A Novel PHEX Gene Mutation in a Patient with Sporadic Hypophosphatemic Rickets

강예은,홍준화,김지민,정경혜,김현진,구본정,김군순 대한내분비학회 2014 Endocrinology and metabolism Vol.29 No.2

Phosphate regulating gene with homologies to endopeptidases on the X-chromosome (PHEX) is a common cause of X-linked hypophosphatemic (XLH) rickets. Diverse PHEX gene mutations have been reported; however, gene mutations in sporadic rickets are less common than in XLH rickets. Herein, we describe a 50-year-old female patient with sporadic hypophosphatemic rickets harboring a novel splicing-site mutation in the PHEX gene (c.663+1G>A) at the exon 5-intron 5 boundary. The patient had recently suffered from right thigh pain and an aggravated waddling gait. She also presented with very short stature, generalized bone pain, and muscle weakness. Despite low serum phosphate levels, her phosphate reabsorption rate was lower than normal. Additionally, her 1,25-dihydroxyvitamin D3 concentration was lower than normal, although FGF23 level was normal. After treatment with alfacalcidol and elemental phosphate, her rachitic symptoms subsided, and callus formation was observed in the fracture site on the right femur.

Increased Pro-Inflammatory T Cells, Senescent T Cells, and Immune-Check Point Molecules in the Placentas of Patients With Gestational Diabetes Mellitus

강예은,Yi Hyon-Seung,Yeo Min-Kyung,Kim Jung Tae,Park Danbit,Jung Yewon,Kim Ok Soon,이성은,Kim Ji Min,Joung Kyong Hye,Lee Ju Hee,Ku Bon Jeong,Lee Mina,Kim Hyun Jin 대한의학회 2022 Journal of Korean medical science Vol.37 No.48

Background: Gestational diabetes mellitus (GDM) is the most common metabolic complication of pregnancy. To define the altered pathway in GDM placenta, we investigated the transcriptomic profiles from human placenta between GDM and controls. Methods: Clinical parameters and postpartum complications were reviewed in all participants. Differentially expressed canonical pathways were analyzed between the GDM and control groups based on transcriptomic analysis. CD4+ T, CD8+ T, and senescent T cell subsets were determined by flow cytometry based on staining for specific intracellular cytokines. Results: Gene ontology analysis revealed that the placenta of GDM revealed upregulation of diverse mitochondria or DNA replication related pathways and downregulation of T-cell immunity related pathways. The maternal placenta of the GDM group had a higher proportion of CD4+ T and CD8+ T cells than the control group. Interestingly, senescent CD4+ T cells tended to increase and CD8+ T cells were significantly increased in GDM compared to controls, along with increased programmed cell death-1 (CD274+ ) expression. Programmed death-ligand 1 expression in syncytotrophoblasts was also significantly increased in patients with GDM. Conclusion: This study demonstrated increased proinflammatory T cells, senescent T cells and immune-check point molecules in GDM placentas, suggesting that changes in senescent T cells and immune-escape signaling might be related to the pathophysiology of GDM.

Regulation of Systemic Glucose Homeostasis by T Helper Type 2 Cytokines

강예은,김현진,송민호 대한당뇨병학회 2019 Diabetes and Metabolism Journal Vol.43 No.5

Obesity results in an inflammatory microenvironment in adipose tissue, leading to the deterioration of tissue protective mechanisms. Although recent studies suggested the importance of type 2 immunity in an anti-inflammatory microenvironment in adiposetissue, the regulatory effects of T helper 2 (Th2) cytokines on systemic metabolic regulation are not fully understood. Recently,we identified the roles of the Th2 cytokine (interleukin 4 [IL-4] and IL-13)-induced adipokine, growth differentiation factor 15(GDF15), in adipose tissue in regulating systemic glucose metabolism via signal transducer and activator of transcription 6(STAT6) activation. Moreover, we showed that mitochondrial oxidative phosphorylation is required to maintain these macrophage-regulating autocrine and paracrine signaling pathways via Th2 cytokine-induced secretion of GDF15. In this review, we discusshow the type 2 immune response and Th2 cytokines regulate metabolism in adipose tissue. Specifically, we review the systemicregulatory roles of Th2 cytokines in metabolic disease and the role of mitochondria in maintenance of type 2 responses in adiposetissue homeostasis.

