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Secreted protein

Carlos Fernandez-Patron, Zamaneh Kassiri, Dickson Leung
Matrix metalloproteinase-2 (MMP-2) is a 72-kDa zinc- and calcium-dependent endopeptidase with intracellular and extracellular functions ranging from the modulation of extracellular matrix remodeling to cell growth and migration, angiogenesis, inflammation, and metabolism. An upregulation of MMP-2 activity has the potential to deregulate lipid metabolism through the cleavage of numerous metabolic mediators including plasma lipoproteins and cell surface receptors of lipoproteins. Paradoxically, MMP-2 deficiency induces inflammation and deregulates metabolism...
September 15, 2016: Comprehensive Physiology
Yurinskaya M M, Kochetkova O Yu, Shabarchina L I, Antonova O Yu, Suslikov A V, Evgen'ev M B, Vinokurov M G
Human heat shock protein Hsp70 was experimentally inserted into polyelectrolyte microcapsules. Encapsulated recombinant Hsp70 was studied in terms of its effects on neutrophil apoptosis, the production of reactive oxygen species, and the secretion of tumor necrosis factor alpha by promonocytic THP-1 cells. It was found that encapsulated Hsp70 effectively inhibits neutrophil apoptosis, unlike free exogenous protein used in solution. In THP-1 cells, encapsulated and free Hsp70 reduced LPS-induced tumor necrosis factor alpha production with a similar efficiency...
October 26, 2016: Cell Stress & Chaperones
Giulio Mari, Jacopo Crippa, Andrea Costanzi, Michele Mazzola, Michele Rossi, Dario Maggioni
BACKGROUND: Enhanced Recovery After Surgery (ERAS) program applied to colorectal laparoscopic surgery is well known to reduce hospitalization improving short-terms outcomes. Its goal is to minimize the surgical stress response in order to maintain the physiological homeostasis altered by surgery. However, there is little knowledge about the involved dynamics in the reduction of the surgical stress that these programs allow. The primary aim of this study was to compare the level of immune and nutritional serum investigators across surgery in patients undergoing elective colorectal laparoscopic surgery within an ERAS protocol or according to a standard care program...
October 25, 2016: Surgical Laparoscopy, Endoscopy & Percutaneous Techniques
Susmita Barman, Krishnapura Srinivasan
The cause and effect relationship between diabetes and zinc is complex and unclear. This animal study has examined the potential of zinc supplementation in beneficial modulating hyperglycemia, insulin secretion, and metabolic abnormalities associated with diabetes. The study was conducted in streptozotocin-induced diabetic rats. Groups of hyperglycemic rats were subjected to dietary interventions for 6 weeks with zinc supplementation (5 times and 10 times the normal level). Supplemental-zinc-fed diabetic groups showed significant control on hyperglycemia and hypoinsulinemia...
August 7, 2016: Canadian Journal of Physiology and Pharmacology
Ryan Pekson, Vladimir Poltoratsky, Samir Gorasiya, Sruthi Sundaram, Charles R Ashby, Ivana Vancurova, Sandra E Reznik
Previously, we have shown that N,N-dimethylacetamide (DMA) prevents inflammation-induced preterm birth in a murine model, inhibits LPS-induced increases in placental pro-inflammatory cytokines and up-regulates the anti-inflammatory cytokine Interleukin-10 (IL-10). However, DMA's mechanism of action remains to be elucidated. In the current study we investigate how DMA produces its anti-inflammatory effect. Using in vitro and ex vivo models, we show that DMA suppresses secretion of pro-inflammatory cytokines in lipopolysaccharide (LPS)-induced RAW 264...
October 24, 2016: Molecular Medicine
Vincent Kuek, Zhifan Yang, Shek Man Chim, Sipin Zhu, Huazi Xu, Siu To Chow, Jennifer Tickner, Vicki Rosen, Wendy Erber, Xiucheng Li, Qin An, Yu Qian, Jiake Xu
Angiogenesis plays an important role in bone development and remodeling and is mediated by a plethora of potential angiogenic factors. However, data regarding specific angiogenic factors that are secreted within the bone microenvironment to regulate osteoporosis is lacking. Here, we report that Nephronectin (NPNT), a member of the epidermal growth factor (EGF) repeat superfamily proteins and a homologue of EGFL6, is expressed in osteoblasts. Intriguingly, the gene expression of NPNT is reduced in the bone of C57BL/6J ovariectomised mice and in osteoporosis patients...
October 26, 2016: Scientific Reports
Carrie S Shemanko, Yingying Cong, Amanda Forsyth
The normal developmental program that prolactin generates in the mammary gland is usurped in the cancerous process and can be used out of its normal cellular context at a site of secondary metastasis. Prolactin is a pleiotropic peptide hormone and cytokine that is secreted from the pituitary gland, as well as from normal and cancerous breast cells. Experimental and epidemiologic data suggest that prolactin is associated with mammary gland development, and also the increased risk of breast tumors and metastatic disease in postmenopausal women...
