Czech Academy of Sciences, Institute of Experimental Medicine

Нарушение мозгового кровотока при артериальной гипертензии приводит к развитию нейровоспаления, активными участниками которого являются микроглия и макрофаги головного мозга. Целью работы было изучение функциональной активности и иммунофенотипа микроглии и макрофагов в области барьеров головного мозга спонтанно-гипертензивных крыс (SHR). Использовали материал головного мозга крыс-самцов Вистар и SHR (возраст 3–4 месяца, n = 10). Работа выполнена с применением методов иммуногистохимического анализа и конфокальной лазерной микроскопии. Оценивали наличие маркера М2 активации (CD206) и фагоцитарной активности (CD68) в популяции микроглии и макрофагов. Показано, что белок CD206 присутствует в периваскулярных клетках, число которых значительно увеличено у крыс SHR (40,69 ± 4,87 клеток на 1 мм2 против 28,73 ± 1,39 у крыс Вистар; t-test, р = 0,0007). Проведенный количественный анализ позволил выявить тенденцию увеличения доли фагоцитирующих клеток в головном мозге у крыс SHR по сравнению с крысами Вистар. Изменений в распределении белка CD68 у крыс SHR не выявлено, следовательно, активация микроглии и макрофагов не сопровождается усилением фагоцитарной активности. Полученные результаты свидетельствуют об альтернативной активации макрофагов головного мозга при нейровоспалении, вызванном артериальной гипертензией.

Introduction. Complement is a key humoral participant of immunity involved in defensive and pathological processes. Human lysozyme (hLZ), hen egg white lysozyme (HEWL) and lactoferrin (LF) are classical constituents of innate immunity. Complement and proteins of innate immunity are often co-localized but their interaction is poorly understood. The aim of the work was to characterize functional interaction of LF and hLZ/HEWL with complement. Materials and methods. Human blood serum was used as a source of complement. The complement classical and alternative pathway models contained antibody-sensitized sheep erythrocytes and rabbit erythrocytes respectively. The level of complement activation was estimated as serum hemolytic activity and anaphylatoxins production measured by ELISA. The bactericidal effect was estimated in colony-count assay. Permeabilization of outer and inner membranes of Escherichia coli ML-35p was evaluated with the use of chromogenic substrates of periplasmic and cytoplasmic enzymes. Enzymatic activity of lysozymes was measured in turbidimetric assay. Results. We confirmed the data that LF selectively inhibits the classical pathway (IC50 ~ 160 μg/mL; ~ 2 μM). We demonstrated for the first time that hLZ at high concentrations (40—160 μg/mL) moderately enhances the activity of the both complement pathways (C3 and C5 conversion as well as lytic activity) while HEWL at concentrations up to 160 μg/mL does not influence on complement activation. LF and hLZ modulated the classical pathway in an independent manner. LF did not prevent E. coli killing by serum but instead slightly increased bacterial viability in diluted serum. Lysozymes cooperated with complement in bacterial killing but LF partially prevented this in 5% serum. hLZ and HEWL accelerated bacterial inner membrane disruption regardless the presence of LF. The two enzymes accelerated the bactericidal effect of 50% serum, and hLZ did it slightly better than HEWL. Conclusion. LF and hLZ produce opposing and independent effects on complement. We refine the idea of the interaction between complement and lysozyme and propose a new model in which hLZ cooperates with complement to accelerate bacterial killing via promotion of the classical and alternative pathways activation as well as synergism with membrane-attack complex. LF does not inhibit bacterial killing by serum but can oppose hLZ and complement synergism in diluted serum.

Introduction Monitoring and real-time detection of soil heavy metal pollution are crucial to ensuring the safety of agricultural food products. Conventional methods for determining heavy metal concentrations require substantial time and costs. This study investigates intelligent modeling approaches for online detection of heavy metal contamination in soils. Based on Internet of Things communication, large‐scale near-infrared (NIR) spectral data were collected from distributed sensors for federated analysis. Methods In chemometric studies, the improved binary firefly algorithm (IBFA) is proposed for evolutionary variable selection, and the modified method of maximum information coefficient (MMIC) is designed to estimate the nonlinear correlation of unevenly distributed samples. Experimental soil data are collected from the Karst geology on the north side of Guangxi ZAR, China. The NIR calibration model is established by fusion of the IBFA and the MMIC methods (denoted as IBFA + MMIC). The fusion model is applied for quantitative prediction targeting of four heavy metals in the Karst soil samples. Results The IBFA + MMIC model can observe correlation coefficients higher than 0.9 and the lowest prediction errors during model training. It is tested with the correlations very close to 0.9, while the testing errors are acceptably low. These results outperform the counterpart models established by other cross combinations of firefly algorithm (FA)/IBFA and maximum information coefficient (MIC)/MMIC. Discussion The proposed modeling methodology is effectively validated for quantitative NIR analysis of different heavy metals in Karst soil data. Meanwhile, it provides critical technical support for the federated analytical performance of distributed sensing data, thereby facilitating precision soil management practices.

