Fas ligand (FasL, CD178) belongs to classical apoptotic molecules, however, recent evidence expands the spectrum of FasL functions into non-apoptotic processes which also applies for the bone. Tgfb subfamily members (Tgfb1, Tgfb2, Tgfb3) represent major components in osteogenic pathways and extracellular matrix. Their possible association with FasL has not yet been investigated but can be postulated. To test such a hypothesis, FasL deficient (gld) calvaria-derived cells were examined with a focus on the expression of Tgfb receptor ligands. The qPCR analysis revealed significantly increased expression of Tgfb1, Tgfb2 and Tgfb3 in gld cells. To check the vice versa effect, the gld cells were stimulated by soluble FasL. As a consequence, a dramatic decrease in expression levels of all three ligands was observed. This phenomenon was also confirmed in IDG-SW3 (osteoblastic cells of endochondral origin). TFLink gateway identified Fosl2 as an exclusive candidate of FasL capable to impact expression of all three Tgfb ligands. However, Fosl2 siRNA did not cause any significant changes in expression of Tgfb ligands. Therefore, the upregulation of the three ligands is likely to occur separately. In this respect, we tested the only exclusive candidate transcription factor for Tgfb3, Prrx1. Additionally, an overlapping candidate for Tgfb1 and Tgfb2, Mef2c capable to modulate expression of sclerostin, was examined. Prrx1 as well as Mef2c were found upregulated in gld samples and their expression decreased after addition of FasL. The same effect of FasL treatment was observed in the IDG-SW3 model. Taken together, FasL deficiency causes an increase in the expression of Tgfb ligands and stimulation by FasL reduces Tgfb expression in osteoblastic cells. The candidates mediating the effect comprise Prrx1 for Tgfb3 and Mef2c for Tgfb1/2. These results indicate FasL as a novel cytokine interfering with Tgfb signaling and thus the complex osteogenic network. The emerging non-apoptotic functions of FasL in bone development and maintenance should also be considered in treatment strategies such as the anti-osteoporotic factor.
- Klíčová slova
- ECM, Fas ligand, Fosl2, Mef2c, Prrx1, Tgfb,
- MeSH
- buněčné linie MeSH
- ligand Fas * metabolismus MeSH
- myši MeSH
- osteoblasty * metabolismus MeSH
- signální transdukce * MeSH
- transformující růstový faktor beta metabolismus MeSH
- transformující růstový faktor beta1 metabolismus farmakologie MeSH
- transformující růstový faktor beta2 metabolismus farmakologie MeSH
- transformující růstový faktor beta3 * metabolismus genetika MeSH
- transkripční faktory MEF2 metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ligand Fas * MeSH
- Mef2c protein, mouse MeSH Prohlížeč
- transformující růstový faktor beta MeSH
- transformující růstový faktor beta1 MeSH
- transformující růstový faktor beta2 MeSH
- transformující růstový faktor beta3 * MeSH
- transkripční faktory MEF2 MeSH
Caspases are enzymes with protease activity. Despite being known for more than three decades, caspase investigation still yields surprising and fascinating information. Initially associated with cell death and inflammation, their functions have gradually been revealed to extend beyond, targeting pathways such as cell proliferation, migration, and differentiation. These processes are also associated with disease mechanisms, positioning caspases as potential targets for numerous pathologies including inflammatory, neurological, metabolic, or oncological conditions. While in vitro studies play a crucial role in elucidating molecular pathways, they lack the context of the body's complexity. Therefore, laboratory animals are an indispensable part of successfully understanding and applying caspase networks. This paper aims to summarize and discuss recent knowledge, understanding, and challenges in caspase knock-out mice.
- Klíčová slova
- Animal model, Apoptotic, Caspases, Deficiency, Mouse, Non-apoptoic,
- MeSH
- apoptóza MeSH
- kaspasy * metabolismus genetika MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myši knockoutované * MeSH
- myši MeSH
- zánět enzymologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- kaspasy * MeSH
Reducing the size of a catalyst to a single atom (SA) level can dramatically change its physicochemical properties and significantly boost its catalytic activity. However, the massive synthesis of SA catalysts still remains a grand challenge mainly because of the aggregation and nucleation of the generated atoms during the reaction. Here, we design and implement a spatially confined synthetic strategy based on a porous-hollow carbon nitride (p-CN) coordinated with 1-butyl-3-methylimidazole hexafluorophosphate, which can act as a nanoreactor and allow us to obtain metal SA catalysts (p-CN@M SAs). This relatively easy and highly effective method provides a way to massively synthesize single/multiple atoms (p-CN@M SAs, M = Pt, Pd, Cu, Fe, etc.). Moreover, the amorphous NiB-coated p-CN@Pt SAs can further increase the loading amount of Pt SAs to 3.7 wt %. The synthesized p-CN@Pt&NiB electrocatalyst exhibits an extraordinary hydrogen evolution reaction activity with the overpotential of 40.6 mV@10 mA/cm-2 and the Tofel slope of 29.26 mV/dec.
- Klíčová slova
- hydrogen evolution, ionic liquid, massive synthesis, single atom, spatially confined synthetic strategy,
- Publikační typ
- časopisecké články MeSH
Valence engineering has been proved an effective approach to modify the electronic property of a catalyst and boost its oxygen evolution reaction (OER) activity, while the limited number of elements restricts the structural diversity and the active sites. Also, the catalyst performance and stability are greatly limited by cationic dissolution, ripening, or crystal migration in a catalytic system. Here we employed a widely used technique to fabricate heteroepitaxial pyrite selenide through dual-cation substitution and a boron dopant to achieve better activity and stability. The overpotential of Ni-pyrite selenide catalyst is decreased from 543 mV to 279.8 mV at 10 mA cm-2 with a Tafel slope from 161 to 59.5 mV dec-1. Our theoretical calculations suggest both cation and boron doping can effectively optimize adsorption energy of OER intermediates, promote the charge transfer among the heteroatoms, and improve their OER property. This work underscores the importance of modulating surface electronic structure with the use of multiple elements and provides a general guidance on the minimization of activity loss with valence engineering.
- Klíčová slova
- boron doping, multimetallic compound, oxygen evolution reaction, pyrite selenide, valence engineering,
- Publikační typ
- časopisecké články MeSH
