Uncovering the complex role of interferon-gamma in suppressing type 2 immunity to cancer

Cytokine, Journal Year: 2023, Volume and Issue: 171, P. 156376 - 156376

Published: Sept. 23, 2023

Language: Английский

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Luteolin: A promising multifunctional natural flavonoid for human diseases

Phytotherapy Research, Journal Year: 2024, Volume and Issue: 38(7), P. 3417 - 3443

Published: April 26, 2024

Abstract Natural products are closely associated with human health. Luteolin (LUT), a flavonoid polyphenolic compound, is widely found in fruits, vegetables, flowers, and herbs. It noteworthy that LUT exhibits variety of beneficial pharmacological properties holds significant potential for clinical applications, particularly antitumor, anti‐convulsion, diabetes control, anti‐inflammatory, neuroprotection, anti‐oxidation, anti‐cardiovascular, other aspects. The mechanism action has been partially elucidated, including the mediation NF‐κB, toll‐like receptor, MAPK, Wnt/β‐catenin, PI3K/Akt, AMPK/mTOR, Nrf‐2, among others. review aimed to comprehensively consolidate essential information on natural sources, effects, therapeutic preventive potential, as well mechanisms LUT. objective establish theoretical basis continued development application

Language: Английский

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Klotho attenuates epithelial‑mesenchymal transition of retinal pigment epithelial cells in subretinal fibrosis by suppressing the ERK1/2 and Wnt/β‑catenin signaling pathways

International Journal of Molecular Medicine, Journal Year: 2025, Volume and Issue: 55(3)

Published: Jan. 10, 2025

Retinal pigment epithelial (RPE) cells undergoing epithelial‑mesenchymal transition (EMT) are a key factor in promoting the progression of subretinal fibrosis. The klotho protein and gene exert anti‑fibrotic effects multiple fibrotic diseases. However, mechanisms involved role unclear aim present study was to explore on fibrosis induced by laser photocoagulation mice EMT TGF‑β1 RPE underlying molecular mechanisms. In vitro, overexpression or knockdown performed ARPE‑19 (adult retinal Pigment Epithelial‑19), then treatment applied. Using western blotting, expression markers (zonula occludens‑1), mesenchymal signs (α‑smooth muscle actin, α‑SMA, N‑cadherin, N‑cad collagen I), ERK1/2 Wnt/β‑catenin signaling pathways were assessed. proliferative ability examined CCK‑8 EdU test, migratory wound healing Transwell assays. Furthermore, pathway overexpression, RNA‑sequencing (seq) performed. vivo, used induce mice, which occurs as result choroidal neovascularization (CNV), recombinant mouse administered intravitreally. Upregulation downregulation demonstrated that prevented TGF‑β1‑induced EMT; resulted opposite effects. Additionally, suppressed cell proliferation migration attenuated activated TGF‑β1. RNA‑seq results several pathways, including cellular senescence TNF pathway, associated with overexpression. areas following laser‑induced CNV lesions, illustrated immunofluorescence Masson staining eyes. Western blotting levels significantly downregulated those upregulated. In summary, suggested may have therapeutic value management vitreoretinal disorders such

Language: Английский

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Recent advances of smart materials for ocular drug delivery

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 200, P. 115006 - 115006

Published: July 13, 2023

Language: Английский

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Wnt5a/β-catenin-mediated epithelial-mesenchymal transition: a key driver of subretinal fibrosis in neovascular age-related macular degeneration

