Patient‐specific 17‐segment myocardial modeling on a bull's‐eye map

Jung, Joonho,Kim, Young&#x2010,Hak,Kim, Namkug,Yang, Dong Hyun unknown 2016 Journal of applied clinical medical physics Vol.17 No.5

<P>The purpose of this study was to develop and validate cardiac computed tomography (CT) quantitative analysis software with a patient‐specific, 17‐segment myocardial model that uses electrocardiogram (ECG)‐gated cardiac CT images to differentiate between normal controls and severe aortic stenosis (AS) patients. ECG‐gated cardiac CT images from 35 normal controls and 144 AS patients were semiautomatically segmented to create a patient‐specific, 17‐segment myocardial model. Two experts then manually determined the anterior and posterior interventricular grooves to be boundaries between the 1st and 2nd segments and between the 3rd and 4th segments, respectively, to correct the model. Each segment was automatically identified as follows. The outer angle of two boundaries was divided to differentiate the 1st, 4th, 5th, and 6th segments in the basal plane, whereas the inner angle divided the 2nd and 3rd segments. The segments of the midplane were similarly divided. Segmental area distributions were quantitatively evaluated on the bull's‐eye map on the basis of the morphological boundaries by measuring the area of each segment. Segmental areas of severe AS patients and normal controls were significantly different (t‐test, all p‐values<0.011) in the proposed model because the septal regions of the severe AS patients were smaller than those of normal controls and the difference was enough to divide the two groups. The capabilities of the 2D segmental areas (p<0.011) may be equivalent to those of 3D segmental analysis (all p‐values<0.001) for differentiating the two groups (t‐test, all p‐values<0.001). The proposed method is superior to the conventional 17‐segment in relation to reflection of patient‐specific morphological variation and allows to obtain a more precise mapping between segments and the AHA recommended nomenclature. It can be used to differentiate severer AS patients and normal controls and also helps to understand the left ventricular morphology at a glance.</P><P>PACS number(s): 87.57.N‐, 87.57.R‐, 87.57.qp</P>

Naringenin targets ERK 2 and suppresses UVB ‐induced photoaging

Jung, Sung Keun,Ha, Su Jeong,Jung, Chang Hwa,Kim, Yun Tai,Lee, Hoo&#x2010,Keun,Kim, Myoung Ok,Lee, Mee&#x2010,Hyun,Mottamal, Madhusoodanan,Bode, Ann M.,Lee, Ki Won,Dong, Zigang John Wiley and Sons Inc. 2016 Journal of Cellular and Molecular Medicine Vol.20 No.5

<P><B>Abstract</B></P><P>A number of natural phytochemicals have anti‐photoaging properties that appear to be mediated through the inhibition of matrix metalloproteinase‐1 (MMP‐1) expression, but their direct target molecule(s) and mechanism(s) remain unclear. We investigated the effect of naringenin, a major flavonoid found in citrus, on UVB‐induced MMP‐1 expression and identified its direct target. The HaCaT human skin keratinocyte cell line and 3‐dimensional (3‐D) human skin equivalent cultures were treated or not treated with naringenin for 1 hr before exposure to UVB. The mechanism and target(s) of naringenin were analysed by kinase assay and multiplex molecular assays. Dorsal skins of hairless mice were exposed to UVB 3 times per week, with a dose of irradiation that was increased weekly by 1 minimal erythema dose (MED; 45 mJ/cm<SUP>2</SUP>) to 4 MED over 15 weeks. Wrinkle formation, water loss and water content were then assessed. Naringenin suppressed UVB‐induced MMP‐1 expression and AP‐1 activity, and strongly suppressed UVB‐induced phosphorylation of Fos‐related antigen (FRA)‐1 at Ser265. Importantly, UVB irradiation‐induced FRA1 protein stability was reduced by treatment with naringenin, as well as with a mitogen‐activated protein kinase (MEK) inhibitor. Naringenin significantly suppressed UVB‐induced extracellular signal‐regulated kinase 2 (ERK2) activity and subsequently attenuated UVB‐induced phosphorylation of p90<SUP>RSK</SUP> by competitively binding with ATP. Constitutively active MEK (CA‐MEK) increased FRA1 phosphorylation and expression and also induced MMP‐1 expression, whereas dominant‐negative ERK2 (DN‐ERK2) had opposite effects. U0126, a MEK inhibitor, also decreased FRA1 phosphorylation and expression as well as MMP‐1 expression. The photoaging data obtained from mice clearly demonstrated that naringenin significantly inhibited UVB‐induced wrinkle formation, trans‐epidermal water loss and MMP‐13 expression. Naringenin exerts potent anti‐photoaging effects by suppressing ERK2 activity and decreasing FRA1 stability, followed by down‐regulation of AP‐1 transactivation and MMP‐1 expression.</P>

