Initial CT-based radiomics nomogram for predicting in-hospital mortality in patients with traumatic brain injury: a multicenter development and validation study.

OBJECTIVE: To develop and validate a radiomic prediction model using initial noncontrast computed tomography (CT) at admission to predict in-hospital mortality in patients with traumatic brain injury (TBI). METHODS: A total of 379 TBI patients from three cohorts were categorized into training, internal validation, and external validation sets. After filtering the unstable features with the minimum redundancy maximum relevance approach, the CT-based radiomics signature was selected by using the least absolute shrinkage and selection operator (LASSO) approach. A personalized predictive nomogram incorporating the radiomic signature and clinical features was developed using a multivariate logistic model to predict in-hospital mortality in patients with TBI. The calibration, discrimination, and clinical usefulness of the radiomics signature and nomogram were evaluated. RESULTS: The radiomic signature consisting of 12 features had areas under the curve (AUCs) of 0.734, 0.716, and 0.706 in the prediction of in-hospital mortality in the internal and two external validation cohorts. The personalized predictive nomogram integrating the radiomic and clinical features demonstrated significant calibration and discrimination with AUCs of 0.843, 0.811, and 0.834 in the internal and two external validation cohorts. Based on decision curve analysis (DCA), both the radiomic features and nomogram were found to be clinically significant and useful. CONCLUSION: This predictive nomogram incorporating the CT-based radiomic signature and clinical features had maximum accuracy and played an optimized role in the early prediction of in-hospital mortality. The results of this study provide vital insights for the early warning of death in TBI patients.

GNG5 is an unfavourable independent prognostic indicator of gliomas.

Gliomas are the most common primary brain tumours, and glioblastomas (GBMs) are subgrouped into four distinct molecular subtypes. This study aimed to identify the potential gene related to glioma progression. Weighted gene co-expression network analysis (WGCNA) was used to explore the related gene. Correlation, ROC, survival and Cox regression analyses were performed. Blue module was strongly associated with WHO grade (r = .65, P = 1e-19). GNG5 in gliomas was overexpressed compared with normal samples and associated with clinicopathologic characteristics. GNG5 was frequent in Mesenchymal subtype and lowly expressed in Proneural subtype of GBMs. Survival and Cox regression analyses showed that glioma patients with GNG5 overexpression had shorter survival time, and GNG5 was an independent prognostic indicator of overall survival. Overall, GNG5 expression is closely associated with clinicopathologic characteristics and is an independent prognostic indicator for glioma patients, as well as a promising subtype-associated biomarker in molecular classification of gliomas.

Betulinic acid induces apoptosis and ultrastructural changes in MDA-MB-231 breast cancer cells.

The aim of this study is to investigate the effects of betulinic acid (BA) on triple-negative breast cancer MDA-MB-231 cells and observe the ultrastructural changes. The concentration of BA required to induce apoptosis in MDA-MB-231 cells has been previously reported. In this study, a cell counting kit-8 proliferation assay was used to measure cell viability and the apoptosis rate. Western blotting was performed to observe the protein expression levels of Bcl-2. Cell morphology and changes in cell density were observed by microscopy. Electron microscopy revealed pyknotic nuclei as well as vacuoles. Collectively, our results showed the morphological mechanisms by which BA impairs the ultrastructure of MDA-MB-231 cells.

Large animal models of traumatic brain injury.

Purpose/Aim: Animal models of traumatic brain injury (TBI) provide powerful tools to study TBI in a controlled, rigorous and cost-efficient manner. The mostly used animals in TBI studies so far are rodents. However, compared with rodents, large animals (e.g. swine, rabbit, sheep, ferret, etc.) show great advantages in modeling TBI due to the similarity of their brains to human brain. The aim of our review was to summarize the development and progress of common large animal TBI models in past 30 years. MATERIALS AND METHODS: Mixed published articles and books associated with large animal models of TBI were researched and summarized. RESULTS: We majorly sumed up current common large animal models of TBI, including discussion on the available research methodologies in previous studies, several potential therapies in large animal trials of TBI as well as advantages and disadvantages of these models. CONCLUSIONS: Large animal models of TBI play crucial role in determining the underlying mechanisms and screening putative therapeutic targets of TBI.

Sodium butyrate-induced apoptosis and ultrastructural changes in MCF-7 breast cancer cells.

