Background Blood counting and the liver function tests, as the routine examinations, can reflect the immune and nutritional status of the body, our aim is to assess the prognostic significance of serum gamma-glutamyltransferase (GGT) levels and AST/ALT in primary hepatic carcinoma. Methods Clinico-pathological data of 414 patients with primary hepatic carcinoma in the 1st Affiliated Hospital of Anhui Medical College between January 2007 to January 2014 was analyzed retrospectively in this study. Survival curves were described by Kaplan-Meier method and compared by Log-rank test, univariate and multivariate analysis were used to identify the prognostic factors. Results GGT was positively correlated with the tumor size( P = 0.000), tumor volume ( P = 0.000), tumor volume percent ( P = 0.004), TNM stage( P = 0.009), 1-year survival rate ( P = 0.000), 3- years survival rate ( P = 0.000) and 5-years survival rate( P = 0.000). The serum ALT/AST was significantly correlated with age ( P = 0.047), tumor size( P = 0.002), tumor volume ( P = 0.010), tumor volume percent ( P = 0.005), TNM stage( P = 0.006), liver cirrhosis( P = 0.003), 3- years survival rate ( P = 0.032) and 5-years survival rate( P = 0.000). The Kaplan-Meier curves showed that the patients with primary hepatic carcinoma had a longer time in the low GGT group and low AST/ALT group, showing a significant difference ( P < 0.05). The univariate and multivariate analyses showed that TNM stage, differentiation grade, tumor volume, GGT and AST/ALT were independent factors for predicting overall survival rate of primary hepatic carcinoma patients. Conclusions GGT and AST/ALT were independent factors for predicting overall survival rate of primary hepatic carcinoma patients.

Background: Breast cancer is a very common cancer with significant premature mortality in women. In this study, we show that HKDC1 expression in breast cancer cells is increased significantly. We aim to investigate the detailed mechanism for the regulation of HKDC1 expression and its potential contribution to tumorigenesis. Methods: Gene expression was evaluated by real time PCR, western blotting, and immunohistochemistry. The mechanism for PGC1β/SREBP1-mediated HKDC1 expression was investigated using luciferase reporter assay, chromatin immunoprecipitation, and siRNA techniques. In addition, HKDC1 was overexpressed or knocked down by lentivirus to evaluate the potential effect on in vitro cell proliferation, glucose uptake, mitochondrial function, apoptosis, and reactive oxygen species (ROS) formation. Furthermore, an in vivo xenograft tumor development study was employed to investigate the effect of HKDC1 on tumor growth and mouse survival. Results: HKDC1 is highly expressed in both breast cancer cells and clinical tumor tissues. HKDC1 expression is upregulated and co-activated by PGC1β through SREBP1 binding motif on the HKDC1 promoter. HKDC1 is located on the mitochondrial membrane and regulates the permeability transition pore opening by binding with VDAC1, subsequently modulating glucose uptake and cell proliferation. Overexpression of HKDC1 increases while knockdown of HKDC1 decreases in vitro breast cancer cell proliferation and in vivo tumor growth, metastasis, and mouse survival. Conclusions: PGC1β regulates breast cancer tumor growth and metastasis by SREBP1-mediated HKDC1 expression. This provides a novel therapeutic strategy through targeting the PGC1β/HKDC1 signaling pathway for breast cancer treatment.

