Role of the Immune System and Bioactive Lipids in Trafficking Bone Marrow-Derived Stem Cells in Patients with Ischemic Heart Disease

Acute myocardial infarction (AMI) triggers the mobilization of stem/progenitor cells from bone marrow (BMSPCs) into peripheral blood (PB). The underlying mechanisms orchestrating this mobilization and subsequent homing of BMSPCs to the myocardium are poorly understood. While the role of traditional chemokines in the mobilization and homing of hematopoietic stem cell (HSCs) to BM niches is undisputed, their role in directing BMSPCs to the highly proteolytic environment of the ischemic myocardium is debatable and other redundant mechanism may exist. Based on our observation that bioactive lipids, such as sphingosine-1 phosphate (S1P) and ceramide-1 phosphate (C1P), play an important role in regulating trafficking of HSCs; we explored if they also direct trafficking of BMSPCs in the setting of myocardial ischemia. While BMSPCs expressed S1P receptors regardless of the source, the expression of S1P receptor 1 (S1PR1) and receptor 3 (S1PR3), which are responsible for migration and chemotaxis, was elevated in BMSPCs in naïve BM cells and was reduced following mobilization. This expression correlated to differential response of BMSPCs to S1P in chemotaxis assays. By employing flow cytometry analyses, we observed an increase in circulating PB CD34+, CD133+ and CXCR4+ lineage negative (Lin-)/CD45- cells that are enriched in non-HSCs (P \u3c 0.05 vs. controls). This corroborated our mass spectrometry studies showing a temporal increase in S1P and C1P plasma levels. At the same time, plasma obtained in the early phases following AMI strongly chemoattracted human BM-derived CD34+/Lin- and CXCR4+/Lin- cells in Transwell chemotaxis assays in an S1P dependent fashion. We examined other mechanisms that may contribute to the homing of BMSPCs to the infarcted myocardium due to the reduction of S1PRs upon mobilization. We observed that hypoxia induced higher expression of cathelicidins in cardiac tissues. Indeed, PB cells isolated from patients with AMI migrated more efficiently to low, yet physiological, gradient of SDF-1 in Transwell migration assays compared to SDF-1 alone. Together, these observations suggest that while elevated S1P plasma levels early in the course of AMI may trigger mobilization of non-HSCs into PB, cathelicidins appear to play an important role in their homing to ischemic and damaged myocardium

The role of losartan and enalapril in the protection against stress-induced gastric mucosal ulceration in rats

Background: Angiotensin II (ANG II) is a stress hormone and its level dramatically increases in the stomach during stress. In addition, it generates reactive oxygen species (ROS) with cellular damage and inflammation. So the aim of this study is to evaluate the mechanism of losartan and enalapril in the prevention of stress-induced gastric ulcer through their action on mucosal prostaglandin (PGs) and antioxidant enzymes and compare between them.Methods: Thirty- six adult male wistar albino rats weighing 180-200 g were divided into 6 groups; n= 6. Groups 1, 2, and 3 were received saline (normal control), losartan (3 mg/kg/day) and enalapril (10 mg/kg/day) i.p respectively for 4 weeks. Groups 4, 5, and 6 were pretreated with saline (ulcer control), losartan (3 mg/kg/day) and enalapril (10 mg/kg/day) i.p respectively for 4 weeks duration. On 29th day, group 4, 5 and 6 were submitted to gastric ulcer by water immersion method, then animals of all groups were sacrificed, stomachs were excised for gross and microscopic examination and determination of the mucosal levels of prostaglandin E2 (PGE2), superoxide dismutase (SOD), nitric oxide (NO) and catalase (CAT).Results: Stress produced gastric ulcer and a significant decrease in all measured gastric parameters compared to normal control group. Pre-treatment of rats with losartan or enalapril decreased the stress-induced alterations in mucosal parameters, but only losartan caused a significant increase in CAT activity in addition.Conclusions: Antagonize the action of ANG II by losartan and enalapril have preventive advantages in stress-induced gastric ulcer and losartan has better influence as it has an additional effect on CAT activity

The Nature of Domestic Demand for Authentic Ethnic Experiences in Egypt: Exploring Egyptian Visitors’ Perspectives and Assessments of Bedouin Cultural Attractions

Much emphasis in the literature on Bedouin tourism in the Arab world has been given to the demands, perceptions, motivations and experiences of international tourists while domestic demands are not fully understood. Thus, this study challenges the status quo, being one of a few studies in which Egyptians are represented as tourists consuming Egyptian ethnic culture. A mix of qualitative research methods, including 29 semi-structured interviews with domestic visitors, observational data and document analysis, was employed to explore Egyptian visitors’ perspectives and assessments of Bedouin cultural attractions in Egypt. The findings revealed that the concept of experiencing existential authenticity through interactions with the workers and performers appeared to be outside the visitors’ sphere of thought, as they focused almost exclusively on tangible elements of the site offerings. This study has important implications for Bedouin tourism suppliers as well as tourism researchers. Egyptian visitors can be viewed as a powerful potential market for Bedouin attractions. Thus, site management should reconsider their approach to Egyptian visitors, as well as rethink the mission and goals of their site. Theoretically, the findings of this study strongly contest the notion that objective authenticity is no longer essential in ethnic tourism

Handling multi-collinearity using principal component analysis with the panel data model

When designing a statistical model, applied researchers strive to make the model consistent, unbiased, and efficient. Labor productivity is an important economic indicator that is closely linked to economic growth, competitiveness, and living standards within an economy. This paper proposes the one-way error component panel data model for labor productivity. One of the problems that we can encounter in panel data is the problem of multi-collinearity. Therefore, multi-collinearity problem is considered. This problem has been detected. After that, the principal component technique is used to get new good unrelated estimators. For the purposes of our analysis, the multi-collinearity problem between the explanatory variables was examined, using principal component techniques with the application of the panel data model focused on the impact of public capital, private capital stock, labor, and state unemployment rate on gross state products. The analysis was based on three estimation methods: fixed effect, random effect, and pooling effect. The challenge is to get estimators with good properties under reasonable assumptions and to ensure that statistical inference is valid throughout robust standard errors. And after application, fixed effect estimation turned out to play a key role in the estimation of panel data models. Based on the results of hypothesis testing, the real data result showed that the fixed effect model was more accurate compared to the two models of random effect and pooling effect. In addition, robust estimation was used to get more efficient estimators since heteroscedasticity has been confirme

エジプト産のカリステモン種からの強力な栄養飢餓耐性解除抗がん物質の探索とそれらのヒト膵臓がん細胞株PANC-1に対する作用機序

富山大学・富医薬博甲第345号・Ahmed Mohammed Abdel Latif Mohammed Tawila・2020/09/28・★論文非公開★富山大

Cardiac Cell Therapy: Insights into the Mechanisms of Tissue Repair

Stem cell-based cardiac therapies have been extensively studied in recent years. However, the efficacy of cell delivery, engraftment, and differentiation post-transplant remain continuous challenges and represent opportunities to further refine our current strategies. Despite limited long-term cardiac retention, stem cell treatment leads to sustained cardiac benefit following myocardial infarction (MI). This review summarizes the current knowledge on stem cell based cardiac immunomodulation by highlighting the cellular and molecular mechanisms of different immune responses to mesenchymal stem cells (MSCs) and their secretory factors. This review also addresses the clinical evidence in the field