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Objective: There are no effective clinically applicable treatments for neuronal dysfunction after mild traumatic brain injury (TBI). Here, we evaluated the therapeutic effect of a new delivery method of mouse neural stem cell (mNSC) spheroids using a hydrogel, in terms of improvement in damaged cortical lesions and cognitive impairment after mild TBI. Methods: mNSCs were isolated from the subventricular zone and subgranular zone by a hydrogel-based culture system. GFP-transduced mNSCs were generated into spheroids and wrapped into a sheet for transplantation. Male C57BL/6J mice were randomly divided into four groups: sham operation, TBI, TBI with mNSC spheroids, and TBI with mNSC spheroid sheet transplantation covering the damaged cortex. Histopathological and immunohistochemical features and cognitive function were evaluated 7, 14, and 28 days after transplantation following TBI. Results: Hydrogel-based culture systems and mNSC isolation were successfully established from the adult mice. Essential transcription factors for NSCs, such as SOX2, PAX6, Olig2, nestin, and doublecortin (DCX), were highly expressed in the mNSCs. A transplanted hydrogel-based mNSC spheroid sheet showed good engraftment and survival ability, differentiated into TUJ1-positive neurons, promoted angiogenesis, and reduced neuronal degeneration. Also, TBI mice treated with mNSC spheroid sheet transplantation exhibited a significantly increased preference for a new object, suggesting improved cognitive function compared to the mNSC spheroids or no treatment groups. Conclusion: Transplantation with a hydrogel-based mNSC spheroid sheet showed engraftment, migration, and stability of delivered cells in a hostile microenvironment after TBI, resulting in improved cognitive function via reconstruction of the damaged cortex. : This study presents the therapeutic effect of a new delivery method of mouse neural stem cells spheroids using a hydrogel, in terms of improvement in damaged cortical lesions and cognitive impairment after traumatic brain injury. Collagen/fibrin hydrogel allowed long-term survival and migratory ability of NSCs spheroids. Furthermore, transplanted hydrogel-based mNSCs spheroids sheet showed good engraftment, migration, and stability of delivered cells in a hostile microenvironment, resulting in reconstruction of the damaged cortex and improved cognitive function after TBI. Therefore, we suggest that a hydrogel-based mNSCs spheroids sheet could help to improve cognitive impairment after TBI. [Display omitted] [ABSTRACT FROM AUTHOR]

Endogenous cardiac stem cells (CSCs) are known to play a certain role in the myocardial homeostasis of the adult heart. The extracellular matrix (ECM) surrounding CSCs provides mechanical signals to regulate a variety of cell behaviors, yet the impact in the adult heart of these mechanical properties of ECM on CSC renewal and fate decisions is mostly unknown. To elucidate CSC mechanoresponses at the individual cell and myocardial level, we used the sol-to-gel transitional gelatin-poly(ethylene glycol)-tyramine (GPT) hydrogel with a tunable mechanical property to construct a three-dimensional (3D) matrix for culturing native myocardium and CSCs. The elastic modulus of the GPT hydrogel was controlled by adjusting cross-linking density using hydrogen peroxide. The GPT hydrogel showed an ability to transduce integrin-mediated signals into the myocardium and to permit myocardial homeostatic processes in vitro , including CSC migration and proliferation into the hydrogel from the myocardium. Decreasing the elastic modulus of the hydrogel resulted in upregulation of phosphorylated integrin-mediated signaling molecules in CSCs, which were associated with significant increases in cell spreading, migration, and proliferation of CSCs in a modulus-dependent manner. However, increasing the elastic modulus of hydrogel induced the arrest of cell growth but led to upregulation of cardiomyocyte-associated mRNAs in CSCs. This work demonstrates that tunable 3D-engineered microenvironments created by GPT hydrogel are able to control CSC behavior and to direct cardiomyogenic fate. Our system may also be appropriate for studying the mechanoresponse of CSCs in a 3D context as well as for developing therapeutic strategies for in situ myocardial regeneration. Statement of Significance The extracellular matrix (ECM) provides a physical framework of myocardial niches in which endogenous cardiac stem cells (CSCs) reside, renew, differentiate, and replace cardiac cells. Interactions between ECM and CSCs might be critical for the maintenance of myocardial homeostasis in the adult heart. Yet most studies done so far have used irrelevant cell types and have been performed at the individual cell level, none able to reflect the in vivo situation. By the use of a chemically defined hydrogel to create a tunable 3D microenvironment, we succeeded in controlling CSC behavior at the myocardial and individual cell level and directing the cardiomyogenic fate. Our work may provide insight into the design of biomaterials for in situ myocardial regeneration as well as for tissue engineering. [ABSTRACT FROM AUTHOR]

