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The evaluation of trauma after surgery through objective analysis of biochemical markers can help in selecting the most appropriate therapy. Thus the aim of the study was the evaluation of the concentration of selected inflammatory cytokines (IL-6, IL-8, CXCL5, IL-33), C-reactive protein (CRP), and damaged-associated molecular patterns (DAMPs): HMGB-1, HSP-70 in the plasma of children in response to bone fracture and 12-14 hours after subsequent surgery performed by closed reduction with percutaneous Kirschner wire fixation (CRKF). The study will answer the question if the CRFK procedure leads to excessive production of inflammatory and damage markers. Blood samples from 29 children with distal forearm fractures were collected 30 min. before CRKF procedure and 12-14 hours after performance of the procedure. The control group was composed of 17 healthy children. IL-6 and CRP concentrations were analyzed using routinely performed in vitro diagnostics tests; the remaining proteins were analyzed with the use of the ELISA method. Increased values of IL-6, CRP, and HSP-70 represented an early inflammatory response to distal forearm fractures classified as SH-II type according to the Salter-Harris classification system. However, the median CRP concentration was within the reference values not indicative of inflammation. The CRKF procedure may be a good solution for the treatment of bone fractures, as damaged associated molecular patterns – HMGB-1 and HSP-70 – did not significantly differ 12-14 hours after the approach was applied as compared to the control group. Moreover, the increase in IL-6 concentration after the CRKF procedure was 1.5-fold to the level before CRKF, while the increase of this marker in response to the distal forearm fracture was 4.3-fold compared to the control group. Based on this data, it appears reasonable to suggest that the CRKF approach caused less damage and inflammatory response in comparison to the response to the fracture itself.

For the comparison of the DNA interactions with drugs, two newly synthesized prospective anticancer drugs, 6-(1H-imidazo[4,5-b]phenasine-2-yl)benzene-1,3-diol (IPBD) and, its-Cl derivative (Cl-IPBD) have been compared with doxorubicin, a drug widely used in medicine, and with Vitamin C. These compounds were accumulated at a supercoiled scpUC19 plasmid layer formed on a glassy carbon electrode (GCE). Stability of the drug-plasmid/GCE layer was achieved by initial plasmid accumulation using prolonged potential cycling for ca. 200 min. from highly diluted scpUC19 solutions (8 pg/mL), followed by accumulation of the drugs from 1 mM 50 mM. Electrochemical properties in terms of the redox potentials of the compounds and capacitative/resistive characteristics of the layers have been tested using, in sequence, four voltammetric methods: Square Wave (SWV), Differential Pulse (DPV) and Alternating Current (ACV) with phase detection 0 degrees and 90 degrees. Importantly, with progressive drug accumulation in the plasmid, for Cl-IPBD, but not for IPBD, an increase in peak (I) at -0.42 V vs. SCE was observed, while biological tests revealed a higher cytotoxic activity for Cl-IPBD vs. IPBD. Moreover, an additional redox signal of Cl-IPBD was observed with the compound reductive accumulation at the plasmid layer in the presence of Vitamin C. (C) 2020 Published by Elsevier B.V.

Hydrotherapy is a natural treatment and health protection method. Treatments using natural mineral water are gaining popularity as an alternative to pharmacotherapy or as additional support to pharmacotherapy in many types of diseases. The aim of the study was to determine the effective dose obtained as a result of baths and inhalations using popular mineral water samples. A total of 18 commercially available water samples used in hydrotherapy were tested for their radioactive isotope content. The following isotopes were found: 40K, 208Tl, 212Bi, 212Pb, 214Bi, 214Pb, 226Ra, 228Ac, 234Th. Effective doses received by patients during inhalation and bathing using the tested mineral water samples were determined. The collected sample activity was measured using gamma spectrometry. The effective doses received by patients from a series of inhalation treatments ranged from 170.4 to 22.9 µSv. Infants receive the highest effective dose as a result of inhalation of mineral water. The doses received by patients as a result of bathing in the studied mineral water samples were in the range of from 0.04 to 1.1 µSv and were comparable with doses from ordinary baths in tap water (0.06 µSv). The determined doses are very low; thus, they are unlikely to cause noticeable biological effects.

