Localization of Piezo 1 and Piezo 2 in Lateral Line System and Inner Ear of Zebrafish (Danio rerio).

Piezo proteins have been identified as mechanosensitive ion channels involved in mechanotransduction. Several ion channel dysfunctions may be associated with diseases (including deafness and pain); thus, studying them is critical to understand their role in mechanosensitive disorders and to establish new therapeutic strategies. The current study investigated for the first time the expression patterns of Piezo proteins in zebrafish octavolateralis mechanosensory organs. Piezo 1 and 2 were immunoreactive in the sensory epithelia of the lateral line system and the inner ear. Piezo 1 (28.7 ± 1.55 cells) and Piezo 2 (28.8 ± 3.31 cells) immunopositive neuromast cells were identified based on their ultrastructural features, and their overlapping immunoreactivity to the s100p specific marker (28.6 ± 1.62 cells), as sensory cells. These findings are in favor of Piezo proteins' potential role in sensory cell activation, while their expression on mantle cells reflects their implication in the maintenance and regeneration of the neuromast during cell turnover. In the inner ear, Piezo proteins' colocalization with BDNF introduces their potential implication in neuronal plasticity and regenerative events, typical of zebrafish mechanosensory epithelia. Assessing these proteins in zebrafish could open up new scenarios for the roles of these important ionic membrane channels, for example in treating impairments of sensory systems.

Comparative characterisation of extracellular vesicles from canine and human plasma: a necessary step in biomarker discovery.

Extracellular Vesicles (EV) have become an interesting focus as novel biomarkers of disease and are increasingly reported upon in humans and other species. The Minimal Information for Studies of Extracellular Vesicles 2018 (MISEV2018) guidelines were published to improve rigor and standardisation within the EV field and provide a framework for the reliable isolation and characterisation of EV populations. However, this rigor and standardisation has been challenging in the area of comparative medicine. Herein we present the successful isolation of EVs from human and canine plasma using Size Exclusion Chromatography and characterise these EVs according to best international practice. This study provides evidence for the reliable comparison of human and canine EVs isolated by this approach, and a baseline description of the EVs from healthy dogs to inform future biomarker studies. This work also demonstrates that the MISEV2018 guidelines can be successfully applied to EVs isolated from canine plasma.

Reversible Contraception in Males: An Obtainable Target?

The last few decades have brought contraception to the forefront of research, with great strides made in effectively targeting and optimizing the physiology, pharmacology, and delivery processes that prevent pregnancy. However, these advances still predominantly target female contraceptives for the prevention of contraception, whereas targeting the male sex has lagged far behind. This has led to a marked deficiency in safe and effective male contraceptive agents, resulting in a heavy dependence on female contraceptives to prevent unwanted and unplanned pregnancies. Current research in the veterinary field and in rodents highlights several promising avenues whereby novel, safe, and effective male contraceptive alternatives are being developed-with an emphasis on reduced side effects and reversibility potential. This review aims to discuss current and novel male contraceptives (both human and veterinary formulations) while highlighting their efficacy, advantages, and disadvantages.

Comparative aspects of targeted sentinel lymph node mapping in veterinary and human medicine: opportunities for future research.

There is a significant overlap in the genetic, metabolic and epigenetic alterations between human and companion animal cancers, including those of the oral cavity, breast, bladder, skin, lungs and pancreas. In many cancer types, the identification and removal of affected lymph nodes are essential for accurate cancer management, including treatment and prognosis. Historically, lymphadenectomy and subsequent radical resection based on regional anatomy, palpation and lymph node aspirates were considered sufficient; however, modern approaches with sentinel lymph node mapping (SLN) mapping have increased the accuracy of surgical decision-making. Preoperative and intraoperative SLN mapping techniques in veterinary patients parallel those used in human medicine. While many of these techniques are highly successful, the main challenges with current methodologies are their sensitivity and specificity for the presence of cancer, which can be overcome via precision medicine and targeted SLN mapping agents. Given the large population of dogs and cats with cancer, the crossover of knowledge between species can help to deepen our understanding of many of these cancers and can be useful in evaluating new drugs and/or therapies. In this review, we discuss SLN mapping techniques in veterinary medicine and the concept of precision medicine as it relates to targeted SLN mapping imaging agents. The large number of companion animals affected by cancer is an underutilized resource to bridge the translational gap and we aim to provide a reference for the use of dogs and cats as a comparative model for human SLN mapping.

