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1.
Front Biosci (Landmark Ed) ; 29(5): 191, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38812328

ABSTRACT

BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with pronounced oxidative stress, leading to the development of various virus-associated pathologies. A wealth of evidence suggests that, along with canonical enzymes of reactive oxygen species regulation, human blood contains antibodies with peroxidase, superoxide dismutase, and catalase activities. Here we show that the catalase activity of IgGs and their κκ-IgG, λλ-IgG, and κλ-IgG subfractions of HIV-infected individuals is significantly different compared to the healthy donors. METHODS: Protein G-Sepharose sorbent was used to resolve IgG from blood of healthy donors and HIV-infected patients by affinity chromatography. Subfractions of κκ-IgG, λλ-IgG, and κλ-IgG were separated from IgGs samples of each group by affinity chromatography on sorbents containing immobilized antibodies to κ or λ light human chains. The IgG catalase activity level was measured spectrophotometrically by evaluating the decrease in optical density (A240) due to hydrogen peroxide decomposition. RESULTS: The relative catalase activity of antibodies from HIV-infected patients (kcat = (1.41 ± 0.92) × 103 min-1, 95% CI: [1.01-1.81]) was statistically significant, 1.6 times higher (p = 0.014) compared to apparently healthy donors ((0.86 ± 0.49) × 103, 95% CI: [0.69-1.03]). The activity level of κκ-IgG HIV-infected patients ((0.44 ± 0.04) × 103 min-1) was 1.4 times higher than that of λλ-IgGs ((0.31 ± 0.025) × 103 min-1); the opposite was observed for κκ-IgGs from apparently healthy donors, which activity ((0.17 ± 0.015) × 103 min-1) was 3.1 times lower compared to λλ-IgGs ((0.53 ± 0.045) × 103 min-1). CONCLUSIONS: Thus, the data obtained may indicate that IgG with increased catalase activity may prevent harmful processes arising from oxidative stress in HIV-infected patients, acting as an additional natural molecular mechanism of regulation of hydrogen peroxide level.


Subject(s)
Catalase , HIV Infections , Immunoglobulin G , Immunoglobulin kappa-Chains , Humans , Catalase/blood , Catalase/immunology , Catalase/metabolism , Immunoglobulin G/blood , Immunoglobulin G/immunology , HIV Infections/immunology , HIV Infections/blood , Immunoglobulin kappa-Chains/blood , Immunoglobulin kappa-Chains/immunology , Immunoglobulin lambda-Chains/blood , Immunoglobulin lambda-Chains/immunology , Adult , Case-Control Studies , Male , Female , Chromatography, Affinity/methods , Oxidative Stress , Middle Aged
2.
Biomedicines ; 12(5)2024 May 02.
Article in English | MEDLINE | ID: mdl-38790969

ABSTRACT

Antibodies are protein molecules whose primary function is to recognize antigens. However, recent studies have demonstrated their ability to hydrolyze specific substrates, such as proteins, oligopeptides, and nucleic acids. In 2023, two separate teams of researchers demonstrated the proteolytic activity of natural plasma antibodies from COVID-19 convalescents. These antibodies were found to hydrolyze the S-protein and corresponding oligopeptides. Our study shows that for antibodies with affinity to recombinant structural proteins of the SARS-CoV-2: S-protein, its fragment RBD and N-protein can only hydrolyze the corresponding protein substrates and are not cross-reactive. By using strict criteria, we have confirmed that this proteolytic activity is an intrinsic property of antibodies and is not caused by impurities co-eluting with them. This discovery suggests that natural proteolytic antibodies that hydrolyze proteins of the SARS-CoV-2 virus may have a positive impact on disease pathogenesis. It is also possible for these antibodies to work in combination with other antibodies that bind specific epitopes to enhance the process of virus neutralization.