This study investigated the effects of sodium butyrate (NaB) on Michigan Cancer Foundation-7 (MCF-7) breast cancer cells and analyzed the relevant mechanism. Here, we demonstrated that a certain concentration of NaB effectively induced MCF-7 cell apoptosis. Cell counting kit-8 (CCK-8) assay was used to detect cell viability and the apoptosis rate. Western blotting was used to detect changes in the Bcl-2 expression level. We observed cell shape changes with microscopy. Immunofluorescence revealed some apoptotic nuclei. Electron microscopy revealed thick nucleoli, chromatin margination, reduced mitochondria, and dramatic vacuoles. Collectively, our findings elucidated the morphological mechanism by which NaB changed the ultrastructure of MCF-7 cells.

Inhibition of human glioma U251 cells growth in vitro and in vivo by hydroxyapatite nanoparticle-assisted delivery of short hairpin RNAs against SATB1.

Special AT-rich sequence-binding protein-1 (SATB1) has been reported to be over-expressed in many human tumors and knockdown of SATB1 can inhibit tumor growth. The present study was designed to determine the role of SATB1 in the growth of human glioma U251 cells using the plasmid-based SATB1 short hairpin RNA (shRNA) delivered by hydroxyapatite nanoparticles in vitro and in vivo. The in vitro growth, invasion and angiogenesis assays of human glioma U251 cells were done. U251 cells tumor blocks were transplanted into the nude mice. CaCl2-modified hydroxyapatite nanoparticles carrying shRNA-SATB1 plasmids were injected into the tumors. The apoptosis of the tumor U251 cells was examined with TUNEL assay and flow cytometer (FCM). The tumor growth and immunohistochemistry were measured. The expression level of SATB1 mRNA was investigated by RT-PCR. The expression levels of SATB1, Cyclin D1, MMP-2, VEGF, Bax and Caspase-9 protein were determined by western blot analysis. The results showed that hydroxyapatite nanoparticles-delivered shRNA-SATB1 could significantly inhibit the growth, invasion and angiogenesis of U251 cells in vitro and the growth of U251 cells in vivo. FCM results showed that Nano HAP-shRNA-SATB1-induced apoptosis (up to 67.8 %). SATB1 expression was strongly down-regulated in the tumor U251 cells. Cyclin D1, MMP-2 and VEGF were also down-regulated in the tumor tissues that also displayed significant increased in Bax expression and Caspase-9 activity. These results show that Nano HAP-shRNA-SATB1 can inhibit the growth of human glioma U251 cells in vitro and in vivo, and hydroxyapatite nanoparticles can be used for the in vitro and in vivo delivery of plasmid-based shRNAs into U251 cells.

Where are we in the modelling of traumatic brain injury? Models complicated by secondary brain insults.

BACKGROUND: Traumatic brain injury (TBI) contributes to a substantial number of deaths and cases of disability. Despite well-established experimental models and years of carefully conducted research, a clinical therapeutic breakthrough in TBI has lagged. This may be due, in part, to the discrepancies between commonly used experimental models and clinical scenarios. METHOD: Secondary insults, such as hypotension and hypoxemia, have been well demonstrated as powerful determinants of outcomes from TBI. Despite the frequency of secondary insults in patients with TBI, they are rarely incorporated into most existing models of TBI. This review focuses on the combined injury models, especially coupled with systemic secondary insults, and aims to provide a new view to guiding future research endeavors in this field. RESULTS: A growing number of experimental models of TBI complicated by certain secondary insult have been gradually introduced and characterized. Correspondingly, the pathophysiological changes following combined injuries and the interactive effects of primary injury with secondary insults can be studied more in-depth. CONCLUSION: A more complete understanding of the interactions between the injured brain and secondary insults represents a potentially fruitful avenue that may increase the likelihood of developing effective therapies. Experimental models of TBI should not only attempt to model the focal or diffuse changes resulting from external forces, but also integrate, when appropriate, secondary insults reminiscent of human situations.

Predictive value of the SLC22A18 protein expression in glioblastoma patients receiving temozolomide therapy.

