• Toxicological Research
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• 제31권1호
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• pp.33-40
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• 2015

Bee venom (BV) has long been used in traditional Eastern and Western medicine for chronic inflammation, pain and skin therapy. Human exposure to BV, however, often causes unwanted adverse effects and is even fatal in some cases. Phospholipase $A_2$ ($PLA_2$) of BV is now suspected to play a key role in these adverse effects. We investigated the potential use of $PLA_2$-free bee venom (PBV) as a replacement for BV in cosmetic products. PBV prepared by molecular weight cut-off ultrafiltration exhibits a superior profile in comparison with regular BV, by inhibiting elastase activity and suppressing the induction of nitric oxide (NO) and metalloproteinase-9 (MMP-9), while retaining the effects of cell proliferation and protection against ultraviolet B (UVB)-induced damage in human dermal fibroblast cells. PBV thus appears to be more promising than BV as a cosmetic ingredient with a reduced potential for adverse reactions in the recipient.

• Clinical and Experimental Reproductive Medicine
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• 제47권2호
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• pp.94-100
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• 2020

The inverse correlation between maternal age and pregnancy rate represents a major challenge for reproductive endocrinology. The high embryo ploidy error rate in failed in vitro fertilization (IVF) cycles reflects genetic misfires accumulated by older oocytes over time. Despite the application of different follicular recruitment protocols during IVF, gonadotropin modifications are generally futile in addressing such damage. Even when additional oocytes are retrieved, quality is frequently poor. Older oocytes with serious cytoplasmic and/or chromosomal errors are often harvested from poorly perfused follicles, and ovarian vascularity and follicular oxygenation impact embryonic chromosomal competency. Because stimulation regimens exert their effects briefly and immediately before ovulation, gonadotropins alone are an ineffective antidote to long-term hypoxic pathology. In contrast, the tissue repair properties (and particularly the angiogenic effects) of platelet-rich plasma (PRP) are well known, with applications in other clinical contexts. Injection of conventional PRP and/or its components (e.g., isolated platelet-derived growth factors as a cell-free substrate) into ovarian tissue prior to IVF has been reported to improve reproductive outcomes. Any derivative neovascularity may modulate oocyte competence by increasing cellular oxygenation and/or lowering concentrations of intraovarian reactive oxygen species. We propose a mechanism to support intrastromal angiogenesis, improved follicular perfusion, and, crucially, embryo ploidy rescue. This last effect may be explained by mRNA upregulation coordinated by PRP-associated molecular signaling, as in other tissue systems. Additionally, we outline an intraovarian injection technique for platelet-derived growth factors and present this method to help minimize reliance on donor oocytes and conventional hormone replacement therapy.

• Archives of Pharmacal Research
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• 제27권1호
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• pp.99-105
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• 2004

Isoflavones have been a central subject in research on the natural phytoestrogens found in Leguminosae. Their effects on bone formation and remodeling are important in that they can act like estrogen by binding on estrogen receptors on the target cell surface. We, therefore, believed that isoflavones may help in the treatment of patients with estrogen deficiency disease such as estrogen replacement therapy (ERT) for osteoporosis. As commonly known, osteoporosis is one of the hormonal deficiency diseases, especially in menopausal women. When estrogen is no longer produced in the body a remarkable bone remodeling process occurs, and the associated events are regulated by growth factors in the osteoblast lineage. In the present study, we investigated whether isoflavones (Isocal) extracted from Sophorae fructus affect the growth factors IGF-I and TGF-$\beta$ that have been known to be related with bone formation. In the study, we found that the active control (PIII) effectively enhanced the level of nitric oxide (NO) and growth factors, and thereby inhibited osteoclastogenesis. The most efficient concentration was $10^{-8}$% within five days, whereas the comparative control (soybean isoflavone) was not as effective even at a lower concentration. In conclusion, the products which contain enriched glucosidic isoflavone and nutrient supplements such as shark cartilage and calcium can be used for osteoporosis therapy by enhancing the production of IGF-I and TGF-$\beta$. Furthermore, the NO produced through endothelial constitutive NO synthase (ecNOS) may playa role in inhibiting bone reabsorption.

