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        Vascular regeneration effect of adipose-derived stem cells with light-emitting diode phototherapy in ischemic tissue.

        Park, In-Su,Mondal, Arindam,Chung, Phil-Sang,Ahn, Jin Chul Baillière Tindall ; Springer London 2015 LASERS IN MEDICAL SCIENCE Vol.30 No.2

        <P>The objective of this study was to investigate the effects on the vascular regeneration of adipose-derived stem cells (ASCs) by using red light-emitting diode (LED) irradiation in ischemic hind limbs. Low-level light therapy (LLLT) has been shown to enhance proliferation and cytokine secretion of a number of cells. ASCs are an attractive cell source for vascular tissue engineering. This approach is hindered because transplanted ASCs decline rapidly in the recipient tissue. Ischemic hind limbs were treated with LLLT from an LED array (660?nm) at an irradiance of 50?mW/cm(2) and a radiant exposure of 30?J/cm(2). LLLT, ASC transplantation, and ASC transplantation with LLLT (ASC + LLLT) were applied to ischemic limbs, and cell survival and differentiation, and secretion of vascular endothelial growth factor and basic fibroblast growth factor of the ASCs were evaluated by immunostaining and Western blot analyses. Vascular regeneration was assessed by immunostaining and hematoxylin and eosin staining. In the ASC + LLLT group, the survival of ASCs was increased due to the decreased apoptosis of ASCs. The secretion of growth factors was stimulated in this group compared with ASCs alone. The ASC + LLLT group displayed improved treatment efficacy including neovascularization and tissue regeneration compared with ASCs alone. In particular, quantitative analysis of laser Doppler blood perfusion image ratio showed that blood perfusion was enhanced significantly (p?<?0.05) by ASC + LLLT treatment. These data suggest that LLLT is an effective biostimulator of ASCs in vascular regeneration, which enhances the survival of ASCs and stimulates the secretion of growth factors in ischemic limbs.</P>

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        Apoptotic effect of pheophorbide a-mediated photodynamic therapy on DMBA/TPA-induced mouse papillomas.

        Zhang, Xianglan,Choi, Eun Joo,Zheng, Zhenlong,Zhu, Lianhua,Cho, Sung Bin,Kim, Ki-Yoel,Kim, Jin,Cha, In-Ho Baillière Tindall ; Springer London 2015 LASERS IN MEDICAL SCIENCE Vol.30 No.1

        <P>Pheophorbide a (Pa) is a chlorine-based photosensitizer, and Pa-mediated photodynamic therapy (PDT) reportedly exhibits antitumor activity against various malignancies. The aim of our study was to investigate the therapeutic effect of Pa-mediated PDT on 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorobol-13-acetate (TPA)-induced mouse papillomas. Thirty mice received a topical application of DMBA/TPA on their backs to induce mouse papillomas. One week after two sessions of Pa-mediated PDT, immunohistochemical stains and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were performed to evaluate the apoptotic effects thereof on the papillomas. Among 63 mouse papillomas treated with Pa-mediated PDT, 17.5% of the lesions were completely removed 1 week after the first treatment, while 31.7% disappeared 1 week after the second treatment. Statistical analyses revealed significant differences in therapeutic outcomes for the Pa-mediated PDT group in comparison to a solvent-PDT group and a Pa group. Additionally, a marked downregulation of proliferating cell nuclear antigen expression, as well as upregulation of cleaved caspase 3 and cleaved poly(ADP-ribose) polymerase expression, was noted in the Pa-PDT group, compared to the solvent-PDT group and Pa group. TUNEL assay revealed higher apoptotic cell counts in the Pa-PDT group, although the difference was not statistically significant. Our data demonstrated that Pa-mediated PDT is effective in treating DMBA/TPA-induced mouse papillomas.</P>

      • The effects of minimally invasive laser needle system on suppression of trabecular bone loss induced by skeletal unloading.

