• Title/Summary/Keyword: Protein phosphatase 4

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In Silico Analysis of Potential Antidiabetic Phytochemicals from Matricaria chamomilla L. against PTP1B and Aldose Reductase for Type 2 Diabetes Mellitus and its Complications

  • Hariftyani, Arisvia Sukma;Kurniawati, Lady Aqnes;Khaerunnisa, Siti;Veterini, Anna Surgean;Setiawati, Yuani;Awaluddin, Rizki
    • Natural Product Sciences
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    • v.27 no.2
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    • pp.99-114
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    • 2021
  • Type 2 diabetes mellitus (T2DM) and its complications are important noncommunicable diseases with high mortality rates. Protein tyrosine phosphatase 1B (PTP1B) and aldose reductase inhibitors are recently approached and advanced for T2DM and its complications therapy. Matricaria chamomilla L. is acknowledged as a worldwide medicinal herb that has many beneficial health effects as well as antidiabetic effects. Our research was designed to determine the most potential antidiabetic phytochemicals from M. chamomilla employing in silico study. 142 phytochemicals were obtained from the databases. The first screening employed iGEMdock and Swiss ADME, involving 93 phytochemicals. Finally, 30 best phytochemicals were docked. Molecular docking and visualization analysis were performed using Avogadro, AutoDock 4.2., and Biovia Discovery Studio 2016. Molecular docking results demonstrate that ligand-protein interaction's binding affinities were -5.16 to -7.54 kcal/mol and -5.30 to -12.10 kcal/mol for PTP1B and aldose reductase protein targets respectively. In silico results demonstrate that M. chamomilla has potential antidiabetic phytochemical compounds for T2DM and its complications. We recommended anthecotulide, quercetin, chlorogenic acid, luteolin, and catechin as antidiabetic agents due to their binding affinities against both PTP1B and aldose reductase protein. Those phytochemicals' significant efficacy and potential as antidiabetic must be investigated in further advanced research.

Discovery of Novel DUSP4 Inhibitors through the Virtual Screening with Docking Simulations

  • Park, Hwangseo;Jeon, Tae Jin;Chien, Pham Ngoc;Park, So Ya;Oh, Sung Min;Kim, Seung Jun;Ryu, Seong Eon
    • Bulletin of the Korean Chemical Society
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    • v.35 no.9
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    • pp.2655-2659
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    • 2014
  • Dual specificity protein phosphatase 4 (DUSP4) has been considered a promising target for the development of therapeutics for various human cancers. Here, we report the first example for a successful application of the structure-based virtual screening to identify the novel small-molecule DUSP4 inhibitors. As a consequence of the virtual screening with the modified scoring function to include an effective molecular solvation free energy term, five micromolar DUSP4 inhibitors are found with the associated $IC_{50}$ values ranging from 3.5 to $10.8{\mu}M$. Because these newly identified inhibitors were also screened for having desirable physicochemical properties as a drug candidate, they may serve as a starting point of the structure-activity relationship study to optimize the medical efficacy. Structural features relevant to the stabilization of the new inhibitors in the active site of DUSP4 are discussed in detail.

Changes of Serum Chemistry Values on Size and Cultured Method in Korean Rockfish, Sebastes schlegeli (사육방법 및 크기에 따른 조피볼락의 혈청 화학성분 변화)

  • Jung, Sung-Hee;Seo, Jung-Soo;Choi, Hye-Sung
    • Journal of Fisheries and Marine Sciences Education
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    • v.26 no.4
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    • pp.695-704
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    • 2014
  • The purpose of this study was to obtain reference values of serum chemistry in Korean rockfish (Sebastes schlegeli), 5 juvenile (n=25) and 3 broodstock (n=15) subpopulations which were differentiated by cultured method. Serum samples were analyzed for the following commercial clinical kits: total protein, albumin, glucose, AST (aspartate aminotransferase), ALT (alanine aminotransferase), total cholesterol, free cholesterol, LDH (lactate dehydrogenase) and ALP (alkaline phosphatase). Significant differences were observed in the values of total protein, albumin, total cholesterol, AST, ALT, LDH and ALP between juvenile and broodstock subpopulations. In the comparison of total protein, albumin, total cholesterol and ALP, broodstock subpopulations showed higher levels. On the other hand, increased AST, ALT and LDH were observed in juvenile subpopulations. These results indicate that cultured method are major contributors to health-related physiology of Korean rockfish, juveniles and broodstocks.

