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Keywords notch signaling inhibitors and...

notch signaling inhibitors and stimulators

https://read.qxmd.com/read/36764280/blocking-notch-signalling-reverses-mir-155-mediated-inflammation-in-allergic-rhinitis
#21
JOURNAL ARTICLE
Ziling Zhong, Xueying Huang, Shaojie Zhang, Shaochuan Zheng, Xiqiao Cheng, Rongrong Li, Di Wu, Liping Mo, Shenhong Qu
Although recent studies have shown that the Notch signalling pathway induces the production of Th2-related immune factors, the exact mechanism through which Notch signalling exacerbates allergic rhinitis (AR) remains unknown. To investigate the roles of Notch in AR, serum, nasal mucosa and spleen samples were isolated from BALB/c mice. Paraffin sections were stained with haematoxylin and eosin (H&E) or periodic acid-Schiff (PAS) to assess inflammation. Flow cytometry was performed to detect group 2 innate lymphoid cells (ILC2s) in the serum samples, and cytokine levels were measured by enzyme-linked immunosorbent assays (ELISAs)...
February 8, 2023: International Immunopharmacology
https://read.qxmd.com/read/36739740/a-potential-requirement-for-smad3-phosphorylation-in-notch-mediated-emt-in-colon-cancer
#22
JOURNAL ARTICLE
Alexander G Clark, Fred E Bertrand, George Sigounas
Colorectal cancer (CRC) remains a challenging disease to treat due to several factors including stemness and epithelial to mesenchymal transition (EMT). Dysfunctional signaling pathways such as Notch and TGF-β contribute to these phenomena. We previously found that cells expressing constitutively active Notch1 also had increased expression of Smad3, an important member of the TGF-β signaling pathway. We hypothesized that Smad3, mediates the Notch-induced stemness and EMT observed in CRC cells. The human colorectal carcinoma cell line HCT-116, stably transduced with constitutively active Notch-1 (ICN) or a GFP-vector control was treated with different combinations of TGF-β1, DAPT (a Notch inhibitor), or SIS3 (a Smad3 inhibitor)...
January 28, 2023: Advances in Biological Regulation
https://read.qxmd.com/read/36635975/caveolin-1-inhibition-mediates-the-opposing-effects-of-alcohol-on-%C3%AE-secretase-activity-in-arterial-endothelial-and-smooth-muscle-cells
#23
JOURNAL ARTICLE
Naresh K Rajendran, Weimin Liu, Paul A Cahill, Eileen M Redmond
Notch is important to vessel homeostasis. We investigated the mechanistic role of caveolin-1 (Cav-1) in mediating the effects of alcohol (Ethanol/EtOH) on the γ-secretase proteolytic activity necessary for Notch signaling in vascular cells. Human coronary artery endothelial cells (HCAEC) were treated with EtOH (0-50 mM), Notch ligand delta-like ligand 4 (Dll4), and the γ-secretase inhibitor DAPT. EtOH stimulated Notch signaling in HCAEC as evidenced by increased Notch receptor (N1, N4) and target gene (hrt2, hrt3) mRNA levels with the most robust response achieved at 25 mM EtOH...
January 2023: Physiological Reports
https://read.qxmd.com/read/36632915/histone-deacetylase-inhibitor-butyrate-inhibits-the-cellular-immunity-and-increases-the-serum-immunity-of-pearl-oyster-pinctada-fucata-martensii
#24
JOURNAL ARTICLE
Jingmiao Yang, Shuai Yang, Yongshan Liao, Yuewen Deng, Yu Jiao
Histone acetylation is a dynamic epigenetic modification and sensitive to the changes in extracellular environment. Butyrate, a histone deacetylase inhibitor, can inhibit the deacetylation process of histones. In this study, we found that the acetylation level of H3 was enhanced at 12 h after lipopolysaccharide (LPS) stimulation and increased at 6 h after combining treatment with LPS and butyrate in pearl oyster Pinctada fucata martensii. Transcriptome analysis indicated that butyrate counter-regulated 29...
