Publications by authors named "A N Kiseleva"

181 Publications

The Double Mutation -p.S363X and -p.D278X Is Associated with Left Ventricular Non-Compaction Cardiomyopathy: Case Report.

Int J Mol Sci 2021 Jun 24;22(13). Epub 2021 Jun 24.

National Research Center for Therapy and Preventive Medicine, Petroverigskiy Lane 10, 101990 Moscow, Russia.

Left ventricular non-compaction cardiomyopathy (LVNC) is a rare heart disease, with or without left ventricular dysfunction, which is characterized by a two-layer structure of the myocardium and an increased number of trabeculae. The study of familial forms of LVNC is helpful for risk prediction and genetic counseling of relatives. Here, we present a family consisting of three members with LVNC. Using a next-generation sequencing approach a combination of two (likely) pathogenic nonsense mutations -p.S363X and -p.D278X was identified in all three patients. encodes the cardiac T-box transcription factor 20. encodes desmoglein-2, which is part of the cardiac desmosomes and belongs to the cadherin family. Since the identified nonsense variant (-p.S363X) is localized in the extracellular domain of , we performed in vitro cell transfection experiments. These experiments revealed the absence of truncated at the plasma membrane, supporting the pathogenic relevance of -p.S363X. In conclusion, we suggest that in the future, these findings might be helpful for genetic screening and counseling of patients with LVNC.
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http://dx.doi.org/10.3390/ijms22136775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268202PMC
June 2021

The Prevalence of Heterozygous Familial Hypercholesterolemia in Selected Regions of the Russian Federation: The FH-ESSE-RF Study.

J Pers Med 2021 May 24;11(6). Epub 2021 May 24.

National Medical Research Center for Cardiology, 3-ya Cherepkovskaya Street, 15A, 121552 Moscow, Russia.

Heterozygous familial hypercholesterolemia (HeFH) is one of the most common genetic conditions but remains substantially underdiagnosed. The aim of our study was to investigate the prevalence of HeFH in the population of 11 different regions of Russia. Individuals were selected from the Epidemiology of Cardiovascular Risk Factors and Diseases in Regions of the Russian Federation Study. All participants who had low-density lipoprotein cholesterol (LDL-C) higher than 4.9 mmol/L, or LDL-C lower than 4.9 mmol/L, but had statin therapy, were additionally examined by FH experts. FH was diagnosed using the Dutch Lipid Clinic Network criteria, incorporating genetic testing. HeFH prevalence was assessed for 18,142 participants. The prevalence of patients with definite or probable HeFH combined was 0.58% (1 in 173). A total of 16.1% of patients with definite or probable HeFH had tendon xanthomas; 36.2% had mutations in one of the three genes; 45.6% of FH patients had coronary artery disease; 63% of HeFH patients received statins; one patient received an additional PCSK9 inhibitor; no patients received ezetimibe. Only 3% of patients reached the LDL-C goal based on 2019 ESC/EAS guidelines. Underdiagnosis and undertreatment of FH in Russia underline the need for the intensification of FH detection with early and aggressive cholesterol-lowering treatment.
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http://dx.doi.org/10.3390/jpm11060464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225162PMC
May 2021

Native Spider Silk-Based Antimicrobial Hydrogels for Biomedical Applications.

Polymers (Basel) 2021 May 29;13(11). Epub 2021 May 29.

SCAMT Institute, ITMO University, Lomonosova str.9, 191002 Saint Petersburg, Russia.

Novel antimicrobial natural polymeric hybrid hydrogels based on hyaluronic acid (HA) and spider silk (Ss) were prepared using the chemical crosslinking method. The effects of the component ratios on the hydrogel characteristics were observed parallel to the primary physicochemical characterization of the hydrogels with scanning electron microscopic imaging, Fourier-transform infrared spectroscopy, and contact angle measurements, which confirmed the successful crosslinking, regular porous structure, exact composition, and hydrophilic properties of hyaluronic acid/spider silk-based hydrogels. Further characterizations of the hydrogels were performed with the swelling degree, enzymatic degradability, viscosity, conductivity, and shrinking ability tests. The hyaluronic acid/spider silk-based hydrogels do not show drastic cytotoxicity over human postnatal fibroblasts (HPF). Hydrogels show extraordinary antimicrobial ability on both gram-negative and gram-positive bacteria. These hydrogels could be an excellent alternative that aids in overcoming antimicrobial drug resistance, which is considered to be one of the major global problems in the biomedical industry. Hyaluronic acid/spider silk-based hydrogels are a promising material for collaborated antimicrobial and anti-inflammatory drug delivery systems for external use. The rheological properties of the hydrogels show shear-thinning properties, which suggest that the hydrogels could be applied in 3D printing, such as in the 3D printing of antimicrobial surgical meshes.
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http://dx.doi.org/10.3390/polym13111796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198725PMC
May 2021