Serum R-Spondin 1 Is a New Surrogate Marker for Obesity and Insulin Resistance

강예은,김지민,이현승,정경혜,이주희,김현진,구본정 대한당뇨병학회 2019 Diabetes and Metabolism Journal Vol.43 No.3

Background: Recent in vivo studies indicated that R-spondin 1 (RSPO1) regulates food intake and increases insulin secretion, but its role in humans remains unknown. This study investigated the association between serum levels of RSPO1 and diverse metabolic parameters in humans. Methods: The study population consisted of 43 subjects with newly diagnosed diabetes mellitus, and 79 non-diabetic participants. Serum levels of RSPO1 were measured using the enzyme-linked immunosorbent assay. The relationships between circulating RSPO1 and diverse metabolic parameters were analyzed. Results: Circulating RSPO1 levels increased to a greater extent in the obese group than in the lean group. Moreover, serum levels of RSPO1 were higher in the insulin-resistant group than in the insulin-sensitive group. Serum levels of RSPO1 were significantly correlated with a range of metabolic parameters including body mass index, fasting C-peptide, homeostasis model assessment of insulin resistance index, and lipid profile. Moreover, levels were significantly associated with insulin resistance and obesity in nondiabetic subjects. Conclusion: This study demonstrated the association between serum levels of RSPO1 and a range of metabolic parameters in humans. Serum levels of RSPO1 are significantly related to obesity and insulin resistance, although the precise mechanisms remain unknown.

Prognostic Significance of Sirtuins Expression in Papillary Thyroid Carcinoma

강예은,송민호,김진만,구본석 대한갑상선학회 2018 International Journal of Thyroidology Vol.11 No.2

Background and Objectives: Sirtuins (SIRTs) play important roles in cellular and organismal homeostasis. They have distinct gene expression patterns in various cancers; however, the relationship between SIRT expression and the progression of thyroid cancer is unclear. We investigated the expression of SIRTs in patients with papillary thyroid carcinoma (PTC) and their role as biomarkers for predicting the aggressiveness of this disease. Materials and Methods: We used immunohistochemical staining to evaluate the expression of SIRT1 and SIRT3 in tumor specimens from 270 patients with PTC. We also evaluated the potential association between SIRT expression and diverse clinicopathological features. Results: High SIRT1 expression was negatively correlated with lymphovascular invasion, central lymph node metastasis, and lateral lymph node metastasis. Multivariate analyses revealed that high SIRT1 expression was a negative independent risk factor for lateral lymph node metastasis. By contrast, high SIRT3 expression was positively correlated with locoregional recurrence. Interestingly, when patients were grouped by tumor SIRT expression patterns, the group with low SIRT1 expression and high SIRT3 expression was correlated with more aggressive cancer phenotypes including central lymph node metastasis and lateral lymph node metastasis. Conclusion: Our results suggest that SIRTs play dual roles in tumor progression, and the combination of decreased SIRT1 expression and increased SIRT3 expression is significantly associated with a poor prognosis in patients with PTC.

Sub-nanogram Level Biomarker Capturing by Nanoporous Microneedles

강예은,성금용,임상구,이예찬,양승윤 한국고분자학회 2018 한국고분자학회 학술대회 연구논문 초록집 Vol.43 No.2

The Role of Circulating Slit2, the One of the Newly Batokines, in Human Diabetes Mellitus

강예은,정소림,이주희,김현진,구본정 대한내분비학회 2017 Endocrinology and metabolism Vol.32 No.3

Background: Slit2 is a new secreted protein from adipose tissue that improves glucose hemostasis in mice; however, there is no study about the serum levels and precise role of Slit2 in human. The aim of this study is to explore the serum level of Slit2 in human, and to identify the role of Slit2 in diabetes mellitus (DM). Methods: The participants of this study consist of 38 subjects with newly diagnosed DM, and 75 healthy subjects as a control group. Serum Slit2 levels were measured using an enzyme-linked immunosorbent assay. Relationship between circulating Slit2 and diabetic related factors was investigated in diabetic group compared with non-diabetic group. Additionally, the correlations between the serum level of Slit2 and diverse metabolic parameters were analyzed. Results: Circulating Slit2 level was more decreased in diabetic group than in control group, but there was no significant difference statistically. Interestingly, serum levels of Slit2 were significantly negatively correlated to the serum concentrations of fasting glucose (coefficient r=–0.246, P=0.008), the serum concentrations of postprandial glucose (coefficient r=–0.233, P=0.017), and glycosylated hemoglobin (HbA1c; coefficient r=–0.357, P<0.001). Conclusion: From our study, the first report of circulating Slit2 levels in human, circulating Slit2 level significantly negatively correlated with serum glucose and HbA1c. Our results suggest that the circulating Slit2 may play a role in maintainence of glucose homeostasis in human, even though exact contribution and mechanism are not yet known.

