Candidacidal effects of Rev (11-20) derived from HIV-1 Rev protein

Lee, Juneyoung,Lee, Dong Hwan,Lee, Dong Gun Springer-Verlag 2009 Molecules and cells Vol.28 No.4

Changes in High-Density Lipoprotein Cholesterol and Risks of Cardiovascular Events: A Post Hoc Analysis from the PICASSO Trial

Eun-Jae Lee,Sun U. Kwon,Jong-Ho Park,Yong-Jae Kim,Keun-Sik Hong,Sungwook Yu,Yang-Ha Hwang,Ji Sung Lee,Juneyoung Lee,Joung-Ho Rha,Sung Hyuk Heo,Sung Hwan Ahn,Woo-Keun Seo,Jong-Moo Park,Ju-Hun Lee,Jee-H 대한뇌졸중학회 2020 Journal of stroke Vol.22 No.1

Background and purpose Whether pharmacologically altered high-density lipoprotein cholesterol (HDL-C) affects the risk of cardiovascular events is unknown. Recently, we have reported the Prevention of Cardiovascular Events in Asian Patients with Ischaemic Stroke at High Risk of Cerebral Haemorrhage (PICASSO) trial that demonstrated the non-inferiority of cilostazol to aspirin and superiority of probucol to non-probucol for cardiovascular prevention in ischemic stroke patients (clinicaltrials.gov: NCT01013532). We aimed to determine whether on-treatment HDL-C changes by cilostazol and probucol influence the treatment effect of each study medication during the PICASSO study. Methods Of the 1,534 randomized patients, 1,373 (89.5%) with baseline cholesterol parameters were analyzed. Efficacy endpoint was the composite of stroke, myocardial infarction, and cardiovascular death. Cox proportional hazards regression analysis examined an interaction between the treatment effect and changes in HDL-C levels from randomization to 1 month for each study arm. Results One-month post-randomization mean HDL-C level was significantly higher in the cilostazol group than in the aspirin group (1.08 mmol/L vs. 1.00 mmol/L, P<0.001). The mean HDL-C level was significantly lower in the probucol group than in the non-probucol group (0.86 mmol/L vs. 1.22 mmol/L, P<0.001). These trends persisted throughout the study. In both study arms, no significant interaction was observed between HDL-C changes and the assigned treatment regarding the risk of the efficacy endpoint. Conclusions Despite significant HDL-C changes, the effects of cilostazol and probucol treatment on the risk of cardiovascular events were insignificant. Pharmacologically altered HDL-C levels may not be reliable prognostic markers for cardiovascular risk.

Association between Daily Aspirin Therapy and Hepa-tocellular Carcinoma According to Metabolic Risk Factor Burden in Patients with Chronic Hepatitis B

( Cheol-hyung Lee ),( Yun Bin Lee ),( Hyemi Moon ),( Eun Ju Cho ),( Jeong-hoon Lee ),( Su Jong Yu ),( Yoon Jun Kim ),( Juneyoung Lee ),( Jung-hwan Yoon ) 대한간학회 2021 춘·추계 학술대회 (KASL) Vol.2021 No.1

Internet-based Control Recruitment for a Case–Control Study of Major Risk Factors for Stroke in Korea: Lessons from the Experience

Park, Jong-Moo,Cho, Yong-Jin,Lee, Kyung Bok,Park, Tai Hwan,Lee, Soo Joo,Han, Moon-Ku,Ko, Youngchai,Lee, Jun,Cha, Jae-Kwan,Lee, Byung-Chul,Yu, Kyung-Ho,Oh, Mi-Sun,Lee, Ji Sung,Lee, Juneyoung,Bae, Hee-J Elsevier 2014 Journal of stroke and cerebrovascular diseases Vol.23 No.10

