Functional characterization of novel compound heterozygous missense gene variants causing congenital dyshormonogenic hypothyroidism.

Introduction: The sodium/iodide symporter (NIS) mediates active iodide accumulation in the thyroid follicular cell. Biallelic loss-of-function variants in the NIS-coding gene cause congenital dyshormonogenic hypothyroidism due to a defect in the accumulation of iodide, which is required for thyroid hormonogenesis.

Objective: We aimed to identify, and if so to functionally characterize, novel pathogenic gene variants in a patient diagnosed with severe congenital dyshormonogenic hypothyroidism characterized by undetectable radioiodide accumulation in a eutopic thyroid gland, as well as in the salivary glands.

Biomarkers of endothelial dysfunction and cytokine levels in hypothyroidism: a series of meta-analyses.

Background: Hypothyroidism (HT) is associated with different comorbidities comprising increased arterial stiffness and decreased flow-mediated dilatation. The exact pathological mechanism of endothelial activation and dysfunction (ED) in HT remains unknown. We conducted a systematic review and meta-analyses to provide an overview of the pathogenesis of ED in HT.

Systematic review and meta-analyses of adipokine levels in hypothyroidism: a role for retinol-binding protein 4.

Background: Hypothyroidism (HT) is associated with numerous well-characterized comorbidities and established biomarkers for subclinical atherosclerosis which may lead to an elevated risk of cardiovascular disease; however, the precise molecular mechanism underlying these pathological features remains elusive. Increased levels of adipokines may have adverse effects on multiple atherosclerotic risk factors in HT. Different studies have evaluated the association between HT and adipokines with conflicting results.

KBTBD4-mediated reduction of MYC is critical for hematopoietic stem cell expansion upon UM171 treatment.

Ex vivo expansion of hematopoietic stem cells (HSCs) is gaining importance for cell and gene therapy, and requires a shift from dormancy state to activation and cycling. However, abnormal or excessive HSC activation results in reduced self-renewal ability and increased propensity for myeloid-biased differentiation. We now report that activation of the E3 ligase complex CRL3KBTBD4 by UM171 not only induces epigenetic changes through CoREST1 degradation but also controls chromatin-bound master regulator of cell cycle entry and proliferative metabolism (MYC) levels to prevent excessive activation and maintain lympho-myeloid potential of expanded populations.