Discovery of urinary metabolomic biomarkers for early detection of acute kidney injury

Won, A Jin,Kim, Siwon,Kim, Yoon Gyoon,Kim, Kyu-Bong,Choi, Wahn Soo,Kacew, Sam,Kim, Kyeong Seok,Jung, Jee H.,Lee, Byung Mu,Kim, Suhkmann,Kim, Hyung Sik The Royal Society of Chemistry 2016 Molecular bioSystems Vol.12 No.1

<P>The discovery of new biomarkers for early detection of drug-induced acute kidney injury (AKI) is clinically important. In this study, sensitive metabolomic biomarkers identified in the urine of rats were used to detect cisplatin-induced AKI. Cisplatin (10 mg kg(-1), i.p.) was administered to Sprague-Dawley rats, which were subsequently euthanized after 1, 3 or 5 days. In cisplatin-treated rats, mild histopathological alterations were noted at day 1, and these changes were severe at days 3 and 5. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at days 3 and 5. The levels of new urinary protein-based biomarkers, including kidney injury molecule-1 (KIM-1), glutathione S-transferase-alpha (GST-alpha), tissue inhibitor of metalloproteinase-1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, neutrophil, neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin, were significantly elevated at days 3 and 5. Among urinary metabolites, trigonelline and 3-indoxylsulfate (3-IS) levels were significantly decreased in urine collected from cisplatin-treated rats prior to histological kidney damage. However, carbon tetrachloride (CCl4), a hepatotoxicant, did not affect these urinary biomarkers. Trigonelline is closely associated with GSH depletion and results in insufficient antioxidant capacity against cisplatin-induced AKI. The predominant cisplatin-induced AKI marker appeared to be reduced in urinary 3-IS levels. Because 3-IS is predominantly excreted via active secretion in proximal tubules, a decrease is indicative of tubular damage. Further, urinary excretion of 3-IS levels was markedly reduced in patients with AKI compared to normal subjects. The area under the curve receiver operating characteristics (AUC-ROC) for 3-IS was higher than for SCr, BUN, lactate dehydrogenase (LDH), total protein, and glucose. Therefore, low urinary or high serum 3-IS levels may be more useful for early detection of AKI than conventional biomarkers.</P>

Characterization and spatiotemporal expression of gonadotropin-releasing hormone in the Pacific abalone, <i>Haliotis discus hannai</i>

Kim, Tae Ha,Kim, Mi Ae,Kim, Kyeong Seop,Kim, Jae Won,Lim, Han Kyu,Lee, Jung Sick,Sohn, Young Chang Elsevier 2017 Comparative biochemistry and physiology. Part A, M Vol.209 No.-

<P><B>Abstract</B></P> <P>Gonadotropin-releasing hormone (GnRH) is a key neuropeptide regulating reproduction in humans and other vertebrates. Recently, GnRH-like cDNAs and peptides were reported in marine mollusks, implying that GnRH-mediated reproduction is an ancient neuroendocrine system that arose prior to the divergence of protostomes and deuterostomes. Here, we evaluated the reproductive control system mediated by GnRH in the Pacific abalone <I>Haliotis discus hannai</I>. We cloned a prepro-GnRH cDNA (<I>Hdh-GnRH</I>) from the pleural-pedal ganglion (PPG) in <I>H. discus hannai</I>, and analyzed its spatiotemporal gene expression pattern. The open reading frame of <I>Hdh-GnRH</I> encodes a protein of 101 amino acids, consisting of a signal peptide, a GnRH dodecapeptide, a cleavage site, and a GnRH-associated peptide. This structure and sequence are highly similar to GnRH-like peptides reported for mollusks and other invertebrates. Quantitative polymerase chain reaction demonstrated that <I>Hdh-GnRH</I> mRNA was more strongly expressed in the ganglions (PPG and cerebral ganglion [CG]) than in other tissues (gonads, gills, intestine, hemocytes, muscle, and mantle) in both sexes. In females, the expression levels of <I>Hdh-GnRH</I> mRNA in the PPG and branchial ganglion (BG) were significantly higher at the ripe and partial spent stages than at the early and late active stages. In males, <I>Hdh-GnRH</I> mRNA levels in the BG showed a significant increase in the partial spent stage. Unexpectedly, <I>Hdh-GnRH</I> levels in the CG were not significantly different among the examined stages in both sexes. These results suggest that <I>Hdh-GnRH</I> mRNA expression profiles in the BG and possibly the PPG are tightly correlated with abalone reproductive activities.</P>

