Molecular determinants of enhanced response to somatostatin receptor ligands after debulking in large GH-producing adenomas.

Objective: Large somatotrophic adenomas depict poor response to somatostatin receptor ligands (SRLs). Debulking has shown to enhance SRLs effect in some but not all cases and tumour volume reduction has been proposed as the main predictor of response. No biological studies have been performed so far in this matter.

Impact of a Home Telehealth Program After a Hospitalized COPD Exacerbation: A Propensity Score Analysis.

Introduction: Currently there is lack of data regarding the impact of a home telehealth program on readmissions and mortality rate after a COPD exacerbation-related hospitalization.

Objective: To demonstrate if a tele-monitoring system after a COPD exacerbation admission could have a favorable effect in 1-year readmissions and mortality in a real-world setting.

Methods: This is an observational study where we compared an intervention group of COPD patients treated after hospitalization that conveyed a telehealth program with a followance period of 1 year with a control group of patients evaluated during one year before the intervention began.

Methylation Levels in Leukocytes From Women With Breast Cancer Is Modulated by Adiposity, Menopausal State, and the Mediterranean Diet.

The methylation levels of in breast tumors has been previously identified as a possible epigenetic mark of breast cancer associated with obesity. The aim of the current study was to investigate differences in methylation levels of depending on obesity, menopausal state and dietary pattern in blood leukocytes, a non-invasive sample. The methylation levels of of two CpG sites (CpGs) located in promoter and island previously identified as differentially methylated according to adiposity and menopausal state by 450 k array (cg10635122, cg03562414) were evaluated by pyrosequencing in DNA from the blood leukocytes of breast cancer patients [ = 90; = 64 (71.

Essential role of the C148-C227 disulphide bridge in the human 5-HT homodimeric receptor.

The 5-HT receptor is a homodimeric G protein-coupled receptor implied in multiple diseases, including schizophrenia. Recently, its co-crystallisation with the antipsychotic drugs zotepine and risperidone has revealed the importance of its extracellular domains in its pharmacology. Previous studies have shown that the non-specific disruption of extracellular disulphide bridges in the 5-HT receptor decreases ligand binding and receptor activation.

Anisakis Sensitization in the Croatian fish processing workers: Behavioral instead of occupational risk factors?

We undertook the first study systematically evaluating the risk of Anisakis-sensitization in Croatian fish-processing workers and potential genetic susceptibility to anisakiasis. Anti-Anisakis IgE seroprevalence and risk factors for 600 employees of Croatian fish processing facilities and 466 blood donor controls, were assessed by indirect ELISA targeted with: recombinant Ani s 1 and Ani s 7 allergens, an Anisakis crude extract, the commercial ImmunoCAP kit, and questionnaires. Genetic susceptibility to anisakiasis was evaluated by genotypisation of human leukocytes alleles (HLA).

An energy restriction-based weight loss intervention is able to reverse the effects of obesity on the expression of liver tumor-promoting genes.

The epidemiological evidence regarding the association of obesity with liver disease and possibly hepatocellular carcinoma highlights the need for investigations of whether obesity itself could induce the differential expression of genes commonly associated with the initial phase of liver tumorigenesis, and whether such phenomenon could be reversed after a weight loss intervention. In this study, obese Zucker rats were found to have dysregulated cell proliferation, antioxidative defenses, and tumor suppressor gene expression in association with liver dysfunction parameters, as well as oxidative stress and inflammation. Importantly, after a 4-week weight loss protocol of energy restriction and/or exercise, this effect on the liver carcinogenesis-related genes was reversed concomitantly with reductions in the fat mass, hepatic lipid content, oxidative stress, and inflammation.

Proteomic investigation on bio-corona of Au, Ag and Fe nanoparticles for the discovery of triple negative breast cancer serum protein biomarkers.

Nowadays, there are no targeted therapeutic modalities for triple negative breast cancer (TNBC). This disease is associated with poor prognosis and worst clinical outcome because of the aggressive nature of the tumor, delayed diagnosis, and non-specific symptoms in the early stages. Therefore, identification of novel specific TNBC serum biomarkers for screening and therapeutic purposes remains an urgent clinical requirement.

