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Light-emitting organic semiconductors have attracted considerable attention for the nanoscale fabrication of organic-based displays and their potential application in optoelectronics, plasmonics, and photonics. In this study, core-shell hybrid nanostructures of organic rubrene coated on Ag nanoparticles (NPs) have been synthesized using a chemical reduction method. The thickness of the rubrene shell was 2.6–6.0 nm and the diameter of the Ag core was 30–70 nm. The optical and structural properties of the Ag/rubrene core-shell NPs were tuned by hydrothermal (HT) treatment at 190 °C. The Ag/rubrene core-shell NPs were characterized by high-resolution transmission electron microscopy and energy-dispersive X-ray (EDX) spectroscopy before and after the HT treatment, and their structural properties were confirmed through X-ray diffraction (XRD) analysis. XRD peaks related to an orthorhombic phase were observed along with the original triclinic crystal structure of the rubrene shell, and the triclinic crystal domain size increased from 28.2 nm to 30.8 nm owing to the HT treatment. Interestingly, the green light emission (λem = 550 nm) of the Ag/rubrene core-shell NPs changed to blue light emission (λem = 425 nm), increasing in intensity through the HT treatment. This is caused by the crystal change with H-type aggregation and enhanced energy transfer from a surface plasmon resonance.

Highlights • Minimally invasive thyroidectomy (MIT) is useful and famous technique that is being applied to thyroid carcinoma. • MIT without remote access is useful and applicable in thyroid disease and carcinoma in terms of cost effect and cosmetic outcome. • MIT without remote access can be feasible method for thyroid carcinoma with gross extra-thyroidal extension, especially, upper pole carcinoma., Introduction Minimally invasive thyroidectomy (MIT) is technically less damaging tissue and is better cosmetic results with small neck scar, decreasing postoperative pain and neck discomfort. We present the experience of MIT without remote access with case of grossly extra-thyroidal extension positive papillary thyroid carcinoma. Presentation of case A 44-year-old, female presented 1.6 cm irregular hypoechoic nodule at upper pole in Right thyroid gland and diagnosed to papillary thyroid carcinoma. The tumor was suspicious to have extra-thyroidal extension. We performed MIT without remote access for this patient with 2 cm cervical incision. Postoperative course was uneventful and patient was discharged on the 3th postoperative day. At present, she is taking 100mcg levothyroxine and is free of disease 3 years post-surgery. Conclusion If experienced surgeons can get sufficient resection margin and control bleeding of superior thyroid artery, MIT without remote access can be feasible method for thyroid carcinoma with gross extra-thyroidal extension, especially, upper pole carcinoma.

Perception of threats is essential for survival. Previous findings suggest that parallel pathways independently relay innate threat signals from different sensory modalities to multiple brain areas, such as the midbrain and hypothalamus, for immediate avoidance. Yet little is known about whether and how multi-sensory innate threat cues are integrated and conveyed from each sensory modality to the amygdala, a critical brain area for threat perception and learning. Here, we report that neurons expressing calcitonin gene-related peptide (CGRP) in the parvocellular subparafascicular nucleus in the thalamus and external lateral parabrachial nucleus in the brainstem respond to multi-sensory threat cues from various sensory modalities and relay negative valence to the lateral and central amygdala, respectively. Both CGRP populations and their amygdala projections are required for multi-sensory threat perception and aversive memory formation. The identification of unified innate threat pathways may provide insights into developing therapeutic candidates for innate fear-related disorders.

Cytotoxic T-lymphocyte-associated protein 4-Ig (CTLA4-Ig) produced using Chinese hamster ovary (CHO) cell lines is a fusion protein of CTLA4 and the Fc region of antibody. In the present study, we identified and overexpressed genes capable of increasing sialic acid levels in CTLA4-Ig to develop cell lines using glycoengineering technology. CTLA4-Ig was produced using CHO cells overexpressing N-acetylglucosaminyltransferase (GnT) and α2,6-sialyltransferase (α2,6-ST). The conditions were wild type (WT), overexpression (GnT-IV, GnT-V, and α2,6-ST), and co-overexpression (GnT-IV and α2,6-ST, and GnT-V and α2,6-ST). GnT-IV and GnT-V were transfected into CHO cells to determine tri-antennary structure formation in CTLA4-Ig. CHO

Chinese hamster ovary (CHO) cells have been widely used for the production of glycoproteins due to various advantages such as high productivity, ease of genetic manipulation, adaptability to serum-free media, and human-like glycosylation. Glycosylation, which occurs sequentially using nucleotide sugars as donor substrates, can affect the therapeutic function of glycoproteins. Terminal sialic acid residues of N-glycans play an important role in determining in vivo half-life of glycoproteins. Therefore, various strategies have been developed to enhance sialylation of glycoproteins. In this study, a nucleotide sugar precursor feeding strategy was optimized to increase sialic acid content of albumin-erythropoietin (Alb-EPO). Glucosamine, galactose, and N-acetylmannosamine were added to CHO cell cultures in lag (day 0) or exponential phase (day 3). Central composite design and response surface methodology were used to evaluate the effects of nucleotide sugar precursors on cell growth, titer, and sialic acid content. For the exponential feeding strategy, culture performance was not altered by addition of optimal precursor concentrations, whereas sialic acid contents increased 1.43-fold compared to the control. Consequently, our nucleotide sugar precursor feeding strategy can provide an efficient culture process for production of highly sialylated glycans on Alb-EPO.

Background The aim of this study was to investigate the effect of a six-week-long exercise program using outdoor exercise equipment on fitness, insulin resistance and adipocytokines among Korean elderly. Methods A total of 47 participants were randomized into one of the following three groups; control, resistance exercise or combined exercise (aerobic and resistance exercise). The resistance exercise group completed three resistance types of exercise. The combined exercise group completed five exercises, including three resistance types of exercise and two aerobic types of exercise. Participants’ body composition, fitness level, homeostasis model assessment of insulin resistance (HOMA-IR), and adipocytokines were measured at baseline and at the end of six weeks. Results After six weeks of exercise training, participants in the combined exercise group exhibited significant reduction in insulin, HOMA-IR and chemerin levels, while significant reduction was observed in HOMA-IR only in the resistance exercise group compared with the control group. Meanwhile, six weeks of exercise training, whether resistance exercise alone or combined, significantly improved upper body muscular strength/endurance and physical function compared to the control group. Conclusions Six weeks of combined exercise using outdoor exercise equipment was effective in improving fitness, HOMA-IR, circulating chemerin levels, and other known risk factors of chronic diseases.

Introduction This study was conducted to evaluate the efficacy of traditional acupuncture (TA) for treatment of hot flashes (HFs) in peri -menopausal and post-menopausal women based on a systematic review of randomized controlled trials (RCTs). Methods The following international electronic databases: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI), and four Korean medical databases were searched for randomized controlled trials (KISS; Korean-studies Information Service System, Korean Traditional Knowledge Portal, NDSL; National Discovery for Science Leaders, KiSTi; Korean Institute of Science and Technology Information, OASIS; Oriental Medicine Advanced Searching Integrated System). The Cochrane Collaboration's risk of bias was used for quality assessment. The efficacy outcomes were frequency and severity of HFs and quality of life were analyzed using the mean differences in the random effects model. The RevMan 5.3 program was used for meta -analysis. Results Eleven RCTs were included in this systematic review, and nine were included in the meta -analysis. Traditional acupuncture (TA) showed statistically significant improvement relative to sham acupuncture (SA) in HF severity without heterogeneity. However, HF frequency and quality of life (QOL) did not differ between TA and SA. Nevertheless, TA showed significant improvement of HF frequency and severity, and QOL when compared to the control (wait list or no treatment). Conclusion The evidence suggested that TA can improve HF in menopausal women and could be a potential treatment for menopausal women.

