Cellular and Molecular Signatures of Oxidative Stress in Bronchial Epithelial Cell Models Injured by Cigarette Smoke Extract

Exposure of the airways epithelium to environmental insults, including cigarette smoke, results in increased oxidative stress due to unbalance between oxidants and antioxidants in favor of oxidants. Oxidative stress is a feature of inflammation and promotes the progression of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). Increased oxidative stress leads to exhaustion of antioxidant defenses, alterations in autophagy/mitophagy and cell survival regulatory mechanisms, thus promoting cell senescence. All these events are amplified by the increase of inflammation driven by oxidative stress. Several models of bronchial epithelial cells are used to study the molecular mechanisms and the cellular functions altered by cigarette smoke extract (CSE) exposure, and to test the efficacy of molecules with antioxidant properties. This review offers a comprehensive synthesis of human in-vitro and ex-vivo studies published from 2011 to 2021 describing the molecular and cellular mechanisms evoked by CSE exposure in bronchial epithelial cells, the most used experimental models and the mechanisms of action of cellular antioxidants systems as well as natural and synthetic antioxidant compounds.     

PET Recycling – Contributions of Crystallization to Sustainability

Polyethylene terephthalate (PET) is one of the most common thermoplastic polymers and its durability has become a major environmental concern. The current public debate on plastic debris also triggered the revision of PET recycling technologies. This Research Article focuses on the chemical recycling of PET by means of methanolysis. The process degrades PET into two main reaction products, dimethyl terephthalate (DMT) and ethylene glycol (EG). Subsequent separation by distillation combined with crystallization removes critical impurities and non-PET components from co-polymers, providing monomers of high purity needed for re-polymerization purposes.     

Amine-impregnated natural zeolite as filler in mixed matrix membranes for CO2/CH4 separation

Flat mixed matrix membranes (MMMs) comprising polysulfone and clinoptilolite-type natural zeolite were prepared by casting. Zeolite was modified with three alkylamines: ethanolamine (EA), bis(2-hydroxypropyl)amine (BHPA), and polyethylenimine (PEI) by the impregnation method. Impregnated zeolite samples were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, and N₂ adsorption–desorption. The alkylamine loading extent determined by thermogravimetric analysis was 5.2, 4.8, and 8.5% for EA, BHPA, and PEI, respectively. Analyses of MMMs showed that the incorporation of impregnated zeolite affected the glass-transition temperature (T_g) and mixed-gas transport properties. In this regard, a decreasing trend of the T_g values from 185.5 °C for the polymeric membrane up to 176.6 °C for Clino-EA-based MMM was recorded. In addition, the gas separation performance was evaluated at two different feed pressures. At 50 psi, MMMs showed an enhancement up to 30% on the CO₂ permeability (22.79 Barrer) and 55% on the CO₂/CH₄ selectivity (45.78) in comparison with the polymeric membrane (CO₂ permeability 17.34 Barrer; CO₂/CH₄ selectivity 29.38). These values varied depending on the alkylamine, BHPA being the most selective. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48286.     

New WS9326A Derivatives and One New Annimycin Derivative with Antimalarial Activity are Produced by Streptomyces asterosporus DSM 41452 and Its Mutant

In this study, we report that Streptomyces asterosporus DSM 41452 is a producer of new molecules related to the nonribosomal cyclodepsipeptide WS9326A and the polyketide annimycin. S. asterosporus DSM 41452 is shown to produce six cyclodepsipeptides and peptides, WS9326A to G. Notably, the compounds WS9326F and WS9326G have not been described before. The genome of S. asterosporus DSM 41452 was sequenced, and a putative WS9326A gene cluster was identified. Gene‐deletion experiments confirmed that this cluster was responsible for the biosynthesis of WS9326A to G. Additionally, a gene‐deletion experiment demonstrated that sas16 encoding a cytochrome P450 monooxygenase was involved in the synthesis of the novel (E)‐2,3‐dehydrotyrosine residue found in WS9326A and its derivatives. An insertion mutation within the putative annimycin gene cluster led to the production of a new annimycin derivative, annimycin B, which exhibited modest inhibitory activity against Plasmodium falciparum.     

