Antimycobacterial effect of selenium nanoparticles on Mycobacterium tuberculosis.

Tuberculosis remains the leading cause of death from a single infection agent worldwide. In recent years, the occurrence of tuberculosis cases caused by drug-resistant strains has spread, and is expected to continue to grow. Therefore, the development of new alternative treatments to the use of antibiotics is highly important. In that sense, nanotechnology can play a very relevant role, due to the unique characteristics of nanoparticles. In fact, different types of nanoparticles have already been evaluated both as potential bactericides and as efficient drug delivery vehicles. In this work, the use of selenium nanoparticles has been evaluated to inhibit the growth of two types of mycobacteria: Mycobacterium smegmatis and Mycobacterium tuberculosis. The results showed that selenium nanoparticles are able to inhibit the growth of both types of mycobacteria by damaging their cell envelope integrity. These results open a new opportunity for the use of this type of nanoparticles as antimycobacterial agents by themselves, or for the development of novel nanosystems that combine the action of these nanoparticles with other drugs

Transcriptome Analysis Identifies Novel Mechanisms Associated with the Antitumor Effect of Chitosan‐Stabilized Selenium Nanoparticles.

Selenium nanoparticles (SeNPs) have been receiving special attention in recent years due to their antioxidant capacity and antitumor properties. However, the mechanisms associated with these properties remain to be elucidated. For this reason, a global transcriptome analysis has been designed in this work and it was carried out using human hepatocarcinoma cells and chitosan‐ stabilized SeNPs (Ch‐SeNPs) to identify new targets and pathways related to the antitumor mechanisms associated with Ch‐SeNPs. The results obtained confirm the alteration of the cell cycle and the effect of Ch‐SeNPs on different tumor suppressors and other molecules involved in key mechanisms related to cancer progression. Furthermore, we demonstrated the antioxidant properties of these nanoparticles and their capacity to induce senescence, which was further confirmed through the measurement of β‐galactosidase activity

Herpesvirus Antibodies, Vitamin D and Short-Chain Fatty Acids: Their Correlation with Cell Subsets in Multiple Sclerosis Patients and Healthy Controls

Although the etiology of multiple sclerosis (MS) is still unknown, it is commonly accepted that environmental factors could contribute to the disease. The objective of this study was to analyze the humoral response to Epstein-Barr virus, human herpesvirus 6A/B and cytomegalovirus, and the levels of 25-hydroxyvitamin D (25(OH)D) and the three main short-chain fatty acids (SCFA), propionate (PA), butyrate (BA) and acetate (AA), in MS patients and healthy controls (HC) to understand how they could contribute to the pathogenesis of the disease. With this purpose, we analyzed the correlations among them and with different clinical variables and a wide panel of cell subsets. We found statistically significant differences for most of the environmental factors analyzed when we compared MS patients and HC, supporting their possible involvement in the disease. The strongest correlations with the clinical variables and the cell subsets analyzed were found for 25(OH)D and SCFAs levels. A correlation was also found between 25(OH)D and PA/AA ratio, and the interaction between these factors negatively correlated with interleukin 17 (IL-17)-producing CD4+ and CD8+ T cells in untreated MS patients. Therapies that simultaneously increase vitamin D levels and modify the proportion of SCFA could be evaluated in the future

Inhibition of paclitaxel-induced proteasome activation influences paclitaxel cytotoxicity in breast cancer cells in a sequence-dependent manner

This article is an Open Access.Although the anti-tumor effects of paclitaxel result mainly from mitotic arrest, recent evidences suggest alternative mechanisms of cytotoxicity. Cell cycle, cell death and gene expression assays were used to understand the molecular mechanisms of paclitaxel cytotoxicity in breast cancer cells. G 2/M cell cycle arrest and cell death coincided with the regulation of genes involved in cell death, cell cycle control, microtubule-based processes, oxidative stress, and ubiquitin-proteasome system. Induction of proteasome genes was also correlated with an accumulation of protein for proteasome subunits. Furthermore, a schedule-dependent regulation of paclitaxel-induced cytotoxicity was observed after combining paclitaxel and the proteasome inhibitor MG132. Proteasome inhibition after paclitaxel exposure induced the highest rate of growth inhibition and apoptosis, with no effect on mitotic arrest. These findings give support to clinical combinations of taxanes with proteasome inhibitors, outlining the importance of considering the sequence when designing such regimens. ©2007 Landes Bioscience.This work was supported by Ministerio de Educación y Ciencia, Grant Reference PTR1995-0753-OP and Ministerio de Ciencia y Tecnología SAF2001-0065 and SAF2004-08258-C02-01.Peer Reviewe

Human Mesenchymal Stem/Stromal Cells from Umbilical Cord Blood and Placenta Exhibit Similar Capacities to Promote Expansion of Hematopoietic Progenitor Cells In Vitro

Mesenchymal stem/stromal cells (MSCs) from bone marrow (BM) have been used in coculture systems as a feeder layer for promoting the expansion of hematopoietic progenitor cells (HPCs) for hematopoietic cell transplantation. Because BM has some drawbacks, umbilical cord blood (UCB) and placenta (PL) have been proposed as possible alternative sources of MSCs. However, MSCs from UCB and PL sources have not been compared to determine which of these cell populations has the best capacity of promoting hematopoietic expansion. In this study, MSCs from UCB and PL were cultured under the same conditions to compare their capacities to support the expansion of HPCs in vitro. MSCs were cocultured with CD34+CD38−Lin− HPCs in the presence or absence of early acting cytokines. HPC expansion was analyzed through quantification of colony-forming cells (CFCs), long-term culture-initiating cells (LTC-ICs), and CD34+CD38−Lin− cells. MSCs from UCB and PL have similar capacities to increase HPC expansion, and this capacity is similar to that presented by BM-MSCs. Here, we are the first to determine that MSCs from UCB and PL have similar capacities to promote HPC expansion; however, PL is a better alternative source because MSCs can be obtained from a higher proportion of samples

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective