Сибирское Медицинское Обозрение. 2021. № 2 View full textКоличество просмотров : 1001
Tskhay V.B., Polstyanoy A.M.
Deep infiltrating endometriosis with bowel involvement. Literature review
Tskhaу VB, Khudyakov A, Terjung A, Polstianoy АМ, von Westernhagen M, Avazashvili Z, Füllers U, Friedrich M, PolstianayОY. Deep infiltrating endometriosis with bowel involvement. Literature review. Siberian Medical Review. 2021; (2):5-11. DOI 10.20333/2500136-2021-2-5-11
Tskhay Vitaly Borisovich Dr. Med. Sc, Professor, Head of the Department of Perinatology, Obstetrics and Gynecology; Professor V.F. Voyno-Yasenetsky Krasnoyarsk State Medical University; email@example.com
Polstyanoy A. M. ; Siberian clinical centre of the federal medical and biological agency; firstname.lastname@example.org
Endometriosis is a prevalent disease in females of the childbearing age. It may be accompanied by bowel involvement. In such cases, the most frequently observed lesion locations are the rectum and the rectosigmoid with the occurrence rate of 3-37 %. Treatment of severe forms of deep infi ltrating endometriosis with bowel wall involvement is one of the most challenging problems of modern gynaecology. Apart from general intra- and postoperative risks (haemorrhage, infection, direct damage to the organs) or bowel and bladder dysfunction, one of the most severe complications is the development of anastomotic leaks. Th is article presents a review of literatures dated 2010-2020 searched for in PubMed and Google Scholar databases and devoted to operative treatment of patients with deep infi ltrating endometriosis. We made an emphasis on the effi cacy of the multidisciplinary approach to operative treatment of patients with deep infi ltrating endometriosis and bowel involvement. Multidisciplinary laparoscopic treatment has become a standard of medical aid in deep infi ltrating endometriosis. Depending on the size of endometrial lesion and the location of bowel involvement, complete removal of the infi ltrate or bowel resection is performed in cooperation with an experienced colorectal surgeon. The operative tactics in laparoscopic endometriosis resection, including bowel resection, may provide advantages for both the patients and the healthcare system. Th e optimal model is to be chosen drawing on the basis of the maximum benefit for the patient
Keywords: deep infiltrating endometriosis, colorectal endometriosis, laparoscopy, operative treatment, bowel resection, organ preservation treatment
Borzykh OB, Petrova MM, Shnayder NA, Nasyrova RF. Problems of implementation of personalized medicine in medical cosmetology in Russia. Siberian Medical Review. 2021; (2):12-22. DOI 10.20333/2500136-2021-2-12-22
At the present time, the 4P concept (predictive, preventive, personalised and participatory) is a prospective trend in development of clinical medicine. The concept is being actively introduced into diff erent medical specialities. However, the development of personalised approach in medical cosmetology as a speciality at the intersection of medical sciences (dermatology, maxillofacial surgery, plastic surgery, restorative medicine, general practice, psychiatry, clinical pharmacology, etc.) is at the stage of discussion. The concept of 4P medicine suggests, among other things, analysis of genetic risks and development of preventive procedures based thereon that would decrease the risk of cosmetological complications development. Th e review includes analysis of literature dated 2010-2020. The following databases in Russian and foreign languages were searched using the keywords and advanced search builders: E-Library, PubMed, Springer, Clinicalkeys, Google Scholar. In this paper, we introduce a novel compilation of the known gene polymorphisms that may be used for determination of the genetic risks in cosmetological patients.
Keywords: medical cosmetology, personalised medicine, problems, cosmetologist, skin diagnosis, complications
Comparative evaluation of antibacterial activity of silver oxides with different oxygen content
Gordina EM, Bozhkova SA, Erusin AA. Comparative evaluation of antibacterial activity of silver oxides with different oxygen content. Siberian Medical Review. 2021; (2):23-28. DOI 10.20333/2500136-2021-2-23-28
Aim of the study. To study the presence of antibacterial properties in silver oxides with diff erent oxygen content in relation to sensitive and methicillinresistant Staphylococcus aureus strains. Material and Methods. Films of silver and its oxides were coated on paper surface in vacuum via the method of ion-plasma arc sputtering of the metallic target. Antibacterial activity of the obtained samples of silver oxides and pure silver against Staphylococcus aureus АТСС 29213 and Staphylococcus aureus ATCC 43300 was studied applying the diff usion method as well as in liquid nutrient broth with consequent measuring of optical density. Results. As a result of antibacterial activity investigation of the samples obtained via the diff usion method and liquid nutrient broth, it was revealed that all samples possessed antibacterial activity in relation to type strains of S. aureus. Th erewith, the effi cacy of the samples with pure silver was significantly lower than that of silver oxides (Ag0,2O, Ag0,4O, Ag1 O, Ag1,5O, Ag2 O). It was shown that the activity of silver oxides did not depend on the oxygen concentration in them. Thus, statistically signifi cant diff erences in optical density of the nutrient medium with bacteria and the medium with incubated S. aureus АТСС 29213 (MSSA) and Agx O (р<0.001). Analogical results were obtained after studying of infl uence exerted by silver on S. aureus АТСС 43300 (MRSA). Conclusion. All silver oxides samples created were characterised by antibacterial activity against S. aureus. The data obtained point at the prospects in application of silver oxide with low oxygen content for prevention and treatment of Staphylococcus aureus strains infection.
