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Maria Bogdanova, Aleksandra Kostina, Katarina Zihlavnikova Enayati, Arsenii Zabirnyk, Anna Malashicheva, Kåre-Olav Stensløkken, Gareth John Sullivan, Mari-Liis Kaljusto, John-Peder Escobar Kvitting, Anna Kostareva, Jarle Vaage, Arkady Rutkovskiy
Background: Aortic valve calcification is an active proliferative process, where interstitial cells of the valve transform into either myofibroblasts or osteoblast-like cells causing valve deformation, thickening of cusps and finally stenosis. This process may be triggered by several factors including inflammation, mechanical stress or interaction of cells with certain components of extracellular matrix. The matrix is different on the two sides of the valve leaflets. We hypothesize that inflammation and mechanical stress stimulate osteogenic differentiation of human aortic valve interstitial cells (VICs) and this may depend on the side of the leaflet...
2018: Frontiers in Physiology
Valentine N Nfonsam, Landry E Nfonsam, Debbie Chen, Pamela N Omesiete, Alejandro Cruz, Raymond B Runyan, Jana Jandova
BACKGROUND: About 1.2 million new cases of colon cancer (CC) and 0.6 million deaths are reported every year, establishing CC as an important contributor to worldwide cancer morbidity and mortality. Although the overall incidence and mortality of CC have declined over the past 3 decades, the number of early-onset colon cancer ([EOCC], patients <50 y old) continues to rise alarmingly. These young patients are often diagnosed at a more advanced stage and tend to have poor survival. Our recently published data showed that the cartilage oligomeric matrix protein (COMP) is overexpressed in early-onset colon cancer patients...
January 2019: Journal of Surgical Research
Qing Zhang, Chen Wang, William A Cliby
OBJECTIVE: Mesenchymal (MES) subtype of high-grade serous ovarian cancer (HGSOC) is associated with worse outcomes including survival and resectability compared with other molecular subtypes. Molecular subtypes have historically been derived from 'tumor', consisting of both cancer and stromal cells. We sought to determine the origins of multiple MES subtype gene signatures in HGSOC. METHODS: Fifteen patients with MES subtype of HGSOC diagnosed between 2010 and 2013 were identified...
November 15, 2018: Gynecologic Oncology
Rui Zhang, Xia-Hui Lin, Min Ma, Jie Chen, Jun Chen, Dong-Mei Gao, Jie-Feng Cui, Rong-Xin Chen
BACKGROUND: Incomplete thermal ablation may induce invasiveness of hepatocellular carcinoma (HCC). Here, we investigated whether activated hepatic stellate cells (HSCs) would accelerate the progression of residual HCC after sublethal heat treatment, and thus sought to identify the potential targets. METHODS: Hepatocellular carcinoma cells were exposed to sublethal heat treatment and then cultured with the conditioned medium from activated HSCs (HSC-CM). The cell proliferation, migration, invasion and parameters of epithelial-mesenchymal transition (EMT) were analyzed...
November 6, 2018: Journal of Translational Medicine
Pornrat Kongkavitoon, Patcharavadee Butta, Anapat Sanpavat, Pattarasinee Bhattarakosol, Pattarin Tangtanatakul, Benjawan Wongprom, Pisit Tangkijvanich, Nattiya Hirankarn, Tanapat Palaga
Notch signaling is involved in both differentiation of hepatocyte progenitors and hepatocellular carcinoma (HCC). The mechanism whereby Notch signaling regulates cellular transformation in hepatocytes is still controversial. This study investigated the impact of overexpressing truncated intracellular Notch1 (NICD1) on transcriptomic profiles of immortalized human hepatocytes. RNA sequencing and gene ontology enrichment analysis revealed that extracellular matrix organization and hyaluronan biosynthesis process gene sets are among those affected by Notch hyperactivation...
