Functional and Physiological Characterization of Tyrosine Decarboxylases from L. Involved in the Synthesis of the Main Phenolics in Olive Fruit and Virgin Olive Oil.

The phenolic composition of virgin olive oil (VOO) primarily depends on the phenolic content of the olive fruit. The purpose of this work was to characterize the first metabolic step in the synthesis of tyrosol (Ty) and hydroxytyrosol (HTy), whose derivatives are by far the predominant phenolics in both olive fruit and VOO. To this end, two genes encoding tyrosine/DOPA decarboxylase enzymes, and , have been identified and functionally and physiologically characterized.

Accumulation Patterns of Metabolites Responsible for the Functional Quality of Virgin Olive Oil during Olive Fruit Ontogeny.

The health-promoting antioxidant properties of virgin olive oil (VOO) are today considered priority targets in the new olive breeding programs. Given that these properties depend mainly on its phenolic fraction, whose origin lies in the phenolic compounds present in olive fruit, the objective of this study was to provide further insight into the accumulation dynamics of the main antioxidant compounds, including both polar phenolics and lipophilic tocopherols, during the ontogeny of the olive fruit. Data obtained show that, albeit with significant differences, all the studied genotypes share just after fruit set an intense increase in the synthesis of tyrosol and hydroxytyrosol derivatives, by far the main phenolic compounds of the olive fruit, and a subsequent steady decrease along fruit development and ripening.

Network of GRAS transcription factors in plant development, fruit ripening and stress responses.

The plant-specific family of GRAS transcription factors has been wide implicated in the regulation of transcriptional reprogramming associated with a diversity of biological functions ranging from plant development processes to stress responses. Functional analyses of GRAS transcription factors supported by o structural and comparative analyses are emerging and clarifying the regulatory networks associated with their biological roles. In this review, a detailed analysis of GRAS proteins' structure and biochemical features as revealed by recent discoveries indicated how these characteristics may impact subcellular location, molecular mechanisms, and function.

[Gene therapy: Where are we? Where are we going?].

Gene therapy has achieved significant advancements in the treatment of genetic diseases, especially in rare and monogenic diseases. Gene therapies have been developed and approved to treat diseases such as spinal muscular atrophy, offering hope to patients and demonstrating the effectiveness of this therapy. Currently, numerous clinical trials are being conducted to evaluate the safety and efficacy of gene therapy in various diseases, particularly in the field of pediatric neurology.

Associations of accumulated persistent organic pollutants in breast adipose tissue with the evolution of breast cancer after surgery.

Chronic exposure to persistent organic pollutants (POPs) is suspected to contribute to the onset of breast cancer, but the impact on the evolution of patients after diagnosis is unclear. We aimed to analyze the contribution of long-term exposure to five POPs to overall mortality, cancer recurrence, metastasis, and development of second primary tumors over a global follow-up of 10 years after surgery in breast cancer patients in a cohort study. Between 2012 and 2014, a total of 112 newly diagnosed breast cancer patients were recruited from a public hospital in Granada, Southern Spain.

Innovative Computerized Dystrophin Quantification Method Based on Spectral Confocal Microscopy.

Several clinical trials are working on drug development for Duchenne and Becker muscular dystrophy (DMD and BMD) treatment, and, since the expected increase in dystrophin is relatively subtle, high-sensitivity quantification methods are necessary. There is also a need to quantify dystrophin to reach a definitive diagnosis in individuals with mild BMD, and in female carriers. We developed a method for the quantification of dystrophin in DMD and BMD patients using spectral confocal microscopy.

DLin-MC3-Containing mRNA Lipid Nanoparticles Induce an Antibody Th2-Biased Immune Response Polarization in a Delivery Route-Dependent Manner in Mice.

mRNA-based vaccines have made a leap forward since the SARS-CoV-2 pandemic and are currently used to develop anti-infectious therapies. If the selection of a delivery system and an optimized mRNA sequence are two key factors to reach in vivo efficacy, the optimal administration route for those vaccines remains unclear. We investigated the influence of lipid components and immunization route regarding the intensity and quality of humoral immune responses in mice.

VE-Cadherin modulates β-catenin/TCF-4 to enhance Vasculogenic Mimicry.

