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https://www.readbyqxmd.com/read/28436940/disruption-of-spatiotemporal-hypoxic-signaling-causes-congenital-heart-disease-in-mice
#1
Xuejun Yuan, Hui Qi, Xiang Li, Fan Wu, Jian Fang, Eva Bober, Gergana Dobreva, Yonggang Zhou, Thomas Braun
Congenital heart disease (CHD) represents the most prevalent inborn anomaly. Only a minority of CHD cases are attributed to genetic causes, suggesting a major role of environmental factors. Nonphysiological hypoxia during early pregnancy induces CHD, but the underlying reasons are unknown. Here, we have demonstrated that cells in the mouse heart tube are hypoxic, while cardiac progenitor cells (CPCs) expressing islet 1 (ISL1) in the secondary heart field (SHF) are normoxic. In ISL1+ CPCs, induction of hypoxic responses caused CHD by repressing Isl1 and activating NK2 homeobox 5 (Nkx2...
April 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28431315/effects-of-pm2-5-exposure-on-the-notch-signaling-pathway-and-immune-imbalance-in-chronic-obstructive-pulmonary-disease
#2
Xing-Yu Gu, Xu Chu, Xiao-Li Zeng, Hai-Rong Bao, Xiao-Ju Liu
Chronic Obstructive Pulmonary Disease (COPD) is associated with T lymphocytes subset (Th1/Th2, Th17/Treg) imbalance. Notch signaling pathway plays a key role in the development of the adaptive immunity. The immune disorder induced by fine particulate matter (PM2.5) is related to COPD. The aim of this study was to investigate the mechanism by which PM2.5 influences the Notch signaling pathway leading to worsening immune disorder and accelerating COPD development. A COPD mouse model was established by cigarette smoke exposure...
April 18, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28428712/notch-signaling-mediated-by-tgf-%C3%AE-smad-pathway-in-concanavalin-a-induced-liver-fibrosis-in-rats
#3
Yi Wang, Ruo-Wu Shen, Bing Han, Zhen Li, Le Xiong, Feng-Yu Zhang, Bei-Bei Cong, Bei Zhang
AIM: To explore the exact interaction between Notch and transforming growth factor (TGF)-β signaling in liver fibrosis. METHODS: We established a rat model of liver fibrosis induced by concanavalin A. Peripheral blood mononuclear cells (PBMCs) were isolated from the modeled rats, and cultured with γ-secretase inhibitor DAPT and TGF-β inhibitor for 24 h. The mRNA levels of Notch and TGF-β signaling were detected by quantitative real-time polymerase chain reaction...
April 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28423742/novel-potential-predictive-markers-of-sunitinib-outcomes-in-long-term-responders-versus-primary-refractory-patients-with-metastatic-clear-cell-renal-cell-carcinoma
#4
Javier Puente, Nuria Laínez, Marta Dueñas, María José Méndez-Vidal, Emilio Esteban, Daniel Castellano, Mónica Martinez-Fernández, Laura Basterretxea, María José Juan-Fita, Luis Antón, Luis León, Julio Lambea, Begoña Pérez-Valderrama, Sergio Vázquez, Cristina Suarez, Xavier Garcia Del Muro, Enrique Gallardo, José Pablo Maroto, M Luz Samaniego, Beatriz Suárez-Paniagua, Julián Sanz, Jesús M Paramio, Sogug Spanish Oncology Genitourinary Group
BACKGROUND: Several potential predictive markers of efficacy of targeted agents in patients with metastatic renal cell carcinoma (mRCC) have been identified. Interindividual heterogeneity warrants further investigation. PATIENTS AND METHODS: Multicenter, observational, retrospective study in patients with clear-cell mRCC treated with sunitinib. Patients were classified in two groups: long-term responders (LR) (progression-free survival (PFS)≥22 months and at least stable disease), and primary refractory (PR) (progressive disease within 3-months of sunitinib onset)...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423527/hes1-promotes-extracellular-matrix-protein-expression-and-inhibits-proliferation-and-migration-in-human-trabecular-meshwork-cells-under-oxidative-stress
#5
Linqi Xu, Yan Zhang, Ruru Guo, Wencui Shen, Yan Qi, Qingsong Wang, Zhenglong Guo, Chen Qi, Haifang Yin, Jiantao Wang
Glaucoma is the leading cause of irreversible blindness. The most prevalent form of glaucoma is primary open-angle glaucoma (POAG). Oxidative stress is one of the major pathogenic factors of the POAG, and can elicit molecular and functional changes in trabecular meshwork cells, causing increased aqueous humor outflow resistance and elevated intraocular pressure. However, the regulatory mechanisms underlying oxidative stress-induced cell phenotypic changes remain elusive. Herein, we exposed primary human trabecular meshwork cells to the oxidative stress induced by 300 μM H2O2 for 2 h, and found significantly up-regulated expression of extracellular matrix proteins and a transcription factor, hairy and enhancer of split-1 (HES1)...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416750/annonaceous-acetogenins-mediated-up-regulation-of-notch2-exerts-growth-inhibition-in-human-gastric-cancer-cells-in-vitro
