[Show abstract][Hide abstract] ABSTRACT: Distraction osteogenesis (DO) is a promising tool for bone and tissue regeneration. However, prolonged healing time remains a major problem. Various materials including cells, cytokines, and growth factors have been used in an attempt to enhance bone formation. We examined the effect of percutaneous injection of demineralized bone matrix (DBM) during the consolidation phase on bone regeneration after distraction.
The immature rabbit tibial DO model (20 mm length-gain) was used. Twenty-eight animals received DBM 100 mg percutaneously at the end of distraction. Another 22 animals were left without further procedure (control). Plain radiographs were taken every week. Postmortem bone dual-energy X-ray absorptiometry and micro-computed tomography (micro-CT) studies were performed at the third and sixth weeks of the consolidation period and histological analysis was performed.
The regenerate bone mineral density was higher in the DBM group when compared with that in the saline injection control group at the third week postdistraction. Quantitative analysis using micro-CT revealed larger trabecular bone volume, higher trabecular number, and less trabecular separation in the DBM group than in the saline injection control group. Cross-sectional area and cortical thickness at the sixth week postdistraction, assessed using micro-CT, were greater in the regenerates of the DBM group compared with the control group. Histological evaluation revealed higher trabecular bone volume and trabecular number in the regenerate of the DBM group. New bone formation was apparently enhanced, via endochondral ossification, at the site and in the vicinity of the injected DBM. DBM was absorbed slowly, but it remained until the sixth postoperative week after injection.
DBM administration into the distraction gap at the end of the distraction period resulted in a significantly greater regenerate bone area, trabecular number, and cortical thickness in the rabbit tibial DO model. These data suggest that percutaneous DBM administration at the end of the distraction period or in the early consolidation period may stimulate regenerate bone formation and consolidation in a clinical situation with delayed bone healing during DO.
Clinics in orthopedic surgery 09/2015; 7(3):383-91. DOI:10.4055/cios.2015.7.3.383
[Show abstract][Hide abstract] ABSTRACT: A chromosome territory is composed of chromosomal subdomains. The internal structure of chromosomal subdomains provides a structural framework for many genomic activities such as replication and DNA repair, and thus is key to determining the basis of their mechanisms. However, the internal structure and regulating proteins of a chromosomal subdomain remains elusive. Previously, we showed that the chromosome territory expanded after BAF53 knockdown. Because the integrity of chromosomal subdomains is a deciding factor of the volume of a chromosome territory, we examined here the effect of BAF53 knockdown on chromosomal subdomains. We found that BAF53 knockdown led to the disintegration of histone H2B-GFP-visualized chromosomal subdomains and BrdUlabeled replication foci. In addition, the size of DNA loops measured by the maximum fluorescent halo technique increased and became irregular after BAF53 knockdown, indicating DNA loops were released from the residual nuclear structure. These data can be accounted for by the model that BAF53 is prerequisite for maintaining the structural integrity of chromosomal subdomains.
[Show abstract][Hide abstract] ABSTRACT: Fluoxetine was originally developed as an antidepressant, but it has also been used to treat obesity. Although the anti-appetite effect of fluoxetine is well-documented, its potential effects on human adipose-derived stem cells (ASCs) or mature adipocytes have not been investigated. Therefore, we investigated the mechanisms underlying the inhibitory effects of fluoxetine on the proliferation of ASCs. We also investigated its inhibitory effect on adipogenic differentiation. Fluoxetine significantly decreased ASC proliferation, and signal transduction PCR array analysis showed that it increased expression of autophagy-related genes. In addition, fluoxetine up-regulated SQSTM1 and LC3B protein expression as detected by western blotting and immunofluorescence. The autophagy inhibitor, 3-methyladenine (3-MA), significantly attenuated fluoxetine-mediated effects on ASC proliferation and SQSTM1/LC3B expression. In addition, 3-MA decreased the mRNA expression of two autophagy-related genes, beclin-1 and Atg7, in ASCs. Fluoxetine also significantly inhibited lipid accumulation and down-regulated the levels of PPAR-γ and C/EBP-α in ASCs. Collectively, these results indicate that fluoxetine decreases ASC proliferation and adipogenic differentiation. This is the first in vitro evidence that fluoxetine can reduce fat accumulation by inhibiting ASC proliferation and differentiation.
