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Wnt inflammation

Khosrow Siamak Houschyar, Malcolm P Chelliah, Susanne Rein, Zeshaan N Maan, Kristian Weissenberg, Dominik Duscher, Ludwik K Branski, Frank Siemers
Despite the development of modern intensive care and new antimicrobial agents, the mortality of patients with severe sepsis and septic shock remains high. Systemic inflammation is a consequence of activation of the innate immune system. It is characterized by the intravascular release of proinflammatory cytokines and other vasoactive mediators, with concurrent activation of innate immune cells. The Wnt signaling pathway plays a critical role in the development of multicellular organisms. Abnormal Wnt signaling has been associated with many human diseases, ranging from inflammation and degenerative diseases to cancer...
March 1, 2018: International Journal of Artificial Organs
QiangYue Jiang, Lingyan Ma, RuiChao Li, JianHai Sun
The occurrence and development of colon cancer is closely related to inflammation. Therefore, this study was conducted a current retrospective research to study the effect of IL-35 (interleukin 35), a newly identified anti-infective factor, on colon cancer development. The expression of IL-35 in colon cancer samples and their adjacent normal mucosa by real-time PCR, ELISA (enzyme-linked immunosorbent assay). The effect of IL-35 on patient survival, colon cancer progression, and its effect on Wnt/β-catenine signaling pathway was also assessed...
February 23, 2018: Oncotarget
Yanhong Yang, Na Zhang, Kundong Li, Juan Chen, Lang Qiu, Jufeng Zhang
Purpose: Berberine (BBR) is a traditional Chinese medicine normally used for gastroenteritis, and recent research found that it could fight against tumors. In this study, we focused on integrating miRNA sequencing and RNA sequencing of SGC-7901 gastric cancer cells treated by BBR to elucidate their underlying mechanisms. Materials and methods: WST-1 assay and flow cytometry were used to check the effects of BBR on SGC-7901. miRNA sequencing and RNA sequencing were used to establish the miRNA and mRNA profiles of BBR-treated SGC-7901...
2018: Drug Design, Development and Therapy
Morgan Preziosi, Minakshi Poddar, Sucha Singh, Satdarshan P Monga
Activation of the Wnt/β-catenin signaling is reported in large subsets of hepatocellular carcinoma (HCC). Upregulationof Wnt genes is one contributing mechanism. In the current study, we sought to address the role of hepatocyte-derived Wnts in a model of hepatic injury, fibrosis and carcinogenesis. We subjected hepatocyte-specific Wntless knockout mice (HP-KO), unable to secrete Wnts from hepatocytes, and littermate controls (HP-CON), to diethylnitrosamine and carbon tetrachloride (DEN/CCl4) and harvested at 3, 5, and 6 months for histological and molecular analysis...
March 8, 2018: Gene Expression
Claire E Macdougall, Elizabeth G Wood, Jakob Loschko, Valeria Scagliotti, Féaron C Cassidy, Mark E Robinson, Niklas Feldhahn, Leandro Castellano, Mathieu-Benoit Voisin, Federica Marelli-Berg, Carles Gaston-Massuet, Marika Charalambous, M Paula Longhi
Visceral adipose tissue (VAT) has multiple roles in orchestrating whole-body energy homeostasis. In addition, VAT is now considered an immune site harboring an array of innate and adaptive immune cells with a direct role in immune surveillance and host defense. We report that conventional dendritic cells (cDCs) in VAT acquire a tolerogenic phenotype through upregulation of pathways involved in adipocyte differentiation. While activation of the Wnt/β-catenin pathway in cDC1 DCs induces IL-10 production, upregulation of the PPARγ pathway in cDC2 DCs directly suppresses their activation...