3.
Int J Mol Sci ; 25(7)2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38612590

ABSTRACT

Spinal cord injury (SCI) presents a complex challenge in neurorehabilitation, demanding innovative therapeutic strategies to facilitate functional recovery. This study investigates the effects of treadmill training on SCI recovery, emphasizing motor function enhancement, neural tissue preservation, and axonal growth. Our research, conducted on a rat model, demonstrates that controlled treadmill exercises significantly improve motor functions post-SCI, as evidenced by improved scores on the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and enhanced electromyography readings. Notably, the training facilitates the preservation of spinal cord tissue, effectively reducing secondary damage and promoting the maintenance of neural fibers in the injured area. A key finding is the significant stimulation of axonal growth around the injury epicenter in trained rats, marked by increased growth-associated protein 43 (GAP43) expression. Despite these advancements, the study notes a limited impact of treadmill training on motoneuron adaptation and highlights minimal changes in the astrocyte and neuron-glial antigen 2 (NG2) response. This suggests that, while treadmill training is instrumental in functional improvements post-SCI, its influence on certain neural cell types and glial populations is constrained.


Subject(s)
Astrocytes , Spinal Cord Injuries , Animals , Rats , Humans , Neuroglia , Electromyography , Motor Neurons , Spinal Cord Injuries/therapy , Axons
4.
Vaccines (Basel) ; 12(4)2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38675808

ABSTRACT

The rapid development of vaccines is a crucial objective in modern biotechnology and molecular pharmacology. In this context, conducting research to expedite the selection of a potent immunogen is imperative. The candidate vaccine should induce the production of antibodies that can recognize the immunogenic epitopes of the target protein, resembling the ones found in recovered patients. One major challenge in vaccine development is the absence of straightforward and reliable techniques to determine the extent to which the spectrum of antibodies produced after vaccination corresponds to antibodies found after recovery. This paper describes a newly developed method to detect antibodies specific to immunogenic epitopes of the target protein in blood plasma and to compare them with antibody spectra generated post vaccination. Comparing the antibody pool generated in the human body after recovering from an infectious disease with the pool formed through vaccination can become a universal method for screening candidate vaccines. This method will enable the identification of candidate vaccines that can induce the production of antibodies similar to those generated in response to a natural infection. Implementing this approach will facilitate the rapid development of new vaccines, even when faced with a pandemic.

5.
Plants (Basel) ; 12(24)2023 Dec 05.
Article in English | MEDLINE | ID: mdl-38140401

ABSTRACT

This review covers the literature data on plant growth-promoting bacteria in soil, which can fix atmospheric nitrogen, solubilize phosphates, produce and secrete siderophores, and may exhibit several different behaviors simultaneously. We discuss perspectives for creating bacterial consortia and introducing them into the soil to increase crop productivity in agrosystems. The application of rhizosphere bacteria-which are capable of fixing nitrogen, solubilizing organic and inorganic phosphates, and secreting siderophores, as well as their consortia-has been demonstrated to meet the objectives of sustainable agriculture, such as increasing soil fertility and crop yields. The combining of plant growth-promoting bacteria with mineral fertilizers is a crucial trend that allows for a reduction in fertilizer use and is beneficial for crop production.

6.
Microorganisms ; 11(12)2023 Nov 26.
Article in English | MEDLINE | ID: mdl-38138008

ABSTRACT

Plant growth-promoting bacteria are commonly used in agriculture, particularly for seed inoculation. Multispecies consortia are believed to be the most promising form of these bacteria. However, designing and modeling bacterial consortia to achieve desired phenotypic outcomes in plants is challenging. This review aims to address this challenge by exploring key antimicrobial interactions. Special attention is given to approaches for developing soil plant growth-promoting bacteria consortia. Additionally, advanced omics-based methods are analyzed that allow soil microbiomes to be characterized, providing an understanding of the molecular and functional aspects of these microbial communities. A comprehensive discussion explores the utilization of bacterial preparations in biofertilizers for agricultural applications, focusing on the intricate design of synthetic bacterial consortia with these preparations. Overall, the review provides valuable insights and strategies for intentionally designing bacterial consortia to enhance plant growth and development.

