• Molecules and Cells
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• v.41 no.6
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• pp.523-531
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• 2018

Tumour metastasis is one of the most serious challenges of cancer as it is the major cause of mortality in patients with solid tumours, including osteosarcoma (OS). In this regard, anti-metastatic genes have potential for metastasis inhibition strategies. Recent evidence showed the importance of breast cancer metastasis suppressor 1 (BRMS1) in control of OS invasiveness, but the regulation of BRMS1 in OS remains largely unknown. Here, we used bioinformatics analyses to predict BRMS1-targeting microRNAs (miRNAs), and the functional binding of miRNAs to BRMS1 mRNA was evaluated using a dual luciferase reporter assay. Among all BRMS1-targeting miRNAs, only miR-151b, miR-7-5p and miR-3200-5p showed significant expression in OS specimens. Specifically, we found that only miR-3200-5p significantly inhibited protein translation of BRMS1 via pairing to the 3'-UTR of the BRMS1 mRNA. Moreover, we detected significantly lower BRMS1 and significantly higher miR-3200-5p in the OS specimens compared to the paired adjacent non-tumour bone tissues. Furthermore, BRMS1 and miR-3200-5p levels were inversely correlated to each other. Low BRMS1 was correlated with metastasis and poor patient survival. In vitro, overexpression of miR-3200-5p significantly decreased BRMS1 levels and promoted OS cell invasion and migration, while depletion of miR-3200-5p significantly increased BRMS1 levels and inhibited OS cell invasion and migration. Thus, our study revealed that miR-3200-5p may be a critical regulator of OS cell invasiveness.

• Korean Journal of Microbiology
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• v.44 no.4
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• pp.277-281
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• 2008

HIV affects many organ systems. Patients with HIV infection have substantially increased risk of developing various cancers, primarily by opportunistic infection with oncogenic viruses due to their immunocompromised status. However, extensive evidence also indicates that the viral protein, Tat itself, may playas a major factor in the development of AIDS-related neoplasms. The molecular mechanism underlying Tat's oncogenic activity may include deregulation of cellular genes. Therefore, in this study, we examined the effect of HIV-l Tat on CD99 as one of the target cellular genes, which is a well-known tumor marker in several cancers. By using established HeLa clones that are stably expressing Tat, we found that CD99 is upregulated by endogenous Tat, whereas STAT3 is down regulated. Upon the screening of genes differentially expressed between Tat-stable cells and the control cells by using the gene fishing technique, DEG, we detected 3 genes which expression is affected by the presence of Tat. Furthermore, the methylation specific PCR analysis of the stably Tat expressing cell lines revealed that the CD99 promoter is de methylated in the presence of Tat. Taken together, these results open a potential role of CD99 in AIDS-related oncogenesis via epigenetic regulation by HIV-1 Tat.

• Journal of Korean Ophthalmic Optics Society
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• v.13 no.3
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• pp.103-109
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• 2008

Purpose: This review illustrates an importance of oxidative stress caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation in association with eye disease, especially of cataract, and discusses an important role of lipid peroxide as a mediator of oxidative stress-related ocular dysfunction. Methods: Oxidative stress, resulted from the cellular production of ROS and RNS, is known to cause various forms of cellular damages such as protein oxidation, DNA breaks, apoptosis, and lipid peroxidation. These damages can be developed to human diseases. Accumulating evidence strongly suggests that continuous or constant exposure of eye tissues to oxidative stress is a main cause of cataractogenesis. Therefore, we investigated the action of oxidative stress in ocular dysfunction. Results: The ocular lens is continuously attacked by ROS inevitable generated from the process of cellular metabolism and the chronic exposure to ultraviolet. Excessive generation of ROS, resulting in degradation, oxidation, crosslinking and aggregation of lens proteins, is regarded as an important factor in development of cataract. Conclusions: These oxidative stress and oxidant/antioxidant imbalance produces the excess ROS which can lead to eye dysfunction. Even though known results, it should be noted that there is limited information on the molecular mechanism which can be better defined with the interrelation of oxidative stress and optic abnormalities.

