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To explore the effect of ligustrazine on the migration of bone marrow mesenchymal stem cells (BMSCs) and protein expressions of matrix metalloproteinase-2 and-9 (MMP-2 and MMP-9) in vitro.BMSCs were in vitro isolated and cultured using whole bone marrow adherent method, and phenotypes [surface positive antigens (CD29 and CD90) and negative antigens (CD34 and CD45)] identified using flow cytometry. BMSCs were divided into the blank control group, 25, 50, 100 µmol/L ligustrazine group, and the GM6001 group (100 µmol/L ligustrazine +MMPs inhibitor GM6001 ). The migration of BMSCs was tested by Transwell chamber test and wound healing assay after treated with ligustrazine for 24 h. The protein expressions of MMP-2 and MMP-9 were detected by Western blot.The third passage BMSCs grew well in uniform morphology. The expression rate of CD29, CD90, CD34, and CD45 was 96.9%, 97.3%, 0.2%, and 3.0%, respectively. Compared with the blank control group, the number of migrated cells and relative distance of cell invasion increased, and the protein expressions of MMP-2 and MMP-9 were elevated in each ligustrazine group (P0.05, P0.01). Compared with 100 µmol/L ligustrazine group, the number of migrated cells and relative distance of cell invasion decreased in 25 and 50 µmol/L ligustrazine groups and the GM6001 group (P0.01). Protein expression of MMP-2 decreased in 25 and 50 µmol/L ligustrazine groups (P0.01).Ligustrazine could promote the migration of BMSCs in vitro, and its mechanism might be related to up-regulating expression levels of MMP-2 and MMP-9 protein.

Aims We previously reported that minocycline attenuates acute brain injury and inflammation after focal cerebral ischemia, and this is partly mediated by inhibition of 5-lipoxygenase (5-LOX) expression. Here, we determined the protective effect of minocycline on chronic ischemic brain injury and its relation with the inhibition of 5-LOX expression after focal cerebral ischemia. Main methods Focal cerebral ischemia was induced by 90 min of middle cerebral artery occlusion followed by reperfusion for 36 days. Minocycline (45 mg/kg) was administered intraperitoneally 2 h and 12 h after ischemia and then every 12 h for 5 days. Sensorimotor function was evaluated 1–28 days after ischemia and cognitive function was determined 30–35 days after ischemia. Thereafter, infarct volume, neuron density, astrogliosis, and 5-LOX expression in the brain were determined. Key findings Minocycline accelerated the recovery of sensorimotor and cognitive functions, attenuated the loss of neuron density, and inhibited astrogliosis in the boundary zone around the ischemic core, but did not affect infarct volume. Minocycline significantly inhibited the increased 5-LOX expression in the proliferated astrocytes in the boundary zone, and in the macrophages/microglia in the ischemic core. Significance Minocycline accelerates functional recovery in the chronic phase of focal cerebral ischemia, which may be partly associated with the reduction of 5-LOX expression.

Cysteinyl leukotrienes (CysLTs) induce inflammatory responses mediated by activating CysLT 1 and CysLT 2 receptors. We have recently reported that CysLT 1 receptor expression is increased in rat brain after focal cerebral ischemia and the increased expression is spatio-temporally related to acute neuronal injury and late astrocyte proliferation. Here we report spatio-temporal expression of CysLT 2 receptor mRNA in rat brain after focal cerebral ischemia induced by 30 min of middle cerebral artery occlusion. We found that the neuron density was gradually decreased or disappeared in the ischemic core and boundary zone during 14 days after reperfusion, and the astrocyte population in the boundary zone was increased 3–14 days after reperfusion. In the ischemic core, the expression of CysLT 2 receptor mRNA was increased at 6, 12 and 24 h and then recovered at 3, 7 and 14 days after reperfusion. In the boundary zone, the expression was significantly increased 3, 7 and 14 days after reperfusion. The results suggest that CysLT 2 receptor may be related to the acute neuronal injury and late astrocyte proliferation in the ischemic brain.

