The effect of synthetic cannabinoids and their combination with TGF-β3 on wound healing of cell cultured human bone cell monolayers and 3D models. The role of synthetic cannabinoid HU308 and HU308/TGF-β3 combinations on cellular adhesion, proliferation, wound healing, nitric oxide, MMP-2 and ECM protein regulation of MG-63 osteoblast monolayers and 3D models

Despite the ongoing political debate regarding the legality of medical marijuana, clinical investigations of the therapeutic use of cannabinoids are now more prevalent than at any time in history. Cannabinoids have been shown to have analgesic, anti-spasmodic, anticonvulsant, anti-tremor, anti-psychotic, anti-inflammatory, anti-oxidant, anti-emetic and appetite-stimulant properties. There are mainly two well-known cannabinoid receptors, CB1 and CB2, located in the central (CB1) and peripheral (CB2) nervous systems as well as the immune system. More recently, endocannabinoids (ligands) and their receptors have also been found in the skeleton which appear as the main body system and physiologically regulated by CB2. This study aimed to examine the effect of both CB1 and CB2 receptor stimulation on wound closure response of MG-63 osteoblast bone cell monolayers using different treatments with cannabinoid such as Winn55,212-2, URB602 and HU308. Also, cell adhesion, cell proliferation and cell length was investigated. The study also aimed to examine the effect of HU308 treatments in combination with TGF-β3 (transforming growth factor beta -3) on wound healing, cell adhesion and extracellular matrix up regulation (collagen type I, fibronectin and protien S-100A6) as well as other biological factors such as secretion of matrix metalloproteinase (MMP-2) and nitric oxide (NO). Finally, this study investigated HU308/TGF-β3 combination treatment on the regulation of extracellular matrix (collagen type I, fibronectin and protien S-100A6) in a 3D multilayer system of MG-63 osteoblast bone cells. Wound healing assays of MG-63 monolayers revealed accelerated wound repair as well as increased cell proliferation mainly regulated through CB2 receptors, and that treatments with HU308 and HU308/TGF-β3 achieved minimum closure timings compared with control groups (P<0.05). Our finding suggested that proliferation rate with 500nM HU308 was significantly higher than control and TGF-β3/HU308 combination groups (P<0.05). Interestingly, percentage of wound remained open after 15 hours for combination groups was 17.6%±1.32 whereas treatment with 500nM HU308 had 20%±2.25 indicating that the combination groups took the lead throughout wound healing. It was also observed that bridge formation in all treatment groups was taking place between 15 to 20 hour periods whereas within control treatments bridge formation started to take place after 25 hours. Cell surface attachment was examined via the trypsinization assay in which the time taken to trypsinize cells from the surface provided a means of assessing the strength of attachment. The results indicated that higher concentrations of HU308 (2μM), induced significant force of cell attachment compared with control and concentrations of 500nM and 1μM (P<0.05). However, groups treated with TGF-β3 and combination HU308/TGF-β3 indicated reduced cell surface attachment compared with control groups, indicating enhanced cell migration. Immunofluorescence staining as well as Elisa based semi-quantification technique indicated that both collagen type I and fibronectin were unregulated using higher concentrations of HU308 with decreased cell proliferation compared to lower concentrations. Nevertheless, protein S-100A6 was up-regulated in treatments with HU308, TGF-β3 and their combination HU308/TGF-β3 (P<0.05), indicating the positive role of these treatments in promoting cell differentiation. MMP-2 levels in the current study were also shown to be concentration-dependent, i.e. higher concentrations of HU308 significantly reduced MMP-2 secretion leading to decreased cell migration, while HU308/TGF-β3 combination treatment increased MMP-2 levels, indicating an increase in cell migration. The current study also examined levels of nitric oxide synthesis in relation to different treatments with HU308, TGF-β3 and HU308/TGF-β3 combination. It was found that nitric oxide up-regulation influences rate of MG-63 osteoblast wound healing in a concentration dependent manner. Lastly, UpCell culture dishes proved to have efficacy in obtaining a multilayer model of MG-63 osteoblast system in-vitro through changes in cell morphology. It was also found that treatments with HU308, TGF-β3 and HU308/TGF-β3 combination influenced collagen type I, fibronecton and protein S-100A6 secretion. These findings supported the earlier Elisa based semi-quantification results obtained for monolayer cultures

The effect of WIN55, 212-2 on protein S100, matrix metalloproteinase-2 and nitric oxide expression of chondrocyte monolayer

YesStudies have been conducted to highlight the anti-inflammatory and immunosuppressive properties of synthetic cannabinoids as well as their potential for cartilage repair. Various wound healing techniques can be used to investigate the mechanisms of chondrocyte repair in monolayers or three dimensional tissues constructs. In this work the effect of WIN55, 212-2 (WIN-2) on nitric oxide (NO) and matrix metalloproteinase-2 (MMP-2) expressed by wounded chondrocyte monolayers was investigated. Moreover, expression of collagen type-I and type-II, fibronectin and S100 proteins were detected using immunofluorescence and quantitatively verified using ELISA based techniques following treatment with 1 μM and 2 μM of WIN-2. Treating chondrocytes with 1 μM of WIN-2 significantly increased expression of collagen type-II, fibronectin and S100, and significantly reduced collagen type-I expressions as compared to the control groups. On the other hand, both concentrations of WIN-2 significantly reduced the expression of the inflammation markers NO and MMP-2 in a dose dependent manner. These findings highlight the potential use of the synthetic cannabinoids for improving cartilage healing properties as well as acting as an anti-inflammatory agent which could be used to enhance tissue engineering protocols aimed at cartilage repair