Background : This study was conducted to demonstrate the effectiveness and safety of herbal medicine and acupuncture treatment in unexplained infertile females. Methods : One hundred patients were recruited from 3 Korean Medicine hospitals in Korea and they voluntarily signed informed consent agreements. Participants took the Onkyeong-tang (120cc) twice daily between menstrual cycle day (MCD) 3 and 12, and herbal medicine for ovulation and implantation (120cc) twice daily between MCD 13 and 28. They also received acupuncture and moxibustion treatment during 4 menstrual cycles. After the 4 menstrual cycle treatment period, there were 3 menstrual cycle observation periods. The primary outcome is signified by clinical pregnancy rates (CPR) and the secondary outcomes were implantation rates (IR), ongoing pregnancy rates (OPR), and live birth rates. Results : 90 patients completed the study. 13 of the 90 subjects became pregnant. The CPR and IR was 14.44%. 7 of 13 pregnant subjects had continuing pregnancy for over 12 weeks, so that the OPR was 53.85%. The birth rate was 7.78%. All 7 pregnant patients gave birth to their babies and all the babies were live singletons and healthy. There were no serious adverse events. Conclusions : The findings of this study may provide the possibility of effectiveness and safety of Korea medicine treatment for unexplained infertile women. However, further study is required because of several limitations including lack of control and small sample size.

Cinnamaldehyde (CA) is a food compound that has previously been observed to be protective against obesity and hyperglycemia in mouse models. In this study, we aimed to elucidate the mechanisms behind this protective effect by assessing the cell-autonomous response of primary adipocytes to CA treatment.Primary murine adipocytes were treated with CA and thermogenic and metabolic responses were assessed after both acute and chronic treatments. Human adipose stem cells were differentiated and treated with CA to assess whether the CA-mediated signaling is conserved in humans.CA significantly activated PKA signaling, increased expression levels of thermogenic genes and induced phosphorylation of HSL and PLIN1 in murine primary adipocytes. Inhibition of PKA or p38 MAPK enzymatic activity markedly inhibited the CA-induced thermogenic response. In addition, chronic CA treatment regulates metabolic reprogramming, which was partially diminished in FGF21KO adipocytes. Importantly, both acute and chronic effects of CA were observed in human adipose stem cells isolated from multiple donors of different ethnicities and ages and with a variety of body mass indexes (BMI).CA activates thermogenic and metabolic responses in mouse and human primary subcutaneous adipocytes in a cell-autonomous manner, giving a mechanistic explanation for the anti-obesity effects of CA observed previously and further supporting its potential metabolic benefits on humans. Given the wide usage of cinnamon in the food industry, the notion that this popular food additive, instead of a drug, may activate thermogenesis, could ultimately lead to therapeutic strategies against obesity that are much better adhered to by participants.

Background Acupuncture and herbal medicine have been used as additional treatments for infertility or as an adjuvant treatment of assisted reproductive technology (ART) in infertility. Many systematic reviews (SRs) and meta-analyses (MA) have been published. This paper reviews the SRs and MA of acupuncture and herbal medicine on infertility to provide evidence for clinical decision making. Methods A comprehensive literature search of SRs and MA for the effects of acupuncture and herbal medicine on infertility was conducted using nine databases. Two independent reviewers extracted the data of the selected SR and MA and evaluated their methodological quality using the ‘Assessment of multiple systematic reviews 2 (AMSTAR2)’. Results Twenty-one studies were included in this analysis. Eight studies were published in China, and three studies each were published in the USA, UK, and Australia. Conflicting evidence on the efficacy of acupuncture for infertile women has been reported. Herbal medicine for infertile women undergoing ART, women with anovulation, and women with polycystic ovary syndrome helped improve the clinical pregnancy rate. The methodological quality of SRs and MAs evaluated by AMSTAR 2 was low or very low because the protocol or list of excluded studies were omitted. Conclusion Herbal medicine tended to be effective in infertility, but acupuncture had low evidence of an effect on infertility. The methodological quality of the published SRs and MAs was underestimated because AMSTAR2 is a more rigorous assessment tool than the previous version.

Background This study aimed to obtain the symptom, prescription and therapeutic patterns for the treatment of patients with menopausal syndrome in major Korean medicine (KM) hospitals. Methods We used a retrospective chart review of climacteric disorder and postmenopausal syndrome patients by examining medical records (ICD-10, menopausal and female climacteric states: N95.1, Menopausal and perimenopausal disorder, unspecified: N95.9) from eight university KM hospitals in South Korea. Results The main symptoms of 1,682 patients with menopausal disorders visiting 8 college-affiliated oriental medicine hospitals were hot flush, hyperhidrosis, fatigue, insomnia, and chest tightness. Guipi-tang (decoction), Siwu Guipi-tang (decoction), Qingxin Lianzi-yin (decoction), Jiawei Xiaoyao-san (powder) and Guipi Wendan-tang (decoction) were the most commonly prescribed herbal medicines for menopausal disorders. Patients were most often treated with a combination of herbal medicine and acupuncture. Conclusion Our study shows that the current prescribed herbal medicines were used for treating menopausal disorders in Korean medicine hospitals. However, the objectivity of the efficacy assessment should be studied further.

Elevated circulating insulin is associated with increased risk of recurrence and cancer mortality in early-stage colorectal cancer (CRC). We conducted a randomized controlled trial to determine the effect of a 12-week home-based exercise program on fasting insulin, adipocytokines, and physical function in CRC survivors.One hundred and twenty-three stage II-III CRC patients were randomly assigned to either a home-based exercise (n=62) or standard care control group (n=61) for 12weeks. Home-based exercise consisted of aerobic and resistance training, with a goal of obtaining ≥18 metabolic equivalent task (MET)-h/wk. Participants in the exercise group were instructed to participate in18MET-h/wk. of aerobic and resistance exercise while the participants in the control group were asked to maintain their usual daily activity. The primary outcome was fasting insulin levels. Secondary outcomes were adiponectin, TNF-α levels and 6min walk distance from baseline to post-intervention.After the 12-weeks, moderate-vigorous physical activity participation increased from 9.1±14.7MET-h/wk. to 26.6±21.7MET-h/wk. in the exercise group, with no change in the control group (p0.01 for group and time interaction). Circulating insulin level decreased by 1μU/ml (6.0±3.9 vs. 5.0±3.5, p=0.009) in the exercise group with no change in the control group (p=0.022 for group and time interaction). A similar trend was observed in TNF-α (p=0.030 for group and time interaction). Six minute walk distance increased by 25.2m in the exercise group with no change in the control group (p=0.061 for group and time interaction).The 12week home-based exercise program increased level of physical activity and decreased circulating insulin levels in CRC survivors.

