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Background Colorectal cancer (CRC) is the third most common cancer. It is a heterogeneous disease, including both hereditary and sporadic types of tumors. CRC results from complex interactions between various genetic and environmental factors. Inflammatory bowel disease is an important risk factor for developing CRC. Despite growing understanding of the CRC biology, preclinical models are still needed to investigate the etiology and pathogenesis of the disease, as well as to find new methods of treatment and prevention. Objectives The purpose of this review is to describe existing murine models of CRC with a focus on the models of colitis-associated CRC. This manuscript could be relevant for experimental biologists and oncologists. Methodology We checked PubMed and Google from 01/2018 to 05/2023 for reviews of CRC models. In addition, we searched PubMed from 01/2022 to 01/2023 for articles using the azoxymethane (AOM)/dextran sulfate sodium (DSS) CRC model. Results Existing murine models of CRC include spontaneous, genetically engineered, transplantation, and chemically induced models. For the study of colitis-associated cancer (CAC), the AOM/DSS model is predominantly used. This model is very similar in histological and molecular characteristics to the human CAC, and is highly reproducible, inexpensive, and easy to use. Despite its popularity, the AOM/DSS model is not standardized, which makes it difficult to analyze and compare data from different studies. Conclusions Each model demonstrates particular advantages and disadvantages, and allows to reproduce different subtypes or aspects of the pathogenesis of CRC.

Individual hypoxia tolerance is a major influence on the course and outcome of infectious and inflammatory diseases. Macrophages, which play central roles in systemic inflammatory response and other immunity reactions, are subject to functional activation orchestrated by several transcription factors including hypoxia inducible factors (HIFs). HIF-1 expression levels and the lipopolysaccharide (LPS)-induced systemic inflammatory response severity have been shown to correlate with hypoxia tolerance. Molecular and functional features of macrophages, depending on the organisms resistance to hypoxia, can determine the severity of the course of infectious and inflammatory diseases, including the systemic inflammatory response. The purpose is the comparative molecular and functional characterization of non-activated and LPS-activated bone marrow-derived macrophages under normoxia in rats with different tolerance to oxygen deprivation. Hypoxia resistance was assessed by gasping time measurement in an 11,500 m altitude-equivalent hypobaric decompression chamber. Based on the outcome, the animals were assigned to three groups termed ‘tolerant to hypoxia’ (n = 12), ‘normal’, and ‘susceptible to hypoxia’ (n = 13). The ‘normal’ group was excluded from subsequent experiments. One month after hypoxia resistance test, the blood was collected from the tail vein to isolate monocytes. Non-activated and LPS-activated macrophage cultures were investigated by PCR, flow cytometry and Western blot methods. Gene expression patterns of non-activated cultured macrophages from tolerant and susceptible to hypoxia animals differed. We observed higher expression of VEGF and CD11b and lower expression of Tnfa, Il1b and Epas1 in non-activated cultures obtained from tolerant to hypoxia animals, whereas HIF-1α mRNA and protein expression levels were similar. LPS-activated macrophage cultures derived from susceptible to hypoxia animals expressed higher levels of Hif1a and CCR7 than the tolerant group; in addition, the activation was associated with increased content of HIF-1α in cell culture medium. The observed differences indicate a specific propensity toward pro-inflammatory macrophage polarization in susceptible to hypoxia rats.

Microplastic pollution poses a threat to human health. It is possible that the increase in the incidence of inflammatory bowel disease is associated with exposure to microplastics. We investigated the effect of the consumption of polystyrene microparticles with a diameter of 5 μm at a dose of 2.3 mg/kg/day for 6 weeks on morphological changes in the colons of healthy male C57BL/6 mice and of mice with acute colitis induced by a 1% dextran sulfate sodium solution (DSS). In healthy mice, microplastics caused an increase in the number of endocrine cells, an increase in the content of highly sulfated mucins in goblet cells, an increase in the number of cells in the lamina propria, and a decrease in the volume fraction of macrophages. Microplastic consumption caused more severe acute colitis, which is characterized by a greater prevalence of ulcers and inflammation and a decrease in the content of neutral mucins in goblet cells.

