1.The Effect of Saccharin on the Gene Expression of NF-κB and Inflammatory Cytokines in LPS-Stimulated SW480 Colon Cancer Cells
Hyunji CHOI ; Sunlim KIM ; Hyeonjung KANG ; Myunghwan KIM ; Wookyoung KIM
Journal of the Korean Dietetic Association 2019;25(3):217-228
There have been no published studies concerning the anti-inflammatory effects of corn silk on colon cancer cells. Thus, this study was conducted to investigate the effect of corn silk extract containing high levels of maysin on inflammation and its mechanism of action in colon cancer cells. SW 480 human colon cancer cells were treated with 1 µg/mL of lipopolysaccharide (LPS) to induce inflammation, and next they were treated with different concentrations of corn silk extract (0, 5, 10 and 15 µg/mL). The concentrations of nitric oxide (NO) were determined. The mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor α (TNF-α), interleukin-1beta (IL-1β) and interleukin-6 (IL-6), were determined. Western blot analysis was performed to determine the protein expressions of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases, and the latter consists of extracellular signal-related kinase (ERK), c-jun NH2-terminal kinase (JNK) and p38 MAP kinase (p38). The concentration of NO and the mRNA expression of iNOS were significantly and dose-dependently decreased in the corn silk-treated groups (P<0.05). The mRNA expression of TNF-α, IL-1β and IL-6 were significantly increased in the LPS-treated group (P<0.05), but these expressions were significantly and dose-dependently decreased in the corn silk treated groups (P<0.05). The protein expressions of NF-κB (in a dose-dependent fashion), ERK (at 10 and 15 µg/mL), JNK (at 15 µg/mL) and p38 (at 10 and 15 µg/mL) were significantly decreased with corn silk treatments (P<0.05). In conclusion, corn silk extract containing high levels of maysin seems to inhibit the LPS-induced inflammatory responses in SW480 colon cancer cells via the NF-κB pathway.
Blotting, Western
;
Colon
;
Colonic Neoplasms
;
Cyclooxygenase 2
;
Cytokines
;
Gene Expression
;
Humans
;
Inflammation
;
Interleukin-1beta
;
Interleukin-6
;
Mitogen-Activated Protein Kinases
;
Nitric Oxide
;
Nitric Oxide Synthase Type II
;
p38 Mitogen-Activated Protein Kinases
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Phosphotransferases
;
RNA, Messenger
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Saccharin
;
Silk
;
Tumor Necrosis Factor-alpha
;
Zea mays
2.Comparison of IRIS Iq200, UF-1000i, and Cobas u701 Module Automated Urine Sediment Analyzers
Hyunji CHOI ; Dahae YANG ; Sun Ja KWON ; Poo Reum KANG ; Hasung PARK ; Teayun KIM ; Hyunyong HWANG
Laboratory Medicine Online 2020;10(4):283-294
Background:
We sought to compare the performance of three commercially available automated urine sediment analyzers that represent the current urine sediment analysis technology.
Methods:
A total of 232 patient samples were analyzed using manual microscopy and three automated analyzers: IRIS Iq200 (Beckman Coulter, USA), UF-1000i (Sysmex, Japan), and Cobas u701 (Roche, Switzerland). We analyzed precision, linearity, carry-over, concordance rate, and agreement between the three analyzers and manual microscopy.
Results:
The repeatability and within-laboratory precision showed results similar to those of previous studies. All analyzers showed excellent linearity. The carry-over rates were within 1%. The correlation coefficient (r) between the three analyzers and manual microscopy was good. Regarding red blood cell (RBC), the UF-1000i showed a better concordance rate (90.52%) with manual microscopy than the other two analyzers and the agreement was substantial for UF-1000i (κ=0.63) and IRIS Iq200 (κ=0.61). Regarding white blood cell (WBC), Cobas u701 showed the best concordance rate (96.55%) and the agreement was moderate for IRIS Iq200 (κ=0.57) and Cobas u701 (κ=0.56), and fair for UF-1000i (κ=0.47). Regarding epithelial cell (EPI), IRIS Iq200 showed the highest concordance rate (99.2%) and the agreement was moderate for IRIS Iq200 (κ=0.59) and Cobas u701 (κ=0.54), and fair for UF-1000i (κ=0.40).