Ulcerative colitis (UC) is characterized by pronounced dysbiosis of the gut microbiota, with previous studies implicating multiple bacterial taxa in disease pathogenesis. This study investigated the species-level diversity of Blautia in 24 UC patients and 15 healthy controls (HC) using 16S rRNA gene sequencing and MALDI-TOF mass spectrometry for species identification. Results demonstrated a marked 10.9-fold increase in Blautia abundance in UC patients (mean 44.6% vs. 5.26% in HC, p=0.0003), with four species - B. obeum, B. luti, B. faecis, and unidentified Blautia sp. (ID 375)-accounting for >80% of the genus. Notably, B. luti showed 100% prevalence in UC patients versus 79.2% in HC (p=0.0086). This Blautia expansion paradoxically correlated with reduced abundance of protective bacteria, including Faecalibacterium duncaniae, Anaerostipes hadrus, and Dorea longicatena, and was associated with increased disease severity. Although Blautia species are known butyrate producers with anti-inflammatory properties, their overabundance in UC represents functional dysbiosis, in which the microbiota attempts metabolic compensation but fails to effectively deliver short-chain fatty acids in the pathologically altered colonic environment. The concurrent depletion of mucus-layer-associated bacteria indicates compromised intestinal barrier integrity. These findings establish Blautia diversity as a potential marker of dysbiosis for UC severity, opening new diagnostic and therapeutic avenues for disease stratification and targeted interventions aimed at restoring eubiotic composition through selective bacterial modulation.

The article presents a comprehensive review that systematizes current data on extragastric manifestations of Helicobacter pylori infection. In addition to the well-established association of the microbe with gastrointestinal pathologies (gastritis, ulcer, gastric cancer), H. pylori can persist in other organs and exert a systemic negative influence on the body. The article examines four main pathways for the development of extragastric manifestations during the persistence of the microorganism: direct migration of the bacteria and colonization of other organs, the development of chronic systemic inflammation and endotoxinemia, the phenomenon of molecular mimicry leading to autoimmune reactions, and an indirect influence through disruption of the gut microbiota (dysbiosis). It is emphasized that Helicobacter pylori infection and intestinal dysbiosis are links in the same pathogenetic chain. Eradication therapy can exacerbate dysbiosis, highlighting the potential benefit of using probiotics.

Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system, characterized by inflammatory demyelination and neurodegeneration. Increasing attention has been directed to the “microbiota-gut-brain” axis, as intestinal barrier dysfunction and alterations in gut microbiota composition have been reported to precede the clinical onset of MS, although their association with disease severity remains uncertain. Experimental autoimmune encephalomyelitis (EAE) in rodents is a well-established model that reproduces the key immunological and morphological features of MS. However, comparative investigations addressing both the taxonomic structure of the microbiota and intestinal morphological changes across different severities of EAE remain scarce. To compare the taxonomic composition of the gut microbiota and structural alterations of the intestinal epithelium in rats with different severities of experimental autoimmune encephalomyelitis (EAE). The study was conducted on 39 female Wistar rats (intact, n=9; EAE-induced, n=30). EAE was induced by a single subcutaneous injection of spinal cord homogenate in complete Freund’s adjuvant. Morphological and ultrastructural changes in the intestinal epithelium were assessed using histological techniques and electron microscopy. The taxonomic composition of the gut microbiota was analyzed by 16S rRNA gene sequencing. When comparing the intestinal microbiome of mildly and severely ill rats, significant differences were observed in the representation of 4 phyla: Bacillota, Bacteroidota, Actinomycetota and Cyanobacteriota. In the baseline microbiome of severely affected rats, the abundance of the class Epsilonproteobacteria (Pseudomonadota) was increased. Clinical symptoms developed in both groups against the background of a decreased number of Bacteroidota (family Prevotellaceae). During the recovery phase, the abundance of Bacteroidota was restored only in mildly affected and recovered animals, whereas in rats with severe EAE the proportion of Actinomycetota increased. At the genus level, distinct group-specific dynamics during EAE were identified for 9 genera (unclassified Clostridiaceae and Peptoscreptococaceae, Allobaculum, Turicibacter, Prevotella, Parabacteroides, Desulfovibrio and Bifidobacterium). Alongside more pronounced alterations in the gut microbiome, rats with severe EAE displayed significant morphological changes in the intestine. At the peak of the disease, leukocyte infiltration of the mucosa, reduction in goblet cells numbers, shortened and thickened small intestinal villi and decreased crypt depth in the colon were observed, all correlating with the severity of the disease. Ultrastructural analysis further revealed mitochondrial and microvilli damage in enterocytes and colonocytes, which was more pronounced in severely affected animals. These findings support the involvement of the “microbiota-gut-brain” axis in the development of autoimmune demyelinating CNS disorders. The observed association between intestinal morphological alterations, gut microbiota composition, and EAE severity highlights the potential of targeting intestinal inflammation and barrier function for therapeutic strategies in multiple sclerosis

