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Aim. This study aimed to examine the effect of Larifan on metabolic characteristics of human blood monocytes and granulocytes in vitro. Methods. Four healthy adult men aged 21-26 years were recruited to participate in the study as blood donors. The metabolic profile of human blood monocytes and granulocytes was evaluated by phagocytic activity, reactive oxygen species production, nitric oxide generation, and arginase activity. Phagocytosis of FITC-labeled inactivated Staphylococcus aureus and reactive oxygen species generation were estimated by flow cytometry. Arginase activity was assessed in cell lysates, and nitric oxide generation in supernatants was examined using the Griess reaction. Results. Phagocytic index and reactive oxygen species generation were found to be lower in both human blood monocytes and granulocytes treated with Larifan. The drug caused a dose-dependent increase in nitric oxide production, as well as a decrease in the arginase activity of blood monocytes. Conclusions. Our results indicate the ability of Larifan to reinforce the antiviral properties of resting phagocytes along with containment of oxidative stress development.

Members of Ralstonia solanacearum species complex (RSSC) are causal agents of vascular wilt disease in more than 450 crop species, including solanaceous plants such as potatoes, tomatoes, bell pepper, eggplant, etc. These phytopathogens cause serious yield loss mostly in solanaceous crops which are grown in tropical, subtropical, and temperate regions of the world. Yield losses comprise 80%–100% in potato, up to 91% for tomato, 10%–30% in tobacco, 33%–90% in banana, and reduce crop productivity and yield. PCR-methods are specific, sensitive and cost-effective approaches for the detection and identification of RSSC members. The objective of this study was to compare specificity of routinely used primer mix for PCR RSSC detection with the newly developed pairs of species-specific primers for ease of use diagnostics in a laboratory. Materials and Methods. The conserved genomic regions of the 16S rRNA sequences of R. solanacearum, R. pseudosolanacearum, and R. syzygii were selected for the design of primers for this study. Newly created primer species specificity was tested in PCR using the DNA of the two targets and 13 non-target strains of bacteria. Results. Three pairs of newly created primers Rs-28(F)/Rs-193(R), Rs-28(F)/OLI-160(R), Rs28(F)/OLI248(R) produced single specific fragments for bacterial strains of Ralstonia solanacearum: 166 bp, 132 bp, and 220 bp. products respectively. No PCR products were obtained during amplification with the negative control or non-target DNA templates from other bacterial species. Conclusion. Designed primers can be used for the development of PCR system for the qualitative and quantitative detection of RSSC members.

Hematological and immunological markers of systemic inflammation were studied in 6-hydroxydopamine (6-OHDA)- and lipopolysaccharide (LPS)-induced models of Parkinson’s disease (PD). Experiments were carried out on adult male Wistar rats: 1 – intact animals; 2 – sham-operated animals and 3 – 6-OHDA- and LPS-lesioned animals. PD development was confirmed by the results of behavioral testing (apomorphine test, open field test) and immunohistochemical detection of the loss of dopaminergic neurons. Hematological indices (complete blood count and differential leukocyte count (DLC)) were examined using hematological analyser. Immunological indices included phenotypic (CD206 and CD80/86) and metabolic (oxidative metabolism and phagocytic activity) characteristics of circulating monocytes (Mo) and granulocytes (Gr), which were determined by flow cytometry, as well as plasma levels of C-reactive protein, which were determined by ELISA. LPS-induced PD was associated with neutrophilia, 1.9 times increased neutrophil-to-lymphocyte ratio, 3 times increased platelet-to-lymphocyte ratio, and 3 times increased systemic immune inflammation index as compared to intact animals. Functional profile of circulating phagocytes from LPS-lesioned animals was characterized by the pro-inflammtory metabolic shift, as was indicated by 5 times increased oxidative metabolism indices and up-regulated CD80/86 expression along with decreased phagocytic activity and CD206 expression. 6-OHDA-lesioned rats demonstrated decreased DLC indices as compared to intact and sham-operated rats. Functional profile of circulating phagocytes in this model was characterized by anti-inflammatory shift. The results obtained from this study demonstrated that stereotaxic LPS-induced PD is appropriate rodent model for the study of systemic inflammation which is inherent for the disease pathophysiology.