• Molecules and Cells
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• v.37 no.1
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• pp.66-73
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• 2014

Myeloid-derived suppressor cells (MDSCs) play an important role in impairing the function of T cells. We characterized MDSCs in two chronic hepatitis C (CHC) cohorts: a cross-sectional group that included 61 treatment-naive patients with CHC, 14 rapid virologic response (RVR) cases and 22 early virologic response (EVR) cases; and a longitudinal group of 13 cases of RVR and 10 cases of EVR after pegylated-interferon-${\alpha}$/ribavirin treatment for genotype 1b HCV infection. Liver samples from 32 CHC patients and six healthy controls were subjected to immunohistochemical analysis. MDSCs frequency in treatment-naive CHC was significantly higher than in RVR, EVR, or healthy subjects and was positively correlated with HCV RNA. Patients infected with HCV genotype 2a had a significantly higher frequency of MDSCs than those infected with genotype 1b. Decreased T cell receptor (TCR) ${\zeta}$ expression on $CD8^+$ T cells was significantly associated with an increased frequency of MDSCs in treatment-naive CHC patients and was restored by L-arginine treatment in vitro. Increased numbers of liver arginase-$1^+$ cells were closely associated with the histological activity index in CHC. The TCR ${\zeta}$ chain was significantly downregulated on hepatic $CD8^+$ T cells in CHC. During antiviral follow up, MDSCs frequency in peripheral blood mononuclear cells was directly correlated with the HCV RNA load in the plasma and inversely correlated with TCR ${\zeta}$ chain expression in $CD8^+$ T cells in both RVR and EVR cases. Notably, the RVR group had a higher frequency of MDSCs at baseline than the EVR group. Collectively, this study provides evidence that MDSCs might be associated with HCV persistence and downregulation of CD8 ${\zeta}$ chain expression.

• Journal of Genetic Medicine
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• v.14 no.1
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• pp.8-17
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• 2017

Purpose: Pulse wave velocity (PWV) is an indicator of arterial stiffness, and is considered a marker of vascular damage. However, a genome-wide association study analyzing single nucleotide polymorphisms (SNPs) associated with brachial-ankle PWV (baPWV) has not been conducted in healthy populations. We performed this study to identify SNPs associated with baPWV in healthy populations in Korea. Materials and Methods: Genomic SNPs data for 2,407 individuals from three sites were analyzed as part of the Korean Genomic Epidemiologic Study. Without replication samples, we performed multivariable analysis as a post hoc analysis to verify the findings in site adjusted analysis. Healthy subjects aged between 40 and 70 years without self-reported history or diagnosis of hypertension, diabetes, hyperlipidemia, heart disease, cerebrovascular disease and cancer were included. We excluded subjects with a creatinine level >1.4 mg/dL (men) and 1.2 mg/dL (women). Results: In the site-adjusted association analysis, significant associations (P<$5{\times}10^{-8}$) with baPWV were detected for only 5 SNPs with low minor allele frequency. In multivariable analysis adjusted by age, sex, height, body mass index, mean arterial pressure, site, smoking, alcohol, and exercise, 11 SNPs were found to be associated (P<$5{\times}10^{-8}$) with baPWV. The 5 SNPs (P<$5{\times}10^{-8}$) linked to three genes (OPCML, PRR35 and RAB40C) were common between site-adjusted analysis and multivariable analysis. However, meta-analysis of the result from three sites for the 11 SNPs showed no significant associations. Conclusion: Using the recent standard for genome-wide association study, we did not find any evidence of significant association signals with baPWV.

• Proceedings of the Ginseng society Conference
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• 2002.10a
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• pp.66-83
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• 2002

