Regulatory T cells (Tregs) and T helper 17 (Th17) cells contribute to cancer progression and prognosis. However, regulatory factors associated with Tregs-Th17 balance were not completely understood. We previously demonstrated an immune-modulatory capacity by Notch signaling inactivation to reverse Tregs-Th17 disequilibrium in chronic hepatitis C. Thus, the aim of current study was to assess the role of Notch signaling in modulation Tregs and Th17 cells function in gastric cancer (GC) patients. A total of 51 GC patients and 18 normal controls (NCs) were enrolled. Notch1 and Notch2 mRNA expressions were semiquantified by real-time polymerase chain reaction. Tregs/Th17 percentages, transcriptional factors, and cytokines production were investigated in response to the stimulation of Notch signaling inhibitor DAPT. Both Notch1 and Notch2 mRNA expressions were elevated in GC tissues and peripheral bloods in GC patients. CD4CD25CD127 Tregs and Th17 cells percentage was also elevated in GC patients compared with in NCs. DAPT treatment did not affect frequency of either circulating Tregs or Th17 cells, however, reduced FoxP3/RORγt mRNA expression and interleukin (IL)-35/IL-17 production in purified CD4 T cells from GC patients. Moreover, blockade of Notch signaling also inhibited the suppressive function of purified CD4CD25CD127 Tregs from GC patients, which presented as elevation of cellular proliferation and IL-35 secretion. The current data further provided mechanism underlying Tregs-Th17 balance in GC patients. The link between Notch signaling and Th cells might lead to a new therapeutic target for GC patients.
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http://dx.doi.org/10.1042/BSR20182044 | DOI Listing |
J Biol Chem
January 2025
The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada, M5G 1X8; Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, ON, Canada, M5G 2M9. Electronic address:
The NUMB gene encodes a conserved adaptor protein with roles in asymmetric cell division and cell fate determination. First described as an inhibitor of Notch signaling, multi-functional NUMB proteins regulate multiple cellular pathways through protein complexes with ubiquitin ligases, polarity proteins and the endocytic machinery. The vertebrate NUMB protein isoforms were identified over two decades ago, yet the majority of functional studies exploring NUMB function in endocytosis, cell migration and adhesion, development and disease have largely neglected the potential for distinct isoform activity in design and interpretation.
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2025
State Key Laboratory of Fire Science, University of Science and Technology of China, 443 Huangshan Road, Hefei 230027, P. R.China.
The next generation of stretchable electronics seeks to integrate superior mechanical properties with sustainability and sensing stability. Ionically conductive and liquid-free elastomers have gained recognition as promising candidates, addressing the challenges of evaporation and leakage in gel-based conductors. In this study, a sustainable polymeric deep eutectic system is synergistically integrated with amino-terminated hyperbranched polyamide-modified fibers and aluminum ions, forming a conductive supramolecular network with significant improvements in mechanical performance.
View Article and Find Full Text PDFSensors (Basel)
January 2025
Laboratory of Vibration and Noise, Naval University of Engineering, Wuhan 430033, China.
Pulsation noise in the piping system generated by the excitation of the pump source seriously affects the reliability of the pipeline system and mechanical equipment. The active noise control can effectively suppress the low-frequency noise in the liquid-filled pipeline. Active control methods with intrusive secondary sources generally use dynamic pressure sensors or hydrophones to collect signals, which destroy the structure of the pipe.
View Article and Find Full Text PDFMaterials (Basel)
January 2025
Laboratory for Testing and Materials, Department of Mechanics, School of Applied Mathematical and Physical Sciences, National Technical University of Athens, Zografou Campus, 157 73 Athens, Greece.
The fracture process of heterogeneous materials is studied here in the framework of the discipline of Non-Extensive Statistical Mechanics. Acoustic emission data provided by an experimental protocol with concrete specimens, plain or fiber-reinforced, under bending are taken advantage of. This innovation of the study lies in the fact that the analysis of the acoustic activity is implemented in terms of the energy content of the acoustic signals rather than of their interevent time or their interevent distance.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Biochemistry and Biophysics, "Carol Davila" University of Medicine and Pharmacy of Bucharest, 050474 Bucharest, Romania.
Cancer stem cells (CSC) are known to be the main source of tumor relapse, metastasis, or multidrug resistance and the mechanisms to counteract or eradicate them and their activity remain elusive. There are different hypotheses that claim that the origin of CSC might be in regular stem cells (SC) and, due to accumulation of mutations, these normal cells become malignant, or the source of CSC might be in any malignant cell that, under certain environmental circumstances, acquires all the qualities to become CSC. Multiple studies indicate that lifestyle and diet might represent a source of wellbeing that can prevent and ameliorate the malignant phenotype of CSC.
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