Metabolic profiling and combined therapeutic strategies unveil the cytotoxic potential of selenium-chrysin (SeChry) in NSCLC cells.

Lung cancer ranks as the predominant cause of cancer-related mortalities on a global scale. Despite progress in therapeutic interventions, encompassing surgical procedures, radiation, chemotherapy, targeted therapies and immunotherapy, the overall prognosis remains unfavorable. Imbalances in redox equilibrium and disrupted redox signaling, common traits in tumors, play crucial roles in malignant progression and treatment resistance.

Ligand-free Tc-polyurea dendrimer complexes: nanoradiotheranostics targeting ovarian cancer.

A folic acid-targeted polyurea (PURE) dendrimer was easily radiolabelled with Technetium-99m (Tc-PURE-FA) avoiding the use of additional ligands and bioconjugation chemistry. This straightforward strategy is enabled in PURE dendrimers due to their favourable surface terminal groups configuration, showing coordination capabilities and turning these biodendrimers into attractive platforms for nanoradiotheranostics.

Ibuprofen-Immobilized Thin Films: A Novel Approach to Improve the Clearance of Protein-Bound Uremic Toxins.

Chronic kidney disease (CKD), a pressing global health issue, affects millions and leads to end-stage renal disease (ESRD). Hemodialysis (HD) is a crucial treatment for ESRD, yet its limited efficiency in removing protein-bound uremic toxins (PBUTs) results in high morbidity and mortality rates. A high affinity of pharmaceutical drugs for human serum albumin (HSA) can be leveraged to compete effectively with PBUTs for the same HSA binding sites, thereby enabling them to be capable of displacing these toxins.

Zooplankton biodiversity and temporal dynamics (2005-2015) in a coastal station in western Portugal (Northeastern Atlantic Ocean).

Long-term monitoring of zooplankton assemblages provides essential knowledge to assess key factors impacting marine ecosystems. Despite the importance of this type of data, monitoring stations worldwide are spatially and temporally limited due to the difficulty of maintaining them. In the northeastern Atlantic area, Cascais-Watch is one monitoring site operating since 2005, despite some constraints throughout the years, and has allowed the collection of important data on the zooplankton communities of the area.

A Novel Strategy for Enhanced Sequestration of Protein-Bound Uremic Toxins Using Smart Hybrid Membranes.

Currently available hemodialysis (HD) membranes are unable to safely remove protein-bound uremic toxins (PBUTs), especially those bonded to human serum albumin (HSA). To overcome this issue, the prior administration of high doses of HSA competitive binders, such as ibuprofen (IBF), has been proposed as a complementary clinical protocol to increase HD efficiency. In this work, we designed and prepared novel hybrid membranes conjugated with IBF, thus avoiding its administration to end-stage renal disease (ESRD) patients.

Molecular mechanisms underlying the neuroprotection of environmental enrichment in Parkinson's disease.

Parkinson's disease is the most common movement disorder, affecting about 1% of the population over the age of 60 years. Parkinson's disease is characterized clinically by resting tremor, bradykinesia, rigidity and postural instability, as a result of the progressive loss of nigrostriatal dopaminergic neurons. In addition to this neuronal cell loss, Parkinson's disease is characterized by the accumulation of intracellular protein aggregates, Lewy bodies and Lewy neurites, composed primarily of the protein α-synuclein.

Biochemical and behavioral effects of rosmarinic acid treatment in an animal model of Parkinson's disease induced by MPTP.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. The main therapeutic approach available nowadays relieves motor symptoms but does not prevent or stop neurodegeneration. Rosmarinic acid (RA), an ester of caffeic and 3,4-dihydroxyphenylacetic acids, is obtained from numerous plant species such as Salvia officinalis L.

Gas Permeability and Mechanical Properties of Polyurethane-Based Membranes for Blood Oxygenators.

The production of medical devices follows strict guidelines where bio- and hemocompatibility, mechanical strength, and tear resistance are important features. Segmented polyurethanes (PUs) are an important class of polymers that fulfill many of these requirements, thus justifying the investigation of novel derivatives with enhanced properties, such as modulated carbon dioxide and oxygen permeability. In this work, three segmented polyurethane-based membranes, containing blocks of hard segments (HSs) dispersed in a matrix of soft segment (SS) blocks, were prepared by reacting a PU prepolymer (PUR) with tris(hydroxymethyl)aminomethane (TRIS), Congo red (CR) and methyl-β-cyclodextrin (MBCD), rendering PU/TRIS, PU/CR and PU/MBCD membranes.