Aim. This study aimed to investigate the circadian rhythm of the murine peritoneal macrophage (PM) metabolic profile. Methods. The metabolic profile of PM was characterized by phagocytic activity, reactive oxygen species (ROS) generation, and by the expression of phenotypic markers, associated with a pro- and anti-inflammatory metabolic shift. Phagocytosis of FITC-labeled inactivated Staphylococcus aureus, ROS generation, CD80, CD86, and CD206 expression were estimated by flow cytometry at a regular 4h interval over the daily light-dark cycle. Results. The phagocytic index and percentage of ROS-producing PM were found to be lower in the resting phase (ZT4) as compared to the active phase. In contrast, the level of CD86 expression was the highest in the inactive phase (ZT8). There was also a statistically significant peak in the proportion of ROS-producing PM, as well as in the level of ROS production per cell at the time of awakening (ZT12). As opposed to ROS generation, ZT12 was characterized by the lowest level of cell-surface CD206 expression. Conclusions. Our results indicate that there is a circadian rhythm in functional polarization of murine PM with an anti-inflammatory activation state in the resting phase in comparison to the active phase.

Cancer metastasis and recurrence are the leading causes of cancer-related death. Tumor cells which leave the primary or secondary tumors and shed into the bloodstream are called circulating tumor cells (CTC). These cells are the key drivers of cancer dissemination to surrounding tissues and to distant organs. The use of CTC in clinical practice necessitates the deep insight into their biology, as well as into their role in cancer evasion of immune surveillance, tumor resistance to chemo- radio- and immunotherapies and metastatic dormancy. Aim. The purpose of the work was to review the current knowledge on the CTC biology, as well as the prospects for their use for the diagnosis and targeted treatment of metastatic disease. Methods. The work proposed the integrative literature review using MEDLINE, Biological Abstracts and EMBASE databases. Results. This review summarizes and discusses historical milestones and current data concerning СTС biology, the main stages of their life cycle, their role in metastatic cascade, clinical prospects for their use as markers for the diagnosis and prognostication of the disease course, as well as targets for cancer treatment. Conclusions. Significant progress in the area of CTC biology and their use in cancer theranostics convincingly proved the attractiveness of these cells as targets for cancer prognosis and therapy. The effective use of liquid biopsy with quantitative and phenotypic characteristics of CTCs is impeded by the imperfection of the methodology for taking biological material and by the lack of reliable markers for assessing the metastatic potential of CTCs of various origins. The variety of mechanisms of tumor cells migration and invasion requires the development of complex therapeutic approaches for anti-metastatic therapy targeting CTCs. Efforts to address these key issues could help developing new and effective cancer treatment strategies.

Deep insight into compositional and functional features of endophytic bacterial communities residing in wheat grains opens the way to the use of their plant growth promoting and biocontrol abilities in agricultural biotechnology. The aim of this work was to compare grain-residing endophytes from winter wheat varieties with different sensitivity to Pseudomonas syringae pv. atrofaciens (McCulloch) and to examine their plant-beneficial traits and antagonistic effects. Grain-residing bacteria were isolated from surface-sterilized grains of three wheat varieties sown in Ukraine following a culture-dependent protocol, and were screened for their plant growth promotion (PGP) and antagonistic properties. Bacterial morphotypes were represented by gram-negative rods, endospore-forming bacilli and gram-positive cocci. Different resistance to phytopathogenic pseudomonads was associated with distinctive quantitative and functional features of grain-residing endophytic communities. High resistance to P. syringae was coupled with the prevalence of gram-negative rods in the endophytic community, the highest proportion of endophytic bacteria possessing three PGP activities (phosphate solubilization, nitrogen fixation and production of indolic compounds) simultaneously, and with the most potent antagonistic activity of grain-residing endospore-forming bacilli. In total, five grain-residing isolates, which were obtained from three wheat varieties (two isolates from varieties with medium and high resistance and one – from a low-resistant variety), demonstrated ability to restrain P. syringae pv. atrofaciens (McCulloch) growth. Two isolates (P6 and P10) which were obtained from the high-resistant wheat variety Podolyanka and were assigned to Paenibacillus and Brevibacillus genera according to their biochemical profiling and MS-DS identification, showed the most potent antagonistic effects as indicated by maximum inhibition zone in agar well diffusion assay. These results shed light on the association of the features of grain-residing endophytic bacteria with wheat resistance to phytopathogenic pseudomonads. Isolates from the high-resistant wheat variety can be recommended for grain dressing as plant growth promoting and biocontrol agents for P. syringae pv. atrofaciens (McCulloch).

