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Biomedical subjects

Dae Hyun Kim

Publications and source records attributed to Dae Hyun Kim.

At least 19 recordsLinked to original sources
PubMed2024

S100A9 induces tissue remodeling of human nasal epithelium in chronic rhinosinusitis with nasal polyp.

BACKGROUND: Chronic inflammation triggers tissue remodeling in human nasal epithelial (HNE) cells. S100A9, a protein secreted by inflammatory cells, exhibits potent proinflammatory activity. However, its effect on HNE cell remodeling, such as squamous metaplasia, remains unclear. Therefore, this study aimed to determine the effects and underlying pathways of S100A9 on HNE cell remodeling and investigate its clinical implications in chronic rhinosinusitis (CRS). METHODS: Cultured HNE cells were treated with S100A9. Bulk RNA sequencing was performed to analyze gene ontology (GO). Ingenuity pathway analysis (IPA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were also analyzed. Additionally, immunohistochemistry and multiplex immunofluorescence were performed on tissue samples obtained from 60 patients, whose clinical informations were also reviewed. RESULTS: GO enrichment analysis indicated that S100A9 induced tissue remodeling in HNE cells toward squamous metaplasia. IPA and KEGG commonly showed that S100A9 affected HNE cells associated with the IL-17 signaling pathway, including target molecules such as matrix metalloproteinase 1 (MMP1) and small proline-rich protein 2A (SPRR2A). Squamous metaplasia with a marked expression of S100A9 was observed in 50% of CRS with nasal polyps (CRSwNPs). In addition, in multiplex immunofluorescence, the S100A9 in sub-epithelium was co-expressed with myeloperoxidase, a neutrophil marker, and MMP1 and SPRR2A were strongly expressed in epithelial remodeling. Clinically, the expression of S100A9 correlated with sino-nasal outcome test-22 (r = 0.294, p = 0.022) and Lund-Mackay scores (r = 0.348, p = 0.006). CONCLUSION: S100A9 induces tissue remodeling in HNE cells. Its increased expression in CRSwNP, particularly squamous epithelium, correlates with disease severity. This suggests the clinical potential of S100A9 as a biomarker for CRS severity.

Humans↗
PubMed2006

Four-color DNA sequencing by synthesis using cleavable fluorescent nucleotide reversible terminators.

DNA sequencing by synthesis (SBS) on a solid surface during polymerase reaction offers a paradigm to decipher DNA sequences. We report here the construction of such a DNA sequencing system using molecular engineering approaches. In this approach, four nucleotides (A, C, G, T) are modified as reversible terminators by attaching a cleavable fluorophore to the base and capping the 3'-OH group with a small chemically reversible moiety so that they are still recognized by DNA polymerase as substrates. We found that an allyl moiety can be used successfully as a linker to tether a fluorophore to 3'-O-allyl-modified nucleotides, forming chemically cleavable fluorescent nucleotide reversible terminators, 3'-O-allyl-dNTPs-allyl-fluorophore, for application in SBS. The fluorophore and the 3'-O-allyl group on a DNA extension product, which is generated by incorporating 3'-O-allyl-dNTPs-allyl-fluorophore in a polymerase reaction, are removed simultaneously in 30 s by Pd-catalyzed deallylation in aqueous buffer solution. This one-step dual-deallylation reaction thus allows the reinitiation of the polymerase reaction and increases the SBS efficiency. DNA templates consisting of homopolymer regions were accurately sequenced by using this class of fluorescent nucleotide analogues on a DNA chip and a four-color fluorescent scanner.

Base Sequence↗
PubMed2006

Short-term feeding of baicalin inhibits age-associated NF-kappaB activation.

