The SAFE pathway is involved in the postconditioning mechanism of oxytocin in isolated rat heart

Publication date: Available online 7 April 2018
Source:Peptides
Author(s): Mirali Polshekan, Vahid Khori, Ali Mohammad Alizadeh, Majid Ghayour-Mobarhan, Mohsen Saeidi, Yahya Jand, Maryam Rajaei, Gholamreza Farnoosh, Khadijeh Jamialahmadi
Oxytocin (OT) has a postconditioning effect against the ischemia-reperfusion (I/R) injury. However, its precise cardioprotection mechanism at the early reperfusion phase remains under debate. Our previous study revealed that OT postconditioning (OTpost) is cardioprotective by activating the Reperfusion Injury Salvage Kinase (RISK) pathway. Therefore, the present study is aimed to determine the biological effects of OTpost via the OT receptor and the activation of the JAK/STAT3 signaling pathway, mitochondrial adenosine triphosphate-dependent potassium channel (mitoKATP), nitric oxide (NO) release, and its anti-apoptotic effects against I/R injury in an isolated rat heart model.Sixty-three rats were randomly allocated to one of nine groups. OT was perfused 40 min prior to the regional ischemia or 15 min at the early reperfusion phase. AG490 (a JAK/STAT3 inhibitor), 5HD (a mitoKATP blocker), atosiban (an OT receptor antagonist), L-NAME (a nonspecific nitric oxide synthase inhibitor) were applied either alone or in combination with OT during the pre-ischemia phase and/or in the early reperfusion phase. Myocardial infarct size, hemodynamic factor, ventricular arrhythmia, coronary flow, cardiac biochemical marker, and the apoptosis index were determined at the end of reperfusion.Oxytocin postconditioning reduced infarct size, lactate dehydrogenase activity, arrhythmia score, ventricular fibrillation, and apoptosis. Moreover, AG490, 5HD, atosiban, and L-NAME abrogated the cardioprotective effects of OT.Our results demonstrated that the cardioprotective effects of OT are mediated by NO release, and the activation of mitoKATP and the SAFE pathway through the JAK/STAT3 signaling cascade that finally lead to decrease in the apoptosis index during the early reperfusion phase.



https://ift.tt/2GJidQQ

Computational Design and Experimental Characterization of a Novel β-Common Receptor Inhibitory Peptide

Publication date: Available online 7 April 2018
Source:Peptides
Author(s): Cody R. Kilar, Sivakumar Sekharan, Larysa Sautina, YanPeng Diao, Shahar Keinan, Yong Shen, Jorg Bungert, Rajesh Mohandas, Mark S. Segal
In short-term animal models of ischemia, erythropoietin (EPO) signaling through the heterodimeric EPO receptor (EPOR)/β-common receptor (βCR) is believed to elicit tissue protective effects. However, large, randomized, controlled trials demonstrate that targeting a higher hemoglobin level by administering higher doses of EPO, which are more likely to activate the heterodimeric EPOR/βCR, is associated with an increase in adverse cardiovascular events. Thus, inhibition of long-term activation of the βCR may have therapeutic implications. This study aimed to design and evaluate the efficacy of novel computationally designed βCR inhibitory peptides (βIP). These novel βIPs were designed based on a truncated portion of Helix-A from EPO, specifically residues 11 to 26 (VLERYLLEAKEAEKIT). Seven novel peptides (P1 to P7) were designed. Peptide 7 (P7), VLERYLHEAKHAEKIT, demonstrated the most robust inhibitory activity. We also report here the ability of P7 to inhibit βCR-induced nitric oxide (NO) production and angiogenesis in human umbilical vein endothelial cells (HUVECs). Specifically, we found that P7 βIP completely abolished EPO-induced NO production. The inhibitory effect could be overcome with super physiological doses of EPO, suggesting a competitive inhibition. βCR-induced angiogenesis in HUVEC's was also abolished with treatment of P7 βIP, but P7 βIP did not inhibit vascular endothelial growth factor (VEGF)-induced angiogenesis. In addition, we demonstrate that the novel P7 βIP does not inhibit EPO-induced erythropoiesis with use of peripheral blood mononuclear cells (PBMCs). These results, for the first time, describe a novel, potent βCR peptide inhibitor that inhibit the actions of the βCR without affecting erythropoiesis.



