👤 Jung Suh

This study explores the therapeutic potential of hydrogel-encapsulated neurospheres derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) in mitigating traumatic brain injury (TBI) and enhancing functional recovery in a rodent model. Trans-septal (intranasal) transplantation of these neurospheres demonstrated significant neurological improvement, reduced neuronal damage, and preserved neuronal structures and functions. The hUC-MSCs cultured in a customized bioreactor retained essential MSC characteristics, including marker expression and multi-lineage differentiation potential, ensuring their therapeutic efficacy. Following neural induction, hUC-MSCs formed neurospheres that promoted cell aggregation, differentiation, and neuroprotective effects. Encapsulation within a hydrogel provided a stable environment, significantly reducing TBI-induced cell death in co-cultured HT22 cells and improving Show less

Osteomas are benign, slow-growing bony tumors that commonly develop in the craniofacial region; however, standardized diagnostic and treatment protocols remain limited. This study aimed to establish a systematic approach for the diagnosis, genetic evaluation, and surgical management of craniofacial osteomas, with emphasis on lesion distribution and gender prevalence. A retrospective review was conducted on 141 patients with craniofacial osteomas at Kyungpook National University Hospital between October 2011 and September 2025. All patients underwent clinical examinations and 3-dimensional computed tomography for diagnostic confirmation. Surgical excision was performed using direct, endoscopic, or bicoronal approaches based on lesion characteristics. Whole exome sequencing was performed in patients with multiple large osteomas to evaluate mutations in EXT1, EXT2, APC, MSH2, and MLH1 genes associated with Gardner syndrome. A total of 148 osteomas were identified. The frontal bone was the most common site (60.1%), followed by the parietal, mandibular, and occipital bones. Females accounted for 79.1% of cases. Genetic testing revealed no pathogenic variants related to Gardner syndrome, and no recurrences were observed during 6 months of follow-up. Craniofacial osteomas are benign, slow-growing lesions most frequently found in the frontal bone and are more prevalent among females. The integration of imaging-based diagnosis, tailored surgical techniques, and selective genetic testing allows for accurate evaluation, effective treatment, and favorable postoperative outcomes. Show less

Sex is a key piece of patient information but is often not actively considered in drug use. This is partly due to the lack of molecular evidence at the gene expression level beyond sex chromosomes and sex hormones. We aim to investigate how sex differences in tissue-specific gene expression relate to FDA-approved drugs using the latest database of The Genotype-Tissue Expression (GTEx) V10. Our analysis reveals that 91.4% of FDA-approved drug target genes exhibit sex-differential expression in at least one tissue. The tissues with the most pronounced sex differences include subcutaneous adipose tissue, skeletal muscle, and the pituitary gland, while sex differences are less pronounced in the liver, other brain regions, and the spleen. Sex-differential disease-related genes include those associated with obesity (PPARG, INSR), cancer (FGFR1, CD22), and immunity (IL6R, IL3RA). Based on our findings, we advocate for a policy shift that integrates sex-based molecular data into preclinical studies, drug development, and clinical practices. This paradigm aligns biomedical research with precision medicine, mitigates drug-related risks, and promotes equitable healthcare outcomes. Show less

Sex is a critical determinant of health and disease, yet it remains underrepresented in biomedical research. The identification of blood-based biomarkers facilitates early diagnosis and intervention for various diseases; however, sex-differential differences in the plasma proteome have not been sufficiently explored in mouse models. Understanding the molecular features associated with sex is essential for enhancing the translational potential of clinical research. We utilized Olink technology to analyze sex- and strain-differential plasma protein expression in two widely used mouse strains, C57BL/6 and BALB/c. A total of 36 mice (n = 9 per strain and sex) were analyzed using the 'Olink Target 48 Mouse Cytokine' and 'Olink Target 96 Mouse Exploratory' panels. Differences in normalized protein expression (NPX) were compared between groups, and proteins with a P-value < 0.05 were considered significantly different. Our analysis identified 55 strain-differential proteins and 33 sex-differential proteins among the 87 proteins analyzed in mouse plasma. Importantly, LPL (Lipoprotein lipase) and GHRL (Appetite-regulating hormone) were also more highly expressed in females in human datasets, suggesting a conserved sex-biased expression pattern across species. This study characterized sex- and strain-differential differences in the plasma proteomes of C57BL/6 and BALB/c mice. Among the identified proteins, LPL and GHRL were significantly elevated in females, consistent with human gene and plasma protein expression trends. These findings highlight the presence of sex-based molecular differences in energy and lipid metabolism and provide a valuable foundation for future mechanistic studies. Show less

