Loss of weight was limited after prophylactic gastrostomy placement and early tube feeding. Moreover, the complication rate was low. In 82% of the NED patients the PEG could eventually be removed.

Unmitigated UV radiation (UVR) induces skin photoaging and multiple forms of cutaneous carcinoma by complex pathways that include those mediated by UV-induced reactive oxygen species (ROS). Upon UVR exposure, a cascade of events is induced that overwhelms the skin’s natural antioxidant defenses and results in DNA damage, intracellular lipid and protein peroxidation, and the dysregulation of pathways that modulate inflammatory and apoptotic responses. To this end, natural products with potent antioxidant properties have been developed to prevent, mitigate, or reverse this damage with varying degrees of success. Mitochondria are particularly susceptible to ROS and subsequent DNA damage as they are a major intracellular source of oxidants. Therefore, the development of mitochondrially targeted agents to mitigate mitochondrial oxidative stress and resulting DNA damage is a logical approach to prevent and treat UV-induced skin damage. We summarize evidence that some existing natural products may reduce mitochondrial oxidative stress and support for synthetically generated mitochondrial targeted cyclic nitroxides as potential alternatives for the prevention and mitigation of UVR-induced skin damage.

CCR5 is thought to play a central role in orchestrating migration of cells in response to inflammation. CCR5 antagonists can reduce inflammatory disease processes, which has led to an increased interest in using CCR5 antagonists in a wide range of inflammation-driven diseases. Paradoxically, these antagonists appear to function without negatively affecting host immunity at barrier sites. We reasoned that the resolution to this paradox may lie in the CCR5+ T cell populations that permanently reside in tissues. We used a single-cell analysis approach to examine the human CCR5+ T cell compartment in the blood, healthy, and inflamed mucosal tissues to resolve these seemingly contradictory observations. We found that 65% of the CD4 tissue-resident memory T (TRM) cell compartment expressed CCR5. These CCR5+ TRM cells were enriched in and near the epithelial layer and not only limited to TH1-type cells but also contained a large TH17-producing and a stable regulatory T cell population. The CCR5+ TRM compartment was stably maintained even in inflamed tissues including the preservation of TH17 and regulatory T cell populations. Further, using tissues from the CHARM-03 clinical trial, we found that CCR5+ TRM are preserved in human mucosal tissue during treatment with the CCR5 antagonist Maraviroc. Our data suggest that the human CCR5+ TRM compartment is functionally and spatially equipped to maintain barrier immunity even in the absence of CCR5-mediated, de novo T cell recruitment from the periphery.

Bill & Melinda Gates Foundation.