Identification of a physiologic vasculogenic fibroblast state to achieve tissue repair.

Tissue injury to skin diminishes miR-200b in dermal fibroblasts. Fibroblasts are widely reported to directly reprogram into endothelial-like cells and we hypothesized that miR-200b inhibition may cause such changes. We transfected human dermal fibroblasts with anti-miR-200b oligonucleotide, then using single cell RNA sequencing, identified emergence of a vasculogenic subset with a distinct fibroblast transcriptome and demonstrated blood vessel forming function in vivo. Anti-miR-200b delivery to murine injury sites likewise enhanced tissue perfusion, wound closure, and vasculogenic fibroblast contribution to perfused vessels in a FLI1 dependent manner. Vasculogenic fibroblast subset emergence was blunted in delayed healing wounds of diabetic animals but, topical tissue nanotransfection of a single anti-miR-200b oligonucleotide was sufficient to restore FLI1 expression, vasculogenic fibroblast emergence, tissue perfusion, and wound healing. Augmenting a physiologic tissue injury adaptive response mechanism that produces a vasculogenic fibroblast state change opens new avenues for therapeutic tissue vascularization of ischemic wounds.

Epigenetic basis of diabetic vasculopathy.

Type 2 diabetes mellitus (T2DM) causes peripheral vascular disease because of which several blood-borne factors, including vital nutrients fail to reach the affected tissue. Tissue epigenome is sensitive to chronic hyperglycemia and is known to cause pathogenesis of micro- and macrovascular complications. These vascular complications of T2DM may perpetuate the onset of organ dysfunction. The burden of diabetes is primarily because of a wide range of complications of which nonhealing diabetic ulcers represent a major component. Thus, it is imperative that current research help recognize more effective methods for the diagnosis and management of early vascular injuries. This review addresses the significance of epigenetic processes such as DNA methylation and histone modifications in the evolution of macrovascular and microvascular complications of T2DM.

Divergent changes: abstinence and higher-frequency substance use increase among racial/ethnic minority young adults during the COVID-19 global pandemic.

BACKGROUND: Identifying factors influencing substance use among racial/ethnic minorities (REM) is important given the disproportionate impact of the COVID-19 pandemic on this population. OBJECTIVES: We examined factors in four domains and hypothesized that poor mental health, negative coping behaviors, negative environmental aspects, and belonging to more vulnerable social groups would be associated with increased substance use during the pandemic. METHODS: Multiple regression was applied to longitudinal data from a college sample assessed prior (fall 2017 to spring 2019) and during (spring 2020) the pandemic (n= 323; 81.5% cisgender women; 34.5% African-American, 36.1% Asian-American, 15.5% Hispanic/Latinx, 11.8% multi-racial) to identify factors predicting current alcohol, cannabis, and nicotine use frequency (spring 2020) and change in frequency of use between springs 2019 and 2020. RESULTS: While infrequent substance use (monthly or less) decreased during the pandemic, abstinence rates increased (alcohol 39%; cannabis 18%; nicotine 18%) and higher-frequency alcohol use increased (207%-1600% 2-3 times+/week) compared to spring 2019. The strongest protective factor was change in living situation during the pandemic, associated with lower current alcohol and cannabis use. Risk factors included a history of trouble with police and impulsivity since the pandemic, both associated with higher current and increased alcohol and cannabis use. REM did not differ on most factors and the outcomes. However, a higher percentage of Asian-Americans than other REM reported living situation changes. CONCLUSION: Substance use rates diverged during the pandemic, with both increased abstinence and higher-frequency use, attributed mostly to mental health and environmental domain factors with few REM differences.