There is great interest in the development of cardiac stem cells (CSCs) cell-based therapeutics; thus, clinical translation requires an efficient method for attaining therapeutic quantities of these cells. Furthermore, an in vitro model to investigate the mechanisms regulating the cardiac homeostasis is crucial. We sought to develop a simple myocardial culture method for enabling both the recapitulation of myocardial homeostasis and the simultaneous isolation of CSCs. The intact myocardial fragments were encapsulated 3-dimensionally into the fibrin and cultured under dynamic conditions. The fibrin provided secure physical support and substratum to the myocardium, which mediated integrin-mediated cell signaling that allowed in situ renewal, outgrowth and cardiomyogenic differentiation of CSCs, mimicking myocardial homeostasis. Since our culture maintained the myocardial CSCs niches, it was possible to define the identity of in vitro renewed CSCs that situated in the interstitium between cardiomyocytes and microvessels. Lastly, the use of matrix-restricted fibrinolysis enabled the selective isolation of outgrown CSCs that retained the clonogenicity, long-term growth competency and cardiovascular commitment potential. Collectively, this myocardial culture might be used as an alternative tool for studying cardiac biology and developing cell-based therapeutics. [ABSTRACT FROM AUTHOR]

We studied the applicability of the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score II (SAPS II) in patients admitted to the intensive care unit (ICU) with acute stroke and compared the results with the Glasgow Coma Scale (GCS) and National Institutes of Health Stroke Scale (NIHSS). We also conducted a comparative study of accuracy for predicting hemorrhagic and ischemic stroke mortality. Between January 2011 and December 2012, ischemic or hemorrhagic stroke patients admitted to the ICU were included in the study. APACHE II and SAPS II-predicted mortalities were compared using a calibration curve, the Hosmer–Lemeshow goodness-of-fit test, and the receiver operating characteristic (ROC) curve, and the results were compared with the GCS and NIHSS. Overall 498 patients were included in this study. The observed mortality was 26.3%, whereas APACHE II and SAPS II-predicted mortalities were 35.12% and 35.34%, respectively. The mean GCS and NIHSS scores were 9.43 and 21.63, respectively. The calibration curve was close to the line of perfect prediction. The ROC curve showed a slightly better prediction of mortality for APACHE II in hemorrhagic stroke patients and SAPS II in ischemic stroke patients. The GCS and NIHSS were inferior in predicting mortality in both patient groups. Although both the APACHE II and SAPS II systems can be used to measure performance in the neurosurgical ICU setting, the accuracy of APACHE II in hemorrhagic stroke patients and SAPS II in ischemic stroke patients was superior. [ABSTRACT FROM AUTHOR]

Abstract: Conventional systems for isolating adipose-derived stem cells (ASC) require enzymatic digestion of adipose tissue (AT), followed by monolayer culture to the enrich the stem cell population. However, these systems are hindered by low cell yields and a lack of reproducibility. The present study was aimed at developing a unique strategy for isolating ASC based on fibrin matrix-supported three-dimensional (3-D) organ culture of native AT. Furthermore, we tried to optimize the fibrin composition by adjusting the fibrinogen and thrombin concentrations to allow rapid outgrowth and proliferation of ASC in the 3-D fibrin matrix. Human cutaneous AT fragments were encapsulated within the fibrin matrix to construct a 3-D environment and cultured under dynamic conditions. During in vitro culture the fibrin matrix provided physical support for the AT and also allowed selective outgrowth of ASC from embedded AT fragments. In situ expanded outgrown cells were recovered from the fibrin matrix by selective fibrinolysis and propagated under monolayer culture conditions. The cultured cells fulfilled the following criteria for ASC: adhesion to culture plastic, multipotent differentiation, correct immunophenotypic profile. Fibrin matrix-supported 3-D organ culture produced ASC that with high competency in terms of growth and differentiation capabilities, and resulted in a larger and more consistent cell yield than obtained with conventional culture systems. The fibrinogen and thrombin concentrations inversely affected spreading, migration, and ASC outgrowth from native AT. Our results indicate that this 3-D organ culture system for AT can be used as an efficient and reproducible method for ASC isolation. [Copyright &y& Elsevier]

