AbstractSepsis-induced lung injury was the most common cause of death in patients. Topiroxostat, a novel xanthine oxidoreductase inhibitors, possessed obvious organ protectives effects. Xanthine oxidase played a vital role in acute lung injury. The study aimed to investigate the roles of Topiroxostat in sepsis-induced lung injury. The sepsis rats were established using cecum ligation and perforation. The lung damage induced by sepsis was evaluated by Hematoxylin and Eosin staining and lung tissue wet to dry ratio. The oxidative stress was detected by measurement of reactive oxygen species, malondialdehyde, myeloperoxidase and superoxide dismutase (SOD). The pro-inflammatory mediators, tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and monocyte chemotactic protein 1, were measured by Enzyme-Linked Immunosorbent Assay. The cell apoptosis in lung was detected by TUNNEL staining and western blot analysis of apoptosis-related proteins including pro-apoptosis proteins, Bax, cleaved caspase9, cleaved caspase3 and anti-apoptosis protein Bcl2. The results showed that Topiroxostat significantly reduced lung damage, along with decreased oxidative stress, inflammation response and apoptosis in sepsis rats. Topiroxostat exerted markedly protective effects in sepsis-induced lung injury and could be an antioxidant in treating sepsis-induced lung injury.
Background: Novel insights into the pathophysiology of GVHD highlighted the relevant role of the host inflammatory response governed by Bruton tyrosine kinase (BTK) signaling pathway. Ibrutinib is a first class, once daily inhibitor of BTK with proven efficacy in B cell lympho-proliferative diseases, was recently employed in corticosteroid-refractory chronic GVHD with encouraging overall response rates(Miklos et all, Blood 2017). We previously reported the results of 14 patients who received ibrutinib treatment for steroid-refractory cGVHD (Ilhan et all, ASH 2018) Aims: Herein, we share a real-life experience using ibrutinib in the treatment of streoid-refractory cGVHD in 30 patients from centers in Turkey. Methods: This multicenter retrospective study conducted in 9 stem cell transplant centers from Turkey included 30 adult patients diagnosed with steroid-refractory cGVHD. We treated off-label these patients from June 2017 to July 2018 with ibrutinib with a dose of 420 mg P.O. qday. Organ sites affected and cGVHD grading before starting ibrutinib were classified according to the National Institues of Health (NIH) 2014 criteria. Steroid refractory cGVHD was defined as any disease that failed to respond to previous immunosuppressive therapy with steroids at least 4 weeks or inability to taper it with or without additional immunosuppressive drugs.
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