Laser Microdissection of Woody and Suberized Plant Tissues for RNA-Seq Analysis.

An accurate profile of gene expression at a cellular level can contribute to a better understanding of biological processes and complexities involved in regulatory mechanism of woody plants. Laser microdissection is one technique that allows isolation of specific, target cells or tissue from a heterogeneous cell population. This technique entails microscopic visualization of the selected tissue and use a laser beam to separate the desired cells from surrounding tissue.

Core-shell polycationic polyurea pharmadendrimers: new-generation of sustainable broad-spectrum antibiotics and antifungals.

The efficacy of conventional antimicrobials is falling to critical levels and raising alarming concerns around the globe. In this scenery, engineered nanoparticles emerged as a solid strategy to fight growing deadly infections. Here, we show the and performance of pharmadendrimers, a novel class of engineered polyurea dendrimers that are synthetic mimics of antibacterial peptides, against a collection of both Gram-positive and Gram-negative bacteria and fungi.

The Activation of Endothelial Cells Relies on a Ferroptosis-Like Mechanism: Novel Perspectives in Management of Angiogenesis and Cancer Therapy.

The activation of endothelial cells (ECs) is a crucial step on the road map of tumor angiogenesis and expanding evidence indicates that a pro-oxidant tumor microenvironment, conditioned by cancer metabolic rewiring, is a relevant controller of this process. Herein, we investigated the contribution of oxidative stress-induced ferroptosis to ECs activation. Moreover, we also addressed the anti-angiogenic effect of Propranolol.

Nonpharmacological interventions used in the perioperative period to prevent anxiety in adolescents: a scoping review.

Objective: The objective of this scoping review was to examine and map the range of nonpharmacological interventions used in the perioperative period to prevent anxiety in adolescents.

Introduction: Undergoing surgery involves experiencing fears and uncertainties that lead to an increase in anxiety levels. The interventions used to prevent anxiety in the perioperative period in adolescents must be appropriate to their developmental stage.

High-Throughput Sequencing of BACHD Mice Reveals Upregulation of Neuroprotective miRNAs at the Pre-Symptomatic Stage of Huntington's Disease.

Huntington's disease (HD) is a genetic disorder marked by transcriptional alterations that result in neuronal impairment and death. MicroRNAs (miRNAs) are non-coding RNAs involved in post-transcriptional regulation and fine-tuning of gene expression. Several studies identified altered miRNA expression in HD and other neurodegenerative diseases, however their roles in early stages of HD remain elusive.

Intrinsic acetamide brush-off by polyurea biodendrimers.

The presence of genotoxic impurities in active pharmaceutical ingredients (APIs) is a major concern for the pharmaceutical industry. Acetamide is a common genotoxic byproduct found in synthetic routes of many APIs, mainly due to acetonitrile hydrolysis, and selective scavenging is a still a challenging task. Herein, as a proof-of-concept, we evaluate polyurea (PURE) biodendrimers as strategic nanopolymers to prepare safe drug nanoformulations from mixtures containing acetamide, using (S)-ibuprofen (IBF) as a model drug.

Carbapenem-Resistant Clinical Isolates: In Vivo Virulence Assessment in and Potential Therapeutics by Polycationic Oligoethyleneimine.

, one of the most common pathogens found in hospital-acquired infections, is often resistant to multiple antibiotics. In fact, multidrug-resistant (MDR) producing KPC or OXA-48-like carbapenemases are recognized as a serious global health threat. In this sense, we evaluated the virulence of KPC(+) or OXA-48(+) aiming at potential antimicrobial therapeutics.

Polygala sabulosa A.W. Bennett extract mitigates motor and cognitive deficits in a mouse model of acute ischemia.

Stroke is considered one of the leading causes of death worldwide. The treatment is limited; however, the Brazilian flora has a great source of natural products with therapeutic potentials. Studies with the medicinal plant Polygala sabulosa W.

Osteogenic Differentiation of Human Mesenchymal Stem Cells by the Single Action of Luminescent Polyurea Oxide Biodendrimers.

Polyurea oxide (PURO) biodendrimers are a class of dendrimers that can trigger osteogenic differentiation of human mesenchymal stem cells (hMSCs). PURO biodendrimers are prepared by simple, solventless oxidation of polyurea dendrimers using hydrogen peroxide as the oxidant in quantitative yield, retaining both biocompatibility (up to 10 mg/mL for higher generations) and the non-traditional intrinsic luminescence. The effect of PURO biodendrimers in the differentiation of hMSCs was found by the single addition to a standard growth medium for MSCs differentiation (without differentiation inducers).

