• IMMUNE NETWORK
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• 제6권4호
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• pp.204-210
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• 2006

Background: Nitric oxide (NO) in articular chondrocytes regulates dedifferentiation and inflammatory responses by modulating MAP kinases. In this study, we investigated whether the Src kinase in chondrocytes regulates NO-induced dedifferentiation and cyclooxygenase-2 (COX-2) expression. Methods: Primary chondrocytes were treated with various concentrations of SNP for 24 h. The COX-2 and type II collagen expression levels were determined by immunoblot analysis, and prostaglandin $E_2\;(PGE_2)$ was determined by using a $PGE_2$ assay kit. Expression and distribution of p-Caveolin and COX-2 in rabbit articular chondrocytes and cartilage explants were determined by immunohistochemical staining and immunocytochemical staining, respectively. Results: SNP treatment stimulated Src kinase activation in a dose-dependent manner in articular chondrocytes. The Src kinase inhibitors PP2 [4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo(3,4-d)pyrimidine], a significantly blocked SNP-induced p38 kinase and caveolin-1 activation in a dose-dependent manner. Therefore, to determine whether Src kinase activation is associated with dedifferentiation and/or COX-2 expression and $PGE_2$ production. As expected, PP2 potentiated SNP-stimulated dedifferentiation, but completely blocked both COX-2 expression and $PGE_2$ production. And also, levels of p-Caveolin and COX-2 protein expression were increased in SNP-treated primary chondrocytes and osteoarthritic and rheumatoid arthritic cartilage, suggesting that p-Caveolin may playa role in the inflammatory responses of arthritic cartilage. Conclusion: Our previously studies indicated that NO caused dedifferentiation and COX-2 expression is regulated by p38 kinase through caveolin-1 (1). Therefore, our results collectively suggest that Src kinase regulates NO-induced dedifferentiation and COX-2 expression in chondrocytes via p38 kinase in association with caveolin-1.

• Earthquakes and Structures
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• 제7권3호
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• pp.317-331
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• 2014

An experimental study was performed to investigate the seismic performance of solid steel reinforced concrete (SRC) frames with special-shaped columns that are composed of SRC special-shaped columns and reinforced concrete beams. For this purpose, two models of two-bay and three-story frame, including an edge frame and a middle frame, were designed and tested. The failure process and patterns were observed. The mechanical behaviors such as load-displacement hysteretic loops and skeleton curves, load bearing capacity, drift ratio, ductility, energy dissipation and stiffness degradation of test specimens were analyzed. Test results show that the failure mechanism of solid SRC frame with special-shaped columns is the beam-hinged mechanism, satisfying the seismic design principle of "strong column and weak beam". The hysteretic loops are plump, the ductility is good and the capacity of energy dissipation is strong, indicating that the solid SRC frame with special-shaped columns has excellent seismic performance, which is better than that of the lattice SRC frame with special-shaped columns. The ultimate elastic-plastic drift ratio is larger than the limit value specified by seismic code, showing the high capacity of collapse resistance. Compared with the edge frame, the middle frame has higher carrying capacity and stronger energy dissipation, but the ductility and speed of stiffness degradation are similar. All these can be helpful to the designation of solid SRC frame with special-shaped columns.

• Biomolecules & Therapeutics
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• 제29권1호
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• pp.41-51
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• 2021