Vasculogenic Mimicry (VM) refers to the capacity to form a blood network from aggressive cancer cells in an independent way of endothelial cells, to provide nutrients and oxygen leading to enhanced microenvironment complexity and treatment failure. In a previous study, we demonstrated that VE-Cadherin and its phosphorylation at Y658 modulated kaiso-dependent gene expression (CCND1 and Wnt 11) through a pathway involving Focal Adhesion kinase (FAK). In the present research, using a proteomic approach, we have found that β-catenin/TCF-4 is associated with nuclear VE-cadherin and enhances the capacity of malignant melanoma cells to undergo VM in cooperation with VE-Cadherin; in addition, preventing the phosphorylation of Y658 of VE-cadherin upon FAK disabling resulted in VE-Cadherin/β-catenin complex dissociation, increased β-catenin degradation while reducing TCF-4-dependent genes transcription (C-Myc and Twist-1).

An undifferentiated, pleomorphic cardiac sarcoma masquerading as myxoma.

Unlabelled: Cardiac sarcoma is a very rare cause of primary cardiac tumor. We present a case of an undifferentiated, pleomorphic cardiac sarcoma, masquerading as a cardiac myxoma on multimodal imaging evaluation, which was definitively diagnosed on intra-operative histopathologic examination followed by surgical resection.

Learning Objective: Evaluate and diagnose a rare primary cardiac tumor via multimodal imaging and a multidisciplinary approach.

[Guillain-Barré syndrome and other autoimmune neurophaties: current therapy].

Guillain-Barré syndrome (GBS) is characterized by rapidly progressive and generally ascending symmetrical muscle weakness, accompanied by decreased or absent osteotendinous reflexes. The inflammatory process may affect the myelin or the axon. There are 4 clinical forms of GBS: 1) acute inflammatory demyelinating polyradiculoneuropathy, 2) acute motor axonal neuropathy, 3) acute sensory and motor axonal neuropathy, and 4) the Miller-Fisher variant, which is characterized by ophthalmoplegia, ataxia and areflexia, with little muscle weakness.

Validation of motor and functional scales for the evaluation of adult patients with 5q spinal muscular atrophy.

Background And Purpose: Mos scales currently used to evaluate spinal muscular atrophy (SMA) patients have only been validated in children. The aim of this study was to assess the construct validity and responsiveness of several outcome measures in adult SMA patients.

Methods: Patients older than 15 years and followed up in five referral centres for at least 6 months, between October 2015 and August 2020, with a motor function scale score (Hammersmith Functional Motor Scale Expanded [HFMSE], Revised Upper Limb module [RULM]) were included.

Comparison of Physicochemical Properties of LipoParticles as mRNA Carrier Prepared by Automated Microfluidic System and Bulk Method.

Polymeric and/or lipid platforms are promising tools for nucleic acid delivery into cells. We previously reported a lipid-polymer nanocarrier, named LipoParticles, consisting of polylactic acid nanoparticles surrounded by cationic lipids, and allowing the addition of mRNA and cationic LAH4-1 peptide at their surface. Although this mRNA platform has shown promising results in vitro in terms of mRNA delivery and translation, the bulk method used to prepare LipoParticles relies on a multistep and time-consuming procedure.

Combining an optimized mRNA template with a double purification process allows strong expression of transcribed mRNA.

mRNA is a blooming technology for vaccination and has gained global attention during the SARS-CoV-2 pandemic. However, the recent clinical trials have highlighted increased reactogenicity when using high mRNA doses. Intending to increase the potency of mRNA therapeutics and to decrease the therapeutic dose, we designed a mRNA backbone and optimized the mRNA purification process.

Correlation of phytoplankton satellite observations and radiological doses in molluscs.

In this work data of salinity, temperature, suspended particulate matter (SPM), chlorophyll-a, and phytoplankton concentration in the Gibraltar Strait coast, in the confluence of the Mediterranean Sean and the Atlantic Ocean, were analyzed together with Po, K, Pb and Th activity concentration in different types of bivalve molluscs at the same time-period. The physicochemical parameters were evaluated using the Copernicus Marine Environment Monitoring Service (CMEMS) products based on satellite observations. A multivariate statistical analysis, including contrasted natural radioactivity contents, allowed the discrimination of bivalve molluscs from Atlantic and Mediterranean coasts.

Adipose Tissue Redox Microenvironment as a Potential Link between Persistent Organic Pollutants and the 16-Year Incidence of Non-hormone-Dependent Cancer.

