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https://www.readbyqxmd.com/read/29777136/functional-proteomic-profiling-of-secreted-serine-proteases-in-health-and-inflammatory-bowel-disease
#1
Alexandre Denadai-Souza, Chrystelle Bonnart, Núria Solà Tapias, Marlène Marcellin, Brendan Gilmore, Laurent Alric, Delphine Bonnet, Odile Burlet-Schiltz, Morley D Hollenberg, Nathalie Vergnolle, Céline Deraison
While proteases are essential in gastrointestinal physiology, accumulating evidence indicates that dysregulated proteolysis plays a pivotal role in the pathophysiology of inflammatory bowel disease (IBD). Nonetheless, the identity of overactive proteases released by human colonic mucosa remains largely unknown. Studies of protease abundance have primarily investigated expression profiles, not taking into account their enzymatic activity. Herein we have used serine protease-targeted activity-based probes (ABPs) coupled with mass spectral analysis to identify active forms of proteases secreted by the colonic mucosa of healthy controls and IBD patients...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29777051/cd36-initiates-the-secretory-phenotype-during-the-establishment-of-cellular-senescence
#2
Mengyang Chong, Tao Yin, Rui Chen, Handan Xiang, Lifeng Yuan, Yi Ding, Christopher C Pan, Zhen Tang, Peter B Alexander, Yinjun Jia, Qi-Jing Li, Xiao-Fan Wang
Cellular senescence is a unique cell fate characterized by stable proliferative arrest and the extensive production and secretion of various inflammatory proteins, a phenomenon known as the senescence-associated secretory phenotype (SASP). The molecular mechanisms responsible for generating a SASP in response to senescent stimuli remain largely obscure. Here, using unbiased gene expression profiling, we discover that the scavenger receptor CD36 is rapidly upregulated in multiple cell types in response to replicative, oncogenic, and chemical senescent stimuli...
May 18, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29776716/two-step-senescence-focused-cancer-therapies
#3
REVIEW
Cynthia J Sieben, Ines Sturmlechner, Bart van de Sluis, Jan M van Deursen
Damaged cells at risk of neoplastic transformation can be neutralized by apoptosis or engagement of the senescence program, which induces permanent cell-cycle arrest and a bioactive secretome that is implicated in tumor immunosurveillance. While from an evolutionary perspective senescence is beneficial in that it protects against malignancies, the accumulation of senescent cells in tissues and organs with aging and at sites of various pathologies is largely detrimental. Because induction of senescence in cancer cells is emerging as a therapeutic concept, it will be important to consider these detrimental effects, including tumor-promoting properties that may drive the formation of secondary tumors or cancer relapse...
May 15, 2018: Trends in Cell Biology
https://www.readbyqxmd.com/read/29775058/multiple-click-selective-trna-synthetases-expand-mammalian-cell-specific-proteomics
#4
Andrew C Yang, Haley du Bois, Niclas Olsson, David Gate, Benoit Lehallier, Daniela Berdnik, Kyle D Brewer, Carolyn R Bertozzi, Joshua E Elias, Tony Wyss-Coray
Bio-orthogonal tools enable cell-type-specific proteomics, a prerequisite to understanding biological processes in multicellular organisms. Here we report two engineered aminoacyl-tRNA synthetases for mammalian bio-orthogonal labeling: a tyrosyl ( ScTyrY34G ) and a phenylalanyl ( MmPheT412G ) tRNA synthetase that incorporate azide-bearing noncanonical amino acids specifically into the nascent proteomes of host cells. Azide-labeled proteins are chemoselectively tagged via azide-alkyne cycloadditions with fluorophores for imaging or affinity resins for mass spectrometric characterization...
May 18, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29773673/lysosomal-proteome-and-secretome-analysis-identifies-missorted-enzymes-and-their-non-degraded-substrates-in-mucolipidosis-iii-mouse-cells
#5
Giorgia Di Lorenzo, Renata Voltolini Velho, Dominic Winter, Melanie Thelen, Shiva Ahmadi, Michaela Schweizer, Raffaella De Pace, Kerstin Cornils, Timur Alexander Yorgan, Saskia Grüb, Irm Hermans-Borgmeyer, Thorsten Schinke, Sven Müller-Loennies, Thomas Braulke, Sandra Pohl
Targeting of soluble lysosomal enzymes requires mannose 6-phosphate (M6P) signals whose formation is initiated by the hexameric N-acetylglucosamine (GlcNAc)-1-phosphotransferase complex (α2β2γ2). Upon proteolytic cleavage by site-1 protease, the α/β-subunit precursor is catalytically activated but the functions of γ-subunits (Gnptg) in M6P modification of lysosomal enzymes are unknown. To investigate this, we analyzed the Gnptg expression in mouse tissues, primary cultured cells, and in Gnptg reporter mice in vivo, and found high amounts in the brain, eye, kidney, femur, vertebra and fibroblasts...
