Five years of advances in electrochemical analysis of protein biomarkers in lung cancer: a systematic review.

Lung cancer is the leading cause of cancer death in both men and women. It represents a public health problem that must be addressed through the early detection of specific biomarkers and effective treatment. To address this critical issue, it is imperative to implement effective methodologies for specific biomarker detection of lung cancer in real clinical samples.

Development of Biocompatible Cu(I)-Microdevices for Bioorthogonal Uncaging and Click Reactions.

Transition-metal-catalyzed bioorthogonal reactions emerged a decade ago as a novel strategy to implement spatiotemporal control over enzymatic functions and pharmacological interventions. The use of this methodology in experimental therapy is driven by the ambition of improving the tolerability and PK properties of clinically-used therapeutic agents. The preclinical potential of bioorthogonal catalysis has been validated in vitro and in vivo with the in situ generation of a broad range of drugs, including cytotoxic agents, anti-inflammatory drugs and anxiolytics.

Discovery of pyrazolopyrimidines that selectively inhibit CSF-1R kinase by iterative design, synthesis and screening against glioblastoma cells.

Glioblastoma multiforme (GBM) is the most aggressive type of brain cancer in adults, with an average life expectancy under treatment of approx. 15 months. GBM is characterised by a complex set of genetic alterations that results in significant disruption of receptor tyrosine kinase (RTK) signaling.

Single-cell transcriptomics reveals that tumor-infiltrating natural killer cells are activated by localized ablative immunotherapy and share anti-tumor signatures induced by immune checkpoint inhibitors.

Rationale: Natural killer (NK) cells provide protective anti-cancer immunity. However, the cancer therapy induced activation gene signatures and pathways in NK cells remain unclear.

Methods: We applied a novel localized ablative immunotherapy (LAIT) by synergizing photothermal therapy (PTT) with intra-tumor delivering of the immunostimulant N-dihydrogalactochitosan (GC), to treat breast cancer using a mammary tumor virus-polyoma middle tumor-antigen (MMTV-PyMT) mouse model.

Bioorthogonal Catalysis by Encapsulated Nanoalloys: Overcoming Intracellular Deactivation.

Bioorthogonal metallocatalysis has opened up a xenobiotic route to perform nonenzymatic catalytic transformations in living settings. Despite their promising features, most metals are deactivated inside cells by a myriad of reactive biomolecules, including biogenic thiols, thereby limiting the catalytic functioning of these abiotic reagents. Here we report the development of cytocompatible alloyed nanoparticles with the capacity to elicit bioorthogonal depropargylations with high efficiency in biological media.

A Novel, Quick, and Reliable Smartphone-Based Method for Serum PSA Quantification: Original Design of a Portable Microfluidic Immunosensor-Based System.

We describe a versatile, portable, and simple platform that includes a microfluidic electrochemical immunosensor for prostate-specific antigen (PSA) detection. It is based on the covalent immobilization of the anti-PSA monoclonal antibody on magnetic microbeads retained in the central channel of a microfluidic device. Image flow cytometry and scanning electron microscopy were used to characterize the magnetic microbeads.

Truly-Biocompatible Gold Catalysis Enables Vivo-Orthogonal Intra-CNS Release of Anxiolytics.

Being recognized as the best-tolerated of all metals, the catalytic potential of gold (Au) has thus far been hindered by the ubiquitous presence of thiols in organisms. Herein we report the development of a truly-catalytic Au-polymer composite by assembling ultrasmall Au-nanoparticles at the protein-repelling outer layer of a co-polymer scaffold via electrostatic loading. Illustrating the in vivo-compatibility of the novel catalysts, we show their capacity to uncage the anxiolytic agent fluoxetine at the central nervous system (CNS) of developing zebrafish, influencing their swim pattern.

Truly-Biocompatible Gold Catalysis Enables Vivo-Orthogonal Intra-CNS Release of Anxiolytics.

Being recognized as the best-tolerated of all metals, the catalytic potential of gold (Au) has thus far been hindered by the ubiquitous presence of thiols in organisms. Herein we report the development of a truly-catalytic Au-polymer composite by assembling ultrasmall Au-nanoparticles at the protein-repelling outer layer of a co-polymer scaffold via electrostatic loading. Illustrating the in vivo-compatibility of the novel catalysts, we show their capacity to uncage the anxiolytic agent fluoxetine at the central nervous system (CNS) of developing zebrafish, influencing their swim pattern.

Small Molecule Kinase Inhibitor Drugs (1995-2021): Medical Indication, Pharmacology, and Synthesis.

The central role of dysregulated kinase activity in the etiology of progressive disorders, including cancer, has fostered incremental efforts on drug discovery programs over the past 40 years. As a result, kinase inhibitors are today one of the most important classes of drugs. The FDA approved 73 small molecule kinase inhibitor drugs until September 2021, and additional inhibitors were approved by other regulatory agencies during that time.

A Conformation Selective Mode of Inhibiting SRC Improves Drug Efficacy and Tolerability.

Despite the approval of several multikinase inhibitors that target SRC and the overwhelming evidence of the role of SRC in the progression and resistance mechanisms of many solid malignancies, inhibition of its kinase activity has thus far failed to improve patient outcomes. Here we report the small molecule eCF506 locks SRC in its native inactive conformation, thereby inhibiting both enzymatic and scaffolding functions that prevent phosphorylation and complex formation with its partner FAK. This mechanism of action resulted in highly potent and selective pathway inhibition in culture and .

Dietary Intake, Nutritional Adequacy, and Food Sources of Protein and Relationships with Personal and Family Factors in Spanish Children Aged One to <10 Years: Findings of the EsNuPI Study.

