Yu. V. Cheburkin, G. A. Shulmeister, A. B. Bondarenko, A. V. Chistyakova, D. V. Korolev
{"title":"Development of a prototype of a theranostic system based on silica nanoparticles with immobilized fluorescent dyes and VEGF targeting ligand.","authors":"Yu. V. Cheburkin, G. A. Shulmeister, A. B. Bondarenko, A. V. Chistyakova, D. V. Korolev","doi":"10.18705/2311-4495-2023-10-6-522-534","DOIUrl":"https://doi.org/10.18705/2311-4495-2023-10-6-522-534","url":null,"abstract":"Background. Administration of certain drugs causes undesirable effects associated with the systemic effect of the active substance on the entire body. Selective targeting of the drug to the affected tissue promotes a selective increase in the concentration of the substance in the area of interest, thereby reducing the systemic effect and enhancing the local therapeutic effect.Objective. Development of a targeted delivery system for theranostic agents using recombinant human vascular endothelial growth factor type A (rhVEGF-A121) as a targeting ligand.Design and method. To create the theranostic complex, commercially available reagents were used: the recombinant protein rhVEGF-A121 (cat.#: PSG140-10, LLC CyStorLab, Skolkovo, Russia) and fumed silica Aerosil (A-200, Degussa AG, Germany). The tosyl spacer that interconnects both components was synthesized in the laboratory. Protein conjugation with fluorophores was also carried out in-house. Indocyanine green (ICG; Sigma-Aldrich, USA) and rhodamine B (JSC Lenreaktiv, St. Petersburg, Russia) were taken for immobilization.Results. In the course of the work, functionalization of silica nanoparticles (SiNPs) with a tosyl spacer was carried out, conjugates of SiNPs with rhVEGF-A121 were synthesized, and theranostic constructs based on SiNPs were obtained, including rhVEGF-A121 as a targeting ligand, and ICG/Rhodamine B as a visualizing label.Conclusion. In the presented study, a prototype of a complex for targeted delivery of a theranostic agent to tissues with an active angiogenesis process, for example, to tumor and ischemic tissues, was developed. To solve the problem, we immobilized on the surface of SiNP a recombinant protein of human vascular endothelial growth factor (rhVEGF) to use as a guide ligand. Such a synthetic construct will help to deliver diagnostic and/ or medicinal substances packed in SiNP directly to cells that overexpress extracellular specific receptors of the VEGFR family. In subsequent in vivo experiments, delivery efficiency will be assessed by tissue accumulation of the fluorophores ICG and rhodamine B, which have been conjugated to the targeting ligand protein. The physicochemical characteristics of the obtained samples were studied by the methods of spectrophotometry and dynamic light scattering.","PeriodicalId":23243,"journal":{"name":"Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140494067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
O. N. Kukalia, A. A. Meshcheryakov, G. O. Iurev, P. A. Andoskin, K. N. Semenov, O. E. Molchanov, D. N. Maistrenko, I. V. Murin, V. Sharoyko
{"title":"Prospects for the application of water-soluble derivatives of light fullerenes in medicine.","authors":"O. N. Kukalia, A. A. Meshcheryakov, G. O. Iurev, P. A. Andoskin, K. N. Semenov, O. E. Molchanov, D. N. Maistrenko, I. V. Murin, V. Sharoyko","doi":"10.18705/2311-4495-2023-10-6-507-521","DOIUrl":"https://doi.org/10.18705/2311-4495-2023-10-6-507-521","url":null,"abstract":"One of the most promising areas for the use of fullerenes and their derivatives is biology and medicine. This is due to the fact that fullerenes are highly reactive due to the presence of double bonds capable of attaching various radicals, and demonstrate high antioxidant activity, the ability to penetrate through the lipid bilayer, and modulate transmembrane ion transport. The review considers the main biological properties of water-soluble derivatives of light fullerenes, which determine their application in biomedicine.","PeriodicalId":23243,"journal":{"name":"Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140509609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
O. V. Kalinina, D. B. Sambur, E. E. Koroleva, A. S. Golovkin
