Complex Biological Products Research Articles

Bacterial live therapeutics for human diseases.

The genomic revolution has fueled rapid progress in synthetic and systems biology, opening up new possibilities for using live biotherapeutic products (LBP) to treat, attenuate or prevent human diseases. Among LBP, bacteria-based therapies are particularly promising due to their ability to colonize diverse human tissues, modulate the immune system and secrete or deliver complex biological products. These bacterial LBP include engineered pathogenic species designed to target specific diseases, and microbiota species that promote microbial balance and immune system homeostasis, either through local administration or the gut-body axes. This review focuses on recent advancements in preclinical and clinical trials of bacteria-based LBP, highlighting both on-site and long-reaching strategies.

Synergistic effect of human uterine cervical mesenchymal stem cell secretome and paclitaxel on triple negative breast cancer

BackgroundTriple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer and, despite its adverse effects, chemotherapy is the standard systemic treatment option for TNBC. Since, it is of utmost importance to consider the combination of different agents to achieve greater efficacy and curability potential, MSC secretome is a possible innovative alternative.MethodsIn the present study, we proposed to investigate the anti-tumor effect of the combination of a chemical agent (paclitaxel) with a complex biological product, secretome derived from human Uterine Cervical Stem cells (CM-hUCESC) in TNBC.ResultsThe combination of paclitaxel and CM-hUCESC decreased cell proliferation and invasiveness of tumor cells and induced apoptosis in vitro (MDA-MB-231 and/or primary tumor cells). The anti-tumor effect was confirmed in a mouse tumor xenograft model showing that the combination of both products has a significant effect in reducing tumor growth. Also, pre-conditioning hUCESC with a sub-lethal dose of paclitaxel enhances the effect of its secretome and in combination with paclitaxel reduced significantly tumor growth and even allows to diminish the dose of paclitaxel in vivo. This effect is in part due to the action of extracellular vesicles (EVs) derived from CM-hUCESC and soluble factors, such as TIMP-1 and − 2.ConclusionsIn conclusion, our data demonstrate the synergistic effect of the combination of CM-hUCESC with paclitaxel on TNBC and opens an opportunity to reduce the dose of the chemotherapeutic agents, which may decrease chemotherapy-related toxicity.

ОСОБЕННОСТИ ГЕМАТОЛОГИЧЕСКОГО ПРОФИЛЯ ГЛУБОКОСТЕЛЬНЫХ И НОВОТЕЛЬНЫХ КОРОВ НА ФОНЕ ПРИМЕНЕНИЯ БИОСТИМУЛЯТОРОВ (сообщение 2)

This article data on differentiated counting of the number of leukocytes are given, as well as the dynamics of total protein and protein fractions in the blood of animals, indicating the level of metabolic processes in a living organism, is determined. It has been established that intramuscular application of experimental biological preparations to cows 65-60, 45-40 and 25-20 days before calving stimulates the process of hematopoiesis, activates cellular factors of non-specific resistance (physiological leukocytosis, moderate eosinophilia and neutropenia with a right shift of the nucleus, lymphocytosis). The most pronounced effect was noted with three injections of the complex biological product Prevention-N-A-M. Biological preparations Prevention-N-A-M and PS-7 stimulate protein synthesis (albumins, α-, β-, γ-globulins) in the body before and after calving. The obtained results testify to the effectiveness of the tested biopreparations and make it possible to scientifically substantiate the feasibility of their use in animal husbandry as an effective way to increase the resistance of the body of cows, which can significantly improve their health and reduce the risk of diseases.

