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Daisong Wang, Chunye Liu, Jingqiang Wang, Yingying Jia, Xin Hu, Hai Jiang, Zhi-Ming Shao, Yi Arial Zeng
The protein C receptor (PROCR) has emerged as a stem cell marker in several normal tissues and has also been implicated in tumor progression. However, the functional role of PROCR and the signaling mechanisms downstream of PROCR remain poorly understood. Here, we dissected the PROCR signaling pathways in breast cancer cells. Combining protein array, knockdown, and overexpression methods, we found that PROCR concomitantly activates multiple pathways. We also noted that PROCR-dependent ERK and PI3k-Akt-mTOR signaling pathways proceed through Src kinase and transactivation of insulin-like growth factor 1 receptor (IGF-1R)...
January 26, 2018: Journal of Biological Chemistry
N C Olson, L M Raffield, L A Lange, E M Lange, W T Longstreth, G Chauhan, S Debette, S Seshadri, A P Reiner, R P Tracy
ESSENTIALS: Essentials A fraction of coagulation factor VII circulates in blood as an activated protease (FVIIa). We evaluated FVIIa and FVIIa-antithrombin (FVIIa-AT) levels in the Cardiovascular Health Study. Polymorphisms in the F7 and PROCR loci were associated with FVIIa and FVIIa-AT levels. FVIIa may be an ischemic stroke risk factor in older adults and FVIIa-AT may assess mortality risk. SUMMARY: Background A fraction of coagulation factor (F) VII circulates as an active protease (FVIIa)...
January 2018: Journal of Thrombosis and Haemostasis: JTH
Wei Liu, Ting Wu, Xiaobing Dong, Yi Arial Zeng
Wnt/β-catenin signaling is instrumental for the development of mammary gland and the properties of mammary stem cells (MaSCs). The Wnt signaling downstream effectors that engage in regulating MaSCs have not been extensively studied. Here, we report that Neuropilin-1 (Nrp1) expression is induced by Wnt/β-catenin signaling in MaSCs, and its function is critical for the activity of MaSCs. Nrp1 is particularly expressed in MaSCs that are marked by the expression of Protein C Receptor (Procr). Knockdown of Nrp1 by shRNA diminishes MaSCs' in vitro colony formation and in vivo mammary gland reconstitution ability...
September 8, 2017: Scientific Reports
Qing Cissy Yu, Wenqian Song, Dengwen Lai, Yi Arial Zeng
Endothelial cells (ECs) are the fundamental building blocks of the vascular architecture and mediate vascular growth and remodeling to ensure proper vessel development and homeostasis. However, studies on endothelial lineage hierarchy remain elusive due to the lack of tools to gain access as well as to directly evaluate their behavior in vivo. To address this shortcoming, a new tissue model to study angiogenesis using the mammary fat pad has been developed. The mammary gland develops mostly in the postnatal stages, including puberty and pregnancy, during which robust epithelium proliferation is accompanied by extensive vascular remodeling...
August 3, 2017: Journal of Visualized Experiments: JoVE
Qiu Yan, Zhong Xiaorong, Zhang Zhang, Wei Bing, Ye Feng, Bu Hong
Recently, PROCR is reported to play an important role in cell growth, apoptosis, proliferation and tumor relapse. Some researchers thought that PROCR(+) cells had cancer stem cell ability, which might contribute to progressive behavior in breast cancer. Our study was to assess the expression of PROCR in invasive ductal carcinoma tissues with their prognostic implications. We enrolled formalin fixed paraffin-embedded tumor tissues of 271 patients diagnosed as invasive ductal breast cancer with clinical stage II or III into our study...