Background The environmental pollution by microplastics is a global problem arising from the extensive production and use of plastics. Small particles of different plastics, measured less than 5 mm in diameter, are found in water, air, soil, and various living organisms around the globe. Humans constantly inhale and ingest these particles. The associated health risks raise major concerns and require dedicated evaluation. Objectives In this review we systematize and summarize the effects of microplastics on the health of different animals. The article would be of interest to ecologists, experimental biologists, environmental physicians, and all those concerned with anthropogenic environmental changes. Methodology We searched PubMed and Scopus from the period of 01/2010 to 09/2021 for peer-reviewed scientific publications focused on (1) environmental pollution with microplastics; (2) uptake of microplastics by humans; and (3) the impact of microplastics on animal health. Results The number of published studies considering the effects of microplastic particles on aquatic organisms is considerable. In aquatic invertebrates, microplastics cause a decline in feeding behavior and fertility, slow down larval growth and development, increase oxygen consumption, and stimulate the production of reactive oxygen species. In fish, the microplastics may cause structural damage to the intestine, liver, gills, and brain, while affecting metabolic balance, behavior, and fertility; the degree of these harmful effects depends on the particle sizes and doses, as well as the exposure parameters. The corresponding data for terrestrial mammals are less abundant: only 30 papers found in PubMed and Scopus deal with the effects of microplastics in laboratory mice and rats; remarkably, about half of these papers were published in 2021, indicating the growing interest of the scientific community in this issue. The studies demonstrate that in mice and rats microplastics may also cause biochemical and structural damage with noticeable dysfunctions of the intestine, liver, and excretory and reproductive systems. Conclusions Microplastics pollute the seas and negatively affect the health of aquatic organisms. The data obtained in laboratory mice and rats suggest a profound negative influence of microplastics on human health. However, given significant variation in plastic types, particle sizes, doses, models, and modes of administration, the available experimental data are still fragmentary and controversial.

Hypoxia tolerance of the organism depends on many factors, including age. High newborn organisms tolerance and high level of oxidative stress throughout aging were demonstrated by many studies. However, there is lack of investigations reflecting the expression of key hypoxia-inducible factor HIF in different age organisms in correlation to levels of pro-inflammatory and anti-inflammatory cytokines. Liver is a sensitive to hypoxia organ, and is an important organ in providing an acute reaction to infections – it synthesizes acute inflammation phase proteins, in particular, C-reactive protein. The aim of study was to determine relationship between age-related tolerance to hypoxia and HIF-1 and PHD2 (prolyl hydroxylase domain protein) expression levels in the liver and the production of cytokines in the spleen in newborn, prepubertal and adult Wistar rats. Newborn rats are characterized by high mRNA Hif-1α expression level in the liver, accompanied by a low content of HIF-1 protein and high level of PHD2. The growth in HIF-1α protein level throughout age is accompanied by the growth of pro-inflammatory cytokines level. Prepubertal animals are the least hypoxia resistant and their HIF-1α mRNA expression level was higher than in adult animals. The PHD2 activity in prepubertal animals was significantly reduced in comparison to newborn rats, and the HIF-1α protein level did not change. Further studies require the identification of additional mechanisms, determining the regulation of the HIF-1α level in prepubertal animals.

The modification of the optical characteristics of LiNbO3:Zn and LiNbO3:Mg crystals grown by the Czochralski method was investigated using β and γ radiation. The photorefractive effect was found to be inhibited by ionizing radiation in the LiNbO3:Zn ([ZnO] ≈ 2.1 mol%) crystal, which belonged to a below-threshold concentration range. The inhibition was attributed to a stepwise radiation annealing of charged defects. Ionizing radiation increased the general optical uniformity of above-threshold crystals LiNbO3:Zn ([ZnO] ≈ 5.9 mol%) and LiNbO3:Mg([MgO] ≈ 5.6 mol%). In addition, we determined that radiation annealing substantially influenced photorefraction dynamics in lightly doped LiNbO3:Zn ([ZnO] ≈ 0.1 mol%) crystals, which widens their application areas.