        Ko, Chang-Yong,Kang, Heesung,Ryu, Yeonhang,Jung, Byungjo,Kim, Hyunsoo,Jeong, Daewon,Shin, Hong-In,Lim, Dohyung,Kim, Han Sung Baillière Tindall ; Springer London 2013 Lasers in medical science Vol.28 No.6

        <P>This study was aimed to evaluate the effects of low-level laser therapy (LLLT) in the treatment of trabecular bone loss induced by skeletal unloading. Twelve mice have taken denervation operation. At 2 weeks after denervation, LLLT (wavelength, 660 nm; energy, 3 J) was applied to the right tibiae of 6 mice (LASER) for 5 days/week over 2 weeks by using a minimally invasive laser needle system (MILNS) which consists of a 100 μm optical fiber in a fine needle (diameter, 130 μm) [corrected]. Structural parameters and histograms of bone mineralization density distribution (BMDD) were obtained before LLLT and at 2 weeks after LLLT. In addition, osteocyte, osteoblast, and osteoclast populations were counted. Two weeks after LLLT, bone volume fraction, trabeculae number, and trabeculae thickness were significantly increased and trabecular separations, trabecular bone pattern factor, and structure model index were significantly decreased in LASER than SHAM (p?<?0.05). BMDD in LASER was maintained while that in SHAM was shifted to lower mineralization. Osteocyte and osteoblast populations were significantly increased but osteoclast population was significantly decreased in LASER when compared with those in SHAM (p?<?0.05). The results indicate that LLLT with the MILNS may enhance bone quality and bone homeostasis associated with enhancement of bone formation and suppression of bone resorption.</P>

      • Effect of 635 nm irradiation on high glucose-boosted inflammatory responses in LPS-induced MC3T3-E1 cells.

        Kwon, HyukIl,Lim, WonBong,Kim, JiSun,Jeon, SangMi,Kim, SangWoo,Karna, Sandeep,Cha, HyunRok,Kim, OkJoon,Choi, HongRan Baillière Tindall ; Springer London 2013 Lasers in medical science Vol.28 No.3

        <P>Hyperglycemia occurs in patients with poorly controlled diabetes mellitus and contributes to bone resorption and increased susceptibility to bacterial infections. Hyperglycemia can incite low-grade inflammation that can contribute to the resorption of bone, especially the periodontal bone. The increased susceptibility to periodontal infections can contribute to bone resorption through the activation of osteoclasts. In this study, the osteoblastic, clonal cell line, MC3T3-E1, was used in an in vitro model of hyperglycemia and lipopolysaccharide-induced reactive oxygen species generation to determine the potential anti-inflammatory effect of 635 nm light-emitting diode (LED) irradiation or whether 635 nm LED irradiation can be a potential anti-inflammatory treatment. LED irradiation of MC3T3-E1 cells stimulated with lipopolysaccharide in a high glucose-containing medium decreased the level of cyclooxygenase gene and protein expression and reduced the level of prostaglandin E2 expression by decreasing the amount of reactive oxygen species generation. LED irradiation also inhibited the osteoclastogenesis in MC3T3-E1 cells by regulating the receptor activator of nuclear factor kappa-B ligand and osteoprotegerin. These findings reveal the mechanisms which are important in the pathogenesis of diabetic periodontitis and highlight the beneficial effects of 635 nm LED irradiation in reducing the adverse effects of diabetic periodontitis.</P>

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        Therapeutic effects of systemic photodynamic therapy in a leukemia animal model using A20 cells.

        Wen, Lan Ying,Bae, Su-Mi,Chun, Heung-Jae,Park, Kye-Shin,Ahn, Woong Shick Baillière Tindall ; Springer London 2012 LASERS IN MEDICAL SCIENCE Vol.27 No.2

