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Previous investigations in gene expression changes in blood after radiation exposure have highlighted its potential to provide biomarkers of exposure. Here, FDXR transcriptional changes in blood were investigated in humans undergoing a range of external radiation exposure procedures covering several orders of magnitude (cardiac fluoroscopy, diagnostic computed tomography (CT)) and treatments (total body and local radiotherapy). Moreover, a method was developed to assess the dose to the blood using physical exposure parameters. FDXR expression was significantly up-regulated 24 hr after radiotherapy in most patients and continuously during the fractionated treatment. Significance was reached even after diagnostic CT 2 hours post-exposure. We further showed that no significant differences in expression were found between ex vivo and in vivo samples from the same patients. Moreover, potential confounding factors such as gender, infection status and anti-oxidants only affect moderately FDXR transcription. Finally, we provided a first in vivo dose-response showing dose-dependency even for very low doses or partial body exposure showing good correlation between physically and biologically assessed doses. In conclusion, we report the remarkable responsiveness of FDXR to ionising radiation at the transcriptional level which, when measured in the right time window, provides accurate in vivo dose estimates.

Background. Psoriasis vulgaris is a chronic autoimmune disease associated with systemic inflammation. Increased levels of numerous cytokines, chemokines, growth factors, and other molecules were found in the skin and in the circulation of psoriatic patients. Alarmins, also known as danger signals, are intracellular proteins, which are released to an extracellular space after infection or damage. They are the markers of cell destructive processes. Objective. The aim of the present study was to evaluate the suitability of selected alarmins (HMGB1, IL-33, S100A7, and S100A12) as potential biomarkers of severity of psoriasis and to explore possible relationships between these proteins for the purpose of better understanding their roles in the immunopathology of psoriasis. Methods. The serum levels of selected alarmins were measured in 63 psoriatic patients and 95 control individuals. The levels were assessed by the ELISA technique using commercial kits. The data were statistically processed with MedCalc version 19.0.5. Results. In psoriatic patients, we found significantly increased levels of HMGB1 (p<0.05), IL-33 (p<0.01), S100A7 (p<0.0001), and S100A12 (p<0.0001). In addition, we found a significant relationship between HMGB1 and S100A7 (Spearman’s rho=0.276, p<0.05) in the patients and significant relationship between HMGB1 and IL-33 in the controls (Spearman’s rho=0.416, p<0.05). We did not find any relationship between observed alarmins and the disease severity. Conclusions. The alarmins HMGB1, IL-33, S100A7, and S100A12 were significantly elevated in the serum of patients, which states the hypothesis that they play specific roles in the immunopathology of psoriasis. However, we have not yet found a relationship between observed alarmins and the disease severity. The discovery of the relationship between HMGB1 and S100A7 is a novelty that should be studied in the future to further clarify its role and importance.

The increasing risk of acute large-scale radiological/nuclear exposures of population underlines the necessity of developing new, rapid and high throughput biodosimetric tools for estimation of received dose and initial triage. We aimed to compare the induction and persistence of different radiation exposure biomarkers in human peripheral blood in vivo. Blood samples of patients with indicated radiotherapy (RT) undergoing partial body irradiation (PBI) were obtained soon before the first treatment and then after 24 h, 48 h, and 5 weeks; i.e. after 1, 2, and 25 fractionated RT procedures. We collected circulating peripheral blood from ten patients with tumor of endometrium (1.8 Gy per fraction) and eight patients with tumor of head and neck (2.0-2.121 Gy per fraction). Incidence of dicentrics and micronuclei was monitored as well as determination of apoptosis and the transcription level of selected radiation-responsive genes. Since mitochondrial DNA (mtDNA) has been reported to be a potential indicator of radiation damage in vitro, we also assessed mtDNA content and deletions by novel multiplex quantitative PCR. Cytogenetic data confirmed linear dose-dependent increase in dicentrics (p < 0.01) and micronuclei (p < 0.001) in peripheral blood mononuclear cells after PBI. Significant up-regulations of five previously identified transcriptional biomarkers of radiation exposure (PHPT1, CCNG1, CDKN1A, GADD45, and SESN1) were also found (p < 0.01). No statistical change in mtDNA deletion levels was detected; however, our data indicate that the total mtDNA content decreased with increasing number of RT fractions. Interestingly, the number of micronuclei appears to correlate with late radiation toxicity (r2 = 0.9025) in endometrial patients suggesting the possibility of predicting the severity of RT-related toxicity by monitoring this parameter. Overall, these data represent, to our best knowledge, the first study providing a multiparametric comparison of radiation biomarkers in human blood in vivo, which have potential for improving biological dosimetry.