https://ift.tt/2qfTxnU

Vaccine options for influenza: thinking small

Publication date: August 2018
Source:Current Opinion in Immunology, Volume 53
Author(s): Bert Schepens, Dorien De Vlieger, Xavier Saelens
Vaccines that direct the immune response towards conserved B cell epitopes of influenza viruses can provide broad protection. In many instances, this requires the design of vaccine antigens that stimulate the immune system to levels that far exceed the natural responses towards such antigens. Here we focus on the matrix protein 2 ectodomain (M2e) as a 'universal' influenza A vaccine candidate. Thanks to its small size and high solubility, M2e can be expressed and delivered in almost any format. Protection against experimental influenza A virus challenge by M2e-based vaccines has been demonstrated in natural host of influenza and clinical studies demonstrated that such vaccines are safe and immunogenic. M2e-specific antibodies protect mainly by Fc receptor-mediated antibody-dependent cellular phagocytosis activity, which is reminiscent to how antibodies directed against the hemagglutinin stalk protect in vivo. Fighting influenza with a broadly protective influenza vaccine will likely require a blend of conserved antigens. M2e deserves its place in such a blend.



https://ift.tt/2GHP3S9

Modulation of innate and adaptive immunity by P2X ion channels

Publication date: June 2018
Source:Current Opinion in Immunology, Volume 52
Author(s): Francesco Di Virgilio, Alba Clara Sarti, Fabio Grassi
Extracellular ATP is a major component of the inflammatory microenvironment where it accumulates following cell and tissue injury but also as a consequence of non-lytic release from activated inflammatory cells. In the inflammatory microenvironment ATP binds and activates nucleotide receptors of the P2Y and P2X subfamilies expressed by immune cells. P2Y receptors are G-protein-coupled, while P2X receptors are cation-selective channels. Changes in the intracellular ion homeostasis triggered by P2X receptor stimulation trigger multiple key responses crucial for initiation, propagation, and resolution of inflammation. In the P2X receptor family, the P2X7 subtype has an important role in the activation of lymphocyte, granulocyte, macrophage and dendritic cell responses. Although clinical studies have been so far rather inconclusive, it is believed that P2X7 receptor targeting might offer novel perspectives for anti-inflammatory therapy.



https://ift.tt/2qdu4eE

Ion channelopathies of the immune system

Publication date: June 2018
Source:Current Opinion in Immunology, Volume 52
Author(s): Martin Vaeth, Stefan Feske
Ion channels and transporters move ions across membrane barriers and are essential for a host of cell functions in many organs. They conduct K⁺, Na⁺ and Cl⁻, which are essential for regulating the membrane potential, H⁺ to control intracellular and extracellular pH and divalent cations such as Ca²⁺, Mg²⁺ and Zn²⁺, which function as second messengers and cofactors for many proteins. Inherited channelopathies due to mutations in ion channels or their accessory proteins cause a variety of diseases in the nervous, cardiovascular and other tissues, but channelopathies that affect immune function are not as well studied. Mutations in ORAI1 and STIM1 genes that encode the Ca²⁺ release-activated Ca²⁺ (CRAC) channel in immune cells, the Mg²⁺ transporter MAGT1 and the Cl⁻ channel LRRC8A all cause immunodeficiency with increased susceptibility to infection. Mutations in the Zn²⁺ transporters SLC39A4 (ZIP4) and SLC30A2 (ZnT2) result in nutritional Zn²⁺ deficiency and immune dysfunction. These channels, however, only represent a fraction of ion channels that regulate immunity as demonstrated by immune dysregulation in channel knockout mice. The immune system itself can cause acquired channelopathies that are associated with a variety of diseases of nervous, cardiovascular and endocrine systems resulting from autoantibodies binding to ion channels. These autoantibodies highlight the therapeutic potential of functional anti-ion channel antibodies that are being developed for the treatment of autoimmune, inflammatory and other diseases.



