Deficiency of thioredoxin-interacting protein results in age-related thrombocytopenia due to megakaryocyte oxidative stress.

Background: Platelets are generated from megakaryocytes (MKs), mainly located in the bone marrow (BM). Megakaryopoiesis can be affected by genetic disorders, metabolic diseases, and aging. The molecular mechanisms underlying platelet count regulation have not been fully elucidated.

Additive Effect of CD73 Inhibitor in Colorectal Cancer Treatment With CDK4/6 Inhibitor Through Regulation of PD-L1.

Background & Aims: Although cancer immunotherapies are effective for advanced-stage cancers, there are no clinically approved immunotherapies for colon cancers (CRCs). Therefore, there is a high demand for the development of novel therapies. Extracellular adenosine-mediated signaling is considered a promising target for advanced-stage cancers that are nonresponsive to programmed death 1 (PD-1)-/programmed death-ligand 1 (PD-L1)-targeted immunotherapies.

Emerging Approaches for Solid Tumor Treatment Using CAR-T Cell Therapy.

Cancer immunotherapy is becoming more important in the clinical setting, especially for cancers resistant to conventional chemotherapy, including targeted therapy. Chimeric antigen receptor (CAR)-T cell therapy, which uses patient's autologous T cells, combined with engineered T cell receptors, has shown remarkable results, with five US Food and Drug Administration (FDA) approvals to date. CAR-T cells have been very effective in hematologic malignancies, such as diffuse large B cell lymphoma (DLBCL), B cell acute lymphoblastic leukemia (B-ALL), and multiple myeloma (MM); however, its effectiveness in treating solid tumors has not been evaluated clearly.

The Gata1 murine megakaryocyte-erythroid progenitor cells expand robustly and alter differentiation potential.

GATA1 is a master transcription factor of megakaryopoiesis and erythropoiesis, and loss-of-function mutation can induce accumulation of megakaryocyte-erythroid progenitors (MEPs) in mice and humans. Accordingly, the murine MEP cell line (termed G1ME2 cells) encoding doxycycline (dox)-inducible anti-Gata1 shRNA on Hprt locus has been developed. The cells were CD41CD71KIT, expand under dox, stem cell factor, and thrombopoietin (TPO), and terminally differentiate into erythroid cells or megakaryocytes upon removal of dox.

Graft bending angle of the reconstructed posterior cruciate ligament gradually decreases as knee flexion increases.

Purpose: The purpose of the study was to determine the change in the graft bending angles at the femoral and tibial tunnel aperture in single-bundle posterior cruciate ligament (PCL) reconstruction. It was hypothesized that different knee flexion and different tunnel directions may affect changes of the femoral and tibial graft bending angle.

Methods: The right knees of 12 male subjects were scanned with a high-resolution computed tomography scanner at 4 different knee flexion angles (0°, 45°, 90° and 135°).