Thermal treatment at 500 °C significantly reduces the reaction to irregular tricalcium phosphate granules as foreign bodies: An in vivo study.

Evaporation of phosphate species during thermal treatment (> 400 °C) of calcium phosphates leads to the formation of an alkaline layer on their surface. The aim of this study was to evaluate the hypothesis that the biological response of thermally treated calcium phosphates is modified by the presence of such an alkaline layer on their surface. For this purpose, 0.

Soluble suppression of tumorigenicity-2 predicts pneumonia in patients with inhalation injury: Results of a pilot study.

Introduction: Several mechanisms play a role in the development of pneumonia after inhalation injury. Our aim was to analyze whether higher concentrations of inflammatory markers or of biomarkers of epithelial injury are associated with a higher incidence of pneumonia in patients with inhalation injury.

Material And Methods: Secondary analysis of a single-center prospective observational cohort pilot study, performed over a two-year period (2015-2017) at the Burns Unit of the Plastic and Reconstructive Surgery Department of Vall d'Hebron University Hospital.

Cytotoxic effects of mithramycin DIG-MSK can depend on the rise of autophagy.

DIG-MSK (demycarosil-3D-β-D-digitoxosyl mithramycin SK; EC-8042), a novel analogue of mithramycin A, induced autophagy in HCT116 human colon carcinoma and, to a lesser extent, in A2780 human ovarian carcinoma cell lines, which was followed by apoptosis and/or necrotic cell death in a time-dependent way. The effects of DIG-MSK included changes in the expression of a set of genes involved in autophagy, the progression of cells through the different phases of cell cycle, and their halting at the checkpoints. Cells treated with the glucose analogue 2-DG (2-deoxy-D-glucose), which induces autophagy because it impairs cell metabolism, or co-treated with 2-DG plus DIG-MSK, also showed altered gene expression and autophagy.

Sp1 transcription factor: A long-standing target in cancer chemotherapy.

Sp1 (specificity protein 1) is a well-known member of a family of transcription factors that also includes Sp2, Sp3 and Sp4, which are implicated in an ample variety of essential biological processes and have been proven important in cell growth, differentiation, apoptosis and carcinogenesis. Sp1 activates the transcription of many cellular genes that contain putative CG-rich Sp-binding sites in their promoters. Sp1 and Sp3 proteins bind to similar, if not the same, DNA tracts and compete for binding, thus they can enhance or repress gene expression.

Autophagy modulates the effects of bis-anthracycline WP631 on p53-deficient prostate cancer cells.

Treatment of p53-deficient PC-3 human prostate carcinoma cells with nanomolar concentrations of bis-anthracycline WP631 induced changes in gene expression, which resulted in G2/M cell cycle arrest, autophagy and cell death. The presence of 2-deoxy-D-glucose (2-DG), which induces metabolic stress and autophagy, enhanced the antiproliferative effects of WP631. Changes induced by WP631, 2-DG, or co-treatments with both compounds, in the expression of a variety of genes involved in autophagy and apoptosis were quantified by real-time PCR.

In vitro and in vivo studies for assessing the immune response and protection-inducing ability conferred by Fasciola hepatica-derived synthetic peptides containing B- and T-cell epitopes.

Fasciolosis is considered the most widespread trematode disease affecting grazing animals around the world; it is currently recognised by the World Health Organisation as an emergent human pathogen. Triclabendazole is still the most effective drug against this disease; however, resistant strains have appeared and developing an effective vaccine against this disease has increasingly become a priority. Several bioinformatics tools were here used for predicting B- and T-cell epitopes according to the available data for Fasciola hepatica protein amino acid sequences.

Genome-wide modulation of gene transcription in ovarian carcinoma cells by a new mithramycin analogue.