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: March 26, 2024

Abstract Background Neovascular age-related macular degeneration (nAMD), accounts for up to 90% of AMD-associated vision loss, ultimately resulting in the formation fibrotic scar region. The pathogenesis subretinal fibrosis nAMD involves process epithelial–mesenchymal transition (EMT) occurring retinal pigment epithelium (RPE). Here, we aim investigate underlying mechanisms involved Wnt signaling during EMT RPE cells and pathological secondary nAMD. Methods In vivo, induction was performed male C57BL/6J mice through laser photocoagulation. Either FH535 (a β-catenin inhibitor) or Box5 Wnt5a intravitreally administered on same day 14 days following induction. RPE-Bruch's membrane-choriocapillaris complex (RBCC) tissues were collected subjected Western blot analysis immunofluorescence examine fibrovascular Wnt-related markers. vitro, transforming growth factor beta 1 (TGFβ1)-treated ARPE-19 co-incubated with without FH535, Foxy-5 Wnt5a-mimicking peptide), Box5, shRNA, respectively. changes EMT- molecules, as well cell functions assessed using qRT-PCR, nuclear-cytoplasmic fractionation assay, blot, immunofluorescence, scratch assay transwell migration assay. viability determined Cell Counting Kit (CCK)-8. Results vivo demonstrated Wnt5a/ROR1, but not Wnt3a, upregulated RBCCs laser-induced CNV compared normal control group. Intravitreal injection effectively reduced protein expression. Both attenuated EMT, activation mice, evidenced by significant reduction areas positive fibronectin, alpha-smooth muscle actin (α-SMA), collagen I, active labeling. β-catenin, some other molecules TGFβ1-induced model cells. Co-treatment shRNA markedly suppressed Wnt5a, nuclear translocation TGFβ1-treated Conversely, treatment independently resulted abovementioned subsequent Conclusions Our study reveals a reciprocal between mediate pivotal driver This feedback loop provides valuable insights into potential therapeutic strategies treat patients.

Language: Английский

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YAP in development and disease: Navigating the regulatory landscape from retina to brain

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116703 - 116703

Published: May 6, 2024

The distinctive role of Yes-associated protein (YAP) in the nervous system has attracted widespread attention. This comprehensive review strategically uses retina as a vantage point, embarking on an extensive exploration YAP's multifaceted impact from to brain development and pathology. Initially, we explore crucial roles YAP embryonic cerebral development. Our focus then shifts retinal development, examining detail regulatory influence pigment epithelium (RPE) progenitor cells (RPCs), its significant effects hierarchical structure functionality retina. We also investigate essential contributions maintaining homeostasis, highlighting precise regulation cell proliferation survival. In terms retinal-related diseases, epigenetic connections pathophysiological diabetic retinopathy (DR), glaucoma, proliferative vitreoretinopathy (PVR). Lastly, broaden our brain, emphasizing research paradigm "retina: window brain." Special is given emerging studies disorders such Alzheimer's disease (AD) Parkinson's (PD), underlining potential therapeutic value neurodegenerative neuroinflammation.

Language: Английский

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Astilbin inhibited neutrophil extracellular traps in gouty arthritis through suppression of purinergic P2Y6 receptor

Phytomedicine, Journal Year: 2024, Volume and Issue: 130, P. 155754 - 155754

Published: May 17, 2024

Language: Английский

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A review on decoding the roles of YAP/TAZ signaling pathway in cardiovascular diseases: Bridging molecular mechanisms to therapeutic insights

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 271, P. 132473 - 132473

Published: May 23, 2024

Language: Английский

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Precision nutrition based on food bioactive components assisted by delivery nanocarriers for ocular health

Trends in Food Science & Technology, Journal Year: 2025, Volume and Issue: unknown, P. 104923 - 104923

Published: Feb. 1, 2025

Language: Английский

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Unraveling the role of CRX as a potent intrinsic suppressor of epithelial-mesenchymal transition in retinal pigment epithelial cells

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is one the significant pathogenic mechanisms for formation subretinal fibrosis in age-related macular degeneration (AMD). Multiple signaling pathways that promote EMT have been well described, yet endogenous inhibit within RPE remain largely elusive. In this study, we confirmed expression CRX human and embryonic stem cell-derived (ESC-RPE) cells. By employing sub-culture to disrupt intercellular connections thereby Hippo pathway, combined with TGF-β1 treatment vitro mimic microenvironment fibrosis, it was revealed Hippo/YAP1 synergistically promoted nuclear translocation β-catenin, latter bound TCF7 CRX. Overexpression capable suppressing occurrence ESC-RPE exerted its inhibitory effect on partly by upregulating PPP2R2B. laser-induced choroidal neovascularization mouse model, took place cells, overexpression played an role fibrosis. This study has identified as molecule inhibits provided a new research target strategy wet AMD inhibition formation.

Language: Английский

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