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In this study, parylene-C films from plasma deposition as well as thermal deposition were pyrolyzed to prepare a carbon electrode for application in electrochemical immunoassays. Plasma deposition could prepare parylene-C in a faster deposition rate and more precise control over the thickness in comparison with the conventional thermal deposition. To analyze the influence of the deposition method, the crystal and electronic structures of the pyrolyzed parylene-C films obtained

Oral squamous cell carcinoma (OSCC) frequently invades nearby bone and bone involvement determines the prognosis of patients. Growth factors, stored in the bone matrix and released during bone destruction, are known as key components in the bone-tumor interaction. However, the coordination of growth factor signals and the precise mechanism of bone destruction in oral cancer are still unclear. In the study, we investigated the differential cytokine expression profile of oral cancer cells by TGF-β treatment and the function of altered expression of cytokines on the osteoclast differentiation. We established TGFBR2-knockdown cells using small hairpin RNA. TGF-β was treated to both TGFBR2 expressing and knockdown cells and the culture supernatants were analyzed using a cytokine array kit. We found that the TGF-β inhibited IGFBP3 level and enhanced MMP9 level. We confirmed this regulation of IGFBP3 and MMP9 by TGF-β using ELISA and zymography, respectively. IGFBP3 is known as to modulate the bioavailability of IGF1, which is abundant in the bone microenvironment and regulates osteoclast differentiation. Therefore, we further analyzed the function of IGFBP3 on osteoclastogenesis. Although IGFBP3 increased the viability of murine bone marrow macrophages, the osteoclast differentiation of these cells was blocked by IGFBP3 in a dose-dependent manner. These results revealed a novel pathway for the regulation of osteoclastogenesis by oral cancer cells, which may be a new therapeutic target for osteolysis induced by oral cancer infiltrating into the bone.

Osteoarthritis (OA) is a common joint disease that results from the disintegration of joint cartilage and the underlying bone. Because cartilage and chondrocytes lack the ability to self-regenerate, efforts have been made to utilize stem cells to treat OA. Although various methods have been used to differentiate stem cells into functional chondrocytes, the currently available methods cannot induce stem cells to undergo differentiation into chondrocyte-like cells without inducing characteristics of hypertrophic chondrocytes, which finally lead to cartilage disintegration and calcification. Therefore, an optimized method to differentiate stem cells into chondrocytes that do not display undesired phenotypes is needed. This study focused on differentiating adipose-derived stem cells (ASCs) into functional chondrocytes using a small molecule that regulated the expression of Sox9 as a key factor in cartilage development and then explored its ability to treat OA. We selected ellipticine (ELPC), which induces chondrocyte differentiation of ASCs, using a GFP-Sox9 promoter vector screening system. An in vivo study was performed to confirm the recovery rate of cartilage regeneration with ASC differentiation into chondrocytes by ELPC in a collagenase-induced animal model of OA. Taken together, these data indicate that ellipticine induces ASCs to differentiate into mature chondrocytes without hypertrophic chondrocytes in vitro and in vivo, thus overcoming a problem encountered in previous studies. These results indicate that ELPC is a novel chondrocyte differentiation-inducing drug that shows potential as a cell therapy for OA., Osteoarthritis: Drug-induced stem cell differentiation shows therapeutic promise A novel method of generating healthy cartilage cells from stem cells could repair and regenerate joints and bones damaged by osteoarthritis. The cells that produce and maintain cartilage tissue are known as chondrocytes. Stem cell therapy could potentially re-start cartilage and bone regeneration in patients with osteoarthritis, however scientists have struggled to successfully induce stem cells to differentiate into functioning chondrocytes. A new method developed by Soyeon Lim and Ki-Chul Hwang at the Catholic Kwandong University, Gangneung, South Korea, and co-workers uses a drug called ellipticine to boost the expression of Sox-9, a key protein involved in cartilage development. The researchers found that the ellipticine-based method induced a mature, healthy chondrocyte population in cell cultures and rat models of osteoarthritis. Rats injected with these cells recovered from cartilage damage, suggesting a potential osteoarthritis therapy.

Background/aim We investigated the clinical role of the molecular targets, APEX1 and Jagged-1, and the Apex1 - Jagged-1 cascade in gastric cancer cells. Materials and methods We used 6 human gastric cancer cell lines (SNU-1, SNU-5, SNU-16, NCI-N87, KATO- III and AGS), and demonstrated the chemosensitivity of APEX1 and Jagged-1 through the MTT assay and immunoblotting. Tumor growth was assayed following cisplatin and 5-FU treatment using a xenograft model injected with KATO-III cells. Moreover, gastric tumor samples from 9 patients, divided in 2 groups according to chemotherapy response, were examined by immunocytochemical (IHC) staining, and protein expression levels were scored. Results Following APEX1 knockdown, the MTT assay revealed that the IC50 of cisplatin and 5-FU in AGS cells was decreased approximately 7% and 15%, respectively, however, their decrease in chemoresistant KATO-III cells was decreased by approximately 21% and 67% for cisplatin and 5-FU, respectively. The tumor volume of KATO-III/sicontrol mice treated with cisplatin and 5-FU was affected less, compared with KATO-III/siAPEX1 mice treated with cisplatin and 5-FU. Also, the expression levels of APEX1, Jagged-1 and CD133, assayed by IHC staining, were higher in the chemorefractory group than in the chemoresponsive group. Conclusion Jagged-1-activated signaling by APEX1 plays a role in advanced gastric cancer.

Oral squamous cell carcinoma (OSCC) frequently invades the maxillary or mandibular bone, and this bone invasion is closely associated with poor prognosis and survival. Here, we show that CCL28 functions as a negative regulator of OSCC bone invasion. CCL28 inhibited invasion and epithelial-mesenchymal transition (EMT), and its inhibition of EMT was characterized by induced E-cadherin expression and reduced nuclear localization of β-catenin in OSCC cells with detectable RUNX3 expression levels. CCL28 signaling via CCR10 increased retinoic acid receptor-β (RARβ) expression by reducing the interaction between RARα and HDAC1. In addition, CCL28 reduced RANKL production in OSCC and osteoblastic cells and blocked RANKL-induced osteoclastogenesis in osteoclast precursors. Intraperitoneally administered CCL28 inhibited tumor growth and osteolysis in mouse calvaria and tibia inoculated with OSCC cells. RARβ expression was also increased in tumor tissues. In patients with OSCC, low CCL28, CCR10, and RARβ expression levels were highly correlated with bone invasion. Patients with OSCC who had higher expression of CCL28, CCR10, or RARβ had significantly better overall survival. These findings suggest that CCL28, CCR10, and RARβ are useful markers for the prediction and treatment of OSCC bone invasion. Furthermore, CCL28 upregulation in OSCC cells or CCL28 treatment can be a therapeutic strategy for OSCC bone invasion.

Chemiluminescence immunoassays have been widely employed for diagnosing various diseases. However, because of the extremely low intensity chemiluminescence signals, highly sensitive transducers, such as photomultiplier tubes and image sensors with cooling devices, are required to overcome this drawback. In this study, a hypersensitive photosensor was developed based on cesium lead bromide (CsPbBr

The acute demise of stem cells following transplantation significantly compromises the efficacy of stem cell-based cell therapeutics for infarcted hearts. As the stem cells transplanted into the damaged heart are readily exposed to the hostile environment, it can be assumed that the acute death of the transplanted stem cells is also inflicted by the same environmental cues that caused massive death of the host cardiac cells. Pyroptosis, a highly inflammatory form of programmed cell death, has been added to the list of important cell death mechanisms in the damaged heart. However, unlike the well-established cell death mechanisms such as necrosis or apoptosis, the exact role and significance of pyroptosis in the acute death of transplanted stem cells have not been explored in depth. In the present study, we found that M1 macrophages mediate the pyroptosis in the ischemia/reperfusion (I/R) injured hearts and identified miRNA-762 as an important regulator of interleukin 1β production and subsequent pyroptosis. Delivery of exogenous miRNA-762 prior to transplantation significantly increased the post-transplant survival of stem cells and also significantly ameliorated cardiac fibrosis and heart functions following I/R injury. Our data strongly suggest that suppressing pyroptosis can be an effective adjuvant strategy to enhance the efficacy of stem cell-based therapeutics for diseased hearts.

