Lactate promotes vascular smooth muscle cell switch to a synthetic phenotype by inhibiting miR-23b expression
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- The Korean Journal of Physiology and Pharmacology
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- v.26 no.6
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- pp.519-530
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- 2022
Recent research indicates that lactate promotes the switching of vascular smooth muscle cells (VSMCs) to a synthetic phenotype, which has been implicated in various vascular diseases. This study aimed to investigate the effects of lactate on the VSMC phenotype switch and the underlying mechanism. The CCK-8 method was used to assess cell viability. The microRNAs and mRNAs levels were evaluated using quantitative PCR. Targets of microRNA were predicted using online tools and confirmed using a luciferase reporter assay. We found that lactate promoted the switch of VSMCs to a synthetic phenotype, as evidenced by an increase in VSMC proliferation, mitochondrial activity, migration, and synthesis but a decrease in VSMC apoptosis. Lactate inhibited miR-23b expression in VSMCs, and miR-23b inhibited VSMC's switch to the synthetic phenotype. Lactate modulated the VSMC phenotype through downregulation of miR-23b expression, suggesting that overexpression of miR-23b using a miR-23b mimic attenuated the effects of lactate on VSMC phenotype modulation. Moreover, we discovered that SMAD family member 3 (SMAD3) was the target of miR-23b in regulating VSMC phenotype. Further findings suggested that lactate promotes VSMC switch to synthetic phenotype by targeting SMAD3 and downregulating miR-23b. These findings suggest that correcting the dysregulation of miR-23b/SMAD3 or lactate metabolism is a potential treatment for vascular diseases.
In an environment where English is a foreign language, English learners can use AI voice chatbots in English-speaking practice activities to enhance their speaking motivation, provide opportunities for communication practice, and improve their English speaking ability. In this study, we propose a teaching-style AI voice chatbot that can be easily utilized by lower elementary school students and enhance their learning. To apply the Teachable Agent system to language learning, which is an activity based on tense, context, and memory, we proposed a new method of TA by applying the Teachable Agent to reflect the learner's English pronunciation and level and generate the agent's answers according to the learner's errors and implemented a Teachable Agent AI chatbot prototype. We conducted usability evaluations with actual elementary English teachers and elementary school students to demonstrate learning effects. The results of this study can be applied to motivate students who are not interested in learning or elementary school students to voluntarily participate in learning through role-switching.
Objectives: Parabens are widely used as antimicrobial agents in pharmaceuticals and cosmetics as well as by the food industry. Parabens have been reported to show weak estrogenic activity and be related to health effects such as allergic reactions and skin and breast cancer. We evaluated an online solid phase extraction (SPE) method coupled with LC-MS/MS technique using free and conjugated parent parabens in human urine for assessing human exposure to parabens. Methods: We employed LC/MS/MS through online solid phase extraction and column-switching techniques and analyzed free and conjugated parabens as biomarkers of human exposure. Four major parabens, methyl-paraben (MP), ethyl-paraben (EP), propyl-paraben (PP) and butyl-paraben (BP), were analyzed. Method validation was performed by sensitivity, accuracy, precision and comparison of the results of online SPE with offline SPE. Results: The limits of detection (LOD) were in the range of 0.2-2 ng/mL, and actual limits of quantification (LOQ) were in the range of 0.7-6 ng/mL urine, depending upon the compound. Accuracy was in the range of 98.3-106.4%, and precision was in the range of 1.3-8.7% (CV) depending upon the compound. We found a good correlation between the results of analysis by online SPE method and that by off-line SPE method. Conclusions: The online SPE method showed proper LOD and validated accuracy, precision and good correlation with the offline method for analyzing parabens in urine.