Effect of Extreme Long-Distance Running on Hepatic Metabolism and Renal Function in Middle-Aged Men

  • Shin, Kyung-A;Kim, Young-Joo
    • Biomedical Science Letters
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    • v.24 no.4
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    • pp.411-417
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    • 2018
  • The aim of this study was to investigate the impact of participation in the 622 km hyper-ultra-marathon on hepatic metabolism and renal function in middle-aged men. Healthy middle-aged male amateur ultra-marathoners between the ages of 40 and 60. Blood was collected at the pre-race, immediately after 300 km, 622 km hyper-ultra marathon race, 72 hours (3 day) and 144 hours (6 day) after the race, AST (aspartate aminotransferase), ALT (alanine aminotransferase), ALP (alkaline phosphatase), ${\gamma}$-GTP (gamma glutamyl transferase), T-Bil (total bilirubin), D-Bil (direct bilirubin), T-protein (total protein), albumin, uric acid, BUN (blood urea nitrogen), creatinne were analyzed. ALP was significantly increased at 300 km, 622 km, day 3 and day 6 than the pre-race. ${\gamma}$-GTP, T-protein, albumin, uric acid, BUN and creatinine were not significantly different between the distances and the recovery period respectively. AST and ALT were significantly increased at 300 km, 622 km, day 3 and day 6 than the pre-race, respectively (P<0.05) at day 3 and day 6 they showed significant decrease from 300 km and 622 km, respectively (P<0.05). T-Bil and D-Bil increased significantly at 300 km and 622 km, respectively (P<.05) and significantly decreased at day 3 (P<0.05) compared to the pre-race, at day 3 and day 6 they were decreased significantly than 300 km and 622 km, respectively (P<0.05). In conclusion, no disturbance of renal function was observed according to the distances and between the recovery period of 622 km hyper-ultra marathon race, but reversible hepatocyte function could be degraded and some hemolysis of blood vessels was induced.

