Salvaging donated kidneys from prolonged warm ischemia during ex vivo hypothermic oxygenated perfusion.

Prolonged warm ischemic is the main cause discarding donated organs after cardiac death. Here, we identified that prolonged warm ischemic time induced disseminated intravascular coagulation and severe capillary vasospasm after cardiac death of rat kidneys. Additionally, we found a significant accumulation of fibrinogen in a hypoxic cell culture of human umbilical vein epithelial cells and in isolated kidneys exposed to prolonged warm ischemic following flushing out of blood. However, pre-flushing the kidney with snake venom plasmin in a 90-minute warm ischemic model maximized removal of micro thrombi and facilitated the delivery of oxygen and therapeutic agents. Application of carbon monoxide-releasing CORM-401 during ex vivo hypothermic oxygenated perfusion achieved multipath protective effects in prolonged warm ischemic kidneys. This led to significant improvements in perfusion parameters, restoration of the microcirculation, amelioration of mitochondrial injury, oxidative stress, and apoptosis. This benefit resulted in significantly prolonged warm ischemic kidney recipient survival rates of 70%, compared with none in those receiving ex vivo hypothermic oxygenated perfusion alone. Significantly, ex vivo hypothermic oxygenated perfusion combined with cytoprotective carbon monoxide releasing CORM-401 treatment meaningfully protected the donated kidney after cardiac death from ischemia-reperfusion injury by reducing inflammation, oxidative stress, apoptosis, and pathological damage. Thus, our study suggests a new combination treatment strategy to potentially expand the donor pool by increasing use of organs after cardiac death and salvaging prolonged warm ischemic kidneys.

The Relationship between Locomotive Syndrome and Depression in Young Chinese College Students.

OBJECTIVES: This study investigates the relationship between locomotive syndrome (LS) and mental disorder (depression) in young Chinese college students. METHODS: Our study population (n = 165; mean age of 19.82 ±1.90 years) comprises college student residents at Tsinghua University in Beijing, China. Three screening methods were used to evaluate LS: 25-question Geriatric Locomotive Function Scale (GLFS-25), a two-step test, and a stand-up test. Depression was screened by the Chinese version of the Zung Self-Rating Depression Scale (ZSDS). RESULTS: The prevalence of LS and depression was 20.1% and 30.9%, respectively. The LS group had lower grip strength and higher ZSDS scores than the non-LS group. CONCLUSION: Young Chinese college students have a relatively high prevalence of LS, and LS and GLFS-25 scores were significantly related to depression. The present results suggest that management strategies for LS should consider depressive symptoms among young adults.

DDX55 promotes hepatocellular carcinoma progression by interacting with BRD4 and participating in exosome-mediated cell-cell communication.

The involvement of DEAD-box helicase 55 (DDX55) in oncogenesis has been suggested, but its biological role in hepatocellular carcinoma (HCC) remains unknown. The present study verified the upregulation of DDX55 in HCC tissues compared with non-tumor controls. DDX55 displayed the highest prognostic values among the DEAD-box protein family for recurrence-free survival and overall survival of HCC patients. In addition, the effects of DDX55 in the promotion of HCC cell proliferation, migration, and invasion were determined ex vivo and in vivo. Mechanistically, we revealed that DDX55 could interact with BRD4 to form a transcriptional regulatory complex that positively regulated PIK3CA transcription. Following that, ß-catenin signaling was activated in a PI3K/Akt/GSK-3ß dependent manner, thus inducing cell cycle progression and epithelial-mesenchymal transition. Intriguingly, both DDX55 mRNA and protein were identified in the exosomes derived from HCC cells. Exosomal DDX55 was implicated in intercellular communication between HCC cells with high or low DDX55 levels and between HCC cells and endothelial cells, thereby promoting the malignant phenotype of HCC cells and angiogenesis. In conclusion, DDX55 may be a valuable prognostic biomarker and therapeutic target in HCC.