Hypoxia inducible factor 1α-driven steroidogenesis impacts systemic hematopoiesis.

Background: Glucocorticoids (GCs) are key regulators of hematopoiesis, but the effects of chronically elevated endogenous GC levels on hematopoietic stem cell (HSC) function and immune cell development remain poorly understood.

Methods: We used a mouse model with adrenocortical cell-specific deletion of hypoxia-inducible factor-1 alpha (HIF1α; P2H1), which results in sustained and systemic elevation of GC. Hematopoietic stem and progenitor cell (HSPC) populations were analyzed phenotypically and functionally.

HIF1α controls steroidogenesis under acute hypoxic stress.

Background: Hypoxia is a critical physiological and pathological condition known to influence various cellular processes, including steroidogenesis. While previous studies, including our own, have highlighted the regulatory effects of Hypoxia-Inducible Factor 1α (HIF1α) on steroid production, the specific molecular mechanisms remain poorly understood. This study investigates the role of hypoxia and HIF1α in steroid biosynthesis across multiple experimental models during acute exposure to low oxygen levels.

Glutamine withdrawal leads to the preferential activation of lipid metabolism in metastatic colorectal cancer.

Introduction: Glutamine is a non-essential amino acid that is critical for cell growth. However, the differential metabolism of l-glutamine in metastatic versus primary colorectal cancer (CRC) has not been evaluated adequately.

Materials And Methods: Differential expression of glutamine-related genes was determined in primary versus metastatic CRC.

Optimized Inhibitors of MDM2 via an Attempted Protein-Templated Reductive Amination.

Innovative and efficient hit-identification techniques are required to accelerate drug discovery. Protein-templated fragment ligations represent a promising strategy in early drug discovery, enabling the target to assemble and select its binders from a pool of building blocks. Development of new protein-templated reactions to access a larger structural diversity and expansion of the variety of targets to demonstrate the scope of the technique are of prime interest for medicinal chemists.