Overexpression of <i>OsERF48</i> causes regulation of <i>OsCML16</i> , a calmodulin‐like protein gene that enhances root growth and drought tolerance

Jung, Harin,Chung, Pil Joong,Park, Su&#x2010,Hyun,Redillas, Mark Christian Felipe Reveche,Kim, Youn Shic,Suh, Joo&#x2010,Won,Kim, Ju&#x2010,Kon BLACKWELL 2017 PLANT BIOTECHNOLOGY JOURNAL Vol.15 No.10

<P><B>Summary</B></P><P>The AP2/ERF family is a plant‐specific transcription factor family whose members have been associated with various developmental processes and stress tolerance. Here, we functionally characterized the drought‐inducible <I>OsERF48</I>, a group Ib member of the rice ERF family with four conserved motifs, CMI‐1, ‐2, ‐3 and ‐4. A transactivation assay in yeast revealed that the C‐terminal CMI‐1 motif was essential for OsERF48 transcriptional activity. When <I>OsERF48</I> was overexpressed in an either a root‐specific (ROXO<SUP><I>s</I></SUP>ERF<SUP><I>48</I></SUP>) or whole‐body (OXO<SUP><I>s</I></SUP>ERF<SUP><I>48</I></SUP>) manner, transgenic plants showed a longer and denser root phenotype compared to the nontransgenic (NT) controls. When plants were grown on a 40% polyethylene glycol‐infused medium under <I>in vitro</I> drought conditions, ROXO<SUP><I>s</I></SUP>ERF<SUP><I>48</I></SUP> plants showed a more vigorous root growth than OXO<SUP><I>s</I></SUP>ERF<SUP><I>48</I></SUP> and NT plants. In addition, the ROXO<SUP><I>s</I></SUP>ERF<SUP><I>48</I></SUP> plants exhibited higher grain yield than OXO<SUP><I>s</I></SUP>ERF<SUP><I>48</I></SUP> and NT plants under field‐drought conditions. We constructed a putative <I>OsERF48</I> regulatory network by cross‐referencing ROXO<SUP><I>s</I></SUP>ERF<SUP><I>48</I></SUP> root‐specific RNA‐seq data with a co‐expression network database, from which we inferred the involvement of 20 drought‐related genes in <I>OsERF48</I>‐mediated responses. These included genes annotated as being involved in stress signalling, carbohydrate metabolism, cell‐wall proteins and drought responses. They included, <I>OsCML16</I>, a key gene in calcium signalling during abiotic stress, which was shown to be a direct target of OsERF48 by chromatin immunoprecipitation‐qPCR analysis and a transient protoplast expression assay. Our results demonstrated that OsERF48 regulates <I>OsCML16</I>, a calmodulin‐like protein gene that enhances root growth and drought tolerance.</P>

Anti‐inflammatory mechanism of ginsenoside Rh1 in lipopolysaccharide‐stimulated microglia: critical role of the protein kinase A pathway and hemeoxygenase‐1 expression