DETOXIFICATION OF USED SYNTHETIC MOTOR OILS WITH BIOCOMPOSITIONS BASED ON HUMIC ACIDS IN WATER

Among the modern technologies of remediation of oil-contaminated wastewater, the most promising are technologies based on biological methods of purification, namely, on the process of self-purification using various consortia of microorganisms characterized by an increased ability to biodegrade hydrocarbons of oil and petroleum products. This article is devoted to the assessment of the detoxifying ability of new biocompositions based on microorganisms-oil destructors in combination with natural dispersants – humic acids in relation to used synthetic motor oil in water. Biocompositions based on humic acids isolated from the peat of the Tula region: reed lowland and black-alder lowland, and microorganisms-oil destructors of the genus Rhodococcus, producing biological surfactants and capable oxidizing a wide range of petroleum hydrocarbons due to the presence of enzymatic systems, have been studied. The detoxifying ability of biocompositions was determined by the method of biotesting by assessing the toxic effect on the test object duckweed small. The reduction of the toxic effect by the detoxification coefficient was achieved by more than 50%. Attention is focused on the advantages of biotesting in comparison with analytical methods, which consist in ease of use, expressiveness in determining results, cost–effectiveness and, most importantly, the ability to judge how dangerous a specific amount of xenobiotic is for the vital activity of organisms. The experiments carried out prove that the developed biocomposition affects the dispersed state of used synthetic engine oil in water, and also contributes to the degradation of its components. The obtained biocompositions can be used as complex biological products for biotechnological remediation of aquatic environments using in situ technology.

Regulatory Framework, Challenges, and Initial Strategic Planning for Advanced Therapy Products (PTAs) Development in Brazil.

Advanced Therapies are a class of innovative complex biological products used for therapeutic purposes, encompassing cell therapy, tissue engineering, and gene therapy products. These are promising therapeutic strategies for several complex diseases with low or non-existent therapeutic alternatives. The proper transposition of basic research in this area into medicinal products must comply with regulatory requirements. Here we review the main regulatory recommendations, emphasizing on the Brazilian regulation. The critical points are the manufacturing process, challenges in characterizing the product, development of non-clinical trials, lack of adequate animal models representative of the clinical situation, and absence of valid and measurable therapeutic endpoints. Based on that, we propose a framework for strategic planning of pre-clinical studies in this field. The detailed example involves producing a nonviral vector-based gene editing product, but the regulations and methods may be extrapolated for developing different types of advanced therapies.

Advanced Therapy Medicinal Products for Age-Related Macular Degeneration; Scaffold Fabrication and Delivery Methods.

Retinal degenerative diseases such as age-related macular degeneration (AMD) represent a leading cause of blindness, resulting in permanent damage to retinal cells that are essential for maintaining normal vision. Around 12% of people over the age of 65 have some form of retinal degenerative disease. Whilst antibody-based drugs have revolutionised treatment of neovascular AMD, they are only effective at an early stage and cannot prevent eventual progression or allow recovery of previously lost vision. Hence, there is a clear unmet need to find innovative treatment strategies to develop a long-term cure. The replacement of damaged retinal cells is thought to be the best therapeutic strategy for the treatment of patients with retinal degeneration. Advanced therapy medicinal products (ATMPs) are a group of innovative and complex biological products including cell therapy medicinal products, gene therapy medicinal products, and tissue engineered products. Development of ATMPs for the treatment of retinal degeneration diseases has become a fast-growing field of research because it offers the potential to replace damaged retinal cells for long-term treatment of AMD. While gene therapy has shown encouraging results, its effectiveness for treatment of retinal disease may be hampered by the body's response and problems associated with inflammation in the eye. In this mini-review, we focus on describing ATMP approaches including cell- and gene-based therapies for treatment of AMD along with their applications. We also aim to provide a brief overview of biological substitutes, also known as scaffolds, that can be used for delivery of cells to the target tissue and describe biomechanical properties required for optimal delivery. We describe different fabrication methods for preparing cell-scaffolds and explain how the use of artificial intelligence (AI) can aid with the process. We predict that combining AI with 3D bioprinting for 3D cell-scaffold fabrication could potentially revolutionise retinal tissue engineering and open up new opportunities for developing innovative platforms to deliver therapeutic agents to the target tissues.

