CKAP4 inhibited growth and metastasis of hepatocellular carcinoma through regulating EGFR signaling.

CKAP4, one kind of type II trans-membrane protein, plays an important role to maintain endoplasmic reticulum structure and inhibits the proliferation of bladder cancer cells by combining its ligand anti-proliferative factor (APF). However, the biological function of CKAP4 in the progression of liver cancer has not been clearly demonstrated. In the present study, we knocked down or overexpressed CKAP4 in hepatocellular carcinoma (HCC) cells and cell proliferation, invasion, and migration capacities were investigated by CCK-8 and transwell assays. In vivo tumor model in mice was used to evaluate the role of CKAP4 on growth and metastasis of HCC. The data documented that HCC cells with high CKAP4 levels were featured by low proliferation capability as well as low invasion potential. Interestingly, we found that CKAP4 suppressed the activation of epithelial growth factor receptor (EGFR) signaling, which may partly explain the role of CKAP4 in cell biological behavior of HCC. Further study revealed that CKAP4 could associate with EGFR at basal status and the complex was reduced upon EGF stimulation, leading to release EGFR into cytoplasm. Thus, we demonstrate the novel mechanism, for the first time, expression of CKAP4 regulates progression and metastasis of HCC and it may provide therapeutic values in this tumor.

Promoting lumbar spinal fusion by adenovirus-mediated bone morphogenetic protein-4 gene therapy.

OBJECTIVE: To determine whether an adenoviral construct containing bone morphogenetic protein-4 (BMP-4) gene can be used for lumbar spinal fusion. METHODS: Twelve New Zealand white rabbits were randomly divided into two groups, 8 in the experimental group and 4 in the control group. Recombinant, replication-defective type 5 adenovirus with the cytomegalovirus (CMV) promoter and BMP-4 gene (Ad-BMP-4) was used. Another adenovirus constructed with the CMV promoter and beta-galactosidase gene (Ad-beta-gal) was used as control. Using collagen sponge as a carrier, Ad-BMP-4 (2.9 multiply 10(8) pfu/ml ) was directly implanted on the surface of L(5)-L(6) lamina in the experimental group, while Ad-beta-gal was implanted simultaneously in the control group. X-ray was obtained at 3, 6, and 12 weeks postoperatively to observe new bone formation. When new bone formation was identified, CT scans and three-dimensional reconstruction were obtained. After that, the animals were killed and underwent histological inspection. RESULTS: In 12 weeks after operation, new bone formation and fusion were observed on CT scans in the experimental group, without the evidence of ectopic calcification in the canal. Negative results were found in the control group. Histological analysis demonstrated endochondral bone formation at the operative site and fusion at early stage was testified. CONCLUSIONS: In vivo gene therapy using Ad-BMP-4 for lumbar posterolateral spinal fusion is practicable and effective.

Biomechanical and clinical study on screw hook fixation after direct repair of lumbar spondylolysis.

OBJECTIVE: To evaluate the biomechanical effect and clinical results of hook screw fixation after direct repair of lumbar spondylous defects in the pars interarticularis. METHODS: L(2)-L(6) spines of 8 fresh-frozen and thawed calf cadavers were used for mechanical testing. Bilateral spondylous defects were created in the L(4)vertebra. The intervertebral rotation ranges between L(4) and L(5) were scanned and computerized in various states of motion, such as flexion/extension, lateral bending and torsional loadings applied on the intact spine and the spondylous spine when the spondylous spine was fixed with modified Scott's fixation, hook screw fixation and Buck's fixation sequentially and respectively. Between July 2002 and February 2004, 14 young male patients (aged 15-31 years) suffering from symptomatic lumbar spondylolysis were treated with TSRH hook screw fixation after direct repair of the defects. MacNab criteria were used to assess their pre-and post-operative status. RESULTS: Each fixation technique could significantly increase the intervertebral rotational stiffness and made the stiffness return to nearly the intact level. Hook screw technique provided more rotational stability than the others. Hook screw and Buck's techniques provided more flexion/extension stability than modified Scott's technique. Neither complication nor instrumental failure was observed in this study. The mean follow-up period was 21 months. All the patients except one acquired union during the follow-up period. Thirteen patients had a "good" or "excellent" result according to MacNab criteria. CONCLUSIONS: Hook screw fixation shows biomechanical advantages and is safe and effective for young patients with lumbar spondylolysis.

Analysis of the prognostic risk factors of idiopathic membranous nephropathy using a new surrogate end-point.

Idiopathic membranous nephropathy (IMN) is one of the most common causes of nephrotic syndrome (NS) in adults. The latest study of the chronic kidney disease-prognosis consortium showed that a 30% decrease in the estimated glomerular filtration rate (eGFR) within 2 years could cover more patients and showed a better correlation with end-stage renal disease (ESRD), as compared with serum creatinine (SCr). The aim of the present study was to analyze prognostic factors of ESRD using a 30% decrease in eGFR within 2 years as the end-point. The medical records of patients who were diagnosed as having IMN by clinical pathology between February 2011 and August 2012 and had been followed up for ≥24 months were analyzed retrospectively. A 30% decrease in eGFR or the occurrence of ESRD were the end-points. Factors affecting the prognosis were analyzed by the χ2 test and multivariate logistic regression analysis, and the cumulative risk of risk factors was analyzed by Kaplan-Meier curve. A total of 73 patients with IMN were confirmed by clinical pathology. Blood pressure, tubulointerstitial injury area (TIA), glomerular sclerosis ratio, SCr, blood urea nitrogen, cystatin C, serum albumin and 24-h urine protein. In total, 28 patients (38.4%) reached the observation end-point. Multivariate logistic regression analysis showed that only age ≥60 years, serum albumin <25 g/l and TIA >25% were independent risk factors for predicting the occurrence of end-point events in the two groups (P<0.05), which increased the risk of the occurrence of end-point events in IMN patients by 3.471-, 3.195- and 6.724-fold, respectively. Kaplan-Meier curve showed that the occurrence of end-point events within 2 years was significantly higher in IMN patients whose age was ≥60 years, serum albumin <25 g/l and TIA >25% (log-rank P=0.004, P=0.024 and P=0.001). The results of the present study revealed that age ≥60 years, low serum albumin concentrations and severe tubulointerstitial injury are independent risk factors for the occurrence of ESRD in IMN patients.

Ethanol extract from portulaca oleracea L. attenuated acetaminophen-induced mice liver injury.

Acetaminophen-induced liver injury represents the most frequent cause of drug-induced liver failure in the world. Portulaca oleracea L., a widely distributed weed, has been used as a folk medicine in many countries. Previously, we reported that the ethanol extracts of Portulaca oleracea L. (PO) exhibited significant anti-hypoxic activity. In the present study, we investigated the role of PO on acetaminophen (APAP) induced hepatotoxicity. The results demonstrated that PO was an effective anti-oxidative agent, which could, to some extent, reverse APAP-induced hepatotoxicity by regulating the reactive oxygen species (ROS) in the liver of mice. At the same time, PO treatment significantly decreased mice serum levels of IL-6 and TNFα and their mRNA expression in liver tissue IL-α and TNFα play an important role during APAP-induced liver injury. Furthermore, PO inhibited APAP and TNFα-induced activation of JNK, whose activation play an important effect during APAP induced liver injury. These findings suggested that administration of PO may be an effective strategy to prevent or treat liver injury induced by APAP.