Radiation-Induced Changes in Serum Lipidome of Head and Neck Cancer Patients

Cancer radiotherapy (RT) induces response of the whole patient’s body that could be detected at the blood level. We aimed to identify changes induced in serum lipidome during RT and characterize their association with doses and volumes of irradiated tissue. Sixty-six patients treated with conformal RT because of head and neck cancer were enrolled in the study. Blood samples were collected before, during and about one month after the end of RT. Lipid extracts were analyzed using MALDI-oa-ToF mass spectrometry in positive ionization mode. The major changes were observed when pre-treatment and within-treatment samples were compared. Levels of several identified phosphatidylcholines, including (PC34), (PC36) and (PC38) variants, and lysophosphatidylcholines, including (LPC16) and (LPC18) variants, were first significantly decreased and then increased in post-treatment samples. Intensities of changes were correlated with doses of radiation received by patients. Of note, such correlations were more frequent when low-to-medium doses of radiation delivered during conformal RT to large volumes of normal tissues were analyzed. Additionally, some radiation-induced changes in serum lipidome were associated with toxicity of the treatment. Obtained results indicated the involvement of choline-related signaling and potential biological importance of exposure to clinically low/medium doses of radiation in patient’s body response to radiation.     

Dexamethasone and 1,25-Dihydroxyvitamin D3 Reduce Oxidative Stress-Related DNA Damage in Differentiating Osteoblasts

The process of osteoblast differentiation is regulated by several factors, including RUNX2. Recent reports suggest an involvement of RUNX2 in DNA damage response (DDR), which is important due to association of differentiation with oxidative stress. In the present work we explore the influence of two RUNX2 modifiers, dexamethasone (DEX) and 1,25-dihydroxyvitamin D3 (1,25-D3), in DDR in differentiating MC3T3-E1 preosteoblasts challenged by oxidative stress. The process of differentiation was associated with reactive oxygen species (ROS) production and tert-butyl hydroperoxide (TBH) reduced the rate of differentiation. The activity of alkaline phosphatase (ALP), a marker of the process of osteoblasts differentiation, increased in a time-dependent manner and TBH further increased this activity. This may indicate that additional oxidative stress, induced by TBH, may accelerate the differentiation process. The cells displayed changes in the sensitivity to TBH in the course of differentiation. DEX increased ALP activity, but 1,25-D3 had no effect on it. These results suggest that DEX might stimulate the process of preosteoblasts differentiation. Finally, we observed a protective effect of DEX and 1,25-D3 against DNA damage induced by TBH, except the day 24 of differentiation, when DEX increased the extent of TBH-induced DNA damage. We conclude that oxidative stress is associated with osteoblasts differentiation and induce DDR, which may be modulated by RUNX2-modifiers, DEX and 1,25-D3.     

Optimization of 1,2,5‐Thiadiazole Carbamates as Potent and Selective ABHD6 Inhibitors

At present, inhibitors of α/β‐hydrolase domain 6 (ABHD6) are viewed as a promising approach to treat inflammation and metabolic disorders. This article describes the development of 1,2,5‐thiadiazole carbamates as ABHD6 inhibitors. Altogether, 34 compounds were synthesized, and their inhibitory activity was tested using lysates of HEK293 cells transiently expressing human ABHD6 (hABHD6). Among the compound series, 4‐morpholino‐1,2,5‐thiadiazol‐3‐yl cyclooctyl(methyl)carbamate (JZP‐430) potently and irreversibly inhibited hABHD6 (IC₅₀=44 nM ) and showed ～230‐fold selectivity over fatty acid amide hydrolase (FAAH) and lysosomal acid lipase (LAL), the main off‐targets of related compounds. Additionally, activity‐based protein profiling indicated that JZP‐430 displays good selectivity among the serine hydrolases of the mouse brain membrane proteome. JZP‐430 has been identified as a highly selective, irreversible inhibitor of hABHD6, which may provide a novel approach in the treatment of obesity and type II diabetes.     