Src family kinases (SFKs), an important group of non-receptor tyrosine kinases, are suggested to be excessively activated during various types of tissue fibrosis. The present study investigated the effect of KF-1607, an orally active and a newly synthesized Src kinase inhibitor (SKI) with proposed low toxicity, in preventing the progression of renal interstitial fibrosis. Unilateral ureteral obstruction (UUO) surgery was performed in 6-week-old male C57BL/6 mice to induce renal interstitial fibrosis. Either KF-1607 (30 mg/kg, oral gavage) or PP2 (2 mg/kg, intraperitoneal injection), a common experimental SKI, was administered to mice for seven days, started one day prior to surgery. UUO injury-induced SFK expression, including Src, Fyn, and Lyn kinase. SFK inhibition by KF-1607 prevented the progression of tubular injury in UUO mice, as indicated by decreases in albuminuria, urinary KIM-1 excretion, and kidney NGAL protein expression. Renal tubulointerstitial fibrosis was attenuated in response to KF-1607, as shown by decreases in α-SMA, collagen I and IV protein expression, along with reduced Masson's trichrome and collagen-I staining in kidneys. KF-1607 also inhibited inflammation in the UUO kidney, as exhibited by reductions in F4/80 positive-staining and protein expression of p-NFκB and ICAM. Importantly, the observed effects of KF-1607 were similar to those of PP2. A new pan Src kinase inhibitor, KF-1607, is a potential pharmaceutical agent to prevent the progression of renal interstitial fibrosis.

• The Korean Journal of Physiology and Pharmacology
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• 제25권2호
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• pp.159-166
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• 2021

Nicotinamide adenine dinucleotide phosphate oxidases (NOXs) are the major enzymatic source of reactive oxygen species (ROS). NOX2 and NOX4 are expressed in the heart but its role in hypoxia-induced atrial natriuretic peptide (ANP) secretion is unclear. This study investigated the effect of NOX on ANP secretion induced by hypoxia in isolated beating rat atria. The results showed that hypoxia significantly upregulated NOX4 but not NOX2 expression, which was completely abolished by endothelin-1 (ET-1) type A and B receptor antagonists BQ123 (0.3 μM) and BQ788 (0.3 μM). ET-1-upregulated NOX4 expression was also blocked by antagonists of secreted phospholipase A2 (sPLA2; varespladib, 5.0 μM) and cytosolic PLA2 (cPLA2; CAY10650, 120.0 nM), and ET-1-induced cPLA2 expression was inhibited by varespladib under normoxia. Moreover, hypoxia-increased ANP secretion was evidently attenuated by the NOX4 antagonist GLX351322 (35.0 μM) and inhibitor of ROS N-Acetyl-D-cysteine (NAC, 15.0 mM), and hypoxia-increased production of ROS was blocked by GLX351322. In addition, hypoxia markedly upregulated Src expression, which was blocked by ET receptors, NOX4, and ROS antagonists. ET-1-increased Src expression was also inhibited by NAC under normoxia. Furthermore, hypoxia-activated extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (Akt) were completely abolished by Src inhibitor 1 (1.0 μM), and hypoxia-increased GATA4 was inhibited by the ERK1/2 and Akt antagonists PD98059 (10.0 μM) and LY294002 (10.0 μM), respectively. However, hypoxia-induced ANP secretion was substantially inhibited by Src inhibitor. These results indicate that NOX4/Src modulated by ET-1 regulates ANP secretion by activating ERK1/2 and Akt/GATA4 signaling in isolated beating rat hypoxic atria.

• 한국발생생물학회:학술대회논문집
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• 한국발생생물학회 2003년도 전기 한국발생생물학회 제16차 학술대회논문집
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• pp.28-28
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• 2003

• BMB Reports
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• 제46권6호
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• pp.316-321
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• 2013

Gastric cancer remains the main cause of cancer death all around the world, and upregulated activation of the nonreceptor tyrosine kinase c-SRC (SRC) is a key player in the development. In this study, we found that expression of Src is also increased in clinical gastric cancer samples, with the protein level increased more significantly than that at the RNA level. Further study revealed that miR34a and miR203, two tumor suppressive miRNAs, inversely correlate with the expression of Src. Restoration of miR34a and miR203 decreased Src expression in gastric cancer cell lines, which in turn inhibited cell growth and cell migration. In summary, our study here revealed that posttranscriptional regulation of Src contributes to the deregulated cell growth and metastasis in gastric cancer, and targeting Src by miR34a or miR203 mimics would be a promising strategy in therapy.

