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Biomedical subjects

Jin Hee Kim

Publications and source records attributed to Jin Hee Kim.

At least 19 recordsLinked to original sources

Stratifying Lung Adenocarcinoma Risk with Multi-ancestry Polygenic Risk Scores in East Asian Never-Smokers.

BACKGROUND: Lung adenocarcinoma (LUAD) in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve LUAD risk prediction. METHODS: PRSs were developed using genome-wide association study summary statistics from East Asian (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. Single-ancestry models included PRS-25, PRS-CT, and LDpred2; multi-ancestry models included LDpred2+PRS-EUR128, PRS-CSx, and CT-SLEB. Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium (FLCCA) and externally validated in the Nanjing Lung Cancer Cohort (NJLCC). We assessed predictive accuracy via AUC, with 10-year and (age 30-80) absolute risks estimates. RESULTS: The best multi-ancestry PRS, using East Asian and European data via CT-SLEB (clumping and thresholding, super learning, empirical Bayes), outperformed the best East Asian-only PRS (LDpred2; AUC=0.629, 95% CI:0.618,0.641), achieving an AUC of 0.640 (95% CI:0.629,0.653) and odds ratio of 1.71 (95% CI:1.61,1.82) per SD increase. NJLCC Validation confirmed robust performance (AUC =0.649, 95% CI: 0.623, 0.676). The top 20% PRS group had a 3.92-fold higher LUAD risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year LUAD risk at age 50 (0.42%) by age 41, nine years earlier. CONCLUSIONS: Multi-ancestry PRS approaches enhance LUAD risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

East Asian never smokers↗

Association of GABRB3 polymorphisms with autism spectrum disorders in Korean trios.

BACKGROUND/AIMS: Autism spectrum disorders (ASD) are complex neuropsychiatric disorders having a genetic risk factor. The association and linkage study for the gamma-aminobutyric acid type A receptor beta3 subunit gene (GABRB3), located within the chromosome 15q11-q13 autism candidate region, and ASD have been evaluated. The aim of this study was to investigate the association between GABRB3 and ASD in the Korean population. METHODS: The present study was conducted with the detection of four single-nucleotide polymorphisms (rs1426217, rs2081648, rs890317, rs981778) in GABRB3 and association analysis in 104 Korean ASD trios using the transmission disequilibrium test. RESULTS: The transmission disequilibrium test demonstrated that an allele at rs2081648 showed preferential transmission (p = 0.027). One haplotype, including all examined markers in GABRB3, demonstrated significant association (p = 0.043), but the global chi2 test for haplotype transmission did not reveal an association between GABRB3 and ASD (chi2 = 15.516, d.f. = 15). CONCLUSION: Our finding suggested that single-nucleotide polymorphisms in GABRB3 may play a significant role in the genetic predisposition to ASD in the Korean population.

Adolescent↗

Aryl hydrocarbon receptor gene polymorphisms affect lung cancer risk.

To evaluate the role of genetic polymorphisms of AhR related to the carcinogen metabolism and cell proliferation, genotypes of three AhR polymorphisms Ex1+185A>G, IVS7+33T>G and Ex10+501G>A were determined in 616 lung cancer cases and 616 lung cancer-free controls. When the effect of each AhR allele on lung cancer risk was evaluated, any AhR genotype did not show the association with lung cancer risk. However, when haplotypes were composed of three AhR SNP sites, non-smokers with GGG haplotype (adjusted OR=1.7, 95% CI, 1.06-2.71) and smokers without GGG haplotype (adjusted OR=2.5, 95% CI, 1.64-3.74) showed significantly increased risk of lung cancer compared to non-smokers without GGG haplotype. Moreover, smokers with GGG haplotype showed the highest risk (adjusted OR=3.2, 95% CI, 2.10-4.74). Particularly, the synergistic effect between AhR haplotype and smoking was more apparent in squamous cell carcinoma (adjusted OR=6.1, 95% CI, 2.53-14.68). This result suggests that haplotypes of AhR gene play an important role in the development of lung cancer and there is a synergistic interaction between AhR gene and smoking for lung cancer risk.

Aged↗

Polymorphisms of the methylenetetrahydrofolate reductase gene and clinical outcomes in HLA-matched sibling allogeneic hematopoietic stem cell transplantation.

