당뇨병환자에서 게이트심장혈액풀신티그라피를 이용한 심기능 평가

윤상임,송치운,이진홍,안미애,성기양,송민호,이강욱,신영태,김영건,노흥규 충남대학교 의과대학 지역사회의학연구소 1993 충남의대잡지 Vol.20 No.2

Major cardiovascular complications of diabetes are coronary atherosclerosis, diabetic dilated cardiomyopathy, autonomic neuropathy and those are major causes of morbidity and mortality in diabetic patients. Gated blood pool heart scan is noninvasive and useful method for evaluation of functional status of heart in diabetics. We evaluated 52 patients with diabetes and divided 3 groups. Group 1 were 11 patients without proteinuria or with proteinuria less than 550mng during 24 hours. Group 2 were 9 patients with proteinuria more than 550mg during 24 hours and group 3 were 32 patients with endstage renal diasese due to diabetes. We performed 99mTc-HSA cardiac gated blood pool scan and used left ventricular ejection fraction(LVEF), peak ejection rate(PEF) to indices of LV systolic function and peak filling rate(PER) to index of LV diastolic function. The results were follows : 1) LVEF, PER were significantly lower in diabetics with ESRD than diabetics without ESRD, but there were no significant difference between normal controls and diabetics without ESRD 2) PFR was significantly lower in diabetics than normal controls, but there were no significant differences in diabetics with or without nephropathy. 3) There were negative correlation between PER, PFR and duration of diabetes. On the basis of results, PFR is a LV functional index of GBPS which can disclose early change of LV dysfunction in patients with diabetes.

국내산 및 제초제 내성 콩(HS2906)의 일반성분, 무기질 및 지방산 조성

양윤형,이정희,김형진,윤원기,김환묵,김미리 동아시아식생활학회 2005 동아시아식생활학회지 Vol.15 No.1

Proximate analysis, mineral and fatty acid composition of three conventional domestic soybean cultivars and two imported ones including glyphosate-tolerant HS2906 were evaluated by AOAC method, ICP-AES and gas chromatography. There were several differences in the proximate analysis among three conventional domestic soybean cultivars ; higher crude fat in the cultivar Hwanggumkong, higher crude protein in Pungsankong, and higher carbohydrate and crude ash in Duyukong. The ranges of contents of proximate components of domestic cultivars were similar to the data previously reported. There were no significant differences in proximate analysis between conventional soybean WS82 and glyphosate-tolerant HS2906 ; 23.55~23.90% of crudefat, 34.22~35.55% of crude protein, 6.25~6.45% of crude ash, and 25.35~26.47% of carbohydrate. The mineral and fatty acid compositions of HS2906 were similar to those of conventional soybeans previously reported.

중이, 외이도 및 측두하와에 국한된 편평상피유두종 1예

윤병문,박성원,민경식,홍기수,조미연,양석우 대한이비인후과학회 1999 대한이비인후과학회지 두경부외과학 Vol.42 No.7

혈액투석중인 만성신부전 환자에서 골대사 지표로써의 Osteocalcin치

송치운,이진홍,안미애,윤환중,윤상임,성기양,이강현,송민호,이강욱,신영태,김영건,노흥규 충남대학교 의과대학 지역사회의학연구소 1993 충남의대잡지 Vol.20 No.2

Background : Serum osteocalcin is synthesized by osteoblast and has been shown to be sensitive indicator of bone turnover inpatients with various metabolic bone disease. In renal osteodystrophy, serum osteocalcin is elevated due to decreased renal clearance and elevated level of PTH. This study was done to evaluate the usefulness of serum osteocalcin as a marker of bone metabolism and the correlation with other biochemical markers of bone metabolism. Methods : We measured serum osteocalcin, calcium, phosphorus, ALP(alkaline phosphatase) and PTH(parathyroid hormone) in 37 patients with end stage renal disease on hemodialysis. Osteocalcin was determined by radioimmunoassay and PTH was determined by radioimmunometric assay. Results : 1) The mean level of serum osteocalcin in ESRD patients was 233.8± 218.2ng/ml which was significantly higher than that of controls(p<0.0001). 2) The mean level of serum PTH in ESRD patients was 40.5± 43.8pg/ml was significantly higher than that of controls(p<0.005). 3) There was a significant positive correlation between the level of serum PTH, ALP and the level of serum osteocalcin in ESRD patients. 4) By using multiple regression, PTH is most reliable factor that affect to elevated level of serum osteocalcin ( beta coefficient = 0.687, Sig T<0.05). Conclusion : Serum osteocalcin as a marker of bone metabolism in ESRD patients is more useful than other biochemical marker such as serum calcium, phosphorus, ALP and PTH is a most reliable factor that affect to elevated level of serum osteocalin.