Candida antarctica Lipase B Immobilized onto Chitin Conjugated with POSS? Compounds: Useful Tool for Rapeseed Oil Conversion

A new method is proposed for the production of a novel chitin-polyhedral oligomeric silsesquioxanes (POSS) enzyme support. Analysis by such techniques as X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy confirmed the effective functionalization of the chitin surface. The resulting hybrid carriers were used in the process of immobilization of the lipase type b from Candida antarctica (CALB). Fourier transform infrared spectroscopy (FTIR) confirmed the effective immobilization of the enzyme. The tests of the catalytic activity showed that the resulting support-biocatalyst systems remain hydrolytically active (retention of the hydrolytic activity up to 87% for the chitin + Methacryl POSS^® cage mixture (MPOSS) + CALB after 24 h of the immobilization), as well as represents good thermal and operational stability, and retain over 80% of its activity in a wide range of temperatures (30–60 °C) and pH (6–9). Chitin-POSS-lipase systems were used in the transesterification processes of rapeseed oil at various reaction conditions. Produced systems allowed the total conversion of the oil to fatty acid methyl esters (FAME) and glycerol after 24 h of the process at pH 10 and a temperature 40 °C, while the Methacryl POSS^® cage mixture (MPOSS) was used as a chitin-modifying agent.     

Graphene oxide influence on selected properties of polymer fuel cells based on Nafion

Graphene oxide (GO) was used as an additive to the anode, to modify the electrochemical properties of polymer fuel cells (PEMFC) based on Nafion. GO was obtained by modified Hummers method and fully characterized by Raman, FTIR, X-ray, TEM, electrochemically (CV) and Surface Area and Porosity Analyzer. PEMFC with a GO-based anode containing about 30% less Pt, was constructed and compared with a cell with standard anodes. The electrodes were electrochemically tested at 25 and 60 °C. A maximum power density of 134 mW/cm² with a current density of 374 mA/cm² was achieved for PEMFC with GO-based anode at 60 °C. The electrochemical surface area (ECSA) of the PEMFC with GO-based anode was about two times higher than that of the reference device. The electrochemical characterization as well as the Brunauer–Emmett–Teller (BET) and Barrett–Joyner–Halenda (BJH) analysis indicate that GO in the anode reduced Pt agglomeration, as a consequence of the increased surface area and decreased average pore width, compared with the reference electrode. Well-fitted equivalent circuits were proposed and discussed after an electrochemical impedance spectroscopy study of the constructed devices.     

Legionella dumoffii Utilizes Exogenous Choline for Phosphatidylcholine Synthesis

Phosphatidycholine (PC) is the major membrane-forming phospholipid in eukaryotes but it has been found in only a limited number of prokaryotes. Bacteria synthesize PC via the phospholipid N-methylation pathway (Pmt) or via the phosphatidylcholine synthase pathway (Pcs) or both. Here, we demonstrated that Legionella dumoffii has the ability to utilize exogenous choline for phosphatidylcholine (PC) synthesis when bacteria grow in the presence of choline. The Pcs seems to be a primary pathway for synthesis of this phospholipid in L. dumoffii. Structurally different PC species were distributed in the outer and inner membranes. As shown by the LC/ESI-MS analyses, PC15:0/15:0, PC16:0/15:0, and PC17:0/17:1 were identified in the outer membrane and PC14:0/16:0, PC16:0/17:1, and PC20:0/15:0 in the inner membrane. L. dumoffii pcsA gene encoding phosphatidylcholine synthase revealed the highest sequence identity to pcsA of L. bozemanae (82%) and L. longbeachae (81%) and lower identity to pcsA of L. drancourtii (78%) and L. pneumophila (71%). The level of TNF-α in THP1-differentiated cells induced by live and temperature-killed L. dumoffii cultured on a medium supplemented with choline was assessed. Live L. dumoffii bacteria cultured on the choline-supplemented medium induced TNF-α three-fold less efficiently than cells grown on the non-supplemented medium. There is an evident effect of PC modification, which impairs the macrophage inflammatory response.     

Antimony substituted lanthanum orthoniobate proton conductor – Structure and electronic properties

X-ray and neutron diffraction have been utilized to analyze the crystalline and electronic structure of lanthanum orthoniobate substituted by antimony. Using X-ray absorption spectroscopy and photoelectron spectroscopy, changes in the electronic structure of the material upon substitution have been analyzed. The structural transition temperature between fergusonite and scheelite phases for 30 mol% antimony substitution was found to be 15°C. Based on the neutron data, the oxygen nonstoichiometry was found to be relatively low. Moreover no influence on the position of the valence band maximum was observed. The influence of the protonation on the electronic structure of constituent oxides has been studied. Absorption data show that the incorporation of protonic defects into the lanthanum orthoniobate structure leads to changes in lanthanum electronic structure and a decrease in the density of unoccupied electronic states.