Support of intelligent emergent materials to combat COVID-19 pandemic

The COVID-19 pandemic, associated with SARS-CoV-2 infection transmitted via human to human and cause lifethreatening respiratory diseases, has emerged as an everincreasing global health and economic crisis since its declaration by the World Health Organization (WHO) in early Jan 2020. Despite the development of several vaccines and initiation of vaccination programs, it is very likely that we will have to continue our lives under now became normal preventative measures for several more years.While this global battle against the pandemic is carried out on the frontlines by healthcare providers, another major effort are underway by scientists and engineers in research labs around the globe for investigating better therapies, detection systems, and safety aspects. In this unprecedented scenario, experts are seeking fast, practical, and effective ways to support healthcare providers in treating patients and prevent or slow further spread of the virus. In this dazzling race against time, materials science is one of the fields that is contributing significantly, due to a substantial cumulative knowledge that can be translated rapidly to clinical practice. Novel material approaches of tunable performance can be useful for various multi-tasking applications such as accurate diagnosis of viral infection from patient samples, sanitizing or preventing viral accumulation on surfaces, alternative sources and sanitation for personal protective equipment, effective delivery and binding of antiviral agents to the virus, reprogramming of the immune system, and even development of injectable synthetic compounds to compete with the virus in binding to viral receptors.Qatar National Research Fun

Generating an imagingbased approach for enhanced structural and functional analysis of zebrafish cardiovascular systems

Cardiovascular diseases (CVDs) have latterly become one of the leading cause of death and impairment worldwide. According to the World Health Organization (WHO), data estimation in 2008 were about 17.3, 7.3 and 6.2 million death cases for CVDs, heart attacks, and strokes, respectively [1]. Congenital heart defects (CHDs) are important forms of CVDs affecting about 1% of the population. According to Dr. Ahmad Sallehuddin (Consultant and Chief of Pediatric Cardiac Surgery at HMC), CHD incidence in Qatar is about 6-8 in every 1,000 births and about 100 new patients with CHDs require surgery every year [4]. Both genetic and environmental factors were shown to contribute to CVDs. Human genetic studies are not sufficient alone to explain the genetic basis of CVDs due to disease heterogeneity, inconsistent penetrance, and predominantly a delayed onset of symptoms. Therefore, animal models are necessary to investigate and distinguish novel genes that contribute to the pathology of CVDs and also to unravel environmental factors that play role [5]. More recently, the Danio rerio (Zebrafish) has emerged to become an intriguing vertebral model in medical science research. This model has several advantages, such as an almost entirely sequenced genome that is highly preserved with humans: approximately 70% of the human genes are estimated to have orthologue genes in the zebrafish genome [2,8]. The features of the zebrafish over mammals as a vertebral model include its simplicity of genetic manipulation, a large quantity of offspring, and their external and fast development [5,8]. Transparency of zebrafish embryos provide precise observation of the heart beats, heart chambers and circulating blood in vivo via light microscopy [5]. Additionally, passive diffusion is sufficient for oxygen delivery during early stages of zebrafish embryos development because they are independent of circulatory system [7]. Therefore, embryos having intensive cardiac faults survive early development, which enables investigation of mutations whereas mammalian models are not appropriate. There are many genetic cardiovascular models for zebrafish that allow researchers to investigate cardiovascular diseases. Novel techniques are needed for these models to assess comprehensive and quantitative phenotyping of mutant hearts and blood vessels. These analyses involve determination of the cardiac atrial and ventricular shortening fractions, examination of the blood flow velocities and recording of the electrocardiograms. In addition to genetic studies, cardiotoxicity investigations for drugs or teratogens necessitate heart function and morphology assessment. For the current study, the aim is to adapt previously established experimental and image analysis techniques to zebrafish studies, which will enhance structural and functional analysis of the zebrafish cardiovascular systems in biomedical research Methodology: This project involves generation of two main protocols, which are for structural and functional analysis of zebrafish embryos. Both these analyses are required to be performed to assess the severity of induced heart defects in zebrafish embryos. For the structural analysis, we will perfuse zebrafish (3 -5 days post fertilization (dpf)) hearts with microfilm, a CT- dense agent. Once it polymerises, a cast is generated for heart lumen. The embryos are then fixed with paraformaldehyde and scanned via micro-CT. This procedure provides 3D images for the cardiovascular systems of the animals enabling measurement of the volumes of the heart chambers. This technique enables us to measure the effect of induced heart mutations on the heart morphology during the embryonic growth of the animal. We have previously used this technique for visualization of cardiac chambers for embryonic chicken successfully [3,10]. The approach is adapted for zebrafish studies in the current work. For the functional analysis, image sequences of the beating ventricles and the red blood cell (RBC) movements of the zebrafish larvae (3 -5 dpf) are recorded at a camera speed of 70 fps and above. This imaging is done by taking videos using Micromanager Program that is connected to a stereomicroscope. To take image sequences, zebrafish larvae are placed on its lateral side, in which the right side will be on top. A variety of measurements and calculations are performed using Image J Program to assess heart functions. The parameters that are calculated include myocardial wall velocities for assessment of severity of induced heart muscle defects, and measurement of RBC blood flow velocities for assessment of rhythmic beating defects of the heart. Other parameters are fractional area change, fractional shortening, heart rate, stroke volume, cardiac output and ejection fraction [9]. Stroke volume, is the blood volume that is ejected from the heart in each beat, cardiac output, is the amount of circulating blood across the heart in each minute, and ejection fraction, is the measurement of blood that is ejected from the ventricle with each beat. This will provide more precise and accurate evaluation on the heart function for genetically mutated animals to be compared with the normal ones. Several zebrafish mutants display phenotypic features resembling human cardiac diseases. These mutants whose molecular damages have been determined like mutations in regulatory myosin light chain, titin, cardiac troponin T, essential myosin light chain, and beta-myosin heavy chain, have been linked with cardiomyopathy in humans [6]. Therefore, reduced contractility, myocardial wall velocities, and cardiac output can be studied as a sign of having cardiomyopathy. Accordingly, opening ways to apply drugs for morphological and structural evaluation of the heart. In conclusion, in this study, we are developing imaging-based techniques for accurate structural and functional analysis of the zebrafish hearts through adapting previously established methods on another animal systems. Once we establish our approach, analysis methods will be readily available for other Zebrafish researchers