International Journal of Molecular Sciences 07/2015; 16(7):16655-68. DOI:10.3390/ijms160716655 · 2.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Phospholipid derivatives, such as lysophosphatidic acid (LPA), exhibit mitogenic effects on mesenchymal stem cells; however, the molecular mechanism underlying this stimulation has yet to be identified. The aims of the present study were as follows: To evaluate the stimulatory effects of LPA on the proliferation and migration of adipose‑derived stem cells (ASCs); to study the association between reactive oxygen species (ROS) and LPA signaling in ASCs; and to investigate the microRNAs upregulated by LPA treatment in ASCs. The results of the present study demonstrated that LPA increased the proliferation and migration of ASCs, and acted as a mitogenic signal via extracellular signal‑regulated kinases 1/2 and the phosphoinositide 3‑kinase/Akt signaling pathways. The LPA1 receptor is highly expressed in ASCs, and pharmacological inhibition of it by Ki16425 significantly attenuated the proliferation and migration of ASCs. In addition, LPA treatment generated ROS via NADPH oxidase 4, and ROS were able to function as signaling molecules to increase the proliferation and migration of ASCs. The induction of ROS by LPA treatment also upregulated the expression of miR‑210. A polymerase chain reaction array assay demonstrated that the expression levels of adrenomedullin and Serpine1 were increased following treatment with LPA. Furthermore, transfection with Serpine1‑specific small interfering RNA attenuated the migration of ASCs. In conclusion, the present study is the first, to the best of our knowledge, to report that ROS generation and miR‑210 expression are associated with the LPA‑induced stimulation of ASCs, and that Serpine1 mediates the LPA‑induced migration of ASCs. These results further suggest that LPA may be used for ASC stimulation during stem cell expansion.
Molecular Medicine Reports 07/2015; DOI:10.3892/mmr.2015.4023 · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Red tides – discolorations of the sea surface due to dense plankton blooms – occur regularly in coastal and offshore waters along much of the world's coastline. Red tides often cause large-scale mortalities of fish and shellfish and significant losses to the aquaculture and tourist industries of many countries. Therefore, understanding and predicting the mechanisms controlling the outbreak, persistence, spread, and decline of red tides are important concerns to scientists, officials, industry, and the public. With increasing knowledge of red-tide species and red-tide events, new mechanisms have been discovered. Based on the nutrition and behaviors of red-tide organisms and biological interactions among them, red-tide outbreaks can be categorized into a hierarchy of four generation mechanisms (GM1–GM4). In the simplest, GM1, all phototrophic red-tide species were treated as exclusively autotrophic organisms without the ability to swim. However, this GM cannot explain red-tide outbreaks in oligotrophic surface waters offshore. Vertical migration (considered in GM2) and mixotrophy (GM3) enable red-tide flagellates to acquire growth factors from nutrient-rich deep waters or co-occurring prey, respectively. In natural environments, all red tides occur by those species outgrowing co-occurring organisms; red-tide species dominate communities by eliminating other species or reducing their abundances. Thus, GM4 contains the direct biological interactions (i.e., inhibition by physical contact or chemical effects) and indirect biological interactions (i.e., acquiring resources faster than others) that can affect the dominance of red-tide species under given conditions. Correctly choosing one of these four GMs for red tides dominated by one causative species is important because the accuracy of predictions may be outweighed by the costs and time required to acquire the relevant information. In this study, mechanisms describing the outbreak, persistence, and decline of red tides were reviewed, the advantages and limitations of each mechanism were evaluated, and insights about the evolution of the mechanisms were developed.
