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https://www.readbyqxmd.com/read/29782891/review-article-a-translational-view-of-cells-secretome-analysis-from-untargeted-proteomic-to-potential-circulating-biomarkers
#1
REVIEW
Sandra I Anjo, Bruno Manadas
The identification of circulating biomarkers capable of being used as routine for diagnosis, prognosis, risk stratification and therapeutic monitoring is still the major aim at clinical proteomics. However, the direct search in blood samples or other clinical relevant biofluids is frequently associated with technical limitations that makes the biomarker discovery process extremely difficult when using these types of samples. In this sense, the use of different approaches, such as the analysis of cells' secretomes, can be an important and promising complementary method for the identification and pre-selection of potential circulating biomarkers...
May 18, 2018: Biochimie
https://www.readbyqxmd.com/read/29777136/functional-proteomic-profiling-of-secreted-serine-proteases-in-health-and-inflammatory-bowel-disease
#2
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/29773673/lysosomal-proteome-and-secretome-analysis-identifies-missorted-enzymes-and-their-non-degraded-substrates-in-mucolipidosis-iii-mouse-cells
#3
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/29760587/the-role-of-adipokines-in-skeletal-muscle-inflammation-and-insulin-sensitivity
#4
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/29751771/unique-and-shared-inflammatory-profiles-of-human-brain-endothelia-and-pericytes
#5
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/29749438/oct4-suppresses-ir%C3%A2-induced-premature-senescence-in-breast-cancer-cells-through-stat3-and-nf%C3%A2-%C3%AE%C2%BAb-mediated-il%C3%A2-24-production
#6
Jeong-Yub Kim, Jeong-Chul Kim, Ji-Yun Lee, Myung-Jin Park
Breast cancer stem cells (BCSCs) are a small subpopulation of breast cancer cells that have been proposed to be a primary cause of failure of therapies, including ionizing radiation (IR). Their embryonic stem-like signature is associated with poor clinical outcome. In the present study, the function of octamer-binding transcription factor 4 (Oct4), an embryonic stem cell factor, in the resistance of BCSCs to IR was investigated. Mammosphere cells exhibited increased expression of stemness-associated genes, including Oct4 and sex‑determining region Y‑box 2 (Sox2), and were more resistant to IR compared with serum-cultured monolayer cells...
May 2, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29727591/alpha-linolenic-acid-and-linoleic-acid-differentially-regulate-the-skeletal-muscle-secretome-of-obese-zucker-rats
#7
Alex Rajna, Heather Gibling, Ousseynou Sarr, Sarthak Matravadia, Graham P Holloway, David M Mutch
Evidence shows that proteins secreted from skeletal muscle influence a broad range of metabolic signaling pathways. We previously reported that essential polyunsaturated fatty acids (PUFA) improved whole-body glucose homeostasis in obese Zucker rats; however, the mechanisms underlying these benefits remain enigmatic. While PUFA and obesity influence skeletal muscle function, their effects on the secretome are unknown. The aim of this work was to determine if improvements in whole-body glucose homeostasis in obese Zucker rats fed diets supplemented with either linoleic acid (LA) or alpha-linolenic acid (ALA) for 12-wks are related to changes in the skeletal muscle secretome...
May 4, 2018: Physiological Genomics
https://www.readbyqxmd.com/read/29726981/dickkopf-3-in-aberrant-endothelial-secretome-triggers-renal-fibroblast-activation-and-endothelial-mesenchymal-transition
#8
Mark Lipphardt, Hassan Dihazi, Noo Li Jeon, Sina Dadafarin, Brian B Ratliff, David W Rowe, Gerhard A Müller, Michael S Goligorsky
Background: Our laboratory has previously demonstrated that Sirt1endo-/- mice show endothelial dysfunction and exaggerated renal fibrosis, whereas mice with silenced endothelial transforming growth factor beta (TGF-β) signaling are resistant to fibrogenic signals. Considering the fact that the only difference between these mutant mice is confined to the vascular endothelium, this indicates that secreted substances contribute to these contrasting responses. Methods: We performed an unbiased proteomic analysis of the secretome of renal microvascular endothelial cells (RMVECs) isolated from these two mutants...
May 3, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29722001/cystatin-c-takes-part-in-melanoma-microglia-cross-talk-possible-implications-for-brain-metastasis
#9
Adi Moshe, Sivan Izraely, Orit Sagi-Assif, Roshini Prakash, Alona Telerman, Tsipi Meshel, Thomas Carmichael, Isaac P Witz
The development of melanoma brain metastasis is largely dependent on mutual interactions between the melanoma cells and cells in the brain microenvironment. Here, we report that the extracellular cysteine protease inhibitor cystatin C (CysC) is involved in these interactions. Microglia-derived factors upregulated CysC secretion by melanoma. Similarly, melanoma-derived factors upregulated CysC secretion by microglia. Whereas CysC enhanced melanoma cell migration through a layer of brain endothelial cells, it inhibited the migration of microglia cells toward melanoma cells...
