Hyun Ju Yoo

MethodsUrinary ttMA was measured by an ultraperformance liquid chromatograph-tandem mass spectrometer in 242 mothers COCOA birth cohort. Diagnosis of asthma at age 7 was determined using questionnaire. The serum concentrations of 11 cytokines were measured at age 7. The Nrf2 (rs6726395) and NAT2 (rs4271002) polymorphisms of cord blood were genotyped by using a TaqMan assay (ABI, Foster City, CA, USA).ResultsMaternal urinary ttMA increased the risk of pediatric asthma (aOR: 1.003, 95% CI: 1.000-1.006). IL-4 was increased in children with higher maternal urinary ttMA and IL-4 was highest in children with asthma and higher maternal urinary ttMA. Maternal urinary ttMA had significant associations with asthma in children with NAT2 GG and NRF2 GA/AA genotype (aOR: 1.004, 95% CI: 1.000-1.009 and aOR: 3.817, 95% CI: 1.312-11.103).ConclusionsThis study suggests that maternal …

BackgroundSphingolipids are signaling molecules and structural components of the axolemma and myelin sheath. Plasma sphingolipid levels may reflect disease status of neuromyelitis optica spectrum disorder (NMOSD). We aimed to examine plasma sphingolipids as disease severity biomarkers for NMOSD and compare their characteristics with those of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP).MethodsWe measured plasma sphingolipids, sNfL, and sGFAP levels in NMOSD cases with anti-aquaporin-4-antibody. An unbiased approach, partial least square discriminant analysis (PLS-DA), was utilized to determine whether sphingolipid profiles differ according to the disease state of NMOSD (presence, moderate-to-severe disability [Expanded Disease Severity Scale, (EDSS) > 3.0], and relapses).ResultsWe investigated 81 patients and 10 controls. PLS-DA models utilizing …

In vitro and animal experiments demonstrated that lumican exerts anabolic effects on bone and muscle by stimulating osteoblastogenesis, suppressing osteoclastogenesis and increasing myogenesis. However, the relationship between circulating lumican and musculoskeletal phenotypes in humans remains unclear. We aimed to analyze the relationship between serum lumican levels and osteosarcopenia in older adults. Blood samples were collected from 134 participants (age: 65 years and older) who underwent comprehensive assessment of bone and muscle phenotypes. Osteoporosis and sarcopenia were diagnosed based on World Health Organization and Asian consensus guidelines, respectively. Osteosarcopenia was defined as the simultaneous presence of osteoporosis and sarcopenia. After adjusting for sex, age, and body mass index, older adults with osteosarcopenia had 20.2 % lower serum …

BackgroundMenopause, a dramatical estrogen-deficient condition, is considered the most significant milestone in women’s health.PurposeTo investigate the metabolite changes attributed to estrogen deficiency using random forest (RF)-based machine learning (ML) modeling strategy in ovariectomized (OVX) mice as well as determine the clinical relevance of selected metabolites in older women.Methods and resultsUntargeted and targeted metabolomic analyses revealed that metabolites related to TCA cycle, sphingolipids, phospholipids, fatty acids, and amino acids, were significantly changed in the plasma and/or muscle of OVX mice. Subsequent ML classifiers based on RF algorithm selected alpha-ketoglutarate (AKG), arginine, carnosine, ceramide C24, phosphatidylcholine (PC) aa C36: 6, and PC ae C42: 3 in plasma as well as PC aa 34: 1, PC aa C34: 3, PC aa C36: 5, PC aa C32: 1, PC aa C36: 2, and …

Proper placental development in early pregnancy ensures a positive outcome later on. The developmental relationship between the placenta and embryonic organs, such as the heart, is crucial for a normal pregnancy. However, the mechanism through which the placenta influences the development of embryonic organs remains unclear. Trophoblasts fuse to form multinucleated syncytiotrophoblasts (SynT), which primarily make up the placental materno-fetal interface. We discovered that endogenous progesterone immunomodulatory binding factor 1 (PIBF1) is vital for trophoblast differentiation and fusion into SynT in humans and mice. PIBF1 facilitates communication between SynT and adjacent vascular cells, promoting vascular network development in the primary placenta. This process affected the early development of the embryonic cardiovascular system in mice. Moreover, in vitro experiments showed that …

