RESUMO
Abstract-This study explored the role of the non-canonical STING-PERK signaling pathway in sepsis-associated acute kidney injury (SA-AKI). Gene expression data from the GEO database and serum STING protein levels in patients with SA-AKI were analyzed. An LPS-induced mouse model and an in vitro model using HK-2 cells were used to investigate the role of STING in SA-AKI. STING expression was suppressed using shRNA silencing technology and the STING inhibitor C176. Kidney function, inflammatory markers, apoptosis, and senescence were measured. The role of the STING-PERK pathway was investigated by silencing PERK in HK-2 cells and administering the PERK inhibitor GSK2606414. STING mRNA expression and serum STING protein levels were significantly higher in patients with SA-AKI. Suppressing STING expression improved kidney function, reduced inflammation, and inhibited apoptosis and senescence. Silencing PERK or administering GSK2606414 suppressed the inflammatory response, cell apoptosis, and senescence, suggesting that PERK is a downstream effector in the STING signaling pathway. The STING-PERK signaling pathway exacerbates cell senescence and apoptosis in SA-AKI. Inhibiting this pathway could provide potential therapeutic targets for SA-AKI treatment.
RESUMO
This paper focuses on evaluating the systemic risk in interbank networks, proposing a series of measurements: risk distance, risk degree and m-order risk degree. The proposed measurements are formally proven to have good basic and extended properties that are able to reflect the effect of bank size, liability size, liability distribution, and the discount factor on the default risk, not only of a single bank, but also of the entire system. Additionally, the abovementioned properties and the relationship between risk distance and financial contagion indicate the rationality embodied in the proposed measurements. This paper also provides some implications on how to decrease or prevent the systemic risk in an interbank system.