The aim of the work was to explore fatty acid composition of purslane seed water extract and its effect on the metabolic profile of murine peritoneal macrophages. Fatty acid composition was evaluated by gas chromatography–mass spectrometry. Collection of murine macrophages from the peritoneal cavity was done without preliminary sensitization. Reactive oxygen species generation was assayed by flow cytometry and nitroblue tetrazolium test. Phagocytic activity was evaluated by flow cytometry. Nitric oxide production was analyzed in cell supernatants by Griess reaction. Arginase activity was measured in cell lysates by standard colorimetric assay. Reactive oxygen species and nitric oxide production were significantly lower in murine macrophages simultaneously treated with purslane seed water extract and lipopolysaccharide in comparison to macrophages treated with lipopolysaccharide only. Also, the studied extract caused statistically significant increase in arginase activity of unsensitized peritoneal macrophages. That is consistent with the fatty acid content of this extract, since it contained comparatively higher proportion of unsaturated fatty acids exhibiting anti-inflammatory properties, than saturated fatty acids known for their pro-inflammatory effects.

Herbal preparations are widely used in the complementary treatment of inflammatory diseases including hepatobiliary disorders, among which chronic cholecystitis is one of the most common. This study was aimed to investigate the effect of the water extract from polyherbal composition consisting of eight medicinal plants (Helichrysum arenarium, Mentha piperita, Calendula officinalis, Taraxacum officinale, Polygonum aviculare, Matricaria chamomilla, Portulaca oleracea, Hypericum perforatum) on biochemical and haematologic indices as well as on immune reactivity parameters in patients with chronic cholecystitis. It was found that consumption of polyherbal tea during 45 days was followed by normalization of liver biochemical indices (serum level of cholesterol, alanine aminotransferase and aspartate aminotransferase activity, total and unconjugated bilirubin levels and diminution of hematological (leukocytosis, increased erythrocyte sedimentation rate and neutrophil-to-lymphocyte ratio) and immunological (increased serum level of pro-inflammatory cytokines) signs of systemic inflammation in patients with hepatobiliary disorder. The results of the research showed that the studied polygerbal composition can be recommended as a component of the complementary therapy for patients with chronic cholecystitis.

Hepatobiliary system diseases represent an important medical and social problem due to increasing morbidity rates worldwide. Liver and biliary diseases are characterized by complex pathophysiology as well as by multi- and comorbidity. The treatment of such diseases necessitates multitarget drug development. The effectiveness of current drugs in the treatment of hepatobiliary disorders remains low and the incidence of side-effects are profound. This actualizes the search and development of highly effective hepatoprotectors with a low incidence of side effects. Medicinal plants potentially constitute a sourse of such preparations. The review summarizes the data concerning mechanisms of hepatoprotective and immunomodulatory effects of medicinal plants and their phytoconstituents. The prospects for the development and use of herbal remedies in the treatment of hepatobiliary diseases are outlined.

