Cytokine Profiling of Plasma and Atherosclerotic Plaques in Patients Undergoing Carotid Endarterectomy.

Atherosclerotic plaques are sites of chronic inflammation with diverse cell contents and complex immune signaling. Plaque progression and destabilization are driven by the infiltration of immune cells and the cytokines that mediate their interactions. Here, we attempted to compare the systemic cytokine profiles in the blood plasma of patients with atherosclerosis and the local cytokine production, using ex vivo plaque explants from the same patients. The developed method of 41-plex xMAP data normalization allowed us to differentiate twenty-two cytokines produced by the plaque that were not readily detectable in free circulation and six cytokines elevated in blood plasma that may have other sources than atherosclerotic plaque. To verify the xMAP data on the putative atherogenesis-driving chemokines MCP-1 (CCL2), MIP-1α (CCL3), MIP-1ß (CCL4), RANTES (CCL5), and fractalkine (CX3CL1), qPCR was performed. The MIP1A (CCL3), MIP1B (CCL4), FKN (CX3CL1), and MCP1 (CCL2) genes were expressed at high levels in the plaques, whereas RANTES (CCL5) was almost absent. The expression patterns of the chemokines were restricted to the plaque cell types: the MCP1 (CCL2) gene was predominantly expressed in endothelial cells and monocytes/macrophages, MIP1A (CCL3) in monocytes/macrophages, and MIP1B (CCL4) in monocytes/macrophages and T cells. RANTES (CCL5) was restricted to T cells, while FKN (CX3CL1) was not differentially expressed. Taken together, our data indicate a plaque-specific cytokine production profile that may be a useful tool in atherosclerosis studies.

Inflammatory and Anti-Inflammatory Parameters in PCOS Patients Depending on Body Mass Index: A Case-Control Study.

BACKGROUND: it has been suggested that chronic low-grade inflammation plays an important role in the pathogenesis of polycystic ovary syndrome (PCOS). According to previous studies, it remains unclear which cytokines influence the development of this syndrome and whether their increase is associated with the presence of excess weight/obesity or is an independent factor. The aim of our research was to determine the parameters of chronic inflammation in women with PCOS in comparison with healthy women in the normal weight and the overweight subgroups. METHODS: This case-control study included 44 patients with PCOS (19 women with a body mass index (BMI) < 25 kg/m² and 25 women with a BMI ≥ 25 kg/m²) and 45 women without symptoms of PCOS (22 women with a BMI < 25 kg/m² and 23 women with a BMI ≥ 25 kg/m²). Thirty-two cytokines were analyzed in the plasma of the participants using Immunology multiplex assay HCYTA-60K-PX48 (Merck Life Science, LLC, Germany). RESULTS: Cytokines: interleukin-1 receptor antagonist (IL-1 RA), IL-2, IL-6, IL-17 E, IL-17 A, IL-18, and macrophage inflammatory protein-1 alpha (MIP-1 α) were increased in women with PCOS compared to controls, both in lean and overweight/obese subgroups (p < 0.05). Moreover, only lean women with PCOS had higher levels of IL-1 alpha, IL-4, IL-9, IL-12, IL-13, IL-15, tumor necrosis factor (TNF- α) alpha and beta, soluble CD40 and its ligand (SCD40L), fractalkine (FKN), monocyte-chemotactic protein 3 (MCP-3), and MIP-1 ß compared to the control group (p < 0.05). IL-22 was increased in the combined group of women with PCOS (lean and overweight/obese) compared to the control group (p = 0.012). CONCLUSION: Chronic low-grade inflammation is an independent factor affecting the occurrence of PCOS and does not depend on the presence of excess weight/obesity. For the first time, we obtained data on the increase in such inflammatory parameters as IL-9, MCP-3, and MIP-1α in women with PCOS.

Cancer Relevance of Circulating Antibodies Against LINE-1 Antigens in Humans.