Conclusions
IRIS Iq200 offered the best agreement with manual microscopy for WBC and EPI count, while UF-1000i showed a better agreement for RBC count. The agreement is insufficient for fully replacing the manual microscopy.
3.Comparative analysis of commonly used peak calling programs for ChIP-Seq analysis
Hyeongrin JEON ; Hyunji LEE ; Byunghee KANG ; Insoon JANG ; Tae-Young ROH
Genomics & Informatics 2020;18(4):e42-
Chromatin immunoprecipitation coupled with high-throughput DNA sequencing (ChIP-Seq) is a powerful technology to profile the location of proteins of interest on a whole-genome scale. To identify the enrichment location of proteins, many programs and algorithms have been proposed. However, none of the commonly used peak calling programs could accurately explain the binding features of target proteins detected by ChIP-Seq. Here, publicly available data on 12 histone modifications, including H3K4ac/me1/me2/me3, H3K9ac/me3, H3K27ac/me3, H3K36me3, H3K56ac, and H3K79me1/me2, generated from a human embryonic stem cell line (H1), were profiled with five peak callers (CisGenome, MACS1, MACS2, PeakSeq, and SISSRs). The performance of the peak calling programs was compared in terms of reproducibility between replicates, examination of enriched regions to variable sequencing depths, the specificity-to-noise signal, and sensitivity of peak prediction. There were no major differences among peak callers when analyzing point source histone modifications. The peak calling results from histone modifications with low fidelity, such as H3K4ac, H3K56ac, and H3K79me1/me2, showed low performance in all parameters, which indicates that their peak positions might not be located accurately. Our comparative results could provide a helpful guide to choose a suitable peak calling program for specific histone modifications.
4.Comparison of IRIS Iq200, UF-1000i, and Cobas u701 Module Automated Urine Sediment Analyzers
Hyunji CHOI ; Dahae YANG ; Sun Ja KWON ; Poo Reum KANG ; Hasung PARK ; Teayun KIM ; Hyunyong HWANG
Laboratory Medicine Online 2020;10(4):283-294
Background:
We sought to compare the performance of three commercially available automated urine sediment analyzers that represent the current urine sediment analysis technology.
Methods:
A total of 232 patient samples were analyzed using manual microscopy and three automated analyzers: IRIS Iq200 (Beckman Coulter, USA), UF-1000i (Sysmex, Japan), and Cobas u701 (Roche, Switzerland). We analyzed precision, linearity, carry-over, concordance rate, and agreement between the three analyzers and manual microscopy.
Results:
The repeatability and within-laboratory precision showed results similar to those of previous studies. All analyzers showed excellent linearity. The carry-over rates were within 1%. The correlation coefficient (r) between the three analyzers and manual microscopy was good. Regarding red blood cell (RBC), the UF-1000i showed a better concordance rate (90.52%) with manual microscopy than the other two analyzers and the agreement was substantial for UF-1000i (κ=0.63) and IRIS Iq200 (κ=0.61). Regarding white blood cell (WBC), Cobas u701 showed the best concordance rate (96.55%) and the agreement was moderate for IRIS Iq200 (κ=0.57) and Cobas u701 (κ=0.56), and fair for UF-1000i (κ=0.47). Regarding epithelial cell (EPI), IRIS Iq200 showed the highest concordance rate (99.2%) and the agreement was moderate for IRIS Iq200 (κ=0.59) and Cobas u701 (κ=0.54), and fair for UF-1000i (κ=0.40).
Conclusions
IRIS Iq200 offered the best agreement with manual microscopy for WBC and EPI count, while UF-1000i showed a better agreement for RBC count. The agreement is insufficient for fully replacing the manual microscopy.
