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https://read.qxmd.com/read/30770653/silk-fibroin-scaffolds-loaded-with-angiogenic-genes-in-adenovirus-vectors-for-tissue-regeneration
#1
Weiwei Wang, Yanni Yu, Yi Jiang, Jing Qu, Longxing Niu, Jicheng Yang, Mingzhong Li
Vascularization remains a critical challenge in dermal tissue regeneration. In this study, a vascular endothelial growth factor (VEGF165) and angiopoietin-1 (Ang-1) dual gene co-expression vector that encoded green fluorescent protein (GFP) was constructed from an Arg-Gly-Asp-modified adenovirus. Silk fibroin (SF) scaffolds loaded with adenovirus vectors were fabricated by freeze-drying method. In vitro, the human endothelial-derived cell line EA.hy926 was infected with adenovirus vectors and then expressed GFP, secreted VEGF165 and Ang-1, and promoted cell proliferation effectively...
February 15, 2019: Journal of Tissue Engineering and Regenerative Medicine
https://read.qxmd.com/read/30768867/towards-second-generation-cardiomyogenic-and-anti-cardiofibrotic-1-4-dihydropyridine-class-of-tgf%C3%AE-inhibitors
#2
Daniel Laengle, Tessa R Werner, Fabian Wesseler, Elena S Reckzeh, Niklas Schaumann, Lauren Drowley, Magnus Polla, Alleyn T Plowright, Marc N Hirt, Thomas Eschenhagen, Dennis Schade
Innovative therapeutic modalities for pharmacological intervention of TGFβ-dependent diseases are of great value. b-Annelated 1,4-dihydropyridines (DHPs) might be such a class as they induce TGFβ receptor type-II degradation. However, intrinsic drawbacks are associated with this compound class and were systematically addressed in the presented study. It was possible to install polar functionalities and bioisosteric moieties at distinct sites of the molecules while keeping TGFβ inhibiting activities. The introduction of a 2-amino group or 7-N-alkyl modification proved successful strategies...
February 15, 2019: ChemMedChem
https://read.qxmd.com/read/30764571/indoxyl-sulfate-induces-apoptosis-through-oxidative-stress-and-mitogen-activated-protein-kinase-signaling-pathway-inhibition-in-human-astrocytes
#3
Yi-Ting Lin, Ping-Hsun Wu, Yi-Chun Tsai, Ya-Ling Hsu, Han Ying Wang, Mei-Chuan Kuo, Po-Lin Kuo, Shang-Jyh Hwang
Uremic toxins accumulated in chronic kidney disease (CKD) increases the risk of cognitive impairment. Indoxyl sulfate (IS) is a well-known protein-bound uremic toxin that is correlated with several systemic diseases, but no studies on human brain cells are available. We investigated the effect of IS on primary human astrocytes through next-generation sequencing and cell experiment confirmation to explore the mechanism of IS-associated brain damage. Total RNAs extracted from IS-treated and control astrocytes were evaluated by performing functional and pathway enrichment analysis...
February 5, 2019: Journal of Clinical Medicine
https://read.qxmd.com/read/30755493/developmental-synaptic-changes-at-the-transient-olivocochlear-inner-hair-cell-synapse
#4
Graciela Kearney, Javier Zorrilla de San Martín, Lucas G Vattino, Ana Belén Elgoyhen, Carolina Wedemeyer, Eleonora Katz
In the mature mammalian cochlea, inner hair cells (IHCs) are mainly innervated by afferent fibers that convey sound information to the central nervous system. During postnatal development, however, medial olivocochlear (MOC) efferent fibers transiently innervate the IHCs. The MOC-IHC synapse, functional from postnatal day (P)0 to hearing onset (P12), undergoes dramatic changes in the sensitivity to acetylcholine (ACh) and in the expression of key postsynaptic proteins. To evaluate whether there are associated changes in the properties of ACh release during this period, we used a cochlear preparation from mice of either sex at P4, P6-7 and P9-11 and monitored transmitter release from MOC terminals in voltage-clamped IHCs in the whole-cell configuration...
February 12, 2019: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://read.qxmd.com/read/30744497/tumor-suppressors-rb1-and-cdkn2a-cooperatively-regulate-cell-cycle-progression-and-differentiation-during-cardiomyocyte-development-and-repair-implications-for-stimulating-neomyogenesis-with-cell-based-therapy
#5
Konstantinos E Hatzistergos, Adam R Williams, Derek M Dykxhoorn, Michael A Bellio, Wendou Yu, Joshua M Hare
RATIONALE: Although rare cardiomyogenesis is reported in the adult mammalian heart, whether this results from differentiation or proliferation of cardiomyogenic cells remains controversial. The tumor suppressor genes RB1 and CDKN2a are critical cell-cycle regulators, but their roles in human cardiomyogenesis remains unclear. OBJECTIVE: We hypothesized that developmental activation of RB1 and CDKN2a cooperatively cause permanent cell-cycle withdrawal of human cardiac precursors (CPCs) driving terminal differentiation into mature cardiomyocytes (CM), and that dual inactivation of these tumor suppressor genes promotes myocyte cell-cycle re-entry...