Highly N-doped SiC was presented as an optimal electrode for electrochemical immunoassays with a far higher sensitivity than chemiluminescence detection. As the first step, the electrochemical properties of highly N-doped SiC, such as the double-layer capacitance (Cdl), rate constant for electron transfer (kapp) and ideal polarizable potential range (electrochemical window) were analyzed and compared with those of Au, Pt, and graphite electrodes. The highly N-doped SiC electrode was used for the quantification of oxidized 3,3′,5,5′-tetramethylbenzidine (TMB) which was widely used as chromogenic substrate for commercialized immunoassay kits. In order to enhance the sensitivity for the quantification of the oxidized TMB the chronoamperometry was applied to avoid the background current of i-V measurement. Finally, the chronoamperometry based on the highly N-doped SiC electrode was applied to commercial immunoassay kits for the medical diagnosis of the human immunodeficiency virus (HIV) and the human hepatitis B surface antigen (hHBsAg). The chronoamperometric measurement based on the highly N-doped SiC electrode was proved to detect at far lower limits in comparison with the conventional optical density measurement as well as the chemiluminescence assay based on luminol as a chemiluminescent probe.

Vertically paired electrodes (VPEs) with multiple electrode pairs were developed for the enhancement of capacitive measurements by optimizing the electrode gap and number of electrode pairs. The electrode was fabricated using a conductive polymer layer of PEDOT:PSS instead of Ag and Pt metal electrodes to increase the VPE fabrication yield because the PEDOT:PSS layer could be effectively etched using a reactive dry etching process. In this study, sensitivity enhancement was realized by decreasing the electrode gap and increasing the number of VPE electrode pairs. Such an increase in sensitivity according to the electrode gap and the number of electrode pairs was estimated using a model analyte for an immunoassay. Additionally, a computer simulation was performed using VPEs with different electrode gaps and numbers of VPE electrode pairs. Finally, VPEs with multiple electrode pairs were applied for SARS-CoV-2 nucleoprotein (NP) detection. The capacitive biosensor based on the VPE with immobilized anti-SARS-CoV-2 NP was applied for the specific detection of SARS-CoV-2 in viral cultures. Using viral cultures of SARS-CoV-2, SARS-CoV, MERS-CoV, and CoV-strain 229E, the limit of detection (LOD) was estimated to satisfy the cutoff value (dilution factor of 1/800) for the medical diagnosis of COVID-19, and the assay results from the capacitive biosensor were compared with commercial rapid kit based on a lateral flow immunoassay.

Previous studies have reported that Hedyotis diffusa Willdenow extract shows various biological activities on cerebropathia, such as neuroprotection and short-term memory enhancement. However, there has been a lack of studies on the inhibitory activity on neurodegenerative diseases such as Alzheimer’s disease (AD) through enzyme assays of H. diffusa. Therefore, H. diffusa extract and fractions were evaluated for their inhibitory effects through assays of enzymes related to AD, including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and on the formation of advanced glycation end-product (AGE). In this study, ten bioactive compounds, including nine iridoid glycosides 1–9 and one flavonol glycoside 10, were isolated from the ethyl acetate and n-butanol fractions of H. diffusa using a bioassay-guided approach. Compound 10 was the strongest inhibitor of cholinesterase, BACE1, and the formation of AGEs of all isolated compounds, while compound 5 had the lowest inhibitory activity. Compounds 3, 6, and 9 exhibited better inhibitory activity than other compounds on AChE, and two pairs of diastereomeric iridoid glycoside structures (compounds 4, 8, and 6, 7) showed higher inhibitory activity than others on BChE. In the BACE1 inhibitory assay, compounds 1–3 were good inhibitors, and compound 10 showed higher inhibitory activity than quercetin, the positive control. Moreover, compounds 1 and 3 were stronger inhibitors of the formation of AGE than aminoguanidine (AMG), the positive control. In conclusion, this study is significant since it demonstrated that the potential inhibitory activity of H. diffusa on enzymes related to AD and showed the potential use for further study as a natural medicine for AD treatment on the basis of the bioactive components isolated from H. diffusa.

Herein, we present switching-peptides for a one-step immunoassay, without the need for additional antibody treatment or washing steps to detect antigen–antibody interactions. Fluorescently labeled switching-peptides were dissociated from the immobilized antibody soon after the antigens were bound to the binding pockets. In this study, four different parts of the antibody (IgG) frame regions were chemically synthesized, and these peptides were bound to immobilized antibodies as switching-peptides. We presented the design principle of switching-peptides and used Pymol software, based on the changes in thermodynamic parameters, to study the interaction between antibodies and switching-peptides. The binding properties of switching-peptides were analyzed based on Forster resonance energy transfer between switching-peptides as well as between switching-peptides and antibodies (IgGs) isolated from different animals. The binding constants of the four switching-peptides to antibodies were estimated to be in the range of 1.48–3.29 μM. Finally, the feasibility of using switching-peptides for the quantitative one-step immunoassay was demonstrated by human hepatitis B surface antigen (hHBsAg) detection and statistical comparison of the assay results with those of conventional ELISA. The limit of detection for HBsAg was determined to be 56 ng/mL, and the dynamic range was estimated to be 136 ng/mL–33 μg/mL. These results demonstrate the feasibility of the one-step immunoassay for HBsAg.

Patients with oral squamous cell carcinoma (OSCC) bone invasion are surgically treated with bone resection, which results in severe physical and psychological damage. Here, we investigated the potential of fractalkine (CX3CL1), which is regulated by transforming growth factor (TGF-β), as a novel biomarker for correct prediction and early detection of OSCC-associated bone invasion. TGF-β knockdown and treatment with a TGF-β-neutralizing antibody decreased the level of fractalkine in the culture media of HSC-2 and YD10B OSCC cells. Treatment with a fractalkine-neutralizing antibody reduced TGF-β-stimulated invasion by HSC-2 and YD10B cells. Fractalkine treatment increased the viability, invasion, and uPA secretion of both OSCC cell lines. Furthermore, OSCC cell bone invasion was assessed following subcutaneous inoculation of wild-type or TGF-β knockdown OSCC cells in mouse calvaria. TGF-β knockdown prevented erosive bone invasion, reduced the number of osteoclasts at the tumor-bone interface, and downregulated fractalkine expression in mouse tumor tissues. Our results indicate that the production of fractalkine is stimulated by TGF-β and mediates TGF-β-induced cell invasion in several OSCC cell lines showing an erosive pattern of bone invasion. Fractalkine may be a useful predictive marker and therapeutic target for OSCC-induced bone destruction.