7.
Int J Mol Sci ; 24(18)2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37762643

ABSTRACT

Antibodies recognizing RBD and the S-protein have been previously demonstrated to be formed in humans after SARS-CoV-2 infection and vaccination with the Sputnik V adenovirus vaccine. These antibodies were found to be active when hydrolyzing FITC-labeled oligopeptides corresponding to linear epitopes of the S-protein. The thin-layer chromatography method allows the relative accumulation of the reaction product to be estimated but cannot identify hydrolysis sites. This study used the MALDI-TOF MS method to establish oligopeptide hydrolysis sites. Using the MALDI-TOF MS method in combination with the analysis of known hydrolysis sites characteristic of canonical proteases allowed us to establish the unique hydrolysis sites inherent only to catalytically active antibodies. We have discovered two 12-mer oligopeptides to have six hydrolysis sites equally distributed throughout the oligopeptide. The other three oligopeptides were found to have two to three closely spaced hydrolysis sites. In contrast to trypsin and chymotrypsin proteases, the catalytically active antibodies of COVID-19 patients have their peptide bond hydrolyzed mainly after proline, threonine, glycine, or serine residues. Here, we propose a new high-throughput experimental method for analyzing the proteolytic activity of natural antibodies produced in viral pathology.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Hydrolysis , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Antibodies , Oligopeptides , Peptide Hydrolases , Antibodies, Viral
8.
Vaccines (Basel) ; 11(9)2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37766170

ABSTRACT

The S-protein is the major antigen of the SARS-CoV-2 virus, against which protective antibodies are generated. The S-protein gene was used in adenoviral vectors and mRNA vaccines against COVID-19. While the primary function of antibodies is to bind to antigens, catalytic antibodies can hydrolyze various substrates, including nucleic acids, proteins, oligopeptides, polysaccharides, and some other molecules. In this study, antibody fractions with affinity for RBD and S-protein (RBD-IgG and S-IgG) were isolated from the blood of COVID-19 patients vaccinated with Sputnik V. The fractions were analyzed for their potential to hydrolyze 18-mer oligopeptides corresponding to linear fragments of the SARS-CoV-2 S-protein. Here, we show that the IgG antibodies hydrolyze six out of nine oligopeptides efficiently, with the antibodies of COVID-19-exposed donors demonstrating the most significant activity. The IgGs of control donors not exposed to SARS-CoV-2 were found to be inactive in oligopeptide hydrolysis. The antibodies of convalescents and vaccinated patients were found to hydrolyze oligopeptides in a wide pH range, with the optimal pH range between 6.5 and 7.5. The hydrolysis of most oligopeptides by RBD-IgG antibodies is inhibited by thiol protease inhibitors, whereas S-IgG active centers generally combine several types of proteolytic activities. Ca2+ ions increase the catalytic activity of IgG preparations containing metalloprotease-like active centers. Thus, the proteolytic activity of natural antibodies against the SARS-CoV-2 protein is believed to be due to the similarity of catalytic antibodies' active centers to canonical proteases. This work raises the question of the possible physiological role of proteolytic natural RBD-IgG and S-IgG resulting from vaccination and exposure to COVID-19.

9.
Biochemistry (Mosc) ; 88(9): 1205-1214, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37770389

ABSTRACT

Antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein (RBD S-protein) contribute significantly to the humoral immune response during coronavirus infection (COVID-19) and after vaccination. The main focus of the studies of the RBD epitope composition is usually concentrated on the epitopes recognized by the virus-neutralizing antibodies. The role of antibodies that bind to RBD but do not neutralize SARS-CoV-2 remains unclear. In this study, immunochemical properties of the two mouse monoclonal antibodies (mAbs), RS17 and S11, against the RBD were examined. Both mAbs exhibited high affinity to RBD, but they did not neutralize the virus. The epitopes of these mAbs were mapped using phage display: the epitope recognized by the mAb RS17 is located at the N-terminal site of RBD (348-SVYAVNRKRIS-358); the mAb S11 epitope is inside the receptor-binding motif of RBD (452-YRLFRKSN-459). Three groups of sera were tested for presence of antibodies competing with the non-neutralizing mAbs S11 and RS17: (i) sera from the vaccinated healthy volunteers without history of COVID-19; (ii) sera from the persons who had a mild form of COVID-19; (iii) sera from the persons who had severe COVID-19. Antibodies competing with the mAb S11 were found in each group of sera with equal frequency, whereas presence of the antibodies competing with the mAb RS17 in the sera was significantly more frequent in the group of sera obtained from the patients recovered from severe COVID-19 indicating that such antibodies are associated with the severity of COVID-19. In conclusion, despite the clear significance of anti-RBD antibodies in the effective immune response against SARS-CoV-2, it is important to analyze their virus-neutralizing activity and to confirm absence of the antibody-mediated enhancement of infection by the anti-RBD antibodies.


