9 results on '"Skvortsov, Dmitry A."'
Search Results
2. Gait analysis and knee joint kinematics before a and 6 month after of corrective valgus osteotomy at patients with medial knee arthritis.
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Skvortsov, Dmitry, Kaurkin, Sergey, Prizov, Alexey, Altukhova, Alyona, Goncharov, Evgeny, and Nikitin, Artem
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TIBIA surgery , *KNEE osteoarthritis , *KNEE joint , *OSTEOTOMY , *KINEMATICS - Abstract
Purpose: A varus deformity (VD) of the lower limbs results in greater loading of the medial compartment of the knee joint (KJ), leading to its degenerative changes and, eventually, to progressive osteoarthritis (OA) of the joint. The aim of the study was to investigate the mid-term changes in gait biomechanics and clinical symptoms in patients with VD of KJ and OA before and six months after surgical correction.Methods: The study enrolled 25 patients with medial OA of grade 2-3 according to Kellgren-Lawrence and a VD of > 3°, who underwent arthroscopic lavage and debridement of the knee joint followed by corrective osteotomy. The control group included 20 healthy adults. Clinical and biomechanical assessments were done twice: immediately prior to and six months after the surgical treatment. Biomechanical parameters of gait were recorded using an inertial sensor system.Results: According to our findings, there was a statistically significant post-operative increase in the knee extension amplitude by 1.4° in female patients and an insignificant extension increase in male patients. The mean postoperative KOOS score was 66.7 points (46 to 91) in the patient group, 67.1 points (54 to 91) in males, and 59.5 points (46 to 64) in females. As early as six months after a valgus osteotomy, we already observed improved biomechanics of the KJ motions compared to pre-operative data. By that time, the swing flexion amplitude of the affected KJ had increased and became symmetrical, which had not been the case before surgery. We observed a total of three changes in the KJ kinematics after surgery: increased swing flexion amplitudes in both KJs, a decreased extension amplitude in the affected KJ, and increased first flexion amplitudes in both KJs.Conclusion: According to our study, the midterm outcomes after a valgus osteotomy showed clinical improvements based on the VAS and KOOS scores, which were however less pronounced than in similar studies with a longer assessment term after surgery. We also found a significant increase in the amplitude of joint extension, but only in females. As the function of the operated joint is concerned, valgus osteotomy restored the kinematics of walking movements to a nearly normal gait with increased first and second flexion amplitudes. The function of KJ becomes symmetric though the non-operative side. Thus, the healthy and functionally more capable side is copying the movement pattern of the affected side. Hence, the non-operative leg is functioning less efficiently than it is required by the walking pace. [ABSTRACT FROM AUTHOR]- Published
- 2022
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3. Conserved long-range base pairings are associated with pre-mRNA processing of human genes.
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Kalmykova, Svetlana, Kalinina, Marina, Denisov, Stepan, Mironov, Alexey, Skvortsov, Dmitry, Guigó, Roderic, and Pervouchine, Dmitri
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HUMAN genes ,NON-coding RNA ,NUCLEIC acids ,RNA editing ,RNA splicing ,BASE pairs ,SMALL nuclear RNA - Abstract
The ability of nucleic acids to form double-stranded structures is essential for all living systems on Earth. Current knowledge on functional RNA structures is focused on locally-occurring base pairs. However, crosslinking and proximity ligation experiments demonstrated that long-range RNA structures are highly abundant. Here, we present the most complete to-date catalog of conserved complementary regions (PCCRs) in human protein-coding genes. PCCRs tend to occur within introns, suppress intervening exons, and obstruct cryptic and inactive splice sites. Double-stranded structure of PCCRs is supported by decreased icSHAPE nucleotide accessibility, high abundance of RNA editing sites, and frequent occurrence of forked eCLIP peaks. Introns with PCCRs show a distinct splicing pattern in response to RNAPII slowdown suggesting that splicing is widely affected by co-transcriptional RNA folding. The enrichment of 3'-ends within PCCRs raises the intriguing hypothesis that coupling between RNA folding and splicing could mediate co-transcriptional suppression of premature pre-mRNA cleavage and polyadenylation. Functional RNA secondary structure is important for the pre-mRNA processing including splicing, cleavage and polyadenylation, and RNA editing. Here the authors present a catalog of conserved long-range RNA structures in the human transcriptome by defining pairs of conserved complementary regions (PCCR) in pre-aligned evolutionarily conserved regions. [ABSTRACT FROM AUTHOR]
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- 2021
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4. Panel of potential lncRNA biomarkers can distinguish various types of liver malignant and benign tumors.
