T Cell‐Derived Apoptotic Extracellular Vesicles Hydrolyze cGAMP to Alleviate Radiation Enteritis via Surface Enzyme ENPP1

Advanced Science, Год журнала: 2024, Номер 11(31)

Опубликована: Июнь 18, 2024

Abstract Radiation enteritis is the most common complication of pelvic radiotherapy, but there no effective prevention or treatment drug. Apoptotic T cells and their products play an important role in regulating inflammation maintaining physiological immune homeostasis. Here it shown that systemically infused cell‐derived apoptotic extracellular vesicles (ApoEVs) can target mice irradiated intestines alleviate radiation enteritis. Mechanistically, elevates synthesis intestinal 2′3′ cyclic GMP‐AMP (cGAMP) activates synthase (cGAS)‐stimulator interferon genes (STING) proinflammatory pathway. After systemic infusion ApoEVs, ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) enriches on surface ApoEVs hydrolyze cGAMP, resulting inhibition cGAS‐STING pathway activated by irradiation. Furthermore, after are phagocytosed phagocytes, ENPP1 hydrolyzed intracellular which serves as cGAMP hydrolyzation mode, thereby alleviating The findings shed light hydrolysis capacity regulation.

Язык: Английский

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T Cell-Derived Apoptotic Extracellular Vesicles Ameliorate Bone Loss via CD39 and CD73-Mediated ATP Hydrolysis

International Journal of Nanomedicine, Год журнала: 2025, Номер Volume 20, С. 1083 - 1100

Опубликована: Янв. 1, 2025

Osteoporosis is a major public health concern characterized by decreased bone density. Among various therapeutic strategies, apoptotic extracellular vesicles (ApoEVs) have emerged as promising agents in tissue regeneration. Specifically, T cell-derived ApoEVs shown substantial potential facilitating However, it remains unclear whether can promote mass recovery through enzymatic activity mediated membrane surface molecules. Therefore, this study aimed to investigate could osteoporosis mice and reveal the underlying mechanisms. were isolated sequential centrifugation, their proteomic profiles identified via spectrometry. Western blot immunogold staining confirmed enrichment of CD39 CD73 on ApoEVs. The role hydrolyzing adenosine triphosphate (ATP) was evaluated quantifying levels ATP adenosine. Inhibitors CD73, an A2BR antagonist used explore molecular mechanism promoting significantly reduced loss osteogenic differentiation BMMSCs ovariectomy (OVX) mice. We observed increased decrease key enzymes ATP-to-adenosine conversion marrow OVX found that are enriched with membranes, which enable hydrolysis both vitro vivo. generated inhibits inflammatory response promotes osteogenesis downstream PKA signaling. enabling them hydrolyze adenosine, thereby regeneration signaling pathway. Our data underscore substantive treat osteoporosis, thus providing new ideas for development ApoEVs-based therapies

Язык: Английский

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Butyrate-engineered yeast activates Nppa and Sgcg genes and reduces radiation-induced heart damage via the gut-heart axis

Pharmacological Research, Год журнала: 2025, Номер unknown, С. 107642 - 107642

Опубликована: Фев. 1, 2025

Radiotherapy is a method of treating cancer through radiation aimed at killing cells or inhibiting their growth. However, radiotherapy has numerous side effects because it kills tumors while causing damage to normal tissues. The literature shows that can cause heart tissue. This study found engineered yeast produced butyrate maintain small intestinal barrier function by recovering GPR109A reduce caused abdominal irradiation in mice. We unexpectedly could mitigate irradiation-induced via the gut-heart axis. Mechanistically, enhanced taurine and nicotinamide metabolism increasing relative abundance Akkermansia Lachnospiraceae_NK4A136; then, modulated cardiac activating Sgcg Nppa genes attenuate induced irradiation. Finally, we confirmed mitigated total body irradiation, which protected other vital organs tract. profound impact on treatment, emergence will alleviate benefit patients.

Язык: Английский

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Apoptotic vesicles derived from bone marrow mesenchymal stem cells increase angiogenesis in a hind limb ischemia model via the NAMPT/SIRT1/FOXO1 axis

Stem Cell Research & Therapy, Год журнала: 2025, Номер 16(1)

Опубликована: Март 1, 2025

Abstract Background Chronic limb-threatening ischemia (CLTI) is the most severe form of peripheral arterial disease (PAD). Mesenchymal stem cell (MSC) transplantation holds promise as a treatment for CLTI; however, harsh local environment poses challenges to its effectiveness. Apoptotic vesicles (ApoVs) are extracellular produced by cells undergoing apoptosis, and they can carry various biomolecules from their parent cells, including proteins, RNA, DNA, lipids, ions, gas neurotransmitters. ApoVs play significant roles in anti-inflammatory responses, anti-tumor activities, tissue regeneration through intercellular communication, have demonstrated potential drug carriers. In this study, we investigated bone marrow (BMSC)-derived treating CLTI. Methods vivo, explored therapeutic effect on hindlimb model Laser Doppler, matrigel plug assay, histological analysis. vitro, analyzed effects proliferation, migration, angiogenesis HUVECs uptake process ApoVs. addition, Proteomic analysis, western blotting, quantitative real-time PCR, shRNA, siRNA were used analyze ApoVs-induced activation downstream signaling pathways. Results BMSCs showed improvement hind limb model, still exists after apoptosis BMSCs. Subsequently, isolated found improve mouse vivo. be ingested dynamin-, clathrin-, caveolin-mediated endocytosis promote angiogenesis. Mechanistically, transferred NAMPT HUVECs, therefore activating NAMPT/SIRT1/FOXO1 axis, influencing transcriptional activity FOXO1, promoting Conclusions Our results demonstrate that transplanted ameliorate releasing during apoptosis. The main mechanism axis. This study provides different insights into mechanisms suggests promising direction transplantation. Clinical trial number Not applicable. Graphical

Язык: Английский

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Therapeutic potential of apoptotic vesicles in modulating inflammation, immune responses, and tissue regeneration

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 1, 2025

Abstract The process of apoptosis plays a crucial role in tissue homeostasis, immune system regulation, and organ formation. Apoptotic vesicles (ApoEVs) are involved efferocytosis, the by which phagocytes ingest dead cells. ApoEVs also have potential therapeutic applications cancer treatment, ischemic diseases, their anti-inflammatory properties make them incredibly versatile for medical applications. These can induce cells, provide tumor antigens vaccines, even serve as effective drug delivery systems. Moreover, they target hypoxic inhibit inflammatory cell death pathways, promote regeneration. Also, addressing disorders such gastrointestinal ailments, osteoarthritis, diabetes is promising. Additionally, polarize cells suppress responses viable option unmet need novel medications. Despite wealth reviews examining ApoEVs, very few thoroughly investigated mechanisms underlying effects. This distinctive approach positions current review timely immensely relevant, illuminating intriguing ways these entities function beyond established advantages. Graphical

Язык: Английский

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Metabolomic and Transcriptomic Analysis Reveals Metabolic-Immune Interactions in Choroid Neovascularization

Experimental Eye Research, Год журнала: 2024, Номер 251, С. 110227 - 110227

Опубликована: Дек. 26, 2024

Язык: Английский

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