Maryam Farzaneh

Pathogenic mechanisms following ischemic stroke

Stroke is the second most common cause of death and the leading cause of disability worldwide. Brain injury following stroke results from a complex series of pathophysiological events including excitotoxicity, oxidative and nitrative stress, inflammation, and apoptosis. Moreover, there is a mechanistic link between brain ischemia, innate and adaptive immune cells, intracranial atherosclerosis, and also the gut microbiota in modifying the cerebral responses to ischemic insult. There are very few treatments for stroke injuries, partly owing to an incomplete understanding of the diverse cellular and molecular changes that occur following ischemic stroke and that are responsible for neuronal death. Experimental discoveries have begun to define the cellular and molecular mechanisms involved in stroke injury, leading to the development of numerous agents that target various injury pathways. In the present article, we review the underlying pathophysiology of ischemic stroke and reveal the intertwined pathways that are promising therapeutic targets.

Emerging Roles of microRNAs in Ischemic Stroke: As Possible Therapeutic Agents

Stroke is one of the leading causes of death and physical disability worldwide. The consequences of stroke injuries are profound and persistent, causing in considerable burden to both the individual patient and society. Current treatments for ischemic stroke injuries have proved inadequate, partly owing to an incomplete understanding of the cellular and molecular changes that occur following ischemic stroke. MicroRNAs (miRNA) are endogenously expressed RNA molecules that function to inhibit mRNA translation and have key roles in the pathophysiological processes contributing to ischemic stroke injuries. Potential therapeutic areas to compensate these pathogenic processes include promoting angiogenesis, neurogenesis and neuroprotection. Several miRNAs, and their target genes, are recognized to be involved in these recoveries and repair mechanisms. The capacity of miRNAs to simultaneously regulate several target genes underlies their unique importance in ischemic stroke therapeutics. In this Review, we focus on the role of miRNAs as potential diagnostic and prognostic biomarkers, as well as promising therapeutic agents in cerebral ischemic stroke.

The Interplay of MicroRNAs in the Inflammatory Mechanisms Following Ischemic Stroke

Immunity and inflammation are important parameters of the pathophysiology of stroke, a destructive illness that is the second most common cause of death worldwide. Following ischemic stroke, neuroinflammation plays a critical role in neurodegeneration and brain injury. MicroRNAs (miRNAs) are a class of endogenously expressed, noncoding RNA molecules that function to inhibit mRNA translation. Recent studies demonstrate that miRNAs are key regulators of inflammatory processes contributing to ischemic stroke injuries. Several miRNAs, and their target genes, have been shown to play a critical role in the innate inflammatory responses mediated by immune cells. The capacity of miRNAs to regulate several target genes demonstrates their exceptional importance in neuroinflammatory therapeutics following ischemic stroke. In this review, we focus on the miRNAs associated with ischemic neuroinflammation and describe the potential of miRNAs as biomarkers of neuroinflammation and promising therapeutic agents for modulation of deleterious inflammatory responses following ischemic stroke.

Avian embryos and related cell lines: A convenient platform for recombinant proteins and vaccine production

Chick embryos are a significant historical research model in basic and applied sciences. The embryonated eggs have been used for virus inoculation in order to vaccine production for nearly a century. Recently, avian eggs and cell lines derived from embryonated eggs have found wide application in biotechnology. This review will discuss about the unique characteristics of avian eggs in terms of safety, large scale and economical production of recombinant proteins. This system also provides the human‐like glycosylation on target proteins and therefore can be considered as a suitable host for biomanufacturing of humanized monoclonal antibodies and therapeutic proteins. Avian derived cell lines are an alternative for rapid vaccine manufacturing during a pandemic. Based on the latest knowledge in cell and animal transgenesis, the currently available germ cell‐mediated gene transfer system provides a more efficient strategy in gene targeting and creation of transgenic birds that lead to advancements in industrial, biotechnology, and biological research applications. This review covers the recent development of avian fertilized eggs and related cell lines in a variety of human biopharmaceuticals and viral vaccine manufacturing.

