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HES1 Inhibitor

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https://www.readbyqxmd.com/read/29323051/notch-pathway-inhibitor-dapt-enhances-atoh1-activity-to-generate-new-hair-cells-in-situ-in-rat-cochleae
#1
Wen-Wei Luo, Zhao Han, Dong-Dong Ren, Xin-Wei Wang, Fang-Lu Chi, Juan-Mei Yang
Atoh1 overexpression in cochlear epithelium induces new hair cell formation. Use of adenovirus-mediated Atoh1 overexpression has mainly focused on the rat lesser epithelial ridge and induces ectopic hair cell regeneration. The sensory region of rat cochlea is difficult to transfect, thus new hair cells are rarely produced in situ in rat cochlear explants. After culturing rat cochleae in medium containing 10% fetal bovine serum, adenovirus successfully infected the sensory region as the width of the supporting cell area was significantly increased...
December 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29298131/a-systematic-review-of-p53-regulation-of-oxidative-stress-in-skeletal-muscle
#2
Kaitlyn Beyfuss, David A Hood
BACKGROUND: p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis. METHODS: A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases...
January 3, 2018: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/29251326/isoliquiritigenin-inhibits-the-proliferation-and-induces-the-differentiation-of-human-glioma-stem-cells
#3
Yuliang Lin, Hongjun Sun, Ying Dang, Zhiyun Li
Glioma stem cells (GSCs) have been proven to be resistant to various therapeutic strategies, such as temozolomide chemotherapy and radiotherapy, leading to glioma recurrence. Isoliquiritigenin (ISL), a menber of the flavonoids isolated from liquorice has been found to be a potent stimulator of cell differentiation and has potential application for treating various types of cancer including human brain glioma. However, the antitumor activity of ISL on GSCs and the signaling pathway underlying its therapeutic effects are poorly understood...
February 2018: Oncology Reports
https://www.readbyqxmd.com/read/29230705/crosstalk-between-tlr4-and-notch1-signaling-in-the-iga-nephropathy-during-inflammatory-response
#4
Xuxiang Sheng, Xiaoyan Zuo, Xihui Liu, Yang Zhou, Xia Sun
PURPOSE: IgA nephropathy (IgAN) is an immune complex-mediated disease involved in the kidney disease. Recent studies have revealed that Notch signaling-related genes are aberrantly expressed in various cell types and maybe associate with inflammation-induced carcinogenesis. The aim of our study was to investigate the function of Notch1 in the inflammatory response of IgAN. METHODS: The expression of Notch1, Jagged1 and NICD1 in 52 IgAN renal tissues and 20 control renal tissues was first determined using quantitative real-time PCR and Western blot...
December 11, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/29206299/microrna-137-promotes-endothelial-progenitor-cell-proliferation-and-angiogenesis-in-cerebral-ischemic-stroke-mice-by-targeting-nr4a2-through-the-notch-pathway
#5
Xing-Li Liu, Gang Wang, Wei Song, Wei-Xin Yang, Jian Hua, Liang Lyu
Cerebral ischemic stroke (CIS) is one of the common causes of death and disability worldwide. This study aims to investigate effect of miR-137 on endothelial progenitor cells and angiogenesis in CIS by targeting NR4A2 via the Notch pathway. Brain tissues were extracted from CIS and normal mice. Immunohistochemistry was used to determine positive rate of NR4A2 expression. Serum VEGF, Ang, HGF and IκBα levels were determined by ELISA. RT-qPCR and western blotting were used to determine expression of related factors...
December 5, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29175872/notch-pathway-inhibition-targets-chemoresistant-insulinoma-cancer-stem-cells
#6
Ylenia Capodanno, Floryne O Buishand, Lisa Y Pang, Jolle Kirpensteijn, Jan A Mol, David J Argyle
Insulinomas (INS) are the most common neuroendocrine pancreatic tumours in humans and dogs. The long-term prognosis for malignant INS is still poor due to a low success rate of the current treatment modalities, particularly chemotherapy. A better understanding of the molecular processes underlying the development and progression of INS is required to develop novel targeted therapies. Cancer stem cells (CSCs) are thought to be critical for the engraftment and chemoresistance of many tumours, including INS. This study was aimed to characterise and target INS CSCs in order to develop novel targeted therapies...