February 12, 2019: Circulation Research
https://read.qxmd.com/read/30743137/white-matter-pathways-and-semantic-processing-intrasurgical-and-lesion-symptom-mapping-evidence
#6
Joanna Sierpowska, Andreu Gabarrós, Alejandro Fernández-Coello, Àngels Camins, Sara Castañer, Montserrat Juncadella, Clément François, Antoni Rodríguez-Fornells
In the present study, we aimed to test the association between the correct function of the left ventral white matter pathways and semantic processing (dual stream models for language processing, Hickok & Poeppel, 2004), using a new set of language tasks during intraoperative electrical stimulation at white matter level. Additionally, we evaluated brain regions needed for correct performance on the different semantic tasks using lesion-symptom analyses (voxel lesion-symptom mapping and track-wise lesion analysis) in a sample of 62 candidates for the awake brain surgery...
January 31, 2019: NeuroImage: Clinical
https://read.qxmd.com/read/30742147/two-way-communication-between-ex-vivo-tissues-on-a-microfluidic-chip-application-to-tumor-lymph-node-interaction
#7
Sangjo Shim, Maura C Belanger, Alexandra R Harris, Jennifer M Munson, Rebecca R Pompano
Experimentally accessible tools to replicate the complex biological events of in vivo organs offer the potential to reveal mechanisms of disease and potential routes to therapy. In particular, models of inter-organ communication are emerging as the next essential step towards creating a body-on-a-chip, and may be particularly useful for poorly understood processes such as tumor immunity. In this paper, we report the first multi-compartment microfluidic chip that continuously recirculates a small volume of media through two ex vivo tissue samples to support inter-organ cross-talk via secreted factors...
February 11, 2019: Lab on a Chip
https://read.qxmd.com/read/30739341/a-potential-contribution-of-decreased-galectin-7-expression-in-stratified-epithelia-to-the-development-of-cutaneous-and-esophageal-manifestations-in-systemic-sclerosis
#8
Ryosuke Saigusa, Takashi Yamashita, Shunsuke Miura, Megumi Hirabayashi, Kouki Nakamura, Takuya Miyagawa, Yuki Fukui, Ayumi Yoshizaki, Shinichi Sato, Yoshihide Asano
BACKGROUNDS: Stratified epithelia have caught much attention as potential contributors to the development of dermal and esophageal fibrosis in systemic sclerosis (SSc). Galectin-7 is a marker of all types of stratified epithelia, which is involved in the maintenance of epidermal homeostasis. So far, the role of galectin-7 has not been studied in SSc. OBJECTIVES: To investigate the potential contribution of galectin-7 to the development of clinical manifestations in SSc...
February 9, 2019: Experimental Dermatology
https://read.qxmd.com/read/30738928/the-biphasic-effects-of-the-oxldl-%C3%AE-2-gpi-anti-%C3%AE-2-gpi-complex-on-vsmc-proliferation-and-apoptosis
#9
Ting Wang, Hong Zhou, Yudan Chen, Peng Zhang, Ting Wang
In our previous study, the oxLDL/β2 GPI/anti-β2 GPI complex was demonstrated to further enhance the foam cell formation and migration of VSMC, as well as the expression of inflammatory cytokines, via the TLR4/NF-κB pathway. However, sparse information is available on other pro-atherogenic pathogenic effects of the oxLDL/β2 GPI/anti-β2 GPI complex, such as effects on proliferation and apoptosis. In the present study, we focused on the biphasic effects and underlying mechanisms of the oxLDL/β2 GPI/anti-β2 GPI complex on VSMC survival...
February 7, 2019: Cellular Signalling
https://read.qxmd.com/read/30738371/high-and-low-on-treatment-platelet-reactivity-to-p2y-12-inhibitors-in-a-contemporary-cohort-of-acute-coronary-syndrome-patients-undergoing-percutaneous-coronary-intervention
#10
José Luis Ferreiro, David Vivas, Jesús María De La Hera, Ana Lucrecia Marcano, Leslie Marisol Lugo, Juan Carlos Gómez-Polo, Iria Silva, Antonio Tello-Montoliu, Francisco Marín, Inmaculada Roldán
INTRODUCTION: There is compelling evidence supporting the association between high on-treatment platelet reactivity (HPR) and low on-treatment platelet reactivity (LPR) to clopidogrel with atherothrombotic and bleeding events, respectively. However, it is uncertain if current cutoff values should be used in prasugrel- or ticagrelor-treated subjects. The objective of this analysis was to evaluate the pharmacodynamic (PD) efficacy of P2Y12 antagonists in a contemporary real-world population...
