Role of Cyclooxygenase-2 in Head and Neck Tumorigenesis

The cyclooxygenase-2 (COX-2) is a potent enzyme that converts arachidonic acid to prostaglandins (PG), including PGE2, a key mediator of inflammation and angiogenesis. Importantly, COX-2 is activated in response to inflammatory stimuli, where it is also believed to promote the development and progression of head and neck cancers (HNC). COX-2 can mediate its protumorigenic effect through various mechanisms, such as inducing cell proliferation, inhibition of apoptosis, and suppressing the host’s immune response. Furthermore, COX-2 can induce the production of vascular endothelial growth factors, hence, promoting angiogenesis. Indeed, the ability of COX-2 inhibitors to selectively restrict the proliferation of tumor cells and mediating apoptosis provides promising therapeutic targets for cancer patients. Thus, in this comprehensive review, we summarized the reported differential expression patterns of COX-2 in different stages of head and neck carcinogenesis—from potentially premalignant lesions to invasive carcinomas. Furthermore, we examined the available meta-analysis evidence for COX-2 role in the carcinogenesis of HNC. Finally, further understanding of the biological processes of COX-2 and its role in orchestrating cell proliferation, apoptosis, and angiogenesis may give therapeutically beneficial insight to develop the management plan of HNC patients and improve their clinical outcomes.     

Radon and moisture impacts from interventions integrated with housing energy retrofits

Energy retrofits can reduce air exchange, raising the concern of whether indoor radon and moisture levels could increase. This pre/post-intervention study explored whether simple radon interventions implemented in conjunction with energy retrofits can prevent increases in radon and moisture levels. Treatment homes (n = 98) were matched with control (no energy retrofits or radon intervention) homes (n = 12). Control homes were matched by geographic location and foundation type. t-tests were used to determine whether post-energy retrofit radon and moisture level changes in treatment homes significantly differed from those in control homes. The radon interventions succeeded in preventing statistically significant increases in first floor radon using arithmetic (p = 0.749) and geometric means (p = 0.120). In basements, arithmetic (p = 0.060) and geometric (p = 0.092) mean radon levels statistically significantly increased, consistent with previous studies which found that basement radon levels may increase even if first floor levels remain unchanged. Changes in infiltration were related to changes in radon (p = 0.057 in basements; p = 0.066 on first floors). Only 58% of the change in infiltration was due to air sealing, with the rest due to weather changes. There was no statistically significant association between air sealing itself and radon levels on the first floor (p = 0.664). Moisture levels also did not significantly increase.     

Vacuum impregnation of chitosan‐based edible coating in minimally processed pumpkin

The goal of this research was to evaluate the use of vacuum impregnation (VI) and soaking techniques (ST) in the application of edible coatings of chitosan and chitosan + lauric acid to minimally processed pumpkins (MPP). The vacuum impregnation method led to greater component incorporation (5.9% and 1.75%, respectively) in the pumpkins when compared to soaking and consequently the formation of more uniform, thicker coatings (25.6 and 22.3 μm, respectively). However, VI caused greater changes in pH, acidity, colour and firmness. Relating to water content and carotenoid content, noncoated pumpkins presented greater losses during the storage period, regardless of impregnation method. The pumpkins with edible coatings, regardless of method, presented lower numbers of psychrotrophic micro‐organisms and coliforms during the storage period. Therefore, soaking was considered the best method for the application of chitosan‐based edible coatings to minimally processed pumpkins, as it led to smaller changes in the properties of the product.     

Phospholipid Cyclosporine Prodrugs Targeted at Inflammatory Bowel Disease (IBD) Treatment: Design,Synthesis, and in Vitro Validation

Novel phospholipid (PL)-cyclosporine conjugates were prepared and studied as potential prodrugs for inflammatory bowel disease (IBD). Our approach relies on phospholipase A₂ (PLA₂), which is overexpressed in the inflamed intestinal tissues, as the prodrug activator to potentially release cyclosporine at the site of inflammation. PL-cyclosporine prodrug conjugates with methylene linkers of various lengths between the sn-2 position of the PL and cyclosporine were synthesized and evaluated for in vitro activation. Surprisingly, despite previous work indicating that conjugates with six methylene linkers between the lipid and drug would suffer rapid enzymatic hydrolysis, with cyclosporine this was not observed. However, compounds with longer linkers (n=10, 12 methylene units) display complete release of the drug by PLA₂-catalyzed hydrolysis, thus demonstrating the importance and profound impact of structural fine-tuning. This study represents a proof-of-concept for our hypothesis and a first step towards a truly targeted IBD treatment with cyclosporine that could be administered throughout the GI tract.     

