BACKGROUND: Mammalian target of rapamycin (mTOR) is known to regulate self-renewal ability and potency of embryonic stem cells (ESCs) and adult stem cells in opposite manners. However, its effects vary even among adult stem cells and are not reported in fetal stem/progenitor cells. This study investigated the role of mTOR in the function of human fetal cartilage-derived progenitor cells (hFCPCs). METHODS: mTOR activity in hFCPCs was first examined via the level of phosphor-mTOR until passage 19, together with doubling time of cells and senescence-associated b-galactosidase (SA-bGal). Then, the effect of 100 nM rapamycin, the inhibitor of mTOR, was investigated on self-renewal ability, proliferation rate and osteogenic/adipogenic potential of hFCPCs in vitro. Expression of stemness genes (Oct-4, Sox2 and Nanog) and cell cycle regulators (CDK4 and Cyclin D1) was measured at mRNA or protein levels. RESULTS: mTOR activity was maintained constantly at high levels in hFCPCs until passage 19, while their proliferation rate was decreasing from 48 h at passage 13 to 70 h at passage 9 and senescent cells were observed at passage 18 (8.3 ± 1.2%) and 19 (15.6 ± 1.9%). Inhibition of mTOR in hFCPCs impaired their colony forming frequency (CFU-F) by 4 folds, while showing no change in their doubling time and expression of CDK4 and Cyclin D1. Upon mTOR inhibition, Oct4 expression decreased by 2 folds and 4 folds at the mRNA and protein levels, respectively, while that of Sox2 and Nanog did not change significantly. Finally, mTOR inhibition reduced osteogenic and adipogenic differentiation of hFCPCs in vitro. CONCLUSION This study has shown that mTOR plays an important role in the self-renewal ability of hFCPCS but not in their proliferation, The effect of mTOR appears to be associated with Oct-4 expression and important in the osteogenic and adipogenic differentiation ability of hFCPCs.

Purpose: We aimed to assess the humoral response to and reactogenicity of coronavirus disease 2019 (COVID-19) vaccination according to the vaccine type and to analyze factors associated with immunogenicity in actively treated solid cancer patients (CPs). Materials and Methods: Prospective cohorts of CPs, undergoing anticancer treatment, and healthcare workers (HCWs) were established. The participants had no history of previous COVID-19 and received either mRNA-based or adenovirus vector–based (AdV) vaccines as the primary series. Blood samples were collected before the first vaccination and after 2 weeks for each dose vaccination. Spike-specific binding antibodies (bAbs) in all participants and neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type, Delta, and Omicron variants in CPs were analyzed and presented as the geometric mean titer. Results: Age-matched 20 HCWs and 118 CPs were included in the analysis. The bAb seroconversion rate and antibody concentrations after the first vaccination were significantly lower in CPs than in HCWs. After the third vaccination, antibody levels in CPs with a primary series of AdV were comparable to those in HCWs, but nAb titers against the Omicron variant did not quantitatively increase in CPs with AdV vaccine as the primary series. The incidence and severity of adverse reactions post-vaccination were similar between CPs and HCWs. Conclusion CPs displayed delayed humoral immune response after SARS-CoV-2 vaccination. The booster dose elicited comparable bAb concentrations between CPs and HCWs, regardless of the primary vaccine type. Neutralization against the Omicron variant was not robustly elicited following the booster dose in some CPs, implying the need for additional interventions to protect them from COVID-19.

We investigated the distribution of medical service uses for Bell’s palsy and Ramsay Hunt syndrome between medicine and traditional Korean medicine using the National Health Insurance Service National Sample Cohort data of Korea from 2006 to 2015. Patients were identified with diagnostic codes and medication or treatment claim codes. For Bell’s palsy, there were 5,970 (68.8%) patients who used traditional Korean medical service only, whereas for Ramsay Hunt syndrome, there were 749 (93.6%) patients who used medical service only.The proportion of traditional Korean medical service use was higher than that of medical service use in patients with Bell’s palsy, while the opposite was found in patients with Ramsay Hunt syndrome.

