Glioblastoma multiforme (GBM) is a primary brain tumor that is very aggressive, resistant to treatment, and characterized by a high degree of anaplasia and proliferation. Routine treatment includes ablative surgery, chemotherapy, and radiotherapy. However, GMB rapidly relapses and develops radioresistance. Here, we briefly review the mechanisms underpinning radioresistance and discuss research to stop it and install anti-tumor defenses. Factors that participate in radioresistance are varied and include stem cells, tumor heterogeneity, tumor microenvironment, hypoxia, metabolic reprogramming, the chaperone system, non-coding RNAs, DNA repair, and extracellular vesicles (EVs). We direct our attention toward EVs because they are emerging as promising candidates as diagnostic and prognostication tools and as the basis for developing nanodevices for delivering anti-cancer agents directly into the tumor mass. EVs are relatively easy to obtain and manipulate to endow them with the desired anti-cancer properties and to administer them using minimally invasive procedures. Thus, isolating EVs from a GBM patient, supplying them with the necessary anti-cancer agent and the capability of recognizing a specified tissue-cell target, and reinjecting them into the original donor appears, at this time, as a reachable objective of personalized medicine.

Glioblastoma multiforme (GBM) stands out as the most tremendous brain tumor, constituting 60% of primary brain cancers, accompanied by dismal survival rates. Despite advancements in research, therapeutic options remain limited to chemotherapy and surgery. GBM molecular heterogeneity, the intricate interaction with the tumor microenvironment (TME), and non-selective treatments contribute to the neoplastic relapse. Diagnostic challenges arise from GBM advanced-stage detection, necessitating the exploration of novel biomarkers for early diagnosis. Using data from the literature and a bioinformatic tool, the current manuscript delineates the molecular interplay between human GBM, astrocytes, and myeloid cells, underscoring selected protein pathways belonging to astroglia and myeloid lineage, which can be considered for targeted therapies. Moreover, the pivotal role of extracellular vesicles (EVs) in orchestrating a favorable microenvironment for cancer progression is highlighted, suggesting their utility in identifying biomarkers for GBM early diagnosis.

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.

Glioblastoma (GBM) is characterized by its unique molecular features, such as self-renewal and tumorigenicity of glioma stem cells that promote resistance, largely resulting in treatment failure. Among the molecular alterations significant to GBM biology and treatment, mutations in isocitrate dehydrogenase (IDH) have assumed particular relevance. IDH-mutant and IDH-wild-type tumors exhibit significantly different metabolic characteristics, clinical behavior, and therapeutic sensitivities, making IDH status a critical determinant in determining prognosis and treatment strategies for GBM. In the context of cancer, chaperones were shown to promote tumor progression by supporting malignant cells over healthy ones. While heat shock proteins (HSPs) have long been implicated in the molecular mechanisms of tumor phenotype progression, recent attention has turned to CCT (chaperonin containing TCP1), orchestrating proteostasis. The chaperonin CCT is being explored as a diagnostic and therapeutic target in many cancers, including GBM, owing to its involvement in key oncogenic signaling pathways such as Wnt, VEGF, EGFR, and PI3K/AKT/mTOR. However, its role in the GBM-tricarboxylic acid (TCA) cycle cascade is still not well understood. Therefore, the present review highlights the potential role of the CCT complex in regulating hypoxia-inducible factor (HIF) activation by modulating enzymes responsive to metabolites derived from glucose metabolism and the TCA cycle in a manner dependent on oxygen availability and IDH mutation status.

Air pollution has increased over the years, causing a negative impact on society due to the many health-related problems it can contribute to. Although the type and extent of air pollutants are known, the molecular mechanisms underlying the induction of negative effects on the human body remain unclear. Emerging evidence suggests the crucial involvement of different molecular mediators in inflammation and oxidative stress in air pollution-induced disorders. Among these, non-coding RNAs (ncRNAs) carried by extracellular vesicles (EVs) may play an essential role in gene regulation of the cell stress response in pollutant-induced multiorgan disorders. This review highlights EV-transported ncRNAs’ roles in physiological and pathological conditions, such as the development of cancer and respiratory, neurodegenerative, and cardiovascular diseases following exposure to various environmental stressors.

Background: The incidence of various types of cancer, for example, papillary thyroid carcinoma (PTC), is on the rise. Since therapeutic success depends greatly on early diagnosis, reliable diagnostic biomarkers must be identified, and easy-to-apply tools for detecting them must urgently be standardized. Here, we contribute to solving this medical challenge by assessing miRNAs suspected of promoting carcinogenesis in extracellular vesicles (EVs) that can be routinely obtained via liquid biopsy. We profit from current progress in cancerology that provides innovations in liquid biopsy and EVs analysis, along with the identification of miRNAs and chaperone system (CS) components implicated in carcinogenesis. Methods: We measured in EVs obtained from circulating blood plasma from PTC patients the levels of three miRNAs implicated in thyroid cancer, hsa-miR-1-3p, hsa-miR-206, and hsa-miR-221-3p, and most likely involved in the regulation of two members of the CS, Hsp60 and CCT. EVs were isolated from the plasma of patients with PTC and controls with benign goiter (BG) and from the culture medium of a PTC cell line (MDAT32) and were appropriately characterized. Results: The levels of miRNAs determined by RT-qPCR were consistently higher in PTC patients and decreased down to control levels after thyroidectomy. Bioinformatics showed that the miRNAs target genes are associated with the molecular pathogenesis of PTC. Conclusions: Our exploratory study reaffirms the potential in clinics of the selected miRNAs in EVs as useful biomarkers of PTC easily accessible via liquid biopsy, which is minimally invasive and amenable to periodic repetition, an improvement compared to the established fine-needle aspirate biopsy.