Crowding Conditions Research Articles

Chiral RuII -PtII Complexes Inducing Telomere Dysfunction against Cisplatin-Resistant Cancer Cells.

The application of G-quadruplex stabilizers presents a promising anticancer strategy. However, the molecular crowding conditions within cells diminish the potency of current G-quadruplex stabilizers. Herein, chiral RuII -PtII dinuclear complexes were developed as highly potent G-quadruplex stabilizers even under challenging molecular crowding conditions. The compounds were encapsulated with biotin-functionalized DNA cages to enhance sub-cellular localization and provide cancer selectivity. The nanoparticles were able to efficiently inhibit the endogenous activities of telomerase in cisplatin-resistant cancer cells and cause cell death by apoptosis. The nanomaterials demonstrated high antitumor activity towards cisplatin-resistant tumor cells as well as tumor-bearing mice. To the best of our knowledge, this study presents the first example of a RuII -PtII dinuclear complex as a G-quadruplex stabilizer with an anti-cancer effect towards drug-resistant tumors inside an animal model.

Chiral Ru II ‐Pt II Complexes Inducing Telomere Dysfunction against Cisplatin‐Resistant Cancer Cells

The application of G-quadruplex stabilizers presents a promising anticancer strategy. However, the molecular crowding conditions within cells diminish the potency of current G-quadruplex stabilizers. Herein, chiral RuII-PtII dinuclear complexes were developed as highly potent G-quadruplex stabilizers even under challenging molecular crowding conditions. The compounds were encapsulated with biotin-functionalized DNA cages to enhance sub-cellular localization and provide cancer selectivity. The nanoparticles were able to efficiently inhibit the endogenous activities of telomerase in cisplatin-resistant cancer cells and cause cell death by apoptosis. The nanomaterials demonstrated high antitumor activity towards cisplatin-resistant tumor cells as well as tumor-bearing mice. To the best of our knowledge, this study presents the first example of a RuII-PtII dinuclear complex as a G-quadruplex stabilizer with an anti-cancer effect towards drug-resistant tumors inside an animal model.

Evaluation of weak interactions of proteins and organic cations with DNA duplex structures

Molecular interactions and reactions in living cells occur with high background concentrations of organic compounds including proteins. Uncharged water-soluble polymers are commonly used cosolutes in studies on molecular crowding, and most studies argue about the effects of intracellular crowding based on results obtained using polymer cosolutes. Further investigations using protein crowders and organic cations are important in understanding the effects of cellular environments on nucleic acids with negatively charged surfaces. We assessed the effects of using model globular proteins, serum proteins, histone proteins, structurally flexible polypeptides, di- and polyamines, and uncharged polymers. Thermal stability analysis of DNA oligonucleotide structures revealed that unlike conventional polymer cosolutes, basic globular proteins (lysozyme and cytochrome c) at high concentrations stabilized long internal and bulge loop structures but not fully matched duplexes. The selective stabilization of long loop structures suggests preferential binding to unpaired nucleotides in loops through weak electrostatic interactions. Furthermore, the ability of the proteins to stabilize the loop structures was enhanced under macromolecular crowding conditions. Remarkably, the effects of basic proteins on the stability of fully matched duplexes were dissimilar to those of basic amino-acid-rich polypeptides and polyamines. This study provides new insights into the interaction of nucleic acid structures with organic cations.

Larval Crowding Did Not Enhance Adult Migration Propensity in Spodoptera frugiperda.

Simple SummaryThe fall armyworm, Spodoptera frugiperda (J. E. Smith), is a typical invasive migratory pest with a strong reproductive capacity, which has caused serious damage to crops. Larvae of S. frugiperda exhibit high levels of cannibalism associated with larval crowding. However, the response of S. frugiperda adults to such stress remains unclear. In this study, we investigated the effects of larval density on flight and reproductive parameters of S. frugiperda adults. We found that S. frugiperda reared under high-larval density conditions exhibited lower pupal and body weights, weaker flight and reproductive capacities than those reared as solitary larvae. This result was different from that of many migratory insects, where larval crowding enhanced migratory propensity of subsequent adults. In contrast, high-larval density conditions did not increase adult migration propensity in S. frugiperda. These findings enhance our understanding of migratory and reproductive behaviors of S. frugiperda in response to larval density.Reproduction and flight are two major adaptive strategies to cope with environmental stress in migratory insects. However, research on density-mediated flight and reproduction in the global migratory agricultural pest Spodoptera frugiperda is lacking. In this study, flight and reproductive performances in response to larval crowding were investigated in S. frugiperda. We found that larval crowding significantly reduced the pupal and body weights of S. frugiperda. Adults reared under the highest density of 30 larvae/jar had the minimum wing expansion, which was significantly smaller than that of larvae reared under solitary conditions. Larval crowding also significantly increased the pre-oviposition period (POP) and period of first oviposition (PFO) but decreased the lifetime fecundity, flight duration and flight distance. Our results showed that S. frugiperda reared under solitary conditions exhibited higher pupal and body weights and stronger reproductive and flight capacities than those reared under high-density conditions. Larval crowding did not enhance the migration propensity in S. frugiperda adults. In conclusion, larval crowding may not be a major factor affecting FAW migration due to high levels of cannibalism. These findings provide new insights into the population dynamics of S. frugiperda under larval crowding conditions.

