Pancreatic cancer-derived S-100A8 N-terminal peptide: a diabetes cause?

BACKGROUND: Our aim was to identify the pancreatic cancer diabetogenic peptide. METHODS: Pancreatic tumor samples from patients with (n=15) or without (n=7) diabetes were compared with 6 non-neoplastic pancreas samples using SDS-PAGE. RESULTS: A band measuring approximately 1500 Da was detected in tumors from diabetics, but not in neoplastic samples from non-diabetics or samples from non-neoplastic subjects. Sequence analysis revealed a 14 amino acid peptide (1589.88 Da), corresponding to the N-terminal of the S100A8. At 50 nmol/L and 2 mmol/L, this peptide significantly reduced glucose consumption and lactate production by cultured C(2)C(12) myoblasts. The 14 amino acid peptide caused a lack of myotubular differentiation, the presence of polynucleated cells and caspase-3 activation. CONCLUSIONS: The 14 amino acid peptide from S100A8 impairs the catabolism of glucose by myoblasts in vitro and may cause hyperglycemia in vivo. Its identification in biological fluids might be helpful in diagnosing pancreatic cancer in patients with recent onset diabetes mellitus

Pancreatic cancer-associated diabetes mellitus: an open field for proteomic applications.

Background: Diabetes mellitus is associated with pancreatic cancer in more than 80% of the cases. Clinical, epidemiological, and experimental data indicate that pancreatic cancer causes diabetes mellitus by releasing soluble mediators which interfere with both beta-cell function and liver and muscle glucose metabolism. Methods: We analysed, by matrix-assisted laser desorption ionization time of flight (MALDI-TOF), a series of pancreatic cancer cell lines conditioned media, pancreatic cancer patients' peripheral and portal sera, comparing them with controls and chronic pancreatitis patients' sera. Results: MALDI-TOF analysis of pancreatic cancer cells conditioned media and patients' sera indicated a low molecular weight peptide to be the putative pancreatic cancer-associated diabetogenic factor. The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of tumor samples from diabetic and non-diabetic patients revealed the presence of a 1500 Da peptide only in diabetic patients. The amino acid sequence of this peptide corresponded to the N-terminal of an S-100 calcium binding protein, which was therefore suggested to be the pancreatic cancer-associated diabetogenic factor. Conclusions: We identified a tumor-derived peptide of 14 amino acids sharing a 100% homology with an S-100 calcium binding protein, which is probably the pancreatic cancer-associated diabetogenic facto

In HspA from Helicobacter pylori vicinal disulfide bridges are a key determinant of domain B structure

Helicobacter pylori produces a heat shock protein A (HspA) that is unique to this bacteria. While the first 91 residues (domain A) of the protein are similar to GroES, the last 26 (domain B) are unique to HspA. Domain B contains eight histidines and four cysteines and was suggested to bind nickel. We have produced HspA and two mutants: Cys94Ala and Cys94Ala/Cys111Ala and identified the disulfide bridge pattern of the protein. We found that the cysteines are engaged in three disulfide bonds: Cys51/Cys53, Cys94/Cys111 and Cys95/Cys112 that result in a unique closed loop structure for the domain

Determination of the gas-liquid reaction kinetic for sulfur dioxide absorption in sodium chlorite aqueous solutions

This study is part of the research activities devoted to the development of new gas-cleaning technologies required to minimize the emissions factors of sulfur compounds in chemical industries and power plants. Among flue gas desulfurization (FGD) processes, wet scrubbing with oxidizing chemicals, e.g. sodium chlorite (NaClO2) has appeared as a viable option for different applications. The present work aims to study the absorption kinetics of the gas-liquid reaction between sulfur dioxide (SO2) and NaClO2, in a lab-scale falling-film absorber, investigating the effects of the main process parameters: liquid and gas flow rates, SO2 gas-phase concentration, NaClO2 liquid-phase concentration, solution pH and process temperature. The experimental activity aims to determine the Enhancement Factor (EL) to develop a kinetic model for reactive absorption. To this end, kinetic parameters are calculated from experiments using the Danckwerts equation for a pseudo-second-order reaction kinetic, determining a maximum prediction error of ±20% compared to the experimental data. Experimental data available in the literature on pilot-scale oxidative FGD scrubbers using chlorite are used to test the validity and robustness of the kinetic model. The kinetic model is able to predict the data with good accuracy within a prediction error range of ±30%

