Chronic rhinosinusitis with eosinophilia (ECRS) is a refractory sinusitis characterized by eosinophilia in the nasal mucosa and peripheral blood. In ECRS, multiple nasal polyps are present in the ethmoid sinuses, and the disease is often accompanied by olfactory dysfunction and asthma. It is a disease that significantly impairs the quality of life of patients by causing persistent nasal congestion and thick nasal discharge, leading to decreased concentration and insomnia. From previous studies, we found that (1) defects in Cu,Zn-SOD in ECRS epithelium contribute to increased IL-17A, macrophage infiltration in the subepithelial tissue, and excessive production of mucin gene (MUC5AC) in the epithelium, thereby potentially exacerbating inflammation and excessive mucus secretion, and (2) reduced HO-1 expression in the epithelium and macrophage infiltration are associated with epithelial damage in CRS accompanied by eosinophil infiltration. These findings suggest that antioxidants may play a crucial role in elucidating the pathophysiology of refractory diseases such as ECRS and may provide new therapeutic strategies. In this paper, three new comprehensive molecular signaling pathway networks of (1) oxidative stress, (2) inflammation inhibition mechanisms and (3) inflammation in ECRS were developed for the first time, based on a critical analysis of scientific literature. In addition, three immunology flowsheets related to oxidative stress, inflammation and carbon monoxide-based inflammation inhibition mechanisms of ECRS were developed for the first time and examined from both clinical and biochemical perspectives. Based on these pathways, this study identified the treatment targets which can be used in future ECRS treatments.

Treatments for advanced head and neck cancer previously relied on radical surgery. However, radiation therapy and concurrent chemoradiotherapy, particularly using cisplatin, have gained preference due to their effectiveness and the preservation of normal tissues and their functions. A significant drawback of radiotherapy is its adverse effects, including oral mucositis, xerostomia, salivary gland dysfunction, neurological disorders, dysphagia, and dysphonia. Research in vitro, in vivo, and clinical trials has demonstrated that antioxidants effectively protect normal tissues from radiation-induced damage. However, the potential for antioxidants to compromise the tumoricidal efficacy of radiotherapy remains a subject of controversy. Clinical studies on head and neck cancer suggest that antioxidant use may negatively impact cancer control and survival outcomes. Consequently, non-selective systemic antioxidant therapy is not generally recommended. Recent advancements in the quantification of oxidative stress and biological antioxidant potential provide new opportunities to customize antioxidant therapies for individual patients. To optimize outcomes, further research is needed to elucidate the complex interactions between antioxidants, reactive oxygen species (ROS), and tumors. The development of novel antioxidant agents that can selectively protect normal tissue is also required. Subsequently, large-scale randomized controlled trials will be necessary to evaluate the efficacy of antioxidant therapies tailored to tumor characteristics and the specific conditions of individual patients. Below is the first part series of a work in progress regarding combinative antioxidant-proapoptotic therapies for head and neck cancer patients during radiotherapy.