Searching for the protein targets of bioactive molecules

The identification of all protein targets of a given drug or bioactive molecule within the human body is a prerequisite for an understanding of its beneficial and deleterious activities. Current approaches to reveal protein targets often fail to reveal physiologically relevant interactions. Here we review a recently introduced yeast-based approach for the identification of the binding partners of small molecules. We discuss the advantages and limitations of the approach using the clinically approved drug sulfasalazine as an example.     

Deactivation of a Ni-Based Reforming Catalyst During the Upgrading of the Producer Gas, from Simulated to Real Conditions

The deactivation of a nickel reforming catalyst during the upgrading of the producer gas obtained by gasification of lignocellulosic biomass was studied. The research involved several steps: the selective deactivation of the catalyst in a laboratory scale; the streaming of the catalyst with the producer gas of a downdraft and an oxygen/steam circulating fluidized bed (CFB) gasifier; and tests in a reformer placed in a slipstream of the CFB gasifier. The information obtained allowed to elucidate the catalyst deactivation mechanisms taking place during the reforming of the producer gas: physical deactivation by deposition of fine ashes, aerosol particulate or carbon; poisoning by H₂S and HCl present in the gas phase and thermal sintering because of the high operation temperatures required to avoid the chemical deactivation. These physical and chemical effects depended on the composition of the biomass fuel.     

Characterization of Crude Watermelon Seed Oil by Two Different Extractions Methods

The aim of this paper was to study the physical–chemical composition of the watermelon seed oil extracted by a mechanical process using an expeller and by a chemical process using hexane as the solvent. The watermelon seed oil had a high concentration of unsaturated fatty acids. The two primary sterols were stigmasterol and β-sitosterol, which corresponded to approximately 47 and 30% of the total phytosterols. The oil had a low tocopherol content (65.19 mg/kg for S and 73.19 mg/kg for E). Comparing the two extraction methods, extraction by expeller produced an oil of superior quality with respect to oxidative stability, carotenoids and Lovibond color. No significant differences were found between the two extraction methods with respect to the minor components of the oil considered as functional, such as phytosterols.     

Synthesis of layered MCM-22(P) in the presence of hexamethonium cations and its transformation into EUO- and MWW-type zeolites

Layered MCM-22(P) was synthesized in the presence of hexamethonium (HM) cations. Compared to zeolite EU-1 (EUO-type structure), which crystallizes in similar conditions, its formation is favored at high HM concentrations (HM/SiO₂ ≥ 0.3) and in the absence of Na₂O. HM-containing MCM-22(P) was used as starting material for zeolite formation. Upon hydrothermal treatment, HM-MCM-22(P) transforms into zeolite EU-1 and upon calcination into a MWW-type zeolite. Transformation mechanisms were studied by standard characterization techniques such as XRD, SEM and TEM. Catalytic properties of the MWW-type zeolite obtained from this precursor were evaluated in a m-xylene isomerization reaction. Compared to zeolite MCM-22 prepared with hexamethyleneimine, a higher catalytic activity and an increased isomerization selectivity were observed and discussed.     

Nanocomposites derived from cellulose acetate and highly branched alkoxysilane

Highly branched alkoxysilane (HB) units were prepared in situ via a Michael‐type reaction between pentaerythrithol triacrylate and aminopropyltriethoxysilane. These units were used as an inorganic component for the modification of cellulose acetate (CA) films using the sol–gel process. The thermal and dynamic‐mechanical behaviors, the morphology, and the dimensional stability of the modified CA films were analyzed. The siloxane‐modified CA films showed thermal stability similar to pure CA, but the residue content at 900°C increased with the addition of HB units. The morphology of these films was characterized by siloxane nanodomains dispersed in the CA matrix, with good interfacial adhesion between the phases. Moreover, the CA/siloxane nanocomposite films showed improved dimensional stability in comparison with CA, i.e., in the presence of HB, the dimensional change was reduced to around 50% of the value observed for pure CA. Finally, a complex dynamic‐mechanical behavior was obtained for the nanocomposite films, as a consequence of the heterogeneous morphology. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Synthesis,characterization, and degradation of block polyesteramides containing poly(L-lactide) segments

Random multiblock polyesteramides (PEAs) having polyester (PE) content of 20–50 wt % have been prepared by low-temperature polycondensation using sebacoyl chloride, 1,6-diaminohexane, and telechelic oligomers of L-lactide with M_n = 600–1500. The PEAs were characterized by IR and ¹H-NMR spectroscopy, wide-angle X-ray diffraction, and thermal analysis. Only the polyamide segments are able to crystallize, and the crystallinity depends on the composition and architecture of the PEAs. From viscosity and IR measurements it was established that the chain degradation of PEA powders or films suspended in buffer solutions occurs by hydrolysis of the ester linkages. The degradation rate is influenced by pH, PE content, and, to a lesser extent, by crystallinity. © 1992 John Wiley & Sons, Inc.     