Unicellular organisms have the prevalent challenge to survive under oxidative stress of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2). ROS are present as by-products of photosynthesis and aerobic respiration. These reactive species are even employed by multicellular organisms as potent weapons against microbes. Although bacterial defences against lethal and sub-lethal oxidative stress have been studied in model bacteria, the role of fluctuating H2O2 concentrations remains unexplored. It is known that sub-lethal exposure of Escherichia coli to H2O2 results in enhanced survival upon subsequent exposure. Here we investigate the priming response to H2O2 at physiological concentrations. The basis and the duration of the response (memory) were also determined by time-lapse quantitative proteomics. We found that a low level of H2O2 induced several scavenging enzymes showing a long half-life, subsequently protecting cells from future exposure. We then asked if the phenotypic resistance against H2O2 alters the evolution of resistance against oxygen stress. Experimental evolution of H2O2 resistance revealed faster evolution and higher levels of resistance in primed cells. Several mutations were found to be associated with resistance in evolved populations affecting different loci but, counterintuitively, none of them was directly associated with scavenging systems. Our results have important implications for host colonisation and infections where microbes often encounter reactive oxygen species in gradients.

Abstract Antimicrobial peptides (AMP) are highly conserved immune effectors across the tree of life and are employed as combinations. In the beetle Tenebrio molitor, a defensin and a coleoptericin are highly expressed in vivo after inoculation with S. aureus. The defensin displays strong in vitro activity but no survival benefit in vivo. The coleoptericin provides a survival benefit in vivo, but no activity in vitro. This suggests a potentiating effect in vivo, and here we wanted to investigate the effects of this combination on resistance evolution using a bottom-approach in vitro starting with a combination of two abundant AMPs only. We experimentally evolved S. aureus in the presence of the defensin and a combination of the defensin and coleoptericin. Genome re-sequencing showed that resistance was associated with mutations in either the pmt or nsa operons. Strains with these mutations show longer lag phases, slower Vmax, and nsa mutants reach lower final population sizes. Mutations in the rpo operon showed a further increase in the lag phase in nsa mutants but not in pmt mutants. In contrast, final MICs (minimum inhibitory concentrations) do not differ according to mutation. All resistant lines display AMP but not antibiotic cross-resistance. Costly resistance against AMPs readily evolves for an individual AMP as well as a naturally occurring combination in vitro and provides broad protection against AMPs. Such non-specific resistance could result in strong selection on host immune systems that rely on cocktails of AMPs.

Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental conditions worldwide. There is growing awareness that ASD is highly comorbid with gastrointestinal distress and altered intestinal microbiome, and that host-microbiome interactions may contribute to the disease symptoms. However, the paucity of knowledge on gut-brain axis signaling in autism constitutes an obstacle to the development of precision microbiota-based therapeutics in ASD. To this end, we explored the interactions between intestinal microbiota, gut physiology and social behavior in a BTBR T+ Itpr3tf/J mouse model of ASD. Here we show that a reduction in the relative abundance of very particular bacterial taxa in the BTBR gut – namely, bile-metabolizing Bifidobacterium and Blautia species, - is associated with deficient bile acid and tryptophan metabolism in the intestine, marked gastrointestinal dysfunction, as well as impaired social interactions in BTBR mice. Together these data support the concept of targeted manipulation of the gut microbiota for reversing gastrointestinal and behavioral symptomatology in ASD, and offer specific plausible targets in this endeavor.

In framework of an international project of brown bear population monitoring, the bear population size and structure were analyzed on the Russian side of the Pasvik-Inari Trilateral Park (Russia, Norway, Finland) in 2015. The paper presents data gathered by two noninvasive methods: DNA analysis of hair samples and feces and the camera traps method. The material was obtained with 5 hair traps of made of barbed wire and scent lure and 4 Boskon Guard camera traps. In addition, feces were collected, as well as hair samples from national border fencing by staff of the Russian Border Authority. In total, 54 hair samples and 10 feces samples were collected. On the basis of the results the brown bear population size was estimated at 20 individuals in the study area: 13 individuals were detected by DNA analysis only, the remaining 7 animals – with the help of camera traps. The records include 9 females and 7 males; 13 adults, 4 yearlings and 3 cubs. The social structure consisted of three family groups, 10 singles, including 1 possible dominant male. Average brown bear density was 100 animals/1000 km². The combined usage of hair and feces collection, camera traps and GIS proved the techniques to be complementary in the analysis of the size and structure of the brown bear population.

