Using Zebrafish for Investigating the Molecular Mechanisms of Drug-Induced Cardiotoxicity

Over the last decade, the zebrafish (Danio rerio) has emerged as amodel organismfor cardiovascular research.Zebrafish have several advantages over mammalian models. For instance, the experimental cost of using zebrafish is comparatively low; the embryos are transparent, develop externally, and have high fecundity making them suitable for large-scale genetic screening. More recently, zebrafish embryos have been used for the screening of a variety of toxic agents, particularly for cardiotoxicity testing. Zebrafish has been shown to exhibit physiological responses that are similar to mammals after exposure to medicinal drugs including xenobiotics, hormones, cancer drugs, and also environmental pollutants, including pesticides and heavy metals. In this review, we provided a summary for recent studies that have used zebrafish to investigate themolecularmechanisms of drug-induced cardiotoxicity. More specifically, we focused on the techniques that were exploited by us and others for cardiovascular toxicity assessment and described several microscopic imaging and analysis protocols that are being used for the estimation of a variety of cardiac hemodynamic parameters.Huseyin C. Yalcin is supported by Qatar National Research Fund (QNRF), National Priority Research Program NPRP 10-0123-170222,and Qatar University internal funds,QUUGBRC-2017-3 and QUST-BRC-SPR\2017-1. The publication of this article was partially funded by the Qatar National Library

Synthesis, Bioapplications, and Toxicity Evaluation of Chitosan-Based Nanoparticles.

The development of advanced nanomaterials and technologies is essential in biomedical engineering to improve the quality of life. Chitosan-based nanomaterials are on the forefront and attract wide interest due to their versatile physicochemical characteristics such as biodegradability, biocompatibility, and non-toxicity, which play a promising role in biological applications. Chitosan and its derivatives are employed in several applications including pharmaceuticals and biomedical engineering. This article presents a comprehensive overview of recent advances in chitosan derivatives and nanoparticle synthesis, as well as emerging applications in medicine, tissue engineering, drug delivery, gene therapy, and cancer therapy. In addition to the applications, we critically review the main concerns and mitigation strategies related to chitosan bactericidal properties, toxicity/safety using tissue cultures and animal models, and also their potential environmental impact. At the end of this review, we also provide some of future directions and conclusions that are important for expanding the field of biomedical applications of the chitosan nanoparticles

Zebrafish larvae as a model to demonstrate secondary iron overload.

Thalassemia is the most common genetically inherited blood disorder arising from a defect in hemoglobin production, resulting in ineffective erythropoiesis and severe hemolytic anemia. While transfusion therapy corrects the anemia, it gives rise to secondary iron overload. Current iron chelation therapy performed using deferoxamine, and the efficiency of this drug was demonstrated here using the zebrafish animal model. Zebrafish larvae were exposed for three days to iron [100 μM ferric ammonium citrate; 3-6 days post fertilization (dpf)]. Then, iron treated larvae were exposed to 100 μM deferoxamine for three days (6 - 9 dpf). Total tissue iron concentration in the whole larvae, assessed by three different assays; inductively coupled plasma mass spectrometry, colorimetry (spectrophotometry), and microscopy using iron staining followed by imaging and quantification. The three assays showed that iron treatment alone resulted in a significant increase in total iron. Deferoxamine treatment of the iron-loaded zebrafish larvae showed a significant decrease in total iron concentration. This study presented a clear evidence of the effectiveness of zebrafish larvae to use as a tool to study iron overload and open the door for studying the efficiency of potential new iron chelating compounds other than commercially available ones. This article is protected by copyright. All rights reserved

Effect of multiple freeze–thaw cycles on the detection of anti-SARS- CoV- 2 IgG antibodies

Several studies have investigated the effect of repeated freeze-thaw (F/T) cycles on RNA detection for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, no data are available regarding the effect of repeated F/T cycles on SARS-CoV-2 antibody detection in serum. We investigated the effect of multiple F/T cycles on anti SARS-CoV-2 IgG detection using an ELISA test targeting the nucleocapsid antibodies. Ten positive and 1 negative SARS-CoV-2 IgG sera from 11 participants, in replicates of 5, were subjected to a total of 16 F/T cycles and stored at 4 °C until tested by ELISA. Statistical analysis was performed to test for F/T cycle effect. None of the 10 positive sera became negative after 16 F/T cycles. There was no significant difference in the OD average reading between the first and last F/T cycles, except for one serum with a minimal decline in the OD. The random effect linear regression of log (OD) on the number of cycles showed no significant trend, with a slope consistent with zero (B=−0.0001; 95% CI −0.0008; 0.0006; P-value= 0.781). These results suggest that multiple F/T cycles had no effect on the ability of the ELISA assay to detect SARS-CoV-2 IgG antibodiesThis work was made possible by grant no. RRC-2-032 from the Qatar National Research Fund (a member of the Qatar Foundation). The statements made herein are solely the responsibility of the author(s). G. K. N. acknowledges funds from Qatar University’s internal grant QUERG-CMED-2020-2. S. R. D. and L. J. A. acknowledges the support of the Biomedical Research Program and the Biostatistics, Epidemiology, and Biomathematics Research Core, both at Weill Cornell Medicine-Qatar

Epidemiology Profile of Viral Meningitis Infections Among Patients in Qatar (2015-2018)

Little is known about the etiology of meningitis in the MENA region, including Qatar. Viral agents are considered the major cause for meningitis worldwide. Here, we present primary data about the etiology and clinical and demographic characteristics of viral meningitis (VM) in Qatar between 2015 and 2018. We retrospectively collected data from Hamad Medical Corporation (HMC), which provides about 80% of healthcare services in Qatar. Data were collected for the period between 2015 and 2018. During this time period, 6,705 specimens were collected from patients with suspected meningitis attending HMC and primary healthcare centers. These specimens were tested for a panel of viruses using the "FTD Viral meningitis" multiplex real-time PCR kit that detects Adenovirus (ADV), Human herpesvirus 1&2 (HSV1 and HSV2), Epstein-Barr virus (EBV), Enteroviruses (EV), Cytomegalovirus (CMV), Varicella zoster virus (VZV), and Parechovirus (PV). Only 10.9% (732/6,705) of all suspected meningitis cases were caused by viral agents. 60.9% of the reported cases were males, compared to 39.1% in females. Most of the infections (73.9%) were reported in children younger than 10 years of age. EV were identified as the main causative agent (68.7%), followed by EBV (7.5%) and ADV (6.8%). Other viral agents including VZV, PV, HSV-1, and HSV-2 were also detected with a lower frequency. Confirmed VM were more prevalent among Qatari subjects compared to other nationalities. We observed no specific seasonality of viral agents, but a slight rise was recorded during the spring seasons (March to June). Fever (59.4%, 435/732) and acute central nervous system (CNS) infection (15.6%, 114/732) were initial symptoms of most cases. This is the first report about the molecular epidemiology of VM in Qatar. In line with the international records, our data showed that EV is responsible for 68.7% of Qatar's VM cases. Further studies are needed to genotype and serotype the identified viruses