Exosomes derived from mesenchymal stem cells enhance radiotherapy-induced cell death in tumor and metastatic tumor foci

We have recently shown that radiotherapy may not only be a successful local and regional treatment but, when combined with MSCs, may also be a novel systemic cancer therapy. This study aimed to investigate the role of exosomes derived from irradiated MSCs in the delay of tumor growth and metastasis after treatment with MSC + radiotherapy (RT). The tumor cell loss rates found after treatment with the combination of MSC and RT and for exclusive RT, were: 44.4% % and 12,1%, respectively. Concomitant and adjuvant use of RT and MSC, increased the mice surviving time 22,5% in this group, with regard to the group of mice treated with exclusive RT and in a 45,3% respect control group. Moreover, the number of metastatic foci found in the internal organs of the mice treated with MSC + RT was 60% less than the mice group treated with RT alone. We reasoned that the exosome secreted by the MSC, could be implicated in tumor growth delay and metastasis control after treatment. Our results show that exosomes derived form MSCs, combined with radiotherapy, are determinant in the enhancement of radiation effects observed in the control of metastatic spread of melanoma cells and suggest that exosome-derived factors could be involved in the bystander, and abscopal effects found after treatment of the tumors with RT plus MSC. Radiotherapy itself may not be systemic, although it might contribute to a systemic effect when used in combination with mesenchymal stem cells owing the ability of irradiated MSCs-derived exosomes to increase the control of tumor growth and metastasis.This work was supported by CNPq, Conselho Nacional de Desenvolvimento Científico e Tecnológico – Brasil, Junta de Andalucía, project of Excellence from Junta de Andalucía P12-CTS-383 to FJO, Spanish Ministry of Economy and Competitiveness SAF2015-70520-R to FJO and JMRdA, RTICC RD12/0036/0026 and CIBER Cáncer ISCIII CB16/12/00421 to FJO

Identification of a Highly Conserved H1 Subtype-Specific Epitope with Diagnostic Potential in the Hemagglutinin Protein of Influenza A Virus

Subtype specificity of influenza A virus (IAV) is determined by its two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). For HA, 16 distinct subtypes (H1–H16) exist, while nine exist for NA. The epidemic strains of H1N1 IAV change frequently and cause annual seasonal epidemics as well as occasional pandemics, such as the notorious 1918 influenza pandemic. The recent introduction of pandemic A/H1N1 IAV (H1N1pdm virus) into humans re-emphasizes the public health concern about H1N1 IAV. Several studies have identified conserved epitopes within specific HA subtypes that can be used for diagnostics. However, immune specific epitopes in H1N1 IAV have not been completely assessed. In this study, linear epitopes on the H1N1pdm viral HA protein were identified by peptide scanning using libraries of overlapping peptides against convalescent sera from H1N1pdm patients. One epitope, P5 (aa 58–72) was found to be immunodominant in patients and to evoke high titer antibodies in mice. Multiple sequence alignments and in silico coverage analysis showed that this epitope is highly conserved in influenza H1 HA [with a coverage of 91.6% (9,860/10,767)] and almost completely absent in other subtypes [with a coverage of 3.3% (792/23,895)]. This previously unidentified linear epitope is located outside the five well-recognized antigenic sites in HA. A peptide ELISA method based on this epitope was developed and showed high correlation (χ2 = 51.81, P<0.01, Pearson correlation coefficient R = 0.741) with a hemagglutination inhibition test. The highly conserved H1 subtype-specific immunodominant epitope may form the basis for developing novel assays for sero-diagnosis and active surveillance against H1N1 IAVs

Identification of a Highly Conserved H1 Subtype-Specific Epitope with Diagnostic Potential in the Hemagglutinin Protein of Influenza A Virus

Subtype specificity of influenza A virus (IAV) is determined by its two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). For HA, 16 distinct subtypes (H1–H16) exist, while nine exist for NA. The epidemic strains of H1N1 IAV change frequently and cause annual seasonal epidemics as well as occasional pandemics, such as the notorious 1918 influenza pandemic. The recent introduction of pandemic A/H1N1 IAV (H1N1pdm virus) into humans re-emphasizes the public health concern about H1N1 IAV. Several studies have identified conserved epitopes within specific HA subtypes that can be used for diagnostics. However, immune specific epitopes in H1N1 IAV have not been completely assessed. In this study, linear epitopes on the H1N1pdm viral HA protein were identified by peptide scanning using libraries of overlapping peptides against convalescent sera from H1N1pdm patients. One epitope, P5 (aa 58–72) was found to be immunodominant in patients and to evoke high titer antibodies in mice. Multiple sequence alignments and in silico coverage analysis showed that this epitope is highly conserved in influenza H1 HA [with a coverage of 91.6% (9,860/10,767)] and almost completely absent in other subtypes [with a coverage of 3.3% (792/23,895)]. This previously unidentified linear epitope is located outside the five well-recognized antigenic sites in HA. A peptide ELISA method based on this epitope was developed and showed high correlation (χ2 = 51.81, P<0.01, Pearson correlation coefficient R = 0.741) with a hemagglutination inhibition test. The highly conserved H1 subtype-specific immunodominant epitope may form the basis for developing novel assays for sero-diagnosis and active surveillance against H1N1 IAVs