Background. Psoriasis is a chronic systemic inflammatory disease associated with a wide range of comorbidities, including metabolic syndrome (MetS). Serum calprotectin, ANGPTL8, and oxidative damage to nucleic acids might be associated with both diseases. The presented study describes the influence of psoriasis and MetS on the serum levels of markers of systemic inflammation (calprotectin and ANGPTL8) and markers of oxidative damage to nucleic acids. The applicability of serum levels of calprotectin and ANGPTL8 for monitoring of the activity of psoriasis (diagnostic markers) is also evaluated. Methods. Clinical examination (PASI score, MetS), enzyme-linked immunosorbent assay (ELISA), and Enzyme Immunoassay (EIA). Serum calprotectin, ANGPTL8, 8-hydroxy-2′-deoxyguanosine, 8-hydroxyguanosine, and 8-hydroxyguanine. Results and Conclusions. The psoriasis significantly increased the serum level of calprotectin and the serum level of oxidative damage to nucleic acids, however not the serum level of ANGPTL8. The presence of MetS did not significantly affect the serum levels of calprotectin, ANGPTL8, and oxidative damage to nucleic acids in either psoriasis patients or controls. It seems that the serum level of calprotectin (but not the serum level of ANGPTL8) could be used as a biomarker for monitoring the activity of psoriasis.

The presented article studies the role of selected inflammatory and anti-inflammatory serum markers of psoriatic patients in the pathogenesis of metabolic syndrome (MS) and psoriasis. The study is based on the comparison between the group of psoriatic patients (74) and the control group (65). We found significantly higher BMI ( p < 0.05 ) and diastolic blood pressure ( p < 0.05 ) in the psoriatic patients. The values of waist circumference and BMI were significantly higher ( p < 0.05 ) in the male patients compared to the men in the control group. The analysis revealed significantly higher CRP ( p < 0.001 ), Lp-PLA2 ( p < 0.001 ), leptin ( p < 0.01 ), and resistin ( p < 0.01 ) levels in the psoriatic patients. Significantly higher levels of CRP ( p < 0.01 ), Lp-PLA2 ( p < 0.001 ), leptin ( p < 0.01 ), and resistin ( p < 0.05 ) were found in the patients with MS compared to the controls with MS. The level of adiponectin was significantly lower ( p < 0.01 ) in the patients with MS. Finally, we found significantly higher level of Lp-PLA2 ( p < 0.001 ) in the group of patients without MS compared to the controls without MS. In conclusion, observed inflammatory and anti-inflammatory markers (CRP, adiponectin, leptin, resistin, and Lp-PLA2) are involved in both pathogenesis of MS and pathogenesis of psoriasis. The level of Lp-PLA2 indicates the presence of subclinical atherosclerosis (cardiovascular risk) in psoriatic patients.

Background Psoriasis vulgaris is a skin autoimmune disease. Psoriatic patients have significantly lowered life expectancy and suffer from various comorbidities. The main goal of the study was to determine whether psoriatic patients experience accelerated aging. As accelerated aging might be the reason for the higher prevalence of comorbidities at lower chronological ages, we also wanted to investigate the relationship between aging and selected parameters of frequent psoriatic comorbidities - endocan, vascular endothelial growth factor and interleukin-17. Samples were obtained from 28 patients and 42 healthy controls. Epigenetic age measurement was based on the Horvath clock. The levels of endocan, vascular endothelial growth factor and interleukin-17 were analyzed using standardized ELISA methods. Results The difference between the epigenetic age and the chronological age of each individual subject did not increase with the increasing chronological age of patients. We cannot conclude that psoriasis causes accelerated aging. However, the epigenetic and chronological age difference was significantly higher in female patients than in female controls, and the difference was correlated with endocan (r = 0.867, p  = 0.0012) and vascular endothelial growth factor (r = 0.633, p  = 0.0365) only in female patients. Conclusions The findings suggest a possible presence of pathophysiological processes that occur only in female psoriatic patients. These processes make psoriatic females biologically older and might lead to an increased risk of comorbidity occurrence. This study also supports the idea that autoimmune diseases cause accelerated aging, which should be further explored in the future.

