Calcium signaling plays a vital role in the regulation of various cellular processes, including activation, proliferation, and differentiation of T-lymphocytes, which is mediated by ORAI1 and potassium (K) channels. These channels have also been identified as highly attractive therapeutic targets for immune-related diseases. Licochalcone A is a licorice-derived chalconoid known for its multifaceted beneficial effects in pharmacological treatments, including its anti-inflammatory, anti-asthmatic, antioxidant, antimicrobial, and antitumorigenic properties. However, its anti-inflammatory effects involving ion channels in lymphocytes remain unclear. Thus, the present study aimed to investigate whether licochalcone A inhibits ORAI1 and K channels in T-lymphocytes. Our results indicated that licochalcone A suppressed all three channels (ORAI1, Kv1.3, and KCa3.1) in a concentration-dependent matter, with IC values of 2.97 ± 1.217 µM, 0.83 ± 1.222 µM, and 11.21 ± 1.07 µM, respectively. Of note, licochalcone A exerted its suppressive effects on the IL-2 secretion and proliferation in CD3 and CD28 antibody-induced T-cells. These results indicate that the use of licochalcone A may provide an effective treatment strategy for inflammation-related immune diseases.
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http://dx.doi.org/10.3390/ijms221910847 | DOI Listing |
Int Urogynecol J
January 2025
Department of Medical Genetics, Warsaw Medical University, Pawinskiego 3C, 02-106, Warsaw, Poland.
Introduction And Hypothesis: Pelvic floor dysfunction usually results in pelvic organ prolapse (POP) and/or urinary incontinence. In women, several factors, including pregnancy and vaginal delivery, can affect pelvic muscle conditions. The aim of the study was to perform a genetic analysis in young women with a family history of pelvic floor dysfunction to find potentially harmful variants or variants that increase the risk of developing pelvic floor disorders.
View Article and Find Full Text PDFSci Adv
January 2025
Fels Cancer Institute for Personalized Medicine, Department of Cancer & Cellular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
Arthritis leads to bone erosion due to an imbalance between osteoclast and osteoblast function. Our prior investigations revealed that the Ca-selective ion channel, Orai1, is critical for osteoclast maturation. Here, we show that the small-molecule ELP-004 preferentially inhibits transient receptor potential canonical (TRPC) channels.
View Article and Find Full Text PDFBMC Med
January 2025
Physiological Institute, University of Regensburg, University Street 31, 93053, Regensburg, Germany.
Background: Dystonia is a common neurological hyperkinetic movement disorder that can be caused by mutations in anoctamin 3 (ANO3, TMEM16C), a phospholipid scramblase and ion channel. We previously reported patients that were heterozygous for the ANO3 variants S651N, V561L, A599D and S651N, which cause dystonia by unknown mechanisms.
Methods: We applied electrophysiology, Ca measurements and cell biological methods to analyze the molecular mechanisms that lead to aberrant intracellular Ca signals and defective activation of K channels in patients heterozygous for the ANO3 variants.
Am J Physiol Cell Physiol
January 2025
Department of Physiology (Cellular Physiology Research Group),Institute of Molecular Pathology Biomarkers (IMPB), University of Extremadura, 10003-Caceres, Spain.
Filamin A (FLNA) is an actin-binding protein that has been reported to interact with STIM1 modulating the activation of Orai1 channels. Cleaving of FLNA by calpain leads to a C-terminal fragment that is involved in a variety of functional and pathological events, including pro-oncogenic activity in different types of cancer. Here we show that full-length FLNA is downregulated in samples from colon cancer patients as well as in the adenocarcinoma cell line HT-29.
View Article and Find Full Text PDFSci Transl Med
December 2024
Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA.
Sjögren's disease (SjD) is an autoimmune disorder characterized by progressive salivary and lacrimal gland dysfunction, inflammation, and destruction, as well as extraglandular manifestations. SjD is associated with autoreactive B and T cells, but its pathophysiology remains incompletely understood. Abnormalities in regulatory T (T) cells occur in several autoimmune diseases, but their role in SjD is ambiguous.
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