Biology subjects

Fricker, A.

Publications and source records attributed to Fricker, A..

2 recordsLinked to original sources

bioRxiv2023

Regulation of BACH1 by hemin improves cardiac function in a mouse model of myocardial infarction

AimsThe BTB and CNC homology 1 (BACH1) transcription factor is a repressor of heme oxygenase-1 (HMOX1), a pivotal enzyme involved in antioxidant response and iron recycling. Here we investigated whether pharmacological modulation of the BACH1 by hemin impacts on antioxidant responses and reparative angiogenesis in a mouse model of myocardial infarction (MI). Methods and resultsIn vitro studies on vascular cells showed hemin treatment downregulates BACH1 gene and protein expression and upregulates HMOX1. This axis was confirmed to be modulated in the murine infarcted heart, with BACH1 being upregulated, and HMOX1 downregulated compared to sham. Treatment with hemin every 3 days for 28 days post-MI significantly decreased BACH1 and increased HMOX1 protein expression, though no decrease in oxidative stress markers was detected. Hemin treated mice showed increases in both capillary and arteriole density, and reduced iron accumulation compared with controls. Furthermore, echocardiology measurements showed hemin treatment induced significant improvements in left ventricular wall thickness, and cardiac function as indicated by increased ejection fraction, fractional shortening, and stroke volume measurements. ConclusionHemin has therapeutic potential to improve revascularisation and cardiac function in the heart post-MI.

molecular biology↗

bioRxiv2023

Interindividual Diversity of Human Gut Mucin-Degrading Microbial Consortia

Mucin is a glycoprotein secreted throughout the mammalian gastrointestinal tract that can support endogenous microorganisms in the absence of complex polysaccharides. While diverse mucin degrading bacteria have been identified, the individual host microbial community differences capable of metabolizing this complex polymer are not well described. To determine whether individuals have taxonomically distinct but functionally similar mucin-degrading communities, we used a ten-day in vitro sequential batch culture fermentation from three human donors with mucin as the sole carbon source. For each donor, 16S rRNA gene amplicon sequencing was used to characterize microbial community succession, and the short-chain fatty acid profile was determined from the final community. Although two of the final communities had genus-level taxonomic differences signified by the presence of Desulfovibrio and Akkermansia, other members, such as Bacteroides, were shared between all three final communities. Metabolic output differences were most notable for one of the donors communities, with significantly less production of acetate and propionate than the other two communities. These findings reinforce the concept of a taxonomically distinct and, at broad levels, a functionally redundant gut microbiome. Furthermore, the mechanisms and efficiencies of mucin degradation across individuals are important for understanding how this community-level process impacts human health.

microbiology↗