Anchoring of Polymer Loops on Enzyme-Immobilized Mesoporous ZIF-8 Enhances the Recognition Selectivity of Angiotensin-Converting Enzyme Inhibitory Peptides

Immobilized angiotensin-converting enzyme (ACE) is a promising material for the rapid screening of antihypertensive drugs, but the nonspecific adsorption is a serious problem in separation processes involving complex biological products. In this study, triblock copolymers with dopamine (DA) block as anchors and PEG block as the main body (DA-PEGx-DA) were attached to an immobilized ACE (ACE@mZIF-8/PDA, AmZP) surface via the "grafting to" strategy which endowed them with anti-nonspecific adsorption. The influence of DA-PEGx-DA chain length on nonspecific adsorption was confirmed. The excellent specificity and reusability of the obtained ACE@mZIF-8/PDA/DA-PEG5000-DA (AmZPP5000) was validated by screening two known ACE inhibitory peptides Val-Pro-Pro (VPP, competitive inhibitory peptides of ACE) and Gly-Met-Lys-Cys-Ala-Phe (GF-6, noncompetitive inhibitory peptides of ACE) from a mixture containing active and inactive compounds. These results demonstrate that anchored polymer loops are effective for high-recognition selectivity and AmZPP5000 is a promising compound for the efficient separation of ACE inhibitors in biological samples.

THE STUDY OF THE PHYSICO-CHEMICAL PROPERTIES OF MODIFIED ORGANIC FERTILIZER AND INVESTIGATION OF THEIR INFLUENCE TO THE PROCESSES OF GROWTH AND DEVELOPMENT OF HEDGE SEEDLINGS

The main objective of the study is to develop an environmentally friendly technology and organize the production of biological products, as well as to conduct laboratory and field tests to determine the effectiveness of the effect of chelate complex biological products based on potassium humate, enriched with NPK and Mo. A description of the technology for obtaining potassium humate is shown, as well as physical and chemical characteristics, chemical composition and mass fraction of humic acids in terms of dry matter. The article presents the results of field trials on the effect of growth-stimulating organic fertilizer on hedge seedlings (elm and spirea) on the territory of the Astana Botanical Garden (Astana). Today, landscaping plays an important role in the development of any city. When choosing plants for hedges, it is necessary to take into account a number of indicators, such as unpretentiousness, stress resistance, adaptation to environmental conditions, etc. An important element in maintaining these factors is the use of additional feeding, in the form of biological preparations based on potassium humate. As a result of vegetation experiments, an effective effect of modified organic biopreparations (MOB with NPK, MOB with Mo) was established, in which a stimulating effect on the growth of new shoots and a significant increase in the biomass of elm seedlings was observed. Biological preparations also had a beneficial effect on spirea hedge bushes, which manifested itself in a significant increase in plant height.

MORPHOLOGICAL FEATURES OF THE INFLUENCE OF CORD BLOOD BIOPREPARATION ON THE THYROID GLAND OF RATS WITH EXPERIMENTAL AUTOIMMUNE THYROIDITITIS

Abstract Relevance. One of the modern medical trends of the 21st century is regenerative medicine – a clinical discipline that aims to use cell therapy to repair damaged organs and tissues. Experimental and clinical studies have proven the great restorative potential of fetoplacental complex (FPC) biological products which is due to a wide range of biologically active substances which determines the prospects and relevance of their study in many laboratories around the world in recent decades. Purpose of research. Determination of histomorphological changes in the thyroid gland which occur during the simulation of experimental autoimmune thyroiditis and after correction of this pathology by a non-cellular preparation of cord blood serum in the early stages of its aftereffect study. Materials and methods. Experimental studies were performed on male Wistar rats with a simulated autoimmune thyroiditis (AT). Administration of the drug "Cryocell-Cryocord" was carried out intramuscularly at a rate of 10 injections every other day at the rate of 0.1 ml of diluted solution per 100 g of body weight. The comparison drug "Levothyroxine" (Berlin-Chemie, Germany) was administered to rat at a dose of 10 μg/kg of the body weight for 10 days. Histological specimens were analyzed using a Primo Star hardware and software complex, a Canon power shwet ATIO camera, a personal computer, and the Morpholog program. Results. Histomorphological analysis of the thyroid gland of rats, after 1 month. after the creation of the model, AIT confirms the stable development of its autoimmune lesions: significant foci of lymphocytic infiltration and connective tissue strands were observed. "Levothyroxine" and "Cryocell-Cryocord" had a positive effect on the histostructure of the rat thyroid gland. The more pronounced effect was observed after the introduction of the biological product "Cryocell-Cryocord". Under its influence, more significant foci were identified in the thyroid gland with signs of normalization of structural elements and restoration of its functional activity. Conclusions. On the basis of morphological and morphometric studies, a conclusion was made about the high efficiency of the use of the cell-free biological product "Cryocell-Cryocord" for the correction of autoimmune damage to the thyroid gland.

