• BMB Reports
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• v.48 no.3
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• pp.184-189
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• 2015

Src homology 2-containing protein tyrosine phosphatase 2 (SHP-2) is known to protect neurons from neurodegeneration during ischemia/reperfusion injury. We recently reported that ROS-mediated oxidative stress promotes phosphorylation of endogenous SHP-2 in astrocytes and complex formation between caveolin-1 and SHP-2 in response to oxidative stress. To examine the region of SHP-2 participating in complex formation with caveolin-1, we generated three deletion mutant constructs and six point mutation constructs of SHP-2. Compared with wild-type SHP-2, binding of the N-SH2 domain deletion mutant of SHP-2 to p-caveolin-1 was reduced greatly, using flow cytometric competitive binding assays and surface plasmon resonance (SPR). Moreover, deletion of the N-SH2 domain of SHP-2 affected $H_2O_2$-mediated ERK phosphorylation and Src phosphorylation at Tyr 419 in primary astrocytes, suggesting that N-SH2 domain of SHP-2 is responsible for the binding of caveolin-1 and contributes to the regulation of Src phosphorylation and activation following ROS-induced oxidative stress in brain astrocytes.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2219-2225
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• 2015

SHP1 negatively regulates the Janus kinase 2/signal transducer and activator of transcription (JAK2/STAT) signaling pathway, which is constitutively activated in myeloproliferative neoplasms (MPNs) and leukemia. Promoter hypermethylation resulting in epigenetic inactivation of SHP1 has been reported in myelomas, leukemias and other cancers. However, whether SHP1 hypermethylation occurs in MPNs, especially in Chinese patients, has remained unclear. Here, we report that aberrant hypermethylation of SHP1 was observed in several leukemic cell lines and bone marrow mononuclear cells from MPN patients. About 51 of 118 (43.2%) MPN patients including 23 of 50 (46%) polycythaemia vera patients, 20 of 50 (40%) essential thrombocythaemia and 8 of 18 (44.4%) idiopathic myelofibrosis showed hypermethylation by methylation-specific polymerase chain reaction. However, SHP1 methylation was not measured in 20 healthy volunteers. Hypermethylation of SHP1 was found in MPN patients with both positive (34/81, 42%) and negative (17/37, 45.9%) JAK2V617F mutation. The levels of SHP1 mRNA were significantly lower in hypermethylated samples than unmethylated samples, suggesting SHP1 may be epigenetically inactivated in MPN patients. Furthermore, treatment with 5-aza-2'-deoxycytidine (AZA) in K562 cells showing hypermethylation of SHP1 led to progressive demethylation of SHP1, with consequently increased reexpression of SHP1. Meanwhile, phosphorylated JAK2 and STAT3 were progressively reduced. Finally, AZA increased the expression of SHP1 in primary MPN cells with hypermethylation of SHP1. Therefore, our data suggest that epigenetic inactivation of SHP1 contributes to the constitutive activation of JAK2/STAT signaling. Restoration of SHP1 expression by AZA may contribute to clinical treatment for MPN patients.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.4117-4123
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• 2016

Background: Methylation of promoter 2 of the SHP1 gene is epithelial cell specific, with reported potential as a lymph node metastatic marker. Objective: To demonstrate SHP1-P2 methylation-specific quantitative PCR effectiveness in detecting colorectal cancer (CRC) DNA in lymph nodes. Materials and Methods: SHP1-P2 methylation levels were measured in lymph nodes of CRC patients and compared with pathological findings and patient prognosis. Results: Lymph nodes of CRC metastatic patients without microscopically detectable cancer cells had higher SHP1-P2 methylation levels than lymph nodes of controls (p<0.001). In addition, a higher SHP1-P2 methylation level was associated with a shorter duration until adverse disease events, metastasis, recurrence and death (r2 = 0.236 and p value = 0.048). Studying two cohorts of 74 CRC patients without microscopic lymph node metastases showed that only the cohort containing samples with high SHP1-P2 methylation levels had a significant hazard ratio of 3.8 (95%CI = 1.02 to 14.2). Conclusions: SHP1-P2 methylation PCR can detect CRC DNA in lymph nodes even if cancer cells are not visible under a microscope, confirming applicability as a potential universal lymph node metastatic marker.

