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Analysis of genes regulated by DUX4 via oxidative stress reveals potential therapeutic targets for treatment of facioscapulohumeral dystrophy
Redox Biology. 2021. Vol. 43. Article 102008.
Karpukhina A., Galkin I., Ma Y., Dib C., Zinovkin R., Pletjushkina O., Chernyak B., Popova E., Vassetzky Y.
Muscles of patients with facioscapulohumeral dystrophy (FSHD) are characterized by sporadic DUX4 expression and oxidative stress which is at least partially induced by DUX4 protein. Nevertheless, targeting oxidative stress with antioxidants has a limited impact on FSHD patients, and the exact role of oxidative stress in the pathology of FSHD, as well as its interplay with the DUX4 expression, remain unclear. Here we set up a screen for genes that are upregulated by DUX4 via oxidative stress with the aim to target these genes rather than the oxidative stress itself. Immortalized human myoblasts expressing DUX4 (MB135-DUX4) have an increased level of reactive oxygen species (ROS) and exhibit differentiation defects which can be reduced by treating the cells with classic (Tempol) or mitochondria-targeted antioxidants (SkQ1). The transcriptome analysis of antioxidant-treated MB135 and MB135-DUX4 myoblasts allowed us to identify 200 genes with expression deregulated by DUX4 but normalized upon antioxidant treatment. Several of these genes, including PITX1, have been already associated with FSHD and/or muscle differentiation. We confirmed that PITX1 was indeed deregulated in MB135-DUX4 cells and primary FSHD myoblasts and revealed a redox component in PITX1 regulation. PITX1 silencing partially reversed the differentiation defects of MB135-DUX4 myoblasts. Our approach can be used to identify and target redox-dependent genes involved in human diseases.
Logvenkov S. A., Известия РАН. Механика жидкости и газа 2026 № 3 С. 59–75
The problem of the evolution of cell volume fraction in a spherical aggregate composed of cells,
extracellular matrix, and fluid is considered. The aggregate is surrounded by extracellular matrix. The
problem formulation employs a multiphase model of a biological continuum, previously developed by the
author, consisting of two actively interacting solid phases and a fluid. The propagation of ...
Added: October 20, 2026
Liaukovich K., Zhurnal Vysshei Nervnoi Deyatelnosti Imeni I.P. Pavlova 2026 Vol. 76 No. 5 P. 587–598
Added: October 19, 2026
Nersisyan A., Frontiers in Molecular Biosciences 2026 Vol. 13 Article 1995001
Antiviral activity is commonly summarized using endpoint measures such as EC50 or EC90, yet these quantities emerge from a dynamic biological system and depend on viral replication kinetics, host-cell properties, experimental design, and the assay used to quantify infection. Infectious-virus titers, viral RNA, infected-cell fractions, viability measurements, and immune readouts capture different components of the ...
Added: October 15, 2026
Тукачев Н. В., González-Jiménez M., Ramakrishnan G. et al., Physical Chemistry Chemical Physics 2021 Vol. 23 No. 23 P. 13250–13260
Low-frequency vibrations play an essential role in biomolecular processes involving DNA such as gene expression, charge transfer, drug intercalation, and DNA–protein recognition. However, understanding the vibrational basis of these mechanisms relies on theoretical models due to the lack of experimental evidence. Here we present the low-frequency vibrational spectra of G-quadruplexes (structures formed by four strands ...
Added: October 14, 2026
Батова О. Н., Савинецкая Л. Е., Проявка С. В. et al., Nature Conservation Research. Заповедная наука 2026 Т. 11 № 4 С. 25–39
Spermophilus suslicus is a threatened species listed in Red Data Books at all levels (from regional Red Data
Books to the IUCN Red List of Threatened Species), and it currently requires special conservation activity.
Over the past 30–50 years, its range has changed from continuous to mosaic, and its population has declined
everywhere. In 2015, in Russia experimental ...
Added: October 13, 2026
Temereva E., Zoologischer Anzeiger 2026 Vol. 325 P. 182–195
Brachiopoda is a group of animals, that is still insufficiently studied at the ultrastructural level, despite the significance of ultrastructure of tissues and organs for analysing the functional morphology, reconstructing the organisation and biology of numerous extinct brachiopods, and establishing relationships among major taxa. In the present study, we provide a revised reconstruction of the ...