Keywords: silver, silver oxide, antibacterial activity, Staphylococcus aureus
Investigation of clinical and laboratory manifestations of rheumatoid arthritis depending on the level of serum fetuin-A
Papichev EV, Zavodovsky BV, Sivordova LE, Akhverdyan YR, Polyakova JV. Investigation of clinical and laboratory manifestations of rheumatoid arthritis depending on the level of serum fetuin-A. Siberian Medical Review. 2021; (2):29-34. DOI 10.20333/2500136-2021-2-29-34
Aim of the study. To study the association between the serum FA in patients with RA and separate clinical and laboratory manifestations of the disease. Material and methods. A total of 140 subjects were enrolled in the study. Among them, 110 were RA patients and 30 were conventionally healthy subjects. The level of serum FA was measured in both groups. All patients underwent complete clinical and laboratory examination and X-ray imaging of the impaired joints. Results. The level of normal FA in healthy subjects calculated as M±2σ totalled 653.55-972.19μg/ml. Th e mean level of FA in RA patients was 765.67±120.67μg/ ml, which is statistically lower than that in the donors: 812.95±76.21μg/ml (t=-2.03; p=0.0437). Th e mean FA level in conventionally healthy patients was statistically higher than the same index in RA-factor positive patients with cyclic citrullinated peptide antibodies, moderate and high activity, late clinical stage, X-ray stages III and IV, functional classes II, III and IV, joint erosion, abarticular manifestations and the presence of complicating diseases. Intra-group analysis (odds ratio and adjusted odd ratio) showed the patients with lower FA level (below 653.55μg/ml) to have a 14-fold higher possibility of CCP antibodies positivity (6-fold aft er adjustment), 1.86-fold higher disease activity (2.39-fold aft er adjustment), 6.6-fold higher probability of X-ray stage IV (with no statistical signifi cance aft er adjustment) and 29-fold higher chance of presence of complications (46-fold aft er adjustment). Conclusion. According to the data obtained in our study, lowering of the serum FA level is characteristic to RA patients. The hepatokine concentration below 653.55μg/ml may suggest 2.39-fold higher chance of higher disease activity and 46-fold higher probability of complicated RA progression.
Keywords: rheumatoid arthritis, fetuin-A, cytokine, hepatokine.
The role of certain genetic polymorphism in development of sudden cardiac death in the Trans-Baikal Territory
Zaitsev DN, Vasilenko PV, Govorin AV, Vasilenko EA, Filev AP, Mudrov VA, Romanyuk SV, Fetisova NV, Taldykina NS, Brizhko AN. The role of certain genetic polymorphism in development of sudden cardiac death in the Trans-Baikal Territory. Siberian Medical Review. 2021; (2):35-42. DOI 10.20333/2500136-2021-2-35-42
Aim of the study. To study genetic polymorphisms rs10798 KCNQ1, rs3010396 CASQ2, rs20455 KIF6, rs2298566 SNX19, rs12143842 NOS1AP of subjects who died due to sudden cardiac death in Trans-Baikal Territory. Material and Methods. Over the period of 2017-2020, a total of 2211 autopsy protocols of subjects who died due to SCD were analysed. These patient constituted the 1st study group (n=113). Th e control group consisted of healthy volunteers (n=70). The groups were comparable in age and gender. Molecular and genetic typing of the studied genes was performed. Results. The CC genotype of the single-nucleotide polymorphism rs3010396 CASQ2 showed statistical signifi cance in comparison with the control group(the chi-squared=26.95, df=2, p=0.001). Th e TT genotype was predominant in the control group amounting to 60% against 19.5% in the study group. Single-nucleotide polymorphism rs2298566 of gene SNX19 was also observed to be of statistical signifi cance in the group of subjects who died from myocardial infarction. In the group of patients with SCD, rs20455 KIF6 and rs12143842 NOS1AP were of signifi cance along with rs3010396 CASQ2. Conclusion. Single-nucleotide polymorphism rs3010396 of the CASQ2 gene can be a predictor of sudden cardiac death, since in the 1st study group with this genotype showed its statistical signifi cance in all nosological groups. However, in the group, in which sudden cardiac death (cases coded I46.1 according to ICD-10) was indicated as the fi nal diagnosis, in addition to their statistical signifi cance single-nucleotide polymorphisms of the gene KIF6 rs20455, rs12143842 NOS1AP gene were noted; in the group where the cause of death was myocardial infarction, rs2298566 SNX19 gene polymorphism had statistical significance. The results obtained make it possible to consider these polymorphisms as possible predictors of sudden cardiac death in the population of the Trans-Baikal Territory.
Keywords: sudden cardiac death, predictors of sudden cardiac death, out-of-hospital mortality.
Lobanov YuS, Lobanov SL, Shapovalov KG. Alteration of macrohaemodynamics in different modes of retropneumoperitoneum. Siberian Medical Review. 2021; (2):43-46. DOI 10.20333/2500136-2021-2-43-46
Aim of the study. To study alterations in macrohaemodynamics in diff erent modes of retropneumoperitoneum during retroperitoneal surgery. Material and methods. A total of 58 patients aged 40-60, both male and female, with previous surgeries on renal cysts through retroperitoneal approach were studied aft er distribution between 2 groups. In the fi rst group, the pressure did not exceed 12 mm Hg. Th e RPP in the second group was observed to be 12-16 mm Hg. During the surgical intervention, analysis of the cardiovascular system values was carried out using the method of volume compression oscillometry. Results. Evaluation of macrohaemodynamics revealed signifi cant deviation of the indices in patients with high RPP (group 2). Elevated true systolic pressure was revealed, as well as cardiac output decrease by 20 %, decrease of the cardiac index by 24 % and decrease of the stroke volume by 11 %. The patients treated with application of the highest gas pressure in the retroperitoneal space were revealed to have decrease in the linear velocity of blood fl ow by 17 % and elevation of total systemic vascular resistance (TSVR) by 12 %. Conclusion. Th erefore, the RPP value of 12-16 mm Hg exerts significant influence on the patient’s macrohaemodynamic status
Keywords: retropneumoperitoneum, retroperitoneal space, macrohaemodynamics, renal cyst, cardiac output
20-years dynamics of tuberculosis and HIV mortality and of their contribution to life expectancy reduction in the population of Krasnoyarsk
Narkevich AN, Vinogradov KA, Narkevich AA, Grjibovski AM. 20-years dynamics of tuberculosis and HIV mortality and of their contribution to life expectancy reduction in the population of Krasnoyarsk. Siberian Medical Review. 2021;(2):47-53. DOI 10.20333/2500136-2021-2-47-53
Aim of the study. To study the dynamics of mortality from tuberculosis and HIV as well as their contribution to life expectancy reduction in Krasnoyarsk Krai population over a period of 20 years. Material and methods. We used primary databases of Krasnoyarsk Krai population mortality for the period from 1999 to 2018. Th e direct method of standardisation according to the European standard of population age structure was applied for calculation of the standardised population mortality ratio. In order to analyse mortality in the population of the WHO European region and the CIS, the data of the European health information gateway were used (https://gateway.euro.who.int). Results. It has been established that female mortality from certain infectious and parasitic diseases has increased signifi cantly (from 13.2 to 22.7 per 100,000 of female population) in the cause of death structure of Krasnoyarsk Krai within the 20-years period. Analysis of Krasnoyarsk Krai mortality from such specifi c conditions as tuberculosis and HIV has shown signifi cant decrease in tuberculosis mortality rate which complies with the global trend in the dynamics of mortality from this disease, while the rate of reduction for this index surpasses that of CIS countries. Th e analysis has established signifi cant growth of HIV mortality in Krasnoyarsk Krai population, especially female (up to 11.6 per 100,000 of female population). Conclusion. Th ere has been a change of the leading mortality cause in the structure of population mortality from certain infectious and parasitic diseases over the period of 2016-2017. From that moment, the leading role in the cause of death structure of Krasnoyarsk Krai in this class of causes belongs to HIV
Keywords: mortality, life expectancy, tuberculosis, HIV, standardised mortality, infectious and parasitic diseases.
