Diabetes mellitus is increasing all over the world and is a serious health problem. Pancreatic islet transplantation is promising treatment for diabetes mellitus, but an imbalance between deceased pancreas donors and recipients limited the widespread clinical application. Therefore, pig islets could be used as an alternative islet source in transplantation. However, a big hurdle to clinical application of islet xenotransplantation is the instant blood mediated inflammatory reaction (IBMIR), which is characterized by activation of the coagulation cascade, platelets and complement systems. Innate immune cells infiltrate the islets in the process of IBMIR and thereby accelerate the early graft loss. Characteristics of IBMIR in islet xenotransplantion are very different from the rejection in solid organ xenotransplantation. Therefore, we focus on the molecules for surmounting IBMIR in order to accomplish successful islet xenotransplantation. To prevent the IBMIR in islet xenotransplantation, development of genetic modified pigs containing anti-coagulant, anti-thrombosis and complement regulatory genes, or capsulation of islet with biomaterials for blocking immune response around islet surface can be tried. Galpha-Gal knockout pigs and the diverse transgenic pigs for complement regulatory protein or anti-coagulant genes have been developed for xenotransplantation. This review summarized on characteristics of rejection in islet xenotransplantation and discusses the strategies for overcoming the rejection.
Biocompatible Materials ; Blood Platelets ; Complement System Proteins ; Diabetes Mellitus ; Genes, Regulator ; Humans ; Islets of Langerhans ; Pancreas ; Rejection (Psychology) ; Swine ; Tissue Donors ; Transplantation, Heterologous ; Transplants

PURPOSE: Wnt signaling plays an essential role in the dental epithelium and mesenchyme during tooth morphogenesis. Deletion of the Wntless (Wls) gene in odontoblasts appears to reduce canonical Wnt activity, leading to inhibition of odontoblast maturation. However, it remains unclear if autonomous Wnt ligands are necessary for differentiation of dental pulp cells into odontoblast-like cells to induce reparative dentinogenesis, one of well-known feature of pulp repair to form tertiary dentin. MATERIALS AND METHODS: To analyze the autonomous role of Wls for differentiation of dental pulp cells into odontoblast-like cells, we used primary dental pulp cells from unerupted molars of Wls-floxed allele mouse after infection with adenovirus for Cre recombinase expression to knockout the floxed Wls gene or control GFP expression. The differentiation of dental pulp cells into odontoblast-like cells was analyzed by quantitative real-time polymerase chain reaction. RESULT: Proliferation rate was significantly decreased in dental pulp cells with Cre expression for Wls knockout. The expression levels of Osterix (Osx), runt-related transcription factor 2 (Runx2), and nuclear factor I-C (Nfic) were all significantly decreased by 0.3-fold, 0.2-fold, and 0.3-fold respectively in dental pulp cells with Wls knockout. In addition, the expression levels of Bsp, Col1a1, Opn, and Alpl were significantly decreased by 0.7-fold, 0.3-fold, 0.8-fold, and 0.6-fold respectively in dental pulp cells with Wls knockout. CONCLUSION: Wnt ligands produced autonomously are necessary for proper proliferation and odontoblastic differentiation of mouse dental pulp cells toward further tertiary dentinogenesis.
Adenoviridae ; Alleles ; Animals ; Dental Pulp* ; Dentin ; Dentinogenesis ; Epithelium ; Ligands ; Mesoderm ; Mice* ; Molar ; Morphogenesis ; NFI Transcription Factors ; Odontoblasts* ; Real-Time Polymerase Chain Reaction ; Recombinases ; Tooth ; Transcription Factors

