Novel anticancer drug discovery efforts targeting glycosylation: the emergence of fluorinated monosaccharides analogs.

Introduction: Glycosylation is an essential enzymatic process of building glycan structures that occur mainly within the cell and gives rise to a diversity of cell surface and secreted glycoconjugates. These glycoconjugates play vital roles, for instance in cellcell adhesion, interaction and communication, activation of cell surface receptors, inflammatory response and immune recognition. This controlled and wellcoordinated enzymatic process is altered in cancer, leading to the biosynthesis of cancerassociated glycans, which impact glycandependent biological roles.

Effect of prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet.

Background: The gluten-free diet (GFD) has limitations, and there is intense research in the development of adjuvant therapies.

Aim: To examine the effects of orally administered prolyl endopeptidase protease (AN-PEP) on inadvertent gluten exposure and symptom prevention in adult celiac disease (CeD) patients following their usual GFD.

Methods: This was an exploratory, double-blind, randomized, placebo-controlled trial that enrolled CeD patients on a long-term GFD.

ST3GalIV drives SLeX biosynthesis in gastrointestinal cancer cells and associates with cancer cell motility.

Expression of sialyl Lewis X (SLeX) is a well-documented event during malignant transformation of cancer cells, and largely associates with their invasive and metastatic properties. Glycoproteins and glycolipids are the main carriers of SLeX, whose biosynthesis is known to be performed by different glycosyltransferases, namely by the family of β-galactoside-α2,3-sialyltransferases (ST3Gals). In this study, we sought to elucidate the role of ST3GalIV in the biosynthesis of SLeX and in malignant properties of gastrointestinal (GI) cancer cells.

Exploring the Effects of Meditation Techniques Used by Mindfulness-Based Programs on the Cognitive, Social-Emotional, and Academic Skills of Children: A Systematic Review.

There is evidence for the positive impact of mindfulness in children. However, little is known about the techniques through which mindfulness practice results in differential outcomes. Therefore, this study intended to systematically review the available evidence about the efficacy of meditation techniques used by mindfulness-based programs on cognitive, socio-emotional, and academic skills of children from 6 to 12 years of age.

Enhancing the resilience of Zostera noltei seagrass meadows against Arenicola spp. bio-invasion: A decision-making approach.

Seagrass meadows provide important and valuable ecosystem services. They are affected by several natural and human-induced stressors, but a combination of natural recovery and management actions have recently inverted the worldwide reduction. The main objectives of this study were to provide science-based knowledge on ecology and restoration, framed on environmental-related policies.

Acute paraplegia as a presentation of acute aortic occlusion.

Acute aortic occlusion is a rare life-threatening event. We present a case of a heavy smoking, 54-year-old man who was admitted in the emergency room with sudden paraplegia, associated to severe lower back and lower limbs pain. A neurologic examination showed paralysis of the lower limbs and cold lower extremities.

Targeting Glycosylation: A New Road for Cancer Drug Discovery.

Cancer is a deadly disease that encompasses numerous cellular modifications. Among them, alterations in glycosylation are a proven reliable hallmark of cancer, with most biomarkers used in the clinic detecting cancer-associated glycans. Despite their clear potential as therapy targets, glycans have been overlooked in drug discovery strategies.

Real-World Gluten Exposure in Patients With Celiac Disease on Gluten-Free Diets, Determined From Gliadin Immunogenic Peptides in Urine and Fecal Samples.

Background & Aims: It is not clear how often patients who are on gluten-free diets (GFDs) for treatment of celiac disease still are exposed to gluten. We studied levels of gluten immunogenic peptides (GIP) in fecal and urine samples, collected over 4 weeks, from patients with celiac disease on a long-term GFD.

Methods: We performed a prospective study of 53 adults with celiac disease who had been on a GFD for more than 2 years (median duration, 8 y; interquartile range, 5-12 y) in Argentina.

β Adrenoceptor-induced cholinergic inhibition in human and rat urinary bladders involves the exchange protein directly activated by cyclic AMP 1 favoring adenosine release.