Subject(s)
COVID-19 , Animals , Mice , Humans , SARS-CoV-2/metabolism , Antibodies, Neutralizing/chemistry , Antibodies, Neutralizing/metabolism , Epitopes, B-Lymphocyte , Antibodies, Viral
10.
Int J Mol Sci ; 24(13)2023 Jun 28.
Article in English | MEDLINE | ID: mdl-37445984

ABSTRACT

Antibody-dependent enhancement (ADE) has been shown previously for SARS-CoV-1, MERS-CoV, and SARS-CoV-2 infection in vitro. In this study, the first monoclonal antibody (mAb) that causes ADE in a SARS-CoV-2 in vivo model was identified. mAb RS2 against the SARS-CoV-2 S-protein was developed using hybridoma technology. mAb RS2 demonstrated sub-nanomolar affinity and ability to neutralize SARS-CoV-2 infection in vitro with IC50 360 ng/mL. In an animal model of SARS-CoV-2 infection, the dose-dependent protective efficacy of mAb RS2 was revealed. However, in post-exposure prophylaxis, the administration of mAb RS2 led to an increase in the viral load in the respiratory tract of animals. Three groups of blood plasma were examined for antibodies competing with mAb RS2: (1) plasmas from vaccinated donors without COVID-19; (2) plasmas from volunteers with mild symptoms of COVID-19; (3) plasmas from patients with severe COVID-19. It was demonstrated that antibodies competing with mAb RS2 were significantly more often recorded in sera from volunteers with severe COVID-19. The results demonstrated for the first time that in animals, SARS-CoV-2 can induce antibody/antibodies that can elicit ADE. Moreover, in the sera of patients with severe COVID-19, there are antibodies competing for the binding of an epitope that is recognized by the ADE-eliciting mAb.


Subject(s)
COVID-19 , Middle East Respiratory Syndrome Coronavirus , Animals , SARS-CoV-2/metabolism , Antibodies, Viral , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing
11.
Int J Mol Sci ; 24(12)2023 Jun 13.
Article in English | MEDLINE | ID: mdl-37373231

ABSTRACT

Coronavirus disease (COVID-19), caused by the SARS-CoV-2 coronavirus, leads to various manifestations of the post-COVID syndrome, including diabetes, heart and kidney disease, thrombosis, neurological and autoimmune diseases and, therefore, remains, so far, a significant public health problem. In addition, SARS-CoV-2 infection can lead to the hyperproduction of reactive oxygen species (ROS), causing adverse effects on oxygen transfer efficiency, iron homeostasis, and erythrocytes deformation, contributing to thrombus formation. In this work, the relative catalase activity of the serum IgGs of patients recovered from COVID-19, healthy volunteers vaccinated with Sputnik V, vaccinated with Sputnik V after recovering from COVID-19, and conditionally healthy donors were analyzed for the first time. Previous reports show that along with canonical antioxidant enzymes, the antibodies of mammals with superoxide dismutase, peroxidase, and catalase activities are involved in controlling reactive oxygen species levels. We here show that the IgGs from patients who recovered from COVID-19 had the highest catalase activity, and this was statistically significantly higher each compared to the healthy donors (1.9-fold), healthy volunteers vaccinated with Sputnik V (1.4-fold), and patients vaccinated after recovering from COVID-19 (2.1-fold). These data indicate that COVID-19 infection may stimulate the production of antibodies that degrade hydrogen peroxide, which is harmful at elevated concentrations.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Humans , Catalase , Antioxidants , Reactive Oxygen Species , Antibodies , Antibodies, Viral , Mammals
12.
Int J Mol Sci ; 24(12)2023 Jun 15.
Article in English | MEDLINE | ID: mdl-37373342

ABSTRACT

Exosomes are nanovesicles 40-120 nm in diameter secreted by almost all cell types and providing humoral intercellular interactions. Given the natural origin and high biocompatibility, the potential for loading various anticancer molecules and therapeutic nucleic acids inside, and the surface modification possibility for targeted delivery, exosomes are considered to be a promising means of delivery to cell cultures and experimental animal organisms. Milk is a unique natural source of exosomes available in semi-preparative and preparative quantities. Milk exosomes are highly resistant to the harsh conditions of the gastrointestinal tract. In vitro studies have demonstrated that milk exosomes have an affinity to epithelial cells, are digested by cells by endocytosis mechanism, and can be used for oral delivery. With milk exosome membranes containing hydrophilic and hydrophobic components, exosomes can be loaded with hydrophilic and lipophilic drugs. This review covers a number of scalable protocols for isolating and purifying exosomes from human, cow, and horse milk. Additionally, it considers passive and active methods for drug loading into exosomes, as well as methods for modifying and functionalizing the surface of milk exosomes with specific molecules for more efficient and specific delivery to target cells. In addition, the review considers various approaches to visualize exosomes and determine cellular localization and bio-distribution of loaded drug molecules in tissues. In conclusion, we outline new challenges for studying milk exosomes, a new generation of targeted delivery agents.


