Studying Signaling Pathway Activation in TRAIL-Resistant Macrophage-Like Acute Myeloid Leukemia Cells.

Acute myeloid leukemia (AML) is a malignant neoplasm characterized by extremely low curability and survival. The inflammatory microenvironment and maturation (differentiation) of AML cells induced by it contribute to the evasion of these cells from effectors of antitumor immunity. One of the key molecular effectors of immune surveillance, the cytokine TRAIL, is considered a promising platform for developing selective anticancer drugs. Previously, under in vitro conditions of the inflammatory microenvironment (a three-dimensional high-density culture of THP-1 AML cells), we demonstrated the emergence of differentiated macrophage-like THP-1ad clones resistant to TRAIL-induced death. In the present study, constitutive activation of proinflammatory signaling pathways, associated transcription factors, and increased expression of the anti-apoptotic BIRC3 gene were observed in TRAIL-resistant macrophage-like THP-1ad AML cells. For the first time, a bioinformatic analysis of the transcriptome revealed the main regulator, the IL1B gene, which triggers proinflammatory activation and induces resistance to TRAIL in THP-1ad macrophage-like cells.

[Effect of erastin and G3139 on rat liver mitochondria in chronic alcoholic intoxication]. / Vliianie érastina i G3139 na mitokhondrii pecheni krys pri khronicheskoi alkogol'noi intoksikatsii.

The effect of modulators of VDAC channels - G3139 and erastin on the mitochondrial permeability transition pore (mPTP) functioning and changes in the content of proteins involved in regulation of mPTP (VDAC, CNPase, and TSPO) has been investigated in liver mitochondria of rats with chronic alcohol intoxication. It was shown that the mitochondria of rats treated with ethanol were more sensitive to mPTP induction. Moreover, ethanol induced changes in the expression of mPTP regulator proteins. G3139 and erastin were also able to influence the studied mitochondrial parameters, and they increased their effect in the liver mitochondria of rats treated with ethanol, as compared to the mitochondria of control rats. We hypothesize that the results of this study may help to elucidate the mechanisms of chronic action of ethanol on mitochondria and contribute to the development of new therapeutic strategies for treating the consequences of ethanol-related diseases.

Study of Biointegration and Elastic-Strength Properties of a New Xenopericardium-Based Biomaterial for Reconstructive Cardiovascular Surgery.

We analyzed biocompatibility, elastic-strength properties, and biointegration potential of a new biomaterial made of xenopericardium for reconstructive cardiovascular surgery. The biomaterial manufactured by the proposed technology demonstrated high biocompatibility and biointegration potential and its elastic-strength properties 2-4-fold surpassed that of native pericardium. The obtained results attested to good prospects of using the proposed technology for preparing biomaterials for reconstructive cardiovascular surgery.