• Clinical and Experimental Pediatrics
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• 제63권11호
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• pp.447-450
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• 2020

Background: Esophageal stricture (ES) is an uncommon clinic entity in pediatrics that may be congenital or acquired in childhood. Acquired noncaustic ES is very rare, and clinical features of affected patients are unknown. Purpose: We aimed to evaluate the clinical findings, and outcomes of patients with acquired noncaustic ES to aid physicians in the early referral of patients to gastroenterologists. Methods: The medical data of patients with acquired noncaustic ES who were followed in our gastroenterology clinic between January 2009 and December 2019 were reviewed. Results: Acquired noncaustic ES was found in 12 of the 4,950 patients (0.24%) who underwent endoscopy during the study period. The main symptoms were dysphagia (58.3%), vomiting (33.3%), and chronic anemia (8.3%). Chronic malnutrition and underweight were found in 66.6% of the patients. The most common etiological factors were radiotherapy, peptic reflux, and achalasia (16.6%, each), while chemotherapy, squamous-cell carcinoma (SC) of the esophagus, eosinophilic esophagitis (EoE), esophageal web, epidermolysis bullosa, and esophageal diverticulum (8.2%, each) were the other etiological factors. Patients with EoE underwent endoscopic bougie dilation in addition to steroid use and elimination diet. Patients with epidermolysis bullosa and esophageal web underwent bougie dilation. Patients with peptic reflux-related ES were initially put on antireflux therapy, but during follow-up, one patient required esophageal replacement with colonic interposition. Patients with radiotherapy-related ES recovered with medical therapy. The patient with initially underwent surgical gastrostomy and tumoral mass excision. The patient then received chemotherapy and radiotherapy and underwent jejunal interposition. Patients with achalasia underwent surgical esophagomyotomy. Conclusion: The presence of solid dysphagia, malnutrition, and an associated disease may alert physicians to the presence of ES.

• 생명과학회지
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• 제10권1호
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• pp.22-36
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• 2000

The mammary gland contains a subpopulation of epithelial cells with large proliferative potentials which are the likely targets for carcinogens. These clonogenic cells can proliferate and differentiate into functional glandular structures. Multicellular secretory alveolar units (AU) develop from these clonogens in grafts of monodispersed rat mammary epithelial cells (RMEC) in gland-free mammary fat pads in intact recipient F344 rats co-grafted with mammotropic hormone-secreting pituitary tumors (MtT F4). Multicellular nonsecretory ductal units (DU) develop in grafts of monodispersed RMEC in gland-free fat pads in adrenalectomized recipient WF rats co-grafted with MtT W10. However, this effect were reversed by hydrocortisone replacement therapy. RMEC were isolated from appropriate donor rats as monodispersed mixed cells or, alternatively, RNA＋ cells were sorted by flow cytometry of mixed RMEC stained with FITC-RNA and PE-anti-Thy-1.1 monoclonal antibody. We grafted mixed or sorted PNA+ cells in gland-free mammary fat pads in recipient rats that were endocrinologically manipulated to induce AU or DU. Cells were also isolated from these AU or DU as mixed or sorted RNA＋ cells and sub-transplanted in recipient rats treated appropriately to induce AU or DU, respectively. Cells obtained from AU in grafts gave rise to clonal AU and from DU in grafts to DU on sub-transplantation in appropriate recipients. When adrenalectomized recipient WF rats co-grafted with MtT W10 received daily subcutaneous injections of hydrocortisone for periods of 21 days following the PHA＋ cell transplantation, AU, instead of DU, were developed. The histologies of these secondary AU and DU were not different from those of the primary AU and DU. Casein and laminin proteins were demonstrated by immunocytochemical staining of primary and secondary AU. Electron micrographs also demonstrated that AU were composed of secretory cells with milk protein in the cytoplasm. DU were composed of little or non-secretory ductal epithelial cells. These AU and DU also secreted large amounts of lipids. Clonogenic cells were more common in DU than in AU. Thus, AU and DU contain persistent subpopulations of clonogenic stem-like cells.