Advances in Comparative Medical Research on Anatomy and Histological Structure of Intervertebral Discs in Humans and Other Animals / 实验动物与比较医学

The 2023 China Health Report on Spine Degeneration noted a significant increase in lumbar surgery among patients under 35 years old in recent years, indicating a trend towards younger onset of cervical and lumbar diseases. Lumbar intervertebral disc herniation has become a major concern, making the study of disc degeneration pathogenesis and treatment methods clinically significant. At present, human intervertebral disc diseases are primarily diagnosed through imaging due to the challenges of obtaining tissue samples from the spine. Therefore, experimental animals have emerged as alternative research subjects because they are cost-effective, have short experimental cycles, and are easily accessible. Given the structural and physiological differences between human and other animal intervertebral discs, comparing their anatomy and histological characteristics forms the foundation of research into human disc degeneration. The purpose of this paper is to collect and review relevant studies on anatomical and histological structures of intervertebral discs in different animals and conduct a comparative analysis from four aspects, namely, intervertebral disc height, lumbar disc geometry, lumbar disc cartilaginous endplate characteristics, and extracellular matrix components. The results show that humans, kangaroos, sheep, pigs, and rats exhibit similar relative heights between the sixth and seventh cervical vertebrae. Mice possess lumbar disc geometries most akin to humans. Compared to other animals, humans have the thickest cartilaginous endplates and the lowest cell densities. The collagen within the fibrous annulus differs most notably in pigs compared to humans, while water content in the nucleus pulposus is consistent across pigs, sheep, rabbits, rats, and humans. Additionally, this paper describes the commonalities and discrepancies in disc degeneration manifestations between humans and animals, and summarizes modeling methods for disc degeneration in different experimental animals. Ultimately, the aims of this paper is to provide fundamental data for selecting suitable experimental animal models for the study of intervertebral disc degeneration.

Ion channel function in translational bovine gallbladder cholangiocyte organoids: establishment and characterization of a novel model system.

The study of biliary physiology and pathophysiology has long been hindered by the lack of in vitro models that accurately reflect the complex functions of the biliary system. Recent advancements in 3D organoid technology may offer a promising solution to this issue. Bovine gallbladder models have recently gained attention in the investigation of human diseases due to their remarkable similarities in physiology and pathophysiology with the human gallbladder. In this study, we have successfully established and characterized bovine gallbladder cholangiocyte organoids (GCOs) that retain key characteristics of the gallbladder in vivo, including stem cell properties and proliferative capacity. Notably, our findings demonstrate that these organoids exhibit specific and functional CFTR activity. We believe that these bovine GCOs represent a valuable tool for studying the physiology and pathophysiology of the gallbladder with human significance.

The Role of NF-κB in Endometrial Diseases in Humans and Animals: A Review.