March 6, 2018: Cell Metabolism
Haitao Sun, Guanxin Chen, Bin Wen, Jialing Sun, Haiyan An, Jie Pang, Wei Xu, Xuemei Yang, Songqi He
Oligo-peptide I-C-F-6 is a Carapax trionycis extract component that has an effect on hepatic fibrosis, however, its mechanism of action is still unclear. This study investigated whether oligo-peptide I-C-F-6 could inhibit liver fibrosis by suppressing NF-κB and Wnt/β-catenin signaling, which are important in liver fibrosis. HSC-T6 cells were treated with oligo-peptide I-C-F-6, and rats were divided randomly into five groups: control (saline), CCl4 , CCl4 plus oligo-peptide I-C-F-6 (0.12 and 0.24 mg/kg), and CCl4 plus colchicine (0...
February 2, 2018: Journal of Pharmacological Sciences
Susanne Roser-Page, Tatyana Vikulina, Daiana Weiss, Mark M Habib, George R Beck, Roberto Pacifici, Timothy F Lane, M Neale Weitzmann
Activated lymphocytes promote inflammation and bone destruction in rheumatoid arthritis (RA), making T cells and B cells therapeutic targets. Indeed, pharmacological blockade of CD28 costimulation using CTLA-4Ig (abatacept), approved for amelioration of RA, renders T cells dormant (anergic). CTLA-4Ig also promotes bone accretion in healthy mice; surprisingly, however, this effect is driven exclusively through upregulation of bone formation, rather than anti-inflammatory effects on resorption. In the study presented here, we utilized T cell receptor β gene and Wnt-10b gene knockout mice to investigate the roles of T cells and Wnt-10b in CTLA-4Ig-induced bone anabolism...
March 3, 2018: Annals of the New York Academy of Sciences
Francesca L'Episcopo, Cataldo Tirolo, Maria F Serapide, Salvatore Caniglia, Nunzio Testa, Loredana Leggio, Silvia Vivarelli, Nunzio Iraci, Stefano Pluchino, Bianca Marchetti
Neuroinflammatory processes are recognized key contributory factors in Parkinson's disease (PD) physiopathology. While the causes responsible for the progressive loss of midbrain dopaminergic (mDA) neuronal cell bodies in the subtantia nigra pars compacta are poorly understood, aging, genetics, environmental toxicity, and particularly inflammation, represent prominent etiological factors in PD development. Especially, reactive astrocytes, microglial cells, and infiltrating monocyte-derived macrophages play dual beneficial/harmful effects, via a panel of pro- or anti-inflammatory cytokines, chemokines, neurotrophic and neurogenic transcription factors...
2018: Frontiers in Aging Neuroscience
Zhenzhen Zhang, Song Wu, Saeed Muhammad, Qian Ren, Chao Sun
Both miR-103 and 107 have been demonstrated to restrain cell proliferation, regulate lipid metabolism and inflammation. However, the effects of miR-103/107 on preadipocytes apoptosis remain unknown. In the present research, we have investigated how miR-103/107 regulated preadipocytes apoptosis. We found that miR-103/107 aggravated Endoplasmic Reticulum (ER) stress mediated apoptosis in preadipocytes. We confirmed that miR-103/107 targeted Wnt3a (WNT family member 3a) in preadipocytes. It was found that overexpressing Wnt3a resulted in suppression of ER stress mediated apoptosis, while restoration of miR-103/107 counteracted the effects of Wnt3a in preadipocytes...
February 26, 2018: Journal of Lipid Research
Xiang Li, Jianru Wang, Zhongping Zhan, Sibei Li, Zhaomin Zheng, Taiping Wang, Kuibo Zhang, Hehai Pan, Zemin Li, Nu Zhang, Hui Liu
OBJECTIVES: To investigate the molecular mechanism underlying the inflammation- related ectopic new bone formation in ankylosing spondylitis (AS). METHODS: Spinal tissues and sera were collected from patients or normal volunteers to detect the expression of Wnt proteins. An in vitro cell culture system mimicking the local inflammatory microenvironment of bone-forming sites was established to study the relationship between inflammation and Wnt expression, the regulatory mechanism of inflammation-induced Wnt expression and the role of Wnt signaling in new bone formation...