{"title":"Zebrafish as a model for studing extracellular vesicles.","authors":"O. V. Kalinina, D. B. Sambur, E. E. Koroleva, A. S. Golovkin","doi":"10.18705/2311-4495-2023-10-6-557-565","DOIUrl":"https://doi.org/10.18705/2311-4495-2023-10-6-557-565","url":null,"abstract":"It was evaluated the feasibility of using Zebrafish as a model to study extracellular vesicles (EVs) based on literature. Particularly, it was described experimental models that were used to assess the contribution of the EVs in the regulation of pathological and physiological processes (ischemic, reperfusion, mechanical damage to tissues and organs, development of local and systemic immune response, tumor growth and metastasis, etc.), the bioavailability and the distribution of injected EVs in different tissues and organs, the effects of exogenous EVs as therapeutic agents.","PeriodicalId":23243,"journal":{"name":"Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140509527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. M. Nifontov, I. S. Trusov, T. T. Khachikyan, A. V. Biryukov, A. Krasichkov, D. S. Shapovalova, I. A. Serdiukovа
{"title":"The influence of thyroid status on long-term complications after stenting in patients with acute coronary syndrome without ST-segment elevation.","authors":"E. M. Nifontov, I. S. Trusov, T. T. Khachikyan, A. V. Biryukov, A. Krasichkov, D. S. Shapovalova, I. A. Serdiukovа","doi":"10.18705/2311-4495-2023-10-6-484-494","DOIUrl":"https://doi.org/10.18705/2311-4495-2023-10-6-484-494","url":null,"abstract":"Backround. It is known that both subclinical hypothyroidism (SHT) and subclinical thyrotoxicosis (STT) can influence the outcome of coronary heart disease. The feasibility of routinely determining thyroid status in patients without obvious signs of thyroid dysfunction with acute coronary syndrome without ST-segment elevation (NSTEACS) to assess the effect on the status of implanted stents has not been determined.Objective. To evaluate the effect of subclinical hypothyroidism and subclinical thyrotoxicosis on lumen loss and the degree of endothelialization of drug-eluting stents after stenting for NSTE-ACS. Design and methods. The study included 173 patients who were urgently stented for NSTE-ACS, and who subsequently underwent repeat coronary angiography within a year on a planned or emergency basis with a targeted assessment of the condition of the installed stents. In 40 patients with everolimus-eluting stents, the condition of the coronary arteries was assessed 6.3 + 0.3 months after stenting using optical coherence tomography (OCT). All patients included in the study had their thyroid status assessed.Results. SHT was detected in 8 (21.6 %) patients with loss of lumen in the stent area and in 26 (19.1 %) patients without loss of lumen, p = 0.73. STT was detected in 2 (5.4 %) and 3 (2.2 %) patients, respectively, p = 0.30. A prognostic analysis performed by logistic regression with forced inclusion as predictors of lumen loss identified the parameters Syntax Score I, stent diameter, and the number of affected coronary arteries. No effect of thyroid status on lumen loss was found. In patients with subclinical hypothyroidism, OCT data revealed insufficient endothelialization of everolimus-eluting stents 6 months after stenting for NSTE-ACS. The percentage of uncovered stent struts depended on TSH levels (r = 0.42, p = 0.007). The higher the TSH level, the higher the healing index and the worse the stent endothelialization (r = 0.37, p = 0.016). Conclusion. Thus, routine determination of thyroid status indicators in patients with NSTE-ACS in order to identify subclinical thyroid dysfunction does not provide significant prognostic information regarding the risk of lumen loss of implanted stents. Considering the potential risk of thrombotic complications associated with insufficient endothelialization of everolimus-eluting stents in the presence of subclinical hypothyroidism, it seems advisable to identify it when deciding on de-escalation of antithrombotic therapy. The question remains open about the need to correct the parameters of subclinical thyroid dysfunction in order to modify the prognosis.","PeriodicalId":23243,"journal":{"name":"Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140511514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Protas, E. A. Popova, O. Mikolaichuk, K. N. Semenov, V. V. Sharoyko, O. E. Molchanov, D. Maistrenko
{"title":"Biomedical use of nanoconjugates based on graphene oxide and fullerenes with cytostatic drugs.","authors":"A. Protas, E. A. Popova, O. Mikolaichuk, K. N. Semenov, V. V. Sharoyko, O. E. Molchanov, D. Maistrenko","doi":"10.18705/2311-4495-2023-10-5-402-411","DOIUrl":"https://doi.org/10.18705/2311-4495-2023-10-5-402-411","url":null,"abstract":"Medicine is one of the most promising and essential fields for the application of modern nanotechnologies. Targeted drug delivery, providing prolonged drug action, diagnostics, and the manufacturing of medical devices are among the promising applications of nanomaterials. The excellent electrical, mechanical, and optical properties of carbon nanoparticles, along with their ease of functionalization, have made them attractive candidates for the development of new materials for biomedical applications. As