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: The current standard of care in glioblastoma multiforme (GBM), as the most morbid brain tumor, is not adequate, despite substantial progress in cancer therapy. Among patients receiving current standard treatments, including surgery, irradiation, and chemotherapy, the overall survival (OS) period with GBM is less than one year. The high mortality frequency of GBM is due to its aggressive nature, including accelerated growth, deregulated apoptosis, and invasion into surrounding tissues. The understanding of the molecular pathogenesis of GBM is, therefore, crucial for identifying, designing, and repurposing potential agents in future therapeutic approaches. In recent decades, it has been apparent that several neurotransmitters, specifically substance P (SP), an undecapeptide in the family of neuropeptides tachykinins, are found in astrocytes. After binding to the neurokinin-1 receptor (NK-1R), the SP controls cancer cell growth, exerts antiapoptotic impacts, stimulates cell invasion/metastasis, and activates vascularization. Since SP/NK-1R signaling pathway is a growth driver in many cancers, this potential mechanism is proposed as an additional target for treating GBM. Following an evaluation of the function of both SP and its NK-1R inhibitors in neoplastic cells, we recommend a unique and promising approach for the treatment of patients with GBM.

Background: Recently, there has been a global demand toward finding new treatments to control the new pandemic of coronavirus (COVID-19). The aim of this systematic review was to study the effects of ozone therapy on COVID-19 patients, as well as reviewing the available supporting evidence. Methods: Electronic databases including MEDLINE (via PubMed), EMBASE, Cochrane Library (CENTRAL), and TRIP, as well as clinical trial registries and preprint sources were searched for published evidence-based articles. In addition, a hand searching was conducted regarding the attained articles published until 6 April 2020 using MeSH and free text keywords with no language limitation. Articles were screened, categorized and extracted for the relative data, which are reported in a descriptive manner. Results: Among 234 articles, 9 were selected to be reviewed for the inclusion criteria. No previously published original articles were found on the efficacy of ozone therapy on COVID-19. Five review studies on the potential role of systemic ozone therapy were found, in which it was concluded that ozone therapy is effective in controlling COVID-19 due to its antiviral, oxygenating, anti-inflammatory, oxidation balancing and immunomodulation effects. Three ongoing clinical trials were registered in China. Moreover, a preliminary report of an ongoing study in Italy on 46 patients (11 intubated and 35 non-intubated) indicated that 39 patients (84%) showed an improvement for the symptoms of the disease. Conclusion: Despite the promising hypothetical background, opinions of the expert arguing about the benefits of this method, and a preliminary report indicating the effectiveness of ozone therapy as a novel treatment option for COVID-19, there is still not enough evidence to prove it. Hosted file Revised Ozone therapy.docx available at https://authorea.com/users/315183/articles/446123-usingozone-therapy-as-an-option-for-treatment-of-covid-19-patients-a-scoping-review