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Multiscale simulations reveal architecture of NOTCH protein and ligand specific features.
Biophys J
December 2024
CSIR-Institute of Genomics and Integrative Biology, New Delhi, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India. Electronic address:
NOTCH, a single-pass transmembrane protein, plays a crucial role in cell fate determination through cell-to-cell communication. It interacts with two canonical ligands, Delta-like (DLL) and Jagged (JAG), located on neighboring cells to regulate diverse cellular processes. Despite extensive studies on the functional roles of NOTCH and its ligands in cellular growth, the structural details of full-length NOTCH and its ligands remain poorly understood.
View Article and Find Full Text PDFSystem Genetics Analysis Reveals Sex Differences in Human Aortic Smooth Muscle Gene Expression.
Bioinform Biol Insights
November 2024
Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
Background: Coronary artery disease (CAD) is one of the leading causes of death worldwide. The buildup of atherosclerotic plaque, including lipids and cellular waste, characterizes this disease. Smooth muscle cells (SMCs) can migrate and proliferate to form a fibrous cap that stabilizes the atherosclerotic plaque in response to plaque buildup.
View Article and Find Full Text PDFDLL4-targeted CAR-T therapy sensitizes neoadjuvant chemotherapy via eliminating cancer stem cells and reshaping immune microenvironment in HER2 breast cancer.
J Immunother Cancer
November 2024
Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China
Background: Neoadjuvant therapy with trastuzumab, pertuzumab and paclitaxel (THP) has significantly improved the prognosis of patients with human epidermal growth factor receptor 2 (HER2) breast cancer (BC). However, there remains a subset of non-responsive patients. Thus, this study sought to identify key regulators of THP neoadjuvant therapy resistance and potential targets to sensitize sensitivity.
View Article and Find Full Text PDFAstrocytic DLL4-NOTCH1 signaling pathway promotes neuroinflammation via the IL-6-STAT3 axis.
J Neuroinflammation
October 2024
Univ. Bordeaux, INSERM, Biology of Cardiovascular Diseases, U1034, 01 avenue de Magellan, Pessac, 33601, France.
Article Synopsis
- Under neuroinflammatory conditions, astrocytes adopt a reactive phenotype that exacerbates inflammation and contributes to neurodegeneration, with the study focusing on the role of astrocytic DLL4 and its interaction with NOTCH1 in regulating this reactivity.
- The research found that during neuroinflammation, DLL4 is upregulated in both mice and humans, leading to increased astrocyte reactivity, blood-brain barrier permeability, and inflammatory responses through the DLL4-NOTCH1 signaling pathway.
- Blocking DLL4 with antibodies showed promise in alleviating symptoms of experimental autoimmune encephalomyelitis in mice, suggesting a new potential therapeutic approach for treating CNS autoimmune diseases.
Inhibition of DLL4/Notch Signaling Pathway Promotes M2 Polarization and Cell Proliferation in Pulmonary Arterial Hypertension.
ACS Omega
September 2024
Institute of Hypertension, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, China.
In this study, we conducted a comprehensive analysis to identify key genes and pathways associated with pulmonary arterial hypertension (PAH) and investigated the role of delta-like ligand 4 (DLL4) in PAH pathogenesis. Through integrated analysis of multiple data sets, we identified 6 candidate differentially expressed genes (DEGs), notably , which showed the highest distinguishing efficiency between PAH and control samples. Functional and pathway enrichment analyses revealed the involvement of in critical biological processes and pathways related to PAH, including notch signaling, immune cell function, and inflammatory responses.
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