Harnessing magnetic-mechano actuation in regenerative medicine and tissue engineering

Mechanical stimulus is of upmost importance in tissues developmental and regeneration processes as well as in maintaining body homeostasis. Classical physiological reactions encompass an increase of blood vessel diameter upon exposure to high blood pressure, or the expansion of cortical bone after continuous high-impact exercise. At a cellular level, it is well established that extracellular stiffness, topography, and remote magnetic actuation are instructive mechanical signals for stem cell differentiation. Based on this, biomaterials and their properties can be designed to act as true stem cell regulators, eventually leading to important advances in conventional tissue engineering techniques. This review identifies the latest advances and tremendous potential of magnetic actuation within the scope of regenerative medicine and tissue engineering

Paclitaxel targets FOXM1 to regulate KIF20A in mitotic catastrophe and breast cancer paclitaxel resistance

FOXM1 has been implicated in taxane resistance, but the molecular mechanism involved remains elusive. In here, we show that FOXM1 depletion can sensitize breast cancer cells and mouse embryonic fibroblasts into entering paclitaxel-induced senescence, with the loss of clonogenic ability, and the induction of senescence-associated beta-galactosidase activity and flat cell morphology. We also demonstrate that FOXM1 regulates the expression of the microtubulin-associated kinesin KIF20A at the transcriptional level directly through a Forkhead response element (FHRE) in its promoter. Similar to FOXM1, KIF20A expression is downregulated by paclitaxel in the sensitive MCF-7 breast cancer cells and deregulated in the paclitaxel-resistant MCF-7TaxR cells. KIF20A depletion also renders MCF-7 and MCF-7TaxR cells more sensitive to paclitaxel-induced cellular senescence. Crucially, resembling paclitaxel treatment, silencing of FOXM1 and KIF20A similarly promotes abnormal mitotic spindle morphology and chromosome alignment, which have been shown to induce mitotic catastrophe-dependent senescence. The physiological relevance of the regulation of KIF20A by FOXM1 is further highlighted by the strong and significant correlations between FOXM1 and KIF20A expression in breast cancer patient samples. Statistical analysis reveals that both FOXM1 and KIF20A protein and mRNA expression significantly associates with poor survival, consistent with a role of FOXM1 and KIF20A in paclitaxel action and resistance. Collectively, our findings suggest that paclitaxel targets the FOXM1-KIF20A axis to drive abnormal mitotic spindle formation and mitotic catastrophe and that deregulated FOXM1 and KIF20A expression may confer paclitaxel resistance. These findings provide insights into the underlying mechanisms of paclitaxel resistance and have implications for the development of predictive biomarkers and novel chemotherapeutic strategies for paclitaxel resistance.Oncogene advance online publication, 11 May 2015; doi:10.1038/onc.2015.152.published_or_final_versio

Developmental Neurotoxicity of Pyrethroid Insecticides: Critical Review and Future Research Needs

Pyrethroid insecticides have been used for more than 40 years and account for 25% of the worldwide insecticide market. Although their acute neurotoxicity to adults has been well characterized, information regarding the potential developmental neurotoxicity of this class of compounds is limited. There is a large age dependence to the acute toxicity of pyrethroids in which neonatal rats are at least an order of magnitude more sensitive than adults to two pyrethroids. There is no information on age-dependent toxicity for most pyrethroids. In the present review we examine the scientific data related to potential for age-dependent and developmental neurotoxicity of pyrethroids. As a basis for understanding this neurotoxicity, we discuss the heterogeneity and ontogeny of voltage-sensitive sodium channels, a primary neuronal target of pyrethroids. We also summarize 22 studies of the developmental neurotoxicity of pyrethroids and review the strengths and limitations of these studies. These studies examined numerous end points, with changes in motor activity and muscarinic acetylcholine receptor density the most common. Many of the developmental neurotoxicity studies suffer from inadequate study design, problematic statistical analyses, use of formulated products, and/or inadequate controls. These factors confound interpretation of results. To better understand the potential for developmental exposure to pyrethroids to cause neurotoxicity, additional, well-designed and well-executed developmental neurotoxicity studies are needed. These studies should employ state-of-the-science methods to promote a greater understanding of the mode of action of pyrethroids in the developing nervous system

Psychometric analysis of the scale for the predisposition to the occurrence of adverse events in nursing care provided in ICUS

OBJECTIVE: to present the result of the validity and reliability studies concerning the Scale for the Predisposition to the Occurrence of Adverse Events (EPEA). METHOD: construct validity was based on Principal Components Analysis. RESULTS: reliability verified through Cronbach's alpha indicated good reliability (structure α=0.80; process α=0.92). CONCLUSION: based on its psychometric indicators, the EPEA can be considered a valid measure to assess the attitudes of nurses in relation to factors that potentially lead to the occurrence of adverse events in ICUs

Supercritical phase inversion of starch-poly(e-caprolactone) for tissue engineering applications