November 24, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29175286/microrna-34a-modulates-the-notch-signaling-pathway-in-mice-with-congenital-heart-disease-and-its-role-in-heart-development
#7
Kai-Hong Wu, Qian-Ru Xiao, Yu Yang, Jia-Li Xu, Feng Zhang, Chao-Ming Liu, Zhao-Ming Zhang, Ying-Qi Lu, Ning-Ping Huang
The objective of the study was to elucidate the mechanism by which microRNA-34a (miR-34a) influences heart development and participates in the pathogenesis of congenital heart disease (CHD) by targeting NOTCH-1 through the Notch signaling pathway. Forty D7 pregnant mice were recruited for the purposes of the study and served as the CHD (n=20, successfully established as CHD model) and normal (n=20) groups. The positive expression of the NOTCH-1 protein was evaluated by means of immunohistochemistry. Embryonic endocardial cells (ECCs) were assigned into the normal, blank, negative control (NC), miR-34a mimics, miR-34a inhibitors, miR-34a inhibitors+siRNA-NOTCH-1, siRNA-NOTCH-1, miR-34a mimics+NOTCH-1 OE and miR-34a mimics+crispr/cas9 (mutant NOTCH-1) groups...
November 22, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29169413/-notch1-signaling-participates-in-the-release-of-inflammatory-mediators-in-mouse-raw264-7-cells-via-activating-nf-%C3%AE%C2%BAb-pathway
#8
Hongwei Zhao, Che Nan Xu, Chao Huang, Jinzhi Jiang, Liangchang Li
Objective To study the effect of Notch1 signaling on the release of inflammatory mediators in lipopolysaccharide (LPS)-induced macrophages and the related mechanism. Methods The expressions of Notch1 and hairy and enhancer of split 1 (Hes1) mRNAs were investigated by reverse transcription PCR (RT-PCR) in mouse RAW264.7 cells after stimulated with 100 ng/mL LPS for 8 hours. Prior to stimulation with LPS, mouse RAW264.7 cells were treated with DAPT (10 μmol/L), an inhibitor of Notch1 signaling, for 1 hour. The concentrations of tumor necrosis factor (TNF-α), interleukin 1β (IL-1β), IL-6, nitric oxide (NO) and prostaglandin E2 (PGE2) in cell culture media were measured by ELISA...
October 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/29123981/coculture-of-endothelial-progenitor-cells-and-mesenchymal-stem-cells-enhanced-their-proliferation-and-angiogenesis-through-pdgf-and-notch-signaling
#9
Tangzhao Liang, Lei Zhu, Wenling Gao, Ming Gong, Jianhua Ren, Hui Yao, Kun Wang, Dehai Shi
The beneficial effects of combined use of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) on tissue repair and regeneration after injury have been demonstrated, but the underlying mechanism remains incompletely understood. This study aimed to investigate the effects of direct contact coculture of human bone marrow-derived EPCs (hEPCs)/human bone marrow-derived MSCs (hMSCs) on their proliferation and angiogenic capacities and the underlying mechanism. hEPCs and hMSCs were cocultured in a 2D mixed monolayer or a 3D transwell membrane cell-to-cell coculture system...
November 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/29100034/down-regulation-of-notch-signaling-pathway-reverses-the-th1-th2-imbalance-in-tuberculosis-patients
#10
Qifeng Li, Hui Zhang, Liang Yu, Chao Wu, Xinhui Luo, He Sun, Jianbing Ding
Th1/Th2 imbalance to Th2 is of significance in the peripheral immune responses in Tuberculosis (TB) development. However, the mechanisms for Th1/Th2 imbalance are still not well determined. Notch signaling pathway is involved in the peripheral T cell activation and effector cell differentiation. However, whether it affects Th1/Th2 imbalance in TB patients is still not known. Here, we used γ-secretase inhibitor (DAPT) to treat the peripheral blood mononuclear cells (PBMCs) from healthy people or individuals with latent or active TB infection in vitro, respectively...
October 28, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29096354/notch-signaling-pathway-dampens-tumor-infiltrating-cd8-t-cells-activity-in-patients-with-colorectal-carcinoma
#11
Weifeng Yu, Yanjun Wang, Peng Guo
CD8(+) T cells play critical role in controlling the metastasis and prognosis of cancer. Controversy remains as to the contribution of Notch signaling pathway in modulation of CD8(+) T cells activity and development of tumorigenesis. Thus, the aim of the current study was to investigate the immunoregulatory role of Notch signaling pathway to peripheral and tumor-infiltrating CD8(+) T cells in patients with colorectal carcinoma. A total of 46 patients with colorectal carcinoma and 20 health individuals were enrolled, and CD8(+) T cells were purified from both peripheral bloods and carcinoma specimens...