January 31, 2019: Thrombosis Research
https://read.qxmd.com/read/30737601/analysis-of-the-factors-related-to-the-effectiveness-of-transcranial-current-stimulation-in-upper-limb-motor-function-recovery-after-stroke-a-systematic-review
#11
María Antonia Fuentes Calderón, Ainhoa Navarro Miralles, Mauricio Jaramillo Pimienta, Jesús María Gonçalves Estella, María José Sánchez Ledesma
Transcranial direct current stimulation is one of the non-invasive techniques whose main mechanism of action is based on its modulation of cortical excitability. The objective of this study is to analyze the variables (i.e, demographics, clinicals, stimulation parameters) that could influence into the responses during rehabilitation of the upper extremity in patients with stroke. Our systematic review has been performed by searching full-text articles published from January 2008 to December 2018 in Embase, Medline, PubMed and Cochrane Library databases...
February 8, 2019: Journal of Medical Systems
https://read.qxmd.com/read/30735811/building-capacity-for-macrophage-modulation-and-stem-cell-recruitment-in-high-stiffness-hydrogels-for-complex-periodontal-regeneration-experimental-studies-in-vitro-and-in-rats
#12
Xiao-Tao He, Xuan Li, Yu Xia, Yuan Yin, Rui-Xin Wu, Hai-Hua Sun, Fa-Ming Chen
Recently, we found that although high-stiffness matrices stimulated osteogenic differentiation of bone marrow-derived stromal cells (BMSCs), the macrophages (Mφs) in high-stiffness transglutaminase crosslinked gelatins (TG-gels) tended to undergo M1 polarization and hence compromised cell osteogenesis. In this study, we hypothesized that the copresentation of interleukin (IL)-4 and stromal cell-derived factor (SDF)-1α in high-stiffness TG-gels may enhance periodontal regeneration by modulating Mφ polarization and promoting endogenous stem cell recruitment...
February 5, 2019: Acta Biomaterialia
https://read.qxmd.com/read/30735499/proximal-recolonization-by-self-renewing-microglia-re-establishes-microglial-homeostasis-in-the-adult-mouse-brain
#13
Lihong Zhan, Grietje Krabbe, Fei Du, Ian Jones, Meredith C Reichert, Maria Telpoukhovskaia, Lay Kodama, Chao Wang, Seo-Hyun Cho, Faten Sayed, Yaqiao Li, David Le, Yungui Zhou, Yin Shen, Brian West, Li Gan
Microglia are resident immune cells that play critical roles in maintaining the normal physiology of the central nervous system (CNS). Remarkably, microglia have an intrinsic capacity to repopulate themselves after acute ablation. However, the underlying mechanisms that drive such restoration remain elusive. Here, we characterized microglial repopulation both spatially and temporally following removal via treatment with the colony stimulating factor 1 receptor (CSF1R) inhibitor PLX5622. We show that microglia were replenished via self-renewal, with no contribution from nonmicroglial lineages, including Nestin+ progenitors and the circulating myeloid population...
February 8, 2019: PLoS Biology
https://read.qxmd.com/read/30734321/influence-of-cognitive-load-on-the-dynamics-of-neurophysiological-adjustments-during-fatiguing-exercise
#14
Cyril Chatain, Rémi Radel, Fabrice Vercruyssen, Tahar Rabahi, Jean-Marc Vallier, Thierry Bernard, Mathieu Gruet
We aimed to determine the neurophysiological mechanisms associated with reduced endurance performance during cognitive-motor dual task at different levels of cognitive load, compared to a motor task alone. Eighteen healthy men performed isometric quadriceps contractions at 15% of maximal voluntary contraction (blocks of 170 s interspaced by neuromuscular evaluations) until exhaustion. This task was performed on three separate days: (a) in the absence of concomitant cognitive task, (b) with concomitant 1-back task, and (c) with concomitant 2-back task...
February 7, 2019: Psychophysiology
https://read.qxmd.com/read/30733541/md001-a-novel-peroxisome-proliferator-activated-receptor-%C3%AE-%C3%AE-agonist-improves-glucose-and-lipid-metabolism
#15
Seok-Ho Kim, Shin Hee Hong, Young-Joon Park, Jong-Hyuk Sung, Wonhee Suh, Kyeong Won Lee, Kiwon Jung, Changjin Lim, Jin-Hee Kim, Hyoungsu Kim, Kyong Soo Park, Sang Gyu Park
Peroxisome proliferator-activated receptor (PPAR)-α/γ dual agonists have been developed to treat metabolic diseases; however, most of them exhibit side effects such as body weight gain and oedema. Therefore, we developed a novel PPARα/γ dual agonist that modulates glucose and lipid metabolism without adverse effects. We synthesised novel compounds composed of coumarine and chalcone, determined their crystal structures, and then examined their binding affinity toward PPARα/γ. We investigated the expression of PPARα and PPARγ target genes by chemicals in HepG2, differentiated 3T3-L1, and C2C12 cells...