Baicalin is a flavonoid isolated from Scutellaria baicalensis and is known to affect multiple biological functions, including the inhibition of aldose reductase, HIV infection, and nitric oxide producing activity. Oxidative stress is considered a major cause of aging and various age-related diseases, and among the key cellular components exquisitely sensitive to oxidative stress is the transcription factor, nuclear factor-kappaB (NF-kappaB). In the present study, we attempted to elucidate the mechanisms underlying the suppression of age-related NF-kappaB activation by baicalin in kidney tissue from old rats. Results showed NF-kappaB activation and the upregulation of NF-kappaB targeting genes, hemoxygenase-1, inducible nitric oxide synthase (iNOS), and COX-2 with age. In contrast, the increased expression of these NF-kappaB targeting genes was effectively inhibited by baicalin. Baicalin was shown to inhibit the NF-kappaB cascade via three signal transduction pathways, NIK/IKK, extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein kinase (MAPK). Our results clearly indicated the anti-oxidative effects of baicalin on age-related redox imbalance. Thus, the significance of the current study is the new information revealing the anti-oxidative properties of baicalin and the role it plays in the regulation of age-related alterations.

Aging↗
PubMed2006

Design and synthesis of a photocleavable fluorescent nucleotide 3'-O-allyl-dGTP-PC-Bodipy-FL-510 as a reversible terminator for DNA sequencing by synthesis.

DNA sequencing by synthesis (SBS) using reversible fluorescent nucleotide terminators is potentially an efficient approach to address the limitations of current DNA sequencing techniques. Here, we report the design and synthesis of a 3'-O-allyl photocleavable fluorescent nucleotide analogue, 3'-O-allyl-dGTP-PC-Bodipy-FL-510, as a reversible terminator for SBS. The nucleotide is efficiently incorporated by DNA polymerase into a growing DNA strand to terminate the polymerase reaction. After that, the fluorophore is photocleaved quantitatively by irradiation at 355 nm, and the allyl group is rapidly and efficiently removed by using a Pd-catalyzed reaction under DNA-compatible conditions to regenerate a free 3'-OH group to reinitiate the polymerase reaction. Two cycles of such steps were successfully demonstrated to sequence a homopolymeric region of a DNA template, facilitating the development of SBS as a viable approach for high-throughput DNA sequencing.

Base Sequence↗
PubMed2006

Design and synthesis of a chemically cleavable fluorescent nucleotide, 3'-O-allyl-dGTP-allyl-bodipy-FL-510, as a reversible terminator for DNA sequencing by synthesis.

We report the construction of a novel chemically cleavable fluorescent labeling system based on an allyl group to modify nucleotide for DNA sequencing by synthesis (SBS). We have found that an allyl moiety can be used successfully as a linker to tether a fluorophore to a 3'-O-allyl-modified nucleotide, forming a chemically cleavable reversible terminator, 3'-O-allyl-dGTP-allyl-Bodipy-FL-510, for application in SBS. The fluorophore and the 3'-allyl group on a DNA extension product, which is generated by incorporating 3'-O-allyl-dGTP-allyl-Bodipy-FL-510, are removed simultaneously in 30 s by Pd-catalyzed deallylation in aqueous buffer solution. The resulting DNA product is successfully used as a primer for further extension in polymerase reaction. This one-pot dual-deallylation reaction thus allows the reinitiation of the polymerase reaction and increases the SBS efficiency.

Allyl Compounds↗
PubMed2006

Successful anticoagulation for bilateral central retinal vein occlusions accompanied by cerebral venous thrombosis.

BACKGROUND: Concurrent development of retinal venous drainage and cerebral venous thrombosis has not been reported. Case Description We describe a 23-year-old man with bilateral central retinal vein occlusions and cerebral venous thrombosis. Initially observed bilateral hemorrhagic retinopathy and thrombus in the right transverse sinus of the patient began to resolve after 2 weeks of low-molecular-weight heparin. Hemorrhagic retinopathy progressively improved to previous visual acuity and the right lateral sinus remained patent by maintenance of anticoagulation with warfarin. CONCLUSION: The present case shows effectiveness of low-molecular-weight heparin for the initial management of hemorrhagic retinopathy of central retinal vein occlusion combined with cerebral venous thrombosis.

Adult↗
PubMed2006

The effect of belly board location in rectal cancer patients treated with preoperative radiotherapy.

