Dihydroxynaphthalene‐based mimicry of fungal melanogenesis for multifunctional coatings

Jeon, Jong‐,Rok,Le, Thao Thanh,Chang, Yoon&#x2010,Seok John Wiley and Sons Inc. 2016 MICROBIAL BIOTECHNOLOGY -BLACKWELL- Vol.9 No.3

<P><B>Summary</B></P><P>Material‐independent adhesive action derived from polycatechol structures has been intensively studied due to its high applicability in surface engineering. Here, we for the first time demonstrate that a dihydroxynaphthalene‐based fungal melanin mimetic, which exhibit a catechol‐free structure, can act as a coating agent for material‐independent surface modifications on the nanoscale. This mimetic was made by using laccase to catalyse the oxidative polymerization of specifically 2,7‐dihydroxynaphthalene. Analyses of the product of this reaction, using Fourier transform infrared‐attenuated total reflectance and X‐ray photoelectron spectroscopy, bactericidal action, charge‐dependent sorption behaviour, phenol content, <I>Zeta</I> potential measurements and free radical scavenging activity, yielded results consistent with it containing hydroxyphenyl groups. Moreover, nuclear magnetic resonance analyses of the product revealed that C‐O coupling and C‐C coupling were the main mechanisms for its synthesis, thus clearly excluding a catechol structure in the polymerization. This product, termed poly(2,7‐DHN), was successfully deposited onto a wide variety of solid surfaces, including metals, polymeric materials, ceramics, biosurfaces and mineral complexes. The melanin‐like polymerization could be used to co‐immobilize other organic molecules, forming functional surfaces. In addition, the hydroxyphenyl group contained in the coated poly(2,7‐DHN) induced secondary metal chelation/reduction and adhesion with proteins, suggesting the potential of this poly(2,7‐DHN) layer to serve as a platform material for a variety of surface engineering applications. Moreover, the novel physicochemical properties of the poly(2,7‐DHN) illuminate its potential applications as bactericidal, radical‐scavenging and pollutant‐sorbing agents.</P>

Surface‐initiated atom‐transfer radical polymerization of 3‐<i>O</i>‐methacryloyl‐1,2:5,6‐di‐ <i>O</i>‐isopropylidene‐α‐ <small>D</small>‐glucofuranoside onto gold surface

Yoon, Kuk Ro,Ramaraj, B.,Lee, Seungho,Yu, Jong‐,Sung,Choi, Insung S. Wiley Subscription Services, Inc., A Wiley Company 2009 Journal of biomedical materials research. Part A Vol.a88 No.3

<P><B>Abstract</B></P><P>A sugar‐containing polymer was grown on gold surface by surface‐initiated atom‐transfer radical polymerization (SI‐ATRP) of methacrylate monomer, 3‐<I>O</I>‐methacryloyl‐1,2:5,6‐di‐<I>O</I>‐isopropylidene‐α‐<SMALL>D</SMALL>‐glucofuranoside (MAIpGIc), using 1,4,8,11‐tetraaza‐1,4,8,11‐tetramethylcyclotetradecane (Me<SUB>4</SUB>Cyclam) as ligand, 2‐bromopropionyl moiety attached on the gold surface as initiator, and Copper(I) bromide as catalyst, respectively, in tetrahydrofuran (THF) medium. The resultant sugar film was characterized by polarized infrared external reflectance spectroscopy (PIERS), X‐ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), field emission scanning electron microscopy (FE‐SEM), ellipsometry, and contact angle goniometry. The IR peaks characteristics of poly(3‐<I>O</I>‐methacryloyl‐α,β‐<SMALL>D</SMALL>‐glucopyranoside) (PMAGlc), broad OH stretch at ∼3400 cm<SUP>−1</SUP>, and CO ester stretch at ∼1748 cm<SUP>−1</SUP> observed in PIERS spectra demonstrate the formation of PMAGlc on the gold surface. The AFM and SEM images show the polymer growth away from the gold surface without visible domain boundaries, and it further confirms the formation of sugar coating. The method described in the article would be beneficial in many areas, such as pathogen detection and biosensors, considering the biological importance of carbohydrate polymers. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009</P>