Abstract: In this paper, the frequency agile antennas made using aluminum nitride ceramic substrate are investigated theoretically and experimentally. The aluminum nitride ceramic substrates are prepared by pressing and sintering aluminum nitride powders. The operating frequency of antenna is designed to operate at 2.45 and 5.80GHz. The shape of the patch attaching on the aluminum nitride substrate was rectangular form, and the dc bias is applied between patch and ground plane. This simple technique is used to implement electronically tunable antenna. Deformation of the antenna due to the applied dc bias is obtained as the computation of thickness and extension strains. The simulated frequency shifts at 2.45 and 5.80GHz, are 7.42 and 7.70MHz, and the experimentally measured frequency shifts at the same frequencies are 7.50 and 8.50MHz, respectively. The theoretically simulated results show an average error of less than 4.45% compared with the experimental results. [Copyright &y& Elsevier]

Abstract: In this study, we developed an immobilized TiO2 semiconductor on an ITO glass substrate (TiO2/ITO) and investigated its photocatalytic and electrochemical performance. The TiO2/ITO samples were prepared via a spin-coating process followed by calcination and were used for the photocatalytic or electrochemical degradation of an organic dye pollutant. The measured photocatalytic performance was comparable to that reported in previous publications; however, a remarkable result was obtained in our electrochemical system. The formation of hydroxyl radicals (OHy dominated the electrochemical system, which resulted in outstanding degradation performance. Therefore, we propose a commercializable photoelectrochemical system that can maximize the degradation of pollutants in wastewater treatment plants. [Copyright &y& Elsevier]

Abstract: This paper presents new approach for a hardware architecture for a digital protective relay. All functions for the measurements and relay co-ordination can be calculated with a generalized COordinate Rotation DIgital Computer (CORDIC) algorithm instead of by approximation and extrapolation. The resulting protective relay has higher processing capability making it more able to handle parallel multi-channel sources than existing digital/numerical relays are. Co-ordination accuracy can be also improved by the use of the CORDIC algorithm. This architecture was successfully implemented in a 0.35μm CMOS technology and then verified. [Copyright &y& Elsevier]

Abstract: Aims: The Wnt/β-catenin pathway plays a critical part in several cell physiology events associated with embryonic development and adult homeostasis, including determination, proliferation, migration, and differentiation. However, the role of Wnt signaling in osteoblastogenesis from mesenchymal stem cells (MSC) remains a controversial matter. Therefore, in the present study, we investigated how ICAT (inhibitor of β-catenin and TCF-4), a negative regulator of the Wnt signaling pathway, influenced differentiation and proliferation of human adipose tissue-derived stromal cells (hASC). Main methods: To mediate ICAT overexpression in hASC, we used a lentiviral gene transfer technique. We further determined the role of ICAT by RNAi technique. Key findings: ICAT-transduced hASC exhibited lower TCF promoter activity and cellular growth capacity than control cells, but ICAT overexpression did not affect hASC attachment efficiency. ICAT overexpression also increased osteogenic differentiation. Conversely, introduction of an ICAT siRNA oligonucleotide increased TCF promoter activity and cellular proliferation, but it inhibited osteogenic differentiation. Significance: Taken together, these findings indicated that ICAT participated in regulating hASC proliferation and differentiation by modulating Wnt signaling. [Copyright &y& Elsevier]

The goal of the present study was to investigate the impact of C3 involvement on the postoperative kyphosis following cervical laminoplasty in patients with high and low T1S. The data from ossification of the posterior longitudinal ligament patients who had undergone laminoplasty between January 2016 and December 2019 were retrospectively reviewed. Patients were divided into low-and high-T1S groups according to preoperative T1S, and the postoperative alignment change was compared between the groups. The relationships between postoperative cervical kyphosis and preoperative variables, including gender, C3 laminoplasty, T1S, cervical lordosis (CL), C2-7 Sagittal Vertical Axis, and T1S minus CL (T1S-CL) were investigated. Eighty-six patients were divided into 2 groups above and below median preoperative T1S (23.70). There were thirty-three patients (38.3%) in low-T1S group and fifty-three patients (61.7%) in high-T1S group. Twenty-three patients (26.7%) were performed with C3 involved laminoplasty. C3 laminoplasty (odds ratio [OR], 9.67; 2.82–33.16; P = 0.000), high T1S (OR, 4.89; 1.54–15.49; P = 0.007), and mismatched T1S-CL (OR, 5.96; 1.83–19.43; P = 0.003) were significantly associated with postoperative kyphosis. In high-T1S group, the loss of CL was significant (P = 0.017) when C3 laminoplasty was performed, whereas, in low-T1S group, the C3 laminoplasty did not show the statistically significant difference. (P = 0.194). C3 laminoplasty, mismatched T1S-CL, and high T1S were found to increase the risk of postoperative kyphosis following cervical laminoplasty. Patients with high T1 slope tended to exhibit a greater loss of CL when the laminoplasty was performed extending to C3 segment. [ABSTRACT FROM AUTHOR]