Ovarian cancer has a poor prognosis due to intrinsic or acquired resistance to some cytotoxic drugs, raising the interest in new DNA-binding agents such as mithramycin analogues as potential chemotherapeutic agents in gynecological cancer. Using a genome-wide approach, we have analyzed gene expression in A2780 human ovarian carcinoma cells treated with the novel mithramycin analogue DIG-MSK (demycarosyl-3D-β-D-digitoxosyl-mithramycin SK) that binds to C+G-rich DNA sequences. Nanomolar concentrations of DIG-MSK abrogated the expression of genes involved in a variety of cell processes including transcription regulation and tumor development, which resulted in cell death.

The activity of a novel mithramycin analog is related to its binding to DNA, cellular accumulation, and inhibition of Sp1-driven gene transcription.

DIG-MSK (demycarosyl-3D-β-D-digitoxosyl-mithramycin SK) is a recently isolated compound of the mithramycin family of antitumor antibiotics, which includes mithramycin A (MTA) and mithramycin SK (MSK). Here, we present evidence that the binding of DIG-MSK to DNA shares the general features of other mithramycins such as the preference for C/G-rich tracts, but there are some differences in the strength of binding and the DNA sequence preferentially recognized by DIG-MSK. We aimed at gaining further insights into the DIG-MSK mechanism of action by direct comparison with the effects of the parental MTA.

A novel rheo-optical device for studying complex fluids in a double shear plate geometry.

A new rheo-optical shearing device was designed to investigate the structural evolution of complex material under shear flow. Seeking to keep the area under study constantly within the field of vision, it was conceived to produce shear flow by relying on the uniaxial translation of two parallel plates. The device features three modes of translation motion: step strain (0.

Novel mithramycins abrogate the involvement of protein factors in the transcription of cell cycle control genes.

The effects of mithramycin SK (MSK) and demycarosyl-3D-β-D-digitoxosyl-mithramycin SK (DIG-MSK; EC-8042), two novel analogs of the antitumor antibiotic mithramycin A, on gene transcription were examined in human HCT116 colon carcinoma cells by quantitative real-time PCR of 89 genes mainly involved in cell cycle control. Each one of the analogs down-regulated a different set of genes, while only five genes were down-regulated by both compounds. Moreover, other genes were significantly up-regulated, among them p21(WAF1)/CDKN1A which is involved in halting cells at the G1 and G2/M checkpoints.

Molecular modeling and in silico characterization of Mycobacterium tuberculosis TlyA: possible misannotation of this tubercle bacilli-hemolysin.

Background: The TlyA protein has a controversial function as a virulence factor in Mycobacterium tuberculosis (M. tuberculosis). At present, its dual activity as hemolysin and RNA methyltransferase in M.

Conserved high activity binding peptides from the Plasmodium falciparum Pf34 rhoptry protein inhibit merozoites in vitro invasion of red blood cells.

Rhoptries are specialized secretory organelles found in all members of the genus Plasmodium whose proteins have been considered as promising vaccine candidates due to their involvement in cell invasion and the formation of the parasitophorous vacuole (PV). The Plasmodium falciparum Pf34 protein was recently identified as a rhoptry-neck protein located in detergent-resistant microdomains (DRMs) that is expressed in mature intraerythrocytic parasite stages, but its biological function is still unknown. Receptor-ligand assays carried out in this study found that peptides 36,051 ((101)DKKFSESLKAHMDHLKILNN(120)Y), 36,053 ((141)KKYIIKEIQNNKYLNKEKKS(160)), 36,055 ((181)WLESVNNIEEKSNILKNIKS(200)Y) and 36,056 ((201)QLLNNIASLNHTLSEEIKNI(220)Y), located in the central portion of Pf34, were found to establish protease-sensitive interactions of high affinity and specificity with receptors on the surface of red blood cell (RBCs).

Computational prediction and experimental assessment of secreted/surface proteins from Mycobacterium tuberculosis H37Rv.

The mycobacterial cell envelope has been implicated in the pathogenicity of tuberculosis and therefore has been a prime target for the identification and characterization of surface proteins with potential application in drug and vaccine development. In this study, the genome of Mycobacterium tuberculosis H37Rv was screened using Machine Learning tools that included feature-based predictors, general localizers and transmembrane topology predictors to identify proteins that are potentially secreted to the surface of M. tuberculosis, or to the extracellular milieu through different secretory pathways.

