1.Applications of Single-Cell Omics Technologies for Induced Pluripotent Stem Cell-Based Cardiovascular Research
Hyunjoon KIM ; Sohee CHOI ; HyoJung HEO ; Su Han CHO ; Yuna LEE ; Dohyup KIM ; Kyung Oh JUNG ; Siyeon RHEE
International Journal of Stem Cells 2025;18(1):37-48
Single-cell omics technologies have transformed our investigation of genomic, transcriptomic, and proteomic landscapes at the individual cell level. In particular, the application of single-cell RNA sequencing has unveiled the complex transcriptional variations inherent in cardiac cells, offering valuable perspectives into their dynamics. This review focuses on the integration of single-cell omics with induced pluripotent stem cells (iPSCs) in the context of cardiovascular research, offering a unique avenue to deepen our understanding of cardiac biology. By synthesizing insights from various single-cell technologies, we aim to elucidate the molecular intricacies of heart health and diseases. Beyond current methodologies, we explore the potential of emerging paradigms such as single-cell/spatial omics, delving into their capacity to reveal the spatial organization of cellular components within cardiac tissues. Furthermore, we anticipate their transformative role in shaping the future of cardiovascular research. This review aims to contribute to the advancement of knowledge in the field, offering a comprehensive perspective on the synergistic potential of transcriptomic analyses, iPSC applications, and the evolving frontier of spatial omics.
2.Applications of Single-Cell Omics Technologies for Induced Pluripotent Stem Cell-Based Cardiovascular Research
Hyunjoon KIM ; Sohee CHOI ; HyoJung HEO ; Su Han CHO ; Yuna LEE ; Dohyup KIM ; Kyung Oh JUNG ; Siyeon RHEE
International Journal of Stem Cells 2025;18(1):37-48
Single-cell omics technologies have transformed our investigation of genomic, transcriptomic, and proteomic landscapes at the individual cell level. In particular, the application of single-cell RNA sequencing has unveiled the complex transcriptional variations inherent in cardiac cells, offering valuable perspectives into their dynamics. This review focuses on the integration of single-cell omics with induced pluripotent stem cells (iPSCs) in the context of cardiovascular research, offering a unique avenue to deepen our understanding of cardiac biology. By synthesizing insights from various single-cell technologies, we aim to elucidate the molecular intricacies of heart health and diseases. Beyond current methodologies, we explore the potential of emerging paradigms such as single-cell/spatial omics, delving into their capacity to reveal the spatial organization of cellular components within cardiac tissues. Furthermore, we anticipate their transformative role in shaping the future of cardiovascular research. This review aims to contribute to the advancement of knowledge in the field, offering a comprehensive perspective on the synergistic potential of transcriptomic analyses, iPSC applications, and the evolving frontier of spatial omics.
3.Applications of Single-Cell Omics Technologies for Induced Pluripotent Stem Cell-Based Cardiovascular Research
Hyunjoon KIM ; Sohee CHOI ; HyoJung HEO ; Su Han CHO ; Yuna LEE ; Dohyup KIM ; Kyung Oh JUNG ; Siyeon RHEE
International Journal of Stem Cells 2025;18(1):37-48
Single-cell omics technologies have transformed our investigation of genomic, transcriptomic, and proteomic landscapes at the individual cell level. In particular, the application of single-cell RNA sequencing has unveiled the complex transcriptional variations inherent in cardiac cells, offering valuable perspectives into their dynamics. This review focuses on the integration of single-cell omics with induced pluripotent stem cells (iPSCs) in the context of cardiovascular research, offering a unique avenue to deepen our understanding of cardiac biology. By synthesizing insights from various single-cell technologies, we aim to elucidate the molecular intricacies of heart health and diseases. Beyond current methodologies, we explore the potential of emerging paradigms such as single-cell/spatial omics, delving into their capacity to reveal the spatial organization of cellular components within cardiac tissues. Furthermore, we anticipate their transformative role in shaping the future of cardiovascular research. This review aims to contribute to the advancement of knowledge in the field, offering a comprehensive perspective on the synergistic potential of transcriptomic analyses, iPSC applications, and the evolving frontier of spatial omics.
