1.Effects of Mycophenolic Acid and Rapamycin on Toll-like Receptor Expression in Hypoxic Human Proximal Tubular Epithelial Cells.
Dahye LEE ; Jehyun PARK ; Yu Seun KIM ; Hyeon Joo JEONG
The Journal of the Korean Society for Transplantation 2009;23(1):15-21
BACKGROUND: Toll like receptor (TLR), an element of innate immunity, is upregulated by Ischemia/reperfusion (IR) injury and may be involved in adaptive immune response. Immunosuppressive agents may increase or attenuate IR injury and TLR expression. To explore the involvement of TLRs in hypoxic tubular injury and modification by mycophenolic acid (MPA) rapamycin (RAP), this study examined TLR expression in hypoxia-induced human renal proximal tubular epithelial cells (HK-2). METHODS: HK-2 cells were cultured in keratinocyte-SFM media supplemented with epidermal growth factor and bovine pituitary extract. The Induction of hypoxia was achieved using GasPak pouch system. TLR 2, 3, and 4 mRNA expression was analyzed by real time RT-PCR using SYBR green and TLR 4 protein expression was evaluated by Western blot analysis. MPA at concentration of 100 nM and 1uM and RAP at concentration of 20, 50, and 100 nM were added to culture medium. RESULTS: TLR4 but noTLR2 or TLR3 mRNA expressions increased in hypoxic HK-2 cells at 24 and 48 hrs. TLR4 protein expression also increased in hypoxic HK-2 cells at 24 and 48 hrs. MPA (100 nM and 1uM) and RAP (20, 50, and 100 nM) decreased hypoxia-induced TLR4 mRNA expression in HK-2 cells compared to normoxia at 24 hrs. However, TLR4 protein expression was decreased only by RAP at 20 and 50 nM. CONCLUSIONS: The results suggest that RAP may modify hypoxic renal tubular damage by decreasing TLR4-mediated inflammatory and immune reactions.
Adaptive Immunity
;
Anoxia
;
Blotting, Western
;
Epidermal Growth Factor
;
Epithelial Cells
;
Humans
;
Immunity, Innate
;
Immunosuppressive Agents
;
Mycophenolic Acid
;
RNA, Messenger
;
Sirolimus
;
Toll-Like Receptors
2.Deep-Learning-Based Segmentation of Predefined Chunks in Connected Speech: A Retrospective Analysis
Jae Yeong KIM ; Jungirl SEOK ; Jehyun LEE ; Jeong Hoon LEE ; Tack-Kyun KWON
Journal of the Korean Society of Laryngology Phoniatrics and Logopedics 2024;35(1):15-23
Background and Objectives:
In institutional settings, manually segmenting connected speech is a time-consuming and labor-intensive process. This study aims to develop a deep-learning model for automating this process, evaluating its accuracy, and determining the minimum dataset size for effective performance.Materials and Method Voice data from 524 individuals with pathological conditions and 502 individuals with normal conditions, totaling 1026 samples, were used. Each voice sample had 17 chunks, including a “summer” sentence (15 chunks) and vowels /α/ and /i/. The deep-learning model employed in this study is based on the multi-layer perceptron-mixer architecture. This study evaluated performance using the Intersection over Union (IoU) metric, commonly employed in artificial intelligence-based image detection for chunk segmentation.
Results:
The accuracy of chunk identification at the frame level was 96.47%. Using IoU metrics, chunk segmentation accuracy was 98.15% at IoU ≥0.6, 96.03% at IoU ≥0.7, and 89.78% at IoU ≥0.8. Optimal dataset size exploration indicated that more than 700 connected speech datasets were needed for successful training, maintaining F1-scores up to 95% at IoU ≥0.7.
Conclusion
The artificial intelligence model is suitable for the development of an automated system that efficiently divides segments in the institutional collection of voice data. This suggests its potential utility in advancing voice research using connected speech.
3.Effects of Tautomycetin on the Proliferation and Fibronectin Secretion in Vascular Smooth Muscle Cells and Glomerular Mesangial Cells.
