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Article ; Online: Pregnenolone and progesterone production from natural sterols using recombinant strain of Mycolicibacterium smegmatis mc

Karpov, Mikhail / Strizhov, Nicolai / Novikova, Ludmila / Lobastova, Tatyana / Khomutov, Sergey / Shutov, Andrei / Kazantsev, Alexey / Donova, Marina

Microbial cell factories

2024 Volume 23, Issue 1, Page(s) 105

Abstract: Background: Pregnenolone and progesterone are the life-important steroid hormones regulating essential vital functions in mammals, and widely used in different fields of medicine. Microbiological production of these compounds from sterols is based on ... ...

Abstract	Background: Pregnenolone and progesterone are the life-important steroid hormones regulating essential vital functions in mammals, and widely used in different fields of medicine. Microbiological production of these compounds from sterols is based on the use of recombinant strains expressing the enzyme system cholesterol hydroxylase/C20-C22 lyase (CH/L) of mammalian steroidogenesis. However, the efficiency of the known recombinant strains is still low. New recombinant strains and combination approaches are now needed to produce these steroid hormones. Results: Based on Mycolicibacterium smegmatis, a recombinant strain was created that expresses the steroidogenesis system (CYP11A1, adrenodoxin reductase, adrenodoxin) of the bovine adrenal cortex. The recombinant strain transformed cholesterol and phytosterol to form progesterone among the metabolites. When 3-methoxymethyl ethers of sterols were applied as bioconversion substrates, the corresponding 3-ethers of pregnenolone and dehydroepiandrosterone (DHEA) were identified as major metabolites. Under optimized conditions, the recombinant strain produced 85.2 ± 4.7 mol % 3-methoxymethyl-pregnenolone within 48 h, while production of 3-substituted DHEA was not detected. After the 3-methoxymethyl function was deprotected by acid hydrolysis, crystalline pregnenolone was isolated in high purity (over 98%, w/w). The structures of steroids were confirmed using TLC, HPLC, MS and Conclusion: The use of mycolicybacteria as a microbial platform for the expression of systems at the initial stage of mammalian steroidogenesis ensures the production of valuable steroid hormones-progesterone and pregnenolone from cholesterol. Selective production of pregnenolone from cholesterol is ensured by the use of 3-substituted cholesterol as a substrate and optimization of the conditions for its bioconversion. The results open the prospects for the generation of the new microbial biocatalysts capable of effectively producing value-added steroid hormones.
MeSH term(s)	Cattle ; Animals ; Progesterone ; Pregnenolone/metabolism ; Sterols ; Steroids ; Cholesterol/metabolism ; Cholesterol Side-Chain Cleavage Enzyme/genetics ; Cholesterol Side-Chain Cleavage Enzyme/metabolism ; Phytosterols ; Mammals/metabolism ; Ethers
Chemical Substances	Progesterone (4G7DS2Q64Y) ; Pregnenolone (73R90F7MQ8) ; Sterols ; Steroids ; Cholesterol (97C5T2UQ7J) ; Cholesterol Side-Chain Cleavage Enzyme (EC 1.14.15.6) ; Phytosterols ; Ethers
Language	English
Publishing date	2024-04-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2091377-1
ISSN	1475-2859 ; 1475-2859
ISSN (online)	1475-2859
ISSN	1475-2859
DOI	10.1186/s12934-024-02385-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Rodent models of pulmonary embolism and chronic thromboembolic pulmonary hypertension.

Karpov, Andrei A / Vaulina, Dariya D / Smirnov, Sergey S / Moiseeva, Olga M / Galagudza, Michael M

Heliyon

2022 Volume 8, Issue 3, Page(s) e09014

Abstract: Pulmonary embolism (PE) is the third most prevalent cardiovascular disease. It is associated with high in-hospital mortality and the development of acute and chronic complications. New approaches aimed at improving the prognosis of patients with PE are ... ...

Abstract	Pulmonary embolism (PE) is the third most prevalent cardiovascular disease. It is associated with high in-hospital mortality and the development of acute and chronic complications. New approaches aimed at improving the prognosis of patients with PE are largely dependent on reliable animal models. Mice, rats, hamsters, and rabbits, are currently most commonly used for PE modeling because of their ethical acceptability and economic feasibility. This article provides an overview of the main approaches to PE modeling, and the advantages and disadvantages of each method. Special attention is paid to experimental endpoints, including morphological, functional, and molecular endpoints. All approaches to PE modeling can be broadly divided into three main groups: 1) induction of thromboembolism, either by thrombus formation
Language	English
Publishing date	2022-02-24
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2022.e09014
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Article: Analysis of Models of Doxorubicin-Induced Cardiomyopathy in Rats and Mice. A Modern View From the Perspective of the Pathophysiologist and the Clinician.