Terminal sialic acids on N-glycan of recombinant human erythropoietin are very important for in vivo half-life, as this glycoprotein has three N-glycosylation sites. N-acetylglucosaminyltransferases I, II, IV, and V (i.e. Mgat1, Mgat2, Mgat4, and Mgat5) catalyze the formation of a glycan antennary structure. These enzymes display different reaction kinetics for a common substrate and generally show low expression in Chinese hamster ovary (CHO) cells. Therefore, genetic control of Mgat expression is an effective method to increase sialic acid contents by enhancing glycan antennarity. To produce highly sialylated albumin-erythropoietin (Alb-EPO), we co-overexpressed the Mgat1 and Mgat4 genes in CHO cells and determined the optimal ratio of Mgat1:Mgat4 gene expression. All transfected cell lines showed increased gene expression of Mgat4, including Mgat1 overexpressing cell line. Sialic acid content of Alb-EPO was highest in co-transfected cells with excess Mgat4 gene, and these cells showed a higher tri- and tetra-antennary structure than control cells. Based on these results, we suggest that co-transfection of the Mgat1 and Mgat4 genes at a ratio of 2:8 is optimal for extension of antennary structures. Also, regulation of Mgat gene expression in the glycan biosynthesis pathway can be a novel approach to increase the terminal sialic acids of N-glycans.

Ethnopharmacological relevance Evodiae Fructus (EF) is the dried, unripe fruit of Evodia rutaecarpa Benth., and one of the main components of traditional herbal prescriptions issued for the treatment of sterility caused by irregular menstruation in Korea. However, scientific evidence regarding the efficacy and action mechanism of EF is lacking. Aim of the study In this study, the authors established an in vitro screening tool to identify promising new drug candidates in herbal medicines for the prevention and treatment of premature ovarian failure. The protective effects of EF extracts against 4-vinylcyclohexene diepoxide (VCD)-induced ovotoxicity were investigated and the molecular mechanism responsible was sought. Material and Methods EF extract was prepared by boiling EF in water and its quality was confirmed by high performance liquid chromatography. CHO-K1 (Chinese hamster ovary cells) and COV434 (human ovarian granulosa cells) cells were plated, pretreated with EF extract for 2 h and then treated with 1.5 mM or 0.5 mM VCD for 24 h, respectively. Cell viabilities were measured using an MTT assay, and protein levels were determined by western blotting. Results VCD significantly suppressed the viability of both CHO-K1 and COV434 cells in a dose-dependent manner and induced the apoptosis of CHO-K1 cells at 1.5 mM. EF extract dose-dependently blocked the ovotoxicity induced by treatment with VCD. Furthermore, EF extract significantly activated Akt and downstream effectors such as mTOR and GSK-3β in CHO-K1 cells. The ability of EF extract to prevent cytotoxicity by VCD was antagonized by pretreatment of LY294002, a PI3K/Akt inhibitor. Conclusion EF has the ability to protect ovary cells against VCD-induced ovotoxicity, probably via Akt activation. These results suggest that the beneficial effects of EF might be useful for preventing premature ovarian failure or unexplained infertility caused by environmental factors.

Introduction Traditional Korean medicine (TKM) has a long history in the treatment of infertility. Many infertile couples are choosing TKM as a primary or adjuvant therapeutic tool to treat infertility in Korea. The purpose of this review was to summarize and evaluate the results on effectiveness and safety from literature published on traditional Korean medicine (TKM) infertility support programs with regards to spontaneous pregnancy rates (SPR) in infertile women in Korea. Methods Pertinent studies and reports conducted from 2009 to 2015 were collected from the Association of Korean Medicine. The primary outcome was live birth rate (LBR); the secondary outcomes were clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR), adverse events (AEs). Results Seven prospective studies (324 participants) were identified. We found that the total LBR (three studies, n = 90) was 21.1%, OPR (five studies, n = 236) was 18.6%, and CPR (six studies, n = 277) was 24.9% after TKM treatment for three to six months. Only one study reported mild AEs of constipation, nausea, and heartburn. Conclusions This review suggests that TKM could be an effective option for infertile women. Further rigorously designed studies are needed to confirm the effectiveness and safety of TKM treatment in infertile women.

A human hybrid cell line, F2N78, was developed by somatic fusion of HEK293 and Namalwa cells for the production recombinant biopharmaceutical proteins. In this study, we performed perfusion culture to verify its potential in culture process used for human cell expression platform. Cell viability could be maintained over 90% and high viable cell density was obtained at higher than 1.0 × 10(7) cells/mL by bleeding process in perfusion culture. The cells were adapted well in both culture modes, but there were apparent differences in protein quality. Compared to fed-batch culture, degalactosylated forms such as G0F and G0 as well as Man5 showed no significant increases in perfusion culture. In terms of charge variants, acidic peaks increased, whereas main peaks constantly decreased according to the length of culture period in both methods.

A series of Cu(II) complexes, [LnCuCl2] (Ln = LA–LF), supported by N′-aromatic-group-substituted N,N-bis((3,5-dimethyl-1H-pyrazol-1-yl)methylamine ligands have been synthesized. Variations of substituents at the ortho position of the aniline moiety influenced the solid-state structures of these complexes. The X-ray structures of [LnCuCl2] (Ln = LA–LC and LF) revealed that ligands are coordinated in a N,N,N-tridentate fashion to Cu(II) center and adopted a distorted square-pyramidal geometry, while [LDCuCl2] with N,N-bidentate coordination adopts distorted tetrahedral geometry. These complexes were capable of polymerizing methyl methacrylate (MMA) in the presence of modified methylaluminoxane (MMAO), with [LFCuCl2] displaying the highest activity (2.81 × 104 g PMMA (mol Cu)−1h−1). Regardless of ligand architecture, syndio-enriched PMMAs have been furnished with a slightly broader polydispersity index (PDI). Additionally, the in situ generated dimethyl derivatives, polymerized rac-LA and furnished PLA with mediocre heterotacticities at room temperature. Importantly, the catalytic efficiencies of the Cu(II) complexes studied have been found to be influenced by the steric and electronic properties of ligand.

Recombinant human acid alpha-glucosidase (rhGAA) from Chinese hamster ovary cells is the only approved treatment for patients with Pompe disease. In this study, rhGAAs were produced in transgenic rice cell suspension cultures under eight different conditions; untreated, 5 μM of 2-fluoro- l -fucose (2-FF), 50 μM of 2-FF, 100 μM of 2-FF, 100 μM of 2-FF + 0.5% Pluronic F-68 (PF-68), 100 μM of 2-FF + 0.05% Tween 20 (Tw 20), 0.5% PF-68, and 0.05% Tw 20. The N-glycans of eight rhGAAs were analyzed using ultra-performance liquid chromatography (UPLC) and tandem mass spectrometry. The relative quantity (%) of each glycan was obtained from the corresponding UPLC peak area per the sum (100%) of individual UPLC peak area. Fifteen N-glycans, comprising seven core-fucosylated glycans (71.5%, sum of each relative quantities) that have immunogenicity-inducing potential, three de-core-fucosylated glycans (15.4%), and five non-core-fucosylated glycans (13.1%), were characterized with high mass accuracy and glycan-generated fragment ions. The increases or decreases of relative quantities of each glycan from seven rhGAAs were compared with those of untreated control. The percentages of the sum of the relative quantities of core-fucosylated glycans divided by the sums of those of de-core- (core-fucose removed) and non-core-fucosylated glycans were calculated, and the lowest percentage was obtained in 100 μM of 2-FF combined with 0.5% PF-68. These results indicate that the relative quantity of each glycan of rhGAA produced in rice cell suspension cultures is significantly affected by their culture condition. This study performed the comparison of the N-glycan profiles of rice cell-derived rhGAA to identify the core-fucosylated glycans using UPLC and tandem mass spectrometry.