INTRODUCTION:In cancer treatment an attempt has been made to pharmacologically regulate the proteasome functions, thus the aim was to test whether 20S proteasome chymotrypsin-like (ChT-L) activity has a role in glial brain tumors. Furthermore, we analyzed the correlation between proteasome activity and IL-8, CCL2, NF-κB1 and NF-κB2 concentrations, which impact on brain tumors has already been indicated.METHODS:Plasma 20S proteasome ChT-L activity was assayed using the fluorogenic peptide substrate Suc-Leu-Leu-Val-Tyr-AMC in the presence of SDS. IL-8, CCL2, NF-κB1 and NF-κB2 concentration was analyzed with the use of ELISA method. Immunohistochemistry for IDH1-R132H was done on 5-microns-thick formalin-fixed, paraffin-embedded tumor sections with the use of antibody specific for the mutant IDH1-R132H protein. Labelled streptavidin biotin kit was used as a detection system.RESULTS:Brain tumor patients had statistically higher 20S proteasome ChT-L activity (0.649 U/mg) compared to non-tumoral individuals (0.430 U/mg). IDH1 wild-type patients had statistically higher 20S proteasome ChT-L activity (1.025 U/mg) compared to IDH1 mutants (0.549 U/mg). 20S proteasome ChT-L activity in brain tumor patients who died as the consequence of a tumor (0.649) in the following 2 years was statistically higher compared to brain tumor patients who lived (0.430 U/mg). In brain tumor patients the 20S proteasome ChT-L activity positively correlated with IL-8 concentration.CONCLUSIONS:Elevated 20S proteasome ChT-L activity was related to the increased risk of death in glial brain tumor patients. A positive correlation between 20S proteasome ChT-L activity and IL-8 concentration may indicate the molecular mechanisms regulating glial tumor biology. Thus research on proteasomes may be important and should be carried out to verify if this protein complexes may represent a potential therapeutic target to limit brain tumor invasion.

The aim of the study was to check whether the plasma levels of brain-derived neurotrophic factor (BDNF), interleukin-8 (IL-8), interleukin-11 (IL-11) and ubiquitin C-terminal hydrolase L1 (UCHL-1) change in children with mild head trauma (N = 29) compared to controls (N = 13). Protein concentration in children with mild head trauma (12 children with mild concussion without loss of consciousness and 17 children with severe concussion and loss of consciousness) and the control group were measured by means of the Enzyme-Linked Immunosorbent Assay (ELISA) method. IL-8 and BDNF concentration was statistically higher in the group of children with mild head trauma (9.89 pg/mL and 2798.00 pg/mL, respectively) compared to the control group (7.52 pg/mL and 1163.20 pg/mL, respectively). BDNF concentration was significantly higher in children with severe concussion and loss of consciousness (3826.00 pg/mL) than in the control group. None of the tested proteins differed significantly between children with mild concussion without loss of consciousness and children with severe concussion and loss of consciousness. BDNF and IL-8 may be sensitive markers of brain response to mild head trauma in children. The lack of statistical differences for BDNF and IL-8 between children with mild or severe concussion could indicate that their elevated levels may not result from significant structural brain damage but rather reflect a functional disturbance.

The aim was the evaluation of IL-6 concentration in peritoneal lavage fluid of children which underwent cholecystectomy to ascertain if there is a difference in early inflammatory response depending on the type of surgical approach (open vs. laparoscopy). The analysis of high-mobility group protein B1 (HMGB1) and heat shock protein 70 (HSP70) was performed to find out if the source of IL-6 was related to tissue damage. IL-6 concentration in peritoneal lavage fluid samples, obtained at the beginning and at the end of the laparoscopic (N = 23) and open cholecystectomy (N = 14), was tested with a routinely used electrochemiluminescence assay. The concentrations of HMGB1 and HSP70 were analyzed with the use of an ELISA method. Statistical analysis was performed using the STATISTICA PL release 12.5 Program. The differences were assessed using the Mann-Whitney U test and Wilcoxon matched pairs test. Correlations were studied by using the Spearman correlation test. Our results demonstrated significant peritoneal lavage fluid IL-6 concentration growth measured at the end of the cholecystectomy as compared to the beginning, regardless of the type of the procedure. IL-6 growth during open cholecystectomy was greater compared to laparoscopic cholecystectomy (62.51-fold vs. 3.19-fold). IL-6 concentration did not correlate with HMGB1 and HSP70, which indicate that the significant growth of this cytokine was not related to mechanical tissue damage due to surgical procedure. A clinical significance of the study could be related to the fact that the evaluation of IL-6 concentration in peritoneal lavage fluid may be useful to assess an early local inflammatory response.

