Long circulating liposomal platform utilizing hydrophilic polymer-based surface modification: preparation, characterisation, and biological evaluation.

Liposomes are one of the most important drug delivery vectors, nowadays used in clinics. In general, polyethylene glycol (PEG) is used to ensure the stealth properties of the liposomes. Here, we have employed hydrophilic, biocompatible and highly non-fouling N-(2-hydroxypropyl) methacrylamide (HPMA)-based copolymers containing hydrophobic cholesterol anchors for the surface modification of liposomes, which were prepared by the method of lipid film hydration and extrusion through 100 nm polycarbonate filters.

Reporting completeness of nutrition and diet-related randomised controlled trials protocols.

Background And Aims: There is a need to consolidate reporting guidance for nutrition randomised controlled trial (RCT) protocols. The reporting completeness in nutrition RCT protocols and study characteristics associated with adherence to SPIRIT and TIDieR reporting guidelines are unknown. We, therefore, assessed reporting completeness and its potential predictors in a random sample of published nutrition and diet-related RCT protocols.

Polymer theranostics with multiple stimuli-based activation of photodynamic therapy and tumor imaging.

Efficient theranostic strategies concurrently bring and use both the therapeutic and diagnostic features, serving as a cutting-edge tool to combat advanced cancers. Here, we develop stimuli-sensitive theranostics consisting of tailored copolymers forming micellar conjugates carrying pyropheophorbide-a (PyF) attached by pH-sensitive hydrazone bonds, thus enabling the tumor microenvironment-sensitive activation of the photodynamic therapy (PDT) effect, fluorescence or phosphorescence. The nanomedicines show superior anti-tumor PDT efficacy and huge tumor-imaging potential, while reducing their accumulation, and potentially side effects, in the liver and spleen.

Octahedral Molybdenum Cluster-Based Nanomaterials for Potential Photodynamic Therapy.

Photo/radiosensitizers, such as octahedral molybdenum clusters (Mo), have been intensively studied for photodynamic applications to treat various diseases. However, their delivery to the desired target can be hampered by its limited solubility, low stability in physiological conditions, and inappropriate biodistribution, thus limiting the therapeutic effect and increasing the side effects of the therapy. To overcome such obstacles and to prepare photofunctional nanomaterials, we employed biocompatible and water-soluble copolymers based on -(2-hydroxypropyl)methacrylamide (pHPMA) as carriers of Mo clusters.

Novel Eco-Friendly Stability Indicating Capillary Zone Electrophoresis Method for Determination of Aripiprazole in Tablet Dosage form: DoE Directed Optimization, Development and Method Validation.

In this work, a novel environment-friendly stability indicating capillary zone electrophoresis (CZE) method has been developed and validated for assaying the aripiprazole (ARP) in tablet dosage form. The separation of ARP from its degradation products and internal standard was achieved using a fused silica capillary column (30.2 cm x 75 μm ID), a background electrolyte containing 6 mmol L ammonium formate buffer (pH 3) with 5% methanol under a potential of 15 kV and detection at 214 nm.

Effectiveness of nutritional interventions to prevent nonprogressive congenital and perinatal brain injuries: a systematic review and meta-analysis of randomized trials.

Context: Nutritional interventions for newborns with brain injury are scarce, and there are gaps in the knowledge of their mechanisms of action in preventing the occurrence of cerebral palsy (CP) or the incidence of other developmental disabilities.

Objective: The objective of this review was to assess the effect of nutritional interventions in preventing nonprogressive congenital or perinatal brain injuries, or in improving outcomes related to neurological development.

Data Sources: Randomized trials on any nutritional intervention for pregnant women at risk of preterm delivery, or for children with low birth weight, preterm, or with confirmed or suspected microcephaly, CP, or fetal alcohol syndrome disorders (FASDs) were retrieved from MEDLINE, Embase, Scopus, Web of Science, LILACS, and CENTRAL databases from inception to September 17, 2020.

Glycopolymers Decorated with 3--Substituted Thiodigalactosides as Potent Multivalent Inhibitors of Galectin-3.

Galectin-3 (Gal-3) participates in many cancer-related metabolic processes. The inhibition of overexpressed Gal-3 by, e.g.

Innovative Approaches to Assess Intermediate Cardiovascular Risk Subjects: A Review From Clinical to Metabolomics Strategies.

Current risk stratification strategies for coronary artery disease (CAD) have low predictive value in asymptomatic subjects classified as intermediate cardiovascular risk. This is relevant because not all coronary events occur in individuals with traditional multiple risk factors. Most importantly, the first manifestation of the disease may be either sudden cardiac death or acute coronary syndrome, after rupture and thrombosis of an unstable non-obstructive atherosclerotic plaque, which was previously silent.

Analytical Platforms for Mass Spectrometry-Based Metabolomics of Polar and Ionizable Metabolites.

