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Layla Kamareddine,1– 3 Crystal M Ghantous,4 Soumaya Allouch,5 Sarah A Al-Ashmar,2,5 Gulsen Anlar,2,5 Surya Kannan,2,5 Laiche Djouhri,2,5 Hesham M Korashy,2,6 Abdelali Agouni,2,6 Asad Zeidan2,5 1Department Biomedical Sciences, College of Health Sciences, QU Health, Qatar University, Doha, Qatar; 2Biomedical and Pharmaceutical Research Unit, QU Health, Qatar University, Doha, Qatar; 3Biomedical Research Center, Qatar University, Doha, Qatar; 4Department of Nursing and Health Sciences, Faculty of Nursing and Health Sciences, Notre Dame University-Louaize, Keserwan, Lebanon; 5Department of Basic Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar; 6Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha, QatarCorrespondence: Asad ZeidanDepartment of Basic Sciences, College of Medicine, QU Health, Qatar University, Doha, QatarEmail a.zeidan@qu.edu.qaAbstract: Cardiac remodeling is the process by which the heart adapts to stressful stimuli, such as hypertension and ischemia/reperfusion; it ultimately leads to heart failure upon long-term exposure. Autophagy, a cellular catabolic process that was originally considered as a mechanism of cell death in response to detrimental stimuli, is thought to be one of the main mechanisms that controls cardiac remodeling and induces heart failure. Dysregulation of the adipokines leptin and adiponectin, which plays essential roles in lipid and glucose metabolism, and in the pathophysiology of the neuroendocrine and cardiovascular systems, has been shown to affect the autophagic response in the heart and to contribute to accelerate cardiac remodeling. The obesity-associated protein leptin is a pro-inflammatory, tumor-promoting adipocytokine whose elevated levels in obesity are associated with acute cardiovascular events, and obesity-related hypertension. Adiponectin exerts anti-inflammatory and anti-tumor effects, and its reduced levels in obesity correlate with the pathogenesis of obesity-associated cardiovascular diseases. Leptin- and adiponectin-induced changes in autophagic flux have been linked to cardiac remodeling and heart failure. In this review, we describe the different molecular mechanisms of hyperleptinemia- and hypoadiponectinemia-mediated pathogenesis of cardiac remodeling and the involvement of autophagy in this process. A better understanding of the roles of leptin, adiponectin, and autophagy in cardiac functions and remodeling, and the exact signal transduction pathways by which they contribute to cardiac diseases may well lead to discovery of new therapeutic agents for the treatment of cardiovascular remodeling.Keywords: inflammation, autophagy, leptin, adiponectin, cardiac cells

Vector-borne diseases have been widely associated with human morbidity and mortality. The predominance of vector-borne diseases is not exclusive to particular areas, as such diseases are dispersed across the globe. Generally, the dynamics of vector borne-disease transmission is affected by a broad spectrum of factors that influence the vector, the host, and/or the pathogen. Here, we discuss the effect of several environmental and anthropogenic factors on disease transmission dynamics. Gaining a proper understanding of the impact of such factors on vector-borne disease prevalence and spread supports future practices directed towards developing effective action plans, surveillance systems, and appropriate strategies for vector-borne disease control.

Colorectal cancer (CRC) is one of the deadliest malignancies in the world. Despite improved treatment, CRC incidence and mortality rates have been increasing lately. Current conventional therapies are associated with severe side effects that affect patients' quality of life. Drug resistance, severe pain, hair loss, and blood abnormalities are the most common side effects. Therefore, novel, and safe alternatives are required to control metastasis and prevent CRC with minimum or no side effects. Recently, natural products became an attractive target as a safe resource for anticancer agents. Flavonoids are a group of biologically active compounds naturally found in a wide range of human dietary. Additionally, flavonoids from natural and synthetic sources, showed significant therapeutic effects against CRC. Elaeagnus Angustifolia (EA) is a natural resource for flavonoids traditionally used to treat different illnesses. Another resource for flavonoids is synthetic chalcone analogs. Previous work from our team explored the effect of EA and chalcone compounds against various types of cancer. In this study, we sought to particularly illustrate the impact of the EA flower’s aqueous extract and the nitrogen-based-synthetically designed chalcone analogs (DK13 and DK14) and their underlying mechanisms of action on CRC using in vitro (the human CRC cell lines [𝐻𝐶𝑇-116 and LoVo]) and in vivo (the Drosophila melanogaster Ras mutant fly lines) model systems. Our results showed that EA extract inhibits cell proliferation and alters cell cycle progression of both CRC cell lines as compared to the control group. Moreover, EA extract significantly reduces colony formation and cell invasive ability of HCT-116 and LoVo cell lines; a phenotype accompanied by a significant upregulation of E-cadherin and a downregulation of vimentin and β-catenin, which are important epithelialmesenchymal transition (EMT) biomarkers. Also, and as detected in our in vivo model, EA-treated Ras85D mutant fly lines exhibited a significantly increased survival rate as compared to their control. Furthermore, molecular pathway analysis in vitro revealed a significant suppression in total and phosphorylated EGFR and AKT expression in EAtreated cells as compared to controls, suggesting the EGFR-RAS and PI3K-AKT pathways as key molecular pathway targeted by EA to control ongoing oncogenic events. Along this, our data related to DK13 and DK14 also revealed that these compounds inhibit cell proliferation and deregulate cell-cycle progression in both cell lines. Additionally, DK13 and DK14 significantly reduce cell invasion and colony formation of both cell lines compared to the action of conventional anticancer 5'fluorouracil (5-FU) and DMSO-treated control. This was translated into a significant increase in the survival rates of D. melanogaster Ras85D mutant fly lines as compared to their controls. Moreover, the molecular pathway analysis of chalcone- treated cells revealed an inhibitory effect of DK13 and DK14 on the expression patterns of both AKT and mTOR, highlighting RAS/MAPK and PI3K/AKT/mTOR pathways as key molecular pathway targeted by DK13 and DK14 to control ongoing oncogenic events. Collectively, our study findings demonstrate an apparent anticancer effect of EA extract and chalcone compounds on CRC, presenting EA, Dk13, and Dk14 as promising chemotherapeutic agents.

