Structure-Activity Studies on Bis-Sulfonamide SHIP1 Activators.

The SH2-containing inositol polyphosphate 5-phosphatase 1 (SHIP1) enzyme opposes the activity of PI3K and therefore is of interest in the treatment of inflammatory disorders. Recent results also indicate that SHIP1 promotes phagolysosomal degradation of lipids by microglia, suggesting that the enzyme may be a target for the treatment of Alzheimer's disease. Therefore, small molecules that increase SHIP1 activity may have benefits in these areas.

Prediction and validation of hematopoietic stem and progenitor cell off-target editing in transplanted rhesus macaques.

The programmable nuclease technology CRISPR-Cas9 has revolutionized gene editing in the last decade. Due to the risk of off-target editing, accurate and sensitive methods for off-target characterization are crucial prior to applying CRISPR-Cas9 therapeutically. Here, we utilized a rhesus macaque model to compare the predictive values of CIRCLE-seq, an in vitro off-target prediction method, with in silico prediction (ISP) based solely on genomic sequence comparisons.

Neurologic Complications in Patients with Left Ventricular Assist Devices: Single Institution Retrospective Review.

Background: Neurologic complications are common complications encountered by patients with left ventricular assist devices (LVADs). This single-center retrospective study aims to identify the incidence and risk factors of neurologic complications and interventions in patients supported with LVADs and define the associated anticoagulation management.

Methods: Between August 2009 and August 2017, 244 patients underwent LVAD implantation.

Driveline Sepsis Presenting As Gout.

In patients with a history of gout, there could be a delay in diagnosis of a septic joint, which increases morbidity and mortality. The literature reports rare instances of coexistent gout and septic arthritis. We present a 64-year-old male with non-ischemic cardiomyopathy, supported by a HeartWare ventricular assist device, who developed a methicillin-resistant Staphylococcus aureus (MRSA) driveline infection four months after device implant.

Therapeutic potential of SH2 domain-containing inositol-5'-phosphatase 1 (SHIP1) and SHIP2 inhibition in cancer.

Many tumors present with increased activation of the phosphatidylinositol 3-kinase (PI3K)-PtdIns(3,4,5)P(3)-protein kinase B (PKB/Akt) signaling pathway. It has long been thought that the lipid phosphatases SH2 domain-containing inositol-5'-phosphatase 1 (SHIP1) and SHIP2 act as tumor suppressors by counteracting with the survival signal induced by this pathway through hydrolysis or PtdIns(3,4,5)P(3) to PtdIns(3,4)P(2). However, a growing body of evidence suggests that PtdInd(3,4)P(2) is capable of, and essential for, Akt activation, thus suggesting a potential role for SHIP1/2 enzymes as proto-oncogenes.