Effect of electrochemical topology on detection sensitivity in MEA assay for drug-induced cardiotoxicity screening.

Cardiotoxicity remains a major challenge in drug development, accounting for 45% of medication withdrawals due to cardiac ischemia and arrhythmogenicity. To overcome the limitations of traditional multielectrode array (MEA)-based cardiotoxicity assays, we developed a Nafion-coated NanoMEA platform with decoupled reference electrodes, offering enhanced sensitivity for electrophysiological measurements. The 'Decoupled' configuration significantly reduced polarization resistance (Rp) from 12.

Maslinic acid solid lipid nanoparticles as hydrophobic anticancer drug carriers: Formulation, in vitro activity and in vivo biodistribution.

Maslinic acid (MA) is a natural pentacyclic triterpenoid with inherent antitumor activity which has a very low solubility in water. MA solid lipid nanoparticles (SLNs) were prepared using Poloxamer 407 and Dicarboxylic acid-Poloxamer 407 as surfactants. Both MA SLNs are monodisperse, with sizes around 130 nm, and stable.

Synthesis, Optical Properties, and Antiproliferative Evaluation of NBD-Triterpene Fluorescent Probes.

A fluorescent labeling protocol for hydroxylated natural compounds with promising antitumor properties has been used to synthesize, in yields of 72-86%, 12 derivatives having fluorescent properties and biological activity. The reagent used for the synthesis of these fluorescent derivatives was 7-nitrobenzo-2-oxa-1,3-diazole chloride (NBD-Cl). The linkers employed to bind the NBD-Cl reagent to the natural compounds were ω-amino acids (Aa) of different chain lengths.

Efficient In Vitro and In Vivo Anti-Inflammatory Activity of a Diamine-PEGylated Oleanolic Acid Derivative.

Recent evidence has shown that inflammation can contribute to all tumorigenic states. We have investigated the anti-inflammatory effects of a diamine-PEGylated derivative of oleanolic acid (OADP), in vitro and in vivo with inflammation models. In addition, we have determined the sub-cytotoxic concentrations for anti-inflammatory assays of OADP in RAW 264.

Synthesis and Biological Activity of Triterpene-Coumarin Conjugates.

A set of 12 maslinic acid-coumarin conjugates was synthesized, with 9 being maslinic acid-diamine-coumarin conjugates at the C-28 carboxylic acid group of triterpene acid and the other three being maslinic acid-coumarin conjugates at C-2/C-3 and/or C-28 of the triterpene skeleton. The cytotoxic effects of these 12 triterpene conjugates were evaluated in three cancer cell lines (B16-F10, HT29, and Hep G2) and compared, respectively, with three nontumor cell lines from the same or similar tissue (HPF, IEC-18, and WRL68). The most potent cytotoxic results were achieved by a conjugate with two molecules of coumarin-3-carboxylic acid coupled through the C-2 and C-3 hydroxy groups of maslinic acid.

A Diamine-PEGylated Oleanolic Acid Derivative Induced Efficient Apoptosis through a Death Receptor and Mitochondrial Apoptotic Pathway in HepG2 Human Hepatoma Cells.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Our recent studies have shown that the diamine-(PEG)ylated oleanolic acid (OADP) has strong anti-tumor effects in HCCs. In this study, we evaluated the anti-tumor mechanisms of OADP in the HepG2 HCC cell line.

Oleanolic Acid Derivatives as Potential Inhibitors of HIV-1 Protease.

Pentacyclic triterpenes, such as oleanolic acid (), are promising scaffolds for diversification through the use of combinatorial methods to obtain derivatives that improve their biological properties, increasing their bioavailability and enhancing their therapeutic efficacy. The purpose of this study was to evaluate the influence that derivatives of oleanolic acid, conjugated with one or two amino acids and an acyl group, might exert on HIV-1 protease inhibition. The in vitro studies conducted suggested that the presence of a carboxyacyl group generally improves the inhibition of HIV-1 protease, especially when a phthaloyl group is present, with IC concentration values below 5 μM.

Novel Oleanolic and Maslinic Acid Derivatives as a Promising Treatment against Bacterial Biofilm in Nosocomial Infections: An in Vitro and in Vivo Study.

Oleanolic acid (OA) and maslinic acid (MA) are pentacyclic triterpenic compounds that abound in industrial olive oil waste. These compounds have renowned antimicrobial properties and lack cytotoxicity in eukaryotic cells as well as resistance mechanisms in bacteria. Despite these advantages, their antimicrobial activity has only been tested in vitro, and derivatives improving this activity have not been reported.

Erratum: Predicting clinically significant prostate cancer using DCE-MRI habitat descriptors.