Translocation of DNA and protein through a sequentially polymerized polyurea nanopore

Kim, Hyung-Jun,Choi, Ui-Jin,Kim, Hyein,Lee, Kidan,Park, Kyeong-Beom,Kim, Hyun-Mi,Kwak, Dong-Kyu,Chi, Seung-Wook,Lee, Jin Seok,Kim, Ki-Bum The Royal Society of Chemistry 2019 Nanoscale Vol.11 No.2

<P>Here, we investigated the translocation of biomolecules, such as DNA and protein, through a sequentially polymerized polyurea nanopore, with a thin (<10 nm) polymer membrane of uniform thickness. The polyurea membrane was synthesized by molecular layer deposition using <I>p</I>-phenylenediisocyanate (PDI) and <I>p</I>-phenylenediamine (PDA) as sequential precursors. The membrane exhibited a hydrophobic surface with a highly negative surface charge density (−51 mC m<SUP>−2</SUP> at pH 8). It was particularly noted that the high surface charge density of the membrane resulted in a highly developed electro-osmotic flow which, in turn, strongly influenced the capture probability of biomolecules, depending on the balance between the electro-osmotic and electrophoretic forces. For instance, the capture frequency of negatively charged DNA was demonstrated to be quite low, since these two forces more or less cancelled each other, whereas that of positively charged MDM2 was much higher, since these two forces were additive. We also identified that the mean translocation time of MDM2 through the polyurea nanopore was 26.1 ± 3.7 μs while that of the SiN nanopore was 14.2 ± 2.0 μs, hence suggesting that the enhanced electrostatic interaction between positively charged MDM2 and the negatively charged pore surface affects the translocation speed.</P>

Experience of surgical treatment in a granular cell tumor in the qscending colon: a case report

Kim In-Kyeong,Ju Young-Tae,Kim Han-Gil,Lee Jin-Kwon,Kim Dong-Chul,Kim Jae-Myung,Cho Jin Kyu,Park Ji-Ho,Kim Ju-Yeon,Jeong Chi-Young,Hong Soon-Chan,Kwag Seung-Jin 대한대장항문학회 2023 Annals of Coloproctolgy Vol.39 No.3

We report a case about successful surgical treatment of a granular cell tumor in the ascending colon. A 36-year-old man underwent screening colonoscopy. An endoscopic examination revealed a 10-mm yellowish and hemispheric mass in the ascending colon, and lower endoscopic ultrasonography revealed a hypoechoic-to-isoechoic mass invaded the submucosal layer. The mass was suspected to be a colonic carcinoid tumor. Based on the preoperative evaluation, endoscopic complete resection was considered difficult. Therefore, the lesion was removed via laparoscopic right hemicolectomy. Histological examination revealed that the tumor consisted of nests of polygonal cells with abundant granular eosinophilic cytoplasm. Immunohistochemical staining revealed diffuse positivity for S100 and CD68. Therefore, the tumor was diagnosed as a granular cell tumor. We suggest that surgical resection should be considered if it is located in the thin-walled ascending colon prone to perforation, difficult to rule out malignant tumor due to submucosal invasion, or to remove endoscopically.

A Sensitive and Rapid LC-MS/MS Method for Determination of Berberine in Human Plasma

Kim, Jae Hee,Mai, Xuan-Lan,Kim, Kyu Yeon,Sim, Min-Seok,Lee, So-Yeon,Seo, Hee-Won,Lee, Gunhee,Kim, Dae-Jung,Kim, Kyeong Ho Korean Society for Mass Spectrometry 2019 Mass spectrometry letters Vol.10 No.2

Coptidis Rhizoma (CR) has been used widely in traditional medicine to treat common diseases. This study aimed to develop a high-sensitivity liquid chromatography-tandem mass (LC-MS) spectrometry method for the evaluation of the pharmacokinetics of a new natural product that contain CR extract with the main bioactive compound, berberine, at trace concentrations. Human plasma samples were pretreated with methanol by a protein precipitation method. Berberine was analyzed on a Kinetex C18 column ($2.1mm{\times}50mm$, $100{\AA}$, $1.7{\mu}m$) using a mobile phase of 10 mM ammonium formate/0.1% formic acid in water (A) and acetonitrile (B) (50:50, v/v) with a flow rate of 0.25 mL/min. The analyte was detected by using electrospray ionization in positive mode with multiple reaction monitoring (MRM). The method was sensitive, with a lower limit of quantification of 1 pg/mL, which has not been previously obtained. The method was validated (over the range of 1-50 pg/mL) and applied successfully for the pharmacokinetic study of human plasma samples.