Phenyl 2‐pyridyl ketoxime induces cellular senescence‐like alterations via nitric oxide production in human diploid fibroblasts

Yang, Kyeong Eun,Jang, Hyun&#x2010,Jin,Hwang, In&#x2010,Hu,Chung, Young&#x2010,Ho,Choi, Jong‐,Soon,Lee, Tae&#x2010,Hoon,Chung, Yun&#x2010,Jo,Lee, Min&#x2010,Seung,Lee, Mi Young,Yeo, Eui&#x2010,J BLACKWELL PUBLISHING 2016 AGING CELL Vol.15 No.2

<P><B>Summary</B></P><P>Phenyl‐2‐pyridyl ketoxime (PPKO) was found to be one of the small molecules enriched in the extracellular matrix of near‐senescent human diploid fibroblasts (HDFs). Treatment of young HDFs with PPKO reduced the viability of young HDFs in a dose‐ and time‐dependent manner and resulted in senescence‐associated β‐galactosidase (SA‐β‐gal) staining and G2/M cell cycle arrest. In addition, the levels of some senescence‐associated proteins, such as phosphorylated ERK1/2, caveolin‐1, p53, p16<SUP>ink4a</SUP>, and p21<SUP>waf1</SUP>, were elevated in PPKO‐treated cells. To monitor the effect of PPKO on cell stress responses, reactive oxygen species (ROS) production was examined by flow cytometry. After PPKO treatment, ROS levels transiently increased at 30 min but then returned to baseline at 60 min. The levels of some antioxidant enzymes, such as catalase, peroxiredoxin II and glutathione peroxidase I, were transiently induced by PPKO treatment. SOD II levels increased gradually, whereas the SOD I and III levels were biphasic during the experimental periods after PPKO treatment. Cellular senescence induced by PPKO was suppressed by chemical antioxidants, such as N‐acetylcysteine, 2,2,6,6‐tetramethylpiperidinyloxy, and L‐buthionine‐(<I>S</I>,<I>R</I>)‐sulfoximine. Furthermore, PPKO increased nitric oxide (NO) production via inducible NO synthase (iNOS) in HDFs. In the presence of NOS inhibitors, such as L‐NG‐nitroarginine methyl ester and L‐NG‐monomethylarginine, PPKO‐induced transient NO production and SA‐β‐gal staining were abrogated. Taken together, these results suggest that PPKO induces cellular senescence in association with transient ROS and NO production and the subsequent induction of senescence‐associated proteins<B>.</B></P>

Assessment of potential jaw‐tracking advantage using control point sequences of VMAT planning

Kim, Jung&#x2010,in,Park, Jong Min,Park, So&#x2010,Yeon,Choi, Chang Heon,Wu, Hong&#x2010,Gyun,Ye, Sung&#x2010,Joon unknown 2014 Journal of applied clinical medical physics Vol.15 No.2

<P>This study aims to evaluate the potential jaw‐tracking advantage using control point sequences of volume volumetric‐modulated arc therapy (VMAT) planning. VMAT plans for patients with prostate and head and neck (H&N) cancers were converted into new static arc (SA) plans. The SA plan consisted of a series of static fields at each control point of the VMAT plan. All other machine parameters of the SA plan were perfectly identical to those of the original VMAT plan. The jaw‐tracking static arc (JTSA) plans were generated with fields that closed the jaws of each SA field into the multileaf collimators (MLCs) aperture. The dosimetric advantages of JTSA over SA were evaluated in terms of a dose‐volume histogram (DVH) of organ at risk (OAR) after renormalizing both plans to make the same target coverage. Both plans were delivered to the MatriXX‐based COMPASS system for 3D volume dose verification. The average jaw size reduction of the JTSA along the X direction was 3.1±0.9 cm for prostate patients and 6.9±1.9 cm for H&N patients. For prostate patients, the organs far from the target showed larger sparing (3.7%—8.1% on aver‐age) in JTSA than the organs adjacent to the target (1.1%—1.5%). For the H&N plans, the mean dose reductions for all organs ranged from 4.3% to 11.9%. The dose reductions were more significant in the dose regions of <SUB>D80</SUB>,<SUB>D90</SUB>, and <SUB>D95</SUB> than the dose regions of <SUB>D5</SUB>,<SUB>D10</SUB>, and <SUB>D20</SUB> for all patients. Likewise, the deliverability and reproducibility of jaw‐tracking plan were validated. The measured dosimetric advantage of JTSA over SA coincided with the calculated one above.</P><P>PACS numbers: 87.55.D‐, 87.55.ne</P>

