Cisplatin is widely used in anti-tumor therapy, but the ototoxicity caused by high-dose cisplatin often limits its efficacy, and the specific mechanism of cisplatin-induced cochlear damage is still not perfect. The Wnt/β-catenin signaling pathway is closely related to aging, embryonic development, and apoptosis. Meanwhile, B lymphoma Moloney murine leukemia virus insertion region 1 (BMI1) plays a certain role in the evolution and development of the inner ear and the occurrence and development of inner ear-related diseases. Our study intends to explore the role and specific mechanism of the Wnt/β-catenin signaling pathway and BMI1 in improving cisplatin ototoxicity. The appropriate experimental concentrations for each drug were selected by CCK-8 cell proliferation assay and Western Blot to detect apoptosis. The lentivirus transfection of HEI-OC1 cochlear hair cells was used to overexpress BMI1. Western Blot, qPCR, and immunofluorescence detected the activation of each component of BMI1 and Wnt/β-catenin signaling pathway in each experimental model. Wnt/β-catenin signaling pathway and BMI1 are jointly involved in cisplatin-induced cell injury. Low lithium chloride (LiCl) concentrations activated the Wnt/β-catenin pathway, increased BMI1 expression, and reduced cisplatin-induced hair cell injury. In contrast, overexpression of BMI1 inhibited the Wnt/β-catenin pathway and reduced hair cell injury. Meanwhile, the increased cisplatin-induced damage to hair cells by inhibiting BMI1 could not be rescued by LiCl. In conclusion, LiCl can ameliorate cisplatin ototoxicity by elevating BMI1 expression through activation of the Wnt/β-catenin pathway. Overexpression of BMI1 inhibits the Wnt/β-catenin pathway and reduces cisplatin-induced hair cell damage.
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http://dx.doi.org/10.1016/j.toxlet.2024.11.009 | DOI Listing |
Development
January 2025
Institute of Molecular Biology, Hannover Medical School, 30625 Hannover, Germany.
In the mammalian ureters, the lamina propria presents as a prominent layer of connective tissue underneath the urothelium. Despite its important structural and signaling functions, little is known how the lamina propria develops. Here, we show that in the murine ureter, the lamina propria arises at late fetal stages and massively increases by fibrocyte proliferation and collagen deposition after birth.
View Article and Find Full Text PDFJ Vet Med Sci
January 2025
Department of Small Animal Internal Medicine II, School of Veterinary Medicine, Kitasato University.
This study investigated the anti-inflammatory effects of water-dispersible hesperetin (WD-Hpt) in an endotoxin-induced uveitis (EIU) rat model. The rats were orally administered 10, 25, or 50 mg/kg WD-Hpt immediately after lipopolysaccharide (LPS) injection at the concentration of 200 μg. Clinical scores, cellular inflammation, the aqueous humor (ApH) protein concentration, as well as the levels of tumor necrosis factor (TNF)-α, cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) in AqH, and histopathological grades were assessed.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Nanjing University of Chinese Medicine/National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing 210029, China; Jiangsu Province Key Laboratory of High Technology Research, Nanjing 210029, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing 210023, China. Electronic address:
In recent years, polysaccharides derived from natural sources have garnered significant attention due to their safety and potential anti-osteoporotic effects. This review provides a comprehensive overview of the sources, distribution, structures, and mechanisms of anti-osteoporosis polysaccharides, as well as an investigation into their structure-activity relationships. Over thirty distinct, homogenous polysaccharides with anti-osteoporosis properties have been extracted from natural sources, primarily categorized as glucans, fructans, galactomannans, glucomannans, and various other heteropolysaccharides.
View Article and Find Full Text PDFDev Biol
January 2025
University of Aberdeen, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK. Electronic address:
Signals from the lens regulate multiple aspects of eye development, including establishment of eye size, patterning of the presumptive iris and ciliary body in the anterior optic cup and migration and differentiation of neural crest cells. To advance understanding of the molecular mechanism by which the lens regulates eye development, we performed transcriptome profiling of embryonic chicken retinas after lens removal. Genes associated with nervous system development were upregulated in lens-removed eyes, but the presumptive ciliary body and iris region did not adopt a neural retina identity following lens removal.
View Article and Find Full Text PDFArch Oral Biol
January 2025
Pharmaceutical Sciences and Technology Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand; Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand; Center of Excellent in Natural Products and Nanoparticles (NP2), Chulalongkorn University, Bangkok, Thailand.
Objective: Asiaticoside has the capacity to induce osteogenic differentiation of human periodontal ligament cells (hPDLCs) through Wnt (Wingless-related integration site) signaling. A modified chemical structure (by removing glycoside side chain), referred to as asiatic acid methyl ester (AA1), has been constructed and evaluated for its capacity to induce osteogenic differentiation.
Design: hPDLCs viability was determined by MTT assay.
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