Neural stem/progenitor cells (NSPCs) are self-renewing and multipotent cells of the central nervous system where they give rise to neurons, astrocytes and oligodendrocytes both during embryogenesis and throughout adulthood, although only in a few discrete niches. NSPC can integrate and send a plethora of signals not only within the local microenvironment but also at distance, including the systemic macroenvironment. Extracellular vesicles (EVs) are currently envisioned as main players in cell-cell communication in basic and translational neuroscience where they are emerging as an acellular alternative in regenerative medicine. At present NSPC-derived EVs represent a largely unexplored area compared to EVs from other neural sources and EVs from other stem cells, i.e., mesenchymal stem cells. On the other hand, available data suggest that NSPC-derived EVs can play key roles on neurodevelopmental and adult neurogenesis, and they are endowed with neuroprotective and immunomodulatory properties, and even endocrine functions. In this review we specifically highlight major neurogenic and “non-neurogenic” properties of NSPC-EVs, the current knowledge on their peculiar cargos and their potential translational value.

Aging is a complex biological process characterized by progressive multiorgan deterioration that compromises the quality of life. Unhealthy aging often associates with cognitive decline and motor-neurological disorders including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Genetic, environmental, and lifestyle factors, which include dietary habits, interact with aging and influence brain health, thus having an impact on the development of neurodegenerative disorders. In this context, fungal-derived bioactive compounds have emerged as promising neuroprotective agents due to their diverse biological properties that include antioxidative, anti-inflammatory, pro-autophagic, and neurotrophic effects. Key fungal metabolites, including polysaccharides, terpenoids, alkaloids, and phenolic compounds have been shown to modulate neuroinflammatory pathways, enhance neuronal survival, stimulate protective autophagy, and promote synaptic plasticity. Still, challenges related to their bioavailability, standardization, and clinical translation remain unresolved. Future deep research will be crucial to unlocking the full therapeutic potential of fungal-derived neuroprotective compounds. This review examines the potential therapeutic role of fungal metabolites, providing a comparative evaluation with a focus on their mechanisms of action in promoting brain health and longevity.

Gravity is a primary physical force that has a profound influence on the stability of the cell cytoskeleton. In our research, we investigated the influence of microgravity on altering the cytoskeletal pathways of glioblastoma cells. The highly infiltrative behavior of glioblastoma is supported by cytoskeletal dynamics and surface proteins that allow glioblastoma cells to avoid stable connections with the tissue environment and other cells. Glioblastoma cell line C6 was exposed to a microgravity environment for 24, 48, and 72 h by 3D-RPM, a laboratory instrument recognized to reproduce the effect of microgravity in cell cultures. The immunofluorescence for GFAP, vinculin, and Connexin-43 was investigated as signals related to cytoskeleton dynamics. The polymerization of GFAP and the expression of focal contact structured by vinculin were found to be altered, especially after 48 and 72 h of microgravity. Connexin-43, involved in several intracellular pathways that critically promote cell motility and invasion of glioma cells, was found to be largely reduced following microgravity exposure. In conclusion, microgravity, by reducing the expression of Connexin-43, alters the architecture of specific cytoskeletal elements such as GFAP and increases the focal contact, which can induce a reduction in glioma cell mobility, thereby inhibiting their aggressive metastatic behavior.

The present work shows that the exposure of mesothelial cells to simulated microgravity changes their cytoskeleton and adhesion proteins, leading to a cell switch from normal towards tumoral cells. Immunohistochemical and molecular data were obtained from both MeT-5A exposed to simulated microgravity and BR95 mesothelioma cell lines. Simulated microgravity was found to affect the expression of actin, vinculin, and connexin-43, altering their quantitative and spatial distribution pattern inside the cell. The analysis of the tumoral markers p27, CD44, Fibulin-3, and NANOG and the expression of genes related to cancer transformation such as NANOG, CDH-1, and Zeb-1 showed that the simulated microgravity environment led to expression patterns in MeT-5A cells similar to those observed in BR95 cells. The alteration in both quantitative expression and structural organization of the cytoskeleton and adhesion/communication proteins can thus be considered a pivotal mechanism involved in the cellular shift towards tumoral progression.

Pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all pancreatic malignancies. Despite the remarkable improvement concerning treatment, late detection and resistance to clinically used chemotherapeutic agents remain major challenges. Trichostatin A (TSA), a histone deacetylase inhibitor, has been recognized as an effective therapeutic agent against PDAC by inhibiting proliferation, inducing apoptosis, and sensitizing PDAC cells to chemotherapeutic agents such as gemcitabine. Microgravity has become a useful tool in cancer research due to its effects on various cellular processes. This paper presents a deep molecular and proteomic analysis investigating cell growth, the modulation of cytokeratins, and proteins related to apoptosis, cellular metabolism, and protein synthesis after TSA treatment in simulated microgravity (SMG)-exposed PaCa44 3D cells. Our analysis concerns the effects of TSA treatment on cell proliferation: the impairment of the cell cycle with the downregulation of proteins involved in Cdc42 signaling and G1/G2- and G2/M-phase transitions. Thus, we observed modification of survival pathways and proteins related to autophagy and apoptosis. We also observed changes in proteins involved in the regulation of transcription and the repair of damaged DNA. TSA treatment promotes the downregulation of some markers involved in the maintenance of the potency of stem cells, while it upregulates proteins involved in the induction and modulation of the differentiation process. Our data suggest that TSA treatment restores the cell phenotype prior to simulated microgravity exposure, and exerts an intriguing activity on PDAC cells by reducing proliferation and inducing cell death via multiple pathways.

This study focused on effects induced by Short-term Simulated Microgravity (SMG) condition on primary cell culture from pre-pubertal Wistar rats testis. Cells were analyzed for cytoskeletal and Sex Hormone Binding Globulin (SHBG/ABP) changes by immunofluorescence technique, for antioxidant system exploiting RT-PCR and cell viability. Cells were cultured for 6 and 24h on a three-dimensional clinostat, Random Positioning Machine (RPM). At the end of each experiment, once stopped the RPM rotation, cells were either fixed in paraformaldehyde or lysed and RNA extracted. In cells exposed to SMG the cytoskeleton became disorganized, microtubules fragmented and SHBG was already undetectable after 6h of treatment. Moreover, various antioxidant systems significantly increased after 24h of SMG exposure. Initially, SMG seemed to disturb antioxidant protection strategies allowing the testes to support sperm production, thus generating an aging-like state of oxidative stress. Studies on changes induced by short-term altered gravity conditions, carried out in real microgravity, could give more information on steroidogenesis and germ cell differentiation within the testis exposed to this condition and confirm the validity of simulation approach.