IntroductionBreast cancer is the most prevalent malignancy among women worldwide. A significant portion of patients possess homologous recombination deficiency (HRD), often caused by BRCA1/2 mutations, which may sensitize tumors to PARP inhibitors and platinum-based chemotherapy through synthetic lethality. Since mutations in BRCA genes have been previously suggested in association with impaired biology of telomeres, in the present study we investigated leukocyte telomere length (LTL) to evaluate its potential utility as a biomarker for BRCA1 mutations and HRD.MethodologyLTL was measured using multiplex monochrome real-time qPCR in four groups: breast cancer patients with pathogenic hereditary BRCA1 mutations (n = 99), age-matched non-cancerous controls carrying the same BRCA1 mutations (n = 99), breast cancer patients with wild-type BRCA1 (n = 105), and age-matched non-cancerous controls with wild-type BRCA1 (n = 107). BRCA1 mutations were tested by the DNA sequencing approach.ResultsA significant negative correlation between age and LTL was observed across all studied groups, except in breast cancer patients carrying pathogenic hereditary BRCA1 mutations. Interestingly, after adjusting for age, BRCA1 mutation carriers had shorter LTL compared to non-carriers, regardless of the presence of cancer (P = 0.024).ConclusionLTL shortening is associated with BRCA1 mutations, regardless of cancer status. Further validation studies are needed.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12672-025-04007-8.

Abstract Bioregenerative life support systems (BLSS) designed to produce food crops in future crewed missions to the Moon or Mars consider in-situ resource utilisation (ISRU). Lunar regolith is, therefore, in focus for future technologies of farming on lunar bases. We tested germination and early growth of broccoli plants ( Brassica oleracea var. botrytis italica ) in Murashige-Skoog liquid medium with addition of leachate from a lunar regolith simulant. As the additions to growth, differently diluted water and acidic leachates were used. Physiological status of the germinating plants was evaluated by chlorophyll fluorescence parameters related to plant vitality (relative fluorescence decline – Rfd) and photosynthetic performance of photosystem II (1) potential (F V /F M ) and (2) effective quantum yield of PSII (Φ PSII ), photochemical quenching referring to number of open PSII reaction centres. Both water and acidic leachates inhibited plant growth, however, the extent of growth limitation was dilution-dependent. Full inhibition of germination was apparent when undiluted acidic leachate was added. However, 50% dilution (and higher) resulted in seed germination and the early growth. No negative effects of the water dilutions on F V /F M as well as Φ PSII , were apparent in 15 days old plants, their cotyledonary and the first primary leaves, in particular. Similarly, qP and Rfd showed no sign of either water or acidic leachate addition effect. Although photosystem II-related parameters exhibited no negative effect of the leachates addition, a growth of plants was found dilution-dependent: higher degree of dilution resulted in a more pronounced reduction in plant projection area. In spite of the growth rate reduction (compared to untreated control), properly diluted water and acidic leachates from lunar regolith and/or its simulants might be used in follow up studies focused on plant species prospective for future cultivation in Moon-based stations with temporary or permanent crew.