1- Introduction

2- In vitro studies

3- In vivo studies

4- Conclusion(s)

References

Abstract

Stem cell, one of the most exciting research areas of 21st century, is considered to have broaden the horizons of the field of biology, in general and medicine, in particular. Stem cells, owing to their unique characteristics like self-renewal, multiplication and differentiation are considered to provide an ‘all-in-one-solution’ for diverse clinical problems. Among various stem cell types, mesenchymal stem cells (MSCs) are being made the subject of the most of the studies on their therapeutic applications. It is attributable to their readily available sources, ability to immunemodulate and differentiate into mesodermal and extra-mesodermal tissues. MSCs in contrast to pluripotent stem cells carry minimal risk of teratoma formation and are free from any ethical concern. MSCs have been evaluated under innumerable studies but the definitive applications of these cells are slow, plausibly due to the incomplete understanding of their cellular physiology. Goat MSCs (gMSCs) have been isolated, culture expanded, characterized from various tissue sources and studied for their potential in vivo applications mostly in relation to human translational models. The current review throws some light on gMSC sources, characterization and potential therapeutic applications.

Introduction

The stem cells constitute an important element in the discipline of regenerative medicine that aims to address numerous incurable diseases through tissue regeneration (Gugjoo and Amarpal, 2018; Gugjoo et al. 2019). The specialized properties of selfrenewal, multiplication and differentiation of stem cells make them potential candidates for an all-in-one therapeutic solution to diverse clinical ailments. Among various stem cell types, mesenchymal stem cells (MSCs) make subject of most of the therapeutic applications (Gugjoo et al. 2019). MSCs are available in almost all the tissue types and have easy isolation and culture processes. The cells are plastic in nature, and have immunomodulatory and/ anti-inflammatory properties with minimal risk of teratogenicity and associated ethical issues unlike that of embryonic stem cells (Song et al. 2013; Gugjoo et al. 2019).

Introduction

Marek’s disease virus

Avian leukosis virus subgroup J

Influenza A virus

Other viruses

Pathways significantly enriched by the targets of dysregulated miRNAs during viral infection

Conclusions

Acknowledgments

References

Abstract

In poultry, viral infections (e.g., Marek’s disease virus, avian leukosis virus, influenza A virus, and so on) can cause devastating mortality and economic losses. Because viruses are solely dependent on host cells to propagate, they alter the host intracellular microenvironment. Thus, understanding the virus-host interaction is important for antiviral immunity and drug development in the poultry industry. MicroRNAs are crucial posttranscriptional regulators of gene expression in a wide spectrum of biological processes, including viral infection. Recently, microRNAs have been identified as key players in virus-host interactions. In this review, we will discuss the intricacies involved in the virus-host cross-talk mediated by host and viral microRNAs in poultry (i.e., chicken and ducks), as well as recent trends and challenges in this field. These findings may provide some insights into the rapidly developing area of research regarding viral pathogenesis and antiviral immunity in poultry production.

Introduction

Many types of viruses will cause high mortality rates and enormous economic losses to the poultry industry. For example, Marek’s disease virus (MDV) and avian leukosis virus can induce neoplastic diseases in chickens. Moreover, influenza A virus (IAV) is highly variable and can spread across species, thereby resulting in a threat to global public health. Therefore, the cross-talk between the host (i.e., chickens) and viruses during infections is critical to understanding viral pathogenesis and antiviral immunity in chicken production. Over the past decade, studies have attempted to depict the cross-talk between the host and virus from different aspects (e.g., microRNA [miRNAs] perspective) and have made progress in this area (Li et al., 2014a; Skalsky and Cullen, 2010).

miRNAs Are short noncoding 18- to 25-nucleotidelong RNAs that regulate gene expression at the posttranscriptional level. Substantial evidence demonstrates that a single miRNA can have extensive and crucial effects on a range of fundamental biological processes, and miRNA dysregulation can result in biological dysfunction and diseases (Bartel, 2004; Ha and Kim, 2014). Pathogen-induced phenotypic changes in hosts are always accompanied by remarkable alterations at the transcriptional level (Jenner and Young, 2005). The miRNA expression profile is profoundly influenced by viral infection and contributes to the repertoire of virus-host interactions. Differential miRNA expression can be attributed to both host antiviral defenses and alterations in cellular environment that are affected by viral factors (Scaria et al., 2007; Skalsky and Cullen, 2010; tenOever, 2013; Harwig et al., 2014; Powdrill et al., 2016; Nejad et al., 2018). Moreover, miRNAs have been reported to be biomarkers of viral infections (Wang et al., 2014) and have roles in viral reactivation from latency (Hicks et al., 2019). Therefore, the identification of deregulated miRNAs in virally infected chickens will provide novel insight into understanding virus-host interaction. In this review, we will summarize recent advances into the critical role of virally influenced poultry and viral miRNAs in the cross-talk between the host and virus to help understand viral pathogenesis and antiviral immunity in the poultry industry.