        <P>Photodynamic therapy (PDT) is attracting attention because of its noticeable inhibitory effects on the growth of dermatological and other solid tumors. Here, we studied the use of PDT in systemic diseases such as leukemia, lymphoma, and metastatic cancer, for which tumor formation areas cannot be clearly compartmentalized. We developed a systemic PDT method and examined its effect in a leukemia mouse model. Growth inhibition of A20 cells (H-2(d), murine B-lymphoma/leukemia, and Balb/c origin) induced by PDT/Photodithazine was evaluated by EZ-Cytox assay. After PDT, changes in cell morphology were assessed by light microscopy. Induction of apoptosis, as well as changes in the cell cycle, were assessed by fluorescence-activated cell sorting (FACS) analysis. A20 cells were injected into Balb/c mice through the tail veins, and PDT was performed. A total of 10 mg kg(-1) body weight of Photodithazine concentration was injected intravenously. After 5 min, micro photofibers (diameter, 200 μm) were inserted into the tail veins and irradiated at 1,200 J with a laser. PDT inhibited growth of A20 cells and resulted in marked morphological changes. PDT also induced apoptosis and G1 arrest. In a leukemia mouse model, systemic PDT increased the survival rate (p < 0.01). This is the first report of the effects of systemic PDT in a leukemia animal model. PDT has been applied only locally in most cases, for example to solid tumors. This study provides experimental evidence that systemic PDT could effectively be applied to systemic and spread tumors, for which tumor formation areas cannot clearly be determined.</P>

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        RUNX3 confers sensitivity to pheophorbide a-photodynamic therapy in human oral squamous cell carcinoma cell lines.

        Moon, Sook,Bae, Jung Yoon,Son, Hwa-Kyung,Lee, Doo Young,Park, Gyeongju,You, Hyun,Ko, Hyojin,Kim, Yong-Chul,Kim, Jin Baillière Tindall ; Springer London 2015 LASERS IN MEDICAL SCIENCE Vol.30 No.2

        <P>Photodynamic therapy (PDT) with photosensitizer is one of the promising modalities for cancer treatment. For clinical use of PDT, screening process should be preceded to enhance sensitivity to PDT. Thus, we investigated a molecular biomarker to determine the sensitivity to pheophorbide a (Pa)-PDT in immortalized human oral keratinocytes (IHOK) and oral squamous cell carcinoma (OSCC) cell lines. Two IHOK and several OSCC cell lines were used. After Pa-PDT, cell viability was reduced by more than 50%, and reactive oxygen species were generated in IHOK and OSCC cell lines. Additionally, apoptosis occurred in PDT-treated cells. IHOK(S) and IHOK(P), the two IHOK cell lines derived from the same source, showed a difference in cytotoxicity after Pa-PDT. To explain this difference in cytotoxicity, we looked at the expression of Wnt signaling-related genes in these two cell lines, for the morphology of IHOK(S) which was spindle like and elongated and distinct from IHOK(P) and the parent cell. Among the relevant genes, runt-related transcription factor 3 (RUNX3), an apoptosis-related gene, was selected as a potential marker that confers sensitivity to PDT. We found that the cytotoxicity by Pa-PDT was proportional to RUNX3 expression in OSCC cell lines. Additionally, knockdown of RUNX3 expression reduced cytotoxicity by Pa-PDT, suggesting that RUNX3 might be a biomarker to determine sensitivity to Pa-PDT. This was the first study to find a new target molecule that enhances Pa-PDT effects in IHOK and OSCC cell lines. Hence, the development of a PDT-dependent biomarker could provide a novel approach to improve the effects of PDT on oral precancerous and cancerous lesions.</P>

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        Efficacy of a vaporization-resection of the prostate median lobe enlargement and vaporization of the prostate lateral lobe for benign prostatic hyperplasia using a 120-W GreenLight high-performance system laser: the effect on storage symptoms.

        Kim, Kang Sup,Choi, Sae Woong,Bae, Woong Jin,Kim, Su Jin,Cho, Hyuk Jin,Hong, Sung-Hoo,Lee, Ji Youl,Hwang, Tae-Kon,Kim, Sae Woong Baillière Tindall ; Springer London 2015 LASERS IN MEDICAL SCIENCE Vol.30 No.4

