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https://www.readbyqxmd.com/read/29656561/advances-in-controlling-differentiation-of-adult-stem-cells-for-peripheral-nerve-regeneration
#1
REVIEW
Metin Uz, Suprem R Das, Shaowei Ding, Donald S Sakaguchi, Jonathan C Claussen, Surya K Mallapragada
Adult stems cells, possessing the ability to grow, migrate, proliferate, and transdifferentiate into various specific phenotypes, constitute a great asset for peripheral nerve regeneration. Adult stem cells' ability to undergo transdifferentiation is sensitive to various cell-to-cell interactions and external stimuli involving interactions with physical, mechanical, and chemical cues within their microenvironment. Various studies have employed different techniques for transdifferentiating adult stem cells from distinct sources into specific lineages (e...
April 14, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29656494/oxidized-ldl-phagocytosis-during-foam-cell-formation-in-atherosclerotic-plaques-relies-on-a-pld2-cd36-functional-interdependence
#2
Ramya Ganesan, Karen M Henkels, Lucile E Wrenshall, Yasunori Kanaho, Gilbert Di Paolo, Michael A Frohman, Julian Gomez-Cambronero
The uptake of cholesterol carried by low-density lipoprotein (LDL) is tightly controlled in the body. Macrophages are not well suited to counteract the cellular consequences of excess cholesterol leading to their transformation into "foam cells," an early step in vascular plaque formation. We have uncovered and characterized a novel mechanism involving phospholipase D (PLD) in foam cell formation. Utilizing bone marrow-derived macrophages from genetically PLD deficient mice, we demonstrate that PLD2 (but not PLD1)-null macrophages cannot fully phagocytose aggregated oxidized LDL (Agg-Ox-LDL), which was phenocopied with a PLD2-selective inhibitor...
April 14, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29656482/kindlin-3-negatively-regulates-the-release-of-neutrophil-extracellular-traps
#3
Zhen Xu, Beiwen Ni, Zhongyuan Cao, Jacek Zielonka, Juan Gao, Fangyuan Chen, Balaraman Kalyanaraman, Gilbert C White, Yan-Qing Ma
Neutrophils fight infections by generating reactive oxygen species (ROS) and extracellular traps (NETs). However, how neutrophils modulate ROS/NET generation is mechanistically unclear. Kindlin-3, an essential integrin activator expressed in hematopoietic cells, is required to support integrin-mediated neutrophil recruitment during inflammation. Here, we report a novel role of kindlin-3 in regulating ROS/NET generation in neutrophils. When overexpressing kindlin-3 in neutrophil-like differentiated HL-60 cells (HL-60N), ROS/NET generation from these cells were significantly suppressed...
April 14, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29656470/mechanical-and-in-vitro-degradation-behavior-of-magnesium-bioactive-glass-composites-prepared-by-sps-for-biomedical-applications
#4
Sourav Dutta, K Bavya Devi, Sanjay Gupta, Biswanath Kundu, Vamsi Krishna Balla, Mangal Roy
In order to make magnesium (Mg) a successful candidate for fracture fixation devices, it is imperative to control the corrosion rate and enhance its elastic modulus. In the present work, we have prepared bioactive glass (BG) reinforced magnesium composite using spark plasma sintering (SPS). Simultaneous application of heat and pressure during SPS decreased the softening point of BG (600°C), allowing it to coat the Mg particles partially. As a result, BG was found along the Mg particle boundaries, which was confirmed by elemental mapping...
April 15, 2018: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/29656465/structural-characterization-of-the-interaction-of-the-fibroblast-growth-factor-receptor-with-a-small-molecule-allosteric-inhibitor
#5
Franziska Kappert, Sridhar Sreeramulu, Hendrik R A Jonker, Christian Richter, Vladimir V Rogov, Ewgenij Proschak, Bruno Hargittay, Krishna Saxena, Harald Schwalbe
The interaction of fibroblast growth factors (FGFs) with their fibroblast growth factor receptors (FGFRs) are important in the signaling network of cell growth and development. SSR128129E (SSR)[1,2], a ligand of small molecular weight with potential anti-cancer properties, acts allosterically on the extracellular domains of FGFRs. Up to now, the structural basis of SSR binding to the D3 domain of FGFR remained elusive. Here, we report the structural characterization of the interaction of SSR with one specific receptor, FGFR3 by NMR spectroscopy...
