Hematopoietic stem cell transplantation (HSCT) is the first field where human stem cell therapy was successful. Flooding interest on human stem cell therapy to cure previously incurable diseases is largely indebted to HSCT success. Allogeneic HSCT has been an important modality to cure various diseases including hematologic malignancies, various non-malignant hematologic diseases, primary immunodeficiency diseases, and inborn errors of metabolism, while autologous HSCT is generally performed to rescue bone marrow aplasia following high-dose chemotherapy for solid tumors or multiple myeloma. Recently, HSCs are also spotlighted in the field of regenerative medicine for the amelioration of symptoms caused by neurodegenerative diseases, heart diseases, and others. Although the demand for HSCs has been growing, their supply often fails to meet the demand of the patients needing transplant due to a lack of histocompatible donors or a limited cell number. This review focuses on the generation and large-scale expansion of HSCs, which might overcome current limitations in the application of HSCs for clinical use. Furthermore, current proof of concept to replenish hematological homeostasis from non-hematological origin will be covered.
Bone Marrow ; Cell Count ; Drug Therapy ; Heart Diseases ; Hematologic Diseases ; Hematologic Neoplasms ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells* ; Homeostasis ; Humans ; Metabolism, Inborn Errors ; Multiple Myeloma ; Neurodegenerative Diseases ; Regenerative Medicine ; Stem Cells ; Tissue Donors

PURPOSE: High frequency oscillatory ventilation (HFOV) is used to support infants with severe respiratory failure unresponsive to conventional ventilation (CV). We reviewed chest radiographs before and after HFOV with clinical correlation in infants with respiratory distress syndrome (RDS). METHODS: Eighteen very low birth weight infants with RDS who had HFOV were included in this study. All patients were diagnosed as having RDS clinically and radiologically. Mean gestational age of infants was 27 weeks (range : 24-31 weeks). The mean duration of HFOV was 3 days (range : 14 hours-9 days). The chest radiographs of these infants within 3 hours before and after application of HFOV were retrospectively reviewed. Radiological findings based on aeration and parenchymal densities were classified into improved, no change, and progressed. Medical records were reviewed for FiO2 levels, clinical outcomes, complications, and causes of death. RESULTS: In 15 of 18 infants, aeration and parenchymal densities were improved and FiO2 levels were also improved after HFOV. Four of these 15 infants who showed improvement of radiological findings developed pneumothorax, sepsis, pulmonary or intestinal bleeding, and subsequently died. In remaining 3 infants in whom chest radiographs after HFOV showed no interval change or progression, oxygenation was also worsened and all died. CONCLUSION: Chest radiographs of HFOV-treated, very low birth weight infants showed improvement of aeration and parenchymal densities in most cases. Clinical outcome was good in infants who showed improvement on chest radiographs compared to those of progression group as far as there was no associated complication. Knowledge of radiological changes after HFOV will help in interpretation of chest radiographs in those HFOV-treated infants.
Cause of Death ; Gestational Age ; Hemorrhage ; Humans ; Infant* ; Infant, Very Low Birth Weight* ; Medical Records ; Oxygen ; Pneumothorax ; Radiography, Thoracic ; Respiratory Insufficiency ; Retrospective Studies ; Sepsis ; Ventilation*

Paragonimiasis was one of the most common causes of cavitary lung lesions until the 1960s, but now it has become a very rare disease in Korea. A 16-year-old boy presented with hemoptysis and several days of cough. His plain chest radiograph showed nodular opacity with a cavity in the left upper lung region. Although his symptoms disappeared after taking antituberculous drugs, his plain chest radiograph and computed tomography images after completion of therapy showed a new nodule with a cavity in the left lung field. Through video-assisted thoracoscopic wedge resection, Paragonimus eggs were found in the lung tissues.
Adolescent ; Cough ; Eggs ; Hemoptysis ; Humans ; Korea ; Lung ; Male ; Ovum ; Paragonimiasis* ; Paragonimus ; Radiography, Thoracic ; Rare Diseases ; Tuberculosis, Pulmonary*

Paragonimiasis was one of the most common causes of cavitary lung lesions until the 1960s, but now it has become a very rare disease in Korea. A 16-year-old boy presented with hemoptysis and several days of cough. His plain chest radiograph showed nodular opacity with a cavity in the left upper lung region. Although his symptoms disappeared after taking antituberculous drugs, his plain chest radiograph and computed tomography images after completion of therapy showed a new nodule with a cavity in the left lung field. Through video-assisted thoracoscopic wedge resection, Paragonimus eggs were found in the lung tissues.
Adolescent ; Cough ; Eggs ; Hemoptysis ; Humans ; Korea ; Lung ; Male ; Ovum ; Paragonimiasis* ; Paragonimus ; Radiography, Thoracic ; Rare Diseases ; Tuberculosis, Pulmonary*