Jung, Ji&#x2010,Sun,Shin, Jin A.,Park, Eun&#x2010,Mi,Lee, Jung‐,Eun,Kang, Young&#x2010,Sook,Min, Sung&#x2010,Won,Kim, Dong&#x2010,Hyun,Hyun, Jin&#x2010,Won,Shin, Chan&#x2010,Young,Kim, Hee&#x201 Blackwell Publishing Ltd 2010 Journal of Neurochemistry Vol.115 No.6

<P> <I>J. Neurochem.</I> (2010) <B>115,</B> 1668–1680.</P><P><B>Abstract</B></P><P>Microglia activation plays a pivotal role in neurodegenerative diseases, and thus controlling microglial activation has been suggested as a promising therapeutic strategy for neurodegenerative diseases. In the present study, we showed that ginsenoside Rh1 inhibited inducible nitric oxide synthase, cyclooxygenase‐2, and pro‐inflammatory cytokine expression in lipopolysaccharide (LPS)‐stimulated microglia, while Rh1 increased anti‐inflammatory IL‐10 and hemeoxygenase‐1 (HO‐1) expression. Suppression of microglial activation by Rh1 was also observed in the mouse brain following treatment with LPS. Subsequent mechanistic studies revealed that Rh1 inhibited LPS‐induced MAPK phosphorylation and nuclear factor‐κB (NF‐κB)‐mediated transcription without affecting NF‐κB DNA binding. As the increase of pCREB (cAMP responsive element‐binding protein) is known to result in suppression of NF‐κB‐mediated transcription, we examined whether Rh1 increased pCREB levels. As expected, Rh1 increased pCREB, which was shown to be related to the anti‐inflammatory effect of Rh1 because pre‐treatment with protein kinase A inhibitors attenuated the Rh1‐mediated inhibition of nitric oxide production and the up‐regulation of IL‐10 and HO‐1. Furthermore, treatment of HO‐1 shRNA attenuated Rh1‐mediated inhibition of nitric oxide and reactive oxygen species production. Through this study, we have demonstrated that protein kinase A and its downstream effector, HO‐1, play a critical role in the anti‐inflammatory mechanism of Rh1 by modulating pro‐ and anti‐inflammatory molecules in activated microglia.</P>

3′‐Sialyllactose as an inhibitor of p65 phosphorylation ameliorates the progression of experimental rheumatoid arthritis

Kang, Li&#x2010,Jung,Kwon, Eun&#x2010,Soo,Lee, Kwang Min,Cho, Chanmi,Lee, Jae&#x2010,In,Ryu, Young Bae,Youm, Tae Hyun,Jeon, Jimin,Cho, Mi Ra,Jeong, Seon&#x2010,Yong,Lee, Sang&#x2010,Rae,Kim, Wook,Yang John Wiley and Sons Inc. 2018 British journal of pharmacology Vol.175 No.23

<P><B>Background and Purpose</B></P><P>3′‐Sialyllactose (3′‐SL) is a safe compound that is present in high levels in human milk. Although it has anti‐inflammatory properties and supports immune homeostasis, its effect on collagen‐induced arthritis (CIA) is unknown. In this study, we investigated the prophylactic and therapeutic effect of 3′‐SL on the progression of rheumatoid arthritis (RA) in <I>in vitro</I> and <I>in vivo</I> models.</P><P><B>Experimental Approach</B></P><P>The anti‐arthritic effect of 3′‐SL was analysed with fibroblast‐like synoviocytes <I>in vitro</I> and an <I>in vivo</I> mouse model of CIA. RT‐PCR, Western blotting and ELISA were performed to evaluate its effects <I>in vitro</I>. Histological analysis of ankle and knee joints of mice with CIA was performed using immunohistochemistry, as well as safranin‐O and haematoxylin staining.</P><P><B>Key Results</B></P><P>3′‐SL markedly alleviated the severity of CIA in the mice by reducing paw swelling, clinical scores, incidence rate, serum levels of inflammatory cytokines and autoantibody production. Moreover, 3′‐SL reduced synovitis and pannus formation and suppressed cartilage destruction by blocking secretion of chemokines, pro‐inflammatory cytokines, https://en.wikipedia.org/wiki/Matrix_metalloproteinases and osteoclastogenesis <I>via</I> NF‐κB signalling. Notably, phosphorylation of p65, which is a key protein in the NF‐κB signalling pathway, was totally blocked by 3′‐SL in the RA models.</P><P><B>Conclusions and Implications</B></P><P>3′‐SL ameliorated pathogenesis of CIA by suppressing catabolic factor expression, proliferation of inflammatory immune cells and osteoclastogenesis. These effects were mediated <I>via</I> blockade of the NF‐κB signalling pathway. Therefore, 3′‐SL exerted prophylactic and therapeutic effects and could be a novel therapeutic agent for the treatment of RA.</P>