Conserved high activity binding peptides are involved in adhesion of two detergent-resistant membrane-associated merozoite proteins to red blood cells during invasion.

Detergent resistant membranes (DRMs) of Plasmodium falciparum merozoites contain a large number of glycosylphosphatidylinositol (GPI)-anchored proteins that have been implicated in interactions between merozoites and red blood cells (RBCs). In this study, two cysteine-rich proteins anchored by GPI to merozoite DRMs (Pf92 and Pf113) were studied with the aim of identifying regions actively involved in RBC invasion. By means of binding assays, high-activity binding peptides (HABPs) with a large number of binding sites per RBC were identified in Pf92 and Pf113.

Sequences of the Plasmodium falciparum cytoadherence-linked asexual protein 9 implicated in malaria parasite invasion to erythrocytes.

In this study, we synthesized the complete sequence of the CLAG-9 protein as 67 20-mer-long non-overlapped peptides and assessed their ability to bind to erythrocytes in receptor-ligand assays. Twenty CLAG-9 peptides were found to have specific high-affinity binding ability to erythrocytes (thereby named as HABPs), with nanomolar dissociation constants. CLAG-9 HABPs interacted with different erythrocyte surface receptors having apparent molecular weights of 85, 63 and 34 kDa.

Peptides from the Mycobacterium tuberculosis Rv1980c protein involved in human cell infection: insights into new synthetic subunit vaccine candidates.

Mycobacterium tuberculosis infection continues to be a major cause of morbidity and mortality throughout the world. The vast complexity of the intracellular pathogen M. tuberculosis and the diverse mechanisms by which it can invade host cells highlight the importance of developing a fully protective vaccine.

Fine mapping of Plasmodium falciparum ribosomal phosphoprotein PfP0 revealed sequences with highly specific binding activity to human red blood cells.

The Plasmodium falciparum P0 ribosomal phosphoprotein (PfP0) was identified for the first time by screening a cDNA expression library of P. falciparum parasites with sera from malaria-immune individuals. Due to its localization on the surface of different parasite life-cycle stages (merozoites and gametocytes) and its recognition by invasion-blocking antibodies, PfP0 has been considered a potential malaria-vaccine component.

Synthetic peptides from conserved regions of the Plasmodium falciparum early transcribed membrane and ring exported proteins bind specifically to red blood cell proteins.

Severe malaria pathology is directly associated with cytoadherence of infected red blood cells (iRBCs) to healthy RBCs and/or endothelial cells occurring during the intraerythrocytic development of Plasmodium falciparum. We synthesized, as 20-mer long peptides, the members of the ring exported (REX) protein family encoded in chromosome 9, as well as the early transcribed membrane proteins (E-TRAMP) 10.2 and 4, to identify specific RBC binding regions in these proteins.

Validating subcellular localization prediction tools with mycobacterial proteins.

Background: The computational prediction of mycobacterial proteins' subcellular localization is of key importance for proteome annotation and for the identification of new drug targets and vaccine candidates. Several subcellular localization classifiers have been developed over the past few years, which have comprised both general localization and feature-based classifiers. Here, we have validated the ability of different bioinformatics approaches, through the use of SignalP 2.

Characterization of Plasmodium falciparum integral membrane protein Pf25-IMP and identification of its red blood cell binding sequences inhibiting merozoite invasion in vitro.

The identification of proteins present on the surface of Plasmodium falciparum-infected red blood cells as well as of free merozoites has been widely considered as one of the main areas of research in the development of an antimalarial vaccine due to their involvement in the parasite's pathogenesis and invasion mechanisms. Major advances had been accomplished in this area thanks to the analysis of the reported genomic sequence of P. falciparum, allowing for the identification of genes encoding for putative integral membrane proteins.

[Social functioning and psychopathologic risk factors in hemophilic children].

Background: Children with hemophilia can experience problems with their mental health status and social functioning.

Aim: To assess the mental health status of hemophilic children.

Material And Methods: Thirty four hemophilic children aged 5 to 13 years were studied.