Inhibition of MicroRNA-15a/16 Expression Alleviates Neuropathic Pain Development through Upregulation of G Protein-Coupled Receptor Kinase 2
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- Biomolecules & Therapeutics
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- v.27 no.4
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- pp.414-422
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- 2019
There is accumulating evidence that microRNAs are emerging as pivotal regulators in the development and progression of neuropathic pain. MicroRNA-15a/16 (miR-15a/16) have been reported to play an important role in various diseases and inflammation response processes. However, whether miR-15a/16 participates in the regulation of neuroinflammation and neuropathic pain development remains unknown. In this study, we established a mouse model of neuropathic pain by chronic constriction injury (CCI) of the sciatic nerves. Our results showed that both miR-15a and miR-16 expression was significantly upregulated in the spinal cord of CCI rats. Downregulation of the expression of miR-15a and miR-16 by intrathecal injection of a specific inhibitor significantly attenuated the mechanical allodynia and thermal hyperalgesia of CCI rats. Furthermore, inhibition of miR-15a and miR-16 downregulated the expression of interleukin-
The present study was designed to investigate whether ethanol extracts of Sophora flavescens (GS), Glycyrrhiza uralensis (GC), Dictamnus dasycarpus (BSP), and their mixtures (GGB-1, -2, -3, and -4) inhibit 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD) in a mouse model. DNCB was topically applied on the dorsal surface of Balb/c mice to induce AD-like skin lesions. The pathological phenotypes of AD, such as erythema, ear thickness, edema, scabs, and discharge, were significantly decreased in the GGB (DNCB + GS:GC:BSP = 3:1:1 mixture)-1-treated groups compared with the other treated groups. The weight of the spleen in immune organs was significantly decreased in the GGB-1-treated groups, whereas the weight of the liver in a control group was similar to that of the groups treated with the samples. Furthermore, toluidine blue staining analysis, a method used to specifically identify mast cells, showed that master cell infiltration into the dermis of the GGB-1-treated group was significantly decreased. The immunoglobulin E concentration was lower in the GGB-1-treated group. In addition, the levels of inflammatory cytokines (interferon-
Background : Acute lung injury (ALI) is a commonly encountered respiratory disease and its prognosis is poor when the treatment is not provided promptly and properly. However no specific pharmacologic treatment is currently available for ALI, although recently several supportive drugs have been under scrutiny. We studied anti-inflammatory effects of pentoxifylline (PF), a methylated xanthine, and ONO-5046, a synthetic neutrophil elastase inhibitor on lipopolysaccharide (LPS)-induced ALI in vitro. Methods : To establish an in vitro model of LPS-induced ALI, primary rat alveolar macrophages and peripheral neutrophils in various ratios (1:0, 5:1, 1:1, 1:5, 0:1) were co-cultured with transformed rat alveolar epithelial cells (L2 cell line) or vascular endothelial cells (IP2-E4 cell line) under LPS stimulation. Each experiment was divided into five groups-control, LPS, LPS+PF, LPS+ONO, and LPS+PF+ONO. We compared LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils in various ratios, and the resultant cytotoxicity on L2 cells or IP2-E4 cells between groups. In addition we also compared the productions of tumor necrosis factor (TNF)-
Alcoholic steatosis is a fundamental metabolic disorder and may precede the onset of more severe forms of alcoholic liver disease. In this study, we isolated enzymatichydrolysate from Semisulcospira libertine by alcalase hydrolysis and investigated the protective effect of Semisulcospira libertine hydrolysate on liver injury induced by alcohol in the mouse model of chronic and binge ethanol feeding (NIAAA). In an in vitro study, the hydrolysate protects HepG2 cells from ethanol toxicity. Liver damage was assessed by histopathological examination, as well as by quantitating activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). After the administration of S. libertina hydrolysate, fat accumulation and infiltration of inflammatory cells in liver tissues were significantly decreased in the NIAAA mouse model. The elevated levels of serum AST, ALT, and ALP activities, along with the lipid contents of a damaged liver, were recovered in experimental mice administrated with S. libertina hydrolysate, suggesting its role in blood enzyme activation and lipid content restoration within damaged liver tissues. Moreover, treatment with S. libertine hydrolysate reduced the expression rate of cyclooxygenase (COX-2), interleukin