Objective. Failure of first-line anti-tumor necrosis factor (TNF) agents in in rheumatoid arthritis patients leads to decisions among second-line biologic agents. To better inform these decisions, the therapeutic effectiveness of rituximab is compared with other second-line biologic agents in this observational study. Methods. Between November 2011 and December 2014, study subjects were observed for 12 month periods. Patients with an inadequate response to initial anti-TNF agent received either rituximab or alternative anti-TNF agents (adalimumab/etanercept/infliximab) based on the preference of patients and physicians. The efficacy end point of this study was the change in 28-joint count Disease Activity Score (DAS28) at six and 12 months from baseline. Safety data were also collected. Results. Ninety patients were enrolled in the study. DAS28 at six months did not change significantly whether the patients were treated with rituximab or alternative anti-TNF agents in intention-to-treat analysis (n=34,
Intracellular pH (pHi) plays an important role in the regulation of cellular processes by influencing the acitivity of various enzymes in cells. Therefore, almost every type of mammalian cell possesses an ability to regulate its pHi. One of the most prominent mechanisms in the regulation of pHi is
The purpose of this study is to find out the improvement plan through the satisfaction survey of the trainees involved in vocational training fraud preventive education. In order to do this, we conducted a satisfaction survey(4,263 persons) of 5,939 people who participated in the prevention education conducted by group education or e-learning in 2017. Finally we collected 4,237 effective responses data. Descriptive statistics and the regression analysis were conducted. The finding of the study were as follows. First, the education service quality(4.42), satisfaction level(4.44), understanding level(4.44) and help level(4.45) were significantly higher than those of participants in the preventive education 4 and above. Second, e-learning participants' perceived level of education service quality, satisfaction, comprehension, and help was higher in all variables than collective education's. Third, all of the sub-factors of preventive education service quality influenced satisfaction, understanding, and help in collective education and e-learning, respectively. In the collective education, the contents of education had the greatest influence, and in e-learning, the data composition had the greatest influence. Fourth, desirable education contents were cases of fraud training(70.7%), disposition regulations(47.9%), NCS course operation instructions(32.8%) and training management best practices(32.4%). Additional requirements also included the establishment of an in-depth course, the provision of anti-fraud education content for trainees, and screen switching and system stability that can be focused on e-learning. Therefore, this study suggests that first, it is necessary to activate e-learning for prevention education more, reflecting satisfaction of e-learning is higher than that of collective education. Second, it is necessary to diversify the content of preventive education and to provide it more abundantly, because it has the biggest influence in common with the satisfaction, understanding and help level of the preventive education. Third, education content next, the factors that have a relatively big influence on satisfaction are shown as delivery method and education place in the collective education. Therefore, it is necessary to prepare education place considering the assignment of instructor and convenience. Fourth, constructing data next, the factor that have a relatively great influence on understanding and help are found to be operator support, and more active operator support activities are required in e-learning. Fifth, it is required to delivery prevention activity for trainees participating in vocational training. Sixth, it is necessary to analyze the educational need to construct the contents of preventive education more systematically.
The wall shear stress in the vicinity of end-to end anastomoses under steady flow conditions was measured using a flush-mounted hot-film anemometer(FMHFA) probe. The experimental measurements were in good agreement with numerical results except in flow with low Reynolds numbers. The wall shear stress increased proximal to the anastomosis in flow from the Penrose tubing (simulating an artery) to the PTFE: graft. In flow from the PTFE graft to the Penrose tubing, low wall shear stress was observed distal to the anastomosis. Abnormal distributions of wall shear stress in the vicinity of the anastomosis, resulting from the compliance mismatch between the graft and the host artery, might be an important factor of ANFH formation and the graft failure. The present study suggests a correlation between regions of the low wall shear stress and the development of anastomotic neointimal fibrous hyperplasia(ANPH) in end-to-end anastomoses. 30523 T00401030523 ^x Air pressure decay(APD) rate and ultrafiltration rate(UFR) tests were performed on new and saline rinsed dialyzers as well as those roused in patients several times. C-DAK 4000 (Cordis Dow) and CF IS-11 (Baxter Travenol) reused dialyzers obtained from the dialysis clinic were used in the present study. The new dialyzers exhibited a relatively flat APD, whereas saline rinsed and reused dialyzers showed considerable amount of decay. C-DAH dialyzers had a larger APD(11.70
The wall shear stress in the vicinity of end-to end anastomoses under steady flow conditions was measured using a flush-mounted hot-film anemometer(FMHFA) probe. The experimental measurements were in good agreement with numerical results except in flow with low Reynolds numbers. The wall shear stress increased proximal to the anastomosis in flow from the Penrose tubing (simulating an artery) to the PTFE: graft. In flow from the PTFE graft to the Penrose tubing, low wall shear stress was observed distal to the anastomosis. Abnormal distributions of wall shear stress in the vicinity of the anastomosis, resulting from the compliance mismatch between the graft and the host artery, might be an important factor of ANFH formation and the graft failure. The present study suggests a correlation between regions of the low wall shear stress and the development of anastomotic neointimal fibrous hyperplasia(ANPH) in end-to-end anastomoses. 30523 T00401030523 ^x Air pressure decay(APD) rate and ultrafiltration rate(UFR) tests were performed on new and saline rinsed dialyzers as well as those roused in patients several times. C-DAK 4000 (Cordis Dow) and CF IS-11 (Baxter Travenol) reused dialyzers obtained from the dialysis clinic were used in the present study. The new dialyzers exhibited a relatively flat APD, whereas saline rinsed and reused dialyzers showed considerable amount of decay. C-DAH dialyzers had a larger APD(11.70