Cuticular Hydrocarbons as Sex Pheromone of the Bee <Emphasis Type="Italic">Colletes cunicularius</Emphasis> and the Key to its Mimicry by the Sexually Deceptive Orchid, <Emphasis Type="Italic">Ophrys exaltata</Emphasis>

Male Colletes cunicularius bees pollinate the orchid, Ophrys exaltata, after being sexually deceived by the orchid’s odor-mimicry of the female bee’s sex pheromone. We detected biologically active volatiles of C. cunicularius by using gas chromatographic–electroantennographic detection (GC-EAD) with simultaneous flame ionization detection. After identification of the target compounds by coupled gas chromatography–mass spectrometry (GC-MS), we performed behavioral tests using synthetic blends of the active components. We detected 22 EAD active compounds in cuticular extracts of C. cunicularius females. Blends of straight chain, odd-numbered alkanes and (Z)-7-alkenes with 21–29 carbon atoms constituted the major biologically active compounds. Alkenes were the key compounds releasing mating behavior, especially those with (Z)-7 unsaturation. Comparison of patterns of bee volatiles with those of O. exaltata subsp. archipelagi revealed that all EAD-active compounds were also found in extracts of orchid labella. Previous studies of the mating behavior in C. cunicularius showed linalool to be an important attractant for patrolling males. We confirmed this with synthetic linalool but found that it rarely elicited copulatory behavior, in accordance with previous studies. A blend of active cuticular compounds with linalool elicited both attraction and copulation behavior in patrolling males. Thus, linalool appears to function as a long-range attractant, whereas cuticular hydrocarbons are necessary for inducing short-range mating behavior.     

Thermal stability of polymers based on acrylamide and 2-acrylamido-2-methylpropane sulfonic acid in different temperature and salinity conditions

Partially hydrolyzed polyacrylamide (PHPA) is the most widely used polymer in enhanced oil recovery (EOR) applications. However, under conditions of high temperature and salinity, the PHPA molecules become hydrolyzed, causing a drastic reduction of the viscosity of the polymer solution due to the presence of negative charges, making the molecules more susceptible to interactions with cations. In this sense, in order to increase the stability of these polymers, an anionic monomer more resistant to cations such as 2-acrylamido-2-methylpropane sulfonic acid (AMPS) has been incorporated into the HPAM molecules. This work evaluated the thermal stability of a copolymer (acrylamide and AMPS - AN125) and a terpolymer (acrylamide, acrylate, and AMPS-FP5115) in the time course of 360 days. The tests were carried out in typical conditions of Brazilian offshore reservoirs, such as absence of oxygen, high temperature, and high salt concentration. The test method involved measurements of intrinsic viscosity in function of time and determination of the hydrolysis degree of the polymers by elemental analysis. The copolymer AN125 was more stable under the test conditions than the terpolymer FP 5115 due to the presence of a higher concentration of AMPS in the copolymer. The AMPS group was hydrolyzed to AA at a temperature of 100 °C, however, the increase in salt concentration delayed the onset of this degradation. The tests indicated that the presence of a higher AMPS content in the copolymer does not prevent the polymer from undergoing hydrolysis, but delays the polymer precipitation step in the solution.     

Microwave-Assisted Synthesis of Phenothiazine and Quinoline Derivatives

Application of a dynamic microwave power system in the chemical synthesis of some phenothiazine and quinoline derivatives is described. Heterocyclic ring formation, aromatic nucleophilic substitution and heterocyclic aldehydes/ketones condensation reactions were performed on solid support, or under solvent free reaction conditions. The microwave-assisted Duff formylation of phenothiazine was achieved. Comparison of microwave-assisted synthesis with the conventional synthetic methods demonstrates advantages related to shorter reaction times and in some cases better reaction yields.     

Peptide Bioconjugates of Electron‐Poor Metallocenes: Synthesis,Characterization, and Anti‐Proliferative Activity