MethodsUrinary concentrations of MnBP was measured in 144 children aged 7 years from the Exposome and Child Health with Omics-Cohort for Childhood of Asthma and Allergic Diseases (ECHO-COCOA) study. Children were stratified into tertiles according to baseline MnBP levels. Diagnosis of AD was conducted by pediatric allergists. Untargeted metabolic profiling using liquid chromatography tandem mass spectrometry (LCMS/MS, Ultimate3000/LTQ Orbitrap XL) was performed. The serum IgE levels were analyzed.ResultsEighteen metabolic features were selected from Kruskal–Wallis test among 4 groups according to AD/normal and MnBP low/high. The level of 10-oxo-8-decenoic acid, metabolites of the breakdown of linoleic acid, was highest in the normal healthy with low MnBP group, and lowest in AD with high MnBP group (P= 0.005). And children with high MnBP levels exhibited a negative correlation …

Heavy metals are commonly released into the environment through industrial processes such as mining and refining. The rapid industrialization that occurred in South Korea during the 1960s and 1970s contributed significantly to the economy of the country; however, the associated mining and refining led to considerable environmental pollution, and although mining is now in decline in South Korea, the detrimental effects on residents inhabiting the surrounding areas remain. The bioaccumulation of toxic heavy metals leads to metabolic alterations in human homeostasis, with disruptions in this balance leading to various health issues. This study used metabolomics to explore metabolomic alterations in the plasma samples of residents living in mining and refining areas. The results showed significant increases in metabolites involved in glycolysis and the surrounding metabolic pathways, such as glucose-6 …

Background Sarcopenia is characterized by a progressive decrease in skeletal muscle mass and function with age. Given that sarcopenia is associated with various metabolic disorders, effective metabolic biomarkers for its early detection are required. We aimed to investigate the metabolic biomarkers related to sarcopenia in elderly men and perform experimental studies using metabolomics. Methods Plasma metabolites from 142 elderly men, comprising a sarcopenia group and an age‐matched control group, were measured using global metabolome profiling. Muscle and plasma samples from an aging mouse model of sarcopenia, as well as cell media and cell lysates during myoblast differentiation, were analysed based on targeted metabolome profiling. Based on these experimental results, fatty acid amides were quantified from human plasma as well as human muscle tissues. The association of fatty acid …

The interaction between the microbial environment and the host is important for immune homeostasis. Recent research suggests that microbiota dysbiosis can be involved in respiratory diseases. Emphysema is a chronic inflammatory disease, but it is unclear whether dysbiosis caused by antibiotics can affect disease progression. Here, we tried to elucidate the effect of systemic antibiotics on smoking-exposed emphysema models. In this study, the antibiotic mixture caused more alveolar destruction and airspace expansion in the smoking group than in the smoking only or control groups. This emphysema aggravation as a result of antibiotic exposure was associated with increased levels of inflammatory cells, IL-6, IFNγ and protein concentrations in bronchoalveolar lavage fluid. Proteomics analysis indicated that autophagy could be involved in antibiotic-associated emphysema aggravation, and increased protein …

Purpose: Age-related macular degeneration (AMD) is the leading cause of visual impairment worldwide. In this study, we aimed to investigate the vitreous humor metabolite profiles of patients with intermediate AMD using untargeted metabolomics.Methods: We performed metabolomics using high-resolution liquid chromatography mass spectrometry on the vitreous humor of 31 patients with intermediate AMD and 30 controls who underwent vitrectomy for epiretinal membrane with or without cataract surgery. Univariate analyses after false discovery rate correction were performed to discriminate the metabolites and identify the significant metabolites of intermediate AMD. For biologic interpretation, enrichment and pathway analysis were conducted using MetaboAnalyst 5.0.Results: Of the 858 metabolites analyzed in the vitreous humor, 258 metabolites that distinguished patients with AMD from controls were identified (P values< 0.05). Ascorbic acid and uric acid levels increased in the AMD group (all P values< 0.05). The acyl carnitines, such as acetyl L-carnitine (1.37-fold), and fatty amides, such as anandamide (0.9-fold) and docosanamide (0.67-fold), were higher in patients with intermediate AMD. In contrast, nicotinamide (− 0.55-fold), and succinic acid (− 1.69-fold) were lower in patients with intermediate AMD. The metabolic pathway related oxidation of branched chain fatty acids and carnitine synthesis showed enrichment.Conclusions: Multiple metabolites related to fatty amides and acyl carnitine were found to be increased in the vitreous humor of patients with intermediate AMD, whereas succinic acid and nicotinamide were reduced …

