• Molecular & Cellular Toxicology
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• 제5권4호
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• pp.354-363
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• 2009

Cytotoxic Nitric oxide (NO) overproduced by inducible NO Synthase (iNOS or NOS2), which was induced in inflammatory reactions and immune responses directly or indirectly affects the functions as host defense and can cause normal tissue damage. Microarray analysis was performed to identify gene profiles of both NO-dependent and -independent transcripts in RAW 264.7 macrophages that use selective NOS2 inhibitors aminoguanidine ($100\;{\mu}M$) and L-canavanine (1 mM). A total of 3,297 genes were identified that were up- or down-regulated significantly over 2-fold in lipopolysaccharide (LPS)-treated macrophages. NO-dependency was determined in the expressed total gene profiles and also within inflammatory conditions-related functional categories. Out of all the gene profiles, 1711 genes affected NO-dependently and -independently in 567 genes. In the categories of inflammatory conditions, transcripts of 16 genes (Pomp, C8a, Ifih1, Irak1, Txnrd1, Ptafr, Scube1, Cd8a, Gpx4, Ltb, Fasl, Igk-V21-9, Vac14, Mbl1, C1r and Tlr6) and 29 geneas (IL-1beta, Mpa2l, IFN activated genes and Chemokine ligands) affected NO-dependently and -independently, respectively. This NO dependency can be applied to inflammatory reaction-related functional classifications, such as cell migration, chemotaxis, cytokine, Jak/STAT signaling pathway, and MAPK signaling pathway. Our results suggest that LPS-induced gene transcripts in inflammation or infection can be classified into physiological and toxic effects by their dependency on the NOS2-mediated NO release.

• Molecules and Cells
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• 제28권6호
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• pp.559-563
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• 2009

Glyceraldehyde-3-phosphate is a key intermediate in several central metabolic pathways of all organisms. Aldolase and glyceraldehyde-3-phosphate dehydrogenase are involved in the production or elimination of glyceraldehyde-3-phosphate during glycolysis or gluconeogenesis, and are differentially expressed under various physiological conditions, including cancer, hypoxia, and apoptosis. In this study, we examine the effects of glyceraldehyde-3-phosphate on cell survival and apoptosis. Overexpression of aldolase protected cells against apoptosis, and addition of glyceraldehyde-3-phosphate to cells delayed apoptosis. Additionally, delayed apoptotic phenomena were observed when glyceraldehyde-3-phosphate was added to a cell-free system, in which artificial apoptotic process was induced by adding dATP and cytochrome c. Surprisingly, glyceraldehyde-3-phosphate directly suppressed caspase-3 activity in a reversible noncompetitive mode, preventing caspase-dependent proteolysis. Based on these results, we suggest that glyceraldehyde-3-phosphate, a key molecule in several central metabolic pathways, functions as a molecule switch between cell survival and apoptosis.

• 한국해양바이오학회지
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• 제9권1호
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• pp.1-7
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• 2017

Perfluorooctane sulfonate (PFOS) is one of the most widely distributed environmental pollutants and causes neurotoxicities. Fucoidan is a main bioactive constituent of the brown sea-weed and has many functions in a variety of physiological conditions. The present study attempted to investigate the potential role of fucoidan as neuroprotective marine polypeptide in environmental pollutant-induced apoptosis of neuronal cells in culture. MTT assay showed that cell viability was significantly reduced to 68 % at $30{\mu}M$ PFOS, which was recovered up to 77% and 92% in the presence of fucoidan 25 and $50{\mu}g/ml$, respectively. Cytotoxicity assay showed that LDH release was significantly increased to 160% at $30{\mu}M$ PFOS but was reduced to 150% and 122% in the presence of fucoidan 25 and $50{\mu}g/ml$, respectively. Caspase-3 activity, a hallmark of apoptosis, was measured to determine the cytotoxicity of PFOS and the cytoprotective effects of fucoidan. PFOS induced a 250% increase of caspase-3 activity at $30{\mu}M$ but the increase was dampened to 180% and 130% in the presence of fucoidan 25 and $50{\mu}g/ml$, respectively. PFOS $30{\mu}M$ induced 180 % increase in ROS accumulation, which was effectively blocked by $50{\mu}g/ml$ fucoidan (120% of control). Our results demonstrated that PFOS is a powerful neurotoxicant and fucoidan may be a protective marine bioactive polypeptide against the neurotoxic environmental pollutants. It may contribute to establishing the potential role of fucoidan as a neuroprotective polypeptide that prevents the risk of neurological disorders from the possible neurotoxic pollutants.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6215-6223
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• 2015