Macromolecular crowding in the development of a three-dimensional organotypic human breast cancer model

Although cell-derived matrices are at the forefront of scientific research and technological innovation for the development of in vitro tumour models, their two-dimensional structure and low extracellular matrix composition restrict their capacity to accurately predict toxicity of candidate molecules. Herein, we assessed the potential of macromolecular crowding (a biophysical phenomenon that significantly enhances and accelerates extracellular matrix deposition, resulting in three-dimensional tissue surrogates) in improving cell-derived matrices in vitro tumour models. Among the various decellularisation protocols assessed (NH4OH, DOC, SDS/EDTA, NP40), the NP40 appeared to be the most effective in removing cellular matter and the least destructive to the deposited matrix. Among the various cell types (mammary, skin, lung fibroblasts) used to produce the cell-derived matrices, the mammary fibroblast derived matrices produced under macromolecular crowding conditions and decellularised with NP40 resulted in significant increase in focal adhesion molecules, matrix metalloproteinases and proinflammatory cytokines, when seeded with MDA-MB-231 cells. Further, macromolecular crowding derived matrices significantly increased doxorubicin resistance and reduced the impact of intracellular reactive oxygen species mediated cell death. Collectively our data clearly illustrate the potential of macromolecular crowding in the development of cell-derived matrices-based in vitro tumour models that more accurately resemble the tumour microenvironment.

Improvement of Protein Solubility in Macromolecular Crowding during Myoglobin Evolution.

The inside of living cells is crowded by extremely high concentrations of biomolecules, and thus globular proteins should have been developed to increase their solubility under such crowding conditions during organic evolution. The O2-storage protein myoglobin (Mb) is known to be expressed in myocytes of diving mammals in much larger quantities than those of land mammals. We have previously resurrected ancient whale and pinniped Mbs and experimentally demonstrated that the diving animal Mbs have evolved to maintain high solubility under the crowding conditions or to increase their tolerance against macromolecular precipitants, rather than solubility in a dilute buffer solution. However, the detail of chemical mechanisms of the precipitant tolerance remains unclear. Here, we investigated pH dependence of the precipitant tolerance (β, slope of the solubility against precipitant concentration) of extant Mbs and plotted the β values, as well as those of ancestral Mbs, against their surface net charges (ZMb). The results demonstrated that the precipitant tolerance was approximated by the square of ZMb, that is, β = aZMb2 + b, in which a and b are constants. This effect of ZMb against the precipitation is not predicted by a classical excluded volume theory that gives constant β for Mbs but can be explained by electrostatic repulsion between Mb molecules. The present study elucidates how Mb molecules have evolved to increase their in vivo solubility and shows the physiological significance of either neutral or basic isoelectric points (pI) of the natural Mbs, rather than acidic pI.

Study of cognitive performance and psychophysiological state of an operator in conditions of isolation and crowding