Effectiveness of ecological rescue for altered soil microbial communities and functions

Soil ecosystems worldwide are subjected to marked modifications caused by anthropogenic disturbances and global climate change, resulting in microbial diversity loss and alteration of ecosystem functions. Despite the paucity of studies, restoration ecology provides an appropriate framework for testing the potential of manipulating soil microbial communities for the recovery of ecosystem functioning. We used a reciprocal transplant design in experimentally altered microbial communities to investigate the effectiveness of introducing microbial communities in degraded soil ecosystems to restore N-cycle functioning. Microbial diversity loss resulted in alternative compositional states associated with impaired N-cycle functioning. Here, the addition of complex microbial communities to these altered communities revealed a pivotal role of deterministic community assembly processes. The diversity of some alternative compositional states was successfully increased but without significant restoration of soil N-cycle functioning. However, in the most degraded alternative state, the introduction of new microbial communities caused an overall decrease in phylogenetic diversity and richness. The successful soil colonization by newly introduced species for some compositional states indicates that priority effects could be overridden when attempting to manipulate microbial communities for soil restoration. Altogether, our result showed consistent patterns within restoration treatments with minor idiosyncratic effects. This suggests the predominance of deterministic processes and the predictability of restoration trajectories, which could be used to guide the effective management of microbial community assemblages for ecological restoration of soils

Structure and properties of oxidatively stabilized viscose rayon fibers impregnated with boric acid and phosphoric acid prior to carbonization and activation steps

The role of boric acid-phosphoric acid (BA-PA) impregnation and oxidation on the structure and properties of viscose rayon fibers was examined in air at temperatures ranging from 150 to 250 A degrees C. The results obtained from the measurements of fiber thickness, linear density, X-ray diffraction, thermal analysis (DSC and TGA), and infrared spectroscopy demonstrated that oxidation temperature had a significant influence on the structure and properties of oxidized viscose rayon fibers. Physical transformations were characterized by fiber thickness and linear density values together with color variations and improved burning behavior with progressing oxidation temperature. The DSC analysis showed that BA-PA impregnation enhanced thermal stability and prevented the evolution of volatile by-products by blocking the primary hydroxyl groups. TGA thermograms revealed an enhancement in the char yields. X-ray diffraction analysis showed the loss of cellulose II crystalline structure caused by the decrystallization process initiated by the gradual loss of intermolecular hydrogen bonds. Analysis of IR spectra revealed gradual and continuous loss of intramolecular and intermolecular hydrogen bonding as part of the simultaneously occurring dehydrogenation and dehydration reactions. Analysis of IR data also demonstrated the disturbance of the cellulose II crystalline structure with increasing oxidation temperature in agreement with the results obtained from X-ray diffraction measurements. The formation of C=C bonds attributed to the crosslinked ladder-like structure was also confirmed by the IR spectra.The role of boric acid–phosphoric acid (BA–PA) impregnation and oxidation on the structure and properties of viscose rayon fibers was examined in air at temperatures ranging from 150 to 250 C. The results obtained from the measurements of fiber thickness, lineardensity, X-ray diffraction, thermal analysis (DSC and TGA), and infrared spectroscopy demonstrated that oxidation temperature had a significant influence on the structure and properties of oxidized viscose rayon fibers. Physical transformations were characterized by fiber thickness and linear density values together with color variations and improved burning behavior with progressing oxidation temperature. The DSC analysis showed that BA–PA impregnation enhanced thermal stability and prevented the evolution of volatile by-products by blocking the primary hydroxyl groups. TGA thermograms revealed an enhancement in the char yields. X-ray diffraction analysis showed the loss of cellulose II crystalline structure caused by the decrystallization process initiated by the gradual lossof intermolecular hydrogen bonds. Analysis of IR spectra revealed gradual and continuous loss of intramolecular and intermolecular hydrogen bonding as part of the simultaneouslyoccurring dehydrogenation and dehydration reactions.Analysis of IR data also demonstrated the disturbance of the cellulose II crystalline structure with increasing oxidation temperature in agreement with the results obtained from X-ray diffraction measurements. The formation of C=C bonds attributed to the crosslinked ladder-like structure was also confirmed by the IR spectra