Gα12/13 signaling in metabolic diseases

Yoon Mee Yang,권다솔,Yeonseok Chung,Hitoshi Kurose,Sang Geon Kim 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-

As the key governors of diverse physiological processes, G protein-coupled receptors (GPCRs) have drawn attention as primary targets for several diseases, including diabetes and cardiovascular disease. Heterotrimeric G proteins converge signals from ~800 members of the GPCR family. Among the members of the G protein α family, the Gα12 family members comprising Gα12 and Gα13 have been referred to as gep oncogenes. Gα12/13 levels are altered in metabolic organs, including the liver and muscles, in metabolic diseases. The roles of Gα12/13 in metabolic diseases have been investigated. In this review, we highlight findings demonstrating Gα12/13 amplifying or dampening regulators of phenotype changes. We discuss the molecular basis of G protein biology in the context of posttranslational modifications to heterotrimeric G proteins and the cell signaling axis. We also highlight findings providing insights into the organ-specific, metabolic and pathological roles of G proteins in changes associated with specific cells, energy homeostasis, glucose metabolism, liver fibrosis and the immune and cardiovascular systems. This review summarizes the currently available knowledge on the importance of Gα12/13 in the physiology and pathogenesis of metabolic diseases, which is presented according to the basic understanding of their metabolic actions and underlying cellular and molecular bases.

AMPK-associated signaling to bridge the gap between fuel metabolism and hepatocyte viability.

Yang, Yoon Mee,Han, Chang Yeob,Kim, Yoon Jun,Kim, Sang Geon WJG Press 2010 WORLD JOURNAL OF GASTROENTEROLOGY Vol.16 No.30

<P>The adenosine monophosphate-activated protein kinase (AMPK) and p70 ribosomal S6 kinase-1 pathway may serve as a key signaling flow that regulates energy metabolism; thus, this pathway becomes an attractive target for the treatment of liver diseases that result from metabolic derangements. In addition, AMPK emerges as a kinase that controls the redox-state and mitochondrial function, whose activity may be modulated by antioxidants. A close link exists between fuel metabolism and mitochondrial biogenesis. The relationship between fuel metabolism and cell survival strongly implies the existence of a shared signaling network, by which hepatocytes respond to challenges of external stimuli. The AMPK pathway may belong to this network. A series of drugs and therapeutic candidates enable hepatocytes to protect mitochondria from radical stress and increase cell viability, which may be associated with the activation of AMPK, liver kinase B1, and other molecules or components. Consequently, the components downstream of AMPK may contribute to stabilizing mitochondrial membrane potential for hepatocyte survival. In this review, we discuss the role of the AMPK pathway in hepatic energy metabolism and hepatocyte viability. This information may help identify ways to prevent and/or treat hepatic diseases caused by the metabolic syndrome. Moreover, clinical drugs and experimental therapeutic candidates that directly or indirectly modulate the AMPK pathway in distinct manners are discussed here with particular emphasis on their effects on fuel metabolism and mitochondrial function.</P>

Decrease of microRNA‐122 causes hepatic insulin resistance by inducing protein tyrosine phosphatase 1B, which is reversed by licorice flavonoid

Yang, Yoon Mee,Seo, So Yeon,Kim, Tae Hyun,Kim, Sang Geon Wiley Subscription Services, Inc., A Wiley Company 2012 Hepatology Vol.56 No.6