The aim of the work was to explore phytochemical characteristics of water extract from polyherbal composition based on P. oleracea and it’s effect on oxidative metabolism of murine peritoneal macrophages. The qualitative phytochemical analysis was conducted by colorimetric method. Quantitative analysis of phenols was performed in the test with gallic acid as a standard. Murine peritoneal macrophages were isolated without previous sensitization. Leukotoxicity of the water extract from polyherbal composition leukotoxicity was evaluated in MTT test. Reactive oxygen species generation was assayed by the nitroblue tetrazolium reduction method. Phytochemical analysis revealed the presence of water-soluble and insoluble phenols, tannins, saponins, flavonoids, cardiac glycosides and coumarins in the studied plant mixture. The water extract from polyherbal composition used in a range of concentration 1–1000 μg/ml (lyophilisate in distilled H2O) didn’t exhibit any toxic effects on murine peritoneal macrophages. Water extract from polyherbal composition caused statistically significant dose-dependent increase in oxidative metabolism of murine peritoneal suggest modulatory effect of studied water extract from polyherbal composition on innate immunity cells.

Glioma-associated microglia/macrophages (GAM) represent an attractive therapeutic target for the development of the alternative methodology in the treatment of gliomas. This study was aimed to investigate the effect of intranasally administered TLR3 agonist Larifan on microglial cell metabolic profile in rats with C6 glioma. Our results demonstrate progressive generation microglial cell population with immunosuppressive and pro-inflammatory properties in C6 glioma-bearing brain. Intranasally delivered TLR3 agonist is capable to abrogate the creation of this pro-tumoral immune infiltrates, probably, through the effect on myeloid-derived suppressor cells, and can be considered as a promising agent for glioma therapy aimed the GAM re-education.

The aim of the work was to investigate the effect of the intracranial catheter placement on the metabolic profile of rat microglia. Microglial cells were isolated by the centrifugation in Percoll gradient. Oxidative metabolism and phagocytic activity were investigated by flow cytometry. Arginase activity was examined by colorimetric method. Nitrite level was assayed in Griess reaction. It was found that intracranial catheter placement caused down-regulation of nitrite synthesis by 3 times, augmentation of the reactive oxygen species generation by 1.5 times, and slightly decreased microglia phagocytic activity. Thus, intracranial catheter placement causes long term anti-inflammatory shift of microglia metabolism in rats.

