Pim-2 regulates bone resorptive activity of osteoclasts via V-ATPase a3 isoform expression in periodontal disease.

Cytoplasmic serine/threonine Pim kinases have emerged as important modulators of immune regulation and oncology. However, their regulatory roles in bone remodeling remain obscure. Here, we aimed to determine the roles of Pim kinases in periodontal disease (PD), focusing on the regulation of osteoclastogenesis and bone resorptive activity. We investigated Pim kinases expression in PD by analyzing data from the online Gene Expression Omnibus database and using ligature-induced periodontitis mouse model. The expression of Pim kinases during receptor activator of nuclear factor kB ligand (RANKL)-induced osteoclastogenesis was assessed in mouse bone marrow-derived macrophages (BMMs) using reverse transcription polymerase chain reaction. Osteoclast differentiation and bone resorption activity were respectively verified by tartrate-resistant acid phosphatase staining and dentin disc-based bone resorption assays. We silenced and overexpressed Pim-2 using small interfering RNA (siRNA) and retroviral vector, respectively, to investigate the molecular mechanisms underlying Pim-2 regulation in RANKL-induced osteoclastogenesis and bone resorption activity. Upregulated expression of Pim-2 was observed in both patients with PD and periodontitis-affected mouse gingival tissues. siRNA-mediated silencing of Pim-2 in BMMs diminished RANKL-induced resorptive activity without affecting osteoclastogenesis. Moreover, RANKL-triggered stimulation of a3 isoform, which is a subunit of vacuolar-type ATPase, was selectively attenuated in BMMs on silencing Pim-2. The overexpression of Pim-2 with a retroviral vector stimulated the a3 subunit, thus inducing bone resorption activity. Taken together, these results suggest that Pim-2 acts as a major modulator of osteoclastic activity by regulating a3 isoform expression in PD.

Effects of photobiomodulation on bone remodeling in an osteoblast-osteoclast co-culture system.

The general bone anabolic effect of photobiomodulation (PBM) is largely accepted. As a result, PBM therapy is expected to be beneficial in the medical fields of dentistry and bone healing. However, most of the previous in vitro studies on PBM and bone metabolism were performed with single-cell cultures of osteoclast-lineage cells or osteoblast-lineage cells. In the present study, the bone-modulating effects of PBM were evaluated in an in vitro osteoblast/osteoclast co-culture system. Mouse bone marrow-derived macrophages (BMMs) and mouse calvarial pre-osteoblasts cells were purified and used as precursor cells for osteoclasts and osteoblasts, respectively. The PBM effects on single-cell culture of osteoclasts or osteoblasts as well as co-culture were examined by 1.2 J/cm2 low-level Ga-Al-As laser (λ = 808 ± 3 nm, 80 mW, and 80 mA; spot size, 1cm2; NDLux, Seoul, Korea) irradiation for 30 s at daily intervals throughout culture period. At the end of culture, the osteoclast differentiation and osteoblast differentiation were assessed by TRAP staining and ALP staining, respectively. The expressions of osteoclastogenic cytokines were evaluated by RT-PCR and Western blot analyses. Under the single-cell culture condition, PBM enhanced osteoblast differentiation but had minor effects on osteoclast differentiation. However, in the co-culture condition, its osteoblastogenic effect was maintained, and osteoclast differentiation was substantially reduced. Subsequent RT-PCR analyses and western blot results revealed marked reduction in receptor activator of NF-κB ligand (RANKL) expression and elevation in osteoprotegerin (OPG) expression by PBM in co-cultured cells. More importantly, these alterations in RANKL/OPG levels were not observed under the single-cell culture conditions. Our results highlight the different effects of PBM on bone cells based on culture conditions. Further, our findings suggest the indirect anti-osteoclastogenic effect of PBM, which is accompanied by a decrease in RANKL expression and an increase in OPG expression.

Prognosis of teeth in mandibular fracture lines.