Recently, we have provided evidence that ginsenosides, the active components of Panax ginseng, utilize pertussis toxin (PTX)-insensitive $G{\alpha}_{q/11}-phospholipase\;C-{\beta}3(PLC-{\beta}3)$ signal transduction pathway for the enhancement of $Ca^{2+}-activated\;Cl^{-}$ current in the Xenopus oocyte (British J. Pharmacol. 132, 641-647, 2001; JBC 276, 48797-48802, 2001). Other investigators have shown that stimulation of receptors linked to $G{\alpha}-PLC$ pathway inhibits the activity of G proteincoupled inwardly rectifying $K^+$ (GIRK) channel. In the present study, we sought to determine whether ginsenosides influenced the activity of GIRK 1 and GIRK 4 (GIRK 1/4) channels expressed in the Xenopus oocyte, and if so, the underlying signal transduction mechanism. In oocyte injected with GIRK 1/4 channel cRNAs, bath-applied ginsenosides inhibited high potassium (HK) solution-elicited GIRK current $(EC_{50}:4.9{\pm}4.3\;{\mu}g/ml).$ Pretreatment of the oocyte with PTX reduced the HK solution-elicited GIRK current by $49\%,$ but it did not alter the inhibitory ginsenoside effect on GIRK current. Prior intraoocyte injection of cRNA(s) coding $G{\alpha}_q,\;G{\alpha}_{11}\;or\;G{\alpha}_q/G{\alpha}_{11},\;but\;not\;G{\alpha}_{i2}\;or\;G{\alpha}_{oA}$ attenuated the inhibitory ginsenoside effect. Injection of cRNAs coding $G{\beta}_{1{\gamma}2}$ also attenuated the ginsenoside effect. Similarly, injection of the cRNAs coding regulators of G protein signaling 1, 2 and 4 (RGS1, RGS2 and RGS4), which interact with $G{\alpha}_i\;and/or\;G{\alpha}_{q/11}$ and stimulates the hydrolysis of GTP to GDP in active GTP-bound $G{\alpha}$ subunit, resulted in a significant reduction of ginsenoside effect on GIRK current. Preincubation of GIRK channel-expressing oocyte in PLC inhibitor (U73122) or protein kinase C (PKC) inhibitor (staurosporine or chelerythrine) blocked the inhibitory ginsenoside effect on GIRK current. On the other hand, intraoocyte injection of BAPTA, a free $Ca^{2+}$ chelator, had no significant effect on the ginsenoside action. Taken together, these results suggest that ginsenosides inhibit the activity of GIRK 1/4 channel expressed in the Xenopus oocyte through a PTX-insensitive and $G{\alpha}_{q/11}$-,PLC-and PKC-mediated signal transduction pathway.

• Korean Journal of Clinical Laboratory Science
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• v.53 no.4
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• pp.309-316
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• 2021

Sepsis is a physiological response to a source of infection that triggers mechanisms that compromise organ function, leading to death if not treated early. Biomarkers with high sensitivity, specificity, speed, and accuracy that could differentiate sepsis from non-infectious systemic inflammatory response syndrome (SIRS) could bring about a revolution in sepsis treatment. Given the limitations and time required for microbial verification of pathogens, the accurate diagnosis of infection before employing antibiotic therapy is important and clinically necessary. Procalcitonin (PCT), lactate, C-reactive protein (CRP), cytokines, and proadrenomedullin (ProADM) are the common biomarkers used for diagnosis. The procalcitonin (PCT)-guided antibiotic treatment in patients with acute respiratory infections effectively reduces antibiotic exposure and side effects while improving survival rates. The evidence regarding sepsis screening in hospitalized patients is limited. Clinicians, researchers, and healthcare decision-makers should consider these findings and limitations when implementing screening tools, future research, or policy on sepsis recognition in hospitalized patients. The use of biomarkers in pediatric sepsis is promising, although such use should always be correlated with clinical evaluation. Biomarkers may also improve the prediction of mortality, especially in the early phase of sepsis, when the levels of certain pro-inflammatory cytokines and proteins are elevated.

• Korean Journal of Breeding Science
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• v.42 no.5
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• pp.495-501
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• 2010

Peaches (Prunus persica) are less popular than the fresh fruits, because their flesh gets soft faster. So many breeders focused on their aim to firmness. Other breeders focused on juiciness, flavor and aroma. Breeding requires much labor, time and money. To reduce these requirements, many scientists develop many SSR, CAPS and SCAR makers. New peach varieties bred in our National Institute of Horticultural & Herbal Science (NIHHS) such as, Cheonhong, Suhong and Harhong are yellow flesh cultivars and Yumyeong, Baekmijosaeng, Baekhyang, Jinmi, Soomee, Mihong, Misshong and Yumee are white flesh cultivars. These peach cultivars are planted in orchard of Korea. To assert breeding cultivar patents and prevent patent disputes, we detected cultivar-specific DNA fragment using 235 sets of Operon RAPD primers, analyzed 134 DNA sequences and constructed SCAR primers. To confirm the cultivar-specific SCAR markers, we applied candidate SCAR primers to 30 peach cultivars widely cultivated in Korea. These selected lines are included father and mother lines that were used to develop new varieties in NIHHS. Using fourteen SCAR primer sets, we characterized thirty cultivars selected. The SCAR marker is expected to serve as molecular evidence distinguishing different peach varieties.