Carbon-based nanomaterials (C-BNM) have recently attracted an increased attention as the materials with potential applications in industry and medicine. Bioresistance and proinflammatory potential of C-BNM is the main obstacle for their medicinal application which was documented in vivo and in vitro. However, there are still limited data especially on graphene derivatives such as graphene platelets (GP). In this work, we compared multi-walled carbon nanotubes (MWCNT) and two different types of pristine GP in their potential to activate inflammasome NLRP3 (The nod-like receptor family pyrin domain containing 3) in vitro. Our study is focused on exposure of THP-1/THP1-null cells and peripheral blood monocytes to C-BNM as representative models of canonical and alternative pathways, respectively. Although all nanomaterials were extensively accumulated in the cytoplasm, increasing doses of all C-BNM did not lead to cell death. We observed direct activation of NLRP3 via destabilization of lysosomes and release of cathepsin B into cytoplasm only in the case of MWCNTs. Direct activation of NLRP3 by both GP was statistically insignificant but could be induced by synergic action with muramyl dipeptide (MDP), as a representative molecule of the family of pathogen-associated molecular patterns (PAMPs). This study demonstrates a possible proinflammatory potential of GP and MWCNT acting through NLRP3 activation.

The evaluation of carbon-based nanomaterials’ (C-BNMs’) interactions with the immune system, notably their ability to cause inflammation, is a critical step in C-BNM health risk assessment. Particular attention should be given to those C-BNMs that do not cause direct cytotoxicity or inflammation on their own. However, the intracellular presence of these non-biodegradable nanomaterials could dysregulate additional cell functions. This is even more crucial in the case of phagocytes, which are the main mediators of defensive inflammation towards pathogens. Hence, our study was focused on multi-walled carbon nanotubes (MWCNTs) and two different types of graphene platelets (GPs) and whether their intracellular presence modulates a proinflammatory response from human primary monocytes towards common pathogens. Firstly, we confirmed that all tested C-BNMs caused neither direct cytotoxicity nor the release of tumour necrosis factor α (TNF-α), interleukin (IL)-6 or IL-10. However, such pre-exposed monocytes showed increased responsiveness to additional bacterial stimuli. In response to several types of bacteria, monocytes pre-treated with GP1 produced a significantly higher quantity of TNF-α, IL-6 and IL-10. Monocytes pre-treated with MWCNTs produced increased levels of IL-10. All the tested C-BNMs enhanced monocyte phagocytosis and accelerated their differentiation towards macrophages. This study confirms the immunomodulatory potential of C-BNMs.

(1) Background: Graphene is a two-dimensional atomic structure with a wide range of uses, including for biomedical applications. However, knowledge of its hazards is still limited. This work brings new cytotoxic, cytostatic, genotoxic and immunotoxic data concerning the in vitro exposure of human cell line to two types of graphene platelets (GP). It also contributes to the formation of general conclusions about the health risks of GP exposure. (2) Methods: In vitro exposure of a THP-1 cell line to three concentrations of two GP over 40 h. The cytotoxic potential was assessed by the measurement of LDH and glutathione (ROS) and by a trypan blue exclusion assay (TBEA); the cytostatic and genotoxic potential were assessed by the cytokinesis-block micronucleus (CBMN) test; and the immunotoxic potential was assessed by the measurement of IL-6, IL-10 and TNF-α. (3) Results: We found a significant dose-dependent increase in DNA damage (CBMN). The lowest observed genotoxic effect levels (LOGEL) were 5 µg/mL (GP1) and 30 µg/mL (GP2). We found no significant leaking of LDH from cells, increase in dead cells (TBEA), induction of ROS, increased levels of cytostasis, or changes in IL-6, IL-10 and TNF-α levels. (4) Conclusions: The genotoxicity increased during the short-term in vitro exposure of THP-1 to two GP. No increase in cytotoxicity, immunotoxicity, or cytostasis was observed.

In the field of science, technology and medicine, carbon-based nanomaterials and nanoparticles (CNMs) are becoming attractive nanomaterials that are increasingly used. However, it is important to acknowledge the risk of nanotoxicity that comes with the widespread use of CNMs. CNMs can enter the body via inhalation, ingestion, intravenously or by any other route, spread through the bloodstream and penetrate tissues where (in both compartments) they interact with components of the immune system. Like invading pathogens, CNMs can be recognized by large numbers of receptors that are present on the surface of innate immune cells, notably monocytes and macrophages. Depending on the physicochemical properties of CNMs, i.e., shape, size, or adsorbed contamination, phagocytes try to engulf and process CNMs, which might induce pro/anti-inflammatory response or lead to modulation and disruption of basic immune activity. This review focuses on existing data on the immunotoxic potential of CNMs, particularly in professional phagocytes, as they play a central role in processing and eliminating foreign particles. The results of immunotoxic studies are also described in the context of the entry routes, impacts of contamination and means of possible elimination. Mechanisms of proinflammatory effect depending on endocytosis and intracellular distribution of CNMs are highlighted as well.