Multiple myeloma (MM) is an incurable hematologic malignancy due to inevitable relapse and chemoresistance development. Our preliminary data show that MM cells express high levels of PGC1β and LDHA. In this study, we investigated the mechanism behind PGC1β‐mediated LDHA expression and its contribution to tumorigenesis, to aid in the development of novel therapeutic approaches for MM. Real‐time PCR and western blotting were first used to evaluate gene expression of PGC1β and LDHA in different MM cells, and then, luciferase reporter assay, chromatin immunoprecipitation, LDHA deletion report vectors, and siRNA techniques were used to investigate the mechanism underlying PGC1β‐induced LDHA expression. Furthermore, knockdown cell lines and lines stably overexpressing PGC1β or LDHA lentivirus were established to evaluate in vitro glycolysis metabolism, mitochondrial function, reactive oxygen species (ROS) formation, and cell proliferation. In addition, in vivo xenograft tumor development studies were performed to investigate the effect of PGC1β or LDHA expression on tumor growth and mouse survival. We found that PGC1β and LDHA are highly expressed in different MM cells and LDHA is upregulated by PGC1β through the PGC1β/RXRβ axis acting on the LDHA promoter. Overexpression of PGC1β or LDHA significantly potentiated glycolysis metabolism with increased cell proliferation and tumor growth. On the other hand, knockdown of PGC1β or LDHA largely suppressed glycolysis metabolism with increased ROS formation and apoptosis rate, in addition to suppressing tumor growth and enhancing mouse survival. This is the first time the mechanism underlying PGC1β‐mediated LDHA expression in multiple myeloma has been identified. We conclude that PGC1β regulates multiple myeloma tumor growth through LDHA‐mediated glycolytic metabolism. Targeting the PGC1β/LDHA pathway may be a novel therapeutic strategy for multiple myeloma treatment.

Periostin (PN) is a kind of secreted glycoprotein, which is closely related to the metastatic potential and prognosis of many kinds of tumors in recent studies. However, the expression level of PN in hepatocellular carcinoma (HCC) and its correlation with tumor angiogenesis and prognosis remain unclear. Here Immunohistochemistry assay was used to determine the expression of PN in HCC and corresponding adjacent tissues from 71 patients. VEGF and CD34 were only examined in HCC tissues of patients mentioned above. Immunohistochemically, the expression of PN in HCC was judged to be positive in 73.2 % (52/71) compared with 19.7 % (14/71) in corresponding adjacent tissues, and it was associated with tumor nodules (P = 0.070), microvascular invasion (P = 0.013), Edmondson grade (P = 0.003), tumor capsula (P = 0.038) and TNM stage (P = 0.000); besides, tumors with PN-positive group expressed higher VEGF (82.7 vs. 26.3 %, χ (2) = 20.195, P = 0.000) and had higher MVD (80.5 ± 36.5 vs. 24.0 ± 19.9, t = -6.395, P = 0.000) than those in PN-negative group. Kaplan-Meier method was used for survival analysis, and Cox regression model was performed for multivariate survival analysis. In particular, the expression of PN was found to be an independent factor for predicting overall and disease-free survival of HCC. It is possible that the expression level of PN in HCC is associated with tumor metastatic potential and angiogenesis. Its abnormal expression could be a predictive factor to anticipate HCC patient's prognosis after surgery.

Peroxiredoxin 1 (Prdx1) is a member of the peroxiredoxin family of antioxidant enzymes and implicated in cell differentiation, proliferation, and apoptosis. The aim of the present study was to determine the expression and diagnostic and prognostic significance of Prdx1 in human hepatocellular carcinoma (HCC). Prdx1 expression was examined in 76 HCC patients and 20 healthy volunteers. The relationships between Prdx1 expression and clinicopathological features were analyzed. Receiver operating characteristics analysis was used to calculate the diagnostic accuracy of serum Prdx1, serum alpha-fetoprotein (AFP), and their combination. The prognostic impact of Prdx1 on overall survival (OS) and disease-free survival (DFS) of HCC patients was investigated. Prdx1-positive rate was significantly (p < 0.05) higher in HCC (77.1 %) than in adjacent non-tumorous liver tissues (18.4 %). Prdx1 immunoreactivity was positively correlated with tumor vascular endothelial growth factor expression and microvessel density. Prdx1 expression was significantly associated with tumor size, microvascular invasion, Edmondson grade, tumor capsula status, serum AFP, and tumor-node-metastasis stage. The combination of serum Prdx1 and AFP had a markedly higher area under the curve than serum Prdx1 alone. Positive Prdx1 expression was associated with unfavorable OS (p = 0.004) and DFS (p = 0.001). Multivariate analysis revealed intra-tumoral Prdx1 staining as an independent poor prognostic marker for OS (p = 0.006) and DFS (p = 0.002). Taken together, our data suggest that increased Prdx1 expression is associated with tumor angiogenesis and progression in HCC and serves as a promising biomarker for detection and prognosis of this malignancy.