Birth weight, dystocia, and neonatal survival

Neonatal adaptation

Neonatal immune function

Summary

References

INTRODUCTION

The greatest loss in ruminant production systems occurs during the neonatal period, that is, between birth and 28 days of life. In extensive production systems, neonatal losses are reportedly between 10% and 30% and 6% and 16% for lambs and calves, respectively. With 90% of these offspring born alive, this is considered a preventable welfare issue1 and a high economic burden to the livestock industry. It is well established that in utero environment3 affects ruminant progeny health and welfare. This phenomenon is known as fetal programming and is contingent upon the particularly long gestation period in ruminants during which physiologic systems develop, such that at birth, the ontogeny of these systems is complete. The effects of this fetal programming in the neonate may be mediated by epigenetic modifications that regulate gene expression in both the placenta and the fetus (Fig. 1). These epigenetic modifications may occur as early as embryogenesis through to late gestation. The placenta mediates fetal supply of nutrients, hormones, and oxygen with both the placenta and the fetus responding to maternal perturbations in a sexually dimorphic manner. This dimorphism has significant consequences because survival in the male fetus, during gestation and at birth, is reduced compared with the female fetus. Significantly for this review, many of the contributing factors associated with increased risk of neonatal mortality, that is, premature birth, birth weight, dystocia, and poor adaptation to the postnatal environment, are consequent to the prevailing prenatal environment.

Abstract

During the last decades, the world has witnessed a dramatic increase in allergy prevalence. Epidemiological evidence shows that growing up on a farm is a protective factor, which is partly explained by the consumption of raw cow’s milk. Indeed, recent studies show inverse associations between raw cow’s milk consumption in early life and asthma, hay fever, and rhinitis. A similar association of raw cow’s milk consumption with respiratory tract infections is recently found. In line with these findings, controlled studies in infants with milk components such as lactoferrin, milk fat globule membrane, and colostrum IgG have shown to reduce respiratory infections. However, for ethical reasons, it is not possible to conduct controlled studies with raw cow’s milk in infants, so formal proof is lacking to date. Because viral respiratory tract infections and aeroallergen exposure in children may be causally linked to the development of asthma, it is of interest to investigate whether cow’s milk components can modulate human immune function in the respiratory tract and via which mechanisms. Inhaled allergens and viruses trigger local immune responses in the upper airways in both nasal and oral lymphoid tissue. The components present in raw cow’s milk are able to promote a local microenvironment in which mucosal immune responses are modified and the epithelial barrier is enforced. In addition, such responses may also be triggered in the gut after exposure to allergens and viruses in the nasal cavity that become available in the GI tract after swallowing. However, these immune cells that come into contact with cow’s milk components in the gut must recirculate into the blood and home to the (upper and lower) respiratory tract to regulate immune responses locally. Expression of the tissue homing-associated markers α4β7 and CCR9 or CCR10 on lymphocytes can be influenced by vitamin A and vitamin D3, respectively. Since both vitamins are present in milk, we speculate that raw milk may influence homing of lymphocytes to the upper respiratory tract. This review focuses on potential mechanisms via which cow’s milk or its components can influence immune function in the intestine and the upper respiratory tract. Unraveling these complex mechanisms may contribute to the development of novel dietary approaches in allergy and asthma prevention.

Introduction

In the Western world, the prevalence of chronic inflammatory diseases, including allergies, has increased dramatically in the last few decades, while the number of serious infectious diseases has declined rapidly (1). An inverse correlation, indicating a “protective effect” of infectious diseases against chronic inflammatory diseases (e.g., allergy and asthma), was postulated in 1989 by Strachan, who formulated the hygiene hypothesis (2). The hygiene hypothesis suggests that the exposure to viruses and bacteria is essential to induce a T-helper (Th)1 response, which balances the immune system and protects against Th2-mediated diseases. With the discovery of additional T cell subsets such as Th17 cells and regulatory T cells (Tregs), this paradigm had to be revised. For example, it was demonstrated that suppressive dendritic cells (DCs) induced by helminths restored the disturbed Th1/Th2 balance by induction of Tregs (3). The immune education of DCs was suggested to be an important step toward understanding the complex relation between infectious diseases and allergies (4). Th2 responses are now known to be enhanced by the production of type 2 cytokines (e.g., TSLP, IL-25, IL-33) secreted by group 2 innate lymphoid cells and epithelial cells (5, 6). Thus, different cell types are responsible for Th2-mediated diseases such as allergies. Allergy is initiated as an aberrant immune response towards a harmless antigen (allergen). Via activation of Th2 cells, the allergen triggers the production of allergen-specific IgE by B cells that binds to high-affinity FcεR1 on effector cells like mast cells and basophils. Effector cells release soluble factors (e.g. histamine) upon secondary exposure to the allergen that cause immediate type I allergic symptoms. The term “atopic march” refers to the sequence of IgE responses and clinical symptoms initiated in early life (7).

