Effect of peiminine on DNCB-induced atopic dermatitis by inhibiting inflammatory cytokine expression <i>in vivo</i> and <i>in vitro</i>

Lim, Jeong-Min,Lee, Bina,Min, Ju-Hee,Kim, Eun-Young,Kim, Jae-Hyun,Hong, SooYeon,Kim, Jwa-Jin,Sohn, Youngjoo,Jung, Hyuk-Sang Elsevier 2018 INTERNATIONAL IMMUNOPHARMACOLOGY Vol.56 No.-

<P><B>Abstract</B></P> <P>Peiminine (PMN) is the main component derived from Fritillaria ussuriensis and is used in traditional medicine in East Asia. The aim of this study was to evaluate the effects of PMN on atopic dermatitis (AD) induced by a dinitrochlorobenzene (DNCB) in Balb/c mice. Inflammatory cytokine expression of PMN was investigated <I>in vitro</I>. Eosinophil infiltration and the thickness of DNCB-induced AD mouse skin were measured. The levels of IgE, IL-4, IL-6, IL-13, and TNF-α in the serum were measured by ELISA. The effects of PMN on the transcription level of MAPK and nuclear factor (NF)-κB were evaluated in mouse skin. In addition, the inhibitory effect of TNF-α, IL-1β, COX-2 and PGE2 were measured in RAW264.7 cells; TARC was investigated in HaCaT cells; and β-hexosaminidase was examined in RBL-2H3 cells. PMN decreased the number of eosinophils in the dermis as well as mast cells and decreased the thickness of the epidermis and dermis. The PMN High group had a significantly reduced serum level of IgE, IL-4, IL-13 and TNF-α. Moreover, P-ERK and P-P38 were inhibited in the PMN High group compared with the DNCB-treated group. PMN additionally attenuated the expression of inflammatory cytokines in cells, including RAW264.7, HaCaT and RBL-2H3 cells. Our results suggest that PMN could be a potential therapeutic candidate for the treatment of AD.</P> <P><B>Highlights</B></P> <P> <UL> <LI> PMN has an inhibitory effect on atopic dermatitis by decreasing inflammatory cytokines. </LI> <LI> PMN reduced the number of eosinophils and mast cells as well as MAPK and NF-κB signaling in tissues. </LI> <LI> PMN decreased COX-2 and prostaglandin E2 in RAW264.7. </LI> <LI> PMN inhibited TARC in human keratinocytes and reduced β-hexosaminidase in RBL-2H3 cells. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Isolation of primitive mouse extraembryonic endoderm (pXEN) stem cell lines

Zhong, Yixiang,Choi, Taewoong,Kim, Minjae,Jung, Kyoung Hwa,Chai, Young Gyu,Binas, Bert Elsevier 2018 Stem cell research Vol.30 No.-

<P><B>Abstract</B></P> <P>Mouse blastocysts contain the committed precursors of the extraembryonic endoderm (ExEn), which express the key transcription factor Oct4, depend on LIF/LIF-like factor-driven Jak/Stat signaling, and initially exhibit lineage plasticity. Previously described rat blastocyst-derived ExEn precursor-like cell lines (XENP cells/HypoSCs) also show these features, but equivalent mouse blastocyst-derived cell lines are lacking. We now present mouse blastocyst-derived cell lines, named primitive XEN (pXEN) cells, which share these and additional characteristics with the XENP cells/HypoSCs, but not with previously known mouse blastocyst-derived XEN cell lines. Otherwise, pXEN cells are highly similar to XEN cells by morphology, lineage-intrinsic differentiation potential, and multi-gene expression profile, although the pXEN cell profile correlates better with the blastocyst stage. Finally, we show that pXEN cells easily convert into XEN-like cells but not vice versa. The findings indicate that (i) pXEN cells are more representative than XEN cells of the blastocyst stage; (ii) mouse pXEN, rather than XEN, cells are homologs of rat XENP cells/HypoSCs, which we propose to call rat pXEN cells.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We present novel mouse extraembryonic endoderm stem cell lines (pXEN cells). </LI> <LI> pXEN cells show preimplantation-stage features not shown by XEN cells. </LI> <LI> pXEN cells are easily converted into XEN-like cells but not vice versa. </LI> <LI> pXEN cells are homologous to previously described rat XENP cells/HypoSCs. </LI> </UL> </P> <P>Graphical abstract</P> <P>[DISPLAY OMISSION]</P>