The expression of genes of various proinflammatory chemokines and cytokines is controlled, among others, by the signaling pathway of the nuclear factor kappaB (NF-κB) superfamily of proteins, providing an impact on immune system functioning. The present review addresses the influence and role of the NF-κB pathway in the development and progression of most vital endometrial diseases in human and animal species. Immune modulation by NF-κB in endometritis, endometrosis, endometriosis, and carcinoma results in changes in cell migration, proliferation, and inflammation intensity in both the stroma and epithelium. In endometrial cells, the NF-κB signaling pathway may be activated by multiple stimuli, such as bacterial parts, cytokines, or hormones binding to specific receptors. The dysregulation of the immune system in response to NF-κB involves aberrant production of chemokines and cytokines, which plays a role in endometritis, endometriosis, endometrosis, and endometrial carcinoma. However, estrogen and progesterone influence on the reproductive tract always plays a major role in its regulation. Thus, sex hormones cannot be overlooked in endometrial disease physiopathology. While immune system dysregulation seems to be NF-κB-dependent, the hormone-independent and hormone-dependent regulation of NF-κB signaling in the endometrium should be considered in future studies. Future goals in this research should be a step up into clinical trials with compounds affecting NF-κB as treatment for endometrial diseases.

A spontaneous compound odontoma in an adult Sprague Dawley rat (Rattus norvegicus).

Reports of compound odontomas in rats are very rare. A 14-month-old adult male Sprague Dawley rat was found to have a hard mass associated with the caudal aspect of the left mandible. After 2 weeks of observation, the rat was euthanized due to the mass growing significantly in size and the rat losing >20% of its body weight. Grossly, the mass was well-circumscribed, 3.7 × 3 × 1.2 cm, hard and heterogeneously coloured white, tan and red. The mass was restricted to the mandibular bone and did not involve surrounding subcutaneous tissue. On cut surface, the mass was a similar colour and brittle. Histologically, there were numerous proto-teeth embedded in ossified stroma. Each proto-tooth had a central mesenchyme pulp surrounded by columnar odontoblasts and dentine matrix. The dentine was often bordered by enamel matrix, which was occasionally bounded by ameloblasts. These histological findings were consistent with a compound odontoma. This is the first report of a spontaneous compound odontoma in the caudal mandible of a rat.

Cleft Palate Syndrome in the Endangered Spectacled Flying Fox (Pteropus conspicillatus): Implications for Conservation and Comparative Research.

Cleft palate syndrome, first observed in the spectacled flying fox population in 1998, has produced sporadic neonatal mortality events over the past two decades, with an estimated incidence of up to 1/1000 births per year. This study presents a rudimentary characterisation of the syndrome, presenting gross pathology of syndromic signs upon visual inspection, a histological examination of palate malformations, and syndrome incidence data representing the past two decades. The syndrome presents with a range of signs, primarily congenital palate malformations ranging from a pinhole cleft to a complete hard and soft palate deficit, resulting in the death or abandonment of neonates shortly after birth. The congenital palate malformations are often associated with claw deformities, wiry facial hair, and in some instances, muscle weakness and neurological signs. The natural occurrence of the lethal congenital orofacial birth defects in the spectacled flying fox presents a unique opportunity for the investigation of putative aetiologies, drawing parallels between bat and other mammalian cleft palate risk factors. Further syndrome investigation has the potential to deliver both biodiversity conservation and comparative veterinary and biomedical outcomes.

Comparison of the morphology of the anterior cruciate ligament and related bony structures between pigs and humans.

Introduction: Pigs are widely used for clinical research on the anterior cruciate ligament (ACL) because of the similarity of the knee structure to the human knee. But evidence to support the suitability of using porcine samples to guide clinical practices is limited. This study aims to explore the qualitative and quantitative morphological features of the porcine knee and ACL, and to compare these with data on humans reported in literature. Methods: Nineteen porcine knees were used for this study. The bone structures were measured on coronal X-ray images. The length of the ACL was measured using a caliper. The ACL bone insertion sites were marked and measured on a digital photograph. The lengths of the long and short axis of the ACL isthmus were measured on the X-ray microscopy reconstructed images. The outcomes were compared with previously reported data on humans using an abstract independent-samples T test. Results: Qualitative observation indicated a similar location, orientation and general morphology of the porcine ACL to human ACLs. The major difference was the location of the ACL tibial insertion with respect to the anterior horn of the lateral meniscus (AHLM). The porcine ACL was split into AM and PL bundles by the AHLM, while the AHLM was adjacent to the anterolateral border of the ACL tibial insertion in human knees. The quantitative comparison showed no significant difference between the human and porcine ACL in terms of the length of the ACL, the width of the femoral condyle and tibial plateau, and the tibial interspinal width. However, the CSA, the lengths of the long and short axis of the ACL isthmus, and the femoral and tibial insertion areas of the porcine ACL were all significantly larger than the reported features in human knees. Conclusion: The location, orientation and basic morphology of the porcine ACL and knee are similar to humans. However, the two-bundle structure is more distinct in a porcine ACL, and the dimensions of the porcine ACL are generally larger. This study may provide useful information to researchers when assessing the feasibility and limitations of using porcine samples for research on the human ACL and knee.