Metabolomics studies rely on the availability of suitable analytical platforms to determine a vast collection of chemically diverse metabolites in complex biospecimens. Liquid chromatography-mass spectrometry operated under reversed-phase conditions is the most commonly used platform in metabolomics, which offers extensive coverage for nonpolar and moderately polar compounds. However, complementary techniques are required to obtain adequate separation of polar and ionic metabolites, which are involved in several fundamental metabolic pathways.

Improving data quality in liquid chromatography-mass spectrometry metabolomics of human urine.

Signal variation is a common drawback in untargeted metabolomics using liquid chromatography-mass spectrometry (LC-MS), mainly due to the complexity of biological matrices and reduced sample preparation, which results in the accumulation of sample components in the column and the ion source. Here we propose a simple, easy to implement approach to improve data quality in untargeted metabolomics by LC-MS. This approach involves the use of a divert valve to direct the column effluent to waste at the beginning of the chromatographic run and during column cleanup and equilibration, in combination with longer column cleanups in between injections.

Evaluation of two highly effective lipid-lowering therapies in subjects with acute myocardial infarction.

For cardiovascular disease prevention, statins alone or combined with ezetimibe have been recommended to achieve low-density lipoprotein cholesterol targets, but their effects on other lipids are less reported. This study was designed to examine lipid changes in subjects with ST-segment elevation myocardial infarction (STEMI) after two highly effective lipid-lowering therapies. Twenty patients with STEMI were randomized to be treated with rosuvastatin 20 mg QD or simvastatin 40 mg combined with ezetimibe 10 mg QD for 30 days.

Polymer-Based Drug-Free Therapeutics for Anticancer, Anti-Inflammatory, and Antibacterial Treatment.

This paper summarizes the area of biomedicinal polymers, which serve as nanomedicines even though they do not contain any anticancer or antiinflammatory drugs. These polymer nanomedicines with unique design are in the literature highlighted as a novel class of therapeutics called "drug-free macromolecular therapeutics." Their therapeutic efficacy is based on the tailored multiple presentations of biologically active vectors, i.

HPMA-Based Copolymers Carrying STAT3 Inhibitor Cucurbitacin-D as Stimulus-Sensitive Nanomedicines for Oncotherapy.

The study describes the synthesis, physicochemical properties, and biological evaluation of polymer therapeutics based on -(2-hydroxypropyl)methacrylamide (HPMA) copolymers intended for a tumor-targeted immuno-oncotherapy. Water-soluble linear and cholesterol-containing HPMA precursors were synthesized using controlled reversible addition-fragmentation chain transfer polymerization to reach molecular weight about 2 × 10 g·mol and low dispersity. These linear or self-assembled micellar conjugates, containing immunomodulatory agent cucurbitacin-D (CuD) or the anticancer drug doxorubicin (Dox) covalently bound by the hydrolytically degradable hydrazone bond, showed a hydrodynamic size of 10-30 nm in aqueous solutions.

Distinct pattern of one-carbon metabolism, a nutrient-sensitive pathway, in invasive breast cancer: A metabolomic study.

Altered cell metabolism is a hallmark of cancer and critical for its development. Particularly, activation of one-carbon metabolism in tumor cells can sustain oncogenesis while contributing to epigenetic changes and metabolic adaptation during tumor progression. We assessed whether increased one-carbon metabolism activity is a metabolic feature of invasive ductal carcinoma (IDC).

Singlet oxygen generation by the reaction of acrolein with peroxynitrite via a 2-hydroxyvinyl radical intermediate.

Acrolein (2-propenal) is an environmental pollutant, food contaminant, and endogenous toxic by-product formed in the thermal decomposition and peroxidation of lipids, proteins, and carbohydrates. Like other α,β-unsaturated aldehydes, acrolein undergoes Michael addition of nucleophiles such as basic amino acids residues of proteins and nucleobases, triggering aging associated disorders. Here, we show that acrolein is also a potential target of the potent biological oxidant, nitrosating and nitrating agent peroxynitrite.

Correction to: The use of clays for chlorhexidine controlled release as a new perspective for longer durability of dentin adhesion.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

High-Affinity -(2-Hydroxypropyl)methacrylamide Copolymers with Tailored -Acetyllactosamine Presentation Discriminate between Galectins.

-Acetyllactosamine (LacNAc; Galβ4GlcNAc) is a typical disaccharide ligand of galectins. The most abundant members of these human lectins, galectin-1 (Gal-1) and galectin-3 (Gal-3), participate in a number of pathologies including cancerogenesis and metastatic formation. In this study, we synthesized a series of fifteen -(2-hydroxypropyl)methacrylamide (HPMA)-based glycopolymers with varying LacNAc amounts and presentations and evaluated the impact of their architecture on the binding affinity to Gal-1 and Gal-3.

Reprogramming of Trypanosoma cruzi metabolism triggered by parasite interaction with the host cell extracellular matrix.

Trypanosoma cruzi, the etiological agent of Chagas' disease, affects 8 million people predominantly living in socioeconomic underdeveloped areas. T. cruzi trypomastigotes (Ty), the classical infective stage, interact with the extracellular matrix (ECM), an obligatory step before invasion of almost all mammalian cells in different tissues.

