Publication date: August 2017
Source:Data in Brief, Volume 13
Author(s): Yeong-Min Yoo, Yung Chul Park
Autophagy is a highly regulated physiologic mechanism in which cells maintain homeostasis by degrading excessive or unnecessary proteins and damaged or aged organelles through the lysosomal machinery (Yorimitsu and Klionsky, 2005) [1]. MyoD is basic helix-loop-helix (bHLH) transcription factors that regulate myoblast proliferation and myogenic differentiation. MyoD is expressed in adult skeletal muscle (Megeney et al., 1996) [2] and adult fibers (Brack et al., 2005) [3]. MyoD is mainly degraded by the ubiquitin-proteasome system (Floyd et al., 2001) [4] and partly by autophagy (Kim et al., 2012) [5]. Data showed that autophagy decreased MyoD protein in C2C12 cells by Western blotting analysis.
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Σάββατο 8 Ιουλίου 2017
Data on MyoD reduction by autophagy in C2C12 cells
Fatty acid and lipidomic data in normal and tumor colon tissues of rats fed diets with and without fish oil
Publication date: August 2017
Source:Data in Brief, Volume 13
Author(s): Zora Djuric, Muhammad Nadeem Aslam, Becky R. Simon, Ananda Sen, Yan Jiang, Jianwei Ren, Rena Chan, Tanu Soni, Thekkelnaycke M. Rajendiran, William L. Smith, Dean E. Brenner
Data is provided to show the detailed fatty acid and lipidomic composition of normal and tumor rat colon tissues. Rats were fed either a Western fat diet or a fish oil diet, and half the rats from each diet group were treated with chemical carcinogens that induce colon cancer (azoxymethane and dextran sodium sulfate). The data show total fatty acid profiles of sera and of all the colon tissues, namely normal tissue from control rats and both normal and tumor tissues from carcinogen-treated rats, as obtained by gas chromatography with mass spectral detection. Data from lipidomic analyses of a representative subset of the colon tissue samples is also shown in heat maps generated from hierarchical cluster analysis. These data display the utility lipidomic analyses to enhance the interpretation of dietary feeding studies aimed at cancer prevention and support the findings published in the companion paper (Effects of fish oil supplementation on prostaglandins in normal and tumor colon tissue: modulation by the lipogenic phenotype of colon tumors, Djuric et al., 2017 [1]).
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Bioreactor-induced mesenchymal progenitor cell differentiation and elastic fiber assembly in engineered vascular tissues
Publication date: Available online 8 July 2017
Source:Acta Biomaterialia
Author(s): Shigang Lin, Kibret Mequanint
In vitro maturation of engineered vascular tissues (EVT) requires the appropriate incorporation of smooth muscle cells (SMC) and extracellular matrix (ECM) components similar to native arteries. To this end, the aim of the current study was to fabricate 4 mm inner diameter vascular tissues using mesenchymal progenitor cells seeded into tubular scaffolds. A dual-pump bioreactor operating either in perfusion or pulsatile perfusion mode was used to generate physiological-like stimuli to promote progenitor cell differentiation, extracellular elastin production, and tissue maturation. Our data demonstrated that pulsatile forces and perfusion of 3D tubular constructs from both the lumenal and ablumenal sides with culture media significantly improved tissue assembly, effectively inducing mesenchymal progenitor cell differentiation to SMCs with contemporaneous elastin production. With bioreactor cultivation, progenitor cells differentiated toward smooth muscle lineage characterized by the expression of smooth muscle (SM)-specific markers smooth muscle alpha actin (SM-α-actin) and smooth muscle myosin heavy chain (SM-MHC). More importantly, pulsatile perfusion bioreactor cultivation enhanced the synthesis of tropoelastin and its extracellular cross-linking into elastic fiber compared with static culture controls. Taken together, the current study demonstrated progenitor cell differentiation and vascular tissue assembly, and provides insights into elastin synthesis and assembly to fibers.Statement of SignificanceIncorporation of elastin into engineered vascular tissues represents a critical design goal for both mechanical and biological functions. In the present study, we seeded porous tubular scaffolds with multipotent mesenchymal progenitor cells and cultured in dual-pump pulsatile perfusion bioreactor. Physiological-like stimuli generated by bioreactor not only induced mesenchymal progenitor cell differentiation to vascular smooth muscle lineage but also actively promoted elastin synthesis and fibre assembly. Gene expression and protein synthesis analyses coupled with histological and immunofluorescence staining revealed that elastin-containing vascular tissues were fabricated. More importantly, co-localization and co-immunoprecipitation experiments demonstrated that elastin and fibrillin-1 were abundant throughout the cross-section of the tissue constructs suggesting a process of elastin protein crosslinking. This study paves a way forward to engineer elastin-containing functional vascular substitutes from multipotent progenitor cells in a bioreactor.