We aimed to assess the relationships among the adipose tissue's (AT) oxidative microenvironment, accumulated persistent organic pollutant (POP) concentrations, and cancer development. POP and oxidative stress levels were quantified in AT samples from 382 adults recruited within the GraMo cohort (2003-2004) in Granada (Spain). The 16-year cancer incidence was ascertained by reviewing health/administrative databases.

Impact of Intravenous Antihypertensives on Outcomes Among Hospitalized Patients.

Background: Many hospitalized patients with acute elevations in blood pressure (BP) are treated with intravenous (IV) antihypertensive medications without evidence of benefit. This study investigated the effects of IV as-needed (PRN) antihypertensives on BP, hospital length of stay, and mortality.

Methods: We included hospitalized patients with an order for an IV PRN antihypertensive medication.

Use of Neurodynamic or Orthopedic Tension Tests for the Diagnosis of Lumbar and Lumbosacral Radiculopathies: Study of the Diagnostic Validity.

Background: Lumbar radiculopathy is a nerve root disorder whose correct diagnosis is essential. The objective of the present study was to analyze the reliability diagnostic validity of eight neurodynamic and/or orthopedic tension tests using magnetic resonance imaging as the Gold Standard.

Methods: An epidemiological study of randomized consecutive cases which was observational, descriptive, transversal, double blinded and was conducted following the Standards for Reporting Diagnostic accuracy studies (STARD) declaration.

Fluorescent perylenylpyridine complexes: an experimental and theoretical study.

The perylene derivative 2-(3-perylenyl)-4-methylpyridine (HPerPy) was prepared and used to synthesize [Ag(HPerPy)(PPh3)(OClO3)], with the perylene ligand bonded to the metal centre only by the pyridine nitrogen. The treatment of HPerPy with [Pd(OAc)2] in methanol or acetic acid led to acetate bridged dimers (μ-OOCCH3)2[Pd(PerPy)]2, six-membered or five-membered cycled at the perylenyl fragment. Substitution reactions afforded mononuclear compounds [Pd(PerPy)(acac)] (six-member or five-member cycled) and [Pd(PerPy)(S2COMe)] (six-member or five-member cycled).

Rationale for the Use of Radiation-Activated Mesenchymal Stromal/Stem Cells in Acute Respiratory Distress Syndrome.

We have previously shown that the combination of radiotherapy with human umbilical-cord-derived mesenchymal stromal/stem cells (MSCs) cell therapy significantly reduces the size of the xenotumors in mice, both in the directly irradiated tumor and in the distant nonirradiated tumor or its metastasis. We have also shown that exosomes secreted from MSCs preirradiated with 2 Gy are quantitatively, functionally and qualitatively different from the exosomes secreted from nonirradiated mesenchymal cells, and also that proteins, exosomes and microvesicles secreted by MSCs suffer a significant change when the cells are activated or nonactivated, with the amount of protein present in the exosomes of the preirradiated cells being 1.5 times greater compared to those from nonirradiated cells.

The efficacy of three-dimensional conformal radiation therapy on pain and quality of life in patients with painful bone metastases: a prospective study.

Aim: To evaluate the efficacy of radiation therapy in alleviating pain and improving the quality of life (QoL) with validated questionnaires in patients with painful bone metastases (BoM).

Methods: This prospective, observational study recruited 167 patients with painful BoM who were treated with palliative radiotherapy (PRT) from February 2015 to February 2018. After the first clinical assessment, the patients filled out specific questionnaires and underwent a fast radiotherapy treatment within 48 hours.

Enhancing the Bystander and Abscopal Effects to Improve Radiotherapy Outcomes.

In this paper, we summarize published articles and experiences related to the attempt to improve radiotherapy outcomes and, thus, to personalize the radiation treatment according to the individual characteristics of each patient. The evolution of ideas and the study of successively published data have led us to envisage new biophysical models for the interpretation of tumor and healthy normal tissue response to radiation. In the development of the model, we have shown that when mesenchymal stem cells (MSCs) and radiotherapy are administered simultaneously in experimental radiotherapy on xenotumors implanted in a murine model, the results of the treatment show the existence of a synergic mechanism that is able to enhance the local and systemic actions of the radiation both on the treated tumor and on its possible metastasis.