The auxiliary beta subunit plays an important role in the regulation of voltage-gated calcium (Ca-V) channels. Recently, it was revealed that beta 2e associates with the plasma membrane through an electrostatic interaction between N-terminal basic residues and anionic phospholipids. However, a molecular-level understanding of beta-subunit membrane recruitment in structural detail has remained elusive. In this study, using a combination of site-directed mutagenesis, liposome-binding assays, and multiscale molecular-dynamics (MD) simulation, we developed a physical model of how the beta 2e subunit is recruited electrostatically to the plasma membrane. In a fluorescence resonance energy transfer assay with liposomes, binding of the N-terminal peptide (23 residues) to liposome was significantly increased in the presence of phosphatidylserine (PS) and phosphatidylinositol 4,5-bisphosphate (PIP2). A mutagenesis analysis suggested that two basic residues proximal to Met-1, Lys-2 (K2) and Trp-5 (W5), are more important for membrane binding of the beta 2e subunit than distal residues from the N-terminus. Our MD simulations revealed that a stretched binding mode of the N-terminus to PS is required for stable membrane attachment through polar and nonpolar interactions. This mode obtained from MD simulations is consistent with experimental results showing that K2A, W5A, and K2A/W5A mutants failed to be targeted to the plasma membrane. We also investigated the effects of a mutated beta 2e subunit on inactivation kinetics and regulation of CaV channels by PIP2. In experiments with voltage-sensing phosphatase (VSP), a double mutation in the N-terminus of beta 2e (K2A/W5A) increased the PIP2 sensitivity of Ca(V)2.2 and Ca(V)1.3 channels by similar to 3-fold compared with wild-type beta 2e subunit. Together, our results suggest that membrane targeting of the beta 2e subunit is initiated from the nonspecific electrostatic insertion of N-terminal K2 and W5 residues into the membrane. The PS-beta 2e interaction observed here provides a molecular insight into general principles for protein binding to the plasma membrane, as well as the regulatory roles of phospholipids in transporters and ion channels.

Introduction The blood stasis pattern in Chinese and Korean traditional Medicine is characterised by stagnation, including extravasated blood and sluggish blood circulation or viscous or congested blood, all of which may become pathogenic factors. Blood stasis is associated with chronic and incurable disease, such as pain, infertility, cancer and health reducing conditions caused by stress, which are not relieved with modern medicine. The aim of the study is to establish a modern concept of blood stasis, develop diagnostic tools and diagnostic indices for blood stasis, identify biological indices related to blood stasis. Methods This community-based, multi-centre trial is designed as an observational study. Data will be collected in order to standardise blood stasis diagnosis in Korea. Patients will be admitted to one of the following 7 hospitals participating in this study: Kyung Hee Oriental Medical Centre, Kyung Hee University Oriental Hospital at Gangdong, Wonkwang Oriental Medical Hospital, Jaseng Hospital of Oriental Medicine, Cha Medical Centre, Pusan National University Korean Medicine Hospital and Dongguk University Ilsan Oriental Hospital. A total of 1400 participants will be recruited through local advertising and doctor referrals from hospitals. At each site, 200–280 participants will be recruited. Ethics and dissemination All of the research aims, the study design, and the specific methods in this study have been approved by the Institutional Review Boards (IRB) of all seven of the participating hospitals. Additionally, the study was approved by the IRB of the Korean Institute of Oriental Medicine. Trial registration CRIS No. KCT 0000916

Glucagon-like peptide-1 receptor (GLP-1R) is closely associated with the onset of diabetes and its complications. However, its roles in diabetic retinopathy are unknown. Retinal pigment epithelial (RPE) cells are a crucial component of the outer blood-retina barrier and their death is related to the progression of diabetic retinopathy. Thus, we examined the pathophysiological role of GLP-1R in RPE cell apoptosis. We found that GLP-1R expression was lower in the isolated neuroretina and RPE cells of streptozotocin-treated rats than in vehicle-treated rats. High-glucose treatment also decreased GLP-1R expression in a human RPE cell line (ARPE-19 cells). GLP-1R was silenced in ARPE-19 cells, in order to elucidate the pathophysiological roles of GLP-1R. This increased intracellular reactive oxygen species (ROS) generation and activated p53-mediated Bax promoter and endoplasmic reticulum (ER) stress signaling. We also found that GLP-1R knockdown-mediated p53 expression was regulated by ER stress. Interestingly, antioxidant treatment and peroxiredoxin 1 (Prx1) overexpression attenuated GLP-1R knockdown-induced ER stress signaling and p53 expression. Finally, to confirm that GLP-1R activation has protective effects, ARPE-19 cells were treated with exendin-4, a synthetic GLP-1R agonist. This attenuated high-glucose-induced ROS generation, ER stress signaling, and p53 expression. Collectively, these results indicated that hyperglycemia decreases GLP-1R expression in RPE cells. Such a decrease generates intracellular ROS, which increases ER stress-mediated p53 expression, and subsequently causes apoptosis by increasing Bax promoter activity. Our data suggested that regulation of GLP-1R expression is a promising approach for the treatment of diabetic retinopathy.

Background & Aims Non-alcoholic fatty liver disease (NAFLD) is strongly associated with obesity and type 2 diabetes. Thioredoxin-interacting protein (TXNIP) regulates the cellular redox state and metabolism and has been linked to many diseases, including diabetes. Therefore, we examined the role of TXNIP in hepatic steatosis in vitro and in vivo . Methods Lipogenic and inflammatory proteins produced by hepatocytes treated with palmitic acid (PA) or transfected with TXNIP or Txnip siRNA were measured by Western blotting. Lipid accumulation was assessed using Oil Red O staining. Protein interactions were assessed by immunoprecipitation and proximity ligation assay. Hepatic protein levels were measured by Western blotting from wild type or Txnip −/− mice fed a high-fat diet (HFD) or chow diet. Livers from NAFLD patients were compared with normal liver by immunohistochemistry. Results PA increased TXNIP, and inflammatory and lipogenic proteins in both AML12 and H4IIE cells. It also increased the peroxisome proliferator-activated receptor gamma co-activator-1α (PGC-1α), which mediated the expression of lipogenic markers and lipid accumulation. In addition, PA increased protein arginine methyltransferase-1 (PRMT1) and PRMT1 siRNA abolished the increase in lipogenic markers with PGC-1α. Furthermore, TXNIP interacted with PRMT1 in PA-treated hepatocytes. In vivo , levels of lipogenic proteins, inflammatory molecules, PGC-1α, and PRMT1 were increased in the livers of HFD mice compared with those fed a chow diet, and were ameliorated in HFD Txnip −/− mice. Moreover, TXNIP, PRMT1, and PGC-1α were elevated in the livers of human NAFLD patients. Conclusions TXNIP mediates hepatic lipogenesis via PRMT1 and PGC-1α regulation and inflammation in vitro and in vivo , implying that targeting TXNIP and PRMT1 is a potential therapeutic approach for treatment of NAFLD.