#6
Yan Li, Jianbin Ye, Zhongbiao Chen, Junjie Wen, Fei Li, Pengpeng Su, Yanqing Lin, Bingxin Hu, Danlin Wu, Lijun Ning, Qi Xue, Hongxiang Gu, Yunshan Ning
BACKGROUND: Gastric cancer (GC) is a global health problem because of limited treatments and poor prognosis. Annonaceous acetogenins (ACGs) has been reported to exert anti-tumorigenic effects in cancer, yet the mechanism underlying its effects on GC remains largely unknown. Notch signaling plays a critical role in cell proliferation, differentiation and apoptosis. Therefore, it may contribute to the development of GC. This study aims to explore the role of Notch2 in ACGs' activities in GC cells...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416482/notch1-signaling-regulates-self-renewal-and-platinum-chemoresistance-of-cancer-stem-like-cells-in-human-non-small-cell-lung-cancer
#7
Yun Zhang, Wei Xu, Huiqin Guo, Yanmei Zhang, Yuexi He, Sau Har Lee, Xin Song, Xiaoyan Li, Yongqing Guo, Yunlong Zhao, Cheng Ding, Fei Ning, Yuanyuan Ma, Qun-Ying Lei, Xiaoyu Hu, Shengnan Li, Wei Guo
Cancer stem-like cells (CSC) are thought to drive tumor initiation, metastasis, relapse and therapeutic resistance, but their specific pathogenic characters in many cancers including non-small cell lung cancer (NSCLC) have yet to be well defined. Here we develop findings that the growth factor HGF promotes CSC sphere formation in NSCLC cell populations. In patient-derived sphere-forming assays (PD-SFA) with HGF, CD49f and CD104 were defined as novel markers of lung CSC (LCSC). In particular, we isolated a subpopulation of CD166(+)CD49f(hi)CD104(-)Lin(-) LCSC present in all human specimens of NSCLC examined, regardless of their histological subtypes or genetic driver mutations...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28402575/impaired-proliferation-and-differentiation-of-the-conducting-airway-epithelium-associated-with-bronchiolitis-obliterans-after-sulfur-mustard-inhalation-injury-in-rats
#8
Matthew D McGraw, Jaqueline S Rioux, Rhonda B Garlick, Raymond C Rancourt, Carl W White, Livia A Veress
RationaleSulfur mustard (SM) is a chemical warfare agent that causes chronic airway remodeling. The current study's objective was to assess for changes to the bronchiolar epithelium after SM exposure to explain its contribution to chronic airway remodeling.Materials and MethodsAdult male rats were exposed to a sub-lethal dose of SM inhalation (1.0 - 1.2 mg/kg) for 50 minutes. Histological sections of the bronchiolar epithelium were analyzed for changes using H&E, trichrome, and immunofluorescent staining for acetylated tubulin (AT) and club cell secretory protein (CCSP)...
April 11, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28400072/notch-signaling-pathway-promotes-the-development-of-ovine-ovarian-follicular-granulosa-cells
#9
Jiongjie Jing, Xiaolong Jiang, Jianwei Chen, Xiaolei Yao, Miaomiao Zhao, Pengfei Li, Yangyang Pan, Youshe Ren, Wenzhong Liu, Lihua Lyu
The Notch signaling pathway regulates cell proliferation, differentiation and apoptosis involved in development of the organs and tissues such as nervous system, cartilage, lungs, kidneys and prostate as well as the ovarian follicles. This study aimed to investigate the mRNA expression and localization of NOTCH2, as the key factor in Notch signaling pathway. This was determined by PCR, real-time PCR and immunohistochemistry. Additionally, the effects of inhibiting Notch signaling pathway with different concentrations (5μM, 10μM and 20μM) of N-[N-(3, 5-Difuorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT), an inhibitor of Notch signaling pathway, on ovine granulosa cells was determined in vitro by detecting estradiol production using enzyme linked immunosorbent assay and expressions of the genes related to the cell cycle and apoptosis using real-time polymerase chain reaction (PCR)...
March 28, 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28391634/chi3l1-regulation-of-inflammation-and-the-effects-on-osteogenesis-in-a-staphylococcus-aureus-induced-murine-model-of-osteomyelitis
#10
Xueqiu Chen, Jian Jiao, XiaoQing He, JianPing Zhang, Hai Wang, YongQing Xu, Tao Jin
Osteomyelitis is an inflammation of the bone and bone marrow that occurs as a consequence of infections mainly attributed to Staphylococcus aureus. In a previous study, we found that expression of the chitinase 3-like 1 (CHI3L1) gene affected mineralization of MC3T3-E1 cells infected with S. aureus and there was increased expression of CHI3L1 in the blood of osteomyelitis patients. In the present study, to further investigate the role of CHI3L1 in osteomyelitis, we developed an S. aureus-induced murine model of the disease...