In search of an evidence-based strategy for quality assessment of human tissue samples: report of the tissue Biospecimen Research Working Group of the Spanish Biobank Network.

The purpose of the present work is to underline the importance of obtaining a standardized procedure to ensure and evaluate both clinical and research usability of human tissue samples. The study, which was carried out by the Biospecimen Science Working Group of the Spanish Biobank Network, is based on a general overview of the current situation about quality assurance in human tissue biospecimens. It was conducted an exhaustive review of the analytical techniques used to evaluate the quality of human tissue samples over the past 30 years, as well as their reference values if they were published, and classified them according to the biomolecules evaluated: (i) DNA, (ii) RNA, and (iii) soluble or/and fixed proteins for immunochemistry.

Potential clinical applications of the personalized, disease-specific protein corona on nanoparticles.

Nanoscale objects lose their original identity once in contact with biological fluids and get a new biological identity, referred to as a protein corona (PC). The PC modifies many of the physicochemical properties of nanoparticles (NPs), including surface charge, size, and aggregation state. These changes, in turn, affect the biological fate of NPs, including their biodistribution, pharmacokinetics, and therapeutic efficacy.

Unmasking a new prognostic marker and therapeutic target from the GDNF-RET/PIT1/p14ARF/p53 pathway in acromegaly.

Background: Acromegaly is produced by excess growth hormone secreted by a pituitary adenoma of somatotroph cells (ACRO). First-line therapy, surgery and adjuvant therapy with somatostatin analogs, fails in 25% of patients. There is no predictive factor of resistance to therapy.

Naturally presented HLA class I-restricted epitopes from the neurotrophic factor S100-β are targets of the autoimmune response in type 1 diabetes.

Type 1 diabetes (T1D) results from the destruction of pancreatic β-cells by the immune system, and CD8 T lymphocytes are critical actors in this autoimmune response. Pancreatic islets are surrounded by a mesh of nervous cells, the peri-insular Schwann cells, which are also targeted by autoreactive T lymphocytes and express specific antigens, such as the neurotrophic factor S100-β. Previous work has shown increased proliferative responses to whole S100-β in both human T1D patients and the nonobese diabetic (NOD) mouse model.

Proteomic analysis of the bio-corona formed on the surface of (Au, Ag, Pt)-nanoparticles in human serum.

Adsorption of biomolecules onto nanoparticles surface in biological samples led to the formation of a bio-corona, it could modified the "identity" of nanoparticles, contributing to the determination of their toxicity and biocompatibility. Gel electrophoresis in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to qualitatively analyze and identify the human serum proteins adsorbed on the surface of three different nanomaterials stabilized with citrate: 10.02 ± 0.

Circulating Pro-Uroguanylin Levels In Children And Their Relation To Obesity, Sex And Puberty.

Uroguanylin is a 16 amino acid peptide that constitutes a key component of the gut- brain axis with special relevance in body weight regulation. In childhood and adolescence, periods of life with notable metabolic changes; limited data exist, with measurements of pro-uroguanylin in adolescence but not in prepubertal children. This study investigates pro-uroguanylin circulating levels in children with obesity and its relationship with obesity, sex and pubertal development.

Mechanisms of Bacterial Tolerance and Persistence in the Gastrointestinal and Respiratory Environments.

Pathogens that infect the gastrointestinal and respiratory tracts are subjected to intense pressure due to the environmental conditions of the surroundings. This pressure has led to the development of mechanisms of bacterial tolerance or persistence which enable microorganisms to survive in these locations. In this review, we analyze the general stress response (RpoS mediated), reactive oxygen species (ROS) tolerance, energy metabolism, drug efflux pumps, SOS response, quorum sensing (QS) bacterial communication, (p)ppGpp signaling, and toxin-antitoxin (TA) systems of pathogens, such as , spp.

Novel functionalized nanomaterials for the effective enrichment of proteins and peptides with post-translational modifications.

