Background. Liver transplantation is limited by the insufficiency of liver organ donors when treating end-stage liver disease or acute liver failure (ALF). Ectodermal mesenchymal stem cells (EMSCs) derived from nasal mucosa have emerged as an alternative cell-based therapy. However, the role of EMSCs in acute liver failure remains unclear. Methods. EMSCs were obtained from the nasal mucosa tissue of rats. First, EMSCs were seeded on the gelatin-chitosan scaffolds, and the biocompatibility was evaluated. Next, the protective effects of EMSCs were investigated in carbon tetrachloride- (CCl₄-) induced ALF rats. Finally, we applied an indirect coculture system to analyze the paracrine effects of EMSCs on damaged hepatocytes. A three-step nontransgenic technique was performed to transform EMSCs into hepatocyte-like cells (HLCs) in vitro. Results. EMSCs exhibited a similar phenotype to other mesenchymal stem cells along with self-renewal and multilineage differentiation capabilities. EMSC-seeded gelatin-chitosan scaffolds can increase survival rates and ameliorate liver function and pathology of ALF rat models. Moreover, transplanted EMSCs can secrete paracrine factors to promote hepatocyte regeneration, targeted migration, and transdifferentiate into HLCs in response to the livers microenvironment, which will then repair or replace the damaged hepatocytes. Similar to mature hepatocytes, HLCs generated from EMSCs possess functions of expressing specific hepatic markers, storing glycogen, and producing urea. Conclusions. These results confirmed the feasibility of EMSCs in acute hepatic failure treatment. To our knowledge, this is the first time that EMSCs are used in the therapy of liver diseases. EMSCs are expected to be a novel and promising cell source in liver tissue engineering.

Purpose. Long noncoding RNAs (lncRNAs) play important roles in regulating various functions of cells at the levels of transcription and posttranscription. Extensive investigations have illustrated that lncRNAs are critical in the glucose metabolism of tumor cells, but their mechanisms of action need to be further explored. This study evaluates the role of lncRNA ZNF674-AS1 on the apoptosis and proliferation of human hepatic carcinoma cells in vitro through the glucose metabolism and its related mechanisms. Methods. Real-time quantitative PCR was employed for detecting the level of expressions for lncRNA ZNF674-AS1 in liver cancer tissues (25 cases), paracancerous tissues, and liver cancer cell lines. The lncRNA ZNF674-AS1 high expression cell strain was constructed by the lentiviral overexpression vector. CCK-8, plate colony formation, transwell assay, lactate production, glucose consumption, and ATP levels were used to detect the change of cell proliferation, colony formation, migration, and invasion, as well as glycolytic capability. Western blot was carried out to detect the expression of HK2, PFKL, PKM2, GLUT1, and PKM1, which are the key proteins of glycolysis in cells. Result. The lncRNA ZNF674-AS1 was undesirably expressed in liver cancer cell lines and tissues. Cell function assessments showed that compared with the blank control group (vector), overexpression of lncRNA ZNF674-AS1 could substantially hinder the proliferation, colony formation, migration, and invasion capability of liver cancer cells. Furthermore, overexpression of lncRNA ZNF674-AS1 could inhibit cell glycolysis (inhibit glucose consumption and reduce intracellular lactate and ATP levels) by inhibiting the expression of key proteins (such as PFKL, HK2, PKM2, and GLUT1) in the process of glycolysis. Conclusion. As a tumor repressor gene, lncRNA ZNF674-AS1 inhibits the expression of key proteins in glycolysis to inhibit glycolysis level, thereby inhibiting cell migration and proliferation. Therefore, lncRNA ZNF674-AS1 could be a potent therapeutic target or a novel diagnostic molecule for patients suffering from liver cancer.

Patients with end-stage liver disease usually have varying degrees of malnutri tion, and severe malnutrition may affect the prognosis of patients after liver transplantation (LT). However, there is no recommended standard for the nutrition assessment of patients waiting for LT, and it is unknown whether malnutrition has an impact on the occurrence of postoperative complications. The study aim was to investigate the value of the controlling nutritional status (CONUT) score and psoas muscle thickness per height (PMTH) in predicting prognosis in LT. We retrospectively analyzed the clinical data of 313 patients who underwent classic orthotopic LT from January 2016 to December 2018 in Tianjin First Central Hospital affiliated with Tianjin Medical University. The CONUT score is derived from the preoperative serum albumin and total cholesterol levels, and total lymphocyte count. Patients were divided into low (≤ 4), medium (5–8), and high (9–12) CONUT score groups perioperative characteristics, Clavien-Dindo grade III/IV/V postoperative complications, graft loss and infection, and cumulative postoperative survival in the three groups were compared 3 mo after LT. PMTH was calculated as the ratio of the transverse thickness of the psoas muscle in the umbilical plane to the height of the patient. The cutoff values of receiver operating characteristic curves were determined separately for men and women. The values were 14.1 cm/m² for women and 17.9 cm/m² for men. The patients were then divided into low and high PMTH groups by the cutoff values. The comparison of data between the two groups was the same as above. Patients with medium and high CONUT scores had lower preoperative serum hemoglobin, more intraoperative red blood cell (RBC) transfusions, longer postoperative intensive care unit stay and hospital stays, higher 7 and 14 preoperative-day serum bilirubin levels, and a higher incidence of postoperative grade III/IV complications and infections than patients with low CONUT scores. Differences in the 3-mo cumulative survival among the three groups were not significant. Patients with a low PMTH had higher preoperative serum urea nitrogen, more intraoperative packed RBC and frozen plasma transfusions, longer times to postoperative ventilator extubation, higher incidence of total postoperative complications, and a lower 3-mo cumulative survival than those with a high PMTH. A CONUT score ≥ 5 and a low PMTH were both associated with poor prognosis in LT. The CONUT score had no predictive value for short-term patient survival after LT, but the PMTH was predictive of short-term patient survival after LT.