Melatonin improves the meiotic maturation of porcine oocytes by reducing endoplasmic reticulum stress during in vitro maturation

Park, Hyo&#x2010,Jin,Park, Jae&#x2010,Young,Kim, Jin&#x2010,Woo,Yang, Seul&#x2010,Gi,Jung, Jae&#x2010,Min,Kim, Min&#x2010,Ji,Kang, Man&#x2010,Jong,Cho, Young Ho,Wee, Gabbine,Yang, Hee&#x2010,Young,Son John Wiley and Sons Inc. 2018 Journal of pineal research Vol.64 No.2

<P><B>Abstract</B></P><P>Under endoplasmic reticulum (ER)‐stress conditions, the unfolded protein response (UPR) generates a defense mechanism in mammalian cells. The regulation of UPR signaling is important in oocyte maturation, embryo development, and female reproduction of pigs. Recent studies have shown that melatonin plays an important role as an antioxidant to improve pig oocyte maturation. However, there is no report on the role of melatonin in the regulation of UPR signaling and ER‐stress during in vitro maturation (IVM) of porcine oocytes. Therefore, the objective of this study was to investigate the antioxidative effects of melatonin on porcine oocyte maturation through the regulation of ER‐stress and UPR signaling. We investigated the changes in the mRNA/protein expression levels of three UPR signal genes (Bip/Grp78, ATF4, P90/50ATF6, sXbp1, and CHOP) on oocytes, cumulus cells, and cumulus‐oocyte complexes (COCs) during IVM (metaphase I; 22 hours and metaphase II; 44 hours) by Western blot and reverse transcription‐polymerase chain reaction analysis. Treatment with the ER‐stress inducer, tunicamycin (Tm), significantly increased expression of UPR markers. Additionally, cumulus cell expansion and meiotic maturation of oocytes were reduced in COCs of Tm‐treated groups (1, 5, and 10 μg/mL). We confirmed the reducing effects of melatonin (0.1 μmol/L) on ER‐stress after pretreatment with Tm (5 μg/mL; 22 hours) in maturing COCs. Addition of melatonin (0.1 μmol/L) to Tm‐pretreated COCs recovered meiotic maturation rates and expression of most UPR markers. In conclusion, we confirmed a role for melatonin in the modulation of UPR signal pathways and reducing ER‐stress during IVM of porcine oocytes.</P>

Global analysis of gene expression profiles in the submandibular salivary gland of klotho knockout mice

Kwon, Sung&#x2010,Min,Kim, Soo&#x2010,A,Yoon, Jung&#x2010,Hoon,Yook, Jong‐,In,Ahn, Sang&#x2010,Gun Liss 2018 Journal of Cellular Physiology Vol.233 No.4

<P>Salivary dysfunction commonly occurs in many older adults and is considered a physiological phenomenon. However, the genetic changes in salivary glands during aging have not been characterized. The present study analyzed the gene expression profile in salivary glands from accelerated aging klotho deficient mice (klotho−/−, 4 weeks old). Microarray analysis showed that 195 genes were differentially expressed (z‐score > 2 in two independent arrays) in klotho null mice compared to wild‐type mice. Importantly, alpha2‐Na<SUP>+</SUP>/K<SUP>+</SUP>‐ATPase (Atp1a2), Ca<SUP>2+</SUP>‐ATPase (Atp2a1), epidermal growth factor (EGF), and nerve growth factor (NGF), which have been suggested to be regulators of submandibular salivary gland function, were significantly decreased. When a network was constructed from the differentially expressed genes, proliferator‐activated receptor‐γ (PPAR γ), which regulates energy homeostasis and insulin sensitivity, was located at the core of the network. In addition, the expression of genes proposed to regulate various PPAR γ‐related cellular pathways, such as Klk1b26, Egfbp2, Cox8b, Gpx3, Fabp3, EGF, and NGFβ, was altered in the submandibular salivary glands of klotho−/− mice. Our results may provide clues for the identification of novel genes involved in salivary gland dysfunction. Further characterization of these differentially expressed genes will be useful in elucidating the genetic basis of aging‐related changes in the submandibular salivary gland.</P>