April 14, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29656244/human-organoid-cultures-transformative-new-tools-for-human-virus-studies
#6
REVIEW
Sasirekha Ramani, Sue E Crawford, Sarah E Blutt, Mary K Estes
Studies of human infectious diseases have been limited by the paucity of functional models that mimic normal human physiology and pathophysiology. Recent advances in the development of multicellular, physiologically active organotypic cultures produced from embryonic and pluripotent stem cells, as well as from stem cells isolated from biopsies and surgical specimens are allowing unprecedented new studies and discoveries about host-microbe interactions. Here, we summarize recent developments in the use of organoids for studying human viral pathogens, including intestinal infections with human rotavirus, norovirus, enteroviruses and adenoviruses (intestinal organoids and enteroids), neuronal infections with Zika virus (cerebral organoids) and respiratory infections with respiratory syncytial virus in (lung bud organoids)...
April 12, 2018: Current Opinion in Virology
https://www.readbyqxmd.com/read/29656216/insights-into-cell-penetrating-peptide-conjugated-gold-nanoparticles-for-internalization-into-bacterial-cells
#7
Munish Kumar, Werner Tegge, Nishima Wangoo, Rahul Jain, Rohit K Sharma
Gold nanoparticles (AuNPs) functionalized with different biomolecules find extensive application in therapy, clinical diagnosis and biomedical imaging. Herein, two derivatives of TAT peptide with sequences YGRKKRRQRRR and YGRKKRRQRRR-(β-ala)3 -Cys-amide were conjugated with tannic acid capped gold nanoparticles which acted as a carrier for cell penetrating peptides (CPPs) into the bacterial cells. The interaction of YGRKKRRQRRR peptide with AuNPs was non-covalent in nature whereas YGRKKRRQRRR-(β-ala)3 -Cys-amide interacted covalently with the AuNPs due to presence of thiol group in cysteine which bind strongly to gold nanoparticles surface...
March 31, 2018: Biophysical Chemistry
https://www.readbyqxmd.com/read/29656201/anti-leishmanial-click-modifiable-thiosemicarbazones-design-synthesis-biological-evaluation-and-in-silico-studies
#8
Mohamed G Temraz, Perihan A Elzahhar, Alaa El-Din A Bekhit, Adnan A Bekhit, Hala F Labib, Ahmed S F Belal
Leishmaniasis is a devastating tropical disease with limited therapeutic options. Depending on recently reported active anti-leishmanial compounds, we designed and synthesized a series of click modifiable 1,2,3-triazole and thiosemicarbazone hybrids. Most of the synthesized compounds showed comparable to superior activity to a well-established anti-leishmanial drug miltefosine. Compounds 2 and 10a showed nanomolar IC50 s against promastigotes of L. major (227.4 nM and 140.3 nM respectively, vs 7.8 μM for miltefosine)...
April 3, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29656197/design-and-synthesis-of-bpr1k653-derivatives-targeting-the-back-pocket-of-aurora-kinases-for-selective-isoform-inhibition
#9
Yi-Yu Ke, Chun-Ping Chang, Wen-Hsing Lin, Chia-Hua Tsai, I-Chen Chiu, Wan-Ping Wang, Pei-Chen Wang, Pei-Yi Chen, Wen-Hsin Lin, Chun-Feng Chang, Po-Chu Kuo, Jen-Shin Song, Chuan Shih, Hsing-Pang Hsieh, Ya-Hui Chi
Twenty five novel chemical analogs of the previously reported Aurora kinase inhibitor BPR1K653 (1-(4-(2-((5-chloro-6-phenylfuro[2,3-d]pyrimidin-4-yl)amino)ethyl)phenyl)-3-(2-((dimethylamino)methyl)phenyl)urea) have been designed, synthesized, and evaluated by Aurora-A and Aurora-B enzymatic kinase activity assays. Similar to BPR1K653, analogs 3b-3h bear alkyl or tertiary amino group at the ortho position of the phenylurea, and showed equal or better inhibition activity for Aurora-B over Aurora-A. Conversely, preferential Aurora-A inhibition activity was observed when the same functional group was moved to the meta position of the phenylurea...
