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notch signaling inhibitors and stimulators

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https://www.readbyqxmd.com/read/29702280/crosstalk-between-toll-like-receptor-3-and-notch-signaling-contributes-to-cd14-monocytes-activity-in-enterovirus-71-infected-hand-foot-and-mouth-disease
#1
Jie Hao, Peiling Li, Yunjiao Tian, Yanhua Wang, Suqing Li, Lina Wang, Shujun Li
Interaction between Toll-like receptor (TLR) and Notch signaling contributes to inflammatory response in nephropathy and fungicidal infection, however, the role of this crosstalk remains not fully elucidated in enterovirus 71 (EV71)-induced hand, foot, and mouth disease (HFMD). The aim of this study was to investigate the crosstalk between TLR and Notch in inflammatory regulation in EV71 infection. Thirty-seven EV-71-indcued HFMD (16 mild and 21 severe cases) and eleven normal control (NC) were enrolled. CD14+ monocytes were purified, and were stimulated with either TLR3/4 agonists [poly(I: C) or LPS] or Notch signaling inhibitor...
April 24, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29620159/foxp3-expression-is-modulated-by-tgf%C3%A2-%C3%AE-1-notch1-pathway-in-human-melanoma
#2
Eva Skarmoutsou, Valentina Bevelacqua, Fabio D' Amico, Angela Russo, Demetrios A Spandidos, Aurora Scalisi, Grazia Malaponte, Claudio Guarneri
Forkhead box protein 3 (FOXP3) transcription factor is expressed by immune cells and several human cancers and is associated with tumor aggressiveness and unfavorable clinical outcomes. NOTCH and transforming growth factor‑β (TGF‑β) protumorigenic effects are mediated by FOXP3 expression in several cancer models; however, their interaction and role in melanoma is unknown. We investigated TGF‑β‑induced FOXP3 gene expression during NOTCH1 signaling inactivation. Primary (WM35) and metastatic melanoma (A375 and A2058) cell lines and normal melanocytes (NHEM) were used...
April 4, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29599924/asiatic-acid-attenuates-lipopolysaccharide-induced-injury-by-suppressing-activation-of-the-notch-signaling-pathway
#3
Xiong Yuyun, Cheng Xi, Yin Qing, Xia Lin, Rui Ke, Sun Bingwei
Sepsis is a severe multisystem disease with high mortality rates and limited treatment options. However, advances during the last decade have opened opportunities to develop novel therapeutic strategies. The Notch signaling pathway plays a critical role in inflammation, and its inhibition offers an avenue to treat inflammatory diseases, such as sepsis. Asiatic acid (AA), a triterpenoid isolated from Centella asiatica, reportedly exerts anti-oxidant, anti-tumor, and anti-inflammatory effects, but its mechanisms remain unclear...
March 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29511449/hdac-inhibitors-suppressed-small-cell-lung-cancer-cell-growth-and-enhanced-the-suppressive-effects-of-receptor-targeting-cytotoxins-via-upregulating-somatostatin-receptor-ii
#4
Lichun Sun, Quanyong He, Cheguo Tsai, Jun Lei, Jing Chen, Lily Vienna Makcey, David H Coy
Small cell lung cancer (SCLC) is a malignant human cancer and patients have very limited benefit from traditional anticancer treatments, with a poor five-year survival rate being 10% less. In present study, we observed that Notch signalling activation induced SCLC cell growth suppression via overexpressing Notch active fragments (ICN1, ICN2, ICN3 and ICN4), implying its tumor suppressive role. The histone deacetylase (HDAC) inhibitors also displayed their suppressive effects. Valproic acid (VPA) as a HDAC inhibitor was found to suppress SCLC cell growth and cell cycle arrest at phase G1, and observed to decrease HDAC4 and increase acetylation of histone H4 (AcH4) while activating Notch signalling with an increase of Notch1, Notch target gene HES1 and p21...
2018: American Journal of Translational Research
https://www.readbyqxmd.com/read/29393429/notch-signaling-molecule-is-involved-in-the-invasion-of-miapaca2-cells-induced-by-cocl2-via-regulating-epithelial%C3%A2-mesenchymal-transition
#5
Ding-Wei Chen, Hong Wang, Ya-Fang Bao, Kun Xie
Pancreatic cancer exhibits a high mortality rate resulting from metastasis and there is currently no effective treatment strategy. Hypoxia serves an important role in cancer cells, where cellular metabolic rate is high. The underlying mechanisms that trigger hypoxia and the invasion of pancreatic cancer cells remain unknown. Investigation of the importance of hypoxia in the invasion of pancreatic cancer cells for potential, novel treatment strategies is of primary concern. Cell Counting Kit‑8 assay, invasion assay, western blotting and reverse transcription‑quantitative polymerase chain reaction were used to investigate invasion and epithelial mesenchymal transition (EMT) and the expression of Notch1 in MiaPaCa2 cells treated with cobalt II chloride (CoCl2)...
