Acceptability of HIV Prevention Approaches Among USA Faith-Based Leaders.

HIV/AIDS disproportionately impacts underserved communities in the USA. This study evaluated the acceptability of partnering with faith communities to improve HIV prevention, screening, and engagement in care with a focus on Hispanic/Latinx (H/L) communities. We engaged faith-based leaders to identify how the cultural competence and foundations of trust within these communities may be leveraged to improve HIV-related healthcare access for underserved groups including H/L individuals. Using a semi-structured qualitative interview approach, we interviewed N = 20 faith-based leaders in Providence County, Rhode Island (RI). Data were analyzed using the framework approach which utilized inductive generation of themes and systematic grouping into predetermined categories. Seven of the 20 interviewees self-identified as H/L faith leaders and discussed needs specific to H/L communities including destigmatization of HIV, increased access to care, and partnerships founded on mutual respect. The other 13 faith leaders did not personally identify as H/L but all served communities with significant H/L populations. We included these individuals given their communities already performed HIV and/or other health outreach and could provide insight into what approaches could be adapted to the needs expressed by H/L leaders. All interviewees were accepting of developing partnerships with outside organizations to engage in HIV prevention, and all identified potential solutions to identified barriers. Results suggested that faith-based outreach should be further investigated as a method of improving HIV prevention in the general and H/L populations.

Oxysterol derivatives Oxy186 and Oxy210 inhibit WNT signaling in non-small cell lung cancer.

BACKGROUND: Developmental signaling pathways such as those of Hedgehog (HH) and WNT play critical roles in cancer stem cell self-renewal, migration, and differentiation. They are often constitutively activated in many human malignancies, including non-small cell lung cancer (NSCLC). Previously, we reported that two oxysterol derivatives, Oxy186 and Oxy210, are potent inhibitors of HH/GLI signaling and NSCLC cancer cell growth. In addition, we also showed that Oxy210 is a potent inhibitor of TGF-ß/SMAD signaling. In this follow-up study, we further explore the mechanism of action by which these oxysterols control NSCLC cell proliferation and tumor growth. RESULTS: Using a GLI-responsive luciferase reporter assay, we show here that HH ligand could not mount a signaling response in the NSCLC cell line A549, even though Oxy186 and Oxy210 still inhibited non-canonical GLI activity and suppressed the proliferation of A549 cells. Further, we uncover an unexpected activity of these two oxysterols in inhibiting the WNT/ß-catenin signaling at the level of LRP5/6 membrane receptors. We also show that in a subcutaneous xenograft tumor model generated from A549 cells, Oxy186, but not Oxy210, exhibits strong inhibition of tumor growth. Subsequent RNA-seq analysis of the xenograft tumor tissue reveal that the WNT/ß-catenin pathway is the target of Oxy186 in vivo. CONCLUSION: The oxysterols Oxy186 and Oxy210 both possess inhibitory activity towards WNT/ß-catenin signaling, and Oxy186 is also a potent inhibitor of NSCLC tumor growth.