• Analytical Science and Technology
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• v.24 no.6
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• pp.533-543
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• 2011

The hERG (human ether-a-go-go related gene) ion channel is a main factor for cardiac repolarization, and the blockade of this channel could induce arrhythmia and sudden death. Therefore, potential hERG ion channel inhibitors are now a primary concern in the drug discovery process, and lots of efforts are focused on the minimizing the cardiotoxic side effect. In this study, $IC_{50}$ data of 202 organic compounds in HEK (human embryonic kidney) cell from literatures were used to develop predictive 2D-QSAR model. Multiple linear regression (MLR), Support Vector Machine (SVM), and artificial neural network (ANN) were utilized to predict inhibition concentration of hERG ion channel as machine learning methods. Population based-forward selection method with cross-validation procedure was combined with each learning method and used to select best subset descriptors for each learning algorithm. The best model was ANN model based on 14 descriptors ($R^2_{CV}$=0.617, RMSECV=0.762, MAECV=0.583) and the MLR model could describe the structural characteristics of inhibitors and interaction with hERG receptors. The validation of QSAR models was evaluated through the 5-fold cross-validation and Y-scrambling test.

• Journal of Chest Surgery
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• v.20 no.1
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• pp.112-127
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• 1987

Myasthenia gravis is a neuromuscular transmission function disorder characterized by fatigue and weakness of voluntary muscles. This muscular weakness is intensified by activity and stress, and improved by the use of anticholinesterase compounds. It was initially described by Erb in 1879 and later named myasthenia gravis by Jolly in 1895. Although the pathogenesis is Known to be an autoimmune related reduction in the number of available acetylcholine receptors at neuromuscular junctions, the role of thymus in myasthenia gravis is still unclear and under investigation. Thymectomy in the management of myasthenia gravis has become increasingly important since Dr. Blalock observed in 1939 that some patients with thymic tumors and myasthenia gravis improved following thymectomy. A clinical study of 102 cases of myasthenia gravis was performed at Yonsei University College of Medicine. Seoul, Korea from Jan. 1976 to Jun. 1986. In order to determine which factors are of prognostic significance, attention is focused upon pre-operative patient evaluation, problems in operative and post-operative care, and long-term follow-up observations. The results were as follows: 1. The sex distribution was 67 females and 35 males, the mean age of onset was 28.95*1.69 years, and the maximal incidence occurred between 21 and 40 years of age [56 cases: 54.9%]. 2. Clinical manifestations of ocular symptoms were seen to 70 patients [68.6%] extremities weakness in 33 [32.3%], bulbar weakness in 29 [28.4%], and dyspnea in 13 [12.7%]. 3. Study cases more than two thirds were classified as mild types [MG 1 and MG 11A] and 6 cases as grave [MG 1V] based on the modified Osserman`s classification system, 4. Thymectomy was performed in 19 cases which presented in severe myasthenia symptoms and showed no improvement with cholinergic drugs. Histologic examination of the excised thymus glands revealed no abnormalities in 4 cases, thymic hyperplasia in 5, benign thymoma in 5, and malignant thymoma in 5. 5. Immediate post-operative complications included 2 cases of pneumothorax which were treated by tube thoracostomies, there was no operative mortality. 6. The response to cholinergic drugs in 36 cases younger than 20 years old and in 27 cases older than 40 years was relatively poor, while that in 35 cases between the ages of 21 and 40 years old was good. 7. Thirty of 39 cases in groups IIB, III & IV improved markedly with medical or surgical management while only 16 of 59 cases in the mild groups [I and IIA] improved, almost all surgical cases improved in all categories. 8. There were 5 deaths. occurring between 7 months and 3 years 3 months of treatment of myasthenia gravis. The causes of death were myasthenic crisis in 2 cases, respiratory failure due to candidiasis & radiation pneumonitis in one case, cerebral hemorrhage due to high blood pressure in two case.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9739-9745
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• 2014

Purpose: We aimed to evaluate the effects of hormone receptor, HER2, and epidermal growth factor receptor (EGFR) expression on epithelial ovarian cancer (EOC) prognosis and investigate whether or not phenotypic subtypes might exist. Materials and Methods: The medical records of 82 patients who were diagnosed with EOC between 2003 and 2012 and treated by platinum-based chemotherapy were retrospectively evaluated. Expression of EGFR, oestrogen (ER), progesterone (PR), and cerbB2 (HER2) receptors were assessed immunohistochemically on paraffin-embedded tissues of these patients. Three phenotypic subtypes were defined according to ER, PR, and HER2 expression and associations of these with EGFR expression, clinicopathologic features, platinum sensitivity, and survival were investigated. Results: When we classified EOC patients into three subtypes, 63.4% had hormone receptor positive (HR(+)) (considering breast cancer subtypes, luminal A), 18.3% had triple negative, and 18.3% had HER2(+) disease. EGFR positivity was observed in 37 patients (45.1%) and was significantly more frequent with advanced disease (p=0.013). However, no significant association with other clinicopathologic features and platinum sensitivity was observed. HER2(+) patients had significantly poorer outcomes than HER2(-) counterparts (triple negative and HR positive patients) (p=0.019). Multivariate analysis demonstrated that the strongest risk factor for death was residual disease after primary surgery. Conclusions: Triple negative EOC may not be an aggressive phenotype as in breast cancer. The HER2 positive EOC has more aggressive behaviour compared to triple negative and HR(+) phenotypes. EGFR expression is more frequent in advanced tumours, but is not related with poorer outcome. Additional ovarian cancer molecular subtyping using gene expression analysis may provide more reliable data.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1725-1729
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• 2013

