Mechanical Stimulation of Anti‐Inflammatory and Antioxidant Hydrogels for Rapid Re‐Epithelialization

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(18)

Published: Jan. 26, 2024

Abstract The epithelium, an essential barrier to protect organisms against infection, exists in many organs. However, rapid re‐epithelialization restore tissue integrity and function adverse environment is challenging. In this work, a long‐term anti‐inflammatory antioxidant hydrogel with mechanical stimulation for re‐epithelialization, mainly composed of the small molecule thioctic acid, biocompatible glycine, γ‐Fe 2 O 3 nanoparticles reported. Glycine‐modified supramolecular acid stable possesses outstanding properties. incorporating providing potential contrast magnetic resonance imaging observation, can propel reconfiguration enhance properties underwater due water‐initiated release Fe 3+ . vitro experiments show that hydrogels effectively reduced intracellular reactive oxygen species, guided macrophages toward M2 polarization, alleviated inflammation. effect ultimately demonstrated long urethral injury model vivo, achieves effective functional replacement accurate remodeling epithelium. Notably, proposed strategy provides advanced alternative treatment patients need large‐area epithelial reconstruction.

Language: Английский

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Akkermansia muciniphila inhibits tryptophan metabolism via the AhR/β-catenin signaling pathway to counter the progression of colorectal cancer

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(14), P. 4393 - 4410

Published: Jan. 1, 2023

Akkermansia muciniphila (A. muciniphila), a gram-negative anaerobic bacterium, is selectively decreased in the fecal microbiota of patients with colorectal cancer (CRC), but its molecular mechanism CRC development remains inconclusive. In this study, we first confirmed inhibitory effect A. on formation and analyzed metabolic role intestinal flora human Polyps, A-CRA (advanced adenoma) samples. To better clarify development, pseudo-germ-free (GF) azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model was established, followed by infection or without muciniphila. Metabolomic analysis RNA-seq showed tryptophan-mediated aryl hydrocarbon receptor (AhR) significantly down-regulated muciniphila-infected mice. Then, mice specific AhR deficiency (AhRfl/fl Cre) were generated used 2 murine models: AOM/DSS treatment as carcinogen-induced colon genetically induced using ApcMin/+ Notably, inhibited growth model. Moreover, inhibited, rather than enhanced, tumor tumor-derived organoids Apc-deficient cells both vivo vitro activating Wnt/β-catenin signaling TCF4/LEF1-dependent transcription. Furthermore, antitumor effectiveness abolished either subcutaneous transplantation AhR-silenced cells, AhR-deficienty spontaneous conclusion, supplementation protected from specifically inhibiting AhR/β-catenin signaling.

Language: Английский

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Transforming Growth Factor Beta Promotes Inflammation and Tumorigenesis in Smad4‐Deficient Intestinal Epithelium in a YAP‐Dependent Manner

Advanced Science, Journal Year: 2023, Volume and Issue: 10(23)

Published: June 1, 2023

Transforming growth factor beta (TGF-β), a multifunctional cytokine, plays critical roles in immune responses. However, the precise role of TGF-β colitis and colitis-associated cancer remains poorly defined. Here, it is demonstrated that promotes colonic inflammation related tumorigenesis absence Smad family member 4 (Smad4). Smad4 loss intestinal epithelium aggravates neoplasia induced by dextran sulfate sodium (DSS) azoxymethane/dextran (AOM/DSS), leading to over-activated responses increased TGF-β1 levels. In Smad4-deficient organoids, stimulates spheroid formation impairs stem cell proliferation lineage specification. YAP, whose expression directly upregulated after deletion, mediates effect interacting with Smad2/3. Attenuation YAP/TAZ prevents TGF-β1-induced Smad4-/- organoids alleviates mice. Collectively, these results highlight an integral TGF-β/Smad4 axis restraining suggest or YAP signaling as therapeutic targets for gastrointestinal diseases intervention.

Language: Английский

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Selenium Attenuates Radiation Colitis by Regulating cGAS‐STING Signaling

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 30, 2024

Abstract Radiation colitis is one of the most common complications in patients undergoing pelvic radiotherapy and there no effective treatment clinic. Therefore, searching for agents radiation urgently needed. Herein, it found that essential element selenium (Se) protective against through inhibiting X‐ray‐induced apoptosis, cell cycle arrest, inflammation with involvement balancing generation reactive oxygen species after irradiation. Mechanistically, Se, especially nanoparticles (SeNPs), induced selenoprotein expression then functioned to effectively restrain DNA damage response, which reduced intestinal injury. Additionally, SeNPs also restrained cyclic GMP‐AMP synthas (cGAS)‐ stimulator interferon genes (STING)‐TBK1‐IRF3 signaling pathway cascade, thereby blocking transcription inflammatory cytokine gene, IL‐6 TNF‐α, thus alleviating inflammation. Moreover, inducing expression, such as GPX4, vivo can regulate microenvironment immunity gut microbiota attenuate radiation‐induced by oxidative stress maintaining homeostasis. Together, these results unravel a previously unidentified modulation role but suppressing cGAS‐STING‐TBK1‐IRF3 cascade.