AIMS: To evaluate the effect of the belly board aperture location on the irradiated small bowel volume in rectal cancer patients treated with preoperative pelvic radiotherapy. MATERIALS AND METHODS: Twenty patients with rectal cancer scheduled to receive preoperative pelvic radiotherapy were evaluated prospectively. Each patient underwent computed tomography with the belly board aperture lower border at three different locations relative to patient anatomy: the lumbosacral junction (location I), the lower end of the sacroiliac joint (location II) and the upper end of the symphysis pubis (location III). The irradiated small bowel volume was calculated for doses between 10 and 100% of the prescribed dose at 10% intervals. For each 10% dose increment, the effect of the belly board aperture at the three different locations on the irradiated small bowel volume was analysed using Wilcoxon signed rank and Wilcoxon rank sum tests. RESULTS: At 10-20% dose levels, the irradiated small bowel volume increased in the order of locations I, II and III, and the differences between each location were significant. At > or = 30% dose levels, the irradiated small bowel volume increased in the order of locations III, II and I, and the differences between locations I and II were significant, but the differences between locations II and III were not significant. CONCLUSION: The belly board aperture location can influence the irradiated small bowel volume differently at each dose level. When considering the use of a belly board in routine clinical practice, we recommend that the clinician take into account the patterns of irradiated small bowel volume according to belly board aperture location.

Adult↗
PubMed2006

Proteomic analysis of nitrated and 4-hydroxy-2-nonenal-modified serum proteins during aging.

Using proteomic techniques, we investigated peroxynitrite (ONOO-) and 4-hydroxy-2-nonenal (HNE) modified serum proteins from young and old Fischer 344 rats. Two-dimensional gel electrophoresis/western blot analysis of nitrotyrosine and HNE-histidine revealed that serum proteins were differentially modified by ONOO- and HNE. Among them, 16 of the modified proteins, identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), are involved in blood coagulation, lipid transport, blood pressure regulation, and protease inhibition. Furthermore, nitration and HNE adduction were found to increase with age, lending support to the oxidative stress hypothesis of aging. Our data showed that proteomic techniques can be valuable tools in the study of protein profiling modifications during aging.

Aging↗
PubMed2006

Association between reduced heart rate variability and cognitive impairment in older disabled women in the community: Women's Health and Aging Study I.

OBJECTIVES: To examine the independent association between heart rate variability (HRV), a marker of cardiac autonomic function, and cognitive impairment. DESIGN: Cross-sectional analysis of baseline data from Women's Health and Aging Study I. SETTING: Urban community in Baltimore, Maryland. PARTICIPANTS: A subset of 311 physically disabled, community-dwelling women aged 65 and older whose HRV data were obtained. MEASUREMENTS: Reduced HRV was defined as the lowest quartile of each of several HRV measures exploring time and frequency domains and compared with the remaining three quartiles. Cognitive impairment was defined as a Mini-Mental State Examination score less than 24. Multiple logistic regression was used to model the independent relationship between reduced HRV and prevalent cognitive impairment. RESULTS: The age-, education-, and race-adjusted prevalence of cognitive impairment was higher in those with reduced HRV than in those with nonreduced HRV. After adjusting for relevant demographic and clinical characteristics, participants with reduced HRV were significantly more likely than those with nonreduced HRV to have cognitive impairment; these findings were consistent across different HRV indices. In particular, reduced high-frequency power, indicative of decreased parasympathetic activity, was associated with 6.7 times greater odds of cognitive impairment (95% confidence interval = 2.27-20.0). CONCLUSION: Cardiac autonomic dysfunction, particularly decreased parasympathetic activity, was independently associated with cognitive impairment in older disabled women in the community. This finding may improve understanding of the pathophysiological basis of cognitive impairment. The potential role of HRV as a cause or consequence of cognitive impairment needs to be elucidated in future studies.

Aged↗
PubMed2005

Usefulness of magnetic resonance volumetric evaluation in predicting response to preoperative concurrent chemoradiotherapy in patients with resectable rectal cancer.