Genome-wide association studies (GWASs) have uncovered over 75 genomic loci associated with risk for late-onset Alzheimer's disease (LOAD), but identification of the underlying causal genes remains challenging. Studies of induced pluripotent stem cell (iPSC)-derived neurons from LOAD patients have demonstrated the existence of neuronal cell-intrinsic functional defects. Here, we searched for genetic contributions to neuronal dysfunction in LOAD using an integrative systems approach that incorporated multi-evidence-based gene mapping and network-analysis-based prioritization. A systematic perturbation screening of candidate risk genes in Caenorhabditis elegans (C. elegans) revealed that neuronal knockdown of the LOAD risk gene orthologs vha-10 (ATP6V1G2), cmd-1 (CALM3), amph-1 (BIN1), ephx-1 (NGEF), and pho-5 (ACP2) alters short-/intermediate-term memory function, the cognitive domain affected earliest during LOAD progression. These results highlight the impact of LOAD risk genes on evolutionarily conserved memory function, as mediated through neuronal endosomal dysfunction, and identify new targets for further mechanistic interrogation. Show less

Due to the large size and high flexibility of the catalytic active site of BACE1 enzyme, the development of nonpeptide inhibitors with optimal pharmacological properties is still highly demanding. In this work, we have discovered 2-aminobenzimidazole-containg ether scaffolds having potent and selective inhibitory potentials against BACE1 enzyme. We have synthesized novel 29 compounds and optimization of aryl linker region resulted in highly potent BACE1 inhibitory activities with EC Show less

Long interspersed element 1 (LINE-1; L1) are a family of transposons that occupy ~17% of the human genome. Though a small number of L1 copies remain capable of autonomous transposition, the overwhelming majority of copies are degenerate and immobile. Nevertheless, both mobile and immobile L1s can exert pleiotropic effects (promoting genome instability, inflammation, or cellular senescence) on their hosts, and L1's contributions to aging and aging diseases is an area of active research. However, because of the cell type-specific nature of transposon control, the catalogue of L1 regulators remains incomplete. Here, we employ an eQTL approach leveraging transcriptomic and genomic data from the GEUVADIS and 1000Genomes projects to computationally identify new candidate regulators of L1 RNA levels in lymphoblastoid cell lines. To cement the role of candidate genes in L1 regulation, we experimentally modulate the levels of top candidates in vitro, including IL16, STARD5, HSD17B12, and RNF5, and assess changes in TE family expression by Gene Set Enrichment Analysis (GSEA). Remarkably, we observe subtle but widespread upregulation of TE family expression following IL16 and STARD5 overexpression. Moreover, a short-term 24-hour exposure to recombinant human IL16 was sufficient to transiently induce subtle, but widespread, upregulation of L1 subfamilies. Finally, we find that many L1 expression-associated genetic variants are co-associated with aging traits across genome-wide association study databases. Our results expand the catalogue of genes implicated in L1 RNA control and further suggest that L1-derived RNA contributes to aging processes. Given the ever-increasing availability of paired genomic and transcriptomic data, we anticipate this new approach to be a starting point for more comprehensive computational scans for regulators of transposon RNA levels. Show less