To evaluate whether the C677T and A1298C polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) are related to the toxicity of methotrexate (MTX) used in allogeneic stem cell transplantation, we performed association analysis between these genetic polymorphisms and the clinical outcomes of patients treated using human leukocyte antigen-matched sibling stem cell transplantation. Patients (n=72) with hematological malignancy or aplastic anemia were given a short course of MTX as a graft-versus-host disease prophylaxis. Patients with the 677TT genotype showed higher total bilirubin levels (677TT vs 677CT vs 677CC, 14.5 vs 8.6 vs 3.8 mg/dl, respectively; p=0.07) and higher aspartic transaminase levels (677TT vs 677CT vs 677CC, 678.9 vs 156.6 vs 111.8 IU/l; p=0.04). Platelet recovery to 20,000/mul was slower for patients with the 677TT genotype than for patients with other genotypes (677TT, 59 days; 677CT, 26 days; 677CC, 26 days; p=0.0075). The influences of the C677T polymorphism on treatment-related mortality (TRM) were also analyzed. One-year cumulative TRMs for patients with the TT genotype and the other genotypes were 66 and 30% (p=0.04) and their respective 1-year overall survivals were 30 and 56% (p=0.11). No association was observed between the A1298C polymorphism and clinical outcome for any of the different genotypes. Therefore, patients at high risk of developing hepatic toxicity and with a poor likelihood of survival could be selected by genotyping MTHFR C677T before allogeneic stem cell transplantation.

Adolescent↗

Association study of polymorphisms in N-methyl-D-aspartate receptor 2B subunits (GRIN2B) gene with Korean alcoholism.

The N-methyl-D-aspartate (NMDA) receptor 2B gene (GRIN2B) was studied as a candidate gene of alcoholism. This study aimed to investigate the association between each of the three GRIN2B polymorphisms (rs1806201, rs1805247, and rs1805502) and alcoholism. This study included 206 alcoholic patients and 189 unrelated control subjects of Korean origin. Associations between genotype, allele, and haplotype frequencies of the polymorphisms and alcoholism were investigated. The genotype frequencies of rs1806201 and the haplotype analysis of SNPs in this study show significantly differences between the case and controls. These findings suggest new candidate SNPs in GRIN2B for studying the genetic susceptibility to alcoholism.

Adult↗

Enhancement of dendritic cell-based vaccine potency by targeting antigen to endosomal/lysosomal compartments.

Dendritic cells (DCs) are the central players in cancer immunotherapy because of their distinct ability to prime immune responses. In previous work with DNA vaccines, we described an intracellular targeting approach that routed a nuclear/cytoplasmic antigen, human papillomavirus (HPV) type 16 E7, into the endosomal and lysosomal compartments. It does so by linking E7 with the sorting signal of lysosome-associated membrane protein 1 (Sig/LAMP-1) to enhance the presentation of E7 antigen to MHC class I-restricted CD8(+) T cells, as well as to MHC class II-restricted CD4(+) T cells. To date, the Sig/LAMP-1 targeting strategy has not been tested in the context of DC-based vaccines. This study was designed to determine whether targeting HPV-16 E7 to the endosomal/lysosomal compartment can enhance the potency of DC vaccines. In immunological studies, DC-Sig/E7/LAMP-1 dramatically increased in vitro activation and in vivo expansion of E7-specific CD4(+) and CD8(+) T cells, compared with DC-E7 and DC-No insert. More importantly, in both tumor prevention and tumor treatment assays, DC-Sig/E7/LAMP-1 generated greater anti-tumor immunity against TC-1 than DC-E7. Our results demonstrate that linkage of the antigen gene to an endosomal/lysosomal targeting signal may greatly enhance the potency of DC-based vaccines.

Animals↗

Genetic polymorphisms of ataxia telangiectasia mutated affect lung cancer risk.

