies on treating candida vaginitis, where it is important to study the viability of both the Candida albicans (C. albicans) and the human vaginal epithelial cells. It is the purpose of this work to conduct ABL experiments on both of these two cells, analyze the effects, and determine the best ABL wavelength out of three candidates, i.e., 405-nm, 415-nm, and 450-nm wavelength. The viability rates of the C. albicans and the human vaginal epithelial cells irradiated by the three blue LED light sources were measured, whose irradiance (power density) were all set to 50 mW/cm. The dynamic viability models of the C. albicans and the epithelial cells were built based on the experimental data. Moreover, in this work, we also built a functional relationship between the viability of these two types of cells, by which we further compared the effects of the blue light irradiation on both the C. albicans and vaginal epithelial cells. The experimental data showed that when an approximately 80% inhibiting rate of the C. albicans was achieved, the survival rates of the epithelial cells were 0.6700, 0.7748, and 0.6027, respectively for the treatment by the 405-nm, 415-nm, and 450-nm wavelength light. On the other hand, by simulating the functional relationship between the viability of the two types of cells, the survival rates of the epithelial cells became 0.5783, 0.6898, and 0.1918 respectively using the 405-nm, 415-nm and 450-nm wavelength light, when the C. albicans was completely inhibited. Therefore, both the experimental data and the model simulation results have demonstrated that the 415-nm light has a more effective anti-fungal result with less damage to the epithelial cells than the 405-nm and 450-nm light.

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PMID: 

Lasers Med Sci. 2019 Dec 17. Epub 2019 Dec 17. PMID: 31845042

Abstract Title: 

Laser photobiomodulation for cartilage defect in animal models of knee osteoarthritis: a systematic review and meta-analysis.

Abstract: 

To review and assess the efficacy of laser photobiomodulation for cartilage defect in animal models of knee osteoarthritis (KOA). Medline, Web of Science, and EMBASE were searched. Studies were considered if the global quality score of cartilage were parallelly reported between laser and untreated control groups. The methodological quality of each study was assessed using a modified 10-item checklist. The effect size was estimated by standardized mean difference (SMD) and pooled based on the random-effects model. Stratified analysis and regression analysis were conducted to partition potential heterogeneity. An adjusted significant level of 0.01 was acceptable. Five hundred eight initial search recordings were identified, of which 14 studies (including 274 animals) were included for quantitative analysis. The global quality scores mostly weighted by the structural integrity and chondrocyte distribution were measured by different four scales including Histologic Histochemical Grading System (HHGS), Osteoarthritis Research Society International (OARSI), Pineda, and Huang. There were considerable variances on laser parameters and irradiation time among those included studies. Overall, a moderate level of methodological qualities was determined. The synthesis results indicated that the SMD effect size was significantly larger in HHGS (z = 2.61, P = 0.01) and Huang (z = 4.90, P 

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PMID: 

Biomed Pharmacother. 2020 Mar ;123:109776. Epub 2020 Jan 3. PMID: 31911295

Abstract Title: 

Combined effects of metformin and photobiomodulation improve the proliferation phase of wound healing in type 2 diabetic rats.

Abstract: 

We determined the impact of Photobiomodulation (PBM) and metformin administration alone and combined on the inflammation and proliferation steps of wound healing of incisions in type two diabetes mellitus (T2DM) rats. 40 rats were divided into 4 groups (n = 10 each group). A non-genetic model of T2DM was induced in all rats, and an incision was made on each rat. There were 4 groups as follows: Group 1 was control group. Group 2 received PBM alone (890 nm, 80 Hz, 0.324 J/cm, daily). Group 3 received metformin alone (50 mg/kg, i.p., daily) and the fourth group received combination of PBM + metformin. At inflammation (day 4) and proliferation (day 7) steps, tensiometerical, stereological, and immunohistochemical examinations were performed. PBM and PBM + metformin treatments significantly increased woundstrength at inflammation and proliferation steps of wound healing respectively. PBM, metformin, and PBM + metformin groups significantly decreased inflammatory cells at inflammation and proliferation steps of wound healing. PBM, metformin, and PBM + metformin groups significantly improved granulation tissue formation by increasing fibroblasts, and new blood vessel formation at inflammation and proliferation steps of wound healing. Metformin significantly increased M2 macrophages than other treatment groups at inflammation and proliferation steps of wound healing. Simultaneously, PBM significantly decreased M2 macrophages than control group. We concluded PBM and PBM + metformin treatments significantly hastened repair at the inflammation and proliferation steps of repairing skin injury in a non-genetic model of T2 DM. PBM + metformin showed a synergistic impact. There werenot a positive relation between M2 macrophage number and wound strength in the studied groups. The details of the molecular mechanisms of PBM, and PBM + metformin treatments of repairing wounds in animals, and treatment of DFUs of patients with T2 DM should be elucidated by further research.

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PMID: 

J Orthop Res. 2020 Jan 22. Epub 2020 Jan 22. PMID: 31965620

Abstract Title: 

Photobiomodulation does not influence maturation and mildly improves functional healing of mouse achilles tendons.