BACKGROUND/AIMS: Teeth in a jaw fracture line, because of the presence of the periodontal ligament, may communicate with the oral cavity. There are no guidelines for the management of teeth in mandibular fracture lines. The aim of this study was to investigate the factors related to dental problems with teeth involved in mandibular fracture lines and to determine the best treatment option. MATERIAL AND METHODS: This retrospective study was based on the medical and radiographic records of patients with mandibular fractures. The relationships among the patient's age, gender, smoking history, amount of bony displacement, surgery, trauma-surgery period, apical involvement, tooth mobility, and periodontal status were investigated. Group comparisons were performed using the chi-squared test, Fisher's exact test, and Mann-Whitney U-test. RESULT: A total of 238 patients (247 fracture lines) with mandibular fractures including a tooth in the line of the fracture were examined. Post-operative dental complications occurred in 42 cases (17.0%). Extraction of related teeth occurred in 34 cases (80.9%) compared to eight cases (19.0%) related to root canal therapy. This study defined "dental problem" as "a case with a tooth extracted or endodontically treated after trauma." The variables associated with an increased risk of dental problems were the amount of bony displacement (p < .01), tooth mobility (p < .01), and pre-existing marginal alveolar bone loss (p = .027). CONCLUSION: The prognosis of teeth in mandibular fracture lines was related to tooth mobility, periodontal state, and the amount of bony displacement.

Role of Luteolin-Induced Apoptosis and Autophagy in Human Glioblastoma Cell Lines.

Background and Objectives: Malignant glioblastoma (GBM) is caused by abnormal proliferation of glial cells, which are found in the brain. The therapeutic effects of surgical treatment, radiation therapy, and chemo-therapy against GBM are relatively poor compared with their effects against other tumors. Luteolin is abundant in peanut shells and is also found in herbs and other plants, such as thyme, green pepper, and celery. Luteolin is known to be effective against obesity and metabolic syndrome. The anti-inflammatory, and anti-cancer activities of luteolin have been investigated. Most studies have focused on the antioxidant and anti-inflammatory effects of luteolin, which is a natural flavonoid. However, the association between the induction of apoptosis by luteolin in GBM and autophagy has not yet been investigated. This study thus aimed to confirm the occurrence of luteolin-induced apoptosis and autophagy in GBM cells and to assess their relationship. Materials and Methods: A172 and U-373MG glioblastoma cell lines were used for this experiment. We confirmed the apoptosis effect of Luteolin on GBM cells using methods such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, immunofluorescence, Flow cytometry (FACS) western blot, and real-time quantitative PCR (qPCR). Results: In the luteolin-treated A172 and U-373MG cells, cell viability decreased in a concentration- and time-dependent manner. In addition, in A172 and U-373MG cells treated with luteolin at concentrations greater than 100 µM, nuclear fragmentation, which is a typical morphological change characterizing apoptosis, as well as fragmentation of caspase-3 and Poly (ADP-ribose) polymerase (PARP), which are apoptosis-related factors, were observed. Autophagy was induced after treatment with at least 50 µM luteolin. Inhibition of autophagy using 3MA allowed for a low concentration of luteolin to more effectively induce apoptosis in A172 and U-373MG cells. Conclusions: Results showed that luteolin induces apoptosis and autophagy and that the luteolin-induced autophagy promotes cell survival. Therefore, an appropriate combination therapy involving luteolin and an autophagy inhibitor is expected to improve the prognosis of GBM treatment.

Anti-inflammatory effects of dexmedetomidine on human amnion-derived WISH cells.