Podyacheva, Ekaterina Yu / Kushnareva, Ekaterina A / Karpov, Andrei A / Toropova, Yana G

Frontiers in pharmacology

2021 Volume 12, Page(s) 670479

Abstract: Today the pharmacological possibilities of treating cancer are expanding and as a result, life expectancy is increasing against the background of chemotherapy and supportive treatment. In the conditions of successful antitumor treatment, complications ... ...

Abstract	Today the pharmacological possibilities of treating cancer are expanding and as a result, life expectancy is increasing against the background of chemotherapy and supportive treatment. In the conditions of successful antitumor treatment, complications associated with its toxic effect on healthy tissues and organs began to come to the fore. Anthracycline cardiomyopathy was the first serious cardiovascular complication to draw the attention of oncologists and cardiologists around the world. Anthracycline drugs such as doxorubicin, epirubicin, idarubicin are still widely used in oncological practice to treat a wide range of solid and hematological malignancies. Doxorubicin-induced cardiomyopathy is closely associated with an increase in oxidative stress, as evidenced by reactive oxygen species (ROS) nduced damage such as lipid peroxidation, and decreased levels of antioxidants. Myofibrillar destruction and dysregulation of intracellular calcium are also important mechanisms, usually associated with doxorubicin-induced cardiotoxicity. Despite the abundance of data on various mechanisms involved in the implementation of doxorubicin-induced cardiotoxicity, a final understanding of the mechanism of the development of doxorubicin cardiomyopathy has not yet been formed. It poses the most significant challenges to the development of new methods of prevention and treatment, as well as to the unambiguous choice of a specific treatment regimen using the existing pharmacological tools. In order to resolve these issues new models that could reflect the development of the chemotherapy drugs effects are needed. In this review we have summarized and analyzed information on the main existing models of doxorubicin cardiomyopathy using small laboratory animals. In addition, this paper discusses further areas of research devoted to the development and validation of new improved models of doxorubicin cardiomyopathy suitable both for studying the mechanisms of its implementation and for the preclinical drugs effectiveness assessment.
Language	English
Publishing date	2021-06-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2021.670479
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Article ; Online: Correction to "Development of Nanocarrier-Based Radionuclide and Photothermal Therapy in Combination with Chemotherapy in Melanoma Cancer Treatment".

Peltek, Oleksii O / Karpov, Timofey E / Rogova, Anna / Postovalova, Alisa / Ageev, Eduard / Petrov, Andrey / Antuganov, Dmitri / Stanzhevsky, Andrei A / Maistrenko, Dmitri N / Zuev, Dmitry / Muslimov, Albert R / Timin, Alexander S / Zyuzin, Mikhail V

ACS applied materials & interfaces

2023 Volume 15, Issue 39, Page(s) 46579

Language	English
Publishing date	2023-09-20
Publishing country	United States
Document type	Published Erratum
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.3c12684
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Article: Prone Position after Liberation from Prolonged Mechanical Ventilation in COVID-19 Respiratory Failure.

Karpov, Andrei / Mitra, Anish R / Crowe, Sarah / Haljan, Gregory

Critical care research and practice

2020 Volume 2020, Page(s) 6688120

Abstract: Design: This is a retrospective case series describing the feasibility and tolerability of postextubation prone positioning (PEPP) and its impact on physiologic parameters in a tertiary intensive care unit during the COVID-19 pandemic. : Conclusions: ...

Abstract	Design: This is a retrospective case series describing the feasibility and tolerability of postextubation prone positioning (PEPP) and its impact on physiologic parameters in a tertiary intensive care unit during the COVID-19 pandemic. Conclusions: The novel practice of PEPP after liberation from prolonged mechanical ventilation in patients with COVID-19 respiratory failure is feasible and well tolerated, and may be associated with favourable clinical outcomes including improvement in oxygenation and respiratory rate and a low rate of reintubation. Larger prospective studies of PEPP are warranted.
Language	English
Publishing date	2020-11-12
Publishing country	Egypt
Document type	Journal Article
ZDB-ID	2573849-5
ISSN	2090-1313 ; 2090-1305
ISSN (online)	2090-1313
ISSN	2090-1305
DOI	10.1155/2020/6688120
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Article: Mechanisms of Regenerative Potential Activation in Cardiac Mesenchymal Cells.

Docshin, Pavel M / Karpov, Andrei A / Mametov, Malik V / Ivkin, Dmitry Y / Kostareva, Anna A / Malashicheva, Anna B

Biomedicines

2022 Volume 10, Issue 6

Abstract: Recovery of the contractile function of the heart and the regeneration of the myocardium after ischemic injury are contemporary issues in regenerative medicine and cell biology. This study aimed to analyze early transcriptional events in cardiac tissue ... ...