[This corrects the article DOI: 10.18632/oncotarget.26437.

Regional Specialization of Pyramidal Neuron Morphology and Physiology in the Tree Shrew Neocortex.

The mammalian cerebral cortex is divided into different areas according to their function and pattern of connections. Studies comparing primary visual (V1) and prefrontal cortex (PFC) of primates have demonstrated striking pyramidal neuron (PN) specialization not present in comparable areas of the mouse neocortex. To better understand PFC evolution and regional PN specialization, we studied the tree shrew, a species with a close phylogenetic relationship to primates.

Predicting clinically significant prostate cancer using DCE-MRI habitat descriptors.

Prostate cancer diagnosis and treatment continues to be a major public health challenge. The heterogeneity of the disease is one of the major factors leading to imprecise diagnosis and suboptimal disease management. The improved resolution of functional multi-parametric magnetic resonance imaging (mpMRI) has shown promise to improve detection and characterization of the disease.

Quantitative NMR analysis of L-Dopa in seeds from two varieties of Mucuna pruriens.

Introduction: L-Dopa, a key neurotransmitter used to treat neural disorders such as Parkinson's disease, is found in the seeds of the genus Mucuna at a sufficient concentration for possible commercial use.

Objective: To develop a simple and reliable method to extract L-Dopa from M. pruriens seeds in an aqueous medium and then quantitate this compound using a H qNMR method (internal standard); and also to evaluate the accuracy and reproducibility of this method with an NMR calibration curve.

Semisynthesis of ω-Hydroxyalkylcarbonate Derivatives of Hydroxytyrosol as Antitrypanosome Agents.

Several lipophilic ω-hydroxyalkylcarbonate hydroxytyrosol derivatives and also their corresponding dimeric derivatives have been synthesized, coupling the primary hydroxy group of this phenolic compound with several terminal diols of different chain lengths, by the use of a carbonate linker. The trypanocidal activity and cytotoxicity of these ω-hydroxyalkylcarbonate derivatives of hydroxytyrosol and known alkylcarbonate derivatives of hydroxytyrosol were assessed. Three of the hydroxytyrosol alkylcarbonate derivatives were active against Trypanosoma brucei: two with an alkyl chain of average size (0.

Diamine and PEGylated-diamine conjugates of triterpenic acids as potential anticancer agents.

A set of 18 amide derivatives of oleanolic or maslinic acid has been semi-synthesised. Twelve were diamine conjugates at C-28 of these triterpenic acids and the other six were PEGylated-diamine derivatives. The cytotoxic effects of these 18 triterpenic derivatives in three cancer-cell lines (B16-F10, HT29, and Hep G2) have been assayed, and have been compared to three non-tumour cell lines of the same or a similar tissue (HPF, IEC-18, and WRL68).

Assessment of the Prosthetic Replacement of Ocular Surface Ecosystem (PROSE) scleral lens on visual acuity for corneal irregularity and ocular surface disease.

Purpose: To describe changes in visual acuity in patients fit with the Prosthetic Replacement of Ocular Surface Ecosystem (PROSE) with irregular corneas compared to those with ocular surface disease, as well as describe patient demographics and fitting indications for PROSE at an academic medical center.

Methods: A retrospective chart review from 2010 to 2016 on a total of 825 eyes from 493 patients fitted with a PROSE lens, and grouped by etiology, either irregular cornea/dystrophy or ocular surface disease and associated sub-etiologies. We compared best corrected visual acuity (BCVA) before and after PROSE fitting.

Synthesis and in vitro antiproliferative evaluation of PEGylated triterpene acids.

A set of PEGylated derivatives of oleanolic and maslinic acids has been semi-synthesised, attaching ethylene glycol, diethylene glycol, triethylene glycol or tetraethylene glycol to the C-28 carboxyl group of these natural triterpenes and some derivatives. Another set of PEGylated derivatives has been semi-synthesised by connecting the same four ethylene glycols to the hydroxyl groups of the A ring of these triterpenic acids, through a carbonate linker, by reaction with trichloromethyl chloroformate. The aqueous solubility of some of these PEGylated derivatives has been compared with that of maslinic acid.

Hydrogen-Treated Rutile TiO Shell in Graphite-Core Structure as a Negative Electrode for High-Performance Vanadium Redox Flow Batteries.

Hydrogen-treated TiO as an electrocatalyst has shown to boost the capacity of high-performance all-vanadium redox flow batteries (VRFBs) as a simple and eco-friendly strategy. The graphite felt-based GF@TiO :H electrode is able to inhibit the hydrogen evolution reaction (HER), which is a critical barrier for operating at high rate for long-term cycling in VRFBs. Significant improvements in charge/discharge and electron-transfer processes for the V /V reaction on the surface of reduced TiO were achieved as a consequence of the formation of oxygen functional groups and oxygen vacancies in the lattice structure.