Ultrasound diagnosis of Budd-Chiari syndrome
Yakimova VB, Zhestovskaya SI, Lebedeva EV, Litvinova SP, EreminaEV. Ultrasound diagnosis of Budd-Chiari syndrome. Siberian Medical Review. 2021;(2):54-59. DOI 10.20333/2500136-2021-2-54-59
An analysis of ultrasound scanning of patients with hepatic veins (HV) pathology in order to clarify sonographic signs of Budd-Chiari syndrome was performed at the premises of the Regional state budget health care facility “Regional Clinical Hospital” in the city of Krasnoyarsk. The occurrence rate of the syndrome in the population was 1:100,000. The patients showed diff erent combinations of sonographic signs. Stenosis (or occlusion) of HV was found in 8 (88.9 %) patients; thrombotic masses in vessel lumens were found in 2 (22.2 %) patients, HV architectonics was compromised in 9 (100 %) patients, HV wall irregularities were registered in 9 (100 %) patients and pylephlebitis symptoms were observed in 4 (44.4 %) patients. HV thrombosis is diagnosed through Doppler ultrasound with the possibility of HV permeability along its entire length and evaluation of perivascular hepatic parenchyma with dynamic control.
Keywords: thrombosis, hepatic veins, cirrhosis, ultrasound diagnosis, Doppler scanning, Budd-Chiari syndrome.
Shevchenko KV, Usachev DYu, Shevchenko EV, Shmigelskiy AV, Galstyan SA. Intracranial chondroma of the falx-cerebi: a clinical case. Siberian Medical Review.2021; (2):60-65. DOI 10.20333/2500136-2021-2-60-65
Intracranial chondroma is a rare pathology with the occurrence of 0.1 % to 0.5 % of all primary intracranial tumours. The mechanism of tumour formation outside cartilaginous tissue is controversial. The majority of data point at a very diverse cellular composition of the Dura mater and the tumour may emerge as a result of fi broblast activation. Frequently, the tumour is a manifestation of multiple enchodromatosis (Ollier’s disease) or Maffucci syndrome. Clinical manifestations of the disease are unspecifi c and generalised. Differential diagnosis of the tumour is complicated due to the absence of pathognomonic neurovisualisation characteristics. Therefore, it is only possible to verify the diagnosis via pathomorphological examination. Chondroma is a benign neoplasm and its complete resection is essential for the positive outcome and longer life duration of the patients. The article presents a clinical case of successful surgical treatment of a patient with intracranial chondroma of falxcerebri.
Keywords: chondroma, intracranial chondroma, chondroma of the falxcerebri, brain tumour, surgical treatment.
Computational approach to design of aptamers to the receptor binding domain of SARS-CoV-2
Artyushenko PV, Mironov VA, Morozov DI, Shchugoreva IA, Borbone N, Tomilin FN, Kichkailo AS. Computational approach to design of aptamers to the receptor binding domain of SARS-CoV-2. Siberian Medical Review. 2021; (2):66-67. DOI 10.20333/2500136-2021-2-66-67
The aim of the research. In this work, in silico selection of DNA-aptamers to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein was performed using molecular modeling methods. Material and methods. A new computational approach to aptamer in silico selection is based on a cycle of simulations, including the stages of molecular modeling, molecular docking, molecular dynamic simulations, and quantum chemical calculations. To verify the obtained calculated results fl ow cytometry, fluorescence polarization, and small-angle X-ray scattering methods were applied. Results. An initial library consisted of 256 16-mer oligonucleotides was modeled. Based on molecular docking results, the only one aptamer (Apt16) was selected from the library as a starting aptamer to the RBD protein. For Apt16/RBD complex, molecular dynamic and quantum chemical calculations revealed the pairs of nucleotides and amino acids whose contribution to the binding between aptamer and RBD is the largest. Taking into account these data, Apt16 was subjected to the structure modifi cations in order to increase the binding with the RBD. Thus, a new aptamer Apt25 was designed. Th e procedure of 1)aptamer structure modeling/modifi cation, 2) molecular docking, 3) molecular dynamic simulations, 4) quantum chemical calculations was performed several times. As a result, four aptamers (Apt16, Apt25, Apt27, Apt31) to the RBD were designed in silico without any preliminary experimental data. Binding of the each modeled aptamer to the RBD was studied in terms of interactions between residues in protein and nucleotides in the aptamers. Based on the simulation results, the strongest binding with the RBD was predicted for two Apt27 and Apt31aptamers. Th e calculated results are in good agreement with experimental data obtained by flow cytometry, fluorescence polarization, and small-angle X-ray scattering methods. Conclusion. The proposed computational approach to selection and refi nement of aptamers is universal and can be used for wide range of molecular ligands and targets.