BACKGROUND: Our previous study showed that SLC22A18 downregulation and promoter methylation were associated with the development and progression of glioma and the elevated expression of SLC22A18 was found to increase the sensitivity of glioma U251 cells to the anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). In this study, we investigated the predictive value of SLC22A18 promoter methylation and protein expression in glioblastoma multiforme (GBM) patients receiving temozolomide (TMZ) therapy. PATIENTS AND METHODS: SLC22A18 promoter methylation and protein expression were examined by methylation-specific polymerase chain reaction (MSP) and Western blotting respectively, then we compared SLC22A18 promoter methylation and protein expression in tumor cell explants in regard to prediction of TMZ response and survival time of 86 GBM patients. RESULTS: SLC22A18 promoter methylation was detected in 61 of 86 (71%) samples, whereas 36 of 86 (42%) cases were scored positive for SLC22A18 protein expression. Overall SLC22A18 promoter methylation was significantly related to SLC22A18 protein expression, but a subgroup of cases did not follow this association. Multivariate Cox regression analysis indicated that SLC22A18 protein expression, but not promoter methylation, was significantly correlated with TMZ therapy. SLC22A18 protein expression predicted a significantly shorter overall survival in 51 patients receiving TMZ therapy, whereas no differences in overall survival were observed in 35 patients without TMZ therapy. CONCLUSIONS: These results show that lack of SLC22A18 protein expression is superior to promoter methylation as a predictive tumor biomarker in GBM patients receiving temozolomide therapy.

Safety and efficacy of symptom-driven CT decision rule in fully conscious paediatric patients with symptoms after mild closed head trauma.

OBJECTS: The aim of the authors is to derive a safe, effective and feasible symptom-driven CT rule in fully conscious children ≥3 years with symptoms after head trauma, based on time-framed clinical course, radiological findings, outcome measures and prognosis of patients. METHODS: Fully conscious but symptomatic children ≥3 years after head injury (1997-2010) with CT performance ≤2 h since injury were included in the study. Additional exclusion criteria were set for patient selection. Evolution of clinical symptoms of patients in 24 h since injury was the focus in current study. Clinical data were extracted from standardised medical records on admission and observation charts. RESULTS: Data of 1897 eligible cases were retrospectively reviewed. Traumatic brain injury (TBI) was revealed radiologically in 73 cases (3.8%). Eight cases underwent surgery. Recursive partitioning analysis identified the following factors in the CT rule: any delayed headache commenced between 4 and 10 h since injury; significantly worsening headaches present between 2 and 12 h since injury; vomiting between 6 and 12 h since injury; and headache without significant changes persisted ≥12 h since injury. It has a sensitivity of 100% (95% CI 95.0% to 100.0%) and specificity of 72.1% (95% CI 70.0% to 74.1%) to predict cases with TBI. CONCLUSIONS: A symptom-driven CT rule has been derived to identify cases at high risk of having TBI in fully conscious, but symptomatic children with mild closed head injury. To be practical, an additional observation rule is added.

[Threshold of Se-rich Soil Based on Available-Se and Influencing Factors of Available-Se].

Available selenium (Se) in soil was the predominant factor affecting the content of Se in crops. In order to reasonably delineate the Se-rich soil range and propose theoretical guidance for the cultivation of natural Se-rich crops in a region where the surface soils had a high level of available-Se and a low level of total-Se, 8814 samples in surface soil and 195 root-crop matching samples were collected in Shizuishan in northern Ningxia. On the basis of the main line of analysis of available-Se, the following research was conducted: by synthetically studying the total-Se and available-Se in surface soil and root soil, the morphology of Se in surface soil, as well as Se in crops, deep and coordinated analyses of content among total-Se, available-Se, and Se in root-crop matching samples were carried out, and the suitable threshold for Shizuishan was confirmed. A multiple regression model of available-Se was established to determine the main physical and chemical indexes affecting available-Se, which were expected to improve the Se enrichment rate of crops through the enhancement of available-Se. The results demonstrated that ω(Se) and ω(Seavailable)in the surface soil in Shizuishan were 0.26 mg·kg-1 and 12.85 µg·kg-1, respectively, and the characteristics of Se and available-Se in root-crop matching samples could represent those in surface soil. Thus, it was recommended to use 0.24 mg·kg-1 as the suitable threshold of Se-rich soil. The multiple regression model of available-Se showed that the increase in total-Se and soil elements affecting soil fertility could promote the enrichment of available-Se.

[Translocation, Accumulation, and Comprehensive Risk Assessment of Heavy Metals in Soil-Crop Systems in an Old Industrial City, Shizuishan, Ningxia, Northwest China].

