Ji-Hee Kim

Background/Objectives: Body mass index (BMI) does not distinguish fat mass from lean mass. Gallagher et al. proposed percentage body fat (%BF) ranges at NIH/WHO BMI cutoffs, but no study has derived %BF ranges for the full set of Asian-specific BMI cutoffs adopted in Korea. This study aimed to develop and externally validate prediction equations for %BF from BMI in Korean adults and to derive %BF ranges corresponding to Korean Society for the Study of Obesity (KSSO) BMI cutoffs. Methods: Sex-specific equations were developed using survey-weighted linear regression with the 1/BMI transformation in adults aged ≥ 19 years from KNHANES 2022 (n = 4466) using InBody 970 BIA, and externally validated in KNHANES 2023 (n = 4778). Predicted %BF values were calculated at each KSSO BMI cutoff (18.5, 23.0, 25.0, 30.0, and 35.0 kg/m²) across age-group midpoints. Results: Final equations were: Men, %BF = 51.98 − 733.89 × (1/BMI) + 0.058 × age (R² = 0.544; SEE = 3.95%); Women, %BF = 64.92 − 731.24 × (1/BMI) (R² = 0.638; SEE = 3.66%). Age was not significant in women (p = 0.82). External validation showed mean bias of −0.10% and calibration slope of 1.02. The predicted %BF at the pre-obese cutoff (BMI 23.0) was 21.5–24.4% in men and 33.1% in women; at class I obesity (BMI 25.0), 24.1–27.0% and 35.7%, respectively. Conclusions: This study provides the first nationally representative %BF ranges for all five KSSO BMI cutoffs. The predicted %BF at BMI 25.0 corresponds to %BF-defined obesity in both sexes, and is consistent with the clinical relevance of the lower obesity cutoff adopted for Asian populations.

Macrophages play a central role in orchestrating inflammation and immune responses, with their polarization states (M1 or M2) exhibiting both pro- and anti-inflammatory, as well as anti-cancer functions. Inducible nitric oxide synthase (iNOS) plays a pivotal role in immune regulation through its impact on macrophage polarization. As a hallmark of M1 macrophages, iNOS drives pro-inflammatory responses, while its suppression favors anti-inflammatory M2 phenotypes. This dual role as both a biomarker and regulatory hub positions iNOS as a promising therapeutic target across diverse disease states. This review examines the roles of iNOS modulation in macrophage polarization across various disease models. Both synthetic and natural iNOS regulators have been shown to modulate iNOS activity, thereby reprogramming macrophages toward either inflammatory or reparative phenotypes. We categorize these regulators into those that directly inhibit enzymatic activity and those that indirectly modulate through signaling pathways. Additionally, recent preclinical and clinical studies on iNOS inhibitors are summarized, highlighting their therapeutic potential in inflammatory, metabolic, and oncologic diseases. Taken together, the evidence underscores the therapeutic relevance of iNOS regulation as a strategy to reprogram macrophage plasticity in disease-specific immune microenvironments.

Epidemiological studies have linked fine dust pollution to depression, yet the underlying mechanisms remain unclear. Oxidative stress and endoplasmic reticulum (ER) stress are known contributors to depression, but their induction by particulate matter (PM), particularly PM2.5, in animal models has been limited. This study aimed to establish a rat model of PM2.5-induced depression-like behaviors and elucidate the underlying molecular mechanisms. Adult male Sprague–Dawley rats received daily intranasal PM2.5 for four weeks. Behavioral assessments, including the open field test (OFT), forced swim test (FST), and light-dark box (LDB) test, were conducted weekly. PM2.5-exposed rats displayed depressive-like behaviors, particularly in the FST, reflecting decreased motivation and learned helplessness. Molecular analyses indicated a specific increase in ER stress markers (CHOP, eIF2α, GRP78, and P16) and NOX4 in the hypothalamus, while other brain regions (striatum, cortex, and hippocampus) were not as pronounced. Additionally, PM2.5 exposure reduced tyrosine hydroxylase (TH) levels in the hypothalamus, suggesting impaired dopamine synthesis. These findings indicate that PM2.5 induces depressive-like behaviors via hypothalamic ER stress and oxidative stress pathways, leading to dopaminergic dysfunction. Targeting oxidative and ER stress within the hypothalamus may offer new therapeutic strategies for treating depression associated with environmental pollutants.