Microwave-assisted extraction versus Soxhlet extraction to determine triterpene acids in olive skins.

Microwave-assisted extraction is compared with a more classical technique, Soxhlet extraction, to determine the content of triterpene acids in olive skins. The samples used in their original unmilled state and milled were extracted with ethyl acetate or methanol as solvents. The optimized operating conditions (e.

Dynamic contrast-enhanced MRI for automatic detection of foci of residual or recurrent disease after prostatectomy.

Purpose: This study aimed to develop an automated procedure for identifying suspicious foci of residual/recurrent disease in the prostate bed using dynamic contrast-enhanced-MRI (DCE-MRI) in prostate cancer patients after prostatectomy.

Materials And Methods: Data of 22 patients presenting for salvage radiotherapy (RT) with an identified gross tumor volume (GTV) in the prostate bed were analyzed retrospectively. An unsupervised pattern recognition method was used to analyze DCE-MRI curves from the prostate bed.

Cellular resolution circuit mapping with temporal-focused excitation of soma-targeted channelrhodopsin.

We describe refinements in optogenetic methods for circuit mapping that enable measurements of functional synaptic connectivity with single-neuron resolution. By expanding a two-photon beam in the imaging plane using the temporal focusing method and restricting channelrhodopsin to the soma and proximal dendrites, we are able to reliably evoke action potentials in individual neurons, verify spike generation with GCaMP6s, and determine the presence or absence of synaptic connections with patch-clamp electrophysiological recording.

Synthesis and Antioxidant Activity of Hydroxytyrosol Alkyl-Carbonate Derivatives.

Three procedures have been investigated for the isolation of tyrosol (1) and hydroxytyrosol (2) from a phenolic extract obtained from the solid residue of olive milling. These three methods, which facilitated the recovery of these phenols, were chemical or enzymatic acetylation, benzylation, and carbomethoxylation, and subsequent carbonylation or acetonation reactions. Several new lipophilic alkyl-carbonate derivatives of hydroxytyrosol have been synthesized, coupling the primary hydroxy group of this phenol, through a carbonate linker, using alcohols with different chain lengths.

Biotransformation of Salpichrolides A, C, and G by Three Filamentous Fungi.

Incubation of salpichrolide A (1) with Rhizomucor miehei produced hydroxylation in rings B and C (C-7 and C-12) and led to C-5-C-6 epoxide opening, while incubation of salpichrolides C (2) and G (3) with R. miehei led to epoxide opening at the C-24-C-25 and C-5-C-6 positions, respectively. Biotransformation of salpichrolide A (1) with Cunninghamella elegans produced stereoselective hydroxylated, oxidized, and reduced derivatives in different positions of the A, B, and C rings and C-5-C-6 epoxide opening.

Identification of gut-derived metabolites of maslinic acid, a bioactive compound from Olea europaea L.

Scope: Maslinic acid has been described to exert a chemopreventive activity in colon cancer. Hereby, we determined maslinic acid and its metabolites in the rat intestine previous oral administration as a first step in elucidating whether this triterpene might be used as a nutraceutical.

Methods And Results: Maslinic acid was orally administered at 1, 2, and 5 mg/kg to male Sprague-Dawley for 2 days.

Semi-synthesis and antiproliferative evaluation of PEGylated pentacyclic triterpenes.

Several PEGylated derivatives of oleanolic and maslinic acids have been semi-synthesized, attaching one acid-PEG reagent to the hydroxyl group/s at C-2 or C-2/C-3 of the A rings of these natural triterpenes, and also to their corresponding C-28 benzyl derivatives. Several monomeric and dimeric PEGylated compounds have also been produced by linking one diamine-PEG reagent to the carboxyl group at C-28 of the same natural triterpenes and also to their corresponding C-2 or C-2/C-3 acetylated derivatives. The cytotoxic effects of 12 triterpenic PEGylated derivatives in three cancer-cell lines (B16F10, HT29, and Hep G2) have been assayed.

Maslinic Acid, a Natural Triterpene, Induces a Death Receptor-Mediated Apoptotic Mechanism in Caco-2 p53-Deficient Colon Adenocarcinoma Cells.

Maslinic acid (MA) is a natural triterpene present in high concentrations in the waxy skin of olives. We have previously reported that MA induces apoptotic cell death via the mitochondrial apoptotic pathway in HT29 colon cancer cells. Here, we show that MA induces apoptosis in Caco-2 colon cancer cells via the extrinsic apoptotic pathway in a dose-dependent manner.