Hyperglycemia-induced apoptosis of retinal pigment epithelial (RPE) cells is considered to be involved in the progression of diabetic retinopathy. Histone arginine methylation catalyzed by protein arginine methyltransferases (PRMTs) has emerged as an important histone modification involved in gene regulation. However, the role of PRMTs in diabetic retinopathy has not been elucidated. Here, we found that expression of coactivator-associated arginine methyltransferase 1 (CARM1; also known as PRMT4) was increased in the high-glucose treated human RPE cell line ARPE-19 and in the RPE layer of streptozotocin-treated rats. In addition, high-glucose induced apoptosis in ARPE-19 cells. To determine the function of CARM1 on RPE cell apoptosis, we performed gain- and loss-of-function studies. CARM1 overexpression increased apoptosis of RPE cells. In contrast, silencing of CARM1 expression by siRNA and pharmacological inhibition of CARM1 activity abolished high-glucose-induced RPE cell apoptosis. Furthermore, we found that inhibition of histone 3 arginine 17 (H3R17) asymmetric dimethylation attenuates both CARM1- and high-glucose-induced apoptosis in RPE cells. Together, these results show that high-glucose-induced CARM1 expression increases RPE cell apoptosis via H3R17 asymmetric dimethylation. Strategies to reduce CARM1 expression or enzymatic activity could be used to prevent apoptosis of RPE cells in the progression of diabetic retinopathy.

ZnO thin films and nanowires (NWs) were precisely treated by focused electron-beam (E-beam) irradiation with a line width between 200 nm and 3 μm. For both ZnO films and NWs, an increased green emission was clearly observed for the E-beam-treated parts. Using a high-resolution laser confocal microscope, the photoluminescence intensities for E-beam-treated ZnO structures increased with increasing dose 1.0 × 1017–1.0 × 1018 electrons/cm2. The resistivity of a single ZnO NW increased from 56 to 1800 Ω cm after the E-beam treatment. From the results for the annealed ZnO thin films, we analyzed that the variations in PL and resistivity were due to the formation of vacancies upon focused E-beam irradiation.

The reaction of [Pd(CH3CN)2Cl2] with N-(pyridin-2-ylmethyl)aniline (L1) and its derivatives (L2–L6) in ethanol yields [(NN′)PdCl2] complexes, namely [LnPdCl2] (Ln = L1–L6). The X-ray crystal structure of Pd(II) complexes revealed that the palladium atom in [LnPdCl2] (Ln = L1–L6) showed a square plane geometry involving two nitrogen atoms of NN′-bidentate and two chlorido ligands. Complex [L4PdCl2] containing 2,4,6-trimethyl-N-(pyridin-2-ylmethyl)aniline (L4) showed the highest catalytic activity for the polymerisation of methyl methacrylate (MMA) in the presence of modified methylaluminoxane (MMAO) with an activity of 1.41 × 105 g PMMA/mol Pd·h at 60 °C and poly(methyl methacrylate) (PMMA) syndiotacticity (characterised using 1H NMR spectroscopy) of ca. 0.70.

A novel series of [(dpca)MX 2 ] (M = Cu, X = Cl; M = Cd, X = Br and M = Zn, X = NO 3 ) complexes were synthesized through the reaction of N , N -di(2-picolyl)cyclohexylamine (dpca) with the corresponding metal starting materials. X-ray crystallographic analysis determined that the metal center in complexes [(dpca)CuCl 2 ], [(dpca)CdBr 2 ] and [(dpca)Zn(NO 3 ) 2 ] showed a distorted 5-coordinated square pyramidal, trigonal bipyramidal, and 7-coordinated pentagonal bipyramidal geometry, respectively, involving coordination of the nitrogen atom of the cyclohexylamine moiety with the metal center. Specifically, the catalytic activity of [(dpca)Zn(NO 3 ) 2 ] (1.04 × 10 5 g PMMA/mol Zn·h) for the polymerization of methyl methacrylate (MMA) in the presence of modified methylaluminoxane (MMAO) at 60 °C was six-fold higher than the reference complex [ZnCl 2 ] (1.73 × 10 4 g PMMA/mol Zn·h).

Carbohydrate response element-binding protein (ChREBP) is a transcription factor responsible for carbohydrate metabolism in the liver. However, the role of ChREBP in diabetic nephropathy has not been elucidated. Thus, we investigated the role of ChREBP in mesangial cells in diabetic nephropathy. Treatment with 25 mm glucose (high glucose; HG) increased cellular O-GlcNAc and O-GlcNAcylated ChREBP in mesangial cells compared with normal 5.5 mm glucose. O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino N-phenylcarbamate (PUGNAc), a drug that increases O-GlcNAc, augmented the expression of ChREBP targets, whereas DON, a drug that decreases O-GlcNAc and O-GlcNAcase overexpression, mitigated the increase with HG. O-GlcNAc augmented the protein stability, transcriptional activity, and nuclear translocation of ChREBP. HG treatment also stimulated lipid accumulation and the contents of triglyceride and cholesterol in mesangial cells. In addition, HG triggered expression of hypoxia-inducible factor 1-α, vascular endothelial growth factor, and extracellular matrix components related to nephrosclerosis. The ChREBP mutant, W130A, did not exhibit HG-induced lipid accumulation and fibrotic proteins, suggesting that the Trp-130 residue in the MCR3 domain is important in the development of glomerulosclerosis. O-GlcNAcylated ChREBP was elevated in mesangium cells of streptozotocin-induced diabetic rats. In conclusion, HG increased the O-GlcNAcylated ChREBP level, which resulted in lipid accumulation and up-regulation of fibrotic proteins in mesangial cells. These effects may lead mesangial cells to an ultimately pathological state.

The reaction of ZnCl2 with ancillary ligands, including 1,4-bis-(N,N-di-(1H-pyrazolyl-1-methyl)amine)benzene (L1) and 4,4′-bis-(N,N-di(1H-pyrazolyl-1-methyl)phenyl)methane (L2), in ethanol yields Zn(II) chloride complexes, i.e., 1,4-bis-(N,N-di-(1H-pyrazolyl-1-methyl)amine)benzene(dichloro)Zn(II) [L1Zn2Cl4] and 4,4′-bis-(N,N-di-(1H-pyrazolyl-1-methyl)phenyl)methane(dichloro)Zn(II) [L2Zn2Cl4]. The X-ray crystal structures of Zn(II) complexes revealed that they are binuclear, and each zinc atom has a distorted tetrahedral geometry which involves a nitrogen atom from two pyrazole groups and two chloro ligands. The catalytic activity of [L1Zn2Cl4] and [L2Zn2Cl4] for the polymerisation of methyl methacrylate (MMA) in the presence of modified methylaluminoxane (MMAO) increased by twofold compared to the corresponding monomeric Zn(II) complex, N,N-bis(1H-pyrazolyl-1-methyl)aniline(dichloro)Zn(II) [LZnCl2], at 60 °C.

