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Biomedical subjects

Young-Hyun Kim

Publications and source records attributed to Young-Hyun Kim.

5 recordsLinked to original sources

Identification and validation of condition-specific candidate reference genes for accurate RT-qPCR normalization in acute and chronic methamphetamine-exposed cynomolgus monkeys.

Reverse transcription quantitative real-time PCR (RT-qPCR) is widely used to quantify gene expression, but its accuracy depends on appropriate normalization using stable reference genes (RGs). Because methamphetamine (METH) exposure induces widespread transcriptional changes, conventional housekeeping genes may not remain stable under these conditions. However, condition-specific RGs have not been systematically evaluated in METH-exposed nonhuman primate models. We evaluated transcriptome-derived candidate RGs together with four commonly used RGs (GAPDH, ACTB, RPS5, and YWHAZ) in blood and tissue samples obtained from acute and chronic METH-exposed cynomolgus monkeys representing multiple age groups. Expression stability was assessed using geNorm, NormFinder, and BestKeeper, and the results were integrated using geometric mean ranking. The impact of RG selection on target-gene quantification was further examined by analyzing the expression of FOSL2, JUN, and NR4A1. The stability rankings of candidate RGs differed across age-stratified groups, exposure paradigms, and sample types. No single gene exhibited consistently stable expression across all experimental conditions. In contrast, the traditionally used RGs generally ranked poorly in most sample groups. Normalization using the most stable and least stable RGs produced different expression patterns of FOSL2 and JUN in acute blood samples, while NR4A1 and JUN expression in chronic blood samples was evaluated using the selected RGs. This study provides condition-specific candidate reference genes for RT-qPCR normalization in acute and chronic METH-exposed cynomolgus monkeys. Rather than identifying universally stable housekeeping genes, our findings demonstrate that reference-gene stability should be empirically validated for each experimental context. These findings provide a practical framework for improving the reliability and reproducibility of gene expression analyses in METH exposure studies.

Cynomolgus monkey↗

Precise progerin targeting using RfxCas13d: A therapeutic avenue for Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS), an extremely rare progressive genetic disorder, is caused by a point mutation in LMNA that induces progerin production, which disrupts cellular function and triggers premature aging and mortality. Despite extensive efforts, HPGS remains incurable. We successfully implemented a strategy using RfxCas13d to selectively target progerin mRNA at specific junction regions, without unintended cleavage and reduce its expression. This technique discriminated between normal lamin A and progerin, thus providing a safe and targeted therapeutic avenue to treat HGPS. Our approach effectively restored aberrant gene expression and progerin-induced cellular phenotypes, including senescence, mitochondrial dysfunction, and DNA damage in cells with HGPS and LMNAG608G/G608G mice. Notably, LMNAG608G/G608G mice exhibited improved progeroid phenotypes, suggesting a potential therapeutic application of this approach for other diseases resulting from abnormal RNA splicing.

Progeria↗

Does arm length indicate cognitive and functional reserve?

BACKGROUND: This study aimed to examine whether arm length and height were associated with cognitive and functional abilities. METHODS: Screening interviews were conducted in 235 community dwelling individuals aged 65 and over. The assessment scales included the Korean version of modified Mini-Mental State Examination (K-mMMSE) for cognition, and the Korean Instrumental Activities of Daily Living (K-IADL) for functional ability. All the participants were examined clinically and a diagnosis of dementia was ascertained. Anthropometric measurements included total arm span and height. RESULTS: Both arm length and height correlated significantly with the cognitive and functional scales. In the multivariate regression models, their associations were significant, independent of age, sex, education, and other variables. Shorter arm length was also significantly associated with dementia; while, height lost significance after an adjustment for the potential confounders. CONCLUSIONS: Arm length and height could indicate cognitive and functional ability. Arm length, which was known to be less prone to degenerative processes, might be more stable as an indicator for cognitive and functional reserve capacity than height.

Activities of Daily Living↗

Does waist indicate dyslipidemia better than BMI in Korean adult population?

Obesity is an independent and modifiable risk factor for cardiovascular disease, and known as a core of the metabolic syndrome. Obesity has been largely diagnosed based upon anthrompometric measurements like waist circumference (WC) and body mass index (BMI). We sought to determine associations between anthropometric measurements and dyslipidemia in a community adult sample composed of 1,032 community residents (356 men, 676 women) aged 50 yr and over in Namwon, Korea. Blood tests for lipid profiles, including total cholesterol (TC) and HDL cholesterol (HDL) were performed, and dyslipidemia was defined as TC/HDL greater than 4. Anthropometric measurements included WC, waist-to-height ratio (WHtR), waist-to-hip ratio, and BMI. All anthropometric measures were categorized into quartiles and evaluated for associations with dyslipidemia. TC/HDL showed the significant associations with the anthropometric measures, independently of potential confounders. In women, increases of obesity indexes by quartile analyses showed linear increases of odds ratios for dyslipidemia (p values <0.01 by trend test). In men, except BMI, same patterns of association were noted. WC and WHtR were significantly associated with dyslipidemia in Korean adult population. As a simple and non-invasive method for a detection of obesity and dyslipidemia, anthropometric measurements could be efficiently used in clinical and epidemiologic fields.

Adult↗

In vitro immunomodulatory activity of Bo-yang-hwan-o-tang.

Bo-yang-hwan-o-tang (BHT), an herbal decoction has been mainly used for improvement of blood flow in oriental medicine. Its in vivo immunomodulation was recently demonstrated but the effective mechanisms have not been described. This study was carried out to evaluate in vitro immunomodulatory activity of BHT. Water extract of BHT significantly promoted in vitro proliferative responses of mouse spleen cells (SPC) and also further enhanced the proliferation of SPC stimulated with anti-CD3 antibody. Unexpectedly, addition of BHT extract did not affect proliferation of both resting and CD3-activated T cells, whereas it showed a strong mitogenic activity on B cells. Flow cytometric analysis of CFSE-stained SPC showed that BHT-mediated enhancement of CD3-activated SPC proliferation is due to T cell, but not B cell, division. Mixed culture experiment combining T and mitomycin C-treated B cells demonstrated that BHT-mediated enhancement of CD3-activated T cell proliferation was dependent on the presence of B cells. However, B cell-derived factors were not involved in BHT effect on T cell proliferation. In the presence of B cells, BHT treatment resulted in a great enhancement in IL-2 production of CD3-activated T cells, and BHT effect on T cell proliferation was completely abrogated by addition of exogenous IL-2, indicating that IL-2 plays a critical role in BHT-mediated enhancement of CD3-activated T cell proliferation. Taken together, our data revealed that BHT possesses a potent B cell mitogenic activity and also can enhance activated T cell response through B cell regulation.

Animals↗