Synthesis and luminescence characteristics of conjugated dendrimers with 2,4,6-triaryl-1,3,5-triazine periphery

Kim, Chae Kyu,Song, Eun Seok,Kim, Hyung Joo,Park, Chiyoung,Kim, Young Chul,Kim, Jai Kyeong,Yu, Jae Woong,Kim, Chulhee Wiley Subscription Services, Inc., A Wiley Company 2006 Journal of polymer science Part A, Polymer chemist Vol.44 No.1

<P>We have synthesized conjugated dendrimer with triazine peripheries, and their luminescence properties were investigated. The dendrimers consist of dendritic triazine wedges for electron transport, distyrylbenzene core as an emitting moiety, and t-butyl peripheral groups for good processing properties. The dendrimers have LUMO values of about −2.7 eV possibly because of the triazine moiety with high electron affinity. Photoluminescence study indicates that energy transfer occurs from the triazine wedges to the stilbene bridge, and finally to the core chromophore units due to a cascade decrease of bandgap from the peripheral wedge to core moiety. Therefore, the emission wavelength was determined by the structure of the core unit. The energy transfer efficiency of distyrylbenzene-cored dendrimers was about 75 and 55% for Trz-1GD-DSB and Trz-2GD-DSB, respectively. A preliminary electroluminescence property also was investigated. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 254–263, 2006</P> <B>Graphic Abstract</B> <P>We have synthesized conjugated dendrimer with triazine peripheries, and their luminescence properties were investigated. PL study indicates that the energy transfer occurs from the triazine wedges to the stilbene bridge, and finally to the core chromophore units because of a cascade decrease of bandgap from the peripheral wedge to core moiety. With increasing the generation from the first to the second, the energy transfer efficiency decreased due to the increase of distance between the donor and acceptor. The dendrimers have LUMO values of about −2.7 eV and the EL spectra of dendrimers showed emission maximum at 460 nm. <img src='wiley_img/0887624X-2006-44-1-POLA21142-gra001.gif' alt='wiley_img/0887624X-2006-44-1-POLA21142-gra001'> </P>

Conjugated dendrimers with triazine peripheries and a distyrylanthracene core

Kim, Chae Kyu,Song, Eun Seok,Kim, Hyung Joo,Park, Chiyoung,Kim, Jai Kyeong,Kim, Young Chul,Yu, Jae Woong,Kim, Chulhee Wiley Subscription Services, Inc., A Wiley Company 2006 Journal of polymer science Part A, Polymer chemist Vol.44 No.20

<P>We describe the synthesis and luminescence characterization of conjugated dendrimers with triazine peripheries and a distyrylanthracene core that are suitable for electroluminescence applications. The dendrimers consist of dendritic triazine wedges with high electron affinity, stilbene branches, and a distyrylanthracene core as an emitting moiety. The dendrimers have lowest unoccupied molecular orbital values of about −2.7 eV. Photoluminescence studies have indicated that a cascade energy transfer occurs from the triazine wedges to the stilbene bridges and finally to the distyrylanthracene core. Thus, the emission wavelength is determined by the distyrylanthracene core unit. The energy-transfer efficiency of the distyrylanthracene-cored dendrimers is about 47 and 20% for the first and second generations, respectively. A preliminary electroluminescence property investigation has also been conducted. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5855–5862, 2006</P> <B>Graphic Abstract</B> <P>We describe the synthesis and luminescence characteristics of conjugated dendrimers with triazine peripheries, stilbene branch units, and a distyrylanthracene core. Photoluminescence studies have indicated that energy transfer occurs from the dendritic wedges to the distyrylanthracene core. Thus, the emission wavelength is determined by the distyrylanthracene core unit. <img src='wiley_img/0887624X-2006-44-20-POLA21656-gra001.gif' alt='wiley_img/0887624X-2006-44-20-POLA21656-gra001'> </P>

Base extrusion is found at helical junctions between right- and left-handed forms of DNA and RNA