Graphical abstract
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Fibrin functionalization with synthetic adhesive ligands interacting with α6β1 integrin receptor enhance neurite outgrowth of embryonic stem cell-derived neural stem/progenitors
Publication date: Available online 8 July 2017
Source:Acta Biomaterialia
Author(s): Joana Silva, Ana R. Bento, Daniela Barros, Tiago L. Laundos, Susana R. Sousa, Pedro Quelhas, Mónica M. Sousa, Ana P. Pêgo, Isabel F. Amaral
To enhance fibrin hydrogel affinity towards pluripotent stem cell-derived neural stem/progenitor cells (NSPCs) and its capacity to support NSPC migration and neurite extension, we explored the tethering of synthetic peptides engaging integrin α6β1, a cell receptor enriched in NSPCs. Six α6β1 integrin ligands were tested for their ability to support integrin α6β1-mediated adhesion of embryonic stem cell-derived NSPCs (ES-NSPs) and sustain ES-NSPC viability, migration, and neuronal differentiation. Due to their better performance, peptides T1, HYD1, and A5G81 were immobilized into fibrin and functionalized gels characterized in terms of peptide binding efficiency, structure and viscoelastic properties. Tethering of T1 or HYD1 successfully enhanced cell outgrowth from ES-NSPC neurospheres (up to 2.4-fold increase), which exhibited a biphasic response to peptide concentration. Inhibition assays evidenced the involvement of α6β1 and α3β1 integrins in mediating radial outgrowth on T1-/HYD1-functionalized gels. Fibrin functionalization also promoted neurite extension of single ES-NSPCs in fibrin, without affecting cell proliferation and neuronal differentiation. Finally, HYD1-functionalized gels were found to provide a permissive environment for axonal regeneration, leading up to a 2.0-fold increase in neurite extension from rat dorsal root ganglia explants as compared to unmodified fibrin, and to significant improved locomotor function after spinal cord injury (complete transection), along with a trend toward a higher area positive for growth associated protein 43 (marker for axonal growth cone formation). Our results suggest that conjugation of α6β1 integrin-binding motifs is of interest to increase the biofunctionality of hydrogels used in 3D platforms for ES-NSPC culture and potentially, in matrix-assisted ES-NSPC transplantation.Impact statementThe transplantation of NSPCs derived from pluripotent stem cells holds much promise for the treatment of central nervous system disorders. Moreover, the combinatorial use of biodegradable hydrogels with NSPCs was shown to contribute to the establishment of a more permissive environment for survival and integration of transplanted cells. In this study, fibrin hydrogels functionalized with a synthetic peptide engaging integrin α6β1 (HYD1) were shown to promote neurite extension of ES-NSPCs, which is fundamental for the formation of functional neuronal relay circuits after NSPC transplantation. Notably, HYD1-functionalized fibrin per se led to enhanced axonal regeneration ex vivo and to an improvement in locomotor function after implantation in a rat model of spinal cord injury. Conjugation of α6β1 integrin-binding motifs may therefore be of interest to confer bioactivity to NSPC hydrogel vehicles.