October 22, 2016: International Journal of Molecular Sciences
Roy Marshal Wagner, Kamesh Sivagnanam, William Andrew Clark, Jonathan M Peterson
: C1q TNF Related Protein 3 (CTRP3) is a novel adipose tissue derived secreted factor, or adipokine, which has been linked to a number of beneficial biological effects on metabolism, inflammation, and survival signaling in a variety of tissues. However, very little is known about CTRP3 in regards to human health. The purpose of this project was to examine circulating CTRP3 levels in a clinical population, patients with symptoms requiring heart catheterization in order to identify the presence of obstructive coronary artery disease (CAD)...
2016: PeerJ
L P Mesquita, F R P Bruhn, P C Maiorka, E W Howerth
The vesicular stomatitis virus (VSV) causes encephalitis in mice when inoculated intranasally. The deer mouse (Peromyscus maniculatus), a native New World rodent, is also susceptible to VSV infection and develops similar central nervous system (CNS) lesions to those observed in other rodent species. Chemokines, such as regulated on activation, normal T-cell expressed and secreted (RANTES; CCL-5) and monocyte chemoattractant protein (MCP)-1 (CCL-2), which are important for chemotaxis and activation of inflammatory cells, are expressed during the course of VSV encephalitis...
October 22, 2016: Journal of Comparative Pathology
Hui Ren, Nigel P Birch, Vinod Suresh
Robust and reproducible in vitro models are required for investigating the pathways involved in fluid homeostasis in the human alveolar epithelium. We performed functional and phenotypic characterisation of ion transport in the human pulmonary epithelial cell lines NCI-H441 and A549 to determine their similarity to primary human alveolar type II cells. NCI-H441 cells exhibited high expression of junctional proteins ZO-1, and E-cadherin, seal-forming claudin-3, -4, -5 and Na+-K+-ATPase while A549 cells exhibited high expression of pore-forming claudin-2...
2016: PloS One
Jun Ye, Wei Chen, Zhi-Yong Wu, Jin-Hui Zhang, He Fei, Li-Wen Zhang, Ya-Hui Wang, Ya-Ping Chen, Xiao-Mei Yang
Epithelial ovarian cancer (EOC) is the major cause of deaths from gynecologic malignancies, and metastasis is the main cause of cancer related death. Collagen triple helix repeat containing-1 (CTHRC1) is a secreted protein that has the ability to inhibit collagen matrix synthesis. In this study, we found that high CTHRC1 expression was associated with poor prognosis of EOC. In vitro experiments showed that CTHRC1 promoted migration and invasion of ovarian cancer cells. CTHRC1 had no effect on ovarian cancer cells viability...
October 24, 2016: Oncology Reports
E Gregoraszczuk, M Slupecka, J Wolinski, A Hejmej, B Bilinska, E Fiedor, N Piwnicka, A Rak
This study investigated the effect of a high-fat (HF) diet on plasma adiponectin and steroid hormones levels, and the protein expression of adiponectin and its receptors, in the gonads and gonadal (periovarian and epididymal) white adipose tissue (WAT) of dams and their offspring. Female Wistar rats were fed a HF diet (30% fat) or a standard breeding (BD) diet (5% fat) during pregnancy and lactation. At 21 days of lactation, mothers and both sexes of prepubertal offspring were killed by decapitation. Plasma adiponectin, testosterone (T) and oestradiol (E2) levels were analyzed by ELISA...
August 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Hideaki Kouzaki, Koji Matsumoto, Hirotaka Kikuoka, Tomohisa Kato, Ichiro Tojima, Shino Shimizu, Hirohito Kita, Takeshi Shimizu
RATIONALE: Cystatin A and SPINK5 are endogenous protease inhibitors (EPIs) that may play key roles in epithelial barrier function. OBJECTIVE: The purpose of this study was to investigate the roles of EPIs in the pathogenesis of chronic rhinosinusitis (CRS). METHODS: We examined the expression of cystatin A and SPINK5 in the nasal epithelial cells of patients with CRS. Additionally, the in vitro effects of recombinant EPIs on the secretion of the epithelial-derived cytokines, interleukin (IL)-25, IL-33 and thymic stromal lymphopoietin (TSLP), in airway epithelial cells, and the in vivo effects of recombinant EPIs in the nasal epithelium of mice exposed to multiple airborne allergens (MAA) were examined...
October 25, 2016: American Journal of Respiratory and Critical Care Medicine
Vaibhav Sidarala, Anjan Kowluru
BACKGROUND: Glucose-stimulated insulin secretion (GSIS) from the pancreatic β-cell involves several intracellular metabolic events which lead to the translocation of insulin granules towards the membrane for fusion and release. It is well established that loss of β-cell function and decreased GSIS underlie the pathogenesis of diabetes. Evidence from several laboratories, including our own, demonstrated requisite roles of Rac1 and phagocyte-like NADPH oxidase (Nox2)-derived reactive oxygen species (ROS) in optimal function of the pancreatic β-cell, including GSIS...