Diet in the first years of life is an important factor in growth and development. Dietary protein is a critical macronutrient that provides both essential and nonessential amino acids required for sustaining all body functions and procedures, providing the structural basis to maintain life and healthy development and growth in children. In this study, our aim was to describe the total protein intake, type and food sources of protein, the adequacy to the Population Reference Intake (PRI) for protein by the European Food Safety Authority (EFSA), and the Recommended Dietary Allowance (RDA) by the Institute of Medicine (IoM).

Bioorthogonal Uncaging of Cytotoxic Paclitaxel through Pd Nanosheet-Hydrogel Frameworks.

The promising potential of bioorthogonal catalysis in biomedicine is inspiring incremental efforts to design strategies that regulate drug activity in living systems. To achieve this, it is not only essential to develop customized inactive prodrugs and biocompatible metal catalysts but also the right physical environment for them to interact and enable drug production under spatial and/or temporal control. Toward this goal, here, we report the first inactive precursor of the potent broad-spectrum anticancer drug paclitaxel (a.

Usual Dietary Intake, Nutritional Adequacy and Food Sources of Calcium, Phosphorus, Magnesium and Vitamin D of Spanish Children Aged One to <10 Years. Findings from the EsNuPI Study.

Bone problems in the population begin to be establish in childhood. The present study aims to assess the usual calcium, phosphorus, magnesium, and vitamin D intakes, along with the food sources of these nutrients, in Spanish children participating in the EsNuPI (Estudio Nutricional en Población Infantil Española) study. Two 24 h dietary recalls were applied to 1448 children (1 to <10 years) divided into two sub-samples: one reference sample (RS) of the general population [ = 707] and another sample which exclusively included children consuming enriched or fortified milks, here called "adapted milks" (AMS) [ = 741].

Energy Intake, Macronutrient Profile and Food Sources of Spanish Children Aged One to <10 Years-Results from the EsNuPI Study.

The present study aimed to assess energy intake, nutrient profile and food sources in Spanish children participating in the EsNuPI ("Estudio Nutricional en Población Infantil Española") study. Plausibility of energy intake and adequacy of nutrient intakes to international recommendations were analyzed in a final sample of 1448 subjects (728 boys and 720 girls) and one group representative of the 1 to <10 years old urban Spanish children (reference sample ( = 707)) who consumed milk and one of the same age who consumed adapted milk over the last year (adapted milk consumers sample ( = 741)) were compared. Both groups completed data of a face-to-face and a telephone 24-h dietary recalls.

Pyrazolopyrimide library screening in glioma cells discovers highly potent antiproliferative leads that target the PI3K/mTOR pathway.

The search for novel targeted inhibitors active on glioblastoma multiforme is crucial to develop new treatments for this unmet clinical need. Herein, we report the results from a screening campaign against glioma cell lines using a proprietary library of 100 structurally-related pyrazolopyrimidines. Data analysis identified a family of compounds featuring a 2-amino-1,3-benzoxazole moiety (eCF309 to eCF334) for their antiproliferative properties in the nM range.

Breakfast Consumption in Spain: Patterns, Nutrient Intake and Quality. Findings from the ANIBES Study, a Study from the International Breakfast Research Initiative.

This study aimed to investigate energy, nutrient and food group intakes at breakfast in Spain and to examine for the first time, their relationship to the overall Diet Quality (DQ). The data used were from the Spanish ANIBES (anthropometric data, macronutrients and micronutrients intake, practice of physical activity, socioeconomic data and lifestyles in Spain), a cross-sectional study using a nationally representative sample of the Spanish population (9⁻75 years old). DQ was assessed using the Nutrient Rich Foods Index, adapted to total diets (NRF9.

Drug "Clicking" on Cell-Penetrating Fluorescent Nanoparticles for In Cellulo Chemical Proteomics.

Chemical proteomics approaches are widely used to identify molecular targets of existing or novel drugs. This manuscript describes the development of a straightforward approach to conjugate azide-labeled drugs via click chemistry to alkyne-tagged cell-penetrating fluorescent nanoparticles as a novel tool to study target engagement and/or identification inside living cells. A modification of the Baeyer test for alkynes allows monitoring the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, guaranteeing the presence of the drug on the solid support.

Metallofluorescent Nanoparticles for Multimodal Applications.

Herein, we describe the synthesis and application of cross-linked polystyrene-based dual-function nano- and microparticles containing both fluorescent tags and metals. Despite containing a single dye, these particles exhibit a characteristic dual-band fluorescence emission. Moreover, these particles can be combined with different metal ions to obtain hybrid metallofluorescent particles.

Dietary Intake of Individual (Free and Intrinsic) Sugars and Food Sources in the Spanish Population: Findings from the ANIBES Study.

The consumption of total and individual sugars is controversial and little is known about consumption and dietary sources in Spain. The purpose was to examine free and intrinsic sugar intake and food and beverage sources. The ANIBES Study (Anthropometry, Intake and Energy Balance in Spain), a cross-sectional study of a representative sample of the Spanish population (9-75 years old; = 2009) carried out in 2013, was used.

β-adrenoceptor Arg389Gly polymorphism confers differential β-arrestin-binding tropism in cardiac myocytes.

Aim: The β-adrenergic receptor (AR) Arg389Gly polymorphism affects efficacy of its procontractile signaling in cardiomyocytes and carriers' responses to β-blockers. To identify molecular mechanisms underlying functional differences between Arg389 and Gly389 βARs, we examined their binding to β-arrestins (βarr-1 and -2), which mediate βAR signaling, in neonatal rat ventricular myocytes.

Methods: We tested the βAR-βarr interaction via βAR immunoprecipitation followed by βarr immunoblotting.