Triple combination of vemurafenib, cobimetinib, and atezolizumab in real clinical practice in the Russian Federation: results of the A1 cohort of the ISABELLA study.

Background: Among several treatment options for BRAF-mutant metastatic melanoma, a combination of BRAF inhibitor, MEK inhibitor, and anti-PDL1 antibody seems to be a new emergent approach recently registered in the Russian Federation. It is still not clear which patient population benefits more from this simultaneous use of three drugs instead of its sequencing.

Aim: This study aimed to evaluate patients' characteristics treated in real practice in 14 Russian regions by triple combination and to analyze their outcomes depending on biomarkers (PD-L1 expression).

Exposure of volunteers to microgravity by dry immersion bed over 21 days results in gene expression changes and adaptation of T cells.

The next steps of deep space exploration are manned missions to Moon and Mars. For safe space missions for crew members, it is important to understand the impact of space flight on the immune system. We studied the effects of 21 days dry immersion (DI) exposure on the transcriptomes of T cells isolated from blood samples of eight healthy volunteers.

The impact of short-term confinement on human innate immunity.

During space missions cosmonauts are exposed to a myriad of distinct stressors such as radiation, overloads, weightlessness, radiation, isolation in artificial environmental conditions, which causes changes in immune system. During space flights it is very difficult to determine the particular factor associated with the observed immunological responses. This makes ground-based experiments examining the effect of each space flight associated factor along of particular value.

Epileptiform GluN2B-driven excitation in hippocampus as a therapeutic target against temporal lobe epilepsy.

GluN2B is an NMDAR subunit that displays restricted expression in the mature hippocampus - a structure playing a major role in temporal lobe epilepsy. However, the contribution of GluN2B to the pathophysiology of the condition has not been fully explored. Here we combined status epilepticus models of temporal lobe epilepsy, protein expression studies, and patch-clamp experiments to demonstrate the profound change in the nature of glutamatergic transmission mediated in the epileptiform hippocampus by a subpopulation of GluN2B-containing NMDAR receptors.

New Hybrid Compounds Combining Fragments of Usnic Acid and Thioether Are Inhibitors of Human Enzymes TDP1, TDP2 and PARP1.

Tyrosyl-DNA phosphodiesterase 1 (TDP1) catalyzes the cleavage of the phosphodiester bond between the tyrosine residue of topoisomerase 1 (TOP1) and the 3' phosphate of DNA in the single-strand break generated by TOP1. TDP1 promotes the cleavage of the stable DNA-TOP1 complexes with the TOP1 inhibitor topotecan, which is a clinically used anticancer drug. This article reports the synthesis and study of usnic acid thioether and sulfoxide derivatives that efficiently suppress TDP1 activity, with IC values in the 1.