1. Introduction Today Internet is recognized as an important way for the transaction of products and services. According to the data surveyed by the National Statistical Office, the on-line transaction in 2007 for a year, 15.7656 trillion, shows a 17.1%(2.3060 trillion won) increase over last year, of these, the amount of B2C has been increased 12.0%(10.2258 trillion won). Like this, because the entry barrier of on-line market of Korea is low, many retailers could easily enter into the market. So the bigger its scale is, but on the other hand, the tougher its competition is. Particularly due to the Internet and innovation of IT, the existing market has been changed into the perfect competitive market(Srinivasan, Rolph & Kishore, 2002). In the early years of on-line business, they think that the main reason for success is a moderate price, they are awakened to its importance of on-line service quality with tough competition. If it's not sure whether customers can be provided with what they want, they can use the Web sites, perhaps they can trust their products that had been already bought or not, they have a doubt its viability(Parasuraman, Zeithaml & Malhotra, 2005). Customers can directly reserve and issue their air tickets irrespective of place and time at the Web sites of travel agencies or airlines, but its empirical studies about these Web sites for reserving and issuing air tickets are insufficient. Therefore this study goes on for following specific objects. First object is to measure service quality and service recovery of Web sites for reserving and issuing air tickets. Second is to look into whether above on-line service quality and on-line service recovery have an impact on overall service quality. Third is to seek for the relation with overall service quality and customer satisfaction, then this customer satisfaction and loyalty intention. 2. Theoretical Background 2.1 On-line Service Quality Barnes & Vidgen(2000; 2001a; 2001b; 2002) had invented the tool to measure Web sites' quality four times(called WebQual). The WebQual 1.0, Step one invented a measuring item for information quality based on QFD, and this had been verified by students of UK business school. The Web Qual 2.0, Step two invented for interaction quality, and had been judged by customers of on-line bookshop. The WebQual 3.0, Step three invented by consolidating the WebQual 1.0 for information quality and the WebQual2.0 for interactionquality. It includes 3-quality-dimension, information quality, interaction quality, site design, and had been assessed and confirmed by auction sites(e-bay, Amazon, QXL). Furtheron, through the former empirical studies, the authors changed sites quality into usability by judging that usability is a concept how customers interact with or perceive Web sites and It is used widely for accessing Web sites. By this process, WebQual 4.0 was invented, and is consist of 3-quality-dimension; information quality, interaction quality, usability, 22 items. However, because WebQual 4.0 is focusing on technical part, it's usable at the Website's design part, on the other hand, it's not usable at the Web site's pleasant experience part. Parasuraman, Zeithaml & Malhorta(2002; 2005) had invented the measure for measuring on-line service quality in 2002 and 2005. The study in 2002 divided on-line service quality into 5 dimensions. But these were not well-organized, so there needed to be studied again totally. So Parasuraman, Zeithaml & Malhorta(2005) re-worked out the study about on-line service quality measure base on 2002's study and invented E-S-QUAL. After they invented preliminary measure for on-line service quality, they made up a question for customers who had purchased at amazon.com and walmart.com and reassessed this measure. And they perfected an invention of E-S-QUAL consists of 4 dimensions, 22 items of efficiency, system availability, fulfillment, privacy. Efficiency measures assess to sites and usability and others, system availability measures accurate technical function of sites and others, fulfillment measures promptness of delivering products and sufficient goods and others and privacy measures the degree of protection of data about their customers and so on. 2.2 Service Recovery Service industries tend to minimize the losses by coping with service failure promptly. This responses of service providers to service failure mean service recovery(Kelly & Davis, 1994). Bitner(1990) went on his study from customers' view about service providers' behavior for customers to recognize their satisfaction/dissatisfaction at service point. According to them, to manage service failure successfully, exact recognition of service problem, an apology, sufficient description about service failure and some tangible compensation are important. Parasuraman, Zeithaml & Malhorta(2005) approached the service recovery from how to measure, rather than how to manage, and moved to on-line market not to off-line, then invented E-RecS-QUAL which is a measuring tool about on-line service recovery. 