Graphical abstract
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Laminin Mimetic Peptide Nanofibers Regenerate Acute Muscle Defect
Publication date: Available online 8 July 2017
Source:Acta Biomaterialia
Author(s): Cagla Eren Cimenci, Gozde Uzunalli, Ozge Uysal, Fatih Yergoz, Ebru Karaca Umay, Mustafa O. Guler, Ayse B. Tekinay
Skeletal muscle cells are terminally differentiated and require the activation of muscle progenitor (satellite) cells for their regeneration. There is a clinical need for faster and more efficient treatment methods for acute muscle injuries, and the stimulation of satellite cell proliferation is promising in this context. In this study, we designed and synthesized a laminin-mimetic bioactive peptide (LM/E-PA) system that is capable of accelerating satellite cell activation by emulating the structure and function of laminin, a major protein of the basal membrane of the skeletal muscle. The LM/E-PA nanofibers enhance myogenic differentiation in vitro and the clinical relevance of the laminin-mimetic bioactive scaffold system was demonstrated further by assessing its effect on the regeneration of acute muscle injury in a rat model. Laminin mimetic peptide nanofibers significantly promoted satellite cell activation in skeletal muscle and accelerated myofibrillar regeneration following acute muscle injury. In addition, the LM/E-PA scaffold treatment significantly reduced the time required for the structural and functional repair of skeletal muscle. This study represents one of the first examples of molecular- and tissue-level regeneration of skeletal muscle facilitated by bioactive peptide nanofibers following acute muscle injury.Significance StatementSports, heavy lifting and other strength-intensive tasks are ubiquitous in modern life and likely to cause acute skeletal muscle injury. Speeding up regeneration of skeletal muscle injuries would not only shorten the duration of recovery for the patient, but also support the general health and functionality of the repaired muscle tissue. In this work, we designed and synthesized a laminin-mimetic nanosystem to enhance muscle regeneration. We tested its activity in a rat tibialis anterior muscle by injecting the bioactive nanosystem. The evaluation of the regeneration and differentiation capacity of skeletal muscle suggested that the laminin-mimetic nanosystem enhances skeletal muscle regeneration and provides a suitable platform that is highly promising for the regeneration of acute muscle injuries. This work demonstrates for the first time that laminin-mimetic self-assembled peptide nanosystems facilitate myogenic differentiation in vivo without the need for additional treatment.
Graphical abstract
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Functionalized bioengineered spider silk spheres improve nuclease resistance and activity of oligonucleotide therapeutics providing a strategy for cancer treatment.
Publication date: Available online 8 July 2017
Source:Acta Biomaterialia
Author(s): Anna Karolina Kozlowska, Anna Florczak, Maciej Smialek, Ewelina Dondajewska, Andrzej Mackiewicz, Marcin Kortylewski, Hanna Dams-Kozlowska
Cell-selective delivery and sensitivity to serum nucleases remain major hurdles to the clinical application of RNA-based oligonucleotide therapeutics, such as siRNA. Spider silk shows great potential as a biomaterial due to its biocompatibility and biodegradability. Self-assembling properties of silk proteins allow for processing into several different morphologies such as fibers, scaffolds, films, hydrogels, capsules and spheres. Moreover, bioengineering of spider silk protein sequences can functionalize silk by adding peptide moieties with specific features including binding or cell recognition domains.We demonstrated that modification of silk protein by adding the nucleic acid binding domain enabled the development of a novel oligonucleotide delivery system that can be utilized to improve pharmacokinetics of RNA-based therapeutics, such as CpG-siRNA. The MS2 bioengineered silk was functionalized with poly-lysine domain (KN) to generate hybrid silk MS2KN. CpG-siRNA efficiently bound to MS2KN in contrary to control MS2. Both MS2KN complexes and spheres protected CpG-siRNA from degradation by serum nucleases. CpG-siRNA molecules encapsulated into MS2KN spheres were efficiently internalized and processed by TLR9-positive macrophages. Importantly, CpG-STAT3siRNA loaded in silk spheres showed delayed and extended target gene silencing compared to naked oligonucleotides. The prolonged Stat3 silencing resulted in the more pronounced downregulation of interleukin 6 (IL-6), a proinflammatory cytokine and upstream activator of STAT3, which limits the efficacy of TLR9 immunostimulation.Our results demonstrate the feasibility of using spider silk spheres as a carrier of therapeutic nucleic acids. Moreover, the modified kinetic and activity of the CpG-STAT3siRNA embedded into silk spheres is likely to improve immunotherapeutic effects in vivo.Statement of SignificanceWe demonstrated that modification of silk protein by adding the nucleic acid binding domain enabled the development of a novel oligonucleotide delivery system that can be utilized to improve pharmacokinetics of RNA-based therapeutics. Although, the siRNA constructs have already given very promising results in the cancer therapy, the in vivo application of RNA-based oligonucleotide therapeutics still is limited due to their sensitivity to serum nucleases and some toxicity. We propose a carrier for RNA-based therapeutics that is made of bioengineered spider silk. We showed that functionalized bioengineered spider silk spheres not only protected RNA-based therapeutics from degradation by serum nucleases, but what is more important the embedding of siRNA into silk spheres delayed and extended target gene silencing compared with naked oligonucleotides. Moreover, we showed that plain silk spheres did not have unspecific effect on target gene levels proving not only to be non-cytotoxic but also very neutral vehicles in terms of TLR9/STAT3 activation in macrophages. We demonstrated advantages of novel delivery technology in safety and efficacy comparing with delivery of naked CpG-STAT3siRNA therapeutics.
