Clinical Impact of Exosomal microRNA as a Novel Biomarker of Liver Fibrosis

( Young Chang ),( Jae-a Han ),( Suk Min Kang ),( Soung Won Jeong ),( Tom Ryu ),( Han Seul Park ),( Jeong-ju Yoo ),( Sae Hwan Lee ),( Sang Gyune Kim ),( Young Seok Kim ),( Hong Soo Kim ),( So Young Jin 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Many approaches have been suggested for the non-invasive diagnosis of liver fibrosis, including the use of serum biomarkers and ultrasound-based elastography, but none has yet replaced liver biopsy. MicroRNAs (miRNAs) have been suggested as potential diagnostic tools for liver diseases. We investigated alterations in the expression of serum exosomal miRNAs with the progression of liver fibrosis and evaluated their clinical applicability as biomarkers. Methods: This study prospectively enrolled 71 patients who underwent liver biopsy at a large-volume academic hospital in Korea. Exosomes were extracted from serum samples, and next-generation sequencing (NGS) of miRNAs was conducted in patients from different stages of liver fibrosis. Differential expression of miRNAs was quantified using targeted real-time quantitative polymerase chain reaction (RT-qPCR). A model was derived to discriminate advanced fibrosis based on miRNA levels using multivariate logistic regression. The performance of this model was evaluated and compared using area under the receiver operator characteristic (ROC) curve (AUC) and De- Long’s test. Results: NGS data revealed the relationship between exosomal miR-122 expression and liver fibrosis progression. The level of miR-122 decreased as the pathologic fibrosis grade progressed from stage 0 to 4. Patients with biopsy-proven advanced fibrosis had significantly lower levels of exosomal miR-122 (P<0.001) than those without advanced fibrosis. Exosomal miR-122 exhibited a fair performance in discriminating advanced fibrosis with an AUC of 0.77, which improved to 0.86 in combination with fibrosis-4 score (FIB-4) and transient elastography (TE). This value was higher than that reported for any other non-invasive modalities, including TE (AUC of 0.80) or FIB-4 (AUC of 0.57) alone. In a subgroup of patients with a non-viral etiology of liver disease, the performance of exosomal miR-122 as a biomarker improved, evident from the increase in the AUC value to 0.87. In this subpopulation, the combination model of miR- 122, FIB-4, and TE showed the best discrimination ability (AUC of 0.90), which was significantly higher than that of TE alone (AUC of 0.83; DeLong’s test P=0.046). Inhibition of miR-122 expression increased the proliferation of the human hepatic stellate cell line, LX-2, and upregulated the expression of collagen- 1A, a-smooth muscle actin, fibronectin, and transforming growth factor-ß. Conclusions: Exosomal miR-122 may serve as a novel biomarker for discriminating advanced liver fibrosis, and its accuracy may enhanced in combination with other non-invasive tests such as FIB-4 and TE.

Preparation and characterization of a poly(vinylbenzyl sulfonic acid)-grafted FEP membrane

Fei, Geng,Shin, Junhwa,Kang, Sung-A,Ko, Beom-Seok,Kang, Phil-Hyun,Lee, Youn-Sik,Nho, Young Chang Wiley Subscription Services, Inc., A Wiley Company 2010 Journal of polymer science Part A, Polymer chemist Vol.48 No.3