This study provides analysis of the effectiveness of domestic marketing strategies of the Korean coffee shop "Caffe Bene". It bases its evaluation on statistical outputs of 'choice attributes,' "market segmentation," demographic characteristics," and "satisfaction differences." The results are summarized in four points. First, five choice attributes were extracted from factor analysis: price, atmosphere, comfort, taste, and location; these are related to coffee shop selection behavior. Based on these five factors, cluster analysis was conducted, with statistical results classifying customers into three major groups: atmosphere oriented; comfort oriented; and taste oriented. Second, discriminant analysis tested cluster analysis and showed two discriminant functions: location and atmosphere. Third, cross-tabulation analysis based on demographic characteristics showed distinctive demographic characteristics within the three groups. Atmosphere oriented group, early-20s, as women of all ages was found to be 'walking down the street 'and 'through acquaintances' in many cases, as the cognitive path, and mostly found the store through 'outdoor advertising', and 'introduction'. Comfort oriented group was mainly women who are students in their early twenties or professionals, and appeared as a group to be very loyal because of high recommendation to other customers compared to other groups. Taste oriented group, unlike the other group, was mainly late-20s' college graduates, and was confirmed, as low loyalty, with lower recommendation activity. Fourth, to analyze satisfaction differences, one-way ANOVA was conducted. It shows that groups which show high satisfaction in the five main factors also show high menu satisfaction and high overall satisfaction. This results show that segmented marketing strategies are necessary because customers are considering price, atmosphere, comfort, taste, location when they choose coffee shop and demographics show different attributes based on segmented groups. For example, atmosphere oriented group is satisfied with shop interior and comfort while dissatisfied with price because most of the customers in this group are early 20s and do not have great financial capability. Thus, price discounting marketing strategies based on individual situations through CRM system is critical. Comfort oriented group shows high satisfaction level about location and shop comfort. Also, in this group, there are many early 20s female customers, students, and self-employed people. This group customers show high word of mouth tendency, hence providing positive brand image to the customers would be important. In case of taste oriented group, while the scores of taste and location are high, word of mouth score is low. This group is mainly composed of educated and professional many late 20s customers, therefore, menu differentiation, increasing quality of coffee taste and price discrimination is critical to increase customers' satisfaction. However, it is hard to generalize the results of study to other coffee shop brand, because this study have researched only one domestic coffee shop, Caffe Bene. Thus if future study expand the scope of locations, brands, and occupations, the results of the study would provide more generalizable results. Finally, research of customer satisfactions of menu, trust, loyalty, and switching cost would be critical in the future study.
This paper undertakes a conceptual review of transaction cost to broaden the understanding of the transaction cost analysis (TCA) approach. More than 40 years have passed since Coase's fundamental insight that transaction, coordination, and contracting costs must be considered explicitly in explaining the extent of vertical integration. Coase (1937) forced economists to identify previously neglected constraints on the trading process to foster efficient intrafirm, rather than interfirm, transactions. The transaction cost approach to economic organization study regards transactions as the basic units of analysis and holds that understanding transaction cost economy is central to organizational study. The approach applies to determining efficient boundaries, as between firms and markets, and to internal transaction organization, including employment relations design. TCA, developed principally by Oliver Williamson (1975,1979,1981a) blends institutional economics, organizational theory, and contract law. Further progress in transaction costs research awaits the identification of critical dimensions in which transaction costs differ and an examination of the economizing properties of alternative institutional modes for organizing transactions. The crucial investment distinction is: To what degree are transaction-specific (non-marketable) expenses incurred? Unspecialized items pose few hazards, since buyers can turn toalternative sources, and suppliers can sell output intended for one order to other buyers. Non-marketability problems arise when specific parties' identities have important cost-bearing consequences. Transactions of this kind are labeled idiosyncratic. The summarized results of the review are as follows. First, firms' distribution decisions often prompt examination of the make-or-buy question: Should a marketing activity be performed within the organization by company employees or contracted to an external agent? Second, manufacturers introducing an industrial product to a foreign market face a difficult decision. Should the product be marketed primarily by captive agents (the company sales force and distribution division) or independent intermediaries (outside sales agents and distribution)? Third, the authors develop a theoretical extension to the basic transaction cost model by combining insights from various theories with the TCA approach. Fourth, other such extensions are likely required for the general model to be applied to different channel situations. It is naive to assume the basic model appliesacross markedly different channel contexts without modifications and extensions. Although this study contributes to scholastic research, it is limited by several factors. First, the theoretical perspective of TCA has attracted considerable recent interest in the area of marketing channels. The analysis aims to match the properties of efficient governance structures with the attributes of the transaction. Second, empirical evidence about TCA's basic propositions is sketchy. Apart from Anderson's (1985) study of the vertical integration of the selling function and John's (1984) study of opportunism by franchised dealers, virtually no marketing studies involving the constructs implicated in the analysis have been reported. We hope, therefore, that further research will clarify distinctions between the different aspects of specific assets. Another important line of future research is the integration of efficiency-oriented TCA with organizational approaches that emphasize specific assets' conceptual definition and industry structure. Finally, research of transaction costs, uncertainty, opportunism, and switching costs is critical to future study.