• Korean Journal of Clinical Laboratory Science
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• v.55 no.4
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• pp.284-290
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• 2023

Adefovir dipivoxil (ADV) is used for the treatment of hepatitis and acquired immunodeficiency syndrome, but long-term use can cause osteoporosis. In this study, the effect of ADV on the osteocyte maturation process was evaluated at the level of undifferentiated cells using mesenchymal stem cells (MSCs) and osteoblasts (MG63). First, MSCs and MG63 cells were treated with ADV at different concentrations, and then a Cell Counting Kit-8 analysis was performed to determine the effect on the proliferation of each cell. Additionally, crystal violet and Hoechst staining were performed for the morphological analysis of each cell and nucleus. To determine the cause of cell hypertrophy, the transforming growth factor-beta (TGF-β) expression was investigated, and alkaline phosphatase (ALP) staining and activity were measured to determine the degree of differentiation of the MSCs and MG63 cells into mature osteocytes. The results confirmed that the ADV increases the expression of TGF-β in MSCs and MG63 cells, causing cellular and nuclear hypertrophy, and can cause osteoporosis by inhibiting cell proliferation and affecting the differentiation of mature osteocytes. Therefore, it is believed that these results can be used as a basis for understanding the adverse effects of ADV at a cytological level in basic medicine and clinical research.

• Journal of the Korean Society of Radiology
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• v.82 no.4
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• pp.1018-1023
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• 2021

A meandering pulmonary vein (MPV) is a rare pulmonary vascular anomaly characterized by an abnormal course of the pulmonary vein draining into the left atrium. We report the case of a 55-year-old female who was diagnosed with a right MPV on pulmonary angiography. Enhanced chest CT revealed a vascular structure with an abnormal course that drained into the right superior pulmonary vein in the right upper lobe, which resembled a pulmonary arteriovenous malformation (AVM). Pulmonary angiography performed to discriminate between an MPV and pulmonary AVM showed no feeding artery, normal parenchymal staining, and drainage to the left atrium via the culprit vessel. Thus, the patient was diagnosed with MPV. When an MPV is difficult to differentiate from other vascular anomalies on enhanced chest CT, pulmonary angiography can be helpful. By recognizing the angiographic findings of an MPV, unnecessary treatment can be prevented.

• Korean Journal of Radiology
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• v.25 no.5
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• pp.481-492
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• 2024

Objective: To evaluate the clinical and imaging characteristics of SARS-CoV-2 breakthrough infection in hospitalized immunocompromised patients in comparison with immunocompetent patients. Materials and Methods: This retrospective study analyzed consecutive adult patients hospitalized for COVID-19 who received at least one dose of the SARS-CoV-2 vaccine at two academic medical centers between June 2021 and December 2022. Immunocompromised patients (with active solid organ cancer, active hematologic cancer, active immune-mediated inflammatory disease, status post solid organ transplantation, or acquired immune deficiency syndrome) were compared with immunocompetent patients. Multivariable logistic regression analysis was performed to evaluate the effect of immune status on severe clinical outcomes (in-hospital death, mechanical ventilation, or intensive care unit admission), severe radiologic pneumonia (≥ 25% of lung involvement), and typical CT pneumonia. Results: Of 2218 patients (mean age, 69.5 ± 16.1 years), 274 (12.4%), and 1944 (87.6%) were immunocompromised an immunocompetent, respectively. Patients with active solid organ cancer and patients status post solid organ transplantation had significantly higher risks for severe clinical outcomes (adjusted odds ratio = 1.58 [95% confidence interval {CI}, 1.01-2.47], P = 0.042; and 3.12 [95% CI, 1.47-6.60], P = 0.003, respectively). Patient status post solid organ transplantation and patients with active hematologic cancer were associated with increased risks for severe pneumonia based on chest radiographs (2.96 [95% CI, 1.54-5.67], P = 0.001; and 2.87 [95% CI, 1.50-5.49], P = 0.001, respectively) and for typical CT pneumonia (9.03 [95% CI, 2.49-32.66], P < 0.001; and 4.18 [95% CI, 1.70-10.25], P = 0.002, respectively). Conclusion: Immunocompromised patients with COVID-19 breakthrough infection showed an increased risk of severe clinical outcome, severe pneumonia based on chest radiographs, and typical CT pneumonia. In particular, patients status post solid organ transplantation was specifically found to be associated with a higher risk of all three outcomes than hospitalized immunocompetent patients.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.27 no.3
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• pp.158-167
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• 2024

