• Journal of Microbiology and Biotechnology
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• v.19 no.9
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• pp.1070-1076
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• 2009

Telomerase reverse transcriptase (TERT), which prolongs the replicative life span of cells, is highly upregulated in 85-90% of human cancers, whereas most normal somatic tissues in humans express limited levels of the telomerase activity. Therefore, TERT has been a potential target for anticancer therapy. Recently, we described a new approach to human cancer gene therapy, which is based on the group I intron of Tetrahymena thermophila. This ribozyme can specifically mediate RNA replacement of human TERT (hTERT) transcript with a new transcript harboring anticancer activity through a trans-splicing reaction, resulting in selective regression of hTERT-positive cancer cells. However, to validate the therapeutic potential of the ribozyme in animal models, ribozymes targeting inherent transcripts of the animal should be developed. In this study, we developed a Tetrahymena-based trans-splicing ribozyme that can specifically target and replace the mouse TERT (mTERT) RNA. This ribozyme can trigger transgene activity not only also in mTERT-expressing cells but hTERT-positive cancer cells. Importantly, the ribozyme could selectively induce activity of the suicide gene, a herpes simplex virus thymidine kinase gene, in cancer cells expressing the TERT RNA and thereby specifically hamper the survival of these cells when treated with ganciclovir. The mTERT-targeting ribozyme will be useful for evaluation of the RNA replacement approach as a cancer gene therapeutic tool in the mouse model with syngeneic tumors.

• Development and Reproduction
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• v.11 no.2
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• pp.67-77
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• 2007

Replacement of insulin-producing cells represents an almost ideal treatment for patients with diabetes mellitus type 1. Transplantation of pancreatic islets of Langerhans is limited by the lack of donor organs. Therefore, generation of insulin-producing cells from human embryonic stem cells represents an attractive alternative. The present review summarizes the current knowledge on the differentiation of insulin-producing cells from human embryonic stem cells and their application to the cell therapy for treating diabetes mellitus.

• Journal of Digestive Cancer Research
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• v.11 no.2
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• pp.61-65
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• 2023

Globally, esophageal cancer is the seventh most common cancer, and the male-to-female ratio in esophageal adenocarcinoma (EAC) is significantly imbalanced at 4:1 to 8:1. Obesity, reflux, and smoking are known risk factors for this sex difference; however, fully explaining this remains challenging. Studies have investigated the link between exogenous sex hormones and esophageal cancer occurrence. A meta-analysis revealed a lower risk of EAC in female who had undergone hormone replacement therapy. Androgen-deprivation therapy in patients with prostate cancer was associated with a decreased risk of EAC. Tissue-based studies have reported varied results regarding the relationship between estrogen receptor expression and survival in female patients with esophageal squamous cell carcinoma (ESCC). Circulating hormone studies have suggested that higher testosterone and luteinizing hormone levels decreased EAC risk in men, and free testosterone was inversely correlated in female with ESCC. However, a high androgen-estrogen ratio in male patients with EAC was linked to increased odds of EAC. Sex hormones influence carcinogenesis, affecting cell proliferation, differentiation, metabolism, inflammation, and cell death. The studies were limited by the small sample size and varying hormone measurement methods; thus, future studies with definitive conclusions on the association between esophageal cancer and sex hormones are warranted.

• Biomolecules & Therapeutics
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• v.31 no.3
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• pp.264-275
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• 2023

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by tremors, bradykinesia, and rigidity. PD is caused by loss of dopaminergic (DA) neurons in the midbrain substantia nigra (SN) and therefore, replenishment of DA neurons via stem cell-based therapy is a potential treatment option. Astrocytes are the most abundant non-neuronal cells in the central nervous system and are promising candidates for reprogramming into neuronal cells because they share a common origin with neurons. The ability of neural progenitor cells (NPCs) to proliferate and differentiate may overcome the limitations of the reduced viability and function of transplanted cells after cell replacement therapy. Achaete-scute complex homolog-like 1 (Ascl1) is a well-known neuronal-specific factor that induces various cell types such as human and mouse astrocytes and fibroblasts to differentiate into neurons. Nurr1 is involved in the differentiation and maintenance of DA neurons, and decreased Nurr1 expression is known to be a major risk factor for PD. Previous studies have shown that direct conversion of astrocytes into DA neurons and NPCs can be induced by overexpression of Ascl1 and Nurr1 and additional transcription factors genes such as superoxide dismutase 1 and SRY-box 2. Here, we demonstrate that astrocytes isolated from the ventral midbrain, the origin of SN DA neurons, can be effectively converted into DA neurons and NPCs with enhanced viability. In addition, when these NPCs are inducted to differentiate, they exhibit key characteristics of DA neurons. Thus, direct conversion of midbrain astrocytes is a possible cell therapy strategy to treat neurodegenerative diseases.

