15,738 results match your criteria notch signaling


Biological Significance of NOTCH Signaling Strength.

Front Cell Dev Biol 2021 26;9:652273. Epub 2021 Mar 26.

Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, China.

The evolutionarily conserved NOTCH signaling displays pleotropic functions in almost every organ system with a simple signaling axis. Different from many other signaling pathways that can be amplified via kinase cascades, NOTCH signaling does not contain any intermediate to amplify signal. Thus, NOTCH signaling can be activated at distinct signaling strength levels, disruption of which leads to various developmental disorders. Read More

View Article and Full-Text PDF

Identification of Candidate Biomarkers for Idiopathic Thrombocytopenic Purpura by Bioinformatics Analysis of Microarray Data.

Iran J Pharm Res 2020 ;19(4):275-289

Department of Radiology, Ziyaian Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Idiopathic Thrombocytopenic Purpura (ITP) is a multifactorial disease with decreased count of platelet that can lead to bruising and bleeding manifestations. This study was intended to identify critical genes associated with chronic ITP. The gene expression profile was downloaded from the Gene Expression Omnibus database to recognize Differentially Expressed Genes (DEGs) by R software. Read More

View Article and Full-Text PDF
January 2020

TIGIT-Fc as a Potential Therapeutic Agent for Fetomaternal Tolerance.

Front Immunol 2021 25;12:649135. Epub 2021 Mar 25.

Department of Biophysics, College of Basic Medical Sciences, Second Military Medical University, Shanghai, China.

The perfect synchronization of maternal immune-endocrine mechanisms and those of the fetus is necessary for a successful pregnancy. In this report, decidual immune cells at the maternal-fetal interface were detected that expressed TIGIT (T cell immunoreceptor with Ig and ITIM domains), which is a co-inhibitory receptor that triggers immunological tolerance. We generated recombinant TIGIT-Fc fusion proteins by linking the extracellular domain of TIGIT and silent Fc fragments. Read More

View Article and Full-Text PDF

FGF-MAPK signaling regulates human deep-layer corticogenesis.

Stem Cell Reports 2021 Mar 30. Epub 2021 Mar 30.

The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC 3010, Australia.

Despite heterogeneity across the six layers of the mammalian cortex, all excitatory neurons are generated from a single founder population of neuroepithelial stem cells. However, how these progenitors alter their layer competence over time remains unknown. Here, we used human embryonic stem cell-derived cortical progenitors to examine the role of fibroblast growth factor (FGF) and Notch signaling in influencing cell fate, assessing their impact on progenitor phenotype, cell-cycle kinetics, and layer specificity. Read More

View Article and Full-Text PDF

Age-associated expression of p21and p53 during human wound healing.

Aging Cell 2021 Apr 9:e13354. Epub 2021 Apr 9.

Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.

In mice, cellular senescence and senescence-associated secretory phenotype (SASP) positively contribute to cutaneous wound healing. In this proof-of-concept study, we investigated the expressions of p16, p21, and other senescence-associated biomarkers during human wound healing in 24 healthy subjects using a double-biopsy experimental design. The first punch biopsy created the wound and established the baseline. Read More

View Article and Full-Text PDF

Using lncRNA Sequencing to Reveal a Putative lncRNA-mRNA Correlation Network and the Potential Role of PCBP1-AS1 in the Pathogenesis of Cervical Cancer.

Front Oncol 2021 23;11:634732. Epub 2021 Mar 23.

Department of Gynaecology and Obstetrics, Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China.

Background/aims: Long non-coding RNAs (lncRNAs) play important roles in many diseases and participate in posttranscriptional regulatory networks in tumors. However, the functions of major lncRNAs in cervical cancer are unclear. Therefore, the aim of this study was to construct a lncRNA-mRNA coexpression functional network and analyze lncRNAs that might contribute to the pathogenesis of cervical cancer. Read More

View Article and Full-Text PDF

FZD2 promotes TGF-β-induced epithelial-to-mesenchymal transition in breast cancer via activating notch signaling pathway.

Cancer Cell Int 2021 Apr 8;21(1):199. Epub 2021 Apr 8.

Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002, China.

