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The recent acknowledgement of depleted uranium (DU) munitions utilization in the Ukrainian conflict has sparked renewed apprehensions regarding the safety of DU, its toxicological profile, and the health ramifications of exposure. Historical data from conflicts like the Gulf War, Bosnia, and Kosovo have recorded an upsurge in neoplastic ailments among soldiers in close proximity to DU deployment. Nevertheless, establishing a direct causal connection between DU exposure and the development of neoplastic diseases remains elusive, as indicated by meta-analyses and studies on animal models. We posit that the absence of a conclusive causal correlation between DU exposure and neoplastic diseases may be ascribed to the constraints of current study models, which fail to encapsulate the intricate interactions between DU and the human immune system, pathophysiology, particularly in the context of chronic, low-level exposure. Nowadays evidences suggests that DU exposure contributes to a cumulative immunotoxic effect, culminating in a compromised immune surveillance system and an escalated risk of neoplastic diseases over time. To investigate this hypothesis, we advocate for the advancement of pioneering research models, such as human ex-vivo body-on-a-chip systems, which can more accurately replicate the human physiological response to DU exposure and cancer pathophysiology. These models should encompass the examination of immune system modifications along with the potential for DU to interact with diverse organs and tissues, thereby furnishing a more comprehensive understanding of the enduring health impacts of DU.

Bidirectional communication between the central nervous system (CNS) and peripheral organs and tissue has been widely documented in physiological and pathological conditions. This communication relies on the bilateral transmission of signaling molecules and substances that circulate throughout the body and reach their target site(s) via the blood and other biological fluids (e.g., the cerebrospinal fluid, the lymph). One of the mechanisms by which these molecular messengers are exchanged is through the secretion of extracellular vesicles (EVs). EVs are known to mediate cell-to-cell communication by delivering biological molecules, including nucleic acids, proteins, lipids, and various other bioactive regulators. Moreover, EVs can cross the blood–brain barrier (BBB), enabling direct communication between the periphery and the brain. In particular, the delivery of microRNAs (miRNAs) can modulate the expression profiles of recipient cells, thereby influencing their functions. This review synthesizes current findings about the brain–periphery cross-talk mediated by EVs-delivered miRNAs. Although this mechanism has been definitively shown in a few cases, much evidence indirectly indicates that it could mediate brain–peripherical organs/tissue communication, especially in pathological conditions. Therefore, understanding this process could provide valuable insights for the treatment and management of neurological and systemic diseases.

In recent years, the increasing number of long-duration space missions has prompted the scientific community to undertake a more comprehensive examination of the impact of microgravity on the human body during spaceflight. This review aims to assess the current knowledge regarding the consequences of exposure to an extreme environment, like microgravity, on the human body, focusing on the role of heat-shock proteins (HSPs). Previous studies have demonstrated that long-term exposure to microgravity during spaceflight can cause various changes in the human body, such as muscle atrophy, changes in muscle fiber composition, cardiovascular function, bone density, and even immune system functions. It has been postulated that heat-shock proteins (HSPs) may play a role in mitigating the harmful effects of microgravity-induced stress. According to past studies, heat-shock proteins (HSPs) are upregulated under simulated microgravity conditions. This upregulation assists in the maintenance of the proper folding and function of other proteins during stressful conditions, thereby safeguarding the physiological systems of organisms from the detrimental effects of microgravity. HSPs could also be used as biomarkers to assess the level of cellular stress in tissues and cells exposed to microgravity. Therefore, modulation of HSPs by drugs and genetic or environmental techniques could prove to be a potential therapeutic strategy to reduce the negative physiological consequences of long-duration spaceflight in astronauts.

Over the last ten years, with the progress of in vitro culture methods, it has been possible to build increasingly reliable models to effectively mimic in vivo ones. The translational methodological approach that combined biotechnology and biomedical engineering has produced remarkable results, such as the development of ex vivo 3D culture models, the construction of on-a-chip organoids, and the construction of complex systems capable of bypassing the static nature of the two-dimensional cultural models that have been typical of in vitro studies conducted to date. However, nowadays, there is still reluctance to completely abandon the animal model as an essential reference or as an integrated step for the validation of a model or a proposed study. This is due to the partially correct conviction of the impossibility of reproducing, in vitro or ex vivo, the complexity of pathological models or the spatial communication between different cytotypes, as well as, more generally, the lack of systems capable of mimicking the dynamism of a complex in vivo system. In this study, we will compare different methodological approaches in the study of the three most common types of respiratory diseases: chronic obstructive pulmonary disease (COPD), asthma, and lung carcinomas. The purpose of this comparative study is to evaluate the most current methodological approaches to understand how far research is from being independent from animal models. Animal studies are generally considered necessary, but are still questioned because of the ethics and the cost–benefit ratio involved.