Tyrosine phosphorylation plays an important role in regulating human physiological and pathological processes. Functional stabilization of tyrosine phosphorylation largely contributes to the balanced, coordinated regulation of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Research has revealed PTPs play an important suppressive role in carcinogenesis and progression by reversing oncoprotein functions. Receptor-type protein tyrosine phosphatase O (PTPRO) as one member of the PTPs family has also been identified to have some roles in tumor development. Some reports have shown PTPRO over-expression in tumors can not only inhibit the frequency of tumor cell division and induce tumor cell death, but also suppress migration. However, the tumor-suppression mechanisms are very complex and understanding is incomplete, which in some degree blocks the further development of PTPRO. Hence, in order to resolve this problem, we here have summarized research findings to draw meaningful conclusions. We found tumor-suppression mechanisms of PTPRO to be diverse, such as controlling G0/G1 of the tumor cell proliferation cycle, inhibiting substrate phosphorylation, down-regulating transcription activators and other activities. In clinical anticancer efforts, expression level of PTPRO in tumors can not only serve as a biomarker to monitor the prognosis of patients, but act as an epigenetic biomarker for noninvasive diagnosis. In addition, the re-activation of PTPRO in tumor tissues, not only can induce tumor volume reduction, but also enhance the susceptibility to chemotherapy drugs. So, we can propose that these research findings of PTPRO will not only support new study ideas and directions for other tumor-suppressors, importantly, but also supply a theoretical basis for researching new molecular targeting agents in the future.

• Journal of Dairy Science and Biotechnology
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• 제23권2호
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• pp.149-153
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• 2005

Lactic acid bacteria had been widely utilized in fermented foods such as fermented dairy products, traditional sauces, kimchi, fermented sausages, medicines or probiotic feed additives for a long time. LAB are also widely distributed in the mammalian gastrointestinal tracts, oral cavity, vagina, and various foods or soils. The most familiar examples of using LAB would be the fermented milk products, and those had become one of the favorite foods in Korea f3r more than 34 years of history. The main benefits of the fermented milk products were originally the improvement of the balance of intestinal flora to control diarrhea and congestion disorders, and gradually, they were chosen by the consumer preference of the taste. The very beginning of the fermented milk products in Korea was the Yakult type products in 1971, and it was the commencement of the solid foundation of the dairy industry and the understanding beneficial effect of probiotic yogurt. After middle of 80's, stirred type fermented milk products had been firstly produced, and it was the time that the domestic dairy industry took root in Korea. From 90's, functional fermented milk products were produced, and drink type yogurt sales a mount increased drastically, and these products began to be chosen not only with the values of nutrition but also with physiological functions. The health claims are classified into intestinal health, gastric health and hepatic health. The prospects for the Korean market are as follows; The majority of leading products would be the premium functional yogurt products as it was last year. It is because the sales of lower cost products shows slow-down, and industries tend to increase the commercial advertisements of premium functional yogurt products through mass media. These tendencies would make the market situation become more competitive.

• 동의생리병리학회지
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• 제17권5호
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• pp.1281-1287
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• 2003

In this research 2 sample compounds are made and analyzed in terms of the in vivo and in vitro effects on the ovariectomized rats. The 2 compounds are prescribed based on pathologic patterns of osteoporosis, and added calcium citrate from tuna bone powder. SG is for menopausal women(Type I osteoporosis) and GN is for senile men(Type II osteoporosis). Through these, SG manifested Significant effects on the T4, osteocalcin level, and through the histological changes of osteoid tissues and lipocytes. On the other hand GN showed significant increase on the biochemical markers of osteocalcin, TALP, even in histological features and bone mineral density and intensity of femur it showed meaningful changes. But In the results of RT-PCR on the IL-1β, IL-6, TNF α, there weren't coherent results with in vivo test, that is they were increased in the sample compound group than control group. These increase of bone resorption was seemed that those cytokines had the osteoclasts promote their own resorptive functions after fragments of bone tissues were increased in the cavity. And this clearance of inner fragments help the bone to strengthen its own substance. Putting together above facts, the sample compounds, SG and GN, made of tuna bone powder and herbal solutions are predicted that there would be pharmacological actions improving the osteoporosis initiated from the disorders of calcic absorption and increase of bone resorption. And GN has more effective actions than SG at least in the animal model.

• 동의생리병리학회지
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• 제20권2호
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• pp.333-344
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• 2006

The Blood paralysis(血痺) is infected by a poisonous factor of wind and it disturbs the circulation of meridian. This disease is similar phenomenon to the Blutsaure(血柱) and belongs to the category like the Radial nerve paralysis, the Ulna nerve paralysis and the unstability syndrome of the lower limbs. This dissertation will inquire into symptoms, the way of treatment and the prescriptions of this disease based on the Synopsis of Golden Chamber. The Weakness and fatigue(虛勞) is occurred by several causes. This disease means all the functions of body weakened. This dissertation will inquire into pulse conditions according to the type of the Weakness and fatigue(虛勞), symptoms, the way of treatment and the prescriptions of this disease based on the Synopsis of Golden Chamber.