April 3, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29656185/exogenous-serp1-attenuates-restenosis-by-restoring-glp-1-receptor-activity-in-diabetic-rats-following-vascular-injury
#10
Lishuai Feng, Jianbo Wang, Xu Ma
The activity of glucagon-like peptide 1 (GLP-1R) is essential for preventing restenosis following vascular injury; however, the mechanism of dysfunctional GLP-1R glycosylation and ways to enhance the activity of GLP-1R on vascular surfaces in diabetic patients are poorly understood. In the present study, we investigated the N-glycosylation level and role of stress-associated endoplasmic reticulum protein 1 (SERP1) in preventing restenosis following carotid injury in diabetic rats. Our results showed that N-glycosylation levels in both rat aortic endothelial cells (RAOECs) and rat vascular smooth muscle cells (VSMCs) decreased gradually following glucose treatment in a concentration dependant manner...
April 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29656089/microbiology-catches-the-cryo-em-bug
#11
REVIEW
Lesley A Earl, Veronica Falconieri, Sriram Subramaniam
Over the past few years, the advances in technology and methods that have revolutionized cryo-EM are allowing for key insights in a variety of areas in biology, and microbiology is no exception. A wide range of important macromolecular assemblies in prokaryotic and eukaryotic cells, as well as intact viruses, have now become accessible to investigation by new methods in 3D electron microscopy. We focus here on selected examples that illustrate this breadth, and review the application of methods in single particle cryo-EM and cryo-electron tomography to progress in the structural biology of CRISPR systems, visualization of small molecule drugs in membrane proteins, in situ visualization of bacterial nanomachines, and the analysis of antigen-antibody interactions to drive vaccine design...
April 12, 2018: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29655887/engineering-riboswitch-in-l-major-from-prediction-to-conceptualization
#12
Pruthvi Raj Bejugam, Shailza Singh
Post-transcriptional gene regulation is a vital process to regulate expression of the key genes in the eukaryotic cell. Such processes are essential for pathogens which reside inside the host cell. One such pathogen is Leishmania major, which causes cutaneous leishmaniasis. The parasite lives inside the macrophages of mammalian host (mostly human). Inside the macrophage, Leishmania genes show complex host-pathogen interaction regulating a plethora of gene expression. Till date, most of the studies have shown this kind of regulation with respect to the host macrophages...
April 12, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29655789/interleukin-enhanced-binding-factor-2-interacts-with-nlrp3-to-inhibit-the-nlrp3-inflammasome-activation
#13
Jing Jin, Aixin Li, Wenbiao Wang, Jianguo Wu
The activation of the NLRP3 inflammasome is a key process of host immune response that establishes the first line of defense against pathogen infections and cellular stresses, whereas excessive inflammasome activation may damage the hosts, and thus it must be precisely controlled. However, the mechanism underlying the repression of the NLRP3 inflammasome activation remains largely unknown. In this study, by establishing and using a reconstructed NLRP3 inflammasome activation system, we reveal that the NLRP3 inflammasome activation, pro-caspase-1 cleavage, and pro-interleukin-1β (pro-IL-1β) activation are repressed by the interleukin-enhanced binding factor 2 (ILF2)...
April 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29655729/in-vitro-effects-of-rebaudioside-a-stevioside-and-steviol-on-porcine-cytochrome-p450-expression-and-activity
#14
Rebekka Thøgersen, Bjørn Petrat-Melin, Galia Zamaratskaia, Kai Grevsen, Jette Feveile Young, Martin Krøyer Rasmussen
The physiological effects of the Stevia-derived compounds, rebaudioside A, stevioside and steviol have been the focus of several studies due to their use as sweeteners in food. Despite that, little is known about their potential food-drug interactions. In the present study, IPEC-J2 cells and primary hepatocytes were used to investigate the effect of rebaudioside A, stevioside and steviol on cytochrome p450 (CYP) mRNA expression. Moreover, hepatic microsomes were used to investigate direct interactions between the compounds and specific CYP activity...
August 30, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29655705/spatially-correlated-gene-expression-in-bacterial-groups-the-role-of-lineage-history-spatial-gradients-and-cell-cell-interactions
#15
Simon van Vliet, Alma Dal Co, Annina R Winkler, Stefanie Spriewald, Bärbel Stecher, Martin Ackermann
Gene expression levels in clonal bacterial groups have been found to be spatially correlated. These correlations can partly be explained by the shared lineage history of nearby cells, although they could also arise from local cell-cell interactions. Here, we present a quantitative framework that allows us to disentangle the contributions of lineage history, long-range spatial gradients, and local cell-cell interactions to spatial correlations in gene expression. We study pathways involved in toxin production, SOS stress response, and metabolism in Escherichia coli microcolonies and find for all pathways that shared lineage history is the main cause of spatial correlations in gene expression levels...