5.Comparative analysis of commonly used peak calling programs for ChIP-Seq analysis
Hyeongrin JEON ; Hyunji LEE ; Byunghee KANG ; Insoon JANG ; Tae-Young ROH
Genomics & Informatics 2020;18(4):e42-
Chromatin immunoprecipitation coupled with high-throughput DNA sequencing (ChIP-Seq) is a powerful technology to profile the location of proteins of interest on a whole-genome scale. To identify the enrichment location of proteins, many programs and algorithms have been proposed. However, none of the commonly used peak calling programs could accurately explain the binding features of target proteins detected by ChIP-Seq. Here, publicly available data on 12 histone modifications, including H3K4ac/me1/me2/me3, H3K9ac/me3, H3K27ac/me3, H3K36me3, H3K56ac, and H3K79me1/me2, generated from a human embryonic stem cell line (H1), were profiled with five peak callers (CisGenome, MACS1, MACS2, PeakSeq, and SISSRs). The performance of the peak calling programs was compared in terms of reproducibility between replicates, examination of enriched regions to variable sequencing depths, the specificity-to-noise signal, and sensitivity of peak prediction. There were no major differences among peak callers when analyzing point source histone modifications. The peak calling results from histone modifications with low fidelity, such as H3K4ac, H3K56ac, and H3K79me1/me2, showed low performance in all parameters, which indicates that their peak positions might not be located accurately. Our comparative results could provide a helpful guide to choose a suitable peak calling program for specific histone modifications.
6.Glutamate Permeability of Chicken Best1
Jung Moo LEE ; Changdev Gorakshnath GADHE ; Hyunji KANG ; Ae Nim PAE ; C. Justin LEEC
Experimental Neurobiology 2022;31(5):277-288
Bestrophin-1 (Best1) is a calcium (Ca 2+ )-activated chloride (Cl - ) channel which has a phylogenetically conserved channel structure with an aperture and neck in the ion-conducting pathway. Mammalian mouse Best1 (mBest1) has been known to have a permeability for large organic anions including gluconate, glutamate, and D-serine, in addition to several small monovalent anions, such as Cl - , bromine (Br - ), iodine (I - ), and thiocyanate (SCN - ). However, it is still unclear whether non-mammalian Best1 has a glutamate permeability through the ion-conducting pathway. Here, we report that chicken Best1 (cBest1) is permeable to glutamate in a Ca 2+ -dependent manner. The molecular docking and molecular dynamics simulation showed a glutamate binding at the aperture and neck of cBest1 and a glutamate permeation through the ion-conducting pore, respectively. Moreover, through electrophysiological recordings, we calculated the permeability ratio of glutamate to Cl - (P Glutamate /P Cl ) as 0.28 based on the reversal potential shift by ion substitution from Cl - to glutamate in the internal solution. Finally, we directly detected the Ca 2+ -dependent glutamate release through cBest1 using the ultrasensitive two-cell sniffer patch technique. Our results propose that Best1 homologs from non-mammalian (cBest1) to mammalian (mBest1) have a conserved permeability for glutamate.
7.Disruption of Microtubules Sensitizes the DNA Damage-induced Apoptosis Through Inhibiting Nuclear Factor kappaB (NF-kappaB) DNA-binding Activity.