Background: To maintain the normal pregnancy, suppression of inflammatory signaling pathway is a crucial physiologic response. Dexmedetomidine has been used for labor analgesia or supplement of inadequate regional analgesia during delivery. And it has been reported that dexmedetomidine has an anti-inflammatory effect. In this study, we examined the influence of dexmedetomidine on the expression of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) and inflammatory cytokines in lipopolysaccharide (LPS)-stimulated human amnion-derived WISH cells. In addition, we evaluated the association of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathway in anti-inflammatory effect of dexmedetomidine. Methods: Human amnion-derived WISH cells were pretreated with various concentrations of dexmedetomidine (0.001-1 µg/ml) for 1 h and after then treated with LPS (1 µg/ml) for 24 h. MTT assay was conducted to evaluate the cytotoxicity. Nitric oxide (NO) production was analyzed using Griess-reaction microassay. RT-PCR was performed for analysis of mRNA expressions of COX-2, PGE2, tumor necrosis factor (TNF)-α and interlukin (IL)-1ß. Protein expressions of COX-2, PGE2, p38 and NF-κB were analyzed by western blotting. Results: LPS and dexmedetomidine had no cytotoxic effect on WISH cells. There was no difference in NO production after dexmedetomidine pretreatment. The mRNA and protein expressions of COX-2 and PGE2 were decreased by dexmedetomidine pretreatment in LPS-treated WISH cells. Dexmedetomidine also attenuated the LPS-induced mRNA expression of TNF-α and IL-1ß. The activation of p38 and NF-κB was suppressed by dexmedetomidine pretreatment in LPS-treated WISH cells. Conclusion: We demonstrated that dexmedetomidine pretreatment suppressed the expressions of inflammatory mediators increased by LPS. In addition, this study suggests that anti-inflammatory effect of dexmedetomidine on WISH cells was mediated by the inhibitions of p38 and NF-κB activation.

Zoledronate Enhances Osteocyte-Mediated Osteoclast Differentiation by IL-6/RANKL Axis.

Bisphosphonates are one of the most widely used synthetic pyrophosphate analogues for the treatment of bone resorbing diseases such as osteoporosis, multiple myeloma, and bone metastases. Although the therapeutic usefulness of bisphosphonates mainly depends on their anti-osteoclastogenic effect, a severe side-effect of bisphosphonates called bisphosphonate-related osteonecrosis of the jaw (BRONJ) could not be explained by the anti-osteoclastogenic effect of bisphosphonates. In the present study, we have evaluated the changes in osteoclastogenesis- or osteoblastogenesis-supporting activities of osteocytes induced by bisphosphonates. Zoledronate, a nitrogen-containing bisphosphonate, markedly increased both the receptor activator of nuclear factor kB ligand (RANKL) as well as sclerostin in osteocyte-like MLO-Y4 cells, which were functionally revalidated by osteoclast/osteoblast generating activities of the conditioned medium obtained from zoledronate-treated MLO-Y4 cells. Of note, the zoledronate treatment-induced upregulation of the RANKL expression was mediated by autocrine interleukin-6 (IL-6) and subsequent activation of the signal transducer and activator of transcription 3 (STAT3) pathway. These results were evidenced by the blunted RANKL expression in the presence of a Janus activated kinase (JAK2)/STAT3 inhibitor, AG490. Also, the osteoclastogenesis-supporting activity was significantly decreased in zoledronate-treated MLO-Y4 cells in the presence of IL-6 neutralizing IgG compared to that of the control IgG. Thus, our results show previously unanticipated effects of anti-bone resorptive bisphosphonate and suggest a potential clinical importance of osteocytes in BRONJ development.

Cytoprotective effect of flavonoid-induced autophagy on bisphosphonate mediated cell death in osteoblast.

With rapid economic growth and further developments in medical science, the entry into the aging population is currently increasing, as is the number of patients with metabolic diseases, such as hypertension, hyperlipidemia, heart disease, and diabetes. The current treatments for metabolic bone diseases, which are also on the rise, cause negative side effects. Bisphosphonates, which are used to treat osteoporosis, inhibit the bone resorption ability of osteoclasts and during prolonged administration, cause bisphosphonate-related osteonecrosis of the jaw (BRONJ). Numerous studies have shown the potential role of natural plant products as flavonoids in the protection against osteoporosis and in the influence of bone remodeling. Autophagy occurs after the degradation of cytoplasmic components within the lysosome and serves as an essential cytoprotective response to pathologic stress caused by certain diseases. In the present study, we hypothesized that the cytoprotective effects of flavonoids might be related to those associated with autophagy, an essential cytoprotective response to the pathologic stress caused by certain diseases, in osteoblasts. We demonstrated the cytoprotective effect of flavonoid-induced autophagy against the toxicity of zoledronate and the induction of autophagy by flavonoids to support osteogenic transcription factors, leading to osteoblast differentiation and bone formation. Further studies are necessary to clarify the connections between autophagy and osteogenesis. It would be helpful to shed light on methodological challenges through molecular biological studies and new animal models. The findings of the current study may help to delineate the potential role of flavonoids in the treatment of metabolic bone disease.