Long interspersed nuclear element-1 (LINE-1 or L1), the most abundant family of autonomous retrotransposons occupying over 17% of human DNA, is epigenetically silenced in normal tissues by the mechanisms involving p53 but is frequently derepressed in cancer, suggesting that L1-encoded proteins may act as tumor-associated antigens recognized by the immune system. In this study, we established an immunoassay to detect circulating autoantibodies against L1 proteins in human blood. Using this assay in >2,800 individuals with or without cancer, we observed significantly higher IgG titers against L1-encoded ORF1p and ORF2p in patients with lung, pancreatic, ovarian, esophageal, and liver cancers than in healthy individuals. Remarkably, elevated levels of anti-ORF1p-reactive IgG were observed in patients with cancer with disease stages 1 and 2, indicating that the immune response to L1 antigens can occur in the early phases of carcinogenesis. We concluded that the antibody response against L1 antigens could contribute to the diagnosis and determination of immunoreactivity of tumors among cancer types that frequently escape early detection. SIGNIFICANCE: The discovery of autoantibodies against antigens encoded by L1 retrotransposons in patients with five poorly curable cancer types has potential implications for the detection of an ongoing carcinogenic process and tumor immunoreactivity.

Antimicrobial activity of phytofabricated silver nanoparticles using Carica papaya L. against Gram-negative bacteria.

Background and Aim: Antibiotic resistance, especially in Gram-negative bacteria, is a major public health risk affecting all industries requiring the use of antibiotics, including agriculture and animal breeding. This study aimed to use papaya extracts to synthesize silver nanoparticles (AgNPs) and evaluate their antimicrobial activity against various Gram-negative bacteria. Materials and Methods: Silver nanoparticles were synthesized from the aqueous extracts of papaya seed, root, and bark, with AgNO3 used as a reducing agent. The phytofabricated AgNPs were analyzed by ultraviolet-visible absorbance, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy, and photon cross-correlation spectroscopy (PCCS). The disc-diffusion method was used to perform antibacterial analysis, and the minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations were determined. We also investigated the antibiofilm activity of AgNPs and attempted to elucidate the potential mechanism of action on Escherichia coli ATCC 25922. Results: Phytofabrication of AgNPs was successful with papaya root (PR-AgNPs) and papaya seed (PS-AgNPs), but not with papaya bark. Silver nanoparticles using papaya root and PS-AgNPs were both cubic and showed maximum absorbances of 2.6 and 0.3 AUs at 411.6 and 416.8 nm wavelengths and average hydrodynamic diameters X50 of 59.46 ± 7.03 and 66.57 ± 8.89 nm, respectively. The Ag in both AgNPs was confirmed by X-ray fluorescence by a distinctive peak in the spectrum at the silver Kα line of 22.105 keV. Both AgNPs exhibited broad-spectrum antimicrobial and antibiofilm activity against all Gram-negative bacteria, and PR-AgNPs were slightly better than AgNPs-PS. The MIC ranged from 16 µg/mL-128 µg/mL and 16 µg/mL-64 µg/mL, respectively, for PS-AgNPs and PR-AgNPs. The elucidation of the mechanism of action revealed interference with E. coli ATCC 25922 growth kinetics and inhibition of H+-ATPase proton pumps. Conclusion: Papaya seed and root extracts were efficient reducing agents for the biogenic synthesis of AgNPs, with noteworthy antibacterial and antibiofilm activities. Future studies should be conducted to identify the phytochemicals and the mechanism involved in AgNPs synthesis.

Motility provides specific adhesion patterns and improves Listeria monocytogenes invasion into human HEp-2 cells.