In order to explore the environmental geochemistry characteristics of heavy metals (HMs) in soil-crop systems in an old industrial city, the concentration and fraction of HMs in the paddy, wheat, and maize root soil and their seeds were detected and analyzed. Subsequently, statistical methods, risk assessment coding (RAC), the bio-enrichment coefficient factor (BCF), influence index of comprehensive quality (IICQ), and ArcGIS spatial interpolation were used to conduct the translocation, accumulation, and comprehensive risk assessment of HMs in soil-crop systems. The results showed that the average concentrations of As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn in root soil were ranked respectively as follows:12.56, 0.19, 63.48, 23.52, 0.038, 28.86, 21.68, and 69.47 mg·kg-1. HMs in root soil were accumulated to some extent in comparison with the soil background value in Ningxia, especially Cd and Hg, but did not exceed the soil environmental pollution screening value (GB 14618-2018). The average concentrations of the eight aforementioned elements in supporting crop seeds were 0.0149, 0.0112, 0.075, 6.7, 0.0015, 0.67, 0.0427, and 20.48 mg·kg-1 in turn. The over-limit ratio of As, Pb, and Cr in crop seeds was 4%, 3%, and 1%, respectively, relative to the national food safety standards (GB 2762-2017), whereas the other five elements were within the allowable range. In comparison to those in paddy and wheat, HMs hardly tended to translocate to maize seeds from root soil. According to the results of IICQ in soil-crop systems, the cultivated soil was in the state of slight sub-contamination regionally, and only 10% of sampling points showed slight (sub-)contamination-submoderate contamination, where we could replant maize to reduce HMs contamination risk.

Upregulation of SATB1 is associated with the development and progression of glioma.

BACKGROUND: Special AT-rich sequence-binding protein-1 (SATB1) has been reported to be expressed in several human cancers and may have malignant potential. This study was aimed at investigating the expression and potential role of SATB1 in human glioma. METHOD: The relationship between SATB1 expression, clinicopathological parameters, Ki67 expression and MGMT promoter methylation status was evaluated, and the prognostic value of SATB1 expression in patients with gliomas was analyzed. SATB1-specific shRNA sequences were synthesized, and U251 cells were transfected with SATB1 RNAi plasmids. Expression of SATB1 mRNA and protein was investigated by RT-PCR and immunofluoresence staining and western blotting. The expression of c-Met, SLC22A18, caspase-3 and bcl-2 protein was determined by western blotting. U251 cell growth and adherence was detected by methyl thiazole tetrazolium assay. The apoptosis of U251 cells was examined with a flow cytometer. The adherence, invasion, and in vitro angiogenesis assays of U251 cells were done. The growth and angiogenesis of SATB1 low expressing U251 cells was measured in an in vivo xenograft model. RESULTS: Of 70 tumors, 44 (62.9%) were positive for SATB1 expression. SATB1 expression was significantly associated with a high histological grade and with poor survival in univariate and multivariate analyses. SATB1 expression was also positively correlated with Ki67 expression but negatively with MGMT promoter methylation in glioma tissues. SATB1 shRNA expression vectors could efficiently induce the expression of SLC22A18 protein, increase the caspase-3 protein, inhibit the expression of SATB1, c-Met and bcl-2 protein, the growth, invasion, metastasis and angiogenesis of U251 cells, and induce apoptosis in vitro. Furthermore, the tumor growth of U251 cells expressing SATB1 shRNA were inhibited in vivo, and immunohistochemical analyses of tumor sections revealed a decreased vessel density in the animals where shRNA against SATB1 were expressed. CONCLUSIONS: SATB1 may have an important role as a positive regulator of glioma development and progression, and that SATB1 might be a useful molecular marker for predicting the prognosis of glioma.

Promoter methylation and downregulation of SLC22A18 are associated with the development and progression of human glioma.

