Low-Density Lipoproteins Increase Proliferation, Invasion, and Chemoresistance via an Exosome Autocrine Mechanism in MDA-MB-231 Chemoresistant Cells.

Dyslipidemias involving high concentrations of low-density lipoproteins (LDLs) increase the risk of developing triple-negative breast cancer (TNBC), wherein cholesterol metabolism and protein translation initiation mechanisms have been linked with chemoresistance. Doxorubicin (Dox) treatment, a member of the anthracycline family, represents a typical therapeutic strategy; however, chemoresistance remains a significant challenge. Exosomes (Exs) secreted by tumoral cells have been implicated in cell communication pathways and chemoresistance mechanisms; the content of exosomes is an outcome of cellular cholesterol metabolism.

Inhibitory Activity of 4-Benzylidene Oxazolones Derivatives of Cinnamic Acid on Human Acetylcholinesterase and Cognitive Improvements in a Mouse Model.

We synthesized seven ()-benzylidene-2-()-styryloxazol-5(4)-ones derivatives of cinnamic acid and evaluated the ability of these compounds to inhibit human acetylcholinesterase (hAChE). The most potent compound was evaluated for cognitive improvement in short-term memory. The seven compounds reversibly inhibited the hAChE between 51 and 75% at 300 μM, showed an affinity () from 2 to 198 μM, and an IC from 9 to 246 μM.

Synthesis of Aza-BODIPYs, Their Differential Binding for Cu(II), and Results of Bioimaging as Fluorescent Dyes of Langerhans β-Cells.

Cellular labeling through the use of dyes is of great interest to the biomedical sciences for the characterization of the location and distribution of biomolecules and also for the tracking of the course of biological processes in both health and illness. This paper reports the synthesis, characterization, and subsequent evaluation as metal sensors and cell staining probes of four aza-BODIPY compounds [herein referred to as ()]. Compounds () were found to display an outstanding selectivity for Cu(II) because their emission band at 720 nm was progressively quenched by this metal, presenting fluorescence quenching between 75 and 95%.

Lipid Modulation in the Formation of β-Sheet Structures. Implications for De Novo Design of Human Islet Amyloid Polypeptide and the Impact on β-Cell Homeostasis.

Human islet amyloid polypeptide (hIAPP) corresponds to a 37-residue hormone present in insulin granules that maintains a high propensity to form β-sheet structures during co-secretion with insulin. Previously, employing a biomimetic approach, we proposed a panel of optimized IAPP sequences with only one residue substitution that shows the capability to reduce amyloidogenesis. Taking into account that specific membrane lipids have been considered as a key factor in the induction of cytotoxicity, in this study, following the same design strategy, we characterize the effect of a series of lipids upon several polypeptide domains that show the highest aggregation propensity.

Functional Display of an Amoebic Chitinase in Escherichia coli Expressing the Catalytic Domain of EhCHT1 on the Bacterial Cell Surface.

Poor solubility is the main drawback of the direct industrial exploitation of chitin, the second most abundant biopolymer after cellulose. Chemical methods are conventional to solubilize chitin from natural sources. Enzymatic hydrolysis of soluble chitinous substrates is a promising approach to obtain value-added by-products, such as N-acetylglucosamine units or low molecular weight chito-oligomers.

Preparation of Polymeric Films of PVDMA-PEI Functionalized with Fatty Acids for Studying the Adherence and Proliferation of Langerhans β-Cells.

This study reports the synthesis of thin polymeric films by the layer-by-layer deposition and covalent cross-linking of polyvinyl dimethylazlactone and polyethylene imine, which were functionalized with lauric (12-C), myristic (14-C), and palmitic (16-C) saturated fatty acids, whose high levels in the bloodstream are correlated with insulin resistance and the potential development of type 2 diabetes mellitus. Aiming to assess the effect of the fatty acids on the adhesion and proliferation of Langerhans β-cells, all prepared films (35 and 35.5 bilayers with and without functionalization with the fatty acids) were characterized in terms of their physical, chemical, and biological properties by a battery of experimental techniques including H and C NMR, mass spectrometry, attenuated total reflectance-Fourier transform infrared spectroscopy, field emission scanning electron microscopy, atomic force microscopy, cell staining, and confocal laser scanning microscopy among others.