Arterial macrophage cholesterol accumulation and impaired cholesterol efflux lead to foam cell formation and the development of atherosclerosis. Modified lipoproteins interact with toll-like receptors (TLR), causing an increased inflammatory response and altered cholesterol homeostasis. We aimed to determine the effects of TLR antagonists on cholesterol efflux and foam cell formation in human macrophages. Stimulated monocytes were treated with TLR antagonists (MIP2), and the cholesterol efflux transporter expression and foam cell formation were analyzed. The administration of MIP2 attenuated the foam cell formation induced by lipopolysaccharides (LPS) and oxidized low-density lipoproteins (ox-LDL) in stimulated THP-1 cells ( Show less

Mitochondrial dysfunction is a well-known contributor to aging and age-related diseases. The precise mechanisms through which mitochondria impact human lifespan, however, remain unclear. We hypothesize that humans with exceptional longevity harbor rare variants in nuclear-encoded mitochondrial genes (mitonuclear genes) that confer resistance against age-related mitochondrial dysfunction. Here we report an integrated functional genomics study to identify rare functional variants in ~ 660 mitonuclear candidate genes discovered by target capture sequencing analysis of 496 centenarians and 572 controls of Ashkenazi Jewish descent. We identify and prioritize longevity-associated variants, genes, and mitochondrial pathways that are enriched with rare variants. We provide functional gene variants such as those in MTOR (Y2396Lfs*29), CPS1 (T1406N), and MFN2 (G548*) as well as LRPPRC (S1378G) that is predicted to affect mitochondrial translation. Taken together, our results suggest a functional role for specific mitonuclear genes and pathways in human longevity. Show less

Environmental temperature during early life may have prolonged effects on growth and fatty acid metabolism, which could strongly influence overwintering survival in the first year of life for temperate-zone fish. In the present study, we examined how temperature during early life history might influence growth performance and fatty acid metabolism in age-0 Lake Sturgeon (Acipenser fulvescens) when exposed to cold temperatures at later stages. Fish were initially at 16 °C and subsequently held at 16 °C or 20 °C for 60 days beginning at 34 days post fertilization (dpf). Then, all fish were subsequently raised at the same temperature of 16 °C until the onset of cold conditioning at 158 dpf where temperature was gradually decreased to 3.5 °C and remained there for two weeks. Samples were collected before (151 dpf) and after cold conditioning (199 dpf) to measure total length, body mass, whole body metabolic rate, fatty acid profile in phospholipids and triglycerides and mRNA expression of genes associated with fatty acid desaturation, elongation and β-oxidation. Results revealed that before cold conditioning, total length and body mass did not differ between temperature groups, but fish raised at 20 °C showed a lower condition factor. During the cold conditioning, only fish raised at 16 °C grew significantly longer and heavier. There was no difference in metabolic rates between treatments. Significant increases in total monounsaturated fatty acids with decreases in total saturated fatty acids were identified in phospholipids and triglycerides in both temperature groups after the cold conditioning; however, the 20 °C group did not significantly increase levels of gene expression associated with fatty acid desaturation (SCD and FADS1) whereas the 16 °C group did. Our results suggest that thermal experience during early life may influence overwintering survival of age-0 Lake Sturgeon. Show less