Objectives: Low back pain becomes a common orthopaedic disease today. It is mainly induced by the degeneration of the intervertebral disc. In this study, we tried to reveal the pathogenesis of the degeneration and the relative therapeutic strategy, which are still elusive. Materials and Methods:We collected 15 degenerative intervertebral tissues and five healthy donors. Nucleus pulposus and annulus fibrosus cells were subcultured. miR-640 expression was determined by qPCR. Computer analysis and luciferase reporter assay were used to confirm miR-640 target genes. Immunohistochemical and immunocytochemical staining was used to trace the proinflammatory cytokines and key transductor of signalling pathways. We also used β-galactosidase staining, flow cytometry, and cell viability assay to monitor the degenerative index.Results: miR-640 overexpressed in patients derived degenerative nucleus pulposus tissues and cells. The inflammatory environment promoted miR-640 expression via NF-κB signalling pathway. In addition, miR-640 targeted to LRP1 and enhances NF-κB signal activity, which built a positive feedback loop. miR-640 inhibited the expression of β-catenin and EP300, therefore, restrained WNT signal and induced the degeneration in nucleus pulposus cells. miR-640 inhibitor treatment exhibited the effects of anti-inflammation, reverse WNT signalling pathway exhaustion, and remission of degenerative characteristics in vitro.Conclusions: miR-640 plays an important role in the degeneration of intervertebral disc and the relative inflammatory microenvironment. It is a promising potential therapeutic target for the low back pain biotherapy.

The accumulation of toxic bile acids (BAs) is closely related to liver injury, inflammation and tumorigenesis. The aim of the present study was to determine the role of the serum BA spectrum in the diagnosis and progression of liver cirrhosis. This was a prospective observational study involving patients with chronic hepatitis (n=23), liver cirrhosis (n=101), and cirrhosis complicated with hepatocellular carcinoma (CC-HCC; n=56). The 6-month survival of cirrhotic patients was recorded after blood collection. Comparisons of serum total BAs and individual BAs between different groups were performed using the Mann-Whitney U or Kruskal-Wallis tests. Correlation analysis was conducted by Spearman's correlation. Diagnosis and prediction analyses were performed using receiver operating characteristic curves. Survival was analyzed using the Kaplan-Meier method and multivariable Cox regression analysis. The concentrations of total BAs, glycocholic acid (GCA), glycochenodeoxycholic acid (GCDCA), taurocholic acid (TCA), taurochenoxycholic acid and tauroursodeoxycholic acid (TUDCA) were increased significantly in patients with early cirrhosis compared to patients with chronic hepatitis (P<0.05) and were associated with the diagnosis of cirrhosis (P=0.049, 0.004, 0.002, 0.003, 0.010 and 0.009, respectively). The levels of total BAs, primary conjugated BAs, and TUDCA increased as liver cirrhosis progressed (P<0.05). Serum total BAs, GCA, GCDCA, and TCA predicted the 6-month survival of patients with liver cirrhosis (P=0.0003, 0.005, 0.002, and 0.010 respectively). Based on multivariate Cox regression analysis, the level of total BAs was an independent predictor of mortality in cirrhotic patients (hazard ratios, 4.046; 95% CI, 1.620–10.108; P=0.003). In the early-stage cirrhosis group, the concentrations of total BAs and primary conjugated BAs were significantly elevated in patients with CC-HCC compared with patients with cirrhosis alone. In conclusion, total and individual BAs, especially primary conjugated BAs, are effective non-invasive markers in the diagnosis and prognosis of liver cirrhosis, and may be potential indicators in the occurrence of hepatocellular carcinoma in patients with early cirrhosis.

Key Points The small molecule Me6TREN is a new potent and efficacious mobilizing agent of HSPCs and works more effectively than G-CSF or AMD3100. Me6 mobilizes murine HSPCs and functions by upregulating MMP-9 expression and disrupting the SDF-1α/CXCR4 axis.