February 26, 2018: Arthritis & Rheumatology
Guillaume Courbon, Raphaëlle Lamarque, Maude Gerbaix, Robin Caire, Marie-Thérèse Linossier, Norbert Laroche, Mireille Thomas, Thierry Thomas, Laurence Vico, Hubert Marotte
Periarticular bone loss in rheumatoid arthritis (RA) is considered to be mainly related to synovial inflammation. However, strong bone loss has also described at the time of arthritis onset. Recently, a paradoxical exacerbation of joint damage was described when blocking sclerostin in various arthritis models. Thus, we aimed to determine kinetics of bone loss and its mechanisms in the adjuvant induced arthritis (AIA) rat model of RA. AIA was induced (n = 35) or not (n = 35) at day 0. In addition to well-known arthritis at day 12, we showed with 3D-imaging and histomorphometry that bone microstructural alterations occurred early from day 8 post-induction, characterized by cortical porosity and trabecular bone loss...
February 22, 2018: Scientific Reports
Francesco Boccellato, Sarah Woelffling, Aki Imai-Matsushima, Gabriela Sanchez, Christian Goosmann, Monika Schmid, Hilmar Berger, Pau Morey, Christian Denecke, Juergen Ordemann, Thomas F Meyer
OBJECTIVE: Helicobacter pylori causes life-long colonisation of the gastric mucosa, leading to chronic inflammation with increased risk of gastric cancer. Research on the pathogenesis of this infection would strongly benefit from an authentic human in vitro model. DESIGN: Antrum-derived gastric glands from surgery specimens served to establish polarised epithelial monolayers via a transient air-liquid interface culture stage to study cross-talk with H. pylori and the adjacent stroma...
February 21, 2018: Gut
Anthony Mukwaya, Anton Lennikov, Maria Xeroudaki, Pierfrancesco Mirabelli, Mieszko Lachota, Lasse Jensen, Beatrice Peebo, Neil Lagali
Inflammation in the normally immune-privileged cornea can initiate a pathologic angiogenic response causing vision-threatening corneal neovascularization. Inflammatory pathways, however, are numerous, complex and are activated in a time-dependent manner. Effective resolution of inflammation and associated angiogenesis in the cornea requires knowledge of these pathways and their time dependence, which has, to date, remained largely unexplored. Here, using a model of endogenous resolution of inflammation-induced corneal angiogenesis, we investigate the time dependence of inflammatory genes in effecting capillary regression and the return of corneal transparency...
February 14, 2018: Angiogenesis
Yanmei Zhou, Yifang Kuang, Jianhua Zhou
AIM: This study aimed to investigate the effect and mechanism of Klotho in lipopolysaccharide (LPS)-induced inflammation injury in HK-2 cells. METHODS: We established LPS-induced inflammation injury model in HK-2 cells. The LPS-induced HK-2 cells were transfected with pc-Klotho, pcDNA3.1, siKlotho or siNC. Cell viability, apoptosis and reactive oxygen species (ROS) level were detected by MTT assay, Annexin V-FITC/PI Apoptosis Detection kit and 2,7-dichlorofluorescein diacetate, respectively...
April 1, 2017: Die Pharmazie
Michele Maria Luchetti, Francesco Ciccia, Chiara Avellini, Devis Benfaremo, Giuliana Guggino, Alessia Farinelli, Monia Ciferri, Matteo Rossini, Silvia Svegliati, Tatiana Spadoni, Laura Bolognini, Giammarco Fava, Piergiorgio Mosca, Rosaria Gesuita, Edlira Skrami, Giovanni Triolo, Armando Gabrielli
OBJECTIVE: The early diagnosis of inflammatory bowel disease (IBD)-associated spondyloarthritis (SpA/IBD) in patients affected by IBD represents a major topic in clinical practice; in particular, to date there are no available serum biomarkers revealing the presence of joint inflammation in these patients. Sclerostin (SOST), an antagonist of the Wnt/β-catenin pathway, and antisclerostin-immunoglobulin G (anti-SOST-IgG) have been recently studied in patients with ankylosing spondylitis (AS) as a putative marker of disease activity...