The method of single-cell RNA sequencing has been rapidly developed, and numerous experiments have been conducted over the past decade. Their results allow us to recognize various subpopulations and rare cell states in tissues, tumors, and immune systems that are previously unidentified, and guide us to understand fundamental biological processes that determine cell identity based on single-cell gene expression profiles. However, it is still challenging to understand the principle of comprehensive gene regulation that determines the cell fate only with transcriptome, a consequential output of the gene expression program. To elucidate the mechanisms related to the origin and maintenance of comprehensive single-cell transcriptome, we require a corresponding single-cell epigenome, which is a differentiated information of each cell with an identical genome. This review deals with the current development of single-cell epigenomic library construction methods, including multi-omics tools with crucial factors and additional requirements in the future focusing on DNA methylation, chromatin accessibility, and histone post-translational modifications. The study of cellular differentiation and the disease occurrence at a single-cell level has taken the first step with single-cell transcriptome and is now taking the next step with single-cell epigenome.

This review aims to define the 4 types of the metaverse and to explain the potential and limitations of its educational applications. The metaverse roadmap categorizes the metaverse into 4 types: augmented reality, lifelogging, mirror world, and virtual reality. An example of the application of augmented reality in medical education would be an augmented reality T-shirt that allows students to examine the inside of the human body as an anatomy lab. Furthermore, a research team in a hospital in Seoul developed a spinal surgery platform that applied augmented reality technology. The potential of the metaverse as a new educational environment is suggested to be as follows: a space for new social communication; a higher degree of freedom to create and share; and the provision of new experiences and high immersion through virtualization. Some of its limitations may be weaker social connections and the possibility of privacy impingement; the commission of various crimes due to the virtual space and anonymity of the metaverse; and maladaptation to the real world for students whose identity has not been established. The metaverse is predicted to change our daily life and economy beyond the realm of games and entertainment. The metaverse has infinite potential as a new social communication space. The following future tasks are suggested for the educational use of the metaverse: first, teachers should carefully analyze how students understand the metaverse; second, teachers should design classes for students to solve problems or perform projects cooperatively and creatively; third, educational metaverse platforms should be developed that prevent misuse of student data.

Porcine epidemic diarrhea virus (PEDV), a porcine enteropathogenic coronavirus, causes lethal watery diarrhea in piglets, resulting in large economic losses because of high mortality. In November 2013, PEDV reemerged in Korea, and these outbreaks have since continuously occurred. In the present study, we determined the full-length nucleocapsid (N) gene sequences of three Korean PEDV field isolates collected in 2014-2015. Sequence and phylogenetic analysis of N genes revealed that recent prevalent Korean PEDV isolates were very closely related to the US PEDV isolates in 2013. Interestingly, the phylogenetic tree based on the nucleotide sequencing of the PEDV N gene was similar to the tree topology of the PEDV complete genomes. Therefore, our data provide a better understanding of the genetic diversity and contribute to the accurate diagnosis and development of vaccines against PEDV.
Coronavirus ; Diagnosis ; Diarrhea ; Disease Outbreaks ; Genetic Variation* ; Genome ; Korea* ; Mortality ; Nucleocapsid* ; Porcine epidemic diarrhea virus* ; Trees ; Vaccines

Purpose: In this study, we aimed to determine the clinicopathologic, radiologic, and molecular significance of the tumor invasiveness to further stratify the patients with high-grade (HG) upper tract urothelial carcinoma (UTUC) who can be treated less aggressively. Materials and Methods: Clinicopathologic and radiologic characteristics of 166 surgically resected HG UTUC (48 noninvasive, and 118 invasive) cases were evaluated. Six noninvasive UTUC cases with intratumoral tumor grade heterogeneity were selected for whole-exome sequencing (WES) to understand the underlying molecular pathophysiology. Barcode-tagging sequencing was done for validation of the target genes from WES data. Results: Patients with noninvasive UTUC showed no cancer-specific death with better cancer-specific survival (p < 0.001) and recurrence-free survival (p < 0.001) compared to the patients with invasive UTUC. Compared to the invasive UTUC, noninvasive UTUC was correlated to a low grade (LG) on the preoperative abdominal computed tomography (CT) grading system (p < 0.001), histologic intratumoral tumor grade heterogeneity (p=0.018), discrepancy in preoperative urine cytology diagnosis (p=0.018), and absence of urothelial carcinoma in situ (p < 0.001). WES of the heterogeneous components showed mutually shared HRAS and FGFR3 mutations shared between the HG and LG components. HRAS mutation was associated with the lower grade on preoperative abdominal CT and intratumoral tumor grade heterogeneity (p=0.045 and p < 0.001, respectively), whereas FGFR3 mutation was correlated to the absence of carcinoma in situ (p < 0.001). Conclusion According to our comprehensive analysis, HG noninvasive UTUC can be preoperatively suspected based on distinct preoperative radiologic, cytologic, histologic, and molecular features. Noninvasive HG UTUC shows excellent prognosis and thus should be treated less aggressively.