Background: The usage of T cells engineered with a tumor-specific chimeric antigen receptor (CAR) for the therapeutic treatment of some types of hematological malignancies demonstrated great clinical success. However, the manufacturing of these medicinal products is commonly performed in an autologous setting, with a relatively lengthy and complex process. Therefore, not all the patients with the defined blood cancer can have access to this type of therapy. Allogenic CAR-T cells, due to their "off-the-shelf" availability can overcome some of the limitations associated with the use of the autologous approach. The principal aim of this study was to optimize the generation of "off-the-shelf" CAR-T cells utilizing the umbilical cord blood (UCB) as a source of T lymphocytes. Methods: UCBs were collected at Sidra Medicine from newborn babies at the time of birth. T lymphocytes where isolated by magnetic selection and then activated in vitro using anti-CD3/CD28 agonistic monoclonal antibodies. The activated T cells were then transduced with lentiviral vectors encoding for two types of CARs, CD19-CD28? and CD19-4-1BB? CARs. The characterization of the efficiency of transduction, the in vitro expansion, phenotype analyses and anti-tumor activity of these CD19-CAR-T cells was performed. PBMCs were utilized as source of CAR-T cells as reference of our experiments. Results: UCB-derived CD19-CAR-T cells showed an enrichment of CAR-T cells at early stage of differentiation (T stem cell memory/central memory T cells) associated with different activation markers. These cells demonstrated high in vitro expansion and exerted an efficient anti-tumor activity against target cell lines. Conclusions: Our results allowed to identify the method for the efficient isolation ex vivo of UCB-derived CD19-CAR-T cells. UCB can be considered an efficient source of T lymphocytes to generate "off the shelf" CAR-T cells endowed with anti-tumor activity and favorable phenotypic properties.

Background: In four years from now, Qatar will host the 2022 World Cup competition which requires high level of preparedness and readiness in different sectors including health care. Among different sub-sections of health, the blood bank and the Blood Donor Center will have a major role in this event especially in case of unforeseen incidences. Accordingly, a proper assessment of the current blood resource availability and a prediction of future blood needs helps in overcoming any obstacle that could be faced during the event. Objectives: (1) Highlight the process of the blood supply chain, with a detailed delineation of the needed amount of blood components for both routine and emergency situations services, and outline the proper measures taken to deliver the safest and most appropriate blood units and reduce wastage of blood component. (2) Assess the current standing of the Blood Donor Center and corresponding units in Qatar. (3) Develop a forecast model that predicts the number of blood donors in the next four years as a method to evaluate the readiness of the Blood Donor facility to host the world cup event. (4) Explore the potential challenges that could be faced when meeting the benchmark of donation and established an action plan to overcome these anticipated challenges. Materials and Methods: Both qualitative (interviews) and a quantitative (data collection and analysis) approaches have been implemented in our study. We also established a time series forecast model using Autoregressive Integrated Moving Average (ARIMA). Results: The number of donors in the next four years, which is predicted to increase by 26%, will not be able to get accommodated in the current Blood Donor Center facility. Therefore, the established blood stock benchmark will not be met despite that the Center and its corresponding units are fully equipped with high standard equipment and follow international guidelines in the process of blood withdrawal. Conclusion: Infrastructure improvements and logistics support for Hamad Medical Corporation Blood Donor Center are required to support the continuously increasing numbers of blood donors for daily demand and during mega events.