Publications by authors named "A A Kostina"

21 Publications

Network-based screen in iPSC-derived cells reveals therapeutic candidate for heart valve disease.

Science 2021 02 10;371(6530). Epub 2020 Dec 10.

Gladstone Institute of Cardiovascular Disease, San Francisco, CA, USA.

Mapping the gene-regulatory networks dysregulated in human disease would allow the design of network-correcting therapies that treat the core disease mechanism. However, small molecules are traditionally screened for their effects on one to several outputs at most, biasing discovery and limiting the likelihood of true disease-modifying drug candidates. Here, we developed a machine-learning approach to identify small molecules that broadly correct gene networks dysregulated in a human induced pluripotent stem cell (iPSC) disease model of a common form of heart disease involving the aortic valve (AV). Gene network correction by the most efficacious therapeutic candidate, XCT790, generalized to patient-derived primary AV cells and was sufficient to prevent and treat AV disease in vivo in a mouse model. This strategy, made feasible by human iPSC technology, network analysis, and machine learning, may represent an effective path for drug discovery.
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http://dx.doi.org/10.1126/science.abd0724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880903PMC
February 2021

[Multifocal electroretinography in the study of focal and diffuse damage to the rabbit retina].

Vestn Oftalmol 2020 ;136(4):47-56

State Research and Experimental Institute of Military Medicine, Saint Petersburg, Russia.

Purpose: To evaluate the possibility of using the system "Neuro-ERG" (with a module for multifocal ERG) in the study of focal and diffuse pathology in laboratory animals (rabbits).

Material And Methods: Focal retinal damage was modelled in 5 eyes of 5 rabbits by singular laser pulses (532 nm, 100 ms, power 30, 60, 100, 150 and 200 mW) and diffuse retinal damage was modelled in 5 eyes of 5 rabbits by exposure to polychromatic light for 14 days (9500 lm, 6400 K, 230 mW/cm2, 8 h/day). The pair of eyes and areas of intact retina in the eyes with focal retinal damage were used for control. Multifocal electroretinography (mfERG) was recorded using the «Neuro-ERG» system (Neurosoft, Russia) before exposure, after 1 hour (in focal damage model), and 1, 7 and 14 days after exposure. In addition, three-time recording of mfERG was made before and after the experiments. Analysis included the amplitude and time characteristics of mfERG components, as well as the level of reproducibility of mfERG at each recording.

Results: In the modeling of focal damage of the rabbit retina, significant changes in mfERG (pattern stimulus consisted of 61 hexagons) were detected when the retinal damage area was more than 170 µm in diameter or more than 35% of the hexagon area in the pattern-stimulus. A significant moderate inverse correlation (0.52<<0.71, <0.01) was found between the damage area and the amplitude P1 and density of the bioelectric response of the P1 component. When modeling diffuse damage, significant changes in mfERG (an increase of implict-time of P1 and a decrease in the amplitude and density of the bioelectric response of the P1 component) were detected on the 7th day after the beginning of exposure. Variability of mfERG recording on each registration averaged 5%.

Conclusion: Multifocal ERG registration systems, including «Neuro-ERG» (Neurosoft, Russia), can be used in experimental studies of vitreoretinal pathology with rabbits as biological objects.
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http://dx.doi.org/10.17116/oftalma202013604147DOI Listing
August 2020

Generation of two iPSC lines (FAMRCi007-A and FAMRCi007-B) from patient with Emery-Dreifuss muscular dystrophy and heart rhythm abnormalities carrying genetic variant LMNA p.Arg249Gln.

Stem Cell Res 2020 Jun 29;47:101895. Epub 2020 Jun 29.

Almazov National Medical Research Centre, Saint-Petersburg, Russia; Saint Petersburg State University, Saint-Petersburg, Russia; Institute of Cytology RAS, Saint-Petersburg, Russia. Electronic address:

Human iPSC lines were generated from peripheral blood mononuclear cells of patient carrying LMNA mutation associated with Emery-Dreifuss muscular dystrophy accompanied by atrioventricular block and paroxysmal atrial fibrillation. Reprogramming factors OCT4, KLF4, SOX2, CMYC were delivered using Sendai virus transduction. iPSCs were characterized in order to prove the pluripotency markers expression, normal karyotype, ability to differentiate into three embryonic germ layers. Generated iPSC lines would be useful model to investigate disease development associated with genetic variants in LMNA gene.
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http://dx.doi.org/10.1016/j.scr.2020.101895DOI Listing
June 2020

Corrigendum to "Notch signaling in the pathogenesis of thoracic aortic aneurysms: A bridge between embryonic and adult states" [Biochim. Biophys. Acta Mol. Basis Dis. 1866 (3) (Mar 1 2020) 165631].

Biochim Biophys Acta Mol Basis Dis 2020 Jun 27;1866(6):165732. Epub 2020 Feb 27.

Almazov National Medical Research Centre, Akkuratova, 2, 197341 Saint Petersburg, Russia.

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http://dx.doi.org/10.1016/j.bbadis.2020.165732DOI Listing
June 2020