Formaldehyde (FA) is toxic to the respiratory system, and nitric oxide (NO) dysfunction stimulates the onset of respiratory diseases. The involvement of dimethylarginine dimethylaminohydrolase (DDAH), the l-arginine analogue asymmetric dimethylarginine (ADMA) degrading enzyme, in FA-induced cell death in lung epithelial cells has not been investigated. In this study, we assessed the effect of FA on DDAH expression and endoplasmic reticulum (ER) stress in A549 cells. We also investigated the preventive effect of DDAH overexpression on ER stress and apoptosis in FA-induced cell death. FA decreased viability in A549 cells and decreased DDAH1 and DDAH2 mRNA and protein expression in a time-dependent manner (>4h). This coincided with increased phosphorylation of the ER stress proteins IRE1α, PERK, and eIF-2α, as well as increased expression of pro-apoptotic proteins such as Bax, C/EPB homologous protein (CHOP), cleaved PARP, and cleaved caspase-3, but decreased expression of the anti-apoptotic protein Bcl-2. ADMA treatment mimicked the effect of FA. Overexpression of DDAH1, but not DDAH2, prevented FA-induced decreases in cell viability, phosphorylation of IRE1α, PERK, and eIF2α, and expression of CHOP. Effects of DDAH1 overexpression, but not DDAH2 overexpression, restored FA-induced increases in Bax, CHOP, cleaved PARP, cleaved caspase-3 and decreases in Bcl-2. In conclusion, FA induces apoptosis of lung epithelial cells via a decrease of DDAH1 through ER stress.

The reaction of Pd(CH3CN)2Cl2 and NaClO4 with the ancillary ligands N,N-di(2-picolyl)cyclopentylamine (L1), N,N-di(2-picolyl)cyclohexylamine (L2) and N,N-di(2-picolyl)cycloheptylamine (L3) in ethanol yielded a new series of [(N,N′,N)-PdCl]ClO4 complexes, i.e., [PdL1]ClO4, [PdL2]ClO4 and [PdL3]ClO4, respectively. The reaction of Pt(CH3CN)2Cl2 and NaClO4 with the ancillary ligands L1–L3 gave only the stable [PtL2]ClO4 complex. The Pd and Pt atoms of all of the complexes had an almost square-planar geometry involving three nitrogen atoms and a chloro ligand. Moreover, the unit cell included a ClO 4 - anion as the counterion. The bond lengths between the metal and nitrogen atoms are a little affected by the substituted cycloalkyl group, however those between the metal and the chloro ligand are not affected. The catalytic activity of the Pd(II) and Pt(II) complexes toward the polymerisation of methyl methacrylate in the presence of modified methylaluminoxane resulted in a high molecular weight and a narrow polydispersity index; the highest activity was measured for [PdL3]ClO4 at 60 °C.

Chemerin is a recently discovered adipocytokine, associated with adiposity and insulin sensitivity. The current study investigated the effects of lifestyle intervention on circulating chemerin level and its association with insulin resistance and adiponectin in human.Forty male and 20 female obese adults (mean age: 29.7±5.7 y, mean BMI: 29.3±4.5 kg/m(2)) completed an 8-week lifestyle intervention program, which consisted of a home-based diet and exercise program. Anthropometric measurements and biomarkers were assessed at the baseline and at the end of the study.Eight weeks of lifestyle intervention reduced body weight, visceral fat and subcutaneous fat by 3.8%, 15.3% and 11.5%, respectively. The lifestyle intervention further reduced fasting insulin (10.9±6.6 vs. 7.6±5.3 μU/ml, p0.001) and homeostasis assessment of insulin resistance (HOMA-IR) (2.3±1.5 vs. 1.6±1.2, p0.001), chemerin (103.3±20.7 vs. 96.5±19.5 ng/ml, p0.001) and hs-CRP levels (1.3±1.8 vs. 0.2±0.2 mg/dl, p0.001) while it increased fasting pentraxin (PTX) 3 (0.6±0.7 vs. 0.7±0.4 ng/ml, p=0.049) level. The Δ chemerin levels correlated with Δ insulin (r=0.349, p=0.024) and HOMA-IR (r=0.333, p=0.36) even after adjusting for age and gender.The lifestyle intervention reduced circulating chemerin levels independent of visceral fat mass and adiponectin. Chemerin levels are associated with insulin resistance at the baseline and after the lifestyle intervention.

This paper presents the design, fabrication, and experimental demonstration of an artificial hair sensor made of polymer materials. Long polymer hair structures embedded with flexible three-dimensional piezoresistive sensors were formed on a flexible substrate in two-dimensional arrays to detect an applied external force. The flexible piezoresistor was implemented using a carbon nanotube-polydimethylsiloxane (CNT-PDMS) composite prepared by the mixing of multi-wall carbon nanotubes with PDMS. A CNT-PDMS composite with high conductivity and a high gauge factor was obtained by increasing the CNT concentration in PDMS. In this study, we used a 13% CNT-PDMS composite for fabricating the sensing element that was embedded in the proposed hair sensor. The hair sensor is 4 mm in height and 700 μm in diameter. The implemented device shows a linear and sensitive response in the on-axis mode with a sensitivity of 2900 ppm/μm.

A fed-batch process for the production of biosimilar monoclonal antibody was developed. Since the brand product is produced by perfusion process, the impact of process change from perfusion to fed-batch on product quality and cell performance was evaluated. Perfusion culture was performed at 0.47–1.00 (v/v/d) perfusion rate by spin-filter method with 15–17 μm mesh. Culture parameters such as pH (6.8–7.2), dissolved oxygen (40–70% air saturation), temperature (37 °C) and agitation speed (250 rpm) were applied in both culture modes. In terms of cell performance, volumetric productivity increased 3.7 times while process performance increased 7.5 times in fed-batch culture due to 10 times higher scalability. Considering the glycosylation pattern and charge variants, no significant changes in product quality were observed upon process change, although intact IgG level slightly decreased in fed-batch mode. The change of production media showed more effect on glycosylation patterns than the operation in different culture modes. Furthermore, there were no differences in biological activity, including TNFα, FcγRIIIa, and C1q-binding affinity. Through a scale-up study from 3 L to 12,500 L, it was confirmed that cell performance and product quality could be maintained. In conclusion, product quality of the fed-batch process was comparable to that of the reference product.