To study the effect of Buyang Huanwu decoction (BYHWD) inducing angiogenesis on the neuroblast migration from the subventricular zone and its mechanisms after focal cerebral ischemia.The middle cerebral artery occlusion (MCAO) was performed to mice for 30 minutes to establish the model. The rats were divided into sham group, model group, BYHWD group and endostatin group. BYHWD (20 g x kg(-1), ig) and endostatin (10 μg, sc) were administered 24 h after ischemia once a day for consecutively 14 days. At 14 d after ischemia, the density of micro-vessel and the number of neuroblasts in the ischemia border zone were determined by immunofluorescence staining. The mRNA and protein expression of cell-derived factor-1 (SDF-1) and brain-derived neurotrophic (BDNF) were examined by real-time PCR and Western blot.Compared with the model group, BYHWD significantly increased the density of micro-vessel and the number of DCX positive cells in the ischemia border zone (P0.01), and significantly increased the SDF-1 and BDNF mRNA and protein expression (P0.01). Compared with BYHWD group, endostatin significantly reduced the density of micro-vessel and the number of DCX positive cells in the ischemia border zone (P0.01), as well as the SDF-1, BDNF mRNA and protein expression (P0.01).BYHWD could promote the neuroblast migration from the subventricular zone via inducing angiogenesis after cerebral ischemia, the mechanism may be correlated with up-regulating the expression of SDF-1 and BDNF.

Past studies on service innovation in the manufacturing industry mainly focused on industrial transformation, business strategy, and servitization models. This paper presents a case study of PCC, a representative manufacturer in Taiwan. We gathered secondary data for the decade from 2004 to 2013, and then determined and coded service innovation events during the period. Horizontal and vertical market segments were examined together with service innovation matrices to identify different service innovation strategies. We then conducted in-depth interviews with experts based on analysis results to establish the content and meaning of service innovation. Five service innovation strategies were identified: 1. Lean OEM service; 2. One-stop shopping service; 3. Multi-brand channel service; 4. High-tech alliance; 5. TDS system service.

Aim: To investigate the effects of caffeic acid on early and delayed injuries after focal cerebral ischemia in rats, and the possible relation to 5-lipoxygenase inhibition. Methods: Transient focal cerebral ischemia was induced by middle cerebral artery occlusion in Sprague-Dawley rats. Caffeic acid (10 and 50 mg/kg) was ip injected for 5 d after ischemia. The brain injuries were observed, and the levels of cysteinyl leukotrienes and leukotriene B4 in the brain tissue were measured. Results: Caffeic acid (50 mg/kg) ameliorated neurological dysfunction and neuron loss, and decreased infarct volume 24 h after ischemia; it attenuated brain atrophy, infarct volume, and particularly astrocyte proliferation 14 d after ischemia. In addition, it reduced the production of leukotrienes (5-lipoxygenase metabolites) in the ischemic hemispheres 3 h and 7 d after ischemia. Conclusion: Caffeic acid has protective effect on both early and delayed injuries after focal cerebral ischemia in rats; and this effect may partly relate to 5-lipoxygenase inhibition.

Cysteinyl leukotrienes are potent pro-inflammatory mediators. Cysteinyl leukotriene receptor 1 is one of the two cysteinyl leukotriene receptors cloned. We recently reported that cysteinyl leukotriene receptor 1 antagonists protected against cerebral ischemic injury, and an inducible expression of cysteinyl leukotriene receptor 1 was found in neuron- and glial-appearing cells after traumatic injury in human brain. To determine the role of cysteinyl leukotriene receptor 1 in ischemic brain injury, we investigated the temporal and spatial profile of cysteinyl leukotriene receptor 1 expression in rat brain from 3 h to 14 days after 30 min of middle cerebral artery occlusion, and observed the effect of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, on the ischemic injury. We found that cysteinyl leukotriene receptor 1 mRNA expression was up-regulated in the ischemic core both 3-12 h and 7-14 days, and in the boundary zone 7-14 days after reperfusion. In the ischemic core, cysteinyl leukotriene receptor 1 was primarily localized in neurons 24 h, and in macrophage/microglia 14 days after reperfusion; while in the boundary zone it was localized in proliferated astrocytes 14 days after reperfusion. Pranlukast attenuated neurological deficits, reduced infarct volume and ameliorated neuron loss in the ischemic core 24 h after reperfusion; it reduced infarct volume, ameliorated neuron loss and inhibited astrocyte proliferation in the boundary zone 14 days after reperfusion. Thus, we conclude that cysteinyl leukotriene receptor 1 mediates acute neuronal damage and subacute/chronic astrogliosis after focal cerebral ischemia.