A STUDY ON THE RESPONSES OF OSTEOBLASTS TO VARIOUS SURFACE-TREATED TITANIUM

  • Lee Joung-Min;Kim Yung-Soo;Kim Chang-Whe;Jang Kyung-Soo;Lim Young-Jun
    • The Journal of Korean Academy of Prosthodontics
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    • v.42 no.3
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    • pp.307-326
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    • 2004
  • Statement of problem. The long-term success of implants is the development of a stable direct connection between bone and implant surface, which must be structural and functional. To improve a direct implant fixation to the bone, various strategies have been developed focusing on the surface of materials. Among them, altering the surface properties can modify cellular responses such as cell adhesion, cell motility and bone deposition. Purpose. This study was to evaluate the cellular behaviors on the surface-modified titanium by morphological observation, cellular proliferation and differentiation. Material and methods. Specimens were divided into five groups, depending on their surface treatment: electropolishing(EP) anoclizing(AN), machining(MA), blasting with hydroxyapatite particle(RBM) and electrical discharge machining(EDM). Physicochemical properties and microstructures of the specimens were examined and the responses of osteoblast-like cells were investigated. The microtopography of specimens was observed by scanning electron microscopy(SEM). Surface roughness was measured by a three-dimensional roughness measuring system. The microstructure was analyzed by X-ray diffractometer(XRD) and scanning auger electron microscopy(AES). To evaluate cellular responses to modified titanium surfaces, osteoblasts isolated from neonatal rat were cultured. The cellular morphology and total protein amounts of osteoblast-like cell were taken as the marker for cellular proliferation, while the expression of alkaline phosphatase was used as the early differentiation marker for osteoblast. In addition, the type I collagen production was determined to be a reliable indicator of bone matrix synthesis. Results. 1. Each prepared specimen showed specific microtopography at SEM examination. The RBM group had a rough and irregular pattern with reticulated appearance. The EDM-treated surface had evident cracks and was heterogeneous consisting of broad sheet or plate with smooth edges and clusters of small grains, deep pores or craters. 2. Surface roughness values were, from the lowest to the highest, electropolished group, anodized group, machined group, RBM group and EDM group. 3. All groups showed amorphous structures. Especially anodized group was found to have increased surface oxide thickness and EDM group had titaniumcarbide(TiC) structure. 4. Cells on electropolished, anodized and machined surfaces developed flattened cell shape and cells on RBM appeared spherical and EDM showed both. After 14 days, the cells cultured from all groups were formed to be confluent and exhibited multilayer proliferation, often overlapped or stratified. 5. Total protein amounts were formed to be quite similar among all the group at 48 hours. At 14 days, the electropolished group and the anodized group induced more total protein amount than the RBM group(P<.05). 6. There was no significant difference among five groups for alkaline phosphatase(ALP) activity at 48 hours. The AN group showed significantly higher ALP activity than any other groups at 14 days(P<.05). 7. All the groups showed similar collagen synthesis except the EDM group. The amount of collagen on the electropolished and anodized surfaces were higher than that on the EDM surface(P<.05).

Effects of an in vitro vitamin D treatment on the inflammatory responses in visceral adipose tissue from Ldlr-/- mice

  • Deok Hoon Kwon;Jungwon Hwang;Hyeyoung You;Na Young Kim;Ga Young Lee;Sung Nim Han
    • Nutrition Research and Practice
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    • v.18 no.1
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    • pp.19-32
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    • 2024
  • BACKGROUND/OBJECTIVES: Atherosclerosis is associated with increased inflammation in the visceral adipose tissue (VAT). Vitamin D has been reported to modulate the inflammatory responses of stromal vascular cells (SVCs) and adipocytes in adipose tissue, but the role of vitamin D in atherosclerosis biology is unclear. This study examined the effects of in vitro 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) treatment on the inflammatory responses of SVCs and adipocytes from atherosclerotic mice. MATERIALS/METHODS: C57BL/6J (B6) mice were divided randomly into 2 groups and fed a 10% kcal fat control diet (control group, CON) or 41% kcal fat, 0.21% cholesterol (high fat + cholesterol, HFC) diet (obese group, OB), and B6.129S7-Ldlrtm1Her/J (Ldlr-/-) mice were fed a HFC diet (obese with atherosclerosis group, OBA) for 16 weeks. SVCs and adipocytes isolated from VAT were pre-incubated with 1,25(OH)2D3 for 24 h and stimulated with lipopolysaccarides for the next 24 h. Proinflammatory cytokine production by adipocytes and SVCs, the immune cell population in SVCs, and the expression of the genes involved in the inflammatory signaling pathway in SVCs were determined. RESULTS: The numbers of total macrophages and SVCs per mouse were higher in OB and OBA groups than the CON group. The in vitro 1,25(OH)2D3 treatment significantly reduced macrophages/SVCs (%) in the OBA group. Consistent with this change, the production of interleukin-6 and monocyte chemoattractant protein 1 (MCP-1) by SVCs from the OBA group was decreased by 1,25(OH)2D3 treatment. The 1,25(OH)2D3 treatment significantly reduced the toll-like receptor 4 and dual-specificity protein phosphatase 1 (also known as mitogen-activated protein kinase phosphatase 1) mRNA levels in SVCs and MCP-1 production by adipocytes from all 3 groups. CONCLUSIONS: These findings suggest that vitamin D can attribute to the inhibition of the inflammatory response in VAT from atherosclerotic mice by reducing proinflammatory cytokine production.

