Breast cancer (BC) is a major public health problem, with key pieces of information needed for developing preventive and curative measures still missing. For example, the participation of the chaperone system (CS) in carcinogenesis and anti-cancer responses is poorly understood, although it can be predicted to be a crucial factor in these mechanisms. The chief components of the CS are the molecular chaperones, and here we discuss four of them, Hsp27, Hsp60, Hsp70, and Hsp90, focusing on their pro-carcinogenic roles in BC and potential for developing anti-BC therapies. These chaperones can be targets of negative chaperonotherapy, namely the elimination/blocking/inhibition of the chaperone(s) functioning in favor of BC, using, for instance, Hsp inhibitors. The chaperones can also be employed in immunotherapy against BC as adjuvants, together with BC antigens. Extracellular vesicles (EVs) in BC diagnosis and management are also briefly discussed, considering their potential as easily accessible carriers of biomarkers and as shippers of anti-cancer agents amenable to manipulation and controlled delivery. The data surveyed from many laboratories reveal that, to enhance the understanding of the role of the CS in BS pathogenesis, one must consider the CS as a physiological system, encompassing diverse members throughout the body and interacting with the ubiquitin–proteasome system, the chaperone-mediated autophagy machinery, and the immune system (IS). An integrated view of the CS, including its functional partners and considering its highly dynamic nature with EVs transporting CS components to reach all the cell compartments in which they are needed, opens as yet unexplored pathways leading to carcinogenesis that are amenable to interference by anti-cancer treatments centered on CS components, such as the molecular chaperones.

Hsp60 is one of the most ancient and evolutionarily conserved members of the chaperoning system. It typically resides within mitochondria, in which it contributes to maintaining the organelle’s proteome integrity and homeostasis. In the last few years, it has been shown that Hsp60 also occurs in other locations, intracellularly and extracellularly, including cytosol, plasma-cell membrane, and extracellular vesicles (EVs). Consequently, non-canonical functions and interacting partners of Hsp60 have been identified and it has been realized that it is a hub molecule in diverse networks and pathways and that it is implicated, directly or indirectly, in the development of various pathological conditions, the Hsp60 chaperonopathies. In this review, we will focus on the multi-faceted role of this chaperonin in human cancers, showing the contribution of intra- and extracellular Hsp60 in cancer development and progression, as well as the impact of miRNA-mediated regulation of Hsp60 in carcinogenesis. There are still various aspects of this intricate biological scenario that are poorly understood but ongoing research is steadily providing new insights and we will direct attention to them. For instance, we will highlight the possible applications of the Hsp60 involvement in carcinogenesis not only in diagnosis, but also in the development of specific anti-cancer therapies centered on the use of the chaperonin as therapeutic target or agent and depending on its role, pro- or anti-tumor.

Background/Objectives: Recent studies have highlighted the role of the gut–muscle axis, suggesting that modulation of the gut microbiota may indirectly benefit skeletal muscle. This study aimed to evaluate the effects of Lactobacillus fermentum (L. fermentum) supplementation in a model of muscle atrophy induced by chronic ethanol (EtOH) intake, focusing on inflammatory and antioxidant mechanisms. Methods: Sixty 12-month-old female Balb/c mice were divided randomly into three groups (n = 20/group): (1) Ethanol (EtOH) group, receiving ethanol daily for 8 and 12 weeks to induce systemic oxidative stress and inflammation; (2) Ethanol + Probiotic (EtOH + P) group, receiving both ethanol and L. fermentum supplementation for the same durations; and (3) Control (Ctrl) group, receiving only water. Muscle samples were analyzed for the fiber morphology, inflammatory markers, oxidative stress indicators, and satellite cell (SC) activity. All data were tested for normality using the Shapiro–Wilk test before applying a parametric analysis. A statistical analysis was performed using one-way ANOVA followed by a Bonferroni post-hoc test. The level of significance was set at p < 0.05. Results: EtOH exposure caused significant atrophy in all muscle fiber types (type I, IIa, and IIb), with the most pronounced effects on oxidative fibers. L. fermentum supplementation significantly reversed atrophy in type I and IIa fibers, accompanied by a significant reduction in IL-6, TNF-α, and Hsp60 expression levels, indicating the protective effect of L. fermentum against oxidative stress and inflammation. Moreover, the probiotic treatment increased MyoD expression in SCs, suggesting enhanced regenerative activity, without histological evidence of fibrosis. Conclusions: These findings suggest that L. fermentum supplementation could counteract EtOH-induced skeletal muscle damage by reducing inflammation and oxidative stress and promoting muscle repair, indicating its potential as an adjuvant, in the therapeutic strategy of models of muscle degeneration.