Abstract: 

Tendon rupture can occur at any age and is commonly treated nonoperatively, yet can result in persisting symptoms. Thus, a need exists to improve nonoperative treatments of injured tendons. Photobiomodulation (PBM) therapy has shown promise in the clinic and is hypothesized to stimulate mitochondrial-related metabolism and improve healing. However, the effect of PBM therapy on mitochondrial function during tendon maturation and healing are unknown, and its effect on tendon structure and function remain unclear. In this study, near-infrared light (980:810 nm blend, 2.5 J/cm) was applied at low (30 mW/cm) or high (300 mW/cm) irradiance to unilateral Achilles tendons of CD-1 mice during postnatal growth (maturation) as well as adult mice with bilateral Achilles tenotomy (healing). The chronic effect of PBM therapy on tendon structure and function was determined using histology and mechanics, and the acute effect of PBM therapy on mitochondrial-related gene expression was assessed. During maturation and healing, collagen alignment, cell number, and nuclear shape were unaffected by chronic PBM therapy. We found a sex-dependent effect of PBM therapy during healing on mechanical outcomes (eg, increased stiffness and Young's modulus for PBM-treated females, and increased strain at ultimate stress for PBM-treated males). Mitochondria-related gene expression was marginally influenced by PBM therapy for both maturation and healing studies. This study was the first to implement PBM therapy during both growth and healing of the murine tendon. PBM therapy resulted in marginal and sex-dependent effects on the murine tendon. Clinical significance: PBM may be beneficial for tendon healing because functional remodeling improves without adverse effects.

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PMID: 

J Maxillofac Oral Surg. 2020 Mar ;19(1):93-97. Epub 2019 Apr 2. PMID: 31988570

Abstract Title: 

Photobiomodulation Therapy for Myofascial Pain in Temporomandibular Joint Dysfunction: A Double-Blinded Randomized Clinical Trial.

Abstract: 

Aims: Temporomandibular disorder (TMD) is a complex process that affects the temporomandibular joint (TMJ). The multifactorial process is of unknown etiology and has many manifestations and thus many management options. Photobiomodulation therapy has been suggested for management of TMD, despite the lack of understanding of its exact mechanism. The aim of this study is to examine the effectiveness of photobiomodulation in the treatment of myofascial type TMD.Methods: Patients with unilateral TMJ and masticatory muscles pain during function were recruited and divided into two groups: a control group that received a sham laser treatment every 48 h for 10 days and a test group that received the same frequency of treatment to deliver a dose of 257 J per treatment and a total dose of 1285 J for the entire treatment. Pain was assessed using the visual analog scale (VAS).Results: There was a significant difference in VAS scores between the test and control groups with the test group scoring lower.Conclusion: Photobiomodulation therapy proved to be an effective short-term therapeutic modality for myofascial TMD pain. It is non-invasive, easy to apply with no systemic side effects. Its long-term effect and its effect on different subtypes of TMD need further investigation.

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PMID: 

J Photochem Photobiol B. 2020 Mar ;204:111791. Epub 2020 Jan 17. PMID: 31981991

Abstract Title: 

Photobiomodulation and the expression of genes related to the JAK/STAT signalling pathway in wounded and diabetic wounded cells.

Abstract: 

Photobiomodulation therapy (PBMT) is a curative technique that uses low intensity light to relegate pain and inflammation, and accelerate tissue repair. At a molecular level, the effects of photobiomodulation (PBM) are not fully established. The present study aimed to assess the impact of PBM on the alteration of genes linked to Janus kinase-Signal transducer and activator of transcription (JAK-STAT) signalling in wounded and diabetic wounded cells in vitro. Cells were irradiated using a diode laser at a wavelength of 660 nm and an energy density of 5 J/cm. RNA was extracted from cells 48 h post-irradiation, and was used to synthesise complementary deoxyribonucleic acid (cDNA) that was used in PCR arrays to profile for 84 JAK/STAT signalling related genes. Irradiation at a wavelength of 660 nm and an energy density of 5 J/cmsignificantly regulated genes related to the JAK/STAT signalling pathway in wounded and diabetic wounded cells. In irradiated wounded cells, 19 genes were significantly regulated, of which two were up-regulated and 17 were down-regulated, while 73 genes were significantly regulated in irradiated diabetic wounded cells of which 46 were up-regulated and 27 were down-regulated. This data suggests that PBM modulates gene transcription for protein synthesis and activates cellular signalling, and may indeed be helpful in enhancing diabetic wound repair.

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PMID: 

Free Radic Biol Med. 2020 Jan 31. Epub 2020 Jan 31. PMID: 32014500

Abstract Title: 

Photobiomodulation (450 nm) alters the infection of periodontitis bacteria via the ROS/MAPK/mTOR signaling pathway.

Abstract: 

We aimed to investigate the effects of photobiomodulation (PBM) on periodontitis. A periodontitis model was established via Porphyromonas gingivalis infection in beagles. Mandibular second and third premolars were removed, and implants were positioned immediately after tooth extraction. Left gingiva was irradiated with PBM (450 nm) as the LG group, and right side without irradiation was regarded as the CG (control) group. PBM treatment increased oxidative stress by increasing the levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The elevated levels of HO(a biomarker of oxidative stress) and the free radicals (NOand O) reduced the concentration of dominant pathogens and regulated ROS/RNS/AMP-activated protein kinase (AMPK)/mTOR pathway by affecting p-AMPK, Runt-related transcription factor 2 (RUNX2), p-c-Jun N-terminal kinase (JNK)/mammalian target of rapamycin (mTOR), and acetyl-CoA carboxylase 1 (ACC1). PBM therapy increased salivary levels of interleukin-1 receptor antagonist (IL-1ra), interleukin (IL)-10, total antioxidant capacity (TAC) and catalase (CAT), and reduced the levels of tumor necrosis factor (TNF)α and interleukin (IL)-1β, malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) (p 

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