Resveratrol Induces Mitochondrial Apoptosis and Inhibits Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma Cells.

OSCC is the most common malignant cancer of the head and neck. EMT is an essential cellular process critical to the morphogenesis and homeostasis of solid tissues. It is also involved in the initial stage of cancer metastasis and invasion in which cells lose epithelial characteristics. While cancer therapy protocols such as surgery, radiation, and chemotherapy are effective and useful, the drug tolerance and toxicity of OSCC patients remain a problem. Resveratrol is mainly produced in red grape skin and exhibits anti-oxidative, anti-inflammatory, anti-proliferative, and anti-cancer properties. This study was undertaken to investigate the underlying mechanisms giving rise to the induction of apoptosis by resveratrol in the human tongue squamous cell carcinoma cell line. Resveratrol treatment resulted in a time- and dose-dependent decrease in cell viability and increased the apoptotic cell ratio in CAL-27, SCC15, and SCC25 cells. Resveratrol treatment of CAL-27 cells showed that several lines of apoptotic manifestation and decreased cell migration, invasion, and EMT-inducing transcription factor. Taken together, our findings demonstrate the inhibitory effect of resveratrol in human OSCC cells via the mitochondrial pathway and that resveratrol is able to inhibit cell invasion and migration by inhibiting the EMT-inducing transcription factors.

Evaluation of Intersegmental Displacement After Mandibular Setback Split Ramus Osteotomy Using Modified L-Shaped Monocortical Plate: Cone-Beam Computed Tomography Superimposition.

PURPOSE: The purpose of the current study is to compare intersegmental displacements after mandibular setback sagittal split ramus osteotomy (SSRO) using 4 types of osteosynthesis methods. PATIENTS AND METHODS: This is a retrospective study of 53 subjects who presented underwent bilateral setback SSRO at Pusan National University Hospital from January 2009 to December 2013. The subjects were divided into 4 groups according to the osteosynthesis method applied: group A-modified L-type monocortical plate; B-conventional miniplate; group C-bicortical screws; group D-metal and absorbable screws. To obtain the intersegmental displacement, the mean of the differences of the 3-dimensional from T0 (2 days after surgery) to T1 (6 months after surgery) was calculated for the right and left condylar heads (condylion, Cd) and the right and left coronoid processes (Cps) using 3-dimensional imaging software (Ondemand 3D; Cybermed Co, Seoul, Korea). RESULTS: For the condylion in the x, y, z coordinate system, in group A, there were significant differences in the y-axis for the right and left Cd; in group B, significant differences in the y-axis for the right Cd and in the y- and z-axes for the left Cd; in group C, no significant differences in the axis for the Cd; and in group D, there were significant differences in the y- and z-axes for the right Cd and in the x- and y-axes for the left Cd. For the Cps, the results are not much different from the condylion movement in all group. CONCLUSION: In the current study, group C manifested the greatest displacement for the healing period. Group A did not show the significant difference to group B. In view of these results, modified L-shaped monocortical plate can be applied for osteosynthesis effectively.

The Effects of Kaempferol-Inhibited Autophagy on Osteoclast Formation.