July 1, 2017: Pathology, Research and Practice
Joanna M M Howson, Wei Zhao, Daniel R Barnes, Weang-Kee Ho, Robin Young, Dirk S Paul, Lindsay L Waite, Daniel F Freitag, Eric B Fauman, Elias L Salfati, Benjamin B Sun, John D Eicher, Andrew D Johnson, Wayne H H Sheu, Sune F Nielsen, Wei-Yu Lin, Praveen Surendran, Anders Malarstig, Jemma B Wilk, Anne Tybjærg-Hansen, Katrine L Rasmussen, Pia R Kamstrup, Panos Deloukas, Jeanette Erdmann, Sekar Kathiresan, Nilesh J Samani, Heribert Schunkert, Hugh Watkins, Ron Do, Daniel J Rader, Julie A Johnson, Stanley L Hazen, Arshed A Quyyumi, John A Spertus, Carl J Pepine, Nora Franceschini, Anne Justice, Alex P Reiner, Steven Buyske, Lucia A Hindorff, Cara L Carty, Kari E North, Charles Kooperberg, Eric Boerwinkle, Kristin Young, Mariaelisa Graff, Ulrike Peters, Devin Absher, Chao A Hsiung, Wen-Jane Lee, Kent D Taylor, Ying-Hsiang Chen, I-Te Lee, Xiuqing Guo, Ren-Hua Chung, Yi-Jen Hung, Jerome I Rotter, Jyh-Ming J Juang, Thomas Quertermous, Tzung-Dau Wang, Asif Rasheed, Philippe Frossard, Dewan S Alam, Abdulla Al Shafi Majumder, Emanuele Di Angelantonio, Rajiv Chowdhury, Yii-Der Ida Chen, Børge G Nordestgaard, Themistocles L Assimes, John Danesh, Adam S Butterworth, Danish Saleheen
Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls...
July 2017: Nature Genetics
Iman Fares, Jalila Chagraoui, Bernhard Lehnertz, Tara MacRae, Nadine Mayotte, Elisa Tomellini, Léo Aubert, Philippe P Roux, Guy Sauvageau
A small subset of human cord blood CD34+ cells express endothelial protein C receptor (EPCR/CD201/PROCR) when exposed to the hematopoietic stem cell (HSC) self-renewal agonist UM171. In this article, we show that EPCR-positive UM171-treated cells, as opposed to EPCR-negative cells, exhibit robust multilineage repopulation and serial reconstitution ability in immunocompromised mice. In contrast to other stem cell markers, such as CD38, EPCR expression is maintained when cells are introduced in culture, irrespective of UM171 treatment...
June 22, 2017: Blood
C Mary Schooling, Yi Zhong
Protein C is an environmentally modifiable anticoagulant, which protects against venous thrombosis, whether it also protects against ischaemic heart disease is unclear, based on observational studies and relatively small genetic studies. It was our study aim to clarify the role of protein C in ischaemic heart disease. The risk of coronary artery disease/myocardial infarction (CAD/MI) was assessed according to genetically predicted protein C in very large studies. Associations with lipids and diabetes were similarly assessed to rule out effects via traditional cardiovascular disease risk factors...
January 26, 2017: Thrombosis and Haemostasis
Yasuhiro Kishi, Takaaki Kondo, Sheng Xiao, Nir Yosef, Jellert Gaublomme, Chuan Wu, Chao Wang, Norio Chihara, Aviv Regev, Nicole Joller, Vijay K Kuchroo
Th17 cells are key players in defense against pathogens and maintaining tissue homeostasis, but also act as critical drivers of autoimmune diseases. Based on single-cell RNA-seq profiling of pathogenic versus nonpathogenic Th17 cells, we identified protein C receptor (PROCR) as a cell surface molecule expressed in covariance with the regulatory module of Th17 cells. Although PROCR expression in T cells was controlled by the cooperative action of the Th17 lineage-specific transcription factors RORγt, IRF4, and STAT3, PROCR negatively regulated Th17 differentiation...
October 17, 2016: Journal of Experimental Medicine
O Brew, M H F Sullivan, A Woodman
Pre-eclampsia (PE) is a serious multi-factorial disorder of human pregnancy. It is associated with changes in the expression of placental genes. Recent transcription profiling of placental genes with microarray analyses have offered better opportunities to define the molecular pathology of this disorder. However, the extent to which placental gene expression changes in PE is not fully understood. We conducted a systematic review of published PE and normal pregnancy (NP) control placental RNA microarrays to describe the similarities and differences between NP and PE placental gene expression, and examined how these differences could contribute to the molecular pathology of the disease...