Experimental and modelling study of ammonia-based FGD scrubbers

In this work, we propose an experimental and modelling study to define the mass-transfer aspects of SO2 absorption in ammonia (NH3) aqueous solution, also accounting for the kinetics of the chemical reaction by determining the Enhancement factors (EL) of the reactive absorption. The Enhancement factor (EL) for the overall SO2 chemical absorption reaction is evaluated in a falling-film absorber under different experimental conditions and it is correlated to the Hatta number (Ha) by means of the Danckwerts equation (a pseudo-mth, nth-order non-reversible reaction kinetic), valid for very fast gas–liquid reactions, and finding the model parameters from best fitting of the experimental data. Finally, the ammonia-based FGD model consisting of the combined use of the Danckwerts equation with mass transfer coefficients and thermodynamic equilibrium correlations is used to predict the performance of reactive absorption in a lab-scale packed column whose data are reported in the literature, providing a maximum error prediction of ±25 %

Use of biochar-based cathodes and increase in the electron flow by pseudomonas aeruginosa to improve waste treatment in microbial fuel cells

In this paper, we tested the combined use of a biochar-based material at the cathode and of Pseudomonas aeruginosa strain in a single chamber, air cathode microbial fuel cells (MFCs) fed with a mix of shredded vegetable and phosphate buffer solution (PBS) in a 30% solid/liquid ratio. As a control system, we set up and tested MFCs provided with a composite cathode made up of a nickel mesh current collector, activated carbon and a single porous poly tetra fluoro ethylene (PTFE) diffusion layer. At the end of the experiments, we compared the performance of the two systems, in the presence and absence of P. aeruginosa, in terms of electric outputs. We also explored the potential reutilization of cathodes. Unlike composite material, biochar showed a life span of up to 3 cycles of 15 days each, with a pH of the feedstock kept in a range of neutrality. In order to relate the electric performance to the amount of solid substrates used as source of carbon and energy, besides of cathode surface, we referred power density (PD) and current density (CD) to kg of biomass used. The maximum outputs obtained when using the sole microflora were, on average, respectively 0.19 Wm(-2)kg(-1) and 2.67 Wm(-2)kg(-1), with peaks of 0.32 Wm(-2)kg(-1) and 4.87 Wm(-2)kg(-1) of cathode surface and mass of treated biomass in MFCs with biochar and PTFE cathodes respectively. As to current outputs, the maximum values were 7.5 Am-2 kg(-1) and 35.6 Am(-2)kg(-1) in MFCs with biochar-based material and a composite cathode. If compared to the utilization of the sole acidogenic/acetogenic microflora in vegetable residues, we observed an increment of the power outputs of about 16.5 folds in both systems when we added P. aeruginosa to the shredded vegetables. Even though the MFCs with PTFE-cathode achieved the highest performance in terms of PD and CD, they underwent a fouling episode after about 10 days of operation, with a dramatic decrease in pH and both PD and CD. Our results confirm the potentialities of the utilization of biochar-based materials in waste treatment and bioenergy production

CMS: A web-based system for visualization and analysis of genome-wide methylation data of human cancers

DNA methylation of promoter CpG islands is associated with gene suppression, and its unique genome-wide profiles have been linked to tumor progression. Coupled with high-throughput sequencing technologies, it can now efficiently determine genome-wide methylation profiles in cancer cells. Also, experimental and computational technologies make it possible to find the functional relationship between cancer-specific methylation patterns and their clinicopathological parameters.Cancer methylome system (CMS) is a web-based database application designed for the visualization, comparison and statistical analysis of human cancer-specific DNA methylation. Methylation intensities were obtained from MBDCap-sequencing, pre-processed and stored in the database. 191 patient samples (169 tumor and 22 normal specimen) and 41 breast cancer cell-lines are deposited in the database, comprising about 6.6 billion uniquely mapped sequence reads. This provides comprehensive and genome-wide epigenetic portraits of human breast cancer and endometrial cancer to date. Two views are proposed for users to better understand methylation structure at the genomic level or systemic methylation alteration at the gene level. In addition, a variety of annotation tracks are provided to cover genomic information. CMS includes important analytic functions for interpretation of methylation data, such as the detection of differentially methylated regions, statistical calculation of global methylation intensities, multiple gene sets of biologically significant categories, interactivity with UCSC via custom-track data. We also present examples of discoveries utilizing the framework.CMS provides visualization and analytic functions for cancer methylome datasets. A comprehensive collection of datasets, a variety of embedded analytic functions and extensive applications with biological and translational significance make this system powerful and unique in cancer methylation research. CMS is freely accessible at: http://cbbiweb.uthscsa.edu/KMethylomes/

Mass transfer intensification by modifying structured packing surface properties produced with 3D foam-printing technology