Keywords: selection, aptamer, receptor-binding domain, SARS-CoV-2
Risha Y, Susevski V, Hüttmann N, Poolsup S, Minic Z, Berezovski MV. Proteome of breast cancer derived microvesicles. Siberian Medical Review. 2021;(2):68-71. DOI 10.20333/2500136-2021-2-68-71
The aim of the research. To examine the proteomic profi le of breast cancer exosomes. Material and methods. Cell lines used for this study were MDA-MB-231 female epithelial breast cancer cells (ATCC HTB-26) and MCF10A non-tumorigenic epithelial breast tissue cells. MVs were isolated using diff erential ultracentrifugation. Samples were lysed, reduced, alkylated, digested, and analyzed by an Orbitrap Fusion mass spectrometer. MS raw fi les were analyzed using MaxQuant version 18.104.22.168. Peptides were searched against the human UniProt FASTA database using the Andromeda search engine, integrated into MaxQuant. Results. MVs derived from MCF10A and MDA-MB-231 cell lines were analyzed, and 1427 and 547 proteins were identifi ed in the MDA-MB-231 and MCF10A-derived MVs, respectively. In total, 455 proteins were common to both MDA-MB-231 and MCF10A MVs. MVs derived from MCF10A and MDAMB-231 cell lines were analyzed, and 1427 and 547 proteins were identifi ed in the MDA-MB-231 and MCF10A-derived MVs, respectively. In total, 455 proteins were common to both MDA-MB-231 and MCF10A MVs. The unique MDA-MB-231 MV proteins were searched against the DisGeNET human diseases database. Out of 972 MDA-MB-231 MV proteins, 112 were cancer-related while 32 were specifically associated with BC. In the MDA-MB-231 MV proteome, 23 Wnt signaling pathway proteins were identified based on their GO biological process. Proteomic analysis identifi ed enzymes OAT, TALDO1, and BLMH were only in MVs from metastatic MDA-MB-231 cell line. The specific activity of OAT and TALDO1 was higher in MV fractions of MDA-MB-231 in comparison to the non-cancerous MCF10A cell line-derived MVs. These findings might suggest that these enzymes might play a role in BC. In our present study, we found that some enzymes identifi ed from MV fractions were already proposed to play a role in cancer therapy as therapeutic targets (OAT, TALDO1) and resistance against chemotherapy agents (BLMH)
Keywords: proteomic analysis, breast cancer, ATCC HTB-26
Esposito CL, Nuzzo S, Ibba ML, Grinev IP, Gorbushin А, Grek D, Voronkovskii I, Kolovskaya OS, Zamay TN, Morozov E, Koshmanova A, Narodov AA, Khorzhevskii VA, Erakhtin EE, Krat AV, Yakovlev A, Shesternya PA, Kichkailo AS, Condorelli G, Catuogno S, de Franciscis V. STAT3 targeting by an aptamer-based conjugate for glioblastoma multiforme therapy. Siberian Medical Review. 2021; (2):72-73. DOI 10.20333/2500136-2021-2-72-73
The receptor-binding domain: aptamers (SARS-CoV-2) binding investigation by isothermal titration calorimetry
Vicente Dominguez Arca. The receptor-binding domain: aptamers (SARS-CoV-2) binding investigation by isothermal titration calorimetry. Siberian Medical Review. 2021; (2):74-75.. DOI 10.20333/2500136-2021-2-74-75
The aim of the research. To optimize the calorimetry method, which allows to study the binding of the receptor-binding domain (RBD) protein of the coronavirus COVID-19 to aptamer 27 obtained using a computational method. Material and methods. Computational modeling and calorimetry methods were used to optimize the method. Results. The results showed that the calorimetry method makes it possible to assess the binding of the RBD protein to the aptamer. Conclusion. These experiments will be run as soon as will be possible to determine the optimal conditions to functionalize gold substrates with the previously thiolated aptamers.
Keywords: aptamer, isothermal titration calorimetry, Spike protein RBD, SARS-CoV-2
Moryachkov RV, Nikolaeva PA, Spiridonova VA. Structure approaches to study of DNA aptamers in solution. Siberian Medical Review. 2021;(2):76-78. DOI 10.20333/2500136-2021-2-76-78
The high potential of aptamers – specific molecular agents based on short single-stranded nucleic acids – makes high demands on the molecules under development for the efficiency of interaction with target biomolecules. In this work, approaches are considered for studying the spatial structure of DNA aptamers in solution using various complementary methods, which make it possible to obtain a more complete picture of the formation of the structure and conformational changes, to track the interaction with the target protein, the tendency to oligomerization, and to characterize the spatial structure of both individual molecules and complexes
Keywords: biomolecules in solution, tertiary structure, small-angle X-ray scattering (SAXS), structure analysis
Nanoscalpel based on magnetic discs and aptamers effectively and targeted destroy tumor cell
Zamay SS, Prokopenko VS, Lukyanenko KA, Sokolov AE. Nanoscalpel based on magnetic discs and aptamers eff ectively and targeted destroy tumor cell. Siberian Medical Review. 2021; (2):79-82. DOI 10.20333/2500136-2021-2-79-82
The aim of the research. To investigate the antitumor effi cacy of three-layer magnetic nanodiscs (Au / Ni / Au) with a quasi-dipole structure, functionalized with biorecognizing molecules of a tumor. Material and methods. Th ree-layer magnetic nanodiscs (Au / Ni / Au) 500 nm in size (were obtained by micro- and nanoelectronic technologies. Aptamers to ascites cells of Ehrlich carcinoma were used to functionalize magnetic nanodiscs. Thiol groups were used to bind disks to aptamers. As a model of tumor cells Ehrlich’s ascites carcinoma cells were used, and the cells were magnetically infl uenced by an alternating magnetic fi eld (50 Hz, 100 Oe). Results. Magnetic nanodiscs have magnetic anisotropy, which proves their high sensitivity to magnetic stimuli. Magnetic nanodiscs start the processes of cell death in the culture of ascites cells for two hours. Presumably, magnetic nanodiscs use aptamers to bind to the cell membrane protein fi lamin A, a structural component of the cytoskeleton that plays an important role in cell signaling and, when exposed to a variable magnetic, cause destruction of the cell membrane and cell death. Conclusion. Microsurgery of malignant tumors using a nanoscalpel based on functionalized ligands that recognize tumor sites can be used to remove single tumor cells during surgery.