February 7, 2019: Scientific Reports
https://read.qxmd.com/read/30733244/mechanism-based-pharmacokinetic-pharmacodynamic-model-describing-dextroamphetamine-exposure-and-striatal-dopamine-response-in-rats-and-non-human-primates-following-a-single-intravenous-dose-of-dextroamphetamine
#16
Marcel van Gaalen, Christina Schlumbohm, Joost Folgering, Saugat Adhikari, Chandrali Bhattacharya, Douglas Steinbach, Robert E Stratford
Acute CNS exposure to dextroamphetamine (D-amphetamine) elicits a multitude of effects, including dual action on the dopamine transporter (DAT) to increase extracellular dopamine, and induction of a negative feedback response to limit the dopamine increase. A semi-mechanistic pharmacokinetic and pharmacodynamic (PK/PD) model based on consideration of these multiple effects was developed. Integrated pharmacokinetics of D-amphetamine in plasma, brain extracellular fluid (ECF) via microdialysis, and cerebrospinal fluid (CSF) were characterized using a population approach...
February 7, 2019: Journal of Pharmacology and Experimental Therapeutics
https://read.qxmd.com/read/30721791/poly-n-isopropylacrylamide-polydopamine-clay-nanocomposite-hydrogels-with-stretchability-conductivity-and-dual-light-and-thermo-responsive-bending-and-adhesive-properties
#17
Xiang Di, Yanke Kang, Feifan Li, Rui Yao, Qin Chen, Chen Hang, Yue Xu, Yanming Wang, Pingchuan Sun, Guolin Wu
Conducting hydrogels have attracted attention as a special functional class of smart soft materials and have found applications in various advanced fields. However, acquiring all the characteristics such as conductivity, adequate adhesiveness, self-healing ability, stretchability, biocompatibility, and stimulating deformation responsiveness still remains a challenge. Inspired by the mechanism of bioadhesion in marine mussels, a multifunctional nanocomposite hydrogel with excellent adhesiveness to a broad range of substrates including human skin was developed with the help of synergistic multiple coordination bonds between clay, poly(N-isopropylacrylamide) (PNIPAM), and polydopamine nanoparticles (PDA-NPs)...
January 29, 2019: Colloids and Surfaces. B, Biointerfaces
https://read.qxmd.com/read/30721327/-surgical-treatment-of-proximal-femoral-fractures-in-high-risk-geriatric-patients-under-peripheral-regional-anesthesia-a-clinical-case-series
#18
R Seidel, E Barbakow
The authors describe in a clinical case series (n = 7) of older (age 78-95 years) high-risk patients the successful surgical treatment of proximal femoral fractures in a peripheral regional anesthesia technique. After positioning on the non-fractured side, a double injection technique (dual guidance concept: sonography plus nerve stimulation) was chosen. The injections were performed parasacrally (blockade of the sacral plexus under the piriformis muscle) and lumbar-paravertebrally (psoas compartment block and transmuscular quadratus lumborum block)...
February 5, 2019: Der Anaesthesist
https://read.qxmd.com/read/30717444/characterization-of-a-novel-third-generation-anti-cd24-car-against-ovarian-cancer
#19
Rüdiger Klapdor, Shuo Wang, Michael Morgan, Thilo Dörk, Ulrich Hacker, Peter Hillemanns, Hildegard Büning, Axel Schambach
Novel therapeutic approaches against ovarian cancer (OC) are urgently needed because of its high rate of recurrence even after extensive surgery and multi-agent chemotherapy. We aimed to develop a novel anti-CD24 chimeric antigen receptor (CAR) as an immunotherapeutic approach against OC cells and cancer stem cells (CSC). CSC represents a subpopulation of the tumor characterized by enhanced chemoresistance as well as the increased capability of self-renewal and metastasis. We designed a codon-optimized third-generation CAR containing the highly active single chain variable fragment (scFv) "SWA11" against CD24...
February 3, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30717138/crosstalk-between-autophagy-and-type-i-interferon-responses-in-innate-antiviral-immunity
#20
REVIEW
Yu Tian, Ming-Li Wang, Jun Zhao
Autophagy exhibits dual effects during viral infections, promoting the clearance of viral components and activating the immune system to produce antiviral cytokines. However, some viruses impair immune defenses by collaborating with autophagy. Mounting evidence suggests that the interaction between autophagy and innate immunity is critical to understanding the contradictory roles of autophagy. Type I interferon (IFN-I) is a crucial antiviral factor, and studies have indicated that autophagy affects IFN-I responses by regulating IFN-I and its receptors expression...
February 1, 2019: Viruses
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