Red blood cell pyruvate kinase properties in Townes and Berkeley sickle cell disease mouse models - Of mice and men.

Pyruvate kinase (PK), a key ATP-generating enzyme in glycolysis, is a target for novel sickle cell disease (SCD) therapies. Enhancing PK activity lowers 2,3-diphosphyglycerate (2,3-DPG), increases adenosine triphosphate (ATP), and may prevent red blood cell (RBC) sickling. Townes and Berkeley SCD mouse models are commonly used for the development of novel drugs for SCD, but differ from humans in 2,3-DPG and ATP levels, which could be related to underlying differences in PK properties.

A novel composition of endogenous metabolic modulators improves red blood cell properties in sickle cell disease.

The most common forms of sickle cell disease (SCD) are sickle cell anemia (SCA; HbSS) and HbSC disease. In both, especially the more dense, dehydrated and adherent red blood cells (RBCs) with reduced deformability are prone to hemolysis and sickling, and thereby vaso-occlusion. Based on plasma amino acid profiling in SCD, a composition of 10 amino acids and derivatives (RCitNacQCarLKHVS; Axcella Therapeutics, USA), referred to as endogenous metabolic modulators (EMMs), was designed to target RBC metabolism.

Primary cerebral immunoglobulin light chain amyloidoma in a patient with multiple sclerosis.

A man in his 60s, known with multiple sclerosis, presented with seizures and paresis of the left arm and leg. Brain imaging showed a white matter lesion, right parietal, which was progressive over the last 6 years and not typical for multiple sclerosis. Brain biopsy showed a B-cell infiltrate with IgA lambda monotypic plasma cell differentiation and amyloid deposits, typed as lambda immunoglobulin light chain (AL).

Association of genetic variations in ACE2, TIRAP and factor X with outcomes in COVID-19.

Background: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can manifest with varying disease severity and mortality. Genetic predisposition influences the clinical course of infectious diseases. We investigated whether genetic polymorphisms in candidate genes ACE2, TIRAP, and factor X are associated with clinical outcomes in COVID-19.