The ataxia telangiectasia mutated (ATM) gene is known to be activated by DNA damage and involved in cell cycle arrest, apoptosis and DNA repair. Therefore, ATM gene polymorphisms may act as important factors predicting individual susceptibility to lung cancer. To evaluate the role of ATM gene polymorphisms in lung cancer development, genotypes of the ATM polymorphisms, -4518A>G, IVS21-77C>T, IVS61-55T>C, and IVS62+60G>A, were determined in 616 lung cancer patients and 616 cancer-free controls. When the effects of selected ATM genotypes were evaluated separately, only one ATM genotype (IVS62+60G>A) showed an association with lung cancer risk. Subjects with the A allele at the site (IVS62+60G>A) have significantly higher risk of lung cancer than those with the G allele [odds ratio (OR)=1.6, 95% confidence interval (CI) 1.1-2.1]. When the haplotypes of four ATM single nucleotide polymorphism sites (-4518A>G, IVS21-77C>T, IVS61-55T>C and IVS62+60G>A) were studied, the ATTA haplotype showed significantly increased risk of lung cancer compared with the GCCA haplotype, the most common haplotype (OR=7.6, 95% CI 1.7-33.5). Furthermore, subjects with the (NN)TA haplotype showed highly significant and increased risk of lung cancer when compared with those without the (NN)TA haplotype (OR=13.2, 95% CI 3.1-56.1). Therefore, our results suggest that polymorphisms or haplotypes of the ATM gene play an important role in the development of lung cancer.

Aged↗

Rengyolone inhibits inducible nitric oxide synthase expression and nitric oxide production by down-regulation of NF-kappaB and p38 MAP kinase activity in LPS-stimulated RAW 264.7 cells.

Nitric oxide (NO) is recognized as a mediator and regulator of inflammatory responses. Rengyolone, a cyclohexylethanoid isolated from the fruits of Forsythia koreana, exhibits anti-inflammatory activity with unknown mechanism. In this study, we found that rengyolone has a strong inhibitory effect on the production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha). Rengyolone also inhibited inducible nitric oxide synthase (iNOS) gene expression and cyclooxygenase 2 (COX-2) by lipopolysaccharide (LPS). In order to explore the mechanism responsible for the inhibition of iNOS gene expression by rengyolone, we investigated its effect on LPS-induced nuclear factor-kappaB (NF-kappaB) activation. The LPS-induced DNA binding activity of NF-kappaB was significantly inhibited by rengyolone, and this effect was mediated through inhibition of the degradation of inhibitory factor-kappaBalpha and phosphorylation of p38 MAP kinase. Furthermore, rengyolone suppressed the expression of ICE protein in IL-1beta-treated D10S cells. Taken together, these results suggest that rengyolone attenuates the inflammation through inhibition of NO production and iNOS expression by blockade of NF-kappaB and p38 MAPK activation in LPS-stimulated RAW 264.7 cells.

Animals↗

Single nucleotide polymorphisms in the multidrug resistance 1 gene in Korean epileptics.

PURPOSE: P-glycoprotein 170 encoded by the multidrug resistance 1 (MDR1) gene exports various antiepileptic drugs out of the CNS, which leads to multidrug resistance. This study was performed to elucidate the relationship between single nucleotide polymorphisms (SNPs) in the MDR1 gene and drug resistance in Koreans with epilepsy. SUBJECTS AND METHODS: Three SNPs at nucleotide position 1236 in exon 12, 2677 in exon 21 and 3435 in exon 26 of the MDR1 gene were genotyped in 207 Korean epileptics. Subjects were classified according to whether they had drug-resistant (RS group; N=99) or drug-responsive epilepsy (RP group; N=108). The frequencies of genotype and haplotype were compared between the RS and RP groups. RESULTS: The frequencies of genotype and haplotype in the RS group were not statistically different from those in the RP group. CONCLUSIONS: In Korean epileptics, there was no significant relationship between three known SNPs in MDR1 and drug resistance. And there was no association of MDR1 haplotype based on above three sites with pharmacoresistance.

Adolescent↗

Enhancement of natural pigment extraction using Bacillus species xylanase.