Rice biofortification with Zinc (Zn) can improve the Zn status of rice-consuming populations. However, the metabolic impact in humans consuming Zn-biofortified rice is unknown. To determine the effects of Zn-biofortified rice on lipid metabolism in normolipidemic men. The men consumed a rice-based diet containing 6 mg Zn/d and 1.5 g phytate (phytate/Zn ratio = 44) for 2 wk followed by a 10-mg Zn/d diet without phytate for 4 wk. An ad libitum diet supplemented with 25 mg Zn/d was then fed for 3 wk. Fasting blood samples were taken at baseline and at the end of each metabolic period for measuring plasma zinc, glucose, insulin, triglyceride (TG), LDL and HDL cholesterol, fatty acids, oxylipins, and fatty acid desaturase activities. Statistical differences were assessed by linear mixed model. Fatty acid desaturase (FADS) 1 activity decreased by 29.1% (P = 0.007) when the 6-mg Zn/d diet was consumed for 2 wk. This change was associated with significant decreases in HDL and LDL cholesterol. The alterations in FADS1, HDL cholesterol, and TG remained unchanged when Zn intakes were increased to 10 mg/d for 4 wk. Supplementation with 25 mg Zn/d for 3 wk normalized these metabolic changes and significantly increased LDL cholesterol at the end of this metabolic period compared with baseline. FADS1 activity was inversely correlated with FADS2 (rmcorr = -0.52; P = 0.001) and TG (rmcorr = -0.55; P = 0.001) at all time points. A low-zinc, high-phytate rice-based diet reduced plasma HDL cholesterol concentrations and altered fatty acid profiles in healthy men within 2 wk. Consuming 10 mg Zn/d without phytate for 4 wk did not improve the lipid profiles, but a 25-mg Zn/d supplement corrects these alterations in lipid metabolism within 3 wk. Show less

To investigate potential target genes associated with the diabetic condition in mouse cavernous endothelial cells (MCECs) for the treatment of diabetes-induced erectile dysfunction (ED). Mouse cavernous tissue was embedded into Matrigel, and sprouted cells were subcultivated for other studies. To mimic diabetic conditions, MCECs were exposed to normal-glucose (NG, 5 mmoL) or high-glucose (HG, 30 mmoL) conditions for 72 hours. An RNA-sequencing assay was performed to evaluate gene expression profiling, and RT-PCR was used to validate the sequencing data. We isolated MCECs exposed to the two glucose conditions. MCECs showed well-organized tubes and dynamic migration in the NG condition, whereas tube formation and migration were significantly decreased in the HG condition. RNA-sequencing analysis showed that MCECs had different gene profiles in the NG and HG conditions. Among the significantly changed genes, which we classified into 14 major gene categories, we identified that aging-related (9.22%) and angiogenesis-related (9.06%) genes were changed the most. Thirteen genes from the two gene categories showed consistent changes on the RNA-sequencing assay, and these findings were validated by RT-PCR. Our gene expression profiling studies showed that Show less

Zinc intake is associated with reduced risk of metabolic disease in adults, possibly due in part to zinc's role in essential fatty acid (EFA) desaturation. Although plasma zinc is the accepted indicator of zinc status, product-to-precursor activity indices of fatty acid desaturase (FADS) 1 and 2 have also been proposed as response indicators for changes in zinc intake. To examine zinc supplement effects on plasma zinc concentration (PZC) and estimated FADS 1 and 2 activities, when zinc supplements are taken with food compared with fasted. Apparently healthy adult men were randomly allocated to take 25 mg zinc as zinc gluconate either in the fasted state 30 min before breakfast [zinc before breakfast (ZBB)] or with breakfast [zinc with breakfast (ZWB)] daily for 13 d. Fasting PZC was measured by inductively coupled plasma optical emission spectrometry. Selected EFAs for FADS activity indices were measured by LC-MS/MS at study baseline and end. A total of 35 men completed the study (ZBB, n = 18; ZWB, n = 17). Mean ± SEM PZC was 86.2 ± 1.64 μg/dL at baseline. After 2 wk of zinc supplementation, the PZCs were 18% higher in the ZBB compared with the ZWB groups (105 ± 5.88 compared with 88.7 ± 2.36 μg/dL, P = < 0.05). However, the geometric mean (95% CI) FADS1 activity indices were 15% higher in the ZWB than the ZBB participants, 6.45 (5.84, 7.13) compared with 5.57 (5.05, 6.14), P < 0.05. These data demonstrate a lack of congruence between the effects of zinc supplements on PZC and EFA metabolism in response to whether a zinc supplement is taken with or without food. Additional research is needed to determine how absorbed zinc may be directed differently toward metabolic processes, when coabsorbed with food. This trial was registered at clinicaltrials.gov as NCT03619421. Show less