The deubiquitinating enzyme, ubiquitin‐specific peptidase 50, regulates inflammasome activation by targeting the ASC adaptor protein

Lee, Jae Young,Seo, Dongyeob,You, Jiyeon,Chung, Sehee,Park, Jin Seok,Lee, Ji&#x2010,Hyung,Jung, Su Myung,Lee, Youn Sook,Park, Seok Hee John Wiley and Sons Inc. 2017 FEBS letters Vol.591 No.3

<P>NOD‐like receptor family protein 3 (NLRP3)‐mediated inflammasome activation promotes caspase‐1‐dependent production of interleukin‐1β (IL‐1β) and requires the adaptor protein ASC. Compared with the priming and activation mechanisms of the inflammasome signaling pathway, post‐translational ubiquitination/deubiquitination mechanisms controlling inflammasome activation have not been clearly addressed. We here demonstrate that the deubiquitinating enzyme USP50 binds to the ASC protein and subsequently regulates the inflammasome signaling pathway by deubiquitinating the lysine 63‐linked polyubiquitination of ASC. USP50 knockdown in human THP‐1 cells and mouse bone marrow‐derived macrophages shows a significant decrease in procaspase‐1 cleavage, resulting in a reduced secretion of IL‐1β and interleukin‐18 (IL‐18) upon treatment with NLRP3 stimuli and a reduction in ASC speck formation and oligomerization. Thus, we elucidate a novel regulatory mechanism of the inflammasome signaling pathway mediated by the USP50 deubiquitinating enzyme.</P>

DMSO‐ and Serum‐Free Cryopreservation of Wharton's Jelly Tissue Isolated From Human Umbilical Cord

Shivakumar, Sharath Belame,Bharti, Dinesh,Subbarao, Raghavendra Baregundi,Jang, Si&#x2010,Jung,Park, Ji&#x2010,Sung,Ullah, Imran,Park, Ji&#x2010,Kwon,Byun, June&#x2010,Ho,Park, Bong&#x2010,Wook,Rho, G John Wiley and Sons Inc. 2016 Journal of cellular biochemistry Vol.117 No.10