Background: Breast cancer is the second leading cancer causing death in women. Circulating tumor cells are among the prognostic factors while tumor markers are of diagnostic value and can be used for follow-up. The aim of this study was to investigate the correlation between the prognostic significance of the serum CA15-3 levels, number of circulating tumor cells and histopathological tumor factors. Materials and Methods: Thirty patients recently diagnosed with breast cancer were included in the study. Number of circulating tumor cells and serum CA15-3 level were assessed when metastasis was detected and diagnostic value was assessed. Presence of associations with estrogen and progesterone receptors, c-erbB2, Ki-67 proliferation index and histological grade were also evaluated. Results: Median overall survival of the patients with serum CA15-3 levels of >108 ng/dl was 19 months whereas for those with a low serum level it was 62 months. Median overall survival for CTC ${\geq}5$ vs CTC<5 patients was 19 months and 40 months respectively. The difference between the two groups was statistically significant. Conclusions: Prognostic significance of the CTC count and CA15-3 levels in metastatic breast cancer patients was demonstrated.

• Pediatric Infection and Vaccine
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• v.16 no.2
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• pp.199-204
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• 2009

Purpose : Various proteins encoded in the early region 3 (E3) of adenoviruses protect cells from being killed by cytotoxic T cells and death-inducing cytokines. We sought to find out whether the genetic heterogeneity of the E3 gene might contribute to the molecular diversity of adenoviruses. Methods : Sequences in the E3 region were analyzed for 14 adenovirus type 3 (Ad3) strains that were isolated from children with lower respiratory tract infections in the Seoul National University Children's Hospital during the period 1991-2000. Full-length adenoviral DNA was purified from the infected A549 cell lysates using a modified Hirt procedure. Results : There was 98% homology between 14 Korean Ad3 strains with a reference strain (M15952). Homology within the Korean Ad3 strains was 98.7%. Variation was found in the region of transcripts 20.1 kDa, 20.6 kDa, truncated 7.7 kDa, 10.3 kDa, 14.9 kDa, and 15.3 kDa. In particular, all 14 Korean strains showed a missense single point mutation at the start codon of the truncated 7.7 kDa. In addition, a deletion was found in the truncated 7.7 kDa region by 58 base pairs in 10 strains and 94 base pairs in 4 strains. Variations in amino acids were observed in the receptor internalization and degradation complex (10.3 kDa/14.9 kDa) which stimulates the clearance from the cell surface and subsequent degradation of the receptors for the Fas ligand and TRAIL, while no variations were observed in another immunoregulatory transcript, 19 kDa. Conclusion : Sequence analysis of the immunoregulatory region of adenovirus E3 shows that genetic heterogeneities are related to genome type patterns.

• Journal of Ginseng Research
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• v.45 no.3
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• pp.390-400
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• 2021

Background: We recently showed that gintonin, an active ginseng ingredient, exhibits antibrain neurodegenerative disease effects including multiple target mechanisms such as antioxidative stress and antiinflammation via the lysophosphatidic acid (LPA) receptors. Amyotrophic lateral sclerosis (ALS) is a spinal disease characterized by neurodegenerative changes in motor neurons with subsequent skeletal muscle paralysis and death. However, pathophysiological mechanisms of ALS are still elusive, and therapeutic drugs have not yet been developed. We investigate the putative alleviating effects of gintonin in ALS. Methods: The G93A-SOD1 transgenic mouse ALS model was used. Gintonin (50 or 100 mg/kg/day, p.o.) administration started from week seven. We performed histological analyses, immunoblot assays, and behavioral tests. Results: Gintonin extended mouse survival and relieved motor dysfunctions. Histological analyses of spinal cords revealed that gintonin increased the survival of motor neurons, expression of brain-derived neurotrophic factors, choline acetyltransferase, NeuN, and Nissl bodies compared with the vehicle control. Gintonin attenuated elevated spinal NAD(P) quinone oxidoreductase 1 expression and decreased oxidative stress-related ferritin, ionized calcium-binding adapter molecule 1-immunoreactive microglia, S100β-immunoreactive astrocyte, and Olig2-immunoreactive oligodendrocytes compared with the control vehicle. Interestingly, we found that the spinal LPA1 receptor level was decreased, whereas gintonin treatment restored decreased LPA1 receptor expression levels in the G93A-SOD1 transgenic mouse, thereby attenuating neurological symptoms and histological deficits. Conclusion: Gintonin-mediated symptomatic improvements of ALS might be associated with the attenuations of neuronal loss and oxidative stress via the spinal LPA1 receptor regulations. The present results suggest that the spinal LPA1 receptor is engaged in ALS, and gintonin may be useful for relieving ALS symptoms.