Biofortification is a novel method for improving the nutritional value of grains. Wheat is widely consumed worldwide. Thus, wheat zinc biofortification may improve the zinc status of populations. We determined the effect of consuming zinc-biofortified wheat on plasma zinc concentrations and biomarkers of zinc-dependent functions in a controlled feeding study. Thirty-six healthy adult men, aged 18 to 51 y, participated in a 10-wk zinc-controlled feeding trial. After a 2-wk run-in period [metabolic period (MP) 1] (9.3 mg zinc/d and 2.1 g total phytate/d) to standardize zinc status, the participants consumed bread made from zinc-biofortified wheat (10.9 mg zinc/d) with no additional phytate (0.6 g/d total phytate) for 6 wk (MP2). During the final 2 wk (MP3), half of the men took a 25-mg zinc supplement daily to determine if the supplement further altered zinc status biomarkers. Repeated-measures linear regression methods were used to compare plasma zinc concentrations, fatty acid desaturase (FADS) activities, glutathione (GSH) concentrations, and DNA strand breaks assessed at enrollment and the end of each metabolic period. Plasma zinc concentrations did not change throughout the study. From the end of MP1 to the end of MP2, the conversion of linoleic acid to γ-linolenic acid (FADS2 activity) increased from 0.020 to 0.025 (P = 0.02), and the conversion of dihomo-γ-linolenic acid to arachidonic acid (FADS1 activity) decreased from 6.37 to 5.53 (P = 0.01). GSH concentrations and DNA strand breaks did not change. Zinc supplementation (25 mg/d) in MP3 did not alter any of the endpoints. In healthy adult men, a 1.6-mg/d increase in dietary zinc from biofortified wheat modified FADS2 and FADS1 activities without changing DNA damage, plasma zinc, or GSH concentrations, demonstrating that FADS activities are more sensitive to small changes in zinc consumed with a meal. This trial was registered at clinicaltrials.gov as NCT03451214. Show less

Pancreatitis is the inflammation of the pancreas. However, little is known about the genes associated with pancreatitis severity. Our microarray analysis of pancreatic tissues from mild and severe acute pancreatitis mice models identified angiopoietin-like 4 (ANGPTL4) as one of the most significantly upregulated genes. Clinically, ANGPTL4 expression was also increased in the serum and pancreatic tissues of pancreatitis patients. The deficiency in ANGPTL4 in mice, either by gene deletion or neutralizing antibody, mitigated pancreatitis-associated pathological outcomes. Conversely, exogenous ANGPTL4 exacerbated pancreatic injury with elevated cytokine levels and apoptotic cell death. High ANGPTL4 enhanced macrophage activation and infiltration into the pancreas, which increased complement component 5a (C5a) level through PI3K/AKT signaling. The activation of the C5a receptor led to hypercytokinemia that accelerated acinar cell damage and furthered pancreatitis. Indeed, C5a neutralizing antibody decreased inflammatory response in LPS-activated macrophages and alleviated pancreatitis severity. In agreement, there was a significant positive correlation between C5a and ANGPTL4 levels in pancreatitis patients. Taken together, our study suggests that targeting ANGPTL4 is a potential strategy for the treatment of pancreatitis. Show less