We compared left and right vascular anatomy at the L5-S1 disc space and validated the anatomical feasibility of the right oblique approach for L5-S1 oblique lumbar interbody fusion. Axial T2-weighted magnetic resonance imaging studies at the L5-S1 disc level were used to study 274 subjects (164 women and 110 men; average age, 62.97 years). The distance from the center of the L5-S1 disc to the medial wall of the left or right vessel was measured. Using the vessel position, 3 groups were established: medial, middle, and lateral. To describe the morphological configuration, the vessel type and the presence of perivascular adipose tissue (PVAT) around the vessels were identified on both sides. The vessels on the left L5-S1 disc space were located 12.47 mm from the midline and most subjects (209 subjects; 76.3%) were included in the medial or middle group. On the right side, the vessels were located more laterally (16.93 mm; P = 0.000) and most subjects (248 subjects; 90.5%) were in the middle or lateral group. On the left side, vessels were mostly veins (260 subjects; 94.9%) and 139 subjects (50.7%) had PVAT. On the right side, the vessels were mostly arteries (213 subjects; 77.7%) and 242 (88.3%) had PVAT. The vessels on the right side of the L5-S1 disc were located more laterally, and most vessels on the right side were arteries accompanying PVAT, which might minimize vessel manipulation. These results indicate that the right side of the L5-S1 disc could provide feasible access for oblique lumbar interbody fusion at L5-S1. [ABSTRACT FROM AUTHOR]

Background To investigate changes of oblique corridor in patients with lumbar degenerative scoliosis and determine proper working angle with respect to the direction of vertebral axial rotation during the oblique lumbar interbody fusion procedure. Methods The distance of oblique corridor and the rotational angle of the left or right apex group were measured on axial T2 magnetic resonance images and then compared with those of the propensity score-matched control group. Results Fifty-five patients of the left apex group and 57 patients of the right apex group were compared with the equal number of patients of the propensity score-matched control group. The distance of oblique corridor in the left apex group was shorter than that in the control group at the levels of L1-2 and L2-3. In contrast, the distance of oblique corridor in the right apex group was longer than that of the control group at the level of L2-3. Patients of the left apex group showed the vertebral body rotating to the left side from L1-2 to L5-S1, whereas in the right apex group, the vertebral body rotated to the right side at the levels of L1-2, L2-3, and L3-4. Conclusions In the left apex group, the oblique corridor was decreased from psoas overlap, and coupled axial rotation to the left side might increase the risk of contralateral nerve root injury during orthogonally working. Thus, surgeons should pay attention to the state of coupled vertebral axial rotation of lumbar degenerative scoliosis for the oblique lumbar interbody fusion procedure. [ABSTRACT FROM AUTHOR]

Highlights • An evaluation method of the interfacial resistance of a TEG device is proposed. • Analytic expressions for the V OC and I SC have been derived. • The electrical contact resistance of a thermoelectric device calculated. • The evaluation method can be used as an index to improve the soldering process. Abstract Research on the methodology for predicting and analyzing the performance of a thermoelectric device (TED) can offer various possibilities for enhancing its energy conversion characteristics. In this work, the methodology to determine the electrical contact resistance and the interfacial thermal resistance of a TED was studied. Based on one-dimensional heat transfer equations of power generation mode that includes electrical contact resistance and interfacial thermal resistance, we derived explicit expressions for the open circuit voltage and the short circuit current as the limiting cases of the external electrical load. The measurements of the open circuit voltage and the short-circuit current of TED were carried out for various thermal interface materials (TIMs) between the TED and heat reservoirs under varying compressive forces. The electrical contact resistance and the interfacial thermal resistance of a TED were determined by matching the measured values of the open circuit voltage and the short circuit current of a TED to the results of the analytic model. The electrical contact resistivity of the TED tested was approximately 3 × 10−9 Ωm2, irrespective of the compressive force, the hot-side temperature, and the TIMs. The interfacial thermal resistance varied sensitively with the TIMs and decreased with the compressive forces. [ABSTRACT FROM AUTHOR]