Effect of flow-induced shear stress in nanomaterial uptake by cells: Focus on targeted anti-cancer therapy

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Recently, nanomedicines have gained a great deal of attention in diverse biomedical applications, including anti-cancer therapy. Being different from normal tissue, the biophysical microenvironment of tumor cells and cancer cell mechanics should be considered for the development of nanostructures as anti-cancer agents. Throughout the last decades, many efforts devoted to investigating the distinct cancer environment and understanding the interactions between tumor cells and have been applied bio-nanomaterials. This review highlights the microenvironment of cancer cells and how it is different from that of healthy tissue. We gave special emphasis to the physiological shear stresses existing in the cancerous surroundings, since these stresses have a profound effect on cancer cell/nanoparticle interaction. Finally, this study reviews relevant examples of investigations aimed at clarifying the cellular nanoparticle uptake behavior under both static and dynamic conditions

Fabrication and In Vitro Characterization of a Tissue Engineered PCL-PLLA Heart Valve.

Heart valve diseases are among the leading causes of cardiac failure around the globe. Nearly 90,000 heart valve replacements occur in the USA annually. Currently, available options for heart valve replacement include bioprosthetic and mechanical valves, both of which have severe limitations. Bioprosthetic valves can last for only 10-20 years while patients with mechanical valves always require blood-thinning medications throughout the remainder of the patient's life. Tissue engineering has emerged as a promising solution for the development of a viable, biocompatible and durable heart valve; however, a human implantable tissue engineered heart valve is yet to be achieved. In this study, a tri-leaflet heart valve structure is developed using electrospun polycaprolactone (PCL) and poly L-lactic acid (PLLA) scaffolds, and a set of in vitro testing protocol has been developed for routine manufacturing of tissue engineered heart valves. Stress-strain curves were obtained for mechanical characterization of different valves. The performances of the developed valves were hemodynamically tested using a pulse duplicator, and an echocardiography machine. Results confirmed the superiority of the PCL-PLLA heart valve compared to pure PCL or pure PLLA. The developed in vitro test protocol involving pulse duplicator and echocardiography tests have enormous potential for routine application in tissue engineering of heart valves

A novel in ovo model to study cancer metastasis using chicken embryos and GFP expressing cancer cells.

Cancer metastasis is the leading cause of cancer-related mortality worldwide. To date, several in vitro methodologies have been developed to understand the mechanisms of cancer metastasis and to screen various therapeutic agents against it. Nevertheless, mimicking an in vivo microenvironment in vitro is not possible; while in vivo experiments are complex, expensive and bound with several regulatory requirements. Herein, we report a novel in ovo model that relies on chicken embryo to investigate cancer cell invasion and metastasis to various organs of the body. In this model, we directly inject green fluorescent protein (GFP) expressing cancer cells to the heart of chicken embryo at 3 days of incubation, then monitor cell migration to various organs. To this end, we used a simple tissue processing technique to achieve rapid imaging and quantification of invasive cells. We were able to clearly observe the migration of GFP expressing cancer cells into various organs of chicken embryo. Organ specific variation in cell migration was also observed. Our new slide pressing based tissue processing technique improved the detectability of migrated cells. We herein demonstrate that the use of GFP expressing cancer cells allows easy detection and quantification of migrated cancer cells in the chicken embryo model, which minimizes the time and effort required in this types of studies compared to conventional histopathological analysis. In conclusion, our investigation provides a new cancer metastasis model that can be further improved to include more complex aspects, such as the use of multiple cell lines and anti-metastatic agents, thus opening new horizons in cancer biology and pharmaceutical research