Ji-Hee Kim, Kyu-Hee Hwang, Jiyeon Oh, Sung-Eun Kim, Mi-Young Lee, Tae Sic Lee, and Seung-Kuy Cha. Korean J Physiol Pharmacol 2025;29:33-43. https://doi.org/10.4196/kjpp.24.126

Urban air pollution, a significant environmental hazard, is linked to adverse health outcomes and increased mortality across various diseases. This study investigates the neurotoxic effects of particulate matter (PM), specifically PM2.5 and PM10, by examining their role in inducing oxidative stress and subsequent neuronal cell death. We highlight the novel finding that PM increases mitochondrial ROS production via stimulating NOX4 activity, not through its expression level in Neuro-2A cells. Additionally, PMs provoke ROS production via increasing the expression and activity of NOX2 in SH-SY5Y human neuroblastoma cells, implying differential regulation of NOX proteins. This increase in mitochondrial ROS triggers the opening of the mitochondrial permeability transition pore (mPTP), leading to apoptosis through key mediators, including caspase3, BAX, and Bcl2. Notably, the voltage-dependent anion-selective channel 1 (VDAC1) increases at 1 µg/mL of PM2.5, while PM10 triggers an increase from 10 µg/mL. At the same concentration (100 µg/mL), PM2.5 causes 1.4 times higher ROS production and 2.4 times higher NOX4 activity than PM10. The cytotoxic effects induced by PMs were alleviated by NOX inhibitors GKT137831 and Apocynin. In SH-SY5Y cells, both PM types increase ROS and NOX2 levels, leading to cell death, which Apocynin rescues. Variability in NADPH oxidase sources underscores the complexity of PM-induced neurotoxicity. Our findings highlight NOX4-driven ROS and mitochondrial dysfunction, suggesting a potential therapeutic approach for mitigating PM-induced neurotoxicity.

Purpose: Patient-derived organoid (PDO) and patient derived xenografts (PDX) models has been shown strong potential as experimental and preclinical research model which preserve original tumor characteristics. Here we represent our protocols setup process for ovarian cancer organoid establishment and PDX after data review and cell line xenograft experiments. Methods: First, we reviewed the histologic subtype of ovarian cancer of biobank in national cancer center, Korea then tried to match common subtype ovarian cancer cell line by literature review for xenograft experiments. Patient specimens were collected from histologically confirmed cancer patients under informed consent (NCC2020-0219). We obtained fresh tumor tissue from standard primary surgery of ovarian cancer patient and tissue was dissociated. Then we plated cells in matrigel with modified growth factors media. Organoids were passaged with diameter larger than 50µm and genetic analysis were performed to compare with original tumor. For PDX condition establishment, xenograft models using OVCAR3 in athymic nude and NOG mouse strains were compared, then SKOV3, SNU840, SNU251, and ES2 cell line subcutaneous xenograft growth were observed in NOG mouse. Results: Frequency of subtype of ovarian cancers (n=733) in biobank represented as following: serous adenocarcinoma (70%, n=509), endometrioid tumors (11%), clear cell tumors (10%), mucinous tumors (4%) and others (5%). After adjustment of organoid culture condition, PDOs (10 patients and 11 samples) were successfully long term cultured over 5 passages and the subtypes were including high grade serous type (n=5, 50%), clear cell carcinoma (n=2), mucinous carcinoma (n=2) and low grade serous type (n=1). The median age was 65 (28-82) years and stage III-IV (n=6) were frequent. Among them, number of recurred patients was three. Currently, the genetic information of each organoid is ongoing with CNV analysis, and the sensitivity and comparative analysis of the drug will be performed. Xenografts of OVCAR3 represented higher tumor growth rate in NOG mice than in athymic nude mice (p=0.03) then comparison of growth between cell lines in NOG mice showed fast as following in order: ES2, SKOV3, OVCAR3, SNU840, and SNU251 Conclusions: PDO from ovarian cancer were established and it might provide tools for personalized drug screening. To improve success rate we are continuing adjustment of PDO culture condition and PDX. (This work was supported by National Research Foundation of Korea grant, founded by the Korea government (MSIT) [No.2020R1A2C2010566]) Citation Format: Jihee Kim, Ji Hyeong Seo, Yun-Hee Kim, YoHan Woo, Yeon Jee Lee, Yena Kim, Wonyoung Choi, Young Ju Kim, Chong Woo Yoo, Sang Yoon Park, Myong Cheol Lim, Sun-Young Kong. Developing patient-derived organoids and tumor xenograft model for ovarian cancer for preclinical therapeutic evaluation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6042.