Beyond the bright side : Investigating dark aspects of independent entrepreneurship, family entrepreneurship, and corporate entrepreneurship

Entrepreneurship is often perceived as a driving force for employment, innovation, and knowledge creation and is linked to poverty alleviation and economic growth. While entrepreneurship is often seen as a pathway for economic development and societal welfare, it does not consistently deliver the expected outcomes and, in certain instances, may exacerbate poverty, impede development, and present challenges to societal well-being and equality. This paradox within entrepreneurship emphasizes the necessity of exploring the negative (dark) aspects pertaining to entrepreneurship. Neglecting these negative aspects can lead to an incomplete understanding of entrepreneurship. Accordingly, this dissertation challenges the conventional positive view of entrepreneurship by (1) investigating some negative (i.e., dark) aspects of independent entrepreneurship, family entrepreneurship, and corporate entrepreneurship and (2) what might potentially mitigate these negative aspects. This is essential for achieving a balanced and comprehensive understanding of entrepreneurship’s role in the economy and society at large. I draw on the theory of entrepreneurial allocation, which posits that entrepreneurship can be productive, unproductive, or destructive, as the main theoretical perspective of this dissertation. This dissertation includes three empirical papers, each focusing on a distinct type of ownership: owner-manager ownership (independent entrepreneurship), family ownership (family entrepreneurship), and external investor ownership (corporate entrepreneurship). Together, they offer different insights into the potential negative aspects pertaining to entrepreneurship. Each paper draws on different theoretical perspectives and aligns with particular Sustainable Development Goals (SDGs). In paper 1, we draw on the scale-up, firm growth, and well-being literature, taking an employee perspective to examine the impact of scaling on employee well-being. Using data from 10,908 employees in new Swedish ventures, we find a positive association between scaling and employee burnout, along with a negative association with job satisfaction. This emphasizes that scaling, often associated with a positive view, can also bring challenges to employee well-being. Meanwhile, we show that employees with managerial roles and prior new venture experience are two groups of employees who are less likely to experience the negative consequences of scaling. Paper 2 investigates how family dynamics (the upbringing environment) within entrepreneurial families can influence offspring career choices. In this paper, we draw on the birth order literature, which adopts an evolutionary theory perspective, to suggest that offspring are exposed to a different upbringing environment due to the unequal distribution of parental resources, potentially affecting their personality and behaviors and thus resulting in unequal career opportunities. In this paper, we use data comprising 205,247 offspring residents in Sweden to show that later-born offspring, though more likely to join the parent’s business, often have a higher tendency to leave compared to their early-born siblings. However, these later-borns can be particularly advantageous in competitive or challenging business situations. In an additional analysis, we show that earlier-born offspring are more inclined toward independent entrepreneurship. Lastly, paper 3 focuses on the negative aspects pertaining to corporate entrepreneurship. Drawing on agency theory, paper 3 shows that institutional investors (e.g., investment banks, insurance companies, etc.), while they are usually viewed positively because of their known sophisticated investment strategies and long-term horizons, induce negative effects and have a potential dark side on corporate entrepreneurs. Specifically, I argue that the extant literature views institutional investors as a homogenous group in terms of their innovation preferences. This oversimplified view overlooks the possible variations within these institutional investors. Following an empirics-first (EF) approach, I segment institutional investors based on their innovation preferences, using portfolio data and historical trading information. This analysis identifies three distinct segments: innovation-friendly, innovation-unfriendly, and innovation-investment-oriented. Using a sample of 6,438 U.S. publicly traded firms, I find that firms predominantly owned by innovation-unfriendly institutional investors experience a decrease in innovation productivity and overall firm value compared to those dominated by innovation-friendly investors. Moreover, I show that firms can strategically position themselves to attract innovation-friendly institutional investors in order to mitigate the negative effects enacted by innovation-unfriendly investors. This dissertation offers several contributions to the field of entrepreneurship. First, it contributes to the potential (social) costs of entrepreneurship by investigating some negative aspects pertaining to independent, family, and corporate entrepreneurship. Second, it adds to the ongoing discussion on how to mitigate these negative aspects. Third, this dissertation contributes to the theory of entrepreneurial allocation by revealing that beyond traditional institutional actors like governments, there are other influential forces, suh as the entrepreneur, entrepreneurial firm, and institutional investors, that can direct entrepreneurial activities towards productive, unproductive, or destructive paths. This dissertation provides implications for policymaking relevant to four specific Sustainable Development Goals: SDG 3 (promoting well-being), SDG 8 (fostering a decent work environment), SDG 10 (addressing inequalities), and SDG 9 (enhancing innovation). It also has implications for practitioners such as entrepreneurs and their followers (i.e., employees)