Background: Breast cancer (BC) is one of the commonest female cancers, which is characterized with high incidence. Although treatments have been improved, the prognosis of BC patients in advanced stages remains unsatisfactory. Thus, exploration of the molecular mechanisms underneath BC progression is necessary to find novel therapeutic methods. Read More

View Article and Full-Text PDF

Research progress on the molecular mechanisms of hepatic metastasis in lung cancer: a narrative review.

Ann Palliat Med 2021 Mar 24. Epub 2021 Mar 24.

Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China.

The liver is one of the most common sites of metastatic spread of lung cancer, and the process of metastasis is regulated by many factors. A number of genes, including multiple tumor suppressor 1 (mts1), p120 catenin, and CT45A1, increase the possibility of hepatic metastasis in lung cancer, whereas Tip30/ CC3, CUL5, and SOCS3 expression in lung tumors inhibit tumor metastasis. microRNAs (miRNAs), such as miRNA-126, miRNA-338, and miRNA-218, can affect the metastasis of lung cancer cells to the liver. Read More

View Article and Full-Text PDF

Intracellular trafficking of Notch orchestrates temporal dynamics of Notch activity in the fly brain.

Nat Commun 2021 04 7;12(1):2083. Epub 2021 Apr 7.

Mathematical Neuroscience Unit, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa, Ishikawa, Japan.

While Delta non-autonomously activates Notch in neighboring cells, it autonomously inactivates Notch through cis-inhibition, the molecular mechanism and biological roles of which remain elusive. The wave of differentiation in the Drosophila brain, the 'proneural wave', is an excellent model for studying Notch signaling in vivo. Here, we show that strong nonlinearity in cis-inhibition reproduces the second peak of Notch activity behind the proneural wave in silico. Read More

View Article and Full-Text PDF

SerpinB13 antibodies promote β cell development and resistance to type 1 diabetes.

Sci Transl Med 2021 Apr;13(588)

Department of Laboratory Medicine and Pathology, University of Minnesota, 420 Washington Ave. SE, Minneapolis, MN 55455, USA.

Pancreatic endocrine cell development is dependent on the rescue of the neurogenin3 (Ngn3) transcription factor from repression by Notch. The signals that prevent Notch signaling, thereby allowing the formation of pancreatic endocrine cells, remain unclear. We show that inhibiting serpinB13, a cathepsin L (CatL) protease inhibitor expressed in the pancreatic epithelium, caused in vitro and in vivo cleavage of the extracellular domain of Notch1. Read More

View Article and Full-Text PDF

Quinomycin A reduces cyst progression in polycystic kidney disease.

FASEB J 2021 May;35(5):e21533

Departments of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA.

Polycystic kidney disease (PKD) is a genetic disorder characterized by aberrant renal epithelial cell proliferation and formation and progressive growth of numerous fluid-filled cysts within the kidneys. Previously, we showed that there is elevated Notch signaling compared to normal renal epithelial cells and that Notch signaling contributes to the proliferation of cystic cells. Quinomycin A, a bis-intercalator peptide, has previously been shown to target the Notch signaling pathway and inhibit tumor growth in cancer. Read More

View Article and Full-Text PDF

The Notch Signaling Pathway Regulates Differentiation of NG2 Cells into Oligodendrocytes in Demyelinating Diseases.

Cell Mol Neurobiol 2021 Apr 7. Epub 2021 Apr 7.

Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, No. 17 Yongwai Zheng Street, Nanchang, 330006, Jiangxi, People's Republic of China.

NG2 cells are highly proliferative glial cells that can self-renew or differentiate into oligodendrocytes, promoting remyelination. Following demyelination, the proliferative and differentiation potentials of NG2 cells increase rapidly, enhancing their differentiation into functional myelinating cells. Levels of the transcription factors Olig1 and Olig2 increase during the differentiation of NG2 cells and play important roles in the development and repair of oligodendrocytes. Read More

View Article and Full-Text PDF

Alagille syndrome and non-syndromic paucity of the intrahepatic bile ducts.

Transl Gastroenterol Hepatol 2021 5;6:22. Epub 2021 Apr 5.

Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

The observation of bile duct paucity is an important diagnostic finding in children, occurring in roughly 11% of pediatric liver biopsies. Alagille syndrome (ALGS) is a well-defined syndromic form of intrahepatic bile duct paucity that is accompanied by a number of other key features, including cardiac, facial, ocular, and vertebral abnormalities. In the absence of these additional clinical characteristics, intrahepatic bile duct paucity results in a broad differential diagnosis that requires supplementary testing and characterization. Read More

View Article and Full-Text PDF

Maheshvara regulates JAK/STAT signaling by interacting and stabilizing hopscotch transcripts which leads to apoptosis in Drosophila melanogaster.

Cell Death Dis 2021 Apr 6;12(4):363. Epub 2021 Apr 6.

Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India.

Maheshvara (mahe), an RNA helicase that is widely conserved across taxa, regulates Notch signaling and neuronal development in Drosophila. In order to identify novel components regulated by mahe, transcriptome profiling of ectopic mahe was carried out and this revealed striking upregulation of JAK/STAT pathway components like upd1, upd2, upd3, and socs36E. Further, significant downregulation of the pathway components in mahe loss-of-function mutant as well as upon lowering the level of mahe by RNAi, supported and strengthened our transcriptome data. Read More

View Article and Full-Text PDF

Chemotherapy-elicited exosomal miR-378a-3p and miR-378d promote breast cancer stemness and chemoresistance via the activation of EZH2/STAT3 signaling.

J Exp Clin Cancer Res 2021 Apr 6;40(1):120. Epub 2021 Apr 6.

Third Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.

Background: Not all breast cancer (BC) patients who receive neoadjuvant chemotherapy achieve a pathologic complete response (pCR), but the reasons for this are unknown. Previous studies have shown that exosomes produced in the tumor microenvironment in response to chemotherapy promote a chemotherapy-resistant phenotype in tumors. However, the role of BC chemotherapy-elicited exosomes in regulating chemoresistance is poorly understood. Read More

View Article and Full-Text PDF

Dynamic spatiotemporal coordination of neural stem cell fate decisions occurs through local feedback in the adult vertebrate brain.

Cell Stem Cell 2021 Apr 2. Epub 2021 Apr 2.

Zebrafish Neurogenetics Unit, Institut Pasteur, UMR3738, CNRS, team supported by La Ligue Nationale Contre le Cancer, 75015 Paris, France. Electronic address:

Neural stem cell (NSC) populations persist in the adult vertebrate brain over a lifetime, and their homeostasis is controlled at the population level through unknown mechanisms. Here, we combine dynamic imaging of entire NSC populations in their in vivo niche over several weeks with pharmacological manipulations, mathematical modeling, and spatial statistics and demonstrate that NSCs use spatiotemporally resolved local feedback signals to coordinate their decision to divide in adult zebrafish brains. These involve Notch-mediated short-range inhibition from transient neural progenitors and a dispersion effect from the dividing NSCs themselves exerted with a delay of 9-12 days. Read More

View Article and Full-Text PDF

The FBXW7-NOTCH interactome: A ubiquitin proteasomal system-induced crosstalk modulating oncogenic transformation in human tissues.

Cancer Rep (Hoboken) 2021 Apr 6:e1369. Epub 2021 Apr 6.

Department of Biotechnology, School of Engineering & Technology (SET), Sharda University, Greater Noida, Uttar Pradesh, 201310, India.

Background: Ubiquitin ligases or E3 ligases are well programmed to regulate molecular interactions that operate at a post-translational level. Skp, Cullin, F-box containing complex (or SCF complex) is a multidomain E3 ligase known to mediate the degradation of a wide range of proteins through the proteasomal pathway. The three-dimensional domain architecture of SCF family proteins suggests that it operates through a novel and adaptable "super-enzymatic" process that might respond to targeted therapeutic modalities in cancer. Read More

View Article and Full-Text PDF

Transcriptomic profiling as biological markers of depression- a pilot study in unipolar and bipolar women.

World J Biol Psychiatry 2021 Apr 6:1-31. Epub 2021 Apr 6.

Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poland.

Objectives: A significant challenge in psychiatry is the differential diagnosis of depressive episodes in the course of mood disorders. Gene expression profiling may provide an opportunity for such distinguishment.