Introduction. In the context of the pandemic of the new coronavirus and the measures taken to contain the spread of infection, including quarantine measures and transfer to remote work, there is a lack of knowledge about the effects of short- and long-term isolation on psychological well-being and cognitive performance of a person. In this situation, the closest model for studying the processes of adaptation to the conditions of isolation and crowding are isolation experiments. The study aims to research the cognitive performance and psychophysiological state of a person in conditions of isolation and crowding. Materials and methods. Scientists conducted a 14-day isolation experiment simulating a flight to the moon at the Institute of Biomedical Problems of the Russian Academy of Sciences: 6 subjects (4 men, 2 women) worked for two weeks and lived in a hermetic volume with an area of 12 sq2. With the help of situational anxiety assessment, acoustic speech analysis, cognitive and sensorimotor tests, experts obtained data on the relationship between the psychophysiological state of a person and his productivity. Results. Researchers have identified significant correlations between situational anxiety and acoustic characteristics of speech. On days when the subjects spoke at a lower volume (p<0,0001) and had more pauses in their speech (p<0,01), and there was additional variability in the voice amplitude of the speech signal (shimmer effect) (p<0,0001), the subjects noted greater anxiety. Subjectively perceived anxiety correlated with cognitive performance. In a more anxious state, the subjects made more mistakes in mathematical calculations (p<0.01), they needed more time to solve (p<0.001); lability (p<0.01) and errors (p<0.0001) also increased when performing the sensorimotor RDO test. Limitations. The limitations of this study were a small sample size, the duration of isolation exposure, as well as a limited number of methods used to study the physiological state of a person. Conclusions. The researchers found reliable connections between the indicator of situational anxiety, acoustic characteristics of speech and cognitive performance. The psychophysiological state of the subjects affected the quality of the operator's tasks. Isolation and crowding by themselves did not become significant psychological stressors in this experiment, this was due to the motivation of the subjects. Experts found an increase in anxiety a few days before the experiment due to changes in the usual lifestyle, feelings of insecurity and a large number of examinations. Ethics. The Commission on Biomedical Ethics of the State Scientific Center of the Russian Federation (Institute of Biomedical Problems of the Russian Academy of Sciences) approved experimental program No. 573 dated April 1, 2021 in accordance with the principles of the Helsinki Declaration of 1964. Each study participant voluntarily signed an informed consent after having the potential risks, bene ts and nature of the upcoming study explained to her/him.

Development of a Smart Fluorescent Probe Specifically Interacting with C-Myc I-Motif.

I-motifs play key regulatory roles in biological processes, holding great potential as attractive therapeutic targets. In the present study, we developed a novel fluorescent probe G59 with strong and selective binding to the c-myc gene promoter i-motif. G59 had an i-motif-binding carbazole moiety conjugated with naphthalimide fluorescent groups. G59 could differentiate the c-myc i-motif from other DNA structures through selective activation of its fluorescence, with its apparent visualization in solution. The smart probe G59 showed excellent sensitivity, with a low fluorescent detection limit of 154 nM and effective stabilization to the c-myc i-motif. G59 could serve as a rapid and sensitive probe for label-free screening of selective c-myc i-motif binding ligands under neutral crowding conditions. To the best of our knowledge, G59 is the first fluorescent probe with high sensitivity for recognizing the i-motif structure and screening for selective binding ligands.

Association between living in municipalities with high crowding conditions and poverty and mortality from COVID-19 in Mexico.

BackgroundThe World Health Organization stated a pandemic by severe acute respiratory syndrome coronavirus SARS-Cov2 (COVID-19) on March, 2020 with devastating implications for populations, healthcare systems, and economies globally.ObjectiveThe present study explores the association between patients living in municipalities with crowding conditions and poverty and mortality from COVID-19 in Mexico; specifically evaluating the socioeconomic characteristics of the municipality in which the patients reside and some individual characteristics.MethodsIn the present study, we examined public information collected from the National Epidemiological Surveillance System informing all persons tested for SARS-CoV-2 and published by the Ministry of Health. The present analysis was restricted to those with the date of registration to October 12, 2021. The association between the main exposures (overcrowded conditions and poverty) and the outcomes of interest (death by COVID-19) was explored using Cox proportional hazard regression models, including frailty penalties to accommodate multilevel data and random effects for the municipality of case occurrence.ResultsA total of 9619917 subjects were included in the Epidemiological Surveillance System for viral respiratory disease platform. Of those for which results were available, 6141403 were negative for COVID-19 and 3478514 were positive for COVID-19; with a total of 273216 deaths in those who tested positive. Among those positive to COVID-19 mean age was 46.9. Patients living in municipalities with high rates of crowding conditions increased the risk of dying from COVID-19 by 8% (95% CI: 1.03, 1.14). Individuals living in municipalities with indigenous background was associated with an increased risk of dying from COVID-19 (HR = 1.10; 95% CI: 1.04, 1.17). Individuals living in municipalities with illiteracy (HR = 1.09; 95% CI: 1.03, 1.11), poverty (HR = 1.17; 95% CI: 1.14, 1.19), food insecurity (HR = 1.094; 95% CI 1.02, 1.06), limited access to social security (HR = 1.10; 95% CI: 1.08, 1.13) and health services (HR = 1.06; 95% CI: 1.04, 1.08) had a higher risk of mortality from COVID-19.ConclusionOur data suggest that patients living in municipalities with higher rates of crowding conditions and higher rates of poverty had elevated risk of mortality from COVID-19. In Mexico, the COVID-19 pandemic is a systemic crisis linked to human development since we have seen that it affects less developed and more vulnerable municipalities. Policies to reduce vulnerabilities and develop strategies to deal with health crises like the current one needs to be considered.