Ji Hye KIM ; Tae Young LEE ; Jehyun PARK ; Hunjoo HA ; Shin Wook KANG ; Yu Seun KIM
The Journal of the Korean Society for Transplantation 2005;19(1):8-13
PURPOSE: Proliferation and extracellular matrix (ECM) accumulation in the vascular smooth muscle cell (VSMC) and glomerular mesangial cell (MC) play key roles in the development and the progression of transplant glomerulosclerosis and chronic allograft nephropathy. Tautomycetin (TMC), a newly developed immunosuppressive agent, induces T-lymphocyte apoptosis through the inhibition of tyrosine kinase and protein phosphatase 1. We examined the effects of TMC on platelet-derived growth factor (PDGF)-induced proliferation and ECM synthesis in cultured VSMCs and MCs of Sprague- Dawley rats, and investigated the molecular mechanisms that are involved. METHODS: Different concentrations of TMC were administered 1 hour before the addition of PDGF 10 ng/mL into the growth-arrested and synchronized cells. Cell proliferation was assessed by methylthiazoletetrazolium (MTT) assay. Caspase-3 cleavage, fibronectin secretion, and the activation of Akt, ERK, and p38 MAPK were assessed by Western blot analysis, respectively. RESULTS: PDGF 10 ng/ mL increased cell proliferation, fibronectin secretion, and the activation of Akt, ERK, and p38 MAPK in both VSMCs and MCs. In both cultured cells, TMC at above 1 microgram/mL significantly reduced basal MTT and increased cleavage caspase-3 in a dose-dependent manner. TMC at 100 ng/mL decreased the PDGF-induced VSMC and MC proliferation without cytotoxicity. However, fibronectin secretion and the activation of Akt, ERK, and p38 MAPK were not affected at this low concentration of TMC, respectively. CONCLUSION: The present data demonstrated that low-dose TMC reduced PDGF-induced VSMC and MC proliferation without affecting the fibronectin secretion and cellular kinase activation.
Allografts
;
Animals
;
Apoptosis
;
Blotting, Western
;
Caspase 3
;
Cell Proliferation
;
Cells, Cultured
;
Extracellular Matrix
;
Fibronectins*
;
Mesangial Cells*
;
Muscle, Smooth, Vascular*
;
p38 Mitogen-Activated Protein Kinases
;
Phosphotransferases
;
Platelet-Derived Growth Factor
;
Protein Phosphatase 1
;
Protein-Tyrosine Kinases
;
Rats
;
T-Lymphocytes
4.Increased Intracellular Reactive Oxygen Species in Peripheral Blood Mononuclear Cells from Renal Transplant Recipients with Decreased Graft Function.
Ji Hye KIM ; Jehyun PARK ; Hunjoo HA ; Hi Bahl LEE ; Kyu Ha HUH ; Myoung Soo KIM ; Soon Il KIM ; Yu Seun KIM ; Kiil PARK
The Journal of the Korean Society for Transplantation 2003;17(2):131-136
PURPOSE: Oxidative stress plays an important role in the development and progression of renal injury. However, the role of reactive oxygen species (ROS) in renal allograft dysfunction is not clear. The present study examined the level of intracellular ROS in healthy control (kidney donor, n=37), end-stage renal disease (ESRD) patients (n=36), transplant recipients with serum creatinine (Scr) less than 1.5 mg% (n=33), and recipients with Scr between 1.5 and 5.0 mg% (n=36) at least one year after renal transplantation. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated by Ficoll-Hypaque gradient method. Dichlorofluorescein (DCF)-sensitive ROS was measured by flow cytometry and expressed as an arbitrary unit. RESULTS: Basal ROS production in PBMC was significantly increased in ESRD patients compared to healthy control. Basal ROS production in both transplant patient groups was not significantly different from healthy control. Phorbol-12-myristate-13- acetate (PMA) and hydrogen peroxide significantly enhanced intracellular ROS in all 4 groups. PMA- and hydrogen peroxide-induced cellular ROS was significantly higher in renal recipients with Scr between 1.5 and 5.0 mg% than in both healthy control and patients with Scr below 1.5 mg%. In regression analysis all, PMA- and hydrogen peroxide- induced as well as basal intracellular ROS in PBMC was correlated with Scr. CONCLUSION: Our results demonstrate that oxidative stress correlates with the declining of renal graft function.