Methods: We studied differentially expressed genes in women with a depressive episode in the course of unipolar depression (UD) (n = 24) and bipolar disorder types I (BDI) (n = 13) and II (BDII) (n = 19), and healthy controls (n = 15). Read More

View Article and Full-Text PDF

Pharmacological disruption of the Notch1 transcriptional complex inhibits tumor growth by selectively targeting cancer stem cells.

Cancer Res 2021 Apr 5. Epub 2021 Apr 5.

Molecular Oncology Program, Division of Surgical Oncology, Dewitt Daughtry Family Department of Surgery, and Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami

In many human cancers, deregulation of the Notch pathway has been shown to play a role in the initiation and maintenance of the neoplastic phenotype. Aberrant Notch activity also plays a central role in the maintenance and survival of cancer stem cells, which underlie metastasis and resistance to therapy. For these reasons, inhibition of Notch signaling has become an exceedingly attractive target for cancer therapeutic development. Read More

View Article and Full-Text PDF

Long non-coding RNA TUG1 knockdown hinders the tumorigenesis of multiple myeloma by regulating the microRNA-34a-5p/NOTCH1 signaling pathway.

Open Life Sci 2020 9;15(1):284-295. Epub 2020 Jun 9.

Department of Hematology, Ji'ning No. 1 People's Hospital, Ji'ning, Shandong, China.

Multiple myeloma (MM) is a serious health issue in hematological malignancies. Long non-coding RNA taurine-upregulated gene 1 (TUG1) has been reported to be highly expressed in the plasma of MM patients. However, the functions of TUG1 in MM tumorigenesis along with related molecular basis are still undefined. Read More

View Article and Full-Text PDF

Gamma-Secretase Inhibitor (DAPT), a potential therapeutic target drug, caused neurotoxicity in planarian regeneration by inhibiting Notch signaling pathway.

Sci Total Environ 2021 Mar 26;781:146735. Epub 2021 Mar 26.

College of Life Science, Henan Normal University, Xinxiang 453007, Henan, China. Electronic address:

DAPT (N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-s-phenylglycinet-butyl ester) is a γ-secretase inhibitor that indirectly blocks the activity of Notch pathway. It is a potential therapeutic target drug for many diseases, such as cancer, neurological, cardiovascular, and cerebrovascular diseases. However, the pharmacological action and specific mechanisms of DAPT are not clear. Read More

View Article and Full-Text PDF

Reduced RECK levels accelerate skeletal muscle differentiation, improve muscle regeneration, and decrease fibrosis.

FASEB J 2021 May;35(5):e21503

Centro de Regeneración y Envejecimiento (CARE), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.

The muscle regeneration process requires a properly assembled extracellular matrix (ECM). Its homeostasis depends on the activity of different matrix-metalloproteinases (MMPs). The reversion-inducing-cysteine-rich protein with kazal motifs (RECK) is a membrane-anchored protein that negatively regulates the activity of different MMPs. Read More

View Article and Full-Text PDF

Large Scale Molecular Studies of Pituitary Neuroendocrine Tumors: Novel Markers, Mechanisms and Translational Perspectives.

Cancers (Basel) 2021 Mar 19;13(6). Epub 2021 Mar 19.

Latvian Biomedical Research and Study Centre, Ratsupites Str. 1-k1, LV-1067 Riga, Latvia.

Pituitary neuroendocrine tumors (PitNETs) are non-metastatic neoplasms of the pituitary, which overproduce hormones leading to systemic disorders, or tumor mass effects causing headaches, vertigo or visual impairment. Recently, PitNETs have been investigated in large scale (exome and genome) molecular analyses (transcriptome microarrays and sequencing), to uncover novel markers. We performed a literature analysis on these studies to summarize the research data and extrapolate overlapping gene candidates, biomarkers, and molecular mechanisms. Read More

View Article and Full-Text PDF

Distinct Age-Specific miRegulome Profiling of Isolated Small and Large Intestinal Epithelial Cells in Mice.

Int J Mol Sci 2021 Mar 29;22(7). Epub 2021 Mar 29.

Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.

The intestinal epithelium serves as a dynamic barrier to protect the host tissue from exposure to a myriad of inflammatory stimuli in the luminal environment. Intestinal epithelial cells (IECs) encompass differentiated and specialized cell types that are equipped with regulatory genes, which allow for sensing of the luminal environment. Potential inflammatory cues can instruct IECs to undergo a diverse set of phenotypic alterations. Read More

View Article and Full-Text PDF

Notch Signaling Regulation in HCC: From Hepatitis Virus to Non-Coding RNAs.