4.Gut microbiome and metabolome signatures in liver cirrhosis-related complications
Satya Priya SHARMA ; Haripriya GUPTA ; Goo-Hyun KWON ; Sang Yoon LEE ; Seol Hee SONG ; Jeoung Su KIM ; Jeong Ha PARK ; Min Ju KIM ; Dong-Hoon YANG ; Hyunjoon PARK ; Sung-Min WON ; Jin-Ju JEONG ; Ki-Kwang OH ; Jung A EOM ; Kyeong Jin LEE ; Sang Jun YOON ; Young Lim HAM ; Gwang Ho BAIK ; Dong Joon KIM ; Ki Tae SUK
Clinical and Molecular Hepatology 2024;30(4):845-862
Background/Aims:
Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis.
Methods:
Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to timeof-flight mass spectrometry. Correlation analyses were performed targeting the gut-microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased).
Results:
Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella_uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC >0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites.
Conclusions
Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.
5.KCTD17-mediated Ras stabilization promotes hepatocellular carcinoma progression
Young Hoon JUNG ; Yun Ji LEE ; Tam DAO ; Kyung Hee JUNG ; Junjie YU ; Ah-Reum OH ; Yelin JEONG ; HyunJoon GI ; Young Un KIM ; Dongryeol RYU ; Michele CARRER ; Utpal B. PAJVANI ; Sang Bae LEE ; Soon-Sun HONG ; KyeongJin KIM
Clinical and Molecular Hepatology 2024;30(4):895-913
Background/Aims:
Potassium channel tetramerization domain containing 17 (KCTD17) protein, an adaptor for the cullin3 (Cul3) ubiquitin ligase complex, has been implicated in various human diseases; however, its role in hepatocellular carcinoma (HCC) remains elusive. Here, we aimed to elucidate the clinical features of KCTD17, and investigate the mechanisms by which KCTD17 affects HCC progression.
Methods:
We analyzed transcriptomic data from patients with HCC. Hepatocyte-specific KCTD17 deficient mice were treated with diethylnitrosamine (DEN) to assess its effect on HCC progression. Additionally, we tested KCTD17-directed antisense oligonucleotides for their therapeutic potential in vivo.
Results:
Our investigation revealed the upregulation of KCTD17 expression in both tumors from patients with HCC and mouse models of HCC, in comparison to non-tumor controls. We identified the leucine zipper-like transcriptional regulator 1 (Lztr1) protein, a previously identified Ras destabilizer, as a substrate for KCTD17-Cul3 complex. KCTD17-mediated Lztr1 degradation led to Ras stabilization, resulting in increased proliferation, migration, and wound healing in liver cancer cells. Hepatocyte-specific KCTD17 deficient mice or liver cancer xenograft models were less susceptible to carcinogenesis or tumor growth. Similarly, treatment with KCTD17-directed antisense oligonucleotides (ASO) in a mouse model of HCC markedly lowered tumor volume as well as Ras protein levels, compared to those in control ASO-treated mice.
Conclusions
KCTD17 induces the stabilization of Ras and downstream signaling pathways and HCC progression and may represent a novel therapeutic target for HCC.
6.Evaluation of cryoablation using a prototype cryoablation needle in swine liver
Hyunjoon SON ; Jonghyun LEE ; Sung Yong HAN ; Tae In KIM ; Dong Uk KIM ; Daejin KIM ; Gun-Ho KIM
Clinical Endoscopy 2024;57(5):675-682
Background/Aims:
Pancreatic cancer poses significant challenges due to its tendency for late-stage diagnosis and high mortality rates. Cryoablation, a technique used to treat various types of cancer, has shown potential in enhancing the prognosis of pancreatic cancer when combined with other therapies. However, its implementation is often limited by the need for lengthy procedures and specialized equipment. This study aims to develop a cryoablation needle optimized for endoscopic ultrasonography to simplify its application in treating pancreatic cancer.
Methods:
The study involved conducting cryoablation experiments on swine liver tissue. It utilized cryo-needles to evaluate the extent of cell death across various temperatures and durations of cryoablation.