Restrains Autophagy to Limit Growth of Early Stage Non-Small Cell Lung Cancer.

Cancer Res 2021 Jul 18;81(13):3717-3726. Epub 2021 May 18.

Program in Molecular Therapeutics Fox Chase Cancer Center, Philadelphia, PA.

Non-small cell lung cancer (NSCLC) is the most common cancer worldwide. With overall 5-year survival estimated at <17%, it is critical to identify factors that regulate NSCLC disease prognosis. NSCLC is commonly driven by mutations in and , with activation of additional kinases such as SRC promoting tumor invasion. In this study, we investigated the role of NEDD9, a SRC activator and scaffolding protein, in NSCLC tumorigenesis. In an inducible model of NSCLC dependent on mutation and loss ( mice), deletion of ( mice) led to the emergence of larger tumors characterized by accelerated rates of tumor growth and elevated proliferation. Orthotopic injection of and tumors into the lungs of -wild-type and -null mice indicated the effect of loss was cell-autonomous. Tumors in mice displayed reduced activation of SRC and AKT, indicating that activation of these pathways did not mediate enhanced growth of KPN tumors. NSCLC tumor growth has been shown to require active autophagy, a process dependent on activation of the kinases LKB1 and AMPK. tumors contained high levels of active LKB1 and AMPK and increased autophagy compared with tumors. Treatment with the autophagy inhibitor chloroquine completely eliminated the growth advantage of KPN tumors. These data for the first time identify NEDD9 as a negative regulator of LKB1/AMPK-dependent autophagy during early NSCLC tumor growth. SIGNIFICANCE: This study demonstrates a novel role for the scaffolding protein NEDD9 in regulating LKB1-AMPK signaling in early stage non-small cell lung cancer, suppressing autophagy and tumor growth.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-3626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277748PMC
July 2021

Hemi- and Homozygous Loss-of-Function Mutations in DSG2 (Desmoglein-2) Cause Recessive Arrhythmogenic Cardiomyopathy with an Early Onset.

Int J Mol Sci 2021 Apr 6;22(7). Epub 2021 Apr 6.

Erich and Hanna Klessmann Institute, Heart and Diabetes Center NRW, University Hospital of the Ruhr-University Bochum, Georgstrasse 11, 32545 Bad Oeynhausen, Germany.

About 50% of patients with arrhythmogenic cardiomyopathy (ACM) carry a pathogenic or likely pathogenic mutation in the desmosomal genes. However, there is a significant number of patients without positive familial anamnesis. Therefore, the molecular reasons for ACM in these patients are frequently unknown and a genetic contribution might be underestimated. Here, we used a next-generation sequencing (NGS) approach and in addition single nucleotide polymor-phism (SNP) arrays for the genetic analysis of two independent index patients without familial medical history. Of note, this genetic strategy revealed a homozygous splice site mutation (DSG2-c.378+1G>T) in the first patient and a nonsense mutation (DSG2-p.L772X) in combination with a large deletion in DSG2 in the second one. In conclusion, a recessive inheritance pattern is likely for both cases, which might contribute to the hidden medical history in both families. This is the first report about these novel loss-of-function mutations in DSG2 that have not been previously identi-fied. Therefore, we suggest performing deep genetic analyses using NGS in combination with SNP arrays also for ACM index patients without obvious familial medical history. In the future, this finding might has relevance for the genetic counseling of similar cases.
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http://dx.doi.org/10.3390/ijms22073786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038858PMC
April 2021
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