Kaempferol, a flavonoid compound, is derived from the rhizome of Kaempferia galanga L., which is used in traditional medicine in Asia. Autophagy has pleiotropic functions that are involved in cell growth, survival, nutrient supply under starvation, defense against pathogens, and antigen presentation. There are many studies dealing with the inhibitory effects of natural flavonoids in bone resorption. However, no studies have explained the relationship between the autophagic and inhibitory processes of osteoclastogenesis by natural flavonoids. The present study was undertaken to investigate the inhibitory effects of osteoclastogenesis through the autophagy inhibition process stimulated by kaempferol in murin macrophage (RAW 264.7) cells. The cytotoxic effect of Kaempferol was investigated by MTT assay. The osteoclast differentiation and autophagic process were confirmed via tartrate-resistant acid phosphatase (TRAP) staining, pit formation assay, western blot, and real-time PCR. Kaempferol controlled the expression of autophagy-related factors and in particular, it strongly inhibited the expression of p62/SQSTM1. In the western blot and real time-PCR analysis, when autophagy was suppressed with the application of 3-Methyladenine (3-MA) only, osteoclast and apoptosis related factors were not significantly affected. However, we found that after cells were treated with kaempferol, these factors inhibited autophagy and activated apoptosis. Therefore, we presume that kaempferol-inhibited autophagy activated apoptosis by degradation of p62/SQSTM1. Further study of the p62/SQSTM1 gene as a target in the autophagy mechanism, may help to delineate the potential role of kaempferol in the treatment of bone metabolism disorders.

The role of kaempferol-induced autophagy on differentiation and mineralization of osteoblastic MC3T3-E1 cells.

BACKGROUND: Kaempferol, a kind of flavonol, has been reported to possess various osteogenic biological activities, such as inhibiting bone resorption of osteoclasts and promoting the differentiation and mineralization of preosteoblasts. However, the precise cellular mechanism of action of kaempferol in osteogenesis is elusive. Autophagy is a major intracellular degradation system, which plays an important role in cell growth, survival, differentiation and homeostasis in mammals. Recent studies showed that autophagy appeared to be involved in the degradation of osteoclasts, osteoblasts and osteocytes, potentially pointing to a new pathogenic mechanism of bone homeostasis and bone marrow disease. The potential correlation between autophagy, osteogenesis and flavonoids is unclear. METHODS: The present study verified that kaempferol promoted osteogenic differentiation and mineralization and that it elevated osteogenic gene expression based on alkaline phosphatase (ALP) activity, alizarin red staining and quantitative PCR. And then we found that kaempferol induced autophagy by acridine orange (AO) and monodansylcadaverine (MDC) staining and autophagy-related protein expression. The correlation between kaempferol-induced autophagy and the osteogenic process was confirmed by the autophagy inhibitor 3-methyladenine (3-MA). RESULTS: Kaempferol promoted the proliferation, differentiation and mineralization of osteoblasts at a concentration of 10 µM. Kaempferol showed cytotoxic properties at concentrations above 50 µM. Concentrations above 10 µM decreased ALP activity, whereas those up to 10 µM increased ALP activity. Kaempferol at concentrations up to 10 µM also increased the expression of the osteoblast- activated factors RUNX-2, osterix, BMP-2 and collagen I according to RT-PCR analyses. 10 µM or less, the higher of the concentration and over time, kaempferol promoted the activity of osteoblasts. Kaempferol induced autophagy. It also increased the expression of the autophagy-related factors beclin-1, SQSTM1/p62 and the conversion of LC3-II from LC3-I. The application of 3-MA decreased the activity of ALP and the autophagy induced by kaempferol. In the RT-PCR analysis, the expression of RUNX-2, osterix, BMP-2 and collagen I was decreased. CONCLUSION: The present study showed that kaempferol stimulated the osteogenic differentiation of cultured osteoblasts by inducing autophagy.

Therapeutic angiogenesis in a murine model of limb ischemia by recombinant periostin and its fasciclin I domain.