The heat shock protein 60 (Hsp60) is a highly conserved molecular chaperonin belonging to the chaperone system, a complex network that maintains proteostasis and regulates numerous cellular processes beyond protein folding. Initially described as a mitochondrial protein essential for the folding of newly imported polypeptides, Hsp60 is now recognized as a multifunctional molecule. Its expression, localization, and post-translational modifications dynamically influence cell fate and tissue homeostasis. Alterations in Hsp60 quantity, structure, or distribution underlie a heterogeneous group of disorders known as chaperonopathies, which may occur “by defect,” “by excess,” or “by mistake” (also called “by collaborationism”). Genetic Hsp60’s chaperonopathies are associated with rare neurodegenerative and cardiovascular diseases, whereas acquired forms contribute to widespread conditions, including autoimmune, inflammatory, and malignant pathologies. This review provides a comprehensive overview of Hsp60 biology across human systems, emphasizing its structural plasticity, context-dependent functions, and dual role in health as both a biomarker and a therapeutic target. The emerging paradigm of chaperonotherapy, encompassing positive strategies to restore protective chaperones and negative strategies to inhibit pathogenic ones, highlights the translational potential of targeting Hsp60. Understanding the molecular mechanisms governing its activity will be essential for developing precision medicine approaches aimed at modulating the chaperone system in human disease.

This study explores immunophenotypic and angiogenic profiles in salivary gland tumors (SGTs), focusing on epithelial–mesenchymal dynamics and immune–stromal interactions. Immunohistochemical analysis of E-cadherin, Vimentin, mast cell tryptase (MCT), CD300a, CK18, CD31, and vascular endothelial growth factor (VEGF) was performed in normal salivary tissue, pleomorphic adenomas (PA), and squamous cell carcinomas (SCCs) to assess epithelial plasticity, mast cell (MC) involvement, and vascular remodeling. Normal glands showed compartmentalized E-cadherin (epithelial) and Vimentin (mesenchymal) expression, with stromal MCs positive for MCT and CD300a. PA exhibited reduced E-cadherin, increased Vimentin, and atypical co-localization of CK18 with MCT/CD300a in ductal cells, indicating immune–epithelial plasticity. SCC displayed epithelial–mesenchymal transition (EMT), architectural disruption, and reduced MCT/CD300a. Notably, diminished MCT may reflect either decreased MCs density or prior degranulation, with possible diffuse MCT in stroma. Angiogenic profiling showed maximal CD31 in PA and minimal in SCC, while VEGF peaked in normal tissue, suggesting deregulated angiogenesis. SGT progression involves immune–epithelial plasticity, vascular deregulation, and stromal reprogramming. Immune marker localization within epithelial cells challenges histogenetic models and may inform prognostic assessment and targeted therapeutic strategies.

Backgrond/Objectives: Human anatomy education has traditionally relied on cadaveric dissection as the reference standard for acquiring anatomical knowledge. However, decreasing availability of donated bodies, curricular changes, and rapid technological advances have encouraged the progressive integration of complementary educational resources, including historical anatomical collections, physical models, plastinated specimens, and digital technologies. At the same time, anatomical museums have evolved from repositories of scientific heritage into dynamic educational environments that promote public engagement, accessibility, and lifelong learning. Methods: This article presents the educational experience of the Human Anatomy and Histology Institute of the University of Palermo, where historical anatomical collections, cadaveric dissection, plastination, three-dimensional (3D) digitization, virtual anatomy, and interactive educational technologies have been integrated within a single multimodal teaching framework. Results: The strengths and limitations of each educational resource are discussed in relation to contemporary anatomy education and museum communication. Our experience suggests that digital technologies achieve their greatest educational value when they complement rather than replace traditional anatomy teaching. Conclusions: Integrating historical collections with cadaveric study, physical models, and immersive digital tools offers a comprehensive educational approach capable of enhancing anatomical understanding, improving accessibility, and promoting more engaging learning experiences for students and the wider public.