[Show abstract][Hide abstract] ABSTRACT: Aripiprazole (ARI) is a commonly prescribed medication used to treat schizophrenia and bipolar disorder. To date, there have been no studies regarding the molecular pathological and immunotoxicological profiling of aripiprazole. Thus, in the present study, we prepared two different formulas of aripiprazole [Free base crystal of aripiprazole (ARPGCB) and cocrystal of aripiprazole (GCB3004)], and explored their effects on the patterns of survival and apoptosis-regulatory proteins under acute toxicity and cytotoxicity test conditions. Furthermore, we also evaluated the modulatory activity of the different formulations on the immunological responses in macrophages primed by various stimulators such as lipopolysaccharide (LPS), pam3CSK, and poly(I:C) via toll-like receptor 4 (TLR4), TLR2, and TLR3 pathways, respectively. In liver, both ARPGCB and GCB3004 produced similar toxicity profiles. In particular, these two formulas exhibited similar phospho-protein profiling of p65/nuclear factor (NF)-κB, c-Jun/activator protein (AP)-1, ERK, JNK, p38, caspase 3, and bcl-2 in brain. In contrast, the patterns of these phospho-proteins were variable in other tissues. Moreover, these two formulas did not exhibit any cytotoxicity in C6 glioma cells. Finally, the two formulations at available in vivo concentrations did not block nitric oxide (NO) production from activated macrophage-like RAW264.7 cells stimulated with LPS, pam3CSK, or poly(I:C), nor did they alter the morphological changes of the activated macrophages. Taken together, our present work, as a comparative study of two different formulas of aripiprazole, suggests that these two formulas can be used to achieve similar functional activation of brain proteins related to cell survival and apoptosis and immunotoxicological activities of macrophages.
Korean Journal of Physiology and Pharmacology 07/2015; 19(4):365-72. DOI:10.4196/kjpp.2015.19.4.365 · 1.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cordyceps species including Cordyceps bassiana are a notable anti-cancer dietary supplement. Previously, we identified several compounds with anti-cancer activity from the butanol fraction (Cb-BF) of Cordyceps bassiana. To expand the structural value of Cb-BF-derived anti-cancer drugs, we employed various chemical moieties to produce a novel Cb-BF-derived chemical derivative, KTH-13-amine-monophenyl [4-isopropyl-2-(1-phenylethyl) aniline (KTH-13-AMP)], which we tested for anti-cancer activity. KTH-13-AMP suppressed the proliferation of MDA-MB-231, HeLa, and C6 glioma cells. KTH-13-AMP also dose-dependently induced morphological changes in C6 glioma cells and time-dependently increased the level of early apoptotic cells stained with annexin V-FITC. Furthermore, the levels of the active full-length forms of caspase-3 and caspase-9 were increased. In contrast, the levels of total forms of caspases-3, caspase-8, caspase-9, and Bcl-2 were decreased in KTH-13-AMP treated-cells. We also confirmed that the phosphorylation of STAT3, Src, and PI3K/p85, which is linked to cell survival, was diminished by treatment with KTH-13-AMP. Therefore, these results strongly suggest that this compound can be used to guide the development of an anti-cancer drug or serve as a lead compound in forming another strong anti-proliferative agent.
Biomolecules and Therapeutics 07/2015; 23(4):367-73. DOI:10.4062/biomolther.2015.021 · 1.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cordyceps militaris is one of well-known medicinal mushrooms with anti-inflammatory, anti-cancer, anti-diabetic, and anti-obesity activities.
The objective of the following study is to isolate chemical components from the ethanol extract (Cm-EE) from Cordyceps militaris and to evaluate their anti-inflammatory activities.
Column chromatographic separation was performed and anti-inflammatory roles of these compounds were also examined by using NO production and protein kinase B (AKT) activity assays.