The value of broad taxonomic comparisons in evolutionary medicine: Disease is not a trait but a state of a trait!

In this short paper, we argue that there is a fundamental connection between the medical sciences and evolutionary biology as both are sciences of biological variation. Medicine studies pathological variation among humans (and domestic animals in veterinary medicine) and evolutionary biology studies variation within and among species in general. A key principle of evolutionary biology is that genetic differences among species have arisen first from mutations originating within populations. This implies a mechanistic continuity between variation among individuals within a species and variation between species. This fact motivates research that seeks to leverage comparisons among species to unravel the genetic basis of human disease vulnerabilities. This view also implies that genetically caused diseases can be understood as extreme states of an underlying trait, that is, an axis of variation, rather than distinct traits, as often assumed in GWAS studies. We illustrate these points with a number of examples as diverse as anatomical birth defects, cranio-facial variation, preeclampsia and vulnerability to metastatic cancer.

Glaucoma through Animal's Eyes: Insights from the Evolution of Intraocular Pressure in Mammals and Birds.

Glaucoma, an eye disorder caused by elevated intraocular pressure (IOP), is the leading cause of irreversible blindness in humans. Understanding how IOP levels have evolved across animal species could shed light on the nature of human vulnerability to glaucoma. Here, we studied the evolution of IOP in mammals and birds and explored its life history correlates. We conducted a systematic review, to create a dataset of species-specific IOP levels and reconstructed the ancestral states of IOP using three models of evolution (Brownian, Early burst, and Ornstein-Uhlenbeck (OU)) to understand the evolution of glaucoma. Furthermore, we tested the association between life history traits (e.g., body mass, blood pressure, diet, longevity, and habitat) and IOP using phylogenetic generalized least squares (PGLS). IOP in mammals and birds evolved under the OU model, suggesting stabilizing selection toward an optimal value. Larger mammals had higher IOPs and aquatic birds had higher IOPs; no other measured life history traits, the type of tonometer used, or whether the animal was sedated when measuring IOP explained the significant variation in IOP in this dataset. Elevated IOP, which could result from physiological and anatomical processes, evolved multiple times in mammals and birds. However, we do not understand how species with high IOP avoid glaucoma. While we found very few associations between life history traits and IOP, we suggest that more detailed studies may help identify mechanisms by which IOP is decoupled from glaucoma. Importantly, species with higher IOPs (cetaceans, pinnipeds, and rhinoceros) could be good model systems for studying glaucoma-resistant adaptations.

Factors Limiting the Translatability of Rodent Model-Based Intranasal Vaccine Research to Humans.

The intranasal route of vaccination presents an attractive alternative to parenteral routes and offers numerous advantages, such as the induction of both mucosal and systemic immunity, needle-free delivery, and increased patient compliance. Despite demonstrating promising results in preclinical studies, however, few intranasal vaccine candidates progress beyond early clinical trials. This discrepancy likely stems in part from the limited predictive value of rodent models, which are used frequently in intranasal vaccine research. In this review, we explored the factors that limit the translatability of rodent-based intranasal vaccine research to humans, focusing on the differences in anatomy, immunology, and disease pathology between rodents and humans. We also discussed approaches that minimize these differences and examined alternative animal models that would produce more clinically relevant research.