In this work phospholipid quantification was carried out using an enzymatic assay based on cyclic voltammetry of the condensation product of N-ethyl-N-(2-hydroxy-3-sulfopropyl)-3,5-dimethoxyaniline sodium salt (DAOS) and 4-aminoantipyrine (4-AP) with a graphite electrode. For the optimization of electrochemical measurement for the product, electrochemical properties such as the electrochemical window, double layer capacitance (Cdl) and electron transfer rate (kapp) were analyzed for a graphite-electrode and Au-electrode. The phospholipid enzymatic assay based the on electrochemical measurement using the graphite electrode was applied to the diagnosis of sepsis for sera from healthy volunteers (n = 16), patients with systemic inflammatory response syndrome (SIRS, n = 16) and severe sepsis patients (n = 24). Finally, the phospholipid quantification results from the electrochemical measurement were statistically compared with the conventional method based on optical density measurement.

The present study translated the Vocal Tract Discomfort Scale (VTDS) into Korean (K-VTDS) and evaluated its reliability and validity.This was a prospective study.The VTDS was first translated into Korean and validated. One hundred and fifty-nine patients with voice disorders were divided into three different diagnostic groups (functional, structural, and neurologic voice disorder) and 131 vocally healthy adults were also included. All participants completed the K-VTDS and the Korean version of the Voice Handicap Index (K-VHI) and Korean versions of the Voice-Related Quality of Life (K-VRQOL). The internal consistency of the K-VTDS was analyzed through Cronbach's α coefficient. The VTDS score differences related to the diagnostic groups were assessed with t test and analysis of variance. We assessed the correlation between the K-VTDS, the K-VHI, and the K-VRQOL using Pearson's correlation analysis.High internal consistency and the test-retest reliability of the K-VTDS were found. The voice disorder group had significantly higher K-VTDS scores for the subscales and total scores than those in the healthy group (P0.001). The K-VTDS scores for the subscale of frequency and total scores were highest in the functional voice disorder group. We found a significant difference in frequency and total score of the K-VTDS between the functional voice disorder group and the structural voice disorder group (P0.05). We observed a strong positive correlation among the scores for the subscales of frequency and severity, and total scores in the K-VTDS. The K-VTDS showed moderate correlation with the K-VHI and the K-VRQOL.The K-VTDS is a reliable and valid instrument for voice assessment for voice disorders in Korean-speaking patients.

Background/Aims: Bone metastasis of cancer cells decreases patient survival and quality of life. Hybridization via the covalent coupling of two bioactive natural products is a useful strategy for developing more potent anticancer agents by enhancing their bioavailability and avoiding drug resistance. Methods: The in vivo activities of artemisinin-daumone hybrid 15 (ARTD) were estimated in cancer cell-inoculated mice and ovariectomized mice. The viability, migration, and invasion of cancer cells were measured via MTT, wound-healing, and transwell invasion assays. ARTD-regulated transcription factors were detected with an RT2 profiler PCR array kit and Western blotting. Osteoclastogenesis and osteoclast activity were detected with tartrate-resistant acid phosphatase staining, a pit formation assay, gelatin zymography, and a cathepsin K ELISA assay. Results: ARTD blocked cancer-associated osteolysis more potently than artemisinin in mice with intratibially inoculated breast cancer or lung cancer cells. ARTD inhibited the viability, migration, and invasion of breast and lung cancer cells in the absence or presence of transforming growth factor-β1. ARTD treatment induced the expression of tumor suppressive activating transcription factor 3 and inhibited oncogenic E2F transcription factor 1 expression at the mRNA and protein levels. ARTD inhibited receptor activator of nuclear factor kappa-B ligand-induced osteoclast formation and bone resorbing activity by reducing the secreted levels of matrix metalloproteinase-9 and cathepsin K. Furthermore, ARTD prevented estrogen deficiency-induced bone loss in ovariectomized mice. Conclusion: ARTD may be a promising candidate for inhibiting cancer-induced bone destruction. The application of ARTD may be extended to patients with chemotherapy-induced ovarian failure or postmenopausal osteoporosis.

As a potent and selective allosteric inhibitor of MEK, TAK-733 has been shown to exert anti-cancer effects for a wide range of cancers both in vitro and in vivo. However, its effects on inhibiting growth have never been investigated in the cardiovascular system, where regulation of abnormal vascular smooth muscle cell growth in neointimal hyperplasia is an important area of focus. Angiotensin II was used to mimic inflammatory neointimal hyperplasia in an in vitro environment, and balloon catheter-induced injury with an infusion of angiotensin II was used to generate an in vivo rat restenosis model under inflammatory conditions. TAK-733 exerted anti-proliferative and anti-migratory effects on human vascular smooth muscle cells. These multiple effects of TAK-733 were evaluated using various assays, such as cell cycle analysis and wound healing. Interestingly, TAK-733 did not induce apoptosis in smooth muscle cells but only reduced the proliferation rate; additionally, it did not affect EC viability. TAK-733 also exhibited anti-inflammatory activity, as observed by attenuated monocyte adhesion to smooth muscle cells via inhibition of ICAM1 and VCAM1 overexpression. The in vivo study demonstrated that neointimal hyperplasia after balloon injury and angiotensin II stimulation was suppressed by TAK-733, and downregulation of the inflammatory signal and enhanced re-endothelialization were observed. TAK-733 may have therapeutic potential for treating neointimal hyperplasia by attenuating smooth muscle cell proliferation, migration, and inflammation. Thus, TAK-733 could be a promising drug candidate for treating patients with restenosis., Atherosclerosis: Potential therapy based on prospective cancer drug Drug undergoing trials as a cancer treatment shows promise in tackling the narrowing of blood vessels in other diseases. The thickening of arterial walls and consequent restriction of blood flow, typical of conditions like atherosclerosis, increases the risk of heart attacks and strokes. Soyeon Lim and Ki-Chul Hwang at the Catholic Kwandong University, South Korea, and co-workers have investigated the efficacy of a prospective cancer drug called TAK-733 against atherosclerosis both in cell culture and in trials on rat models of the disease. The team hypothesized that TAK-733’s anti-cancer effects could prove useful in treating other conditions. They demonstrated that TAK-733 successfully blocked the proliferation and migration of vascular smooth muscle cells, the overexpression of which is a dominant factor in the development of atherosclerosis.

In this work, the chronoamperometry-based redox cycling of 3,3',5,5'-tetramethylbenzidine (TMB) was performed by using interdigitated electrode (IDE). The signal was obtained from two sequential chronoamperometric profiles: (1) with the generator at the oxidative potential of TMB and the collector at the reductive potential of TMB, and (2) with the generator at the reductive potential of TMB and the collector at the oxidative potential of TMB. The chronoamperometry-based redox cycling (dual mode) showed a sensitivity of 1.49 μA/OD, and the redox cycling efficiency was estimated to be 94% (n = 10). The sensitivities of conventional redox cycling with the same interdigitated electrode and chronoamperometry using a single working electrode (single mode) were estimated to be 0.67 μA/OD and 0.18 μA/OD, respectively. These results showed that the chronoamperometry-based redox cycling (dual mode) could be more effectively used to quantify the oxidized TMB than other amperometric methods. The chronoamperometry-based redox cycling (dual mode) was applied to immunoassays using a commercial ELISA kit for medical diagnosis of the human hepatitis B virus surface antigen (hHBsAg). Finally, the chronoamperometry-based redox cycling (dual mode) provided more than a 10-fold higher sensitivity than conventional chronoamperometry using a single working electrode (single mode) when applied to a commercial ELISA kit for medical diagnosis of hHBsAg.