Treatment with Gefitinib, an Epidermal Growth Factor Receptor Inhibitor, Decreases Serum Cholesterol in Patients with Lung Cancer

강예은,김지민,김현진,구본정 대한비만학회 2016 The Korean journal of obesity Vol.25 No.4

Background: Statins are used to treat hypercholesterolemia; however, major cardiovascular events are decreased only 30% by statin treatment. Treatment with an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been reported to decrease serum glucose levels and improved insulin sensitivity in mice and humans, but there was no study in serum cholesterol levels. This study examined the effect of gefitinib, an EGFR tyrosine kinase inhibitor, on cholesterol metabolism in humans. Methods: We retrospectively reviewed the medical records of 299 patients with primary lung cancer treated with gefitinib for ≥1 month and 72 patients with other treatments. Serum cholesterol, serum triglycerides, and body mass index were measured before and after treatment. The changes in serum cholesterol, serum triglycerides, and body mass index were compared between the gefitinib treatment group and the control group and were also analyzed according to the presence or absence of EGFR mutations. Results: Serum cholesterol levels decreased significantly from 178.9 to 164.4 mg/dL after 1-month of gefitinib treatment. A total of 54 of the 299 patients underwent examination for the presence of the EGFR mutations. Serum cholesterol was significantly decreased in the group with the activating EGFR mutation (Δ=21.3 mg/dL) compared to that of those without the EGFR mutation (Δ=-3.1 mg/dL) after treatment with gefitinib. In contrast, there was no significantly difference between the two groups in control patients. Conclusion: Treatment with gefitinib decreased serum cholesterol in lung cancer patients, particularly in those with activating mutations in EGFR. These data suggest that EGFR tyrosine kinase inhibitors provide a novel and attractive strategy for the treatment of hypercholesterolemia.

The Significance of Transcriptomic Signatures in the Multifocal Papillary Thyroid Carcinoma: Two mRNA Expression Patterns with Distinctive Clinical Behavior from The Cancer Genome Atlas (TCGA) Database

강예은,황보영,이주희,송민호,이현승,구본석,이동진 대한갑상선학회 2020 International Journal of Thyroidology Vol.13 No.1

Background and Objectives: The association between multifocal papillary thyroid carcinoma (PTC) and tumor aggressiveness remains controversial. The aim of study is to evaluate molecular subtypes of multifocal PTCs using multiplatform genomic analysis. Materials and Methods: Statistical analysis and genomic analysis were performed for gene expression data and clinical data of multifocal PTCs in The Cancer Genome Atlas data. Clinicopathologic findings, recurrence-free survival (RFS), copy number alteration and somatic mutation status in patients in relation to molecular subtypes were analyzed. Results: Multiplatform genomic analysis revealed that multifocal PTCs (n=226) were divided into two distinct molecular subgroups. Participants in cluster 2 showed significantly increased risk of extrathyroidal extension, lymph node metastasis, and BRAFV600E mutation compared to patients in cluster 1. To exclude the effect of BRAF mutation and RAS mutation on tumor aggressiveness, we compared clinical parameters between two clusters in patients without BRAF or RAS mutation. Cluster 2 showed significantly higher risk of lymph node metastasis compared to cluster 1. Conclusion: Multifocal PTC has two distinct molecular subtypes with distinctive clinical behaviors. Our data suggested the clinical implications of the transcriptomic signature to predict clinical outcomes of multifocal PTC.

Fabrication and Thickness Control of TiO₂ Thin Films by Spin Coating Process

강예은,송경호,박준환,오성근 한국공업화학회 2011 한국공업화학회 연구논문 초록집 Vol.2011 No.1