Graphical abstract
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Phase transitions during compression and decompression of clots from platelet-poor plasma, platelet-rich plasma and whole blood
Publication date: Available online 8 July 2017
Source:Acta Biomaterialia
Author(s): Xiaojun Liang, Irina Chernysh, Prashant K. Purohit
Blood clots are required to stem bleeding and are subject to a variety of stresses, but they can also block blood vessels and cause heart attacks and ischemic strokes. We measured the compressive response of human platelet-poor plasma (PPP) clots, platelet-rich plasma (PRP) clots and whole blood clots and correlated these measurements with confocal and scanning electron microscopy to track changes in clot structure. Stress-strain curves revealed four characteristic regions, for compression-decompression: 1) linear elastic region; 2) upper plateau or softening region; 3) non-linear elastic region or re-stretching of the network; 4) lower plateau in which dissociation of some newly made connections occurs. Our experiments revealed that compression proceeds by the passage of a phase boundary through the clot separating rarefied and densified phases. This observation motivates a model of fibrin mechanics based on the continuum theory of phase transitions, which accounts for the pre-stress caused by platelets, the adhesion of fibrin fibers in the densified phase, the compression of red blood cells (RBCs), and the pumping of liquids through the clot during compression/decompression. Our experiments and theory provide insights into the mechanical behavior of blood clots that could have implications clinically and in the design of fibrin-based biomaterials.Statement of significationThe objective of this paper is to measure and mathematically model the compression behavior of various human blood clots. We show by a combination of confocal and scanning electron microscopy that compression proceeds by the passage of a front through the sample that separates a densified region of the clot from a rarefied region, and that the compression/decompression response is reversible with hysteresis. These observations form the basis of a model for the compression response of clots based on the continuum theory of phase transitions. Our studies may reveal how clot rheology under large compression in vivo due to muscle contraction, platelet retraction and hydrodynamic flow varies under various pathophysiological conditions and could inform the design of fibrin based biomaterials.
Graphical abstract
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A Combination of Thenar and Hypothenar Hammer Syndrome
Publication date: Available online 6 July 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): K.M. Nikolakopoulos, C.P. Papageorgopoulou
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Scholar : These new articles for Amyloid are available online
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Scholar : Canadian Society of Forensic Science Journal, Volume 50, Issue 3, September 2017 is now available online on Taylor & Francis Online
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Scholar : Computer-Aided Design and Applications, Volume 14, Issue 6, October 2017 is now available online on Taylor & Francis Online
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Scholar : These new articles for Cogent Arts & Humanities are available online
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Scholar : These new articles for a/b: Auto/Biography Studies are available online
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Scholar : Shakespeare, Volume 13, Issue 2, June 2017 is now available online on Taylor & Francis Online
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Scholar : These new articles for Critique: Studies in Contemporary Fiction are available online
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Scholar : These new articles for ANQ: A Quarterly Journal of Short Articles, Notes and Reviews are available online
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Methodologic considerations of household-level methicillin-resistant Staphylococcus aureus decolonization among persons living with HIV.
| Related Articles |
Methodologic considerations of household-level methicillin-resistant Staphylococcus aureus decolonization among persons living with HIV.