Subject(s)
Antineoplastic Agents , Exosomes , Animals , Cattle , Female , Humans , Exosomes/metabolism , Milk/metabolism , Drug Delivery Systems , Drug Carriers/metabolism
13.
Int J Mol Sci ; 24(9)2023 May 05.
Article in English | MEDLINE | ID: mdl-37176001

ABSTRACT

A spinal cord injury (SCI) initiates a number of cascades of biochemical reactions and intercellular interactions, the outcome of which determines the regenerative potential of the nervous tissue and opens up capacities for preserving its functions. The key elements of the above-mentioned processes are microglia. Many assumptions have been put forward, and the first evidence has been obtained, suggesting that, depending on the severity of SCI and the post-traumatic period, microglia behave differently. In this regard, we conducted a study to assess the microglia behavior in the model of mild, moderate and severe SCI in vitro for various post-traumatic periods. We reported for the first time that microglia make a significant contribution to both anti- and pro-inflammatory patterns for a prolonged period after severe SCI (60 dpi), while reduced severities of SCI do not lead to prolonged activation of microglia. The study also revealed the following trend: the greater the severity of the SCI, the lower the proliferative and phagocytic activity of microglia, which is true for all post-traumatic periods of SCI.


Subject(s)
Microglia , Spinal Cord Injuries , Humans , Spinal Cord
14.
Biology (Basel) ; 11(12)2022 Dec 19.
Article in English | MEDLINE | ID: mdl-36552362

ABSTRACT

Spinal cord injury (SCI) is a serious neurological condition that causes severe disability. One of the approaches to overcoming the complications of SCI is stem cell-derived extracellular vesicle (EV) therapy. In this research, we performed a comparative evaluation of rat spinal cord post-traumatic regeneration efficacy using different methods of mesenchymal stem cell-derived EV transplantation (local vs. systemic) followed by evaluation of their minimal therapeutic dose. The results suggested that MSC-EV therapy could improve locomotor activity over 60 days after the SCI, showing a dose-dependent effect on the recovery of spinal cord motor pathways. We also established the possibility of maintaining a population of mature oligodendrocytes by MSC-EVs. It was observed that in the spinal cord injury area, intravenous transplantation of MSC-EVs showed more pronounced therapeutic effects compared to the treatment of fibrin matrix-encapsulated MSC-EVs.

15.
Plants (Basel) ; 11(22)2022 Nov 12.
Article in English | MEDLINE | ID: mdl-36432794

ABSTRACT

Siderophores are synthesized and secreted by many bacteria, yeasts, fungi, and plants for Fe (III) chelation. A variety of plant-growth-promoting bacteria (PGPB) colonize the rhizosphere and contribute to iron assimilation by plants. These microorganisms possess mechanisms to produce Fe ions under iron-deficient conditions. Under appropriate conditions, they synthesize and release siderophores, thereby increasing and regulating iron bioavailability. This review focuses on various bacterial strains that positively affect plant growth and development through synthesizing siderophores. Here we discuss the diverse chemical nature of siderophores produced by plant root bacteria; the life cycle of siderophores, from their biosynthesis to the Fe-siderophore complex degradation; three mechanisms of siderophore biosynthesis in bacteria; the methods for analyzing siderophores and the siderophore-producing activity of bacteria and the methods for screening the siderophore-producing activity of bacterial colonies. Further analysis of biochemical, molecular-biological, and physiological features of siderophore synthesis by bacteria and their use by plants will allow one to create effective microbiological preparations for improving soil fertility and increasing plant biomass, which is highly relevant for sustainable agriculture.