We have recently reported the neuroprotective effect of pranlukast (ONO-1078), a cysteinyl leukotriene receptor-1 (CysLT1) antagonist, on cerebral ischemia in rats and mice. In this study, we further determined whether the effect of pranlukast is long lasting and related to the formation of a glial scar in cerebral ischemic mice. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO). After ischemia, pranlukast (0.1 mg/kg) was injected intraperitoneally for 5 consecutive days. Neurological deficits and sensorimotor function were determined during 70 days after ischemia. Brain lesion and glial scar formation were detected at the end of the experiment. Pranlukast did not reduce mortality, but significantly improved neurological deficits and promoted sensorimotor recovery during 70 days. At the end of the experiment, pranlukast significantly reduced lesion volume, and increased neuron densities in the cortex and hippocampal CA1 region in the ischemic hemispheres. Importantly, pranlukast also remarkably reduced the thickness of a scar wall in the ischemic hemispheres. These findings indicate that pranlukast has a long-lasting protective effect on focal cerebral ischemia in mice, and inhibit the ischemia-induced glial scar formation, providing further evidence of the therapeutic potential of pranlukast in the treatment of ischemic stroke.

To explore the effect of Buyang Huanwu Decoction (BYHWD) and its disassembled recipes on rats' neurogenesis after focal cerebral ischemia and to investigate its underlying molecular mechanisms.Focal cerebral ischemia model was induced by occlusion of the right middle cerebral artery for 90 min using the intraluminal filament model. Rats were divided into the sham-operation group, the model group, the BYHWD group, the qi supplementing group, and the blood activating group. Medication was performed by gastrogavage 24 h after ischemia for 14 successive days. 5-bromodeoxyuridine (BrdU) (at 50 mg/kg) was intraperitoneally injected, once per day for 14 successive days. The neurological function was assessed using modified neurological severity score (mNSS) and the corner test at day 1, 7, and 14 after ischemia. BrdU/Nestin, BrdU/NeuN, and BrdU/GFAP positive cells were examined by double immunofluorescence at day 14 after ischemia. The protein expression of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were detected by Western blot at day 14 after ischemia.Compared with the model group, the score of mNSS and the frequency of turning right significantly decreased in the BYHWD group and the qi supplementing group (P0.01), the number of BrdU/Nestin in the subventricular zone of the lateral ventricle, and BrdU/ NeuN and BrdU/GFAP positive cells in the peripheral ischemic cortex increased (P0.05, P0.01), protein expression of BDNF and VEGF increased (P0.05, P0.01). In the qi supplementing group, there was no statistical difference in BrdU/GFAP. But there was no statistical difference in each index of the blood activating group (P0.05). Compared with BYHWD group, the number of BrdU/Nestin, BrdU/ NeuN, and BrdU/GFAP positive cells significantly decreased (P0.01), and the protein expression of BDNF and VEGF were significantly reduced in the qi supplementing group and the blood activating group (P0.01).BYHWD could significantly improve neurogenesis and neurological function recovery after focal cerebral ischemia in rats. Its mechanisms might be related to up-regulating protein expression of BDNF and VEGF. Drugs for qi supplementing and drugs for blood activating had synergistic effects.

Two hospitals implementing evidence-based medicine system, an example of service innovations, are selected as research sites. This study adopts a two-stage method. First, unstructured interviews from key informants are analyzed by the technique of grounded theory. Second, structured interviews are analyzed using factor analysis and cluster analysis. This study induces user behavior as five types: instrument-oriented, emotion-oriented, communication-oriented, uselessness-oriented and anxiety-oriented behavior. Next, the subjects are grouped as four clusters: mastered, absorbed, fatigued and explored type. Furthermore, this study finds that the user behavior forms an evolution path, going through the explored stage, absorbed stage, mastered stage and fatigued stage. The derived outcomes can provide an effective managerial strategy for hospital managers to diffuse an innovation.

Continuous innovation, research and development in technology, manufacturing and production provide the basis for continuous growth and profit. This paper examines how start-up enterprises achieve their operational success. Literature review and the case study method were applied to support the factors of sixteen enterprises within the Hsin-Chu Science Park. This research explore their entrepreneurial motives and opportunities, and factors on how to achieve entrepreneurial success in high-tech start-ups. The results showed the successful business model for start-up enterprises lies in scale economy, cost controlling, and after-sale service. The most concerned risks are in whether the customer relationship is steady and its avoidance of bad debts, while having enterprises also found more success when led by market opportunities rather than by new technologies. It is often agreed that innovation is the key for an enhanced economic performance. Thus, this paper aims at finding strategies entrepreneurial motives and opportunities, and factors on how to achieve entrepreneurial success for high-tech start-ups.