Olig2 is expressed late in human eosinophil development and controls Siglec-8 expression

Hwang, Sae Mi,Uhm, Tae Gi,Lee, Seol Kyung,Kong, Su-Kang,Jung, Kyung Hwa,Binas, Bert,Chai, Young Gyu,Park, Sung Woo,Chung, Il Yup Wiley (John WileySons) 2016 Journal of leukocyte biology Vol.100 No.4

<P>Oligodendrocyte transcription factor 2, a basic helix-loop-helix transcription factor that binds to E-box motifs, is known to have a key role in determining lineage specification of oligodendrocytes and motor neurons. In the present study, we report that oligodendrocyte transcription factor 2 is expressed in human eosinophils and involved in transcriptional activation of the gene encoding sialic acid binding immunoglobulin-like lectin 8 (Siglec-8), a late eosinophil-differentiation marker known to exert eosinophil apoptosis. When cord blood CD34(+) hematopoietic stem cells differentiated toward eosinophils during a 24-d culture period, oligodendrocyte transcription factor 2 protein was expressed in cord blood eosinophils on d 24, a time when cord blood eosinophils are considered fully differentiated, whereas it was not detectable on d 18 or at earlier time points. Oligodendrocyte transcription factor 2 protein was also abundantly expressed in human peripheral-blood eosinophils but not in neutrophils, monocytes, lymphocytes, or cord blood mast cells. RNA sequencing analysis showed that numerous genes, especially those encoding eosinophil surface molecules, were highly up-regulated along with OLIG2. Among the genes examined, SIGLEC-8 messenger RNA and protein were markedly downregulated in parallel with OLIG2 by an oligodendrocyte transcription factor 2 small interfering RNA or a short hairpin RNA, as evidenced by real-time polymerase chain reaction, fluorescence-activated cell sorting, and Western blot analyses. In reporter gene and chromatin immunoprecipitation experiments, an E-box in the first intron was found to stimulate SIGLEC-8 gene transcription and to bind oligodendrocyte transcription factor 2. Hence, at least one important aspect of eosinophil differentiation is regulated by oligodendrocyte transcription factor 2, a transcription factor that has not previously been reported, to our knowledge, in normal granulocytes.</P>

<i>Lycopus lucidus</i> Turcz Inhibits the Osteoclastogenesis in RAW 264.7 Cells and Bone Loss in Ovariectomized Rat Model

Jeong, Da-Won,Kim, Eun-Young,Kim, Jae-Hyun,Lee, Bina,Hong, SooYeon,Park, Jae Ho,Jung, Hyuk-Sang,Sohn, Youngjoo Hindawi 2019 Evidence-based Complementary and Alternative Medic Vol.2019 No.-