        <P>GreenLight laser photoselective vaporization of the prostate (PVP) was established as a minimally invasive procedure to treat patients with benign prostatic hyperplasia (BPH). However, it may be difficult to achieve adequate tissue removal from a large prostate, particularly those with an enlarged median lobe. The purpose of this study was to investigate the feasibility and clinical effect of a 120-W GreenLight high-performance system laser vaporization-resection for an enlarged prostate median lobe compared with those of only vaporization. A total of 126 patients from January 2010 to January 2014 had an enlarged prostate median lobe and were included in this study. Ninety-six patients underwent vaporization only (VP group), and 30 patients underwent vaporization-resection for an enlarged median lobe (VR group). The clinical outcomes were International Prostate Symptoms Score (IPSS), quality of life (QOL), maximum flow rate (Q max), and post-void residual urine volume (PVR) assessed at 1, 3, 6, and 12 months postoperatively between the two groups. The parameters were not significantly different preoperatively between the two groups, except for PVR. Operative time and laser time were shorter in the VR group than those in the VP group. (74.1 vs. 61.9 min and 46.7 vs. 37.8 min; P?=?0.020 and 0.013, respectively) and used less energy (218.2 vs. 171.8 kJ, P?=?0.025). Improved IPSS values, increased Q max, and a reduced PVR were seen in the two groups. In particular, improved storage IPSS values were higher at 1 and 3 months in the VR group than those in the VP group (P?=?0.030 and 0.022, respectively). No significant complications were detected in either group. Median lobe tissue vaporization-resection was complete, and good voiding results were achieved. Although changes in urinary symptoms were similar between patients who received the two techniques, shorter operating time and lower energy were superior with the vaporization-resection technique. In addition, vaporization-resection may have a beneficial effect on storage symptoms.</P>

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        Inflammatory cytokines are suppressed by light-emitting diode irradiation of P. gingivalis LPS-treated human gingival fibroblasts: inflammatory cytokine changes by LED irradiation.

        Choi, HongRan,Lim, WonBong,Kim, InAe,Kim, JiSun,Ko, YoungJong,Kwon, Hyukil,Kim, SangWoo,Kabir, K M Ahsan,Li, Xiaojie,Kim, Oksu,Lee, YoungJoon,Kim, SeoYune,Kim, OkJoon Baillière Tindall ; Springer London 2012 LASERS IN MEDICAL SCIENCE Vol.27 No.2

        <P>Human gingival fibroblasts (hGFs) play an important role in the inflammatory reaction to lipopolysaccharide (LPS) from P. gingivalis, which infects periodontal connective tissue. In addition, although light-emitting diode (LED) irradiation has been reported to have biostimulatory effects, including anti-inflammatory activity, the pathological mechanisms of these effects are unclear. This study examined the effects of 635-nm irradiation of P. gingivalis LPS-treated human gingival fibroblasts on inflammatory cytokine profiles and the mitogen-activated protein kinase (MAPK) pathway, which is involved in cytokine production. Gingival fibroblasts treated or not treated with P. gingivalis LPS were irradiated with 635-nm LED light, and cytokine profiles in the supernatant were assessed using a human inflammation antibody array. Expression of cyclooxyginase-2 (COX-2) protein and phosphorylation of extracellular signal-regulated kinase (ERK 1/2), p38, and c-Jun-N-terminal kinase (JNK) were assessed by Western-blot analysis to determine the effects on the MAPK pathway, and prostaglandin E(2) (PGE(2)) in the supernatant was measured using an enzyme-linked immunoassay. COX-2 protein expression and PGE(2) production were significantly increased in the LPS-treated group and decreased by LED irradiation. LPS treatment of gingival fibroblasts led to the increased release of the pro-inflammatory-related cytokines interleukin-6 (IL-6) and IL-8, whereas LED irradiation inhibited their release. Analysis of MAPK signal transduction revealed a considerable decrease in p38 phosphorylation in response to 635-nm radiation either in the presence or absence of LPS. In addition, 635-nm LED irradiation significantly promoted JNK phosphorylation in the presence of LPS. LED irradiation can inhibit activation of pro-inflammatory cytokines, mediate the MAPK signaling pathway, and may be clinically useful as an anti-inflammatory tool.</P>

      • Effects of low-intensity laser therapy on periodontal tissue remodeling during relapse and retention of orthodontically moved teeth.