May 2, 2018: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/29713426/extracellular-vesicles-from-bone-marrow-derived-mesenchymal-stromal-cells-support-ex-vivo-survival-of-human-antibody-secreting-cells
#10
Doan C Nguyen, Holly C Lewis, Chester Joyner, Vivien Warren, Haopeng Xiao, Haydn T Kissick, Ronghu Wu, Jacques Galipeau, F Eun-Hyung Lee
Extracellular vesicles (EVs) from bone marrow (BM)-derived mesenchymal stromal cells (BM-MSC) are novel mechanisms of cell-cell communication over short and long distances. BM-MSC have been shown to support human antibody secreting cells (ASC) survival ex vivo , but whether the crosstalk between the MSC-ASC interaction can occur via EVs is not known. Thus, we evaluated the role of EVs in ASC survival and IgG secretion. EVs were isolated from irradiated and non-irradiated primary BM-MSC and were quantified. They were further characterized by electron microscopy (EM) and CD63 and CD81 immuno-gold EM staining...
2018: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/29700415/comparative-systems-analysis-of-the-secretome-of-the-opportunistic-pathogen-aspergillus-fumigatus-and-other-aspergillus-species
#11
R P Vivek-Ananth, Karthikeyan Mohanraj, Muralidharan Vandanashree, Anupam Jhingran, James P Craig, Areejit Samal
Aspergillus fumigatus and multiple other Aspergillus species cause a wide range of lung infections, collectively termed aspergillosis. Aspergilli are ubiquitous in environment with healthy immune systems routinely eliminating inhaled conidia, however, Aspergilli can become an opportunistic pathogen in immune-compromised patients. The aspergillosis mortality rate and emergence of drug-resistance reveals an urgent need to identify novel targets. Secreted and cell membrane proteins play a critical role in fungal-host interactions and pathogenesis...
April 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29696081/proteomic-analysis-reveals-different-composition-of-extracellular-vesicles-released-by-two-trypanosoma-cruzi-strains-associated-with-their-distinct-interaction-with-host-cells
#12
Kleber Silva Ribeiro, Camilla Ioshida Vasconcellos, Rodrigo Pedro Soares, Maria Tays Mendes, Cameron C Ellis, Marcela Aguilera-Flores, Igor Correia de Almeida, Sergio Schenkman, Leo Kei Iwai, Ana Claudia Torrecilhas
Trypanosoma cruzi , the aetiologic agent of Chagas disease, releases vesicles containing a wide range of surface molecules known to affect the host immunological responses and the cellular infectivity. Here, we compared the secretome of two distinct strains (Y and YuYu) of T. cruzi , which were previously shown to differentially modulate host innate and acquired immune responses. Tissue culture-derived trypomastigotes of both strains secreted extracellular vesicles (EVs), as demonstrated by electron scanning microscopy...
2018: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/29695634/tumor-independent-host-secretomes-induced-by-angiogenesis-and-immune-checkpoint-inhibitors
#13
Michalis Mastri, Christina R Lee, Amanda Tracz, Robert S Kerbel, Melissa Dolan, Yuhao Shi, John M L Ebos
The levels of various circulating blood proteins can change in response to cancer therapy. Monitoring therapy-induced secretomes (TIS) may have use as biomarkers for establishing optimal biological effect (such as dosing) or identifying sources of toxicity and drug resistance. While TIS can derive from tumor cells directly, non-tumor 'host' treatment responses can also impact systemic secretory programs. For targeted inhibitors of the tumor microenvironment, including antiangiogenic and immune-checkpoint therapies, host TIS could explain unexpected collateral 'side-effects' of treatment...
April 25, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29686328/a-microfluidic-device-for-studying-chemotaxis-mechanism-of-bacterial-cancer-targeting
#14
Jing Song, Yu Zhang, Chengqian Zhang, Xiaohui Du, Zhe Guo, Yanbin Kuang, Yingyan Wang, Peng Wu, Kun Zou, Lijuan Zou, Jianxin Lv, Qi Wang
Bacterial cancer targeting may become an efficacious cancer therapy, but the mechanisms underlying bacterial specificity for cancer cells need to be explored prior to adopting it as a new clinical application. To characterize the mechanism of bacterial chemotactic preference towards cancer cells, we developed a microfluidic device for in vitro study. The device consists of a cell culture chamber on both sides of a central bacteria channel, with micro-channels used as barriers between them. The device, when used as model for lung cancer, was able to provide simultaneous three-dimensional co-culture of multiple cell lines in separate culture chambers, and when used as model for bacterial chemotaxis, established constant concentration gradients of biochemical compounds in a central channel by diffusion through micro-channels...
April 23, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29686097/reactivity-of-o-2-versus-h-2-o-2-with-polysaccharide-monooxygenases
#15
John A Hangasky, Anthony T Iavarone, Michael A Marletta
Enzymatic conversion of polysaccharides into lower-molecular-weight, soluble oligosaccharides is dependent on the action of hydrolytic and oxidative enzymes. Polysaccharide monooxygenases (PMOs) use an oxidative mechanism to break the glycosidic bond of polymeric carbohydrates, thereby disrupting the crystalline packing and creating new chain ends for hydrolases to depolymerize and degrade recalcitrant polysaccharides. PMOs contain a mononuclear Cu(II) center that is directly involved in C-H bond hydroxylation...