<P><B>Background</B></P> <P>This study aimed to estimate the population-attributable risks (PARs) of 9 major risk factors for stroke in Korea through a case–control study and to test the feasibility and validity of internet-based control recruitment.</P> <P><B>Methods</B></P> <P>From April 2008 to September 2009, controls were enrolled via internet after providing consent for participation through a web-based survey. The cases included patients who were admitted to the participating centers due to acute stroke or transient ischemic attack within 7 days of onset during the study period. Each control was age- and sex-matched with 2 cases. Adjusted odd ratios, age-standardized prevalence, and PARs were estimated for the 9 major risk factors using the prevalence of risk factors in the control group and the age and sex characteristics from Korea's national census data.</P> <P><B>Results</B></P> <P>In total, 1041 controls were matched to 2082 stroke cases. Because of a shortage of elderly controls in the internet-based recruitment, 248 controls were recruited off-line. The PARs were 23.44%, 10.95%, 51.32%, and 6.35% for hypertension, diabetes, smoking, and stroke history, respectively. Hypercholesterolemia, atrial fibrillation, obesity, coronary heart disease, and a family history of stroke were not associated with stroke. Comparison with education and religion of the control group with that mentioned in the national census data showed a notable difference.</P> <P><B>Conclusions</B></P> <P>The study results imply that internet-based control recruitment for a case–control study requires careful selection of risk factors with high self-awareness and effective strategies to facilitate the recruitment of elderly participants.</P>

Acute Stroke Care in Korea in 2013–2014: National Averages and Disparities

Jun Yup Kim,Keon-Joo Lee,Jihoon Kang,Beom Joon Kim,김성은,Hyunji Oh,Hong-Kyun Park,Yong Jin Cho,Jong-Moo Park,Kwang-Yeol Park,Kyung Bok Lee,Soo Joo Lee,Tackeun Kim,Ji Sung Lee,Juneyoung Lee,Ki Hwa Yang,A 대한의학회 2020 Journal of Korean medical science Vol.35 No.20

Background: This study aimed to describe the current status of acute stroke care in Korea and explore disparities among hospitals and regions. Methods: The 2013 and 2014 national stroke audit data and the national health insurance claims data were linked and used for this study. Stroke patients hospitalized via emergency rooms within 7 days of stroke onset were selected. Results: A total of 19,608 patients treated in 216 hospitals were analyzed. Among them 76% had ischemic stroke; 15%, intracerebral hemorrhage (ICH); and 9%, subarachnoid hemorrhage (SAH). Of the hospitals, 31% provided inpatient stroke unit care. Ambulances were used in 56% of cases, and the median interval from onset to arrival was 4.5 hours. One-quarter of patients were referred from other hospitals. Intravenous thrombolysis (IVT) and endovascular treatment (EVT) rates were 11% and 4%, respectively. Three-quarters of the analyzed hospitals provided IVT and/or EVT, whereas 47% of hospitals providing IVT and 67% of hospitals providing EVT had less than one case per month. Decompressive surgery was performed on 28% of ICH patients, and clipping and coiling were performed in 17.2% and 14.3% of SAH patients, respectively. There were noticeable regional disparities between the various interventions, ambulance use, arrival time, and stroke unit availability. Conclusion: This study describes the current status of acute stroke care in Korea. Despite quite acceptable quality of stroke care, it suggests regional and hospital disparities. Expansion of stroke units, stroke center certification or accreditation, and connections between stroke centers and emergency medical services are highly recommended.

Novel Antifungal Mechanism of Resveratrol: Apoptosis Inducer in Candida albicans

Lee, Juneyoung,Lee, Dong Gun Springer-Verlag 2015 Current microbiology Vol.70 No.3

<P>Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a well-known natural polyphenolic compound that has garnered considerable interest because of its bioavailability and pharmacokinetics in humans. Although the antimicrobial activity of resveratrol has recently been focused, however, the antifungal activity and its mechanism are still largely unknown. Here, we report for the first time the potential of resveratrol as an apoptosis inducer in the human pathogenic fungus Candida albicans. The results showed that resveratrol exerted its effects from the early to the late stages of apoptosis and involved the activity of reactive oxygen species, particularly hydroxyl radicals ((???)OH). DiOC6(3) and JC-1 staining indicated that loss of mitochondrial membrane potential (??과 m) is a key event in resveratrol-induced apoptosis. Finally, we investigated metacaspase activation resulting from mitochondrial dysfunction. The result showed that resveratrol strongly activated metacaspase and promoted cytochrome c release. In summary, resveratrol induces fungal apoptosis through a caspase-dependent mitochondrial pathway and is a potential agent for treating human fungal diseases.</P>

A Novel Antifungal Analog Peptide Derived from Protaetiamycine

Juneyoung Lee,Hyun Joo Hong,Jin-Kyoung Kim,Jae-Sam Hwang,김양미,이동건 한국분자세포생물학회 2009 Molecules and cells Vol.28 No.5