A STUDY ON OSTEOBLAST-LIKE CELL RESPONSES TO SURFACE-MODIFIED TITANIUM

  • Hong Min-Ah;Kim Yung-Soo;Kim Chang-Whe;Jang Kyung-Su;Lee Jae-Il
    • The Journal of Korean Academy of Prosthodontics
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    • v.41 no.3
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    • pp.300-318
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    • 2003
  • Statement of problem: The success of implants depends on intimate and direct contact of implant material on bone tissue and on functional relationship with soft tissue contact. Creation and maintenance of osseointegration depend on the understanding of the tissue's healing, repairing, and remodeling capacity and these capacities rely on cellular behavior. Altering the surface properties can modify cellular responses such as cell adhesion, cell motility, bone deposition, Therefore, various implant surface treatment methods are being developed for the improved bone cell responses. Purpose: The purpose of this study was to evaluate the responses of osteoblast-like cells to surface-modified titanium. Materials and Methods: The experiment was composed of four groups. Group 1 represented the electropolished surface. Group 2 surfaces were machined surface. Group 3 and Group 4 were anodized surfaces. Group 3 had low roughness and Group 4 had high roughness. Physicochemical properties and microstructures of the discs were examined and the responses of osteoblast-like cells to the discs were investigated. The microtopography was observed by SEM. The roughness was measured by three-dimension roughness measuring system. The microstructure was analyzed by XRD, AES. To evaluate cell responses to modified titanium surfaces, osteoblasts isolated from calvaria of neonatal rat were cultured. Cell count, morphology, total protein measurement and alkaline phosphatase activities of the cultures were examined. Results and Conclusion: The results were as follows 1. The four groups showed specific microtopography respectively. Anodized group showed grain structure with micropores. 2. Surface roughness values were, from the lowest to the highest, electropolished group, machined group, low roughness anodized group, and high roughness anodized group. 3. Highly roughened anodized group was found to have increased surface oxide thickness and surface crystallinity. 4. The morphology of cells, flattened or spherical, were different from each other. In the electropolished group and machined group, the cells were almost flattened. In two anodized groups, some cells were spherical and other cells were flattened. And the 14 day culture cells of all of the groups were nearly flattened due to confluency. 5. The number of attached cells was highest in low roughness anodized group. And the machined group had significantly lower cell count than any other groups(P<.05). 6. Total protein contents showed no difference among groups. 7. The level of alkaline phosphatase activities was higher in the anodized groups than electropolished and machined groups(P<.05).

Effects of Pre-heat Treatments on Milk Protein and Microorganism Aspects in Raw Milk (예열처리(豫熱處理)가 원유(原乳)의 단백질(蛋白質) 및 미생물(微生物)에 미치는 영향(影響))

  • Kim, Seung Sub;Kim, Jong Woo
    • Korean Journal of Agricultural Science
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    • v.20 no.2
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    • pp.153-166
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    • 1993
  • The experiments were conducted to improve raw milk quality during storage, the chemical composition and microbiological aspect of raw milk, milk thermized at $65^{\circ}C$ for 30 second, and $75^{\circ}C$ for 2 second stored at $5^{\circ}C$ for 4 days were investigated. The result obtained were summarized as follows : 1. During storage of raw and thermized milk, in the composition of milk fat, milk protein, lactose and total solid did not change significantly. 2. The range of pH and acidity for the raw milk were 6.73~5.94 and 0.16~0.27% respectively and those of the thermized milk were 6.79~6.62 and 0.16~0.17% respectively. The phosphatase test were negative in heated milk. 3. The composition of total nitrogen, NCN and whey protein were decreased, wherease those of NPN and casein were increased in heat treated milk. 4. The compositions of total nitrogen and casein were decreased as the storage period advanced, wherese those of NCN and NPN were increased. However, the composition of whey protein did not significantly change. 5. The number of coliform bacteria was not found in thermized milk. but were gradually increased in raw milk during storage period. 6. Raw milk had total bacteria count as $5.6{\times}10^6/ml$, psychrotrophic bacteria $1.8{\times}10^6/ml$ and thermoduric bacteria $1.6{\times}10^5/ml$, as the heat treatment increased microorganism counts decreased to milk thermized at $75^{\circ}C$, for 2 sec. $3.0{\times}10^3/ml$, $1.5{\times}10/ml$ and $2.7{\times}10^3/ml$ respectively. 7. The count of thermoduric bacteria, psychrotrophic bacteria and total bacteria were increased during storage period, and more rapidly increased in raw milk than in heat treated milk.

