Advances in experimental medicine and biology最新文献

Autoimmune diseases arise from a complex interplay between genetic predisposition and environmental factors, including chemical exposures, infections, and psychological stress. These conditions occur when the immune system mistakenly targets the body's own healthy cells, resulting in tissue and organ damage. Both humoral and cellular immune mechanisms contribute to autoimmune disorders, leading to chronic inflammation and progressive tissue injury.Autoimmune diseases have diverse and often overlapping symptoms, significantly impacting patients' quality of life. Early diagnosis is crucial for effective disease management; however, the clinical similarity among autoimmune disorders and the lack of definitive diagnostic tests in many cases pose major challenges to timely identification.Notably, in many autoimmune conditions, oral manifestations are among the earliest or, in some cases, only clinical signs, as the oral epithelium is a frequent target of autoimmune responses. These manifestations often present as erosions and ulcers, causing pain and discomfort. Identifying oral lesions at an early stage can facilitate early diagnosis and improve patient outcomes. This chapter provides a comprehensive overview of autoimmune conditions and their oral manifestations.Since immune dysregulation is central to autoimmune disease pathogenesis, local and systemic corticosteroids are commonly prescribed to control symptoms, including oral lesions. In severe or refractory cases, immunosuppressive therapies may be essential to prevent disease progression and tissue destruction.

Birds are among the most diverse and threatened vertebrates on the planet. Occupying a vast array of global ecosystems, avian species are adapted to a variety of climates and enduring a range of stressors including anthropogenic and climate-related challenges. However, despite their adaptations to varied ecosystems, avian populations are declining at an alarming rate as seen in data from various global regions. In addition, illegal trade and loss of habitat impose significant stress on birds. It is critical to understand the life history of short- and long-lived birds, unique characteristics of birds including migratory patterns, effects of environmental chemicals, and other stressors on vulnerable life stages. Moreover, the ability to monitor wild populations is critical, and field-friendly health metrics must be developed. Understanding avian biology across the diversity of species and their critical resource requirements is critical to conservation. Although the hypothalamic-pituitary-gonadal (HPG) axis and neuroendocrine regulation of reproduction have many conserved mechanisms, the unique characteristics of avian physiology must be understood for effective conservation. The deleterious effects of developmental exposures to environmental chemicals, especially endocrine-disrupting chemicals (EDCs), can alter lifetime reproduction, and the adverse effects are exerted differentially in songbirds (altricial) versus precocial species. Examples are provided for the involved physiological mechanisms, with consideration of neuroendocrine mechanisms that modulate responses to environmental stressors. In addition, the role of vultures as scavengers and the demise of Old World vultures are presented as a case study.

Prolactin is a key hormone that plays significant roles in reproduction, extending far beyond its well-known function in mammalian lactation. It is vital for reproductive success across diverse taxa, including birds, fish, reptiles, and amphibians, where it regulates critical reproductive behaviors and physiological processes like parental care, pregnancy maintenance, embryonic diapause, immunity, osmoregulation, metamorphosis, and molting. Environmental cues often fine-tune its actions to ensure reproduction occurs under optimal conditions. Conversely, dysregulation of prolactin can severely impact reproduction. While hyperprolactinemia is the most common pituitary disorder affecting fertility in women and other species, including elephants, hypoprolactinemia can lead to inadequate parental care due to poor milk production or inadequate brooding. Environmental stressors such as pollution and climate change can further disrupt prolactin levels, compounding reproductive failures. Its sensitivity to social and environmental stressors has led to its increasing recognition as a valuable biomarker for animal welfare assessment. Elucidating prolactin's multifaceted functions can substantially advance our comprehension of reproductive strategies across diverse taxa. These insights could potentially inform and enhance conservation efforts for threatened species ex situ and in situ, contributing to more effective wildlife management and preservation strategies. Here, we review the role of prolactin in reproduction, health, and welfare across species, with a particular emphasis on elephants. Nearly three decades of elephant studies, facilitated by accessible blood sampling, have yielded valuable insights into its physiological roles and association with reproductive dysfunction. While many prolactin mechanisms in elephants have similarities to those observed in other species and humans, there are notable differences that warrant further study to enhance our understanding of its role in physiology and behavior and contribute to our broader knowledge of reproductive endocrinology across species.

