Inventory: A selection of Blood studies dated August 13, 2020.

New predictive model of drug-induced bleeding risk https://doi.org/10.1182/blood.2019004234 Drug-induced bleeding leads to higher morbidity and mortality.
, but the mechanism of bleeding disease caused by most drugs is unclear.
Most bleeding abnormalities are associated with coagulation factor dysfunction, and researchers recently established a cell-based analysis method to determine drugs that may have off-target effects that affect active vitamin K dependence (VKD) coagulation factor biosynthesis.
the study screened 727 drugs in the NIH Clinical Inclusion (NCC) library and identified 9 drugs, including the most commonly developed anticoagulant, huafarin.
complications associated with these drugs have been clinically reported, but the pathogenesis of these drugs is not clear.
further indications of the inhibitory effect of VKD on 9 commonly used drugs show that Huafarin, Lansolaquine and nitroquine are mainly targeted at vitamin K epoxy reductase (VKOR), while Aedes aegypti, chlorofazimin and AM404 mainly act on vitamin K reductase (VKR) in the vitamin K oxidation cycle.
three other drugs mainly affect the effectiveness of vitamin K in cells.
. Supplemental IL-2 can improve prognosis https://doi.org/10.1182/blood.2019001347 anaemia (AA) with two main characteristics: autoimmune response and regulatory Tregs defects for hematopoietic stem cells/progenitive cells.
researchers recently studied the mechanisms of Treg sub-group imbalances and their potential for therapeutic interventions.
, researchers have identified two mechanisms that cause confusion in Treg composition in AA patients: apoptosis of FasL-mediated dispenser interactions and relative deprivation of IL-2.
researchers found that an increase in IL-2 could improve the above-mentioned adverse mechanisms, and that when high concentrations of IL-2 were added to Treg in in-body culture, Treg, which was sourced from AA patients, could be amplification.
amplification cells express high levels of p-BCL2, leading to apoptosis tolerance.
researchers further tested the function and stability of amplification of AA Tregs cells by transplanting tumor mouse models and found that these Tregs cells inhibited the macro-clinical characteristics and tissue performance of T-cell-mediated grafts against host disease.
: New decethylation drug OR-2100 targets treatment of DNA abnormally ultra-methylation-driven ATL leukemia https://doi.org/10.1182/blood.2 019003084 Adult T-cell Leukemia-Lymphoma (ATL) is an invasive CD4-T cell blood malignancies converted by human T-cell lymphatic virus-1 (HTLV-1).
most individuals infected with HTLV-1 are asymptomatic, and only 3-5% of HTLV-1 carriers develop ATL.
recently examined the contribution of DNA methylation abnormalities to ATL leukemia.
the T cells infected with HTLV-1 and the un infected T cells can be isolated according to the expression state of CADM1 and CD7, respectively, and the differenced methylation location (DMPs) of the T cells of HTLV-1 infection can be identified by the whole genome DNA methylation spectrum.
accumulation of DNA at ultra-methylation DMPs is closely related to the development of ATL.
found 22 genes in T-cells infected with HTLV-1 that were expressed by the launcher hyper methylation, including THIPS, LAIR1, and RNF130, which negatively regulate T-cell receptoir (TCR) signaling.
in the cell line infected with HTLV-1, the phosphorylation of the TCR signal transdulator ZAP-70 is abnormal, but the phosphorylation of ZAP-70 can be normalized by REMIS re-expression.
in mouse models, tetumated (DAC) and OR-2100 (OR21) inhibit ATL cell growth, accompanied by low methylation of the overall DNA.
. Immune regulator molecular target CRBN regulatory CD8-T cell activation https://doi.org/10.1182/blood.2019003257 immunomodyning drugs (e.g. saridodamine) can enhance the effect of T-cell function.
Cereblon (CRBN), a substate receptor of the DDB1-cullin-RING E3 Ubiquitin enzyme complex, is the only confirmed target for immunomodulated drug action.
researchers recently examined the role of CRBN in the feedback loop that uses antigen-specific CD8-T cell effect responses.
studies have found that the lack of CD8-T cell CRBN in mice enhances their central metabolism, manifested in increased bioeneminal energy, increased polyamine hyperphysiological levels after the transport of glucose and amino acids, and increased expression of metabolic enzymes (polyamine biosynthetic enzyme bird ammonia deacetase).
important, treating with Cyleblon regulatory compounds can similarly enhance the central metabolism of human CD8-T cells.
it is worth noting that the lack of metabolic regulation of CD8-T cells by regulating compounds or CRBN is associated with the increase and continuous expression of myC, the main metabolic regulatory factor.
Finally, CRBN defective T-cells have enhanced antigen-specific cell dissolution activity in melanoma cells, both in and out of the body, and can promote accelerated highly invasive graft resistance to host disease.
source: MedSci original !-- end of the show -- !-- determine whether the login ends.