Extracellular cold‐inducible RNA‐binding protein (CIRP) is a proinflammatory mediator that aggravates ischaemia‐reperfusion injury (IRI). Normothermic machine perfusion (NMP) could effectively alleviate the IRI of the liver, but the underlying mechanism remains to be explored. We show that human DCD livers secreted a large amount of CIRP during static cold storage (CS), which is released into the circulation after reperfusion. The expression of CIRP was related to postoperative IL‐6 levels and liver function. In a rat model, the CIRP expression was upregulated during warm ischaemia and cold storage. Then, rat DCD livers were preserved using CS, hypothermic oxygenated machine perfusion (HOPE) and NMP. C23, a CIRP inhibitor, was administrated in the HOPE group. Compared with CS, NMP significantly inhibited CIRP expression and decreased oxidative stress by downregulating NADPH oxidase and upregulating UCP2. NMP markedly inhibited the mitochondrial fission‐related proteins Drp‐1 and Fis‐1. Further, NMP increased the mitochondrial biogenesis‐related protein, TFAM. NMP significantly reduced inflammatory reactions and apoptosis after reperfusion, and NMP‐preserved liver tissue had higher bile secretion and ICG metabolism compared to the CS group. Moreover, C23 administration attenuated IRI in the HOPE group. Additionally, HL‐7702 cells were stimulated with rhCIRP and C23. High rhCIRP levels increased oxidative stress and apoptosis. In summary, NMP attenuates the IRI of DCD liver by inhibiting CIRP‐mediated oxidative stress and mitochondrial fission.
Helicenes exhibit promise as active layer materials for circularly polarized light (CPL) detectors due to their strong chiroptical activity. However, their practical application is limited by the complicated synthesis and loosely solid-state packing. This study introduces a chiral induction strategy towards the synthesis of helicene derivatives, chiral tetrachlorinated diperylene diimides ((SSSS)-4CldiPDI or (RRRR)-4CldiPDI). When incorporating the chiral (S/R)-1-cyclohexylethyl (Cy) substituents, the chirality is directly transferred to the π-aromatic core and forms the PP- or MM-helicene subunit. Notably, (SSSS)-Cy induces preferred PP helicity while (RRRR)-Cy leads to the MM helicity in the monomers. However, these molecules exhibit reversed chirality in crystals, where (SSSS)-Cy controls MM helicity and (RRRR)-Cy induces PP helicity. Theoretical calculations reveal that the (SSSS)-PP structure demonstrates lower energy distribution in monomers, whereas the (SSSS)-MM structure exhibits lower energy in crystals. Then, the CPL detection based on n-type PDI-helicene derivatives is achieved by using (SSSS)-4CldiPDI or (RRRR)-4CldiPDI crystals. The maximum photocurrent dissymmetry factor gph of +0.16 for (RRRR)-4CldiPDI and −0.15 for (SSSS)-4CldiPDI is obtained. Our work demonstrates a novel chiral induction strategy for designing helicene-based materials with both high dissymmetry factor and large charge carrier mobility, which offers great potential for the advancement of CPL detection.
Using a decellularized liver matrix (DLM) to reengineer liver tissue is a promising therapy for end-stage liver disease. However, the limited supply of donor organs still hampers its potential clinical application, while a xenogenic decellularized matrix may bring a risk of zoonosis and immunological rejection. Therefore, an appropriate alternative scaffold is needed. In this research, we established a decellularized splenic matrix (DSM) in a rodent model, which preserved the 3D ultrastructure, the components of the extracellular matrix (ECM) and the native vascular network. The DSM and DLM had similar components of ECM, and similar mechanical properties. Hepatocytes were seeded to the DSM and DLM for dynamic culturing up to 6 d, and distributed both in decellularized sinusoidal spaces and around the vessels. The TUNEL-positive cell percentage in a dynamic culturing decellularized splenic matrix (dDSM) was 10.7% ± 3.6% at 3d and 25.8% ± 5.6% at 5d, although 14.2% ± 4.5% and 24.8% ± 2.9%, respectively, in a dynamic culturing decellularized liver matrix (dDLM) at the same time point (p > 0.05). Primary hepatocytes in the dDSM and dDLM expressed albumin, G6pc and Ugt1a1. The gene expression of Cyp2b1, Cyp1a2 and HNF1α in the gene transcription level revealed hepatocytes had lower gene expression levels in the dDSM compared with the dDLM at 3d, but better than those in a sandwich culture. The cumulative albumin production at 6 d of culture was 80.7 ± 9.6 μg per million cells in the dDSM and 89.6 ± 4.6 μg per million cells in the dDLM (p > 0.05). In summary, the DSM is a promising 3D scaffold for hepatocyte cultivation in vitro.
To address the problem of thrombosis, anticoagulant coatings have been developed for extracorporeal membrane oxygenation circuits. This article reviews commercial and novel anticoagulant coatings recently and proposes a new classification of them.
12 September 2020 in Molecular and Cellular Biochemistry
Background Systemic inflammation contributes to cardiac surgery–associated acute kidney injury (AKI). Cardiomyocytes and other organs experience hypothermia and hypoxia during cardiopulmonary bypass (CPB), which induces the secretion of cold-inducible RNA-binding protein (CIRP). Extracellular CIRP may induce a proinflammatory response. Materials and Methods The serum CIRP levels in 76 patients before and after cardiac surgery were determined to analyze the correlation between CIRP levels and CPB time. The risk factors for AKI after cardiac surgery and the in-hospital outcomes were also analyzed. Results The difference in the levels of CIRP (ΔCIRP) after and before surgery in patients who experienced cardioplegic arrest (CA) was 26-fold higher than those who did not, and 2.7-fold of those who experienced CPB without CA. The ΔCIRP levels were positively correlated with CPB time (r = 0.574, p < 0.001) and cross-clamp time (r = 0.54, p < 0.001). Multivariable analysis indicated that ΔCIRP (odds ratio: 1.003; 95% confidence interval: 1.000–1.006; p = 0.027) was an independent risk factor for postoperative AKI. Patients who underwent aortic dissection surgery had higher levels of CIRP and higher incidence of AKI than other patients. The incidence of AKI and duration of mechanical ventilation in patients whose serum CIRP levels more than 405 pg/mL were significantly higher than those less than 405 pg/mL (65.8 vs. 42.1%, p = 0.038; 23.1 ± 18.2 vs. 13.8 ± 9.2 hours, p = 0.007). Conclusion A large amount of CIRP was released during cardiac surgery. The secreted CIRP was associated with the increased risk of AKI after cardiac surgery.