Periostin, an extracellular matrix protein, is expressed in injured tissues, such as the heart with myocardial infarction, and promotes angiogenesis and tissue repair. However, the molecular mechanism associated with periostin-stimulated angiogenesis and tissue repair is still unclear. In order to clarify the role of periostin in neovascularization, we examined the effect of periostin in angiogenic potentials of human endothelial colony forming cells (ECFCs) in vitro and in an ischemic limb animal model. Recombinant periostin protein stimulated the migration and tube formation of ECFCs. To identify the functional domains of periostin implicated in angiogenesis, five fragments of periostin, including four repeating FAS-1 domains and a carboxyl terminal domain, were expressed in Escherichia coli and purified to homogeneity. Of the five different domains, the first FAS-1 domain stimulated the migration and tube formation of human ECFCs as potent as the whole periostin. Chemotactic migration of ECFCs induced by the full length and the first FAS-1 domain of periostin was abrogated by blocking antibodies against ß3 and ß5 integrins. Intramuscular injection of the full length and the first FAS-1 domain of periostin into the ischemic hindlimb of mice attenuated severe limb loss and promoted blood perfusion and homing of intravenously administered ECFCs to the ischemic limb. These results suggest that the first FAS-1 domain is responsible for periostin-induced migration and angiogenesis and it can be used as a therapeutic tool for treatment of peripheral artery occlusive disease by stimulating homing of ECFCs.

Growth properties of cardiac stem cells are a novel biomarker of patients' outcome after coronary bypass surgery.

BACKGROUND: The efficacy of bypass surgery in patients with ischemic cardiomyopathy is not easily predictable; preoperative clinical conditions may be similar, but the outcome may differ significantly. We hypothesized that the growth reserve of cardiac stem cells (CSCs) and circulating cytokines promoting CSC activation are critical determinants of ventricular remodeling in this patient population. METHODS AND RESULTS: To document the growth kinetics of CSCs, population-doubling time, telomere length, telomerase activity, and insulin-like growth factor-1 receptor expression were measured in CSCs isolated from 38 patients undergoing bypass surgery. Additionally, the blood levels of insulin-like growth factor-1, hepatocyte growth factor, and vascular endothelial growth factor were evaluated. The variables of CSC growth were expressed as a function of the changes in wall thickness, chamber diameter and volume, ventricular mass-to-chamber volume ratio, and ejection fraction, before and 12 months after surgery. A high correlation was found between indices of CSC function and cardiac anatomy. Negative ventricular remodeling was not observed if CSCs retained a significant growth reserve. The high concentration of insulin-like growth factor-1 systemically pointed to the insulin-like growth factor-1-insulin-like growth factor-1 receptor system as a major player in the adaptive response of the myocardium. hepatocyte growth factor, a mediator of CSC migration, was also high in these patients preoperatively, as was vascular endothelial growth factor, possibly reflecting the vascular growth needed before bypass surgery. Conversely, a decline in CSC growth was coupled with wall thinning, chamber dilation, and depressed ejection fraction. CONCLUSIONS: The telomere-telomerase axis, population-doubling time, and insulin-like growth factor-1 receptor expression in CSCs, together with a high circulating level of insulin-like growth factor-1, represent a novel biomarker able to predict the evolution of ischemic cardiomyopathy following revascularization.

Effect of low-level laser therapy on oral keratinocytes exposed to bisphosphonate.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a side effect of bisphosphonate therapy. However, its pathophysiology is not yet fully elucidated, and effective treatment of BRONJ remains unclear. The aim of this study is to investigate the effects of alendronate on oral keratinocytes and of low-level laser therapy (LLLT) on alendronate-treated keratinocytes, specifically by evaluating their viability, apoptosis, and wound healing function after irradiation. Oral keratinocyte cells (HaCaT) were exposed to 25 µM alendronate. Then, laser irradiation was performed with a low-level Ga-Al-As laser (λ = 808 ± 3 nm, 80 mW, and 80 mA; NDLux, Seoul, Korea) using 1.2 J/cm(2) energy dose. Viability was analyzed using MTT assay. Apoptosis was measured by Hoechst staining, caspase assay. Changes in secretion of IL-8, VEGF, and collagen type I were studied by ELISA and immunofluorescence microscopy. Scratch wound assays were also performed to measure cellular migration. Our results show that alendronate inhibits keratinocyte viability, expression of IL-8, VEGF, and collagen type I which are intimately related to healing events and cell migration while promoting apoptosis. Our results serve to demonstrate the utility of LLLT in partially overcoming the inhibitory effects of this bisphosphonate. From these results, the authors believe that the present study will provide an experimental basis for a fuller explanation of the clinical effects of LLLT as a BRONJ treatment modality.