Experience in the use of biological products in grain production

The article presents the data of industrial experience of using biological preparations in the technology of cultivation of winter wheat in the zone of unstable moistening of the Krasnodar Territory. Based on the results of the studies, it was found that the use of the complex biological product Albit and the concentrated humic fertilizer Lignogumat improves the biometric parameters of plants (elongation of the ear by 5.6%, an increase in the number of grains per ear by 17.9% and the weight of 1000 grains by 5.9%), there was an increase in yield by 3.0 c/ha (or 5.1%) and an increase in profit by 4027 rubles/ha.

Botulinum Toxins for Esthetic Facial Injections: A Scientific Review to Support Evidence-Based Best Practice

Botulinum toxins (BoNT) are complex biological products. Each licensed BoNT type A (BoNTA) has its own individual characteristics resulting into different attributes, some of them being of clinical relevance. Besides profound anatomical knowledge and understanding of esthetic principles, the responsible injecting physician should be aware of those pharmaceutical and clinical properties. Especially against the background of new BoNTA formulations receiving approval by the authorities, a critical and dedicated discussion on the individual characteristics should take place, and the potential relevance on the treatment outcome should be taken into consideration.

Влияние штамма Pseudomonas sp. на горох при действии кадмия

Bacteria Pseudomonas sp. have great potential as rhizospheric bacteria that stimulate plant growth (PGPR) (including for obtaining microbiological biological products) to protect plants from phytopathogens, heavy metals, increase plant yield and plant growth under stress conditions. The purpose of this work was to determine the inhibitory concentration of cadmium salts on the growth of the strain Pseudomonas sp. OBA 2.4.1 and to analyze its effect on the growth and germination of seeds of pea (Pisum sativum L.) at different concentrations of cadmium salts. The studied strain was identified as Pseudomonas sp., its siderophoric activity and the ability to form biofilms were shown. In addition, treatment with this strain of seeds of pea plants led to an increase in the average length of seedlings by 2.6 times compared with untreated seeds. When growing pea seeds with Pseudomonas treatment in the presence of 100 µM of CdCl2, the length of seedlings increased by 62%, at 200 µM – by 20%, at 300 microns – by 36%, at 400 µM – by 51%, at 500 µM – by 118% relative to control uninoculated seeds. The results obtained show that the strain Pseudomonas sp. OBA 2.4.1 improves the growth and development of pea Pisum sativum under cadmium stress, which can be used to create complex biological products designed both to protect agricultural plants from the effects of heavy metals and for use in bioremediation.

Antifungal Activity of Carboxymethyl Cellulose Edible Films Enriched with Propolis Extracts and Their Role in Improvement of the Storage Life of Kashkaval Cheese

Propolis (bee glue) is a complex biological product known for its antimicrobial activity and antioxidant potential, and widely used as food additive and biopreservative. The aim of the present research was to examine the effects of propolis on the improvement of the storage life of ripened kashkaval cheese. For this purpose, three types of 1% carboxymethyl cellulose edible films containing three different ethanolic propolis extracts in concentration of 1% were prepared. Double-layer edible films were applied on the kashkaval cheese surface, and the samples were designated as T1, T2, and T3. An untreated sample was kept as a control. The four experimental groups (T1, T2, T3, and control) were then stored under refrigeration conditions at 4°C and 75% relative humidity (RH) for 56 days. During the storage period, the cheese was observed for visible changes, and samples for physicochemical and microbiological analyses were taken. The results from physicochemical analysis demonstrated that values of titratable acidity decreased in all experiment groups during the storage period. The results from microbiological analysis revealed that three types of edible films T1, T2, and T3 did not affect the decreasing number of lactic acid bacteria, a normal process for the period after the cheese ripening. The application of T1, T2, and T3 edible films did not affect the increasing number of yeasts in kashkaval cheese through the storage period. However, T1 and T2 edible films effectively inhibited the fungal growth on cheese surface, and no signs of spoilage were observed until the end of the storage for 56 days. In contrast, T3 treatment delayed but did not inhibit the fungal growth, and the first signs of fungal decay appeared between the 35th and 42nd day of the storage, compared to the control (28th day). Thus, the application of propolis can be considered an effective means for the prevention of fungal spoilage of kashkaval cheese.