2016: PloS One
Shiri Gur-Cohen, Tsvee Lapidot
Generation and growth of the blood vasculature network is a highly synchronized process, requiring coordinated efforts of endothelial cells and pericytes to maintain blood vessel integrity and regeneration. In a recent paper published in Cell Research, Yu et al. identified and characterized bipotent Procr-expressing vascular endothelial stem cells, which give rise to both endothelial cells and pericytes.
October 2016: Cell Research
P Suchon, F Al Frouh, M Ibrahim, G Sarlon, G Venton, M-C Alessi, D-A Trégouët, P-E Morange
Identifying women at risk of venous thrombosis (VT) under combined oral contraceptives (COC) is a major public health issue. The aim of this study was to investigate in COC users the impact on disease of genetic polymorphisms recently identified to associate with VT risk in the general population. Nine polymorphisms located on KNG1, F11, F5, F2, PROCR, FGG, TSPAN and SLC44A2 genes were genotyped in a sample of 766 patients and 464 controls as part of the PILGRIM (PILl Genetic Risk Monitoring) study. Cases were women who experienced an episode of documented VT during COC use, while controls were women with no history of VT using COC at the time of inclusion...
January 2017: Clinical Genetics
Qing Cissy Yu, Wenqian Song, Daisong Wang, Yi Arial Zeng
Vascular growth and remodeling are dependent on the generation of new endothelial cells from stem cells and the involvement of perivascular cells to maintain vessel integrity and function. The existence and cellular identity of vascular endothelial stem cells (VESCs) remain unclear. The perivascular pericytes in adult tissues are thought to arise from the recruitment and differentiation of mesenchymal progenitors during early development. In this study, we identified Protein C receptor-expressing (Procr+ ) endothelial cells as VESCs in multiple tissues...
October 2016: Cell Research
Wei-Ching Chen, Chih-Yang Wang, Yu-Hsuan Hung, Tzu-Yang Weng, Meng-Chi Yen, Ming-Derg Lai
Dysregulated lipid metabolism contributes to cancer progression. Our previous study indicates that long-chain fatty acyl-Co A synthetase (ACSL) 3 is essential for lipid upregulation induced by endoplasmic reticulum stress. In this report, we aimed to identify the role of ACSL family in cancer with systematic analysis and in vitro experiment. We explored the ACSL expression using Oncomine database to determine the gene alteration during carcinogenesis and identified the association between ACSL expression and the survival of cancer patient using PrognoScan database...
2016: PloS One
Stefano Giuliani, Yew-Wei Tan, Dongling Zheng, Evmorfia Petropoulou, Ali Sohail, Sarah Bradley, Justin Richards, Nigel Kennea, Yalda Jamshidi
OBJECTIVES: Coagulopathy and mesenteric thrombosis are common in premature neonates with necrotizing enterocolitis (NEC). This pilot study aimed to investigate the hypothesis that there are changes in the gene expression related to the coagulation and anticoagulation systems in NEC. METHODS: Consecutive neonates (n = 11) with NEC (Bell stages 2-3) were recruited. Two comparison groups, matched for birth weight and corrected gestational age, were selected based on the absence of inflammation and coagulopathy (healthy control, n = 10), or the presence of a confirmed blood infection (sepsis control, n = 12)...
December 2016: Journal of Pediatric Gastroenterology and Nutrition
Elizabeth A Staiger, Chia T Tseng, Donald Miller, Jennifer M Cassano, Lubna Nasir, Dorian Garrick, Samantha A Brooks, Douglas F Antczak
The common equine skin tumors known as sarcoids have been causally associated with infection by bovine papillomavirus (BPV). Additionally, there is evidence for host genetic susceptibility to sarcoids. We investigated the genetic basis of susceptibility to sarcoid tumors on a cohort of 82 affected horses and 270 controls genotyped on a genome-wide platform and two custom panels. A Genome Wide Association Study (GWAS) identified candidate regions on six chromosomes. Bayesian probability analysis of the same dataset verified only the regions on equine chromosomes (ECA) 20 and 22...
