Vitamin A Status Modulates Epithelial Mesenchymal Transition in the Lung: The Role of Furin.

Vitamin A deficiency (VAD) induced TGF-β hyperactivation and reduced expression of cell adhesion proteins in the lung, suggesting that the disruption of retinoic acid (RA) signaling leads to epithelial-mesenchymal transition (EMT). To elucidate the role of lung vitamin A status in EMT, several EMT markers and the expression of the proprotein convertase furin, which activates TGF-β, were analyzed in two experimental models. Our in vivo model included control rats, VAD rats, and both control rats and VAD rats, treated with RA.

Calpains, the proteases of two faces controlling the epithelial homeostasis in mammary gland.

Calpain-1 and calpain-2 are calcium-dependent Cys-proteases ubiquitously expressed in mammalian tissues with a processive, rather than degradative activity. They are crucial for physiological mammary gland homeostasis as well as for breast cancer progression. A growing number of evidences indicate that their pleiotropic functions depend on the cell type, tissue and biological context where they are expressed or dysregulated.

Identification of circulating miRNAs differentially expressed in patients with Limb-girdle, Duchenne or facioscapulohumeral muscular dystrophies.

Background: Limb-girdle muscular dystrophy (LGMD) is a rare neuromuscular disease including a growing and heterogeneous number of subtypes with variable phenotype. Their clinical and histopathological characteristics frequently overlap with other neuromuscular dystrophies. Our goal was to identify, by a non-invasive method, a molecular signature including biochemical and epigenetic parameters with potential value for patient prognosis and stratification.

From genetics to epigenetics to unravel the etiology of adolescent idiopathic scoliosis.

Scoliosis is defined as the three-dimensional (3D) structural deformity of the spine with a radiological lateral Cobb angle (a measure of spinal curvature) of ≥10° that can be caused by congenital, developmental or degenerative problems. However, those cases whose etiology is still unknown, and affect healthy children and adolescents during growth, are the commonest form of spinal deformity, known as adolescent idiopathic scoliosis (AIS). In AIS management, early diagnosis and the accurate prediction of curve progression are most important because they can decrease negative long-term effects of AIS treatment, such as unnecessary bracing, frequent exposure to radiation, as well as saving the high costs of AIS treatment.

Role of Vitamin A in Mammary Gland Development and Lactation.

Vitamin A (all--retinol), its active derivatives retinal and retinoic acid, and their synthetic analogues constitute the group of retinoids. It is obtained from diet either as preformed vitamin A or as carotenoids. Retinal plays a biological role in vision, but most of the effects of vitamin A are exerted by retinoic acid, which binds to nuclear receptors and regulates gene transcription.

Vitamin A Deficiency and the Lung.

Vitamin A (all--retinol) is a fat-soluble micronutrient which together with its natural derivatives and synthetic analogues constitutes the group of retinoids. They are involved in a wide range of physiological processes such as embryonic development, vision, immunity and cellular differentiation and proliferation. Retinoic acid (RA) is the main active form of vitamin A and multiple genes respond to RA signalling through transcriptional and non-transcriptional mechanisms.

Correction: New localization and function of calpain-2 in nucleoli of colorectal cancer cells in ribosomal biogenesis: effect of KRAS status.

[This corrects the article DOI: 10.18632/oncotarget.23888.

How Glutamate Is Managed by the Blood-Brain Barrier.

A facilitative transport system exists on the blood-brain barrier (BBB) that has been tacitly assumed to be a path for glutamate entry to the brain. However, glutamate is a non-essential amino acid whose brain content is much greater than plasma, and studies in vivo show that glutamate does not enter the brain in appreciable quantities except in those small regions with fenestrated capillaries (circumventricular organs). The situation became understandable when luminal (blood facing) and abluminal (brain facing) membranes were isolated and studied separately.

Isoform-specific function of calpains in cell adhesion disruption: studies in postlactational mammary gland and breast cancer.

Cleavage of adhesion proteins is the first step for physiological clearance of undesired cells during postlactational regression of the mammary gland, but also for cell migration in pathological states such as breast cancer. The intracellular Ca(2+)-dependent proteases, calpains (CAPNs), are known to cleave adhesion proteins. The isoform-specific function of CAPN1 and CAPN2 was explored and compared in two models of cell adhesion disruption: mice mammary gland during weaning-induced involution and breast cancer cell lines according to tumor subtype classification.

Involvement of Different networks in mammary gland involution after the pregnancy/lactation cycle: Implications in breast cancer.

Early pregnancy is associated with a reduction in a woman's lifetime risk for breast cancer. However, different studies have demonstrated an increase in breast cancer risk in the years immediately following pregnancy. Early and long-term risk is even higher if the mother age is above 35 years at the time of first parity.

In vivo genome-wide binding of Id2 to E2F4 target genes as part of a reversible program in mice liver.

The inhibitor of differentiation Id2, a protein lacking the basic DNA-binding domain, is involved in the modulation of a number of biological processes. The molecular mechanisms explaining Id2 pleiotropic functions are poorly understood. Id2 and E2F4 are known to bind simultaneously to c-myc promoter.

Metabolomics in the diagnosis of acute myocardial ischemia.