Listeria monocytogenes is motile at 22°C and non-motile at 37°C. In contrast, expression of L. monocytogenes virulence factors is low at 22°C and up-regulated at 37°C. Here, we studied a character of L. monocytogenes near surface swimming (NSS) motility and its effects on adhesion patterns and invasion into epithelial cells. L. monocytogenes and its saprophytic counterpart L. innocua both grown at 22°C showed similar NSS characteristics including individual velocities, trajectory lengths, residence times, and an asymmetric distribution of velocity directions. Similar NSS patterns correlated with similar adhesion patterns. Motile bacteria, including both pathogenic and saprophytic species, showed a preference for adhering to the periphery of epithelial HEp-2 cells. In contrast, non-motile bacteria were evenly distributed across the cell surface, including areas over the nucleus. However, the uneven distribution of motile bacteria did not enhance the invasion into HEp-2 cells unless virulence factor production was up-regulated by the transient shift of the culture to 37°C. Motile L. monocytogenes grown overnight at 22°C and then shifted to 37°C for 2 h expressed invasion factors at the same level and invaded human cells up to five times more efficiently comparatively with non-motile bacteria grown overnight at 37°C. Taken together, obtained results demonstrated that (i) NSS motility and correspondent peripheral location over the cell surface did not depend on L. monocytogenes virulence traits; (ii) motility improved L. monocytogenes invasion into human HEp-2 cells within a few hours after the transition from the ambient temperature to the human body temperature.

Cilia impairment in bronchial epithelial cells detected in autopsy material of SARS-CoV-2-infected patient.

Recent studies indicate that cilia impairment, accompanied by the axonema loss and the basal body misorientation, is a common pathological feature of SARS-CoV-2-infected bronchial epithelial cells. However, these data were obtained using either cultured cells, or animal models, while in human postmortem material, cilia impairment has not been described yet. Here, we present direct observation of cilia impairment in SARS-CoV-2-infected bronchial epithelial cells using transmission electron microscopy of the autopsy material. We were able to observe only single infected cells with cilia impairment in one of twelve examined specimens, while the large number of desquamated bronchial epithelial cells with undisturbed ciliary layer was visible in the bronchial lumens. Thus, it seems that in the lungs of infected patients, the majority of bronchial cells do not die as a direct result of infection, which may explain the rarity of this finding in the autopsy material.

Elevated Levels of Serum Biomarkers Associated with Damage to the CNS Neurons and Endothelial Cells Are Linked with Changes in Brain Connectivity in Breast Cancer Patients with Vestibulo-Atactic Syndrome.

Vestibulo-atactic syndrome (VAS), which represents a combination of motor and vestibular disorders, can be manifested as a clinical complication of breast cancer treatment and has a significant impact on patients' quality of life. The identification of novel potential biomarkers that might help to predict the onset of VAS and its progression could improve the management of this group of patients. In the current study, the levels of intercellular cell adhesion molecule 1 (ICAM-1), platelet/endothelial cell adhesion molecule 1 (PECAM-1), NSE (neuron-specific enolase), and the antibodies recognizing NR-2 subunit of NMDA receptor (NR-2-ab) were measured in the blood serum of BC survivor patients with vestibulo-atactic syndrome (VAS) and associated with the brain connectome data obtained via functional magnetic resonance imaging (fMRI) studies. A total of 21 patients were registered in this open, single-center trial and compared to age-matched healthy female volunteers (control group) (n = 17). BC patients with VAS demonstrated higher serum levels of ICAM-1, PECAM-1, and NSE and a lower value of NR-2-ab, with values of 654.7 ± 184.8, 115.3 ± 37.03, 49.9 ± 103.9, and 0.5 ± 0.3 pg/mL, respectively, as compared to the healthy volunteers, with 230.2 ± 44.8, 62.8 ± 15.6, 15.5 ± 6.4, and 1.4 ± 0.7 pg/mL. According to the fMRI data (employing seed-to-voxel and ROI-to-ROI methods), in BC patients with VAS, significant changes were detected in the functional connectivity in the areas involved in the regulation of postural-tonic reflexes, the coordination of movements, and the regulation of balance. In conclusion, the detected elevated levels of serum biomarkers may reveal damage to the CNS neurons and endothelial cells that is, in turn, associated with the change in the brain connectivity in this group of patients.

Targeted Blood Plasma Proteomics and Hemostasis Assessment of Post COVID-19 Patients with Acute Myocardial Infarction.

