Controllable All-in-One Biomimetic Hollow Nanoscaffold Initiating Pyroptosis-Mediated Antiosteosarcoma Targeted Therapy and Bone Defect Repair DOI

Qiming Ma,

Shenglin Xu,

Qian Wang

и другие.

ACS Applied Materials & Interfaces, Год журнала: 2024, Номер 16(49), С. 67424 - 67443

Опубликована: Ноя. 27, 2024

Pyroptosis has gained attention for its potential to reinvigorate the immune system within tumor microenvironment. However, current approaches employing pyroptosis inducers suffer from limitations. They primarily rely on single agents, lack precise targeting, and potentially disrupt intricate bone formation microenvironment, hindering local repair of tumor-induced defects. Therefore, a therapeutic strategy is urgently needed that can effectively trigger while simultaneously promoting regeneration. This research introduces an all-in-one construct designed address these It combines cell-camouflaged shell with autosynergistic reactive oxygen species (ROS) generating polymer. incorporates hollow core manganese dioxide (HMnO2) embedded photosensitizer IR780 disguised by cell membrane M1 macrophage. The macrophage grants stealth-like properties, enabling it accumulate selectively at site. Upon laser irradiation, acts as exogenous ROS generation converting light energy into heat. Additionally, structure HMnO2 serves efficient carrier IR780. Furthermore, Mn4+ ions released deplete glutathione (GSH) tumor, further amplifying production. synergistic cascade ultimately culminates in induction through caspase-3-mediated cleavage gasdermin E (GSDME) upon activation. Meanwhile, depletion GSH microenvironment (TME) leads Mn2+ ions. These establish supportive milieu, which promotes transformation marrow mesenchymal stem cells (BMSCs) mature cells. This, turn, defects rat femurs. Our findings strongly indicate may be osteosarcoma treatment, presents robust versatile approach targeted therapy tissue regeneration this patient population.

Язык: Английский

Cell life-or-death events in osteoporosis: All roads lead to mitochondrial dynamics DOI Creative Commons
Zhichao Li,

Songlin Liang,

Liqing Ke

и другие.

Pharmacological Research, Год журнала: 2024, Номер 208, С. 107383 - 107383

Опубликована: Авг. 28, 2024

Mitochondria exhibit heterogeneous shapes and networks within among cell types tissues, also in normal or osteoporotic bone tissues with complex types. This dynamic characteristic is determined by the high plasticity provided mitochondrial dynamics stemmed from responding to survival functional requirements of various cells a specific microenvironments. In contrast, dysfunction, induced dysregulation dynamics, may act as trigger death signals, including common apoptosis other forms programmed (PCD). These PCD processes consisting tightly structured cascade gene expression events, can further influence remodeling facilitating cells. Mitochondrial therefore, drive stand at crossroads life integrating external signals altering metabolism, shape, signal-response properties mitochondria. implies that targeting displays significant potential treatment osteoporosis. Considerable effort has been made osteoporosis emphasize parallel roles mitochondria regulating energy calcium signal transduction, oxidative stress, inflammation, death. However, emerging field dynamics-related not well understood. Herein, bridge gap, we outline latest knowledge on during

Язык: Английский

Процитировано

2

Bazi Bushen attenuates osteoporosis in SAMP6 mice by regulating PI3KAKT and apoptosis pathways DOI Creative Commons
Zhe Xu, Zeyu Zhang,

Huifang Zhou

и другие.

Journal of Cellular and Molecular Medicine, Год журнала: 2024, Номер 28(20)

Опубликована: Окт. 1, 2024

Abstract Osteoporosis (OP), a systemic skeletal disease, is characterized by low bone mass, tissue degradation and microarchitecture disturbance. Bazi Bushen, Chinese patented medicine, has been demonstrated to be effective in attenuating OP, but the pharmacological mechanism remains predominantly unclear. In this study, senescence‐accelerated mouse prone 6 (SAMP6) model was used explore homeostasis treated intragastrically for 9 weeks with Bushen. vivo experiments showed that Bushen treatment not only upregulated levels of mineral density content also increased RUNX2 OSX. Furthermore, primary culture mesenchymal stem cells (BMSCs) SAMP6 mice verify effects on balance differentiation between osteoblasts adipocytes, as well ROS aging levels. Finally, OP investigated through network pharmacology experimental verification, we found could significantly orchestrate attenuate progression stimulating PI3K‐Akt inhibiting apoptosis. summary, our work sheds light first evidence attenuates regulating PI3K‐AKT apoptosis pathways homeostasis.

Язык: Английский

Процитировано

2

Milk-Derived Small Extracellular Vesicles Promote Osteogenic Differentiation and Inhibit Inflammation via microRNA-21 DOI Open Access

Runyuan Liu,

Shuo Liu, Saixuan Wu

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(18), С. 13873 - 13873

Опубликована: Сен. 8, 2023

Chronic apical periodontitis (CAP) is a disease with characteristics of inflammation and bone loss. In this study, our objective was to examine the function small extracellular vesicles (sEVs) obtained from milk in encouraging osteogenic differentiation inhibiting by miR-21 CAP. The expression detected using qRT-PCR human CAP samples. impact on process investigated CCK-8, qRT-PCR, immunofluorescence staining, Western blot analysis. evaluation RAW 264.7 cell polarization assessment inflammatory factor were conducted through qRT-PCR. influence sEVs MC3T3-E1 cells examined, particular emphasis involvement miR-21. samples, decrease observed. MiR-21 increased osteogenesis-related genes M2 while decreasing M1 cytokines. Treatment milk-derived also promoted osteogenesis inflammation. Conversely, addition inhibitors resulted opposite effects. Our results indicated that derived had positive effect formation activation anti-inflammatory (M2) macrophages simultaneously reduced regulating

Язык: Английский

Процитировано

5

Antler blood enhances the ability of stem cell-derived exosomes to promote bone and vascular regeneration DOI Creative Commons

Renjie Zuo,

Quan Liao, Zi‐Wei Ye

и другие.