November 30, 2018: Biochemical and Biophysical Research Communications
Yuqing Mo, Kan Zhang, Yuchen Feng, Lingling Yi, Yuxia Liang, Wenliang Wu, Jian-Ping Zhao, Zhenxiang Zhang, Yongjian Xu, Qinghua Hu, Jianguo He, Guohua Zhen
Serine peptidase inhibitor, clade B, member 10 (SERPINB10) expression is increased in IL-13-stimulated human bronchial epithelial cells and in a murine model of allergic airway inflammation. However, the role of SERPINB10 in asthma remains unknown. We examined the association between epithelial SERPINB10 expression and airway eosinophilia in subjects with asthma and the role of Serpinb10 in allergic airway inflammation in animal model. Epithelial SERPINB10 mRNA and protein expression were markedly increased in subjects with asthma ( n = 60) compared with healthy controls ( n = 25)...
November 1, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Pooja A Sankardas, Vamsi Lavu, Bhaskar V K S Lakakula, Suresh R Rao
AIM: The aim of the present study was to determine and compare the expression profile of periostin (POSTN), sclerostin (SOST), receptor activator nuclear factor-κB (RANK), and RANK ligand (RANKL) genes in gingival tissue samples collected from healthy gingiva (control) and severe chronic periodontitis sites. METHODS: Fifty systemically-healthy individuals was enrolled in the present case-control study. Gingival tissue samples were obtained from healthy gingiva (N = 25) and sites with severe chronic periodontitis (N = 25)...
October 29, 2018: Journal of Investigative and Clinical Dentistry
Bidur Bhandary, Qinghang Meng, Jeanne James, Hanna Osinska, James Gulick, Iñigo Valiente-Alandi, Michelle A Sargent, Md Shenuarin Bhuiyan, Burns C Blaxall, Jeffery D Molkentin, Jeffrey Robbins
Background Transforming growth factor beta ( TGF -β) is an important cytokine in mediating the cardiac fibrosis that often accompanies pathogenic cardiac remodeling. Cardiomyocyte-specific expression of a mutant αB-crystallin (Cry ABR 120G ), which causes human desmin-related cardiomyopathy, results in significant cardiac fibrosis. During onset of fibrosis, fibroblasts are activated to the so-called myofibroblast state and TGF -β binding mediates an essential signaling pathway underlying this process. Here, we test the hypothesis that fibroblast-based TGF -β signaling can result in significant cardiac fibrosis in a disease model of cardiac proteotoxicity that has an exclusive cardiomyocyte-based etiology...
October 16, 2018: Journal of the American Heart Association
Yanhua Lei, Ping Guo, Jun An, Chao Guo, Fengxiang Lu, Minglei Liu
BACKGROUND: Allergic rhinitis (AR) is the main cause of irreversible blindness in older individuals. Our study aims to identify the key genes and upstream regulators in AR. METHODS: To screen pathogenic genes of AR, an integrated analysis was performed by using the microarray datasets in AR derived from the Gene Expression Omnibus (GEO) database. The functional annotation and potential pathways of differentially expressed genes (DEGs) were further discovered by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis...
December 2018: International Journal of Pediatric Otorhinolaryngology
K Clarysse, C M Pfaff, Y Marquardt, L Huth, I Kortekaas Krohn, D Kluwig, B Lüscher, J Gutermuth, J Baron
BACKGROUND: Janus kinase (JAK) inhibition may be a promising new treatment modality for inflammatory (skin) diseases. However, little is known about direct effects of kinase inhibitors on keratinocyte differentiation and function as well as skin barrier formation. OBJECTIVE: Our aim was to address the direct impact of kinase inhibition of the JAK1/3 pathways by tofacitinib on keratinocyte immune function and barrier formation in atopic dermatitis (AD) and psoriasis...
October 25, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Binbin Yu, Kailiu Wu, Xu Wang, Jianjun Zhang, Lizhen Wang, Yingying Jiang, Xueqin Zhu, Wantao Chen, Ming Yan
Protein tyrosine kinase 7 (PTK7) and cancer-associated fibroblasts (CAFs) play important roles in cancer stemness, respectively. However, little is known about interaction between CAFs and PTK7 in cancers. In this study, we showed that PTK7 was significantly correlated with the Wnt/β-Catenin pathway and aggressive clinicopathologic features in human head and neck squamous cell carcinoma (HNSCC). Meanwhile, animal experiments showed that PTK7 enhanced chemoresistance and lung metastasis of HNSCC in vivo. In addition, co-immunoprecipitation (co-IP) assay demonstrated that POSTN secreted by CAFs was a potential upstream ligand of PTK7 which might act as a receptor...
