Ji-Hyeon Oh

Background/Objectives: Chronic ethanol (EtOH) consumption is a major cause of metabolic dysfunction and multi-organ injury, particularly in the liver and pancreas. Because oxidative stress and endoplasmic reticulum (ER) stress are central mechanisms in both organs, this study evaluated the protective efficacy of 4-hexylresorcinol (4HR) against EtOH-induced hepato-pancreatic injury. Methods: Male C57BL/6J mice (6 weeks old) were assigned to four groups (n = 10/group): control, EtOH, EtOH + 4HR (5 mg/kg), and EtOH + 4HR (10 mg/kg). After a 1-week adaptation period, mice were fed a liquid EtOH diet for 5 weeks. Glucose tolerance, fasting glucose, serum insulin, and insulinogenic index were assessed. Liver and pancreas were analyzed by histology, immunohistochemistry, Western blotting, periodic acid-Schiff staining, Oil Red O staining, and malondialdehyde assay. Results: Chronic EtOH exposure impaired glucose homeostasis, reduced the insulinogenic index, increased hepatic inflammation and ALT levels, depleted hepatic glycogen, elevated pancreatic lipid peroxidation, and upregulated GADD153 (CHOP) expression in both the liver and pancreas. 4HR administration, particularly at 10 mg/kg, attenuated several of these alterations. 4HR treatment was associated with reduced hepatic inflammatory changes and ALT elevation, decreased pancreatic malondialdehyde levels, and suppressed GADD153 expression in both organs. Although PAS staining in the 4HR-treated group showed a qualitative tendency toward increased hepatic glycogen deposition, quantitative analysis did not demonstrate significant recovery relative to the EtOH group. Conclusions: 4HR showed protective effects against several aspects of chronic EtOH-induced hepatic and pancreatic injury, including hepatic inflammation, pancreatic lipid peroxidation, and ER stress-related GADD153 expression. However, quantitative PAS analysis did not support significant restoration of EtOH-induced hepatic glycogen depletion by 4HR. These findings suggest that 4HR may serve as a potential multi-organ protective agent against alcohol-induced inflammatory, oxidative stress-, and ER stress-related injury, although its effect on hepatic glycogen metabolism remains limited under the present experimental conditions.

Background: Skeletal muscle insulin resistance in diabetes is characterized by impaired GLUT4 availability and dysregulated AMP-activated protein kinase (AMPK) signaling. We investigated whether 4-hexylresorcinol (4HR) modulates glucose metabolism and AMPK–acetyl-CoA carboxylase (ACC)–GLUT4 signaling in vitro and in streptozotocin (STZ)–induced diabetic rats. Methods: Differentiated C2C12 myotubes were treated with 4HR (0.1–10 µM) and assessed for glucose uptake, GLUT4 translocation, protein stability, proteasome involvement, and AMPK/ACC phosphorylation. In vivo, streptozotocin (STZ)–induced diabetic rats received subcutaneous 4HR (10 mg·kgL¹, 5 times/week for 7 weeks). Glycemic control, insulin secretion, muscle glycogen content, and serum protein profiles were evaluated. Results: 4HR markedly increased glucose uptake (>5-fold vs. control, p<0.05), accompanied by increased phosphorylation of AMPK (Thr172) and ACC (Ser79), and redistribution of GLUT4 toward the cell periphery. Cycloheximide chase and proteasome inhibition experiments indicated partial stabilization of GLUT4. In diabetic rats, 4HR reduced fasting glycemia, improved glucose tolerance, elevated circulating insulin, and restored glycogen-rich fibers in skeletal muscle. Serum profiling revealed a metabolic and anti-inflammatory shift, with increased AMPKα, p-ACC, GLUT1, LGR4, LDHA, and PGC-1α, alongside suppression of NF-κB and TNF-α. Conclusion: 4HR improves skeletal muscle glucose metabolism in STZ-induced diabetes, associated with activation of AMPK–ACC signaling, preservation of GLUT4 expression, and restoration of glycogen content. These findings highlight 4HR as a promising candidate for further investigation in diabetic muscle dysfunction and metabolic disease.