<P><B>ABSTRACT</B></P><P>The facile nature of mesenchymal stem cell (MSC) acquisition in relatively large numbers has made Wharton's jelly (WJ) tissue an alternative source of MSCs for regenerative medicine. However, freezing of such tissue using dimethyl sulfoxide (DMSO) for future use impedes its clinical utility. In this study, we compared the effect of two different cryoprotectants (DMSO and cocktail solution) on post‐thaw cell behavior upon freezing of WJ tissue following two different freezing protocols (Conventional [−1°C/min] and programmed). The programmed method showed higher cell survival rate compared to conventional method of freezing. Further, cocktail solution showed better cryoprotection than DMSO. Post‐thaw growth characteristics and stem cell behavior of Wharton's jelly mesenchymal stem cells (WJMSCs) from WJ tissue cryopreserved with a cocktail solution in conjunction with programmed method (Prog‐Cock) were comparable with WJMSCs from fresh WJ tissue. They preserved their expression of surface markers, pluripotent factors, and successfully differentiated in vitro into osteocytes, adipocytes, chondrocytes, and hepatocytes. They also produced lesser annexin‐V‐positive cells compared to cells from WJ tissue stored using cocktail solution in conjunction with the conventional method (Conv‐Cock). Real‐time PCR and Western blot analysis of post‐thaw WJMSCs from Conv‐Cock group showed significantly increased expression of pro‐apoptotic factors (BAX, p53, and p21) and reduced expression of anti‐apoptotic factor (BCL2) compared to WJMSCs from the fresh and Prog‐Cock group. Therefore, we conclude that freezing of fresh WJ tissue using cocktail solution in conjunction with programmed freezing method allows for an efficient WJ tissue banking for future MSC‐based regenerative therapies. J. Cell. Biochem. 117: 2397–2412, 2016. © 2016 The Authors. <I>Journal of Cellular Biochemistry</I> published by Wiley Periodicals, Inc.</P>

3′‐Sialyllactose protects against osteoarthritic development by facilitating cartilage homeostasis

Jeon, Jimin,Kang, Li&#x2010,Jung,Lee, Kwang Min,Cho, Chanmi,Song, Eun Kyung,Kim, Wook,Park, Tae Joo,Yang, Siyoung John Wiley and Sons Inc. 2018 JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Vol.22 No.1

<P><B>Abstract</B></P><P>3′‐Sialyllactose has specific physiological functions in a variety of tissues; however, its effects on osteoarthritic development remain unknown. Here, we demonstrated the function of 3′‐sialyllactose on osteoarthritic cartilage destruction. <I>In vitro</I> and <I>ex vivo</I>, biochemical and histological analysis demonstrated that 3′‐sialyllactose was sufficient to restore the synthesis of Col2a1 and accumulation of sulphated proteoglycan, a critical factor for cartilage regeneration in osteoarthritic development, and blocked the expression of Mmp3, Mmp13 and Cox2 induced by IL‐1β, IL‐6, IL‐17 and TNF‐α, which mediates cartilage degradation. Further, reporter gene assays revealed that the activity of Sox9 as a transcription factor for Col2a1 expression was accelerated by 3′‐sialyllactose, whereas the direct binding of NF‐κB to the <I>Mmp3</I>,<I> Mmp13</I> and <I>Cox2</I> promoters was reduced by 3′‐sialyllactose in IL‐1β‐treated chondrocytes. Additionally, IL‐1β induction of Erk phosphorylation and IκB degradation, representing a critical signal pathway for osteoarthritic development, was totally blocked by 3′‐sialyllactose in a dose‐dependent manner. <I>In vivo</I>, 3′‐sialyllactose protected against osteoarthritic cartilage destruction in an osteoarthritis mouse model induced by destabilization of the medial meniscus, as demonstrated by histopathological analysis. Our results strongly suggest that 3′‐sialyllactose may ameliorate osteoarthritic cartilage destruction by cartilage regeneration <I>via</I> promoting Col2a1 production and may inhibit cartilage degradation and inflammation by suppressing Mmp3, Mmp13 and Cox2 expression. The effects of 3′‐sialyllactose could be attributed in part to its regulation of Sox9 or NF‐κB and inhibition of Erk phosphorylation and IκB degradation. Taken together, these effects indicate that 3′‐sialyllactose merits consideration as a natural therapeutic agent for protecting against osteoarthritis.</P>

Caveolin‐1 deficiency induces premature senescence with mitochondrial dysfunction