Abstract	Recovery of the contractile function of the heart and the regeneration of the myocardium after ischemic injury are contemporary issues in regenerative medicine and cell biology. This study aimed to analyze early transcriptional events in cardiac tissue after infarction and to explore the cell population that can be isolated from myocardial tissue. We induced myocardial infarction in Wistar rats by permanent ligation of the left coronary artery and showed a change in the expression pattern of Notch-associated genes and
Language	English
Publishing date	2022-05-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10061283
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Article: Rodent models of pulmonary embolism and chronic thromboembolic pulmonary hypertension

Karpov, Andrei A. / Vaulina, Dariya D. / Smirnov, Sergey S. / Moiseeva, Olga M. / Galagudza, Michael M.

Heliyon. 2022 Mar., v. 8, no. 3

2022

Abstract	Pulmonary embolism (PE) is the third most prevalent cardiovascular disease. It is associated with high in-hospital mortality and the development of acute and chronic complications. New approaches aimed at improving the prognosis of patients with PE are largely dependent on reliable animal models. Mice, rats, hamsters, and rabbits, are currently most commonly used for PE modeling because of their ethical acceptability and economic feasibility. This article provides an overview of the main approaches to PE modeling, and the advantages and disadvantages of each method. Special attention is paid to experimental endpoints, including morphological, functional, and molecular endpoints. All approaches to PE modeling can be broadly divided into three main groups: 1) induction of thromboembolism, either by thrombus formation in vivo or by injection of in vitro prepared blood clots; 2) introduction of particles of non-thrombotic origin; and 3) surgical procedures. The choice of a specific model and animal species is determined based on the objectives of the study. Rodent models of chronic thromboembolic pulmonary hypertension (CTEPH), which is the most devastating complication of PE, are also described. CTEPH models are especially challenging because of insufficient knowledge about the pathogenesis and high fibrinolytic activity of rodent plasma. The CTEPH model should demonstrate a persistent increase in pulmonary artery pressure and stable reduction of the vascular bed due to recurrent embolism. Based on the analysis of available evidence, one might conclude that currently, there is no single optimal method for modeling PE and CTEPH.
Keywords	economic feasibility ; embolism ; ethics ; hypertension ; mortality ; pathogenesis ; prognosis ; pulmonary artery ; thrombosis
Language	English
Dates of publication	2022-03
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2022.e09014
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Use of fibrinogen concentrate for trauma-related bleeding: A systematic-review and meta-analysis.

Stabler, Sarah N / Li, Siying Shari / Karpov, Andrei / Vu, Erik N

The journal of trauma and acute care surgery

2020 Volume 89, Issue 6, Page(s) 1212–1224

Abstract: Background: Trauma-induced coagulopathy contributes to significant morbidity and mortality in patients who experience trauma-related bleeding. This study aimed to synthesize the evidence supporting the efficacy and safety of preemptive and goal-directed ...

Abstract	Background: Trauma-induced coagulopathy contributes to significant morbidity and mortality in patients who experience trauma-related bleeding. This study aimed to synthesize the evidence supporting the efficacy and safety of preemptive and goal-directed fibrinogen concentrate (FC) in the management of trauma-related hemorrhage. Methods: PubMed, Medline, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform were systematically searched. All trial designs, except individual case reports, which evaluated the preemptive or goal-directed use of FC for trauma-related bleeding/coagulopathy, in patients older than 16 years, were included in the systematic review. For the included randomized controlled trials comparing FC with control, meta-analysis was performed and a risk-of bias-assessment was completed using the Cochrane Methodology and Preferred Reporting Items Systematic Reviews and Meta-analysis guidelines. Results: A total of 2,743 studies were identified; 26 were included in the systematic review, and 5 randomized controlled trials (n = 238) were included in the meta-analysis. For the primary outcome of mortality, there was no statistically significant difference between the groups, with 22% and 23.4% in the FC and comparator arms, respectively (risk ratio, 1.00 [95% confidence interval, 0.39 to 2.56]; p = 0.99). In addition, there was no statistical difference between FC and control in packed red blood cell, fresh frozen plasma, or platelet transfusion requirements, and thromboembolic events. Overall, the quality of evidence was graded as low to moderate because of concerns with risk of bias, imprecision, and inconsistency. Conclusion: Further high-quality, adequately powered studies are needed to assess the impact of FC in trauma, with a focus on administration as early as possible from the point of entry into the trauma system of care. Level of evidence: Systematic review and Meta-analysis, level II.
MeSH term(s)	Blood Coagulation Factors/therapeutic use ; Fibrinogen/therapeutic use ; Hemorrhage/drug therapy ; Hemorrhage/mortality ; Hemorrhage/prevention & control ; Hemostatics ; Humans ; Randomized Controlled Trials as Topic ; Wounds and Injuries/complications
Chemical Substances	Blood Coagulation Factors ; Hemostatics ; Fibrinogen (9001-32-5)
Language	English
Publishing date	2020-09-17
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	2651070-4
ISSN	2163-0763 ; 2163-0755
ISSN (online)	2163-0763
ISSN	2163-0755
DOI	10.1097/TA.0000000000002920
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Article ; Online: Development of Nanocarrier-Based Radionuclide and Photothermal Therapy in Combination with Chemotherapy in Melanoma Cancer Treatment.

