The class B scavenger receptors BI (SR-BI) and BII (SR-BII) are HDL receptors that recognize various pathogens, including bacteria and their products. It has been reported that SR-BI/II-null mice are more sensitive than normal mice to endotoxin-induced inflammation and sepsis. Since the SR-BI/II-knockout model demonstrates multiple immune and metabolic disorders we investigated the role of each receptor in the LPS-induced inflammatory response and tissue damage using transgenic mice with pLiv-11-directed expression of human SR-BI or SR-BII. Six hours after intraperitoneal LPS injection, transgenic hSR-BI and hSR-BII mice demonstrated markedly higher serum levels of pro-inflammatory cytokines and 2-3-fold increased expression levels of inflammatory mediators in the liver and kidney, compared to wild type (WT) mice. LPS-stimulated iNOS expression was 3-6-fold higher in the liver and kidney of both transgenic strains, although serum NO levels were similar in all mice. Despite the lower HDL plasma levels, both transgenic strains responded to LPS by a 5-fold increase of plasma corticosterone levels which were only moderately lower than in WT animals. LPS treatment resulted in MAPKs activation in tissues of all mice; however, the strongest response was detected for hepatic ERK1/2 and kidney JNK of both transgenic mice. Histological examination of hepatic and renal tissue from LPS-challenged mice revealed more injury in hSR-BII but not hSR-BI transgenic mice vs WT controls. Our findings demonstrate that hSR-BII, and to a lesser extent hSR-BI, significantly increase LPS-induced inflammation and contribute to LPS-induced tissue injury in the liver and kidney, two major organs susceptible to LPS toxicity.

Background: Alopecia is a common chief complaint and is challenging to treat. As such, regenerative treatments to promote hair growth are an emerging area of research. Exosomes, which are extracellular vesicles involved in cell communication, homeostasis, differentiation, and organogenesis, have been shown to play a central role in hair morphogenesis and regeneration with potential for use as alopecia treatment.Aims: This review summarizes and assesses the body of literature surrounding exosomes as regenerative therapeutics for alopecia and identifies areas for improvement in future research.Methods: A review was conducted using a comprehensive list of keywords including "exosome," "alopecia," and "hair loss" on PubMed, EMBASE, and Google Scholar databases published from inception to February 2022. Reference lists of identified articles were included. 47 studies were included. Clinical trial databases were searched using the term "exosome"; however, no trials relevant to hair growth were identified.Results: Our updated and comprehensive review details the history of exosome use in medicine, postulated underlying mechanisms in treating hair loss, and current clinical studies. Preclinical studies demonstrate clear benefits of exosome therapeutics in regenerative medicine and for hair loss treatment. Clinical trials demonstrate safety of exosome use in medicine, but data showing efficacy and safety of exosome therapy for alopecia are lacking. We identified several gaps in knowledge required for effective clinical translation including safety, exosome source, and optimal treatment delivery mechanism and dosage. Conclusion:Exosomes are on the horizon as an exciting therapeutic for the treatment of alopecia. Further studies and clinical trials are required.

LBA12003 Background: Radiation dermatitis (RD) secondary to radiation therapy (RT) to treat cancer reduces quality of life (QoL) and can lead to treatment interruption. The exact etiology of RD is unknown, and bacteria play a role in other inflammatory dermatoses. As our group recently showed nasal colonization with Staphylococcus aureus (SA) prior to RT was an independent predictor of grade ≥2 RD, we conducted a randomized controlled trial evaluating efficacy of bacterial decolonization (BD) to prevent RD and improve QoL. Methods: This is a randomized phase II trial comparing BD to standard of care (SC) for adult patients with breast cancer or head and neck cancer to receive fractionated (≥ 15 fractions) RT. Patients were randomized 1:1 to the BD intervention of intranasal mupirocin ointment twice daily and chlorhexidine body wash once daily for 5 consecutive days before RT start and repeated for 5 days every other week during RT or the SC arm of emollient use as needed. The primary endpoint was development of grade ≥2 RD using Criteria for Adverse Events v4.03, and planned sample size was 80 patients. Evaluation of a preliminary cohort showed wide variability of disease in grade 2 RD, so grade 2 RD was further differentiated for more refined statistical analysis: “moderate to brisk erythema” defined as grade 2 and “patchy moist desquamation” defined as grade 2 with moist desquamation (2-MD). The secondary endpoint was patient-reported QoL assessed via the SKINDEX-16 (SD-16) questionnaire before and after RT. Bacterial culture swabs of the nares and skin at RT beginning, middle, and end were obtained for both groups. Results: 80 patients were randomized 1:1 to each arm (40 BD, 40 SC) June 2019-August 2021. 78 breast and 2 head and neck cancer patients were enrolled instead of the projected 40 of each cancer type. 76 patients were included for analysis (38 BD, 38 SC). Clinical and demographic characteristics were well balanced between arms. We demonstrated prevention of RD grades 2-MD or higher in the BD arm compared to the SC arm (0/38, 0% vs 9/38, 23.68%; P=0.002). Additionally, BD resulted in a significantly lower median RD grade compared to SC (1.19±0.7 vs 1.58±0.75, P=0.019). Finally, a linear regression model showed a significant association between BD and decreased RD grade (estimate=-0.431, 95% CI: -0.7516, -0.1054; p=0.010), even when adjusting for other RD risk factors. Most patients reported no difficulty with BD and only one patient discontinued due to itch. There was no difference in QoL outcomes between arms. Conclusions: Our results support the use of a BD regimen to prevent moist desquamation in patients receiving RT for breast or head and neck cancer. Our study included mainly breast cancer patients; thus BD efficacy needs to be tested in other solid tumors receiving RT. This is the first study demonstrating efficacy of BD to reduce RD. Given the safety and availability of this regimen, we suggest adding BD to RD prophylaxis protocols. Clinical trial information: NCT03883828.