Sphingolipid metabolism in colorectal adenomas varies depending on histological architecture of polyps and grade of nuclear dysplasia

Incidence of colorectal cancer (CRC) is growing worldwide. Pathogenetic mechanisms responsible for its onset and progression need further clarification. Colorectal adenomatous polyps are precancerous lesions with malignant potential dependent on histological architecture and grade of nuclear dysplasia. One of the factors conditioning CRC development are abnormalities in sphingolipid metabolism. The aim of this study was to assess the levels of sphingolipids in human colorectal adenomas. The control group (C, n = 12) consisted of patients with no colonic polyps. The examined group consisted of patients with prior diagnosed colonic polyps, qualified to endoscopic polypectomy. This group was further divided due to histological architecture into tubular adenomas group (TA, n = 10), tubulovillous adenomas with low‐grade dysplasia (LGD‐TVA, n = 10), and tubulovillous adenomas group with high‐grade dysplasia (HGD‐TVA, n = 11). In tissue samples, sphingolipd metabolite contents were measured using high performance liquid chromatography (HPLC). In cases of polypoid lesions with low malignancy potential (tubular adenomas), concentration of ceramide, which is characterized by proapoptotic and anti‐proliferative properties, increases compared with control group (p < 0.05), whereas content of sphingosine‐1‐phosphate with anti‐apoptotic and stimulating cellular proliferation properties is reduced in comparison with control group (p < 0.05). On the contrary, in cases of more advanced form of adenomatous polyps (tubulovillous adenomas with high‐grade dysplasia), the ceramide level decreases compared with control group (p < 0.05) while sphingosine‐1‐phosphate concentration is elevated (p < 0.05). We found that concentrations of pro‐apoptotic ceramide are decreased and pro‐proliferative S1P levels are increased in polypoid lesions with high malignancy potential, and it was the opposite in those with low malignancy potential.     

Cinnamamide Derivatives for Central and Peripheral Nervous System Disorders—A Review of Structure–Activity Relationships

The cinnamamide scaffold has been incorporated in to the structure of numerous organic compounds with therapeutic potential. The scaffold enables multiple interactions, such as hydrophobic, dipolar, and hydrogen bonding, with important molecular targets. Additionally, the scaffold has multiple substitution options providing the opportunity to optimize and modify the pharmacological activity of the derivatives. In particular, cinnamamide derivatives have exhibited therapeutic potential in animal models of both central and peripheral nervous system disorders. Some have undergone clinical trials and were introduced on to the pharmaceutical market. The diverse activities observed in the nervous system included anticonvulsant, antidepressant, neuroprotective, analgesic, anti‐inflammatory, muscle relaxant, and sedative properties. Over the last decade, research has focused on the molecular mechanisms of action of these derivatives, and the data reported in the literature include targeting the γ‐aminobutyric acid type A (GABA_A) receptors, N‐methyl‐D ‐aspartate (NMDA) receptors, transient receptor potential (TRP) cation channels, voltage‐gated potassium channels, histone deacetylases (HDACs), prostanoid receptors, opioid receptors, and histamine H₃ receptors. Here, the literature data from reports evaluating cinnamic acid amide derivatives for activity in target‐based or phenotypic assays, both in vivo and in vitro, relevant to disorders of the central and peripheral nervous systems are analyzed and structure–activity relationships discussed.     

Duplex Healing of Selectively Thiolated Guanosine Mismatches through a Cd2+ Chemical Stimulus

The on‐column selective conversion of guanosine to thioguanosine (tG) yields modified oligomers that exhibit destabilisation over the fully complementary duplex. Restoration to a stabilised duplex is induced through thio‐directed Cd²⁺ coordination; a route for healing DNA damage. Short oligomers are G‐specifically thiolated through a modified on‐column protocol without the need for costly thioguanosine phosphoramidites. Addition of Cd²⁺ ions to a duplex containing a highly disrupted tG central mismatch sequence, 3′‐A₆tG₄T₆‐5′, suggests a (tG)₈Cd₂ central coordination regime, resulting in increased base stacking and duplex stability. Equilibrium molecular dynamic calculations support the hypothesis of metal‐induced healing of the thiolated duplex. The 2 nm displacement of the central tG mismatched region is dramatically reduced after the addition of a chemical stimuli, Cd²⁺ ions, returning to a minimized fluctuational state comparable to the unmodified fully complementary oligomer.     

Cardiovascular and inflammatory mechanisms in healthy humans exposed to air pollution in the vicinity of a steel mill

Background

There is a paucity of mechanistic information that is central to the understanding of the adverse health effects of source emission exposures. To identify source emission-related effects, blood and saliva samples from healthy volunteers who spent five days near a steel plant (Bayview site, with and without a mask that filtered many criteria pollutants) and at a well-removed College site were tested for oxidative stress, inflammation and endothelial dysfunction markers.

Methods

Biomarker analyses were done using multiplexed protein-array, HPLC-Fluorescence, EIA and ELISA methods. Mixed effects models were used to test for associations between exposure, biological markers and physiological outcomes. Heat map with hierarchical clustering and Ingenuity Pathway Analysis (IPA) were used for mechanistic analyses.

