Data on the effects of low iron diet on serum lipid profile in HCV transgenic mouse model

Here, we presented new original data on the effects of iron depletion on the circulating lipid profile in B6HCV mice, a murine model of HCV-related dyslipidemia. Male adult B6HCV mice were subjected to non-invasive iron depletion by low iron diet. Serum iron concentration was assessed for evaluating the effects of the dietary iron depletion. Concentrations of circulating triglycerides, total cholesterol, Low Density Lipoproteins (LDLs), High Density Lipoproteins (HDLs) were analyzed and reported by using stacked line charts. The present data indicated that low serum iron concentration is associated to i) lower serum triglycerides concentrations and ii) increased circulating LDLs. The presented original data have not been published elsewhere

Molecular mediators of RNA loading into extracellular vesicles

In the last decade, an increasing number of studies have demonstrated that non-coding RNA (ncRNAs) cooperate in the gene regulatory networks with other biomolecules, including coding RNAs, DNAs and proteins. Among them, microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are involved in transcriptional and translation regulation at different levels. Intriguingly, ncRNAs can be packed in vesicles, released in the extracellular space, and finally internalized by receiving cells, thus affecting gene expression also at distance. This review focuses on the mechanisms through which the ncRNAs can be selectively packaged into extracellular vesicles (EVs)

DESIGN AND ANALYSIS OF AN INNOVATIVE CUBESAT THERMAL CONTROL SYSTEM FOR BIOLOGICAL EXPERIMENT IN LUNAR ENVIRONMENT

After about 50 years since the Apollo missions, Space Agencies are planning new manned missions beyond LEO, aiming to full functional Lunar and Martian outposts. Leaving the protection of Earth’s magnetic field, human body will be exposed by a huge amount of harmful radiations coming from both solar wind and cosmic rays, which represent a risk for the astronauts. In order to prepare for future manned exploration missions, many biological experiments have been conducted inside and outside the International Space Station (ISS). From these experiments, engineers and scientists gained knowledge about biological degradation after a long period of exposure to space radiations. Similar experiments were also carried out in small free-flyers. For example, the O/OREOS mission is built with a 3U CubeSat that is evaluating how microorganisms can survive and can adapt to the harsh orbit environment. Small platforms, such as CubeSats, are gaining interest for many applications including science experiments. Biological payloads require very stable environmental conditions, implying that environment requirements are very stringent and that existing passive thermal control systems may not be sufficient to support these class of experiments. The goal of this paper is to describe and discuss the design of an active environmental control system suitable for supporting biological payloads hosted onboard nanosatellites. In particular, we focused the attention on the case of a payload constituted by a bacterial culture that needs oxygen supply for growing up. The rate of growth and vitality are measured through bacteria metabolic parameters. The reference mission is built with a 6U CubeSat in Lunar Polar Orbit, with the main scientific objective of measuring the effect of the lunar radiation environment on a culture of “Bacterium Deinococcus Radiodurans”. This kind of bacteria exhibits significant resistance to ionising radiation and the survival temperature range is 30°C ± 10°C. The thermal control system (TCS) is constituted by Stirling cryocooler, Peltier cells and heaters. The aforementioned pieces of equipment operate on the oxygen tank and test chamber in order to control temperature of the oxygen necessary for the growth of the bacteria. To verify the temperature requirements, two kinds of analysis are performed: radiative analysis, to have information about the heat fluxes from space environment; and lastly, a thermo-fluid dynamics analysis, to gather data about temperature in the test chamber. As result, it is possible to confirm that, with the chosen TCS, the temperature requirement is verified during the mission

SILAC labeling coupled to shotgun proteomics analysis of membrane proteins of liver stem/hepatocyte allows to candidate the inhibition of TGF-beta pathway as causal to differentiation

Background: Despite extensive research on hepatic cells precursors and their differentiated states, much remains to be learned about the mechanism underlying the self-renewal and differentiation.Results: We apply the SILAC (stable isotope labeling by amino acids in cell culture) approach to quantitatively compare the membrane proteome of the resident liver stem cells (RLSCs) and their progeny spontaneously differentiated into epithelial/hepatocyte (RLSCdH). By means of nanoLC-MALDI-TOF/TOF approach, we identified and quantified 248 membrane proteins and 57 of them were found modulated during hepatocyte differentiation. Functional clustering of differentially expressed proteins by Ingenuity Pathway Analysis revealed that the most of membrane proteins found to be modulated are involved in cell-to-cell signaling/interaction pathways. Moreover, the upstream prediction analysis of proteins involved in cell-to-cell signaling and interaction unveiled that the activation of the mesenchymal to epithelial transition (MET), by the repression of TGFB1/Slug signaling, may be causal to hepatocyte differentiation.Conclusions: Taken together, this study increases the understanding of the underlying mechanisms modulating the complex biological processes of hepatic stem cell proliferation and differentiation. © 2014 Montaldo et al.; licensee BioMed Central Ltd