2.3 Customer Satisfaction The definition of customer satisfaction can be divided into two points of view. First, they approached customer satisfaction from outcome of comsumer. Howard & Sheth(1969) defined satisfaction as 'a cognitive condition feeling being rewarded properly or improperly for their sacrifice.' and Westbrook & Reilly(1983) also defined customer satisfaction/dissatisfaction as 'a psychological reaction to the behavior pattern of shopping and purchasing, the display condition of retail store, outcome of purchased goods and service as well as whole market.' Second, they approached customer satisfaction from process. Engel & Blackwell(1982) defined satisfaction as 'an assessment of a consistency in chosen alternative proposal and their belief they had with them.' Tse & Wilton(1988) defined customer satisfaction as 'a customers' reaction to discordance between advance expectation and ex post facto outcome.' That is, this point of view that customer satisfaction is process is the important factor that comparing and assessing process what they expect and outcome of consumer. Unlike outcome-oriented approach, process-oriented approach has many advantages. As process-oriented approach deals with customers' whole expenditure experience, it checks up main process by measuring one by one each factor which is essential role at each step. And this approach enables us to check perceptual/psychological process formed customer satisfaction. Because of these advantages, now many studies are adopting this process-oriented approach(Yi, 1995). 2.4 Loyalty Intention Loyalty has been studied by dividing into behavioral approaches, attitudinal approaches and complex approaches(Dekimpe et al., 1997). In the early years of study, they defined loyalty focusing on behavioral concept, behavioral approaches regard customer loyalty as "a tendency to purchase periodically within a certain period of time at specific retail store." But the loyalty of behavioral approaches focuses on only outcome of customer behavior, so there are someone to point the limits that customers' decision-making situation or process were neglected(Enis & Paul, 1970; Raj, 1982; Lee, 2002). So the attitudinal approaches were suggested. The attitudinal approaches consider loyalty contains all the cognitive, emotional, voluntary factors(Oliver, 1997), define the customer loyalty as "friendly behaviors for specific retail stores." However these attitudinal approaches can explain that how the customer loyalty form and change, but cannot say positively whether it is moved to real purchasing in the future or not. This is a kind of shortcoming(Oh, 1995). 3. Research Design 3.1 Research Model Based on the objects of this study, the research model derived is
Infection with hepatitis B virus (HBV) is a major health problem worldwide. Although a tremendous amount has been known about HBV, there have been obstacles in the study of HBV due to the narrow host range of HBV limited to humans and primates. In the present study, we investigated the susceptibility to HBV infection of mouse hepatoma cell line, Hepa-1c1c7. In addition, based on that human hepatocytes infected by HBV increase the expression of the pro-inflammatory cytokine TNF-a, the inducibility of TNF-a expression by HBV in the cells was determined. HBV surface antigen (HBsAg) secretion was measured by the microparticle enzyme immunoassay and steady state mRNA expression was analyzed by quantitative competitive RT-PCR. Transient transfection of Hepa-1c1c7 cells with HBV expression vector resulted in a dose-dependent induction of TNF-a expression. Infection of Hepa-1c1c7 cells with the serum of HBV carrier also increased TNF-a mRNA expression. Both in the transfected and infected cells, HBV mRNA was expressed and significant HBsAg secretion was detected. There was no significant variation in
Aconitum pesudo-laeve var erectum has been known to possess anti-inflammatory activity and modulate the intestinal immune system. In addition, it has traditionally been used for the treatment of water retention in the body. In this study, the anti-aging and anti-diabetes effects of water and ethanol extracts from Aconitum pesudo-laeve var. erectum were investigated. The activities of each extract were measured by antioxidant tests such as DPPH and ABTS radical scavenging activity, antioxidant protection factor (PF), TBARs content, and
