Doklady Biochemistry and Biophysics最新文献

Today, breast cancer (BC) occupies a leading position in prevalence and mortality from oncological diseases among the female population worldwide. Ferroptosis is a special type of cell death associated with peroxidation of intracellular lipids. It is a promising option for the therapy of BC resistant to traditional methods of treatment. The ELOVL5 gene, involved in the elongation of long-chain polyunsaturated fatty acids (LC-PUFA), was previously associated with BC progression. In this work, the effect of ELOVL5 knockdown on the dynamics of ferroptosis induction in MDA-MB-231 cells under the influence of docosahexaenoic acid (DHA) and erastin was investigated. A comparative analysis of changes in the expression of individual genes under the influence of these agents was also carried out. It was shown that a decrease in ELOVL5 expression increases cell sensitivity to both agents, while DHA causes earlier cell death. The protective effect of ferroptosis inhibitors (ferrostatin-1 and deferoxamine) confirmed the involvement of this pathway in the observed effects. Differences in the expression of genes associated with oxidative stress, inflammation and proliferation were also revealed, indicating different molecular trajectories of ferroptosis in cells with different ELOVL5 gene expression. Thus, the present study deepens the understanding of the contribution of the ELOVL5 gene to the regulation of ferroptosis and can be used in the development of targeted therapy for breast cancer.

The tomato gene Mi-1,2 is currently the only commercially available source of resistance to the root-knot nematode Meloidogyne incognita, which loses activity when soil temperatures exceed 28°C. The study aimed to investigate the components of the tomato immune system to root-knot nematode associated with salicylic acid (SA) at elevated (34°C) and normal (25°C) temperatures. The obtained results showed that the Mi-1,2-mediated immune response is disrupted at 34°C. At elevated temperatures in plants infested with nematodes, the synthesis of salicylic acid and the activity of phenylalanine ammonia lyase are reduced, and catalase is inhibited, a decrease in the activity of which was discovered at the stage of nematode penetration into the roots and the creation of feeding structures-giant cells. Elevated temperature decreased the activity of the PR-1 gene, a marker of systemic plant resistance. These results provide important information on the sensitivity temperature of the Mi-1.2 resistance gene and the effect of elevated temperature on SA-dependent components of the immune system that are associated with tomato resistance to the nematode.

The interplay between innate immunity and other signaling pathways remains a central focus in immunological research, with considerable ongoing investigation. Of particular interest are studies exploring the influence of the hormonal system on the innate immunity of Drosophila melanogaster. In this study, we performed a comprehensive analysis of the combined effects of the insect hormone 20-hydroxyecdysone (20E) and spores from the fungus Metarhizium anisopliae on the innate immune response in D. melanogaster S2 cell culture, addressing this interaction for the first time. Our results demonstrate that, compared to cells exposed solely to M. anisopliae spores, pretreatment with 20E followed by fungal challenge led to a reduction in the transcription of antimicrobial peptide genes CecropinA1 and Drosocin. In contrast, expression of the Metchnikowin (Mtk) gene was upregulated. No significant alterations were observed in the transcription levels of Drosomycin or in genes encoding key receptors, transcription factors, or other components of innate immune signaling pathways. Furthermore, knockdown of the transcription factor Relish markedly decreased Mtk expression, highlighting its central role in hormone-modulated antifungal immunity. These findings reveal complex hormonal-immune crosstalk that differentially regulates AMP gene expression in Drosophila.

MLE/DHX9 is a DNA/RNA helicase that performs important functions in gene expression regulation in eukaryotes. However, the specific role of MLE and the mechanisms by which this regulation is carried out remain poorly understood. This work is devoted to the study of the effect of MLE on the constitutive expression of nuclear receptor genes in D. melanogaster. The nuclear receptors Eip75B, DHR3, and Hr4 are evolutionarily conserved and have orthologs in humans. In D. melanogaster, Eip75B, DHR3, and Hr4 are activated in the ecdysone cascade, but they are also expressed at a stable level in various tissues and at various stages of development. The experiments were carried in vivo at the imago stage in females and in S2 cell culture. Taken together, the results indicate that MLE is involved in activating the expression of these genes. At the same time, the helicase activity of MLE is not necessary for activation. The results obtained extend knowledge about the functions of MLE beyond dosage compensation, as potentially conserved in evolution, and contribute to understanding the mechanisms of regulation of nuclear receptor expression.