Allografts
;
Creatinine
;
Flow Cytometry
;
Humans
;
Hydrogen
;
Hydrogen Peroxide
;
Kidney Failure, Chronic
;
Kidney Transplantation
;
Oxidative Stress
;
Reactive Oxygen Species*
;
Tissue Donors
;
Transplantation*
;
Transplants*
5.Association of Microbial Dysbiosis with Gallbladder Diseases Identified by Bile Microbiome Profiling
Seong Ji CHOI ; Yeseul KIM ; Jehyun JEON ; Ho-Jin GWAK ; Mimi KIM ; Kyojin KANG ; Yohan KIM ; Jaemin JEONG ; Yun Kyung JUNG ; Kyeong Geun LEE ; Ho Soon CHOI ; Dong-Hwan JUNG ; Sung-Gyu LEE ; Yangsoon LEE ; Su-Jin SHIN ; Kiseok JANG ; Mina RHO ; Dongho CHOI
Journal of Korean Medical Science 2021;36(28):e189-
Background:
Cholecystitis is an important risk factor for gallbladder cancer, but the bile microbiome and its association with gallbladder disease has not been investigated fully.We aimed to analyze the bile microbiome in normal conditions, chronic cholecystitis, and gallbladder cancer, and to identify candidate bacteria that play an important role in gallbladder carcinogenesis.
Methods:
We performed metagenome sequencing on bile samples of 10 healthy individuals, 10 patients with chronic cholecystitis, and 5 patients with gallbladder cancer, and compared the clinical, radiological, and pathological characteristics of the participants.
Results:
No significant bacterial signal was identified in the normal bile. The predominant dysbiotic bacteria in both chronic cholecystitis and gallbladder cancer were those belonging to the Enterobacteriaceae family. Klebsiella increased significantly in the order of normal, chronic cholecystitis, and gallbladder cancer. Patients with chronic cholecystitis and dysbiotic microbiome patterns had larger gallstones and showed marked epithelial atypia, which are considered as precancerous conditions.
Conclusion
We investigated the bile microbiome in normal, chronic cholecystitis, and gallbladder cancer. We suggest possible roles of Enterobacteriaceae, including Klebsiella, in gallbladder carcinogenesis. Our findings reveal a possible link between a dysbiotic bile microbiome and the development of chronic calculous cholecystitis and gallbladder cancer.
6.Association of Microbial Dysbiosis with Gallbladder Diseases Identified by Bile Microbiome Profiling
Seong Ji CHOI ; Yeseul KIM ; Jehyun JEON ; Ho-Jin GWAK ; Mimi KIM ; Kyojin KANG ; Yohan KIM ; Jaemin JEONG ; Yun Kyung JUNG ; Kyeong Geun LEE ; Ho Soon CHOI ; Dong-Hwan JUNG ; Sung-Gyu LEE ; Yangsoon LEE ; Su-Jin SHIN ; Kiseok JANG ; Mina RHO ; Dongho CHOI
Journal of Korean Medical Science 2021;36(28):e189-
Background:
Cholecystitis is an important risk factor for gallbladder cancer, but the bile microbiome and its association with gallbladder disease has not been investigated fully.We aimed to analyze the bile microbiome in normal conditions, chronic cholecystitis, and gallbladder cancer, and to identify candidate bacteria that play an important role in gallbladder carcinogenesis.
Methods:
We performed metagenome sequencing on bile samples of 10 healthy individuals, 10 patients with chronic cholecystitis, and 5 patients with gallbladder cancer, and compared the clinical, radiological, and pathological characteristics of the participants.