May 17, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29770568/injection-of-synthetic-mesenchymal-stem-cell-mitigates-osteoporosis-in-rats-after-ovariectomy
#6
Miaoda Shen, Ronghuan Wu, Rilong Jin, Jun Pan, Fang Guo, Zhuoyang Li, Xiangjin Lin, Sanzhong Xu
Osteoporosis is a severe skeletal disorder. Patients have a low bone mineral density and bone structural deterioration. Mounting lines of evidence suggest that inappropriate apoptosis of osteoblasts/osteocytes leads to maladaptive bone remodelling in osteoporosis. It has been suggested that transplantation of stem cells, including mesenchymal stem cells, may alter the trajectory of bone remoulding and mitigate osteoporosis in animal models. However, stem cells needed to be carefully stored and characterized before usage...
May 16, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29770299/regenerative-medicine-therapy-for-single-ventricle-congenital-heart-disease
#7
REVIEW
Chetan Ambastha, Gregory J Bittle, David Morales, Nathaniel Parchment, Progyaparamita Saha, Rachana Mishra, Sudhish Sharma, Alexander Vasilenko, Muthukumar Gunasekaran, Manal T Al-Suqi, Deqiang Li, Peixin Yang, Sunjay Kaushal
One of the most complex forms of congenital heart disease (CHD) involving single ventricle physiology is hypoplastic left heart syndrome (HLHS), characterized by underdevelopment of the left ventricle (LV), mitral and aortic valves, and narrowing of the ascending aorta. The underdeveloped LV is incapable of providing long-term systemic flow, and if left untreated, the condition is fatal. Current treatment for this condition consists of three consecutive staged palliative operations: the first is conducted within the first few weeks of birth, the second between 4 to 6 months, and the third and final surgery within the first 4 years...
April 2018: Translational Pediatrics
https://www.readbyqxmd.com/read/29769543/the-cytokine-secretion-profile-of-mesenchymal-stromal-cells-is-determined-by-surface-structure-of-the-microenvironment
#8
Daniëlle G Leuning, Nick R M Beijer, Nadia A du Fossé, Steven Vermeulen, Ellen Lievers, Cees van Kooten, Ton J Rabelink, Jan de Boer
Mesenchymal stromal cells (MSC) secrete factors that contribute to organ homeostasis and repair in a tissue specific manner. For instance, kidney perivascular mesenchymal stromal cells (kPSCs) can facilitate renal epithelial repair through secretion of hepatocyte growth factor (HGF) while the secretome of bone marrow MSCs gives rise to immunosuppression. Stromal cells function in a complex 3-dimensional (3D) connective tissue architecture that induces conformational adaptation. Here we tested the hypothesis that surface topography and associated cell adaptations dictate stromal cell function through tuning of the cytokines released...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29768965/the-therapeutic-potential-of-the-mesenchymal-stem-cell-secretome-in-ischaemic-stroke
#9
Catriona J Cunningham, Elena Redondo-Castro, Stuart M Allan
Mesenchymal stem cells (MSCs) hold great potential as a regenerative therapy for stroke, leading to increased repair and functional recovery in animal models of cerebral ischaemia. While it was initially hypothesised that cell replacement was an important mechanism of action of MSCs, focus has shifted to their paracrine actions or the so called "bystander" effect. MSCs secrete a wide array of growth factors, chemokines, cytokines and extracellular vesicles, commonly referred to as the MSC secretome...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29768194/extracellular-forms-of-a%C3%AE-and-tau-from-ipsc-models-of-alzheimer-s-disease-disrupt-synaptic-plasticity
#10
Neng-Wei Hu, Grant T Corbett, Steven Moore, Igor Klyubin, Tiernan T O'Malley, Dominic M Walsh, Frederick J Livesey, Michael J Rowan
The early stages of Alzheimer's disease are associated with synaptic dysfunction prior to overt loss of neurons. To identify extracellular molecules that impair synaptic plasticity in the brain, we studied the secretomes of human iPSC-derived neuronal models of Alzheimer's disease. When introduced into the rat brain, secretomes from human neurons with either a presenilin-1 mutation, amyloid precursor protein duplication, or trisomy of chromosome 21 all strongly inhibit hippocampal long-term potentiation. Synaptic dysfunction caused by presenilin-1 mutant and amyloid precusor protein duplication secretomes is mediated by Aβ peptides, whereas trisomy of chromosome 21 (trisomy 21) neuronal secretomes induce dysfunction through extracellular tau...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29764562/osteoclast-derived-slit3-is-a-coupling-factor-linking-bone-resorption-to-bone-formation
#11
Jung-Min Koh
We identified osteoclast-derived SLIT3 as a new coupling factor using fractionated secretomics. Coupling links bone resorption to bone formation. SLIT3 stimulated the recruitment and proliferation of osteoblasts into bone remodeling sites via activation of β-catenin. Autocrine signaling by SLIT3 also inhibited bone resorption by suppressing the fusion and differentiation of pre-osteoclasts. All mice lacking Slit3 or its receptor Robo1 showed an osteopenic phenotype with low bone formation and high bone resorption...