The reaction of anhydrous ZnCl2 with ancillary ligands, including N,N-bis(1H-pyrazolyl-1-methyl)aniline (L1), N,N-bis(1H-pyrazolyl-1-methyl)-p-methoxyaniline (L2), N,N-bis(1H-pyrazolyl-1-methyl)-p-fluoroaniline (L3) and N,N-bis(3,5-dimethyl-1H-pyrazolyl-1-methyl)aniline (L4), in ethanol yields Zn(II) chloride complexes, i.e., L1ZnCl2, L2ZnCl2, L3ZnCl2 and L4ZnCl2. X-ray crystallographic analysis revealed that the Zn atoms of all of the synthesized complexes have a distorted tetrahedral geometry involving a nitrogen atom from each of two pyrazole groups and two chloro ligands. However, the nitrogen atom of the aniline group is not coordinated to the Zn center, resulting in the formation of an eight-membered chelate ring. The catalytic activity of the Zn(II) complexes in the polymerization of methyl methacrylate (MMA) in the presence of modified methylaluminoxane (MMAO) results in a higher molecular weight and a narrow polydispersity index (PDI) range.

Mesenchymal stem cells (MSCs) are capable of crossing germinative layer borders and are obtainable in high numbers via in vitro cultures. Therefore, many researchers have searched for diverse sources of MSCs. Recently the generation of glucose-responsive insulin-producing cells (IPCs) from MSCs has shown immense potential for the treatment of type 1 diabetes mellitus (T1DM) due to a lack of pancreas donors. In this study, we compared the growth potency of four kinds of MSCs derived from bone marrow, Wharton's jelly, adipose tissue, and the periosteum. In addition, in vitro differentiation of these MSCs into IPCs was also investigated. After 2 weeks of IPCs differentiation, we compared the expression of the insulin gene and protein using RT-qPCR and immunofluorescence staining. Only IPCs derived from periosteum-derived progenitor cells (PDPCs) showed a response to glucose concentration. Glucose stimulated insulin secretion was conclusive evidence of the potential functionality of IPCs. Therefore, PDPCs are a promising alternative stem cell source for IPCs differentiation.

Sulfonated poly(tetra phenyl ether ketone sulfone)s SPTPEKS were successfully synthesized for proton exchange membrane. Poly(tetra phenyl ether ketone sulfone)s PTPEKS were prepared by the 4,4′-dihydroxydiphenylsulfone with 1,2-bis(4-fluorobenzoyl)-3,4,5,6-tetraphenylbenzene (BFBTPB) and 4,4′-difluorodiphenylsulfone, respectively, at 210 °C using potassium carbonate in sulfolane. PTPEKS were followed by sulfonation using chlorosulfonic acid and concentrated sulfuric acid at two stage reactions. Different contents of sulfonated unit of SPTPEKS (17, 20, 23 mol% of BFBTPB) were studied by FT-IR, 1H NMR spectroscopy, and thermo gravimetric analysis (TGA). Sorption experiments were conducted to observe the interaction of sulfonated polymers with water. The ion exchange capacity (IEC) and proton conductivity of SPTPEKS were evaluated with increase of degree of sulfonation. The water uptake of synthesized SPTPEKS membranes exhibit 25–61% compared with 28% of Nafion 211®. The SPTPEKS membranes exhibit proton conductivities (25 °C) of 11.7–25.3 × 10−3 S/cm compared with 33.7 × 10−3 S/cm of Nafion 211®.

Pure iron metal target was sputtered onto carbon nanotube grown on carbon paper to fabricate iron-based catalysts for the oxygen reduction reaction (ORR). The carbon nanotube-supported Fe-based catalysts have active sites which are believed to include iron cations coordinated by pyridinic nitrogen functionalities between the graphitic sheets. A Fe-based electrocatalyst treated at 950 °C displayed the highest mass activity. The treated sample at lower temperature could not form the Fe/N/CNT sufficiently. On the other hand, the formed Fe/N/CNTs were degraded thermally at higher temperature. Cyclic voltammetry of the Fe-based electrocatalysts showed similar trends with mass activity which is the largest value at 950 °C. Even though the catalytic activity is not comparable with that of Pt/C catalysts yet, sputtered Fe-based electrocatalysts are promising to explore the non-precious metal electrocatalysts.

Acupuncture is increasingly popular for the treatment of many medical complaints, including gynaecologic conditions. The aim of this study was to summarise the evidence from systematic reviews (SRs) and meta-analyses assessing the efficacy of acupuncture in treating common gynaecologic conditions. Six electronic databases, including two major English-language databases (PubMed and the Cochrane Library) and four Korean databases, were systematically searched for SRs and meta-analyses concerned with acupuncture and common gynaecologic diseases. The following English search terms were used: (gynaecologic disease in MeSH terms) AND (acupuncture or acup*) AND (systematic review OR meta-analysis). In addition, three Korean traditional medicine journals (The Journal of the Korean Acupuncture and Moxibustion Society, The Journal of Korean Oriental Medicine and The Journal of Oriental Obstetrics and Gynaecology) were searched. The quality of the included studies was assessed using the Overview Quality Assessment Questionnaire. Of the 55 potentially relevant studies that were found, 16 SRs were included in this report. These reviews evaluated the efficacy of acupuncture for treating the side effects of breast cancer chemotherapy, menstrual disturbances, menopausal symptoms, female infertility, uterine fibroids and polycystic ovary syndrome. Acupuncture was clearly beneficial in the management of chemotherapy-induced nausea and vomiting. In addition, current evidence suggests that acupuncture administered close to embryo transfer during in vitro fertilisation treatment improves the rates of pregnancy and live birth. In conclusion, there is no convincing evidence of the efficacy of acupuncture except for specific conditions, which include acupuncture administered with embryo transfer to improve the outcome of in vitro fertilisation and acupuncture for the management of chemotherapy-induced nausea and vomiting. More well-designed trials using rigorous methodology are required to evaluate the efficacy of acupuncture in treating gynaecologic conditions.

This paper presents the design, fabrication, and characterization of a microfluidic biochip with integrated actuation electrodes used to manipulate a cell and a microbead by dielectrophoresis and sensing electrodes to detect the trapping by using the impedance detection method. Combining deflective dielectrophoretic barriers with controlled pressure-driven liquid flows allows the accurate control of a cell/microbead in suspensions. The threshold voltage for microbead trapping was experimentally verified at various flow rates. The impedance change caused by the blockage of the electrical conducting path between sensing electrodes with the trapping of an MCF7 cell and a polystyrene microbead was measured. The impedance before the trapping of an MCF7 cell was 10.9 MΩ at 1 kHz and increased to 12 MΩ when the cell was placed between sensing electrodes.

RAmy3D promoter is capable of expressing high levels of recombinant proteins in response to the depletion of sugar in transgenic rice cell suspension cultures. For this reason, it is necessary to change the growth medium into sugar-free production medium to produce the target protein, human cytotoxic T-lymphocyte antigen 4-immunoglobulin (hCTLA4Ig), using the inducible RAmy3D promoter. Since the two-stage culture is a complex process to perform in large-scale, a fed-batch method was evaluated with the addition of concentrated amino acids before the depletion of sugar to induce hCTLA4Ig production. This fed-batch culture was found to be effective and the production of hCTLA4Ig was enhanced up to 1.2-fold compared to that of two-stage cultures with medium exchange. In addition, when this fed-batch culture was performed in a 15-l stirred-tank bioreactor, maximum hCTLA4Ig level was 76.5 mg l−1 at day 10.