Differences in seasonal distribution of wild and stocked juvenile lake trout by depth and temperature in Lake Champlain

Lake trout (Salvelinus namaycush) reared in hatcheries are exposed to an environment and feeding regime that is different from wild lake trout, and are stocked at substantially larger sizes with higher lipid reserves. In addition to differences in diet and growth, this early experience may alter habitat use compared to the wild cohort. We used seasonal data on the depth and temperature distribution of wild and stocked juvenile lake trout to test for differences in habitat use and inform sampling strategies to evaluate annual recruitment. Bottom trawling was conducted from 2015 to 2019 in the central basin of Lake Champlain every two to four weeks during the ice-free season. Differences in distribution of wild and stocked lake trout were most pronounced during thermal stratification, when wild juveniles were more abundant than stocked juveniles at shallower depths and warmer temperatures and stocked juveniles were more abundant at deeper depths and colder temperatures. Temperature preferences may be a consequence of different early rearing environments; wild lake trout are acclimated to lake temperatures and forage, whereas stocked fish entered the lake with high lipid content and little foraging experience. Unbiased assessment of the proportion of wild lake trout and growth and survival of the entire juvenile lake trout population using bottom trawl sampling should either take place in the pre- and post-stratification seasons when wild and stocked fish are at the same depths, or include the full range of depths and temperatures that wild and stocked fish occupy during the stratified period.     

Perfluorocarbons in Chemical Biology

Perfluorocarbons, saturated carbon chains in which all the hydrogen atoms are replaced with fluorine, form a separate phase from both organic and aqueous solutions. Though perfluorinated compounds are not found in living systems, they can be used to modify biomolecules to confer orthogonal behavior within natural systems, such as improved stability, engineered assembly, and cell-permeability. Perfluorinated groups also provide handles for purification, mass spectrometry, and ¹⁹F NMR studies in complex environments. Herein, we describe how the unique properties of perfluorocarbons have been employed to understand and manipulate biological systems.     

The Fifth WS/DGAT Enzyme of the Bacterium Marinobacter aquaeolei VT8

Wax esters (WE) belong to the class of neutral lipids. They are formed by an esterification of a fatty alcohol and an activated fatty acid. Dependent on the chain length and desaturation degree of the fatty acid and the fatty alcohol moiety, WE can have diverse physicochemical properties. WE derived from monounsaturated long-chain acyl moieties are of industrial interest due to their very good lubrication properties. Whereas WE were obtained in the past from spermaceti organs of the sperm whale, industrial WE are nowadays mostly produced chemically from fossil fuels. In order to produce WE more sustainably, attempts to produce industrial WE in transgenic plants are steadily increasing. To achieve this, different combinations of WE producing enzymes are expressed in developing Arabidopsis thaliana or Camelina sativa seeds. Here we report the identification and characterization of a fifth wax synthase from the organism Marinobacter aquaeolei VT8, MaWSD5. It belongs to the class of bifunctional wax synthase/acyl-CoA:diacylglycerol O-acyltransferases (WSD). The protein was purified to homogeneity. In vivo and in vitro substrate analyses revealed that MaWSD5 is able to synthesize WE but no triacylglycerols. The protein produces WE from saturated and monounsaturated mid- and long-chain substrates. Arabidopsis thaliana seeds expressing a fatty acid reductase from Marinobacter aquaeolei VT8 and MaWSD5 produce WE. Main WE synthesized are 20:1/18:1 and 20:1/20:1. This makes MaWSD5 a suitable candidate for industrial WE production in planta.     

Yttrium doping of Ba0.5Sr0.5Co0.8Fe0.2O3-δ part II: Influence on oxygen transport and phase stability

Ba_0.5Sr_0.5Co_0.8Fe_0.2O_3-δ (BSCF) in its cubic perovskite phase has attracted much interest for potential use as oxygen transport membrane (OTM) due to its very high oxygen permeability at high temperatures. However, performance degradation due to a sluggish phase decomposition occurs when BSCF is operated below 840?°C. Partial B-site substitution of the transition metal cations in BSCF by larger and redox-stable cations has emerged as a potential strategy to improve the structural stability of cubic BSCF. In this study, the influence of yttrium doping (0…10?mol-%) on oxygen transport properties and stability of the cubic BSCF phase is assessed by in situ electrical conductivity relaxation (ECR) and electrical conductivity measurements during long-term thermal annealing both at 700?°C and 800?°C. Detailed phase analysis is performed by scanning electron microscopy (SEM) after long-term annealing of the samples in air at different temperatures.     

Microscopic investigation of the formation of a thermoset wheat gluten network in a model system relevant for bread making

Although the impact of heat on molecular properties of wheat gluten is well understood, changes in its microstructure have rarely been studied. Here, formation of the thermoset gluten network in a model system relevant for bread baking was studied with confocal laser scanning microscopy and protein network analysis. From 65 °C onwards, gluten converts from thick aligned protein strands in a highly branched and homogeneous network of small thin protein threads. Neither gliadin incorporation in the network nor application of aqualysin 1, the thermo-active serine peptidase from Thermus aquaticus which recently has been reported to hydrolyse gluten proteins in dough only at temperatures exceeding 80 °C, impacts on the gluten microstructure. As starch causes structure setting itself and thereby decreases protein mobility, molecular scale changes in the gluten network at temperatures exceeding 80 °C brought about by aqualysin 1 do not impact its microstructure.