Jin-Woo Kim, Sung-Hye Kong, Jae-Young Kim, Mi Kyung Kwak, Jun-Young Kim, Ji-Hyeon Oh, Hyung-Youl Park, BeomTaek Kim, Young-Kyun Lee, Jeong Joon Han, Moon-Young Kim, Yong Jun Choi, Yong-Dae Kwon, Kwang-Sup Song, Beom-Jun Kim, Sun-Jong Kim, Seung-Hoon Baek, Dong Ock Lee, Han Seok Choi, Ha Young Kim, Tae-Geon Kwon; The Committee for the Korean Position Paper on Medication-Related Osteonecrosis of the Jaw, representing the Korean Society for Bone and Mineral Research, the Korean Association of Oral and Maxillofacial Surgeons, the Korean Association of Maxillofacial Plastic and Reconstructive Surgeons, the Korean Society of Osteoporosis, and the Korean Endocrine Society. JKAOMS 2025;51:333-53. https://doi.org/10.5125/jkaoms.2025.51.6.333

Collagen-based biomaterials are widely used, but their relatively rapid biodegradation can limit functional duration. Such collagen constructs are widely used as barrier membranes in guided tissue and bone regeneration, where controlled degradation is essential for maintaining function. Although conventional crosslinking methods extend stability, they may introduce cytotoxicity, alter mechanical behavior, or hinder tissue integration. This study evaluated whether incorporating L-serine, a polar amino acid capable of hydrogen bonding, could modulate collagen structure and slow degradation without chemical crosslinking. L-Serine was selected because its hydroxyl-containing side chain can engage in biocompatible, hydrogen-bond–mediated interactions that offer a mild, non-crosslinking means of stabilizing collagen. Collagen scaffolds, prepared by incorporating L-serine into a collagen hydrogel followed by drying, were produced with 0–40 wt% L-serine and characterized using X-ray diffraction, Fourier-transform infrared spectroscopy, circular dichroism, and scanning electron microscopy. In vivo degradation was assessed in a subcutaneous mouse model comparing unmodified collagen, collagen containing 40 wt% L-serine, and a commercially available bilayer porcine collagen membrane (Bio-Gide^®, composed of type I and III collagen), with residual area quantified by serial sonography and histological evaluation. Low-to-moderate L-serine incorporation preserved triple-helical features, while 40 wt% led to crystalline domain formation and β-sheet enrichment. L-serine–treated collagen exhibited significantly greater residual area (2.70 ± 1.45 mm²) than unmodified collagen (0.37 ± 0.22 mm², p < 0.05), although Bio-Gide^® remained the most persistent (5.64 ± 2.76 mm²). These findings demonstrate that L-serine incorporation can modulate collagen structure and degradation kinetics through a simple, aqueous, and non-crosslinking approach. The results provide preliminary feasibility data supporting amino acid–assisted tuning of collagen resorption properties and justify further evaluation using membrane-specific fabrication and application-relevant testing.

Postmenopausal osteoporosis is characterized by progressive bone loss and deterioration of trabecular microarchitecture, yet safe and effective nutritional interventions remain limited. This study investigated the skeletal effects of whole sericin compared to isolated L-serine and calcium-only formulations in an ovariectomized (OVX) rat model. Forty female Sprague–Dawley rats underwent either sham surgery or OVX, followed by 8 weeks of daily oral administration with vehicle (calcium + vitamin D, NS), sericin formulation (S55), or L-serine. Sham and untreated OVX groups served as controls. Serum D-serine concentrations and femoral trabecular microarchitecture were assessed using fluorometric assays and micro-computed tomography (μCT), respectively. OVX significantly decreased bone volume fraction (BV/TV), bone mineral density (BMD), and trabecular number, while increasing trabecular separation. Sericin supplementation markedly improved BV/TV, BMD, trabecular thickness, and trabecular number, and reduced trabecular separation compared to both vehicle and untreated OVX controls. Sericin improved multiple trabecular parameters compared with L-serine. Serum D-serine levels were significantly elevated in the sericin group relative to calcium-only controls, though comparable to sham. These findings suggest that whole sericin exerts skeletal benefits beyond those attributable to its primary amino acid component, supporting its potential as a functional food ingredient for enhancing postmenopausal bone health.