October 22, 2018: Cell Death & Disease
Eunae You, Yun-Hyun Huh, Jieun Lee, Panseon Ko, Jangho Jeong, Seula Keum, Jaegu Kim, Ahreum Kwon, Woo Keun Song, Sangmyung Rhee
Alterations in mechanical properties in the extracellular matrix are modulated by myofibroblasts and are required for progressive fibrotic diseases. Recently, we reported that fibroblasts depleted of SPIN90 showed enhanced differentiation into myofibroblasts via increased acetylation of microtubules in the soft matrix; the mechanisms of the underlying signaling network, however, remain unclear. In this study, we determine the effect of depletion of SPIN90 on FAK/ROCK signaling modules. Transcriptome analysis of Spin90 KO mouse embryonic fibroblasts (MEF) and fibroblasts activated by TGF-β revealed that Postn is the most significantly upregulated gene...
October 20, 2018: Journal of Cellular Physiology
Hilde M Norum, Annika E Michelsen, Tove Lekva, Satish Arora, Kari Otterdal, Maria Belland Olsen, Xiang Yi Kong, Einar Gude, Arne K Andreassen, Dag Solbu, Kristjan Karason, Göran Dellgren, Lars Gullestad, Pål Aukrust, Thor Ueland
Cardiac allograft vasculopathy (CAV) causes heart failure after heart transplantation (HTx), but its pathogenesis is incompletely understood. Notch signaling, possibly modulated by everolimus (EVR), is essential for processes involved in CAV. We hypothesized that circulating Notch ligands would be dysregulated after HTx. We studied circulating delta-like Notch ligand 1 (DLL1) and periostin (POSTN) and CAV in de novo HTx recipients (n=70) randomized to standard or EVR-based, calcineurin inhibitor-free immunosuppression and in maintenance HTx recipients(n=41)...
October 12, 2018: American Journal of Transplantation
Zachary D Fox, Guihua Jiang, Kenneth K Y Ho, Kendal A Walker, Allen P Liu, Shaun M Kunisaki
BACKGROUND: The purpose of this study was to employ a novel ex vivo lung model of congenital diaphragmatic hernia (CDH) to determine how a mechanical compression affects early pulmonary development. METHODS: Day-15 whole fetal rat lungs (n = 6-12/group) from nitrofen-exposed and normal (vehicle only) dams were explanted and cultured ex vivo in compression microdevices (0.2 or 0.4 kPa) for 16 h to mimic physiologic compression forces that occur in CDH in vivo...
November 2018: Journal of Surgical Research
Tsuguhisa Nakayama, Naoki Sugimoto, Naoko Okada, Tadao Tsurumoto, Ryoto Mitsuyoshi, Shinya Takaishi, Daiya Asaka, Hiromi Kojima, Mamoru Yoshikawa, Yasuhiro Tanaka, Shin-Ichi Haruna
OBJECTIVE: Recently, JESREC score and mucosal eosinophil count have been used to diagnose eosinophilic chronic rhinosinusitis (ECRS) in Japan. However, it remains unknown whether the subtypes of CRS diagnosed by these criteria have different endotypes. In the present study, we investigated whether JESREC score and mucosal eosinophil count were appropriate for classification of CRS subgroups into endotypes. METHODS: A cross-sectional study involving 71 consecutive patients with CRS with nasal polyps (CRSwNP) and 13 control patients was performed...