AZD1208, a pan‐Pim kinase inhibitor, inhibits adipogenesis and induces lipolysis in 3T3‐L1 adipocytes

Park, Yu&#x2010,Kyoung,Obiang&#x2010,Obounou, Brice Wilfried,Lee, Kyung&#x2010,Bok,Choi, Jong‐,Soon,Jang, Byeong&#x2010,Churl John Wiley and Sons Inc. 2018 JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Vol.22 No.4

<P><B>Abstract</B></P><P>The proviral integration moloney murine leukaemia virus (Pim) kinases, consisting of Pim‐1, Pim‐2 and Pim‐3, are involved in the control of cell growth, metabolism and differentiation. Pim kinases are emerging as important mediators of adipocyte differentiation. AZD1208 is a pan‐Pim kinase inhibitor and is known for its anti‐cancer activity. In this study, we investigated the effect of AZD1208 on adipogenesis and lipolysis in 3T3‐L1 cells, a murine preadipocyte cell line. AZD1208 markedly suppressed lipid accumulation and reduced triglyceride contents in differentiating 3T3‐L1 cells, suggesting the drug's anti‐adipogenic effect. On mechanistic levels, AZD1208 reduced not only the expressions of CCAAT/enhancer‐binding protein‐α (C/EBP‐α), peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), fatty acid synthase (FAS), acetyl‐CoA carboxylase (ACC) and perilipin A but also the phosphorylation of signal transducer and activator of transcription‐3 (STAT‐3) in differentiating 3T3‐L1 cells. Remarkably, AZD1208 increased cAMP‐activated protein kinase (AMPK) and LKB‐1 phosphorylation while decreased intracellular ATP contents in differentiating 3T3‐L1 cells. Furthermore, in differentiated 3T3‐L1 adipocytes, AZD1208 also partially promoted lipolysis and enhanced the phosphorylation of hormone‐sensitive lipase (HSL), a key lipolytic enzyme, indicating the drug's HSL‐dependent lipolysis. In summary, the findings show that AZD1208 has anti‐adipogenic and lipolytic effects on 3T3‐L1 adipocytes. These effects are mediated by the expression and/or phosphorylation levels of C/EBP‐α, PPAR‐γ, FAS, ACC, perilipin A, STAT‐3, AMPK and HSL.</P>

PTEN inhibits replicative senescence‐induced MMP ‐1 expression by regulating NOX 4‐mediated ROS in human dermal fibroblasts

Noh, Eun&#x2010,Mi,Kim, Jeong&#x2010,Mi,Hong, On&#x2010,Yu,Song, Hyun&#x2010,Kyung,Kim, Jong‐,Suk,Kwon, Kang&#x2010,Beom,Lee, Young&#x2010,Rae CAROL DAVILA UNIVERSITY PRESS 2017 JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Vol.21 No.11

<P><B>Abstract</B></P><P>The biological function of NADPH oxidase (NOX) is the generation of reactive oxygen species (ROS). ROS, primarily arising from oxidative cell metabolism, play a major role in both chronological ageing and photoageing. ROS in extrinsic and intrinsic skin ageing may be assumed to induce the expression of matrix metalloproteinases. NADPH oxidase is closely linked with phosphatidylinositol 3‐OH kinase (PI3K) signalling. Protein kinase C (PKC), a downstream molecule of PI3K, is essential for superoxide generation by NADPH oxidase. However, the effect of PTEN and NOX4 in replicative‐aged MMPs expression has not been determined. In this study, we confirmed that inhibition of the PI3K signalling pathway by PTEN gene transfer abolished the NOX‐4 and MMP‐1 expression. Also, NOX‐4 down‐expression of replicative‐aged skin cells abolished the MMP‐1 expression and ROS generation. These results suggest that increase of MMP‐1 expression by replicative‐induced ROS is related to the change in the PTEN and NOX expression.</P>

