Role of migratory inhibition factor in age-related susceptibility to radiation lung injury via NF-E2-related factor-2 and antioxidant regulation.

Microvascular injury and increased vascular leakage are prominent features of radiation-induced lung injury (RILI), and often follow cancer-associated thoracic irradiation. Our previous studies demonstrated that polymorphisms in the gene (MIF) encoding macrophage migratory inhibition factor (MIF), a multifunctional pleiotropic cytokine, confer susceptibility to acute inflammatory lung injury and increased vascular permeability, particularly in senescent mice. In this study, we exposed wild-type and genetically engineered mif(-/-) mice to 20 Gy single-fraction thoracic radiation to investigate the age-related role of MIF in murine RILI (mice were aged 8 wk, 8 mo, or 16 mo). Relative to 8-week-old mice, decreased MIF was observed in bronchoalveolar lavage fluid and lung tissue of 8- to 16-month-old wild-type mice. In addition, radiated 8- to 16-month-old mif(-/-) mice exhibited significantly decreased bronchoalveolar lavage fluid total antioxidant concentrations with progressive age-related decreases in the nuclear expression of NF-E2-related factor-2 (Nrf2), a transcription factor involved in antioxidant gene up-regulation in response to reactive oxygen species. This was accompanied by decreases in both protein concentrations (NQO1, GCLC, and heme oxygenase-1) and mRNA concentrations (Gpx1, Prdx1, and Txn1) of Nrf2-influenced antioxidant gene targets. In addition, MIF-silenced (short, interfering RNA) human lung endothelial cells failed to express Nrf2 after oxidative (H2O2) challenge, an effect reversed by recombinant MIF administration. However, treatment with an antioxidant (glutathione reduced ester), but not an Nrf2 substrate (N-acetyl cysteine), protected aged mif(-/-) mice from RILI. These findings implicate an important role for MIF in radiation-induced changes in lung-cell antioxidant concentrations via Nrf2, and suggest that MIF may contribute to age-related susceptibility to thoracic radiation.

The impact of yoga in medically underserved populations: A mixed-methods study.

OBJECTIVES: We evaluated the acceptability, access, and impact of yoga among participants in yoga classes co-located in community health centers. DESIGN: Participants were invited to complete a mixed-methods program evaluation consisting of a pre/post survey at their first class and structured interviews at 4 months. SETTING: The study took place at two community health centers on the South Side of Chicago, IL, USA. INTERVENTIONS: Four weekly 1-1.5 hour yoga classes were provided by four certified yoga instructors trained to teach to all ability levels. MEASURES: Our primary outcome measures were pain and stress before and after the first class, and at 4-months. We gathered data about participant demographics, their health problems, how they accessed the classes, and motivations and barriers to attending. We also extracted themes from participants' qualitative feedback about their experiences. RESULTS: Overall, 70 participants completed the initial surveys; 44 completed the 4-month interviews. A racially and ethnically diverse group of middle- and low-income adult patients and community members attended, with flyers and word of mouth the major routes to the class. A single yoga class provided statistically significant decreases in pain and stress, but these benefits were not demonstrated at the 4-month follow-up. The primary motivators for yoga class attendance were stress relief, exercise, and overall health improvement. Primary barriers included family issues, schedule, illness, and work conflicts. Primary benefits included physical benefits, relaxation, emotional benefits, and community connectedness. CONCLUSIONS: Co-locating yoga classes in community health centers provides a variety of benefits and is a viable pathway to addressing disparities in yoga access.