Capillary electrophoresis with dual diode array detection and tandem mass spectrometry to access cardiovascular biomarkers candidates in human urine: Trimethylamine-N-Oxide and l-carnitine.

A capillary electrophoresis with diode array and tandem mass spectrometry detection (CE-UV-MS/MS) method has been developed for the targeted assessment of cardiovascular biomarkers candidates, trimethylamine-N-Oxide (TMAO) and l-carnitine, and creatinine in human urine samples. The dual detection was applied due to the high concentration of creatinine (monitored by UV detection at 200 nm) in relation to TMAO and l-carnitine (quantified by selected reaction monitoring (SRM) mass spectrometry), in human urine. All instrumental parameters, sheath liquid (SHL) and background electrolyte (BGE) compositions were optimized with a pool of urine provided by adult healthy volunteers and evaluated by signal-to-noise ratio (SNR) and peak shape of TMAO.

Stereochemical and structural effects of (2R,6R)-hydroxynorketamine on the mitochondrial metabolome in PC-12 cells.

Background: Impairment in mitochondrial biogenesis and function plays a key role in depression and anxiety, both of which being associated with changes in fatty acid and phospholipid metabolism. The antidepressant effects of (R,S)-ketamine have been linked to its conversion into (2S,6S;2R,6R)-hydroxynorketamine (HNK); however, the connection between structure and stereochemistry of ketamine and HNK in the mitochondrial homeostatic response has not yet been fully elucidated at a metabolic level.

Methods: We used a multi-platform, non-targeted metabolomics approach to study the change in mitochondrial metabolome of PC-12 cells treated with ketamine and HNK enantiomers.

Preparation of Poly(D,L-lactic--glycolic acid) Nanoparticles Through Solvent Displacement and Structural Evaluation Using Time-Domain Nuclear Magnetic Resonance.

The present study obtained coated poly(lactic-co-glycolic acid) nanoparticles using the solvent displacement method aiming to evaluate the effect of the polymer concentration in the pharmaceutical formulations' and polymer properties. Nanosuspensions were evaluated by fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), zeta potential (ZP), thermogravimetric analysis (TGA), X-ray diffraction (XRD) and time-domain nuclear magnetic resonance (TD-NMR). Uniform nanoparticles could be obtained using this method and higher polymer concentrations led to an increase in particle size and negatively charged surfaces were observed.

CE-MS for the Analysis of Amino Acids.

Amino acids play an important role in clinical analysis. Capillary electrophoresis-electrospray ionization-mass spectrometry (CE-ESI-MS) has proven to possess several characteristics that make it a powerful and useful tool for the analysis of amino acids in clinical studies. Here we present a method for the separation and quantitative analysis of 27 amino acids in urine based on CE-ESI-MS.

Effects of four antiplatelet/statin combined strategies on immune and inflammatory responses in patients with acute myocardial infarction undergoing pharmacoinvasive strategy: Design and rationale of the B and T Types of Lymphocytes Evaluation in Acute Myocardial Infarction (BATTLE-AMI) study: study protocol for a randomized controlled trial.

Background: Early reperfusion of the occluded coronary artery during acute myocardial infarction is considered crucial for reduction of infarcted mass and recovery of ventricular function. Effective microcirculation and the balance between protective and harmful lymphocytes may have roles in reperfusion injury and may affect final ventricular remodeling.

Methods/design: BATTLE-AMI is an open-label, randomized trial comparing the effects of four therapeutic strategies (rosuvastatin/ticagrelor, rosuvastatin/clopidogrel, simvastatin plus ezetimibe/ticagrelor, or simvastatin plus ezetimibe/clopidogrel) on infarcted mass and left ventricular ejection fraction (LVEF) (blinded endpoints) in patients with ST-segment elevation myocardial infarction submitted to fibrinolytic therapy before coronary angiogram (pharmacoinvasive strategy).

Development and characterization of poly(lactic-co-glycolic) acid nanoparticles loaded with copaiba oleoresin.

Copaiba oleoresin (CPO), obtained from Copaifera landgroffii, is described as active to a large number of diseases and more recently in the endometriosis treatment. In this work, poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing CPO were obtained using the design of experiments (DOE) as a tool to optimize the production process. The nanoparticles optimized by means of DOE presented an activity in relation to the cellular viability of endometrial cells.

Strategies Involving Mass Spectrometry Combined with Capillary Electrophoresis in Metabolomics.

This chapter focuses on the important contribution of CE-MS in metabolomics, describing the nature of CE-MS coupling and the technical improvements that have led to the interfaces used in modern instrumentation. Moreover, it will discourse how the variety of electrolyte compositions and additives, which has conferred CE the exceptional selectivity of its multiple separation modes, has been handled to allow interfacing with MS without compromising ionization efficiency and the spectrometer integrity. Finally, the methodologies of CE-MS in current use for metabolomics will be discussed in detail.