April 8, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28386145/significance-of-stat3-signaling-in-epithelial-cell-differentiation-of-fetal-mouse-lungs
#11
Hiroki Kameyama, Shinji Kudoh, Jun Hatakeyama, Akira Matuo, Takaaki Ito
To study the significance of signal transducer and activator of transcription (Stat) 3 in lung epithelial development of fetal mice, we examined fetal mouse lungs, focusing on the expression of Clara cell secretory protein (CCSP), Forkhead box protein J1 (Foxj1), calcitonin gene-related peptide (CGRP), phosphorylated Stat3 (Tyr705), and hairy/enhancer of split (Hes) 1, and observed cultured fetal lungs upon treatment with IL-6, a Stat3 activator, or cucurbitacin I, a Stat3 inhibitor. Moreover, the interaction of Stat3 signaling and Hes1 was studied using Hes1 gene-deficient mice...
February 28, 2017: Acta Histochemica et Cytochemica
https://www.readbyqxmd.com/read/28379941/myt1l-safeguards-neuronal-identity-by-actively-repressing-many-non-neuronal-fates
#12
Moritz Mall, Michael S Kareta, Soham Chanda, Henrik Ahlenius, Nicholas Perotti, Bo Zhou, Sarah D Grieder, Xuecai Ge, Sienna Drake, Cheen Euong Ang, Brandon M Walker, Thomas Vierbuchen, Daniel R Fuentes, Philip Brennecke, Kazuhiro R Nitta, Arttu Jolma, Lars M Steinmetz, Jussi Taipale, Thomas C Südhof, Marius Wernig
Normal differentiation and induced reprogramming require the activation of target cell programs and silencing of donor cell programs. In reprogramming, the same factors are often used to reprogram many different donor cell types. As most developmental repressors, such as RE1-silencing transcription factor (REST) and Groucho (also known as TLE), are considered lineage-specific repressors, it remains unclear how identical combinations of transcription factors can silence so many different donor programs. Distinct lineage repressors would have to be induced in different donor cell types...
April 13, 2017: Nature
https://www.readbyqxmd.com/read/28351214/extremely-low-frequency-electromagnetic-field-promotes-astrocytic-differentiation-of-human-bone-marrow-mesenchymal-stem-cells-by-modulating-sirt1-expression
#13
Won-Yong Jeong, Jun-Beom Kim, Hyun-Jung Kim, Chan-Wha Kim
It has been shown that extremely low-frequency electromagnetic fields (ELFMF) affect regulation of cell fate and differentiation. Thus, the aim of this study was to investigate the role of ELFMFs in the enhancement of astrocytic differentiation. ELFMF exposure reduced the rate of proliferation and enhanced astrocytic differentiation. The ELFMF-treated cells showed increased levels of the astrocyte marker (GFAP), while those of the early neuronal marker (Nestin) and stemness marker (OCT3/4) were downregulated...
March 29, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28323899/lawsonia-intracellularis-exploits-%C3%AE-catenin-wnt-and-notch-signalling-pathways-during-infection-of-intestinal-crypt-to-alter-cell-homeostasis-and-promote-cell-proliferation
#14
Yang W Huan, Rebecca J Bengtsson, Neil MacIntyre, Jack Guthrie, Heather Finlayson, Sionagh H Smith, Alan L Archibald, Tahar Ait-Ali
Lawsonia intracellularis is an obligate intracellular bacterial pathogen that causes proliferative enteropathy (PE) in pigs. L. intracellularis infection causes extensive intestinal crypt cell proliferation and inhibits secretory and absorptive cell differentiation. However, the affected host upstream cellular pathways leading to PE are still unknown. β-catenin/Wnt signalling is essential in maintaining intestinal stem cell (ISC) proliferation and self-renewal capacity, while Notch signalling governs differentiation of secretory and absorptive lineage specification...
2017: PloS One
https://www.readbyqxmd.com/read/28286920/blockade-of-notch-signaling-promotes-acetaminophen-induced-liver-injury
#15
Longfeng Jiang, Michael Ke, Shi Yue, Wen Xiao, Youde Yan, Xiaozhao Deng, Qi-Long Ying, Jun Li, Bibo Ke
Liver injury after experimental acetaminophen treatment is mediated both by direct hepatocyte injury through a P450-generated toxic metabolite and indirectly by activated liver Kupffer cells and neutrophils. This study was designed to investigate the role of Notch signaling in the regulation of innate immune responses in acetaminophen (APAP)-induced liver injury. Using a mouse model of APAP-induced liver injury, wild-type (WT) and toll-like receptor 4 knockout (TLR4 KO) mice were injected intraperitoneally with APAP or PBS...