16.
Int J Mol Sci ; 23(22)2022 Nov 08.
Article in English | MEDLINE | ID: mdl-36430159

ABSTRACT

Since the onset of the COVID-19 pandemic, numerous publications have appeared describing autoimmune pathologies developing after a coronavirus infection, with several papers reporting autoantibody production during the acute period of the disease. Several viral diseases are known to trigger autoimmune processes, and the appearance of catalytic antibodies with DNase activity is one of the earliest markers of several autoimmune pathologies. Therefore, we analyzed whether IgG antibodies from blood plasma of SARS-CoV-2 patients after recovery could bind and hydrolyze DNA. We analyzed how vaccination of patients with adenovirus Sputnik V vaccine influences the production of abzymes with DNase activity. Four groups were selected for the analysis, each containing 25 patients according to their relative titers of antibodies to S-protein: with high and median titers, vaccinated with Sputnik V with high titers, and a control group of donors with negative titers. The relative titers of antibodies against DNA and the relative DNase activity of IgGs depended very much on the individual patient and the donor, and no significant correlation was found between the relative values of antibodies titers and their DNase activity. Our results indicate that COVID-19 disease and vaccination with adenoviral Sputnik V vaccine do not result in the development or enhancement of strong autoimmune reactions as in the typical autoimmune diseases associated with the production of anti-DNA and DNA hydrolyzing antibodies.


Subject(s)
Antibodies, Catalytic , COVID-19 , Viral Vaccines , Humans , SARS-CoV-2 , Pandemics , Antibodies, Antinuclear , DNA , Immunoglobulin G , Deoxyribonucleases
17.
Plants (Basel) ; 11(16)2022 Aug 15.
Article in English | MEDLINE | ID: mdl-36015422

ABSTRACT

Phosphates are known to be essential for plant growth and development, with phosphorus compounds being involved in various physiological and biochemical reactions. Phosphates are known as one of the most important factors limiting crop yields. The problem of phosphorus deficiency in the soil has traditionally been solved by applying phosphate fertilizers. However, chemical phosphate fertilizers are considered ineffective compared to the organic fertilizers manure and compost. Therefore, increasing the bioavailability of phosphates for plants is one of the primary goals of sustainable agriculture. Phosphate-solubilizing soil microorganisms can make soil-insoluble phosphate bioavailable for plants through solubilization and mineralization. These microorganisms are currently in the focus of interest due to their advantages, such as environmental friendliness, low cost, and high biological efficiency. In this regard, the solubilization of phosphates by soil microorganisms holds strong potential in research, and inoculation of soils or crops with phosphate-solubilizing bacteria is a promising strategy to improve plant phosphate uptake. In this review, we analyze all the species of phosphate-solubilizing bacteria described in the literature to date. We discuss key mechanisms of solubilization of mineral phosphates and mineralization of organic phosphate-containing compounds: organic acids secreted by bacteria for the mobilization of insoluble inorganic phosphates, and the enzymes hydrolyzing phosphorus-containing organic compounds. We demonstrate that phosphate-solubilizing microorganisms have enormous potency as biofertilizers since they increase phosphorus bioavailability for the plant, promote sustainable agriculture, improve soil fertility, and raise crop yields. The use of phosphate-solubilizing microbes is regarded as a new frontier in increasing plant productivity.

18.
Int J Mol Sci ; 23(12)2022 Jun 15.
Article in English | MEDLINE | ID: mdl-35743119

ABSTRACT

Only some human organs, including the liver, are capable of very weak self-regeneration. Some marine echinoderms are very useful for studying the self-regeneration processes of organs and tissues. For example, sea cucumbers Eupentacta fraudatrix (holothurians) demonstrate complete restoration of all organs and the body within several weeks after their division into two parts. Therefore, these cucumbers are a prospective model for studying the general mechanisms of self-regeneration. However, there is no data available yet concerning biomolecules of holothurians, which can stimulate the processes of organ and whole-body regeneration. Investigation of these restoration mechanisms is very important for modern medicine and biology because it can help to understand which hormones, nucleic acids, proteins, enzymes, or complexes play an essential role in self-regeneration. It is possible that stable, polyfunctional, high-molecular-weight protein complexes play an essential role in these processes. It has recently been shown that sea cucumbers Eupentacta fraudatrix contain a very stable multiprotein complex of about 2000 kDa. The first analysis of possible enzymatic activities of a stable protein complex was carried out in this work, revealing that the complex possesses several protease and DNase activities. The complex metalloprotease is activated by several metal ions (Zn2+ > Mn2+ > Mg2+). The relative contribution of metalloproteases (~63.4%), serine-like protease (~30.5%), and thiol protease (~6.1%) to the total protease activity of the complex was estimated. Metal-independent proteases of the complex hydrolyze proteins at trypsin-specific sites (after Lys and Arg). The complex contains both metal-dependent and metal-independent DNases. Mg2+, Mn2+, and Co2+ ions were found to strongly increase the DNase activity of the complex.