BACKGROUND: Downregulation of the putative tumor suppressor gene SLC22A18 has been reported in a number of human cancers. The aim of this study was to investigate the relationship between SLC22A18 downregulation, promoter methylation and the development and progression of human glioma. METHOD: SLC22A18 expression and promoter methylation was examined in human gliomas and the adjacent normal tissues. U251 glioma cells stably overexpressing SLC22A18 were generated to investigate the effect of SLC22A18 on cell growth and adherence in vitro using the methyl thiazole tetrazolium assay. Apoptosis was quantified using flow cytometry and the growth of SLC22A18 overexpressing U251 cells was measured in an in vivo xenograft model. RESULTS: SLC22A18 protein expression is significantly decreased in human gliomas compared to the adjacent normal brain tissues. SLC22A18 protein expression is significantly lower in gliomas which recurred within six months after surgery than gliomas which did not recur within six months. SLC22A18 promoter methylation was detected in 50% of the gliomas, but not in the adjacent normal tissues of any patient. SLC22A18 expression was significantly decreased in gliomas with SLC22A18 promoter methylation, compared to gliomas without methylation. The SLC22A18 promoter is methylated in U251 cells and treatment with the demethylating agent 5-aza-2-deoxycytidine increased SLC22A18 expression and reduced cell proliferation. Stable overexpression of SLC22A18 inhibited growth and adherence, induced apoptosis in vitro and reduced in vivo tumor growth of U251 cells. CONCLUSION: SLC22A18 downregulation via promoter methylation is associated with the development and progression of glioma, suggesting that SLC22A18 is an important tumor suppressor in glioma.

Integrated Transcriptomic Analysis Reveals the Molecular Mechanism of Meningiomas by Weighted Gene Coexpression Network Analysis.

Meningiomas are the most common primary intracranial tumor in adults. However, to date, systemic coexpression analyses for meningiomas fail to explain its pathogenesis. The aim of the present study was to construct coexpression modules and identify potential biomarkers associated with meningioma progression. Weighted gene coexpression network analysis (WGCNA) was performed based on GSE43290, and module preservation was tested by GSE74385. Functional annotations were performed to analyze biological significance. Hub genes were selected for efficacy evaluations and correlation analyses using two independent cohorts. A total of 14 coexpression modules were identified, and module lightcyan was significantly associated with WHO grades. Functional enrichment analyses of module lightcyan were associated with tumor pathogenesis. The top 10 hub genes were extracted. Ten biomarkers, particularly AHCYL2, FGL2, and KCNMA1, were significantly related to grades and prognosis of meningioma. These findings not only construct coexpression modules leading to the better understanding of its pathogenesis but also provide potential biomarkers that represent specific on tumor grades and identify recurrence, predicting prognosis and progression of meningiomas.

Integrated Transcriptome Analyses and Experimental Verifications of Mesenchymal-Associated TNFRSF1A as a Diagnostic and Prognostic Biomarker in Gliomas.

Gliomas are the most prevalent malignant primary brain tumors with poor outcome, and four different molecular subtypes (Mesenchymal, Proneural, Neural, and Classical) are popularly applied in scientific researches and clinics of gliomas. Public databases contain an abundant genome-wide resource to explore the potential biomarker and molecular mechanisms using the informatics analysis. The aim of this study was to discover the potential biomarker and investigate its effect in gliomas. Weighted gene co-expression network analysis (WGCNA) was used to construct the co-expression modules and explore the biomarker among the dataset CGGA mRNAseq_693 carrying 693 glioma samples. Functional annotations, ROC, correlation, survival, univariate, and multivariate Cox regression analyses were implemented to investigate the functional effect in gliomas, and molecular experiments in vitro were performed to study the biological effect on glioma pathogenesis. The brown module was found to be strongly related to WHO grade of gliomas, and KEGG pathway analysis demonstrated that TNFRSF1A was enriched in MAPK signaling pathway and TNF signaling pathway. Overexpressed TNFRSF1A was strongly related to clinical features such as WHO grade, and functioned as an independent poor prognostic predictor of glioma patients. Notably, TNFRSF1A was preferentially upregulated in the Mesenchymal subtype gliomas (Mesenchymal-associated). Knockdown of TNFRSF1A inhibited proliferation and migration of glioma cell lines in vitro. Our findings provide a further understanding of the progression of gliomas, and Mesenchymal-associated TNFRSF1A might be a promising target of diagnosis, therapy, and prognosis of gliomas.

BMX activates Wnt/ß-catenin signaling pathway to promote cell proliferation and migration in breast cancer.