Yei-Jin Kang, Ji-Hyeon Oh. JKAOMS 2025;51:188. https://doi.org/10.5125/jkaoms.2025.51.3.188

Yei-Jin Kang, Min-Keun Kim, Seong-Gon Kim, Young-Wook Park, Ji-Hyeon Oh. JKAOMS 2025;51:33-40. https://doi.org/10.5125/jkaoms.2025.51.1.33

Background: Oral ulcers are painful mucosal lesions prone to infection and inflammation. To evaluate the effectiveness of treatments, a suitable experimental animal model with an appropriate healing period is required. The aim of this study was to develop an animal model for oral ulcer research by comparing oral burn wounds of different sizes and locations in diabetic rats. Methods: Forty-four male Sprague–Dawley rats with induced diabetes were divided into six groups based on burn wound location and size: T5 (n = 10, tongue 5 mm), T3 (n = 10, tongue 3 mm), P5 (n = 10, palate 5 mm), P3 (n = 10, palate 3 mm), CT (n = 2, control tongue), and CP (n = 2, control palate). The burn wounds were induced by applying a heated device (100–120 °C) for 3 s. At 1- and 2-weeks post-surgery, macroscopic examination, histological staining, immunohistochemistry, and Western blot analysis were performed to compare the healing progress. Results: Healing progressed more rapidly in the second week than in the first for all groups, with burns on the tongue (Groups T5 and T3) showing more advanced healing compared to burns on the palate (Groups P5 and P3). By the second week, Group T3 was almost completely healed, while Group T5 had some remaining wounds. In contrast, Groups P5 and P3 showed minimal healing. This faster healing on the tongue was further supported by significantly lower expression levels of TNF-α and IL-1β and a reduction in ulcer size, particularly on the tongue compared to the palate. Conclusion: A 3 mm or 5 mm burn wound on the tongue of diabetic rats can serve as a useful animal model for evaluating new treatments for wound healing, particularly up to the first week. However, for studies extending to the second week, the 5 mm burn wound model on the tongue might be more advantageous.

Background: Osteoporosis, characterized by decreased bone mineral density due to an imbalance between osteoblast and osteoclast activity, poses significant challenges in bone healing, particularly in postmenopausal women. Current treatments, such as bisphosphonates, are effective but associated with adverse effects like medication-related osteonecrosis of the jaw, necessitating safer alternatives. Methods: This study investigated the use of L-serine-incorporated gelatin sponges for bone regeneration in calvarial defects in an ovariectomized rat model of osteoporosis. Thirty rats were divided into three groups: a control group, a group treated with a gelatin sponge containing an amino acid mixture, and a group treated with a gelatin sponge containing L-serine. Bone regeneration was assessed using micro-computed tomography (micro-CT) and histological analyses. Results: The L-serine group showed a significant increase in bone volume (BV) and bone area compared to the control and amino acid groups. The bone volume to total volume (BV/TV) ratio was also significantly higher in the L-serine group. Immunohistochemical analysis demonstrated that L-serine treatment suppressed the expression of cathepsin K, a marker of osteoclast activity, while increasing serine racemase activity. Conclusion: These findings suggest that L-serine-incorporated gelatin sponges not only enhance bone formation but also inhibit osteoclast-mediated bone resorption, providing a promising and safer alternative to current therapies for osteoporosis-related bone defects. Further research is needed to explore its clinical applications in human patients.

This study investigates the potential of 4-hexylresorcinol (4HR) as a novel antidiabetic agent by assessing its effects on blood glucose levels, Glut4 expression, AMPK phosphorylation, and Histone H3 acetylation (Ac-H3) in the liver. In vitro experiments utilized Huh7 and HepG2 cells treated with varying concentrations of 4HR. Glut4, p-AMPK, and Ac-H3 expression levels were quantified via Western blotting. Additionally, GAPDH activity and glucose uptake were evaluated. In vivo experiments employed streptozotocin (STZ)-induced diabetic rats, with or without 4HR treatment, monitoring blood glucose, body weight, and hepatic levels of Glut4, p-AMPK, and Ac-H3. In vitro, 4HR treatment increased GAPDH activity and glucose uptake. Elevated Glut4, p-AMPK, and Ac-H3 levels were observed 8 h after 4HR administration. Inhibition of p-AMPK using compound C reduced 4HR-mediated Glut4 expression. In STZ-induced diabetic rats, 4HR significantly upregulated Glut4, p-AMPK, and Ac-H3 expression in the liver. Periodic 4HR injections mitigated weight loss and lowered blood glucose levels in STZ-injected animals. Histological analysis revealed increased glycogen storage in hepatocytes of the 4HR-treated group. Overall, 4HR enhanced Glut4 expression through upregulation of AMPK activity and histone H3 acetylation in vitro and in vivo, improving hepatic glucose homeostasis and suggesting potential as a candidate for diabetes treatment.