This study is a case study of Chung-Hwa Telecom. Based on a framework of cloud service, this study develops an innovation model of medical cloud services (MCS) and explores the evolution of the model. Through collecting the related secondary data of the case from 2002 to 2011 and in-depth interviews, this study has collected 274 events of service innovation. Each event is treated as an analysis unit. The findings are: 1) MCS innovations focus on CaaS, IaaS and PaaS, while SaaS and DaaS are insufficient; 2) MCS innovation evolution is from PaaS to IaaS; 3) The critical factors facilitating MCS concern infrastructure technology and network technology; 4) The quantity of both general and enterprise users served by MCS shows a U-type trend; the quantity of both government institutions and specific communities served by MCS shows an inverted U-type trend; the quantity of both education institutions and medical institutions served by MCS shows an increasing trend.

This paper is a comparative case study using Hofstede's theory to explore cultural differences in trading website management between Mainland China and Taiwan. Taobao.com and Yahoo! Taiwan are the selected cases. This study collected 3,243 credit appraisals of the auctioneers whose sales ranked the first among eight fields of industry, respectively. To conclude, five propositions were formulated: In comparison with mainland China, Taiwan trading website communities have lower power distance and higher uncertainty avoidance. They tend to be individualism-oriented and long-term oriented. Of particular note, there are slightly differences in terms of masculinity vs. femininity.

This study adopts a comparative case study to explore managerial difference of trading websites between mainland China and Taiwan. Taobao.com in mainland China and Yahoo! Taiwan are the selected cases. Through the credit rating system of the cases, this study collects a total of 3,243 appraisals of the sellers whose sale ranks first in eight industries. Each appraisal is used as a unit of analysis. Firstly there are 13 key management factors induced in this study. Then the comparative case study between mainland China and Taiwan is carried out according to these 13 factors. Finally this study derives three propositions. These propositions hint some managerial implications for both storekeepers in mainland China and Taiwan.

This study aims to explore evidence-based medicine (EBM) acceptance process of physicians. The perspective of customer experience management is applied to this study. A total of 32 in-depth interviews were conducted with 23 key informants and analyzed using the techniques of grounded theory. The result shows the acceptance process consisting of six stages: 1) perceived instrumental advantage; 2) perceived emotional advantage; 3) perceived anxiety; 4) communication improvement; 5) behavior influence; 6) omnipotent myth. This study provides an effective management strategy for hospital managers to diffuse an EBM system.

Financial tsunami impacted the world with economic downturns. However, cultural industry and its related sectors all went opposite direction, prospering under the severe economic circumstances. This study will explore the innovative activities of Taiwanese culture parks in terms of their cultural values. Current researches merely focus on the architectural design and space reutilization, not so much to the innovative service activities in culture parks. Therefore, the purpose of this study is to probe into innovative service activities of the cultural parks. The primary research method is collecting secondary data for analysis and further discussion. The findings include, first of all, that the cultural values of innovative service activities in Taiwanese culture parks consist mainly in spiritual values, social values and historical values. Secondly, creative Taiwanese culture parks convey cultural values into social value. Thirdly, innovative activities of Taiwanese culture parks do not contain any actual characteristics of the cultural value.

There were few studies focused on the acceptance of service innovations. A technology-based service innovation is usually more complicated, thus learning of this innovation is essentially required. We use the case of evidence-based medicine (EBM) realization, one kind of technology-based service innovations, to explore the acceptance of service innovations based on social learning theory. A total of 18 in-depth interviews were conducted with key informants and analyzed using the techniques of grounded theory. Finally, we propose a technology-based service innovation acceptance model and develop three propositions. The model concerns 'perceived advantage' and 'perceived anxiety' of users (antecedents), 'learning intention' (mediator), and 'learning infusion' (consequence). The 'perceived advantage' is the positive outcome observed by individuals and it includes perceived cognitive advantage and perceived emotional advantage. The 'perceived anxiety' is the negative outcome observed by individuals and it includes information anxiety, patient education, patient misunderstanding, colleague competitiveness and coercive force of institution. This study theoretically initiates the perspective towards accepting technology-based service innovations based on social learning theory and practically provides a more specific and complete viewpoint for the acceptance of technology-based service innovations.