Radioactivity measurements of 61 therapeutic peat mud samples from the Podsokoldy deposits, near Suprasl, were performed using gamma spectrometry. The authors identified the presence of 13 isotopes with the arithmetic mean of activity (in Bq kg−1): 137Cs-7, 40K-24, 208Tl-1, 212Bi-3, 212Pb-2, 228Ac-2, 210Pb-33, 214Bi-11, 214Pb-11, 226Ra-53, 234Th–47. The effective dose obtained during treatment with 15 peat mud baths (lasting 30 min) was 0.078 μSv. Use of peat mud compresses in the same number and period of exposure to the entire body surface caused absorption of a dose of 0.153 μSv. The authors discuss the probability of tissue radiation from isotopes present in the peat mud. In light of radiobiological knowledge, the therapeutic effect of ionizing radiation during peat mud therapy appears to be very unlikely.

At the beginning of the year 2016, the representatives of the Polish Radon Centre decided to organize proficiency tests (PTs) for measurements of radon gas and radon decay products in the air, involving radon monitors and laboratory passive techniques. The Silesian Centre for Environmental Radioactivity of the Central Mining Institute (GIG), Katowice, became responsible for the organization of the PT exercises. The main reason to choose that location was the radon chamber in GIG with a volume of 17 m 3 , the biggest one in Poland. Accordingly, 13 participants from Poland plus one participant from Germany expressed their interest. The participants were invited to inform the organizers about what types of monitors and methods they would like to check during the tests. On this basis, the GIG team prepared the proposal for the schedule of exercises, such as the required level(s) of radon concentrations, the number and periods of tests, proposed potential alpha energy concentration (PAEC) levels and also the overall period of PT. The PT activity was performed between 6th and 17th June 2016. After assessment of the results, the agreement between radon monitors and other measurement methods was confirmed. In the case of PAEC monitors and methods of measurements, the results of PT exercises were consistent and confirmed the accuracy of the calibration procedures used by the participants. The results of the PAEC PTs will be published elsewhere; in this paper, only the results of radon intercomparison are described.

In this paper we report the design and synthesis of novel derivatives of the 4H-3,1-benzothiazinone type and heterocyclic analogues, i.e. benzofuro-, azolo- and thieno-1,3-thiazin-4-ones possessing 2,4-dihydroxyphenyl substituent. The compounds were obtained by the one-step reaction of aminobenzamides or heterocyclic aminocarboxamides with aryl-modified sulfinylbis[(2,4-dihydroxyphenyl)methanethione]. Evaluation of their antiproliferative potency against human cancer cell lines showed that the activity of some analogues was similar to that of cisplatin. The highest activity and low toxicity were found for 6-tert-butyl-2-(5-chloro-2,4-dihydroxyphenyl)-4H-thieno[3,2-d][1,3]thiazin-4-one. The structure–activity elucidation reveals that the most active compounds are those with a thienothiazin-4-one and benzofuro[3,2-d][1,3]thiazin-4-one skeleton and the presence of the hydrophobic substituent (Et, Cl) in the benzenediol moiety increases their antiproliferative potency. The ADMET properties of selected compounds including metabolic stability and toxicity profile were estimated in silico.

Weekly measurements of air 7Be concentrations (n = 769) were performed in the years 1992-2010 in Bialystok (north-eastern Poland) using gamma spectrometry. The arithmetic mean (AM) concentration of 7Be was 2.51 mBq m-3, and the median (M) was 2.24 mBq m-3 (range 0.47-7.81 mBq m-3). The observed 7Be concentrations were within the range of levels recorded in Europe. Typical seasonal variability was observed. Concentrations of 7Be in the warm season (May, June, July) were almost twice as high as those in the cold season (November, December, January). A correlation was found between weekly 7Be concentrations and mean weekly values of relative humidity, temperature, and wind speed throughout the observation period. Pearson's correlation coefficients were -0.63, p < 0.001; 0.477, p < 0.001; -0.288, p < 0.001, respectively. The correlation coefficient between sunspot number and mean annual 7Be concentrations in the air in the years 1992-2010 was -0.609.