Fishes are by far the most species-rich group of vertebrates, with 36,105 species currently recognized, approximately the same number of species as that of all non-fish vertebrates combined. Recent decades have witnessed dramatic population declines for many fish species, together with a loss in overall fish biodiversity. Globally, fish biodiversity is being threatened by a multitude of anthropogenic impacts including overfishing, habitat loss, pollution, aquaculture, loss of river connectivity, climate change and the impact of alien species. Nowhere is the world's biodiversity crisis more acute than in freshwater ecosystems. While rivers, lakes and wetlands cover less than 1% of the planet's total surface, they are home to over half the world´s fish species. One-third of freshwater fishes are now threatened with extinction, and 80 species have become extinct in recent years. This review covers the main drivers of declining fish biodiversity and details remedial strategies aimed at conserving both marine and freshwater fish biodiversity. The preservation of genetic resources through the cryobanking of reproductive cells and tissues, collectively known as germplasm, will increasingly become a valuable tool in the conservation of fish biodiversity. It is expected that the ability to establish cryobanks for the full range of fish germplasm, including sperm, oocytes, embryos and germ cells will be of key importance to the conservation of threatened fish species, as well as to fishery management and aquaculture. With the help of a range of emerging reproductive technologies, frozen germplasm will play a key role in future in situ and ex situ conservation initiatives. The rapid advance in next-generation sequencing technologies, together with the proliferation of resources such as fully sequenced fish genomes, is expected to result in a rapid expansion in the application of conservation genomics to the field of fish conservation and be instrumental in formulating future management strategies directed at conserving fish biodiversity, through both in situ and ex situ conservation initiatives.

The field of structural biology has undergone a remarkable transformation over the past decade, fueled by cutting-edge advancements in X-ray crystallography and cryo-electron microscopy (cryo-EM). Central to both approaches is the critical step of sample preparation, which includes heterologous expression of membrane proteins in host systems and extraction from the membrane environment using suitable membrane mimetics. In crystallography, enhanced techniques, such as lipidic cubic phase (LCP) crystallization and serial femtosecond crystallography (SFX), have pushed the boundaries of structure determination to microcrystals and conformationally labile targets. In cryo-EM, technical advancements across many levels have fueled the "resolution revolution," enabling cryo-EM to reach near-atomic resolution and driving single-particle analysis of increasingly small, dynamic, and heterogeneous macromolecular assemblies. Emerging modalities further extend our capability to tackle previously inaccessible questions. Cryo-electron tomography (cryo-ET) is extracting structural insights from native cellular environments, and micro-electron diffraction (MicroED) has opened new frontiers for nanoscale structural studies from submicron crystals at unprecedented resolution. Collectively, these advances have improved our ability to study the structure of challenging targets, with profound implications for structure-based drug discovery, and an evolving paradigm shift toward dynamic visualization of biomolecular processes, signaling the dawn of a new era in structural biology.

This review investigates the decline in sperm DNA quality in humans and various animal species, with a focus on sperm DNA fragmentation (SDF), its impact on reproductive outcomes, and its management in the context of assisted reproduction. The review underscores the significance of universally observed phenomena in human reproduction and proposes the application of insights gained from human studies to enhance reproductive strategies in animals and endangered species, where sperm quality research is limited and gametes for assisted reproduction are scarce.Universal aspects of the nature and origin of sperm DNA damage and repair are examined. It emphasizes the analysis of DNA breaks related to biological factors, such as histone-to-protamine exchange, oxidative stress, DNase activity, environmental pressures, and the unavoidable effects of iatrogenic DNA damage, particularly affecting processes related to assisted reproduction. The mechanisms underlying the repair of persistent DNA breaks that reach oocytes transported by sperm are also discussed.Methodologies for assessing SDF and differentiating between single- and double-stranded DNA breaks are explained. Various strategies to mitigate high levels of SDF in the ejaculate have been explored, and their potential applications in both humans and animal species have been discussed.A key conclusion is that SDF assessment offers valuable insights into semen quality, particularly in the era of assisted reproduction and specifically in intracytoplasmic sperm injection (ICSI), where traditional sperm parameters such as concentration, motility, and membrane quality evaluation are less critical. The causes of high SDF levels are multifactorial and complex, necessitating the establishment of standard protocols to control its negative effects on assisted reproduction. This is especially pertinent for endangered species, for which information on male fertility factors is limited. In humans, personalized treatment is essential to optimize the retrieval of high-quality gametes during fertilization. Similarly, assisted reproductive strategies for endangered species must be tailored to the specific sperm characteristics of each species. Various strategies to improve sperm DNA quality are now available, many of which are designed to mimic natural sperm behaviour shaped by evolutionary selection processes unique to each species. Exploring the synergistic effects of these strategies could enhance sperm availability and efficacy during fertilization.

