Biological Effects of Transforming Growth Factor Beta in Human Cholangiocytes

: TGF-β is a cytokine implicated in multiple cellular responses, including cell cycle regulation, fibrogenesis, angiogenesis and immune modulation. In response to pro-inflammatory and chemotactic cytokines and growth factors, cholangiocytes prime biliary damage, characteristic of cholangiopathies and pathologies that affect biliary tree. The effects and signaling related to TGF-β in cholangiocyte remains poorly investigated. In this study, the cellular response of human cholangiocytes to TGF-β was examined. Wound-healing assay, proliferation assay and cell cycle analyses were used to monitor the changes in cholangiocyte behavior following 24 and 48 h of TGF-β stimulation. Moreover, proteomic approach was used to identify proteins modulated by TGF-β treatment. Our study highlighted a reduction in cholangiocyte proliferation and a cell cycle arrest in G0/G1 phase following TGF-β treatment. Moreover, proteomic analysis allowed the identification of four downregulated proteins (CaM kinase II subunit delta, caveolin-1, NipSnap1 and calumin) involved in Ca2+ homeostasis. Accordingly, Gene Ontology analysis highlighted that the plasma membrane and endoplasmic reticulum are the cellular compartments most affected by TGF-β. These results suggested that the effects of TGF-β in human cholangiocytes could be related to an imbalance of intracellular calcium homeostasis. In addition, for the first time, we correlated calumin and NipSnap1 to TGF-β signaling

A gel-free approach in vascular smooth muscle cell proteome: perspectives for a better insight into activation

<p>Abstract</p> <p>Background</p> <p>The use of chromatography coupled with mass spectrometry (MS) analysis is a powerful approach to identify proteins, owing to its capacity to fractionate molecules according to different chemical features. The first protein expression map of vascular smooth muscle cells (VSMC) was published in 2001 and since then other papers have been produced. The most detailed two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) map was presented by Mayr et al who identified 235 proteins, corresponding to the 154 most abundant unique proteins in mouse aortic VSMC. A chromatographic approach aimed at fractionating the VSMC proteome has never been used before.</p> <p>Results</p> <p>This paper describes a strategy for the study of the VSMC proteome. Our approach was based on pre-fractionation with ion exchange chromatography coupled with matrix assisted laser desorption-time of flight mass spectrometry analysis assisted by a liquid chromatography (LC-MALDI-TOF/TOF). Ion exchange chromatography resulted in a good strategy designed to simplify the complexity of the cellular extract and to identify a large number of proteins. Selectivity based on the ion-exchange chemical features was adequate if evaluated on the basis of protein pI. The LC-MALDI approach proved to be highly reproducible and sensitive since we were able to identify up to 815 proteins with a concentration dynamic range of 7 orders of magnitude.</p> <p>Conclusions</p> <p>In our opinion, the large number of identified proteins and the promising quantitative reproducibility made this approach a powerful method to analyze complex protein mixtures in a high throughput way and to obtain statistical data for the discovery of key factors involved in VSMC activation and to analyze a label-free differential protein expression.</p

Tailoring of silica-based nanoporous pod by spermidine multi-activity

Ubiquitous in nature, polyamines (PAs) are a class of low-molecular aliphatic amines critically involved in cell growth, survival and differentiation. The polycation behavior is validated as a successful strategy in delivery systems to enhance oligonucleotide loading and cellular uptake. In this study, the chemical features and the functional roles of the PA spermidine are synergistically exploited in the synthesis and bioactive functionalization of SiO2-based structures. Inspired by biosilicification, the role of spermidine is assessed both as catalyst and template in a biomimetic one-pot synthesis of dense silica-based particles (SPs) and as a competitive agent in an interfacial reassembly strategy, to empty out SPs and generate spermidine-decorated hollow silica nanoporous pods (spd-SNPs). Spermidine bioactivity is then employed for targeting tumor cell over-expressed polyamine transport system (PTS) and for effective delivery of functional miRNA into melanoma cells. Spermidine decoration promotes spd-SNP cell internalization mediated by PTS and along with hollow structure enhances oligonucleotide loading. Accordingly, the functional delivery of the tumor suppressor miR-34a 3p resulted in intracellular accumulation of histone-complexed DNA fragments associated with apoptosis. Overall, the results highlight the potential of spd-SNP as a multi-agent anticancer therapy