Despite recent advances in the diagnosis of myocardial ischemia, its biochemical identification in patients with acute chest pain is still a challenge, and alternative approaches for further improvement are needed. Metabolic alterations are the first consequences of acute myocardial ischemia. Metabolomics coupled with potent multivariate analyses allows for a simultaneous and relative quantification of thousands of different metabolites within a given sample.

Metabolomic profile of human myocardial ischemia by nuclear magnetic resonance spectroscopy of peripheral blood serum: a translational study based on transient coronary occlusion models.

Objectives: The aim of this study was to investigate the metabolomic profile of acute myocardial ischemia (MIS) using nuclear magnetic resonance spectroscopy of peripheral blood serum of swine and patients undergoing angioplasty balloon-induced transient coronary occlusion.

Background: Biochemical detection of MIS is a major challenge. The validation of novel biosignatures is of utmost importance.

NF-ĸB as node for signal amplification during weaning.

Post-lactational involution has been reported to share common features with breast tumor development. A deep characterization of the signaling triggered after weaning would help to unveil the complex relationship between involution and breast cancer. NF-κB, a crucial factor in the involuting gland, might be an important regulatory node for signal amplification after weaning; however there is limited information about the identity of NF-κB-target genes and the molecular mechanisms leading to the selection of genes involved in a particular biological process.

Evaluation of the quality of publications on randomized clinical trials using the Consolidated Standards of Reporting Trials (CONSORT) statement guidelines in a Spanish tertiary hospital.

The main reason for conducting a clinical trial (CT) is to test the effect of a drug or medical procedure to improve treatment of a disease. CTs contribute most when they are rigorously conducted and the results are published adequately. The aim of this study is to assess, using the CONSORT statement guidelines, the quality of reporting of completed CTs conducted at a tertiary hospital to determine which sections of the articles should be improved.

Molecular mechanisms of Id2 down-regulation in rat liver after acetaminophen overdose. Protection by N-acetyl-L-cysteine.

Id2 is a pleiotropic protein whose function depends on its expression levels. Id2-deficient cells show increased cell death. This study explored the molecular mechanisms for the modulation of Id2 expression elicited by GSH and oxidative stress in the liver of acetaminophen (APAP)-intoxicated rats.

Nitric oxide triggers mammary gland involution after weaning: remodelling is delayed but not impaired in mice lacking inducible nitric oxide synthase.

During mammary gland involution, different signals are required for apoptosis and tissue remodelling. To explore the role of NO in the involution of mammary tissue after lactation, NOS2 (inducible nitric oxide synthase)-KO (knockout) mice were used. No apparent differences were observed between NOS2-KO and WT (wild-type) animals during pregnancy and lactation.

Triple-negative breast cancer: molecular features, pathogenesis, treatment and current lines of research.

Breast cancer is a heterogeneous disease with different morphologies, molecular profiles, clinical behaviour and response to therapy. The triple negative is a particular type of breast cancer defined by absence of oestrogen and progesterone receptor expression as well as absence of ERBB2 amplification. It is characterized by its biological aggressiveness, worse prognosis and lack of a therapeutic target in contrast with hormonal receptor positive and ERBB2+ breast cancers.

Glutamate permeability at the blood-brain barrier in insulinopenic and insulin-resistant rats.

The influence of diabetes on brain glutamate (GLU) uptake was studied in insulinopenic (streptozotocin [STZ]) and insulin-resistant (diet-induced obesity [DIO]) rat models of diabetes. In the STZ study, adult male Sprague-Dawley rats were treated with STZ (65 mg/kg intravenously) or vehicle and studied 3 weeks later. The STZ rats had elevated plasma levels of glucose, ketone bodies, and branched-chain amino acids; brain uptake of GLU was very low in both STZ and control rats, examined under conditions of normal and greatly elevated (by intravenous infusion) plasma GLU concentrations.

In vivo GSH depletion induces c-myc expression by modulation of chromatin protein complexes.

We hypothesize that glutathione (GSH) fluctuations could have a prominent role in the modulation of c-myc expression through a mechanism affecting chromatin remodeling complexes. This could lead to an open chromatin structure accessible to transcription factors. We studied the in vivo effect of GSH depletion on these complexes bound to the c-myc promoter in the liver of l-buthionine-(S,R)-sulfoximine (BSO)-treated rats.

Nitration of cathepsin D enhances its proteolytic activity during mammary gland remodelling after lactation.

Proteomic studies in the mammary gland of control lactating and weaned rats have shown that there is an increased pattern of nitrated proteins during weaning when compared with controls. Here we report the novel finding that cathepsin D is nitrated during weaning. The expression and protein levels of this enzyme are increased after 8 h of litter removal and this up-regulation declines 5 days after weaning.

Pyroglutamate stimulates Na+ -dependent glutamate transport across the blood-brain barrier.

Regulation of Na(+)-dependent glutamate transport was studied in isolated luminal and abluminal plasma membranes derived from the bovine blood-brain barrier. Abluminal membranes have Na(+)-dependent glutamate transporters while luminal membranes have facilitative transporters. This organization allows glutamate to be actively removed from brain.