Subject(s)
Sea Cucumbers , Animals , Deoxyribonucleases/metabolism , Endopeptidases/metabolism , Humans , Metalloproteases/metabolism , Peptide Hydrolases/metabolism , Proteolysis , Sea Cucumbers/metabolism
19.
Vaccines (Basel) ; 10(3)2022 Mar 02.
Article in English | MEDLINE | ID: mdl-35335016

ABSTRACT

Unlike many other viruses, HIV-1 is highly variable. The structure of the viral envelope changes as the infection progresses and is one of the biggest obstacles in developing an HIV-1 vaccine. HIV-1 infection can cause the production of various natural autoantibodies, including catalytic antibodies hydrolyzing DNA, myelin basic protein, histones, HIV-integrase, HIV-reverse transcriptase, ß-casein, serum albumin, and some other natural substrates. Currently, there are various directions for the development of HIV-1 vaccines: stimulation of the immune response on the mucous membranes; induction of cytotoxic T cells, which lyse infected cells and hold back HIV-infection; immunization with recombinant Env proteins or vectors encoding Env; mRNA-based vaccines and some others. However, despite many attempts to develop an HIV-1 vaccine, none have been successful. Here we review the entire spectrum of antibodies found in HIV-infected patients, including neutralizing antibodies specific to various viral epitopes, as well as antibodies formed against various autoantigens, catalytic antibodies against autoantigens, and some viral proteins. We consider various promising targets for developing a vaccine that will not produce unwanted antibodies in vaccinated patients. In addition, we review common problems in the development of a vaccine against HIV-1.

20.
Molecules ; 27(6)2022 Mar 17.
Article in English | MEDLINE | ID: mdl-35335321

ABSTRACT

Metal ions and other elements play many different critical roles in all biological processes. They can be especially important in high concentrations for the functioning of organisms living in seawater. It is important to understand how much the concentrations of different trace elements in such organisms can be higher than in seawater. Some marine organisms capable of rapid recovery after different injuries are fascinating in this regard. Sea cucumbers Eupentacta fraudatrix can completely restore all organs and the whole body within several weeks after their division into two parts. Here, for the first time, a comparison of the content of different elements in seawater, sea cucumber, and its very stable multiprotein complex (2000 kDa) was performed using two-jet plasma atomic emission spectrometry. Among the 18 elements we found in sea cucumbers, seawater contained only six elements in detectable amounts, and their content decreased in the following order: Mg > Ca > B > Sr ≈ Si > Cr (0.13−930 µg/g of seawater). The content of these elements in sea cucumbers was higher compared with seawater (-fold): Ca (714) > Sr (459) > Cr (75) > Si (42)> B (12) > Mg (6.9). Only four of them had a higher concentration in the protein complex than in seawater (-fold): Si (120.0) > Cr (31.5) > Ca (9.1) > Sr (8.8). The contents of Mg and B were lower in the protein complex than in seawater. The content of elements additionally found in sea cucumbers decreased in the order (µg/g of powder) of P (1100) > Fe (47) > Mn (26) > Ba (15) > Zn (13) > Al (9.3) > Mo (2.8) > Cu (1.4) > Cd (0.3), and in the protein complex, in the order of P (290) > Zn (51) > Fe (23) > Al (14) ≈ Ni (13) > Cu (7.5) > Ba (2.5) ≈ Co (2.0) ≈ Mn (1.6) > Cd (0.7) >Ag (0.2). Thus, sea cucumbers accumulate various elements, including those contained in very low concentrations in seawater. The possible biological roles of these elements are discussed here.


Subject(s)
Sea Cucumbers , Trace Elements , Animals , Molecular Weight , Seawater , Spectrum Analysis/methods , Trace Elements/analysis
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