Introduction Previous occasional successes after delayed replantation suggest that the presence of viable cells may not be the only factor for successful periodontal regeneration in delayed replantation. Various other factors such as proteins or the extracellular matrix (ECM) may play a role in this process. The purpose of this study was to characterize changes in the proteome components of periodontal ligament (PDL) tissue after hypothermic preservation of the tooth. Methods Extracted teeth were divided into 4 groups: immediate sampling, sampling after 1 week of preservation at 4°C, sampling after 2 weeks of preservation at 4°C, and sampling after 1 week of dry storage at room temperature as a negative control. PDL tissues were collected from the root and stored immediately in liquid nitrogen. The tissues were subjected to 2-dimensional gel electrophoresis, and spot selection was executed. Selected spots that maintained the protein volume were then processed with matrix-assisted laser desorption and ionization time-of-flight mass spectrometry to identify the nature of the proteins. Results Thirty-five selected spots were analyzed. Sixteen spots were identified as vimentin, and 3 spots were type VI collagen. The size of the 16 vimentin spots decreased gradually with increasing storage time, from 0 to 2 weeks, and decreased rapidly after dry storage. However, only the dry storage group differed significantly from the immediately sampled group. Conclusions Vimentin was the most prominent protein followed by type VI collagen in volumetrically maintained protein spots. Although these proteins are known to be closely related with ECM integrity, the role of these proteins in delayed replantation is beyond the scope of this study. Further studies are needed to elucidate the possible role of these proteins for periodontal healing of delayed replantation.

// Junhee Park 1, 2 , Hyun-Jeong Kim 2 , Ki Rim Kim 3 , Sun Kyoung Lee 2 , Hyungkeun Kim 2, 4 , Kwang-Kyun Park 1, 2, 4 , Won-Yoon Chung 1, 2, 4 1 Department of Dentistry, Graduate School, Yonsei University, Seoul 120-749, Republic of Korea 2 Department of Oral Biology, Oral Cancer Research Institute, and BK21 PLUS Project, Yonsei University College of Dentistry, Seoul 120-752, Republic of Korea 3 Department of Dental Hygiene, Kyungpook National University, Sangju 742-711, Korea 4 Department of Applied Life Sciences, Graduate School, Yonsei University, Seoul 120-749, Republic of Korea Correspondence to: Won-Yoon Chung, email: wychung@yuhs.ac Kwang-Kyun Park, email: biochelab@yuhs.ac Keywords: oral squamous cell carcinoma, bone invasion, runt-related transcription factor 3, transforming growth factor-β Received: October 08, 2015 Accepted: December 15, 2016 Published: December 21, 2016 ABSTRACT High recurrence and lower survival rates in patients with oral squamous cell carcinoma (OSCC) are associated with its bone invasion. We identified the oncogenic role of RUNX3 during bone invasion by OSCC. Tumor growth and the generation of osteolytic lesions were significantly inhibited in mice that were subcutaneously inoculated with RUNX3-knockdown human OSCC cells. RUNX3 knockdown enhanced TGF-β-induced growth arrest and inhibited OSCC cell migration and invasion in the absence or presence of transforming growth factor-β (TGF-β), a major growth factor abundant in the bone microenvironment. RUNX3 knockdown induced cell cycle arrest at the G1 and G2 phases and promoted G2 arrest by TGF-β in Ca9.22 OSCC cells. RUNX3 knockdown also inhibited both the basal and TGF-β-induced epithelial-to-mesenchymal transition by increasing E-cadherin expression and suppressing the nuclear translocation of β-catenin. In addition, the expression and TGF-β-mediated induction of parathyroid hormone-related protein (PTHrP), one of key osteolytic factors, was blocked in RUNX3-knockdown OSCC cells. Furthermore, treating human osteoblastic cells with conditioned medium derived from RUNX3-knockdown OSCC cells reduced the receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin ratio compared with treatment with conditioned medium from RUNX3-expressing cells. These findings indicate that RUNX3 expression in OSCC cells contributes to their bone invasion and the resulting osteolysis by inducing their malignant behaviors and production of osteolytic factors. RUNX3 alone or in combination with TGF-β and PTHrP may be a useful predictive biomarker and therapeutic target for bone invasion by oral cancer.

Tonsillectomy is the most common type of surgical procedure performed in preschool children. Due to short period of hospitalization, mothers are expected to manage their children's care at home. However, they are rarely provided with sufficient information about postoperative management. This study aims to determine the effectiveness of providing caregivers with information on tonsillectomy care by smartphone text messaging in increasing their mothers' knowledge, reducing the anxiety, and improving the sick-role behavior of pediatric tonsillectomy patients.A sample of 61 pediatric patients and their mothers was recruited. Participants were randomly assigned into either the experimental group (n = 27) or the control group (n = 34). The control group was given information about the tonsillectomy by conventional textual and verbal means, whereas the experimental group received the same information in the form of 10 text messages during the period from hospitalization to their first follow-up visits.Results of mixed design, two-way analysis of variance indicated significant interaction effects between time points and groups for mothers' knowledge (F = 4.26, p = 0.043) and children's anxiety (F = 3.32; p = 0.037). Thus, the results do support the effectiveness of tonsillectomy education using smartphone text messaging in increasing mothers' knowledge and reducing children's anxiety.These results can be applied to preoperative and postoperative interventions for children not only for tonsillectomy but also for many other operations. The development of various educational programs using smartphone text messaging for postoperative patient management would also be valuable.

Background/aim Colorectal cancer (CRC) is one of the most common in the world and its prevalence is rapidly increasing. Jagged-1-activated Notch signaling by apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) promotes CRC, and high expression of Jagged-1 is associated with poor prognosis. However, its clinical implication is unknown. The aim of this study was to investigate the clinical role of Jagged-1-activated Notch signaling by APEX1. Materials and methods The 5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the anti-cancer efficacy of 5-fluorouracil (5-FU), oxaliplatin, and irinotecan. Tissue from CRC patients was analyzed to assess the clinical specificity of Jagged-1 activated by APEX1. Results The half-maximal inhibitory concentration (IC50) in cells co-expressing APEX1 and Jagged-1 cells was higher than that in cells expressing only APEX1. These results indicated that the simultaneous expression of APEX1 and Jagged-1 might be associated with chemoresistance toward 5-FU, oxaliplatin, and irinotecan. Analysis of tissue from CRC patients revealed that high expression of Jagged-1 was associated with a statistically significantly low response to chemotherapy. Conclusion Overexpression of Jagged-1 by APEX1 might serve as a predictor of response to chemotherapy and of poor prognosis, and moreover may be a therapeutic target for chemotherapy of advanced CRC.

Objective Hearing loss is a major side effect of cisplatin chemotherapy. Although cell death in cisplatin-induced ototoxicity is primarily caused by apoptosis, the exact mechanism behind the ototoxic effects of cisplatin is not fully understood. Autophagy is generally known as a pro-survival mechanism that protects cells under starvation or stress conditions. However, recent research has reported that autophagy plays a functional role in cell death also. This study aimed to investigate the role of autophagy in cisplatin-induced ototoxicity in an auditory cell line. Methods Cultured HEI-OC1 cells were exposed to 30 μM cisplatin for 48 h, and cell viability was tested using MTT assays. To evaluate whether autophagy serves to cell death after cisplatin exposure, western blotting and immunofluorescence staining for LC3-II were performed. Markers of two autophagy-related pathways, mTOR and class III PI3K, were also investigated. Results The formation of the autophagic protein LC3-II in response to 30 μM cisplatin increased with time. The early upregulation of autophagy exerted cytoprotective activity via the class III PI3K pathway. But later increase in autophagy induced cell death by suppressing the mTOR pathway. Conclusion Our results prove that autophagy could induce cell death during cisplatin-induced ototoxicity, and modulating the autophagic pathway might be another strategy against cisplatin-induced ototoxicity.