Bis-quaternary ammonium gemini surfactants for gene therapy: Effects of the spacer hydrophobicity on the DNA complexation and biological activity.

Gemini surfactants (GS) have been highlighted as attractive gene carriers for a few years now; however, key aspects of the role of the GS chemical structure on the DNA-GS complexation and subsequent biological activity remain to be determined. Aiming to elucidate the effects of the GS spacer hydrophobicity, this work was focused on the biophysical characterization of the self-assembly, DNA complexation, cytocompatibility, and DNA transfection of a series of bis-quaternary ammonium GS with fixed side alkyl chains of 14 carbons and varying head-to-head alkyl chain spacers of 4, 6, and 14 carbons (referred to as GS4, GS6, and GS14, respectively). The characterization was carried out by a battery of experimental techniques including UV-vis and fluorescence sprectroscopies, ζ potential, dynamic light scattering (DLS), isothermal titration calorimetry (ITC), and flow cytometry, among others.

Photocrosslinked Alginate-Methacrylate Hydrogels with Modulable Mechanical Properties: Effect of the Molecular Conformation and Electron Density of the Methacrylate Reactive Group.

Hydrogels for load-bearing biomedical applications, such as soft tissue replacement, are required to be tough and biocompatible. In this sense, alginate-methacrylate hydrogels (H-ALGMx) are well known to present modulable levels of elasticity depending on the methacrylation degree; however, little is known about the role of additional structural parameters. In this work, we present an experimental-computational approach aimed to evaluate the effect of the molecular conformation and electron density of distinct methacrylate groups on the mechanical properties of photocrosslinked H-ALGMx hydrogels.

Fatty Acid and Lipopolysaccharide Effect on Beta Cells Proteostasis and its Impact on Insulin Secretion.

Metabolic overload by saturated fatty acids (SFA), which comprises β-cell function, and impaired glucose-stimulated insulin secretion are frequently observed in patients suffering from obesity and type 2 diabetes mellitus. The increase of intracellular Ca triggers insulin granule release, therefore several mechanisms regulate Ca efflux within the β-cells, among others, the plasma membrane Ca-ATPase (PMCA). In this work, we describe that lipotoxicity mediated mainly by the saturated palmitic acid (PA) (16C) is associated with loss of protein homeostasis (proteostasis) and potentially cell viability, a phenomenon that was induced to a lesser extent by stearic (18C), myristic (14C) and lauric (12C) acids.

Modulation of Amyloidogenesis Controlled by the C-Terminal Domain of Islet Amyloid Polypeptide Shows New Functions on Hepatocyte Cholesterol Metabolism.

The islet amyloid polypeptide (IAPP) or amylin maintains a key role in metabolism. This 37-residues-peptide could form pancreatic amyloids, which are a characteristic feature of diabetes mellitus type 2. However, some species do not form amyloid fibril structures.

Soluble expression of an amebic cysteine protease in the cytoplasm of Escherichia coli SHuffle Express cells and purification of active enzyme.

Background: Recombinant production of amebic cysteine proteases using Escherichia coli cells as the bacterial system has become a challenging effort, with protein insolubility being the most common issue. Since many of these enzymes need a native conformation stabilized by disulfide bonds, an elaborate process of oxidative folding is usually demanded to get a functional protein. The cytoplasm of E.

Synthesis and antioxidant evaluation of enantiomerically pure bis-(1,2,3-triazolylmethyl)amino esters from modified α-amino acids.

The efforts for synthesis of enantiomerically pure bis-(1,2,3-triazolylmethyl)amino esters 6 are reported in good yields from an in situ generated α-azidomethyl ketone. Optimum experimental conditions were established for preparation of α-halomethyl ketones 10 and α-N,N-dipropargylamino esters 11, all derived from α-amino acids. The starting materials reacted under conventional click chemistry conditions, revealing a specific reactivity of bromomethyl ketones over chloromethyl ketones.