A simple, efficient, green and solvent-free procedure for the synthesis of pyrano[3,2- c ]chromen-5-ones has been developed by multi-component condensation of 4-hydroxycoumarin, aldehydes and ( E )- N -methyl-1-(methylthio)-2-nitroethenamine in the presence of a catalytic amount of silica-supported tungstic acid (STA). The reaction transformation presumably occurs via Knoevenagel condensation, Michael addition, imine-enamine tautomerism intramolecular, O -cyclization, elimination of MeSH. The present environmentally benign protocol offers several advantages such as shorter reaction times, a wide range of functional group tolerance, use of an inexpensive heterogeneous catalyst, and high yield of products via a simple experimental and work-up procedure. The catalyst can be recovered and reused for at least four runs without any significant impact on the product yields. [ABSTRACT FROM AUTHOR]

Abstract: This work reports on the preparation of modified TiO2 electrodes, which could be applied to the photoanodes of dye-sensitized solar cells (DSSCs). TiO2 layers were formed on fluorine-doped tin oxide glasses via doctor-blade method followed by heat treatment. Then, the various metal hydroxides were individually incorporated onto the TiO2 layers via simple dip coating process to give modified TiO2 electrodes to DSSCs. When the surface-treated electrodes were employed, photovoltaic efficiencies of DSSCs were improved by ca. 16% compared to those of the cell fabricated with a bare TiO2 electrode. [ABSTRACT FROM AUTHOR]

A highly efficient and environmentally benign protocol has been developed for the construction of various potentially biologically active N -methyl-2-nitro-aryl-1 H -benzo[ f ]chromen-3-amine derivatives using one-pot, multi-component cascade reaction of various naphthalen-2-ol, aldehydes, and ( E )- N -methyl-1-(methylthio)-2-nitroethenamine under catalyst-free conditions in the presence of green solvent medium (ethanol–water) is described. The significant features of this protocol are short reaction times, provide excellent yields, avoidance of toxic solvents and catalysts, no column chromatographic purification, atom-economy and uses ethanol–water as a green solvent which is considered to be relatively environmentally benign. This is the first example of the condensation of naphthalen-2-ol, aldehydes, and ( E )- N -methyl-1-(methylthio)-2-nitroethenamine to provide a novel series of 1 H -benzo[ f ]chromen-3-amine derivatives. [ABSTRACT FROM AUTHOR]

Abstract: Poly(methyl methacrylate) (PMMA) was grafted onto Fe3O4 magnetic nanoparticles (MNPs) by using a thiol-lactam initiated radical polymerization (TLIRP) via grafting from approach. The surface of the MNPs was treated with the (3-mercaptopropyl)trimethoxysilane coupling agent to give thiol functionalized MNPs (MNPs-SH). Subsequently, the polymerization of MMA performed in the presence of the MNPs-SH and butyrolactam efficiently afforded PMMA-g-MNPs. The grafting of PMMA on the surface of the MNPs was investigated by FT-IR, 1H NMR, TGA, XPS, and EDX analyses. The morphology of the core/shell type PMMA-g-MNPs was confirmed by HR-TEM. GPC analysis showed that the molecular weight of PMMA and monomer conversion increased with the reaction time. The amount of the grafted polymer on the surface of the MNPs was found to be ca. 82.5% as estimated from TGA analysis. The MNPs and PMMA-g-MNPs were subjected to magnetic property investigation by SQUID, and the PMMA-g-MNPs showed relatively high saturated magnetization (53.3emu/g) without any remanence or coercivity, which made the nanocomposites easily separable from solid–liquid phases suggesting their superparamagnetic character. The magnetic nanocomposites had an exceptionally good dispersibility in organic solvents as demonstrated by UV–Vis spectroscopy as well as time-dependent digital photographic monitoring. [Copyright &y& Elsevier]