analyzed from contemporary literature, a significant amount of research in experimental oncology has been dedicated to the development of methods for targeted delivery of antitumor agents to biological targets, including the use of nanoparticles. Thus, the creation of antitumor drugs based on conjugates of cytostatic drugs with carbon nanostructures is one of the actively developing directions in medicinal chemistry. This review discusses scientific achievements in the synthesis and study of properties of nanocomposites based on graphene oxide and fullerenes with cytostatic drugs (such as paclitaxel, carboplatin, cisplatin, doxorubicin, gemcitabine, etc.), their mechanisms of action, and practical applications in biomedicine. Special attention is given to the requirements imposed on nanocarriers, methods of targeted delivery of nanocomposites to biological targets, and the advantages of using antitumor agents in the composition of nanoconjugates based on carbon nanostructures. Additionally, the review summarizes and iden- tifies the current challenges in the application of carbon nanostructures in biomedicine.","PeriodicalId":23243,"journal":{"name":"Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139217294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fluorescence polarization immunoassay for the determination and screening of medicines.","authors":"L. I. Mukhametova, S. A. Eremin","doi":"10.18705/2311-4495-2023-10-5-412-422","DOIUrl":"https://doi.org/10.18705/2311-4495-2023-10-5-412-422","url":null,"abstract":"Modern clinical medicine with its achievements has helped a person to get rid of many infectious and non-communicable diseases, restore health, preserve and improve the quality of life of people with chronic dis- eases. Tens of thousands of medicines are used in medical practice. However, paradoxical as it sounds, having created medicines for almost all diseases, humanity has not become healthier and the need for medicines is only growing every year. More than 20 % of people receiving medications during therapy have various complications. Therefore, the search for medicines does not stop, but only increases at the present time. Another important problem is the detecting drugs in environmental objects and food products. Most drugs that get into wastewater from pharmaceutical factories and farms, even after treatment at wastewater treatment plants, are still diagnosed in the water. The method of fluorescence polarization is extremely widespread in clinical and biomedical fields. Thanks to the introduction into laboratory diagnostics of devices capable of measuring the signal of fluorescence polarization on microplates, polarization fluorescent analysis is used not only in the traditional format: the detection of drugs in human physiological fluids, environmental objects and food, but also in high-tech screening of drugs, significantly speeding up and facilitating the process of identifying new drugs.","PeriodicalId":23243,"journal":{"name":"Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139224526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. S. Mosoyan, D. A. Fedorov, E. Gilev, N. A. Aysina
{"title":"Aspiration-irrigation in laparoscopic and robot-assisted surgery. Historical aspects and modern devices","authors":"M. S. Mosoyan, D. A. Fedorov, E. Gilev, N. A. Aysina","doi":"10.18705/2311-4495-2023-10-5-354-362","DOIUrl":"https://doi.org/10.18705/2311-4495-2023-10-5-354-362","url":null,"abstract":"Visualization is one of the key factors for successful operation in endovideosurgery. Aspiration and irrigation play a critical role in ensuring adequate visualization at all stages of operations in general surgery, urology, gynecology and other areas of surgery. It is almost impossible to imagine any minimally invasive surgery without the use of an aspirator-irrigator. It is necessary to protect the intra-abdominal space from contamination and/or removal of blood, clots or other fluid during surgery, which in turn is essential to ensure adequate visualization of the surgical area. This article identifies the main historical stages in the introduction of aspiration and irrigation in minimally invasive surgery, as well as the main devices for removing biological fluids during laparoscopic and robotic operations, used in modern surgery.","PeriodicalId":23243,"journal":{"name":"Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139220376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. A. Mironov, N. S. Mamina, S. Y. Voronin, A. A. Bayramov