Photoconductivity and photoluminescence under bias in GaInNAs/GaAs MQW p-i-n structures

The low temperature photoluminescence under bias (PLb) and the photoconductivity (PC) of a p-i-n GaInNAs/GaAs multiple quantum well sample have been investigated. Under optical excitation with photons of energy greater than the GaAs bandgap, PC and PLb results show a number of step-like increases when the sample is reverse biased. The nature of these steps, which depends upon the temperature, exciting wavelength and intensity and the number of quantum wells (QWs) in the device, is explained in terms of thermionic emission and negative charge accumulation due to the low confinement of holes in GaInNAs QWs. At high temperature, thermal escape from the wells becomes much more dominant and the steps smear out.     

Visceral Obesity and Its Shared Role in Cancer and Cardiovascular Disease: A Scoping Review of the Pathophysiology and Pharmacological Treatments

The association between obesity, cancer and cardiovascular disease (CVD) has been demonstrated in animal and epidemiological studies. However, the specific role of visceral obesity on cancer and CVD remains unclear. Visceral adipose tissue (VAT) is a complex and metabolically active tissue, that can produce different adipokines and hormones, responsible for endocrine-metabolic comorbidities. This review explores the potential mechanisms related to VAT that may also be involved in cancer and CVD. In addition, we discuss the shared pharmacological treatments which may reduce the risk of both diseases. This review highlights that chronic inflammation, molecular aspects, metabolic syndrome, secretion of hormones and adiponectin associated to VAT may have synergistic effects and should be further studied in relation to cancer and CVD. Reductions in abdominal and visceral adiposity improve insulin sensitivity, lipid profile and cytokines, which consequently reduce the risk of CVD and some cancers. Several medications have shown to reduce visceral and/or subcutaneous fat. Further research is needed to investigate the pathophysiological mechanisms by which visceral obesity may cause both cancer and CVD. The role of visceral fat in cancer and CVD is an important area to advance. Public health policies to increase public awareness about VAT’s role and ways to manage or prevent it are needed.     

Design and characterization of PNVCL-based nanofibers and evaluation of their potential applications as scaffolds for surface drug delivery of hydrophobic drugs

In this work, nanofiber scaffolds for surface drug delivery applications were obtained by electrospinning poly(N-vinylcaprolactam) (PNVCL) and its blends with poly(ε-caprolactone) and poly(N-vinylcaprolactam)-b-poly(ε-caprolactone). The process parameters to obtain smooth and beadless PNVCL fibers were optimized. The average fibers diameter was less than 1 μm, and it was determined by scanning electron microscopy analyses. Their affinity toward water was evaluated by measuring the contact angle with water. The ketoprofen release behavior from the fibers was analyzed using independent and model-dependent approaches. The low values of the release exponent (n < 0.5) obtained for 20 and 42 °C, indicating a Fickian diffusion mechanism for all formulations. Dissolution efficiencies (DEs) revealed the effect of polymer composition, methodology used in the electrospinning process, and temperature on the release rate of ketoprofen. PNVCL/poly(N-vinylcaprolactam)-b-poly(ε-caprolactone)-based nanofibers showed greater ability to control the in vitro release of ketoprofen, in view of reduced kinetic constant and DE, making this material promising system for controlling release of hydrophobic drugs. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48472.     

Copper(I/II), α/β‐Synuclein and Amyloid‐β: Menage à Trois?

Copper binding to α‐synuclein (aS) and to amyloid‐β (Ab) has been connected to Parkinson's and Alzheimer's disease (AD), respectively, because Cu ions can modulate the peptide aggregation, and these Cu ? peptide complexes can catalyse the production of reactive oxygen species (ROS). In a significant proportion of AD brains, aggregation of aS and Ab has been detected, and it was proposed that Ab and aS interact with each other. Thus, we investigated the potential interactions of Ab and aS through their binding of copper(I) and copper(II). Additionally, β‐synuclein (bS) was investigated, due to its additional methionine residue, a potential Cu^I ligand. We found that: 1) the peptides containing the Cu‐binding domains Ab1–16, aS1–15 and bS1–15 have similar affinities towards Cu^II and towards Cu^I, with Ab1–16 being slightly stronger, 2) in the case of Cu^I, the additional Met residue in bS1–15 increased the affinity slightly, 3) the exchange of Cu^I/II between the two peptides is rapid (≤ms), 4) a/bS1–15 and Ab1–16 form a heterodimeric complex with Cu^II, 5) Cu^I probably promotes a transient ternary complex, 6) the different Cu^I/II coordination of Ab1–16, aS1–15 and bS1–15 impacts the capacity to produce ROS and to oxidise catechol, and 7) when Ab1–16, aS1–15 and Cu are present, the ROS production more closely resembles that by Ab1–16. The work gives insights into the coordination chemistry of these related peptides, and the relevance of coordination differences, the ternary complex and ROS production are discussed.