Previously, the 9-mer analog peptides, 9Pbw2 and 9Pbw4, were designed based on a defensin-like peptide, protaetia-mycine isolated from Protaetia brevitarsis. In this study, antifungal effects of the analog peptides were investigated. The antifungal susceptibility testing exhibited that 9Pbw4 contained more potent antifungal activities than 9Pbw2. A PI influx assay confirmed the effects of the analog peptides and demonstrated that the peptides exerted their activity by a membrane-active mechanism, in an energy-independent manner. As the noteworthy potency of 9Pbw4, the mecha-nism(s) of 9Pbw4 were further investigated. The membrane studies, using rhodamine-labeled giant unilamellar vesicle (GUV) and fluorescein isothiocyanate (FITC)-dextran loaded liposome, suggested that the membrane-active mechanism of 9Pbw4 could have originated from the pore-forming ac-tion and the radii of pores was presumed to be anywhere from 1.8 nm to 3.3 nm. These results were confirmed by 3D-flow cytometric contour-plot analysis. The present study suggests a potential of 9Pbw4 as a novel antifungal pep-tide.

Melittin triggers apoptosis in Candida albicans through the reactive oxygen species-mediated mitochondria/caspase-dependent pathway.

Lee, Juneyoung,Lee, Dong Gun Published by Elsevier/North Holland on behalf of t 2014 FEMS microbiology letters Vol.355 No.1

<P>Melittin is one of the best-studied antimicrobial peptides, and many studies have focused on the membrane underlying its membrane-disruptive activity. We previously showed that melittin could cause some hallmarks of apoptosis in Candida albicans. Here, we first report the exact mechanism of melittin-induced fungal apoptosis. We first characterized the reactive oxygen species generated by melittin. The results showed that melittin strongly produced highly reactive hydroxyl radicals (OH), which contribute to cell death. Next, we showed that melittin also disrupted the mitochondrial membrane potential (δψm) and induced the Ca(2+) release from the endoplasmic reticulum and its remarkable accumulation in mitochondria. Finally, we investigated the role of caspase in the apoptotic pathway. The results showed that melittin activated metacaspase, which was mediated by cytochrome c release. To summarize, melittin is involved in the mitochondria- and caspase-dependent apoptotic pathway in C.?albicans. Our findings suggest that melittin possesses a dual antimicrobial mechanism, including membrane-disruptive and apoptotic actions.</P>

Structure-antimicrobial activity relationship between pleurocidin and its enantiomer

Juneyoung Lee,이동건 생화학분자생물학회 2008 Experimental and molecular medicine Vol.40 No.4

To develop novel antibiotic peptides useful as therapeutic drugs, the enantiomeric analogue of pleurocidin (Ple), which is a well known 25-mer antimicrobial peptide, was designed for proteolytic resistance by D-amino acids substitution. The proteolytic resistance was confirmed by using HPLC after the digestion with various proteases. To investigate the antibiotic effect of L- and D-Ple, the antibacterial activity and hemolytic effect were tested against human erythrocytes. The D-Ple showed a decreased antibacterial activity and a dramatically decreased hemolytic activity compared with L-Ple. The hemolytic effect of analogue was further confirmed by using calcein leakage measurement with liposome. To elucidate these results, the secondary structure of the peptides was investigated by using circular dichroism spectroscopy. The results revealed that D-Ple, as well as L-Ple, had typical α-helical structures which were mirror images, with a different helicity. These results suggested that the discrepancy of the structure between the two peptides made their antibacterial activity distinct.

Candidacidal Effects of Rev (11-20) Derived from HIV-1 Rev Protein

Juneyoung Lee,Dong Hwan Lee,이동건 한국분자세포생물학회 2009 Molecules and cells Vol.28 No.4

Rev is an essential regulatory protein for HIV-1 replication. Rev (11-20) is known as the significant region regarding the function of a nuclear entry inhibitory signal (NIS) of Rev. In this study, anticandidal effects and mechanism of action of Rev (11-20) were investigated. The result exhib-ited that Rev (11-20) contained candidacidal activities. To understand target site(s) of Rev (11-20), the intracellular localization of the peptide was investigated. The result showed that Rev (11-20) rapidly accumulated in the fungal cell surface. The cell wall regeneration test also indicated that Rev (11-20) exerted its anticandidal activity to fungal plasma membrane rather than cell wall. The fluorescent study using 1,6-diphenyl-1,3,5-hexatriene (DPH) further confirmed the membrane-disruption mechanism(s) of Rev (11-20). The present study suggests that Rev (11-20) pos-sesses significant potential regarding therapeutic agents for treating fungal diseases caused by Candida species in humans.