CK2 Phosphorylation of Schistosoma mansoni HMGB1 Protein Regulates Its Cellular Traffic and Secretion but Not Its DNA Transactions

parasite resides in mesenteric veins where fecundated female worms lay hundred of eggs daily. Some of the egg antigens are trapped in the liver and induce a vigorous granulomatous response. High Mobility Group Box 1 (HMGB1), a nuclear factor, can also be secreted and act as a cytokine. Schistosome HMGB1 (SmHMGB1) is secreted by the eggs and stimulate the production of key cytokines involved in the pathology of schistosomiasis. Thus, understanding the mechanism of SmHMGB1 release becomes mandatory. Here, we addressed the question of how the nuclear SmHMGB1 can reach the extracellular space. eggs of infected animals and that SmHMGB1 that were localized in the periovular schistosomotic granuloma were phosphorylated.We showed that secretion of SmHMGB1 is regulated by phosphorylation. Moreover, our results suggest that egg-secreted SmHMGB1 may represent a new egg antigen. Therefore, the identification of drugs that specifically target phosphorylation of SmHMGB1 might block its secretion and interfere with the pathogenesis of schistosomiasis

Therapeutic treatments of mtDNA diseases at the earliest stages of human development.

More than 150 pathogenic mitochondrial DNA (mtDNA) mutations associated with a range of illnesses have been described in humans. These mutations are carried by one in 400 people and their inheritance is exclusively maternal. Currently there is no method to prevent mtDNA diseases, which highlights the need for strategies to predict their transmission. Here we outline the scientific background and unique difficulties in understanding the transmission of mtDNA diseases, explaining why their management has lagged so far behind the genetics revolution. Moreover, both current and future management options, including cytoplasmic and nuclear transfer, are also discussed

High Bcl-2/Bax ratio in Walker tumor cells protects mitochondria but does not prevent H2O2-induced apoptosis via calcineurin pathways

It has been previously shown that Walker 256 tumor cells express a high content of the anti-apoptotic protein Bcl-2 which protects mitochondria against the damaging effects of Ca2+. In the present study, we analyze H2O2-induced apoptotic death in two different types of tumor cells: Walker 256 and SCC-25. Treatment with H2O2 (4mM) increased reactive oxygen species generation and the concentration of cytosolic free Ca2+. These alterations preceded apoptosis in both cell lines. In Walker cells, which show a high Bcl-2/Bax ratio, apoptosis was dependent on calcineurin activation and independent of changes in mitochondrial membrane potential (Delta psi(m)), as well as cytochrome c release. In contrast, in SCC-25 cells, which show a lower Bcl-2/Bax ratio, apoptosis was preceded by a decrease in Delta psi(m), mitochondrial permeability transition, and cytochrome c release. Caspase-3 activation occurred in both cell lines. The data suggest that although the high Bcl-2/Bax ratio protected the mitochondria of Walker cells from oxidative stress, it was not sufficient to prevent apoptosis through calcineurin pathways.39218619

Distinct features of rabbit and human adipose-derived mesenchymal stem cells: implications for biotechnology and translational research

Helena Debiazi Zomer,1,2 Kelly CS Roballo,2 Thais Borges Lessa,2 Fabiana Fernandes Bressan,2 Natália Nardeli Gonçalves,2 Flávio Vieira Meirelles,2,3 Andrea Gonçalves Trentin,1 Carlos Eduardo Ambrósio2,3 1Department of Cell Biology, Embryology and Genetic, Faculty of Biological Sciences, Santa Catarina Federal University (UFSC), Florianópolis, Brazil; 2Department of Surgery, Sector Anatomy, Faculty of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil; 3Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, São Paulo, Brazil Introduction: Owing to their similarity with humans, rabbits are useful for multiple applications in biotechnology and translational research from basic to preclinical studies. In this sense, mesenchymal stem cells (MSCs) are known for their therapeutic potential and promising future in regenerative medicine. As many studies have been using rabbit adipose-derived MSCs (ASCs) as a model of human ASCs (hASCs), it is fundamental to compare their characteristics and understand how distinct features could affect the translation to human medicine.Objective: The aim of this study was to comparatively characterize rabbit ASCs (rASCs) and hASCs to further uses in biotechnology and translational studies.Materials and methods: rASCs and hASCs were isolated and characterized by their immunophenotype, differentiation potential, proliferative profile, and nuclear stability in vitro.Results and discussion: Both ASCs presented differentiation potential to osteocytes, chondrocytes, and adipocytes and shared similar immunophenotype expression to CD105+, CD34–, and CD45–, but rabbit cells expressed significantly lower CD73 and CD90 than human cells. In addition, rASCs presented greater clonogenic potential and proliferation rate than hASCs but no difference in nuclear alterations.Conclusion: The distinct features of rASCs and hASCs can positively or negatively affect their use for different applications in biotechnology (such as cell reprogramming) and translational studies (such as cell transplantation, tissue engineering, and pharmacokinetics). Nevertheless, the particularities between rabbit and human MSCs should not prevent rabbit use in preclinical models, but care should be taken to interpret results and properly translate animal findings to medicine.Keywords: characterization, comparison, MSC, iPS, immunophenotype, proliferation&nbsp

Cat amniotic membrane multipotent cells are nontumorigenic and are safe for use in cell transplantation

Atanasio S Vidane,1 Aline F Souza,1 Rafael V Sampaio,1 Fabiana F Bressan,2 Naira C Pieri,1 Daniele S Martins,2 Flavio V Meirelles,2 Maria A Miglino,1 Carlos E Ambrósio2 1Department of Surgery, Faculty of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil; 2Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, São Paulo, Brazil Abstract: Amnion-derived mesenchymal stem cells (AMSCs) are multipotent cells with an enhanced ability to differentiate into multiple lineages. AMSCs can be acquired through noninvasive methods, and therefore are exempt from the typical ethical issues surrounding stem cell use. The objective of this study was to isolate and characterize AMSCs from a cat amniotic membrane for future application in regenerative medicine. The cat AMSCs were harvested after mechanical and enzymatic digestion of amnion. In culture medium, the cat AMSCs adhered to a plastic culture dish and displayed a fibroblast-like morphology. Immunophenotyping assays were positive for the mesenchymal stem cell-specific markers CD73 and CD90 but not the hematopoietic markers CD34, CD45, and CD79. Under appropriate conditions, the cat AMSCs differentiated into osteogenic, chondrogenic, and adipogenic cell lineages. One advantage of cat AMSCs was nonteratogenicity, assessed 4 weeks post injection of undifferentiated AMSCs into immunodeficient mice. These findings suggest that cat amniotic membranes may be an important and useful source of mesenchymal stem cells for clinical applications, especially for cell or tissue replacement in chronic and degenerative diseases. Keywords: amnion, cats, cell differentiation, fetal membranes, mesenchymal cell

NUCLEAR REPROGRAMMING AND ITS EPIGENETIC CONSEQUENCES IN SOMATIC CELL NUCLEAR TRANSFER DERIVED ANIMALS

Somatic cell nuclear transfer (SCNT) is a powerful tool to understand the mechanisms driving the cellular reprogramming, as well as addressing fundamental questions on developmental biology. Hundreds of animals have already been generated through this technology, however its large-scale use is still hampered by the low efficiency and disrupted phenotypes reported in SCNT derived newborns. Therefore, this review aims to expose some of the consequences often seen in cloned animals, as well as to discuss and propose some possibilities and perspectives to avoid epigenetic failures during reprogramming