This study was undertaken to evaluate the effect of simvastatin, a cholesterol-lowering agent, on the Akt-mediated signaling pathway and neurogenesis in the dentate gyrus (DG) of the hippocampus in rats after traumatic brain injury (TBI). Adult male Wistar rats were divided into three groups: (1) sham group (n = 8); (2) saline control group (n = 40); and (3) simvastatin-treated group (n = 40). Controlled cortical impact (CCI) injury was performed over the left parietal lobe. Simvastatin was administered orally at a dose of 1 mg/kg starting at day 1 after TBI and then daily for 14 days. Bromodeoxyuridine (BrdU) was injected intraperitoneally into rats. A modified Morris Water Maze (WM) task was performed between 31 and 35 days after treatment to test spatial memory (n = 8/group). Animals were sacrificed at 1, 3, 7, 14, and 35 days after treatment (n = 8/group/time point). Western blot was utilized to investigate the changes in the Akt-mediated signaling pathway. Enzyme-linked immunosorbent assay (ELISA) analyses were employed to measure vascular endothelial growth factor (VEGF) and brain-derived neurotrophin factor (BDNF) expression. Immunohistochemical and fluorescent staining were performed to detect the BrdU- and neuronal nuclei (NeuN)/BrdU-positive cells. Our data show that simvastatin treatment increases phosphorylation of v-akt murine thymoma viral oncogene homolog (Akt), glycogen synthase kinase-3beta (GSK-3beta), and cAMP response element-binding proteins (CREB); elevates the expression of BDNF and VEGF in the DG; increases cell proliferation and differentiation in the DG; and enhances the recovery of spatial learning. These data suggest that the neurorestorative effect of simvastatin may be mediated through activation of the Akt-mediated signaling pathway, subsequently upregulating expression of growth factors and inducing neurogenesis in the DG of the hippocampus, thereby leading to restoration of cognitive function after TBI in rats.

PURPOSE To compare the survival outcomes of neoadjuvant three-dimensional conformal radiotherapy (RT) followed by hepatectomy with hepatectomy alone in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). PATIENTS AND METHODS A randomized, multicenter controlled study was conducted from January 2016 to December 2017 in patients with resectable HCC and PVTT. Patients were randomly assigned to receive neoadjuvant RT followed by hepatectomy (n = 82) or hepatectomy alone (n = 82). The modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines were used to evaluate the therapeutic effects of RT. The primary end point was overall survival. The expression of interleukin-6 (IL-6) in patients’ serum before RT and in surgical specimens was correlated with response to RT. RESULTS In the neoadjuvant RT group, 17 patients (20.7%) had partial remission. The overall survival rates for the neoadjuvant RT group at 6, 12, 18, and 24 months were 89.0%, 75.2%, 43.9%, and 27.4%, respectively, compared with 81.7%, 43.1%, 16.7%, and 9.4% in the surgery-alone group ( P < .001). The corresponding disease-free survival rates were 56.9%, 33.0%, 20.3%, and 13.3% versus 42.1%, 14.9%, 5.0%, and 3.3% ( P < .001). On multivariable Cox regression analyses, neoadjuvant RT significantly reduced HCC-related mortality and HCC recurrence rates compared with surgery alone (hazard ratios, 0.35 [95% CI, 0.23 to 0.54; P < .001] and 0.45 [95% CI, 0.31 to 0.64; P < .001]). Increased expressions of IL-6 in pre-RT serum and tumor tissues were significantly associated with resistance to RT. CONCLUSION For patients with resectable HCC and PVTT, neoadjuvant RT provided significantly better postoperative survival outcomes than surgery alone. IL-6 may predict response to RT in these patients.

This study was aimed to investigate the prognostic value of neutrophil-to-lymphocyte ratio (NLR) in patients with prostate cancer (PCa). A meta-analysis including 14 publications (15 cohorts) with 16,266 patients was performed to evaluate the association between NLR and overall survival (OS), progression-free survival (PFS)/recurrence-free survival (RFS) in PCa using hazard ratio (HR) and 95% confidence intervals (95% CI). The combining data showed that increased NLR predict poor OS (HR = 1.38, 95%CI: 1.22–1.56) and PFS/RFS (HR = 1.24, 95%CI 1.05–1.46) in PCa. Stratified analysis by PCa type, sample size, ethnicity and NLR cut-off value revealed that NLR showed consistent prognostic value in metastatic castration-resistant prostate cancer (mCRPC) patients and predict poor PFS/RFS in Asians, but not in Caucasians. These statistical data suggested that increased NLR could predict poor prognosis in patients with PCa.

Metabolic switch from oxidative phosphorylation to aerobic glycolysis, which is also called the Warburg effect, is a hallmark of osteosarcoma (OS) and leads to the enhancement of cell chemoresistance, growth, metastasis, and invasion. Emerging evidence indicates that long non-coding RNA (lncRNA) plays a crucial role in the Warburg effect of cancer cells. Here, we report that lncRNA KCNQ1OT1 was upregulated in OS. Meanwhile, functional experiments demonstrated that the KCNQ1OT1 facilitated proliferation and suppressed apoptosis of OS cells. In addition, KCNQ1OT1 contributed to the Warburg effect by stimulating aldolase A (ALDOA) expression. Furthermore, using bioinformatics analysis, luciferase reporter, RNA immunoprecipitation, and RNA pull-down assay, we identified that KCNQ1OT1 functions as a competing endogenous RNA (ceRNA) by sponging miR-34c-5p, which inhibited ALDOA expression by directly targeting its 3ʹUTR. Taken together, these data identified a key role of KCNQ1OT1 in glucose metabolism reprogramming of OS. Targeting the KCNQ1OT1/miR-34c-5p/ALDOA axis may be a potential therapeutic target in OS treatment.