Autoantibodies in inflammatory arthritis

Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterized by extensive synovitis resulting in erosions of articular cartilage and marginal bone with joint destruction. The lack of immunological tolerance in RA represents the first step toward the development of autoimmunity. Susceptible individuals, under the influence of environmental factors, such as tobacco smoke, and silica exposure, develop autoimmune phenomena that result in the presence of autoantibodies. HLA and non-HLA haplotypes play a major role in determining the development of specific autoantibodies differentiating anti-citrullinated antibodies (ACPA)-positive and negative RA patients. Rheumatoid factor (RF) and ACPA are the serological markers for RA, and during the preclinical immunological phase, autoantibody titers increase with a progressive spread of ACPA antigens repertoire. The presence of ACPA represents an independent risk factor for developing RA in patients with undifferentiated arthritis or arthralgia. Moreover, anti-CarP antibodies have been identified in patients with RA as well as in individuals before the onset of clinical symptoms of RA. Several autoantibodies mainly targeting post-translational modified proteins have been investigated as possible biomarkers to improve the early diagnosis, prognosis and response to therapy in RA patients. Psoriatic arthritis (PsA) is distinguished from RA by infrequent positivity for RF and ACPA, together with other distinctive clinical features. Actually, specific autoantibodies have not been described. Recently, anti-CarP antibodies have been reported in sera from PsA patients with active disease. Further investigations on autoantibodies showing high specificity and sensibility as well as relevant correlation with disease severity, progression, and response to therapy are awaited in inflammatory arthritides

Famotidine use and quantitative symptom tracking for COVID-19 in non-hospitalised patients: a case series.

OBJECTIVE: Treatment options for non-hospitalised patients with coronavirus disease 2019 (COVID-19) to reduce morbidity, mortality and spread of the disease are an urgent global need. The over-the-counter histamine-2 receptor antagonist famotidine is a putative therapy for COVID-19. We quantitively assessed longitudinal changes in patient reported outcome measures in non-hospitalised patients with COVID-19 who self-administered high-dose famotidine orally. DESIGN: Patients were enrolled consecutively after signing written informed consent. Data on demographics, COVID-19 diagnosis, famotidine use, drug-related side effects, temperature measurements, oxygen saturations and symptom scores were obtained using questionnaires and telephone interviews. Based on a National Institute of Health (NIH)-endorsed Protocol to research Patient Experience of COVID-19, we collected longitudinal severity scores of five symptoms (cough, shortness of breath, fatigue, headaches and anosmia) and general unwellness on a four-point ordinal scale modelled on performance status scoring. All data are reported at the patient level. Longitudinal combined normalised symptom scores were statistically compared. RESULTS: Ten consecutive patients with COVID-19 who self-administered high-dose oral famotidine were identified. The most frequently used famotidine regimen was 80 mg three times daily (n=6) for a median of 11 days (range: 5-21 days). Famotidine was well tolerated. All patients reported marked improvements of disease related symptoms after starting famotidine. The combined symptom score improved significantly within 24 hours of starting famotidine and peripheral oxygen saturation (n=2) and device recorded activity (n=1) increased. CONCLUSIONS: The results of this case series suggest that high-dose oral famotidine is well tolerated and associated with improved patient-reported outcomes in non-hospitalised patients with COVID-19

po 162 long non coding rna h19 inch19 is required for the hypoxia mediated multiple myeloma progression