Hyunji LEE ; Juhee JEON ; Young Sue RYU ; Jae Eun JEONG ; Sanghee SHIN ; Tiejun ZHANG ; Seong Wook KANG ; Jang Hee HONG ; Gang Min HUR
Journal of Korean Medical Science 2010;25(11):1574-1581
The massive reorganization of microtubule network involves in transcriptional regulation of several genes by controlling transcriptional factor, nuclear factor-kappa B (NF-kappaB) activity. The exact molecular mechanism by which microtubule rearrangement leads to NF-kappaB activation largely remains to be identified. However microtubule disrupting agents may possibly act in synergy or antagonism against apoptotic cell death in response to conventional chemotherapy targeting DNA damage such as adriamycin or comptothecin in cancer cells. Interestingly pretreatment of microtubule disrupting agents (colchicine, vinblastine and nocodazole) was observed to lead to paradoxical suppression of DNA damage-induced NF-kappaB binding activity, even though these could enhance NF-kappaB signaling in the absence of other stimuli. Moreover this suppressed NF-kappaB binding activity subsequently resulted in synergic apoptotic response, as evident by the combination with Adr and low doses of microtubule disrupting agents was able to potentiate the cytotoxic action through caspase-dependent pathway. Taken together, these results suggested that inhibition of microtubule network chemosensitizes the cancer cells to die by apoptosis through suppressing NF-kappaB DNA binding activity. Therefore, our study provided a possible anti-cancer mechanism of microtubule disrupting agent to overcome resistance against to chemotherapy such as DNA damaging agent.
Animals
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Antibiotics, Antineoplastic/therapeutic use
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*Apoptosis
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Caspases/metabolism
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Cell Line
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Colchicine/pharmacology
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DNA/metabolism
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*DNA Damage
;
Doxorubicin/therapeutic use
;
Humans
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Mice
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Microtubules/chemistry/*drug effects/metabolism
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NF-kappa B/antagonists & inhibitors/*metabolism
;
Neoplasms/drug therapy
;
Nocodazole/pharmacology
;
Protein Binding
;
Signal Transduction
;
Tubulin Modulators/*pharmacology
;
Vinblastine/pharmacology
8.Patterns of Spontaneous Adverse Events Reporting on Human Papillomavirus Vaccines according to the Applicability of Brighton Collaboration Criteria in Korea from 2008 to 2017
Myo-Song KIM ; Seung-Hun YOU ; Hye Min PARK ; Min-Taek LEE ; Ye-Jin KANG ; Hyunji KOO ; Sun-Young JUNG
Korean Journal of Clinical Pharmacy 2020;30(1):19-30
Objective:
To describe patterns of spontaneous reporting on adverse events following immunization (AEFIs) using the human papilloma virus (HPV) vaccine according to the Brighton Collaboration (BC) criteria.
Methods:
We used the Korea Adverse Event Reporting System (KAERS) database including vaccinations between 2008 and 2017. To apply BC criteria, we classified 58 BC AEFIs into World Health Organization Adverse Reaction Terminology (WHO-ART) codes. We applied MedDRA standard medical queries that were pre-defined as five BC AEFIs. Terminology mapping between MedDRA and WHO-ART terms was performed by three researchers. Descriptive statistics of individual case safety reports were analyzed according to BC applicability.Disproportionality analyses were performed on each BC AEFI and each preferred AEFI term according to the case-noncase approach; reporting odds ratio (ROR) and 95% confidence intervals (CI) were calculated.
Results:
Among the 30,266 reports of vaccinations between 2008 and 2017, 2,845 reports included the HPV vaccine. Of these reports, 1,511 (53.1%) included at least one BC AEFI. Reports from physicians or manufacturers included more BC AEFIs than from other reporters. Injection site reactions and fever were frequently reported in BC AEFIs; spontaneous abortion and ectopic pregnancy (ROR, 14.29 [95% CI, 4.30-47.49]) and vasculitic peripheral neuropathy (ROR, 8.57 [95% CI, 2.61-28.10]) showed the highest ROR. Among non-BC AEFIs, dizziness or myalgia were frequently reported; exposure during pregnancy (ROR, 23.95 [95% CI, 16.27-35.25]) and inappropriate schedule of administration (ROR, 22.89 [95% CI, 16.74-31.31]) showed the highest ROR.
Conclusion
BC criteria would be applicable for labeled AEFIs, whereas analyzing non-BC AEFIs would be useful for detecting unlabeled AEFIs.