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Characterization of distinct Arctic aerosol accumulation modes and their sources

Publication date: June 2018
Source:Atmospheric Environment, Volume 183
Author(s): R. Lange, M. Dall'Osto, H. Skov, J.K. Nøjgaard, I.E. Nielsen, D.C.S. Beddows, R. Simo, R.M. Harrison, A. Massling
In this work we use cluster analysis of long term particle size distribution data to expand an array of different shorter term atmospheric measurements, thereby gaining insights into longer term patterns and properties of Arctic aerosol. Measurements of aerosol number size distributions (9–915 nm) were conducted at Villum Research Station (VRS), Station Nord in North Greenland during a 5 year record (2012–2016). Alongside this, measurements of aerosol composition, meteorological parameters, gaseous compounds and cloud condensation nuclei (CCN) activity were performed during different shorter occasions. K-means clustering analysis of particle number size distributions on daily basis identified several clusters. Clusters of accumulation mode aerosols (main size modes > 100 nm) accounted for 56% of the total aerosol during the sampling period (89–91% during February–April, 1–3% during June–August). By association to chemical composition, cloud condensation nuclei properties, and meteorological variables, three typical accumulation mode aerosol clusters were identified: Haze (32% of the time), Bimodal (14%) and Aged (6%). In brief: (1) Haze accumulation mode aerosol shows a single mode at 150 nm, peaking in February–April, with highest loadings of sulfate and black carbon concentrations. (2) Accumulation mode Bimodal aerosol shows two modes, at 38 nm and 150 nm, peaking in June–August, with the highest ratio of organics to sulfate concentrations. (3) Aged accumulation mode aerosol shows a single mode at 213 nm, peaking in September–October and is associated with cloudy and humid weather conditions during autumn. The three aerosol clusters were considered alongside CCN concentrations. We suggest that organic compounds, that are likely marine biogenic in nature, greatly influence the Bimodal cluster and contribute significantly to its CCN activity. This stresses the importance of better characterizing the marine ecosystem and the aerosol-mediated climate effects in the Arctic.



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Four years of highly time resolved measurements of elemental and organic carbon at a rural background site in Central Europe

Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Saliou Mbengue, Michal Fusek, Jaroslav Schwarz, Petr Vodička, Adéla Holubová Šmejkalová, Ivan Holoubek
Elemental carbon (EC) and organic carbon (OC) in fine atmospheric aerosols (PM2.5: aerodynamic diameter smaller than 2.5 μm) have been measured with a semi-automatic instrument during a 4-year survey at the National Atmospheric Observatory Košetice (NAOK), Czech Republic. Ground based measurements were performed from March 2013 to December 2016 with a field Semi-Continuous OCEC Aerosol Analyzer (Sunset Laboratory Inc., USA). The variation of EC and OC concentrations and the OC/EC ratio was characterized for different seasons and days of the week. During our survey, higher concentrations of EC and OC were observed in winter (0.83 ± 0.67 and 3.33 ± 2.28 μg m⁻³, respectively), and lower concentrations were recorded in summer (0.34 ± 0.18 and 2.30 ± 1.15 μg m⁻³, respectively). Inversely, the OC/EC ratio with mean value (5.1 ± 2.6) characteristic to rural background area was higher in summer (7.33 ± 3.23) in comparison to the other seasons. Since the data contain values below detection and quantification limits of the measuring device (i.e., censored values), statistical methods for censored data have been used in order to compare mean EC and OC concentrations between various seasons. It was found out that there is a significant difference between summer and the other seasons with the exception of mean OC concentrations at noon. In most cases, there was also a significant difference between winter and the other seasons. Moreover, it was found out that when dealing with OC concentrations, it is possible to replace censored values by a constant and still obtain reasonable results. In case of EC concentrations, the method based on censored distributions should be preferred when the sample size is small and the proportion of censored values is high. The diurnal variation of EC and OC is less pronounced in summer. During working days, the EC diurnal pattern displays a morning (between 6:00 and 10:00) and an afternoon/evening (between 18:00 and 22:00) peaks, while for OC, only the afternoon/evening peak is observed. These seasonal, diurnal and weekly variations of EC and OC concentrations and OC/EC ratio are probably related to variability in terms of emission sources (residential heating, traffic), transport characteristic and meteorological conditions. A weaker correlation between EC and OC in summer (r = 0.56) suggests additional sources and/or transport processes during other seasons. The elevated OC/EC ratio, the higher correlation between OC and O3, and the temperature and solar radiation during summer confirmed an increasing contribution of OC from secondary organic carbon (SOC) estimated as at least 59 ± 11% of total carbon in the PM2.5 using the EC tracer method. Backward trajectories of air masses arriving at 100 m AGL calculated in winter and summer show that higher pollution episodes of EC and OC are predominantly associated with continental air masses confined over Central Europe (about 79%), while lower EC and OC levels are mainly associated with episodes of long-range transport of marine air masses. Interestingly, the results reveal that in winter pollutants emitted during workdays could be accumulated above the region and influence the rural background air quality during some prolonged time of the weekend, especially on Saturday.