Glyphosate is the most extensively used herbicide in the world. However, concerns regarding its safety, side effects, and impact on other organisms have increased in recent years. This is the first study to analyze a large set of recent and historical Escherichia coli isolates varying in pathogenicity and beta-lactam resistance from different host species for their susceptibility to glyphosate isopropylamine salt (IPA), the active ingredient of the herbicide, and to a complete glyphosate-containing formulation (Roundup LB Plus). For this, minimum inhibitory concentrations (MIC) were determined for 238 E. coli isolates by broth microdilution in Mueller Hinton I media followed by the statistical analyses using Mann-Whitney-U test, multivariable analysis of variance (ANOVA) and a multivariable proportional-odds ordinal regression model. While the overall MIC distribution was narrow and lacked a highly resistant sub-population for both substances, statistical analyses revealed small but significant associations between glyphosate resistance levels and different factors tested. Mean MIC values for the entire dataset showed a higher level of resistance to the complete glyphosate-containing formulation (40 mg/ml IPA) than to pure glyphosate (10 mg/ml IPA) in E. coli. Isolates that originated from poultry had significantly higher MIC values for both pure glyphosate and the complete formulation. Pathogenic and non-extended-spectrum beta-lactamase (non-ESBL) E. coli isolates each showed significantly higher MIC values compared to commensals and ESBL-producing E. coli in pure glyphosate, but not in the complete formulation. Recently sampled isolates showed statistically higher MICs than the isolates of the historic standard E. coli collection of reference in pure glyphosate, when tested by nonparametric Mann-Whitney-U test, but not in the multivariable model. Further investigations are necessary to confirm whether these associations have a casual relationship with the glyphosate use or are the consequence of co-selection due to the increased application rates of antibiotics, heavy metals or other biocides. A possible accumulation of pathogenic bacteria in livestock animals fed with glyphosate-containing feed should also be considered.

Hypoxia plays an important role in the development of many infectious, inflammatory, and tumor diseases. The predisposition to such disorders is mostly provided by differences in basic tolerance to oxygen deficiency, which we discuss in this review. Except the direct exposure of different-severity hypoxia in decompression chambers or in highland conditions, there are no alternative methods for determining organism tolerance. Due to the variability of the detection methods, differences in many parameters between tolerant and susceptible organisms are still not well-characterized, but some of them can serve as biomarkers of susceptibility to hypoxia. At the moment, several potential biomarkers in conditions after hypoxic exposure have been identified both in experimental animals and humans. The main potential biomarkers are Hypoxia-Inducible Factor (HIF)-1, Heat-Shock Protein 70 (HSP70), and NO. Due to the different mechanisms of various high-altitude diseases, biomarkers may not be highly specific and universal. Therefore, it is extremely important to conduct research on hypoxia susceptibility biomarkers. Moreover, it is important to develop a method for the evaluation of organisms’ basic hypoxia tolerance without the necessity of any oxygen deficiency exposure. This can contribute to new personalized medicine approaches’ development for diagnostics and the treatment of inflammatory and tumor diseases, taking into account hypoxia tolerance differences.

A new gamasid mite species belonging to the genus Arctoseius Thor, 1930 is described from Russia. Arctoseius koltschaki sp. n. is distributed in the plain and mountain tundras from Khibiny Mountains to Chukotka on the north and to West Sayan Mountains on the south. A diagnosis and a key for identification of species comprising the multidentatus species-group (A. multidentatus Evans, 1955; Arctoseius wisniewskii Gwiazdowicz & Kamczyc, 2009; A. sexsetus Lindquist & Makarova, 2011; A. haarlovi Lindquist & Makarova, 2011; and A. koltschaki sp. n.) are given.

We redefine the subfamily Arctoseiinae of the family Ascidae, and describe a new genus, Maxinia gen. n., based on a new species, Maxinia arctomontana sp. n., whose adults display a combination of attri-butes uniquely different from other genera of the subfamily. The geographical range of M. arctomontana is limited by arctic and mountain landscapes of Siberia. This description provides further data on the arctic distribution and morphological diversity of the subfamily Arctoseiinae, which is unusually well represented in that region (26–83 % in local gamasid mite faunas). Conceptual problems with the genus Iphidonopsis Gwiazdowicz, 2004 are reviewed, and a new combination, Iphidonopsis magnanalis (Ma & Yin, 1999) comb. n., is presented for Iphidozercon magnanalis Ma & Yin, 1999 from China. The genus Diseius Lindquist & Evans, 1965 is provisionally moved from the family Ascidae to the Digamasellidae. A new key to the genera of Arctoseiinae is presented.