LED control of gene expression in a nanobiosystem composed of metallic nanoparticles and a genetically modified E. coli strain

BackgroundWithin the last decade, genetic engineering and synthetic biology have revolutionized society´s ability to mass-produce complex biological products within genetically-modified microorganisms containing elegantly designed genetic circuitry. However, many challenges still exist in developing bioproduction processes involving genetically modified microorganisms with complex or multiple gene circuits. These challenges include the development of external gene expression regulation methods with the following characteristics: spatial–temporal control and scalability, while inducing minimal permanent or irreversible system-wide conditions. Different stimuli have been used to control gene expression and mitigate these challenges, and they can be characterized by the effect they produce in the culture media conditions. Invasive stimuli that cause permanent, irreversible changes (pH and chemical inducers), non-invasive stimuli that cause partially reversible changes (temperature), and non-invasive stimuli that cause reversible changes in the media conditions (ultrasound, magnetic fields, and light).MethodsOpto-control of gene expression is a non-invasive external trigger that complies with most of the desired characteristics of an external control system. However, the disadvantage relies on the design of the biological photoreceptors and the necessity to design them to respond to a different wavelength for every bioprocess needed to be controlled or regulated in the microorganism. Therefore, this work proposes using biocompatible metallic nanoparticles as external controllers of gene expression, based on their ability to convert light into heat and the capacity of nanotechnology to easily design a wide array of nanostructures capable of absorbing light at different wavelengths and inducing plasmonic photothermal heating.ResultsHere, we designed a nanobiosystem that can be opto-thermally triggered using LED light. The nanobiosystem is composed of biocompatible gold nanoparticles and a genetically modified E. coli with a plasmid that allows mCherry fluorescent protein production at 37 °C in response to an RNA thermometer.ConclusionsThe LED-triggered photothermal protein production system here designed offers a new, cheaper, scalable switchable method, non-destructive for living organisms, and contribute toward the evolution of bioprocess production systems.

Antagonism of Bacillus thuringiensis to phytopathogenic micromicetes as pathogens of apple trees

Antagonistic microorganisms, producing bactericidal and fungicidal substances, spread in space and occupy various ecological niches. Antagonistic action of microorganisms can be combined with a number of other properties that can be used by humans for their own purposes. Microorganisms — agents of biological products often have a multifunctional effect on the components of the agroecosystem, which under the influence of various environmental factors could have positive and negative consequences. The aim of the study was to study the effect of new highly active entomopathogenic strains of Bacillus thuringiensis on non-target objects — components of the biocenosis of the apple orchard. When developing technologies for biocontrol of the number of apple trees pests using B. thuringiensis revealed an additional positive protective effect — reducing the number of pathogens of fungal diseases on the leaf surface. Treatment of apple leaves with a liquid culture of strain B. thuringiensis 0376 after 72 hours of application reduced the number of scab of Fusicladium dendriticum by 7 times, and the pathogen of monolisis of Monilia fructigena — 9 times. Strain B. thuringiensis 0371 showed the highest level of antagonism, because in vitro completely inhibited the growth and development of micromycetes on the surface of the nutrient medium. On the leaf surface, the application of culture strain 0371 reduced the number of Fusicladium dendriticum by 92%, and Monilia fructigena — by 86% after 72 hours of treatment. In a field experiment when treating apple trees with a culture of this strain, scab development decreased by 7.1%. Strain B. thuringiensis 787 did not show antagonism against phytopathogenicmicromycetes during co-cultivation on nutrient medium, which may be explained by its inability to produce water-soluble exotoxin, in contrast to strains of B. thuringiensis, which are antagonists of scab and apple monolisis. Strain B. thuringiensis 0371 requires further research and development of its formulations, because it is promising for the creation of a complex biological product with insect-fungicidal properties for use in ecological and agriculture friendly technologies.