https://ift.tt/2GJ9Wbv

In situ formation of interpenetrating polymer network using sequential thermal and click crosslinking for enhanced retention of transplanted cells

Publication date: July 2018
Source:Biomaterials, Volume 170
Author(s): Hamid Sadeghi Abandansari, Mohammad Hossein Ghanian, Fahimeh Varzideh, Elena Mahmoudi, Sarah Rajabi, Payam Taheri, Mohammad Reza Nabid, Hossein Baharvand
Injectable hydrogels, which are used as scaffolds in cell therapy, provide a minimally invasive strategy to enhance cell retention and survival at injection site. However, till now, slow in situ gelation, undesired mechanical properties, and weak cell adhesion characteristics of reported hydrogels, have led to improper results. Here, we developed an injectable fully-interpenetrated polymer network (f-IPN) by integration of Diels-Alder (DA) crosslinked network and thermosensitive injectable hydrogel. The proposed DA hydrogels were formed in a slow manner showing robust mechanical properties. Interpenetration of thermosensitive network into DA hydrogel accelerated in situ gel-formation and masked the slow reaction rate of DA crosslinking while keeping its unique features. Two networks were formed by simple syringe injection without the need of any initiator, catalyst, or double barrel syringe. The DA and f-IPN hydrogels showed comparable viscoelastic properties along with outstanding load-bearing and shape-recovery even under high levels of compression. The subcutaneous administration of cardiomyocytes-laden f-IPN hydrogel into nude mice revealed high cell retention and survival after two weeks. Additionally, the cardiomyocyte's identity of retained cells was confirmed by detection of human and cardiac-related markers. Our results indicate that the thermosensitive-covalent networks can open a new horizon within the injection-based cell therapy applications.

Graphical abstract

https://ift.tt/2GJNEq2

Programmed ‘triple-mode’ anti-tumor therapy: Improving peritoneal retention, tumor penetration and activatable drug release properties for effective inhibition of peritoneal carcinomatosis

Publication date: July 2018
Source:Biomaterials, Volume 169
Author(s): Kondareddy Cherukula, Woo Kyun Bae, Jae Hyuk Lee, In-Kyu Park
Peritoneal carcinomatosis (PC) is a fatal condition arising in the gastrointestinal tract. PC patients administered drugs locally in the tumor region, such as in intraperitoneal chemotherapy (IPCh), suffer from low drug retention time and tumor penetration. Herein, we synthesized a lithocholic acid (LCA)-conjugated disulfide-linked polyethyleneimine (ssPEI) micelle (LAPMi) nanoconstruct by covalently conjugating ssPEI and LCA, thereby forming positive charged nanomicellar structures loaded with paclitaxel (PTX) (LAPMi-PTX) for IPCh. The incorporation of a positive surface charge aided in prolonging the peritoneal retention time, presumably via ascites-induced protein corona formation, and the subsequent size expansion caused resistance against undesired clearance through lymphatic openings. Furthermore, preferential tumor penetration by LAPMi-PTX is attributable to the permeation-enhancing properties of LCA, and the subsequent tumor activatable drug release was induced by the presence of disulfide linkages. By integrating these properties, LAPMi exhibited prolonged peritoneal residence time, enhanced tumor permeation and chemotherapeutic effect evidenced by in vitro, tumor spheroid and in vivo studies. Importantly, our strategy enabled significant PC inhibition and increased the overall survival rate of tumor-bearing mice. In conclusion, we provided a new paradigm of intractable PC treatment by enabling the prolonged residence time of the nanoconstruct, thereby enhancing tumor penetration and anti-tumor therapy.



https://ift.tt/2HgoJv8

Cytokine induced killer cells-assisted delivery of chlorin e6 mediated self-assembled gold nanoclusters to tumors for imaging and immuno-photodynamic therapy

