Development of a new micellar formulation of carvedilol and curcumin to enhance blood pressure reduction in a spontaneously hypertensive rat model.

Cardiovascular diseases remain a leading cause of morbidity and mortality worldwide, requiring innovative therapeutic strategies. This project explores a nano-pharmaceutical approach to enhance the efficacy of cardiovascular drugs, focusing on carvedilol and curcumin. These agents, known for their potential cardiovascular benefits, are encapsulated within Soluplus® micelles to form a novel drug delivery system.

Decoding ribosome complexity: role of ribosomal proteins in cancer and disease.

The ribosome is a remarkably complex machinery, at the interface with diverse cellular functions and processes. Evolutionarily conserved, yet intricately regulated, ribosomes play pivotal roles in decoding genetic information into the synthesis of proteins and in the generation of biomass critical for cellular physiological functions. Recent insights have revealed the existence of ribosome heterogeneity at multiple levels.

Dual strategy to improve the oral bioavailability of efavirenz employing nanomicelles and curcumin as a bio-enhancer.

The present investigation was focused on the development of Soluplus®-based nanomicelles (NMs) (10 % w/v) loaded with Efavirenz (EFV) (5 mg/mL) and Curcumin (natural bio-enhancer) (CUR) (5, 10 and 15 mg/mL) to improve the oral bioavalability of EFV. Micellar formulations were obtained employing an acetone-diffusion technique. Apparent aqueous solubility was increased up to ∼1250-fold and 25,000-fold for EFV and CUR, respectively.

Nanomicellar Formulations Loaded with Histamine and Paclitaxel as a New Strategy to Improve Chemotherapy for Breast Cancer.

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Currently, paclitaxel (PTX) represents the first-line therapy for TNBC; however it presents a hydrophobic behavior and produces severe adverse effects. The aim of this work is to improve the therapeutic index of PTX through the design and characterization of novel nanomicellar polymeric formulations composed of a biocompatible copolymer Soluplus (S), surface-decorated with glucose (GS), and co-loaded either with histamine (HA, 5 mg/mL) and/or PTX (4 mg/mL).

Overcoming Paradoxical Kinase Priming by a Novel MNK1 Inhibitor.

Targeting the kinases MNK1 and MNK2 has emerged as a valuable strategy in oncology. However, most of the advanced inhibitors are acting in an adenosine triphosphate (ATP)-competitive mode, precluding the evaluation of different binding modes in preclinical settings. Using rational design, we identified and validated the 4,6-diaryl-pyrazolo[3,4-]pyridin-3-amine scaffold as the core for MNK inhibitors.

The 40-LARP1 complex reprograms the cellular translatome upon mTOR inhibition to preserve the protein synthetic capacity.

Ribosomes execute the transcriptional program in every cell. Critical to sustain nearly all cellular activities, ribosome biogenesis requires the translation of ~200 factors of which 80 are ribosomal proteins (RPs). As ribosome synthesis depends on RP mRNA translation, a priority within the translatome architecture should exist to ensure the preservation of ribosome biogenesis capacity, particularly under adverse growth conditions.

Sex, rurality and socioeconomical status in Spanish centennial population (2017).

World's population is exponentially aging as people reaching 100 years old has increased. The number of areas with the highest centennial population rates (Blue Zones), are significantly higher. Are there any determinant factors that favor this situation in Spain? The goal of this study was to determine the possible influence of sex, rurality and socioeconomic factors (Gross Domestic Product (GDP)) on the prevalence of the centennial population of the Spanish society.

Publisher Correction: ITGB3-mediated uptake of small extracellular vesicles facilitates intercellular communication in breast cancer cells.

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

ITGB3-mediated uptake of small extracellular vesicles facilitates intercellular communication in breast cancer cells.

Metastasis, the spread of malignant cells from a primary tumour to distant sites, causes 90% of cancer-related deaths. The integrin ITGB3 has been previously described to play an essential role in breast cancer metastasis, but the precise mechanisms remain undefined. We have now uncovered essential and thus far unknown roles of ITGB3 in vesicle uptake.

Hypoxia-mediated translational activation of ITGB3 in breast cancer cells enhances TGF-β signaling and malignant features and .

Breast cancer is the most prevalent malignancy in women and there is an urgent need for new therapeutic drugs targeting aggressive and metastatic subtypes, such as hormone-refractory triple-negative breast cancer (TNBC). Control of protein synthesis is vital to cell growth and tumour progression and permits increased resistance to therapy and cellular stress. Hypoxic cancer cells attain invasive and metastatic properties and chemotherapy resistance, but the regulation and role of protein synthesis in this setting is poorly understood.

Autogenous Control of 5′TOP mRNA Stability by 40S Ribosomes.

Ribosomal protein (RP) expression in higher eukaryotes is regulated translationally through the 5′TOP sequence. This mechanism evolved to more rapidly produce RPs on demand in different tissues. Here we show that 40S ribosomes, in a complex with the mRNA binding protein LARP1, selectively stabilize 5′TOP mRNAs, with disruption of this complex leading to induction of the impaired ribosome biogenesis checkpoint (IRBC) and p53 stabilization.