This work deals with the results of fluorescence studies of 4-(5-(methylamino-1,3,4-thiadiazol-2-yl)) benzene-1,3diol (MATB) and 4-(5-(methyl-1,3,4-thiadiazol-2-yl)) benzene-1,3-diol (MTB) in an aqueous solution at various pH. The aqueous solutions of both compounds analysed exhibited interesting fluorescence effects: dual fluorescence for MTB and two clearly separated distinct (partially overlapping) fluorescence emissions for MATB. Such fluorescence effects were observed in the aqueous solutions at pH 1-7 for MTB and pH 1-5 for MATB. At higher pH values, single fluorescence emission band were observed for both compounds. Based on the results reported to date, it was concluded that the observed fluorescence effects were mainly influenced by aggregation factors (induced by concentration changes, conformational effects or other interactions, e.g. formation of hydrogen bonds) and charge transfer effects (pH-induced and structure (substituent)-dependent). The dual fluorescence effect was noted for the analysed MTB compound (which does not have the -NH- secondary amine group), whereas two distinctly separated fluorescence bands were observed for the MATB analogue (which has the secondary amine group). The results presented in this paper highlight the impact of the secondary amine moiety on the fluorescence effects observed a long the range of solvents tested. The experimental research is accompanied by density functional theory-based (DFT) molecular modelling, which provide some hypothesis of the microscopic origins of the phenomena observed.

Surgical tissue damage and the accompanying inflammatory response lead to proteasome activation, initiation of damaged protein degradation, and induction of acute-phase inflammatory response. The aim of this study was to investigate the rate of change in proteasome chymotrypsin-like (ChT-L) activity and C-reactive protein concentration depending on the degree of tissue damage and their correlation with prealbumin concentrations in children before and after abdominal surgery. This experimental study included children who underwent abdominal surgery between 2015 and 2017. Plasma prealbumin concentrations and C-reactive protein levels (CRP) were determined by standard biochemical laboratory procedures. Proteasome activity was assessed using a Suc-Leu-Leu-Val-Tyr-AMC peptide substrate. Elevation of plasma proteasome activity was noted in children after laparoscopic and open abdominal surgeries. However, 20S proteasome activity in children undergoing conventional open surgery was significantly higher (P < 0.05) than in patients subjected to laparoscopy. At the same time, an increase in the CRP level was observed. However, there was no correlation between C-reactive protein concentrations and the type of abdominal surgery while there was a correlation observed in the case of proteasomes. Proteasome activity correlates with the degree of surgical tissue damage and prealbumin concentrations. More invasive surgery leads to a stronger activation of the proteasome involved in removing proteins that were damaged due to the surgical procedure. Proteasomes are more specific markers because there is a correlation between proteasome activity and the type of abdominal surgery in contrast to C-reactive protein concentrations which are not different in response to surgery performed in regard to ovarian cysts or cholelithiasis.

Operations of varying duration cause the release of a number of inflammatory mediators, in particular cytokines which lead to proteasome and acute-phase reactions. The purpose of this novel human study, was to characterize inflammatory response in children undergoing laparoscopic cholecystectomy, by analyzing changes in selected inflammatory mediators: C-reactive protein concentration and circulating 20S proteasome activity following surgical injury and to correlate them with the duration of the surgical procedure. Plasma C-reactive protein concentration (CRP) was determined by standard biochemical laboratory procedures. Proteasome activity in the plasma of children was assessed using Suc-Leu-Leu-Val-Tyr-AMC peptide substrate. Statistically significant increase in the plasma proteasome activity and C-reactive protein concentration, was noted (p<.05) in children after laparoscopic cholecystectomy. We found the correlation between the 20S proteasome activity and the length of the procedure. In children undergoing longer lasting laparoscopic cholecystectomy the proteasome activity was much higher than in patients having shorter surgical procedure. The CRP concentration and 20S proteasome activity significantly increase after surgery, but only 20S proteasome activity correlate with the length of the surgery. This may confirm that CRP is only an indicator of pathological state, while the function of the proteasomes is more complex because of their participation in the processes of repair and wound healing, and in the removal of damaged proteins.