Farm and Companion Animal Organoid Models in Translational Research: A Powerful Tool to Bridge the Gap Between Mice and Humans.

Animal organoid models derived from farm and companion animals have great potential to contribute to human health as a One Health initiative, which recognize a close inter-relationship among humans, animals and their shared environment and adopt multi-and trans-disciplinary approaches to optimize health outcomes. With recent advances in organoid technology, studies on farm and companion animal organoids have gained more attention in various fields including veterinary medicine, translational medicine and biomedical research. Not only is this because three-dimensional organoids possess unique characteristics from traditional two-dimensional cell cultures including their self-organizing and self-renewing properties and high structural and functional similarities to the originating tissue, but also because relative to conventional genetically modified or artificially induced murine models, companion animal organoids can provide an excellent model for spontaneously occurring diseases which resemble human diseases. These features of companion animal organoids offer a paradigm-shifting approach in biomedical research and improve translatability of in vitro studies to subsequent in vivo studies with spontaneously diseased animals while reducing the use of conventional animal models prior to human clinical trials. Farm animal organoids also could play an important role in investigations of the pathophysiology of zoonotic and reproductive diseases by contributing to public health and improving agricultural production. Here, we discuss a brief history of organoids and the most recent updates on farm and companion animal organoids, followed by discussion on their potential in public health, food security, and comparative medicine as One Health initiatives. We highlight recent evolution in the culturing of organoids and their integration with organ-on-a-chip systems to overcome current limitations in in vitro studies. We envision multidisciplinary work integrating organoid culture and organ-on-a-chip technology can contribute to improving both human and animal health.

Implementing Digital Pathology into Veterinary Academics and Research.

The advantages of digital pathology (DP) have been recognized as early as 1963, but only within the last decade or so have the advancements of slide scanners and viewing software made the use and implementation of DP feasible in the classroom and in research. Several factors must be considered prior to undertaking the project of implementing the DP workflow in any setting, but particularly in an academic environment. Sustained and open dialogue with information technology (IT) is critical to the success of this enterprise. In addition to IT, there is a multitude of criteria to consider when determining the best hardware and software to purchase to support the project. The goals and limitations of the laboratory and the requirements of its users (students, instructors, and researchers) will ultimately direct these decisions. The objectives of this article are to provide an overview of the opportunities and challenges associated with the integration of DP in education and research, to highlight some important IT considerations, and to discuss some of the requirements and functionalities of some hardware and software options.

Recommendations for Ethical Review of Veterinary Clinical Trials.

Ethical review of both human and animal research is critical to ensuring that studies are conducted with due regard to the welfare and safety of enrolled subjects and to the integrity of the data. However, differences exist in laws, policies, and best practices between human and animal studies. Ethical review is required for most human studies. While the laws and standards are clear for humans and for laboratory animals, the laws and standards for clinical research for client-owned animals are not as well-defined. Here, we discuss gaps in ethical review of clinical animal research in the United States of America and propose expanded functions for veterinary clinical studies committees as a solution.

Veterinary Big Data: When Data Goes to the Dogs.

Dogs provide an ideal model for study as they have the most phenotypic diversity and known naturally occurring diseases of all non-human land mammals. Thus, data related to dog health present many opportunities to discover insights into health and disease outcomes. Here, we describe several sources of veterinary medical big data that can be used in research. These sources include medical records from primary medical care centers or referral hospitals, medical claims data from animal insurance companies, and datasets constructed specifically for research purposes. No data source provides information that is without limitations, but large-scale, prospective, longitudinally collected data from dog populations are ideal for further research as they offer many advantages over other data sources.

Anatomic Veterinary Usage: Discussion Around Technical Nomenclature Vs. Jargon.

This article discusses some examples of problems derived from the mix of technical jargon and anatomical veterinary words and makes recommendations regarding their use according to specific situations.