BACKGROUND AND AIM Long-term exposure to air pollution can increase the risk of respiratory diseases and adversely affect lung functions. The potential of metabolomics to identify biomarkers linked to respiratory outcomes and environmental exposure is becoming increasingly apparent. However, a mechanistic understanding of the affected metabolic pathways is lacking and literature on long-term exposure to air pollution on the metabolome is limited. Therefore, this study aimed to elucidate the unique plasma metabolite response related to long-term PM10 or NO2 exposure. METHOD We estimated the annual average concentrations of PM10 and NO2 at each participant’s residential address using a spatial prediction model. We performed LC-MS/MS analysis based on targeted metabolic profiling of plasma sample data from 192 participants enrolled in the COPD in Dusty Area (CODA) cohort to identify the …

BackgroundDespite the protective effects of stromal cell-derived factor 1 (SDF-1) in stimulating muscle regeneration shown in experimental research, there is a lack of clinical studies linking circulating SDF-1 concentrations with muscle phenotypes. In order to elucidate the role of SDF-1 as a potential biomarker reflecting human muscle health, we investigated the association of plasma SDF-1 levels with sarcopenia in older adults.MethodsThis cross-sectional study included 97 community-dwelling participants who underwent a comprehensive geriatric assessment at a tertiary hospital in South Korea. Sarcopenia was defined by specific cutoff values applicable to the Asian population, whereas plasma SDF-1 levels were determined using an enzyme immunoassay.ResultsAfter accounting for sex, age, and body mass index, participants with sarcopenia and low muscle mass exhibited plasma SDF-1 levels that were 21 …

This study is firstly, to investigate the presence of microcalcification among the patients who underwent thyroid ultrasound and biopsy and to evaluate the incidence of intrathyroid lymphatic spread and cervical lymph node metastasis of thyroid cancer with thyroid microcalcifications. Also, we compared the diagnostic performance between fine needle aspiration (FNA) and core needle biopsy (CNB) for assessing parenchymal microcalcifications in the thyroid gland. We retrospectively assessed total 66 patients with thyroid microcalcifications on ultrasound. The histopathologic characteristics of the surgical specimens considered as the gold standard for diagnosing malignancy. Patients with surgically proven malignancy were evaluated for multifocality, intrathyroid lymphatic spread in the opposite lobe, or cervical lymph node metastasis. Among the 66 confirmed patients, 53 patients had malignant lesions (80.3%) and …

This study assessed the impact of intensive human activities on organic matter (OM) and heavy metal cycles in Shihwa Lake, South Korea. Sediment oxygen demand (SOD), benthic nutrient flux (BNF), and benthic heavy metal flux were estimated using in situ benthic chambers. The combined analysis of sediment trap and SOD showed that the vertical supply of OM was a major controlling factor for benthic respiration. The BNF accounted for 35–144% and 32–184% of the N and P required, respectively, for primary production (PP) in the water column. The higher SOD may have also accelerated the release of Mn, Fe, Co, and Ni from the sediment. Benthic fluxes of Cr, As, Cd, Pb, Cu, and Zn were highest near the industrial complex, with ranges of 1.3 ± 0.9, 6.4 ± 4.9, 0.2 ± 0.1, 0.5 ± 0.4, 7.7 ± 1.4, and 452 ± 133 μmol m−2 d−1, respectively. Mn, Fe, Co, As, Pb, Ni, and Cu contributed more than 10% of the sediment to the current standing stock at Shihwa Lake.