Anomeric Retention of Carbohydrates in Multistage Cyclic Ion Mobility (IMSn): De Novo Structural Elucidation of Enzymatically Produced Mannosides

Carbohydrates are complex structures that still challenge analysts today because of their different levels of isomerism, notably the anomerism of the glycosidic bond. It has been shown recently that anomerism is preserved upon gas-phase fragmentation and that high-resolution ion mobility (IMS) can distinguish anomers. However, these concepts have yet to be applied to complex biological products. We have used high-resolution IMS on a cyclic device to characterize the reaction products of Uhgb_MS, a novel mannoside synthase of the GH130 family. We designed a so-called IMSn sequence consisting of (i) separating and isolating specific IMS peaks, (ii) ejecting ions to a pre-array store cell depending on their arrival time, (iii) inducing collisional activation upon reinjection, and (iv) performing multistage IMS analysis of the fragments. First, we applied IMS2 sequences to purely linked α1,2- and β1,2-mannooligosaccharides, which provided us with reference drift times for fragments of known conformation. Then, we performed IMSn analyses of enzymatically produced mannosides and, by comparison with the references, we succeeded in determining the intrachain anomerism of a α1,2-mannotriose and a mix-linked β/α1,2-mannotetraose-a first for a crude biological medium. Our results show that the anomerism of glycosides is maintained through multiple stages of collisional fragmentation, and that standalone high-resolution IMS and IMSn can be used to characterize the intrachain anomerism in tri- and tetrasaccharides in a biological medium. This is also the first evidence that a single carbohydrate-active enzyme can synthesize both α- and β-glycosidic linkages.

Advanced Therapy Medicinal Products for the Eye: Definitions and Regulatory Framework.

Advanced therapy medicinal products (ATMPs) are a group of innovative and complex biological products for human use that comprises somatic cell therapy medicinal products, tissue engineered products, gene therapy medicinal products, and the so-called combined ATMPs that consist of one of the previous three categories combined with one or more medical devices. During the last few years, the development of ATMPs for the treatment of eye diseases has become a fast-growing field as it offers the potential to find novel therapeutic approaches for treating pathologies that today have no cure or are just subjected to symptomatic treatments. Therefore, it is important for all professionals working in this field to be familiar with the regulatory principles associated with these types of innovative products. In this review, we outline the legal framework that regulates the development of ATMPs in the European Union and other international jurisdictions, and the criteria that each type of ATMP must meet to be classified as such. To illustrate each legal definition, ATMPs that have already completed the research and development stages and that are currently used for the treatment of eye diseases are presented as examples.

ИММУНОПРОФИЛАКТИКА ОРГАНИЗМА СТЕЛЬНЫХ И НОВОТЕЛЬНЫХ КОРОВ

The research was performed to identify the most effective bio immunostimulant. We used PS-2 and Prevention-N-E biologicals developed on the basis of the Chuvash State Agrarian University, as well as widely used in veterinary practice - PDE and E-selenium. Injection of PS-2 and Prevention-NE preparations to dry cows at a dose of 10.0 ml three times 45-40, 25-20 and 15-10 days before calving, as well as PDE and E-selenium at a dose of 20.0 and 10.0 ml 20 days before calving, respectively, prevents postpartum diseases. The mechanism of action of the PS-2 and Prevention-N-E drugs developed and tested by us is manifested, first of all, due to the consecutive processes of macrophage activation, as a result of the action of polysaccharide corpuscles and drug components on macrophage receptors. Secondly, information from the receptors of macrophages and chemoreceptors is transmitted along the afferent pathway to the cerebral cortex, then the signals go to the hypothalamus, which leads to liberin secretion by the nuclei of the ashen tuber of the hypothalamus. Liberins, in turn, increase the release of hormones by the anterior pituitary gland - the adenohypophysis. The anterior pituitary gland releases tropic hormones: somatotropic hormone, adrenocorticotropic hormone, thyroid-stimulating hormone, follicle-stimulating hormone, etc. These hormones are involved in metabolic processes in the body. Under the influence of preparations, in cows the time of membranes sweep was reduced, the risk of uterus subinvolution and endometritis decreased. In cows, the timing of the onset of estrus, the insemination rate, and the service period were shortened, and the conception rate increased in one estrus. In such a way, against the background of the use of biologicals with the help of nonspecific adaptive reactions, the body retains the relative constancy of the internal environment necessary for life - homeostasis, and it actively resists the adverse effects of the external environment, increasing its phylactic power. Consequently, new opportunities are opening up for the implementation of the reproductive and productive qualities of cattle due to the body immunoprophylaxis with complex biological products of a new generation.

