ERKs and mitochondria-related pathways are essential for glycyrrhizic acid-mediated neuroprotection against glutamate-induced toxicity in differentiated PC12 cells

The present study focuses on the neuroprotective effect of glycyrrhizic acid (GA, a major compound separated from Glycyrrhiza Radix, which is a crude Chinese traditional drug) against glutamate-induced cytotoxicity in differentiated PC12 (DPC12) cells. The results showed that GA treatment improved cell viability and ameliorated abnormal glutamate-induced alterations in mitochondria in DPC12 cells. GA reversed glutamate-suppressed B-cell lymphoma 2 levels, inhibited glutamate-enhanced expressions of Bax and cleaved caspase 3, and reduced cytochrome C (Cyto C) release. Exposure to glutamate strongly inhibited phosphorylation of AKT (protein kinase B) and extracellular signal-regulated kinases (ERKs); however, GA pretreatment enhanced activation of ERKs but not AKT. The presence of PD98059 (a mitogen-activated protein/extracellular signal-regulated kinase kinase [MEK] inhibitor) but not LY294002 (a phosphoinositide 3-kinase [PI3K] inhibitor) diminished the potency of GA for improving viability of glutamate-exposed DPC12 cells. These results indicated that ERKs and mitochondria-related pathways are essential for the neuroprotective effect of GA against glutamate-induced toxicity in DPC12 cells. The present study provides experimental evidence supporting GA as a potential therapeutic agent for use in the treatment of neurodegenerative diseases.

Incidence, risk factors, and prognosis of acute kidney injury following transarterial chemoembolization in patients with hepatocellular carcinoma: A prospective cohort study.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) is an effective first‑line therapy for intermediate stage hepatocellular carcinoma (HCC). Acute renal injury may be induced after transarterial chemoembolization because of iodinated radiocontrast medium, but its incidence, risk factors, and prognosis remain unclear. PATIENTS AND METHODS: This prospective study enrolled 166 HCC patients with a total of 316 TACE treatments. The incidence, risk factors, and prognosis of acute kidney injury (AKI) were examined. RESULTS: The incidence of post‑TACE AKI was 21.84% (69/316) according to Barrett and Parfrey criteria, whereas 7.59% (24/316) according to acute kidney injury network (AKIN) criteria. Multivariate logistic regression analysis showed that serum total bilirubin (TB) (>13.5 μmol/L; odds ratio [OR]: 1.871 95% confidence interval [CI]: 1.044–3.352; P = 0.035) and hemoglobin (HGB) level (<120 g/L; OR: 1.823, 95% CI: 1.019–3.264; P = 0.043) were associated with the development of AKI after TACE procedure in accordance to Barrett and Parfrey criteria. Meanwhile, age (>55 years; OR: 3.456, 95% CI: 1.107–10.790; P = 0.033), post‑TACE AKI history (OR: 7.108, 95% CI: 1.387–36.434, P = 0.019), and serum aminotransferase level (>55 U/L; OR: 4.420, 95% CI: 1.792–10.906; P = 0.001) were associated with the development of AKI after TACE procedure in accordance to AKIN criteria. Total hospitalization cost was significantly higher (P = 0.034) in the patients with AKI after TACE procedure according to Barrett and Parfrey criteria. A post‑TACE AKI diagnosis was associated with mortality in any definition used (P = 0.034 and P = 0.001 for Barrett and Parfrey and AKIN criteria, respectively). CONCLUSION: The present study showed that the incidence of post‑TACE AKI was high in HCC patients (i.e., 7.59–21.84%) depending on criteria used. HGB (<120 g/L), serum TB (>13.5), and aminotransferase level (>55 U/L), age (>55 years) and post‑TACE AKI history may be predictors of post‑TACE AKI in HCC patients. The development of post‑TACE AKI was associated with the risk of renal replacement treatment, prolonged renal insufficiency, or mortality according to AKIN criteria.

In vitro proliferation and differentiation of hepatic oval cells and their potential capacity for intrahepatic transplantation

Hepatic oval cells (HOCs) are recognized as facultative liver progenitor cells that play a role in liver regeneration after acute liver injury. Here, we investigated the in vitro proliferation and differentiation characteristics of HOCs in order to explore their potential capacity for intrahepatic transplantation. Clusters or scattered HOCs were detected in the portal area and interlobular bile duct in the liver of rats subjected to the modified 2-acetylaminofluorene and partial hepatectomy method. Isolated HOCs were positive for c-kit and CD90 staining (99.8% and 88.8%, respectively), and negative for CD34 staining (3.6%) as shown by immunostaining and flow cytometric analysis. In addition, HOCs could be differentiated into hepatocytes and bile duct epithelial cells after leukemia inhibitory factor deprivation. A two-cuff technique was used for orthotopic liver transplantation, and HOCs were subsequently transplanted into recipients. Biochemical indicators of liver function were assessed 4 weeks after transplantation. HOC transplantation significantly prolonged the median survival time and improved the liver function of rats receiving HOCs compared to controls (P=0.003, Student t-test). Administration of HOCs to rats also receiving liver transplantation significantly reduced acute allograft rejection compared to control liver transplant rats 3 weeks following transplantation (rejection activity index score: control=6.3±0.9; HOC=3.5±1.5; P=0.005). These results indicate that HOCs may be useful in therapeutic liver regeneration after orthotopic liver transplantation.

An optimized mini-preparation method toobtain high-quality genomic DNA from mature leaves of sunflower

In order to investigate the mutation characteristics and to further examine the genetic variation of mutant sunflower (Helianthus annuus) obtained in plants grown from seeds exposed to space conditions, only the mature tissues such as leaf and flower could be used for DNA extraction after mutation characteristics were confirmed. The rich contents of polysaccharides, tannins, secondary metabolites, and polyphenolics made it difficult to isolate high-quality DNA from mature leaves of sunflower according to previous reports. Based on the comparison of the differences in previously reported protocols, a modified method for the extraction of high-quality DNA was developed. Using this protocol, the DNA isolated from sunflower was high in quality and suitable for restriction digestion (EcoRI, HindII, BamHI), random amplified polymorphic DNA study and further molecular research. Therefore, the modified protocol was suitable for investigating the genetic variation of sunflower using mature leaf DNA.