BackgroundAcute respiratory distress syndrome (ARDS) is etiologically and clinically a heterogeneous disease. Its diagnostic characteristics and subtype classification, and the application of these features to treatment, have been of considerable interest. Metabolomics is becoming important for identifying ARDS biology and distinguishing its subtypes. This study aimed to identify metabolites that could distinguish sepsis-induced ARDS patients from non-ARDS controls, using a targeted metabolomics approach, and to identify whether sepsis-induced direct and sepsis-induced indirect ARDS are metabolically distinct groups, and if so, confirm their metabolites and associated pathways.MethodsThis study retrospectively analyzed 54 samples of ARDS patients from a sepsis registry that was prospectively collected from March 2011 to February 2018, along with 30 non-ARDS controls. The cohort was divided into direct …

We set up this study to understand the underlying mechanisms of reduced ceramides on immune cells in acute rejection (AR). The concentrations of ceramides and sphingomyelins were measured in the sera from hepatic transplant patients, skin graft mice and hepatocyte transplant mice by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Serum concentrations of C24 ceramide, C24:1 ceramide, C16:0 sphingomyelin, and C18:1 sphingomyelin were lower in liver transplantation (LT) recipients with than without AR. Comparisons with the results of LT patients with infection and cardiac transplant patients with cardiac allograft vasculopathy in humans and in mouse skin graft and hepatocyte transplant models suggested that the reduced C24 and C24:1 ceramides were specifically involved in AR. A ceramide synthase inhibitor, fumonisin B1 exacerbated allogeneic immune responses in vitro …

Myonectin is a muscle-secreted factor that helps maintain homeostasis in the body by regulating several functions, including lipid metabolism. Previous studies suggested that myonectin may play a role in muscle health in an autocrine manner, but its impact on human skeletal muscle is still unclear. We aimed to investigate the relationship of serum myonectin levels with sarcopenia and related muscle parameters. We conducted a cross-sectional study of 142 older adults whose muscle mass, grip strength, gait speed, chair stands, and short physical performance battery (SPPB) were evaluated in the geriatric clinic of a tertiary medical center. Sarcopenia was defined based on Asian-specific cutoff values, and circulating myonectin levels were measured using an enzyme immunoassay. Before and after adjusting for age, sex, and body mass index, the serum myonectin level was not significantly different when the …

BackgroundDiet has a crucial role in the gut microbiota, and dysbiosis in the gut and lungs has been suggested to be associated with chronic obstructive pulmonary disease. We compared the diet, microbiome and metabolome between asymptomatic smokers and those with emphysema.MethodsWe enrolled 10 asymptomatic smokers with preserved lung function and 16 smokers with emphysema with severe airflow limitation. Dietary intake information was gathered by a self-reported questionnaire. Sputum and faecal samples were collected for microbial and metabolomics analysis. A murine model of emphysema was used to determine the effect of metabolite supplementation.ResultsDespite having a similar smoking history with emphysema patients, asymptomatic smokers had higher values of body mass index, fibre intake and faecal acetate level. Linear discriminant analysis identified 17 microbial taxonomic …

The placenta regulates maternal-fetal communication, and its defect leads to significant pregnancy complications. The maternal and embryonic circulations are primitively connected in early placentation, but the function of the placenta during this developmentally essential period is relatively unknown. We thus performed a comparative proteomic analysis of the placenta before and after primary placentation and found that the metabolism and transport of lipids were characteristically activated in this period. The placental fatty acid (FA) carriers in specific placental compartments were upregulated according to gestational age, and metabolomic analysis also showed that the placental transport of FAs increased in a time-dependent manner. Further analysis of two mutant mice models with embryonic lethality revealed that lipid-related signatures could reflect the functional state of the placenta. Our …

PurposeChronic obstructive pulmonary disease (COPD) is a heterogeneous disease presenting as multiple phenotypes, such as declining lung function, emphysema, or persistent airflow limitation caused by several risk factors, including cigarette smoking and air pollution. The inherent complexity of COPD phenotypes propounds difficulties for accurate diagnosis and prognosis. Although metabolomic profiles on COPD have been reported, the role of metabolism in COPD-related phenotypes is yet to be determined. In this study, we investigated the association between plasma sphingolipids and amino acids, and between COPD and COPD-related phenotypes in a Korean cohort.Patients and MethodsBlood samples were collected from 120 patients with COPD and 80 control participants who underwent spirometry and quantitative computed tomography. The plasma metabolic profiling was carried out using LC-MS …