Genetic association and altered gene expression of mir-155 in multiple sclerosis patients

Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system characterized by chronic inflammation, demyelination, and axonal damage. As microRNA (miRNA)-dependent alterations in gene expression in hematopoietic cells are critical for mounting an appropriate immune response, miRNA deregulation may result in defects in immune tolerance. In this frame, we sought to explore the possible involvement of miRNAs in MS pathogenesis by monitoring the differential expression of 22 immunity-related miRNAs in peripheral blood mononuclear cells of MS patients and healthy controls, by using a microbead-based technology. Three miRNAs resulted >2 folds up-regulated in MS vs controls, whereas none resulted down-regulated. Interestingly, the most up-regulated miRNA (mir-155; fold change = 3.30; P = 0.013) was previously reported to be up-regulated also in MS brain lesions. Mir-155 up-regulation was confirmed by qPCR experiments. The role of mir-155 in MS susceptibility was also investigated by genotyping four single nucleotide polymorphisms (SNPs) mapping in the mir-155 genomic region. A haplotype of three SNPs, corresponding to a 12-kb region encompassing the last exon of BIC (the B-cell Integration Cluster non-coding RNA, from which mir-155 is processed), resulted associated with the disease status (P = 0.035; OR = 1.36, 95% CI = 1.05-1.77), suggesting that this locus strongly deserves further investigations.     

Antiviral activity of donkey milk protein fractions on echovirus type 5

Antiviral activity of Ragusano donkeys' milk proteins was investigated for the effect on echovirus type 5, known to infect the gastrointestinal tract of humans. Three protein fractions were tested; casein (CN), whey protein (WP) and a low molecular whey protein fraction (LWP; <30,000 Da). The antiviral activity of WP and LWP was tested on echovirus type 5 at three concentrations (1, 5 and 10 mg mL^?1); CN was assessed only at the lower concentration. All donkey milk protein fractions showed significant inhibition on virus replication at the concentration of 1 mg mL^?1, and both WP and LWP fractions showed significant inhibition on the virus replication at all concentrations tested. The strongest antiviral effect was observed for the WP fraction. These findings show that the different whey proteins in donkey milk, probably acting in synergy, exert antiviral activity on echovirus 5 and might contribute to prevent gastrointestinal virus infections in humans.     

The Role of CXCL16 in the Pathogenesis of Cancer and Other Diseases

CXCL16 is a chemotactic cytokine belonging to the α-chemokine subfamily. It plays a significant role in the progression of cancer, as well as the course of atherosclerosis, renal fibrosis, and non-alcoholic fatty liver disease (NAFLD). Since there has been no review paper discussing the importance of this chemokine in various diseases, we have collected all available knowledge about CXCL16 in this review. In the first part of the paper, we discuss background information about CXCL16 and its receptor, CXCR6. Next, we focus on the importance of CXCL16 in a variety of diseases, with an emphasis on cancer. We discuss the role of CXCL16 in tumor cell proliferation, migration, invasion, and metastasis. Next, we describe the role of CXCL16 in the tumor microenvironment, including involvement in angiogenesis, and its significance in tumor-associated cells (cancer associated fibroblasts (CAF), microglia, tumor-associated macrophages (TAM), tumor-associated neutrophils (TAN), mesenchymal stem cells (MSC), myeloid suppressor cells (MDSC), and regulatory T cells (T_reg)). Finally, we focus on the antitumor properties of CXCL16, which are mainly caused by natural killer T (NKT) cells. At the end of the article, we summarize the importance of CXCL16 in cancer therapy.     

Liquid mixing in gas-liquid two-phase flow by meandering microchannels

The influence of the channel radius on the mass transfer in rectangular meandering microchannels (width and height of ) has been investigated for gas-liquid flow. Laser induced velocimetry measurements have been compared with theoretical results. The symmetrical velocity profile, known from the straight channel, was found to change to an asymmetrical one for the meandering channel configuration. The changes in the secondary velocity profile lead to an enhanced radial mass transfer inside the liquid slug, resulting in a reduced mixing length. In the investigated experimental range (superficial gas velocity and superficial liquid velocity ) the mixing time was reduced eightfold solely due to changes in channel geometry. An experimental study on the liquid slug lengths, the pressure drop and their relation to the mass transfer have also been performed. Experimental results were validated by a simulation done in Comsol Multiphysics^®. To obtain information for higher velocity rates, simulations were performed up to . These velocity variations in the simulation indicate the occurrence of a different flow pattern for high velocities, leading to further mass transfer intensification.     