Oseltamivir is the drug of choice for patients with pandemic influenza (H1N1 2009). However, sporadic cases of oseltamivir resistance have been described worldwide. Up to March 2010, a total of 11 strains (2.2% of tested isolates) of oseltamivir-resistant pandemic influenza (H1N1 2009) have been discovered in South Korea. We report a case of 46-year-old man with acute myeloid leukemia in whom an oseltamivir-resistant pandemic (H1N1) 2009 virus was isolated. Despite high dose oseltamivir therapy for 10 days he had persistent symptoms and showed positive results in repeated real-time RT-PCR for pandemic influenza (H1N1 2009) virus from nasopharyngeal specimen. The patient improved eventually after oseltamivir was replaced by zanamivir inhalation.
Humans ; Influenza, Human ; Inhalation ; Leukemia ; Leukemia, Myeloid, Acute ; Middle Aged ; Oseltamivir ; Pandemics ; Republic of Korea ; Viruses ; Zanamivir

PURPOSE: We conducted a multi-center randomized double-blind study to determine the effects of 6-month therapy with sulodexide on urinary protein excretion in patients with idiopathic Immunoglobulin A (IgA) nephropathy. MATERIALS AND METHODS: A total of seventy-seven patients participated in the study. They were randomly allocated to one of three groups: sulodexide 75 mg or 150 mg daily or the placebo for 6 months. The primary end point was the achievement, at 6 months, of at least 50% reduction in urine protein/creatinine ratio (UPCR) from the baseline value. RESULTS: At 6 months, the primary end point was achieved by 12.5% of the patients assigned to the placebo, 4.0% of the patients assigned to sulodexide 75 mg daily and 21.4% of those assigned to 150 mg (p=0.308). Treatment with sulodexide 150 mg daily for 6 months significantly reduced log UPCR from 6.38+/-0.77 at baseline to 5.98+/-0.94 at 6 months (p=0.045), while treatment with sulodexide 75 mg daily and placebo did not. CONCLUSION: A 6-month treatment with sulodexide did not achieve 50% reduction of urinary protein excretion in IgA nephropathy patients, but showed a tendency to increase the time-dependent anti-proteinuric effect. Therefore, long-term clinical trials on a larger scale are warranted to elucidate the hypothesis that sulodexide affords renal protection in IgA nephropathy patients.
Adult ; Anticoagulants/*therapeutic use ; Double-Blind Method ; Female ; Glomerulonephritis, IGA/complications/*drug therapy ; Glycosaminoglycans/*therapeutic use ; Humans ; Male ; Middle Aged ; Proteinuria/complications/*drug therapy

Objectives: Monkeypox outbreaks in nonendemic countries have been reported since early May 2022. The first case of monkeypox in the Republic of Korea was confirmed in a patient who traveled to Europe in June 2022, and an attempt was made to isolate and identify the monkeypox virus (MPXV) from the patient’s specimens. Methods: Clinical specimens from the patient were inoculated in Vero E6 cells. The isolated virus was identified as MPXV by the observation of cytopathic effects on Vero E6 cells, transmission electron microscopy, conventional polymerase chain reaction (PCR), and sequencing of PCR products. Results: Cytopathic effects were observed in Vero E6 cells that were inoculated with skin lesion swab eluates. After multiple passages from the primary culture, orthopoxvirus morphology was observed using transmission electron microscopy. In addition, both MPXV-specific (F3L and ATI) and orthopoxvirus-specific genes (A39R, B2R, and HA) were confirmed by conventional PCR and Sanger sequencing. Conclusion These results indicate the successful isolation and identification of MPXV from the first patient in the Republic of Korea. The isolated virus was named MPXV-ROK-P1-2022.

Regulation of osteoblast and osteocyte viability is essential for bone homeostasis. Smad4, a major transducer of bone morphogenetic protein and transforming growth factor-β signaling pathways, regulates apoptosis in various cell types through a mitochondrial pathway. However, it remains poorly understood whether Smad4 is necessary for the regulation of osteoblast and osteocyte viability. In this study, we analyzed Smad4Δ(Os) mice, in which Smad4 was subjected to tissue-specific disruption under the control of the 2.3-kb Col1a1 promoter, to understand the functional significance of Smad4 in regulating osteoblast/osteocyte viability during bone formation and remodeling. Smad4Δ(Os) mice showed a significant increase in osteoblast number and osteocyte density in the trabecular and cortical regions of the femur, whereas osteoclast activity was significantly decreased. The proliferation of osteoblasts/osteocytes did not alter, as shown by measuring 5′-bromo-2′deoxyuridine incorporation. By contrast, the percentage of TUNEL-positive cells decreased, together with a decrease in the Bax/Bcl-2 ratio and in the proteolytic cleavage of caspase 3, in Smad4Δ(Os) mice. Apoptosis in isolated calvaria cells from Smad4Δ(Os) mice decreased after differentiation, which was consistent with the results of the TUNEL assay and western blotting in Smad4Δ(Os) mice. Conversely, osteoblast cells overexpressing Smad4 showed increased apoptosis. In an apoptosis induction model of Smad4Δ(Os) mice, osteoblasts/osteocytes were more resistant to apoptosis than were control cells, and, consequently, bone remodeling was attenuated. These findings indicate that Smad4 has a significant role in regulating osteoblast/osteocyte viability and therefore controls bone homeostasis.
Animals ; Apoptosis ; Blotting, Western ; Bone Morphogenetic Proteins ; Bone Remodeling ; Caspase 3 ; Femur ; Homeostasis* ; In Situ Nick-End Labeling ; Mice ; Osteoblasts ; Osteoclasts ; Osteocytes ; Osteogenesis ; Skull ; Transducers

Cell permeable peptide (CPP) is able to transport itself or conjugated molecules such as nucleotides, peptides, and proteins into cells. Since short peptide of human immunodeficiency virus-1 Tat has been discovered as CPP, it has been continuously studied for their ability to transport heterologous cargoes into cells. In this study, we have focused on the fusion protein of respiratory syncytial virus (RSV), which has six basic amino acids in multi basic furin-dependent cleavage site (MBFCS) required to be cationic CPP. To develop more efficient CPP, the sequence, which linked two MBFCS, was synthesized (called RS-CPP). To assess cell permeable efficiency of RS-CPP or MBFCS, the peptides was conjugated with fluorescein isothiocyanate, and cell permeable efficiency was measured by fluorescence-activated cell sorting. Cell permeability of RS-CPP or MBFCS was increased in a dose-dependent manner, but RS-CPP showed more efficient cell permeability than MBFCS in MDCK, HeLa, Vero E6, and A549 cells. To evaluate whether RS-CPP can transport its conjugated functional peptide (VIVIT) in CD8+ T cell, it was confirmed that IL-2 and β-galactosidase expression were significantly inhibited through selective block of nuclear factor activated T-cell. To investigate endocytic pathways, Cre-mediated DNA recombination (loxP-STOP-loxP-LacZ reporter system) was investigated with divergent endocytosis inhibitors in TE671 cells, and RS-CPP endocytosis is occurred via binding cell surface glycosaminoglycan and clathrin-mediated endocytosis, or macropinocytosis. These results indicated that RS-CPP could be a novel cationic CPP, and it would help understanding for delivery of biologically functional molecules based on viral basic amino acids.
Amino Acids, Basic ; DNA ; Endocytosis ; Flow Cytometry ; Fluorescein ; Humans ; Interleukin-2 ; Nucleotides ; Peptides ; Permeability ; Recombination, Genetic ; Respiratory Syncytial Viruses* ; T-Lymphocytes