СОВРЕМЕННЫЕ БИОПРЕПАРАТЫ ДЛЯ ТВЕРДОСЕМЯННЫХ КУЛЬТУР

One of the significant factors of increasing the yield of agricultural crops is the use of fertilizers and pesticides. However, the use of chemicals causes environmental pollution and is accompanied by significant investments of material and energy resources. In addition, there is a decrease in humus in the soil. Therefore, agrotechnical techniques aimed at maintaining the natural fertility of the soil and stimulating the development of soil microflora are very relevant. Currently, natural growth regulators and bacterial preparations designed to activate the metabolic processes of plants and increase their productivity are increasingly used in crop production. Biological products can affect plants at different stages of growth and development. But their influence is most effectively manifested in the process of seed treatment before sowing. Such seeds have a high plasticity to changes in environmental conditions. And the use of drugs has a multifunctional effect. The article presents research materials on the effectiveness of the use of a new-generation biological product and micro-fertilizer, as well as zeolite-containing clays as a pre-sowing treatment of clover seeds. We used "Albit "(a complex biological product), "Polydon Bio Bean" (micro-fertilizer) and a mixture of rhizotorphin with "Alanite" (zeolite-containing clay). The results of the conducted studies revealed differences in the germination energy and germination of seeds of different types of clover. The influence of meteorological conditions and ecological and geographical origin on hard - seeding is determined. The seeds were treated with rhizotorphin and thiamine. Various doses of Alanite were tested in a mixture with risotorphin. The best option is a mixture of 1:5, which increased germination (37%), seed productivity (84%) and nitrogen-fixing ability. Both drugs had a stimulating effect on the germination energy and seed germination (15 – 28%). The acceleration of the development phases, an increase in the number of generative stems, the number of inflorescences, and foliage were noted. The yield of green mass for 2 mowing increased by 130 c/ha. The qualitative composition of the feed mass has also improved.

СОВРЕМЕННЫЕ БИОПРЕПАРАТЫ ДЛЯ ТВЕРДОСЕМЯННЫХ КУЛЬТУР

One of the significant factors of increasing the yield of agricultural crops is the use of fertilizers and pesticides. However, the use of chemicals causes environmental pollution and is accompanied by significant investments of material and energy resources. In addition, there is a decrease in humus in the soil. Therefore, agrotechnical techniques aimed at maintaining the natural fertility of the soil and stimulating the development of soil microflora are very relevant. Currently, natural growth regulators and bacterial preparations designed to activate the metabolic processes of plants and increase their productivity are increasingly used in crop production. Biological products can affect plants at different stages of growth and development. But their influence is most effectively manifested in the process of seed treatment before sowing. Such seeds have a high plasticity to changes in environmental conditions. And the use of drugs has a multifunctional effect. The article presents research materials on the effectiveness of the use of a new-generation biological product and micro-fertilizer, as well as zeolite-containing clays as a pre-sowing treatment of clover seeds. We used "Albit "(a complex biological product), "Polydon Bio Bean" (micro-fertilizer) and a mixture of rhizotorphin with "Alanite" (zeolite-containing clay). The results of the conducted studies revealed differences in the germination energy and germination of seeds of different types of clover. The influence of meteorological conditions and ecological and geographical origin on hard - seeding is determined. The seeds were treated with rhizotorphin and thiamine. Various doses of Alanite were tested in a mixture with risotorphin. The best option is a mixture of 1:5, which increased germination (37%), seed productivity (84%) and nitrogen-fixing ability. Both drugs had a stimulating effect on the germination energy and seed germination (15 – 28%). The acceleration of the development phases, an increase in the number of generative stems, the number of inflorescences, and foliage were noted. The yield of green mass for 2 mowing increased by 130 c/ha. The qualitative composition of the feed mass has also improved.