January 8, 2023: Fish & Shellfish Immunology
https://read.qxmd.com/read/36609902/egfl7-secreted-by-human-bone-mesenchymal-stem-cells-promotes-osteoblast-differentiation-partly-via-downregulation-of-notch1-hes1-signaling-pathway
#25
JOURNAL ARTICLE
Weijun Zhang, Jinwu Bai, Lijun Li, Ye Zhang, Kai Hang, Yibo Wang, Zhongxiang Wang, Chenyi Ye, Deting Xue
BACKGROUND: Epidermal growth factor-like domain protein 7 (EGFL7) is a secreted protein that is differentially expressed in the bone microenvironment; however, the effect of EGFL7 on the osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs) is largely unknown. METHODS: EGFL7 expression in the fracture microenvironment was analyzed based on the Gene Expression Omnibus (GEO) database. Knockdown of EGFL7 by small interfering RNA (siRNA) and in vitro stimulation with recombinant human EGFL7 (rhEGFL7) protein were used to assess alterations in downstream signaling and changes in the osteogenic differentiation and proliferation of hBMSCs...
January 7, 2023: Stem cell reviews and reports
https://read.qxmd.com/read/36562737/regulation-of-notch-signaling-pathway-to-innate-lymphoid-cells-in-patients-with-acute-myocardial-infarction
#26
JOURNAL ARTICLE
Haiwen Yu, Yongjie Wei, Yanyan Dong, Penglei Chen
The Notch signaling pathway is an important regulator in fate decisions and immune responses of innate lymphoid cells (ILCs). However, the function of Notch signaling in ILCs in acute coronary syndrome is still not fully elucidated. Thirty-one unstable angina pectoris (UAP) patients, 21 acute myocardial infarction (AMI) patients, and 20 controls were included in this study. Peripheral blood mononuclear cells (PBMCs) were isolated. The mRNA expression levels of Notch receptors and ligands were measured by real-time PCR, while ILC subsets were measured by flow cytometry...
December 23, 2022: Immunological Investigations
https://read.qxmd.com/read/36435065/manganese-enhances-macrophage-defense-against-mycobacterium-tuberculosis-via-the-sting-tnf-signaling-pathway
#27
JOURNAL ARTICLE
Kaiqiang Qian, Lidong Shan, Shengwen Shang, Tianyue Li, Shuxin Wang, Meili Wei, Bikui Tang, Jun Xi
The host cell antiviral response pathway depends heavily on manganese (Mn), but its role in defense against Mycobacterium tuberculosis (M. tuberculosis) infection is rarely reported. In this study, we found that, in H37Ra-infected macrophages, Mn2+ increases the phosphorylation of stimulator of interferon genes (STING) and P65, as well as triggers the phosphorylation cascade of tumor necrosis factor (TNF) signaling pathway proteins, signal-regulated kinase (ERK), P38, and c-Jun N-terminal kinase (JNK). The activation of the TNF signaling pathway stimulated the expression of downstream inflammatory factors TNF-α, C-X-C Motif Chemokine Ligand 10(CXCL10), CC Motif Chemokine Ligand 20(CCL20), Colony Stimulating Factor 1(CSF1), Colony Stimulating Factor 2(CSF2), and Jagged Canonical Notch Ligand 1(JAG1), thereby triggering a strong inflammatory response in the cells...
November 23, 2022: International Immunopharmacology
https://read.qxmd.com/read/36104669/the-interaction-between-autophagy-and-the-epithelial-mesenchymal-transition-mediated-by-nicd-ulk1-is-involved-in-the-formation-of-diabetic-cataracts
#28
JOURNAL ARTICLE
Jiyuan Ma, Wei Ye, Yunshu Yang, Tong Wu, Yafen Wang, Ji Li, Rui Pei, Mengmei He, Luning Zhang, Jian Zhou
BACKGROUND: Cataracts are the leading cause of blindness and a common ocular complication of diabetes. The epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) and altered autophagic activity occur during the development of diabetic cataracts. The disturbed interaction of autophagy with EMT in LECs stimulated by high glucose levels may participate in cataract formation. METHODS: A rat diabetic cataract model induced by streptozotocin (STZ) and human lens epithelial cells (HLE-B3) stimulated with a high glucose concentration were employed in the study...