Effects of Temperature and X-rays on Plastic Scintillating Fiber and Infrared Optical Fiber.

In this study, we have studied the effects of temperature and X-ray energy variations on the light output signals from two different fiber-optic sensors, a fiber-optic dosimeter (FOD) based on a BCF-12 as a plastic scintillating fiber (PSF) and a fiber-optic thermometer (FOT) using a silver halide optical fiber as an infrared optical fiber (IR fiber). During X-ray beam irradiation, the scintillating light and IR signals were measured simultaneously using a dosimeter probe of the FOD and a thermometer probe of the FOT. The probes were placed in a beaker with water on the center of a hotplate, under variation of the tube potential of a digital radiography system or the temperature of the water in the beaker. From the experimental results, in the case of the PSF, the scintillator light output at the given tube potential decreased as the temperature increased in the temperature range from 25 to 60 °C. We demonstrated that commonly used BCF-12 has a significant temperature dependence of -0.263 ± 0.028%/°C in the clinical temperature range. Next, in the case of the IR fiber, the intensity of the IR signal was almost uniform at each temperature regardless of the tube potential range from 50 to 150 kVp. Therefore, we also demonstrated that the X-ray beam with an energy range used in diagnostic radiology does not affect the IR signals transmitted via a silver halide optical fiber.

Feasibility of Ultra-Thin Fiber-Optic Dosimeters for Radiotherapy Dosimetry.

In this study, prototype ultra-thin fiber-optic dosimeters were fabricated using organic scintillators, wavelength shifting fibers, and plastic optical fibers. The sensor probes of the ultra-thin fiber-optic dosimeters consisted of very thin organic scintillators with thicknesses of 100, 150 and 200 µm. These types of sensors cannot only be used to measure skin or surface doses but also provide depth dose measurements with high spatial resolution. With the ultra-thin fiber-optic dosimeters, surface doses for gamma rays generated from a Co-60 therapy machine were measured. Additionally, percentage depth doses in the build-up regions were obtained by using the ultra-thin fiber-optic dosimeters, and the results were compared with those of external beam therapy films and a conventional fiber-optic dosimeter.

Development of a Small-Sized, Flexible, and Insertable Fiber-Optic Radiation Sensor for Gamma-Ray Spectroscopy.

We fabricated a small-sized, flexible, and insertable fiber-optic radiation sensor (FORS) that is composed of a sensing probe, a plastic optical fiber (POF), a photomultiplier tube (PMT)-amplifier system, and a multichannel analyzer (MCA) to obtain the energy spectra of radioactive isotopes. As an inorganic scintillator for gamma-ray spectroscopy, a cerium-doped lutetium yttrium orthosilicate (LYSO:Ce) crystal was used and two solid-disc type radioactive isotopes with the same dimensions, cesium-137 (Cs-137) and cobalt-60 (Co-60), were used as gamma-ray emitters. We first determined the length of the LYSO:Ce crystal considering the absorption of charged particle energy and measured the gamma-ray energy spectra using the FORS. The experimental results demonstrated that the proposed FORS can be used to discriminate species of radioactive isotopes by measuring their inherent energy spectra, even when gamma-ray emitters are mixed. The relationship between the measured photon counts of the FORS and the radioactivity of Cs-137 was subsequently obtained. The amount of scintillating light generated from the FORS increased by increasing the radioactivity of Cs-137. Finally, the performance of the fabricated FORS according to the length and diameter of the POF was also evaluated. Based on the results of this study, it is anticipated that a novel FORS can be developed to accurately measure the gamma-ray energy spectrum in inaccessible locations such as narrow areas and holes.

Performance Evaluation of a Multichannel All-In-One Phantom Dosimeter for Dose Measurement of Diagnostic X-ray Beam.