BACKGROUND: In this study, we have investigated whether human fetal cartilage progenitor cells (hFCPCs) have antiinflammatory activity and can alleviate osteoarthritis (OA) phenotypes in vitro. METHODS: hFCPCs were stimulated with various cytokines and their combinations and expression of paracrine factors was examined to find an optimal priming factor. Human chondrocytes or SW982 synoviocytes were treated with interleukin-1β (IL-1β) to produce OA phenotype, and co-cultured with polyinosinic-polycytidylic acid (poly(I-C))-primed hFCPCs to address their anti-inflammatory effect by measuring the expression of OA-related genes. The effect of poly(I-C) on the surface marker expression and differentiation of hFCPCs into 3 mesodermal lineages was also examined. RESULTS: Among the priming factors tested, poly(I-C) (1 μg/mL) most significantly induced the expression of paracrine factors such as indoleamine 2,3-dioxygenase, histocompatibility antigen, class I, G, tumor necrosis factor- stimulated gene-6, leukemia inhibitory factor, transforming growth factor-β1 and hepatocyte growth factor from hFCPCs. In the OA model in vitro, co-treatment of poly(I-C)-primed hFCPCs significantly alleviated IL-1b-induced expression of inflammatory factors such as IL-6, monocyte chemoattractant protein-1 and IL-1β, and matrix metalloproteinases in SW982, while it increased the expression of cartilage extracellular matrix such as aggrecan and collagen type II in human chondrocytes. We also found that treatment of poly(I-C) did not cause significant changes in the surface marker profile of hFCPCs, while showed some changes in the 3 lineages differentiation. CONCLUSION These results suggest that poly(I-C)-primed hFCPCs have an ability to modulate inflammatory response and OA phenotypes in vitro and encourage further studies to apply them in animal models of OA in the future.

Background: Folic acid is involved in inflammatory reactions; however, the association between folic acid and allergic diseases, particularly asthma, remains unclear. Thus, this study aimed to evaluate the association between serum folic acid levels and asthma in Koreans. Methods: This study analyzed the serum folic acid levels of 6,615 individuals included in the 2016–2018 Korea National Health and Nutrition Examination Survey. The prevalence of asthma was determined using a questionnaire that identified cases of physician-diagnosed asthma. The relationship between serum folic acid levels and asthma was analyzed using logistic regression analysis. Results: Multiple logistic regression analysis showed that a 1 ng/mL increase in serum folic acid level significantly reduced the risk of asthma after adjusting for confounding factors including sex, age, household income, current smoking, current alcohol use, and body mass index (odds ratio [OR], 0.930; 95% confidence interval [CI], 0.876– 0.987; P=0.017). The relationship between the adjusted odds of asthma and serum folic acid levels were consistently inverse (OR, 2.266; 95% CI, 1.126–4.420; P for trend=0.038). Conclusion Serum folic acid levels are inversely associated with physician-diagnosed asthma in the Korean population.

Objective: Using microRNA (miR) as a biomarker has been a new way for diagnosing many diseases. Although many studies on miR-biomarker have been published, researches on miR-biomarker in ankylosing spondylitis (AS) are limited. Therefore, the objective of this study was to valiate a candidate serum miR as a novel disease-specific novel miR for AS. Methods: Total RNAs were extracted from sera samples of patients with AS (n=57), patients with rheumatoid arthritis (RA) (n=37), or healthy controls (HC) (n=19). Through serum miR screening by microarray, differential levels of miR were subsequently validated by real time PCR. At the time of serum sampling, clinical values such as sex, age, disease duration, AS-disease activity score, uveitis, peripheral arthritis, enthesitis, human leukocyte antigen-B27 presence, and recent medication were evaluated. Results: We found that the expression level of serum miR-3620-3p in AS was notably lower than that in RA or HC. The receiver–operator characteristics curve for determining the diagnostic accuracy showed an area under the curve of 0.919 (p＜0.001) with a sensitivity of 87.1% and a specificity of 86.0%. Correlation studies showed that the expression level of miR-3620-3p was only associated with the development of uveitis (p＜0.05). Conclusion Serum miR-3620-3p can be as a new biomarker for diagnosing AS.