Publication date: July 2018
Source:Biomaterials, Volume 170
Author(s): Fangfang Xia, Wenxiu Hou, Yanlei Liu, Wentao Wang, Yu Han, Meng Yang, Xiao Zhi, Chenlu Li, Daizong Qi, Tianliang Li, Jesus Martinez de la Fuente, Chunlei Zhang, Jie Song, Daxiang Cui
The cytotoxicity and unique tumor-tropic properties of cytokine-induced killer (CIK) cells render them promising in the field of cancer immunotherapy and delivery systems. Here, we report a novel and facile approach to assemble gold nanoclusters (GNCs) into stable and monodispersed nanoparticles (NPs) using Chlorin e6 (Ce6) molecules. Notably, the fluorescence intensity of the GNCs-Ce6 NPs was about 4.5 folds stronger than the GNCs counterparts. The as-prepared GNCs-Ce6 NPs were conjugated with CD3 antibody (Ab) and further employed to label CIK cells to create a CIK cell-based drug delivery system (Ce6-GNCs-Ab-CIK). The Ce6-GNCs-Ab-CIK exhibited high tumor-targeting efficiency and excellent therapeutic efficacy toward MGC-803 tumor-bearing mice. Benefiting from the synergistic therapeutic effect between GNCs-Ce6-Ab NPs and CIK cells, the GNCs-Ce6-Ab-CIK strategy may present an ideal cancer theranostic platform for tumor targeted imaging and combination therapy.



https://ift.tt/2EtKAMx

Decellularized materials derived from TSP2-KO mice promote enhanced neovascularization and integration in diabetic wounds

Publication date: July 2018
Source:Biomaterials, Volume 169
Author(s): Aaron H. Morris, Danielle K. Stamer, Britta Kunkemoeller, Julie Chang, Hao Xing, Themis R. Kyriakides
Decellularized biologic scaffolds are gaining popularity over synthetic biomaterials as naturally derived materials capable of promoting improved healing. Nevertheless, the most widely used biologic material – acellular dermal matrix (ADM) – exhibits slow repopulation and remodeling, which prevents integration. Additionally, engineering control of these materials is limited because they require a natural source for their production. In the current report, we demonstrate the feasibility of using genetically engineered animals to create decellularized biologic scaffolds with favorable extracellular matrix (ECM) properties. Specifically, we utilized skin from thrombospondin (TSP)-2 KO mice to derive various decellularized products. Scanning electron microscopy and mechanical testing showed that TSP-2 KO ADM exhibited an altered structure and a reduction in elastic modulus and ultimate tensile strength, respectively. When a powdered form of KO ADM was implanted subcutaneously, it was able to promote enhanced vascularization over WT. Additionally, when implanted subcutaneously, intact slabs of KO ADM were populated by higher number of host cells when compared to WT. In vitro studies confirmed the promigratory properties of KO ADM. Specifically, degradation products released by pepsin digestion of KO ADM induced greater cell migration than WT. Moreover, cell-derived ECM from TSP-2 null fibroblasts was more permissive to fibroblast migration. Finally, ADMs were implanted in a diabetic wound model to examine their ability to accelerate wound healing. KO ADM exhibited enhanced remodeling and vascular maturation, indicative of efficient integration. Overall, we demonstrate that genetic manipulation enables engineered ECM-based materials with increased regenerative potential.



https://ift.tt/2Hj6PIq

Statistical analysis of bank deposits dataset

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): Pelumi E. Oguntunde, Hilary I. Okagbue, Patience I. Adamu, Omoleye A. Oguntunde, Sola J. Oluwatunde, Abiodun A. Opanuga
This article presents the statistical analysis of the deposit activities in each of the account types of a leading bank in Nigeria. The mean effect of these account types on the bank was determined using analysis of variance (ANOVA). Further test which include the Tukey's simultaneous test for differences of means was also conducted.



https://ift.tt/2HgrRY0

Data of chemical analysis and electrical properties of SnO2-TiO2 composite nanofibers

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): Zinab H. Bakr, Qamar Wali, Jamil Ismail, Naveen Kumar Elumalai, Ashraf Uddin, Rajan Jose
In this data article, we provide energy dispersive X-ray spectroscopy (EDX) spectra of the electrospun composite (SnO2-TiO2) nanowires with the elemental values measured in atomic and weight%. The linear sweep voltammetry data of composite and its component nanofibers are provided. The data collected in this article is directly related to our research article "Synergistic combination of electronic and electrical properties of SnO2 and TiO2 in a single SnO2-TiO2 composite nanowire for dye-sensitized solar cells" [1].



https://ift.tt/2EtavEc

A two-step approach for mining patient treatment pathways in administrative healthcare databases