<P>In this study, a novel polymer electrolyte membrane, poly(vinylbenzyl sulfonic acid)-grafted poly(tetrafluoroethylene-co-hexafluoropropylene) (FEP-g-PVBSA), has been successfully prepared by simultaneous irradiation grafting of vinylbenzyl chloride (VBC) monomer onto a FEP film and taking subsequent chemical modification steps to modify the benzyl chloride moiety to the benzyl sulfonic acid moiety. The chemical reactions for the sulfonation were carried out via the formation of thiouronium salt with thiourea, base-catalyzed hydrolysis for the formation of thiol, and oxidation with hydrogen peroxide. Each chemical conversion process was confirmed by FTIR, elemental analysis, and SEM-EDX. A chemical stability study performed with Fenton's reagent (3% H<SUB>2</SUB>O<SUB>2</SUB> solution containing 4 ppm of Fe<SUP>2+</SUP>) at 70 °C revealed that FEP-g-PVBSA has a higher chemical stability than the poly(styrene sulfonic acid)-grafted membranes (FEP-g-PSSA). © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 563–569, 2010</P> <B>Graphic Abstract</B> <P>A novel polymer electrolyte membrane, FEP-g-PVBSA, has been successfully prepared by using a simultaneous irradiation grafting of vinylbenzyl chloride monomer onto a poly(tetrafluoroethylene-co-hexafluoropropylene) (FEP) film and taking subsequent chemical modification steps to modify the benzyl chloride moiety to the benzyl sulfonic acid moiety. <img src='wiley_img/0887624X-2010-48-3-POLA23762-gra001.gif' alt='wiley_img/0887624X-2010-48-3-POLA23762-gra001'> </P>

동해 남부 연안 해역에서 냉수대 발생이 식물플랑크톤 군집에 미치는 영향

김아람,윤석현,정미희,윤상철,문창호,Kim, A-Ram,Youn, Seok-Hyun,Chung, Mi-Hee,Yoon, Sang-Chol,Moon, Chang-Ho 한국해양학회 2014 바다 Vol.19 No.4

냉수대 발생 전 후의 해양 환경과 식물플랑크톤 군집 구조 및 크기를 파악을 위해 여름철 빈번하게 냉수대가 발생되는 동해 남부 해역(울산 정자~부산 일광) 18개 정점에서 2013년 5월부터 8월까지 냉수대 발생 환경 및 식물플랑크톤 군집 구조를 조사하였다. 냉수대는 7월과 8월에 연안 정점(A1, B1, C1)에서 발생하였고, 표층에서 저온 고염의 특성을 보였다. 이 시기에 영양염은 수온과 유의한 음의 상관관계(DIP, r=-0.218, p<0.01; DIN, r=-0.306, p<0.01; silicate, r=-0.274, p<0.01)를 보여, 찬 해수가 분포하는 표층에 영양염이 풍부함을 알 수 있었다. 출현한 식물플랑크톤은 총 186종이었고, 현존량은 5월(C1, $726{\times}10^3cells\;L^{-1}$)과 7월(A1, $539{\times}10^3cells\;L^{-1}$)에 높았다. 또한, 연안 정점에서 총 chl. a 와 소형플랑크톤 chl. a ($>20{\mu}m$)의 농도가 냉수대 발생 시기인 7, 8월에 뚜렷하게 증가한 반면, 수온약층이 형성된 6월에는 현저하게 낮았다. 6월의 우점종은 Pseudo-nitzschia spp.이었고, 그 세포 크기는 $309{\mu}m^3$로 다른 시기의 식물플랑크톤의 1/10 수준에 머무는 작은 크기였다. 이러한 결과는 7월과 8월에 총 chl. a의 증가와 식물플랑크톤의 크기 증가가 냉수대 발생 시에 표층으로 공급된 영양염의 영향임을 시사한다. 이러한 해양 환경 특성과 식물플랑크톤 출현양상은 연안 정점에서 뚜렷하게 보였고, 외측 정점에서는 관찰되지 않았다. 이 연구에서는 동해 남부 해역에서 냉수대가 발생하면 식물플랑크톤의 현존량 증가와 더불어 비교적 크기가 큰 식물플랑크톤의 출현 빈도가 증가하는 현상을 확인하였다. 결과적으로 하계에도 불구하고 동해 남부 연안 해역에서 냉수대 발생에 따른 영양염 공급은 식물플랑크톤 군집조성과 현존량에 상당한 영향을 미치는 것으로 판단된다. In order to understand environment condition and phytoplankton community before and after coastal upwelling, the influences of upwelling events on phytoplankton community were studied at 18 stations located the Southern part of East Sea, Korea from May to August 2013. The surface water masses showed low temperature and high salinity due to upwelling events at coastal stations (A1, B1, C1). Correlation between temperature and nutrients (DIP, r=-0.218, p<0.01; DIN, r=-0.306, p<0.01; silicate, r=-0.274, p<0.01) was significantly negative. This result could be explained that nutrients were supplied to surface water by the upwelling of bottom water. Phytoplankton communities were composed of 186 species. Phytoplankton abundance were relatively high in May (C1, $726{\times}10^3cells\;L^{-1}$) and July (A1, $539{\times}10^3cells\;L^{-1}$). Total chlorophyll a and micro-size fraction ($>20{\mu}m$) increased at coastal stations in July and August, while phytoplankton abundance and total chl. a was much low in June. Dominant species in June was Pseudo-nitzschia spp. of which the cell size was $309{\mu}m^3$. Cell size of Pseudo-nitzschia spp. was smaller than dominant species in other period. Therefore, the increase in total chloro-phyll a and the size of phytoplankton was resulted in the sufficient supply of nutrients. In contrast, these tendencies were not observed at outside stations. These results suggested that coastal upwelling was an important influencing factor to determine the species composition and standing stock of phytoplankton community in the coastal waters of the Southern part of East Sea, Korea.

