Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease characterized by the involvement of multiple organs. Lupus nephritis (LN) is a major risk factor for overall morbidity and mortality in SLE patients. Hence, designing effective drugs is pivotal for treating individuals with LN. Fisetin plays a senolytic role by specifically eliminating senescent cells, inhibiting cell proliferation, and exerting anti-inflammatory, anti-oxidant, and anti-tumorigenic effects. However, limited research has been conducted on the utility and therapeutic mechanisms of fisetin in chronic inflammation. Similarly, whether the effects of fisetin depend on cell type remains unclear. In this study, we found that LN-prone MRL/lpr mice demonstrated accumulation of Ki-67-positive myofibroblasts and p15INK4B-positive senescent tubular epithelial cells (TECs) that highly expressed transforming growth factor β (TGF-β). TGF-β stimulation induced senescence of NRK-52E renal TECs and proliferation of NRK-49F renal fibroblasts, suggesting that TGF-β promotes senescence and proliferation in a cell type-dependent manner, which is inhibited by fisetin treatment in vitro. Furthermore, fisetin treatment in vivo reduced the number of senescent TECs and myofibroblasts, which attenuated kidney fibrosis, reduced senescence-associated secretory phenotype (SASP) expression, and increased TEC proliferation. These data suggest that the effects of fisetin vary depending on the cell type and may have therapeutic effects in complex and diverse LN pathologies.

Not applicable *Consent to participate -(include appropriate consent statements) Not applicable *Consent for publication -(appropriate statements regarding publishing an individual's data or image) Not applicable *Availability of data and material -(data transparency)The datasets during and/or analysed during the current study available from the corresponding author on reasonable request.

The Omaha System is a popular and standard term used in community health. This scoping review aimed to update the research types and identify new usage trends for the Omaha System through articles published between 2012 and 2019. The bibliography databases PubMed, CINAHL, Scopus, PsycInfo, Ovid, and ICHUSHI and the Omaha System's Web site were used to search for publications. Research articles published between 2012 and 2019 that included "Omaha System" in the title or abstract and were written in English or Japanese were included in this review. After excluding duplicate articles, 305 articles were screened and 82 were included in our analysis. There was a median of 10.3 articles per year. The percentages for each type of use of the Omaha System to "analyze client problem," "analyze clinical process," "analyze client outcomes," and "advanced classification research" were 18.3%, 12.2%, 23.2%, and 4.9%, respectively. The reclassification of the type "others" (41.5%) included "use the Omaha System data for assessment for other than clients," "use the Omaha System data as structured data," "encode by the Omaha System code," "adopt the OS framework," "clinical information system," and "literature review." This newly reclassified category will help capture future research trends using the Omaha System.