Bacteriophage-derived dsRNA (bp-dsRNA), also known as Larifan, is a poly-functional and wide-spectrum antiviral medication with potent interferonogenic activity. In the lungs of golden Syrian hamsters infected with SARS-CoV-2, Larifan substantially reduces viral load and decreases infection-induced pathological lesion severity. Alveolar macrophages (AM) are key sentinel cells in the lung, which play an important role in antiviral innate immune responses and, at the same time, can trigger infection-associated hyper-inflammatory response. This study revealed that treatment with bp-dsRNA (Larifan) in vitro modulates the functional profile of AM from intact Balb/c and C57Bl/6 mice. The pattern of the drug response depends on the animal strain, age and sex. AM from Balb/c mice generated a weaker response to the preparation as compared to cells from C57Bl/6 mice. Most emphatic responses to the treatment with bf-dsRNA (Larifan) were registered in AM from old males of both BALB/c and C57BL/6 strains with the strongest in the latter. AM from old C57BL/6 females were less likely to be influenced by the preparation. In most cases, exposure to bf-dsRNA (Larifan) increased AM phagocytic activity and was more often accompanied by the stimulation of intracellular reactive oxygen species generation, than by its decrease. In most animal groups, treatment with bf-dsRNA (Larifan) did not affect significantly CD206 expression and down-regulated CD80 expression in AM. Taken together, our findings suggest that bf-dsRNA (Larifan) not so much stimulates the bivalent phenotype of AM, as restrains their hyper-inflammatory responses through the control of antigen-presentation while preserving functional signatures typical of patrolling tissue-resident macrophages., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Alzheimer disease (AD) is the most frequent cause of dementia, and the most common neurodegenerative disease, which is characterized by memory impairment, neuronal death, and synaptic loss in the hippocampus. Sporadic late-onset AD, which accounts for over 95 % of disease cases, is a multifactorial pathology with complex etiology and pathogenesis. Nowadays, neuroinflammation is considered the third most important component of AD pathogenesis in addition to amyloid peptide generation and deposition. Neuroinflammation is associated with the impairment of blood-brain barrier and leakage of inflammatory mediators into the periphery with developing systemic inflammatory responses. Systemic inflammation is currently considered one of the therapeutic targets for AD treatment, that necessitates in-depth study of this phenomenon in appropriate non-transgenic animal models. This study was aimed to explore systemic inflammatory manifestations in rats with Aβ 1-40 -induced AD. The impairment of spatial memory and cognitive flexibility in Aβ 1-40 -lesioned rats was accompanied by pronounced systemic inflammation, which was confirmed by commonly accepted biomarkers: increased hematological indices of systemic inflammation (NLR, dNLR, LMR, PLR and SII), signs of anemia of inflammation or chronic diseases, and pro-inflammatory polarized activation of circulating phagocytes. In addition, markers of systemic inflammation strongly correlated with disorders of remote cognitive flexibility in Aβ 1-40 -lesioned rats. These results indicate, that Aβ 1-40 -induced AD model permits the investigation of specific element of the disease - systemic inflammation in addition to well reproduced neuroinflammation and impairment of spatial memory and cognitive flexibility. It increases translational value of this well-known model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting more than 1% of aged people. PD, which was previously identified as movement disorder, now is recognized as a multi-factorial systemic disease with important pathogenetic and pathophysiological role of inflammation. Reproducing local and systemic inflammation, which is inherent in PD, in animal models is essential for maximizing the translation of their potential to the clinic, as well as for developing putative anti-inflammatory neuroprotective agents. This study was aimed to compare activation patterns of microglia/macrophage population and systemic inflammation indices in rats with 6-Hydroxydopamine (6-OHDA)- and Lipopolysaccharide (LPS)-induced PD. Metabolic and phenotypic characteristics of microglia/macrophage population were examined by flow cytometry, systemic inflammatory markers were calculated using hematological parameters in 6-OHDA- and LPS-lesioned Wistar rats 29 days after the surgery. Microglia/macrophages from rats in both models exhibited pro-inflammatory metabolic shift. Nevertheless, in LPS-lesioned animals, highly increased proportion of CD80/86+ cells in microglia/macrophage population was registered alongside increased values of systemic inflammatory indices: neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio and systemic immune inflammation index (SII). There was significant positive correlation between the count of CD80/86+ cells and systemic inflammatory indices in these animals. Microglia/macrophages from 6-OHDA-lesioned rats were characterized by the increased fraction of CD206+ cells alongside decreased proportion of CD80/86+ cells. No signs of systemic inflammation were observed. Negative correlation between quantitation characteristics of CD80/86+ cells and values of systemic inflammatory indices was registered. Collectively, our data show that LPS-PD model unlike 6-OHDA-PD replicates crosstalk between local and systemic inflammatory responses, which is inherent in PD pathogenesis and pathophysiology., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Epidemic scope which obesity has reached in many countries necessitates shifting the emphasis in medicine from traditional reaction to individualized and personalized prevention. Numerous trials convincingly prove sexual dimorphism of obesity in morbidity, pathophysiology, comorbidity, outcomes and prophylaxis efficacy. Obesity is characterized by chronic systemic low-grade inflammation that creates the preconditions for the emergence of numerous comorbidities. Leading role in the initiation, propagation and resolution of inflammation belongs to tissue resident and circulating phagocytes. The outcome of inflammation largely depends on phagocyte functional polarization, which in turn is governed by environmental stimuli. Gut microbiota (GM), whose disturbances are one of the key pathogenetic features in obesity, substantially affect phagocyte functions and can either aggravate or calm obesity-associated inflammation. Probiotics possess promising physiological functions, including microbiota-restoring and anti-inflammatory traits, that may possibly help prevent obesity. However, sex-specific effects of probiotic supplementation for targeted obesity prevention remain unknown. The aim of the current study was aimed to compare the effect of multi-probiotic preparation used in prophylactic regimen on the adiposity, profile of culturable GM and its short-chain fatty acids as well as on functional profile of phagocytes from different locations in male and female rats with monosodium glutamate (MSG)-induced obesity. Obesity was induced by neonatal MSG injections in male and female rats, who were given the multi-species probiotic during juvenile and adult developmental stages. Culturable fecal and mucosa-associated microbiota of the intestine were examined using selective diagnostic media. Short-chain fatty acid profile in fecal samples was determined by GC-MS. Phagocyte functional profile was evaluated using flow cytometry and colorimetric methods. Probiotic supplementation after the administration of MSG prevented weight gain and fat accumulation, inflammatory phagocyte activation and alterations in GM in female rats. In male MSG-injected rats, probiotic supplementation restricted but did not prevent weight gain and fat deposition, alleviated but did not prevent systemic inflammation, prevented the alterations in GM, but with residual imbalance in the ratio of obligate anaerobic to facultative anaerobic bacteria. Our findings emphasize the necessity of sex-centered approaches to the prophylactic use of probiotics in obesity in the context of predictive preventive and personalized medicine., Competing Interests: Iryna Akulenko (PhD student) received research grant from Scientific and Production Company “O.D. Prolisok”., (© 2023 The Authors.)