Aquitalea denitrificans sp. nov., isolated from a Korean wetland.

Lee, Chang-Muk,Weon, Hang-Yeon,Kim, Yoo-Jeong,Son, Jung-A,Yoon, Sang-Hong,Koo, Bon-Sung,Kwon, Soon-Wo Society for General Microbiology 2009 International journal of systematic and evolutiona Vol.59 No.5

<P>A novel bacterium, designated strain 5YN1-3(T), was isolated from wetland peat collected from Yongneup, Korea. The bacterium was facultatively anaerobic, Gram-negative, yellow-coloured, rod-shaped, mesophilic and motile with one polar flagellum. The strain grew optimally at 30 degrees C, at pH 6.0-9.0 and with 0-1 % NaCl (w/v). 16S rRNA gene sequence analysis showed the highest similarity to the sequence from Aquitalea magnusonii TRO-001DR8(T), with 98.7 % sequence similarity. However, strain 5YN1-3(T) showed DNA-DNA relatedness of 43 % (40 % in a reciprocal experiment) with A. magnusonii LMG 23054(T). The strain contained summed feature 3 (iso-C(15 : 0) 2-OH and/or C(16 : 1)omega7c) and C(16 : 0) as major cellular fatty acids. On the basis of DNA-DNA relatedness and physiological and biochemical characterization, strain 5YN1-3(T) should be assigned to a novel species of the genus Aquitalea, for which the name Aquitalea denitrificans sp. nov. is proposed. The type strain is 5YN1-3(T) (=KACC 12729(T) =DSM 21300(T)).</P>

Changes and distributional pattern of microorganism in compost and fruiting body for button mushroom cultivation

Chan-Jung Lee,Na-Na Um,Jong-Chun Cheong,Chang-Sung Jhune,Jin-A Oh,Hye-Su Han,Byeong-Yeol, Yeon 한국버섯학회 2010 한국버섯학회지 Vol.8 No.4