Saturated fatty acids contribute to beta-cell dysfunction in the onset of type 2 diabetes mellitus. Cellular responses to lipotoxicity include oxidative stress, endoplasmic reticulum (ER) stress, and blockage of autophagy. Palmitate induces ER Ca2+ depletion followed by notable store-operated Ca2+ entry. Subsequent elevation of cytosolic Ca2+ can activate undesirable signaling pathways culminating in cell death. Mitochondrial Ca2+ uniporter (MCU) is the major route for Ca2+ uptake into the matrix and couples metabolism with insulin secretion. However, it has been unclear whether mitochondrial Ca2+ uptake plays a protective role or contributes to lipotoxicity. Here, we observed palmitate upregulated MCU protein expression in a mouse clonal beta-cell, MIN6, under normal glucose, but not high glucose medium. Palmitate elevated baseline cytosolic Ca2+ concentration ([Ca2+],) and reduced depolarization-triggered Ca2+ influx likely due to the inactivation of voltage-gated Ca2+ channels (VGCCs). Targeted reduction of MCU expression using RNA interference abolished mitochondrial superoxide production but exacerbated palmitate-induced [Ca2+], overload. Consequently, MCU knockdown aggravated blockage of autophagic degradation. In contrast, co-treatment with verapamil, a VGCC inhibitor, prevented palmitate-induced basal [Ca2+], elevation and defective [Ca2+], transients. Extracellular Ca2+ chelation as well as VGCC inhibitors effectively rescued autophagy defects and cytotoxicity. These observations suggest enhanced mitochondrial Ca2+ uptake via MCU upregulation is a mechanism by which pancreatic beta-cells are able to alleviate cytosolic Ca2+ overload and its detrimental consequences.

Lkhagvadorj S, et al. J Korean Med Sci. 2016 Jun;31(6):879-885. https://doi.org/10.3346/jkms.2016.31.6.879

Over the last decade, it has been established that G-protein-coupled receptors (GPCRs) signal not only through canonical G-protein-mediated mechanisms, but also through the ubiquitous cellular scaffolds β-arrestin-1 and β-arrestin-2. Previous studies have implicated β-arrestins as regulators of actin reorganization in response to GPCR stimulation while also being required for membrane protrusion events that accompany cellular motility. One of the most critical events in the active movement of cells is the cyclic phosphorylation and activation of myosin light chain (MLC), which is required for cellular contraction and movement. We have identified the myosin light chain phosphatase Targeting Subunit (MYPT-1) as a binding partner of the β-arrestins and found that β-arrestins play a role in regulating the turnover of phosphorylated myosin light chain. In response to stimulation of the angiotensin Type 1a Receptor (AT1aR), MLC phosphorylation is induced quickly and potently. We have found that β-arrestin-2 facilitates dephosphorylation of MLC, while, in a reciprocal fashion, β-arrestin 1 limits dephosphorylation of MLC. Intriguingly, loss of either β-arrestin-1 or 2 blocks phospho-MLC turnover and causes a decrease in the contraction of cells as monitored by atomic force microscopy (AFM). Furthermore, by employing the β-arrestin biased ligand [Sar¹,Ile⁴,Ile⁸]-Ang, we demonstrate that AT1aR-mediated cellular motility involves a β-arrestin dependent component. This suggests that the reciprocal regulation of MLC phosphorylation status by β-arrestins-1 and 2 causes turnover in the phosphorylation status of MLC that is required for cell contractility and subsequent chemotaxic motility.