Pseudomonas aeruginosa is the causative agent of chronic respiratory infections and is an important pathogen of cystic fibrosis patients. Adaptive mutations play an essential role for antimicrobial resistance and persistence. The factors that contribute to bacterial mutagenesis in this environment are not clear. Recently it has been proposed that cationic antimicrobial peptides such as LL-37 could act as mutagens in P. aeruginosa. Here we provide experimental evidence that mutagenesis is the product of a joint action of LL-37 and free iron. By estimating mutation rate, mutant frequencies and assessing mutational spectra in P. aeruginosa treated either with LL-37, iron or a combination of both we demonstrate that mutation rate and mutant frequency were increased only when free iron and LL-37 were present simultaneously. Colistin had the same effect. The addition of an iron chelator completely abolished this mutagenic effect, suggesting that LL-37 enables iron to enter the cells resulting in DNA damage by Fenton reactions. This was also supported by the observation that the mutational spectrum of the bacteria under LL-37-iron regime showed one of the characteristic Fenton reaction fingerprints: C to T transitions. Free iron concentration in nature and within hosts is kept at a very low level, but the situation in infected lungs of cystic fibrosis patients is different. Intermittent bleeding and damage to the epithelial cells in lungs may contribute to the release of free iron that in turn leads to generation of reactive oxygen species and deterioration of the respiratory tract, making it more susceptible to the infection.

Cationic antimicrobial peptides are ancient and ubiquitous immune effectors that multicellular organisms use to kill and police microbes whereas antibiotics are mostly employed by microorganisms. As antimicrobial peptides (AMPs) mostly target the cell wall, a microbial 'Achilles heel', it has been proposed that bacterial resistance evolution is very unlikely and hence AMPs are ancient 'weapons' of multicellular organisms. Here we provide a new hypothesis to explain the widespread distribution of AMPs amongst multicellular organism. Studying five antimicrobial peptides from vertebrates and insects, we show, using a classic Luria-Delbrück fluctuation assay, that cationic antimicrobial peptides (AMPs) do not increase bacterial mutation rates. Moreover, using rtPCR and disc diffusion assays we find that AMPs do not elicit SOS or rpoS bacterial stress pathways. This is in contrast to the main classes of antibiotics that elevate mutagenesis via eliciting the SOS and rpoS pathways. The notion of the 'Achilles heel' has been challenged by experimental selection for AMP-resistance, but our findings offer a new perspective on the evolutionary success of AMPs. Employing AMPs seems advantageous for multicellular organisms, as it does not fuel the adaptation of bacteria to their immune defenses. This has important consequences for our understanding of host-microbe interactions, the evolution of innate immune defenses, and also sheds new light on antimicrobial resistance evolution and the use of AMPs as drugs.

Phytoplasmas are bacterial phytopathogens responsible for significant losses in agricultural production worldwide. Several molecular markers are available for identification of groups or strains of phytoplasmas. However, they often cannot be used for identification of phytoplasmas from different groups simultaneously or are too long for routine diagnostics. DNA barcoding recently emerged as a convenient tool for species identification. Here, the development of a universal DNA barcode based on the elongation factor Tu (tuf) gene for phytoplasma identification is reported.We designed a new set of primers and amplified a 420-444 bp fragment of tuf from all 91 phytoplasmas strains tested (16S rRNA groups -I through -VII, -IX through -XII, -XV, and -XX). Comparison of NJ trees constructed from the tuf barcode and a 1.2 kbp fragment of the 16S ribosomal gene revealed that the tuf tree is highly congruent with the 16S rRNA tree and had higher inter- and intra- group sequence divergence. Mean K2P inter-/intra- group divergences of the tuf barcode did not overlap and had approximately one order of magnitude difference for most groups, suggesting the presence of a DNA barcoding gap. The use of the tuf barcode allowed separation of main ribosomal groups and most of their subgroups. Phytoplasma tuf barcodes were deposited in the NCBI GenBank and Q-bank databases.This study demonstrates that DNA barcoding principles can be applied for identification of phytoplasmas. Our findings suggest that the tuf barcode performs as well or better than a 1.2 kbp fragment of the 16S rRNA gene and thus provides an easy procedure for phytoplasma identification. The obtained sequences were used to create a publicly available reference database that can be used by plant health services and researchers for online phytoplasma identification.