Gene Expression Patterns, Journal Year: 2024, Volume and Issue: unknown, P. 119388 - 119388
Published: Dec. 1, 2024
Language: Английский
Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)
Published: Jan. 13, 2025
Ewing's sarcoma (EwS), a common pediatric bone cancer, is associated with poor survival due to lack of therapeutic targets for immunotherapy or targeted therapy. Therefore, more effective treatment options are urgently needed. Since novel immunotherapies may address this need, we performed an integrative analysis involving single-cell RNA sequencing, cell function experiments, and humanized models dissect the immunoregulatory interactions in EwS identify strategies optimizing immunotherapeutic efficacy. infiltrated by immunosuppressive myeloid populations, T B lymphocytes, natural killer cells. We found that SLC40A1 C1QA macrophages were prognosis, whereas CD8+ T-cell infiltration was good prognosis. A comparative paired samples revealed tumors chemotherapeutic response, presented increased antigen presentation reduced release protumor cytokines, cells cytotoxicity exhaustion. An interaction vast network identified MIF-CD74 as crucial target can simultaneously promote M2 polarization inhibit infiltration. Importantly, MIF blockade effectively reshaped tumor immune microenvironment, turning cold hot inhibiting growth. Our MIF/CD74 axis promising Ewing provides rationale immunotherapy.
Language: Английский
Citations
1
Advanced Science, Journal Year: 2024, Volume and Issue: 11(23)
Published: April 8, 2024
Abstract Activating autologous stem cells after the implantation of biomaterials is an important process to initiate bone regeneration. Although several studies have demonstrated mechanism biomaterial‐mediated regeneration, a comprehensive single‐cell level transcriptomic map revealing influence on regulating temporal and spatial expression patterns mesenchymal (MSCs) still lacking. Herein, osteoimmune microenvironment depicted around classical collagen/nanohydroxyapatite‐based repair materials via combining analysis RNA sequencing transcriptomics. A group functional MSCs with high matrix Gla protein ( Mgp ) identified, which may serve as pioneer subpopulation involved in repair. Remarkably, these high‐expressing hi MSCs) exhibit efficient osteogenic differentiation potential orchestrate implanted biomaterials, rewiring polarization osteoclastic macrophages through Mdk/Lrp1 ligand–receptor pair. The inhibition activates pro‐inflammatory programs osteoclastogenesis. Meanwhile, multiple immune‐cell subsets also close crosstalk between secreted phosphoprotein 1 (SPP1) signaling pathway. These cellular profiles interactions characterized this study can broaden understanding MSC subpopulations at early stage regeneration provide basis for materials‐designed strategies that target modulation.
Language: Английский
Citations
7
ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 22, 2025
As one of the most promising means to repair diseased tissues, stem cell therapy with immense potential differentiate into mature specialized cells has been rapidly developed. However, clinical application stem-cell-dominated regenerative medicine was heavily hindered by loss pluripotency during long-term in vitro expansion. Here, a composite three-dimensional (3D) graphene-based biomaterial, denoted as GO-Por-CMP@CaP, hierarchical pore structure (micro- macropore), developed guide directional differentiation human umbilical cord MSCs (hucMSCs) osteoblasts. GO-Por-CMP@CaP could act high-efficiency living material without "dead space", effectively regulating cellular response. The 3D topological generated via two-step modification on two-dimensional graphene mimic natural microenvironment cells, enhancing attachment, which is not only conducive for proliferation but also beneficial osteogenic differentiation. Meanwhile, wide existence interconnected macropores favorable bone ingrowth, capillary formation, well nutrients transportation. Furthermore, concurrent micro- and mesopores significantly promoted extracellular matrix (ECM) adsorption, ensured leading multiscale osteointegration. Both vivo assay demonstrated above three factors collaborated mutually nanosized calcium phosphate (CaP, chemical similarities inorganic components bone), provided abundant adhesive sites adequately induce absence any soluble growth factors. Proteomic analysis experiments confirmed that hucMSCs osteoblasts affecting PI3K-Akt signaling pathway through up-regulation SPP1 protein. Our study offers pure material-based behavior engineering dimension porosity material, provides insights design development substitutes materials.
Language: Английский
Citations
0
Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown
Published: March 4, 2025
Abstract Adipose‐derived stem cells (ADSCs) hold significant promise in bone tissue engineering due to their self‐renewal capacity and easy accessibility. However, limited osteogenic potential remains a critical challenge for clinical application repair. Emerging evidence suggests that circular RNAs (circRNAs) play key role regulating cell fate osteogenesis. Despite this, the specific mechanisms by which circRNAs influence ADSCs context of are largely unexplored. This study introduces novel strategy utilizing circAars, circRNA, modify ADSCs, then incorporated into gelatin methacryloyl (GelMA) hydrogels repair critical‐sized maxillofacial defects. The findings reveal circAars predominantly localizes cytoplasm where it acts as competitive sponge miR‐128‐3p, enhancing differentiation migration capabilities ADSCs. Furthermore, circAars‐engineered facilitate macrophage polarization from M1 M2 phenotype enhance endothelial (EC) angiogenic through paracrine mechanism. Additionally, GelMA scaffolds loaded with accelerate defects synergistically promoting osteogenesis, polarization, angiogenesis. approach offers promising therapeutic treatment
Language: Английский
Citations
0
ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(30), P. 39035 - 39050
Published: July 19, 2024
Given the widespread clinical demand, addressing irregular cranial bone defects poses a significant challenge following surgical procedures and traumatic events. In situ-formed injectable hydrogels are attractive for due to their ease of administration ability incorporate ceramics, ions, proteins into hydrogel. this study, multifunctional hydrogel composed oxidized sodium alginate (OSA)-grafted dopamine (DO), carboxymethyl chitosan (CMCS), calcium ions (Ca2+), nanohydroxyapatite (nHA), magnesium oxide (MgO) (DOCMCHM) was prepared address via dynamic Schiff base chelation reactions. DOCMCHM exhibits strong adhesion wet tissues, self-healing properties, antibacterial characteristics. Biological evaluations indicate that has good biocompatibility, in vivo degradability, promote cell proliferation. Importantly, hydrogel, containing MgO, promotes expression osteogenic protein markers COL-1, OCN, RUNX2, stimulates formation new blood vessels by upregulating CD31. This study could provide meaningful insights ion therapy repair defects.
Language: Английский
Citations
3
Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(6), P. 5052 - 5065
Published: May 22, 2024
A low-calcium microenvironment is imperative for spermatozoa maturation within the epididymis. Our previous work has shown that γ-glutamyl carboxylase (GGCX), carboxylation enzyme of matrix Gla protein (MGP), plays an essential role in epididymal calcium homeostasis and sperm rats GGCX SNP mutation rs699664 was associated with asthenozoospermia (AZS) humans. Here, we investigated expression patterns MGP mouse epididymis generated GgcxK325Q knock-in (KI) mice. We also tested effects this on homeostasis, function, male fertility GgcxK325Q−/− The results showed both were enriched all regions epididymis, especially initial segment Double immunofluorescence staining revealed colocalized epithelial cells caput as well lumen corpus cauda However, mice fertile normal morphology, functions, concentration. Overall, our findings does not exert any discernible effect
Language: Английский
Citations
0
Gene Expression Patterns, Journal Year: 2024, Volume and Issue: unknown, P. 119388 - 119388
Published: Dec. 1, 2024
Language: Английский
Citations
0