Objectives: A polyherbal formulation with hepatoprotective and choleretic properties combining pharmacological potential of eight medicinal plants was developed in Nargiz Medical center (Republic of Azerbaijan) for the use as herbal tea. To explore the effect of polyherbal composition on the metabolism of LPS-stimulated macrophages in vitro ., Methods: The qualitative and quantitative phytochemical analysis was conducted using specific color reactions and gas chromatography-mass spectrometry (GC-MS). Nitric oxide (NO) assay was determined using the Griess reaction. Reactive oxygen species (ROS) generation was measured using ROS-sensitive fluorescence indicator, H2DCFDA, by flow cytometry. Arginase activity was examined by colorimetric method., Results: The studied polyherbal formulation exerted anti-inflammatory activity in LPS-stimulated macrophages which was evidenced by dose-dependent decrease of ROS generation and by shift of arginine metabolism to the increase of arginase activity and decrease of NO release., Conclusions: Our findings suggest that the herbal tea reduces macrophage inflammatory activity, that provide an important rationale to utilize it for the attenuation of chronic inflammation typical of hepatobiliary disorders., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Timing of invasive intervention such as operative pancreatic debridement (OPD) in patients with acute necrotizing pancreatitis (ANP) is linked to the degree of encapsulation in necrotic collections and controlled inflammation. Additional markers of these processes might assist decision-making on the timing of surgical intervention. In our opinion, it is logical to search for such markers among routine laboratory parameters traditionally used in ANP patients, considering simplicity and cost-efficacy of routine laboratory methodologies., Aim: To evaluate laboratory variables in ANP patients in the preoperative period for the purpose of their use in the timing of surgery., Methods: A retrospective analysis of routine laboratory parameters in 53 ANP patients undergoing OPD between 2017 and 2020 was performed. Dynamic changes of routine hematological and biochemical indices were examined in the preoperative period. Patients were divided into survivors and non-survivors. Survivors were divided into subgroups with short and long post-surgery length of stay (LOS) in hospital. Correlation analysis was used to evaluate association of laboratory variables with LOS. Logistic regression was used to assess risk factors for patient mortality., Results: Seven patients (15%) with severe acute pancreatitis (SAP) and 46 patients (85%) with moderately SAP (MSAP) were included in the study. Median age of participants was 43.2 years; 33 (62.3%) were male. Pancreatitis etiology included biliary (15%), alcohol (80%), and idiopathic/other (5%). Median time from diagnosis to OPD was ≥ 4 wk. Median postoperative LOS was at the average of 53 d. Mortality was 19%. Progressive increase of platelet count in preoperative period was associated with shortened LOS. Increased aspartate aminotransferase and direct bilirubin (DB) levels the day before the OPD along with weak progressive decrease of DB in preoperative period were reliable predictors for ANP patient mortality., Conclusion: Multifactorial analysis of dynamic changes of routine laboratory variables can be useful for a person-tailored timing of surgical intervention in ANP patients., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