Liver X receptors are established sensors of lipid and cholesterol homeostasis. Recent studies have reported that these receptors are involved in the regulation of inflammation and immune responses. We attempted to identify single nucleotide polymorphisms (SNPs) of the NR1H3 gene associated with the susceptibility to systemic lupus erythematosus (SLE). SNPs were genotyped using SNaPSHOT assay in 300 Korean patients with SLE and 217 normal controls (NC), and in replication samples (160 SLE patients and 143 NC). Also, the functional effects of NR1H3 gene promoter polymorphisms were analyzed using a luciferase assay, real-time polymerase chain reaction, B cell proliferation assay and an electrophoretic mobility shift assay. We identified five polymorphisms: -1851 T > C (rs3758673), -1830 T > C (rs3758674), -1003 G > A (new), -840 C > A (rs61896015) and -115 G > A (rs12221497). There was a significant and reproducible difference in the -1830 T > C, -1003 G > A and -115 G > A polymorphisms between the SLE and the NC. Luciferase activity of the structure containing -1830 C was less enhanced compared to the structure containing -1830 T in basal, GW3965 and T0901317 treated Hep3B cells (P = 0.009, P = 0.034 and P <0.001, respectively). Proliferation of the -1830 TC type was increased compared to the -1830 TT type in basal, GW3965 and T0901317 treated B cells from SLE patients (P = 0.011, P = 0.040 and P = 0.017, respectively). Transcription factor GATA-3 preferentially bound the -1830 T allele in the promoter. NR1H3 genetic polymorphisms may be associated with disease susceptibility and clinical manifestations of SLE. Specifically, -1830 T > C polymorphism within NR1H3 promoter region may be involved in regulation of NR1H3 expression. Show less

Dual specificity phosphatase 6 (DUSP6) is a member of the MAP kinase phophatase family. DUSP6 inactivates extracellular signal-regulated kinase (ERK), belonging to the MAP kinase family, and can act in tumor suppressive pathways. The aim of this study was to investigate associations of DUSP6 expression with expression of ERK and Ki-67 and with clinicopathological parameters in lung adenocarcinoma and squamous cell carcinoma. A total of 102 squamous cell carcinomas and 66 adenocarcinomas were studied using immunohistochemistry for DUSP6, ERK1/2, and Ki-67. In 66 adenocarcinomas, high DUSP6 expression was positively correlated with ERK1/2 expression. High DUSP6 expression was correlated with lower histological grade and lower Ki-67 index in the adenocarcinomas. In 102 squamous cell carcinomas, high DUSP6 expression was correlated with lower ERK expression, with greater smoking pack-years, but not with the Ki-67 index. These results indicate that DUSP6 acts as a negative feedback regulator of ERK in adenocarcinoma progression, but that DUSP6 does not play a role in the downregulation of ERK in squamous cell carcinoma. The differential expression of DUSP6 correlated with Ki-67 index, suggesting that DUSP6 plays an important role in cancer resistance in different subtypes of non-small cell lung carcinoma. Show less

Many patients with chronic renal failure (CRF) requiring hemodialysis present with hypertriglyceridemia (HTG). But the exact cause of HTG in CRF is still unknown. Genetic variation of the apo AI-CIII-AIV gene cluster was reported to be associated with primary HTG, atherosclerosis and coronary artery disease. This study was designed to evaluate the association between the restriction fragment length polymorphism (RFLP) of the apo AI-CIII-AIV gene cluster and HTG in patients with CRF undergoing hemodialysis. Genetic variations of the apo AI-CIII-AIV gene cluster were analysed in peripheral leukocyte samples from 59 patients with CRF undergoing hemodialysis: 17 patients with HTG (CRF-HTG) and 42 patients without HTG (CRF-NTG). The RFLP was achieved through the digestion of PCR products by two restriction enzymes, SstI and MspI. The frequency of SstI minor allele (S2) in CRF-HTG was 0.44, which was significantly higher than that in CRF-NTG (0.17). Frequencies of MspI minor allele (M2) in CRF-HTG and CRF-NTG were not significantly different (0.5 vs 0.32) (p=0.07). Frequencies of S2-M2 genotype were 0.65 in CRF-HTG, and 0.27 in CRF-NTG (p<0.005). These data indicate that genetic variation of the apo AI-CIII-AIV gene cluster may serve as one of the causes of HTG in CRF. Show less