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.

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.

The critical shortage of donor organs remains the foremost challenge in transplantation medicine. Nevertheless, advancements in robotic-assisted surgery (RAS), artificial intelligence (AI)-enhanced donor–recipient matching, and bioengineering—particularly 3D bioprinting—are revolutionizing the field. Today, RAS has evolved from an innovative technique into a reliable clinical tool, with evidence indicating that it enhances surgical precision and results in better patient outcomes. Meanwhile, AI and machine learning are advancing donor–recipient matching and allocation, producing models that offer superior predictive accuracy for graft survival compared to traditional methods. Additionally, bioengineering strategies, especially 3D bioprinting and tissue engineering, are progressing from the creation of acellular scaffolds to the development of vascularized constructs, marking a significant milestone toward functional organ replacement. Despite persistent challenges such as high costs, regulatory obstacles, new structured formation programs, and the necessity for effective vascularization in engineered tissues, the integration of these disciplines is forging a new paradigm in regenerative medicine. The primary objective of this review is to synthesize multidisciplinary innovations by leveraging clinical studies and technological assessments to delineate future directions in regenerative medicine and organ transplantation.

The mucus layer covering the gastrointestinal tract forms a specialised interface where mucins, microbes, and extracellular vesicles create a dynamic, self-regulating ecosystem. Here, we introduce the concept of the muco-microbiotic layer as an integrated eco-physiological system that maintains mucosal homeostasis through coordinated structural, metabolic, and immune functions. The MuMi layer varies regionally in its biochemical composition, microbial inhabitants, and environmental parameters—from the acidic stomach to the anaerobic colon—thereby generating distinct niches for microbial colonisation and metabolite production. We summarise current evidence on how mucin glycans, mucus-associated microbiota, and vesicle-mediated signalling sustain barrier integrity, nutrient flux, and immune tolerance. Perturbations in any of these components lead to barrier failure, microbial encroachment, and inflammation, contributing to a broad spectrum of disorders, including gastritis, inflammatory bowel disease, colorectal cancer, and metabolic syndrome. Methodological advances such as organoid and mucus-on-chip models, spatial multi-omics, and vesiculomics are now enabling site-specific analyses of this complex system. Conceptually, defining the mucus, microbiota, and vesicular compartments as a single MuMi layer provides a new framework for understanding mucosal physiology and pathophysiology, emphasising the interdependence between structure and function. Integrating this perspective into experimental and clinical research may open new avenues for diagnostics and therapies targeting mucosal health.

The lower airways are a dynamic environment where physical, microbial, and molecular factors intersect to regulate respiratory health and disease. The muco-microbiotic (MuMi) layer, composed of mucus, resident microbes, and extracellular vesicles (EVs), is not just a passive barrier but also an active site for host–microbe communication. This layer integrates epithelial cell biology, microbial activity, and immune responses within the bronchial environment. New transcriptomic and metatranscriptomic technologies show that it is not only which microbes are present but also their gene activity that closely links to airway inflammation and disease. EV-associated RNAs from both host and microbial cells act as key messengers, influencing epithelial responses, immune activity, mucus properties, and microbial behaviour. This review highlights evidence that positions the MuMi layer as central to understanding lower airway disease, particularly asthma and chronic obstructive pulmonary disease (COPD). Distinct gene expression programs and biomarker profiles, such as exhaled nitric oxide, may reflect different disease mechanisms even in cases with similar clinical features, such as eosinophilia. Multi-omic approaches focused on the MuMi layer enable better disease classification, biomarker discovery, and therapy selection. By putting the MuMi interface at the core of precision pulmonology, we provide a framework for advancing personalised care in chronic respiratory diseases.

Heat shock protein 60 (Hsp60) plays a crucial role in cellular homeostasis and stress responses. Recent evidence highlights its involvement in COVID-19 pathophysiology, particularly in immune modulation, inflammation, and endothelial dysfunction. Extracellular Hsp60 can interact with Toll-like receptors, amplifying inflammatory responses and contributing to cytokine storm and tissue damage. Additionally, since the presence of several common epitopes with SARS-CoV-2 proteins, its role in molecular mimicry suggests a potential link also to post-infectious autoimmune disorders. Hsp60 has also been implicated in endothelial damage and thromboembolic complications observed in severe COVID-19 cases. Beyond its pathogenic roles, Hsp60 could emerge as a potential biomarker for disease severity as well as a target for therapeutic strategies aimed at modulating immune responses. Finally, the structural similarity with SARS-CoV-2 proteins raises important considerations regarding both vaccine safety and the unexpected potential for anti-tumor immunity. This review critically examines the multifaceted roles of Hsp60 in COVID-19, specifically from a morpho-functional point of view, highlighting its implications in disease progression, post-viral complications, and therapeutic opportunities.