<P><B>Abstract</B></P><P>Protein tyrosine phosphatase 1B (PTP1B) inhibits hepatic insulin signaling by dephosphorylating tyrosine residues in insulin receptor (IR) and insulin receptor substrate (IRS). MicroRNAs may modulate metabolic functions. In view of the lack of understanding of the regulatory mechanism of PTP1B and its chemical inhibitors, this study investigated whether dysregulation of specific microRNA causes PTP1B‐mediated hepatic insulin resistance, and if so, what the underlying basis is. In high‐fat‐diet‐fed mice or hepatocyte models with insulin resistance, the expression of microRNA‐122 (miR‐122), the most abundant microRNA in the liver, was substantially down‐regulated among those predicted to interact with the 3′‐untranslated region of PTP1B messenger RNA (mRNA). Experiments using miR‐122 mimic and its inhibitor indicated that miR‐122 repression caused PTP1B induction. Overexpression of c‐Jun N‐terminal kinase 1 (JNK1) resulted in miR‐122 down‐regulation with the induction of PTP1B. A dominant‐negative mutant of JNK1 had the opposite effect. JNK1 facilitated inactivating phosphorylation of hepatocyte nuclear factor 4α (HNF4α) responsible for miR‐122 expression, as verified by the lack of HNF4α binding to the gene promoter. The regulatory role of JNK1 in PTP1B induction by a decrease in miR‐122 level was strengthened by cell‐based assays using isoliquiritigenin and liquiritigenin (components in <I>Glycyrrhizae radix</I>) as functional JNK inhibitors; JNK inhibition enabled cells to restore IR and IRS1/2 tyrosine phosphorylation and insulin signaling against tumor necrosis factor alpha, and prevented PTP1B induction. Moreover, treatment with each of the agents increased miR‐122 levels and abrogated hepatic insulin resistance in mice fed a high‐fat diet, causing a glucose‐lowering effect. <I>Conclusion</I>: Decreased levels of miR‐122 as a consequence of HNF4α phosphorylation by JNK1 lead to hepatic insulin resistance through PTP1B induction, which may be overcome by chemical inhibition of JNK. (H<SMALL>EPATOLOGY</SMALL> 2012;56:2209–2220)</P>

Hyaluronan synthase 2–mediated hyaluronan production mediates Notch1 activation and liver fibrosis

Yang, Yoon Mee,Noureddin, Mazen,Liu, Cheng,Ohashi, Koichiro,Kim, So Yeon,Ramnath, Divya,Powell, Elizabeth E.,Sweet, Matthew J.,Roh, Yoon Seok,Hsin, I-Fang,Deng, Nan,Liu, Zhenqiu,Liang, Jiurong,Mena, E American Association for the Advancement of Scienc 2019 Science Translational Medicine Vol.11 No.496

<P>Hyaluronan (HA), a major extracellular matrix glycosaminoglycan, is a biomarker for cirrhosis. However, little is known about the regulatory and downstream mechanisms of HA overproduction in liver fibrosis. Hepatic HA and HA synthase 2 (HAS2) expression was elevated in both human and murine liver fibrosis. HA production and liver fibrosis were reduced in mice lacking HAS2 in hepatic stellate cells (HSCs), whereas mice overexpressing HAS2 had exacerbated liver fibrosis. HAS2 was transcriptionally up-regulated by transforming growth factor–β through Wilms tumor 1 to promote fibrogenic, proliferative, and invasive properties of HSCs via CD44, Toll-like receptor 4 (TLR4), and newly identified downstream effector Notch1. Inhibition of HA synthesis by 4-methylumbelliferone reduced HSC activation and liver fibrosis in mice. Our study provides evidence that HAS2 actively synthesizes HA in HSCs and that it promotes HSC activation and liver fibrosis through Notch1. Targeted HA inhibition may have potential to be an effective therapy for liver fibrosis.</P>

Inhibition of hyaluronan synthesis by 4-methylumbelliferone ameliorates non-alcoholic steatohepatitis in choline-deficient L -amino acid-defined diet-induced murine model

Yoon Mee Yang,Zhijun Wang,Michitaka Matsuda,Ekihiro Seki 대한약학회 2021 Archives of Pharmacal Research Vol.44 No.2