• Korean Journal of Heritage: History & Science
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• v.49 no.4
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• pp.114-125
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• 2016

Lacquer is one of the most widely used natural resin in East Asia since Neolithic Age. As a major ingredient of lacquerware, lacquer is waterproof, insect-proof and rot-proof to be durable and anti-abrasion, generally utilized for mainly painting purpose. According to lacquerware excavated from several sites of Japan and China, lacquerware seems to appear in Neolithic Age. On the other hand in case of excavation research in Korea, lacquerwares are found after the Bronze Age. The initial purpose of lacquer is estimated to be adhesive, regarding the literatures mentioning bitumen(Yeoksceong ), animal glue(Kyeo) and egg alumen(Nanbaek). Especially piece of jar coffin unearthed in Pyeongtaek Daechu-ri site had trace of restoration by lacquer and hemp as an evidence of lacquer for adhesion in Pre-Three Kingdoms period. Since then a trend to restore the broken ceramics with lacquer and decorate with golden foil lasted especially in Joseon Dynasty. In the field of gold plated lacquer method, mother-of-pearl inlaying technique for lacquerware and restoration of buildings, lacquer is still used as adhesive. Due to matter of reversibility lacquer is being avoided for conservation and restoration of cultural heritage. Lacquer as a traditional material for adhesive since ancient times, however, has advantage in adhesion strength and durability. Because synthetic resin adhesive has problem of emission of volatile organic compounds and aging over time, lacquer receives attention recently. On the contrary, by combination adhesive from mixing lacquer and animal glue, already proved the possibility of applicability and chemical modification. A research to utilize lacquer as modern paint or functional material is also conducted continuously also in China and Japan. To put traditional material into practical use and modernize, chemical research from the molecular level of the lacquer is necessary in the near future.

• Biomolecules & Therapeutics
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• v.27 no.4
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• pp.414-422
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• 2019

There is accumulating evidence that microRNAs are emerging as pivotal regulators in the development and progression of neuropathic pain. MicroRNA-15a/16 (miR-15a/16) have been reported to play an important role in various diseases and inflammation response processes. However, whether miR-15a/16 participates in the regulation of neuroinflammation and neuropathic pain development remains unknown. In this study, we established a mouse model of neuropathic pain by chronic constriction injury (CCI) of the sciatic nerves. Our results showed that both miR-15a and miR-16 expression was significantly upregulated in the spinal cord of CCI rats. Downregulation of the expression of miR-15a and miR-16 by intrathecal injection of a specific inhibitor significantly attenuated the mechanical allodynia and thermal hyperalgesia of CCI rats. Furthermore, inhibition of miR-15a and miR-16 downregulated the expression of interleukin-$1{\beta}$ and tumor-necrosis factor-${\alpha}$ in the spinal cord of CCI rats. Bioinformatic analysis predicted that G protein-coupled receptor kinase 2 (GRK2), an important regulator in neuropathic pain and inflammation, was a potential target gene of miR-15a and miR-16. Inhibition of miR-15a and miR-16 markedly increased the expression of GRK2 while downregulating the activation of p38 mitogen-activated protein kinase and $NF-{\kappa}B$ in CCI rats. Notably, the silencing of GRK2 significantly reversed the inhibitory effects of miR-15a/16 inhibition in neuropathic pain. In conclusion, our results suggest that inhibition of miR-15a/16 expression alleviates neuropathic pain development by targeting GRK2. These findings provide novel insights into the molecular pathogenesis of neuropathic pain and suggest potential therapeutic targets for preventing neuropathic pain development.