From Cm-EE, 13 constituents, including trehalose (1), cordycepin (2), 6-hydroxyethyladenosine (3), nicotinic amide (4), butyric acid (5), β-dimorphecolic acid (6), α-dimorphecolic acid (7), palmitic acid (8), linoleic acid (9), cordycepeptide A (10), 4-(2-hydroxy-3-((9E,12E)-octadeca-9,12-dienoyloxy)propoxy)-2-(trimethylammonio)butanoate (11), 4-(2-hydroxy-3-(palmitoyloxy)propoxy)-2-(trimethylammonio)butanoate (12), and linoleic acid methyl ester (13) were isolated. Of these components, compound 2 displayed a significant inhibitory effect on NO production in lipopolysaccharide (LPS)-activated RAW264.7 cells. Furthermore, this compound strongly and directly suppressed the kinase activity of AKT, an essential signalling enzyme in LPS-induced NO production, by interacting with its ATP binding site.
C. militaris could have anti-inflammatory activity mediated by cordycepin-induced suppression of AKT.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate the validity and reliability of the Korean version of the Person-centered Care Assessment Tool (P-CAT).
The English P-CAT was translated into Korean with forward and backward translation. Survey data were collected from 458 staff in 17 long-term care facilities in Korea. Construct validity and criterion related validity were evaluated. Cronbach's alpha was used to assess reliability.
The Korean version of P-CAT was shown to be valid homogeneously by factor, item and content analysis. Internal consistency reliability was satisfactory in which the values of factor 1, factor 2 and the total scale were .84, .77 and .86 respectively. Exploratory factor analysis supported the construct validity with a two-factor solution. Factor loadings of the 13 items ranged in .34~.80. Criterion validity to the Person-centered Climate Questionnaire-staff (PCQ-S) was .74 (p<.001).
The Korean version of the P-CAT was found to be an applicable instrument with satisfactory reliability and validity for further use in measuring successful person-centered care in long-term care facilities for older persons.
Journal of Korean Academy of Nursing 06/2015; 45(3):412-9. DOI:10.4040/jkan.2015.45.3.412 · 0.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Positron emission tomography (PET) images usually suffer from low spatial resolution mainly because of the finite dimension of crystals. To improve the spatial resolution based on wobble scanning, we previously proposed a sinogram-based super-resolution (SR) algorithm using a space-variant blur matrix. However, the algorithm may cause unwanted resolution loss owing to an inevitable interpolation process for preparing evenly spaced projections. In this article, we propose a novel one-step line of response (LOR)-based SR framework for 3D PET images. In the framework, we efficiently determine a large number of space-variant point spread functions (PSFs) in the image space by using the scanner symmetries and the proposed PSF interpolation scheme based on nonrigid registration. Furthermore, to minimize the resolution degradation in the evenly spaced parallel-beam rebinning and to reduce the computational time in the graphics processing unit (GPU) implementation, we introduce parallel-friendly LOR reconstruction based on cone-beam reordering. We then obtain a high resolution image via a one-step super-resolved 3D PET image reconstruction with the determined PSFs. The proposed framework provides noticeable improvement on the spatial resolution of PET images with a considerable reduction of computational time.