Hyaluronan (HA) as a glycosaminoglycan canbind to cell-surface receptors, such as TLR4, to regulateinfl ammation, tissue injury, repair, and fi brosis. 4-methylumbelliferone(4-MU), an inhibitor of HA synthesis, is adrug used for the treatment of biliary spasms. Currently,therapeutic interventions are not available for non-alcoholicsteatohepatitis (NASH). In this study, we investigated theeff ects of 4-MU on NASH using a choline-defi cient aminoacid (CDAA) diet model. CDAA diet-fed mice showedNASH characteristics, including hepatocyte injury, hepaticsteatosis, infl ammation, and fi brogenesis. 4-MU treatmentsignifi cantly reduced hepatic lipid contents in CDAA dietfedmice. 4-MU reversed CDAA diet-mediated inhibitionof Ppara and induction of Srebf1 and Slc27a2 . Analysis ofserum ALT and AST levels revealed that 4-MU treatmentprotected against hepatocellular damage induced by CDAAdiet feeding. TLR4 regulates low molecular weight-HAinducedchemokine expression in hepatocytes. In CDAAdiet-fed, 4-MU-treated mice, the upregulated chemokine/cytokine expression, such as Cxcl1 , Cxcl2 , and Tnf wasattenuated with the decrease of macrophage infi ltration intothe liver. Moreover, HA inhibition repressed CDAA dietinducedmRNA expression of fi brogenic genes, Notch1 , and Hes1 in the liver. In conclusion, 4-MU treatment inhibitedliver steatosis and steatohepatitis in a mouse model ofNASH, implicating that 4-MU may have therapeutic potentialfor NASH.

인간 제대혈 유래 간엽줄기세포의 연골세포 분화

정미현(Mee Hyun Jung),양성은(Sung-Eun Yang),진혜진(Hae Jin Jin),이만경(Man Kyoung Lee),송호선(Ho Sun Song),양정윤(Jung Yoon Yang),양윤선(Yoon Sun Yang),하철원(Chul-Won Ha) 대한정형외과학회 2004 대한정형외과학회지 Vol.39 No.6

목적: 인간 제대혈로부터 간엽성 섬유세포양 세포를 분리, 배양함으로써 제대혈 내의 순환성 간엽줄기세포의 존재여부를 확인하고, 이의 연골세포 분화능을 증명하고자 하였다. 대상 및 방법: 총 50 유니트의 제대혈로부터 분리된 유착성 세포군의 세포형태 및 면역표현형을 분석하였다. BMP-6을 첨가하였거나 또는 첨가하지 않은 연골분화배양액을 이용하여 펠렛 배양의 형태로 연골분화를 유도 배양하였다. 연골세포로의 분화를 관찰하기 위해 역전사 중합효소연쇄반응을 수행하였으며, Safranin-O 염색과 제2형 콜라겐에 관한 면역염색을 시행하였다. 결과: 제대혈 단핵세포로부터 균질성의 섬유세포양 형태의 유착성 세포군이 배양되었다. 이 세포군은 간엽줄기세포 관련 항원 양성, 조혈모세포항원 음성, 조직적합항원 음성, 내피세포 및 파골세포 관련 항원 음성이었다. 연골분화 펠렛 배양 시 BMP-6을 첨가한 군에서 펠렛의 크기 및 연골세포관련 인자의 발현이 증가하였고, Safranin-O 염색과 제2형 콜라겐의 면역염색도 강양성이었다. 결론: 제대혈 내에 순환성 비조혈성 연골형성 간엽줄기세포가 존재함을 확인하였고, 연골분화 배지에 BMP-6을 첨가함으로써 제대혈 유래 비조혈성 간엽줄기세포의 시험관 내 연골분화의 효율을 향상시킬 수 있었다. Purpose: The aim of this study was to demonstrate the existence of circulating mesenchymal stem cells (MSC) in the human umbilical cord blood (hUCB) and to evaluate the chondrogenic differentiation potential of hUCB-derived MSC in vitro. Materials and Methods: Fifty hUCB harvests were cultured in media supplemented with 10% fetal bovine serum. The adherent fibroblast-like cells were characterized by immunophenotyping and induced to differentiate into chondrocytes in the pellet culture with and without BMP-6. This study performed RTPCR of the chondrogenic markers, Safranin-O stain and type Ⅱ collagen immunohistochemical stain. Results: The mononuclear cells isolated from hUCB formed adherent colonies with an attached well-spread fibroblast-like morphology. The cells positively expressed the MSC-related antigens, but did not express the hematopoietic, HLA-DR, endothelial, or osteoclast antigens and could be induced to differentiate into chondrocytes under proper stimulation. BMP-6 increased the size of the pellet and the mRNA levels for aggrecan, type Ⅱ collagen and type Ⅸ collagen and enhanced the levels of proteoglycan synthesis during chondrogenic differentiation. Conclusion: The homogenous fibroblast-like cells developed in cultures from hUCB with chondrogenic differentiation potential were considered to be MSC. Furthermore, it was found that BMP-6 enhanced chondrogenic differentiation of the hUCB-derived MSC in the pellet culture.