The molecular mechanisms underlying cardiovascular complications after the SARS-CoV-2 infection remain unknown. The goal of our study was to analyze the features of blood coagulation, platelet aggregation, and plasma proteomics in COVID-19 convalescents with AMI. The study included 66 AMI patients and 58 healthy volunteers. The groups were divided according to the anti-N IgG levels (AMI post-COVID (n = 44), AMI control (n = 22), control post-COVID (n = 31), and control (n = 27)). All participants underwent rotational thromboelastometry, thrombodynamics, impedance aggregometry, and blood plasma proteomics analysis. Both AMI groups of patients demonstrated higher values of clot growth rates, thrombus size and density, as well as the elevated levels of components of the complement system, proteins modifying the state of endothelium, acute-phase and procoagulant proteins. In comparison with AMI control, AMI post-COVID patients demonstrated decreased levels of proteins connected to inflammation and hemostasis (lipopolysaccharide-binding protein, C4b-binding protein alpha-chain, plasma protease C1 inhibitor, fibrinogen beta-chain, vitamin K-dependent protein S), and altered correlations between inflammation and fibrinolysis. A new finding is that AMI post-COVID patients opposite the AMI control group, are characterized by a less noticeable growth of acute-phase proteins and hemostatic markers that could be explained by prolonged immune system alteration after COVID-19.

Neurotrophin-3 (NT-3) as a Potential Biomarker of the Peripheral Nervous System Damage Following Breast Cancer Treatment.

Damage to the peripheral nervous system (PNS) is a common complication of breast cancer (BC) treatment, with 60 to 80% of breast cancer survivors experiencing symptoms of PNS damage. In the current study, the levels of brain-derived neurotrophic factor (BDNF), galectin-3 (Gal-3), and neurotrophin-3 (NT-3) were measured in the blood serum of BC patients by ELISA as potential biomarkers that might indicate the PNS damage. Sixty-seven patients were enrolled in this multi-center trial and compared to the aged-matched healthy female volunteers (control group) (n = 25). Intergroup comparison of biomarker levels (i.e., Gal-3 and BDNF) did not show significant differences in any of the studied subgroups. However, intriguingly, NT-3 levels were significantly higher in BC patients as compared to healthy volunteers, constituting 14.85 [10.3; 18.0] and 5.74 [4.56; 13.7] pg/mL, respectively (p < 0.001). In conclusion, NT-3 might be employed as a potential biomarker in BC patients with clinical manifestations of PNS damage. However, further studies to validate its correlation to the degree of peripheral nervous system lesions are of high value.

Isotropic and Anisotropic Monolayer Structures in RF Discharge Plasma.

We present the results of an experimental and analytical study of the structural and dynamic properties of a monolayer consisting of dust grains in an electrostatic trap in an RF discharge plasma. The possibility of forming a monolayer with an isotropic distribution for interparticle distance and kinetic energy of particles in the structure has been experimentally shown. Isotropy has crucial importance for the study of various processes in such systems, including the kinetics of phase transitions, the formation of directed flows, wave propagation, and others.

Lung inflammation is associated with lipid deposition.

Lung inflammation, pneumonia, is an acute respiratory disease of varying etiology that has recently drawn much attention during the COVID-19 pandemic as lungs are among the main targets for SARS-CoV-2. Multiple other etiological agents are associated with pneumonias. Here, we describe a newly-recognized pathology, namely abnormal lipid depositions in the lungs of patients who died from COVID-19 as well as from non-COVID-19 pneumonias. Our analysis of both semi-thin and Sudan III-stained lung specimens revealed extracellular and intracellular lipid depositions irrespective of the pneumonia etiology. Most notably, lipid depositions were located within vessels adjacent to inflamed regions, where they apparently interfere with the blood flow. Structurally, the lipid droplets in the inflamed lung tissue were homogeneous and lacked outer membranes as assessed by electron microscopy. Morphometric analysis of lipid droplet deposition area allowed us to distinguish the non-pneumonia control lung specimens from the macroscopically intact area of the pneumonia lung and from the inflamed area of the pneumonia lung. Our measurements revealed a gradient of lipid deposition towards the inflamed region. The pattern of lipid distribution proved universal for all pneumonias. Finally, lipid metabolism in the lung tissue was assessed by the fatty acid analysis and by expression of genes involved in lipid turnover. Chromato-mass spectrometry revealed that unsaturated fatty acid content was elevated at inflammation sites compared to that in control non-inflamed lung tissue from the same individual. The expression of genes involved in lipid metabolism was altered in pneumonia, as shown by qPCR and in silico RNA-seq analysis. Thus, pneumonias of various etiologies are associated with specific lipid abnormalities; therefore, lipid metabolism can be considered to be a target for new therapeutic strategies.