• Molecules and Cells
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• v.23 no.3
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• pp.331-339
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• 2007

It has been suggested that the structure and function of nuclear receptors are evolutionally conserved. Here, we compare the molecular functions of the nile tilapia (Oreochromis niloticus) small heterodimer partner (nSHP/NR0B2) and the Dosage-sensitive sex reversal AHC critical region on X chromosome gene 1 (nDAX-1/NR0B1) with those of human SHP and DAX-1 (hSHP and hDAX-1, respectively). We found that, upon transient cotransfection of human cells, nDAX-1 repressed the activity of tilapia SF-1 (nSF-1) but not that of human SF-1, although the physical interaction with human SF-1 was retained. Similarly, nSHP repressed the activity of nSF-1, whereas hSHP did not, pointing to divergent evolution of SHP/SF-1 in fish and human. We thus propose that the repressive functions of SHP and DAX-1 have been conserved in fish and mammals although with different transcriptional targets and mechanisms. These differences provide new insights into the physiological diversification of atypical orphan nuclear receptors during vertebrate evolution.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.9
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• pp.1196-1201
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• 2008

This study was carried out to investigate the effects of Salicornia herbacea L. powder (SHP) on white bread quality. Crude fiber, crude ash, Fe and Ca contents of bread with SHP were higher than those of control and increased with increasing SHP concentration. The pH of bread with SHP was higher than that of without SHP. Salinity of bread prepared with SHP (0.6, 1.2, 1.8, and 2.4%) did not show any significant difference compared with control. L and b value of the bread were decreased by the addition of SHP. The inside color of SHP (1.8%) added bread did not show significant difference compared with control. The texture (hardness, chewiness, cohesivness, and springiness) of bread prepared with SHP was higher than that of without SHP. DPPH-radical scavenging activity of SHP added bread (0, 0.6, 1.2, 1.8, 2.4, and 6.0%) was 27.95, 30.42, 33.91, 39.51, 41.17 and 63.82%, respectively. DPPH-radical scavenging activity was increased significantly by the addition of SHP. Inhibition of lipid rancidity and total polyphenol contents of the breads were increased by the addition of SHP.

• Journal of the Korean Society of School Health
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• v.31 no.3
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• pp.157-166
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• 2018

Purpose: This review aimed to provide a new perspective on School Heath Promotion (SHP) in the context of Korea's school system. Methods: Relevant literature and reports on SHP were investigated. On the basis of the analysis, this review closely examined how SHP had been developed, and what has been happening in the recent years of SHP in advanced nations. Results: Major findings from this review in terms of finding a new perspective on SHP in Korea were to: 1) share awareness of the fundamentals of SHP; 2) establish a national framework for school-based SHP; 3) build a cooperative SHP governance; 4) strengthen a SHP monitoring and evaluation system; 5) integrate health and education. Conclusion: Recently, serious student health threats have been putting pressure on schools in Korea. This review will serve as a critical implication of how to effectively implement SHP in Korea.

• Journal of Digestive Cancer Research
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• v.6 no.1
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• pp.6-10
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• 2018

The importance of signal transducer and activator of transcription 3 (STAT3) signaling in gastric carcinogenesis was firmly evaluated in the previous studies. Fully activated STAT3 induces various target genes involving tumor invasion and epithelial-mesenchymal transition (EMT), and mediates interaction between cancer cells and microenvironmental immune cells. Thus, suppression of STAT3 activity is an important issue for inhibition of gastric carcinogenesis and invasion. Unfortunately, data from clinical studies of direct inhibitor targeting STAT3 have been disappointing. SH2-containing protein tyrosine phosphatase 1 (SHP-1) effectively dephosphorylates and inhibits STAT3 activity, which has not been extensively studied gastric cancer research field. However, by summarizing recent data, it is evident that protein and gene expression of SHP-1 are minimal in gastric cancer cells, and induction of SHP-1 effectively downregulates phosphorylated STAT3 and inhibits cellular invasion in gastric cancer cells. Several SHP-1 inducers have been investigated in the experimental studies, including proton pump inhibitor, arsenic trioxide, and other natural compounds. Taken together, we suggest that modulation of SHP-1/STAT3 signaling axis may present a new way for treatment of gastric cancer, and development of effective SHP-1 inducer may be an important task in the future search field of gastric cancer.