PURPOSE: We performed magnetic resonance (MR) volumetry before and after neoadjuvant chemoradiation for evaluating response to therapy in T3 and T4 rectal cancer. To investigate the utility of MR volumetry for predicting the response to neoadjuvant chemoradiation, we compared results from MR volumetry before chemoradiation with those after chemoradiation. METHODS AND MATERIALS: A total 112 patients with T3 or T4 rectal cancer who successfully underwent MR volumetry and completed neoadjuvant chemoradiation followed by radical resection for cure were identified. MR volumetries were performed before and after chemoradiation. We compared pre- and postchemoradiation tumor volume and % volume reduction rates of patients whose tumors were down-staged with those of patients that were not down-staged. The same analyses were also performed between those patients having a complete histologic regression and those with residual disease in the operative specimen. We assessed the difference of % volume reduction rate according to Dworak's rectal cancer regression grades. RESULTS: Fifty-seven patients (50.9%) demonstrated a tumor down-staging after chemoradiation therapy. Both pre- and posttreatment MR tumor volumes were significantly less in patients whose tumors were down-staged than in patients that were not down-staged (p = 0.04, 0.031), and % volume reduction rates were significantly higher in patients whose tumors were down-staged (p = 0.024). Sixteen patients (14.3%) showed pathologically complete tumor regression. The differences of MR tumor volumes before and after chemoradiation and % volume reduction rates were not significantly different between patients having a complete histologic regression and those with residual disease (p = 0.688, 0.451, and 0.480). The differences of % volume reduction rates according to Dworak's grades were statistically significant (p = 0.03). CONCLUSION: The MR volumetric examinations before and after chemoradiation demonstrated the significant difference of tumor volume and % volume reduction rate between patients whose tumors were down-staged and those that were not down-staged. The volume reduction rates were significantly different among groups according to Dworak's grades. However, the MR volumetric evaluation could not identify any differences between those patients having a complete histologic regression and those with residual disease.

Adult↗
PubMed2005

Design and synthesis of a 3'-O-allyl photocleavable fluorescent nucleotide as a reversible terminator for DNA sequencing by synthesis.

DNA sequencing by synthesis (SBS) offers an approach for potential high-throughput sequencing applications. In this method, the ability of an incoming nucleotide to act as a reversible terminator for a DNA polymerase reaction is an important requirement to unambiguously determine the identity of the incorporated nucleotide before the next nucleotide is added. A free 3'-OH group on the terminal nucleotide of the primer is necessary for the DNA polymerase to incorporate an incoming nucleotide. Therefore, if the 3'-OH group of an incoming nucleotide is capped by a chemical moiety, it will cause the polymerase reaction to terminate after the nucleotide is incorporated into the DNA strand. If the capping group is subsequently removed to generate a free 3'-OH, the polymerase reaction will reinitialize. We report here the design and synthesis of a 3'-modified photocleavable fluorescent nucleotide, 3'-O-allyl-dUTP-PC-Bodipy-FL-510 (PC-Bodipy, photocleavable 4,4-difluoro-4-bora-3alpha,4alpha-diaza-s-indacene), as a reversible terminator for SBS. This nucleotide analogue contains an allyl moiety capping the 3'-OH group and a fluorophore Bodipy-FL-510 linked to the 5 position of the uracil through a photocleavable 2-nitrobenzyl linker. Here, we have shown that this nucleotide is a good substrate for a DNA polymerase. After the nucleotide was successfully incorporated into a growing DNA strand and the fluorophore was photocleaved, the allyl group was removed by using a Pd-catalyzed reaction to reinitiate the polymerase reaction, thereby establishing the feasibility of using such nucleotide analogues as reversible terminators for SBS.

Base Sequence↗
PubMed2005

Four-color DNA sequencing by synthesis on a chip using photocleavable fluorescent nucleotides.

