RESUMO
Memory CD8+T cells participate in the fight against infection and tumorigenesis as well as in autoimmune disease progression because of their efficient and rapid immune response, long-term survival, and continuous differentiation. At each stage of their formation, maintenance, and function, the cell metabolism must be adjusted to match the functional requirements of the specific stage. Notably, enhanced glycolytic metabolism can generate sufficient levels of adenosine triphosphate (ATP) to form memory CD8+T cells, countering the view that glycolysis prevents the formation of memory CD8+T cells. This review focuses on how glycometabolism regulates memory CD8+T cells and highlights the key mechanisms through which the mammalian target of rapamycin (mTOR) signaling pathway affects memory CD8+T cell formation, maintenance, and function by regulating glycometabolism. In addition, different subpopulations of memory CD8+T cells exhibit different metabolic flexibility during their formation, survival, and functional stages, during which the energy metabolism may be critical. These findings which may explain why enhanced glycolytic metabolism can give rise to memory CD8+T cells. Modulating the metabolism of memory CD8+T cells to influence specific cell fates may be useful for disease treatment.
Assuntos
Memória Imunológica , Serina-Treonina Quinases TOR , Trifosfato de Adenosina/metabolismo , Animais , Linfócitos T CD8-Positivos , Diferenciação Celular , Glicólise , Camundongos , Camundongos Endogâmicos C57BL , Serina-Treonina Quinases TOR/metabolismoRESUMO
Mesenchymal stem cells (MSCs) have gained attraction not only in the field of regenerative medicine but also in the field of autoimmune disease therapies or organ transplantation due to their immunoregulatory and/or immunosuppressive features. Dendritic cells (DCs) play a crucial role in initiating and regulating immune reactions by promoting antigen-specific T cell activation. In this study, we investigated the effect of human jaw periosteal progenitor cells (JPCs) seeded in beta-tricalcium phosphate (ß-TCP) scaffolds on monocyte-derived DC differentiation. Significantly lower numbers of differentiated DCs were observed in the presence of normal (Co) and osteogenically induced (Ob) JPCs-seeded ß-TCP constructs. Gene expression analysis revealed significantly lower interleukin-12 subunit p35 (IL-12p35) and interleukin-12 receptor beta 2 (IL-12Rß2) and pro-inflammatory cytokine interferon-gamma (IFN-γ) levels in DCs under Ob conditions, while interleukin-8 (IL-8) gene levels were significantly increased. Furthermore, in the presence of JPCs-seeded ß-TCP constructs, interleukin-10 (IL-10) gene expression was significantly induced in DCs, particularly under Ob conditions. Analysis of DC protein levels shows that granulocyte-colony stimulating factor (G-CSF) was significantly upregulated in coculture groups. Our results indicate that undifferentiated and osteogenically induced JPCs-seeded ß-TCP constructs have an overall inhibitory effect on monocyte-derived DC maturation.
Assuntos
Fosfatos de Cálcio/farmacologia , Técnicas de Cocultura , Células Dendríticas/efeitos dos fármacos , Arcada Osseodentária/citologia , Células Cultivadas , Células Dendríticas/metabolismo , Humanos , Arcada Osseodentária/metabolismoRESUMO
Zinc (Zn) and its alloys are proposed as promising resorbable materials for osteosynthesis implants. Detailed studies should be undertaken to clarify their properties in terms of degradability, biocompatibility and osteoinductivity. Degradation products of Zn alloys might affect directly adjacent cellular and tissue responses. Periosteal stem cells are responsible for participating in intramembranous ossification during fracture healing. The present study aims at examining possible effects emanating from Zn or Zn-4Ag (wt%) alloy degradation products on cell viability and osteogenic differentiation of a human immortalized cranial periosteal cell line (TAg cells). Therefore, a modified extraction method was used to investigate the degradation behavior of Zn and Zn-4Ag alloys under cell culture conditions. Compared with pure Zn, Zn-4Ag alloy showed almost fourfold higher degradation rates under cell culture conditions, while the associated degradation products had no adverse effects on cell viability. Osteogenic induction of TAg cells revealed that high concentration extracts significantly reduced calcium deposition of TAg cells, while low concentration extracts enhanced calcium deposition, indicating a dose-dependent effect of Zn ions. Our results give evidence that the observed cytotoxicity effects were determined by the released degradation products of Zn and Zn-4Ag alloys, rather than by degradation rates calculated by weight loss. Extracellular Zn ion concentration was found to modulate osteogenic differentiation of TAg cells. These findings provide significant implications and guidance for the development of Zn-based alloys with an optimized degradation behavior for Zn-based osteosynthesis implants.
Assuntos
Implantes Absorvíveis , Ligas , Materiais Biocompatíveis , Teste de Materiais , Osteogênese/efeitos dos fármacos , Periósteo/metabolismo , Zinco , Ligas/química , Ligas/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Corrosão , Humanos , Periósteo/citologia , Zinco/química , Zinco/farmacologiaRESUMO
In this study, zinccopper (ZnCu) alloys were investigated regarding their feasibility as absorbable metals for osteosynthesis implants, especially in the craniomaxillofacial area. Mechanical properties and in vitro corrosion behavior of as-rolled Zn-xCu (xâ¯=â¯1, 2 and 4â¯wt%) alloys were systematically evaluated and screened. The as-rolled Zn4Cu alloy had mechanical properties that were superior to the most absorbable craniomaxillofacial osteosynthesis materials recently reported. The addition of Cu to Zn showed to have no apparent effect on the corrosion rates of the samples. The rolling process on Zn and Zn1Cu resulted in more uniform corrosion than on as-cast counterparts after 28â¯days immersion. Furthermore, the Zn4Cu alloys exhibited no apparent cytotoxic effect towards L929, TAg or Saos-2 cells. Proliferation rates of TAg and Saos-2 cells were shown to be activated by specific Zn ion concentrations in the as-rolled Zn4Cu alloy extracts. Analysis of in vitro antibacterial properties revealed that the as-rolled Zn4Cu alloy possessed the potential to inhibit biofilm formation of mixed oral bacteria. We conclude that the as-rolled Zn4Cu alloy might be a promising material for fabrication of craniomaxillofacial osteosynthesis implants.
Assuntos
Implantes Absorvíveis , Ligas , Materiais Biocompatíveis , Cobre , Fixação Interna de Fraturas , Teste de Materiais , Zinco , Ligas/química , Ligas/farmacologia , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Linhagem Celular Tumoral , Cobre/química , Cobre/farmacologia , Corrosão , Humanos , Camundongos , Zinco/química , Zinco/farmacologiaRESUMO
Designing cost-efficient and durable electrocatalysts toward oxygen evolution reaction (OER) has been of vital significance for the commercial development of various renewable energy systems. Herein, we report the construction of a new class of 3D hollow nanoflower catalysts that assembled by ultrathin nickel-molybdenum phosphide nanosheets. Owing to the increased electronic and ion transport channels, the heteroatom doping, and synergistic effects from the interconnected compositions, the newly-generated 3D MoNiP hollow nanoflowers display superior OER activity than that of Ir/C. And the optimized Mo1Ni1P hollow nanoflowers (Mo1Ni1P HNFs) can afford a current density of 10â¯mAâ¯cm-2 at the overpotential of 275â¯mV in 1.0â¯M KOH solution. More importantly, the resultant Mo1Ni1P HNFs also display excellent stability with negligible activity and morphology decay. This work provides insights for the utilization of earth-abundant and highly efficient electrocatalysts via rationally designing the morphology of electrocatalysts.