April 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29681158/proteomic-analysis-of-cancer-associated-fibroblasts-reveal-a-paracrine-role-for-mfap5-in-human-oral-tongue-squamous-cell-carcinoma
#16
Simona Principe, Salvador Mejia-Guerrero, Vladimir Ignatchenko, Ankit Sinha, Alex Ignatchenko, Wei Shi, Keira Pereira, Susie Su, Shao Hui Huang, Brian O'Sullivan, Wei Xu, David Goldstein, Ilan Weinreb, Laurie Ailles, Fei-Fei Liu, Thomas Kislinger
Bidirectional communication between cells and their microenvironment is crucial for both normal tissue homeostasis and tumor growth. During the development of oral tongue squamous cell carcinoma (OTSCC), cancer-associated fibroblasts (CAFs) create a supporting niche by maintaining a bidirectional crosstalk with cancer cells, mediated by classically secreted factors and various nanometer-sized vesicles, termed as extracellular vesicles (EVs). To better understand the role of CAFs within the tumor stroma and elucidate the mechanism by which secreted proteins contribute to OTSCC progression, we isolated and characterized patient-derived CAFs from resected tumors with matched adjacent tissue fibroblasts (AFs)...
April 22, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29674683/amino-acid-signature-in-human-melanoma-cell-lines-from-different-disease-stages
#17
Christine Wasinger, Alexandra Hofer, Oliver Spadiut, Martin Hohenegger
Cancer cells rewire metabolism to sustain high proliferation rates. Beside glycolysis and glutaminolysis, amino acids substitute as energy source, feed fatty acid biosynthesis and represent part of the secretome of transformed cells, including melanoma. We have therefore investigated acetate, pyruvate and the amino acid composition of the secretome of human melanoma cells representing the early slow (WM35, WM278, WM793b and VM21) and metastatic fast (A375, 518a2, 6F and WM8) growth phase in order to identify possible signalling components within these profiles...
April 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29669603/genomics-analysis-of-aphanomyces-spp-identifies-a-new-class-of-oomycete-effector-associated-with-host-adaptation
#18
Elodie Gaulin, Michiel J C Pel, Laurent Camborde, Hélène San-Clemente, Sarah Courbier, Marie-Alexane Dupouy, Juliette Lengellé, Marine Veyssiere, Aurélie Le Ru, Frédéric Grandjean, Richard Cordaux, Bouziane Moumen, Clément Gilbert, Liliana M Cano, Jean-Marc Aury, Julie Guy, Patrick Wincker, Olivier Bouchez, Christophe Klopp, Bernard Dumas
BACKGROUND: Oomycetes are a group of filamentous eukaryotic microorganisms that have colonized all terrestrial and oceanic ecosystems, and they include prominent plant pathogens. The Aphanomyces genus is unique in its ability to infect both plant and animal species, and as such exemplifies oomycete versatility in adapting to different hosts and environments. Dissecting the underpinnings of oomycete diversity provides insights into their specificity and pathogenic mechanisms. RESULTS: By carrying out genomic analyses of the plant pathogen A...
April 18, 2018: BMC Biology
https://www.readbyqxmd.com/read/29651164/genome-wide-analysis-of-the-transition-to-pathogenic-lifestyles-in-magnaporthales-fungi
#19
Ning Zhang, Guohong Cai, Dana C Price, Jo Anne Crouch, Pierre Gladieux, Bradley Hillman, Chang Hyun Khang, Marc-Henri LeBrun, Yong-Hwan Lee, Jing Luo, Huan Qiu, Daniel Veltri, Jennifer H Wisecaver, Jie Zhu, Debashish Bhattacharya
The rice blast fungus Pyricularia oryzae (syn. Magnaporthe oryzae, Magnaporthe grisea), a member of the order Magnaporthales in the class Sordariomycetes, is an important plant pathogen and a model species for studying pathogen infection and plant-fungal interaction. In this study, we generated genome sequence data from five additional Magnaporthales fungi including non-pathogenic species, and performed comparative genome analysis of a total of 13 fungal species in the class Sordariomycetes to understand the evolutionary history of the Magnaporthales and of fungal pathogenesis...
April 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29614953/transcriptome-and-secretome-analysis-of-aspergillus-fumigatus-in-the-presence-of-sugarcane-bagasse
#20
Paula Fagundes de Gouvêa, Aline Vianna Bernardi, Luis Eduardo Gerolamo, Emerson de Souza Santos, Diego Mauricio Riaño-Pachón, Sergio Akira Uyemura, Taisa Magnani Dinamarco
BACKGROUND: Sugarcane bagasse has been proposed as a lignocellulosic residue for second-generation ethanol (2G) produced by breaking down biomass into fermentable sugars. The enzymatic cocktails for biomass degradation are mostly produced by fungi, but low cost and high efficiency can consolidate 2G technologies. A. fumigatus plays an important role in plant biomass degradation capabilities and recycling. To gain more insight into the divergence in gene expression during steam-exploded bagasse (SEB) breakdown, this study profiled the transcriptome of A...
April 3, 2018: BMC Genomics
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