We report four-color DNA sequencing by synthesis (SBS) on a chip, using four photocleavable fluorescent nucleotide analogues (dGTP-PC-Bodipy-FL-510, dUTP-PC-R6G, dATP-PC-ROX, and dCTP-PC-Bodipy-650) (PC, photocleavable; Bodipy, 4,4-difluoro-4-bora-3alpha,4alpha-diaza-s-indacene; ROX, 6-carboxy-X-rhodamine; R6G, 6-carboxyrhodamine-6G). Each nucleotide analogue consists of a different fluorophore attached to the 5 position of the pyrimidines and the 7 position of the purines through a photocleavable 2-nitrobenzyl linker. After verifying that these nucleotides could be successfully incorporated into a growing DNA strand in a solution-phase polymerase reaction and the fluorophore could be cleaved using laser irradiation ( approximately 355 nm) in 10 sec, we then performed an SBS reaction on a chip that contains a self-priming DNA template covalently immobilized by using 1,3-dipolar azide-alkyne cycloaddition. The DNA template was produced by PCR, using an azido-labeled primer, and the self-priming moiety was attached to the immobilized DNA template by enzymatic ligation. Each cycle of SBS consists of the incorporation of the photocleavable fluorescent nucleotide into the DNA, detection of the fluorescent signal, and photocleavage of the fluorophore. The entire process was repeated to identify 12 continuous bases in the DNA template. These results demonstrate that photocleavable fluorescent nucleotide analogues can be incorporated accurately into a growing DNA strand during a polymerase reaction in solution and on a chip. Moreover, all four fluorophores can be detected and then efficiently cleaved using near-UV irradiation, thereby allowing continuous identification of the DNA template sequence. Optimization of the steps involved in this SBS approach will further increase the read-length.

Base Sequence↗
PubMed2005

The effect of age and calorie restriction on HIF-1-responsive genes in aged liver.

Hypoxia inducible factor-1 (HIF-1) regulates transactivation of several genes in response to hypoxia condition. We explore hepatic HIF-1 responsive gene regulation during aging and the age-related changes of the HIF-1 related gene activation in young and old rats. Results indicate that the aging process induces the activation of HIF-1alpha, which is accompanied by increased HIF-1 DNA binding. This increased binding activity is accompanied by the increase of HIF-1-dependent genes, heme oxygenase-1 (HO-1), vascular endothelial growth factor (VEGF), erythropoietin (EPO), and inducible nitric oxide synthase (iNOS), which all showed remarkable up-regulation during aging process. In contrast, the increased HIF-1 related gene expression was effectively blunted by the anti-oxidative action of calorie restriction in aged rat liver. We propose that age-related HIF-1 binding activity may well be influenced by the increased pro-oxidative conditions of aged animals, which up-regulate HIF-1-dependent gene expression.

Aging↗
PubMed2005

Cytoprotective mechanism of baicalin against endothelial cell damage by peroxynitrite.

To evaluate the mechanism responsible for the cytoprotective effects of baicalin, an antioxidant flavonoid isolated from Scutellaria baicalensis, we investigated its effects against peroxynitrite (ONOO-)-induced endothelial cell (EC) damage. Baicalin showed efficient antioxidative actions by its ability to scavenge ONOO and inhibit ONOO(-)-mediated nitrotyrosine formation in vitro. Using an EC (YPEN-1) culture system, baicalin exhibited cytoprotective effects against cell death by ONOO- that was induced exogenously with tert-butyl hydroperoxide (t-BHP) in the YPEN-1 model. Baicalin was also found to reduce the intracellular precursors of ONOO-, NO* and O2(-) in the t-BHP-treated ECs. Evidence from Western blotting further revealed down-regulated expressions of iNOS and COX2, endogenous sources of NO* and O2(-) by baicalin treatment. In addition, pre-incubation of baicalin with EC suppressed t-BHP-induced nuclear factor kappa-B binding activity as determined by the transfection assay and Western blot analysis, further indicating baicalin's inhibition of iNOS and COX-2 expression. Based on the present data, we propose that baicalin scavenges ONOO- and protects cells against injury. Based on these data, it was concluded that baicalin is potentially a useful antioxidant against ONOO- and NO* and an inhibitor of iNOS and COX-2.

Cell Line↗