Am J Infect Control. 2017 Jul 03;:
Authors: Farley JE, Starbird LE, Anderson J, Perrin NA, Lowensen K, Ross T, Carroll KC
Abstract
BACKGROUND: People living with HIV (PLWH) have a higher prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonization and likelihood of recurrent infection than the general population. Simultaneously treating MRSA-colonized household members may improve success with MRSA decolonization strategies. This article describes a pilot trial testing household-level MRSA decolonization and documents methodologic and pragmatic challenges of this approach.
METHODS: We conducted a randomized controlled trial of individual versus individual-plus-household MRSA decolonization to reduce recurrent MRSA. PLWH with a history of MRSA who are patients of an urban HIV clinic received a standard MRSA decolonization regimen. MRSA colonization at 6 months was the primary outcome.
RESULTS: One hundred sixty-six patients were referred for MRSA screening; 77 (46%) enrolled. Of those, 28 (36%) were colonized with MRSA and identified risk factors consistent with the published literature. Eighteen were randomized and 13 households completed the study.
CONCLUSIONS: This is the first study to report on a household-level MRSA decolonization among PLWH. Challenges included provider referral, HIV stigma, confidentiality concerns over enrolling households, and dynamic living situations. Although simultaneous household MRSA decolonization may reduce recolonization, recruitment and retention challenges specific to PLWH limit the ability to conduct household-level research. Efforts to minimize these barriers are needed to inform evidence-based practice.
PMID: 28684128 [PubMed - as supplied by publisher]
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Identifying critical steps towards improved access to innovation in cancer care: a European CanCer Organisation position paper
Source:European Journal of Cancer, Volume 82
Author(s): Matti Aapro, Alain Astier, Riccardo Audisio, Ian Banks, Pierre Bedossa, Etienne Brain, David Cameron, Paolo Casali, Arturo Chiti, Leticia De Mattos-Arruda, Daniel Kelly, Denis Lacombe, Per J. Nilsson, Martine Piccart, Philip Poortmans, Katrine Riklund, Gunnar Saeter, Martin Schrappe, Riccardo Soffietti, Luzia Travado, Hein van Poppel, Suzanne Wait, Peter Naredi
In recent decades cancer care has seen improvements in the speed and accuracy of diagnostic procedures; the effectiveness of surgery, radiation therapy and medical treatments; the power of information technology; and the development of multidisciplinary, specialist-led approaches to care. Such innovations are essential if we are to continue improving the lives of cancer patients across Europe despite financial pressures on our healthcare systems. Investment in innovation must be balanced with the need to ensure the sustainability of healthcare budgets, and all health professionals have a responsibility to help achieve this balance. It requires scrutiny of the way care is delivered; we must be ready to discontinue practices or interventions that are inefficient, and prioritise innovations that may deliver the best outcomes possible for patients within the limits of available resources. Decisions on innovations should take into account their long-term impact on patient outcomes and costs, not just their immediate costs. Adopting a culture of innovation requires a multidisciplinary team approach, with the patient at the centre and an integral part of the team. It must take a whole-system and whole-patient perspective on cancer care and be guided by high-quality real-world data, including outcomes relevant to the patient and actual costs of care; this accurately reflects the impact of any innovation in clinical practice. The European CanCer Organisation is committed to working with its member societies, patient organisations and the cancer community at large to find sustainable ways to identify and integrate the most meaningful innovations into all aspects of cancer care.
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Preoperative breast radiation therapy: Indications and perspectives
Source:European Journal of Cancer, Volume 82
Author(s): S.V. Lightowlers, L.J. Boersma, A. Fourquet, Y.M. Kirova, B.V. Offersen, P. Poortmans, A.N. Scholten, N. Somaiah, C.E. Coles
Preoperative breast radiation therapy (RT) is not a new concept, but older studies failed to change practice. More recently, there has been interest in revisiting preoperative RT using modern techniques. This current perspective discusses the indications, summarises the published literature and then highlights current clinical trials, with particular attention to combining with novel drugs and optimising associated translational research.
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Publication date: September 2017 Source: Free Radical Biology and Medicine, Volume 110 Author(s): Lucía Fernández-del-Río, Anish Nag, Elen...