Serotonin (5-hydroxytryptamine (5-HT)) is a neurotransmitter that regulates a variety of functions in the nervous, gastrointestinal and cardiovascular systems. Despite such importance, 5-HT signaling pathways are not entirely clear. We demonstrated previously that 4-aminopyridine (4-AP)-sensitive voltage-gated K+ (Kv) channels determine the resting membrane potential of arterial smooth muscle cells and that the Kv channels are inhibited by 5-HT, which depolarizes the membranes. Therefore, we hypothesized that 5-HT contracts arteries by inhibiting Kv channels. Here we studied 5-HT signaling and the detailed role of Kv currents in rat mesenteric arteries using patch-clamp and isometric tension measurements. Our data showed that inhibiting 4-AP-sensitive Kv channels contracted arterial rings, whereas inhibiting Ca2+-activated K+, inward rectifier K+ and ATP-sensitive K+ channels had little effect on arterial contraction, indicating a central role of Kv channels in the regulation of resting arterial tone. 5-HT-induced arterial contraction decreased significantly in the presence of high KCl or the voltage-gated Ca2+ channel (VGCC) inhibitor nifedipine, indicating that membrane depolarization and the consequent activation of VGCCs mediate the 5-HT-induced vasoconstriction. The effects of 5-HT on Kv currents and arterial contraction were markedly prevented by the 5-HT2A receptor antagonists ketanserin and spiperone. Consistently, alpha-methyl 5-HT, a 5-HT2 receptor agonist, mimicked the 5-HT action on Kv channels. Pretreatment with a Src tyrosine kinase inhibitor, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, prevented both the 5-HT-mediated vasoconstriction and Kv current inhibition. Our data suggest that 4-AP-sensitive Kv channels are the primary regulator of the resting tone in rat mesenteric arteries. 5-HT constricts the arteries by inhibiting Kv channels via the 5-HT2A receptor and Src tyrosine kinase pathway.
4-Aminopyridine/pharmacology ; Action Potentials ; Animals ; Calcium Channel Blockers/pharmacology ; Calcium Channels/metabolism ; Cells, Cultured ; Ketanserin/pharmacology ; Male ; Mesenteric Arteries/drug effects/*metabolism/physiology ; Muscle Contraction ; Muscle, Smooth, Vascular/cytology/drug effects/metabolism/physiology ; Myocytes, Smooth Muscle/drug effects/metabolism/physiology ; Nifedipine/pharmacology ; Potassium Channel Blockers/pharmacology ; Potassium Channels, Voltage-Gated/antagonists & inhibitors/*metabolism ; Protein Kinase Inhibitors/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, Serotonin, 5-HT2A/*metabolism ; Serotonin/*pharmacology ; Serotonin 5-HT2 Receptor Antagonists/pharmacology ; Spiperone/pharmacology ; *Vasoconstriction ; src-Family Kinases/antagonists & inhibitors/*metabolism

PURPOSE: The mechanism including changes of proteome within cavernosal tissue after cavernous nerve injury were not evaluated. We performed proteomics and functional analysis to identify proteins of penile corpus cavernosum whose expression was or was not altered by cavernous nerve resection (CNR). MATERIALS AND METHODS: Using 8-week-old male WKY rats, sham and CNR operation under microscope were performed. After 8 weeks, penile tissues of sham and CNR group were harvested. We used 2-DE and MALDI-TOF/TOF (AB 4700) to identify of differently expressed penile proteins. 2-DE gels were stained with silver nitrate and the gels were analyzed with PDQuest. RESULTS: We isolated more than 950 proteins on silver-stained gels of whole protein extracts from normal rat penile corpus cavernous. Of these proteins, 48 prominent proteins were identified using MALDI-TOF/TOF. Protein characterization revealed that the most prominent penile corpus cavernous proteins were those with antioxidant, chaperone, or cytoskeletal structure. Moreover, 11 proteins having levels elevated by CNR were annexin proteins, endoplasmic reticulum protein 29, glutathione s-transferase w-1, and others. In addition, Rho-GDP dissociation inhibitor (RhoGDI), a regulator of Rho proteins, was also increased in CNR rats compared with sham-operated control rats. CONCLUSIONS: The apoptotic signals observed in penile tissues was greatly increased in CNR rats than in sham-operated rats. These results suggest that RhoGDI is one of the proteins regulated by CNR in penile smooth muscle strips, and has a crucial role in the early stage of penile apoptosis.
Animals ; Apoptosis ; Caves ; Dissociative Disorders ; Endoplasmic Reticulum ; Erectile Dysfunction ; Gels ; Glutathione Transferase ; Humans ; Male ; Muscle, Smooth ; Proteins ; Proteome ; Proteomics ; Rats ; Rats, Inbred WKY ; rho-Specific Guanine Nucleotide Dissociation Inhibitors ; Salicylamides ; Silver Nitrate