In this work, the gram-negative bacterium Escherichia coli strain BL21(DE3) (with lipopolysaccharide (LPS) in its outer membrane) and its modified ClearColi™ strain (lacking LPS) were used for the separation of anti-LPS antibodies from human serum by the following steps: (1) binding of the serum proteins to BL21(DE3); (2) dissociation of the bound proteins (including anti-LPS antibodies) from BL21(DE3) with acid; (3) filtering of the dissociated proteins using ClearColi to remove unwanted proteins; and (4) separation of the antibody fraction by protein-A column chromatography. The binding properties of the separated antibodies were analyzed by fluorescence-activated cell sorting to confirm their selective binding to LPS on the outer membrane of BL21(DE3), and by thermophoretic immunoassay to estimate their dissociation constant. The in vitro applicability of the separated anti-LPS antibodies was demonstrated through a fluorescence assay of BL21(DE3), after immobilizing the antibodies onto a modified microplate surface. The electrochemical detection of BL21(DE3) was also achieved after immobilizing the anti-LPS antibodies onto a gold electrode.

Background Adipose tissue-derived mesenchymal stem cells (AT-MSCs) offer potential as a therapeutic option for chronic discogenic low back pain (LBP) because of their immunomodulatory functions and capacity for cartilage differentiation. The goal of this study was to assess the safety and tolerability of a single intradiscal implantation of combined AT-MSCs and hyaluronic acid (HA) derivative in patients with chronic discogenic LBP. Methods We performed a single-arm phase I clinical trial with a 12-month follow-up and enrolled 10 eligible chronic LBP patients. Chronic LBP had lasted for more than 3 months with a minimum intensity of 4/10 on a visual analogue scale (VAS) and disability level ≥ 30% on the Oswestry Disability Index (ODI). The 10 patients underwent a single intradiscal injection of combined HA derivative and AT-MSCs at a dose of 2 × 107 cells/disc (n = 5) or 4 × 107 cells/disc (n = 5). Safety and treatment outcomes were evaluated by assessing VAS, ODI, Short Form-36 (SF-36), and imaging (lumbar spine X-ray imaging and MRI) at regular intervals over 1 year. Results No patients were lost at any point during the 1-year clinical study. We observed no procedure or stem cell-related adverse events or serious adverse events during the 1-year follow-up period. VAS, ODI, and SF-36 scores significantly improved in both groups receiving both low (cases 2, 4, and 5) and high (cases 7, 8, and 9) cell doses, and did not differ significantly between the two groups. Among six patients who achieved significant improvement in VAS, ODI, and SF-36, three patients (cases 4, 8, and 9) were determined to have increased water content based on an increased apparent diffusion coefficient on diffusion MRI. Conclusions Combined implantation of AT-MSCs and HA derivative in chronic discogenic LBP is safe and tolerable. However, the efficacy of combined AT-MSCs and HA should be investigated in a randomized controlled trial in a larger population. Trial registration ClinicalTrials.gov NCT02338271 . Registered 7 January 2015.

Antila et al. show that meningeal lymphatic vessels in mice develop postnatally. Interruption of VEGF-C/VEGFR3 signal transduction arrests their development. In adult mice, VEGFR3 deletion and VEGFR3 blockers, including a clinically available tyrosine kinase inhibitor, induce regression of meningeal lymphatic vessels., The recent discovery of meningeal lymphatic vessels (LVs) has raised interest in their possible involvement in neuropathological processes, yet little is known about their development or maintenance. We show here that meningeal LVs develop postnatally, appearing first around the foramina in the basal parts of the skull and spinal canal, sprouting along the blood vessels and cranial and spinal nerves to various parts of the meninges surrounding the central nervous system (CNS). VEGF-C, expressed mainly in vascular smooth muscle cells, and VEGFR3 in lymphatic endothelial cells were essential for their development, whereas VEGF-D deletion had no effect. Surprisingly, in adult mice, the LVs showed regression after VEGF-C or VEGFR3 deletion, administration of the tyrosine kinase inhibitor sunitinib, or expression of VEGF-C/D trap, which also compromised the lymphatic drainage function. Conversely, an excess of VEGF-C induced meningeal lymphangiogenesis. The plasticity and regenerative potential of meningeal LVs should allow manipulation of cerebrospinal fluid drainage and neuropathological processes in the CNS.

Breast cancer mainly spreads to bone, causing decreased survival of patient. Human antigen R (HuR) and chemokines are important molecules associated with mRNA stability and cell-cell interaction in cancer biology. Here, HuR knockdown inhibited bone metastasis and osteolysis of metastatic breast cancer cells in mice and HuR expression promoted the metastatic ability of cancer cells via CCL20 and GM-CSF. In contrast with the findings for GM-CSF, ELAVL1 and CCL20 expressions were markedly increased in breast tumor tissues and ELAVL1 expression showed a strong positive correlation with CCL20 expression in breast cancer subtypes, particularly the basal-like subtype. Metastasis-free survival and overall survival were decreased in the breast cancer patients with high CCL20 expression. We further confirmed the role of CCL20 in breast cancer bone metastasis. Intraperitoneal administration of anti-CCL20 antibodies inhibited osteolytic breast cancer bone metastasis in mice. Treatment with CCL20 noticeably promoted cell invasion and the secretion of MMP-2/9 in the basal-like triple-negative breast cancer cell lines, not the luminal. Moreover, CCL20 elevated the receptor activator of nuclear factors kappa-B ligand/osteoprotegerin ratio in breast cancer and osteoblastic cells and mediated the crosstalk between these cells. Collectively, HuR-regulated CCL20 may be an attractive therapeutic target for breast cancer bone metastasis.

Chondrogenic differentiation of mesenchymal stem cells (MSCs) is critical for successful cartilage regeneration. Several methods have been developed to attempt to chondrogenic differentiation, because chondrogenic differentiated cells can form stable cartilage and induce expression of a cartilage-specific phenotype. In this study, we found that both H-89 and microRNA-23b induced differentiation into chondrocyte of hMSCs through down-regulation of protein kinase A (PKA) signaling. The small molecule, H-89, was identified by PCA analysis as a potential mediator of chondrogenic differentiation. H-89 induced the expression of the chondrocyte marker, aggrecan, as well as miR-23b. We searched that miR-23b regulates protein level of PKA. When miR-23b was transfected into hMSCs, chondrogenic differentiation was induced. We confirmed the target of miR-23b using a reporter gene assay. Furthermore, not only H-89 or miR-23b-treated cells, but also cell co-treated with H-89 and miR-23b differentiated into chondrocytes. Our results indicate that H-89 induces the expression of endogenous miR-23b, thereby inducing chondrogenic differentiation by negatively inhibition of PKA signaling.

Background: Although a number of association studies of gastric cancer (GC) risk have been conducted worldwide, their results have been inconsistent among different populations. The association between GC incidence and Helicobacter pylori ( H. pylori ) infection is somewhat of an enigma that has yet to be clearly explained. Geographically-restricted positive selection due to unique environmental pressures often result in large allele frequency differences between populations. Thus, population differences need to be investigated when attempting to identify genes that contribute to phenotypes that differ greatly between populations. Methods: We analyzed population differences in 18 polymorphisms of 12 GC-associated or immune response-related genes from 3 ethnic groups comprising 50 Koreans, 46 Indians, and 60 Caucasians; these groups differed in H. pylori seropositivity and susceptibility to GC. Results: An interleukin 10 ( IL10 ) polymorphism demonstrated a significantly different genotype distribution ( F ST = 0.306, P = 0.014), indicating a large difference between the Korean and Caucasian populations. The odds ratio of IL10 polymorphism allele between the populations was 38.32 (95% confidence interval, 11.49–127.83). Conclusion: This finding, taken together with previous evidence, provides a possible explanation for previous discrepant association results and supports the idea that IL10 gene polymorphisms can differentially affect GC development among populations.