CCL18 Expression Is Higher in a Glioblastoma Multiforme Tumor than in the Peritumoral Area and Causes the Migration of Tumor Cells Sensitized by Hypoxia

Glioblastoma multiforme (GBM) is a brain tumor with a very poor prognosis. For this reason, researchers worldwide study the impact of the tumor microenvironment in GBM, such as the effect of chemokines. In the present study, we focus on the role of the chemokine CCL18 and its receptors in the GBM tumor. We measured the expression of CCL18, CCR8 and PITPNM3 in the GMB tumor from patients (16 men and 12 women) using quantitative real-time polymerase chain reaction. To investigate the effect of CCL18 on the proliferation and migration of GBM cells, experiments were performed using U-87 MG cells. The results showed that CCL18 expression was higher in the GBM tumor than in the peritumoral area. The women had a decreased expression of PITPNM3 receptor in the GBM tumor, while in the men a lower expression of CCR8 was observed. The hypoxia-mimetic agent, cobalt chloride (CoCl₂), increased the expression of CCL18 and PITPNM3 and thereby sensitized U-87 MG cells to CCL18, which did not affect the proliferation of U-87 MG cells but increased the migration of the test cells. The results indicate that GBM cells migrate from hypoxic areas, which may be important in understanding the mechanisms of tumorigenesis.     

SurA-like and Skp-like Proteins as Important Virulence Determinants of the Gram Negative Bacterial Pathogens

In the Gram-negative bacteria, many important virulence factors reach their destination via two-step export systems, and they must traverse the periplasmic space before reaching the outer membrane. Since these proteins must be maintained in a structure competent for transport into or across the membrane, they frequently require the assistance of chaperones. Based on the results obtained for the model bacterium Escherichia coli and related species, it is assumed that in the biogenesis of the outer membrane proteins and the periplasmic transit of secretory proteins, the SurA peptidyl–prolyl isomerase/chaperone plays a leading role, while the Skp chaperone is rather of secondary importance. However, detailed studies carried out on several other Gram-negative pathogens indicate that the importance of individual chaperones in the folding and transport processes depends on the properties of client proteins and is species-specific. Taking into account the importance of SurA functions in bacterial virulence and severity of phenotypes due to surA mutations, this folding factor is considered as a putative therapeutic target to combat microbial infections. In this review, we present recent findings regarding SurA and Skp proteins: their mechanisms of action, involvement in processes related to virulence, and perspectives to use them as therapeutic targets.     

Galectin-3 in Cardiovascular Diseases

Galectin-3 (Gal-3) is a β-galactoside-binding protein belonging to the lectin family with pleiotropic regulatory activities and several physiological cellular functions, such as cellular growth, proliferation, apoptosis, differentiation, cellular adhesion, and tissue repair. Inflammation, tissue fibrosis and angiogenesis are the main processes in which Gal-3 is involved. It is implicated in the pathogenesis of several diseases, including organ fibrosis, chronic inflammation, cancer, atherosclerosis and other cardiovascular diseases (CVDs). This review aims to explore the connections of Gal-3 with cardiovascular diseases since they represent a major cause of morbidity and mortality. We herein discuss the evidence on the pro-inflammatory role of Gal-3 in the atherogenic process as well as the association with plaque features linked to lesion stability. We report the biological role and molecular mechanisms of Gal-3 in other CVDs, highlighting its involvement in the development of cardiac fibrosis and impaired myocardium remodelling, resulting in heart failure and atrial fibrillation. The role of Gal-3 as a prognostic marker of heart failure is described together with possible diagnostic applications to other CVDs. Finally, we report the tentative use of Gal-3 inhibition as a therapeutic approach to prevent cardiac inflammation and fibrosis.     

Preliminary investigation on the balance of lead and cadmium content in milk and its by-products

Many studies have recently been devoted to the determination of lead and cadmium in milk, in view of the toxicity of these metals and the importance of milk in the diet of infants and children. Enrichment of lead and cadmium in fatty dairy products has been sometimes noted. A systematic study on milk and its primary products (skimmed milk, cream and cheese) obtained from the same batch of milk is considered in order to define a tentative balance of these two metals. Lead and cadmium were determined by atomic-absorption spectrophotometry with graphite furnace on a solution of the ashed sample. As a consequence of the appreciable interference due to the matrix effects, the method of standard additions was adopted to determine the metals in few samples with a statistically acceptable degree of accuracy and precision. The range of the lead and cadmium content found in these products is comparable with recent literature data concerning uncontaminated samples.