The impact of characteristics of intra-organizational environment on entrepreneurial marketing intensity and performance in Egypt

Purpose: The purpose of this paper is to contribute to the entrepreneurial marketing (EM) paradigm by empirically investigating the relationship between intra-organizational environment, EM intensity (EMI) and organizational performance in an emerging market context. Specifically, the paper identifies the elements of the intra-organizational environment that enhances EMI and also examines the impact of EMI on organizational performance. Design/methodology/approach: The data were collected from large-sized companies in Egypt. Data were analyzed by using path analysis on Smart-PLS. Findings: The findings suggest that the characteristics of the intra-organizational environment that support developing and increasing EMI in large-sized companies in emerging markets are cooperative competency, deep locus of planning and institutional support. Also, it was found that the long planning horizon hinders EMI. Finally, it was found that EMI is positively related to organizational performance and competitive advantage. Practical implications: The study provides guidelines for managers of large-sized organizations, especially in emerging economies, on how to develop the intra-organizational environment to enhance EMI. Originality/value: The study of EMI received little or no attention in previous research. Also, there is a paucity of empirical research on the impact of the intra-organizational environment on EMI and also on the impact of EMI on the organizational performance of large-sized companies in emerging markets. Therefore, the results of this research are a step toward filling these gaps

Cell Traction Force Mapping in MG63 and HaCaTs

NoThe ability of a cell to adhere and transmit traction forces to a surface reveals the cytoskeleton integrity of a cell. Shear sensitive liquid crystals were discovered with new function in sensing cell traction force recently. This liquid crystal has been previously shown to be non-toxic, linear viscoelastic and sensitive to localized exerted forces. This paper reports the possibility of extending the application of the proposed liquid crystal based cell force sensor in sensing traction forces of osteoblast-like (MG-63) and human keratinocyte (HaCaT) cell lines exerted to the liquid crystal sensor. Incorporated with cell force measurement software, force distributions of both cell types were represented in force maps. For these lowly contractile cells, chondrocytes expressed regular forces (10 – 90 nN, N = 200) around the circular cell body whereas HaCaT projected forces (0 – 200 nN, N = 200) around the perimeter of poly-hedral shaped body. These forces are associated with the organisation of the focal adhesion expressions and stiffness of the LC substrate. From the results, liquid crystal based cell force sensor system is shown to be feasible in detecting forces of both MG63 and HaCaT

Increased Number of Human Cases of Influenza Virus A(H5N1) Infection, Egypt, 2014–15

During November 2014–April 2015, a total of 165 case-patients with influenza virus A(H5N1) infection, including 6 clusters and 51 deaths, were identified in Egypt. Among infected persons, 99% reported poultry exposure: 19% to ill poultry and 35% to dead poultry. Only 1 person reported wearing personal protective equipment while working with poultry

An exploration of factors influencing the selection of generic and innovator medicines in Saudi Arabia using an observational cross-sectional study

Background and objectives: Generic medications are cost-effective without compromising therapeutic outcomes. Therefore, the goal of this study was to investigate, using a cross-sectional study design, the factors influencing Saudi Arabian consumers' preferences between innovator and generic medications. Methods: This cross-sectional study was carried out in Saudi Arabia using a Google survey form. For data collection, a simple random sampling strategy was used. The recruited participants were surveyed using a validated questionnaire that focused on six influencing domains: physician, pharmacist, perceived effectiveness, price, information availability, and confidence based on prior experience. The obtained data was used to analyze factors that have an association with any of the six domains using multinomial regression analysis. A correlation analysis was performed to examine the relationship between domains. Results: The 317 participants included 64.4 % females, 52 % aged ≥ 26, and a large proportion of Saudi nationals (82.6 %) and university graduates (78.9 %). Being employed (OR:3.029; P = 0.006; CI: 6.715–1.366), a healthcare providers (OR:2.298; P = 0.043; CI: 5.151–1.025), and having insurance coverage (OR:1.908; P = 0.017; CI: 3.245–1.122) had a greater influence on medication selection. Participants with linguistic and business educational backgrounds (OR:3.443; P = 0.022; CI: 9.950–1.191), those living in the northern region of Saudi Arabia (OR:3.174; P = 0.009; CI: 7.585–1.328), having chronic ailments (OR:3.863; P = 0.013; CI: 11.274–1.324), and possess insurance (OR:1.748; P = 0.039; CI: 2.971–1.028) get readily influenced by pharmacist. People who were married and lived in Saudi Arabia's southern region were influenced by perceived effectiveness when choosing medicine. Participants from the northern region were found to be influenced by the price of the medicines, information about the medicines, and confidence based on previous experience. The price of medicines has a significant impact on those suffering from chronic diseases. At a significant level of P = 0.01, all six influencing domains were found to be positively correlated with each other. Conclusion: The study shows that healthcare providers, drug prices, perceived efficacy, and information availability all have a big influence on the Saudi Arabian population's choice of medications. Educational background, location, and chronic disease status are associated with several influencing domains. Aside from public awareness campaigns, healthcare professionals should be involved in the implementation of the generic medication policy