October 30, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29061784/bmi1-inhibitors-down-regulate-notch-signaling-and-suppress-proliferation-of-acute-leukemia-cells
#12
Mika Ohtaka, Mai Itoh, Shuji Tohda
BACKGROUND/AIM: B cell-specific Moloney murine leukemia virus integration site 1 (BMI1) is up-regulated in several cancers; therefore, we investigated the effects of BMI1 inhibitors on leukemia cells. MATERIALS AND METHODS: Four acute myeloid leukemia and two T-lymphoblastic leukemia cell lines were treated with BMI1 inhibitors artemisinin, PRT4165, and PTC-209 and analyzed for cell proliferation and gene expression by microarray and immunoblotting. RESULTS: PTC-209 and PRT4165 suppressed the growth of all cell lines through apoptosis...
November 2017: Anticancer Research
https://www.readbyqxmd.com/read/29048643/novel-transduction-of-nutrient-stress-to-notch-pathway-by-rasgrp3-promotes-malignant-aggressiveness-in-human-esophageal-squamous-cell-carcinoma
#13
Ge Hu, Yuepeng Zhou, Yu Zhu, Ling Zhou, Rui Ling, Dan Wu, Lei Mi, Xuefeng Wang, Dongfang Dai, Chaoming Mao, Deyu Chen
In the process of enlarging of tumors, the dissolving tissue structures and remodeling endothelial cells for restoring gas exchange and nutritional support, further facilitate tumor cell invasion and metastasis. Activation of Ras plays a critical role in the development of esophageal squamous cell carcinoma (ESCC), but the underlying mechanisms remain poorly understood. We therefore investigated whether Ras guanyl-releasing protein 3 (RasGRP3), a Ras activator, could promote metastasis by inducing vascular regeneration and further epithelial-mesenchymal transition under nutrient stress (NS)...
September 25, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29048612/regulation-of-erk-and-akt-pathways-by-hepatitis%C3%A2-b-virus%C3%A2-x-protein-via-the-notch1-pathway-in-hepatocellular-carcinoma
#14
Bo Liao, Honghao Zhou, Huifang Liang, Changhai Li
Hepatitis B virus (HBV) is the dominant risk factor for hepatocellular carcinoma (HCC). HBV X protein (HBx) plays crucial roles in HCC carcinogenesis. HBx interferes with several signaling pathways including the Notch1 pathway in HCC. In this study, we found that Notch1 was highly expressed in HCC, especially in large HCCs. Notch1 and HBx co-localized in HCC and their levels were positively correlated with each other. Notch1 expression was more elevated in HepG2.2.15 cells than that in HepG2 cells. HBx activated the Notch1 pathway in HepG2...
September 15, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29047105/%C3%AE-secretase-inhibitor-reduces-immunosuppressive-cells-and-enhances-tumour-immunity-in-head-and-neck-squamous-cell-carcinoma
#15
Liang Mao, Zhi-Li Zhao, Guang-Tao Yu, Lei Wu, Wei-Wei Deng, Yi-Cun Li, Jian-Feng Liu, Lin-Lin Bu, Bing Liu, Ashok B Kulkarni, Wen-Feng Zhang, Lu Zhang, Zhi-Jun Sun
Immune evasion is a hallmark feature of cancer, and it plays an important role in tumour initiation and progression. In addition, tumour immune evasion severely hampers the desired antitumour effect in multiple cancers. In this study, we aimed to investigate the role of the Notch pathway in immune evasion in the head and neck squamous cell carcinoma (HNSCC) microenvironment. We first demonstrated that Notch1 signalling was activated in a Tgfbr1/Pten-knockout HNSCC mouse model. Notch signalling inhibition using a γ-secretase inhibitor (GSI-IX, DAPT) decreased tumour burden in the mouse model after prophylactic treatment...