Purpose: To evaluate the prevalence of vertebral fracture (VF) in children with chronic liver disease (CLD) with and without liver transplantation (LT) and to determine the associated factors. Methods: A cross-sectional study was conducted. Patients aged 3-21 years with CLD both before and after LT were enrolled in the study. Lateral thoracolumbar spine radiographs were obtained and assessed for VF using Mäkitie's method. Clinical and biochemical data were collected. Results: We enrolled 147 patients (80 females; median age 8.8 years [interquartile range 6.0-11.8]; 110 [74.8%] in the LT group and 37 [25.2%] in the non-LT group). VF was identified in 21 patients (14.3%): 17/110 (15.5%) in the LT group and 4/37 (10.8%) in the non-LT group (p=0.54). Back pain was noted in only three patients with VF. In the univariate analysis, a height z-score below -2.0 (p=0.010), pre-LT hepatopulmonary syndrome (p=0.014), elevated serum direct and total bilirubin levels (p=0.037 and p=0.049, respectively), and vitamin D deficiency at 1-year post-LT (p=0.048) were associated with VF in the LT group. In multivariate analysis, height z-score below -2.0 was the only significant associated factor (odds ratio, 5.94; 95% confidence interval, 1.49-23.76; p=0.012) for VF. All VFs in the non-LT group were reported in males. Conclusion: In children with CLD, VF is common before and after LT. Most patients with VF are asymptomatic. Screening for VF should be considered in patients with a height z-score below -2.0 after LT.

• IMMUNE NETWORK
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• v.22 no.2
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• pp.18.1-18.15
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• 2022

Dysfunction of mitochondrial metabolism is implicated in cellular injury and cell death. While mitochondrial dysfunction is associated with lung injury by lung inflammation, the mechanism by which the impairment of mitochondrial ATP synthesis regulates necroptosis during acute lung injury (ALI) by lung inflammation is unclear. Here, we showed that the impairment of mitochondrial ATP synthesis induces receptor interacting serine/threonine kinase 3 (RIPK3)-dependent necroptosis during lung injury by lung inflammation. We found that the impairment of mitochondrial ATP synthesis by oligomycin, an inhibitor of ATP synthase, resulted in increased lung injury and RIPK3 levels in lung tissues during lung inflammation by LPS in mice. The elevated RIPK3 and RIPK3 phosphorylation levels by oligomycin resulted in high mixed lineage kinase domain-like (MLKL) phosphorylation, the terminal molecule in necroptotic cell death pathway, in lung epithelial cells during lung inflammation. Moreover, the levels of protein in bronchoalveolar lavage fluid (BALF) were increased by the activation of necroptosis via oligomycin during lung inflammation. Furthermore, the levels of ATP5A, a catalytic subunit of the mitochondrial ATP synthase complex for ATP synthesis, were reduced in lung epithelial cells of lung tissues from patients with acute respiratory distress syndrome (ARDS), the most severe form of ALI. The levels of RIPK3, RIPK3 phosphorylation and MLKL phosphorylation were elevated in lung epithelial cells in patients with ARDS. Our results suggest that the impairment of mitochondrial ATP synthesis induces RIPK3-dependent necroptosis in lung epithelial cells during lung injury by lung inflammation.

• IMMUNE NETWORK
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• v.21 no.6
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• pp.41.1-41.13
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• 2021

Correlation between vaccine reactogenicity and immunogenicity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Thus, we investigated to determine whether the reactogenicity after coronavirus disease 2019 vaccination is associated with antibody (Ab) titers and T cell responses. This study was prospective cohort study done with 131 healthcare workers at tertiary center in Seoul, South Korea. The degrees of the local reactions after the 1st and 2nd doses of ChAdOx1 nCov-19 (ChAdOx1) vaccination were significantly associated with the S1-specific IgG Ab titers (p=0.003 and 0.01, respectively) and neutralizing Ab (p=0.04 and 0.10, respectively) in age- and sex-adjusted multivariate analysis, whereas those after the BNT162b2 vaccination did not show significant associations. T cell responses did not show significant associations with the degree of reactogenicity after the ChAdOx1 vaccination or the BNT162b2 vaccination. Thus, high degree of local reactogenicity after the ChAdOx1 vaccine may be used as an indicator of strong humoral immune responses against SARS-CoV-2.

