(1) Background: The continuous improvement in cancer treatment has led to improvement in patients’ survival and a subsequent increase in the number of cancer survivors living with adverse side effects of cancer treatments, sometimes with a high and adverse impact on their health-related quality of life (HRQOL). Side effects of cancer treatments are frequently associated with chronic status of oxidative stress, inflammation, and/or ischemia. The potential for ozone treatment to modulate those processes and improve some of those adverse effects has previously been described. The aim of this study was to evaluate the effect of ozone treatment on the HRQOL and grade of toxicity in symptomatic cancer survivors. (2) Methods: Before and after ozone treatment, we assessed (i) the HRQOL (according to the EQ-5D-5L questionnaire) and (ii) the grade of toxicity (according to the Common Terminology Criteria for Adverse Events of the National Cancer Institute of EEUU (CTCAE v.5.0)) in 26 cancer survivors with chronic side effects of radiotherapy and chemotherapy. (3) Results: There was a significant (p < 0.001) improvement in the EQ-5D-5L index as per the self-reported outcome evaluation of patients’ health status. All the dimensions of the EQ-5D-5L questionnaire (mobility, self-care, activities, pain/discomfort, and anxiety/depression) and the self-evaluation of the health status using the visual analog scale were significantly improved (p < 0.05). The grade of toxicity was also significantly decreased (p < 0.001). (4) Conclusions: In cancer survivors with chronic side effects of cancer treatment, ozone treatment can improve the grade of toxicity and the HRQOL. These results merit additional research. Further studies are ongoing.

ANRIL (Antisense Noncoding RNA in the INK4 Locus), also named CDKN2B-AS1, is a long non-coding RNA with outstanding functions that regulates genes involved in atherosclerosis development. ANRIL genotypes and the expression of linear and circular isoforms have been associated with coronary artery disease (CAD). The CDKN2A and the CDKN2B genes at the CDKN2A/B locus encode the Cyclin-Dependent Kinase inhibitor protein (CDKI) p16INK4a and the p53 regulatory protein p14ARF, which are involved in cell cycle regulation, aging, senescence, and apoptosis. Abnormal ANRIL expression regulates vascular endothelial growth factor (VEGF) gene expression, and upregulated Vascular Endothelial Growth Factor (VEGF) promotes angiogenesis by activating the NF-κB signaling pathway. Here, we explored associations between determinations of the linear, circular, and linear-to-circular ANRIL gene expression ratio, CDKN2A, VEGF and its receptor kinase insert domain-containing receptor (KDR) and cardiovascular risk factors and all-cause mortality in high-risk coronary patients before they undergo coronary artery bypass grafting surgery (CABG). We found that the expression of ANRIL isoforms may help in the prediction of CAD outcomes. Linear isoforms were correlated with a worse cardiovascular risk profile while the expression of circular isoforms of ANRIL correlated with a decrease in oxidative stress. However, the determination of the linear versus circular ratio of ANRIL did not report additional information to that determined by the evaluation of individual isoforms. Although the expressions of the VEFG and KDR genes correlated with a decrease in oxidative stress, in binary logistic regression analysis it was observed that only the expression of linear isoforms of ANRIL and VEGF significantly contributed to the prediction of the number of surgical revascularizations.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy. CIPN can lead to a dose reduction and/or the interruption of chemotherapy, limiting its effectiveness, while chronic CIPN decreases patients’ quality of life. Improvements in cancer treatment and patients’ survival have increased the number of patients living with CIPN. The only evidence-based treatment for CIPN-related pain, duloxetine, provides only modest clinical benefit, and there is no effective clinical management option for numbness and tingling. Several experimental studies and clinical reports suggest that adjuvant ozone treatment may be beneficial in managing CIPN. Methods: This narrative review aims to provide an overview of current knowledge regarding CIPN and ozone therapy. Specifically, it summarizes experimental studies (18) and clinical reports (27) published between 1995 and 2025 that offer preliminary evidence supporting the potential role of ozone treatment in managing CIPN, highlighting the need for ongoing randomized clinical trials to establish its efficacy. Additionally, this review highlights existing gaps in the literature and proposes directions for future research. Results: The hypothesized mechanisms of action and experimental findings suggest that ozone therapy may be a valuable intervention for CIPN, a concept supported by preliminary clinical observations. Conclusions: Clinically relevant approaches for established CIPN are currently unavailable. While preliminary data suggest a potential role of ozone therapy, clinical evidence remains limited. Further high-quality randomized controlled trials are needed to confirm its efficacy and safety in this context; several trials are currently ongoing.