Introduction Multiple myeloma (MM) is a malignant disorder of post-germinal centre B cells, characterised by the clonal proliferation of malignant plasma cells within the bone marrow (BM). The hypoxic condition that develops in the BM niche during progression of MM, has been shown to play a major role in i) the dissemination of MM, ii) the proliferation of MM cells and iii) the induction of drug resistance finally determining a poor prognosis for MM patients. The molecular mechanisms driving hypoxic responses is the activation and nuclear translocation of the Hypoxia-inducible factor 1-alpha, (HIF1α) that, in turns, induce the expression of genes controlling angiogenesis, hypermetabolism, stemnes maintenance, resistance to chemotherapy, and tumour metastasis. The lncRNA H19, an imprinted non-coding RNA which expression was found up-regulated in many tumours including MM, is among the targets of HIF1α. We previously attributed to the lncH19 a role into control of hypoxic response; in particular we demonstrated, in both glioblastoma and colon cancer, that the lncH19, is necessary and required to sustain HIF1α activity. Here we propose to investigate the role of lncH19 in hypoxia mediated MM progression. Material and methods Transcriptional analysis (RT-PCR) of MM cell lines (RPMI and MM1S) exposed to normoxia or hypoxia (1% O 2 ) was done in order to evaluate lncH19 levels under hypoxic stimulation. To investigate the role of lncH19 in hypoxia mediated MM progression, transcriptional, protein and functional assays have been performed on MM cell lines, silenced or not for lncH19, under normoxia or 24 hour hypoxic stimulation in low oxygen chamber Results and discussions Our data indicate that MM cell lines respond to hypoxic stimulation by HIF1α nuclear translocation and activation of hypoxic responsive genes including the lncH19. Our data revealed that lncH19 silencing inhibits HIF1a nuclear translocation with a subsequent reduction in the expression of hypoxia induced genes, associated to MM progression, such as snail and VEGF. Moreover, adhesion assay of MM cells on Mesenchymal Stromal Cells revealed that lncH19 silencing abrogates the increased adhesion induced by hypoxic condition. Conclusion LncH19 is required for the induction of hypoxic responses in MM cells thus representing a new therapeutic target for MM. Further studies are required to better define the molecular mechanism through which H19 may control HIF1α activity

The role of seasonality and photoperiod on the lethality of suicide attempts: A case-control study

Background: The risk factors related to suicidal behaviors are complex and not yet fully known. Several studies underline how suicide results from the combination of psycho-social, biological, cultural, and environmental factors. The aim of this study was to investigate the potential role of seasonality and photoperiod on high-lethality suicide attempts (HLSA) compared with low-lethality suicide attempts (LLSA) in a sample of psychiatric inpatients. Methods: After attempting suicide, subjects were admitted in the emergency/psychiatric ward of the IRCCS Ospedale Policlinico San Martino from 1st August 2013 to 31st July 2018. Socio-demographic and clinical characteristics were collected. Results: The sample consisted of four hundred thirty-two individuals admitted for suicide attempt. One hundred thirty-three subjects (30.8%) of the sample committed a HLSA. The HLSA group peaked in the months with a higher sunlight exposure (June and July). Bivariate correlation analyses between seasonality/photoperiod in the whole sample and HLSA were positively associated with summer and highest solar intensity period. Limitations: Data were limited to a single hospital, patients’ seasonal environment, meteorological variables and psychological factors. In addition, the presence of acute life-events fostering the suicidal crisis has not been investigated. Conclusions: The current study provides a novel perspective on the questions surrounding the impact of seasonality and daylight exposure on lethality of suicide attempts. further studies are needed to provide deeper understandings on the delicate molecular network that links suicide behaviors, seasonality and daylight in order to develop more effective prevention and treatment strategies in the future

The stable repression of mesenchymal program is required for hepatocyte identity: A novel role for hepatocyte nuclear factor 4α

The concept that cellular terminal differentiation is stably maintained once development is complete has been questioned by numerous observations showing that differentiated epithelium may undergo an epithelial-to-mesenchymal transition (EMT) program. EMT and the reverse process, mesenchymal-to-epithelial transition (MET), are typical events of development, tissue repair, and tumor progression. In this study, we aimed to clarify the molecular mechanisms underlying these phenotypic conversions in hepatocytes. Hepatocyte nuclear factor 4α (HNF4α) was overexpressed in different hepatocyte cell lines and the resulting gene expression profile was determined by real-time quantitative polymerase chain reaction. HNF4α recruitment on promoters of both mesenchymal and EMT regulator genes was determined by way of electrophoretic mobility shift assay and chromatin immunoprecipitation. The effect of HNF4α depletion was assessed in silenced cells and in the context of the whole liver of HNF4 knockout animals. Our results identified key EMT regulators and mesenchymal genes as new targets of HNF4α. HNF4α, in cooperation with its target HNF1α, directly inhibits transcription of the EMT master regulatory genes Snail, Slug, and HMGA2 and of several mesenchymal markers. HNF4α-mediated repression of EMT genes induces MET in hepatomas, and its silencing triggers the mesenchymal program in differentiated hepatocytes both in cell culture and in the whole liver. Conclusion: The pivotal role of HNF4α in the induction and maintenance of hepatocyte differentiation should also be ascribed to its capacity to continuously repress the mesenchymal program; thus, both HNF4α activator and repressor functions are necessary for the identity of hepatocytes. Copyright © 2011 American Association for the Study of Liver Diseases