{"title":"Study of acute toxicity of a new drug “AOS” for the treatment of osteoporosis.","authors":"A. A. Mironov, N. S. Mamina, S. Y. Voronin, A. A. Bayramov","doi":"10.18705/2311-4495-2023-10-5-363-375","DOIUrl":"https://doi.org/10.18705/2311-4495-2023-10-5-363-375","url":null,"abstract":"Background. Osteoporosis is one of the most common diseases, which, along with myocardial infarction, stroke, cancer, and sudden death, occupies a leading place in the structure of morbidity and mortality of the population. Postmenopausal women are most vulnerable and are approximately 4 times more likely to be affected than men (80 % of all patients), and osteoporosis-related fractures are responsible for a significant increase in morbidity, disability, and mortality, especially in the elderly.Objective. To study the acute toxicity of the new drug “Antiosteoporosis drug” (patent No. 02-04-16643/15-0 dated February 26, 2015) with a single intragastric administration to mature outbred rats of both sexes.Design and methods. The study was conducted on outbred rats of both sexes according to protocol OECD 420, GOST 32296-2013. The development of a toxic effect was concluded based on behavioral tests, clinical examinations, changes in body weight, the results of pathomorphological examination of organ tissue and biochemical parameters of blood and urine.Results. According to the results of the study, the tested drug was classified according to the active substance into category 5 according to the GHS classification (2000<LD50 (i/g)<5000 mg/kg). An assessment of the dynamics of body weight in experimental animals showed that a single intragastric administration of the test drug had no effect on this indicator. The study of individual behavior as part of the main study on the 14th day after a single intragastric administration of the test drug showed that a single intragastric administration of the test drug at a dose of 2000 mg/kg did not have a delayed effect on the general condition and indicative research activity of experimental animals. Autopsy and pathological examination of animals on the 15th day after a single intragastric administration of the test drug did not reveal the presence of any residual effects associated with the administration of the test drug. The tested drug did not have a local irritant effect on the injection site — the gastrointestinal tract. In all tests, the degree of change in indicators caused by the test drug was the same: there were no statistically significant differences in the recorded parameters between the test drug and the control group.","PeriodicalId":23243,"journal":{"name":"Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139226296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. A. Borovaya, A. S. Ulanova, I. Turabov, V. A. Mitrofanov, A. S. Kulikov
{"title":"Northern State Medical University; Arkhangelsk Regional Children’s Clinical Hospital named after P. G. Vyzhletsov","authors":"A. A. Borovaya, A. S. Ulanova, I. Turabov, V. A. Mitrofanov, A. S. Kulikov","doi":"10.18705/2311-4495-2023-10-5-449-454","DOIUrl":"https://doi.org/10.18705/2311-4495-2023-10-5-449-454","url":null,"abstract":"Intestinal cystous pneumatosis is a rare pathology in pediatric practice, accompanied by a nonspecific clinical picture, which greatly complicates the diagnosis. The literature describes isolated cases of the development of this condition in oncohematological patients of childhood. Intestinal cystous pneumatosis in them can be complicated by life-threatening conditions, and therefore the choice of the correct tactics for managing these patients significantly affects survival. This article describes 2 clinical cases when cystic pneumatosis of the intestine developed during the treatment of an oncological disease.","PeriodicalId":23243,"journal":{"name":"Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139217838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V. V. Fursov, S. V. Ananyev, A. A. Bukhvostov, K. V. Ermakov, D. A. Kuznetsov
{"title":"Carlo method as the basis for in silico-modeling in the study of the pathogenesis of ischemic stroke.","authors":"V. V. Fursov, S. V. Ananyev, A. A. Bukhvostov, K. V. Ermakov, D. A. Kuznetsov","doi":"10.18705/2311-4495-2023-10-5-389-401","DOIUrl":"https://doi.org/10.18705/2311-4495-2023-10-5-389-401","url":null,"abstract":"The paper proposes a new mathematical model of dynamic processes in a typical spatially non-uniform biological system. The mathematical problem of modeling the dynamics of the neurovascular units of the brain under conditions of ischemic stroke is formulated and solved. An investigation of this model is conducted, and a numerical and programmatic implementation of the corresponding mathematical problem is proposed.","PeriodicalId":23243,"journal":{"name":"Translational Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139220546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}