The elastic and viscous properties of lyotropic chromonic liquid crystals have a very sharp, often exponential temperature dependence. Self-propelled bacteria swimming in this viscoelastic medium induce director deformations which can strongly influence their velocity, and we study the temperature behavior of their motility in the whole range of the nematic phase. We observe experimentally that, with increasing temperature, while the viscosity drops exponentially and the frequency of the flagellum rotation grows linearly, the swimmers' speed first conventionally increases but then, above some crossover temperature, slows down and at the same time bacteria-induced director distortions become visible. It is shown that the physics behind this temperature-driven effect is in a sharp rise in the ability of the bacterium's flagellum to induce director deformations. As temperature increases, the splay and bend elastic constants sharply decrease and the anchoring extrapolation length of the flagellum surface gets shorter and shorter. At the crossover temperature the resulting effective anchoring effect dominates the fast dropping viscosity and the distortion strengthens. As a result, a fraction of the torque the flagellum applies for the propulsion is spent for the elastic degrees of freedom, which results in a bacterium slowdown. To find the director distortions, the flagellum is presented as a collection of anchoring-induced elastic monopoles, and the bacterium velocity is found from the balance of the energy spent for the propulsion and the viscous drag and nematodynamic dissipation.

Background : C 60 fullerenes and their derivatives are actively investigated for the use in neuroscience. Applications of these nanoscale materials require the examination of their interaction with different neural cells, especially with microglia, because these cells, like other tissue resident phagocytes, are the earliest and most sensitive responders to nanoparticles. The aim of this study was to investigate the effect of C 60 fullerene and its nanocomplex with doxorubicin (Dox) on the metabolic profile of brain-resident phagocytes-microglia-in vitro. Methods : Resting microglial cells from adult male Wistar rats were used in experiments. Potential C 60 fullerene targets in microglial cells were studied by computer simulation. Microglia oxidative metabolism and phagocytic activity were examined by flow cytometry. Griess reaction and arginase activity colorimetric assay were used to explore arginine metabolism. Results : C 60 fullerene when used alone did not influence microglia oxidative metabolism and phagocytic activity but shifted arginine metabolism toward the decrease of NO generation. Complexation of C 60 fullerene with Dox (C 60 -Dox) potentiated the ability of the latter to stimulate NO generation. Conclusion : The capability of C 60 fullerenes used alone to cause anti-inflammatory shift of microglia arginine metabolism makes them a promising agent for the correction of neuroinflammatory processes involved in neurodegeneration. The potentiating action of C 60 fullerene on the immunomodulatory effect of Dox allows us to consider the C 60 molecule as an attractive vehicle for this antitumor agent.

Purpose: Tumor cell resistance to platinum-based chemotherapeutic agents is one of the major hurdles to successful cancer treatment with these drugs, and is associated with alterations in tumor cell immune evasion and immunomodulatory properties. Immunocyte targeting is considered as a relevant approach to fight drug-resistant cancer. In this study, immunological hallmarks of cis-DDP-resistant Lewis lung carcinoma cells (LLC/R9) were investigated., Methods: Immunological features of LLC/R9 cells cultured in vitro in normoxic and hypoxic conditions as well as of those that were grown in vivo were examined. The expression of immunologically relevant genes was evaluated by RT-PCR. Tumor cell susceptibility to the macrophage contact tumoricidal activity and NK-mediated cytolysis was investigated in MTT test. TNF-α-mediated tumor cell apoptosis as well as macrophage phagocytosis, oxidative metabolism, and CD206 expression after the treatment with conditioned media from normoxic and hypoxic tumor cells were studied by flow cytometry. Flow cytometry was also used to characterize dendritic cell maturity., Results: When growing in vitro, LLC/R9 were characterized by slightly increased immunosuppressive cytokine gene expression. Transition to in vivo growth was associated with the enhancement of transcription of these genes in tumor cells. LLC/R9 cells had lowered sensitivity to contact-dependent macrophage-mediated cytotoxicity and to the TNFα-mediated apoptosis in vitro. Conditioned media from hypoxic LLC/R9 cells stimulated reactive oxygen species generation and CD206 expression in non-sensitized macrophages. Acquisition of drug resistance by LLC/R9 cells was associated with their increased sensitivity to NK-cell-mediated cytolysis. Meanwhile, the treatment of LLCR/9-bearing animals with generated ex vivo and loaded with LLC/R9 cell-lysate dendritic cells (DCs) resulted in profoundly enhanced tumor metastasizing., Conclusion: Decreased sensitivity to macrophage cytolysis, polarizing effect on DCs maturation along with increased susceptibility to NK-cell cytotoxic action promote extensive local growth of chemoresistant LLC/R9 tumors in vivo, but hamper their metastasizing.