Agaricus bisporus grows on a substrate known as compost, which is a product of aerobic fermentation by various microorganisms. These organisms convert and degrade the straw and form lignin humus complex which is utilized later on by the population of organisms. Theses microflora play a key role in the process of composting and can be regarded as the active agents in the preparation of nutrient medium as many of them may ultimately contribute themselves to the nutrition of A. bisporus. The diversity of microflora according to growing farmhouse and fruiting body of Agaricus bisporus were investigated. The aerobic bacteria and Bacillus as longer of turning stage of compost pile were increased. And, thermophilic actinomycetes and fluorescent Pseudomonas sp. showed high density after the pasteurization stage. But Tricoderma sp. was decreased toward the end of turning stage of compost pile. Ten mushroom farms was selected to research of microflora of fruiting body of button mushroom. The microflora showed significant difference according to mushroom farms. The bacteria density was 0.4~41.6×105 cfu/ml and the fungus was 1.3~3.9×103 cfu/ml. But The microorganism density was not significant change for the storage periods. These isolates were classified into Chryseobacterium indologenes(6 strains), Pseudomonas agarici(5 strains), Sphingobacterium multivorum(2 strains), Flavobacterium anhuiense(2 strains), Microbacterium sp.(10 strains), Pseudomonas sp.(13 strains) on the basis of 16 rDNA analysis. The most dominants of these species were Chryseobacterium indologenes and Pseudomonas agarici.

Litsenolide A2: The major anti-inflammatory activity compound in <i>Litsea japonica</i> fruit

Ham, Young-Min,Cho, Su-Hyeon,Song, Sang-Mok,Yoon, Seon-A,Lee, Yong-Bum,Kim, Chang-Sook,Kwon, Seung-Hae,Jeong, Myeong Seon,Yoon, Weon-Jong,Kim, Kil-Nam Elsevier 2017 Journal of Functional Foods Vol.39 No.-

<P><B>Abstract</B></P> <P>In this study, we investigated the anti-inflammatory effect of litsenolide A2 (LNA2) isolated from <I>L. japonica</I> fruit and its mechanism of action in LPS-induced RAW 264.7 cells. LPS-induced production of anti-inflammatory mediators and cytokines such as NO, PGE<SUB>2</SUB>, iNOS, COX-2, TNF-α, and IL-6 was significantly inhibited by LNA2. Next, western blot experiments were performed to investigate the mechanism of action of the anti-inflammatory effect of LNA2. The results indicated that LNA2 markedly reduced the LPS-induced activation of NF-κB and the nuclear translocation of NF-κB p65. Furthermore, LNA2 also inhibited the phosphorylation of MAPK by LPS. LNA2 was the major component in the ethanol extract of <I>L. japonica</I> at 59 mg/g according to high performance liquid chromatography (HPLC). These results indicate that LNA2 can be used as a functional and marker compound for standardization of the manufacturing process when <I>L. japonica</I> fruit is used as a functional food.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We study the anti-inflammatory effect of LNA2 in LPS-activated RAW 264.7 cells. </LI> <LI> LNA2 inhibited production of pro-inflammatory mediator and cytokines. </LI> <LI> LNA2 exhibited anti-inflammatory properties by suppression of NF-κB and MPAKs. </LI> <LI> LNA2 was the major component in the ethanol extract of <I>L. japonica</I> at 59 mg/g. </LI> </UL> </P>

Ferroelectric and Electrical Properties of Lead-Free (K0.44Na0.52Li0.04)(Nb0.86Ta0.10Sb0.04)O3 Thin Films

Ju Sung Kim,Chang Won Ahn,Amir Ullah,Song A. Chae,Ill Won Kim 한국물리학회 2016 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.68 No.12

The Li, Ta, and Sb-substituted lead-free (K0.44Na0.52Li0.04)(Nb0.86Ta0.10Sb0.04)O3 (KNLNTS) thin films were fabricated on Pt(111)/TiO2/SiO2/Si substrates using the radio frequency (RF) magnetron sputtering method. The KNLNTS thin films were annealed at 750 C for 1 h in an oxygen ambient. The film with a thickness of 350 nm exhibited a typical ferroelectric P − E hysteresis loop without fatigue even after 1010 pulses. The KNLNTS thin film exhibited a relatively low leakage current density of 10−7 A/cm2 even up to an applied electric field of 142 kV/cm. A well-saturated piezoelectric hysteresis loop was obtained with a piezoelectric coefficient d33 of 21 pm/V.