Results

Mean CO, SO₂ and ultrafine particles (UFP) levels on the day of biological sampling were higher at the Bayview site compared to College site. Bayview site exposures “without” mask were associated with increased (p?<?0.05) pro-inflammatory cytokines (e.g IL-4, IL-6) and endothelins (ETs) compared to College site. Plasma IL-1β, IL-2 were increased (p?<?0.05) after Bayview site “without” compared to “with” mask exposures. Interquartile range (IQR) increases in CO, UFP and SO₂ were associated with increased (p?<?0.05) plasma pro-inflammatory cytokines (e.g. IL-6, IL-8) and ET-1_(1–21) levels. Plasma/saliva BET-1 levels were positively associated (p?<?0.05) with increased systolic BP. C-reactive protein (CRP) was positively associated (p?<?0.05) with increased heart rate. Protein network analyses exhibited activation of distinct inflammatory mechanisms after “with” and “without” mask exposures at the Bayview site relative to College site exposures.

Conclusions

These findings suggest that air pollutants in the proximity of steel mill site can influence inflammatory and vascular mechanisms. Use of mask and multiple biomarker data can be valuable in gaining insight into source emission-related health impacts.

     

Combustion of coal-water suspensions

Combustion technologies using coal-water suspensions create a number of new possibilities for organising combustion processes so that they fulfil contemporary requirements (e.g., in terms of the environment protection-related issues). Therefore, an in-depth analysis is necessary for examining the technical applications of coal in the form of a suspension as a fuel. The paper undertakes the complex study of coal-water suspension combustion in air and in the fluidised beds. This, according to the author, best simulates the conditions that should be satisfied in order to use the new “fuel” efficiently and ecologically. An important element of the study was the identification of coal-water suspension drops, its complex morphology and evolution in the combustion process. The mathematical model enables the prognosis for change of the surface and the centre temperatures and a mass loss of the coal-water suspension during combustion in air and in the fluidised bed.     

Selective Catalytic Oxidation (SCO) of Ammonia to Nitrogen over Hydrotalcite Originated Mg–Cu–Fe Mixed Metal Oxides

Abstract  

Mg–Cu–Fe oxide systems, obtained from hydrotalcite-like precursors, were tested as catalysts for the selective catalytic oxidation (SCO) of ammonia. Copper containing catalysts were active in low-temperature SCO processes; however, their selectivity to nitrogen significantly decreased at higher temperatures. The optimum composition of the catalyst to guarantee high activity and selectivity to N₂ was proposed. Temperature-programmed experiments, SCO catalytic tests performed with various contact times and additional tests on the samples in the selective catalytic reduction of NO with ammonia showed that the SCO process over the studied calcined hydrotalcites proceeds according to the internal SCR mechanism and oxidation of ammonia to NO is a rate-determining step in the low-temperature range.     

Recombinant cytokines from plants

Plant-based platforms have been successfully applied for the last two decades for the efficient production of pharmaceutical proteins. The number of commercialized products biomanufactured in plants is, however, rather discouraging. Cytokines are small glycosylated polypeptides used in the treatment of cancer, immune disorders and various other related diseases. Because the clinical use of cytokines is limited by high production costs they are good candidates for plant-made pharmaceuticals. Several research groups explored the possibilities of cost-effective production of animal cytokines in plant systems. This review summarizes recent advances in this field.     

Properties of Li4Ti5O12 as an anode material in non-flammable electrolytes

Two non-flammable electrolytes 1 M LiPF₆ in sulfolane (TMS) + 5 wt% VC and 0.7 M lithium bis(trifluoromethanesulphonyl)imide (LiNTf₂) in N-methyl-N-propylpyrrolidinium bis(trifluoromethanesulphonyl)imide (MePrPyrNTf₂) + 10 wt% gamma-butyrolactone (GBL) were tested with Li₄Ti₅O₁₂ (LTO) as highly promising anode material for application in lithium-ion batteries. The results were compared for the titanium anode in the classic electrolyte: 1 M LiPF₆ in propylene carbonate + dimethyl carbonate (PC + DMC, 1:1). The performances of LTO/electrolyte/Li cell were tested using cyclic voltammetry, electrochemical impedance spectroscopy, and galvanostatic charge/discharge and scanning electron microscopy (SEM). SEM images of electrodes and those taken after electrochemical cycling showed changes which may be interpreted as a result of solid-state interface formation. Good charge/discharge capacities and low capacity loss at medium C rates preliminary cycling was obtained for the Li₄Ti₅O₁₂ anode. For LTO/1 M LiPF₆ in PC + DMC/Li system, the best capacity was obtained at C/10 and C/3 (145 and 154 mAh g^?1, respectively). In the case of a system working on the basis of a TMS solution (1 M LiPF₆ in TMS + 5 wt% VC) the best value was obtained at a C/5 current and an average of more than 150 mAh g^?1 (86 % of theoretical capacity). For the 0.7 M LiNTf₂ in MePrPyrNTf₂ + 10 wt% GBL electrolyte, the highest capacitance value (at C/20 current) of about 150 mAh g^?1 was observed. The 1 M LiPF₆ in TMS + 5 wt% VC and 0.7 M LiNTf₂ in MePrPyrNTf₂ + 10 wt% GBL electrolytes had a relatively broad thermal stability range and no decomposition peak was observed below 150 °C.