The aim of the present study is to investigate the role of nordihydroguaiaretic acid (NDGA) on inflammatory cells accumulation after focal cerebral ischemia and the underlying mechanism. Focal cerebral ischemia was induced by 30 min of middle cerebral artery occlusion (MCAO) followed by 72 h of reperfusion. NDGA (5 and 10 mg/kg) was administered intraperitoneally 30 min, 2, 24, 48 h after reperfusion, respectively. The brain injuries were observed by neurological and histological examination. Endogenous IgG exudation, neutrophils and macrophages/microglia accumulation, and intercellular adhesion molecule-1 (ICAM-1) protein expression were determined by immunohistochemistry 72 h after reperfusion. ICAM-1 mRNA was determined by RT-PCR 72 h after reperfusion. The catalysates of 5-lipoxygenase (5-LOX), leukotriene B4 (LTB4) and cysteinyl leukotrienes (CysLTs), were evaluated by ELISA 3 h after reperfusion. The results showed that NDGA ameliorated neurological dysfunction, decreased infarct volume, and inhibited endogenous IgG exudation, neutrophils infiltration, ICAM-1 mRNA and protein expression 72 h after reperfusion. Moreover, NDGA reduced the levels of LTB4 and CysLTs 3 h after reperfusion. However, NDGA did not reduce the accumulation of macrophages/microglia 72 h after reperfusion. These results suggest that NDGA decreases neutrophil infiltration in the subacute phase of focal cerebral ischemia via inhibiting 5-LOX activation.

To determine whether the anti-inflammatory effect of minocycline on postischemic brain injury is mediated by the inhibition of 5-lipoxygenase (5-LOX) expression and enzymatic activation in rats. Focal cerebral ischemia was induced for 30 min with middle cerebral artery occlusion, followed by reperfusion. The ischemic injuries, endogenous IgG exudation, the accumulation of neutrophils and macrophage/microglia, and 5-LOX mRNA expression were determined 72 h after reperfusion. 5-LOX metabolites (leukotriene B4 and cysteinyl leukotrienes) were measured 3 h after reperfusion. Minocycline (22.5 and 45 mg/kg, ip, for 3 d) attenuated ischemic injuries, IgG exudation, and the accumulation of neutrophils and macrophage/microglia 72 h after reperfusion. It also inhibited 5-LOX expression 72 h after reperfusion and the production of leukotrienes 3 h after reperfusion. Minocycline inhibited postischemic brain inflammation, which might be partly mediated by the inhibition of 5-LOX expression and enzymatic activation.

To determine whether pranlukast, a cysteinyl leukotriene receptor-1 antagonist, exerts an anti-inflammatory effect on focal cerebral ischemia in mice.Focal cerebral ischemia in mice was induced by permanent middle cerebral artery occlusion (MCAO). In addition to neurological deficits, infarct volume, degenerated neurons and endogenous IgG exudation, we detected accumulation of neutrophils and macrophage/microglia in the ischemic brain tissue 72 h after MCAO. Pranlukast was ip injected 30 min before and after MCAO.Pranlukast significantly attenuated neurological deficits, infarct volume, neuron degeneration and IgG exudation. Importantly, pranlukast (0.01 and 0.1 mg/kg) inhibited myeloperoxidase-positive neutrophil, but not CD11b-positive macrophage/microglial accumulation in the ischemic cortical tissue.Pranlukast exerts an anti-inflammatory effect on focal cerebral ischemia in the subacute phase that is limited to neutrophil recruitment through the disrupted blood-brain barrier.

Our previous studies showed that cysteinyl leukotriene receptor-1 (CysLT1) antagonist pranlukast has a neuroprotective effect on cerebral ischemia in rats and mice. However, whether the neuroprotective effect of pranlukast is its special action or a common action of CysLT1 receptor antagonists remains to be clarified. This study was performed to determine whether montelukast, another CysLT1 receptor antagonist, has the neuroprotective effect on focal cerebral ischemia in mice, and to observe its dose- and time-dependent properties. Permanent focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO). Montelukast was injected intraperitoneally either as multiple doses (once a day for 3 days and 30 min before MCAO) or as a single dose (at 30 min before, 30 min after, or 1 h after MCAO), respectively, and pranlukast and edaravone were used as controls. The neurological deficits, infarct volumes, brain edema, neuron density, and Evans blue extravasation in the brain were determined 24 h after MCAO. Pretreatments with multiple doses or a single dose of montelukast (0.1 and 1.0 mg/kg) before MCAO significantly attenuated all the ischemic insults. Post-treatment with a single dose of montelukast (0.1 and 1.0 mg/kg) at 30 min after MCAO also significantly decreased brain edema and infarct volume, but not neurological deficits. However, post-treatment with a single dose of montelukast at 1 h after MCAO had no significant effect. Pranlukast showed the same effects as montelukast, but edaravone attenuated the ischemic insults only with multiple doses before MCAO. Thus, montelukast has a dose- and time-dependent neuroprotective effect on permanent focal cerebral ischemia in mice, with an effective dose range of 0.1–1.0 mg/kg and a therapeutic window of 30 min. These findings further support the therapeutic potential of CysLT1 receptor antagonists in the treatment of cerebral ischemia at earlier phases.