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Introduction: The venous outflow profile (VOP) is a crucial yet often overlooked aspect affecting stroke outcomes. It plays a major role in the physiopathology of acute cerebral ischemia, as it accounts for both the upstream arterial collaterals and cerebral microperfusion. This enables it to circumvent the limitations of various arterial collateral evaluation systems, which often fail to consider impaired autoregulation and its impact on cerebral blood flow at the microcirculatory levels.

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It remains unclear why unilateral proximal carotid artery occlusion (UCAO) causes benign oligemia in mice, yet leads to various outcomes (asymptomatic-to-death) in humans. We hypothesized that inhibition of nitric oxide synthase (NOS) both transforms UCAO-mediated oligemia into full infarction and expands pre-existing infarction. Using 900 mice, we i) investigated stroke-related effects of UCAO with/without intraperitoneal administration of the NOS inhibitor (NOSi) N-nitro-L-arginine methyl ester (L-NAME, 400 mg/kg); ii) examined the rescue effect of the NO-donor, molsidomine (200 mg/kg at 30 minutes); and iii) tested the impact of antiplatelet medications.

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A major challenge in the stem cell biology field is the ability to produce fully functional cells from induced pluripotent stem cells (iPSCs) that are a valuable resource for cell therapy, drug screening, and disease modelling. Here, we developed a novel inducible CRISPR-mediated activation strategy (iCRISPRa) to drive the expression of multiple endogenous transcription factors (TFs) important for in vitro cell fate and differentiation of iPSCs to haematopoietic progenitor cells. This work has identified a key role for IGFBP2 in developing haematopoietic progenitors.

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Objective: To establish lactate and glucose differences between affected and non-affected limbs in cats with feline arterial thromboembolism (FATE). To evaluate the correlation between these values and survival to discharge as well as congestive heart failure (CHF).

Methods: Blood glucose and lactate concentrations were prospectively obtained on admission from client-owned FATE cats and client-owned cats presented for other conditions.

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Sox17 and Erg synergistically activate endothelial cell fate in reprogramming fibroblasts.

J Mol Cell Cardiol

December 2024

The McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address:

Sox17-Erg direct reprogramming is a potent tool for the in vitro and in vivo generation of arterial-like induced-endothelial cells from fibroblasts. In this study, we illustrate the pioneering roles of both Sox17 and Erg in the endothelial cell reprogramming process and demonstrate that emergent gene expression only occurs when both factors are co-expressed. Bioinformatic analyses and molecular validation reveal both Bach2 and Etv4 as integral mediators of Sox17-Erg reprogramming with different roles in lung and heart fibroblast reprogramming.

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