In this work, a starch-based polymer, namely a blend of starch-poly(ε-caprolactone) was processed by supercritical assisted phase inversion process. This processing technique has been proposed for the development of 3D structures with potential applications in tissue engineering applications, as scaffolds. The use of carbon dioxide as non-solvent in the phase inversion process leads to the formation of a porous and interconnected structure, dry and free of any residual solvent. Different processing conditions such as pressure (from 80 up to 150 bar) and temperature (45 and 55°C) were studied and the effect on the morphological features of the scaffolds was evaluated by scanning electron microscopy and micro-computed tomography. The mechanical properties of the SPCL scaffolds prepared were also studied. Additionally, in this work, the in vitro biological performance of the scaffolds was studied. Cell adhesion and morphology, viability and proliferation was assessed and the results suggest that the materials prepared are allow cell attachment and promote cell proliferation having thus potential to be used in some for biomedical applications.Ana Rita C. Duarte is grateful for financial support from Fundacao para a Ciencia e Tecnologia through the grant SFRH/BPD/34994/2007

The actin-myosin regulatory MRCK kinases: regulation, biological functions and associations with human cancer

The contractile actin-myosin cytoskeleton provides much of the force required for numerous cellular activities such as motility, adhesion, cytokinesis and changes in morphology. Key elements that respond to various signal pathways are the myosin II regulatory light chains (MLC), which participate in actin-myosin contraction by modulating the ATPase activity and consequent contractile force generation mediated by myosin heavy chain heads. Considerable effort has focussed on the role of MLC kinases, and yet the contributions of the myotonic dystrophy-related Cdc42-binding kinases (MRCK) proteins in MLC phosphorylation and cytoskeleton regulation have not been well characterized. In contrast to the closely related ROCK1 and ROCK2 kinases that are regulated by the RhoA and RhoC GTPases, there is relatively little information about the CDC42-regulated MRCKα, MRCKβ and MRCKγ members of the AGC (PKA, PKG and PKC) kinase family. As well as differences in upstream activation pathways, MRCK and ROCK kinases apparently differ in the way that they spatially regulate MLC phosphorylation, which ultimately affects their influence on the organization and dynamics of the actin-myosin cytoskeleton. In this review, we will summarize the MRCK protein structures, expression patterns, small molecule inhibitors, biological functions and associations with human diseases such as cancer

The effects of symmetry on the dynamics of antigenic variation

In the studies of dynamics of pathogens and their interactions with a host immune system, an important role is played by the structure of antigenic variants associated with a pathogen. Using the example of a model of antigenic variation in malaria, we show how many of the observed dynamical regimes can be explained in terms of the symmetry of interactions between different antigenic variants. The results of this analysis are quite generic, and have wider implications for understanding the dynamics of immune escape of other parasites, as well as for the dynamics of multi-strain diseases.Comment: 21 pages, 4 figures; J. Math. Biol. (2012), Online Firs

Histomorphometric analysis of inflammatory response and necrosis in re-implanted central incisor of rats treated with low-level laser therapy

Low-level laser therapy is a tool employed in the management of post-operative inflammation process and in the enhancement of reparative process. The aim of the study was to perform histological evaluation of dental and periodontal ligament of rats central upper-left incisor teeth re-implanted and irradiated with low-level laser (InGaAl, 685 nm, 50 J/cm2) 15, 30, and 60 days after re-implantation. Seventy-two male rats had the central upper left incisor removed and kept for 15 min on dry gauze before replantation. Laser was irradiated over the root surface and empty alveolus prior replantation and over surrounding mucosa after the re-implantation. After histological procedures, all slices were analyzed regarding external resorption area and histological aspects. We observed an increase of root resorption (p < 0.05) in the control group compared to the laser group at 15, 30, and 60 days. These results showed that the laser groups developed less root resorption areas than the control group in all experimental periods. Additionally, histological analysis revealed less inflammatory cells and necrotic areas in laser groups

B Cells Regulate Neutrophilia during Mycobacterium tuberculosis Infection and BCG Vaccination by Modulating the Interleukin-17 Response

We have previously demonstrated that B cells can shape the immune response to Mycobacterium tuberculosis, including the level of neutrophil infiltration and granulomatous inflammation at the site of infection. The present study examined the mechanisms by which B cells regulate the host neutrophilic response upon exposure to mycobacteria and how neutrophilia may influence vaccine efficacy. To address these questions, a murine aerosol infection tuberculosis (TB) model and an intradermal (ID) ear BCG immunization mouse model, involving both the μMT strain and B cell-depleted C57BL/6 mice, were used. IL (interleukin)-17 neutralization and neutrophil depletion experiments using these systems provide evidence that B cells can regulate neutrophilia by modulating the IL-17 response during M. tuberculosis infection and BCG immunization. Exuberant neutrophilia at the site of immunization in B cell-deficient mice adversely affects dendritic cell (DC) migration to the draining lymph nodes and attenuates the development of the vaccine-induced Th1 response. The results suggest that B cells are required for the development of optimal protective anti-TB immunity upon BCG vaccination by regulating the IL-17/neutrophilic response. Administration of sera derived from M. tuberculosis-infected C57BL/6 wild-type mice reverses the lung neutrophilia phenotype in tuberculous μMT mice. Together, these observations provide insight into the mechanisms by which B cells and humoral immunity modulate vaccine-induced Th1 response and regulate neutrophila during M. tuberculosis infection and BCG immunization. © 2013 Kozakiewicz et al