Abstract: Background: The aim of this study is 2-fold: to analyze a clinical case series in which we used laminar screws for cervical posterior instrumentation and to describe the difference between C2 and C7 laminar screws in terms of technique and anatomy. Methods: Data were obtained from 25 patients who underwent cervical posterior fixation with intralaminar screws at C2 or C7. C2 intralaminar screw instrumentation was used for 7 patients requiring occipitocervical fixation (basilar invagination [3 patients], C1 unstable bursting fracture [1 patient], C1-C2 instability with occipital assimilation [2 patients], and dystopic os odontoideum [1 patient]), 13 patients with C1-C2 instability, 1 patient with C2-C3 subluxation, and 4 patients undergoing C7 fixation due to pseudoarthrosis or cervical instability after trauma. A total of 34 laminar screws were placed including 1 thoracic laminar screw, and the patients were assessed both clinically and radiographically. Results: There were no instances where a screw violated the spinal canal nor any hardware fractures noted during the follow-up period. As for perioperative complications, there were 2 cases of postoperative wound infection, 1 case of dural laceration during dissection, and 2 cases of partial dorsal laminar breach. However, there was no neurologic compromise in any of the cases. The fusion success rate was 100%. Conclusion: These preliminary results support the use of intralaminar screws for posterior instrumentation at C2 and C7. [Copyright &y& Elsevier]

Chemical reaction processes for thermoelectric nanomaterials have received a lot of attention because of subsequent small and uniform nanostructures, causing a remarkable reduction in thermal conductivity; however, they typically showed low electrical properties possibly due to contaminations by chemicals resulting in low ZT. We devised a new chemical process for synthesizing an n-type Bi 2 Te 2.7 Se 0.3 nanocompound without the chemicals causing potential contaminations. The product exhibited a predominant electrical conductivity while retaining the advantage of chemical reaction routes; thus, synergistic effect of the thermoelectric transport properties was greatly induced, resulting in the highest ZT among n-type Bi 2 Te 3 materials in bulk phase. [ABSTRACT FROM AUTHOR]

Abstract: Mesenchymal stem cells (MSCs) have been discovered in a multitude of organs, but their distribution and identity are still uncertain. Furthermore, loose connective tissue (LCT) is dispersed throughout virtually all organs, but its biological role in tissue homeostasis is unclear. Here, we describe a unique organ culture system to explore the omnipresence and in situ identity of MSCs among the LCTs. This culture system included the use of the fibrin hydrogel coupled with dynamic culture conditions, using native LCTs obtained from various organs as starting materials. This culture allowed MSC outgrowth into the hydrogel to be robustly supported, while maintaining the structural integrity of LCTs during in vitro culture. Subcultured outgrown cells fulfilled the minimal requirements for defining MSCs on the basis of clonogenicity, multipotency, and immunophenotypic characteristics. In vitro label-retaining assay demonstrated that the numbers of mobilized and proliferated cells in situ increased in the pericapillary region and expressed both MSCs and pericytes markers, indicating that the in situ identity of MSCs represents a certain population of pericapillary pericytes. Our results indicate that this culture system affords a unique strategy for both isolating MSCs and recapitulating their niche in LCTs. [Copyright &y& Elsevier]

Abstract: Angiogenesis plays a critical role in the pathogenesis of malignant tumor growth and metastases. Since cyclooxygenase (COX)-2 expression is positively correlated with vascular endothelial growth factor (VEGF) expression and enhanced angiogenesis, COX-2 inhibitors have been focused on as angiogenesis-inhibiting drugs that may offer a complementary modality to classical strategies for cancer therapy. In this study, we evaluated the potential antiangiogenic effects of 1-furan-2-yl-3-pyridin-2-yl-propenone (FPP-3), a dual COX/5-LOX inhibitor. In HT1080 cancer cells, FPP-3 significantly suppressed release of VEGF as well as activation of NF-κB, a transcriptional factor required for VEGF expression. In a chick chorioallantoic membrane (CAM) assay, FPP-3 dose-dependently suppressed VEGF- and MCF-7 human breast cancer cell-induced angiogenesis. In experiments with human umbilical vein endothelial cells (HUVECs), FPP-3 dose-dependently decreased not only the cell survival and proliferation but also the tube formation and invasion using Matrigel-coated plates. Such antiangiogenic activity correlated with suppression of VEGF-induced matrix metalloproteinase (MMP)-2 expression, reactive oxygen species (ROS) production, and extracellularly regulated kinase (ERK) phosphorylation. Furthermore, in contrast to the case of NS398, a selective COX-2 inhibitor, FPP-3 did not alter the ratio of tissue factor (TF)/tissue factor pathway inhibitor (TFPI) expression, a coagulation index. These results indicate that FPP-3 could be used as an effective antiangiogenic agent without the risk of developing thrombotic complications. [Copyright &y& Elsevier]