Regenerative Therapy, Год журнала: 2024, Номер 26, С. 1168 - 1180

Опубликована: Июнь 1, 2024

Bone marrow mesenchymal stem cells (BMSC)-derived exosomes (Exos) are important in promoting bone and vascular regeneration. Antler blood (ALB) is a valuable traditional Chinese medicine with potent regenerative effects. However, there still lack of clarity regarding the relationship between ALB BMSC-Exos.

Язык: Английский

Процитировано

1

Effects of miR-214-5p and miR-21-5p in hypoxic endometrial epithelial-cell-derived exosomes on human umbilical cord mesenchymal stem cells DOI Creative Commons
Wanyu Zhang,

Han-Bi Wang,

Chengyan Deng

и другие.

World Journal of Stem Cells, Год журнала: 2024, Номер 16(11), С. 906 - 925

Опубликована: Ноя. 25, 2024

Thin endometrium seriously affects endometrial receptivity, resulting in a significant reduction embryo implantation, and clinical pregnancy live birth rates, there is no gold standard for treatment. The main pathophysiological characteristics of thin are increased uterine arterial blood flow resistance, angiodysplasia, slow growth the glandular epithelium, low expression vascular endothelial factor, epithelial cell (EEC) hypoxia tissue aplasia. Human umbilical cord mesenchymal stem cells (HucMSCs) promote repair regeneration damaged by secreting microRNA (miRNA)-carrying exosomes. However, initiation mechanism HucMSCs to has not yet been clarified. To determine role hypoxic-EEC-derived exosomes function explore potential mechanism. Exosomes were isolated from normal EECs (EEC-exs) hypoxia-damaged (EECD-exs), before characterization using Western blotting, nanoparticle-tracking analysis, transmission electron microscopy. cocultured with EEC-exs or EECD-exs differentially expressed miRNAs determined sequencing. MiR-21-5p miR-214-5p inhibitors miR-21-3p mimics transfected into treated signal transducer activator transcription 3 (STAT3) STAT3 inhibitor. HucMSC migration was assessed Transwell wound healing assays. Differentiation detecting markers stromal lineage (Vimentin CD13) (CK19 CD9) blotting immunofluorescence. binding targets validated dual-luciferase reporter assay. lowly EECD-ex-pretreated HucMSCs. MiR-214-5p miR-21-5p facilitated migratory differentiative potentials targeted protein inhibitor activated STAT3, respectively, negatively regulated phospho-STAT3. MiR-21-5p- miR-214-5p-inhibitor-induced promotive effects on reversed inhibition. overexpression repressed differentiation, while activation these effects. Low miR-21-5p/miR-214-5p promotes differentiation via signaling. Exosomal miR-214-5p/miR-21-5p may as valuable endometrium.

Язык: Английский

Процитировано

1

Collagen Targeting Bmscs-Derived Extracellular Vesicles Coupled with Decellularized Tendon Scaffold for Anterior Cruciate Ligament Reconstruction DOI
Jie Wang, Jing Cui, Liang‐Ju Ning

и другие.

Опубликована: Янв. 1, 2024

Язык: Английский

Процитировано

0

Controllable All-in-One Biomimetic Hollow Nanoscaffold Initiating Pyroptosis-Mediated Antiosteosarcoma Targeted Therapy and Bone Defect Repair DOI

Qiming Ma,

Shenglin Xu,

Qian Wang

и другие.

ACS Applied Materials & Interfaces, Год журнала: 2024, Номер 16(49), С. 67424 - 67443

Опубликована: Ноя. 27, 2024

Pyroptosis has gained attention for its potential to reinvigorate the immune system within tumor microenvironment. However, current approaches employing pyroptosis inducers suffer from limitations. They primarily rely on single agents, lack precise targeting, and potentially disrupt intricate bone formation microenvironment, hindering local repair of tumor-induced defects. Therefore, a therapeutic strategy is urgently needed that can effectively trigger while simultaneously promoting regeneration. This research introduces an all-in-one construct designed address these It combines cell-camouflaged shell with autosynergistic reactive oxygen species (ROS) generating polymer. incorporates hollow core manganese dioxide (HMnO2) embedded photosensitizer IR780 disguised by cell membrane M1 macrophage. The macrophage grants stealth-like properties, enabling it accumulate selectively at site. Upon laser irradiation, acts as exogenous ROS generation converting light energy into heat. Additionally, structure HMnO2 serves efficient carrier IR780. Furthermore, Mn4+ ions released deplete glutathione (GSH) tumor, further amplifying production. synergistic cascade ultimately culminates in induction through caspase-3-mediated cleavage gasdermin E (GSDME) upon activation. Meanwhile, depletion GSH microenvironment (TME) leads Mn2+ ions. These establish supportive milieu, which promotes transformation marrow mesenchymal stem cells (BMSCs) mature cells. This, turn, defects rat femurs. Our findings strongly indicate may be osteosarcoma treatment, presents robust versatile approach targeted therapy tissue regeneration this patient population.

Язык: Английский

Процитировано

0