Piceatannol (3,5,3',4'-tetrahydroxy- trans-stilbene), a resveratrol analogue, is a polyphenol present in the skins of grapes and in wine and other foods. The present study aimed to investigate for the first time the cardioprotective effects of piceatannol on vascular smooth muscle cells (VSMC). The treatment of cells with piceatannol inhibited cell proliferation by reducing extracellular signal-regulated kinase (ERK) 1/2 and JNK activity in cultured VSMC in the presence of tumor necrosis factor-alpha (TNF-alpha). These inhibitory effects were also associated with G1 cell cycle arrest, and resulted in a decrease in cyclin-dependent kinases (CDKs) and cyclins. Piceatannol treatment strongly induced the expression of p21WAF1 via independence of p27KIP and p53 expression. The effect of piceatannol was not restricted to cell proliferation, as TNF-alpha-induced invasion and migration was also suppressed in VSMC. Moreover, piceatannol treatment strongly decreased matrix metalloproteinase-9 (MMP-9) expression and promoter activity in a dose-dependent manner in response to TNF-alpha. It was further demonstrated that piceatannol abrogated the transcriptional activity of nuclear factor kappa B (NF-kappaB), an important nuclear transcription factor involved in MMP-9 expression. Overall, these results demonstrate that piceatannol inhibits proliferation and migration of VSMC treated with TNF-alpha. Therefore, piceatannol may be an effective therapeutic approach to treat atherosclerosis.

The silver-palladium(Ag-Pd) alloy coating as a solid lubricant was investigated for its application to the high temperature stud bolts used in nuclear power plants. A hex bolt sample was prepared in the following steps: 1) bolt surface treatment using alumina grit blasting for cleaning and increasing the surface area; 2) nickel(Ni) film coating as a glue layer on the surface of the bolt; and 3) Ag-Pd alloy coating on the Ni film. The films were deposited by using a direct current(DC) magnetron sputtering system. The thickness and composition of the Ag-Pd alloy film have effect on the friction coefficient, which was determined using axial force measurement. A 500 nm-thick Ag-Pd (80:20, molar ratio) alloy film has the lowest friction coefficient of 0.109. A cyclic test was conducted to evaluate the durability of bolts coated with either the Ag-Pd (80:20) alloy film or N-5000 oil. In a cycle, the bolts were inserted into a block using a torque wrench, which was followed by heating and disassembling. After only one cycle, it was not possible to remove the bolts coated with the N-5000 oil from the block. However, the bolts coated with the Ag-Pd (80:20) alloy could be easily removed up until 15 cycles.

Background The time-dependent association between metabolic syndrome and risk of chronic kidney disease (CKD) is not clear. Study Design Prospective cohort study. Setting & Participants The study cohort was composed of 10,685 healthy men without CKD, hypertension, or diabetes who participated in a health-checkup program at a large work site. Predictor Metabolic syndrome. Outcomes & Measurements CKD was defined as an estimated glomerular filtration rate (GFR) less than 60 mL/min/1.73 m 2 . A standard Cox proportional hazards model and a time-dependent Cox model were used to calculate adjusted hazard ratios (HRs) in the CKD model. Results During 40,616.8 person-years of follow-up, 291 incident cases of CKD developed; 787 patients (7.4%) had metabolic syndrome at baseline and 1,444 (14.4%) developed incident metabolic syndrome during follow-up. After adjustment for age, baseline GFR, γ-glutamyltransferase level, and uric acid level, metabolic syndrome at baseline was associated with a significantly increased risk of CKD (HR, 1.99; 95% confidence interval, 1.46 to 2.73). Metabolic syndrome over time as a time-dependent variable also predicted the development of CKD (HR, 1.75; 95% confidence interval, 1.28 to 2.39). The relationship between metabolic syndrome and incident CKD remained significant, even after further adjustment for the homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein level, current smoking, alcohol consumption, or regular exercise. In addition, there were graded relationships between number of metabolic syndrome traits or quintile of homeostasis model assessment of insulin resistance over time as a time-dependent variable and risk of CKD. Both increased triglyceride and low high-density lipoprotein cholesterol levels among metabolic syndrome traits were associated with significantly increased risk of CKD. These results were effectively unchanged, even after additional adjustment for incident hypertension and incident diabetes. Limitations Estimated GFR was used instead of a directly measured GFR to define CKD. Conclusion Metabolic syndrome is an independent risk factor for the development of CKD in Korean men without hypertension or diabetes, even with changes in status of metabolic syndrome over time.

Readily-synthesised, water-stable Pd(II) complexes of azetidine-based tridentate ligands have been studied as catalysts for the Suzuki–Miyaura coupling reaction. They are highly active for the coupling of aryl bromides with aryl boronates and also effective for the coupling of aryl chlorides.

Cirsium japonicum De Candole is widely used in traditional herbal medicine for the treatment of hemorrhage, hypertension or blood circulation in Korea. In this work, we investigated the vasorelaxant activity of an aqueous extract of C. japonicum whole plant (CjEx) and its possible mechanism in isolated rat thoracic aortic rings constricted with norepinephrine (NE; 300 nmol/l). CjEx elicited an acute relaxation in endothelium-intact rings in a concentration-dependent manner (0.1-1.0 mg/ml). This relaxation was eliminated by the removal of the endothelium and pretreatment with N(G)-nitro-L-arginine (10 micromol/l), methylene blue (1 micromol/l) or diphenylhydramine (10 micromol/l), but indomethacin (10 micromol/l) atropine (100 nmol/l), [D-Pro(2), D-Trp(7,9)] substance P (5 micromol/l) or HOE-140 (10 nmol/l) did not affect the relaxation. The results indicate that the response to CjEx involves enhancement of the nitric oxide-cyclic guanosine monophosphate system, and that it occurs via histamine H(1)-receptor. Our findings may contribute to better understanding of the potential link between the clinical use and its beneficial effects on vascular health.

For successful stem cell-based therapy, not only are alternative good cell sources needed but appropriate scaffolds are key factors. The main purpose of this study was to evaluate the multipotentiality of multilineage progenitor cells (MLPC) and assess the three-dimensional cultivation and chondrogenic differentiation of MLPC in atelocollagen gel for application of tissue-engineered cartilage constructs.MLPC, human umbilical cord blood-derived clonal cell lines, from BioE Inc. were used. Immunophenotypes of MLPC were characterized using a fluorescence-activated cell sorter (FACS). In vitro differentiation potentials into osteogenic, adipogenic and chondrogenic lineages were examined. Differentiated cells were characterized by reverse transcriptase-polymerase chain reaction (RT-PCR), histologic and immunofluorescence staining. RESULTS Clonogenic MLPC maintained immunophenotypes with specific surface markers of mesenchymal stromal cells (MSC). The osteogenic and adipogenic potentials of MLPC were demonstrated by quantitative real-time PCR, alkaline phosphates activity and Oil Red O staining. Furthermore, MLPC were successfully differentiated into chondrocytes in atelocollagen gel, which was confirmed by RT-PCR and immunofluorescence staining for type II collagen protein.Whenever MSC are considered for the treatment of cartilage defects, a variety of scaffolds have been utilized as successful carriers for cell delivery. Our results suggest that MLPC can serve as an alternative source for stem cell-based therapy and transplantation. The chondrogenic potential of MLPC in atelocollagen could be suitable for cartilage tissue engineering.