DYNLT1 gene expression is downregulated in whole blood of patients at different Huntington's disease stages.

Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG nucleotide expansion, which encodes the amino acid glutamine, in the huntingtin gene. HD is characterized by motor, cognitive, and psychiatric dysfunctions. In a previous study, we showed by qPCR that some genes altered in an HD mouse model were also altered in blood of HD patients.

Somatic Embryogenesis from Mature Embryos of L. cv. 'Galega Vulgar' and Long-Term Management of Calli Morphogenic Capacity.

Several olive cultivars, characterized by high-quality olive oil show agronomical issues such as excessive vigor, high susceptibility to biotic and abiotic stresses, and low propagation ability. They are strong candidates for breeding based on new technologies to improve their performance in a short period of time. For this reason, the first step is developing efficient somatic embryogenesis (SE) protocols.

Polyurea Dendrimer Folate-Targeted Nanodelivery of l-Buthionine sulfoximine as a Tool to Tackle Ovarian Cancer Chemoresistance.

Ovarian cancer is a highly lethal disease, mainly due to chemoresistance. Our previous studies on metabolic remodeling in ovarian cancer have supported that the reliance on glutathione (GSH) bioavailability is a main adaptive metabolic mechanism, also accounting for chemoresistance to conventional therapy based on platinum salts. In this study, we tested the effects of the in vitro inhibition of GSH synthesis on the restoration of ovarian cancer cells sensitivity to carboplatin.

Targeting Glutathione and Cystathionine β-Synthase in Ovarian Cancer Treatment by Selenium-Chrysin Polyurea Dendrimer Nanoformulation.

Ovarian cancer is the main cause of death from gynecological cancer, with its poor prognosis mainly related to late diagnosis and chemoresistance (acquired or intrinsic) to conventional alkylating and reactive oxygen species (ROS)-generating drugs. We and others reported that the availability of cysteine and glutathione (GSH) impacts the mechanisms of resistance to carboplatin in ovarian cancer. Different players in cysteine metabolism can be crucial in chemoresistance, such as the cystine/glutamate antiporter system Xc (xCT) and the HS-synthesizing enzyme cystathionine β-synthase (CBS) in the pathway of cysteine catabolism.

l-Buthionine Sulfoximine Detection and Quantification in Polyurea Dendrimer Nanoformulations.

l-Buthionine sulfoximine (l-BSO) is an adjuvant drug that is reported to increase the sensitivity of cancer cells to neoplastic agents. Dendrimers are exceptional drug delivery systems and l-BSO nanoformulations are envisaged as potential chemotherapeutics. The absorption of l-BSO at a low wavelength limits its detection by conventional analytical tools.

Neuronal scaffolding protein spinophilin is integral for cocaine-induced behavioral sensitization and ERK1/2 activation.

Spinophilin is a scaffolding protein enriched in dendritic spines with integral roles in the regulation of spine density and morphology, and the modulation of synaptic plasticity. The ability of spinophilin to alter synaptic strength appears to involve its scaffolding of key synaptic proteins, including the important structural element F-actin, AMPA/NMDA modulator protein phosphatase 1, and neuromodulatory G-protein coupled receptors, including dopamine receptor D2 and metabotropic glutamate receptor 5. Additionally, spinophilin is highly expressed in the striatum, a brain region that is fundamentally involved in reward-processing and locomotor activity which receives both glutamatergic and dopaminergic inputs.

Atropine counteracts the depressive-like behaviour elicited by acute exposure to commercial chlorpyrifos in rats.

Acute organophosphate (OP) poisoning induces well-known signs of toxicosis related to acetylcholinesterase (AChE) inhibition. However, the relationship between acute OP poisoning and the onset of psychiatric disorders remains unclear. Thus, we investigated behavioural and biochemical consequences of acute exposure to the OP chlorpyrifos in male rats and also the effectiveness of the antidotes atropine and pralidoxime on reversing these changes.

POxylated Dendrimer-Based Nano-in-Micro Dry Powder Formulations for Inhalation Chemotherapy.

POxylated polyurea dendrimer (PUREOOx)-based nanoparticles were loaded with paclitaxel (PTX) and doxorubicin (DOX) and micronized with chitosan (CHT) by using supercritical CO-assisted spray drying (SASD). Respirable, biocompatible, and biodegradable dry powder formulations (DPFs) were produced to effectively transport and deliver the chemotherapeutics with a controlled rate to the deep lung. In vitro studies performed with the use of the lung adenocarcinoma cell line showed that DOX@PUREOOx nanoparticles were much more cytotoxic than the free drug.