April 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29383634/soluble-delta-like-1-homolog-dlk1-stimulates-angiogenesis-through-notch1-akt-enos-signaling-in-endothelial-cells
#6
Chao-Cheng Huang, Hsiao-Mei Kuo, Pei-Chang Wu, Shih-Hsuan Cheng, Tzu-Ting Chang, Yi-Chen Chang, Mei-Lang Kung, Deng-Chyang Wu, Jiin-Haur Chuang, Ming-Hong Tai
AIM: Delta-like 1 homolog (DLK1) is a non-canonical ligand of Notch signaling, which plays a pivotal role in vascular development and tumor angiogenesis. This study aimed to elucidate the function and mechanism of DLK1 in angiogenesis. METHODS AND RESULTS: By using in situ hybridization and immunohistochemical studies, expression analysis revealed a unique vascular tropism of DLK1 in vasculature of neuroblastoma and vascular tumors. Thus, it was hypothesized that DLK1 may be cleaved and then bound to endothelial cells, thereby regulating the endothelial function...
May 2018: Angiogenesis
https://www.readbyqxmd.com/read/29378863/notch-suppression-collaborates-with-ascl1-and-lin28-to-unleash-a-regenerative-response-in-fish-retina-but-not-in-mice
#7
Fairouz Elsaeidi, Peter Macpherson, Elizabeth A Mills, Jonathan Jui, John G Flannery, Daniel Goldman
Müller glial (MG) cells in the zebrafish retina respond to injury by acquiring retinal stem-cell characteristics. Thousands of gene expression changes are associated with this event. Key among these changes is the induction of Ascl1a and Lin28a, two reprogramming factors whose expression is necessary for retina regeneration. Whether these factors are sufficient to drive MG proliferation and subsequent neuronal-fate specification remains unknown. To test this, we conditionally expressed Ascl1a and Lin28a in the uninjured retina of male and female fish...
February 28, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29333723/nandrolone-induced-nuclear-accumulation-of-myod-protein-is-mediated-by-numb-a-notch-inhibitor-in-c2c12-myoblasts
#8
Xin-Hua Liu, Rita De Gasperi, William A Bauman, Christopher P Cardozo
Signaling via the androgen receptor (AR) stimulates myogenic progenitor differentiation. In addition, myogenic differentiation factor D (MyoD) and Numb, a Notch inhibitor, play key roles in regulating myogenic differentiation. Nandrolone, an anabolic steroid, upregulates both MyoD and Numb expression in myogenic cells. However, the molecular mechanisms by which MyoD is upregulated by nandrolone are unclear. Moreover, the potential crosstalk between nandrolone, MyoD, and Numb is not well understood. With these considerations in mind, we examined the effects of nandrolone on the expression of MyoD mRNA and protein, and determined the interactions of MyoD and Numb in the presence or absence of nandrolone in differentiating C2C12 myoblasts...
January 2018: Physiological Reports
https://www.readbyqxmd.com/read/29327199/glycogen-synthase-kinase-3%C3%AE-regulates-equilibrium-between-neurogenesis-and-gliogenesis-in-rat-model-of-parkinson-s-disease-a-crosstalk-with-wnt-and-notch-signaling
#9
Sonu Singh, Akanksha Mishra, Sachi Bharti, Virendra Tiwari, Jitendra Singh, Parul, Shubha Shukla
Neurogenesis involves generation of functional newborn neurons from neural stem cells (NSCs). Insufficient formation or accelerated degeneration of newborn neurons may contribute to the severity of motor/nonmotor symptoms of Parkinson's disease (PD). However, the functional role of adult neurogenesis in PD is yet not explored and whether glycogen synthase kinase-3β (GSK-3β) affects multiple steps of adult neurogenesis in PD is still unknown. We investigated the possible underlying molecular mechanism of impaired adult neurogenesis associated with PD...
January 11, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29288204/novel-tcr-mediated-mechanisms-of-notch-activation-and-signaling
#10
Martin Peter Steinbuck, Ksenia Arakcheeva, Susan Winandy
The Notch receptor is an evolutionarily highly conserved transmembrane protein that is essential to a wide spectrum of cellular systems. Notch signaling is especially important to T cell development, and its deregulation leads to leukemia. Although not well characterized, it continues to play an integral role in peripheral T cells, in which a unique mode of Notch activation can occur. In contrast to canonical Notch activation initiated by adjacent ligand-expressing cells, TCR stimulation is sufficient to induce Notch signaling...
February 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29251326/isoliquiritigenin-inhibits-the-proliferation-and-induces-the-differentiation-of-human-glioma-stem-cells
#11
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
#12
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/29212792/differential-effects-of-alcohol-and-its-metabolite-acetaldehyde-on-vascular-smooth-muscle-cell-notch-signaling-and-growth
#13
Ekaterina Hatch, David Morrow, Weimin Liu, Paul A Cahill, Eileen M Redmond
Alcohol (EtOH) consumption can variously affect cardiovascular disease. Our aim was to compare the effects of EtOH and its primary metabolite acetaldehyde (ACT) on vascular smooth muscle Notch signaling and cell growth, which are important for atherogenesis. Human coronary artery smooth muscle cells (HCASMCs) were treated with EtOH (25 mM) or ACT (10 or 25 μM). As previously reported, EtOH inhibited Notch signaling and growth of HCASMCs. In contrast, ACT treatment stimulated HCASMC proliferation (cell counts) and increased proliferating cell nuclear antigen expression, concomitant with stimulation of Notch signaling, as determined by increased Notch receptor (N1 and N3) and target gene (Hairy-related transcription factor 1-3) mRNA levels...