Publication date: Available online 7 April 2018
Source:Artificial Intelligence in Medicine
Author(s): Ahmed Najjar, Daniel Reinharz, Catherine Girouard, Christian Gagné
Clustering electronic medical records allows the discovery of information on healthcare practices. Entries in such medical records are usually composed of a succession of diagnostics or therapeutic steps. The corresponding processes are complex and heterogeneous since they depend on medical knowledge integrating clinical guidelines, the physician's individual experience, and patient data and conditions. To analyze such data, we are first proposing to cluster medical visits, consultations, and hospital stays into homogeneous groups, and then to construct higher-level patient treatment pathways over these different groups. These pathways are then also clustered to distill typical pathways, enabling interpretation of clusters by experts. This approach is evaluated on a real-world administrative database of elderly people in Québec suffering from heart failures.



https://ift.tt/2qg76DA

Glioblastoma Metastatic to the Ovary, a Very Different Krukenberg Tumor?

Publication date: Available online 7 April 2018
Source:Practical Radiation Oncology
Author(s): Robin E. Bonomi, Josh Kovoor, Mark Zaki, Mark Szlaczky, Michael Christensen, William Kupsky, Geoffrey Barger, Steven Miller, Michael M. Dominello




https://ift.tt/2Hiswbg

Injectable hyaluronic acid based microrods provide local micromechanical and biochemical cues to attenuate cardiac fibrosis after myocardial infarction

Publication date: July 2018
Source:Biomaterials, Volume 169
Author(s): Long V. Le, Priya Mohindra, Qizhi Fang, Richard E. Sievers, Michael A. Mkrtschjan, Christopher Solis, Conrad W. Safranek, Brenda Russell, Randall J. Lee, Tejal A. Desai
Repairing cardiac tissue after myocardial infarction (MI) is one of the most challenging goals in tissue engineering. Following ischemic injury, significant matrix remodeling and the formation of avascular scar tissue significantly impairs cell engraftment and survival in the damaged myocardium. This limits the efficacy of cell replacement therapies, demanding strategies that reduce pathological scarring to create a suitable microenvironment for healthy tissue regeneration. Here, we demonstrate the successful fabrication of discrete hyaluronic acid (HA)-based microrods to provide local biochemical and biomechanical signals to reprogram cells and attenuate cardiac fibrosis. HA microrods were produced in a range of physiological stiffness and shown to degrade in the presence of hyaluronidase. Additionally, we show that fibroblasts interact with these microrods in vitro, leading to significant changes in proliferation, collagen expression and other markers of a myofibroblast phenotype. When injected into the myocardium of an adult rat MI model, HA microrods prevented left ventricular wall thinning and improved cardiac function at 6 weeks post infarct.



https://ift.tt/2GE1U7H

Nanoparticle co-delivery of wortmannin and cisplatin synergistically enhances chemoradiotherapy and reverses platinum resistance in ovarian cancer models

Publication date: July 2018
Source:Biomaterials, Volume 169
Author(s): Maofan Zhang, C. Tilden Hagan, Yuangzeng Min, Hayley Foley, Xi Tian, Feifei Yang, Yu Mi, Kin Man Au, Yusra Medik, Kyle Roche, Kyle Wagner, Zachary Rodgers, Andrew Z. Wang
Most ovarian cancer patients respond well to initial platinum-based chemotherapy. However, within a year, many patients experience disease recurrence with a platinum resistant phenotype that responds poorly to second line chemotherapies. As a result, new strategies to address platinum resistant ovarian cancer (PROC) are needed. Herein, we report that NP co-delivery of cisplatin (CP) and wortmannin (Wtmn), a DNA repair inhibitor, synergistically enhances chemoradiotherapy (CRT) and reverses CP resistance in PROC. We encapsulated this regimen in FDA approved poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) NPs to reduce systemic side effects, enhance cellular CP uptake, improve Wtmn stability, and increase therapeutic efficacy. Treatment of platinum-sensitive ovarian cancer (PSOC) and PROC murine models with these dual-drug loaded NPs (DNPs) significantly reduced tumor burden versus treatment with combinations of free drugs or single-drug loaded NPs (SNPs). These results support further investigation of this NP-based, synergistic drug regimen as a means to combat PROC in the clinic.



https://ift.tt/2q90WVU

Ultra-thin, aligned, free-standing nanofiber membranes to recapitulate multi-layered blood vessel/tissue interface for leukocyte infiltration study