September 14, 2022: Molecular Medicine
https://read.qxmd.com/read/35685361/integrative-rna-profiling-of-tbev-infected-neurons-and-astrocytes-reveals-potential-pathogenic-effectors
#29
JOURNAL ARTICLE
Martin Selinger, Pavlína Věchtová, Hana Tykalová, Petra Ošlejšková, Michaela Rumlová, Ján Štěrba, Libor Grubhoffer
Tick-borne encephalitis virus (TBEV), the most medically relevant tick-transmitted flavivirus in Eurasia, targets the host central nervous system and frequently causes severe encephalitis. The severity of TBEV-induced neuropathogenesis is highly cell-type specific and the exact mechanism responsible for such differences has not been fully described yet. Thus, we performed a comprehensive analysis of alterations in host poly-(A)/miRNA/lncRNA expression upon TBEV infection in vitro in human primary neurons (high cytopathic effect) and astrocytes (low cytopathic effect)...
2022: Computational and Structural Biotechnology Journal
https://read.qxmd.com/read/35528192/the-genetic-landscape-of-ocular-adnexa-malt-lymphoma-reveals-frequent-aberrations-in-nfat-and-mef2b-signaling-pathways
#30
JOURNAL ARTICLE
Marco Magistri, Lanie E Happ, Jeremy Ramdial, XiaoQing Lu, Vasileios Stathias, Kranthi Kunkalla, Nitin Agarwal, Xiaoyu Jiang, Stephan C Schürer, Sander R Dubovy, Jennifer R Chapman, Francisco Vega, Sandeep Dave, Izidore S Lossos
A comprehensive constellation of somatic non-silent mutations and copy number (CN) variations in ocular adnexa marginal zone lymphoma (OAMZL) is unknown. By utilizing whole-exome sequencing in 69 tumors we define the genetic landscape of OAMZL. Mutations and CN changes in CABIN1 (30%), RHOA (26%), TBL1XR1 (22%), and CREBBP (17%) and inactivation of TNFAIP3 (26%) were among the most common aberrations. Candidate cancer driver genes cluster in the B-cell receptor (BCR), NFkB, NOTCH and NFAT signaling pathways...
October 2021: Cancer Res Commun
https://read.qxmd.com/read/35489123/notch1-signaling-contributes-to-tlr4-triggered-nf-%C3%AE%C2%BAb-activation-in-macrophages
#31
JOURNAL ARTICLE
Li Li, Jin-Hua Jin, Han-Ye Liu, Xiao-Fei Ma, Dan-Dan Wang, Yi-Lan Song, Chong-Yang Wang, Jing-Zhi Jiang, Guang-Hai Yan, Xiang-Zheng Qin, Liang-Chang Li
Macrophages substantially influence the development, progression, and complications of inflammation-driven diseases. Although numerous studies support the critical role of Notch signaling in most inflammatory diseases, there is limited data on the role of Notch signaling in TLR4-induced macrophage activation and interaction of Notch signaling with other signaling pathways in macrophages during inflammation, such as the NF-κB pathway. This study confirmed that stimulation with lipopolysaccharide (LPS), a TLR4 ligand, upregulated Notch1 expression in monocyte/macrophage-like RAW264...
June 2022: Pathology, Research and Practice
https://read.qxmd.com/read/35385713/e3-ubiquitin-ligase-itch-improves-lps-induced-chondrocyte-injury-by-mediating-jag1-ubiquitination-in-osteoarthritis
#32
JOURNAL ARTICLE
Liang Qi, Min Wang, Jinlong He, Bin Jia, Jing Ren, Shicheng Zheng
ITCH is an E3 ubiquitin ligase associated with some inflammatory diseases, but its role in osteoarthritis (OA) remains to be explored. Here, we investigated the effects of ITCH in OA-induced chondrocyte damage and its potential mechanisms. Here, we found that ITCH was downregulated, while JAG1 was upregulated in OA tissues compared to normal cartilaginous tissues. And primary human chondrocytes were induced by LPS to simulate OA condition. Overexpressing ITCH or silencing JAG1 promoted proliferation, and restrained apoptosis, inflammation and extracellular matrix (ECM) degradation in LPS-stimulated chondrocytes...
