Discussion
respiratory disease, non-metastatic gastric cancer, cancers, dyspnea, fatigue, COVID-19 disease, fever, inflammation, viral infection, ARDS, cough, multiple sclerosis, gastric cancer
ADVERSE REACTIONS, CANCERS, VIRUS, INFILTRATION, AUTOIMMUNE DISORDER, OXIDATIVE STRESS, INFLAMMATION, VIRAL INFECTION, AUTOIMMUNE ENCEPHALOMYELITIS, INFLAMMATION, SYNDROME, MULTIPLE SCLEROSIS, ATYPICAL PNEUMONIA, EVENTS, OXIDATIVE STRESS, ARDS, ACUTE RESPIRATORY DISTRESS SYNDROME, GASTRIC CANCER
CCS is a pathological and systemic inflammatory syndrome involving increased levels of circulating cytokines and immune-cell hyperactivation which can be triggered by various therapies, pathogens, cancers, autoimmune conditions, etc.The clinical signs of COVID-19 range greatly, from moderate to severe cases of atypical pneumonia, with some developing acute respiratory distress syndrome (ARDS), which frequently necessitates invasive mechanical ventilation and is the major cause of mortality. The severity of the respiratory disease caused by SARS-CoV-2 is thought to be largely owing to an increased immunological response to the virus and CCS [Oxidative stress is a hallmark of inflammation and COVID-19 disease, which is connected to the CSS seen in patients with severe COVID-19 [In viral infections, changes occur in the body’s iron metabolism aiming to seize iron and limit the virus’s access to this vital metal. However, these events, which are centered on proinflammatory cytokines including IL-6, lead to altered iron metabolism and increased oxidative stress via the Fenton reaction, which results in ferroptosis and the continuation of oxidative harm to biomolecules that finally damage the organs in the body [Inflammation, oxidative stress, and altered iron homeostasis are inextricably connected at a systemic level [As a result, given the vital role of this element for hemoglobin synthesis and other physiological processes, iron chelation therapy can be used as a strategy for managing iron dis-homeostasis with the aim of iron redistribution and sequestration to make iron inaccessible to viruses, while preventing its excretion. It should be noted that the existing iron chelators have many limitations making them incapable of such smart therapeutic behavior. Among the existing chelators, deferiprone has shown higher capability to redistribute iron in various experiments [In the previous studies, we reported the successful effects of BCc1 nanochelating-based iron chelator in animal and clinical studies. This nanomedicine increased the survival and quality of life of metastatic and non-metastatic gastric cancer patients without any side effects [Given the proven impact of iron and selenium on the immune system and in light of the results of the previously reported study on BCc1 nanomedicine (Fig. The schema of the proposed mechanism for the inhibitory effects of combination therapy by BCc1 and Hep-S nanomedicines on COVID-19. According to the previous studies conducted on BCc1 nanomedicine and the well-known role of selenium and iron elements on inflammatory cytokines level regulation, the immune system response against viral infection and the activity of antioxidant enzymes, the above pathways are suggested as effective mechanisms in combination therapy by these nanomedicinesThe results showed that adding the combination therapy of BCc1 and Hep-S nanomedicines to the standard treatment of hospitalized COVID-19 patients had no negative effect on their hematological and biochemical parameters. As explained in the “Results” section, the characteristics linked to the physiological function of iron, such as hemoglobin, red blood cell count, and hematocrit, were assessed in this study, and the results showed that despite the iron-chelating property of BCc1, the combination therapy of BCc1 and Hep-S had no negative impact on the indices. The results of this study were in line with the results of the study on gastric cancer patients conducted by Hafizi et al., demonstrating that the 18-month consumption of BCc1 nanomedicine had no negative effect on hematological indices compared to the placebo group [Studies have reported an increase in the plasma levels of IL-6 and TNF-alpha in hospitalized COVID-19 patients [Since IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) in COVID-19 patients has been evaluated in numerous studies. Some showed the beneficial effect of this medicine on reducing mortality rate and hospitalization time [In the present study, consuming the combination of BCc1 and Hep-S nanomedicines reduced IL-6 cytokine significantly and could also reduce the numeral value of TNF-α. In addition, the comparison of the treatment and placebo groups showed that these two nanomedicines could decrease the IL-6/IFN-γ ratio; the higher this ratio is, the more serious the CSS and damage to the lungs will be [According to studies on the prevalence of clinical symptoms of COVID-19, cough, fatigue, fever, and dyspnea are the most common hallmarks in COVID-19 patients [Studies show that iron chelation exhibits antiviral and immunomodulatory effects in vitro [Previous studies on nanochelating-based structures have evaluated and proved the immunomodulatory effects of these structures. In an animal model of multiple sclerosis as an autoimmune disorder, Fakharzadeh et al. showed that MSc1 nanochelating-based iron chelator could prompt therapeutic behavior, improve the disabling features of experimental autoimmune encephalomyelitis, and decrease lymphocyte infiltration in the central nervous system [Thus, it seems that the nanochelating technology has presented a new generation of immunomodulators with unique structures that do not suffer from limitations such as adverse reactions.