Keywords: aptamers, magnetic nanodiscs, alternating magnetic fi eld, tumor cells.
Ciccone G, Ibba ML, Coppola G, Petrillo G, Catuogno S, Esposito CL.New aptamer-based approaches for the targeting of cancer associated fi broblast in NSCLC. Siberian Medical Review. 2021;(2):83. DOI 10.20333/2500136-2021-2-83
The aim of the research. Non-small cell lung cancer (NSCLC) represents about 80 % of all lung cancer cases and is often associated with drug resistance, relapses and a poor prognosis. Th erefore, the identifi cation of eff ective therapeutic strategies represents a crucial challenge in oncology. A key limit of conventional anticancer treatments is that they do not target the permissive tumor microenvironment, of which key components are cancer‐associated fibroblasts (CAFs). It has been shown that CAFs are able to regulate malignant progression and drug resistance. However, a detailed characterization of CAF profile and the targeting of their pro-tumor eff ects still remain an ambitious challenge and have a primary importance for the identifi cation of new effective therapies. Material and methods. We aimed to develop innovative strategies based on nucleic acid aptamers to address these fundamental issues. Firstly, we applied an aptamer conjugate (named Gint4.T-STAT3), containing a STAT3 siRNA linked to an aptamer binding and inhibiting the PDGFRβ, to specifi cally silence STAT3 reported as a fundamental player in the cross-talk between CAFs and epithelial NSCLC cells. Results. We demonstrated that this molecule eff ectively delivers STAT3 siRNA in NSCLC cells, blocking CAF-induced cell growth and migration in both continous and primary NSCLC coltures. In addition, in order to address CAF specifi c targeting and profi ling, we developed an innovative diff erential cell-SELEX approach by using primary NSCLC CAFs as selection target. Such a strategy allowed the isolation of diff erent aptamers discriminating NSCLC CAFs from normal lung fibroblasts. Th e analyses of aptamer specifi city and functionality is curently ongoing. Conclusion. Our data represent the first ever attempt in CAF targeting using aptamer-based drugs, and can open innovative horizons in the current therapeutic approaches for NSCLC.
Keywords: aptamers, cancer cell, fibroblast, non-small cell lung cancer
The use of prosthetic groups for synthesis of addressed RFLP molecules for positron emission tomography
Ozerskay AV. Belugin KV, Badmaev ON. Th e use of prosthetic groups for synthesis of addressed RFLP molecules for positron emission tomography. Siberian Medical Review. 2021; (2):84-86. DOI 10.20333/2500136-2021-2-84-86
The aim of the research. An intensive research is underway to create new methods for the synthesis of fl uorine-18 labeled radiopharmaceuticals. Th e aim of this work is to select iodoaliphatic carboxylic acids and esters for radiopharmaceuticals labeling. Material and methods. A simple way to obtain z-yodalifi c carbonic acids and complex esters from commercially available cyclic ketones has been developed. Automatic synthesis of 18F-fl uoroproprostatic groups and 18F fl uoride peptide agents is successfully carried out using new original materials and various purification methods with solid phase cartridges Results. In further work, it is planned to use different 18F-fluoroproproprostatic groups for synthesis with various peptide agents. Conclusion. Based on these compounds 18F-fl uoroproproprostatic groups were synthesized. Octreotid as an analogue of somatostatin, the non-immunoglobulin-specifi c frame proteins (designed ankyrin repeat proteins) for targeted imaging of tumor cells hyperexpressing Her-2/neu, and prostate-specific membrane antigen (PSMA) inhibitor are signifi cant peptide agents.
Keywords: PET, radionuclide, fl uoride-18, RFLP, automated synthesis
Application of full proteomic analysis of blood cells, plasma and urine for differential diagnosis
Glazyrin YE, Veprintsev DV, Berezovski MV. Application of full proteomic analysis of blood cells, plasma and urine for diff erential diagnosis. Siberian Medical Review. 2021; (2):87-89. DOI 10.20333/2500136-2021-2-87-89
Th e paper considers a methodology for creating concepts for new non-invasive diff erential diagnostic systems based on proteomic profiling of blood cells, plasma and urine. In this case, the relative quantitative information about all proteins found in the samples is used simultaneously. In the presented examples, using machine learning methods, it became possible to separate groups of patients with diabetic nephropathy and glomerulonephritis according to proteomic data of blood plasma, and to separate patients with hypertensive nephropathy from these groups using proteomic data of urine. With the help of regression analysis, it was possible to construct a linear model capable of assessing the moment of the need to initiate therapy in the future for patients at an early stage of chronic lymphocytic leukemia.