Preparation of arctiin moleculary imprinted polymers with 4-vinylpyridine and Allyl-β-cyclodextrin as binary monomers under molecular crowding conditions

This paper reported a feasible method to prepare molecularly imprinted polymer (MIPs) using 4-vinylpyridine (4-VP) and Allyl-β-cyclodextrin (β-CD) as binary functional monomer in the presence of polystyrene (PS). This is the first time that a surrounding of macromolecular crowding was established to improve the imprinting effect of cyclodextrins as monomer in organic solvents. The morphological and characteristics of the polymers with macromolecular crowding reagents were investigated by scanning electron microscope (SEM), fourier-transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA) and nitrogen adsorption experiments. The MIPs were synthesized with 4-VP and β-CD as binary functional monomers, a series of experiments were conducted to compare with the control groups. Furthermore, the selectivity of MIP for analogues experiment showed that the β-CD/4-VP MIP has higher specific recognition for arctiin than β-CD/4-VP NIP. A purification method by β-CD/4-VP MIPs coupled with macromolecular crowding reagents was developed for extraction arctiin from Arctium lappa L. In the MIP-SPE process, the optimal washing and eluting reagents are methanol/water (5:5) and methanol/acid (9:1), respectively. When using the β-CD/4-VP MIPs as SPE absorbent, the mean recoveries for arctiin were 87% with purity of 95%. All the results indicate that this synthetic method using 4-VP and β-CD as binary functional monomers in the presence of PS is a promising method for the preparation of selective adsorbents for arctiin analysis in Arctium lappa L.

Impact of molecular crowding conditions on stability, folding landscape, and accessibility of long telomeric sequences

The interior of living cells is very crowded due to high concentrations of soluble and insoluble biomolecules including nucleic acids, proteins, polysaccharides, and metabolites. These biomolecules occupy up to 40% of the volume of a living cell, leading to molecular crowding conditions which significantly impact the stability and kinetics of nucleic acid secondary structures, including G-quadruplexes (GQ). GQs form at the single stranded overhang of telomeres and are important for capping and protecting these otherwise vulnerable genomic regions.

Dielectricity of a molecularly crowded solution accelerates NTP misincorporation during RNA-dependent RNA polymerization by T7 RNA polymerase

In biological systems, the synthesis of nucleic acids, such as DNA and RNA, is catalyzed by enzymes in various aqueous solutions. However, substrate specificity is derived from the chemical properties of the residues, which implies that perturbations of the solution environment may cause changes in the fidelity of the reaction. Here, we investigated non-promoter-based synthesis of RNA using T7 RNA polymerase (T7 RNAP) directed by an RNA template in the presence of polyethylene glycol (PEG) of various molecular weights, which can affect polymerization fidelity by altering the solution properties. We found that the mismatch extensions of RNA propagated downstream polymerization. Furthermore, PEG promoted the polymerization of non-complementary ribonucleoside triphosphates, mainly due to the decrease in the dielectric constant of the solution. These results indicate that the mismatch extension of RNA-dependent RNA polymerization by T7 RNAP is driven by the stacking interaction of bases of the primer end and the incorporated nucleotide triphosphates (NTP) rather than base pairing between them. Thus, proteinaceous RNA polymerase may display different substrate specificity with changes in dielectricity caused by molecular crowding conditions, which can result in increased genetic diversity without proteinaceous modification.

Conformational plasticity of DNA secondary structures: probing the conversion between i-motif and hairpin species by circular dichroism and ultraviolet resonance Raman spectroscopies.