Cells 2021 Mar 1;10(3). Epub 2021 Mar 1.

Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.

The Notch family includes evolutionary conserved genes that encode for single-pass transmembrane receptors involved in stem cell maintenance, development and cell fate determination of many cell lineages. Upon activation by different ligands, and depending on the cell type, Notch signaling plays pleomorphic roles in hepatocellular carcinoma (HCC) affecting neoplastic growth, invasion capability and stem like properties. A specific knowledge of the deregulated expression of each Notch receptor and ligand, coupled with resultant phenotypic changes, is still lacking in HCC. Read More

View Article and Full-Text PDF

Theasaponin E Inhibits Platinum-Resistant Ovarian Cancer Cells through Activating Apoptosis and Suppressing Angiogenesis.

Molecules 2021 Mar 17;26(6). Epub 2021 Mar 17.

College of Science, Technology and Mathematics, Alderson Broaddus University, Philippi, WV 26416, USA.

Novel therapeutic strategies for ovarian cancer treatment are in critical need due to the chemoresistance and adverse side effects of platinum-based chemotherapy. Theasaponin E (TSE1) is an oleanane-type saponin from seeds. Its apoptosis-inducing, cell cycle arresting and antiangiogenesis activities against platinum-resistant ovarian cancer cells were elucidated in vitro and using the chicken chorioallantoic membrane (CAM) assay. Read More

View Article and Full-Text PDF

Selenite Inhibits Notch Signaling in Cells and Mice.

Int J Mol Sci 2021 Mar 3;22(5). Epub 2021 Mar 3.

Department of Biological Sciences, Oakland University, Rochester, MI 48309, USA.

Selenium is an essential micronutrient with a wide range of biological effects in mammals. The inorganic form of selenium, selenite, is supplemented to relieve individuals with selenium deficiency and to alleviate associated symptoms. Additionally, physiological and supranutritional selenite have shown selectively higher affinity and toxicity towards cancer cells, highlighting their potential to serve as chemotherapeutic agents or adjuvants. Read More

View Article and Full-Text PDF

Mural Cells: Potential Therapeutic Targets to Bridge Cardiovascular Disease and Neurodegeneration.

Cells 2021 Mar 8;10(3). Epub 2021 Mar 8.

Heart Research Institute, Sydney, NSW 2042, Australia.

Mural cells collectively refer to the smooth muscle cells and pericytes of the vasculature. This heterogenous population of cells play a crucial role in the regulation of blood pressure, distribution, and the structural integrity of the vascular wall. As such, dysfunction of mural cells can lead to the pathogenesis and progression of a number of diseases pertaining to the vascular system. Read More

View Article and Full-Text PDF

Retinal Genomic Fabric Remodeling after Optic Nerve Injury.

Genes (Basel) 2021 Mar 11;12(3). Epub 2021 Mar 11.

Laboratório de Neurogênese, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.

Glaucoma is a multifactorial neurodegenerative disease, characterized by degeneration of the retinal ganglion cells (RGCs). There has been little progress in developing efficient strategies for neuroprotection in glaucoma. We profiled the retina transcriptome of Lister Hooded rats at 2 weeks after optic nerve crush (ONC) and analyzed the data from the genomic fabric paradigm (GFP) to bring additional insights into the molecular mechanisms of the retinal remodeling after induction of RGC degeneration. Read More

View Article and Full-Text PDF

An experimental model of anti-PD-1 resistance exhibits activation of TGFß and Notch pathways and is sensitive to local mRNA immunotherapy.

Oncoimmunology 2021 Mar 16;10(1):1881268. Epub 2021 Mar 16.

Sanofi Research and Development, Cambridge, MA, USA.

Immune checkpoint blockade elicits durable anti-cancer responses in the clinic, however a large proportion of patients do not benefit from treatment. Several mechanisms of innate and acquired resistance to checkpoint blockade have been defined and include mutations of MHC I and IFNγ signaling pathways. However, such mutations occur in a low frequency of patients and additional mechanisms have yet to be elucidated. Read More

View Article and Full-Text PDF