August 15, 2016: International Journal of Cancer. Journal International du Cancer
David A Hinds, Alfonso Buil, Daniel Ziemek, Angel Martinez-Perez, Rainer Malik, Lasse Folkersen, Marine Germain, Anders Mälarstig, Andrew Brown, Jose Manuel Soria, Martin Dichgans, Nan Bing, Anders Franco-Cereceda, Juan Carlos Souto, Emmanouil T Dermitzakis, Anders Hamsten, Bradford B Worrall, Joyce Y Tung, Maria Sabater-Lleal
Thrombotic diseases are among the leading causes of morbidity and mortality in the world. To add insights into the genetic regulation of thrombotic disease, we conducted a genome-wide association study (GWAS) of 6135 self-reported blood clots events and 252 827 controls of European ancestry belonging to the 23andMe cohort of research participants. Eight loci exceeded genome-wide significance. Among the genome-wide significant results, our study replicated previously known venous thromboembolism (VTE) loci near the F5, FGA-FGG, F11, F2, PROCR and ABO genes, and the more recently discovered locus near SLC44A2 In addition, our study reports for the first time a genome-wide significant association between rs114209171, located upstream of the F8 structural gene, and thrombosis risk...
May 1, 2016: Human Molecular Genetics
Sarah K C Cheung, Po-Kai Chuang, Han-Wen Huang, Wendy W Hwang-Verslues, Candy Hsin-Hua Cho, Wen-Bin Yang, Chia-Ning Shen, Michael Hsiao, Tsui-Ling Hsu, Chuan-Fa Chang, Chi-Huey Wong
The discovery of cancer stem cells (CSCs), which are responsible for self-renewal and tumor growth in heterogeneous cancer tissues, has stimulated interests in developing new cancer therapies and early diagnosis. However, the markers currently used for isolation of CSCs are often not selective enough to enrich CSCs for the study of this special cell population. Here we show that the breast CSCs isolated with CD44(+)CD24(-/lo)SSEA-3(+) or ESA(hi)PROCR(hi)SSEA-3(+) markers had higher tumorigenicity than those with conventional markers in vitro and in vivo...
January 26, 2016: Proceedings of the National Academy of Sciences of the United States of America
Helle Holm Hansson, Louise Turner, Line Møller, Christian William Wang, Daniel T R Minja, Samwel Gesase, Bruno Mmbando, Ib Christian Bygbjerg, Thor G Theander, John P A Lusingu, Michael Alifrangis, Thomas Lavstsen
BACKGROUND: Endothelial protein C receptor (EPCR) was recently identified as a key receptor for Plasmodium falciparum erythrocyte membrane protein 1 mediating sequestration of P. falciparum-infected erythrocytes in patients suffering from severe malaria. Soluble EPCR (sEPCR) inhibits binding of P. falciparum to EPCR in vitro and increased levels of sEPCR have been associated with the H3 haplotype of the EPCR encoding PROCR gene. It has been hypothesized that elevated sEPCR levels, possibly linked to the PROCR H3 genetic variant, may confer protection against severe forms of malaria...
2015: Malaria Journal
R Saigusa, Y Asano, T Yamashita, T Taniguchi, T Takahashi, Y Ichimura, T Toyama, A Yoshizaki, T Miyagaki, M Sugaya, S Sato
BACKGROUND: Endothelial protein C receptor (EPCR), expressed predominantly on endothelial cells, plays a critical role in the regulation of the coagulation system and also mediates various cytoprotective effects by binding and activating protein C. So far, the role of EPCR has not been studied in systemic sclerosis (SSc). OBJECTIVES: To investigate the potential contribution of EPCR to the development of SSc. METHODS: EPCR expression was examined in skin samples and cultivated dermal microvascular endothelial cells by immunostaining, immunoblotting and/or quantitative reverse-transcription polymerase chain reaction...
February 2016: British Journal of Dermatology
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