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Burenina, Olga Y., Lazarevich, Natalia L., Kustova, Inna F., Shavochkina, Daria A., Moroz, Ekaterina A., Kudashkin, Nikolay E., Patyutko, Yuriy I., Metelin, Alexey V., Kim, Eduard F., Skvortsov, Dmitry A., Zatsepin, Timofei S., Rubtsova, Maria P., and Dontsova, Olga A.
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BENIGN tumors ,LINCRNA ,BIOMARKERS ,LIVER cancer ,LIVER tumors - Abstract
Purpose: Liver cancers are among the deadliest malignancies due to a limited efficacy of early diagnostics, the lack of appropriate biomarkers and insufficient discrimination of different types of tumors by classic and molecular methods. In this study, we searched for novel long non-coding RNA (lncRNA) as well as validated several known candidates suitable as probable biomarkers for primary liver tumors of various etiology. Methods: We described a novel lncRNA HELIS (aka "HEalthy LIver Specific") and estimated its expression by RT-qPCR in 82 paired tissue samples from patients with hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), combined HCC-CCA, pediatric hepatoblastoma (HBL) and non-malignant hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH). Additionally, we examined expression of cancer-associated lncRNAs HULC, MALAT1, UCA1, CYTOR, LINC01093 and H19, which were previously studied mainly in HCC. Results: We demonstrated that down-regulation of HELIS strongly correlates with carcinogenesis; whereas in tumors with non-hepatocyte origin (HBL, CCA) or in a number of poorly differentiated HCC, this lncRNA is not expressed. We showed that recently discovered LINC01093 is dramatically down-regulated in all malignant liver cancers; while in benign tumors LINC01093 expression is just twice decreased in comparison to adjacent samples. Conclusion: Our study revealed that among all measured biomarkers only down-regulated HELIS and LINC01093, up-regulated CYTOR and dysregulated HULC are perspective for differential diagnostics of liver cancers; whereas others demonstrated discordant results and cannot be considered as potential universal biomarkers for this purpose. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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5. Synthesis and Biological Evaluation of Novel Dispiro Compounds based on 5-Arylidenehydantoins and Isatins as Inhibitors of p53–MDM2 Protein–Protein Interaction.
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Beloglazkina, Anastasia, Barashkin, Alexander, Polyakov, Vladislav, Kotovsky, German, Karpov, Nikita, Mefedova, Sofia, Zagribelny, Bogdan, Ivanenkov, Yan, Kalinina, Marina, Skvortsov, Dmitry, Tafeenko, Victor, Zyk, Nikolay, Majouga, Alexander, and Beloglazkina, Elena
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PROTEIN-protein interactions ,BIOSYNTHESIS ,CELL lines ,CANCER cells - Abstract
A series of novel hydantoin-based dispiroindolinones as potential small-molecule inhibitors of p53–MDM2 protein–protein interaction were synthesized by two methods, using 2-arylidenehydantoins as starting materials. Some compounds demonstrate moderate cytotoxicity against cancer cell lines with IC50 in micromolar concentration range, which is comparable to nutlin-3. Two of the synthesized dispiroindolinones show p53-related activity in p53 reporter activation test. [ABSTRACT FROM AUTHOR]
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- 2020
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6. Identification of pyrrolo-pyridine derivatives as novel class of antibacterials.
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Veselov, Mark S., Ivanenkov, Yan A., Yamidanov, Renat S., Osterman, Ilya A., Sergiev, Petr V., Aladinskiy, Vladimir A., Aladinskaya, Anastasia V., Terentiev, Victor A., Ayginin, Andrey A., Skvortsov, Dmitry A., Komarova, Katerina S., Chemeris, Alexey V., Baimiev, Alexey Kh., Sofronova, Alina A., Machulkin, Alexey E., Petrov, Rostislav A., Maklakova, Svetlana Yu., Bezrukov, Dmitry S., Filkov, Gleb I., and Zainullina, Liana F.