Yu, Dong&#x2010,Min,Jung, Seung Hee,An, Hyoung&#x2010,Tae,Lee, Sungsoo,Hong, Jin,Park, Jun Sub,Lee, Hyun,Lee, Hwayeon,Bahn, Myeong&#x2010,Suk,Lee, Hyung Chul,Han, Na&#x2010,Kyung,Ko, Jesang,Lee, Jae&# BLACKWELL PUBLISHING 2017 AGING CELL Vol.16 No.4

<P><B>Summary</B></P><P>Paradoxical observations have been made regarding the role of caveolin‐1 (Cav‐1) during cellular senescence. For example, caveolin‐1 deficiency prevents reactive oxygen species‐induced cellular senescence despite mitochondrial dysfunction, which leads to senescence. To resolve this paradox, we re‐addressed the role of caveolin‐1 in cellular senescence in human diploid fibroblasts, A549, HCT116, and Cav‐1<SUP><I>−/−</I></SUP> mouse embryonic fibroblasts. Cav‐1 deficiency (knockout or knockdown) induced cellular senescence via a p53‐p21‐dependent pathway, downregulating the expression level of the cardiolipin biosynthesis enzymes and then reducing the content of cardiolipin, a critical lipid for mitochondrial respiration. Our results showed that Cav‐1 deficiency decreased mitochondrial respiration, reduced the activity of oxidative phosphorylation complex I (CI), inactivated SIRT1, and decreased the NAD<SUP>+</SUP>/NADH ratio. From these results, we concluded that Cav‐1 deficiency induces premature senescence via mitochondrial dysfunction and silent information regulator 2 homologue 1 (SIRT1) inactivation.</P>

Trend analysis of diabetic prevalence and incidence in a rural area of South Korea between 2003–2008

Jeong, Ji Yun,Kim, Jung‐,Guk,Kim, Bo&#x2010,Wan,Moon, Seong Su,Kim, Hye&#x2010,Soon,Park, Keun&#x2010,Gyu,Won, Kyu Chang,Lee, Hyoung Woo,Yoon, Ji Sung,Shon, Ho&#x2010,Sang,Lee, Ji Hyun,Jung, Eui Blackwell Publishing Ltd 2010 Journal of diabetes investigation Vol.1 No.5

<P><B>Abstract</B></P><P><B>Aims/Introduction: </B> This study determined the change in prevalence of diabetes and prediabetes over a period of 5 years in South Korea. The incidence of diabetes and prediabetes and risk factors associated with the development of diabetes were also investigated.</P><P><B>Materials and Methods: </B> The Dalseong population‐based cohort survey recruited 1806 subjects who were over 20‐years‐old in 2003. Five years later, 1287 of the original subjects were re‐evaluated and 187 new subjects were added to the study. All participants completed a questionnaire, were given a physical examination, and provided blood samples for analysis including 2 h oral glucose tolerances.</P><P><B>Results: </B> Age‐adjusted prevalence of diabetes rose from 6.7% in 2003 to 9.1% in 2008. The prevalence of prediabetes also increased from 18.5% in 2003 to 28.4% in 2008. The incidence rates of diabetes and prediabetes were 18.3 per 1000 person‐years and 55.4 per 1000 person‐years, respectively. The development of diabetes was associated with impaired fasting glucose (IFG) (odds ratio [OR] 5.661), impaired glucose tolerance (IGT) (OR: 6.013), age (OR 1.013), and waist‐to‐hip ratio (OR 1.513). After excluding the IFG and IGT, systolic blood pressure (OR 1.023), high‐sensitivity C‐reactive protein (hsCRP; OR 1.097), triglyceride (OR 1.002) and waist‐to‐hip ratio (OR 1.696) were statistically significant risk factors in a multivariate logistic regression analysis.</P><P><B>Conclusions: </B> A significant rise in the prevalence of diabetes and prediabetes was observed between 2003 and 2008. In addition, this study newly demonstrated that waist‐to‐hip ratio and hsCRP were associated with the development of diabetes after adjusting for several confounding factors. <B>(J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00045.x, 2010)</B></P>