Ozone therapy has been widely used in everyday clinical practice over the last few years, leading to significant clinical results in the treatment of herniated discs and pain management. Nevertheless, further studies have demonstrated its potential efficacy and safety under other clinical and experimental conditions. However, some of these studies showed controversial results regarding the safety and efficacy of ozone therapy, thus mining its potential use in an everyday clinical practice. To this regard, it should be considered that extensive literature review reported the use of ozone in a significant different dose range and with different delivery systems. The aim of the present review is to describe the various pharmacological effects of ozone in different organs and clinical conditions and to provide possible biochemical and molecular insights for ozone biological properties, thus providing a possible explanation for various controversial clinical outcomes described in the scientific literature.

In 2021 the World Health Organization published the fifth and latest version of the Central Nervous System tumors classification, which incorporates and summarizes a long list of updates from the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy work. Among the adult-type diffuse gliomas, glioblastoma represents most primary brain tumors in the neuro-oncology practice of adults. Despite massive efforts in the field of neuro-oncology diagnostics to ensure a proper taxonomy, the identification of glioblastoma-tumor subtypes is not accompanied by personalized therapies, and no improvements in terms of overall survival have been achieved so far, confirming the existence of open and unresolved issues. The aim of this review is to illustrate and elucidate the state of art regarding the foremost biological and molecular mechanisms that guide the beginning and the progression of this cancer, showing the salient features of tumor hallmarks in glioblastoma. Pathophysiology processes are discussed on molecular and cellular levels, highlighting the critical overlaps that are involved into the creation of a complex tumor microenvironment. The description of glioblastoma hallmarks shows how tumoral processes can be linked together, finding their involvement within distinct areas that are engaged for cancer-malignancy establishment and maintenance. The evidence presented provides the promising view that glioblastoma represents interconnected hallmarks that may led to a better understanding of tumor pathophysiology, therefore driving the development of new therapeutic strategies and approaches.

Uveal melanoma (UM), the most common primary intraocular cancer in adults, is among the tumors with poorer prognosis. Recently, the role of the oncometabolite lactate has become attractive due to its role as hydroxycarboxylic acid receptor 1 (HCAR1) activator, as an epigenetic modulator inducing lysine residues lactylation and, of course, as a glycolysis end-product, bridging the gap between glycolysis and oxidative phosphorylation. The aim of the present study was to dissect in UM cell line (92.1) the role of lactate as either a metabolite or a signaling molecule, using the known modulators of HCAR1 and of lactate transporters. Our results show that lactate (20 mM) resulted in a significant decrease in cell proliferation and migration, acting and switching cell metabolism toward oxidative phosphorylation. These results were coupled with increased euchromatin content and quiescence in UM cells. We further showed, in a clinical setting, that an increase in lactate transporters MCT4 and HCAR1 is associated with a spindle-shape histological type in UM. In conclusion, our results suggest that lactate metabolism may serve as a prognostic marker of UM progression and may be exploited as a potential therapeutic target.

Background: Intraoperative hypotension is associated with increased postoperative morbidity and mortality. Methods: We randomly assigned patients undergoing major general surgery to early warning system (EWS) and hemodynamic algorithm (intervention group, n = 20) or standard care (n = 20). The primary outcome was the difference in hypotension (defined as mean arterial pressure < 65 mmHg) and as secondary outcome surrogate markers of organ injury and oxidative stress. Results: The median number of hypotensive episodes was lower in the intervention group (−5.0 (95% CI: −9.0, −0.5); p < 0.001), with lower time spent in hypotension (−12.8 min (95% CI: −38.0, −2.3 min); p = 0.048), correspondent to −4.8% of total surgery time (95% CI: −12.7, 0.01%; p = 0.048).The median time-weighted average of hypotension was 0.12 mmHg (0.35) in the intervention group and 0.37 mmHg (1.11) in the control group, with a median difference of −0.25 mmHg (95% CI: −0.85, −0.01; p = 0.025). Neutrophil Gelatinase-Associated Lipocalin (NGAL) correlated with time-weighted average of hypotension (R = 0.32; p = 0.038) and S100B with number of hypotensive episodes, absolute time of hypotension, relative time of hypotension and time-weighted average of hypotension (p < 0.001 for all). The intervention group showed lower Neuronal Specific Enolase (NSE) and higher reduced glutathione when compared to the control group. Conclusions: The use of an EWS coupled with a hemodynamic algorithm resulted in reduced intraoperative hypotension, reduced NSE and oxidative stress.

Neurodegenerative disorders are characterized by the progressive loss of central and/or peripheral nervous system neurons. Within this context, neuroinflammation comes up as one of the main factors linked to neurodegeneration progression. In fact, neuroinflammation has been recognized as an outstanding factor for Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and multiple sclerosis (MS). Interestingly, neuroinflammatory diseases are characterized by dramatic changes in the epigenetic profile, which might provide novel prognostic and therapeutic factors towards neuroinflammatory treatment. Deep changes in DNA and histone methylation, along with histone acetylation and altered non-coding RNA expression, have been reported at the onset of inflammatory diseases. The aim of this work is to review the current knowledge on this field.

Breast cancer is the most frequent tumor and the leading cause of cancer deaths in women. In recent years, lactate metabolism and, in particular, its receptor GPR81 have been shown to play a vital role in cancer biology. GPR81 is upregulated in breast cancer and promotes tumor growth by tumor cell-derived lactate. Therefore, the search for possible crosstalk and the involvement of new molecules capable of generating this pathology is always in continuous development. In this study, the relationship between GPR81 and IGFBP6 protein in tumor growth and oxidative stress in the human breast cancer cell line MDA-MB-231 was studied. Cells were treated with lactate or the GPR81 receptor agonist and antagonist 3,5-DHBA and 3-OBA, respectively. In addition, oxidative stress and proliferation were also evaluated in cells challenged with the recombinant IGFBP6 protein. Our data showed that lactate induced cell proliferation and wound healing of the MDA-231 breast cancer cell through the overexpression of both the lactate receptor GPR81 and IGFBP6. The increase in IGFBP6 was able, in turn, to improve the mitochondrial fitness and redox state, as suggested by the reduced levels of mitochondrial ROS production after IGFBP6 treatment, presumably mediated by the increase in the ROS detoxifying genes HMOX1, GSTK1 and NQO1. In conclusion, our data highlight a novel axis between GPR81 and IGFBP6 in MDA-231 cells able to modulate lactate metabolism and oxidative stress. This complex signaling may represent a new therapeutic target for breast cancer.