[Show abstract][Hide abstract] ABSTRACT: The planktonic phototrophic dinoflagellate Alexandrium pohangense sp. nov. isolated from the coastal waters off Korea is described from living and fixed cells by light and scanning electron microscopy (SEM). DNA sequence data were collected from the small subunit (SSU), the large subunit (LSU), internal transcribed spacer regions (ITS1 and ITS2), and 5.8S of the ribosomal DNA (rDNA). The SSU and LSU rDNA sequences of the new dinoflagellate were 4-7% and 14-17%, respectively, different from those of Alexandrium minutum, Alexandrium ostenfeldii, Alexandrium tamutum, Alexandrium margalefii, and Alexandrium pseudogonyaulax, the most closely related species. In addition, the 5.8S rDNA sequence of the new dinoflagellate was also 12% different from those of A. minutum, A. ostenfeldii, A. tamutum, and Alexandrium peruvianum. In a phylogenetic tree based on LSU rDNA sequences, A. pohangense formed a clade with A. margalefii, and this clade was clearly distinct from the clade of A. minutum, Alexandrium diversaporum, A. tamutum, Alexandrium leei, A. ostenfeldii, and Alexandirum andersoni. Moreover, in a phylogenetic tree based on SSU rDNA sequences, A. pohangense was positioned at the base of the clade containing A. leei and A. diversaporum. Morphological analysis showed that A. pohangense has a Kofoidian plate formula of Po, 4′, 6′′, 6c, 8s, 5′′′, and 2′′′′, which confirmed its assignment to the genus Alexandrium. This dinoflagellate has a wide rectangular 1′ plate, the upper left side of which is slightly bent, protruding, and touching the 2′ plate, unlike A. margalefii, which has a wide rectangular 1′ plate that does not touch the 2′ plate, or A. pseudogonyaulax and Alexandrium camurascutulum, which have a narrower elongated pentagonal 1′ plate that touches the 2′ plate. Furthermore, the 1′ plate of A. pohangense meets the 1′′ plate as a straight vertical line, whereas that of A. camurascutulum meets the 1′′ plate as an inclined line because it is lifted by the intrusion of the 1′′ plate. In addition, A. pohangense had a relatively small ventral pore whose majority was located on the 4′ plate, unlike A. margalefii or A. pseudogonyaulax, which have a relatively large ventral pore whose majority is located on the 1′ plate. Furthermore, A. pohangense had pores of two different sizes on the cell surface, unlike A. margalefii and A. pseudogonyaulax, which have similar pores of only one size. On the basis of morphological and phylogenetic criteria, it is proposed that this is a new species of the genus Alexandrium.
[Show abstract][Hide abstract] ABSTRACT: The Cordyceps species have been widely used for treating various cancer diseases. Although the Cordyceps species have been widely known as an alternative anticancer remedy, which compounds are responsible for their anticancer activity is not fully understood. In this study, therefore, we examined the anticancer activity of 5 isolated compounds derived from the butanol fraction (Cb-BF) of Cordyceps bassiana. For this purpose, several cancer cell lines such as C6 glioma, MDA-MB-231, and A549 cells were employed and details of anticancer mechanism were further investigated. Of 5 compounds isolated by activity-guided fractionation from BF of Cb-EE, KTH-13, and 4-isopropyl-2,6-bis(1-phenylethyl)phenol, Cb-BF was found to be the most potent antiproliferative inhibitor of C6 glioma and MDA-MB-231 cell growth. KTH-13 treatment increased DNA laddering, upregulated the level of Annexin V positive cells, and altered morphological changes of C6 glioma and MDA-MB-231 cells. In addition, KTH-13 increased the levels of caspase 3, caspase 7, and caspase 9 cleaved forms as well as the protein level of Bax but not Bcl-2. It was also found that the phosphorylation of AKT and p85/PI3K was also clearly reduced by KTH-13 exposure. Therefore, our results suggest KTH-13 can act as a potent antiproliferative and apoptosis-inducing component from Cordyceps bassiana, contributing to the anticancer activity of this mushroom.
Evidence-based Complementary and Alternative Medicine 04/2015; 2015:739874. DOI:10.1155/2015/739874 · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Kaempferol (KF) is the most abundant polyphenol in tea, fruits, vegetables, and beans. However, little is known about its in vivo anti-inflammatory efficacy and mechanisms of action. To study these, several acute mouse inflammatory and nociceptive models, including gastritis, pancreatitis, and abdominal pain, were employed. KF was shown to attenuate the expansion of inflammatory lesions seen in EtOH/HCl- and aspirin-induced gastritis, LPS/caerulein (CA)-triggered pancreatitis, and acetic acid-induced writhing This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.