Keywords: proteomic profi ling, mass spectrometry, diff erential diagnosis, machine learning, linear regression
Zamay GS, Kolovskaya OS, Grek DS, Babkin VA, Neverova NA, Patc YuS. Magnetomechanical stimulation of bone tissue regeneration. Siberian Medical Review. 2021; (2):90-93. DOI 10:20333/2500136-2021-2-90-93
Th e aim of the research. To assess the ability of superparamagnetic nanoparticles functionalized with the RGD peptide to accelerate bone tissue recovery after transverse osteotomy under the infl uence of a low-frequency alternating magnetic field. Material and methods. We used superparamagnetic nanoparticles ferroarabinogalactans (FeAG) functionalized with the RGD peptide for targeted binding to integrins. Th e model for assessing the ability of FeAG-RGD to accelerate bone regeneration was the transverse osteotomy of the radius of the ICR mice. To induce the process of bone tissue regeneration after the injection of FeAG-RGD particles, mice were placed in an alternating magnetic field (50 Hz 100 Oe) for 60 min. Th e therapy was performed daily for 5 days. Results. The paper tested the hypothesis about the acceleration of bone tissue regeneration by the method of magnetomechanical therapy using superparamagnetic FeAG-RGD nanoparticles. It has been established that FeAG-RGD under conditions of an alternating magnetic fi eld (50 Hz 100 Oe) are able to change their orientation in space and, thus, cause mechanical stress in the proteins of the cell membrane – integrins, which trigger the process of osteogenic differentiation. The research results showed that 5 procedures of magnetomechanical therapy lead to complete restoration of bone tissue at the site of the transverse osteotomy, while in the group of control animals no fusion of bones is observed. Conclusion. Th e use of the method of magnetomechanical therapy using ferroarabinogalactans functionalized with the targeting ligand RGD for binding to integrins of osteogenic cells is a promising technology for bone tissue regeneration.
Keywords: superparamagnetic nanoparticles, ferroarabinogalactans, RGD peptide, integrins, bone tissue regeneration
Zyuzyukina AV, Vatrushkina MO, Zukov RA. Circulating tumor cells: real-time monitoring of the course of breast cancer. Siberian Medical Review. 2021;(2):94-96. DOI 10.20333/2500136-2021-2-94-96
The aim of the research. This study aims to determine the content of circulating tumor cells (CTCs) in the peripheral blood using the MDA 231 aptamer in the dynamics of the disease. Material and methods. The study included 6 patients with breast cancer, who have been under dispensary supervision since 2017. Detection of CTCs was carried out in 3.5 ml of the blood of BC patients with the help of the MDA 231 aptamer which is affi ne for breast cancer cells, labeled with the fl uorescent Cy-5 dye. Th e count of CTCs in the blood samples was performed using fl uorescent and laser scanning microscopy. Results. Using the MDA231 aptamer, the content of CTCs in the peripheral blood of patients with breast cancer in the dynamics of the disease was analyzed. CTCs were detected in 1 patient, who was subsequently diagnosed with metastatic liver damage. Conclusion. The study demonstrates the possibility of using aptamers to determine the risk of relapse and to evaluate the eff ectiveness of antitumor therapy in patients with breast cancer
Keywords: сirculating tumor cells, aptamers, breast cancer, therapy, diagnostics
Smoliarova TE. Synthesis, properties and functionalization of gold nanostars for medical diagnostics. Siberian Medical Review. 2021;(2):97-99.. DOI 10.20333/2500136-2021-2-97-99
The aim of the research. To evaluate two approaches to colloidal synthesis using two diff erent non-toxic surfactants (PVP and Triton X-100) and their properties for future use. Material and methods. (PVP) Th e solution of GNSs with short tips was prepared in 200 ml vial. 20 mg of PVP (Polyvinylpyrrolidone, 1-ethenylpyrrolidin-2-one) were dissolved in the 200 mL of DMF (N,N-Dimethylmethanamide) (with the sonication to dissolve well). (Triton X-100) In a typical preparation of GNSs with long tips, the seed solution was prepared in a 20mL vial: 5mL of HAuCl4 5∙10-4M in water are added to 5mL of an aqueous solution of TritonX-100 0.1M. To examinate the shape and properties of prepared gold nanostars Cary 100 Bio Spectrophotometer using quartz cuvettes was used to taken on UV-Vis spectra. Transmission Electron Microscopy (TEM) was used to obtain shape and size of prepared GNSs. Results. Microscopy analysis shows that the obtained GNSs have completely different shapes. Th e GNSs fabricated using synthesis approach with PVP have shorter tips and the cores are larger than the GNSs synthesized with Triton X-100 synthesis approach. TEM-images of the second ones show smaller size nanoparticles with the longer and thinner tips. Optical properties of the synthesized GNSs were analyzed using UV-vis-NIR absorbtion spectra, which shows maximum plasmon existence at 800 nm for GNSs synthesized with PVP and at 850 nm for GNSs synthesized with Triton X-100. Conclusion. In summary, we developed GNSs using two colloidal synthesis approaches with the use of two diff erent non-toxic surfactants (PVP and Triton X-100). In the future, gold nanostars are planned to be used to develop highly sensitive methods of medical diagnostics.
Keywords: colloidal synthesis, gold nanostars, absorbtion spectra
Blagodatova AV, Kochkina KV, Komarova MA, Trofina NY, Petrova MM, Protopopov AV. Aptamers selection for platelets using droplet digital PCR. Siberian Medical Review. 2021; (2):100-103. DOI 10.20333/2500136-2021-2-100-103
The aim of the research. To obtain aptamers-inhibitors of platelet glycoprotein IIb / IIIa receptors, blocking platelet aggregation. Material and methods. The selection of aptamers for IIb / IIIa receptors of platelets was carried out according to the SELEX method (Systematic Evolution of Ligands by Exponential Enrichment), modifi ed to select aptamers for a specifi c epitope. The method allows selection and in vitro evolution of aptamers with selectivity to a specific target from a large library of oligonucleotides. The affinity of aptamers for platelet IIb / IIIa receptors was determined using flow cytometry. Results. Pools of aptamers of aptamers with high affi nity for IIb / IIIa platelet receptors were obtained. Th e study of the antiaggregation properties of the pools with the best binding showed that platelet aggregation was minimal when using the aptamers from the pool of the 5th round of selection. Thus, the aptamers of this pool have the greatest potential to be used as an analogue of a synthetic peptide that blocks thromboaggregation. Aptamers from this pool were taken for sequencing in order to obtain sequences of aptamers with the best antiaggregatory properties. Conclusion. Pools of aptamers with high affi nity for IIb / IIIa receptors of platelets and anticoagulant activity were obtained.