Green fluorescent protein is widely used in biological studies including parabiosis models for visualization of cellular structures and cells. However, the growing number of the data is available regarding immunogenicity of this protein, which can interfere with its use in in vivo experiments. In this study, we attempted to induce neonatal immunological tolerance to GFP-labeled karyocytes by intraperitoneal injections of B6.GFP mouse splenocytes to newborn C57/B6 mice. GFP + skin graft integrity was evaluated under UV light at 6weeks after skin grafting. GFP + skin transplants survived up to 6weeks after grafting in all animals that undergone neonatal tolerance induction, whereas all skin grafts were rejected in control naïve mice within first two weeks. Thus, current protocol is suitable for induction of immune tolerance against GFP-labeled karyocytes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The self-organization of C 60 fullerene and cisplatin in aqueous solution was investigated using the computer simulation, dynamic light scattering and atomic force microscopy techniques. The results evidence the complexation between the two compounds. The genotoxicity of С 60 fullerene, Cis and their complex was evaluated in vitro with the comet assay using human resting lymphocytes and lymphocytes after blast transformation. The cytotoxicity of the mentioned compounds was estimated by Annexin V/PI double staining followed by flow cytometry. The results clearly demonstrate that water-soluble C 60 fullerene nanoparticles (0.1 mg/mL) do not induce DNA strand breaks in normal and transformed cells. C 60 fullerene in the mixture with Cis does not influence genotoxic Cis activity in vitro, affects the cell-death mode in treated resting human lymphocytes and reduces the fraction of necrotic cells.

Background: NSC-631570 (ukrain) is a semisynthetic derivative of the Chelidonium majus alcaloids and the alkylans thiotepa. It exerts a selective cytotoxic effect on tumor cells in vitro and in vivo and shows the ability to modulate immunocyte functions. Purpose. The aim of our work was to carry out a comparative investigation of the effects of NSC-631570 alone or in combination with pathogen-associated molecules (PAM) on the growth of low- and high-metastasizing melanoma B16 in mice., Methods: NSC-631570 was administered intravenously and PAM intramuscularly to tumor-bearing mice seven times every third day, starting from the second day after the transplantation of tumor cells. The effect of monotherapy and combined therapy on tumor growth was evaluated by the indices of tumor growth inhibition in experimental animals. Cell cycle distribution of cancer cells was determined by flow cytometry. TAP1 and TAP2 expression was evaluated by RT-PCR. The metabolic activity of phagocytes was determined by NBT-test, phagocytosis was tested by flow cytometry, and arginase activity was estimated by colorimetric determination of urea., Results: Combined therapy and monotherapy with NSC-631570 resulted in significant inhibition of tumor growth in melanoma-bearing mice. Monotherapy with Ukrain was more effective in mice with high-metastasizing tumors. The therapeutic efficacy of NSC-631570 used in combination with PAM was more expressed in mice with low-metastasizing melanoma., Conclusion: The effectiveness of monotherapy and combined therapy with NSC-631570 in the treatment of melanoma B16 depends on the biological properties of the tumor and the immune state of the organism.