To reverse the trend of declining wildlife populations globally, individuals must be provided with conditions that allow them to thrive, not just survive. It is no longer only the remit of conservation breeding programs to ensure animal well-being to promote reproduction; in situ conservation efforts must also consider how environmental and anthropogenic pressures impact wild populations and how to mitigate them, especially with regard to reproduction and survival. Stress and welfare are complex concepts that necessitate an understanding of how stressors affect animals on both individual and population levels, and how the subsequent impact on reproduction can vary. There are species differences in how factors impact well-being, related in part to natural history, which are also shaped by individual perceptions and coping abilities. A multitude of stress-related responses then have the potential to disrupt reproduction on many levels and, ultimately, fitness. A major limitation to advancing welfare science is the lack of definitive tests to verify welfare status, that is, is the animal thriving, or just surviving? While analyses of circulating or excreted glucocorticoids (GCs) have for decades been the primary method of assessing stress, today we recognize the need for more comprehensive indicators that reflect multiple physiological systems, including behavior, to assess both negative and positive welfare states. In this chapter, we discuss the potential for stress not only to disrupt but also sometimes to facilitate reproduction, including the key role that GCs play. We then discuss several other physiological biomarkers that have the potential to assess well-being in the context of reproduction and conclude with multi-biomarker approaches, which, if applied to wildlife, could be powerful tools for conservation and could help to elucidate the complex relationship between stress and reproduction.

Diabesity-obesity and type 2 diabetes mellitus (T2DM)-has a profound effect on oral health, and modulation of the oral immune system may help in managing it. This review aims to elucidate the complex interconnection between diabesity, oral immunity, and oral health consequences. Diabesity affects metabolic homeostasis, leading to changes in the immune system within the oral cavity, and increases the incidence of chronic low-grade inflammation and oral diseases. Alterations in the oral microbiome and the breakdown of immune homeostasis further contribute to oral health problems. The reciprocal relationship between diabesity and oral diseases and how inflammation in the oral cavity can worsen systemic metabolic diseases are also described. Apart from periodontal diseases, diabesity increases susceptibility to dental caries, xerostomia, and oral mucosal lesions. Novel treatment strategies are presented with special emphasis on nutrition, lifestyle changes, new drugs, and immunomodulating therapies. The possibility of using a personalized medicine approach in the prevention and treatment of oral diseases in diabesity patients is discussed with regard to genetic and epigenetic factors, biomarkers, and genetic profiles. A combined strategy focusing on both systemic metabolic and oral immunomodulation is recommended to advance the knowledge of diabesity in oral health and thus improve the oral health and quality of life (QoL) of patients with diabesity.

Medicinal plants have long been recognized for their therapeutic benefits, particularly for their bioactive compounds that enhance quality of life. These plants and their derived compounds possess numerous pharmacological properties, including the modulation of immune system components. Immune responses are crucial for resolving oral infections caused by pathogens such as bacteria, fungi, and viruses, as well as for preventing or managing oral cancer. A robust immune system plays a central role in defending against these stimuli, making it essential to explore and promote the use of medicinal plants that can enhance immune responses or intervene in disease-related processes.This chapter focuses on the immunomodulatory potential of specific plants and plant-derived compounds, specifying their bioactive chemical components responsible for their immune-boosting and anti-inflammatory properties. Many medicinal plants exhibit considerable immunomodulatory activities, primarily through the activation of signaling pathways like NF-κB and MAPK. These pathways are key regulators of inflammatory diseases and cancer, and their modulation by plant compounds holds promise for therapeutic applications. However, further studies are required to fully elucidate the underlying mechanisms of these effects and to explore additional pathways involved in plant-based immunomodulation.Most studies on the immunomodulatory effects of medicinal plants have been conducted in vitro, so it is crucial to expand research into randomized clinical trials in diverse populations. Although many of the plants discussed in this chapter appear to be safe, their toxicological profiles in clinical settings remain underexplored and need further investigation. By advancing clinical research and assessing the safety and efficacy of medicinal plants, these natural products could play an increasingly important role in managing oral infections, cancer, and other immune-related conditions.