We report the synthesis of metallocene compounds Cp₂M with two different electron‐withdrawing substituents on both cyclopentadienyl rings (hexafluoroacetone (HFA) and chlorobenzoyl ( 1 – 5 ); HFA and COOH ( 6 and 7 ), M=Fe or Ru). The COOH‐containing derivatives were used to synthesize peptide bioconjugates with enkephalin ( 8 and 9 ) and neurotensin ( 10 and 11 ) as well as fluorescein‐labeled neurotensin ( 12 ). All the molecules were fully characterized, including X‐ray structures for 6 and 7 . The physicochemical properties (lipophilicity and electrochemistry) and cytotoxicity on MCF‐7, HT‐29, and PT‐45 cancer cells were evaluated for selected compounds. Electrochemical investigation by cyclic voltammetry revealed that all bis‐substituted metallocenes are up to 300 mV harder to oxidize compared to the monosubstituted 2‐ferrocenylhexafluoropropan‐2‐ol (FcHFA: Δ${E{{{\rm f}\hfill \atop 0\hfill}}}$ =214 mV; disubstituted derivatives: up to Δ${E{{{\rm f}\hfill \atop 0\hfill}}}$ =512 mV; both vs. FcH^0/+). For the bis‐substituted compounds, log P determinations by RP‐HPLC showed increased lipophilicity in comparison to the monosubstituted FcHFA and RcHFA. Cellular uptake was investigated by fluorescence microcopy, and this revealed endosomal entrapment for 12 .     

Binding Mode and Structure–Activity Relationships around Direct Inhibitors of the Nrf2–Keap1 Complex

An X‐ray crystal structure of Kelch‐like ECH‐associated protein (Keap1) co‐crystallised with (1S,2R)‐2‐[(1S)‐1‐[(1,3‐dioxo‐2,3‐dihydro‐1H‐isoindol‐2‐yl)methyl]‐1,2,3,4‐tetrahydroisoquinolin‐2‐carbonyl]cyclohexane‐1‐carboxylic acid (compound (S,R,S)‐ 1 a ) was obtained. This X‐ray crystal structure provides breakthrough experimental evidence for the true binding mode of the hit compound (S,R,S)‐ 1 a , as the ligand orientation was found to differ from that of the initial docking model, which was available at the start of the project. Crystallographic elucidation of this binding mode helped to focus and drive the drug design process more effectively and efficiently.     

Untersuchungen zum Transfer pharmakologisch wirksamer Substanzen aus der Nutztierhaltung in Porree und Weißkohl

Investigation on the transfer of pharmacologically active substances used in animal husbandry into leek and cabbage. The potential of leek and cabbage for uptake of highly prescribed veterinary drugs (antibiotics) was tested in hydroponically grown plants. For this purpose the antibiotics sulfadiazine (SFD), enrofloxacine (ENR), tetracycline (TC), chlortetracycline (CTC) and monensine (MON) were chosen. A further aim was to gain data on the situation of vegetables grown in agricultural practise with regard to antibiotic residues. The evident effects of the antibiotics on plants grown hydroponically (each antibiotic was administered at 5 μmol/l nutrient solution) were greatly different: With regard to leek there were no visible effects (MON, SFD), a weak bleaching of the younger leaf sections (CTC), and strong effects of ENR. The (phytotoxic) effects of antibiotics on cabbage were much more distinct. CTC caused a yellowing of the plant vasculature in cabbage. MON induced lesions on some leaves and finally led to leaf wilting. With administration of ENR a nearly complete bleaching of young leaves was observed. Using LC-MS/MS-methods (low-resolution and high-resolution MS) the administered antibiotics, as well as conversion products and metabolites, were separately identified and quantified in various organs of leek (roots, young and old sections of leaves) and cabbage (roots, stalks, young and old leaves). Depending on the type of antibiotic, vegetable species, and plant organ, the detected concentrations of antibiotic residues comprised several orders of magnitude ranging from μg/kg to mg/kg of fresh weight (fw). The highest concentrations of antibiotics were found in roots of both vegetable species: CTC and TC were detected at approximately 10 mg/kg fw in cabbage roots and at approximately 20 mg/kg fw in leek roots and ENR was determined at approximately 12 mg/kg fw in cabbage roots. Low amounts of ENR were metabolised to ciprofloxacine (CIP). ENR occurred at similar concentrations of approximately 7 mg/kg fw in roots and old leaves of cabbage, indicating a high transport rate of this antibiotic in the cabbage plant. In stalks, young and old leaves of cabbage and in young and old leaf sections of leek all administered antibiotics were detected. Within these antibiotics, ENR and CTC and their conversion products, e. g. demeclocycline (DMC) and TC, occurred at the highest concentrations. SFD and MON were found in considerably lower concentrations (<100 μg/kg fw). The results of our experiments in hydroponic cultures, using defined concentrations of antibiotics in the nutrient solution, evidently demonstrate that cabbage and leek have a very high potential for uptake of a number of veterinary antibiotic drugs, especially for tetracycline and ENR.