Results:
The cryoablation system, which employed liquid carbon dioxide, achieved rapid cooling, reaching temperatures below –60 °C within 30 seconds and maintained the cryoablation process for 200 seconds. These conditions resulted in necrosis of the liver tissue. Notable cellular changes were observed up to 15 mm away from the cryoablation needle.
Conclusions
This experimental study successfully demonstrated the efficacy of using a cryo-needle for cryoablation in swine liver tissue. Further trials involving pancreatic tissue are expected to verify its effectiveness, underscoring the importance of continued research to establish its role as a complementary therapy in pancreatic cancer treatment.
7.A study on the effect of denture cleaning utilizing active micro-locomotion of diatom complex
Hye-Rin JANG ; Joo Hun LEE ; Ji-Won CHOI ; Hyunjoon KONG ; Eun-Jin PARK
Korean Journal of Dental Materials 2023;50(1):59-68
This study compared the effectiveness of self-propelling diatom microbubblers to clean dental appliances with commercial denture cleaning agents according to the Ministry of Food and Drug Safety’s guidelines. The microbubbler is made by doping diatoms with MnO2 nanosheets that can decompose hydrogen peroxide to generate oxygen bubbles. Artificial saliva is prepared in accordance with the criteria presented by the American Dental Association, dispensed, and dried in 96 well plates. Experimental groups include 10-15% NaOCl (positive control), distilled water (negative control), diatom microbubbler A (Aulacoseira, MnO2-polydopamine (PDA)-A), diatom microbubbler M (Melosira nummuloids, MnO2-sugar (S)-M), Polident (GlaxoSmithKline, Dungarvan, Ireland), Dentfix-forte (Helago-Phama GmbH&Co, Parchim, Germany). After washing, absorbance (OD 600) was measured. If the absorbance was 70% or higher, the condition was determined to have “cleaning power potency,”Statistical significance was evaluated by one-way ANOVA and Bonferroni correction to compare cleaning effects among groups (p<0.05).The average cleaning rates were 93.8±1.0% in NaOCl (positive control) and 79.1±1.5% in distilled water (negative control).With the diatom microbubbler A, the average cleaning rate was 79.8±4.5% in the 3% H 2O 2 2 mg/mL, 64.7±5.5% in 6% H 2O 2 2 mg/mL, and 81.9±7.9% in 6% H 2O 2 4 mg/mL. The diatom microbubbler M group showed average cleaning rates of 88.5±3.6% in 3% H2O2 2 mg/mL, 75.8±4.0% in 6% H2O2 2 mg/mL, and 84.5±4.5% in 6% H2O2 4 mg/mL. Finally, conventional denture cleaning agents showed average cleaning rates of 88.2±1.2% in Polident and 83.3±3.0% in Dentfix-forte. The positive control group had significant differences from all experimental groups, but the negative control group showed significant differences only in A2 and A3, M1 and M2, M3, Polident, and Dentfix-forte (F=190.141, p<0.001). Among all groups except the positive control group, MnO2 -S-M mixed with 3% H2O2 2 mg/mL showed the highest cleaning rate. As the results of this study show, diatom complexes exhibit cleaning effects compatible with conventional denture cleaning agents. Further studies need to be conducted to narrow down the specific optimal conditions of diatom microbubblers and maximize the cleaning effect.