Pandemos manifest: Debris of an antiviral group

Pandemos es un grupo híbrido, atravesado por la inquietud de enfrentar los desafíos del mundo contemporáneo en el contexto de la pandemia. Discutiendo los modos en los que la lógica del capital opera en los campos en los que desarrollan sus actividades, se proponen intervenir con investigaciones y creaciones que no sólo en sus contenidos sino, sobre todo, en sus propias modalidades construyan vínculos que resistan a sus efectos más negativos. Así, en este texto que dialoga con la tradición de los manifiestos como estrategia para hacer visible las indagaciones de los grupos críticos, asumen el desafío de expresar las distintas voces que configuran puntos de vista simultáneos sobre la pregunta que se formula: “¿Qué es Pandemos?”. Por ello, la respuesta no emerge tanto en su literalidad, como en las cesuras que mantienen unida su potencia sin anular las singularidades que la constituyen.Pandemos is a hybrid group, crossed by the concern to face the challenges of the contemporary world in the context of the pandemic. Discussing the ways in which the logic of capital operates in the fields in which they develop their activities, they propose to intervene with research and creations that not only in their contents but, above all, in their own modalities, build links that resist its most negative effects. Thus, in this text that dialogues with the tradition of manifestos as a strategy to make visible the inquiries of critical groups, they assume the challenge of expressing the different voices that configure simultaneous points of view on the question that is asked: "What is Pandemos?”. Therefore, the answer does not emerge so much in its literalness, as in the caesuras that hold together its power without annulling the singularities that constitute it.Fil: Litvinoff, Diego Ezequiel. Universidad de Buenos Aires. Facultad de Arquitectura, Diseño y Urbanismo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; ArgentinaFil: Ciai, Tam Painé. Universidad de Buenos Aires. Facultad de Arquitectura, Diseño y Urbanismo; ArgentinaFil: Lorenzo, Gustavo. Universidad de Buenos Aires. Facultad de Arquitectura, Diseño y Urbanismo; ArgentinaFil: Capmourteres, Natalia. Universidad de Buenos Aires. Facultad de Arquitectura, Diseño y Urbanismo; Argentina. Universidad del Museo Social Argentino; ArgentinaFil: Tedeschi, Carmen. Universidad de Buenos Aires. Facultad de Arquitectura, Diseño y Urbanismo; ArgentinaFil: Guterman, Geraldine. Universidad de Buenos Aires. Facultad de Arquitectura, Diseño y Urbanismo; ArgentinaFil: Soroka, Lorena. Universidad de Buenos Aires. Facultad de Arquitectura, Diseño y Urbanismo; Argentin

HOW DOES IT WORK A QUALITY/PERFORMANCE MANAGEMENT SYSTEM IN A BIOMEDICAL RESEARCH INSTITUTION? LIGHTS AND SHADOWS

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Integrated sensor system for DNA amplification and separation based on thin film technology

This paper presents the development of a lab-on-chip, based on thin-film sensors, suitable for DNA treatments. In particular, the system performs on-chip DNA amplification and separation of double-strand DNA into single-strand DNA, combining a polydimethylsiloxane microfluidic network, thin-film electronic devices, and surface chemistry. Both the analytical procedures rely on the integration on the same glass substrate of thin-film metal heaters and amorphous silicon temperature sensors to achieve a uniform temperature distribution (within ±1 °C) in the heated area and a precise temperature control (within ±0.5 °C). The DNA separation also counts on the binding between biotinylated dsDNA and a layer of streptavidin immobilized into a microfluidic channel through polymer-brushes-based layer. This approach results in a fast and low reagents consumption system. The tested DNA treatments can be applied for carrying out the on-chip systematic evolution of ligands by exponential enrichment process, a chemistry technique for the selection of aptamers

Quality of care provided by Multiple Sclerosis Centers during Covid-19 pandemic: Results of an Italian multicenter patient-centered survey

Background: Covid-19 pandemic impacted on management of people with Multiple Sclerosis (pwMS). Level of satisfaction of pwMS regarding the care received by the staff of Multiple Sclerosis Centers (MSCs) during the pandemic was not fully investigated. In a large patient-centered multicenter study, the therapeutic adherence and quality of care of MSCs was assessed. Methods: In April-May 2021, an online survey was widespread by 16 Italian MSCs. Frequencies, percentages and/or means and standard deviations were calculated to describe the sample. ANOVAs were performed to evaluate the effect of sociodemographic and clinical variables on overall pwMS' rating of MSC assistance. Results: 1670 pwMS completed the survey (67.3% women). During the pandemic, 88% did not change their disease modifying therapy schedule, and 89.1% reached their MSCs with no or little difficulties. Even if only 1.3% of participants underwent a tele-health follow-up visit with their MSC staff, the 80.1% believed that tele-health services should be improved regardless of pandemic. 92% of participants were satisfied of how their MSC took charge of their needs; ANOVAs revealed an effect of disease duration on pwMS' level of satisfaction on MSCs management during the pandemic. Conclusions: The results revealed an efficient MSCs response to Covid-19 pandemic and provided the basis for the implementing of tele-health services that would further improve the taking charge of patients, particularly those with longer disease, higher disability, and/or living far from their MSC

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London