Exotic pets are commonly considered to be animals that are either non-native to a region or nondomesticated. However, issues such as local collection and keeping of many indigenous species and varying degrees of wild animal domestication infer that definition may prove to be less precise in some cases. Pet keeping (including wild animals) has a long history dating back at least 17,000 years. Historically, acquiring “pets” involved taking local wildlife in various benign or destructive ways, for example, via food inducements or killing of parents and quasiadoption of their offspring (Serpell, 2015). Despite concomitant harm during acquisition of some of these early pets, these animals were largely at liberty to roam between their natural habitat and human “captivity” (Serpell, 2015), and probably often in accordance with natural affiliative behaviors (Warwick, 2015a). Notwithstanding certain undesirable or tragic strategies in primitive pet collection, it has been argued that modern pet sourcing and husbandry are more welfare-negative than ancient methods due to the gross deprivation of freedoms inherent to caged life (Warwick, 2015a). Inarguably, today there is greater understanding in all branches of science relevant to both free-roaming and captive wild animals. In addition, there are local, national, and global legislative frameworks and approaches designed to avoid activities that are inhumane, ecologically unsustainable, and that threaten public health and safety, such as, the Convention on International Trade in Endangered Species of Wild Fauna and Flora, International Air Transport Association guidelines, World Organisation for Animal Health/Office des International Epizooties Code documents, and various animal welfare acts. Regardless of the raft and diversity of “regulations” in operation, all concerns and problems associated with exotic pet trading in particular remain and indeed flourish (Toland, et al., 2012; Grant et al., 2017; Unger et al., 2017). Modern and greater scientific understanding reveals that the biological needs of animals are significantly more complex than previously thought; thus, the more we learn about animals and their natural needs, the more difficult becomes the challenge to humanely provide for them in captivity (Mellor, 2016; Grant et al., 2017). Among many possible examples of these biological needs is recent recognition of play in fishes, frogs, and reptiles, which raises the challenge to provide novel stimulation (Burghardt, 2015). Also, spatial studies regarding free-living lizards and snakes demonstrate extensive home range activity, highlighting longstanding concerns over cage space provisions (Warwick et al., 2013). In addition, behavioral, physiological, and neurological research has enhanced identification and understanding of numerous states, including anxiety, fear, panic, frustration, anger, helplessness, loneliness, “boredom,” and depression (Mellor, 2016). All of these issues and more continue to “raise the bar” for meeting positive states and avoiding negative states. The trade in and keeping of exotic pets has been frequently criticized for the commonly inhumane and harmful practices that are associated with both commercial supply of animals as well as their poor and inadequate maintenance in the home.

As wildlife and wild places edge closer to extinction, humans are leading increasingly urbanized lives (United Nations 2014). With this urbanization comes a growing disconnect between people and the natural world (Turner et al. 2004). Environmental education seeks to reignite this connection and motivate people to take action on behalf of the environment (Hungerford and Volk 1990). A multitude of organizations and groups actively work to conserve wild animals and wild places. A subset of this group – including zoos, aquariums, museums, sanctuaries, shelters, nature centers, and other informal learning facilities – offer opportunities for people to have educational experiences with wildlife and nature. Experiences in these settings are unique in that they provide impactful multisensory interactions with a diversity of animals that have the potential to influence participants’ attitudes and behaviors based on their affective responses (Clayton et al. 2009; Miller et al. 2004). Research conducted in these facilities found visitors already possess an interest in animals and are therefore likely to experience affective responses when observing animals, including connectedness, associative identity, emotional affinity, and empathy (Berenguer 2007; Chawla 2009; Clayton et al. 2009, 2011; Kals et al. 1999; Mayer and Frantz 2004; Myers et al. 2009; Nisbet et al. 2009; Schultz 2000; Schultz and Tabanico 2007; Tam 2013). There is a body of research surrounding many of these affective responses in animal facilities, however there is a lack of substantive empirical research on empathy development in this domain, as it has historically been focused on companion animals in schools, healthcare, and humane education programs. As we will expand upon, empathy is everpresent within zoos, aquariums, and other informal learning institutions wherein animals and their behaviors are constantly being interpreted to differing degrees of accuracy. As ambassadors for their wild counterparts, animals within these facilities and their human interpreters have a critical opportunity to build deep-rooted connections between the public and species in need. As William Godfrey-Smith describes (1979, 318), “The essential step in recognizing an enlarged community involves coming to see, feel, and understand what was previously perceived as alien and apart; it is the evolution of the capacity of empathy.” By not addressing the presence of empathy in the human-animal relationship, we let slip a powerful tool for developing internal motivation for conservation action and we risk supporting the growth of a community of animal-lovers with well-intended but misplaced or uninformed empathy.