8.Adaptive design clinical trials: current status by disease and trial phase in various perspectives
Hyunjoon LEE ; Sejung HWANG ; In-Jin JANG ; Jae-Yong CHUNG ; Jaeseong OH
Translational and Clinical Pharmacology 2023;31(4):202-216
An adaptive design is a clinical trial design that allows for modification of a structured plan in a clinical trial based on data accumulated during pre-planned interim analyses. This flexible approach to clinical trial design improves the success rate of clinical trials while reducing time, cost, and sample size compared to conventional methods. The purpose of this study is to identify the current status of adaptive design and present key considerations for planning an appropriate adaptive design based on specific circumstances. We searched for clinical trials conducted between January 2006 to July 2021 in the Clinical Trials Registry (ClinicalTrials.gov) using keywords specified in the Food and Drug Administration Adaptive Design Clinical Trial Guidelines. In order to analyze the adaptive designs used in selected cases, we classified the results according to the phase of the clinical trial, type of indication, and the specific adaptation method employed. A total of 267 clinical trials were identified on ClinicalTrials.gov. Among them, 236 clinical trials actually applied adaptive designs and were classified according to phase, indication types, and adaptation methods. Adaptive designs were most frequently used in phase 2 clinical trials and oncology research. The most commonly used adaptation method was the adaptive treatment selection design. In the case of coronavirus disease 2019, the most frequently used designs were adaptive platform design and seamless design. Through this study, we expect to provide valuable insights and considerations for the implementation of adaptive design clinical trials in different diseases and stages.
9.The biofilm removal effect of MnO₂-diatom microbubbler from the dental prosthetic surfaces: In vitro study
Eun Hyuk LEE ; Yongbeom SEO ; Ho Bum KWON ; Young Jun YIM ; Hyunjoon KONG ; Myung Joo KIM
The Journal of Korean Academy of Prosthodontics 2020;58(1):14-22
PURPOSE: The aim of this study is to evaluate the effectiveness of MnO₂-diatom microbubbler (DM) on the surface of prosthetic materials as a mouthwash by comparing the biofilm removal effect with those previously used as a mouthwash in dental clinic.MATERIALS AND METHODS: DM was fabricated by doping manganese dioxide nanosheets to the diatom cylinder surface. Scanning electron microscopy (SEM) was used to observe the morphology of DM and to analyze the composition of doped MnO₂. Stereomicroscope was used to observe the reaction of DM in 3% hydrogen peroxide. Non-precious metal alloys, zirconia and resin specimens were prepared to evaluate the effect of biofilm removal on the surface of prosthetic materials. And then Streptococcus mutans and Porphyromonas gingivalis biofilms were formed on the specimens. When 3% hydrogen peroxide solution and DM were treated on the biofilms, the decontamination effect was compared with chlorhexidine gluconate and 3% hydrogen peroxide solution by crystal violet staining.RESULTS: Manganese dioxide was found on the surface of the diatom cylinder, and it was found to produce bubble of oxygen gas when added to 3% hydrogen peroxide. For all materials used in the experiments, biofilms of the DM-treated groups got effectively removed compared to the groups used with chlorhexidine gluconate or 3% hydrogen peroxide alone.CONCLUSION: MnO₂-diatom microbubbler can remove bacterial membranes on the surface of prosthetic materials more effectively than conventional mouthwashes.
Alloys
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Biofilms
;
Chlorhexidine
;
Decontamination
;
Dental Clinics
;
Dental Plaque
;
Diatoms
;
Gentian Violet
;
Hydrogen Peroxide
;
In Vitro Techniques
;
Manganese
;
Membranes
;
Microscopy, Electron, Scanning
;
Mouthwashes
;
Oral Hygiene
;
Oxygen
;
Porphyromonas gingivalis
;
Streptococcus mutans
10.Erratum: The biofilm removal effect of MnO2-diatom microbubbler fromthe dental prosthetic surfaces: In vitro study
Eun-Hyuk LEE ; Yongbeom SEO ; Ho‐Beom KWON ; Young‐Jun LIM ; Hyunjoon KONG ; Myung-Joo KIM
The Journal of Korean Academy of Prosthodontics 2020;58(2):176-
The article ‘The biofilm removal effect of MnO2-diatom microbubbler from the dental prosthetic surfaces: In vitro study’ authored by Eun-Hyuk Lee,Yongbeom Seo, Ho-Bum Kwon, Young-Jun Yim, Hyunjoon Kong, Myung-Joo Kim, published in April issue [Vol 58, No 1] of The Journal of KoreanAcademy of Prosthodontics (2020), has an erratum.The author names were mistakenly given as Ho-Bum Kwon, Young-Jun Yim. It should be corrected as Ho‐Beom Kwon, Young‐Jun Lim. The Journal ofKorean Academy of Prosthodontics apologizes to the readers for this error.

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