The regularities of tumor induction and growth in mice were studied during a single ex vivo irradiation of Ehrlich adenocarcinoma ascites cells with a beam of protons, helium ions (⁴Не), and carbon ions (¹²С) at doses of 10, 20, and 30 Gy. It was shown that, when tumor cells were exposed to all types of radiation, a dose-dependent increase in the antitumor effect was observed in the latent period of tumor appearance, the frequency of their induction, and tumor growth inhibition. According to all indices, ¹²C had the greatest antitumor effect, ⁴He occupied an intermediate position, and protons caused the least effect.

A comparative structural-phylogenetic and expression analysis of the SNAT1 and SNAT2 genes of tomato Solanum lycopersicum and garlic Allium sativum was performed. It was shown that the SNAT1 and SNAT2 are intron-rich and intronless genes, respectively, and may have different evolutionary origins. It was predicted that, unlike the chloroplast protein SNAT1, SNAT2 has features of chloroplast-mitochondrial localization. The highest expression level of SNAT1 and SNAT2 was detected (in silico and qRT-PCR) in leaves, while in roots and mature storage organs it was significantly lower; SNAT2 was not expressed in garlic roots and bulbs. It was found that the expression level of SNAT2 in tomato plant organs is higher than the expression level of SNAT1, while for garlic the opposite ratio was observed.

The effect of low-intensity femtosecond laser radiation (200 fs, 525 nm, 5 mW) on cognitive abilities of mice at late stages after exposure was studied. Open field and Barnes maze tests were performed 5 months after a single irradiation to assess general activity, anxiety level, and spatial learning ability. Irradiated animals retained normal motor skills, did not show anxiety, and demonstrated stable long-term memory when performing spatial learning tasks. Irradiated mice showed no changes in the model of locomotor and psychoemotional behavior or disturbances in spatial learning and memory, while they better preserved the memory trace on the 9th day after training compared to control animals. The obtained results indicate the potential of photobiomodulation with femtosecond pulses as a promising non-drug method for the prevention and correction of cognitive impairment, including those caused by radiation therapy.

The fatty acid (FA) composition of the mantle, foot (muscle), and hepatopancreas of the European pearl mussel Margaritifera margaritifera from the Kem River (estuary), the Ukhta River, and the Vozhma River (Republic of Karelia, Russia) was studied for the first time. All tissues of the pearl mussel from the studied rivers were shown to have a higher content of saturated and polyunsaturated FAs compared to monounsaturated ones, which may be due to the post-spawning period. In the hepatopancreas of the pearl mussel, a predominance of polyunsaturated FAs due to the FAs of n-3 family, as well as a higher amount of 16:1(n-7), 18:1(n-7), 18:3(n-3), 20:5(n-3), and 22:6(n-3) FAs and a lower amount of 16:0, 18:0, 18:1(n-9), 20:1(n-11), and 20:4(n-6) FAs compared to the foot and mantle was shown. An important distinctive feature of M. margaritifera is the high amount of 20:1(n-11) FA. Mollusks from the Kem River estuary were distinguished by a higher content of 18:0 and 20:5(n-3) FAs in all the studied tissues and a lower content of 18:1(n-7), 18:2(n-6), and 22:6(n-3) FAs. The obtained data are important for monitoring work to assess the state of pearl mussel populations in different rivers of the European North (in particular, using physiological and biochemical indices).

Despite significant progress in oncotherapy, oncological diseases continue to pose a serious problem for public health. The limited penetration of nanoscale therapeutic drugs into solid tumors, due to the presence of tight intercellular junctions, does not allow achieving therapeutically effective drug concentrations in distal tumor cells, which leads to the appearance of drug resistance. In this work, to increase the accumulation of HER2-specific small gold nanoparticles (DARPin-AuNPs) in solid tumors, the use of these particles in combination with the protein-opener of desmoglein junctions (junction opener 4, JO-4) is proposed. A quantitative assessment of gold biodistribution in mice showed that co-administration of DARPin-AuNP/JO-4 in vivo increased particle accumulation in tumors by approximately 2.5-fold compared to administration of DARPin-AuNP alone.

The expression profile of the key carotenoid biosynthesis genes (ZmPSY1, ZmPSY2, ZmLcyE) was determined in the dynamics of cold stress and post-stress recovery in the leaves of Zea mays L. plants of four cold-tolerant (breeders’ data) inbred lines (L-5580-1, L-6097-1, L-5254-3, and L-5272-6). It was shown that, under normal growing conditions, the expression level of all three genes in the L-5580-1 line was significantly higher compared to other lines. It was revealed that low-temperature exposure affects the trends of gene expression fluctuations in a similar way between the lines. It was determined that, in the stress dynamics, the co-expression pattern of the ZmPSY1 and ZmPSY2 genes in the leaves of L-5580-1 plants is coordinated with changes in the carotenoid content.