<P><I>Lycopus lucidus</I> (LL) is a perennial herb that is traditionally used in Asia to treat edema, wound healing, and gynecological diseases such as irregular menstruation and menstrual pain. We hypothesized that LL would decrease the risk of developing osteoporosis, which is a condition related to gynecological diseases. In this study, we aimed to investigate the effect of a water extract of LL on osteoclastogenesis<I> in vitro</I> and osteoporosis<I> in vivo</I>.<I> In vitro</I> study, we used RAW 264.7 cells as osteoclast precursor cell. Osteoclast differentiation was induced by receptor activator nuclear factor-kappa B ligand (RANKL). We investigated the effect of LL on RANKL-induced osteoclastogenesis, tartrate-resistant acid phosphatase (TRAP) activity, and osteoclast-related genes.<I> In vivo</I> study, we used ovariectomized- (OVX-) induced osteoporosis rat model. OVX-induced Sprague-Dawley rats were randomly separated into sham, OVX, 17<I>β</I>-estradiol (100 <I>μ</I>g/kg), wLL-L (15.2 mg/kg), and wLL-H (152 mg/kg) groups. Drugs were administered orally once daily for 9 weeks. wLL inhibited the formation of TRAP-positive osteoclasts; TRAP activity; pit formation; transcription factors (the nuclear factor of activated T-cell cytoplasmic 1 and c-fos); and osteoclast-related genes such as TRAP, carbonic anhydrase II, cathepsin K, osteoclast-associated receptor, and the d2 isoform of the vacuolar ATPase Vo domain. Also, wLL prevented loss of the trabecular area in the OVX femur without change of estrogen level. These results indicate that wLL is able to inhibit osteoclastogenesis and protect bone loss in the OVX-induced osteoporosis model without the influence of hormones like estrogen.</P>

난알부민으로 알레르기 비염이 유발된 마우스에서 형개의 개선효과

송대욱 ( Dea Uk Song ),허준 ( Jun Heo ),이성엽 ( Sungyub Lee ),김재현 ( Jae Hyun Kim ),이비나 ( Bina Lee ),민주희 ( Ju Hee Min ),김은영 ( Eun Young Kim ),손영주 ( Youngjoo Sohn ),정혁상 ( Hyuk Sang Jung ) 대한본초학회 2015 大韓本草學會誌 Vol.30 No.6

Objectives : The aim of this study was to evaluate the effect of Schizonepeta Spica water extract (SS) on the OVA-induced BLAB/c mice allergic rhinitis model. Methods : Thirty two BALB/c mice were equally assigned to 4 groups; the sham group, the control group, the cetirizine hydrochloride (Cet) treatment group, and the SS treatment group. Sham group was sensitized and challenged with saline, and the other groups were sensitized and challenged with OVA. The dosage of SS was 7.6 mg /kg·day, and Cet was 10 mg/kg·day. Nasal rubbing and sneezing were measured by the behavior observation. The concentrations of IL-1β, IL-10, TNF-α and MIP-2 in the sera of allergic rhinitis model were measured by mouse cytokine/chemokine magnetic bead panel kits. Total IgE and OVA-specific IgE were measured by ELISA method. Epithelial thickness and eosinophil infiltration of nasal septum was investigated by histological examination. Results : The clinical symptoms that increased in control group were significantly reduced in SS-treated group. Serum total IgE and OVA-specific IgE in the SS-treated group were significantly reduced compared to the control group. The concentration of IL-1β, IL-10, TNF-α and MIP-2 in SS-treated group showed a significant reduction compared to the control group. The infiltration of eosinophil into nasal tissues of SS-treated group decreased markedly compared to control group, and thickness of nasal septum in nasal mucosa showed a significant reduction compared to control group. Conclusions : According to the above result, it is suggested that SS may inhibit the early and late phase of allergic rhinitis reaction.

고삼, 형개, 자초 혼합물(GHJ)의 인간비만세포에서의 항염증 효과

황만기,최영진,김민주,이비나,정혁상,손영주,Hwang, Man Ki,Choi, Young Jin,Kim, Min Ju,Lee, Bina,Jung, Hyuk Sang,Sohn, Youngjoo 대한한의학방제학회 2017 大韓韓醫學方劑學會誌 Vol.25 No.2

Objectives : This study aimed to evaluate inhibitory effects of GHJ on allergic inflammatory response in human mast cells (HMC-1). Methods : To investigate the inhibitory effect of GHJ (62.5, 125, 250, 500, $1000{\mu}g/mL$), HMC-1 cells were stimulated with phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI). Enzyme-linked immunosorbent assays (ELISAs), RT-PCR and Western blot analysis were investigated using GHJ extract. Results : GHJ inhibited levels of $TNF-{\alpha}$ and IL-6 of $1000{\mu}g/mL$ concentration in ELISA and mRNA expression. GHJ had inhibitory effects in level of MAPKs, $p-I{\kappa}B-{\alpha}$ and p-NF-kB also. GHJ attenuated Compound 48/80-stimulated histamine release. In addition, GHJ inhibited PCA reaction in vivo. Conclusion : This study indicated that GHJ extract can inhibit allergic responses in HMC-1 cell.