Breast Cancer Treatment Decreases Serum Levels of TGF-ß1, VEGFR2, and TIMP-2 Compared to Healthy Volunteers: Significance for Therapeutic Outcomes?

Various complications from a breast cancer treatment, in the pathogenesis of which excessive tissue fibrosis plays a leading role, are a common pathology. In this study, the levels of TGF-ß1, VEGFR-2, and TIMP-2 were determined by the immuno-enzyme serum analysis for patients during the long-term period after breast cancer treatment as potential markers of fibrosis. The single-center study enrolled 92 participants, which were divided into two age-matched groups: (1) 67 patients following breast cancer treatment, and (2) 25 healthy female volunteers. The intergroup analysis demonstrated that the patients after breast cancer treatment showed a decrease in the serum levels of TGF-ß1 (U = 666, p < 0.001) and TIMP-2 (U = 637, p < 0.001) as compared to the group of healthy volunteers. The levels of VEGFR-2 in these groups were comparable (U = 1345, p = 0.082). It was also found that the type of treatment, the presence of lymphedema, shoulder joint contracture, and changes in lymphoscintigraphy did not affect the levels of TGF-ß1, VEGFR-2, and TIMP-2 within the group of patients after breast cancer treatment. These results may indicate that these biomarkers do not play a leading role in the maintenance and progression of fibrosis in the long-term period after breast cancer treatment. The reduced levels of TGF-ß1 and TIMP-2 may reflect endothelial dysfunction caused by the antitumor therapy.

CTLs From Patients With Atherosclerosis Show Elevated Adhesiveness and Distinct Integrin Expression Patterns on 2D Substrates.

Atherosclerosis is the major cause of cardiovascular disease that is characterized by plaque formation in the blood vessel wall. Atherosclerotic plaques represent sites of chronic inflammation with diverse cell content that is shifted toward the prevalence of cytotoxic T-lymphocytes (CTLs) upon plaque progression. The studies of CTL recruitment to atherosclerotic plaques require adequate in vitro models accounting for CTL interactions with chemokine-ligands and extracellular matrix fibers via surface chemokine receptors and integrins. Here we applied such a model by investigating CTL adhesion and migration on six types of coated surfaces. We assessed adhesion and motility metrics, the expression of chemokine receptors, and integrins in CTLs of patients with atherosclerosis and healthy donors. Using fibronectin, platelet-poor plasma from patients with atherosclerosis, and conditioned medium from atherosclerotic plaques we revealed the role of substrate in CTL adhesiveness: fibronectin alone and fibronectin combined with platelet-poor plasma and conditioned medium elevated the CTL adhesiveness - in patients the elevation was significantly higher than in healthy donors (p = 0.02, mixed 2-way ANOVA model). This was in line with our finding that the expression levels of integrin-coding mRNAs were elevated in the presence of fibronectin (p < 0.05) and ITGB1, ITGA1, and ITGA4 were specifically upregulated in patients compared to healthy donors (p < 0.01). Our experimental model did not affect the expression levels of mRNAs CCR4, CCR5, and CX3CR1 coding the chemokine receptors that drive T-lymphocyte migration to plaques. Thus, we demonstrated the substrate-dependence of integrin expression and discriminated CTLs from patients and healthy donors by adhesion parameters and integrin expression levels.

Cytokine Storm Signature in Patients with Moderate and Severe COVID-19.