Added: October 11, 2026
Ekaterina D. Riumina, Klink G. V., Alekseeva E. et al., PNAS, США 2026 Vol. 123 No. 35 P. 1–20
The role of escape from the cytotoxic T cell (CTL) response in SARS-CoV-2 evolution remains controversial. Here, we study the origin and spread of SARS-CoV-2 variants whose mutations reduce presentation by the HLA class I alleles common in human populations. We find that 35% of mutations that are characteristic of the variants of concern, and ...
Added: October 2, 2026
Aly Ismailov, Poptsova M., Plos One 2026 Vol. 21 No. 9 Article e0355902
Added: October 2, 2026
Knyazev E., Чеботарева О. Е., М.: Издательский дом НИУ ВШЭ, 2026.
This teaching and learning guide provides a concise overview of the theoretical and practical aspects of the basic skills required to work in a biological laboratory. It also includes protocols for practical classes conducted as part of the introductory professional training placement for first-year students in the Bachelor’s programme in Cell and Molecular Biotechnology at ...
Added: September 30, 2026
Ryskina H., Knyazev E., Вопросы биологической, медицинской и фармацевтической химии 2026 Т. 29 № 9 С. 84–91
Introduction. The active integration of rapidly developing omics and computer technologies in the 21st century has led to a breakthrough in understanding the principles of the functioning of living systems. One of the dynamically developing integrative areas in biology is biological modeling. The fundamental paradigm has been the methodology that allows for the prediction of ...
Added: September 29, 2026
Lin Z., Duan K., Wan R. et al., Advanced Science 2026 P. 1–13
Targeted protein degradation represents a promising therapeutic strategy, yet its broader application is often limited by the scarcity of usable E3 ligases. Glutathione peroxidase 4 (GPX4) is a key target for inducing ferroptosis, but achieving sustained and potent inhibition remains challenging with conventional enzymatic inhibitors. Herein, we report the first small‐molecule GPX4 degraders that incorporate ...
Added: September 26, 2026
Diachkova E., Nikulin D., Кубкин Я. В. et al., American Journal of Respiratory and Critical Care Medicine 2026 Vol. 212
Accurate classification of a patient with pulmonary hypertension (PH) into one of five groups is fundamental for appropriate disease management strategies. The time from disease onset to correct diagnosis is unacceptably long in many cases. Chronic thromboembolic pulmonary hypertension (CTEPH) develops as a consequence of venous thromboemboli, resulting in a more pronounced hereditary predisposition to ...
Added: September 23, 2026
Pogodaeva S. S., Miletina O. O., Mammadova L. V. et al., Frontiers in Bioscience - Landmark 2026 Vol. 31 No. 4 Article 48544
Background: Neuroblastoma (NB), a transcriptionally driven pediatric malignancy, exhibits a remarkable clinical and biological heterogeneity. Two major subtypes, adrenergic and mesenchymal, are differentially governed by distinct subsets of transcription factors that constitute the core regulatory circuitry (CRC). The adrenergic subtype is often associated with MYCN amplification and is particularly aggressive and therapy-resistant, underscoring the need ...
Added: April 15, 2026
Egorov E., Kondratenko N., Averina O. et al., Biochemistry. Biokhimiia 2023 Vol. 88 P. 1987–1996
Transcription factor NRF2 is involved in inflammatory reactions, maintenance of redox balance, metabolism of xenobiotics, and is of particular interest for studying aging. In the present work, the CRISPR/Cas9 genome editing technology was used to generate the NRF2ΔNeh2 mice containing a substitution of eight amino acid residues at the N-terminus of the NRF2 protein, upstream of ...
Added: March 20, 2026
Балакина А. А., Приходченко Т. Р., Якушев И. А. et al., Известия Академии наук. Серия химическая 2023 Т. 72 № 7 С. 1618–1632
The structure of 3-hydroxy-6-methyl-2-ethylpyridinium nitroxysuccinate (2), its cytotoxicity, and its ability to influence the content of intracellular nitrogen monoxide, as well as the formation of reactive oxygen species and lipid peroxidation processes under conditions of induced oxidative stress were studied. It was demonstrated that compound 2 had low cytotoxicity in vitro in both non-cancerous and ...
Added: September 14, 2025
Popova A., Neverov A. D., PLoS Genetics 2021
The mode and rate of evolution of a protein site depends on the effect of its mutations on protein fitness. The fitness effect of a mutation itself can change in the course of evolution for at least two reasons. First, it can be modulated by substitutions occurring at other sites, a phenomenon called epistasis. Second, ...