Objective: Dietary factors are important contributors to obesity and related metabolic disorders. Few studies have evaluated the impact of dietary habits (e.g., breakfast consumption frequency and meal regularity) on metabolic health. We investigated the effects of breakfast consumption frequency and meal time regularity on nutrient intake and cardiometabolic status in Korean adults. Methods: Participants without diagnosed diseases (n=217) were examined for anthropometric and biochemical parameters, lifestyle, dietary habits, and nutrient intake.They were categorized into 4 groups by breakfast consumption frequency (≥6 or <6 times/ week) and meal time regularity (regular or irregular): breakfast ≥6 times/week and regular eating (HBRE), breakfast ≥6 times/week and irregular eating (HBIE), breakfast <6 times/week and regular eating (LBRE) and breakfast <6 times/week and irregular eating (LBIE). Results: Participants in the LBIE group were the youngest, had higher waist circumference, body mass index, triglyceride levels, and inflammation, and consumed the highest daily total caloric intake (TCI), the highest proportion of fats, and the lowest proportion of carbohydrates. The LBIE group also had the lowest proportion of energy intake at breakfast and the highest proportion at dinner. The LBIE group consumed the lowest amounts of fiber, beta-carotene, vitamin K, folate, calcium and iron, and had the highest prevalence of inadequate nutrient intake for TCI, protein, vitamins A, C, B6, and B12, folate, calcium, iron, zinc, and copper. Conclusion Regular breakfast consumption and meal times are related to healthy lifestyle habits and adequate nutrient intake, which affect metabolic health, thereby helping prevent obesity and related metabolic disorders.

BACKGROUND: Chondroitin sulfate glycosaminoglycans (CS-GAGs) are the primary inhibitory GAGs for neuronal growth after central nervous system (CNS) injury. However, the inhibitory or permissive activity of CS-GAG subtypes is controversial and depends on the physiological needs of CNS tissues. In this study, we investigated the characteristics and effects of CS-GAGs on axonal growth, which was isolated from the brain cortices of normal rat embryo at E18, normal adult rat brain and injured adult rat brain. METHODS: Isolated CS-GAGs from embryo, normal adult, and injured adult rat brains were used for analyzing their effect on attachment and axonal growth using modified spot assay with dorsal root ganglion (DRG) explants and cerebellar granule neurons (CGNs). CS-GAGs were separated using high performance liquid chromatography (HPLC), and the subtypes of CS-GAGs were analyzed. RESULTS: CS-GAGs of all three groups inhibited CGN attachment and axonal growth of DRGs. However, CS-GAGs of normal adult rat brain exhibited higher inhibitory activity than those of the other groups in both assays. When subtypes of CS-GAGs were analyzed using HPLC, CS-A (4S) was the most abundant in all three groups and found in largest amount in normal adult rat brain. In contrast, unsulfated CS (CS0) and CS-C (6S) were more abundant by 3–4-folds in E18 group than in the two adult groups. CONCLUSION When compared with the normal adult rat brain, injured rat brain showed relatively similar patterns to that of embryonic rat brain at E18 in the expression of CS subtypes and their inhibitory effect on axonal growth. This phenomenon could be due to differential expression of CS-GAGs subtypes causing decrease in the amount of CS-A and mature-type CS proteoglycan core proteins.

Background: Epidemiological data have shown that vitamin D deficiency is highly prevalent in Korea. Genetic factors influencing vitamin D deficiency in humans have been studied in Europe but are less known in East Asian countries, including Korea. We aimed to investigate the genetic factors related to vitamin D levels in Korean people using a genome-wide association study (GWAS). Methods: We included 12,642 subjects from three different genetic cohorts consisting of Korean participants. The GWAS was performed on 7,590 individuals using linear or logistic regression meta- and mega-analyses. After identifying significant single nucleotide polymorphisms (SNPs), we calculated heritability and performed replication and rare variant analyses. In addition, expression quantitative trait locus (eQTL) analysis for significant SNPs was performed. Results: rs12803256, in the actin epsilon 1, pseudogene (ACTE1P) gene, was identified as a novel polymorphism associated with vitamin D deficiency. SNPs, such as rs11723621 and rs7041, in the group-specific component gene (GC) and rs11023332 in the phosphodiesterase 3B (PDE3B) gene were significantly associated with vitamin D deficiency in both meta- and mega-analyses. The SNP heritability of the vitamin D concentration was estimated to be 7.23%. eQTL analysis for rs12803256 for the genes related to vitamin D metabolism, including glutamine-dependent NAD(+) synthetase (NADSYN1) and 7-dehydrocholesterol reductase (DHCR7), showed significantly different expression according to alleles. Conclusion The genetic factors underlying vitamin D deficiency in Korea included polymorphisms in the GC, PDE3B, NADSYN1, and ACTE1P genes. The biological mechanism of a non-coding SNP (rs12803256) for DHCR7/NADSYN1 on vitamin D concentrations is unclear, warranting further investigations.