• Biomolecules & Therapeutics
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• 제17권2호
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• pp.138-143
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• 2009

We have reported previously on a replication incompetent recombinant adenoviral vector, AdLPCD, in which the expression of cytosine deaminase gene (CD) is driven by the tumor-specific L-plastin promoter. AdLPCD vector had been evaluated for its efficacy of chemosensitization of ovarian cancer cells to 5-FC. In spite of the fact that ovarian cancer cells, i.e., OVCAR-3 and SK-OV-3, are capable for adenoviral transduction judged by LacZ reporter gene analysis, two cell lines demonstrated quite different sensitivities toward AdLPCD/5-FC system. In OVCAR-3 cells, infection of AdLPCD followed by exposure to 5-FC resulted in the suppression of cell growth with statistical significance. On the other hand, SK-OV-3 cells were more resistant to the CD/5-FC strategy compared with OVCAR-3 cells under the same condition. The object of study was to investigate factors that would determine the sensitivity to AdLPCD/5-FC. We evaluated conversion rate of 5-FC to 5-FU after infection of AdLPCD by HPLC analysis, $IC_{50}$ of 5-FU, the expression level of integrin receptors i.e., ${\alpha}v{\beta}3$ and ${\alpha}v{\beta}5$, and status of p53 in OVCAR-3 and SK-OV-3 cells. The results indicated that OVCAR-3 cells have few favorable features compared with SK-OV-3 cells to be more effective to the AdLPCD/5-FC strategy; higher level of ${\alpha}v{\beta}5$ integrin, higher rate of conversion of 5-FC into 5-FC, and lower $IC_{50}$ of 5-FU. The results suggest that the replacement of 5-FU with CD/5-FC in combination chemotherapy would be less toxic and much greater cytotoxicity than the conventional combination chemotherapy in some patients.

• 한국환경보건학회지
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• 제11권2호
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• pp.41-54
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• 1985

This study was conducted for the improvement of milk quality and milk hygiene in public health point of view. Investigation of mastiris infection rate, isolation and identification of causative microorganisms in CMT positive milk, investigation of milk contamination level by measuring the bacteria and soma tic cell counts and investigation of dairy management in farms were performed on 1.605 quarters milk of 434 cows of 20 dairy farms in Gyunggi-area from September 1983 to March 1984. The results were summarized as follows 1. Sixteen (3.7%) of 434 cows were found to be infected with clinical mastiris. 234 (53.9%) of 434 cows and 608(37.9%) of 1, 605 quarters were found to be infected with subclinical mastiris. 2. The causative microorganisms isolated were Staphylococcus aureus (38.3%), Staphylococcus epidermidis(21.0%), Micrococci(13.6%), Streptococcus spp. (12.3%), E. coli (7.4%), Fungus & Yeast (1.6%) and others (5.8%). 3. Total numbers of bacteria were $9.2{\times}10^6$ to $1.21{\times}10^7/ml$(av. $1.805{\times} 10^7/ml$), numbers of coliform bacteria were $4.1{\times} 10^5$ to $9.4{\times} 10^5$/ml(av. $7.05{\times} 10^5$/ml) and somatic cell counts were $4.8{\times} 10^5$ to $1.52{\times} 10^6$ cells/ml (av. $9.5{\times} 10^5$cells/ml) in bulk milk. 4. As comparing with CMT score of +, ++ and +++, somatic cell counts were $3.4{\times} 10^5$ to $1.64{\times} 10^6$ cells/ml (av. $6.41{\times} 10^5$cells/ml), $5.4{\times} 10^5$ to $2.75{\times} 10^6$ cells/ml(av. $1.762{\times} 10^6$cells/ml) and $1.97{\times} 10^6$ to $9.75{\times} 10^6$ cells/ml(av. $7.781{\times} 10^6$cells/ml), respectively. 5. In investigation on dairy management, performance of dry cow therapy, teat dipping after milking, disinfection of milking machine at every milking, replacement of milk liner within 6months and opportunity of acquirement for the mastiris control techniques by dairy education were 65%, 40%, 45%, 55% and 50% in 20 dairy farms, respectively.