• Archives of Pharmacal Research
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• v.28 no.5
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• pp.566-572
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• 2005

The aim of this study was to determine if the isoflavones from Sophorae fructus (SISO) have potential clinical benefit in hormone replacement therapy (HRT) for the treat ment of menopausal signs, such as the levels of total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL) and follicle stimulating hormone (FSH). An additional aim was to present the potential antioxidant effect of SISO in a microglial cell line. For the animal model, the ovaries were removed from adult rats and the indicators of menopause were measured at the pre- and post-administration time points. Although no statistically significant correlation was found, SISO tended to decrease the TC level (p=0.15) and the FSH level (p=0.36), but to increase the HDL level (p=0.303).SISO (< 5${\mu}g$/mL) also exerted antioxidant activity on BV-2 microglial cells by inhibiting lipopolysaccharide-induced nitric oxide. This cytoprotective effect was confirmed by trypan blue staining, which was used to test for cellular damage from H$_2O_2$. In conclusion, this study highlights the anti-menopausal and antioxidant effect of SISO in an ovariectomized rat model, as well as in microglial cells, and provides new clinical targets for the screening of phytoestrogens as potential candidates for HRT in menopausal women.

• 한국생물공학회:학술대회논문집
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• 2003.10a
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• pp.372-373
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• 2003

• Neonatal Medicine
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• v.17 no.2
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• pp.168-180
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• 2010

Acute renal failure (ARF) is common in the neonatal period, however, there are no uniform treatment strategies of ARF. The main treatment strategies are conservative management including medical treatment and the renal replacement therapy. Because ARF in the newborn is commonly acquired by hypoxic ischemic injury and toxic insults, removal of all the offending causes is important. Aminoglycoside, indomethacin, and amphotericin-B are the most common nephrotoxic drugs of ARF. To relieve the possible prerenal ARF, initial fluid challenge can be followed by diuretics. If there is no response, fluid restriction and correction of electrolyte imbalance should begin. Adequate nutritional support and drug dosing according to the pharmacokinetics of such drugs will be difficult problems. Renal replacement therapies may be provided by peritoneal dialysis, intermittent hemodialysis, or hemofiltration. New promising agents, bioartificial kidney, and stem cell will enable us to extend our therapeutic repertoire.

• Clinical and Experimental Pediatrics
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• v.53 no.8
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• pp.786-789
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• 2010

Induced pluripotent stem (iPS) cells are generated by epigenetic reprogramming of somatic cells through the exogenous expression of transcription factors. Recently, the generation of iPS cells from patients with a variety of genetic diseases was found to likely have a major impact on regenerative medicine, because these cells self-renew indefinitely in culture while retaining the capacity to differentiate into any cell type in the body, thereby enabling disease investigation and drug development. This review focuses on the current state of iPS cell technology and discusses the potential applications of these cells for disease modeling; drug discovery; and eventually, cell replacement therapy.

• Journal of mucopolysaccharidosis and rare diseases
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• v.5 no.1
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• pp.12-16
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• 2021

Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is an X-linked lysosomal storage disorder caused by deficiency of the enzyme iduronate-2-sulfatase, leading to the accumulation of glycosaminoglycans (GAGs), which affects multiple organs and systems. Current treatments for MPS II include enzyme replacement therapy (ERT) and hematopoietic cell transplantation (HCT) to reduce the accumulation of GAGs. HCT has the potential advantage that donor-derived enzyme-competent cells can provide a continuous secreting source of the enzyme. However, HCT as a treatment for MPS II remains controversial because its effectiveness is unclear, particularly in terms of neurological symptoms. To date, several clinical experiences with HCT in MPS II have been reported. In this paper, we review post-HCT outcomes in the previously published literature and discuss the effects of HCT on each of the clinical signs and symptoms of MPS II.

• Journal of mucopolysaccharidosis and rare diseases
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• v.4 no.1
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• pp.14-20
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• 2018

Mucopolysaccharidoses (MPSs) are a group of rare inherited metabolic disorders caused by specific lysosomal enzyme deficiencies leading to the sequential degradation of glycosaminoglycans, causing substrate accumulation in various cells and tissues and progressive multiple organ dysfunction. The rare disease medical care team at Mackay Memorial Hospital in Taiwan has been dedicated to the study of MPSs for more than 20 years. Since 1999, more than 50 academic papers focusing on MPSs have been published in international medical journals. Topics of research include the following items regarding MPSs: incidence, natural history, clinical manifestations, gene mutation characteristics, cardiac function, bone mineral density, sleep studies, pulmonary function tests, hearing assessments, percutaneous endoscopic gastrostomy, anesthetic experience, imaging analysis, special biochemical tests, laboratory diagnostics, global expert consensus conferences, prenatal diagnosis, new drug clinical trials, newborn screening, and treatment outcomes. Of these published academic research papers, more than half were cross-domain, cross-industry, and international studies with results in cooperation with experts from European, American and other Asian countries. A cross-specialty collaboration platform was established based on high-risk population screening criteria with the acronym "BECARE" (Bone and joints, Eyes, Cardiac and central nervous system, Abdomen and appearance, Respiratory system, and Ear, nose, and throat involvement). Through this platform, orthopedic surgeons, rheumatologists, ophthalmologists, cardiologists, rehabilitation physicians, gastroenterologists, otorhinolaryngologists, and medical geneticists have been educated with regards to awareness of suspected cases of MPSs patients to allow for a further confirmative diagnosis of MPSs. Because of the progressive nature of the disease, an early diagnosis and early multidisciplinary therapeutic interventions including surgery, rehabilitation programs, symptom-based treatments, hematopoietic stem cell transplantation, and enzyme replacement therapy, are very important.