BACKGROUND/OBJECTIVES: Numerous researches have studied the association between sugar intake and obesity of children in many countries. This study was undertaken to investigate the association between beverage intake and obesity of children by reviewing a database for total sugar contents established in all foods and presented in a nutrition survey by the Korea National Health and Nutrition Examination Survey (KNHANES). SUBJECTS/METHODS: Data of 1,520 children aged 6–11 years in the 6th KNHANES (2013–2015) were analyzed for this study. A database for total sugar intake comprises the total sugar contents of all foods included in the results of a nutrition survey using the 24-hour recall method of 6th KNHANES. Beverages were categorized into carbonated beverages, fruit & vegetable drinks, other drinks, tea, and coffee. RESULTS: The average daily beverage intake of all children was 131.75 g/day, and the average daily total sugar intake in beverages was 13.76 g/day. Carbonated beverages had the highest intake rate (58.85 g/day) and also ranked highest for sugar intake (6.36 g/day). After adjusting for confounding variables, the odds ratio for obesity in children with beverage intake of ≥ 200 mL/day significantly increased by 1.83 times (95% CI, 1.11–3.00) as compared to children with beverage intake of < 200 mL/day. Also, a significant increase was observed in the odds ratio for obesity in total children (2.41 times; 95% CI, 1.35–4.33) and boys (3.15 times; 95% CI, 1.53–6.49) with carbonated beverage intake of ≥ 200 mL/day when compared with children who consumed < 200 mL/day. CONCLUSION: A positive association is observed between beverage intake and obesity in Korean children. In particular, an intake of carbonated beverages has a positive correlation with childhood obesity in boys. This study can therefore be used as scientific evidence for reducing sugar, and for the continuous management and research on beverages.
Beverages* ; Carbohydrates ; Carbonated Beverages ; Child* ; Coffee ; Confounding Factors (Epidemiology) ; Fruit ; Humans ; Korea* ; Methods ; Nutrition Surveys* ; Obesity* ; Odds Ratio ; Pediatric Obesity ; Tea ; Vegetables

Purpose: To report preliminary experience of single-port robotic surgery using the da Vinci SP surgical system in gynecologic tumors. Materials and Methods: This was a retrospective study on 100 consecutive patients who underwent da Vinci SP single-port robotic surgery between November 2018 and January 2021. All procedures were performed by an experienced gynecologic surgeon using a single 2.5-cm umbilical incision. Results: Of the 100 cases, the procedures included myomectomy (n=76), hysterectomy (n=2), endometrial cancer surgical staging (n=14), radical hysterectomy (n=3), radical trachelectomy (n=3), and ovarian cystectomy (n=2). None of the cases was converted to robotic multiport or open surgery. The median docking time was 5.0 minutes [interquartile range (IQR), 3.0–7.0], the median console time was 107.5 minutes (IQR, 78.7–155.8), and the median total operation time was 250.0 minutes (IQR, 215.0–310.0). The median estimated blood loss was 50.0 mL (IQR, 30.0–100.0), and the median change in hemoglobin level was 0.8 g/dL (IQR, 0.3–1.3). The median pain scores rated on a numerical rating scale immediately after and at 6, 12, and 24 hours after surgery were 5, 2, 2, and 2, respectively. The mean duration of postoperative hospitalization was 2.8 days. Conclusion Da Vinci SP single-port robotic surgery was successfully performed in various gynecologic tumors without significant complications. Therefore, this surgical system could be applied in patients who want precise gynecologic surgery while minimizing surgical incision.

We aimed to characterize the genomes of monkeypox virus isolates from the Far East, providing insights into viral transmission and evolution. Genomic analysis was conducted on 8 isolates obtained from patients with monkeypox virus disease in the Republic of Korea between May 2022 and early 2023. These isolates were classified into Clade IIb. Distinct lineages, including B.1.1, A.2.1, and B.1.3, were observed in 2022 and 2023 isolates, with only the B.1.3 lineage detected in six isolates of 2023. These genetic features were specific to Far East isolates (the Republic of Korea, Japan, and Taiwan), distinguishing them from the diverse lineages found in the Americas, Europe, Africa, and Oceania. In early 2023, the prevalence of the B.1.3 lineage of monkeypox virus identified in six patients with no overseas travel history is considered as an indicator of the potential initiation of local transmission in the Republic of Korea.