It has been suggested that the haplotypic relationship between microsatellite markers and single nucleotide polymorphisms (SNPs) is of considerable importance, as microsatellite markers can potentially be incorporated into haplotypes containing SNPs to increase marker density across a region of interest. However, SNPs and microsatellite markers have different mutation rates and durations, and it is conceivable that the linkage disequilibrium (LD) patterns between the genetic markers may considerably differ. We assessed the LD patterns using 1,661 SNPs and 65 microsatellite markers along chromosome 22 and investigated whether common patterns of LD between the two genetic markers are deduced from the results. The results demonstrated that the patterns of LD among microsatellite markers varied considerably and the LD runs of SNPs and microsatellite markers showed distinct patterns. Microsatellite markers have a much higher mutation rate and the evolution of microsatellite markers is a more complex process which has distinct mutation properties from those of SNPs. We consider that these might contribute to the different LD patterns between the two genetic markers. Therefore, it would seem inadvisable to make assumptions about persistence of LD across even a relatively small genetic distance among microsatellite markers and to construct mixed marker haplotypes/LD maps employing microsatellite markers.

IntroductionMesenchymal stem cells (MSCs) have therapeutic potential for the repair of myocardial injury. The efficacy of MSC therapy for myocardial regeneration mainly depends on the survival of cells after transplantation into the infarcted heart. In the transplanted regions, reactive oxygen species (ROS) can cause cell death, and this process depends on caspase activation and autophagosome formation.MethodsA Software TargetScan was utilized to search for microRNAs (miRNAs) that target caspase-3 mRNA. Six candidate miRNAs including let-7b were selected and transfected into human MSCsin vitro. Expression of MEK-EKR signal pathways and autophagy-related genes were detected. Using ischemia/reperfusion model (I/R), the effect of MSCs enriched with let-7b was determined after transplantation into infarcted heart area. Miller catheter was used to evaluate cardiac function.ResultsHere, we report that let-7b targets caspase-3 to regulate apoptosis and autophagy in MSCs exposed to ROS. Let-7b-transfected MSCs (let-7b-MSCs) showed high expression of survival-related proteins, including p-MEK, p-ERK and Bcl-2, leading to a decrease in Annexin V/PI- and TUNEL-positive cells under ROS-rich conditions. Moreover, autophagy-related genes, including Atg5, Atg7, Atg12 and beclin-1, were significantly downregulated in let-7b-MSCs. Using a rat model of acute myocardial infarction, we found that intramyocardial injection of let-7b-MSCs markedly enhanced left ventricular (LV) function and microvessel density, in accordance with a reduced infarct size and the expression of caspase-3.ConclusionsTaken together, these data indicate that let-7b may protect MSCs implanted into infarcted myocardium from apoptosis and autophagy by directly targeting caspase-3 signaling.

Background Despite recent advances in the investigation of myeloproliferative neoplasms (MPN), the impact of genetic heterogeneity on its molecular pathogenesis has not been fully elucidated. Thus, in this study, we aim to characterize the genetic complexity in Korean patients with polycythemia vera (PV) and essential thrombocythemia (ET). Methods We conducted association studies using 84 single-nucleotide polymorphisms (SNPs) in 229 patients (96 with PV and 133 with ET) and 170 controls. Further, whole-genome sequencing was performed in six patients (two with JAK2 V617F and four with wild-type JAK2), and putative somatic mutations were validated in a further 69 ET patients. Clinical and laboratory characteristics were also analyzed. Results Several germline SNPs and the 46 haplotype were significantly associated with PV and ET. Three somatic mutations in MPDZ, IQCH, and CALR genes were selected and validated. The frequency of the CALR mutation was 58.0% (40/69) in ET patients, who did not carry JAK2/MPL mutations. Moreover, compared with JAK2 V617F-positive patients, those with CALR mutations showed lower hemoglobin and hematocrit levels (P = 0.004 and P = 0.002, respectively), higher platelet counts (P =0.008), and a lower frequency of cytoreductive therapy (P = 0.014). Conclusion This study was the first comprehensive investigation of the genetic characteristics of Korean patients with PV and ET. We found that somatic mutations and the 46 haplotype contribute to PV and ET pathogenesis in Korean patients.

BACKGROUND: Low survival rate of transplanted cells compromises the efficacy of cell therapy. Hexokinase II (HKII) is known to have anti-apoptotic activity through its interaction with mitochondria. The objective was to identify miRNAs targeting HKII and investigate whether miRNA-mediated modulation of HKII could improve the survival of mesenchymal stem cells (MSCs) exposed to H2O2. The expression of HKII in MSCs exposed to H2O2 was evaluated, and HKII-targeting miRNA was screened based on miRNA-target prediction databases. The effect of H2O2 on the expression of the selected HKII-targeting miRNA was examined and the effect of modulation of the selected HKII-targeting miRNA using anti-miRNA on H2O2-induced apoptosis of MSC was evaluated. RESULTS: H2O2 (600 μΜ) induced cell death of MSCs and decreased mitochondrial HKII expression. We have identified miR-181a as a HKII-targeting miRNA and H2O2 increased the expression of miR-181a in MSCs. Delivery of anti-miR-181a, which neutralizes endogenous miR-181a, significantly attenuated H2O2-induced decrease of HKII expression and disruption of mitochondrial membrane potential, improving the survival of MSCs exposed to H2O2. CONCLUSIONS: These findings suggest that H2O2-induced up-regulation of miR-181a contributes to the cell death of MSCs by down-regulating HKII. Neutralizing miR-181a can be an effective way to prime MSCs for transplantation into ischemic tissues.

Background Otolaryngologists encounter cases of various foreign bodies in the oral and pharyngeal regions. One commonly found foreign body is a fish bone, ingested in most cases by carelessness or an accident. These foreign materials are removed by endoscopy or through a simple procedure. However, hypopharyngeal damage is rarely caused by a foreign body in the pharynx following the swallowing of a toothbrush. Case presentation A 44-year-old Asian male visited the emergency room with chief complaints of intraoral pain and dysphagia that had started on the same day. The patient had paranoid-type schizophrenia that began 10 years ago; he had been hospitalized and was being treated at another clinic, and was transferred to the emergency room by the medical staff after swallowing a toothbrush. We successfully removed a toothbrush located within the pharynx of a patient with a history of a psychologic disorder via surgery and conservative treatment. Conclusion The case with this patient, and a rapid diagnosis as well as treatment is imperative. The presence and state of a foreign body must be determined through a careful physical examination and imaging, followed by the immediate removal of the foreign body, all while keeping in mind the possibility of accompanying damage to nearby tissues.