Results:
No significant bacterial signal was identified in the normal bile. The predominant dysbiotic bacteria in both chronic cholecystitis and gallbladder cancer were those belonging to the Enterobacteriaceae family. Klebsiella increased significantly in the order of normal, chronic cholecystitis, and gallbladder cancer. Patients with chronic cholecystitis and dysbiotic microbiome patterns had larger gallstones and showed marked epithelial atypia, which are considered as precancerous conditions.
Conclusion
We investigated the bile microbiome in normal, chronic cholecystitis, and gallbladder cancer. We suggest possible roles of Enterobacteriaceae, including Klebsiella, in gallbladder carcinogenesis. Our findings reveal a possible link between a dysbiotic bile microbiome and the development of chronic calculous cholecystitis and gallbladder cancer.
7.Identification and Antifungal Susceptibility Profiles of Cyberlindnera fabianii in Korea
Ji Hyun PARK ; Junsang OH ; Hyunkyu SANG ; Bhushan SHRESTHA ; Hyeyoung LEE ; Jehyun KOO ; Sung Il CHO ; Ji Seon CHOI ; Min Ha LEE ; Jayoung KIM ; Gi Ho SUNG
Mycobiology 2019;47(4):449-456
Invasive fungal infections caused by Cyberlindnera fabianii have recently increased. However, biochemical kits such as API 20 C AUX and Vitek-2C have misidentified this species as other Candida spp. such as C. pelliculosa or C. utilis due to no information of Cy. fabianii in yeast database. During our 2016–2017 surveys, eleven isolates of Cy. fabianii were obtained in International St. Mary's Hospital in Korea. Here, we describe its morphological and molecular characteristics and tested its antifungal susceptibility against nine antifungal agents. The sequences of the ITS region and the D1/D2 region of LSU revealed 100% identity with the sequences of Cy. fabianii. In comparison with the results from MALDI-TOF mass spectrometry, we found that Cy. fabianii can be distinguished from other species. In antifungal susceptibility test, voriconazole and echinocandins exhibited good antifungal activities against the majority of Cy. fabianii isolates despite the absence of standard criteria.
8.Predictive Parameters of Febrile Neutropenia and Clinical Significance of G-CSF Receptor Signaling Pathway in the Development of Neutropenia during R-CHOP Chemotherapy with Prophylactic Pegfilgrastim in Patients with Diffuse Large B-Cell Lymphoma
Do Young KIM ; Jehyun NAM ; Joo-Seop CHUNG ; Byeol Eun JEON ; Ji Hyun LEE ; Jae-Cheol JO ; Sang-Woo KIM ; Ho-Jin SHIN
Cancer Research and Treatment 2022;54(4):1256-1267
Purpose:
Pegfilgrastim is widely used to prevent chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) in patients with diffuse large B-cell lymphoma (DLBCL). We investigated the predictive factors affecting CIN and FN incidence in patients with DLBCL receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy with pegfilgrastim and conducted experiments to find reason for the occurrence of CIN even when pegfilgrastim was used.
Materials and Methods:
We reviewed the CIN and FN events of 200 patients with DLBCL. Based on these data, we investigate the association with predictive factor and the levels of granulocyte-colony stimulating factor (G-CSF) receptor signaling pathway markers (pSTAT3, pAKT, pERK1/2, pBAD, and CXCR4) in bone marrow (BM) samples isolated from patients with DLBCL.
Results:
FN was significantly associated with stage III/IV (hazard ratio [HR], 12.74) and low serum albumin levels (HR, 3.87). Additionally, patients with FN had lower progression-free survival (PFS; 2-year PFS, 51.1 % vs. 74.0%) and overall survival (OS; 2-year OS, 58.2% vs. 85.0%) compared to those without FN. The occurrence of CIN was associated with overexpression of G-CSF receptor signaling pathway markers, and expression levels of these markers were upregulated in BM cells co-cultured with DLBCL cells. The rate of neutrophil apoptosis was also higher in neutrophils co-cultured with DLBCL cells and was further promoted by treatment with doxorubicin.
Conclusion
Our findings suggest that high DLBCL burden may alter the BM environment and G-CSF receptor signaling pathway, even in chemotherapy-naïve state, which may increase CIN frequency during R-CHOP chemotherapy.