• 한국수정란이식학회지
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• 제30권3호
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• pp.249-255
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• 2015

Diabetes mellitus, the most common metabolic disorder, is divided into two types: type 1 and type 2. The essential treatment of type 1 diabetes, caused by immune-mediated destruction of ${\beta}-cells$, is transplantation of the pancreas; however, this treatment is limited by issues such as the lack of donors for islet transplantation and immune rejection. As an alternative approach, stem cell therapy has been used as a new tool. The present study revealed that bone marrowderived mesenchymal stromal cells (BM-MSCs) could be transdifferentiated into pancreatic cells by the insertion of a key gene for embryonic development of the pancreas, the pancreatic and duodenal homeobox factor 1 (PDX1). To avoid immune rejection associated with xenotransplantation and to develop a new cell-based treatment, BM-MSCs from ${\alpha}$-1,3-galactosyltransferase knockout (GalT KO) pigs were used as the source of the cells. Transfection of the EGFP-hPDX1 gene into GalT KO pig-derived BM-MSCs was performed by electroporation. Cells were evaluated for hPDX1 expression by immunofluorescence and RT-PCR. Transdifferentiation into pancreatic cells was confirmed by morphological transformation, immunofluorescence, and endogenous pPDX1 gene expression. At 3~4 weeks after transduction, cell morphology changed from spindle-like shape to round shape, similar to that observed in cuboidal epithelium expressing EGFP. Results of RT-PCR confirmed the expression of both exogenous hPDX1 and endogenous pPDX1. Therefore, GalT KO pig-derived BM-MSCs transdifferentiated into pancreatic cells by transfection of hPDX1. The present results are indicative of the therapeutic potential of PDX1-expressing GalT KO pig-derived BM-MSCs in ${\beta}-cell$ replacement. This potential needs to be explored further by using in vivo studies to confirm these findings.

• Tuberculosis and Respiratory Diseases
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• 제75권6호
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• pp.264-268
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• 2013

A 73-year-old, previously healthy man presented with nausea, vomiting, diarrhea, dry mouth and febrile sensation 3 hours after eating boiled wild mushrooms. After admission, he showed progressive severe respiratory distress, pancytopenia, azotemia, hypotension, hypoxemia and consolidation of the entire left lung on chest radiography. With a preliminary diagnosis of necrotizing pneumonia, he underwent left pneumonectomy in order to remove all necrotic lung tissue. Lung histology showed extensive hemorrhagic necrosis, massive inflammatory cell infiltration, prominent proliferation of young fibroblasts and the formation of an early-stage hyaline membrane along the alveolar wall. Despite aggressive treatment, including mechanical ventilation, continuous renal replacement therapy and administration of granulocyte colony stimulating factor and broad spectrum antibiotics, he died on hospitalization day 13. Subsequently, the mushroom was identified as Podostroma cornu-damae. This is the first case of a histological evidence of lung involvement by Podostroma cornu-damae poisoning in Korea.

• Journal of mucopolysaccharidosis and rare diseases
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• 제4권1호
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• pp.26-36
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• 2018

Mucopolysaccharidosis IIIA is a heritable neurodegenerative disorder resulting from the dysfunction of the lysosomal hydrolase sulphamidase. This leads to the primary accumulation of the complex carbohydrate heparan sulphate in a wide range of tissues and CNS degeneration. Characterization of animal model is the beginning point of the therapeutic clinical trial. Mouse model has a limitation in that it is not a human and does not have all of the disease phenotypes. Therefore, delineate of the phenotypic characteristics of MPS IIIA mouse model prerequisite for the enzyme replace treatment for the diseases. We designed 6-month duration of phenotypic characterization of MPS IIIA mouse biochemically, behaviorally and histologically. We compared height and weight of MPS IIIA mouse with wild type from 4 weeks to 6 months in both male and female. At 6 months, we measured GAG storage in urine kidney, heart, liver, lung and spleen. The brain GAG storage is presented with Alcian blue staining, immunohistochemistry, and electron-microscopy. The neurologic phenotype is evaluated by brain MRI and behavioral study including open field test, fear conditioning, T-maze test and Y-maze test. Especially behavioral tests were done serially at 4month and 6month. This study will show the result of the MPS IIIA mouse model phenotypic characterization. The MPS IIIA mouse provides an excellent model for evaluating pathogenic mechanisms of disease and for testing treatment strategies, including enzyme or cell replacement and gene therapy.