Pigment extracts from the root of Lithospermum erythrorhizon are used as natural red dyes, as well as basic drugs due to their numerous pharmacological activities. In recent years, the demand for such natural pigment materials has increased; however, in natural dye production, the pigment yield is strongly affected by the source of cultivation, extracting conditions, and solvents. Accordingly, this study proposes a method of enzymatic pigment production based on the introduction of hydrolytic enzymes prior to the usual extraction to avoid repeated pigment extraction. The matrix destruction in the epidermal layer of the root by the enzymes was found to improve the pigment extractability, that is, the increment of K(L), the mass transfer coefficient, representing the pigment mobility in the epidermal layer. The root tissue maceration by the hydrolytic enzymes was also measured to evaluate the pigment extractability, and a linear relationship was observed between the K(L) values and the tissue maceration up to the addition of 3000 units/g of xylanase, indicating that the enzymatic maceration proportionally increases the interfacial area between the pigment and the solvent. Bacillus sp. DX107 xylanase only served to increase the extractability of the pigment by loosening the root shell matrix, without affecting the contents and color properties of the pigment, as almost no difference was found in the color between the pigments extracted using xylanase and those extracted according to the traditional method.

Bacillus↗

Association of cognitive status with functional limitation and disability in older adults.

BACKGROUND AND AIMS: Although cognitive status is known to be associated with physical function in older people, the role it plays in the disability process is not well established. This study aimed at determining whether cognitive ability predicts functional limitations, as well as disability, and whether it is associated with the rate of change in physical functions. METHODS: A community-based longitudinal study was conducted, involving 977 older persons aged 65 and older living in an urban community. Physical functions were assessed by tests scoring functional limitations (upper and lower body) and disability (activities of daily living). Cognitive function was evaluated using the Mini-Mental State Examination. Linear regression analyses with generalized estimating equations modeled the two physical function scores separately, as functions of cognitive status and time, in a one-year follow-up, controlling for sociodemographic and health-related characteristics. RESULTS: Cognitive status independently predicted functional limitations as well as disability in older people. In addition, the strength of the association of cognitive status with physical functions increased over time, as revealed by the significant interaction between cognitive ability and time. Cognitive status influenced the rate of change in disability scores, more among women and in those aged 75 or older. The relationship was unaffected by baseline physical functional status, but was significant only among those with no cognitive impairment at baseline. CONCLUSIONS: Cognitive status appears to be a useful indicator of the disablement process in older people. It may play an important role in the development of disability, implying that strategies for early intervention to prevent the progression of disability may need to take cognitive functions into account. The increasing strength of the relationship between cognitive and physical functions over time further attests to its value in monitoring functional change.

Activities of Daily Living↗

Brain-derived neurotrophic factor promotes neurite growth and survival of antennal lobe neurons in brain from the silk moth, Bombyx mori in vitro.

This study was conducted to investigate effects of brain-derived neurotrophic factor on the neurite growth and the survival rate of antennal lobe neurons in vitro, and secretion of brain-derived neurotrophic factor-like neuropeptide from brain into hemolymph in the silk moth, Bombyx mori. In primary culture of antennal lobe neurons with brain-derived neurotrophic factor, it promoted both a neurite extension of putative antennal lobe projection neurons and an outgrowth of branches from principal neurites of putative antennal interneurons with significance (p<0.05). Brain-derived neurotrophic factor also increased significantly a survival rate of antennal lobe neurons (p<0.05). Results from immunolabeling of brain and retrocerebral complex, and ELISA assay of hemolymph showed that brain-derived neurotrophic factor-like neuropeptide was synthesized by both median and lateral neurosecretory cells of brain, then transported to corpora allata for storage, and finally secreted into hemolymph for action. These results will provide valuable information for differentiation of invertebrate brain neurons with brain-derived neurotrophic factor.

Animals↗

Enhancement of tyrosinase inhibition of the extract of Veratrum patulum using cellulase.

Inhibitors of melanin biosynthesis were screened by using three different methods. The extract of Veratrum patulum contains hydroxystilbene compounds that are potent tyrosinase inhibitors. We evaluated the enzyme inhibitory property on the mushroom tyrosinase of hydroxystilbene compounds including resveratrol, oxyresveratrol, and their analogs. Biotransformation using cellulase of the whole extract brought about an increase in the inhibitory activity of the products on mushroom tyrosinase. The enhancement of tyrosinase inhibition is supposed to increase the concentration of aglycon, which has superior inhibitory activity to its glycoside. Eventually, melanin biosynthesis was inhibited by the enhanced tyrosinase inhibitory activity of the extract. This result indicated that deglycosylation of stilbene compounds has exerted more effective inhibition on the enzyme than that of the unprocessed plant extract.