• 복합신소재구조학회 논문집
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• 제5권2호
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• pp.9-14
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• 2014

Main topics in this study is a new structural detail for connection between H-Steel or SRC column and flat plate slab. We carried out to evaluate the punching shear performance of H-steel or SRC column + RC slab system for vertical load and lateral load. From the test results structural characteristics - yield moment, yield rotation, maximum moment, deformation capabilities ect. - are obtained and evaluated. In this paper as a shear reinforcement for supporting region of plate closed stirrup type and shear band are used, and their test results are compared.

• KSII Transactions on Internet and Information Systems (TIIS)
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• 제9권7호
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• pp.2667-2682
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• 2015

Due to the wide application of face recognition (FR) in information security, surveillance, access control and others, it has received significantly increased attention from both the academic and industrial communities during the past several decades. However, partial face occlusion is one of the most challenging problems in face recognition issue. In this paper, a novel method based on linear regression-based classification (LRC) algorithm is proposed to address this problem. After all images are downsampled and divided into several blocks, we exploit the evaluator of each block to determine the clear blocks of the test face image by using linear regression technique. Then, the remained uncontaminated blocks are utilized to partial occluded face recognition issue. Furthermore, an improved Distance-based Evidence Fusion approach is proposed to decide in favor of the class with average value of corresponding minimum distance. Since this occlusion removing process uses a simple linear regression approach, the completely computational cost approximately equals to LRC and much lower than sparse representation-based classification (SRC) and extended-SRC (eSRC). Based on the experimental results on both AR face database and extended Yale B face database, it demonstrates the effectiveness of the proposed method on issue of partial occluded face recognition and the performance is satisfactory. Through the comparison with the conventional methods (eigenface+NN, fisherfaces+NN) and the state-of-the-art methods (LRC, SRC and eSRC), the proposed method shows better performance and robustness.

• Steel and Composite Structures
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• 제17권3호
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• pp.287-303
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• 2014

8 steel reinforced concrete (SRC) columns with the encased steel ratio of 13.12% and 15.04% respectively were tested under the test axial load ratio of 0.33-0.80 and the low-frequency cyclic lateral loading. The cross sectional area of composite columns was $500mm{\times}500mm$. The mechanical properties, failure modes and deformabilities were studied. All the specimens produced flexure failure subject to combined axial force, bending moment and shear. Force-displacement hysteretic curves, strain curves of encased steels and rebars were obtained. The interaction behavior of encased steel and concrete were verified. The hysteretic curves of columns were plump in shapes. Hysteresis loops were almost coincident under the same levels of lateral loading, and bearing capacities did not change much, which indicated that the columns had good energy-dissipation performance and seismic capacity. Based on the equilibrium equation, the suggested practical calculation method could accurately predict the flexural strength of SRC columns with cross-shaped section encased steel. The obtained M-N curves of SRC columns can be used as references for further studies.

• Structural Engineering and Mechanics
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• 제22권4호
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• pp.419-432
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• 2006

Experimental studies on the behaviors of box-shape steel reinforced concrete (SRC) composite beams were conducted. Seven 1:3 scale model composite beams were tested to failure. Each of the beams was simply supported at the ends and two concentrated loads were applied at the one-third span and two-thirds span respectively. Experimental results indicate that the flexural strength can be enhanced when the ratio of flexural reinforcements and flange thickness of the shape steel are increased; the shear strength is enhanced with increase of web thickness of the shape steel. Insignificant effects of concrete in the box-shape steel are found on improving the flexural strength and shear strength of the box-shape SRC composite beams, thus concrete inside the box-shape steel can be saved, and the weight of the SRC beams can be decreased. Shear studs can strengthen the connection and co-work effects between the shape steel and the concrete and enhance the shear strength, but stud design for the composite beams should be further improved. Formulas for flexural and shear strength of the composite beams are proposed, and the calculated results are in good agreement with the experimental results. In general, the box-shape SRC composite beam is a kind of ductile member, and suitable for extensive engineering application.