• Animal Bioscience
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• v.36 no.3
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• pp.404-416
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• 2023

Objective: Daweizi (DWZ) is a famous indigenous pig breed in China and characterized by tender meat and high fat percentage. However, the expression profiles and functions of transcripts in DWZ pigs is still in infancy. The object of this study was to depict the transcript profiles in DWZ pigs and screen the potential pathway influence adipogenesis and fat deposition, Methods: Histological analysis of backfat tissue was firstly performed between DWZ and lean-type Yorkshire pigs, and then RNA sequencing technology was utilized to explore miRNAs, lncRNAs and mRNAs profiles in backfat tissue. 18 differentially expressed (DE) transcripts were randomly selected for quantitative real-time polymerase chain reaction (QPCR) to validate the reliability of the sequencing results. Finally, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were conducted to investigate the potential pathways influence adipocyte differentiation, adipogenesis and lipid metabolism, and a schematic model was further proposed. Results: A total of 1,625 differentially expressed transcripts were identified in DWZ pigs, including 27 upregulated and 45 downregulated miRNAs, 64 upregulated and 119 down-regulated lncRNA, 814 upregulated and 556 downregulated mRNAs. QPCR analysis exhibited strong consistency with the sequencing data. GO and KEGG analysis elucidated that the differentially expressed transcripts were mainly associated with cell growth and death, signal transduction, peroxisome proliferator-activated receptors (PPAR), AMP-activated protein kinase (AMPK), PI3K-Akt, adipocytokine and foxo signaling pathways, all of which are strongly involved in cell development, lipid metabolism and adipogenesis. Further analysis indicated that the BGIR9823_87926/miR-194a-5p/AQP7 network may be effective in the process of adipocyte differentiation or adipogenesis. Conclusion: Our study provides comprehensive insights into the regulatory network of backfat deposition and lipid metabolism in pigs from the point of view of miRNAs, lncRNAs and mRNAs.

• Applied Microscopy
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• v.30 no.4
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• pp.347-355
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• 2000

Zinc is one of the most abundant oligoelements in the living cell. It appears tightly bound to some metalloproteins and nucleic acids, loosely bound to some metallothioneins or even as free ion. Small amounts of zinc ions (in the nanomolar range) regulate a plentitude of enzymatic proteins, receptors and transcription factors, thus rolls need accurate homeostasis of zinc ions. Zinc is an essential catalytic or structural element of many proteins, and a signaling messenger that is released by neural activity at many central excitatory synapses. Growing evidences suggest that zinc may also be a key mediator and modulator of the neuronal death associated with transient global ischemia and sustained seizures, as well as perhaps other neurological disease stoles. Some neurons have developed mechanisms to accumulate zinc in specific membrane compartment ('vesicular zinc') which can be evidenced using histochemical techniques. Substances giving a bright colour or emitting fluorescence when in contact with divalent metal ions are currently used to detect them inside cells; their use leads to the so called 'direct' methods. The fixation and precipitation of metal ions as insoluble salt precipitates, their maintenance along the histological process and, finally, their demonstration after autometallographic development are essential steps for other methods, the so called 'indirect methods'. This study is a short report on the autometallograhical approaches for zinc detection in the central nervous system (CNS) by means of a modified selenium method.

• Journal of Life Science
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• v.32 no.1
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• pp.11-22
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• 2022

N-methyl-D-aspartate (NMDA) receptors have received considerable attention regarding their involvement in glutamate-induced neuronal excitotoxicity. Resveratrol has been shown to exhibit neuroprotective effects against this kind of overactivation, but the underlying cellular mechanisms are not yet clearly understood. In this study, HT-22 neuronal cells were treated with NMDA in Mg²⁺-free buffer and subsequently used as an experimental model of glutamate excitotoxicity to elucidate the mechanisms of resveratrol-induced neuroprotection. We found that NMDA treatment causes a drop in MTT reduction ability, disrupts inside-negative transmembrane potential of mitochondria, depletes cellular ATP levels, and stimulates intracellular ROS production. Double fluorescence imaging studies demonstrated an increased formation of mitochondrial permeability transition (MPT) pores accompanied by apoptotic cell death, while cobalt protoporphyrin and bilirubin showed protective effects against NMDA-induced mitochondrial injury. On the other hand, zinc protoporphyrin IX significantly attenuated the protective effects of resveratrol which was itself shown to enhance heme oxygenase-1 (HO-1) mRNA and protein expression levels. In cells transfected with HO-1 small interfering RNA, resveratrol failed to suppress the NMDA-induced effects on MTT reduction ability and MPT pore formation. The present study suggests that resveratrol may prevent mitochondrial injury in NMDA- treated HT-22 cells and that enhanced expression of HO-1 is involved in the underlying cellular mechanism.