Agaricales↗

Hemodynamic changes during posterior vessel off-pump coronary artery bypass: comparison between deep pericardial sutures and vacuum-assisted apical suction device.

BACKGROUND: Displacement of the heart to expose posterior vessels during off-pump coronary artery bypass may cause hemodynamic derangement. The aims of this study were (1) to elucidate the hemodynamic changes during off-pump coronary artery bypass for the obtuse marginal branch (OM) of the left circumflex artery; and (2) to compare the hemodynamic changes caused by a deep pericardial suture technique with those caused by a vacuum-assisted apical suction device for displacement of the heart. METHODS: Hemodynamic changes during posterior vessel off-pump coronary artery bypass were studied in a prospective randomized manner. A deep pericardial suture technique (group 1, n = 10) or a vacuum-assisted apical suction device (group 2, n = 10) was used to facilitate the exposure of the OM. Hemodynamic variables such as cardiac index, stroke volume index (SVI), mean arterial pressure, mean pulmonary artery pressure, central venous pressure, pulmonary capillary wedge pressure, heart rate, systemic vascular resistance, pulmonary vascular resistance, left ventricular stroke work index, and right ventricular stroke work index were monitored during off-pump coronary artery bypass. Hemodynamic data were obtained before revascularization of the left anterior descending coronary artery at a baseline (T0), 3 minutes after heart displacement for revascularization of OM (T1), 3 minutes after the beginning of OM grafting (T2), and 3 minutes after the completion of OM grafting and heart repositioning (T3). RESULTS: There were no significant differences in the baseline hemodynamic variables (T0) between the two groups. In group 1, SVI, cardiac index, left ventricular stroke work index, and right ventricular stroke work index decreased significantly, and central venous pressure and pulmonary capillary wedge pressure increased significantly, during displacement of the heart (T1, p < 0.05). In group 2, SVI decreased significantly, and central venous pressure, pulmonary capillary wedge pressure, and mean pulmonary artery pressure increased significantly during displacement of the heart (T1, p < 0.05). The percent changes of cardiac index, SVI, and right ventricular stroke work index during OM grafting (T2) in comparison with baseline values (T0) were significantly larger in group 1 than in group 2 (cardiac index, 73% +/- 12% versus 90% +/- 11%; SVI, 69% +/- 12% versus 86% +/- 8%; right ventricular stroke work index, 30% +/- 17% versus 71% +/- 25%, in groups 1 versus 2, respectively; p < 0.05). CONCLUSIONS: Displacement of the heart using either a deep pericardial suture technique or a vacuum-assisted apical suction device caused a significant decrease in SVI. The hemodynamic changes during OM grafting were smaller when using a vacuum-assisted apical suction device.

Blood Pressure↗

Evidence for brain-derived neurotrophic factor-like neuropeptide in brain of the silk moth Bombyx mori during postembryonic periods.

Brain-derived neurotrophic factor-like neuropeptide is produced in the brain of the silk moth, Bombyx mori. Immunocytochemical studies of brain and retrocerebral complex of larvae, prepupae, pupae and adults showed that four pairs of median neurosecretory cells and six pairs of lateral neurosecretory cells which had different immunoreactivities to BDNF peptide. Day-1 adult brains showed no evidence of neurons stained by anti-BDNF antibodies. Those reactivities, which were much stronger in median cells than in lateral cells, were the weakest in an earliest larval stage and a latest pupal stage but the strongest in late larval stage. Median neurosecretory cells projected their axons into the contralateral corpora allata by decussation in the median region, nerve corpora cardiaca (NCC) I, and nerve corpora allata (NCA) I, whereas lateral neurosecretory cells extended their axons to the ipsilateral corpora allata via NCC II and NCA I.

Animals↗

Anti-angiogenic activity of a homoisoflavanone from Cremastra appendiculata.

A homoisoflavanone, 5,7-dihydroxy-3-(3-hydroxy-4-methoxybenzyl)-6-methoxychroman-4-one ( 1), was isolated from the bulb of Cremastra appendiculata (D. Don) Makino (Orchidaceae) as a potent inhibitor of angiogenesis. It inhibited basic fibroblast growth factor (bFGF)-induced in vitro angiogenesis and in vivo angiogenesis of the chorioallantoic membrane (CAM) of chick embryo without showing any toxicity.

Angiogenesis Inhibitors↗