• IMMUNE NETWORK
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• v.21 no.4
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• pp.29.1-29.9
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• 2021

There are limited data directly comparing humoral and T cell responses to the ChAdOx1 nCoV-19 and BNT162b2 vaccines. We compared Ab and T cell responses after first doses of ChAdOx1 nCoV-19 vs. BNT162b2 vaccines. We enrolled healthcare workers who received ChAdOx1 nCoV-19 or BNT162b2 vaccine in Seoul, Korea. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S1 protein-specific IgG Abs (S1-IgG), neutralizing Abs (NT Abs), and SARS-CoV-2-specific T cell response were evaluated before vaccination and at 1-wk intervals for 3 wks after vaccination. A total of 76 persons, comprising 40 injected with the ChAdOx1 vaccine and 36 injected with the BNT162b2 vaccine, participated in this study. At 3 wks after vaccination, the mean levels (±SD) of S1-IgG and NT Abs in the BNT162b2 participants were significantly higher than in the ChAdOx1 participants (S1-IgG, 14.03±7.20 vs. 6.28±8.87, p<0.0001; NT Ab, 183.1±155.6 vs. 116.6±116.2, p=0.035), respectively. However, the mean values of the T cell responses in the 2 groups were comparable after 2 wks. The humoral immune response after the 1st dose of BNT162b2 developed faster and was stronger than after the 1st dose of ChAdOx1. However, the T cell responses to BNT162b2 and ChAdOx1 were similar.

• IMMUNE NETWORK
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• v.21 no.6
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• pp.38.1-38.8
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• 2021

Recently, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (B.1.1.529) Omicron variant originated from South Africa in the middle of November 2021. SARS-CoV-2 is also called coronavirus disease 2019 (COVID-19) since SARS-CoV-2 is the causative agent of COVID-19. Several studies already suggested that the SARS-CoV-2 Omicron variant would be the fastest transmissible variant compared to the previous 10 SARS-CoV-2 variants of concern, interest, and alert. Few clinical studies reported the high transmissibility of the Omicron variant but there is insufficient time to perform actual experiments to prove it, since the spread is so fast. We analyzed the SARS-CoV-2 Omicron variant, which revealed a very high rate of mutation at amino acid residues that interact with angiostatin-converting enzyme 2. The mutation rate of COVID-19 is faster than what we prepared vaccine program, antibody therapy, lockdown, and quarantine against COVID-19 so far. Thus, it is necessary to find better strategies to overcome the current crisis of COVID-19 pandemic.

• IMMUNE NETWORK
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• v.20 no.5
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• pp.41.1-41.11
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• 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is a positive-sense single-stranded RNA (+ssRNA) that causes coronavirus disease 2019 (COVID-19). The viral genome encodes twelve genes for viral replication and infection. The third open reading frame is the spike (S) gene that encodes for the spike glycoprotein interacting with specific cell surface receptor - angiotensin converting enzyme 2 (ACE2) - on the host cell membrane. Most recent studies identified a single point mutation in S gene. A single point mutation in S gene leading to an amino acid substitution at codon 614 from an aspartic acid 614 into glycine (D614G) resulted in greater infectivity compared to the wild type SARS-CoV2. We were interested in investigating the mutation region of S gene of SARS-CoV2 from Korean COVID-19 patients. New mutation sites were found in the critical receptor binding domain (RBD) of S gene, which is adjacent to the aforementioned D614G mutation residue. This specific sequence data demonstrated the active progression of SARS-CoV2 by mutations in the RBD of S gene. The sequence information of new mutations is critical to the development of recombinant SARS-CoV2 spike antigens, which may be required to improve and advance the strategy against a wide range of possible SARS-CoV2 mutations.

• International Journal of Stem Cells
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• v.16 no.2
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• pp.191-201
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• 2023

Background and Objectives: O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung. Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice. Methods and Results: cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSC^cP1P), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSC^cP1P reduce inflammatory response in LPS exposed mice. hdMSC^cP1P further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSC^cP1P treated mice. Conclusions: Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSC^cP1P provide a therapeutic potential for ALI/ARDS treatment.