The promoter regions of important oncogenes such as BCL2 and KRAS contain GC-rich sequences that can form distinctive noncanonical DNA structures involved in the regulation of transcription: G-quadruplexes on the G-rich strand and i-motifs on the C-rich strand. Interestingly, BCL2 and KRAS promoter i-motifs are highly dynamic in nature and exist in a pH-dependent equilibrium with hairpin and even with hybrid i-motif/hairpin species. Herein, the effects of pH and presence of cell-mimicking molecular crowding conditions on conformational equilibria of the BCL2 and KRAS i-motif-forming sequences were investigated by ultraviolet resonance Raman (UVRR) and circular dichroism (CD) spectroscopies. Multivariate analysis of CD data was essential to model the presence and identity of the species involved. Analysis of UVRR spectra measured as a function of pH, performed also by the two-dimensional correlation spectroscopy (2D-COS) technique, showed the role of several functional groups in the DNA conformational transitions, and provided structural and dynamic information. Thus, the UVRR investigation of intramolecular interactions and of local and environmental dynamics in promoting the different species induced by the solution conditions provided valuable insights into i-motif conformational transitions. The combined use of the two spectroscopic tools is emphasized by the relevant possibility of working in the same DNA concentration range and by the heterospectral UVRR/CD 2D-COS analysis. The results of this study shed light on the factors that can influence at the molecular level the equilibrium between the different conformational species putatively involved in the oncogene expression.

Stability and Activity of the 10-23 DNAzyme Under Molecular Crowding Conditions.

DNAzymes are biocatalysts that have been selected in vitro and their function inside cells (in vivo) is extremely low. Thus, almost all studies have been carried out in diluted solutions (in vitro). The cellular presence of molecules such as amino acids, polypeptides, alcohols, and sugars introduces forces that modify the kinetics and thermodynamics of DNAzyme-mediated catalysis. The crowded intracellular environment referred to as molecular crowding can be mimicked by adding high concentrations of natural or synthetic macromolecules to the reaction conditions. Here, we investigate the activity of the 10-23 DNAzyme and the stability of the DNAzyme:RNA complex under molecular crowding conditions. Therefore, we use a Förster resonance energy transfer (FRET)-based activity assay in combination with denaturing urea polyacrylamide gel electrophoresis and circular dichroism (CD) spectroscopy.

A method to estimate the size of single-chain nanoparticles under severe crowding conditions.

Single-chain nanoparticles (SCNPs) result from the folding of isolated polymer chains via intramolecular interactions. Currently, there is no theory able to rationalize the astonishing conformational behaviour of SCNPs under severe crowding conditions (e.g., highly concentrated solutions, all-polymer nanocomposites) and, specifically, the significant size reduction observed in highly crowded solutions of covalent-bonded SCNPs and all-polymer nanocomposites containing SCNPs. Herein, we propose a valuable method to estimate the size of SCNPs under crowding. The method – which is based on combining MD simulations results with scaling concepts – is also useful for ring polymers and nanostructured Janus-shaped SCNPs.

The effects of molecular crowding and CpG hypermethylation on DNA G-quadruplexes formed by the C9orf72 nucleotide repeat expansion

A nucleotide repeat expansion (NRE), (G4C2)n, located in a classically noncoding region of C9orf72 (C9), is the most common genetic mutation associated with ALS/FTD. There is increasing evidence that nucleic acid structures formed by the C9-NRE may both contribute to ALS/FTD, and serve as therapeutic targets, but there is limited characterization of these nucleic acid structures under physiologically and disease relevant conditions. Here we show in vitro that the C9-NRE DNA can form both parallel and antiparallel DNA G-quadruplex (GQ) topological structures and that the structural preference of these DNA GQs can be dependent on the molecular crowding conditions. Additionally, 5-methylcytosine DNA hypermethylation, which is observed in the C9-NRE locus in some patients, has minimal effects on GQ topological preferences. Finally, molecular dynamic simulations of methylated and nonmethylated GQ structures support in vitro data showing that DNA GQ structures formed by the C9-NRE DNA are stable, with structural fluctuations limited to the cytosine-containing loop regions. These findings provide new insight into the structural polymorphic preferences and stability of DNA GQs formed by the C9-NRE in both the methylated and nonmethylated states, as well as reveal important features to guide the development of upstream therapeutic approaches to potentially attenuate C9-NRE-linked diseases.

Glycosylation of rice protein with dextran via the Maillard reaction in a macromolecular crowding condition to improve solubility

The study aims at improving the solubility of rice protein (RP) by covalent coupling of proteins to polysaccharide via Maillard reaction in macromolecular crowding conditions. The formation of RP-dextran conjugates (RPC) was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, size exclusion chromatography and infrared spectra. The optimum conditions for the Maillard reaction between rice protein and dextran were 90 °C, pH 11, 60 min, and the mass ratio of RP to dextran was 1:3. The solubility of the RP-dextran conjugates in the buffer solution of pH 7–9 was greater than 80%. The high solubility of the RP-dextran conjugate was due to the introduction of dextran. Dextran covalently bound to RP has many hydrophilic hydroxyl groups, which reduced the ratio of hydrophobic groups on the surface of RP. At the same time, the emulsification and foaming properties of the RP-dextran conjugates were greatly improved compared to that of original RP. The application of crowded conditions can be used as a new way to enhance the reaction, improve the solubility of rice protein, while retaining the protein structure, thus contributing to the industrialized application of rice proteins.

