Research for the most selective drug delivery to tumors represents a fascinating key target in science. Alongside the artificial delivery systems identified in the last decades (e.g., liposomes), a family of natural extracellular vesicles (EVs) has gained increasing focus for their potential use in delivering anticancer compounds. EVs are released by all cell types to mediate cell-to-cell communication both at the paracrine and the systemic levels, suggesting a role for them as an ideal nano-delivery system. Malignant pleural mesothelioma (MPM) stands out among currently untreatable tumors, also due to the difficulties in achieving an early diagnosis. Thus, early diagnosis and treatment of MPM are both unmet clinical needs. This review looks at indirect and direct evidence that EVs may represent both a new tool for allowing an early diagnosis of MPM and a potential new delivery system for more efficient therapeutic strategies. Since MPM is a relatively rare malignant tumor and preclinical MPM models developed to date are very few and not reliable, this review will report data obtained in other tumor types, suggesting the potential use of EVs in mesothelioma patients as well.

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.

In this paper, we want to refute the notion that the microbiota should be considered an organ, given that an organ comprises tissue of similar or different embryological origin, while the microbiota is a pool of different microbial species originating individually from single replications and not from a common ancestral cellular element. Hence, we would like to propose a new morphological interpretation of its nature, based on the comprehensive context in which these microbes live: a muco-microbiotic layer of hollow organs, such as the airways and the bowel. The above concept should represent not only a new terminological annotation but also a more accurate portrayal of the physiology and pathophysiology of these organs. Indeed, a better understanding of the biological nature of this part of the human body can help scientists develop more specific experimental protocols, potentially leading to the establishment of better therapeutic strategies.

In this brief Opinion paper, the term “muco-microbiotic layer” is introduced to describe the innermost layer of the intestinal wall. This layer may contribute not only to the overall health of the bowel, but also to that of extraintestinal organs. Its constituents, in terms of soluble molecules and nanovesicles, need to be studied further. Moreover, one can hypothesize the existence of an analogous layer in other organs, such as the airways or some parts of the genital tracts. Further studies on it are needed.

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.