October 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29037123/ultrafine-particle-exposure-reveals-the-importance-of-foxo1-notch-activation-complex-for-vascular-regeneration
#16
Kyung In Baek, René R Sevag Packard, Jeffrey J Hsu, Arian Saffari, Zhao Ma, Anh Phuong Luu, Andrew Pietersen, Hilary Yen, Bin Ren, Yichen Ding, Constantinos Sioutas, Rongsong Li, Tzung K Hsiai
AIMS: Redox active ultrafine particles (UFP, d < 0.2 μm) promote vascular oxidative stress and atherosclerosis. Notch signaling is intimately involved in vascular homeostasis, in which forkhead box O1 (FOXO1) acts as a co-activator of the Notch activation complex. We elucidated the importance of FOXO1/Notch transcriptional activation complex to restore vascular regeneration after UFP exposure. RESULTS: In a zebrafish model of tail injury and repair, transgenic Tg(fli1:GFP) embryos developed vascular regeneration at 3 days post amputation (dpa), whereas UFP exposure impaired regeneration (p < 0...
November 17, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29035086/notch-signaling-is-essential-for-maturation-self-renewal-and-tri-differentiation-of-in-vitro-derived-human-neural-stem-cells
#17
Katari Venkatesh, L Vinod Kumar Reddy, Salar Abbas, Madhubanti Mullick, Erfath Thanjeem Begum Moghal, Janardhana Papayya Balakrishna, Dwaipayan Sen
Although neural stem cells (NSCs) have potential applications in treating neurological disorders, much still needs to be understood about the differentiation biology for their successful clinical translation. In this study, we aimed at deriving NSCs from human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) and explored the role of Notch signaling in the differentiation process. The hUCB-MSCs were characterized as per guidelines of the International Society of Cellular Therapy. NSCs were successfully generated from hUCB-MSCs by using epidermal and fibroblast growth factors under serum-free conditions...
October 16, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28959362/inhibition-of-hes1-enhances-lapatinib-sensitivity-in-gastric-cancer-sphere-forming-cells
#18
Luchun Li, Yan Li, Lulu Wang, Zhijuan Wu, Huiwen Ma, Jianghe Shao, Dairong Li, Huiqing Yu, Weiqi Nian, Donglin Wang
It has been considered that the neurogenic locus notch homolog protein (Notch) signaling pathway serves an essential role in cellular differentiation, proliferation and apoptosis. However, the function of the Notch signaling pathway in gastric cancer stem cells (GCSCs) and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) sensitivity remains unclear. The present study aimed to delineate the role of the Notch1 signaling pathway in GCSCs and lapatinib sensitivity. Sphere-forming cells were separated from human gastric cancer MKN45 parental cells...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28941308/in-vivo-and-in-vitro-effects-of-microrna-124-on-human-gastric-cancer-by-targeting-jag1-through-the-notch-signaling-pathway
#19
Hai-Juan Xiao, Qing Ji, Lin Yang, Ren-Ting Li, Cheng Zhang, Jun-Ming Hou
In this study, we aim to determine the function of miR-124 on gastric cancer (GC) cells and the underlying mechanism that involves jaddeg1 (JAG1) and the Notch signaling pathway. GC tissues and adjacent tissues from 100 patients suffering from GC were selected. GC SGC-7901 and AGS cells were selected and grouped into control, mimic-NC, miR-124 mimic, inhibitor-NC, miR-124 inhibitor, and miR-124 inhibitor + si-JAG1 groups. RT-qPCR and a western blotting assay were conducted to detect the expression of miR-124, JAG1 and Notch signaling pathway-related proteins (NICD, HES1 and HES5)...
September 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28881812/a-combination-of-valproic-acid-sodium-salt-chir99021-e-616452-tranylcypromine-and-3-deazaneplanocin-a-causes-stem-cell-like-characteristics-in-cancer-cells
#20
Shuang Sha, Yuanfen Zhai, Chengzhao Lin, Heyong Wang, Qing Chang, Shuang Song, Mingqiang Ren, Gentao Liu
Many studies are based on the hypothesis that recurrence and drug resistance in lung carcinoma are due to a subpopulation of cancer stem-like cells (CSLCs) in solid tumors. Therefore it is crucial to screen for and recognize lung CSLCs. In this study, we stimulated non-small cell lung cancer (NSCLC) A549 cells to display stem cell-like characteristics using a combination of five small molecule compounds. The putative A549 stem cells activated an important CSLC marker, CD133 protein, as well multiple CSLC-related genes including ATP-binding cassette transporter G2 (ABCG2), C-X-C chemokine receptor type 4 (CXCR4), NESTIN, and BMI1...
August 8, 2017: Oncotarget
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