Hypercytokinemia, found in SARS-CoV-2 infection, contributes to multiple organ dysfunctions with acute respiratory distress syndrome, shock etc. The aim of this study was to describe cytokine storm signatures in patients with acute COVID-19 and to investigate their influence on severity of the infection. Plasma levels of 47 cytokines were investigated in 73 patients with moderate and severe COVID-19 (41 and 32, respectively) and 11 healthy donors (HD). The most elevated levels comparing patients and the HD were observed for seven pro-inflammatory cytokines (IL-6, IL-8, IL-15, IL-18, IL-27, IFNγ, TNFα), three chemokines (GROα, IP-10, MIG), two anti-inflammatory cytokines (IL-1RA, IL-10), and two growth factors (G-CSF, M-CSF). The patients with severe disease had significantly higher levels of FGF-2/FGF-basic, IL-1ß, and IL-7 compared to the HD. The two groups of patients differed from each other only based on the levels of EGF, eotaxin, and IL-12 p40. Pneumonia lung injury, characterized by computer tomography, positively correlated with levels of EGF, IP-10, MCP-3 levels and negatively with IL-12 p40. Pro-inflammatory factors including IL-6, TNFα, and IP-10 negatively correlated with the frequency of the circulating T-helper17-like cells (Th17-like) and follicular Th cells that are crucial to develop SARS-CoV-2-specific plasma cells and memory B cells. Obtained data on the cytokine levels illustrate their influence on progression and severity of COVID-19.

Comprehensive Cytokine Profiling of Patients with COVID-19 Receiving Tocilizumab Therapy.

Coronavirus disease 2019 (COVID-19) is characterized by immune activation in response to viral spread, in severe cases leading to the development of cytokine storm syndrome (CSS) and increased mortality. Despite its importance in prognosis, the pathophysiological mechanisms of CSS in COVID-19 remain to be defined. Towards this goal, we analyzed cytokine profiles and their interrelation in regard to anti-cytokine treatment with tocilizumab in 98 hospitalized patients with COVID-19. We performed a multiplex measurement of 41 circulating cytokines in the plasma of patients on admission and 3-5 days after, during the follow-up. Then we analyzed the patient groups separated in two ways: according to the clusterization of their blood cytokines and based on the administration of tocilizumab therapy. Patients with and without CSS formed distinct clusters according to their cytokine concentration changes. However, the tocilizumab therapy, administered based on the standard clinical and laboratory criteria, did not fully correspond to those clusters of CSS. Furthermore, among all cytokines, IL-6, IL-1RA, IL-10, and G-CSF demonstrated the most prominent differences between patients with and without clinical endpoints, while only IL-1RA was prognostically significant in both groups of patients with and without tocilizumab therapy, decreasing in the former and increasing in the latter during the follow-up period. Thus, CSS in COVID-19, characterized by a correlated release of multiple cytokines, does not fully correspond to the standard parameters of disease severity. Analysis of the cytokine signature, including the IL-1RA level in addition to standard clinical and laboratory parameters may be useful to define the onset of a cytokine storm in COVID-19 as well as the indications for anti-cytokine therapy.

A mechanism of self-lipid endocytosis mediated by the receptor Mincle.

Cellular lipid uptake (through endocytosis) is a basic physiological process. Dysregulation of this process underlies the pathogenesis of diseases such as atherosclerosis, obesity, diabetes, and cancer. However, to date, only some mechanisms of lipid endocytosis have been discovered. Here, we show a previously unknown mechanism of lipid cargo uptake into cells mediated by the receptor Mincle. We found that the receptor Mincle, previously shown to be a pattern recognition receptor of the innate immune system, tightly binds a range of self-lipids. Moreover, we revealed the minimal molecular motif in lipids that is sufficient for Mincle recognition. Superresolution microscopy showed that Mincle forms vesicles in cytoplasm and colocalizes with added fluorescent lipids in endothelial cells but does not colocalize with either clathrin or caveolin-1, and the added lipids were predominantly incorporated in vesicles that expressed Mincle. Using a model of ganglioside GM3 uptake in brain vessel endothelial cells, we show that the knockout of Mincle led to a dramatic decrease in lipid endocytosis. Taken together, our results have revealed a fundamental lipid endocytosis pathway, which we call Mincle-mediated endocytosis (MiME), and indicate a prospective target for the treatment of disorders of lipid metabolism, which are rapidly increasing in prevalence.