Purpose : It was studied that the relationship between radiation dose, dose rate and the frequency of chromosomal aberrations in peripheral lymphocytes. Methods and Materials : Peripheral lymphocytes were irradiated in vitro with 6 MeV X-ray at dose ranges from 50 cGy to 800 cGy. The variations of the frequency of chromosomal aberrations were observed according to different radiation dose rate from 20 cGy/min to 400 cGy/min at constant total dose of 400 cGy which it was considered as factor to correct biological radiation dose measurement. Results : The yields of lymphocytes with chromosomal aberrations (dicentric chromosome, ring chromosome, acentric fragment pairs) are 0% at 50 cGy, 9% at 100 cGy, 20% at 200 cGy, 27% at 300 cGy, 55% at 400 cGy, 88% at 600 cGy, and 100% at 800 cGy. The value of Ydr is 0.000 at 50 cGy, 0.093 at 100 cGy, 0.200 at 200 cGy, 0.354 at 300 cGy, 0.612 at 400 cGy, 2.040 at 600 cGy, and 2.846 at 800 cGy. The relationship between radiation (D) and the frequency of dicentrlc chromosomes and ring Chromosomes (Ydr) can be expressed as Ydr=0.188
Customer Relationship Management(CRM) has been a sustainable competitive edge of many companies. CRM analyzes customer data for designing and executing targeted marketing analysing customer behavior in order to make decisions relating to products and services including management information system. It is critical for companies to get and maintain profitable customers. How to manage relationships with customers effectively has become an important issue for both academicians and practitioners in recent years. However, the existing academic literature and the practical applications of customer relationship management(CRM) strategies have been focused on the technical process and organizational structure about the implementation of CRM. These limited focus on CRM lead to the result of numerous reports of failed implementations of various types of CRM projects. Many of these failures are also related to the absence of marketing approach. Identifying successful factors and outcomes focused on marketing concept before introducing a CRM project are a pre-implementation requirements. Many researchers have attempted to find the factors that contribute to the success of CRM. However, these research have some limitations in terms of marketing approach without explaining how the marketing based factors contribute to the CRM success. An understanding of how to manage relationship with crucial customers effectively based marketing approach has become an important topic for both academicians and practitioners. However, the existing papers did not provide a clear antecedent and outcomes factors focused on marketing approach. This paper attempt to validate whether or not such various marketing factors would impact on relational quality and CRM performance in terms of marketing oriented perceptivity. More specifically, marketing oriented factors involving market orientation, customer orientation, customer information orientation, and core customer orientation can influence relationship quality(satisfaction and trust) and CRM outcome(customer retention and customer share). Another major goals of this research are to identify the effect of relationship quality on CRM outcomes consisted of customer retention and share to show the relationship strength between two factors. Based on meta analysis for conventional studies, I can construct the following research model. An empirical study was undertaken to test the hypotheses with data from various companies. Multiple regression analysis and t-test were employed to test the hypotheses. The reliability and validity of our measurements were tested by using Cronbach's alpha coefficient and principal factor analysis respectively, and seven hypotheses were tested through performing correlation test and multiple regression analysis. The first key outcome is a theoretically and empirically sound CRM factors(marketing orientation, customer orientation, customer information orientation, and core customer orientation.) in the perceptive of marketing. The intensification of . 3.2 Hypotheses 3.2.1 The Hypothesis of On-line Service Quality and Overall Service Quality shows, Step 1 and Step 2 are significant, and mediation variable has a significant effect on dependent variables and so does independent variables at Step 3, too. And there needs to prove the partial mediation effect, independent variable's estimate ability at Step 3(Standardized coefficient
shows, Step 1 and Step 2 are significant, and mediation variable has a significant effect on dependent variables and so does independent variables at Step 3, too. And there needs to prove the partial mediation effect, independent variable's estimate ability at Step 3(Standardized coefficient
Hepatitis B Virus-Induced TNF-a Expression in Hepa-lc1c7 Mouse Hepatoma Cell Line
(마우스 Hepa-1c1c7 세포주에서 B형 간염 바이러스에 의한 tumor necrosis factor-a의 발현 유도)
Anti-aging and Anti-diabetes Effects of Aconitum pesudo-laeve var. erectum Extracts
(진범(Aconitum pesudo-laeve var. erectum) 추출물의 항노화 및 항당뇨 효과)
The Frequency of Chromosomal Aberrations of Peripheral Lymphocytes according to Radiation Dose and Dose Rate
(선량 및 선량률 변화에 따른 말초혈액 임파구의 염색체 이상의 빈도)
The Effects on CRM Performance and Relationship Quality of Successful Elements in the Establishment of Customer Relationship Management: Focused on Marketing Approach
(CRM구축과정에서 마케팅요인이 관계품질과 CRM성과에 미치는 영향)
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