The Influence of Social Crowding on Consumer Creativity

The importance of consumer creativity is currently widely recognized, yet the examination of the influence of environmental elements on consumer creativity is still limited. Our research investigates the influence of social crowding on consumer creativity performance. While past research mainly focuses on extreme crowding conditions, our research examines the impact of a moderate level of social crowding, which is more commonly experienced in reality. From two lab experiments, our research shows that compared to consumers in crowded environments, consumers in uncrowded environments perform better on creativity tasks (e.g., designing promotion slogans and identifying solutions to problems). Furthermore, the effect of social crowding is mediated by approach motives. Consumers in an uncrowded (vs. crowded) environment are more likely to trigger approach-based motivation, which enhances their creativity performance. These findings extend our knowledge of social crowding and creativity and can help consumers and companies improve creativity performance in appropriate environments.

Synthesis and Properties of Oligonucleotides Containing 2′‐O,4′‐C‐Ethylene‐Bridged 5‐Methyluridine with Exocyclic Methylene and Methyl Groups in the Bridge

AbstractNovel 2′‐O,4′‐C‐ethylene‐bridged nucleic acid (ENA) analogs with exocyclic methylene and (R)‐methyl groups at the 6′‐position were synthesized. The obtained 6′‐methylene‐ENA and 6′R‐Me‐ENA were incorporated into oligonucleotides, and their properties were compared with those of the corresponding natural, ENA‐, and 6′S‐Me‐ENA‐modified oligonucleotides. The duplex‐stabilizing ability of 6′‐methylene‐ENA and 6′R‐Me‐ENA with single‐stranded RNA (ssRNA) was similar to that of ENA and 6′S‐Me‐ENA under both dilute and molecular crowding conditions. On the other hand, oligonucleotides containing 6′‐methylene‐ENA and 6′R‐Me‐ENA formed stable triplexes with double‐stranded DNA (dsDNA) in comparison with those containing 6′S‐Me‐ENA. Their thermodynamic properties were also calculated to explore the influence of the substituents introduced at the 6′‐position of ENA. Moreover, oligonucleotides with ENA analogs exhibited excellent resistance against nucleases. These results suggest that 6′‐methylene‐ENA and 6′R‐Me‐ENA are promising candidates for targeting ssRNA and dsDNA.

Influence of new lactulose-containing fodder additives on basic morpho-biochical indicators of blood and resistance of broiler chicken

In modern industrial broiler poultry farming, the issue of combating the uncontrolled use of antibiotics in the process of growing poultry is being actively addressed. Currently, scientists are looking for an alternative solution to the issue of eliminating the use of antibiotics for prophylactic purposes. In this connection, researchers are intensively working on the development of innovative feed additives that can solve the problem with the immunostatus of the organism of poultry grown in conditions of great crowding. The article discloses the data of experimental experience on the use of new innovative lactulose-containing additives of domestic origin "Kumelakt-1" and "Laktuvet-1". Their positive effect on the morpho-biochemical parameters of the blood and the resistance of the poultry organism has been established. This information allows to predict in vivo the indicators of the safety of the poultry population and are indicators of the quality of the products obtained. New lactulose-containing innovative additives as a regulator of intestinal microflora improved the morpho-biochemical blood index and increased the resistance of the poultry organism. Namely: increased on average in I and II experimental groups in comparison with the control group, the hemoglobin index by 9.7%, erythrocytes by 10.8%, hematocrit by 5.6%. An increase in the level of urea in the blood serum was established by 10.4 and 9.7% (P <0.01), glucose - by 6.5 and 4.8 6.1 and 9.0% (P <0.05), phosphorus - by 8.2 and 6.6% (P <0.01), magnesium - by 9.9 and 9.1% (P <0.05), potassium - by 1.3 and 1.6% (P <0.05), iron - by 1.4 and 1.6% (P <0.05), respectively. The indicators of phagocytic activity in the experimental groups were determined, it was found that, on average, this indicator increased by 5.2% (P <0.05).