• Journal of Acupuncture Research
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• v.22 no.1
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• pp.1-11
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• 2005

Objective : The present study was carried out to investigate the preventive effect of Several Herb-combind Prescription(SHP) on Streptozotocin (STZ) -induced Diabetes mellitus. Methods : SHP was given to rats with the combination of oral administration and herbal-acupuncture stimulation. The experimental animals were divided into 3 groups : normal group of rats, control group of STZ-induced diabetic rats, sample group with SHP treatment. In vitro test of SHP showed ${\alpha}$-glucosidase inhibition, DPPH radical scavenging activity and inhibition of lipid peroxidation. Experimental diabetes was induced by the injection of STZ(60mg/kg) to the rat via the peritoneum. The effect of SHP on STZ-induced diabetes was observed by measuring the seum level of insulin, glucose, triglyceride, total cholesterol and lipid peroxides. Hepatic activities of catalase and reduced glutathione were examined and insulin granule was observed by immunohistochemical examination. Result : STZ caused hyperglycemia and hypoinsulinemia by a selectively destroying pancreatic ${\beta}$-cell. SHP treatment protected them from the hyperglycemia and hypoinsulinemia. STZ induced increase of serum triglyceride lowered by SHP treatment. And by SHP treatment, pancrease showed a big area with positive immuno-reactivity for presence of insulin with many insulin granules distributed in the ${\beta}$-cells in the islets of Langerhans. Contusions : The SHP treatment showed protective effect on diabetic rat model, and action mechanism of the effect was thought to be concerned with anti-oxidative stress.

• Korean Journal of Animal Reproduction
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• v.15 no.3
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• pp.201-205
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• 1991

This study was carried out to investigate the effects of Ca and BSA on hydrogen ion concentration in sperm washed solution. The results obtained were as follows : 1. The hydrogen concentration in 1st and 2nd sperm washed solutions was signifcinatly(p<0.01) higher when sperm was washed with SHPsolution containing 2mM Ca than when sperm washed with SHP solution or SHP solution containing 10mM Ca. 2. The hydrogen ion concentration in sperm washed solution was significnatly(p<0.05) higher when seprm was washed with SHP solution containing BSA-FAF than when sperm was washed with SHP solution or SHP solution containing BSA-V.

• BMB Reports
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• v.49 no.3
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• pp.173-178
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• 2016

Liver cells experience hypoxic stress when drug-metabolizing enzymes excessively consume O₂ for hydroxylation. Hypoxic stress changes the transcription of several genes by activating a heterodimeric transcription factor called hypoxia-inducible factor-1α/β (HIF-1α/β). We found that hypoxic stress (0.1% O₂) decreased the expression of cytochrome P450 7A1 (CYP7A1), a rate-limiting enzyme involved in bile acid biosynthesis. Chenodeoxycholic acid (CDCA), a major component of bile acids, represses CYP7A1 by activating a transcriptional repressor named small heterodimer partner (SHP). We observed that hypoxia decreased the levels of both CDCA and SHP, suggesting that hypoxia repressed CYP7A1 without inducing SHP. The finding that overexpression of HIF-1α increased the activity of the CYP7A1 promoter suggested that hypoxia decreased the expression of CYP7A1 in a HIF-1-independent manner. Thus, the results of this study suggested that hypoxia decreased the activity of CYP7A1 by limiting its substrate O₂, and by decreasing the transcription of CYP7A1.