March 13, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28259920/identification-of-the-key-genes-implicated-in-the-transformation-of-olp-to-oscc-using-rna-sequencing
#16
Qiaozhen Yang, Bin Guo, Hongying Sun, Jie Zhang, Shangfeng Liu, Saiyin Hexige, Xuedi Yu, Xiaxia Wang
Oral lichen planus (OLP) is a chronic inflammatory disease that may transform to oral squamous cell carcinoma (OSCC), while its carcinogenesis mechanisms are not entirely clear. This study was designed to identify the important genes involved in the malignant transformation of OLP to OSCC. After RNA-sequencing, the differently expressed genes (DEGs) in OLP vs. normal and OSCC vs. normal groups, respectively, were identified by limma package in R language, and then clustering analysis were conducted by Pheatmap package in R language...
April 2017: Oncology Reports
https://www.readbyqxmd.com/read/28256007/targeting-notch-activated-m1-macrophages-attenuates-joint-tissue-damage-in-a-mouse-model-of-inflammatory-arthritis
#17
Wen Sun, Hengwei Zhang, Hua Wang, Yahui Grace Chiu, Christopher T Ritchlin, Amy Kiernan, Brendan F Boyce, Lianping Xing
Expression of Notch signaling molecules are increased in synovium from patients with rheumatoid arthritis (RA). However, it is not known which cell type(s) in RA synovium have Notch activation or if they play a pathogenetic role in RA. Here, we used Hes1-GFP/TNF-transgenic (TNF-Tg) mice to investigate the role of cells with active Notch signaling (GFP +) in RA. The number of GFP+ cells was significantly increased in synovium in Hes1-GFP/TNF-Tg mice and about 60% of them were F4/80+ macrophages expressing the inflammatory macrophage (M1) marker...
March 3, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28245235/the-role-of-the-hes1-crosstalk-hub-in-notch-wnt-interactions-of-the-intestinal-crypt
#18
Sophie K Kay, Heather A Harrington, Sarah Shepherd, Keith Brennan, Trevor Dale, James M Osborne, David J Gavaghan, Helen M Byrne
The Notch pathway plays a vital role in determining whether cells in the intestinal epithelium adopt a secretory or an absorptive phenotype. Cell fate specification is coordinated via Notch's interaction with the canonical Wnt pathway. Here, we propose a new mathematical model of the Notch and Wnt pathways, in which the Hes1 promoter acts as a hub for pathway crosstalk. Computational simulations of the model can assist in understanding how healthy intestinal tissue is maintained, and predict the likely consequences of biochemical knockouts upon cell fate selection processes...
February 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28243115/rnai-for-contactin-2-inhibits-proliferation-of-u87-glioma-stem-cells-by-downregulating-aicd-egfr-and-hes1
#19
Yang Guo, Peidong Zhang, Hongtian Zhang, Peng Zhang, Ruxiang Xu
Glioblastoma is the most common form of malignant brain tumors and has a poor prognosis. Glioma stem cells (GSCs) are thought to be responsible for the aberrant proliferation and invasion. Targeting the signaling pathways that promote proliferation in GSCs is one of the strategies for glioma treatment. In this study, we found increased expression of contactin 2 (CNTN2) and amyloid β precursor protein (APP) in U87-derived GSCs (U87-GSCs). RNA interference (RNAi) for CNTN2 downregulated the expression of APP intracellular domain (AICD), which is the proteolytic product of APP...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28240738/inflammation-induced-mirna-155-inhibits-self-renewal-of-neural-stem-cells-via-suppression-of-ccaat-enhancer-binding-protein-%C3%AE-c-ebp%C3%AE-expression
#20
Kayoko Obora, Yuta Onodera, Toshiyuki Takehara, John Frampton, Joe Hasei, Toshifumi Ozaki, Takeshi Teramura, Kanji Fukuda
Intracerebral inflammation resulting from injury or disease is implicated in disruption of neural regeneration and may lead to irreversible neuronal dysfunction. Analysis of inflammation-related microRNA profiles in various tissues, including the brain, has identified miR-155 among the most prominent miRNAs linked to inflammation. Here, we hypothesize that miR-155 mediates inflammation-induced suppression of neural stem cell (NSC) self-renewal. Using primary mouse NSCs and human NSCs derived from induced pluripotent stem (iPS) cells, we demonstrate that three important genes involved in NSC self-renewal (Msi1, Hes1 and Bmi1) are suppressed by miR-155...
February 27, 2017: Scientific Reports
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