UDP-glucuronosyltransferase 1A1 (UGT1A1) is the key enzyme for bilirubin conjugation. Defects in this enzyme can cause a nonhemolytic unconjugated hyperbilirubinemia, such as Crigler–Najjar syndrome type 1 (CN1) and 2 (CN2) and Gilbert syndrome (GS). In 1991, the cDNA of the human UGT1A1 gene was cloned, and this led to the identification of genetic defects in patients with CN1, CN2, and GS (1)(2)(3). It was shown that homozygous or compound heterozygous mutations of the UGT1A1 gene can lead to these inheritable unconjugated hyperbilirubinemias, and >30 variants have been identified (4)(5). In GS, a TATAA box variant [A(TA)6TAA>A(TA)7TAA] in the promoter region of the UGT1A1 gene has been reported in Caucasian populations, and several polymorphisms in the coding region, including 211G>A (G71R), have been reported to have similar associations with GS in Japanese populations (6)(7)(8). Recently, Sugatani et al. (9) identified a T-to-G substitution in the phenobarbital-responsive enhancer module 3279 bp upstream from the UGT1A1 gene. They suggested that the −3279T>G polymorphism could be another risk factor for the development of mild hyperbilirubinemia Presumably, different combinations of the polymorphisms (haplotypes) in the UGT1A1 gene associated with GS or mild hyperbilirubinemia might produce a variety of serum total bilirubin (T-Bil) concentrations. Because these polymorphisms in the UGT1A1 gene lie in a relatively small region (Fig. 1A⇓ ), a certain extent of linkage disequilibrium (LD) among these polymorphisms is expected. Therefore, haplotype analysis is more reasonable than association analysis using any single polymorphism to reveal the genetic background of an increased serum T-Bil concentration. We analyzed the haplotype structure of the UGT1A1 gene and investigated its relationship to the serum T-Bil concentration in healthy Korean males. The study participants were 324 healthy Korean males [mean (SD) age, 49.8 …

Mesenchymal stem cells (MSCs) have the potential to repair and regenerate ischemic heart tissue; however, the poor viability of transplanted MSCs in the ischemic region is a major obstacle to their therapeutic use. This cell death is caused by Fas and Fas ligand (FasL) interactions under harsh conditions. To investigate improving the survival and therapeutic effects of MSCs, we focused our research on Fas–FasL-mediated cell death. In this study, we found that the poor viability of transplanted MSCs was caused by Fas–FasL interactions between host ischemic myocardial cells and implanted MSCs. In addition, we found that increased Fas expression and the corresponding decrease of cell survival were in close relation to hypoxic MSCs treated with FasL and H2O2. When MSCs were treated with a recombinant Fas/Fc chimera (Fas/Fc) inhibiting Fas–FasL interactions, the expressions of proapoptotic proteins including caspase-8, caspase-3, Bax, and cytochrome-c were attenuated, and the survival of MSCs was recovered. In ischemia–reperfusion injury models, the interaction between FasL in ischemic heart and Fas in implanted MSCs caused a loss of transplanted MSCs, whereas the inhibition of this interaction by Fas/Fc treatment improved cell survival and restored heart function. Thus, our study suggests that Fas–FasL interactions are responsible for activating cell death signaling in implanted stem cells and could be a potential target for improving therapeutic efficacy of stem cells in treating ischemic heart diseases.

The use of synovial fluid-derived mesenchymal stem cells (SFMSCs) obtained from patients with degenerative arthropathy may serve as an alternative therapeutic strategy in osteoarthritis (OA) and rheumatoid arthritis (RA). For treatment of OA and RA patients, autologous transplantation of differentiated MSCs has several beneficial effects for cartilage regeneration including immunomodulatory activity. In this study, we induced chondrogenic differentiation of SFMSCs by inhibiting protein kinase A (PKA) with a small molecule and microRNA (miRNA). Chondrogenic differentiation was confirmed by PCR and immunocytochemistry using probes specific for aggrecan, the major cartilaginous proteoglycan gene. Absorbance of alcian blue stain to detect chondrogenic differentiation was increased in H-89 and/or miRNA-23btransfected cells. Furthermore, expression of matrix metalloproteinase (MMP)-9 and MMP-2 was decreased in treated cells. Therefore, differentiation of SFMSCs into chondrocytes through inhibition of PKA signaling may be a therapeutic option for OA or RA patients.

A lipoblastoma is a rare, benign tumor arising from embryonic white fat. The tumors occur primarily in infancy and early childhood and commonly arise from the limbs and the trunk, but neck involvement is extremely rare. Our case arose in a 22-month-old male presenting with a rapidly enlarging soft mass in the right submandibular area. Lipoblastoma was diagnosed by histologic evaluation, the mass was completely removed, and there was no recurrence at 1-year follow-up.

Successful surgical correction of nasal tip position requires preoperative analysis. Perceived adequate nasal tip position depends on its relationship with other facial features. Nasal tip position can be affected by the subnasal contour, proportion of facial height, and relative facial size and shape. The relation of these factors to the nasolabial angle may not be as important as previously believed.To investigate and compare the factors affecting the ideal location of the tip of the nose in Asian patients using standard photographic measurements.We analyzed measurements of profile photographs and compared different factors that affect nasal tip location, including the nasofrontal, nasolabial, nasomental, and Legan angles and the ratios of the dorsal height to tip projection, the radix height to tip projection, the glabella to subnasale, and the subnasale to mentum.One hundred men, 100 women, 20 to 40 years old, seen for rhinoplasty at the Department of Otorhinolaryngology, Chosun University College of Medicine.Contribution of different facial measurements to the ideal nasal tip position.Nasolabial and nasomental angles exerted a statistically significant effect on ideal nasal tip position, whereas the Legane angle, the ratio of midface to lower face, and the ratio of nasal length to lower face did not show significant effects on nasal tip position.The nasolabial and nasomental angles have important effects on ideal nasal tip position and should be considered together during preoperative evaluation of the location of the nasal tip. Concurrent genioplasty should optimize rhinoplasty outcomes in appropriately selected patients.NA.

A possible prothrombotic effect of elevated thyrotropin (TSH) has been suggested. The mean platelet volume (MPV), which is used to measure the platelet size, can reflect platelet activity. Although limited and inconsistent data regarding the effects of thyroid function on the MPV are available from small-scale case-control studies, no study has been based on a general population, particularly in euthyroid states. The objective of the present study was to determine whether there is an association between the MPV and serum TSH concentrations in an apparently healthy Korean population without overt thyroid disease, but including subjects with unsuspected subclinical hypothyroidism (SCH).We retrospectively studied 6893 asymptomatic Korean adults who were 20 years of age or older and who underwent voluntary regular health check-ups at the Health Promotion Center of Chosun University Hospital. The subjects who met the inclusion and exclusion criteria were subdivided into four groups, such as tertile groups for the TSH reference range and an SCH (TSH ≥4 μIU/mL with a normal free T4 concentration) group according to the TSH level. We compared the mean values of the MPVs among the groups. Multivariate logistic regression analyses were used to identify associations between the highest tertile of the MPV and the TSH subgroups.The mean level of the MPV in all study subjects was 8.12±0.75 femtoliters (fL), and the mean value of the MPV was significantly different in each group. The mean MPV in SCH was significantly higher compared with those of the first tertile (T1) and second tertile (T2). Moreover, the mean MPV increased statistical significantly by increasing tertiles of the TSH concentration and was highest in SCH (T1, 8.08±0.81 fL; T2, 8.09±0.62 fL; T3, 8.13±0.77 fL; SCH, 8.21±0.81 fL; p for trend=0.012). After adjusting for risk factors associated with increasing MPVs and platelet counts, SCH was independently associated with the highest tertile of the MPV (all subjects, odds radio (OR) 1.58 [95% confidence interval (CI) 1.19-2.09]; men, OR 1.70 [CI 1.10-2.64]; women, OR 1.55 [CI 1.06-2.26]).The MPV was positively correlated with the TSH level. SCH is an independently associated factor with the highest tertile of MPV in a general Korean population. We propose that the MPV may contribute to the prothrombotic condition that is associated with SCH and perhaps even in putative euthyroid states where the TSH level is the higher part of the normal range.