Background And Purpose: The mechanism by which β receptor agonists (e.g. mirabegron) control bladder overactivity may involve adenosine release from human and rat detrusor smooth muscle.

Immunochip meta-analysis in European and Argentinian populations identifies two novel genetic loci associated with celiac disease.

Celiac disease (CeD) is a common immune-mediated disease of the small intestine that is triggered by exposure to dietary gluten. While the HLA locus plays a major role in disease susceptibility, 39 non-HLA loci were also identified in a study of 24,269 individuals. We now build on this earlier study by adding 4125 additional Caucasian samples including an Argentinian cohort.

Gluten immunogenic peptide excretion detects dietary transgressions in treated celiac disease patients.

Background: Life-long removal of gluten from the diet is currently the only way to manage celiac disease (CeD). Until now, no objective test has proven useful to objectively detect ingested gluten in clinical practice. Recently, tests that determine consumption of gluten by assessing excretion of gluten immunogenic peptides (GIP) in stool and urine have been developed.

A Prospective Study on Cognitive Impairment in Middle-aged Adults With Newly Diagnosed Celiac Disease.

Aims: Our objectives were to: (1) determine whether celiac disease (CD) patients have cognitive impairment at diagnosis; and (2) compare their cognitive performance with nonceliac subjects who have similar chronic symptoms and healthy controls.

Materials And Methods: Fifty adults (age range: 18 to 50 y) with symptoms and signs compatible with CD were enrolled in a prospective cohort irrespective of the final diagnosis. At baseline, all individuals underwent cognitive functional and psychological evaluation.

Inhibition of cholinergic neurotransmission by β-adrenoceptors depends on adenosine release and A-receptor activation in human and rat urinary bladders.

The direct detrusor relaxant effect of β-adrenoceptor agonists as a primary mechanism to improve overactive bladder symptoms has been questioned. Among other targets, activation of β-adrenoceptors downmodulate nerve-evoked acetylcholine (ACh) release, but there is insufficient evidence for the presence of these receptors on bladder cholinergic nerve terminals. Our hypothesis is that adenosine formed from the catabolism of cyclic AMP in the detrusor may act as a retrograde messenger via prejunctional A receptors to explain inhibition of cholinergic activity by β-adrenoceptors.

Evaluation of a subset of tumor suppressor gene for copy number and epigenitic changes in pleomorphic adenoma and carcinoma ex-pleomorphic adenoma carcinogenesis.

Objective: The progression of pleomorphic adenoma (PA) to carcinoma ex-pleomorphic adenoma (CXPA) encompasses several genomic alterations involving complex pathways. Tumor suppressor genes seem to play important roles in the tumorigenesis of both tumors. The aim of this study was to evaluate copy number and methylation of tumor suppressor genes' status in PA and CXPA samples.

Cellular Proliferation Index between Carcinoma Ex-Pleomorphic Adenoma and Pleomorphic Adenoma.

Carcinoma ex pleomorphic adenoma (CXPA) has been considered an interesting model of carcinogenesis, presenting various histological subtypes and invasiveness phase. The objective was to determine the proliferative index of CXPA and comparing to pleomorphic adenoma (PA). Thirty six cases of CXPA (36 PA) and 22 areas of PA in CXPA (residual PA) were studied by Ki-67 expression.

Analysis of MYB oncogene in transformed adenoid cystic carcinomas reveals distinct pathways of tumor progression.

Adenoid cystic carcinomas can occasionally undergo dedifferentiation, a phenomenon also referred to as high-grade transformation. However, cases of adenoid cystic carcinomas have been described showing transformation to adenocarcinomas that are not poorly differentiated, indicating that high-grade transformation may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form, which may encompass a wide spectrum of carcinomas in terms of aggressiveness. The aim of this study was to gain more insight in the biology of this pathological phenomenon by means of genetic profiling of both histological components.

Entamoeba histolytica: gene expression analysis of cells invading tissues.