Added: June 9, 2025
Silkina M., Razumovskaya A., Timur Kulagin et al., Biochimie 2025 Vol. 234 P. 48–61
Breast cancer remains a major challenge and new therapeutic approaches are needed for its treatment. Ferroptosis is considered a promising alternative cell death mechanism to eliminate resistant cancer cells. In previous works, we identified that lower IGFBP6 gene expression in tumor tissue corresponds to a worse prognosis for breast cancer patients and, at the same, time makes ...
Added: April 9, 2025
Киселевский Д. Б., Samuilova O., Самуилов В. Д., Биохимия 2023 Т. 88 № 2 С. 199–210
Исследованы редокс-свойства компонента зеленого чая галлата эпигаллокатехина (EGCG) in vitro, и испытано его действие на клетки растений (гороха). EGCG проявлял свойства как про-, так и антиоксиданта. В растворах EGCG окислялся кислородом при физиологических (слабощелочных) значениях pH. Снижение pH замедляло этот процесс. Окисление EGCG сопровождалось образованием O2–• и H2O2. С другой стороны, EGCG функционировал в качестве донора электронов для пероксидазы и в комбинации с ней утилизировал H2O2. При воздействии на клетки гороха (высечки листьев или эпидермис) EGCG подавлял дыхание, снижал ...
Added: December 11, 2023
Vyssokikh M., Holtze S., Averina O. et al., Proceedings of the National Academy of Sciences of the United States of America 2020 Vol. 117 No. 12 P. 6491–6501
The mitochondria of various tissues from mice, naked mole rats (NMRs), and bats possess two mechanistically similar systems to prevent the generation of mitochondrial reactive oxygen species (mROS): hexokinases I and II and creatine kinase bound to mitochondrial membranes. Both systems operate in a manner such that one of the kinase substrates (mitochondrial ATP) is ...
Added: December 10, 2022
Pavlyuchenkova A., Roman A. Zinovkin, Makievskaya C. et al., Life Sciences 2022 Vol. 288 Article 120174
FcεRI-dependent activation and degranulation of mast cells (MC) play an important role in allergic diseases. We have previously demonstrated that triphenylphosphonium (TPP)-based antioxidant SkQ1 inhibits mast cell degranulation, but the exact mechanism of this inhibition is still unknown. This study focused on investigating the influence of TPP-based compounds SkQ1 and C12TPP on FcεRI-dependent mitochondrial dysfunction and signaling during MC ...
Added: December 10, 2022
Lyamzaev K., Zinovkin R., Chernyak B., Journal of Cellular Physiology 2022 Vol. 237 No. 5 P. 2345–2356
Mitochondria are dynamic organelles that regulate various intracellular signaling pathways, including the mechanisms of programmed cell death, differentiation, inflammation, and so on. Mitochondria may be extruded as membrane enveloped or as free organelles during developmental processes, inflammatory activation, and in the process of “garbage clearance” of damaged mitochondria in postmitotic cells. Extracellular mitochondria can be ...
Added: December 10, 2022
Zorova L., Kovalchuk S., Popkov V. et al., International Journal of Molecular Sciences 2022 Vol. 23 No. 13 Article 7408
Extracellular vesicles (EV) derived from stem cells have become an effective complement to the use in cell therapy of stem cells themselves, which has led to an explosion of research into the mechanisms of vesicle formation and their action. There is evidence demonstrating the presence of mitochondrial components in EV, but a definitive conclusion about ...
Added: December 10, 2022
Alexey D. Neverov, Popova A., Fedonin G. et al., PLoS Genetics 2021 Vol. 17 No. 1 Article e1008711
The rate of evolution differs between protein sites and changes with time. However, the link between these two phenomena remains poorly understood. Here, we design a phylogenetic approach for distinguishing pairs of amino acid sites that evolve concordantly, i.e., such that substitutions at one site trigger subsequent substitutions at the other; and also pairs of ...
Added: December 8, 2022
Alieva A. K., Zyrin V. S., Rudenok M. M. et al., Molecular Neurobiology 2018 Vol. 55 No. 9 P. 7229–7241
Parkinson's disease (PD) is characterized by degeneration of dopaminergic neurons. A whole-transcriptome analysis of the substantia nigra and striatum of an MPTP-induced mouse models of the earliest stages of PD was performed. Functional clustering of differentially represented transcripts revealed processes associated with the functioning of synapses, dendrites, axons, and myelination of neuronal projections. All of ...
Added: September 9, 2022