Analysis of ANRIL Isoforms and Key Genes in Patients with Severe Coronary Artery Disease.

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.

Effects of ozone therapy on anxiety and depression in patients with refractory symptoms of severe diseases: a pilot study.

Background: Patients with refractory symptoms of severe diseases frequently experience anxiety, depression, and an altered health-related quality of life (HRQOL). Some publications have described the beneficial effect of ozone therapy on several symptoms of this kind of patient. The aim of this study was to preliminarily evaluate, in patients treated because of refractory symptoms of cancer treatment and advanced nononcologic diseases, if ozone therapy has an additional impact on self-reported anxiety and depression. Methods: Before and after ozone treatment, we assessed (i) anxiety and depression according to the Hospital Anxiety and Depression Scale (HADS); (ii) the HRQOL (according to the EQ-5D-5L questionnaire), which includes a dimension on anxiety and depression and a visual analog scale (VAS) measuring self-perceived general health. Results: Before ozone therapy, 56% of patients were on anxiolytic and/or antidepressant treatment. Before and after ozone therapy, the anxiety and depression HADS subscales (i) significantly correlated with the anxiety/depression dimension of the EQ-5D-5L questionnaire and (ii) inversely correlated with the health status as measured by the VAS. After ozone therapy, we found a significant improvement in anxiety and depression measured by both the (i) HADS subscales and (ii) EQ-5D-5L questionnaire. Conclusion: The addition of ozone therapy for patients with refractory symptoms of cancer treatment and advanced chronic nononcologic diseases can decrease anxiety and depression severity levels. Additional, more focused studies are ongoing to provide the needed explanatory information for this finding.

Effects of Ozone Treatment on Health-Related Quality of Life and Toxicity Induced by Radiotherapy and Chemotherapy in Symptomatic Cancer Survivors.

(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.