The evolution of chicken stem cell culture methods

ABSTRACT 1. The avian embryo is an excellent model for studying embryology and the production of pharmaceutical proteins in transgenic chickens. Furthermore, chicken stem cells have the potential for proliferation and differentiation and emerged as an attractive tool for various cell-based technologies. 2. The objective of these studies is the derivation and culture of these stem cells is the production of transgenic birds for recombinant biomaterials and vaccine manufacture, drug and cytotoxicity testing, as well as to gain insight into basic science, including cell tracking. 3. Despite similarities among the established chicken stem cell lines, fundamental differences have been reported between their culture conditions and applications. Recent conventional protocols used for expansion and culture of chicken stem cells mostly depend on feeder cells, serum-containing media and static culture. 4. Utilising chicken stem cells for generation of cell-based transgenic birds and a variety of vaccines requires large-scale cell production. However, scaling up the conventional adherent chicken stem cells is challenging and labour intensive. Development of a suspension cell culture process for chicken embryonic stem cells (cESCs), chicken primordial germ cells (PGCs) and chicken induced pluripotent stem cells (ciPSCs) will be an important advance for increasing the growth kinetics of these cells. 6. This review describes various approaches and suggestions to achieve optimal cell growth for defined chicken stem cells cultures and use in future manufacturing applications.

First scientific record of two cases of partial twinning in the chick embryo, Gallus gallus domesticus

Bicephalia is one of the scarcest malformations reported in birds and needs to be fully investigated in chick embryos. Among 1500 fertilised eggs used to examine the primordial germ cells in 2-day and 5.5-day chick embryos Gallus gallus domesticus, bicephalia was found and the condition of the heads, the heart and other parts of the body was fully described. Each twin had its own head; hearts were not completely separated from each other and the rest of the bodies were externally unique. This investigation urges others including poultry farms to share their data on a bigger scale. It may also encourage the monitoring of abnormalities randomly seen during early chick embryogenesis and consideration of environmental factors when poultry farms are faced with high percentages of unsuccessful hatching. The report can shed some light on developmental processes and may also help to clarify why bicephalia is not more common.

The method of chicken whole embryo culture using the eggshell windowing, surrogate eggshell, and ex-ovo culture system

ABSTRACT 1. The unique accessibility of the avian embryo have made them an ideal model for the study of development and genome editing. Chicken whole embryo culture has provided important insights into toxicity tests, gene manipulation, clarifying gene functions, cell transplantation and cell tracking. 2. A simple technique for chicken manipulation is eggshell windowing, without or with seal, the latter having demonstrated some improvement in hatching rates. 3. Likewise, a surrogate eggshell system provides an accessible model for manipulation during chicken and quail development, with a higher hatchability compared to the simple windowing method. 4. The development of the chicken ex ovo culture systems in a synthetic environment as an efficient technique for imaging and microsurgery applications has enabled the study of important events of live chicken embryos at a specific time point. 5. This short review illustrates recent applications of well-designed whole embryo culture systems as a robust model for research into numerous biological mechanism, drug discovery, gene manipulating and production of functional proteins.

Effects of various culture conditions on pluripotent stem cell derivation from chick embryos

Pluripotent stem cell (PSC) lines derived from embryonated avian eggs are a convenient platform for production of various recombinant proteins and vaccines. In chicks, both embryonic stem cells (ESC) and embryonic germ cells (EGC) are considered to be pluripotent cells obtained from early blastodermal cells (stage X) and gonadal tissues (stage HH28), respectively. However, the establishment and long‐term maintenance of avian PSC lines faces several challenges and differs in efficiency between chick strains. This study aims to determine the effects of PSC culture media, including serum‐based and serum‐free media as well as various feeder layers, growth factors, and small molecules on derivation and maintenance of avian embryonic derived‐PSCs. Our results have shown that among the different culture conditions, N2B27 serum‐free medium supplemented with PD0325901 and SB431542, MEK and TGFβ chemical inhibitors, named as R2i and cytokine leukemia inhibitory factor (LIF) improved PSC derivation from stages X‐ and HH28 embryos. The application of N2B27/R2i + LIF medium validates the effect of defined pluripotency supporting medium on efficient derivation of chick PSCs and facilitates the use of these cells in biotechnology and biobanking of valuable species.