Humanin (HN) and MOTS-c are mitochondrial-derived peptides (MDPs) known for their neuroprotective and metabolic functions. Their circulating and tissue levels decline with age and in neurodegenerative diseases such as Alzheimer’s disease (AD). This study aimed to evaluate whether blood and plasma gene expression and plasma protein levels of HN and MOTS-c are associated with AD markers, their role in the conversion from mild cognitive impairment (MCI) to AD, and their overall association with the disease. A case–control study was conducted, including patients with AD and MCI, and individuals with subjective cognitive decline (SCD) as controls. Gene expression levels were quantified from total RNA isolated from blood and plasma, normalised to mitochondrial DNA copy number (mtDNA-CN). ELISA was used to measure plasma HN and MOTS-c protein concentrations. HN and MOTS-c transcript levels differed significantly among study groups, whereas plasma protein concentrations did not discriminate between AD and MCI. In silico and RNA decay assays revealed faster degradation of HN mRNA and delayed but stable recovery of MOTS-c mRNA. Overall, blood and plasma transcript levels—but not circulating protein levels—of these MDPs were significantly reduced in AD compared to SCD, suggesting their potential as early biomarkers of Alzheimer’s disease.

Background: Canine oral melanoma (COM) is an aggressive and often fatal neoplasm in dogs, with clinical and molecular similarities to human melanoma. Despite its relevance as a comparative oncology model, the molecular mechanisms underlying COM remain poorly understood. This study aimed to characterize gene expression profiles in COM to identify differentially expressed genes (DEGs), potential biomarkers, and therapeutic targets. Methods: In this pilot study, we performed RNA sequencing (RNA-seq) on tumor and healthy oral tissue samples from dogs. Two independent analytical pipelines—Bowtie2-DESeq2 and HISAT-StringTie-Ballgown—were used to ensure robustness in DEG detection. We also conducted pathway enrichment and isoform-level analyses to investigate biological processes and alternative splicing events. Results: Both approaches identified a core set of 929 common DEGs. Key oncogenic pathways, including MAPK/ERK and cell cycle regulation, were significantly affected, with notable upregulation of BRAF, NRAS, CDK4, and MITF (log2FC = 2.86, p < 0.001). The transcription factor SOX10 and the cytokine IL-33, both previously implicated in melanoma progression, were consistently overexpressed. Additionally, NF1, a known RAS pathway inhibitor, was also upregulated. Isoform analysis revealed novel transcript variants, suggesting a complex layer of post-transcriptional regulation in COM. Many DEGs remained uncharacterized, and chromosomal distribution analysis highlighted potential genomic influences. Conclusions: Our findings provide new insights into the molecular landscape of COM, reinforcing its utility as a model for human melanoma. The identification of conserved oncogenic pathways and novel transcript variants opens avenues for further functional studies and the development of targeted therapies in both veterinary and human oncology.

Background: Chronic pelvic toxicity induced by radiotherapy and/or chemotherapy (R/CIPT) is a debilitating sequela in gynecological cancer survivors, often refractory to conventional treatments and potentially linked to gut microbiota dysbiosis. Ozone therapy (OT), particularly rectal insufflation, demonstrates anti-inflammatory and redox-modulating effects through hormetic mechanisms (Nrf2 activation/NF-κB inhibition). We hypothesize that its clinical benefit is mediated, in part, by restoring gut microbial homeostasis. Objective: This manuscript proposes a clinical study to evaluate the impact of rectal OT on the gut microbiota of patients with gynecological cancers and chronic R/CIPT. Proposed Methods: A prospective, observational study of 38 patients is outlined: 19 with CTCAE v5.0 Grade ≥2 chronic R/CIPT receiving compassionate rectal OT (~40 sessions over 4 months), and 19 matched controls without toxicity. Stool samples for 16S rRNA sequencing will be collected from the OT group pre- and post-intervention and once from controls. Primary endpoints are changes in microbiota composition/diversity and pelvic toxicity scores (CTCAE v5.0, EORTC QLQ-CX24). Secondary endpoints include quality of life (EORTC QLQ-C30, EQ-5D-5L), anxiety/depression (HADS), and serum inflammatory/oxidative stress biomarker analysis. Anticipated Results and Conclusion: This will be the first study to prospectively investigate whether rectal OT’s effect correlates with a beneficial shift in the gut microbiota, specifically an increase in commensals (e.g., short-chain fatty acids producers) and a decrease in pathobionts. If successful, OT could be assessed as a novel, microbiota-targeting intervention for R/CIPT. The findings from this pilot study will provide the necessary groundwork for a future randomized controlled trial to definitively establish causality and efficacy.