June 1, 2022: Chemico-biological Interactions
https://read.qxmd.com/read/35059610/identification-of-a-dihydropyridine-scaffold-that-blocks-ryanodine-receptors
#33
JOURNAL ARTICLE
Gihan S Gunaratne, Robyn T Rebbeck, Lindsey M McGurran, Yasheng Yan, Thiago Arzua, Talia Frolkis, Daniel J Sprague, Xiaowen Bai, Razvan L Cornea, Timothy F Walseth, Jonathan S Marchant
Ryanodine receptors (RyRs) are large, intracellular ion channels that control Ca2+ release from the sarco/endoplasmic reticulum. Dysregulation of RyRs in skeletal muscle, heart, and brain has been implicated in various muscle pathologies, arrhythmia, heart failure, and Alzheimer's disease. Therefore, there is considerable interest in therapeutically targeting RyRs to normalize Ca2+ homeostasis in scenarios involving RyR dysfunction. Here, a simple invertebrate screening platform was used to discover new chemotypes targeting RyRs...
January 21, 2022: IScience
https://read.qxmd.com/read/35039472/the-histone-methyltransferase-dot1l-is-a-new-epigenetic-regulator-of-pulmonary-fibrosis
#34
JOURNAL ARTICLE
Di Yang, Peng Xu, Haibi Su, Wen Zhong, Jie Xu, Zhenghua Su, Xinhua Liu
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with increasing occurrence, high death rates, and unfavorable treatment regimens. The pathogenesis underlying IPF is complex and the epigenetic contributions to IPF are largely unknown. Recent studies have shown that DOT1L (Disruptor of telomeric silencing-1 like), a histone H3K79 methyltransferase, contributes to fibrosis response, but its role in IPF remains unclear. DOT1L, H3K79me3, and the profibrotic proteins levels were upregulated in the pulmonary fibrosis models both in vivo and in vitro...
January 17, 2022: Cell Death & Disease
https://read.qxmd.com/read/34883044/numb-as-a-new-therapeutic-target-for-melanoma
#35
JOURNAL ARTICLE
Denitsa M Hristova, Takeshi Fukumoto, Chihiro Takemori, Le Gao, Xia Hua, Joshua X Wang, Ling Li, Marilda Beqiri, Andrea Watters, Adina Vultur, Yusra Gimie, Vito Rebecca, Anastasia Samarkina, Haruki Jimbo, Chikako Nishigori, Jie Zhang, Chaoran Cheng, Zhi Wei, Rajasekharan Somasundaram, Mizuho Fukunaga-Kalabis, Meenhard Herlyn
Upregulation of the adaptor protein NUMB triggers melanocytic differentiation from multipotent skin stem cells, which share many properties with aggressive melanoma cells. Although NUMB acts as a tumor suppressor in various human cancer types, little is known about its role in melanoma. Here, we investigated the role of NUMB in melanoma progression and its regulatory mechanism. Analysis of The Cancer Genome Atlas melanoma datasets revealed that high NUMB expression in melanoma tissues correlates with improved patient survival...
December 6, 2021: Journal of Investigative Dermatology
https://read.qxmd.com/read/34778567/the-multifunctional-role-of-notch-signaling-in-multiple-myeloma
#36
JOURNAL ARTICLE
Hayley M Sabol, Jesus Delgado-Calle
Multiple myeloma (MM) is a hematologic cancer characterized by uncontrolled growth of malignant plasma cells in the bone marrow and currently is incurable. The bone marrow microenvironment plays a critical role in MM. MM cells reside in specialized niches where they interact with multiple marrow cell types, transforming the bone/bone marrow compartment into an ideal microenvironment for the migration, proliferation, and survival of MM cells. In addition, MM cells interact with bone cells to stimulate bone destruction and promote the development of bone lesions that rarely heal...