February 1, 2018: Journal of Rheumatology
Masashi Fujita, Nagahide Matsubara, Ikuo Matsuda, Kazuhiro Maejima, Ayako Oosawa, Tomoki Yamano, Akihiro Fujimoto, Mayuko Furuta, Kaoru Nakano, Aya Oku-Sasaki, Hiroko Tanaka, Yuichi Shiraishi, Raúl Nicolás Mateos, Kenta Nakai, Satoru Miyano, Naohiro Tomita, Seiichi Hirota, Hiroki Ikeuchi, Hidewaki Nakagawa
Inflammatory bowel disease (IBD) increases the risk of colorectal cancer, known as colitis-associated cancer (CAC). It is still unclear what driver mutations are caused by chronic inflammation and lead to CAC development. To get insight into this issue, we investigated somatic alterations in CAC. We performed exome sequencing of 22 fresh CACs and targeted sequencing of 43 genes on 90 archive specimens from Japanese CAC patients, of which 58 were ulcerative colitis (UC) and 32 were Crohn's disease (CD). Consistently with the previous reports, TP53 was commonly mutated (66%) whereas APC, KRAS and SMAD4 were mutated less frequently (16%, 11% and 11%, respectively)...
January 2, 2018: Oncotarget
Li Pan, Hongli Yang, Wenqiang Tang, Cong Xu, Shuangfeng Chen, Zhen Meng, Keyi Li, Haiying Chen
Zinc-finger protein 750 (ZNF750) is the potential anti-cancer gene in oral squamous cell carcinoma (OSCC). The present study was to investigate the expression changes of ZNF750 in OSCC tissue and to reveal the induction of altered mRNA expression profiles caused by over-expressed ZNF750 in CAL-27 cell. The expression level of ZNF750 in tissue specimens from OSCC patients was detected by immunohistochemistry. Gene expression profiling was performed using Human Signal Transduction PathwayFinder RT 2 Profiler™ PCR Array...
January 2, 2018: Oncotarget
Stefan Liebner, Rick M Dijkhuizen, Yvonne Reiss, Karl H Plate, Dritan Agalliu, Gabriela Constantin
The adult quiescent blood-brain barrier (BBB), a structure organised by endothelial cells through interactions with pericytes, astrocytes, neurons and microglia in the neurovascular unit, is highly regulated but fragile at the same time. In the past decade, there has been considerable progress in understanding not only the molecular pathways involved in BBB development, but also BBB breakdown in neurological diseases. Specifically, the Wnt/β-catenin, retinoic acid and sonic hedgehog pathways moved into the focus of BBB research...
February 6, 2018: Acta Neuropathologica
Feihong Deng, Liang Peng, Zhijun Li, Gao Tan, Erbo Liang, Shengbo Chen, Xinmei Zhao, Fachao Zhi
Impaired epithelial regeneration is a crucial pathophysiological feature of ulcerative colitis (UC). Yes-associated protein (YAP1) appears to control cell proliferation and differentiation. In this study, we sought to identify the roles of YAP in intestinal epithelial cell (IEC) self-renewal, regeneration and tumorigenesis. We first observed that YAP was significantly reduced in 62.5% (45/72) of human UC tissues and it was dramatically enhanced during epithelial regeneration in a murine colitis model. Using lentiviral infection, we established a YAP-overexpression (YAPWT ) mouse model...
February 2, 2018: Cell Death & Disease
Yipeng Sui, Zun Liu, Se-Hyung Park, Sean E Thatcher, Beibei Zhu, Joseph P Fernandez, Henrik Molina, Philip A Kern, Changcheng Zhou
Mesenchymal stem cells (MSCs) can give rise to both adipocytes and osteoblasts, but the molecular mechanisms underlying MSC fate determination remain poorly understood. IκB kinase β (IKKβ), a central coordinator of inflammation and immune responses through activation of NF-κB, has been implicated as a critical molecular link between obesity and metabolic disorders. Here, we show that IKKβ can reciprocally regulate adipocyte and osteoblast differentiation of murine and human MSCs through an NF-κB-independent mechanism...
January 25, 2018: JCI Insight
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