Editorial: Emerging mechanisms in cardiovascular disease

Editorial on the Research Topic Emerging mechanisms in cardiovascular disease The leading cause of worldwide mortality is cardiovascular disease (CVD) (Aboukhater et al., 2023). Despite many significant advances in the field, CVD continues to claim more lives than all cancers combined (Sawma et al., 2022). There is then an urgent need for more efficacious treatment modalities or therapeutics that could aid in the management of CVD (Badran et al., 2019; Maaliki et al., 2019; El-Hachem et al., 2021). For such potential new drugs to be determined, a better understanding of the underlying mechanisms and the potential targets is critical. This Research Topic seeks to highlight a few of these emerging mechanisms and targets that could be employed for a better treatment of CVD. Myocardial injury continues to be a major contributor to CVD-associated mortality. In this thematic issue, Liu et al. discuss how they established a model for coronary microembolization (CME) in rats, and report that ferroptosis and inflammation are two key players in CME-induced myocardial injury. The authors then show that suppressing ferroptosis attenuates myocardial injury and inflammation following CME. It appears that Ptgs2, a core factor in ferroptosis, and Hif1a are the two mediators of this suppressed ferroptosis. Importantly, the authors further report that by inhibiting the Hif1a/Ptgs2 axis, atorvastatin was able to suppress ferroptosis-dependent CME-precipitated myocardial injury and inflammation (Liu et al.)

Adaptation of a Mice Doppler Echocardiography Platform to Measure Cardiac Flow Velocities for Embryonic Chicken and Adult Zebrafish.

Ultrasonography is the most widely used imaging technique in cardiovascular medicine. In this technique, a piezoelectric crystal produces, sends, and receives high frequency ultrasound waves to the body to create an image of internal organs. It enables practical real time visualization in a non-invasive manner, making the modality especially useful to image dynamic cardiac structures. In the last few decades, echocardiography has been applied to cardiac disease models, mainly to rodents. While clinical echocardiography platforms can be used for relatively large animals such as pigs and rats, specialized systems are needed for smaller species. Theoretically, as the size of the imaged sample decreases, the frequency of the ultrasound transducer needed to image the sample increases. There are multiple modes of echocardiography imaging. In Doppler mode, erythrocytes blood flow velocities are measured from the frequency shift of the sent ultrasound waves compared to received echoes. Recorded data are then used to calculate cardiac function parameters such as cardiac output, as well as the hemodynamic shear stress levels in the heart and blood vessels. The multi-mode (i.e., b-mode, m-mode, Pulsed Doppler, Tissue Doppler, etc.) small animal ultrasound systems in the market can be used for most cardiac disease models including mice, embryonic chick and zebrafish. These systems are also associated with significant costs. Alternatively, there are more economical single-mode echocardiography platforms. However, these are originally built for mice studies and they need to be tested and evaluated for smaller experimental models. We recently adapted a mice Doppler echocardiography system to measure cardiac flow velocities for adult zebrafish and embryonic chicken. We successfully assessed cardiac function and hemodynamic shear stress for normal as well as for diseased embryonic chicken and zebrafish. In this paper, we will present our detailed protocols for Doppler flow measurements and further cardiac function analysis on these models using the setup. The protocols will involve detailed steps for animal stabilization, probe orientation for specific measurements, data acquisition, and data analysis. We believe this information will help cardiac researchers to establish similar echocardiography platforms in their labs in a practical and economical manner.Qatar National Research Fund (QNRF), National Priority Research Program NPRP 10-0123-170222. The publication of this article was funded by the Qatar National Library

Do changes in ace-2 expression affect sars-cov-2 virulence and related complications: A closer look into membrane-bound and soluble forms

The SARS-CoV-2 virus utilizes angiotensin converting enzyme (ACE-2) for cell entry and infection. This enzyme has important functions in the renin-angiotensin aldosterone system to preserve cardiovascular function. In addition to the heart, it is expressed in many tissues including the lung, intestines, brain, and kidney, however, its functions in these organs are mostly unknown. ACE-2 has membrane-bound and soluble forms. Its expression levels are altered in disease states and by a variety of medications. Currently, it is not clear how altered ACE-2 levels influence ACE-2 virulence and relevant complications. In addition, membrane-bound and soluble forms are thought to have different effects. Most work on this topic in the literature is on the SARS-CoV virus that has a high genetic resemblance to SARS-Co-V-2 and also uses ACE-2 enzyme to enter the cell, but with much lower affinity. More recent studies on SARS-CoV-2 are mainly clinical studies aiming at relating the effect of medications that are thought to influence ACE-2 levels, with COVID-19 outcomes for patients under these medications. This review paper aims to summarize what is known about the relationship between ACE-2 levels and SARS-CoV/SARS-CoV-2 virulence under altered ACE-2 expression states.The publication of this article was covered with a generous support from BARZAN HOLDING

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