Publication date: July 2018
Source:Biomaterials, Volume 169
Author(s): Sang Min Park, HyeMi Kim, Kwang Hoon Song, Seongsu Eom, HyoungJun Park, Junsang Doh, Dong Sung Kim
Leukocyte infiltration plays critical roles in tissue inflammation for pathogen clearance and tumor eradication. This process is regulated by complex microenvironments in blood vessels, including inflamed endothelium, blood flow, and perivascular components. The role of perivascular components in leukocyte infiltration has not been systematically investigated until recently mostly due to lack of technology. In this work, we developed a three-dimensional multi-layered blood vessel/tissue model with a nanofiber membrane, enabling real-time visualization of dynamic leukocyte infiltration and subsequent interaction with perivascular macrophages. We directly fabricated a highly aligned, free-standing nanofiber membrane with an ultra-thin thickness of ∼1 μm in microfluidic systems. Coating the nanofiber membrane with matrigel showed synergetic topographical and biochemical effects on the reconstitution of a well-aligned endothelial monolayer on the membrane. Our 3D multi-layered blood vessel/tissue model will offer a powerful and versatile tool for investigating the mechanism of leukocyte tissue infiltration and subsequent immune responses.



https://ift.tt/2qdF8sp

Clinical evaluation of the bulk fill composite QuiXfil in molar class I and II cavities: 10-year results of a RCT

Publication date: Available online 7 April 2018
Source:Dental Materials
Author(s): Katrin Heck, Juergen Manhart, Reinhard Hickel, Christian Diegritz
ObjectiveThe objective of this RCT was to compare the 10-year clinical performance of QuiXfil with that of Tetric Ceram in posterior single- or multi-surface cavities.Methods46 QuiXfil (Xeno III) and 50 Tetric Ceram (Syntac classic) composite restorations were placed in 14 stress bearing class I and 82 class II cavities in first or second molars. Clinical evaluation was performed at baseline and after up to 10 years by using modified US Public Health Service criteria. At the last recall period, 26 QuiXfil and 30 Tetric Ceram restorations in 11 stress bearing class I and 45 class II cavities, were assessed.ResultsTen failed restorations were observed during the follow-up period, four Tetric Ceram restorations failed due to secondary caries (2), tooth fracture (1) and bulk fracture combined with secondary caries (1) whereas six QuiXfil restorations failed due to secondary caries (1), tooth fracture (2), secondary caries combined with restoration fracture (1), restoration fracture (1) and postoperative sensitivity (1). Fisher's exact test yielded no significant difference between both materials (p=0.487).SignificanceBoth materials, bulk fill QuiXfil restorations and Tetric Ceram restorations, showed highly clinical effectiveness during the 10-year follow-up.



https://ift.tt/2Et5g7E

Geometrical accuracy of metallic objects produced with additive or subtractive manufacturing: A comparative in vitro study

Publication date: Available online 7 April 2018
Source:Dental Materials
Author(s): Michael Braian, David Jönsson, Mir Kevci, Ann Wennerberg
ObjectiveTo evaluate the accuracy and precision of objects produced by additive manufacturing systems (AM) for use in dentistry and to compare with subtractive manufacturing systems (SM).MethodsTen specimens of two geometrical objects were produced by five different AM machines and one SM machine. Object A mimics an inlay-shaped object, while object B imitates a four-unit bridge model. All the objects were sorted into different measurement dimensions (x, y, z), linear distances, angles and corner radius.ResultsNone of the additive manufacturing or subtractive manufacturing groups presented a perfect match to the CAD file with regard to all parameters included in the present study. Considering linear measurements, the precision for subtractive manufacturing group was consistent in all axes for object A, presenting results of <0.050mm. The additive manufacturing groups had consistent precision in the x-axis and y-axis but not in the z-axis. With regard to corner radius measurements, the SM group had the best overall accuracy and precision for both objects A and B when compared to the AM groups.SignificanceWithin the limitations of this in vitro study, the conclusion can be made that subtractive manufacturing presented overall precision on all measurements below 0.050mm. The AM machines also presented fairly good precision, <0.150mm, on all axes except for the z-axis. Knowledge regarding accuracy and precision for different production techniques utilized in dentistry is of great clinical importance. The dental community has moved from casting to milling and additive techniques are now being implemented. Thus all these production techniques need to be tested, compared and validated.



https://ift.tt/2JrkfT8