Enhancement of the antifungal activity of some antimycotics by farnesol and reduction of Candida albicans pathogenicity in a quail model experiment.

Background and Aim: Clinical strains of microorganisms, including pathogenic yeast-like fungi (YLF), are resistant to currently used antifungal agents. Thus, it is relevant to study the combinations of existing antimicrobial drugs and a medicinal extract of plant origin (farnesol). In previous studies, farnesol showed a relatively strong anti-biofilm effect against Candida albicans. This study aimed to determine how much the resistance profile of non-biofilm microorganisms can change. Materials and Methods: Six clinical isolates of C. albicans and one reference strain were used to study the interaction of farnesol with the most used antimycotics. To determine the sensitivity of YLF to antimycotic drugs, such as nystatin (50 µg), amphotericin B (10 µg), ketoconazole (10 µg), clotrimazole (10 µg), voriconazole (10 µg), fluconazole (25 µg), miconazole (10 µg), and intraconazole (10 µg), the classic disk diffusion method was used. In the second stage, one of the six strains was used to simulate candidiasis of the gastrointestinal tract in an in vivo quail model. As an unusual experimental design, this study investigated the effects of pretreated C. albicans in quails, not the in vivo pathogenicity of C. albicans, after treatment with farnesol. Results: The resistance profiles of Candida strains did not improve with farnesol in all strains. All concentrations of farnesol (100, 50, and 25 µM) demonstrated a fungistatic effect (i.e., an increase in drug sensitivity) in 23 of 56 (7×8) cases (41%). The remaining 54% demonstrated no changes in the resistance to antifungal drugs or deterioration of the indicators in rare cases (5%). At 100 µM farnesol, sensitivity improved in 33 of 56 cases (59%). Candidiasis or the severity of clinical disease of the quail digestive tract developed to a lesser extent if fungi were treated with farnesol. Conclusion: Farnesol does not always show a positive result on single cells without biofilm in the laboratory. However, in a biofilm or an in vivo model with biofilms, farnesol can be considered a new antimycotic drug or an additive to existing antimycotics.

Vitamin D Status and Gestational Diabetes in Russian Pregnant Women in the Period between 2012 and 2021: A Nested Case-Control Study.

Several meta-analyses found an association between low maternal serum 25-hydroxyvitamin D (25(OH)D) level and gestational diabetes mellitus (GDM). However, some of them reported significant heterogeneity. We examined the association of serum 25(OH)D concentration measured in the first and in the second halves of pregnancy with the development of GDM in Russian women surveyed in the periods of 2012−2014 and 2018−2021. We conducted a case−control study (including 318 pregnant women) nested on two previous studies. In 2012−2014, a total of 214 women (83 GDM and 131 controls) were enrolled before 15 weeks of gestation and maternal serum 25(OH)D concentrations were measured twice: at 8th−14th week of gestation and simultaneously with two-hour 75 g oral glucose tolerance test (OGTT) at 24th−32nd week of gestation. In the period of 2018−2021, 104 women (56 GDM and 48 controls) were included after OGTT and 25(OH)D concentrations were measured at 24th−32nd week of gestation. Median 25(OH)D levels were 20.0 [15.1−25.7] vs. 20.5 [14.5−27.5] ng/mL (p = 0.565) in GDM and control group in the first half of pregnancy and 25.3 [19.8−33.0] vs. 26.7 [20.8−36.8] ng/mL (p = 0.471) in the second half of pregnancy, respectively. The prevalence rates for vitamin D deficiency (25(OH)D levels < 20 ng/mL) were 49.4% and 45.8% (p = 0.608) in the first half of pregnancy and 26.2% vs. 22.1% (p = 0.516) in the second half of pregnancy in women who developed GDM and in women without GDM, respectively. The frequency of vitamin D supplements intake during pregnancy increased in 2018−2021 compared to 2012−2014 (p = 0.001). However, the third trimester 25(OH)D levels and prevalence of vitamin D deficiency (25.5 vs. 23.1, p = 0.744) did not differ in women examined in the periods of 2012−2014 and 2018−2021. To conclude, there was no association between gestational diabetes risk and maternal 25(OH)D measured both in the first and in the second halves of pregnancy. The increased prevalence of vitamin D supplements intake during pregnancy by 2018−2021 did not lead to higher levels of 25(OH)D.