Keywords: aptamers,SELEX method, platelets, IIb / IIIa receptors, thromboaggregation, von Willebrand factor
Targeting breast cancer exosomes with nucleic aptamers: innovative tools for early diagnosis and therapy
Esposito CL, Quintavalle C, Ingenito F, Rotoli D, Roscigno G, Nuzzo S, Th omas R, Catuogno S, Minic Z, Berezovski M, de Franciscis V, Condorelli Gerolama. Targeting breast cancer exosomes with nucleic aptamers: innovative tools for early diagnosis and therapy. Siberian Medical Review. 2021; (2):104.. DOI 10.20333/2500136-2021-2-104
Exosomes are emerging as promising target for early diagnosis and therapy in different oncological conditions including breast cancer (BC). However, the development of tools able to easily and specifi cally target cancer cell-derived exosomes still represent a fundamental issue that is required to realize their clinical utility. Nucleic-acid aptamers are a promising class of structured single stranded oligonucleotides that serve as high affi nity ligands of disease-associated proteins. Given their high potential in diagnosis and therapy, we addressed the development of aptamers specifi c for BC-derived exosomes. To this end, we developed a novel SELEX strategy by using exosomes purified from primary BC cells as positive selection target. By such a strategy we isolated nuclease resistant RNA aptamers able to specifi cally discriminate BC-derived exosomes from those produced by normal cells. The best sequences were optimized identifying short molecules (about 30-35 mer) that was characterized as tools for exosome detection. Further, we demonstrated that the developed aptamers inhibited exosome cellular uptake antagonizing cancer exosome-induced cell migration. By proteomic approach we identifi ed possible targets that we are characterizing. Our results underline the great potential of isolated aptamers as tools for the development of innovative strategies for BC early diagnosis and therapy.
Keywords: exosomes, aptamers, diagnosis, therapy, oncology
Shchugoreva IA, Artyushenko PV, Tomilin FN, Morozov D, Mironov V, Moryachkov RV, Kichkailo AS.Applying joint theoretical experimental research to aptamer modeling.. Siberian Medical Review. 2021; (2):105-106. DOI 10.20333/2500136-2021-2-105-106
The aim of the research. In this work we studied the structure of LC-18 DNA aptamer, which exhibits specifi c binding to lung adenocarcinoma cells. Obtaining the 3D structure of the aptamer is necessary for understanding the mechanism of binding of the aptamer to the target. Therefore, the aim of the research was modeling of the LC-18 aptamer spatial structure using combination of theoretical methods: DNA folding tools, quantum-chemical calculations and molecular dynamic simulations. Material and methods. The secondary structure of the LC-18 aptamer was predicted by using OligoAnalyzer and MFold online soft ware under the conditions typical small-angle X-ray scattering (SAXS) experiment. Th e molecular modeling of the aptamer was carried out using the Avogadro program. For prediction of the structure two computational methods were used: quantum-mechanical method with third-order density-functional tight-binding (DFTB3) and molecular dynamics (MD) with force fields. Results. In this paper it was shown that molecular simulations can predict structures from the SAXS experiments. OligoAnalyzer and MFold web servers have been used to generate a set of several likely models. However, more accurate calculations have showed that these models do not predict the relative importance of isomers. Meanwhile, application of quantum-chemical and molecular dynamics calculations have showed reliable molecular structures which have a small deviations from the experimental SAXS curves. Conclusion. Th is study demonstrates the approach for modeling 3D structures of DNA-aptamers in solution using both experimental and theoretical methods. It could be very helpful in designing more efficient aptamers based on results obtained from molecular simulations.
Keywords: LC-18, DNA aptamer, lung adenocarcinoma, SAXS, DFTB3.
Electrochemical aptasensors for diagnostics and analysis of biological samples. Important aspects
Shabalina AV. Electrochemical aptasensors for diagnostics and analysis of biological samples. Important aspects. Siberian Medical Review. 2021;(2):107. DOI 10.20333/2500136-2021-2-107
Th e transition to personalized medicine requires a continuous improvement in the quality of diagnostics, and, consequently, improvement and effi ciency of the use of diagnostic tools. Biosensors have high potential in the field of clinical diagnosis, especially in the early stages of diseases. The use of postgenomic technologies, in particular the use of DNA-aptamers, which are recognizing biomolecules, as part of biosensors, in combination with highly sensitive methods of analysis, such as electrochemical ones, can further increase the potential of using biosensor systems. Because it becomes possible to determine the presence of target objects (for example, tumor markers or markers of other diseases) with high sensitivity and selectivity of analysis. However, despite the rapid growth in the number of scientifi c research and publications in the field of the development of electrochemical biosensors based on aptamers (aptasensors), at the moment the commercialization of the products obtained occurs slowly and to a low level. Th e market of biosensors is still dominated by enzymes and antibodies-based sensors that are standardized in the industry. Th is is probably due to the fact that the business originated from enzymes/antibodies utilization at fi rst. But also the general lack of knowledge on the performance of aptasensors in research and in practical use plays an important role . The latter, inter alia, is a consequence of the lack of a proven theoretical base to date, of confirmed key mechanisms and patterns governing the processes of obtaining the response of an electrochemical aptasensor. However, it is obvious that the confi rmed knowledge of the key patterns and mechanisms of the biosensor response formation in the presence of the target object will allow a sufficiently high degree of control of this process to optimize the analysis procedure and increase its efficiency and stability of the aptasensor making it suitable for the practical use. A large variety of approaches are used for new electrochemical aptasensors development. Among them there are diff erent signal amplifi cation strategies, nanoparticles and other biomolecules addition to the aptasensor’s construction, more complicated signal formation schemes, and so on . So, the fi rst important aspect is the fact that every new-developed approach requires theoretical consideration and deep study of the sensing mechanism. Before developing an aptasensor for the commercial purposes, one should consider the target task and the specifi c requirements, namely sampling and samples’ preparation, analyte’s type and the targeted concentration range, the possible composition of the matrix, noise, the fi nal cost of the device, etc. [2-5]. Thus, two next important aspects are the necessity to take into account the real samples’ specifi city and the request for the minimal possible price. The last important point that needs to be highlighted is the analytical signal of the electrochemical aptasensor itself. Normally, for the entire electrochemical response recorded in the form of dependences of one or more parameters on the programmed eff ect (current, potential, frequency), one feature is selected (called an analytical signal), by which all the data is analyzed. More frequently, to detect the presence of the target analyte, the magnitude of the selected feature is compared for the response of the biosensor before and aft er contact with the test sample (for example, ). However, the responses are complex and are composed of many features. Th e signal can be either a nontrivial feature, or it might be their pair or a triple combination. Identifi cation of the informative part of the response is the work of obtaining/generating an aptasensor signal. So, in the present work, four important aspects that need to be considered during electrochemical aptasensor development were pointed out. Not all of them are widely presented in the literature, but still, they require the attention of the researchers.