Entamoeba histolytica is a protozoan parasite that presents a risk to the health of millions of people worldwide. Due to the existence of different clinical forms caused by the parasite and also different virulence levels presented by one strain, one would expect differences in the profile of gene transcripts between virulent and nonvirulent cultures. In this study we used the differential display to select gene segments related to invasiveness of amoeba.

Docking studies in target proteins involved in antibacterial action mechanisms: extending the knowledge on standard antibiotics to antimicrobial mushroom compounds.

In the present work, the knowledge on target proteins of standard antibiotics was extended to antimicrobial mushroom compounds. Docking studies were performed for 34 compounds in order to evaluate their affinity to bacterial proteins that are known targets for some antibiotics with different mechanism of action: inhibitors of cell wall synthesis, inhibitors of protein synthesis, inhibitors of nucleic acids synthesis and antimetabolites. After validation of the molecular docking approach, virtual screening of all the compounds was performed against penicillin binding protein 1a (PBP1a), alanine racemase (Alr), d-alanyl-d-alanine synthetase (Ddl), isoleucyl-tRNA sinthetase (IARS), DNA gyrase subunit B, topoisomerase IV (TopoIV), dihydropteroate synthetase (DHPS) and dihydrofolate reductase (DHFR) using AutoDock4.

Tubular variant of basal cell adenoma shares immunophenotypical features with normal intercalated ducts and is closely related to intercalated duct lesions of salivary gland.

Aims: The morphological criteria for identification of intercalated duct lesions (IDLs) of salivary glands have been defined recently. It has been hypothesised that IDL could be a precursor of basal cell adenoma (BCA). BCAs show a variety of histological patterns, and the tubular variant is the one that presents the strongest resemblance with IDLs.

Probing electron transfer with Escherichia coli: a method to examine exoelectronics in microbial fuel cell type systems.

Escherichia coli require mediators or composite anodes for substantial outward electron transfer, >8A/m(2). To what extent non-mediated direct electron transfer from the outer cell envelope to the anode occurs with E. coli is a debated issue.

Signet-ring cell change in adenoid cystic carcinoma: a clinicopathological and immunohistochemical study of four cases.

Aims: Signet-ring cell (SRC) change has not been reported in adenoid cystic carcinoma (ACC). The aim of this study was to describe the clinicopathological and immunohistochemical findings in four cases of ACC with SRCs (ACC-SRC), in which the relative proportion of the SRC component ranged from 25% to 50%.

Methods And Results: The median age was 58 years (range: 48-81 years), and all patients were women.

Prednisolone and cyclosporine A: effects on an experimental model of ancylostomiasis.

Corticosteroids and cyclosporine A (CsA) are important clinical immunosuppressive drugs used in the maintenance of organ transplants and in suppressing undesired autoimmune or allergic immune responses. To study the effect of CsA and prednisolone on the course of an Ancylostoma ceylanicum infection, hamsters were treated with commercially available prednisolone or CsA. For both drugs, half the recommended dose was sufficient to inhibit the proliferation of more than 70% of hamster lymph node cells.

Levels and patterns of expression of hypoxia-inducible factor-1α, vascular endothelial growth factor, glucose transporter-1 and CD105 in adenoid cystic carcinomas with high-grade transformation.

Aims: To compare the expression of proteins regulated by hypoxia between adenoid cystic carcinoma (ACC) with and without high-grade transformation (HGT).

Methods And Results:   In eight ACC-HGT and 18 ACC without HGT, expression of hypoxia-inducible factor-1 (HIF-1α), vascular endothelial growth factor (VEGF), glucose transporter-1 (GLUT-1) and microvascular density (MVD) by CD105 (a hypoxia-inducible protein expressed in angiogenic endothelial cells) was determined. Expression levels of HIF-1α and VEGF as well as CD105-MVD did not differ significantly between: (i) transformed and conventional areas (TA and CA, respectively) of ACC-HGT, (ii) CA and ordinary ACC.