Differential DNA Methylation as a Potential Biomarker for Stratification of Liver Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease

( Yu Rim Lee ),( Eunhye Lee ),( Se Young Jang ),( Won Young Tak ),( Young Oh Kweon ),( Bina Jung ),( Gyoun Eun Kang ),( Sang Kyung Seo ),( Jung Gil Park ),( Hye Won Lee ),( Young Seok Han ),( Jae Min 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Non-alcoholic fatty liver disease (NAFLD) can progress to advanced liver disease, but only in a minority of patients. Differential liver DNA methylation of peroxisome proliferator-activated receptor gamma (PPARγ) gene promoter has been shown to distinguish patients in terms of fibrosis severity in NAFLD. However, a study of methylation of PPARγ gene promoter in human with a sufficient number of patients is still scarce. We therefore determined the prognostic significance of DNA methylation of PPARγ gene promoter in patients with NAFLD. Methods: This study enrolled 54 biopsy proven NAFLD patients and 18 healthy controls who attended Kyungpook National University Hospital, Republic of Korea between March 2015 and October 2016. We extracted genomic DNA from liver tissue of enrolled patients. Bisulfite modification of genomic DNA was performed and PPARγ methylation level was confirmed with pyrosequencing. Results: The average of 4CpG methylation of PPARγ promoter had significantly lower in the NAFLD group (15.03% DNA methylation) when compared to the healthy controls (19.55%) (P=0.001). Quantitative DNA methylation of PPARγ stratified patients into mild (Kleiner 0-2) and severe (Kleiner 3-4) fibrosis (14.21% vs 17.87%, P=0.007). Moreover, hypermethylation at the PPARγ promoter of liver was also associated with higher age, the presence of DM, NAFLD fibrosis score, the degree of steatosis and fibrosis (P=0.015, 0.024, 0.012, 0.027, 0.009, respectively). However, they were not associated with presence and degree of inflammation, ballooning, NAFLD activity score, the presence of NASH, and other liver function test. Patients with advanced fibrosis exhibited significantly higher NAFLD fibrosis score, FIB-4, and PPARγ DNA methylation (all P<0.05) and showed borderline significance with transient elastography (P=0.084). These markers, including NAFLD fibrosis score, FIB- 4, and PPARγ DNA methylation, had an area under the receiver operating curve (AUROC) of 0.855, 0.778, 0.75, respectively for predicting advanced fibrosis. PPARγ mRNA was also related to the fibrosis and steatosis severity (P<0.05). This showed negative regulation with DNA methylation level (P=0.001). Conclusions: DNA methylation level of PPARγ may be useful in NAFLD patients for stratification and prediction of progressive liver fibrosis, which is a very important factor of NAFLD patients that is currently impossible to predict. It may be possible to generate an algorithm that can predict more precisely which patients are likely to progress on to a severe fibrosis in patients with NAFLD using DNA methylation and other markers related to liver fibrosis.

