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Kim, Hyung-cheol,Lee, Ji-Young,Sung, Hyuna,Choi, Ji-Yeob,Park, Sue K,Lee, Kyoung-Mu,Kim, Young Jin,Go, Min Jin,Li, Lian,Cho, Yoon Shin,Park, Miey,Kim, Dong-Joon,Oh, Ji Hee,Kim, Jun-Woo,Jeon, Jae-Pil,J BioMed Central 2012 Breast cancer research Vol.14 No.2
<P><B>Introduction</B></P><P>Although approximately 25 common genetic susceptibility loci have been identified to be independently associated with breast cancer risk through genome-wide association studies (GWAS), the genetic risk variants reported to date only explain a small fraction of the heritability of breast cancer. Furthermore, GWAS-identified loci were primarily identified in women of European descent.</P><P><B>Methods</B></P><P>To evaluate previously identified loci in Korean women and to identify additional novel breast cancer susceptibility variants, we conducted a three-stage GWAS that included 6,322 cases and 5,897 controls.</P><P><B>Results</B></P><P>In the validation study using Stage I of the 2,273 cases and 2,052 controls, seven GWAS-identified loci [5q11.2/<I>MAP3K1 </I>(rs889312 and rs16886165), 5p15.2/<I>ROPN1L </I>(rs1092913), 5q12/<I>MRPS30 </I>(rs7716600), 6q25.1/<I>ESR1 </I>(rs2046210 and rs3734802), 8q24.21 (rs1562430), 10q26.13/<I>FGFR2 </I>(rs10736303), and 16q12.1/<I>TOX3 </I>(rs4784227 and rs3803662)] were significantly associated with breast cancer risk in Korean women (<I>P</I><SUB>trend </SUB>< 0.05). To identify additional genetic risk variants, we selected the most promising 17 SNPs in Stage I and replicated these SNPs in 2,052 cases and 2,169 controls (Stage II). Four SNPs were further evaluated in 1,997 cases and 1,676 controls (Stage III). SNP rs13393577 at chromosome 2q34, located in the <I>Epidermal Growth Factor Receptor 4 </I>(<I>ERBB4</I>) gene, showed a consistent association with breast cancer risk with combined odds ratios (95% CI) of 1.53 (1.37-1.70) (combined <I>P </I>for trend = 8.8 × 10<SUP>-14</SUP>).</P><P><B>Conclusions</B></P><P>This study shows that seven breast cancer susceptibility loci, which were previously identified in European and/or Chinese populations, could be directly replicated in Korean women. Furthermore, this study provides strong evidence implicating rs13393577 at 2q34 as a new risk variant for breast cancer.</P>
Anti-Inflammatory and Anti-Superbacterial Activity of Polyphenols Isolated from Black Raspberry
Kim, Seong Keun,Kim, Hyuna,Kim, Song Ah,Park, Hee Kuk,Kim, Wonyong The Korean Society of Pharmacology 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.1
The fruit of the black raspberry (Rubus coreanus Miquel) has been employed in traditional medicine, and recent studies have demonstrated its measureable biological activities. However, the root of the black raspberry has not been studied. Therefore, in this study, we evaluated the anti-inflammatory and antibacterial properties of the root and unripe fruit polyphenols of the black raspberry. Both polyphenols proved to have anti-inflammatory activity as evidenced by the decreased nitric oxide (NO), cytokines (IL-$1{\beta}$, IL-6, and IL-10) and prostaglandin E2 ($PGE_2$) levels in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. However, root polyphenols showed stronger anti-inflammatory activity than fruit polyphenols. LPS-induced mRNA and protein expressions of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 levels were also decreased, confirming the anti-inflammatory activity. Root polyphenols showed lethal activity against methicillin-resistant Staphy-lococcus aureus (MRSA), carbapenem-resistant Acinetobacter baumannii (CRAB), and Bacillus anthracis. In contrast, the black raspberry fruit did not demonstrate these properties. These data provide the first demonstration that black raspberry root has potential anti-inflammatory and anti-superbacterial properties that can be exploited as alternatives for use in the food and cosmetic industries and/or as pharmaceuticals.