9.Patterns of Spontaneous Adverse Events Reporting on Human Papillomavirus Vaccines according to the Applicability of Brighton Collaboration Criteria in Korea from 2008 to 2017
Myo-Song KIM ; Seung-Hun YOU ; Hye Min PARK ; Min-Taek LEE ; Ye-Jin KANG ; Hyunji KOO ; Sun-Young JUNG
Korean Journal of Clinical Pharmacy 2020;30(1):19-30
Objective:
To describe patterns of spontaneous reporting on adverse events following immunization (AEFIs) using the human papilloma virus (HPV) vaccine according to the Brighton Collaboration (BC) criteria.
Methods:
We used the Korea Adverse Event Reporting System (KAERS) database including vaccinations between 2008 and 2017. To apply BC criteria, we classified 58 BC AEFIs into World Health Organization Adverse Reaction Terminology (WHO-ART) codes. We applied MedDRA standard medical queries that were pre-defined as five BC AEFIs. Terminology mapping between MedDRA and WHO-ART terms was performed by three researchers. Descriptive statistics of individual case safety reports were analyzed according to BC applicability.Disproportionality analyses were performed on each BC AEFI and each preferred AEFI term according to the case-noncase approach; reporting odds ratio (ROR) and 95% confidence intervals (CI) were calculated.
Results:
Among the 30,266 reports of vaccinations between 2008 and 2017, 2,845 reports included the HPV vaccine. Of these reports, 1,511 (53.1%) included at least one BC AEFI. Reports from physicians or manufacturers included more BC AEFIs than from other reporters. Injection site reactions and fever were frequently reported in BC AEFIs; spontaneous abortion and ectopic pregnancy (ROR, 14.29 [95% CI, 4.30-47.49]) and vasculitic peripheral neuropathy (ROR, 8.57 [95% CI, 2.61-28.10]) showed the highest ROR. Among non-BC AEFIs, dizziness or myalgia were frequently reported; exposure during pregnancy (ROR, 23.95 [95% CI, 16.27-35.25]) and inappropriate schedule of administration (ROR, 22.89 [95% CI, 16.74-31.31]) showed the highest ROR.
Conclusion
BC criteria would be applicable for labeled AEFIs, whereas analyzing non-BC AEFIs would be useful for detecting unlabeled AEFIs.
10.Development of Efficient Brain Age Estimation Method Based on Regional Brain Volume From Structural Magnetic Resonance Imaging
Sunghwan KIM ; Sheng-Min WANG ; Dong Woo KANG ; Yoo Hyun UM ; Hyeonsik YANG ; Hyunji LEE ; Regina EY KIM ; Donghyeon KIM ; Chang Uk LEE ; Hyun Kook LIM
Psychiatry Investigation 2024;21(1):37-43
Objective:
We aimed to create an efficient and valid predicting model which can estimate individuals’ brain age by quantifying their regional brain volumes.
Methods:
A total of 2,560 structural brain magnetic resonance imaging (MRI) scans, along with demographic and clinical data, were obtained. Pretrained deep-learning models were employed to automatically segment the MRI data, which enabled fast calculation of regional brain volumes. Brain age gaps for each subject were estimated using volumetric values from predefined 12 regions of interest (ROIs): bilateral frontal, parietal, occipital, and temporal lobes, as well as bilateral hippocampus and lateral ventricles. A larger weight was given to the ROIs having a larger mean volumetric difference between the cognitively unimpaired (CU) and cognitively impaired group including mild cognitive impairment (MCI), and dementia groups. The brain age was predicted by adding or subtracting the brain age gap to the chronological age according to the presence or absence of the atrophy region.
Results:
The study showed significant differences in brain age gaps among CU, MCI, and dementia groups. Furthermore, the brain age gaps exhibited significant correlations with education level and measures of cognitive function, including the clinical dementia rating sum-of-boxes and the Korean version of the Mini-Mental State Examination.
Conclusion
The brain age that we developed enabled fast and efficient brain age calculations, and it also reflected individual’s cognitive function and cognitive reserve. Thus, our study suggested that the brain age might be an important marker of brain health that can be used effectively in real clinical settings.