January 1, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29126263/notch-signaling-regulates-differentiation-and-steroidogenesis-in-female-mouse-ovarian-granulosa-cells
#14
Rexxi D Prasasya, Kelly E Mayo
The Notch pathway is a highly conserved juxtacrine signaling mechanism that is important for many cellular processes during development, including differentiation and proliferation. Although Notch is important during ovarian follicle formation and early development, its functions during the gonadotropin-dependent stages of follicle development are largely unexplored. We observed positive regulation of Notch activity and expression of Notch ligands and receptors following activation of the luteinizing hormone-receptor in prepubertal mouse ovary...
January 1, 2018: Endocrinology
https://www.readbyqxmd.com/read/29101337/trichostatin-a-ameliorates-renal-tubulointerstitial-fibrosis-through-modulation-of-the-jnk-dependent-notch-2-signaling-pathway
#15
Chun-Wu Tung, Yung-Chien Hsu, Chang-Jhih Cai, Ya-Hsueh Shih, Ching-Jen Wang, Pey-Jium Chang, Chun-Liang Lin
Renal fibrosis is the final common pathological feature in a variety of chronic kidney disease. Trichostatin A (TSA), a histone deacetylase inhibitor, reportedly attenuates renal fibrosis in various kidney disease models. However, the detailed molecular action of TSA in ameliorating renal fibrotic injury is not yet fully understood. In a cultured renal fibroblastic cell model, we showed that TGF-β1 triggers upregulation of α-SMA and fibronectin, two hallmarks of myofibroblastic activation. During the course of TGF-β1 treatment, activation of Smad2/3, p38, ERK, JNK and Notch-2 was also detected...
November 3, 2017: Scientific Reports
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
#16
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
https://www.readbyqxmd.com/read/28772216/minocycline-attenuates-the-development-of-diabetic-neuropathy-by-inhibiting-spinal-cord-notch-signaling-in-rat
#17
Cheng Yang, Jie Gao, Banglin Wu, Nuo Yan, Hui Li, Yiqing Ren, Yufei Kan, Jiamin Liang, Yang Jiao, Yonghao Yu
We studied the effects of minocycline (an inhibitor of microglial activation) on the expression and activity of Notch-1 receptor, and explored the therapeutic efficacy of minocycline combined with Notch inhibitor DAPT in the treatment of diabetic neuropathic pain (DNP). Diabetic rat model was established by intraperitoneal injection (ip) of Streptozotocin (STZ). Expression and activity of Notch-1 and expression of macrophage/microglia marker Iba-1 were detected by WB. Diabetes induction significantly attenuated sciatic nerve conduction velocity, and dramatically augmented the expression and the activity of Notch-1 in the lumbar enlargement of the spinal cord...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28759157/mtor-notch3-signaling-mediates-pulmonary-hypertension-in-hypoxia-exposed-neonatal-rats-independent-of-changes-in-autophagy
#18
Julijana Ivanovska, Sparsh Shah, Mathew J Wong, Crystal Kantores, Amish Jain, Martin Post, Behzad Yeganeh, Robert P Jankov
BACKGROUND/AIM: Mammalian target of rapamycin (mTOR) is a pivotal regulator of cell proliferation, survival, and autophagy. Autophagy is increased in adult experimental chronic pulmonary hypertension (PHT), but its contributory role to pulmonary vascular disease remains uncertain and has yet to be explored in the neonatal animal. Notch is a major pro-proliferative pathway activated by mTOR. A direct relationship between autophagy and Notch signaling has not been previously explored. Our aim was to examine changes in mTOR-, Notch-, and autophagy-related pathways and the therapeutic effects of autophagy modulators in experimental chronic neonatal PHT secondary to chronic hypoxia...
November 2017: Pediatric Pulmonology
https://www.readbyqxmd.com/read/28669599/inactivation-of-stat3-signaling-impairs-hair-cell-differentiation-in%C3%A2-the%C3%A2-developing-mouse-cochlea
#19
Qianqian Chen, Yizhou Quan, Naitao Wang, Chengying Xie, Zhongzhong Ji, Hao He, Renjie Chai, Huawei Li, Shankai Yin, Y Eugene Chin, Xunbin Wei, Wei-Qiang Gao
Although STAT3 signaling is demonstrated to regulate sensory cell differentiation and regeneration in the zebrafish, its exact role is still unclear in mammalian cochleae. Here, we report that STAT3 and its activated form are specifically expressed in hair cells during mouse cochlear development. Importantly, conditional cochlear deletion of Stat3 leads to an inhibition on hair cell differentiation in mice in vivo and in vitro. By cell fate analysis, inactivation of STAT3 signaling shifts the cell division modes from asymmetric to symmetric divisions from supporting cells...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28637014/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...
June 7, 2017: Oncotarget
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