Synthesis of Novel Apio Carbocyclic Nucleoside Analogues as Selective A_(3) Adenosine Receptor Agonists

Hwang, Ki-Jun,Chun, Moon-Woo,Jacobson, Kenneth A.,Jeong, Lak-Shin,Lee, Jeong-A,Moon, Hyung-Ryong,Kim, Hea-Ok,Kim, Kyung-Ran,Lee, Kang-Man,Kim, Bum-Tae 이화여자대학교 약학연구소 2005 藥學硏究論文集 Vol.- No.16

On the basis of the biological activity of neplanocin A and apio-dideoxyadenosine (apio-ddA), novel apio-neplanocin A analogues 5a- d, combining the properties of two nucleosides, were stereoselectively synthesized. The apio moiety of the target nucleosides 5a-d was stereoselectively introduced by treating· lactol 10 with 37% formaldehyde in the presence of potassium carbonate. The carbasugar moiety of neplanocin A was successively built by exposing diene 12 on a Grubbs catalyst in methylene chloride. The final nucleosides 5a-d were synthesized from the condensation of the glycosyl donor 14 with nucleic bases under the standard Mitsunobu conditions. Similarly, apio-aristeromycin 6 and (N)-apio-methanocarbaadenosine 7 were derived from the common intermediate 13 using catalytic hydrogenation and Simmons-Smith cyclopropanation as key steps. All of the final nucleosides 5a-4, 6, and 7 did not show significant inhibitory activity against S-adenosylllolllocysteine hydrolase (SAH) up to 100 ㎛, maybe due to the absence of the secondary hydroxyl group at tile C3'-position, which should be oxidized by cofactor-bound NAD^(+). However, aplo-neplanocin A (5a) showed potent and highly selective binding affinity (K_(i), = 628 ± 69 nM) at the A_(3) adenosine receptor without any binding affinity at the A_(1) and A_(2A) adenosine receptors. In conclusion, we have first developed novel carbocyclic nucleosides with unnatural apio-carbasugarsusing stereoselective hydroxymethylation and RCM reaction and also discovered a new template of human A_(3) adenosine receptor agonist, which play a great rote in developing new A_(3) adenosine receptor agonist as well as in identifying the binding site of the receptor.

Effect of Apoptosis Induction of Ailanthus altissima on Human Lung Carcinoma Cells

Yu-Jin Hwang,Hye-Im Woo,Inhye Kim,Dong-Sik Park,Jaehyun Kim,Ae-Son Om,Kyung-A Hwang 경상대학교 농업생명과학연구원 2011 농업생명과학연구 Vol.45 No.5

We investigated the inhibitory effects of solvent extracts from Ailanthus altissima in A549 human lung cancer cell. A. altissima has been recognized as a traditional healthy food due to its various biological activities against hypertension, strokes, fever, pain, neuralgia, inflammation, and cancer effects. Recently, it has been reported that the extracts of various wild vegetables show strong anti-cancer properties by induction of apoptosis. However, the mechanisms of their cytotoxicity in human lung cancer cells have been poorly understood. The present study was investigated the effects of solvent extracts from A. altissima on cell growth and apoptosis on A549 human lung cancer cells. A treatment of A. altissima inhibited the growth of A549 cells in a dose-dependent manner by inducing apoptosis. Especially, the chloroform fraction showed the highest anti-cancer effect among five kinds of fractions. And also, induction of apoptosis by chloroform fraction were associated with down-regulation of Bcl-2, and up-regulation of pro-apoptotic Bax expression. From these results, A. altissima may have a therapeutic potential in human lung cancer cells and as a functional food.

흉부 방사선 치료후 완전방실차단증과 양측 관동맥구 협착증을 보인 1예

고경환,김정경,이수금,윤재형,조성제,이상훈,홍석근,현민수,황흥곤,김명아,박성훈 대한내과학회 1997 대한내과학회지 Vol.53 No.3S

We have experienced a case of radiation-induced coronary biostial stenosis presented with recurrent syncopal attack, which was confirmed by coronary angiography and pathologic findings. A 60 year-old woman was admitted with the symptoms of recurrent syncopal attack. She had a history of radiation therapy of the chest for lung neoplasm 15 years ago. Initial electrocardiogram showed transient high-degree A-V block followed by third-degree atrioventricular block which was associated with syncope. Echocardiography revealed mild aortic regurgitation without left ventricular dysfunction. The coronary angiogram revealed biostial stenosis of coronary arteries. Initial cardiac symptom subsided after temporary pacemaker implantation. She had a coronary bypass graft surgery on both coronary arteries using saphenous vein. Biopsy findings showed mild fibrosis with intimal thickening of coronary artery.