May 16, 2018: BMB Reports
https://www.readbyqxmd.com/read/29760587/the-role-of-adipokines-in-skeletal-muscle-inflammation-and-insulin-sensitivity
#12
REVIEW
Thomas Nicholson, Chris Church, David J Baker, Simon W Jones
Background: There is currently an unmet clinical need to develop better pharmacological treatments to improve glucose handling in Type II Diabetes patients with obesity. To this end, determining the effect of obesity-associated adipokines on skeletal muscle insulin sensitivity has emerged as an important area of drug discovery research. This review draws together the data on the functional role of adipokines on skeletal muscle insulin signalling, highlights several understudied novel adipokines and provides a perspective on the direction of future research...
2018: Journal of Inflammation
https://www.readbyqxmd.com/read/29757271/the-isolation-and-culture-of-primary-epicardial-cells-derived-from-human-adult-and-fetal-heart-specimens
#13
Esther Dronkers, Asja T Moerkamp, Tessa van Herwaarden, Marie-José Goumans, Anke M Smits
The epicardium, an epithelial cell layer covering the myocardium, has an essential role during cardiac development, as well as in the repair response of the heart after ischemic injury. When activated, epicardial cells undergo a process known as epithelial to mesenchymal transition (EMT) to provide cells to the regenerating myocardium. Furthermore, the epicardium contributes via secretion of essential paracrine factors. To fully appreciate the regenerative potential of the epicardium, a human cell model is required...
April 24, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29756519/adipose-derived-stem-cells-stimulated-with-n-butylidenephthalide-exhibit-therapeutic-effects-in-a-mouse-model-of-parkinson-s-disease
#14
Kang Chi, Ru-Huei Fu, Yu-Chuen Huang, Shih-Yin Chen, Ching-Ju Hsu, Shinn-Zong Lin, Chi-Tang Tu, Li-Hsun Chang, Ping-An Wu, Shih-Ping Liu
Parkinson's disease (PD) causes motor dysfunction and dopaminergic cell death. Drug treatments can effectively reduce symptoms but often cause unwanted side effects. Stem cell therapies using cell replacement or indirect beneficial secretomes have recently emerged as potential therapeutic strategies. Although various types of stem cells have been proposed as possible candidates, adipose-derived stem cells (ADSCs) are easily obtainable, more abundant, less ethically disputed, and able to differentiate into multiple cell lineages...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29753032/enhancement-of-cutaneous-wound-healing-by-dsg2-augmentation-of-upar-secretion
#15
Felicia Cooper, Andrew M Overmiller, Anthony Loder, Donna M Brennan-Crispi, Kathleen P McGuinn, Molly R Marous, Theresa A Freeman, Natalia A Riobo-Del Galdo, Linda D Siracusa, James K Wahl, Mỹ G Mahoney
In addition to playing a role in adhesion, desmoglein 2 (Dsg2) is an important regulator of growth and survival signaling pathways, cell proliferation, migration and invasion, and oncogenesis. While low-level Dsg2 expression is observed in basal keratinocytes and is downregulated in non-healing venous ulcers, overexpression has been observed in both melanomas and non-melanoma malignancies. Here, we show that transgenic mice overexpressing Dsg2 in basal keratinocytes primed the activation of mitogenic pathways, but did not induce dramatic epidermal changes or susceptibility to chemical-induced tumor development...