Keywords: electrochemical aptasensor, aptamer, oncological diseases, voltammetry, impedance measurement.
Addressed delivery of valproic acid to target cells in treatment of epilepsy using aptamers
Zamay TN, Dmitrenko DV, Shnaider NA, Narodova EA, Narodova VV, Usolceva AA, Popov IS. Addressed delivery of valproic acid to target cells in treatment of epilepsy using aptamers. Siberian Medical Review. 2021; (2):108-112. DOI 10.20333/2500136-2021-2-108-112
The aim of the research. To develop a drug based on aptamers that cross the blood-brain barrier, targeting the delivery of valproic acid to the brain. Material and methods. We used the Brain 1 and Co 451 aptamers passing through the blood-brain barrier, obtained using the in vivo-SELEX technology, the affinity of which was determined using flow cytometry fluorescence microscopy. Th e drug for targeted delivery of valproic acid was obtained using the conjugation of Konvulex, biotinylated aptamers, and streptavidin protein. The antiepileptic efficacy of the drug was evaluated in ICR mice with a lithium-pilocarpine model of the development of epilepsy. Aft er the injection of pilocarpine, the animals were monitored using round-the-clock video recording. For the treatment of epilepsy, a valproic acid dose of 130 μg / g of animal weight was used. During treatment with a drug for targeted delivery, the dose of valproic acid was reduced to 5 μg / g. Evaluation of status epilepticus in mice was performed using the Racine Scale. Results. In animals, using the lithium-pilocarpine model, status epilepticus was formed at different stages - from the 1st to the 5th. In all groups of animals, complete overcoming of status epilepticus did not occur in 120 min. In the group of mice treated with valroic acid, no change in their status occurred within 80 minutes. When mice were treated with conjugates based on the Brain 1 and Co 451 aptamers, the blockade of status epilepticus in mice, despite the lower (26 times) doses of the administered antiepileptic drug, occurred faster. Conclusion. A scientific platform has been developed for the development of drugs for targeted delivery of antiepileptic drugs with high efficiency and low toxicity
Keywords: Aptamers, epilepsy, status epilepticus, valproic acid, targeted delivery, streptavidin
Study of the anti-inflammatory activity of the Potentilla anserina L on burn wounds in mice
Savelieva EE, Veselova OF, Gackih IV, Horgevski VA, Aleshencev KG, Perevertov TA. Study of the anti-infl ammatory activity of the Potentilla anserina L on burn wounds in mice. Siberian Medical Review. 2021; (2):113-116. DOI 10.20333/2500136-2021-2-113-116
Th e aim of the research. To investigate the anti-infl ammatory eff ect of Cinquefoil on a model of a thermal wound. Material and methods. A liquid extract in 70 % ethyl alcohol was obtained from dry crushed goose cinquefoil by the percolation method. Th e resulting extracts were evaporated under vacuum at a temperature of 50 °C. Th e dry residue was dissolved in water immediately before treatment at a dose of 250 mg / kg. The evaluation of anti-infl ammatory activity was carried out in an experiment on 20 white male mice. Thermal skin burns were simulated in all animals. The burns were healed in an open way. During the entire experiment, the general condition of the experimental animals was assessed, body weight and temperature were determined, the appearance of wounds, appetite, and activity were assessed. For histological examination, a section of the skin was taken, including the burn zones and intact tissues. Paraffi n sections were stained with hematoxylin and eosin. Results. An analysis of the results of the experimental study showed that all experimental animals, under the infl uence of high temperatures, developed a third degree thermal burn of the skin, characterized by damage to the entire thickness of the skin with complete death of hair follicles, sweat and sebaceous glands. At the site of the burn, the skin was dense, motionless and insensitive to painful stimuli. Th e appearance of the wounds did not diff er between groups of animals. Comparative microscopy of the control and experimental groups showed that the depth of damage to the epidermis and dermis was more pronounced in the experimental group. In addition, in the same group, lymphocytic infiltration of the dermis, hypodermis, the presence of a pronounced vascular reaction and edema of the dermis are more pronounced, which indicates a more pronounced infl ammatory. Conclusion. Th e analysis of the results obtained shows that in the treatment of burn wounds, the local application of the preparation Potentilla goose on the 4th day in the experiment does not lead to a pronounced anti-inflammatory effect. However, the revealed lymphocytic infi ltration of the dermis and other histological parameters indicate more active processes in the tissues, which may subsequently lead to more accelerated wound cleansing and faster regeneration.
Keywords: thermal wound, regeneration, anti-infl ammatory eff ect, Goose cinquefoil.