September 19, 2018: Auris, Nasus, Larynx
Yoshiki Nakashima, Saifun Nahar, Chika Miyagi-Shiohira, Takao Kinjo, Zensei Toyoda, Naoya Kobayashi, Issei Saitoh, Masami Watanabe, Jiro Fujita, Hirofumi Noguchi
Liquid chromatography using a tandem mass spectrometer (LC-MS/MS) is a method of proteomic analysis. A shotgun analysis by LC-MS/MS comprehensively identifies proteins from tissues and cells with high resolution. The hepatic function of mice with acute hepatitis following the intraperitoneal administration of CCL4 was improved by the tail vein administration of the culture conditional medium (CM) of human mesenchymal stem cells from adipose tissue (hMSC-AT). In this study, a secreted protein expression analysis of hMSC-AT was performed using LC-MS/MS; 128 proteins were identified...
October 2018: Cell Transplantation
Denise E Allard, Yan Wang, Jian Joel Li, Bridget Conley, Erin W Xu, David Sailer, Caellaigh Kimpston, Rebecca Notini, Collin-Jamal Smith, Emel Koseoglu, Joshua Starmer, Xiaopei L Zeng, James F Howard, Ahmet Hoke, Steven S Scherer, Maureen A Su
Chronic inflammatory demyelinating polyneuropathy (CIDP) and Guillain-Barre syndrome (GBS) are inflammatory neuropathies that affect humans and are characterized by peripheral nerve myelin destruction and macrophage-containing immune infiltrates. In contrast to the traditional view that the peripheral nerve is simply the target of autoimmunity, we report here that peripheral nerve Schwann cells exacerbate the autoimmune process through extracellular matrix (ECM) protein induction. In a spontaneous autoimmune peripheral polyneuropathy (SAPP) mouse model of inflammatory neuropathy and CIDP nerve biopsies, the ECM protein periostin (POSTN) was upregulated in affected sciatic nerves and was primarily expressed by Schwann cells...
October 1, 2018: Journal of Clinical Investigation
Francois Potus, Charles Colin Thomas Hindmarch, Kimberly J Dunham-Snary, Jeff Stafford, Stephen L Archer
Right ventricular failure (RVF) remains the leading cause of death in pulmonary arterial hypertension (PAH). We investigated the transcriptomic signature of RVF in hemodynamically well-phenotyped monocrotaline (MCT)-treated, male, Sprague-Dawley rats with severe PAH and decompensated RVF (increased right ventricular (RV) end diastolic volume (EDV), decreased cardiac output (CO), tricuspid annular plane systolic excursion (TAPSE) and ventricular-arterial decoupling). RNA sequencing revealed 2547 differentially regulated transcripts in MCT-RVF RVs...
September 12, 2018: International Journal of Molecular Sciences
Yasutaka Mitamura, Mika Murai, Chikage Mitoma, Masutaka Furue
Systemic fibrosing or sclerotic disorders are life-threatening, but only very limited treatment modalities are available for them. In recent years, periostin (POSTN), a major extracellular matrix component, was established by several studies as a novel key player in the progression of systemic fibrotic disease. In this research, we revealed the involvement of oxidative stress in the expression of POSTN induced by TGF- β 1 and IL-13 in dermal fibroblasts. We found that the antioxidant cinnamaldehyde activated the NRF2/HMOX1 pathway...
2018: Oxidative Medicine and Cellular Longevity
Carlo Cattrini, Alessandra Rubagotti, Pier Vitale Nuzzo, Linda Zinoli, Sandra Salvi, Simona Boccardo, Marta Perachino, Luigi Cerbone, Giacomo Vallome, Maria Maddalena Latocca, Elisa Zanardi, Francesco Boccardo
BACKGROUND: Overexpression of periostin (POSTN) is associated with prostate cancer (PCa) aggressiveness. We investigated the prognostic significance of POSTN expression in tumor biopsy samples of patients with PCa. METHODS: We scored POSTN expression by immunohistochemistry analysis on 215 PCa biopsy samples using an anti-POSTN-specific antibody. A total immunoreactive score (T-IRS) was calculated by adding the POSTN staining scores of stromal and epithelial tumor cells...
July 29, 2018: Clinical Genitourinary Cancer
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