We developed a multichannel all-in-one phantom dosimeter system composed of nine sensing probes, a chest phantom, an image intensifier, and a complementary metal-oxide semiconductor (CMOS) image sensor to measure the dose distribution of an X-ray beam used in radiation diagnosis. Nine sensing probes of the phantom dosimeter were fabricated identically by connecting a plastic scintillating fiber (PSF) to a plastic optical fiber (POF). To measure the planar dose distribution on a chest phantom according to exposure parameters used in clinical practice, we divided the top of the chest phantom into nine equal parts virtually and then installed the nine sensing probes at each center of the nine equal parts on the top of the chest phantom as measuring points. Each scintillation signal generated in the nine sensing probes was transmitted through the POFs and then intensified by the image intensifier because the scintillation signal normally has a very low light intensity. Real-time scintillation images (RSIs) containing the intensified scintillation signals were taken by the CMOS image sensor with a single lens optical system and displayed through a software program. Under variation of the exposure parameters, we measured RSIs containing dose information using the multichannel all-in-one phantom dosimeter and compared the results with the absorbed doses obtained by using a semiconductor dosimeter (SCD). From the experimental results of this study, the light intensities of nine regions of interest (ROI) in the RSI measured by the phantom dosimeter were similar to the dose distribution obtained using the SCD. In conclusion, we demonstrated that the planar dose distribution including the entrance surface dose (ESD) can be easily measured by using the proposed phantom dosimeter system.

Proteomic identification of betaig-h3 as a lysophosphatidic acid-induced secreted protein of human mesenchymal stem cells: paracrine activation of A549 lung adenocarcinoma cells by betaig-h3.

Lysophosphatidic acid (LPA) is enriched in the serum and malignant effusion of cancer patients and plays a key role in tumorigenesis and metastasis. LPA-activated mesenchymal stem cells promote tumorigenic potentials of cancer cells through a paracrine mechanism. LPA-conditioned medium (LPA CM) from human adipose tissue-derived mesenchymal stem cells (hASCs) elicited adhesion and proliferation of A549 human lung adenocarcinoma cells. To identify proteins involved in the LPA-stimulated paracrine functions of hASCs, we analyzed the LPA CM using liquid-chromatography tandem mass spectrometry-based shotgun proteomics. We identified ßig-h3, an extracellular matrix protein that is implicated in tumorigenesis and metastasis, as an LPA-induced secreted protein in hASCs. LPA-induced ßig-h3 expression was abrogated by pretreating hASCs with the LPA receptor(1/3) inhibitor Ki16425 or small interfering RNA-mediated silencing of endogenous LPA(1). LPA-induced ßig-h3 expression was blocked by treating the cells with the Rho kinase inhibitor Y27632, implying that LPA-induced ßig-h3 expression is mediated by the LPA(1)- Rho kinase pathway. Immunodepletion or siRNA-mediated silencing of ßig-h3 abrogated LPA CM-stimulated adhesion and proliferation of A549 cells, whereas retroviral overexpression of ßig-h3 in hASCs potentiated it. Furthermore, recombinant ßig-h3 protein stimulated the proliferation and adhesion of A549 human lung adenocarcinoma cells. These results suggest that hASC-derived ßig-h3 plays a key role in tumorigenesis by stimulating the adhesion and proliferation of cancer cells and it can be applicable as a biomarker and therapeutic target for lung cancer.

A fiber-optic sensor using an aqueous solution of sodium chloride to measure temperature and water level simultaneously.

A fiber-optic sensor system using a multiplexed array of sensing probes based on an aqueous solution of sodium chloride (NaCl solution) and an optical time-domain reflectometer (OTDR) for simultaneous measurement of temperature and water level is proposed. By changing the temperature, the refractive index of the NaCl solution is varied and Fresnel reflection arising at the interface between the distal end of optical fiber and the NaCl solution is then also changed. We measured the modified optical power of the light reflected from the sensing probe using a portable OTDR device and also obtained the relationship between the temperature of water and the optical power. In this study, the water level was simply determined by measuring the signal difference of the optical power due to the temperature difference of individual sensing probes placed inside and outside of the water. In conclusion, we demonstrate that the temperature and water level can be obtained simultaneously by measuring optical powers of light reflected from sensing probes based on the NaCl solution. It is anticipated that the proposed fiber-optic sensor system makes it possible to remotely monitor the real-time change of temperature and water level of the spent fuel pool during a loss of power accident.