Kim, Doyoun,Reddy, Sanjith,Kim, Dong Young,Rich, Alexander,Lee, Sangho,Kim, Kyeong Kyu,Kim, Yang-Gyun Oxford University Press 2009 Nucleic acids research Vol.37 No.13

<P>Base extrusion is a major structural feature at the junction between B- and Z-DNA (the B–Z junction) where a base pair is broken, and the two bases are extruded from the double helix. Despite the demonstration of base extrusion at the B–Z junction, it is not clear whether a similar base extrusion occurs at other types of junctions involving the left-handed Z conformation. Here, we investigate structural changes of bases at three Z-form junctions: DNA B–Z and Z–Z and RNA A–Z junctions. By monitoring fluorescently labeled duplex nucleic acids using 2-aminopurines at various positions relative to the junction point, we show that base extrusion occurs not only at the DNA B–Z junction, but also at the RNA A–Z and DNA Z–Z junctions. Our data suggest that base extrusion is a general feature of Z-form nucleic-acid junctions.</P>

SARS-CoV-2 Omicron Mutation Is Faster than the Chase: Multiple Mutations on Spike/ACE2 Interaction Residues

Kim Sinae,Nguyen Tam T.,Taitt Afeisha S.,전현정,Park Ho-Young,Kim Sung-Han,Kim Yong-Gil,Song Eun Young,Lee Youngmin,Yum Hokee,Shin Kyeong-Cheol,Choi Yang Kyu,송창선,Yeom Su Cheong,Kim Byoungguk,Netea Mihai 대한면역학회 2021 Immune Network Vol.21 No.6

Recently, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (B.1.1.529) Omicron variant originated from South Africa in the middle of November 2021. SARS-CoV-2 is also called coronavirus disease 2019 (COVID-19) since SARS-CoV-2 is the causative agent of COVID-19. Several studies already suggested that the SARS-CoV-2 Omicron variant would be the fastest transmissible variant compared to the previous 10 SARS-CoV-2 variants of concern, interest, and alert. Few clinical studies reported the high transmissibility of the Omicron variant but there is insufficient time to perform actual experiments to prove it, since the spread is so fast. We analyzed the SARS-CoV-2 Omicron variant, which revealed a very high rate of mutation at amino acid residues that interact with angiostatin-converting enzyme 2. The mutation rate of COVID-19 is faster than what we prepared vaccine program, antibody therapy, lockdown, and quarantine against COVID-19 so far. Thus, it is necessary to find better strategies to overcome the current crisis of COVID-19 pandemic.

Structural and functional study of ChuY from <i>Escherichia coli</i> strain CFT073

Kim, Hun,Chaurasia, Akhilesh Kumar,Kim, Truc,Choi, Jongkeun,Ha, Sung Chul,Kim, Doyoun,Kim, Kyeong Kyu Elsevier 2017 Biochemical and biophysical research communication Vol.482 No.4

<P><B>Abstract</B></P> <P>The uropathogenic <I>Escherichia coli</I> strain CFT073 contains multiple iron and heme transport systems, which facilitate infection of the host urinary tract. To elucidate the molecular and cellular function of ChuY, a hypothetical gene in the heme degradation/utilization pathway, we solved the crystal structure of ChuY at 2.4 Å resolution. ChuY has high structural homology with human biliverdin and flavin reductase. We confirmed that ChuY has flavin mononucleotide (FMN) reductase activity, using NAD(P)H as a cofactor, and shows porphyrin ring binding affinity. A <I>chuY</I> deletion-insertion strain showed reduced survival potential compared to wild-type and complemented strains in mammalian cells. Current results suggest ChuY acts as a reductase in heme homeostasis to maintain the virulence potential of <I>E</I>. <I>coli</I> CFT073.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Crystal structure of ChuY of uropathogenic <I>E</I>. <I>coli</I> was determined at 2.4 Å resolution. </LI> <LI> ChuY has high structural homology with human biliverdin and flavin reductase. </LI> <LI> ChuY has flavin mononucleotide (FMN) reductase activity using NADPH as a cofactor. </LI> <LI> A <I>chuY</I> knockout strain showed reduced survival potential in mammalian cells. </LI> <LI> ChuY plays a role in heme homeostasis and the virulence potential of <I>E</I>. <I>coli</I> CFT073. </LI> </UL> </P>