- Abstract
A series of 5-oxo-4H-pyrrolo[3,2-b]pyridine derivatives was identified as novel class of highly potent antibacterial agents during an extensive large-scale high-throughput screening (HTS) program utilizing a unique double-reporter system—pDualrep2. The construction of the reporter system allows us to perform visual inspection of the underlying mechanism of action due to two genes—Katushka2S and RFP—which encode the proteins with different imaging signatures. Antibacterial activity of the compounds was evaluated during the initial HTS round and subsequent rescreen procedure. The most active molecule demonstrated a MIC value of 3.35 µg/mL against E. coli with some signs of translation blockage (low Katushka2S signal) and no SOS response. The compound did not demonstrate cytotoxicity in standard cell viability assay. Subsequent structural morphing and follow-up synthesis may result in novel compounds with a meaningful antibacterial potency which can be reasonably regarded as an attractive starting point for further in vivo investigation and optimization. [ABSTRACT FROM AUTHOR]
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- 2020
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7. 2-Pyrazol-1-yl-thiazole derivatives as novel highly potent antibacterials.
- Author
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Ivanenkov, Yan A., Yamidanov, Renat S., Osterman, Ilya A., Sergiev, Petr V., Aladinskiy, Vladimir A., Aladinskaya, Anastasia V., Terentiev, Victor A., Veselov, Mark S., Ayginin, Andrey A., Skvortsov, Dmitry A., Komarova, Katerina S., Sadovnikov, Sergey V., Matniyazov, Rustam, Sofronova, Alina A., Malyshev, Alexander S., Machulkin, Alexey E., Petrov, Rostislav A., Lukianov, Dmitrii, Iarovenko, Svetlana, and Bezrukov, Dmitry S.
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- 2019
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8. Cytotoxicity Test Based on Human Cells Labeled with Fluorescent Proteins: Fluorimetry, Photography, and Scanning for High-Throughput Assay.
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Kalinina, Marina A., Skvortsov, Dmitry A., Rubtsova, Maria P., Komarova, Ekaterina S., and Dontsova, Olga A.
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FLUORESCENT proteins , *ANTINEOPLASTIC agents , *FLUORIMETRY , *MEDICAL photography , *HIGH throughput screening (Drug development) , *SIGNAL-to-noise ratio - Abstract
Purpose: High- and medium-throughput assays are now routine methods for drug screening and toxicology investigations on mammalian cells. However, a simple and cost-effective analysis of cytotoxicity that can be carried out with commonly used laboratory equipment is still required.Procedures: The developed cytotoxicity assays are based on human cell lines stably expressing eGFP, tdTomato, mCherry, or Katushka2S fluorescent proteins. Red fluorescent proteins exhibit a higher signal-to-noise ratio, due to less interference by medium autofluorescence, in comparison to green fluorescent protein. Measurements have been performed on a fluorescence scanner, a plate fluorimeter, and a camera photodocumentation system.Results: For a 96-well plate assay, the sensitivity per well and the measurement duration were 250 cells and 15 min for the scanner, 500 cells and 2 min for the plate fluorimeter, and 1000 cells and less than 1 min for the camera detection. These sensitivities are similar to commonly used MTT (tetrazolium dye) assays. The used scanner and the camera had not been previously applied for cytotoxicity evaluation. An image processing scheme for the high-resolution scanner is proposed that significantly diminishes the number of control wells, even for a library containing fluorescent substances. The suggested cytotoxicity assay has been verified by measurements of the cytotoxicity of several well-known cytotoxic drugs and further applied to test a set of novel bacteriotoxic compounds in a medium-throughput format.Conclusion: The fluorescent signal of living cells is detected without disturbing them and adding any reagents, thus allowing to investigate time-dependent cytotoxicity effects on the same sample of cells. A fast, simple and cost-effective assay is suggested for cytotoxicity evaluation based on mammalian cells expressing fluorescent proteins and commonly used laboratory equipment. [ABSTRACT FROM AUTHOR]- Published
- 2018
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9. Amicoumacin A induces cancer cell death by targeting the eukaryotic ribosome.
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Prokhorova, Irina V., Akulich, Kseniya A., Makeeva, Desislava S., Osterman, Ilya A., Skvortsov, Dmitry A., Sergiev, Petr V., Dontsova, Olga A., Yusupova, Gulnara, Yusupov, Marat M., and Dmitriev, Sergey E.
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- 2016
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