Effects of FGF 21‐secreting adipose‐derived stem cells in thioacetamide‐induced hepatic fibrosis

Kang, Hwansu,Seo, Eunhui,Park, Jong‐,Moon,Han, Na&#x2010,Young,Lee, Hookeun,Jun, Hee&#x2010,Sook John Wiley and Sons Inc. 2018 JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Vol.22 No.10

<P><B>Abstract</B></P><P>Mesenchymal stem cells (MSCs) have been investigated to treat liver diseases, but the efficiency of MSCs to treat chronic liver diseases is conflicting. FGF21 can reduce inflammation and fibrosis. We established FGF21‐secreting adipose derived stem cells (FGF21_ADSCs) to enhance the effects of ADSCs and transplanted them into thioacetamide (TAA)‐induced liver fibrosis mice via the tail vein. Transplantation of FGF21_ADSCs significantly improved liver fibrosis by decreasing serum hyaluronic acid and reducing the expression of fibrosis‐related factors such as α‐smooth muscle actin (α‐SMA), collagen and tissue inhibitor of metalloproteinase‐1 (TIMP‐1) compared with the Empty_ADSCs by inhibition of p‐JNK, NF‐κB and p‐Smad2/3 signalling. α‐lactoalbumin (LA) and lactotransferrin (LTF), secretory factors produced from FGF21_ADSCs inhibited TGF‐β1‐induced expression of α‐SMA and collagen in LX‐2 cells. These results suggest that transplantation of FGF21_ADSCs inhibited liver fibrosis more effectively than Empty_ADSCs, possibly via secretion of α‐LA and LTF.</P>

Safety and efficacy of single‐agent docetaxel ( T axotere) administered weekly in non‐small cell lung carcinoma patients in K orea: An observational study

Lim, Sun Min,Park, Byeong Bae,Park, Keun&#x2010,Chil,Kim, Hoon&#x2010,Kyo,Lee, Jong Seok,Bae, Sung Hwa,Lee, Seung&#x2010,Sei,Kang, Jin&#x2010,Hyoung,Park, Se&#x2010,Hoon,Lee, Gyeong&#x2010,Won,Lee, Hy John Wiley and Sons Inc. 2016 Thoracic cancer Vol.7 No.2

<P><B>Abstract</B></P><P><B>Background</B></P><P>To investigate the efficacy, safety, and tolerability of weekly docetaxel treatment in advanced non‐small cell lung cancer (NSCLC) patients in Korea.</P><P><B>Methods</B></P><P>This prospective observational study included Korean advanced NSCLC patients with Eastern Cooperative Oncology Group performance status <2 who received weekly monotherapy of docetaxel at a dose determined by the physician. Efficacy measurements included tumor response rate, overall survival (OS), progression‐free survival, and one‐year survival rate. Safety was analyzed through recorded incidences of adverse events (AEs), serious adverse events (SAEs), deaths, and other related safety parameters, along with their toxicity grades.</P><P><B>Results: </B></P><P>Of 274 patients analyzed, one patient achieved a complete response and 42 partial responses; thus, the overall response rate was 15.7%. The OS rate at baseline and at one‐year follow‐up was 38.3% and 33.8%, respectively. AEs were reported in 229 (83.6%) patients. The most frequently reported hematologic AE of grade ≥3 was a decrease in neutrophils, with 6.6% of the patients developing neutropenia. In non‐hematologic AEs of grade ≥3, the most common were infection with unknown absolute neutrophil count and death not associated with Common Terminology Criteria for Adverse Events (CTCAE) (4.7% each). The most common SAE reported was death, not associated with CTCAE (7.3%).</P><P><B>Conclusions</B></P><P>In Korean patients, the weekly regimen of docetaxel monotherapy was safe and efficacious against advanced NSCLC.</P>