Phorbaketal A stimulates osteoblast differentiation through TAZ mediated Runx2 activation

Byun, Mi Ran,Kim, A Rum,Hwang, Jun-Ha,Sung, Mi Kyung,Lee, Yeon Kyung,Hwang, Buyng Su,Rho, Jung-Rae,Hwang, Eun Sook,Hong, Jeong-Ho Elsevier 2012 FEBS letters Vol.586 No.8

<P><B>Highlights</B></P><P>► Phorbaketal A stimulates osteogenesis. ► Phorbaketal A increases TAZ-mediated osteoblast marker gene expression. ► ERK is an important kinase for phorbaketal A induced osteogenic differentiation. ► Phorbaketal A is suggested as a potential compound for stimulating bone formation.</P> <P><B>Abstract</B></P><P>Osteoporosis arises from an imbalance between osteoblastic bone formation and osteoclastic bone resorption. In this study, we screened molecules from marine natural products that stimulate osteoblast differentiation. We found that phorbaketal A significantly stimulates osteoblast differentiation in mesenchymal cells. Increased interaction of TAZ and Runx2 stimulated phorbaketal A-induced expression of osteoblastic marker genes. The activation of ERK was important for the stimulation of differentiation because an inhibitor of ERK blocked phorbaketal A-induced osteogenic differentiation. Taken together, the results showed that phorbaketal A stimulates TAZ-mediated osteoblast differentiation through the activation of ERK.</P><P><B>Structured summary of protein interactions</B></P><P><B>TAZ</B> physically interacts with <B>RUNX2</B> by pull down (View interaction)</P>

Effect of IGF-I Rich Fraction from Bovine Colostral Whey on Murine Immunity

Kyung-A Hwang,Woel-Kyu Ha,양희진,이수원 아세아·태평양축산학회 2006 Animal Bioscience Vol.19 No.2

Insulin-like growth factor-I (IGF-I) rich fraction, collected components between 1 kDa and 30 kDa, was fractionated from bovine colostral whey using an ultrafiltration membrane. IGF-I was confirmed in the collected IGF-I rich fraction by both SDSPAGE and Western blotting. The concentration of IGF-I in the IGF-I rich fraction was 10 ng/mg protein. One hundred microliters of the reconstituted IGF-I rich fraction was intraperitoneally injected into ICR male mice for 2 weeks at 24 h intervals. The functions of peritoneal macrophages, including phagocytosis, interleukin (IL)-6 and tumor necrosis factor (TNF)-慣 production, and nitric oxide and hydrogen peroxide production, were enhanced significantly by the administration of the IGF-I rich fraction in a dose-dependent manner (p<0.01). The proliferation of Concanavalin (Con) A-stimulated and Lipopolysaccharide (LPS)-stimulated splenocytes was also determined to have been enhanced significantly by the administration of the IGF-I rich fraction in a dose-dependent manner (p<0.01). Our results indicate that the administration of IGF-I rich fraction obtained from bovine colostral whey enhances both innate and acquired immunity for ICR male mice.

A case of subdural hematoma in patient with chronic myeloid leukemia treated with high-dose imatinib mesylate

Min Sik Kim,Dong Hyun Lee,Yu Rim Lee,Dong Kyun Kim,Suk Hyang Bae,Jin Yeon Hwang,Kyung A Kwon,이수이,한진영,김기욱,김성현 대한혈액학회 2010 Blood Research Vol.45 No.1

Imatinib mesylate (IM) is used to treat a wide range of diseases, including Philadelphia chromosome-positive chronic myeloid leukemia (CML), on account of its high tolerability and low incidence of minor adverse events. Hemorrhage is thought to be a rare complication of IM. Recently, IM has been associated with reduced a2-plasmin inhibitor and platelet dysfunction. We report here the case of a 33-year-old female patient with CML who experienced subdural hematoma after an incremental increase in IM dosage due to a loss of complete molecular response. This case indicates that physicians should be alert to this atypical cause of headache in patients taking high-dose IM.

Inappropriate Gonadotropin Secretion in Polycystic Ovary Syndrome: The Relationship with Clinical, Hormonal and Metabolic Characteristics

( A Ra Shim ),( Yu Im Hwang ),( Kyung Jin Lim ),( Young Mi Choi ),( Young Eun Jeon ),( Seok Kyo Seo ),( Si Hyun Cho ),( Young Sik Choi ),( Byung Seok Lee ) 대한산부인과학회 2011 Obstetrics & Gynecology Science Vol.54 No.11

Objective To evaluate the clinical, hormonal and metabolic characteristics according to luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio in women with polycystic ovary syndrome (PCOS). Methods A total of 225 women with PCOS were included in this study. They were divided into two groups according to LH/FSH ratio; group A (LH/FSH < 2, n=160) and group B (LH/FSH > 2, n=65). We compared clinical, hormonal and metabolic characteristics including age at menarche, body mass index (BMI), blood pressures, ovarian volume, and serum androgen levels between the two groups. Serum glucose and insulin levels, fasting glucose/insulin ratio, homeostatic model assessment of insulin resistance (HOMA-IR), and lipid profi les were also compared between the two groups. Pearson correlation coeffi cients were used to evaluate correlation between the LH/FSH ratio and various parameters. Results Age of menarche in the group B was signifi cantly later than that in the group A. BMI, waist-hip ratio and blood pressures were signifi cantly lower in the group B compared to those of the group A. Ovarian volume and serum levels of LH, estradiol, total testosterone, sex-hormone binding globulin, 17-hydroxyprogesterone (OHP), and high density lipoprotein were signifi cantly higher in the group B. Postprandial 2 hours glucose, insulin and HOMA-IR were signifi cantly higher in the group A. After adjustment of BMI, the LH/FSH ratio was signifi cantly positively correlated with age at menarche, ovarian volume, total testosterone levels, and 17-OHP levels. Conclusion The inappropriate gonadotropin secretion may be negatively correlated with BMI, and positively with age of menarche and increased ovarian androgen production irrespective of BMI in women with PCOS. However, it may not be associated with metabolic characteristics.