ACS applied materials & interfaces

2023 Volume 15, Issue 10, Page(s) 13460–13471

Abstract: Conventional cancer therapy methods have serious drawbacks that are related to the nonspecific action of anticancer drugs that leads to high toxicity on normal cells and increases the risk of cancer recurrence. The therapeutic effect can be significantly ...

Abstract	Conventional cancer therapy methods have serious drawbacks that are related to the nonspecific action of anticancer drugs that leads to high toxicity on normal cells and increases the risk of cancer recurrence. The therapeutic effect can be significantly enhanced when various treatment modalities are implemented. Here, we demonstrate that the radio- and photothermal therapy (PTT) delivered through nanocarriers (gold nanorods, Au NRs) in combination with chemotherapy in a melanoma cancer results in complete tumor inhibition compared to the single therapy. The synthesized nanocarriers can be effectively labeled with
MeSH term(s)	Humans ; Photothermal Therapy ; Antineoplastic Agents/pharmacology ; Phototherapy/methods ; Paclitaxel/pharmacology ; Paclitaxel/therapeutic use ; Melanoma/drug therapy ; Radioisotopes/therapeutic use ; Gold/pharmacology ; Nanotubes ; Cell Line, Tumor
Chemical Substances	Antineoplastic Agents ; Paclitaxel (P88XT4IS4D) ; Radioisotopes ; Gold (7440-57-5)
Language	English
Publishing date	2023-03-03
Publishing country	United States
Document type	Journal Article
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.2c20619
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Article ; Online: Sympathetic Denervation and Pharmacological Stimulation of Parasympathetic Nervous System Prevent Pulmonary Vascular Bed Remodeling in Rat Model of Chronic Thromboembolic Pulmonary Hypertension.

Karpov, Andrei A / Vachrushev, Nikita S / Shilenko, Leonid A / Smirnov, Sergey S / Bunenkov, Nikolay S / Butskih, Maxim G / Chervaev, Al-Khalim A / Vaulina, Dariya D / Ivkin, Dmitry Yu / Moiseeva, Olga M / Galagudza, Michael M

Journal of cardiovascular development and disease

2023 Volume 10, Issue 2

Abstract: Chronic thromboembolic pulmonary hypertension (CTEPH) develops in 1.5-2.0% of patients experiencing pulmonary embolism (PE) and is characterized by stable pulmonary artery obstruction, heart failure, and poor prognosis. Little is known about involvement ... ...

Abstract	Chronic thromboembolic pulmonary hypertension (CTEPH) develops in 1.5-2.0% of patients experiencing pulmonary embolism (PE) and is characterized by stable pulmonary artery obstruction, heart failure, and poor prognosis. Little is known about involvement of autonomic nervous system (ANS) in the mechanisms of CTEPH. This study was aimed at evaluation of the effect of vagal and sympathetic denervation, as well as stimulation of the parasympathetic nervous system, on the outcomes of CTEPH in rats. CTEPH was induced by multiple intravenous injections of alginate microspheres. Sympathetic and vagal denervation was performed using unilateral surgical ablation of the stellate ganglion and vagotomy, respectively. Stimulation of the parasympathetic nervous system was carried out by administering pyridostigmine. The effect of neuromodulatory effects was assessed in terms of hemodynamics, histology, and gene expression. The results demonstrated the key role of ANS in the development of CTEPH. Sympathetic denervation as well as parasympathetic stimulation resulted in attenuated pulmonary vascular remodeling. These salutary changes were associated with altered MMP2 and TIMP1 expression in the lung and decreased FGFb level in the blood. Unilateral vagotomy had no effect on physiological and morphological outcomes of the study. The data obtained contribute to the identification of new therapeutic targets for CTEPH treatment.
Language	English
Publishing date	2023-01-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2777082-5
ISSN	2308-3425 ; 2308-3425
ISSN (online)	2308-3425
ISSN	2308-3425
DOI	10.3390/jcdd10020040
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