Human bone marrow-derived mesenchymal stem cells (hMSCs) are an attractive candidate for cell therapy in heart disease. Low survival and incomplete electromechanical integration between resident cardiomyocytes and transplanted hMSCs remain unsolved. In order for an infarcted heart to tolerate transplantation, differentiation capacity in stem cells must be reinforced. In this study, we found that compound 56, an epidermal growth factor receptor (EGFR) inhibitor, promotes cardiogenic differentiation of hMSCs and the transplantation of hMSCs treated with compound 56 resulted in enhancement of heart functions. Furthermore, hMSCs transfected with microRNA-133a (miR-133a), which targets EGFR, were observed to express cardiac-specific markers. We also discovered that luciferase activity is exclusively decreased by targeting EGFR in hMSCs transfected with miR-133a mimic. These results suggest that EGFR plays a key role in the regulation of cardiogenic differentiation in hMSCs.

To achieve effective regeneration of injured myocardium, it is important to find physiological way of improving the cardiogenic differentiation of stem cells. Previous studies demonstrated that cardiomyocytes from bone marrow-derived mesenchymal stem cells (BMSCs) activated with phorbolmyristate acetate (PMA), a protein kinase C (PKC) activator, restore electromechanical function in infarcted rat hearts. In this study, we investigated the effect of PMA on cardiogenic differentiation of adipose-derived MSCs (ASCs) for clinical applications. To confirm the effect of PMA, ASCs treated with 1 μM PMA were grown for nine days. The expression of cardiac-specific markers (cardiac troponin T, myosin light chain, myosin heavy chain) in PMA-treated MSCs was demonstrated by immunocytochemistry. Alhough few α1A receptors exist in ASCs, α1-adrenergic receptor subtypes were preferentially expressed in PMA-treated ASCs. Moreover, expression of the β-adrenergic and muscarinic receptors increased in PMA-treated ASCs compared to normal cells. The mRNA levels of Ca2+-related factors (SERCA 2a; sarcoplasmic reticulum Ca2+-ATPase, LTCC; L-type Ca2+ channel) in treated ASCs were similar to the levels in cardiomyocytes. Following the transplantation of chemically activated cardiogenic ASCs into infarcted myocardium, histological analysis showed that infarct size, interstitial fibrosis, and apoptotic index were markedly decreased and cardiac function was restored. In conclusion, PMA might induce the cardiogenic differentiation of human ASCs as well as BMSCs. This result suggests successful use of human ASCs in cardiac regeneration therapy.

African populations, including the Sudanese, are underrepresented in warfarin pharmacogenetic studies. We designed a study to determine the associations between the polymorphisms and haplotype structures of CYP2C9 and VKORC1 and warfarin dose response in Sudanese patients, one of the most genetically diverse populations in Africa. The effect of the CYP2C9 polymorphisms (*2, *3, *5, *6, *8, *9, and *11), 20 VKORC1 tag SNPs and haplotypes, and clinical covariates were comprehensively assessed in 203 Sudanese warfarin-treated patients. Patients with the CYP2C9*2,*5,*6, or *11 variant required a daily warfarin dose that was 21% lower than those with CYP2C9*1/*1 (4.7 vs 5.8 mg/day, P

Comparisons of targeted genotyping chips to ready-made chips are important because targeted chips are suitable for fine-scale association mapping with a reasonable cost. Genotypes produced by the Affymetrix Targeted Genotyping (TG) 25K, Affymetrix 500K, and Illumina 550K arrays for regions on chromosomes 2 and 7 of 90 individuals were assessed to investigate genotype accordance between the platforms. The common SNPs in TG the Affymetrix and Illumina arrays showed similar genotype accordance. The consistency rate of the Illumina array to consensus genotypes, i.e., identically called by more than two platforms, was the highest, and that of the Affymetrix array was the lowest. The TG array data showed high accordance and reasonable consistency between platforms.

Proinflammatory genotypes of the IL-1 (interleukin-1) gene have been associated with an increased gastric cancer risk in Caucasians, whereas some studies in Asian populations did not find such association. Furthermore, the risk genotypes differed somewhat between Caucasian and Asian populations. These findings might reflect more complex genetic mechanisms in Asian compared with Caucasian populations. Therefore, we examined a polymorphism (rs1864169) in the general transcription factor 2A1 (GTF2A1) gene as a test of the hypothesis that this transcription factor and IL-IB gene polymorphisms interact in the effects on the gastric cancer risk due to the possible biological relationship between the two genes. Genotyping of the 515 control and 342 case samples was performed by primer extension assay and SNaPshot assays. We found an association between carriage of the IL1B-31C allele and gastric cancer among Koreans, which was observed only in subjects with GTF2A1 GG genotype. The GTF2A1GG/IL1B-31C carrier genotype combination showed stronger association with diffuse type gastric cancer cases. These findings indicate that the effect of the two genetic polymorphisms on risk of gastric cancer is synergistic. Our results also suggest that an additional host genetic factor acting epistatically may differentially contribute to the histogenesis of the diffuse and intestinal subtypes.

The use of mesenchymal stem cells (MSCs) has emerged as a potential new treatment for myocardial infarction. However, the poor viability of MSCs after transplantation critically limits the efficacy of this new strategy. The expression of microRNA-210 (miR-210) is induced by hypoxia and is important for cell survival under hypoxic conditions. Hypoxia increases the levels of hypoxia inducible factor-1 (HIF-1) protein and miR-210 in human MSCs (hMSCs). miR-210 positively regulates HIF-1α activity. Furthermore, miR-210 expression is also induced by hypoxia through the regulation of HIF-1α. To investigate the effect of miR-210 on hMSC survival under hypoxic conditions, survival rates along with signaling related to cell survival were evaluated in hMSCs over-expressing miR-210 or ones that lacked HIF-1α expression. Elevated miR-210 expression increased survival rates along with Akt and ERK activity in hMSCs with hypoxia. These data demonstrated that a positive feedback loop involving miR-210 and HIF-1α was important for MSC survival under hypoxic conditions.

Purpose: This study was conducted to identify the factors that influence nurses’ organizational citizenship behavior. Methods: A cross-sectional design was used, with a convenience sample of 547 nurses from four university hospitals in Seoul and Gyeonggi province. The data were collected through a questionnaire survey done from September 22 to October 10, 2008. The tools used for this study were scales on organizational citizenship behavior (14 items), self-leadership (14 items), empowerment (10 items), organizational commitment (7 items), job satisfaction (8 items) and transformational transactional leadership (14 items). Cronbach’s alpha and factor analysis were examined to test reliability and construct validity of the scale. The data collected were processed using SPSS Window 15.0 Program for actual numbers and percentages, differences in the dependent variable according to general characteristics, and means, standard deviations, correlation coefficients and multiple regression analysis. Results: The factors influencing nurses’ organizational citizenship behavior were identified as self-leadership (β=.247), empowerment (β=.233), job satisfaction (β=.209), organizational commitment (β= .158), and transactional leadership (β=.142). Five factors explained 42.0% of nurses’ organizational citizenship behavior. Conclusion: The results of this study can be used to develop further management strategies for enhancement of nurses’ organizational citizenship behavior.

Background Epithelial-myoepithelial carcinoma is an extremely rare disease that usually occurs in the parotid gland but can occur in a variety of sites such as the nasal cavity, paranasal sinus, and base of the tongue. Case presentation We report a rare case of epithelial-myoepithelial carcinoma, which developed in the subglottic region. A 78-year-old Korean woman visited our hospital complaining of hoarseness, which had developed 1 month previously. Flexible laryngoscopy showed a round mass that blocked approximately 80 % of the tracheal diameter. Complete excision of the mass was carried out under general anesthesia, using a transoral approach. Epithelial-myoepithelial carcinoma was diagnosed following immunohistochemical analysis. Conclusions We report a rare case of epithelial-myoepithelial carcinoma that occurred in the subglottic region. To the best of our knowledge, only one other case has been reported since this disease was first identified approximately 40 years ago.