Gas–liquid contactors have a pivotal importance in chemical engineering, as they influence the mass transfer rate in many processes, e.g. distillation, absorption, and desorption. This study explores the potential of 3D foam-printing technology to enhance structured packing surfaces by integrating both micro-textures and micro-roughness through foaming. The aim of the work is to create advanced and customized contactors with a high gas–liquid interfacial area for packed-bed column applications. By combining 3D printing with foaming techniques several textured sheet samples, representing the repetitive units of structured packing, were produced using biobased polylactic acid (PLA) and CO2 as a foaming agent. Rather than using a full-scale packed column, absorption experiments were performed using a lab-scale setup based on the inclined-wall falling-film system. The setup involved a single rectangular flat sheet under complete wetting conditions to simulate packing performance between loading and flooding points. Textured sheets were compared to smooth sheets and included designs such as rectangular steps, triangular steps, pyramidal, wavy, and wavy triangular steps. Optical analysis (using SEM and confocal microscopy) revealed that texture inclusion via 3D printing increased surface area by 15–22% compared to the benchmark. Foamed samples showed an additional surface area increase of up to 50%, with the highest gain (52%) seen in the wavy triangular step texture. The absorption experiments showed that foamed sheet samples provided higher mass transfer efficiency, confirming that the textures and micro-roughness enhance the gas–liquid interface. Among the textures tested, the wavy triangular step was the most effective although wavy and pyramidal textures (commonly used in commercial packing) have a larger area of about 15–16%. These findings confirm that 3D foam-printing is a viable option for producing the next generation of tailor-made, highly efficient surfaces for advanced packed-bed column applications

Final Results from the First European Real-World Experience on Lusutrombopag Treatment in Cirrhotic Patients with Severe Thrombocytopenia: Insights from the REAl-World Lusutrombopag Treatment in ITalY Study

Background and aims: Management of severe thrombocytopenia poses significant challenges in patients with chronic liver disease. Here, we aimed to evaluate the first real-world European post-marketing cohort of cirrhotic patients treated with lusutrombopag, a thrombopoietin receptor agonist, verifying the efficacy and safety of the drug. Methods: In the REAl-world Lusutrombopag treatment in ITalY (REALITY) study, we collected data from consecutive cirrhotic patients treated with lusutrombopag in 19 Italian hepatology centers, mostly joined to the “Club Epatologi Ospedalieri” (CLEO). Primary and secondary efficacy endpoints were the ability of lusutrombopag to avoid platelet transfusions and to raise the platelet count to ≥50,000/μL, respectively. Treatment-associated adverse events were also collected. Results: A total of 66 patients and 73 cycles of treatment were included in the study, since 5 patients received multiple doses of lusutrombopag over time for different invasive procedures. Fourteen patients (19%) had a history of portal vein thrombosis (PVT). Lusutrombopag determined a significant increase in platelet count [from 37,000 (33,000–44,000/μL) to 58,000 (49,000–82,000), p < 0.001]. The primary endpoint was met in 84% of patients and the secondary endpoint in 74% of patients. Baseline platelet count was the only independent factor associated with response in multivariate logistic regression analysis (OR for any 1000 uL of 1.13, CI95% 1.04–1.26, p 0.01), with a good discrimination power (AUROC: 0.78). Notably, a baseline platelet count ≤ 29,000/μL was identified as the threshold for identifying patients unlikely to respond to the drug (sensitivity of 91%). Finally, de novo PVT was observed in four patients (5%), none of whom had undergone repeated treatment, and no other safety or hemorrhagic events were recorded in the entire population analyzed. Conclusions: In this first European real-world series, lusutrombopag demonstrated efficacy and safety consistent with the results of registrational studies. According to our results, patients with baseline platelet counts ≤29,000/μL are unlikely to respond to the drug

A statistical method for excluding non-variable CpG sites in high-throughput DNA methylation profiling

<p>Abstract</p> <p>Background</p> <p>High-throughput DNA methylation arrays are likely to accelerate the pace of methylation biomarker discovery for a wide variety of diseases. A potential problem with a standard set of probes measuring the methylation status of CpG sites across the whole genome is that many sites may not show inter-individual methylation variation among the biosamples for the disease outcome being studied. Inclusion of these so-called "non-variable sites" will increase the risk of false discoveries and reduce statistical power to detect biologically relevant methylation markers.</p> <p>Results</p> <p>We propose a method to estimate the proportion of non-variable CpG sites and eliminate those sites from further analyses. Our method is illustrated using data obtained by hybridizing DNA extracted from the peripheral blood mononuclear cells of 311 samples to an array assaying 1505 CpG sites. Results showed that a large proportion of the CpG sites did not show inter-individual variation in methylation.</p> <p>Conclusions</p> <p>Our method resulted in a substantial improvement in association signals between methylation sites and outcome variables while controlling the false discovery rate at the same level.</p