1-Benzyl-4-(naphthalen-1-yl)-1H-1,2,3-triazole.

In the title compound, C(19)H(15)N(3), the benzyl group is almost perpendicular to the triazole ring [dihedral angle = 80.64 (8)°], while the napthyl group makes an angle of 30.27 (12)° with the plane of the triazole ring.

Study of the stabilization of zinc phthalocyanine in sol-gel TiO2 for photodynamic therapy applications.

Photodynamic therapy (PDT) has emerged as an alternative and promising noninvasive treatment for cancer. It is a two-step procedure that uses a combination of molecular oxygen, visible light, and photosensitizer (PS) agents; phthalocyanine (Pc) was supported over titanium oxide but has not yet been used for cell inactivation. Zinc phthalocyanine (ZnPc) molecules were incorporated into the porous network of titanium dioxide (TiO(2)) using the sol-gel method.

Preparation of a library of EDTA amide x-aminenaphthalene-y-sulfonic acid derivatives on solid phase and their fluorescence behavior toward transition metals.

In this work, we report the synthesis of a combinatorial library of 80 derivatives of EDTA amide x-aminenaphthalene-y-sulfonic acid on four different supports with variable length linker. The sensing fluorescence behavior of these materials for transitions metals was studied by packing the beads into a conventional flow-through cell in a continuous flow injection set up. The fluorescence emission response of these materials shows that sensors supported in Argopore (a) with the fluorescence moiety of 1-aminenaphthalene-4-sulfonic acid behaves like dosimeter for copper.

Alkylation of 2,4-(1H,3H)-quinazolinediones with dialkyl carbonates under microwave irradiations.

Alkylation is a very important chemical reaction which modifies the biological properties of drugs. Quinazolinedione derivatives are of considerable interest due to their wide array of pharmacological properties.We now report application of a practical alkylation procedure to several quinazolinediones, including pelanserine (5f), which shows antihypertensive properties, 1-methyl-3-(2'-phenylethyl)-1H,3H-quinazoline-2,4-dione (1ab) and 1-methyl-3-[2'-(4'-methoxyphenyl)ethyl]-lH,3H-quinazoline-2,4-dione (1ae), which had been isolated from natural sources.

Totally selective synthesis of enantiopure (3S,5S)- and (3R,5R)-4-amino-3,5-dihydroxypiperidines from aminodiepoxides derived from serine.

The transformation of enantiopure (2R,4R)- and (2S,4S)-N,N-dibenzyl-1,2:4,5-diepoxypentan-3-amine, 1 and 2, into the corresponding enantiopure (3S,5S)- and (3R,5R)-3,5-dihydroxy-3-aminopiperidines, 3 and 4 respectively, is described. The opening of the two epoxide rings with a range of amines takes place with total regioselectivity and high yields, in the presence of LiClO4. A mechanism to explain this transformation is proposed.

Synthesis of metallothionein-mimic decapeptides with heavy atom signaling properties.

The automated parallel solid-phase synthesis of a 17-member library of metallothionein-mimic decapeptides carrying a Lariat ether group is described. The peptides were synthesized in good yield and the identity and quality of each product were performed by mass spectrometry and IR. Subsequently, in the presence of europium(III) ions as fluorescent reporter, each compound was screened, both attached to the resin and cleaved off, for their sensing behavior towards metal ions (Cd(2+),Hg(2+), Cu(2+), Mg(2+) and Ca(2+)) using fluorimetric techniques.

Synthesis of chiral amino epoxyaziridines: useful intermediates for the preparation of chiral trisubstituted piperidines.

Chiral aminoalkyl epoxyaziridine 1 is synthesized in high yield and diastereoselectivity from L-serine. Ring opening of epoxyaziridine 1 with primary amines is carried out with total chemo- and regioselectivity, affording chiral polyfunctionalized piperidines 8. The structure of these trisubstituted piperidines is established by NMR studies.