Immune Cells Are Differentially Affected by SARS-CoV-2 Viral Loads in K18-hACE2 Mice
Jung Ah Kim,Sung-Hee Kim,Jeong Jin Kim,Hyuna Noh,Su-bin Lee,Haengdueng Jeong,Jiseon Kim,Donghun Jeon,Jung Seon Seo,Dain On,Suhyeon Yoon,Sang Gyu Lee,Youn Woo Lee,Hui Jeong Jang,In Ho Park,Jooyeon Oh,S The Korean Association of Immunobiologists 2024 Immune Network Vol.24 No.2
Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019. In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×10<sup>5</sup> plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×10<sup>2</sup> PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×10<sup>2</sup> PFU-virus-infected lungs from 2 dpi, but not in 1×10<sup>5</sup> PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×10<sup>5</sup> PFU; however, 1×1<sup>2</sup> PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.
Anti-Inflammatory and Anti-Superbacterial Activity of Polyphenols Isolated from Black Raspberry
Seong Keun Kim,Hyuna Kim,Song Ah Kim,Hee Kuk Park,Wonyong Kim 대한생리학회-대한약리학회 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.1
The fruit of the black raspberry (Rubus coreanus Miquel) has been employed in traditional medicine, and recent studies have demonstrated its measureable biological activities. However, the root of the black raspberry has not been studied. Therefore, in this study, we evaluated the anti-inflammatory and antibacterial properties of the root and unripe fruit polyphenols of the black raspberry. Both polyphenols proved to have anti-inflammatory activity as evidenced by the decreased nitric oxide (NO), cytokines (IL-1Ղ, IL-6, and IL-10) and prostaglandin E2 (PGE<sub>2</sub>) levels in lipopolysaccharide (LPS)- stimulated RAW 264.7 murine macrophages. However, root polyphenols showed stronger anti- inflammatory activity than fruit polyphenols. LPS-induced mRNA and protein expressions of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 levels were also decreased, confirming the anti- inflammatory activity. Root polyphenols showed lethal activity against methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Acinetobacter baumannii (CRAB), and Bacillus anthracis. In contrast, the black raspberry fruit did not demonstrate these properties. These data provide the first demonstration that black raspberry root has potential anti-inflammatory and anti- superbacterial properties that can be exploited as alternatives for use in the food and cosmetic industries and/or as pharmaceuticals.
Tubulin Beta3 Serves as a Target of HDAC3 and Mediates Resistance to Microtubule-Targeting Drugs
Kim, Youngmi,Kim, Hyuna,Jeoung, Dooil Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.8
We investigated the role of HDAC3 in anti-cancer drug-resistance. The expression of HDAC3 was decreased in cancer cell lines resistant to anti-cancer drugs such as celastrol and taxol. HDAC3 conferred sensitivity to these anti-cancer drugs. HDAC3 activity was necessary for conferring sensitivity to these anti-cancer drugs. The down-regulation of HDAC3 increased the expression of MDR1 and conferred resistance to anti-cancer drugs. The expression of tubulin ${\beta}3$ was increased in drug-resistant cancer cell lines. ChIP assays showed the binding of HDAC3 to the promoter sequences of tubulin ${\beta}3$ and HDAC6. HDAC6 showed an interaction with tubulin ${\beta}3$. HDAC3 had a negative regulatory role in the expression of tubulin ${\beta}3$ and HDAC6. The down-regulation of HDAC6 decreased the expression of MDR1 and tubulin ${\beta}3$, but did not affect HDAC3 expression. The down-regulation of HDAC6 conferred sensitivity to taxol. The down-regulation of tubulin ${\beta}3$ did not affect the expression of HDAC6 or MDR1. The down-regulation of tubulin ${\beta}3$ conferred sensitivity to anti-cancer drugs. Our results showed that tubulin ${\beta}3$ serves as a downstream target of HDAC3 and mediates resistance to microtubule-targeting drugs. Thus, the HDAC3-HDAC6-Tubulin ${\beta}$ axis can be employed for the development of anti-cancer drugs.