麥門冬 에탄올 추출물이 알레르기 염증 반응에 미치는 영향

김호석(Ho Seok Kim),박지혜(Ji hye Park),김현갑(Hyun Kab Kim),김재현(Jae Hyun Kim),이비나(Bina Lee),민주희(Ju Hee Min),김은영(Eun Young Kim),정혁상(Hyuk Sang Jung),이향숙(Hyang Sook Lee),손영주(Young Joo Sohn) 한의병리학회 2014 동의생리병리학회지 Vol.28 No.5

Forkhead box O1 (FOXO1) controls the migratory response of Toll-like receptor (TLR3)-stimulated human mesenchymal stromal cells

Hwa Kim, Sun,Das, Amitabh,In Choi, Hae,Hoon Kim, Ki,Choul Chai, Jin,Ran Choi, Mi,Binas, Bert,Sun Park, Kyoung,Seek Lee, Young,Jung, Kyoung Hwa,Gyu Chai, Young American Society for Biochemistry and Molecular Bi 2019 The Journal of biological chemistry Vol.294 No.21

<P>Mesenchymal stromal cells (MSCs) can potently regulate the functions of immune cells and are being investigated for the management of inflammatory diseases. Toll-like receptor 3 (TLR3)-stimulated human MSCs (hMSCs) exhibit increased migration and chemotaxis within and toward damaged tissues. However, the regulatory mechanisms underlying these migratory activities are unclear. Therefore, we analyzed the migration capability and gene expression profiles of TLR3-stimulated hMSCs using RNA-Seq, wound healing, and transwell cell migration assay. Along with increased cell migration, the TLR3 stimulation also increased the expression of cytokines, chemokines, and cell migration-related genes. The promoter regions of the latter showed an enrichment of putative motifs for binding the transcription factors forkhead box O1 (FOXO1), FOXO3, NF-κB (NF-κB1), and RELA proto-oncogene and NF-κB subunit. Of note, FOXO1 inhibition by the FOXO1-selective inhibitor AS1842856 significantly reduced both migration and the expression of migration-related genes. In summary, our results indicate that TLR3 stimulation induces hMSC migration through the expression of FOXO1-activated genes.</P>

Prognostic Factors Affecting Treatment Outcomes of Acute Variceal Bleeding in Patients with Hepatocellular Carcinoma : A Single Center Prospective Study

( Yu Rim Lee ),( Soo Young Park ),( Won Young Tak ),( Young Oh Kweon ),( Se Young Jang ),( Jun Sik Yoon ),( Bina Jeong ),( Gyoun Eun Kang ),( Sang Kyung ),( Seo Keun Hur ),( Jung Gil Park ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Because acute variceal bleeding is associated with significant morbidity and mortality in cirrhotic patients, the prediction of prognosis is important. We therefore studied about prognostic factors affecting treatment outcomes of acute variceal bleeding. In addition, factors related acute variceal bleeding in patients with HCC were also determined with particular emphasis. Methods: Endoscopy-proven acute variceal bleeding patients admitted to the Kyungpook National University Hospital between 2007 and 2013 were enrolled in this prospective cohort study. Endoscopic procedures including either endoscopic variceal ligation or sclerotherapy with N-butyl-2-cyanoacrylate were performed for the patients within 24 hours after admission. The prognostic factors were identified by applying the multivariate Cox proportional-hazards regression test using significant variables in univariate analysis. Results: 329 patients were finally included in this study. During the study period (median=15.6 months), 186 patients at a median of 4.3 months were expired. Nineteen patients were expired in 5 days, which accounted for 38.8% of 6-week mortality (n=49). Six-week mortality was related to the MELD score and 5-day treatment failure in multivariate analysis in all patients and HCC subgroup (all P<0.05). When the patients were divided into two groups by MELD score, the risk of 6 week mortality was higher in patients with MELD ≥ 15.5 than in those with MELD < 15.5 (log rank test, P<0.001). We also found that 85% of patients with both MELD score ≥ 15.5 and terminal cancer stage including mUICC stage 4 or BCLC stage D expired within six weeks and 6-week mortality risk is about 10 times higher compared to patients with lower MELD score and earlier stage after adjusting other factors (P<0.05). Conclusions: Follow-up strategy and managements are required for the individual patients, depending on these risk factors. According to our study, overly enthusiastic endoscopic treatment in patients with poor liver function and end-stage HCC may be unnecessary.