April 5, 2018: Cell Systems
https://www.readbyqxmd.com/read/29655688/novel-ras-inhibitor-25-o-methylalisol-f-attenuates-epithelial-to-mesenchymal-transition-and-tubulo-interstitial-fibrosis-by-selectively-inhibiting-tgf-%C3%AE-mediated-smad3-phosphorylation
#16
Hua Chen, Tian Yang, Min-Chang Wang, Dan-Qian Chen, Yang Yang, Ying-Yong Zhao
BACKGROUND: Tubulo-interstitial fibrosis (TIF) is the common pathway in the chronic kidney disease (CKD). Epithelial-to-mesenchymal transition (EMT) is a major contributor to the TIF by the increased myofibroblasts. Renin-angiotensin system (RAS) is critical mediator on EMT in progressive CKD. Angiotensin II (ANG) mediates EMT and causes TIF by stimulating transforming growth factor-β1 (TGF-β1). RAS activation could further activate TGF-β1. Inhibition of the RAS is one of the most powerful therapies for progressive CKD...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29655632/ag85a-specific-cd4-t-cell-lines-derived-after-boosting-bcg-vaccinated-cattle-with-ad5-85a-possess-both-mycobacterial-growth-inhibition-and-anti-inflammatory-properties
#17
Hannah J Metcalfe, Lucia Biffar, Sabine Steinbach, Efrain Guzman, Tim Connelley, Ivan Morrison, H Martin Vordermeier, Bernardo Villarreal-Ramos
There is a need to improve the efficacy of the BCG vaccine against human and bovine tuberculosis. Previous data showed that boosting bacilli Calmette-Guerin (BCG)-vaccinated cattle with a recombinant attenuated human type 5 adenovirally vectored subunit vaccine (Ad5-85A) increased BCG protection and was associated with increased frequency of Ag85A-specific CD4+ T cells post-boosting. Here, the capacity of Ag85A-specific CD4+ T cell lines - derived before and after viral boosting - to interact with BCG-infected macrophages was evaluated...
April 11, 2018: Vaccine
https://www.readbyqxmd.com/read/29655483/chromatin-fiber-folding-directed-by-cooperative-histone-tail-acetylation-and-linker-histone-binding
#18
Gavin D Bascom, Tamar Schlick
In eukaryotic chromatin, islands of histone tail acetylation are found near transcription start sites and enhancers, whereas linker histones (LHs) are localized in intergenic regions with wild-type (WT) histone tails. However, the structural mechanisms by which acetylation, in combination with LH binding, modulates chromatin compaction and hence transcription regulation are unknown. To explore the folding propensity by which these features may govern gene expression, we analyze 20 kb fibers that contain regularly spaced acetylation islands of two sizes (2 or 5 kb) with various LH levels by mesoscale modeling...
April 11, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29653410/rescue-of-iciks-transfer-from-pd-1-pd-l1-immune-inhibition-in-patients-with-resectable-tongue-squamous-cell-carcinoma-tscc
#19
Xiaofeng Huang, Jing Zhang, Xiaolong Li, Hongxing Huang, Ying Liu, Mei Yu, Yan Zhang, Hua Wang
OBJECTIVES: The purpose of this study is to evaluate the therapeutic efficacy and the role of PD-1/PD-L1 pathway in tongue squamous cell carcinoma (TSCC) patients treated with radical operation combined with chemotherapy and improving cytokine induced killer cells (iCIKs) transfer. METHODS: Thirteen patients who received radical resection and chemotherapy were enrolled in this study. PD-1/PD-L1 expression was evaluated in TSCC patients. ICIKs were cultured from patient-derived peripheral blood mononuclear cells (PBMCs) in vitro...
April 10, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29653393/antifungal-activity-and-action-mechanisms-of-yeasts-isolates-from-citrus-against-penicillium-italicum
#20
Tatiane da Cunha, Luriany Pompeo Ferraz, Pitt Paul Wehr, Katia Cristina Kupper
Penicillium italicum (Blue mold) is a major postharvest disease of citrus. An alternative to controlling the disease is through the use of yeasts. The purpose of the present study was to screen effective yeast antagonists against P. italicum, isolated from soil, leaves, flowers, and citrus fruits, to assess the action mechanisms of the yeast isolates that were demonstrated to be effective for biocontrol, and to identify the most effective yeast isolates for the biocontrol of blue mold. The in vitro assays showed that six yeast strains inhibited up to 90% of the pathogen's mycelial growth...
March 27, 2018: International Journal of Food Microbiology
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