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Biology subjects

Diaz, M. D.

Publications and source records attributed to Diaz, M. D..

3 recordsLinked to original sources

Uncovering the Regional and Cell Specific Bioactivity of Injectable Extracellular Matrix Biomaterials in Myocardial Infarction through Spatial and Single Nucleus Transcriptomics

Myocardial infarction (MI) remains a global health concern. To mitigate MI pathophysiology, we previously investigated a pro-reparative decellularized extracellular matrix (ECM) hydrogel for treating subacute and chronic MI. Despite increasing interest in biomaterial scaffolds, single cell and spatially resolved transcriptomics have not been used to probe their therapeutic activity in the heart. Here, we utilize spatial transcriptomics and single nucleus RNA sequencing to delineate the regional and cell-specific bioactivity of ECM biomaterials. ECM hydrogel subacute treatment induced cardiac resident macrophage preservation, fibroblast activation, and increased lymphatic, vasculature, smooth muscle and cardiomyocyte development as well as neurogenesis. Chronic treatment elicited macrophage polarization, cardiomyocyte and vasculature development, alongside fibroblast development. When comparing treatment timepoints, subacute administration had stronger immune modulation, while the chronic timepoint demonstrated higher cardiac development markers. Both subacute and chronic administration were associated with fibroblast activation and vasculature development. Thus, we elucidate undiscovered therapeutic targets of the ECM hydrogel, further demonstrating the potential of ECM biomaterials as an MI therapy.

bioengineering↗

Climatic refugia in the coldest neotropical hotspot, the Andean paramo

AimThe Andean paramo is the most biodiverse high-mountain region on Earth and past glaciation dynamics during the Quaternary are greatly responsible for its plant diversification. Here, we aim at identifying potential climatic refugia since the Last Glacial Maximum (LGM) in the paramo, according to plant family, biogeographic origin, and life-form. LocationThe paramo region in the Northern Andes MethodsWe built species distribution models for 664 plant species to generate range maps under current and LGM conditions, using five General Circulation Models (GCMs). For each species and GCM, we identified potential (suitable) and potential active (likely still occupied) refugia where both current and LGM range maps overlap. We stacked and averaged the resulting refugia maps across species and GCMs to generate consensus maps for all species, plant families, biogeographic origins and life-forms. All maps were corrected for potential confounding effect due to species richness. ResultsWe found refugia to be chiefly located in the southern and central paramos of Ecuador and Peru, especially towards the paramo ecotone with lower-elevation forests. However, we found additional specific patterns according to plant family, biogeographic origin and life-form. For instance, endemics showed refugia concentrated in the northern paramos. Main conclusionsOur findings suggest that large and connected paramo areas, but also the transitional Amotape-Huancabamba zone with the Central Andes, are primordial areas for plant species refugia since the LGM. This study therefore enriches our understanding on paramo evolution and calls for future research on plant responses to future climate change.

ecology↗

Injectable Myocardial Matrix Hydrogel Mitigates Negative Left Ventricular Remodeling in a Chronic Myocardial Infarction Model

A first-in-man clinical study on a myocardial-derived decellularized extracellular matrix (ECM) hydrogel yielded evidence for potential efficacy in ischemic heart failure (HF) patients. However, little is understood about the mechanism of action in chronic myocardial infarction (MI). In this study we investigated efficacy and mechanism by which the myocardial matrix hydrogel can mitigate negative left ventricular (LV) remodeling in a chronic model of MI. Assessment of cardiac function via magnetic resonance imaging (MRI) demonstrated preservation of LV volumes and apical wall thickening. Differential gene expression analyses showed the matrix is able to prevent worsening HF in a small animal chronic MI model through modulation of the immune response, downregulation of pathways involved in HF progression and fibrosis, and upregulation of genes important for cardiac muscle contraction.

bioengineering↗