Adhesion Molecules ICAM-1 and PECAM-1 as Potential Biomarkers of Central Nervous System Damage in Women Breast Cancer Survivors.

Breast cancer (BC) is the most common tumor in women worldwide with high mortality rates. Surgical methods followed by radio-chemotherapy are used to treat these tumors. Such treatment can lead to various side effects, including neurological complications. The development of a reliable biomarker to predict the onset of CNS complications could improve clinical outcomes. In the current study, ICAM-1 and PECAM-1 serum levels were measured as potential biomarkers in 45 female patients in a long-term follow-up period after breast cancer treatment, and compared to 25 age-matched female healthy volunteers. Serum levels of both biomarkers, ICAM-1 and PECAM-1 were significantly higher in patients after breast cancer treatment and could be associated with cognitive dysfunction, depression, and vestibulocerebellar ataxia. In conclusion, our results provide a first hint that elevated serum levels of ICAM-1 and PECAM-1 could serve as early predictive biomarkers in breast cancer survivors that might help to improve the management of these patients.

Potential Molecular Biomarkers of Central Nervous System Damage in Breast Cancer Survivors.

Damage of the central nervous system (CNS), manifested by cognitive impairment, occurs in 80% of women with breast cancer (BC) as a complication of surgical treatment and radiochemotherapy. In this study, the levels of ICAM-1, PECAM-1, NSE, and anti-NR-2 antibodies which are associated with the damage of the CNS and the endothelium were measured in the blood by ELISA as potential biomarkers that might reflect pathogenetic mechanisms in these patients. A total of 102 patients enrolled in this single-center trial were divided into four groups: (1) 26 patients after breast cancer treatment, (2) 21 patients with chronic brain ischemia (CBI) and asymptomatic carotid stenosis (ICA stenosis) (CBI + ICA stenosis), (3) 35 patients with CBI but without asymptomatic carotid stenosis, and (4) 20 healthy female volunteers (control group). Intergroup analysis demonstrated that in the group of patients following BC treatment there was a significant increase of ICAM-1 (mean difference: −368.56, 95% CI −450.30 to −286.69, p < 0.001) and PECAM-1 (mean difference: −47.75, 95% CI −68.73 to −26.77, p < 0.001) molecules, as compared to the group of healthy volunteers. Additionally, a decrease of anti-NR-2 antibodies (mean difference: 0.89, 95% CI 0.41 to 1.48, p < 0.001) was detected. The intergroup comparison revealed comparable levels of ICAM-1 (mean difference: −33.58, 95% CI −58.10 to 125.26, p = 0.76), PECAM-1 (mean difference: −5.03, 95% CI −29.93 to 19.87, p = 0.95), as well as anti-NR-2 antibodies (mean difference: −0.05, 95% CI −0.26 to 0.16, p = 0.93) in patients after BC treatment and in patients with CBI + ICA stenosis. The NSE level in the group CBI + ICA stenosis was significantly higher than in women following BC treatment (mean difference: −43.64, 95% CI 3.31 to −83.99, p = 0.03). Comparable levels of ICAM-1 were also detected in patients after BC treatment and in the group of CBI (mean difference: −21.28, 95% CI −111.03 to 68.48, p = 0.92). The level of PECAM-1 molecules in patients after BC treatment was also comparable to group of CBI (mean difference: −13.68, 95% CI −35.51 to 8.15, p = 0.35). In conclusion, among other mechanisms, endothelial dysfunction might play a role in the damage of the CNS in breast cancer survivors.