2021: Journal of Cancer Metastasis and Treatment
https://read.qxmd.com/read/34741867/cross-regulation-of-notch-akt-and-serum-glucocorticoid-regulated-kinase-1-sgk1-in-il-4-stimulated-human-macrophages
#37
JOURNAL ARTICLE
Naunpun Sangphech, Tanapat Palaga
Notch signaling regulates the responses of macrophages to different stimuli in a context-dependent manner. The roles of Notch signaling in proinflammatory macrophages are well characterized, whereas its involvement, if any, in IL-4-stimulated macrophages (M(IL-4)) is still unclear. We observed that Notch signaling is functional in human M(IL-4). We performed transcriptome analysis of the Notch1 intracellular domain (NIC1)-overexpressing human monocytic cell line THP-1 with or without IL-4 stimulation to understand the global impact of Notch signaling in M(IL-4)...
December 2021: International Immunopharmacology
https://read.qxmd.com/read/34717522/notch-signaling-regulates-function-of-human-mucosal-associated-invariant-t-mait-cells
#38
JOURNAL ARTICLE
Pimpayao Sodsai, Siriwan Klinchanhom, Nattiya Hirankarn, Rangsima Reantragoon, Tanapat Palaga
BACKGROUND: Notch signaling plays an important role in the development of T lymphocytes and regulates their effector functions. The regulatory roles of Notch signaling on T cells have been intensely investigated, but whether it involves in effector functions of mucosal-associated invariant T (MAIT) cells has never been reported. OBJECTIVE: To elucidate the expression profiles of Notch receptors/ligands and to investigate their roles in human MAIT cell function. METHODS: Peripheral blood mononuclear cells (PBMCs) from health donors were stimulated with or without anti-CD3/ CD28-coupled beads, recombinant IL-12/IL-18 cytokines, riboflavin- or non-riboflavin-synthesizing bacterial cultured supernatant for 24 hours...
October 31, 2021: Asian Pacific Journal of Allergy and Immunology
https://read.qxmd.com/read/34585422/moderate-dose-alcohol-protects-against-serum-amyloid-protein-a1-induced-endothelial-dysfunction-via-both-notch-dependent-and-notch-independent-pathways
#39
JOURNAL ARTICLE
Naresh K Rajendran, Weimin Liu, Charles C Chu, Paul A Cahill, Eileen M Redmond
BACKGROUND: Arterial endothelium plays a critical role in maintaining vessel homeostasis and preventing atherosclerotic cardiovascular disease (CVD). Low-to-moderate alcohol (EtOH) consumption is associated with reduced atherosclerosis and stimulates Notch signaling in endothelial cells. The aim of this study was to determine whether EtOH protects the endothelium against serum amyloid A1 (SAA1)-induced activation/injury, and to determine whether this protection is exclusively Notch-dependent...
November 2021: Alcoholism, Clinical and Experimental Research
https://read.qxmd.com/read/34543658/substrate-stiffness-modulates-endothelial-cell-function-via-the-yap-dll4-notch1-pathway
#40
JOURNAL ARTICLE
Eri Matsuo, Takayuki Okamoto, Atsushi Ito, Eiji Kawamoto, Kunihiro Asanuma, Koichiro Wada, Motomu Shimaoka, Motoshi Takao, Akira Shimamoto
Endothelial cells adapt their functions as a consequence of sensing extracellular substrate stiffness; these alterations allow them to maintain their vascular structure and function. Substrate stiffness-mediated yes-associated protein 1 (YAP) activation plays an important role in mechano-transduction and pro-angiogenic phenotype of endothelial cells, and Delta-like ligand 4 (Dll4)-Notch1 signaling is closely related to angiogenesis; however, the impact of substrate stiffness-mediated interrelation of these pathways on endothelial cell functions remains elusive...
November 1, 2021: Experimental Cell Research
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