        Kim, Su-Jung,Kang, Yoon-Goo,Park, Jong-Hyun,Kim, Eun-Cheol,Park, Young-Guk Baillière Tindall ; Springer London 2013 Lasers in medical science Vol.28 No.1

        <P>This study was designed to investigate the effects of low-intensity laser therapy (LILT) on periodontal ligament (PDL) remodeling during relapse and retention after the completion of orthodontic movement. The maxillary central incisors (n = 104) of the 52 rats were randomly divided into five groups according to the treatment modality: baseline control group without any intervention (n = 8); relapse group without retainer after tooth movement (n = 24); retention group with fixed retainer after tooth movement (n = 24); lased relapse group without retainer after tooth movement and LILT (n = 24); lased retention group with retainer after tooth movement and LILT (n = 24). LILT was daily performed using a gallium-aluminum-arsenide diode laser in a biostimulation mode: wavelength of 780 nm, continuous waves at 70 mW output power, a preset low intensity of 1.75 W/cm(2) in contact mode, resulting in energy dose of 5 J/cm(2) per irradiation for 3 s. The animals were euthanized on days 1, 3, and 7 after removal of the orthodontic appliance. Real-time RT-PCR was performed for quantitative analysis of matrix metalloproteinases mRNA expression. Immunoreactivities of collagen and tissue inhibitor of metalloproteinase were observed on the compression and tension sides. LILT significantly facilitated the expression of five tested MMP mRNAs in both relapse and retention groups. TIMP-1 immunoreactivity was inhibited by LILT in both groups, whereas Col-I immunoreactivity was increased by LILT only in the retention group. These results indicate that LILT would act differently on the stability after orthodontic treatment according to additional retainer wearing or not. LILT when combined with a retainer on the moved teeth may shorten the retention period by accelerating periodontal remodeling in the new tooth position, whereas, LILT on the moved teeth left without any retainer would rather increase the rate of relapse after treatment.</P>

      • Low-level laser therapy induces the expressions of BMP-2, osteocalcin, and TGF-β1 in hypoxic-cultured human osteoblasts.

        Pyo, Se-Jeong,Song, Won-Wook,Kim, In-Ryoung,Park, Bong-Soo,Kim, Cheul-Hong,Shin, Sang-Hun,Chung, In-Kyo,Kim, Yong-Deok Baillière Tindall ; Springer London 2013 Lasers in medical science Vol.28 No.2

        <P>The aim of this study was to examine the effect of low-level laser therapy (LLLT) on the cell viability and the expression of hypoxia-inducible factor-1s (HIF-1s), bone morphogenic protein-2 (BMP-2), osteocalcin, type I collagen, transforming growth factor-β1 (TGF-β1), and Akt in hypoxic-cultured human osteoblasts. Human fetal osteoblast cells (cell line 1.19) were cultured under 1?% oxygen tension for 72?h. Cell cultures were divided into two groups. At the experimental side, low-level laser (808?nm, GaAlAs diode) was applied at 0, 24, and 48?h. After irradiation, each cell culture was incubated 24?h more under hypoxia. Total energy was 1.2, 2.4, and 3.6?J/cm(2), respectively. Non-irradiated cultures served as controls. Comparisons between the two groups were analyzed by t test; a p value <0.05 was considered statistically significant. Hypoxia resulted in a decrease in the expression of type I collagen, osteocalcin, and TGF-β1 (p?<?0.001, p?<?0.001, and p?<?0.01, respectively). Cell viability and BMP-2 expression were not decreased by hypoxic condition. On the other hand, LLLT on hypoxic-cultured osteoblast promoted the expression of BMP-2, osteocalcin, and TGF-β1 (p?<?0.05, p?<?0.01, and p?<?0.001, respectively). Cell proliferation was also increased time-dependently. However, hypoxia decreased in type I collagen expression (p?<?0.001), and LLLT did not affect type I collagen expression in hypoxic-cultured osteoblasts. Furthermore, LLLT inhibited HIF-1 and Akt expression in hypoxic conditioned osteoblasts. We concluded that LLLT induces the expression of BMP-2, osteocalcin, and TGF- β1 in 1?% hypoxic-cultured human osteoblasts.</P>

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