두 번의 연속적 뇌경색에 의한 양측성 외측연수증후군 1예

조광덕,이덕희,황정숙,민선호,조아현,조경희 대한노인병학회 2004 대한노인병학회지 Vol.8 No.1

Molecular Characterization and Prevalence of 16S Ribosomal RNA Methylase Producing Bacteria in Amikacin Resistant Gram-negative Bacilli Isolated from Clinical Specimens

Kyung-A Shin,Seock Yeon Hwang,Seung Bok Hong 대한의생명과학회 2012 Biomedical Science Letters Vol.18 No.3

Recently, the prevalence of 16S rRNA methylase conferring high-level resistance to aminoglycosides has been increasing in Gram-negative bacilli globally. We determined the prevalence and genotype of these methylase-producing bacteria, and characterized the co-resistance to β-lactam antibiotics and quinolone in Gram-negative clinical isolates collected in 2010 at a hospital in Korea. Among 65 amikacin-resistant isolates screened from 864 Gram-negative bacilli (GNB), 16S rRNA methylase genes were detected from 49 isolates, including Acinetobacter baumannii (43), Klebsiella pneumoniae (2), Proteus mirabilis (2) and Serratia marcescens (1), Empedobacter brevis (1). All of the 16S rRNA methylase genotype was armA and no variant sequences of amplified PCR products for armA were noted. The 16S rRNA methylase producing bacteria showed much higher resistance to aminoglycoside for Enterobacteriaceae and glucose non-fermenting (NF)-GNB and to imipenem for glucose NF-GNB, than the non-producing isolates. All of the 16S rRNA methylase producing Enterobacteriaceae had the extended-spectrum-β-lactamase. In addition, two K. pneumoniae concurrently produced both plasmid-mediated AmpC β-lactamase and qnrB gene. All of the amikacinresistant A. baumannii (43) co-harbored armA 16S rRNA methylase and blaOXA-23 carbapenemase. In conclusion, 16S rRNA methylase producing bacteria were very prevalent among GNB in South Korea, and were commonly associated with co-resistance, including carbapenem and quinolone.

Treatment with Phytoestrogens Reversed Triclosan and Bisphenol A-Induced Anti-Apoptosis in Breast Cancer Cells

( Geum-a Lee ),( Kyung-chul Choi ),( Kyung-a Hwang ) 한국응용약물학회 2018 Biomolecules & Therapeutics(구 응용약물학회지) Vol.26 No.5

Triclosan (TCS) and bisphenol A (BPA) are endocrine-disrupting chemicals that interfere with the hormone or endocrine system and may cause cancer. Kaempferol (Kaem) and 3,3′-diindolylmethane (DIM) are phytoestrogens that play chemopreventive roles in the inhibition of carcinogenesis and cancer progression. In this study, the influence of TCS, BPA, Kaem, and DIM on proliferation and apoptotic abilities of VM7Luc4E2 breast cancer cells were examined. MTT assay revealed that TCS (0.1-10 µM), BPA (0.1-10 µM) and E2 (0.01-0.0001 µM) induced significant cell proliferation of VM7Luc4E2 cells, which was restored to the control (0.1% DMSO) by co-treatment with Kaem (30 µM) or DIM (15 µM). Reactive oxygen species (ROS) production assays showed that TCS and BPA inhibited ROS production of VM7Luc4E2 cells similar to E2, but that co-treatment with Kaem or DIM on VM- 7Luc4E2 cells induced increased ROS production. Based on these results, the effects of TCS, BPA, Kaem, and DIM on protein expression of apoptosis and ROS production-related markers such as Bax and Bcl-xl, as well as endoplasmic reticulum (ER) stress-related markers such as eIF2α and CHOP were investigated by Western blot assay. The results revealed that TCS, and BPA induced anti-apoptosis by reducing ROS production and ER stress. However, Kaem and DIM effectively inhibited TCS and BPA-induced anti-apoptotic processes in VM7Luc4E2 cells. Overall, TCS and BPA were revealed to be distinct xenoestrogens that enhanced proliferation and anti-apoptosis, while Kaem and DIM were identified as natural chemopreventive compounds that effectively inhibited breast cancer cell proliferation and increased anti-apoptosis induced by TCS and BPA.