Low abundance proteins/peptides usually suffer strong interference with highly abundant proteins/peptides as well as other contaminants, resulting in low ionization efficiency in MS analysis. Hence, the enrichment and separation of proteins/peptides from complex mixtures are of great value to their successful identification. In this review we present an overview of the application of different nanocomposites for the specific enrichment of peptides/proteins with post-translational modifications (PTMs), such as phosphorylation and glycosylation.

Uroguanylin: a new actor in the energy balance movie.

Uroguanylin (UGN) is a potential target in the fight against obesity. The mature protein is released after enzymatic cleavage from its natural precursor, proUGN. UGN is mostly produced in the gut, and its production is regulated by nutritional status.

Evolution and bad prognostic value of advanced glycation end products after acute heart failure: relation with body composition.

Aim: The role of advanced glycation end products (AGEs) and their soluble receptor (sRAGE) on the progression and prognosis of acute heart failure (HF) was analysed in relation with metabolic parameters as body composition and nutritional status.

Methods: A hundred and fifty consecutive patients were included in a prospective clinical study during hospitalization by acute HF. Detailed medical history, physical examination, electrocardiogram, echocardiogram and vein peripheral blood were taken for all patients.

Obesity and menopause modify the epigenomic profile of breast cancer.

Obesity is a high risk factor for breast cancer. This relationship could be marked by a specific methylome. The current work was aimed to explore the impact of obesity and menopausal status on variation in breast cancer methylomes.

Long-term outcome of multimodal therapy for giant prolactinomas.

Giant prolactinomas are rare tumors characterized by their large size, compressive symptoms, and extremely high prolactin secretion. The aim of this study is to describe our experience with a series of 16 giant prolactinomas cases in terms of clinical presentation, therapeutic decisions, and final outcomes. Retrospective analysis of adult patients diagnosed with giant prolactinomas at the endocrine departments of three university tertiary hospitals.

Carglumic acid enhances rapid ammonia detoxification in classical organic acidurias with a favourable risk-benefit profile: a retrospective observational study.

Background: Isovaleric aciduria (IVA), propionic aciduria (PA) and methylmalonic aciduria (MMA) are inherited organic acidurias (OAs) in which impaired organic acid metabolism induces hyperammonaemia arising partly from secondary deficiency of N-acetylglutamate (NAG) synthase. Rapid reduction in plasma ammonia is required to prevent neurological complications. This retrospective, multicentre, open-label, uncontrolled, phase IIIb study evaluated the efficacy and safety of carglumic acid, a synthetic structural analogue of NAG, for treating hyperammonaemia during OA decompensation.

The autotaxin-lysophosphatidic acid pathway in pathogenesis of rheumatoid arthritis.

Lysophosphatidic acid (LPA) is a phospholipid that is mainly produced by the hydrolysis of lysophosphatidylcholine (LPC) by lysophospholipase D, which is also called autotaxin (ATX). LPA interacts with specific G-protein coupled receptors and is involved in the regulation of cellular survival, proliferation, differentiation and motility. LPA also has roles in several pathological disorders, such as cancer and pulmonary, dermal and renal fibrosis.

Substraction acetazolamide SPECT co-registered to MRI in moyamoya disease: quantitative cerebrovascular reserve map.

A 48-year-old-woman suffering from recurrent left hemipalsy was referred to the hospital. MRI showed hyperintense lesions in periventricular white matter. Cerebral angiography revealed stenosis in the bilateral internal carotid and hypertrophic collateral vessels at the brain base, compatible with moyamoya syndrome.

The NMR structure of human obestatin in membrane-like environments: insights into the structure-bioactivity relationship of obestatin.

The quest for therapeutic applications of obestatin involves, as a first step, the determination of its 3D solution structure and the relationship between this structure and the biological activity of obestatin. On this basis, we have employed a combination of circular dichroism (CD), nuclear magnetic resonance (NMR) spectroscopy, and modeling techniques to determine the solution structure of human obestatin (1). Other analogues, including human non-amidated obestatin (2) and the fragment peptides (6-23)-obestatin (3), (11-23)-obestatin (4), and (16-23)-obestatin (5) have also been scrutinized.