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Naringin enhances the migration and osteogenic differentiation of human dental pulp stem cells

  • Yeon, Kim;Hyun-Joo, Park;Mi-Kyoung, Kim;Yong-Il, Kim;Soo-Kyung, Bae;Hyung Joon, Kim;Moon-Kyoung, Bae
    • International Journal of Oral Biology
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    • v.47 no.4
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    • pp.55-62
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    • 2022
  • Bioactive flavonoids have been shown to improve the biological activity of stem cells derived from different sources in tissue regeneration. The goal of this study was to see how naringin, a natural flavonoid discovered in citrus fruits, affected the biological properties of human dental pulp stem cells (HDPSCs). In this study, we found that naringin increases the migratory ability of HDPSCs. Naringin increased matrix metalloproteinase-2 (MMP-2) and C-X-C chemokine receptor type 4 (CXCR4) mRNA and protein expression in HDPSCs. ARP100, a selective MMP-2 inhibitor, and AMD3100, a CXCR4 antagonist, both inhibited the naringin-induced migration of HDPSCs. Furthermore, naringin increased osteogenic differentiation of HDPSCs and the expression of the osteogenic-related marker, alkaline phosphatase in HDPSCs. Taken together, our findings suggest that naringin may be beneficial on dental tissue or bone regeneration by increasing the biological activities of HDPSCs.

The Change of Protein Patterns in Follicular Fluid on Ovarian Response Following Controlled Ovarian Hyperstimulation (COH) of Human (사람의 과배란 유도 후 난소 반응별 난포액 내 단백질 변화)

  • Lee, Chae-Sik;Lee, Sang-Chan;Rho, Yong-Ho;Oh, Dae-Sik;Lee, Yong-Seung;Song, Eun-Ji;Cheong, Hee-Tae;Yang, Boo-Keun;Park, Choon-Keun
    • Reproductive and Developmental Biology
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    • v.35 no.3
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    • pp.273-280
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    • 2011
  • It was conducted the experiment, divided into three groups as normal, poor and polycystic ovary syndrome, to detect the change of protein patterns in follicular fluid on ovarian response following controlled ovarian hyperstimulation for human IVF outcome. In the normal group, it was confirmed reproducible 57 spots in the detected total 81 spots. Then 1 spot was not found in the other groups. In the poor responder group, it was found reproducible 53 spots in the detected total 98 spots. 6 spots were down-regulation and 7 spots were up-regulation comparable with normal group. There were not 5 spots in poor responder group comparable with other groups. In the polycystic ovary syndrome group, it was expressed reproducible 53 spots in the detected total 80 spots and 3 spots were just expressed in this group. However, 4 spots were not found in polycystic ovary syndrome. 9 spots were up-regulation comparable with normal group. Significant up and down-regulation spots among the each groups were identified. The results were a cytosolic carboxypeptidase, a signal-induced proliferation-associated protein 1, a ceruloplasmin, a keratin(type II cytoskeletal 1), a polypeptide N-acetylgalactosantinyltransferase 2, a serine/threonine-protein phosphatase 4 regulatory subunit 4. It was identified that 8 spots, 6 kinds of protein are corresponded with NCBInr database research, but 10 spots were failed in the identification. In conclusion, it has been confirmed change and expression of protein on the ovarian response following COH of human.