Inventory: A selection of Blood studies from August 6, 2020.

Inhibition of THEJAK/STAT path to enhance the apoptosis sensitivity of CD8 T cells to desermison-induced https://doi.org/10.1182/blood.2020006075 cytokine storm syndrome (CSS) is a severe hyper-inflammatory state characterized by excessive immune system activation, resulting in organ damage and patient death.
HLH is a typical CSS with a five-year survival rate of only 60%.
current HLH's first-line treatments include the glucocorticoid dexamination (DEX) and the chemotherapy drug etoposide, but many patients are intolerant or relapsed.
Previous studies have shown that cytokine-induced JAK/STAT signals mediat the resistance of T-cell acute lymphocytic leukemia (T-ALL) cells to desemethone, and that the JAK1/2 inhibitor Rusotini (RUX) can effectively reverse resistance.
Through in-body trials, the researchers confirmed that RUX treatment reversible HLH dexamissin resistance, and in HLH mouse models and samples of primary patients, the researchers found that HLH's high-cell kinaseemia reduced the apoptosis potential of CD8 T cells, leading to the relative resistance of dexamination.
exposure to RUX, this apoptosis potential is restored, thereby enhancing the sensitivity of CD8 T cells to dexamisson-induced apoptosis in vitro and significantly reducing the performance of tissue immunopathology and HLH disease in the body.
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . the
study recruited adult patients with medium- and high-risk bone marrow growth abnormal syndrome (MDS) or chronic myeloid mononucleotic leukemia (CMML) to be randomly assigned to oral cedazuridine/tysitaridine or dexitazbin (IV), a second course of exchange therapy;
initially in the dose determination phase, cedazuridine and tysazazine are given as separate capsules and then as single fixed dose combination (FDC) tablets.
end points of the study: average exposure levels, LINE-1 DNA decethylation percentage, and clinical response.
80 patients were treated in random groups.
the average exposure ratios of oral and IV thysin were 93.5% and 97.6%, respectively, in the FDC phase.
line-1 decethylation difference between the two groups does not exceed 1%.
48 (60%) patients received clinical remission, of which 17 (21%) received complete remission.
most common level 3 and above side effects were a decrease in neutral granulocytes (46%), a decrease in plateboard (38%) and a decrease in fever-neutral granulocytes (29%).
LUBAC promotes lymphoma formation by blocking DNA damage-induced cell death https://doi.org/10.1182/blood.2019002654 Linear Ubigen Chain Assembly Complex (LUBAC) is a key regulatory factor in the NF-kB signaling path.
LUBAC's catalytic sub-base HOIP activated mononucleotide polymorphisms were rich in active B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) patients, and HOIP with similar LUBAC activity was expressed in ABC-DLBCL samples.
researchers created a new HOIP model of mice expressing enhanced expression in B cells.
model, the study found that HOIP expression enhancement promoted the generation of DLBCL-like B-cell lymphatic tubes driven by MYD88 activation mutations.
developing lymphoma cells share some somatocytocytogene mutations with human DLBCLs, and the frequency of typical AID mutation patterns increases.
in-body analysis found that HOIP over-expression protects B cells from cell death caused by DNA damage through NF-kB activation, and analysis of human DLBCL database found a positive correlation between HOIP expression and gene labels for the regulation of apoptosis signals and NF-kB signal expression.
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . GPS), also known as alpha storage tank disease, is a rare autosomal recessive genetic hemorrhagic disease, manifested as mild plateroid reduction accompanied by large plateroids, plateboard glycoglobin normal, but plateboard alpha particles and the proteins contained in them decreased or missing.
loss of NBEAL2 (neurobeachin-like 2) function can lead to gray plateboard syndrome, and the absence of plateboard alpha particles indicates that pre-body cytocytes need NBEAL2 to produce platea.
researchers recently looked at the role of the transport protein SEC22B in alpha granules by focusing on cell membranes.
immuno-co-precipitation experiments with labeled proteins expressed by human HEK293 and cytone cell imMKCL showed that NBEAL2 can bind to SEC22B, and NBEAL2 can bind to BOTH22B and P-selectin at the same time.
also observed the binding of endogenic proteins of human macronucleary cells to NBEAL2-SEC22B through immuno-co-precipitation, and a large amount of overlap was detected by immunofluorescence microscopes.
SEC22B binding is located in an area where NBEAL2 spans 1798-1903 amino acids, and two GPS-related misalbid mutations have been found in the region: E1833K and R1839C.
once NBEAL2 has occurred in either of these mutations, it can no longer bind to THE22B, which is expressed by HEK292 cells.
the SEC22B of imMKCL cells using CRISPR/Cas9 mediated, resulting in a decrease in NBEAL2 levels and vice versa.
expression of SEC22B or NBEAL2 can also lead to the failure of alpha particles and reduced particle protein.
source: MedSci original !-- end of the show -- !-- determine whether the login ends.