The article describes basic theories of small doses of ionizing radiation’s impact on an organism and the current views on mechanisms of cancer emergence influenced by radiation. The risk estimation of lung carcinoma caused by inhalation of radon present in human environment was provided.

•Label-free detection of superhelical circular and linear pUC19 plasmid DNA.•AFM confirmation of pUC19 architecture in compact layers on GC plate.•Redox-specific accumulation of the anticancer drug within superhelical and linear pUC19 plasmid layers.•Redox and capacitative/resistive properties of DNA-Cl-IPBD prospective anticancer drug.•Correlation between Differential Pulse and Alternating Current voltammetry signals in studying DNA-drug interactions.•Comparison of Cl-IPBD, riboflavin and rutin accumulation in plasmid layers.

This article presents the results of spectroscopic studies of two compounds from the 1,3,4-thiadiazole group, that is, 4-(5-methyl-1,3,4-thiadiazole-2-yl)benzene-1,3-diol (C1) and 4-(5-heptyl-1,3,4-thiadiazole-2-yl)benzene-1,3-diol (C7), present at different molar concentrations in 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) liposome systems. In the case of both investigated compounds, fluorescence measurements revealed the presence of several emission bands, whose appearance is related to the molecular organization induced by changes in the phase transition in DPPC. On the basis of the interpretation of Fourier transform infrared spectra, we determined the molecular organization of the analyzed compounds in multilayers formed from DPPC and the 1,3,4-thiadiazoles. It was found that the compound with a longer alkyl substituent both occupied the lipid polar head region in the lipid multilayer and interacted with lipid hydrocarbon chains. In turn, the compound with a shorter alkyl substituent interacted more strongly with the membrane polar region. On the basis of the knowledge from previous investigations conducted using different solvents, the fluorescence effects observed were related to the phenomenon of molecular aggregation. The effects were strongly influenced by the structure of the compound and, primarily, by the type of the alkyl substituent used in the molecule. The substantial shortening of fluorescence lifetimes associated with the effect of long-wave emission (with a maximum at 505 nm) decay also confirms the model of aggregation effects in the analyzed systems. Similar effects can be very easily distinguished and associated with respective forms of the compounds in biologically relevant samples.

2-(2,4-Dihydroxyphenyl)thieno-1,3-thiazin-4-ones are a group of new compounds with potential anticancer activity. This type of derivatives was poorly investigated in the area of synthesis and biological activities. In the present study the antiproliferative action of the most active derivative BChTT was described. The aim of biological evaluation was to investigate the ability of the compound to inhibit cancer cell proliferation and identify mechanism involved in its action on the molecular level. BChTT inhibited the proliferation of lung cancer A549, colon cancer HT-29 and glioma C6 cells in the concentration-dependent manner. It was not toxic to normal cells including skin fibroblasts, hepatocytes and oligodendrocytes in the antiproliferative concentrations. BChTT decreased the DNA synthesis in the treated cancer cells and induced cell cycle arrest in the G0/G1 phase. Moreover, the ability of the compound to activate p38 kinase and decrease cyclin D1 expression was estimated. Participation of p38 kinase in the antiproliferative action of the compound was confirmed by the analysis of BChTT activity in the cells with the p38 silenced gene. The obtained results may suggest the ability of the tested derivative to inhibit cancer cells proliferation by induction of p38-mediated cyclin D1 downregulation.

Proteasomes are structures responsible for the elimination of damaged and misfolded proteins. Thus, they also regulate the most important intracellular processes. Changes in their functions can lead to many molecular diseases. There are two possible disorders in the function of proteasomes. Their increasing activity causes excessive degradation of important cell proteins. On the other hand, their insufficiency can inhibit the degradation of pathological proteins and lead to their accumulation. The increase of proteasome activity and the degradation of important proteins are observed in many pathological disorders. Therefore the study of pharmacological methods using proteasome inhibitors has gained growing interest in the last years. This review summarizes recent findings regarding the role of proteasomes in pathogenesis of selected diseases and discusses the potential use of proteasomes in diagnosis of different disorders.