May 9, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29752774/mesenchymal-stem-cells-promote-lymphangiogenic-properties-of-lymphatic-endothelial-cells
#16
Jan W Robering, Annika Weigand, Romy Pfuhlmann, Raymund E Horch, Justus P Beier, Anja M Boos
Lymphatic metastasis is one of the main prognostic factors concerning long-term survival of cancer patients. In this regard, the molecular mechanisms of lymphangiogenesis are still rarely explored. Also, the interactions between stem cells and lymphatic endothelial cells (LEC) in humans have not been well examined. Therefore, the main objective of this study was to assess the interactions between mesenchymal stem cells (MSC) and LEC using in vitro angiogenesis assays. Juvenile LEC were stimulated with VEGF-C, bFGF, MSC-conditioned medium (MSC-CM) or by co-culture with MSC...
May 11, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29751776/negative-effects-of-a-high-tumour-necrosis-factor-%C3%AE-concentration-on-human-gingival-mesenchymal-stem-cell-trophism-the-use-of-natural-compounds-as-modulatory-agents
#17
Chiara Giacomelli, Letizia Natali, Marco Nisi, Marinella De Leo, Simona Daniele, Barbara Costa, Filippo Graziani, Mario Gabriele, Alessandra Braca, M Letizia Trincavelli, Claudia Martini
BACKGROUND: Adult mesenchymal stem cells (MSCs) play a crucial role in the maintenance of tissue homeostasis and in regenerative processes. Among the different MSC types, the gingiva-derived mesenchymal stem cells (GMSCs) have arisen as a promising tool to promote the repair of damaged tissues secreting trophic mediators that affect different types of cells involved in regenerative processes. Tumour necrosis factor (TNF)-α is one of the key mediators of inflammation that could affect tissue regenerative processes and modify the MSC properties in in-vitro applications...
May 11, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29751771/unique-and-shared-inflammatory-profiles-of-human-brain-endothelia-and-pericytes
#18
Leon C D Smyth, Justin Rustenhoven, Thomas I-H Park, Patrick Schweder, Deidre Jansson, Peter A Heppner, Simon J O'Carroll, Edward W Mee, Richard L M Faull, Maurice Curtis, Mike Dragunow
BACKGROUND: Pericytes and endothelial cells are critical cellular components of the blood-brain barrier (BBB) and play an important role in neuroinflammation. To date, the majority of inflammation-related studies in endothelia and pericytes have been carried out using immortalised cell lines or non-human-derived cells. Whether these are representative of primary human cells is unclear and systematic comparisons of the inflammatory responses of primary human brain-derived pericytes and endothelia has yet to be performed...
May 11, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29751628/the-double-face-of-mucin-type-o-glycans-in-lectin-mediated-infection-and-immunity
#19
REVIEW
Vasily Morozov, Julia Borkowski, Franz-Georg Hanisch
Epithelial human blood group antigens (HBGAs) on O-glycans play roles in pathogen binding and the initiation of infection, while similar structures on secretory mucins exert protective functions. These double-faced features of O-glycans in infection and innate immunity are reviewed based on two instructive examples of bacterial and viral pathogens. Helicobacter pylori represents a class 1 carcinogen in the human stomach. By expressing blood group antigen-binding adhesin ( BabA ) and LabA adhesins that bind to Lewis-b and LacdiNAc, respectively, H...
May 11, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29750999/modeling-triple-negative-breast-cancer-heterogeneity-effects-of-stromal-macrophages-fibroblasts-and-tumor-vasculature
#20
Kerri-Ann Norton, Kideok Jin, Aleksander S Popel
A hallmark of breast tumors is its spatial heterogeneity that includes its distribution of cancer stem cells and progenitor cells, but also heterogeneity in the tumor microenvironment. In this study we focus on the contributions of stromal cells, specifically macrophages, fibroblasts, and endothelial cells on tumor progression. We develop a computational model of triple-negative breast cancer based on our previous work and expand it to include macrophage infiltration, fibroblasts, and angiogenesis. In vitro studies have shown that the secretomes of tumor-educated macrophages and fibroblasts increase both the migration and proliferation rates of triple-negative breast cancer cells...
May 8, 2018: Journal of Theoretical Biology
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