Quality change during preservation of cultivation mushrooms, Flammulina velutipes and Agaricus bisporus

Jin-A Oh,Jong-Chun Cheong,Chan-Jung Lee,Chang-Sung Jhune,Young-Bok Yoo 한국버섯학회 2010 한국버섯학회지 Vol.8 No.4

The standard does much to improve merchantable quality, distribution efficiency and fair dealings by shipping of the standard agricultural products. Mushrooms notified as the standard are five items; Pleurotus ostreatus, Pleurotus eryngii, Flammulina velutipes, Agaricus bisporus and Ganoderma lucidum. But many farmers are suffering from a strict standards. So these standard is required modification to fit farmhouse situations. This study was carried out to investigate mushroom quality of farm shipping and quality change during preservation at various treatment. Flammulina velutipes and Agaricus bisporus preserved at different temperature( 4℃, 10℃, 20℃) to investigate quality changes. Pileus diameters of Flammulina velutipes was 67% of first grade and 33% of second grade at the early stage. After two weeks, pileus diameters was not signigicant changes; 50% of first grade, 50% of second grade at 4℃ and 50% of second grade, 50% of third grade at 10℃. Although there were no significant changes of diameter at 20℃, most of the fruit bodies were decayed. In case of Agaricus bisporus, pileus diameter was 15% of first grade, 81% of second grade and 4% of third grade at the early stage. The more storage period longed, the more the color of the fruit body was browned. But pileus diameters was not signigicant changes. Hardness and chromaticity of these mushroom was declined as time passed. Now we are carrying out more research on some mushroom’s standards for improve consumer confidence.

Raman signatures of spin-phonon coupling in a self-intercalated van der Waals magnet Mn3Si2Te6

Kwon Chang Il,Kim Kwangrae,Kim So Young,Susilo Resta A.,Kang Beomtak,Kim Kyoo,Kim Duck Young,Kim Jonghwan,Kim B.J.,Kim Jun Sung 한국물리학회 2023 Current Applied Physics Vol.53 No.-

We report the results of Raman spectroscopy on a self-intercalated van der Waals ferrimagnet Mn3Si2Te6. Using polarization-resolved Raman spectroscopy, we identify twelve phonon modes with Eg and A1g symmetries, in agreement with the first principle calculations. Below the ferrimagnetic transition temperature Tc ∼ 78 K, we observed a significant deviation of the phonon frequency from the anharmonic model, accompanied by a strong line broadening, indicating a substantial spin-phonon coupling in Mn3Si2Te6. Among twelve phonon modes, this spin-phonon coupling is found to be strong mostly in the out-of-plane vibrational modes. These results highlight the dominant role of the interlayer superexchange interaction in determining the magnetic properties, reflecting the self-intercalated van der Waals structure of Mn3Si2Te6.

Darapladib Binds to Lipoprotein-Associated Phospholipase A2 with Meaningful Interactions

Do, Kyoung-Rok,Kim, Chul,Chang, Byungha,An, Seong Soo A.,Shin, Jae-Min,Yea, Sang-Jun,Song, Mi-Young,No, Kyoung Tai,Lee, Jee-Young Korean Chemical Society 2014 Bulletin of the Korean Chemical Society Vol.35 No.1

Lipoprotein-associated phospholipase A2 (Lp-$PLA_2$) is a crucial enzyme in atherosclerosis as a potential drug target. The most remarkable Lp-$PLA_2$ inhibitory drug is Darapladib. We determined the binding pose of Darapladib to Lp-$PLA_2$ through docking study. Darapladib formed two hydrogen bonding interactions with the side chain of Tyr160 and Gln352 and several pi-pi interactions with aromatic and aliphatic hydrophobic residues of Lp-$PLA_2$. It is known that the dietylpropan-amine moiety of Darapladib has influence on the improvement of its oral bioavailability and we supposed this in our docking results.