October 20, 2016: Recent Patents on Endocrine, Metabolic & Immune Drug Discovery
Steven G Thomas, Natalie S Poulter, Danai Bem, Brenda Finney, Laura M Machesky, Stephen P Watson
A dynamic, properly organised actin cytoskeleton is critical for the production and haemostatic function of platelets. The Wiskott Aldrich Syndrome protein (WASp) and Actin-Related Proteins 2 & 3 Complex (Arp2/3 complex) are critical mediators of actin polymerisation and organisation in many cell types. In platelets and megakaryocytes, these proteins have been shown to be important for proper platelet production and function. The cortactin family of proteins (Cttn & HS1) are known to regulate WASp-Arp2/3-mediated actin polymerisation in other cell types and so here we address the role of these proteins in platelets using knockout mouse models...
October 25, 2016: Platelets
Ke Yu, Yuanyuan Ma, Xianxian Li, Xiangnan Wu, Wenjia Liu, Xiaoyu Li, Jiefei Shen, Hang Wang
Lipopolysaccharide (LPS) plays an important role in bone resorption, which involves numerous cytokines through various signaling pathways. RANKL and interleukin (IL)-6 are two important cytokines that are involved in bone remodeling. The aim of this study was to evaluate the effect of LPS on RANKL and IL-6 gene expression, the relationship of RANKL and IL-6, and the role of extracellular signal-regulated kinases 1/2 (ERK1/2) on IL-6 secretion induced by LPS in MLO-Y4 cells. The cells were stimulated by LPS at different concentrations (1, 10, 100, 500 and 1000 ng/ml) for different durations (0...
October 24, 2016: Cell Biology International
Balakumaran Chandrasekar, Tram Ngoc Hong, Renier A L van der Hoorn
Activity-based protein profiling (ABPP) has emerged as a powerful proteomic approach to study the active proteins in their native environment by using chemical probes that label active site residues in proteins. Traditionally, ABPP is classified as either comparative or competitive ABPP. In this protocol, we describe a simple method called convolution ABPP, which takes benefit from both the competitive and comparative ABPP. Convolution ABPP allows one to detect if a reduced signal observed during comparative ABPP could be due to the presence of inhibitors...
2017: Methods in Molecular Biology
Diana Golden, Antonina Kolmakova, Sunitha Sura, Anthony T Vella, Ani Manichaikul, Xin-Qun Wang, Suzette J Bielinski, Kent D Taylor, Yii-Der Ida Chen, Stephen S Rich, Annabelle Rodriguez
BACKGROUND: The lipoprotein scavenger receptor BI (SCARB1) rs10846744 noncoding variant is significantly associated with atherosclerotic disease independently of traditional cardiovascular risk factors. We identified a potentially novel connection between rs10846744, the immune checkpoint inhibitor lymphocyte activation gene 3 (LAG3), and atherosclerosis. METHODS: In vitro approaches included flow cytometry, lipid raft isolation, phosphosignaling, cytokine measurements, and overexpressing and silencing LAG3 protein...
October 20, 2016: JCI Insight
Toshifumi Fujiwara, Shiqiao Ye, Thiago Castro-Gomes, Caylin G Winchell, Norma W Andrews, Daniel E Voth, Kottayil I Varughese, Samuel G Mackintosh, Yunfeng Feng, Nathan Pavlos, Takashi Nakamura, Stavros C Manolagas, Haibo Zhao
Mutations of the Plekhm1 gene in humans and rats cause osteopetrosis, an inherited bone disease characterized by diminished bone resorption by osteoclasts. PLEKHM1 binds to RAB7 and is critical for lysosome trafficking. However, the molecular mechanisms by which PLEKHM1 regulates lysosomal pathways remain unknown. Here, we generated germline and conditional Plekhm1-deficient mice. These mice displayed no overt abnormalities in major organs, except for an increase in trabecular bone mass. Furthermore, loss of PLEKHM1 abrogated the peripheral distribution of lysosomes and bone resorption in osteoclasts...
October 20, 2016: JCI Insight
Yuji Nadatani, Xiaofang Huo, Xi Zhang, Chunhua Yu, Edaire Cheng, Qiuyang Zhang, Kerry B Dunbar, Arianne Theiss, Thai H Pham, David H Wang, Toshio Watanabe, Yasuhiro Fujiwara, Tetsuo Arakawa, Stuart J Spechler, Rhonda F Souza
BACKGROUND & AIMS: Microbial molecular products incite intestinal inflammation by activating Toll-like receptors (TLRs) and inflammasomes of the innate immune system. This system's contribution to esophageal inflammation is not known. Gram-negative bacteria, which dominate the esophageal microbiome in reflux esophagitis, produce lipopolysaccharide (LPS), a TLR4 ligand. TLR4 signaling produces pro-interleukin (IL)1β, pro-IL18, and NOD-like receptor protein 3 (NLRP3), which prime the NLRP3 inflammasome...
July 2016: Cellular and Molecular Gastroenterology and Hepatology
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