• 동의생리병리학회지
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• 제25권1호
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• pp.71-77
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• 2011

Gastric ulcer has multifactorial etiology, and the development of ulcer is known to be caused by gastric acidity, pepsin secretion, gastric motility and gastric mucosal blood flow. The ulcer results from the tissue necrosis and apoptotic cell death triggered by mucosal ischemia, free radical formation and cessation of nutrient delivery. The gastric mucosa is usually exposed to a wide range of aggressive insults, and has developed efficient mechanisms to repair tissue injury. The apoptotic process of gastric mucosa is triggered by the induction of such proapoptotic gene expression, such as BAX. The Bcl-2 family of proteins plays a pivotal role in the regulation of apoptosis. The maintenance of gastric mucosa integrity depends upon the ratio between cell proliferation and cell death. Stress-inducing factors may affect Bcl-2/BAX ratio and thus the rate of apoptosis through modulation of the expression of both proteins depends upon the experimental model. In addition to the regulation of apoptosis, new vessels have to be generated in order to ensure an adequate supply of oxygen and nutrients to the healing gastric mucosa. This events are regulated by several factors. Among them, such polypeptide growth factors, such as vascular endothelial growth factor (VEGF) regulates essential cell functions involved in tissue healing including cell proliferation and differentiation. The purpose of this study was carried to investigate whether Rhei Rhizoma administration might protect apoptotic cell death and promote angiogenesis in gastric mucosa. Sprague-Dawley rats were randomly divided into 4 groups; normal, saline, cimetidine and Rhei Rhizoma-treated group. The saline, cimetidine and Rhei Rhizoma extracts were orally administrated to each group and gastric ulcer was induced by HCl-EtOH solution. After 1 hour, the stomachs were collected for histological observation and immunohistochemistry. In results, Rhei Rhizoma proves to promote to heal wound in gastric ulcer in conclusion and the significant changes of BAX, Bcl-2 and VEGF quantity in gastric mucosa were observed. These results suggest that Rhei Rhizoma extract may promote incision wound healing and has protective effects on gastric ulcer in rats.

• 동의생리병리학회지
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• 제26권6호
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• pp.834-841
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• 2012

We in this paper propose a mobile application for supporting medical treatment based on Korean medicine ontology. It has three processes for treating patients. First, after a pattern is decided for patient' symptoms, a formula for the pattern is selected and medicinal materials constituting the formula is added or removed. Second, formulas are searched and prescribed for patient's symptoms without the process of the pattern decision. Third, after medicinal materials are searched for patient's symptoms, formulas consisting of the medicinal materials are prescribed. Our application aims to help korean medicine doctors treat patients through providing decision supporting functions such as the recommendation of symptoms of diseases accompanying patient's symptom. Doctors generally diagnosis patients according to their experiences and knowledges. Nevertheless, our application can help them, providing diverse forms of information that they may miss in the medical treatment.

• 동의생리병리학회지
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• 제25권1호
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• pp.37-47
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• 2011

This study was aimed to investigate the memory enhancing effect of Jeongjihwan against scopolamine-induced amnesia in C57BL/6 mice. To determine the effect of Jeongjihwan on the memory and cognitive function, we have injected scopolamine (1 mg/kg, i.p.) into C57BL/6 mice 30 min before beginning of behavior tests. We have conducted Y-maze, Morris water-maze, passive avoidance and fear conditioning tests to compare learning and memory functions. Scopolamine-induced behavior changes of memory impairment were significantly restored by oral administration of Jeongjihwan (100 or 200 mg/kg/day). To elucidate the molecular mechanism underlying the memory enhancing effect of Jeongjihwan, we have examined the antioxidant defense system and neurotrophic factors. Jeongjihwan treatment attenuated intracellular accumulation of reactive oxygen species and up-regulated mRNA and protein expression of antioxidant enzymes as assessed by RT-PCR and western blot analysis, respectively. Jeongjihwan also increased protein levels of brain-derived neurotrophic factor (BDNF) compared with those in the scopolamine-treated group. Furthermore, as an upstream regulator, the activation of cAMP response element-binding protein (CREB) via phosphorylation was assessed by Western blot analysis. Jeongjihwan elevated the phosphorylation of CREB (p-CREB), which seemed to be mediated partly by extracellular signal-regulated kinase1/2 (ERK1/2) and protein kinase B/Akt. These findings suggest that Jeongjihwan may have preventive and therapeutic potential in the management of amnesia.