Language: Английский

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Vibrio cholerae arrests intestinal epithelial proliferation through T6SS-dependent activation of the bone morphogenetic protein pathway

Cell Reports, Journal Year: 2024, Volume and Issue: 43(2), P. 113750 - 113750

Published: Feb. 1, 2024

To maintain an effective barrier, intestinal progenitor cells must divide at a rate that matches the loss of dead and dying cells. Otherwise, epithelial breaches expose host to systemic infection by gut-resident microbes. Unlike most pathogens, Vibrio cholerae blocks tissue repair arresting proliferation in Drosophila model. At present, we do not understand how V. circumvents such critical antibacterial defense. We find activating growth inhibitor bone morphogenetic protein (BMP) pathway progenitors. Specifically, show interactions between gut commensals initiate BMP signaling via innate immune defenses. Notably, also activates arrests zebrafish intestines, indicating evolutionarily conserved link failure repair. Our study highlights enteric pathogens engage regulatory pathways disrupt

Language: Английский

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The role of intestinal macrophage polarization in colitis-associated colon cancer

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 5, 2025

Chronic inflammation of the intestine is a significant risk factor in development colorectal cancer. The emergence colitis and cancer complex, multifactorial process involving chronic inflammation, immune regulation, tumor microenvironment remodeling. Macrophages represent one most prevalent cells play pivotal role maintaining intestinal health colitis-associated colon (CAC). are activated mainly two ways resulted three phenotypes: classically macrophages (M1), alternatively (M2). characteristic these pro-inflammatory M1 anti-inflammatory M2 types, which different roles at stages disease. During progresses to cancer, proportion gradually increases. secrete cytokines such as IL-10 TGF-β, promote angiogenesis matrix remodeling, create favorable conditions for cell proliferation, infiltration, migration. Therefore, macrophage polarization has dual effect on progression CAC. combination immunotherapy with reprogrammed anti-tumor drugs may provide an effective means enhancing therapeutic effect. It promising avenue developing novel treatments In this review, we focus CAC review targets relevant targeting

Language: Английский

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The Erk1/2-EGR1 signaling pathway is involved in lipopolysaccharide-induced transforming growth factor-beta 1 expression in mouse macrophages

Microbial Pathogenesis, Journal Year: 2025, Volume and Issue: unknown, P. 107453 - 107453

Published: March 1, 2025

Language: Английский

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The Role of Yes‐Associated Protein in Inflammatory Diseases and Cancer

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: March 1, 2025

Yes-associated protein (YAP) plays a central role in the Hippo pathway, primarily governing cell proliferation, differentiation, and apoptosis. Its significance extends to tumorigenesis inflammatory conditions, impacting disease initiation progression. Given increasing relevance of YAP disorders cancer, this study aims elucidate its pathological regulatory functions these contexts. Specifically, we aim investigate involvement molecular mechanisms various diseases cancers. We particularly focus on how activation, whether through Hippo-dependent or independent pathways, triggers release inflammation mediators respiratory, cardiovascular, digestive conditions. In not only promotes tumor proliferation differentiation but also modulates immune microenvironment, thereby fostering metastasis Additionally, provide an overview current YAP-targeted therapies. By emphasizing YAP's enhance our understanding protein's pivotal processes, intricate related diseases, contribute future drug development strategies targeting YAP.

Language: Английский

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Emerging Role and Mechanism of Mesenchymal Stem Cells-Derived Extracellular Vesicles in Rheumatic Disease

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 6827 - 6846

Published: Sept. 1, 2024

Mesenchymal stem cells (MSCs) are pluripotent derived from mesoderm. Through cell-to-cell contact or paracrine effects, they carry out biological tasks like immunomodulatory, anti-inflammatory, regeneration, and repair. Extracellular vesicles (EVs) the primary mechanism for regulation of MSCs. They deliver proteins, nucleic acids, lipids, other active compounds to various tissues organs, thus facilitating intercellular communication. Rheumatic diseases may be treated using MSCs MSC-derived EVs (MSC-EVs) due their immunomodulatory capabilities, according mounting data. Since MSC-EVs have low immunogenicity, high stability, similar effects as themselves, advantageous over cell therapy potential therapeutic applications in rheumatoid arthritis, systemic erythematosus lupus, sclerosis, Sjogren's syndrome, diseases. This review integrates recent advances characteristics, functions, molecular mechanisms rheumatic provides a new understanding pathogenesis MSC-EV-based treatment strategies.

Language: Английский

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Hippo signaling modulation and its biological implications in urological malignancies

Molecular Aspects of Medicine, Journal Year: 2024, Volume and Issue: 98, P. 101280 - 101280

Published: June 12, 2024

Language: Английский

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