BACKGROUND: Breast cancer has become a dangerous killer for the female, which seriously threatened women's life, leading to huge pressures to society. The present study assessed the mechanism underlying the involvement of bone marrow tyrosine kinase on chromosome X (BMX) in breast cancer development. METHODS: The expression of BMX was examined by qPCR and immunohistochemistry. The effect of BMX on cell proliferation and migration was detected by Clone formation assay and Transwell assay. In vitro study, the correlation of BMX with Wnt/ß-catenin pathway was explored by western blot and TOP/FOP flash assay. RESULTS: In the present study, we found that BMX was up-regulated in breast cancer, which was associated with the tumor differentiation and TNM stage. Oncogenic BMX enhanced the ability of breast cancer cell proliferation and migration. Furthermore, BMX could up-regulate the protein expression levels of p-ß-catenin (Y142), p-ß-catenin(Y654) and inhibit the expression level of p-ß-catenin (S33/37), thus activating Wnt/ß-catenin pathway in MCF-7 and MDA-MB-231 cells. In addition, we revealed that BMX promoted GSK3ß phosphorylation, which suppressed the degradation of ß-catenin. CONCLUSIONS: In this study, we identified that BMX-activated Wnt/ß-catenin signaling pathway, playing an oncogenic role in breast cancer, suggesting that BMX could become a potential treatment target of breast cancer.

c-Met-targeted RNA interference inhibits growth and metastasis of glioma U251 cells in vitro.

Angiogenesis plays an essential role in tumor growth and metastasis and is a promising target for cancer therapy. c-Met, a receptor tyrosine kinase, and its ligand, hepatocyte growth factor (HGF), are critical in cellular proliferation, motility, invasion, and angiogenesis. The present study was designed to determine the role of c-Met in growth and metastasis of glioma U251 cells using RNA interference (RNAi) technology in vitro. We constructed three kinds of shRNA expression vectors aiming at the c-Met gene, then transfected them into glioma U251 cells by lipofectamine(TM) 2000. The level of c-Met mRNA was investigated by real-time polymerse chain reaction (RT-PCR). The protein expression of c-Met was observed by immunofluoresence staining and western blotting. U251 cell growth and adherence was detected by methyl thiazole tetrazolium assay. The apoptosis of U251 cells was examined with a flow cytometer. The adherence, invasion, and in vitro angiogenesis assays of U251 cells were done. We got three kinds of c-Met specific shRNA expression vectors which could efficiently inhibit the growth and metastasis of U251 cells and the expression of c-Met in U251 cells. RT-PCR, immunofluoresence staining and western blotting showed that inhibition rate for c-Met expression was up to 90%, 79% and 85%, respectively. The expression of c-Met can be inhibited by RNA interference in U251 cells, which can inhibit the growth and metastasis of U251 cell and induce cell apoptosis. These results indicate that RNAi of c-Met can be an effective antiangiogenic strategy for glioma.

Stabilization of hepatocyte growth factor mRNA by hypoxia-inducible factor 1.

Hypoxia regulates expression of hepatocyte growth factor (HGF) by increasing its transcription and by stabilizing its mRNA. Despite the pivotal role of hypoxia-inducible factor 1 (HIF-1) in transcriptional activation of hypoxia-responsive genes, it is not known whether HIF-1 mediates hypoxia-induced stabilization of HGF mRNA. We constructed adenoviral vectors expressing either the wild-type HIF-1alpha (Ad2/HIF-1alpha/FL), a constitutively stable hybrid form of HIF-1alpha (Ad2/HIF-1alpha/VP16), or no transgene (Ad2/CMVEV). In rat glioma (C6) cells, human glioma (U251) cells human cardiac, vascular smooth muscle, and endothelial cells, infection with Ad2/HIF-1alpha/VP16 or Ad2/HIF-1alpha/FL increased HGF expression at both the mRNA and protein levels. Under normoxic conditions, the half-life of HGF mRNA was 43 min in C6 and U251 cells. Hypoxia and Ad2/HIF-1alpha/VP16 increased the half-life of HGF mRNA to 3.2 and 2.8 h, respectively, while Ad2/CMVEV had no effect. These studies are the first to demonstrate that overexpression of HIF-1alpha increases HGF mRNA stability. Our results also suggest that stabilization of HGF mRNA by hypoxia is mediated, at least in part, by HIF-1.

Sinus pericranii in the right frontal region and thrombosis.

Sinus pericranii is a rare vascular anomaly in which an abnormal communication exists between the extracranial venous system and the underlying dural venous sinus via the diploe of the skull. We describe a case of a spontaneous thrombosis of the sinus pericranii which was located in the right frontal region and presented as a focal, leathery, and noncompressible mass distinguished in character from the typical manifestation of sinus pericranii. In this case, CT, DSA, MRI, MR venography (MRV), and pathologic examination were performed. The CT showed the bone depression in the skull and the MRI demonstrated the mass, but they were not sufficiently sensitive to detect the thrombus. Pathologic examination and MRV were helpful in depicting the thrombus. She underwent a surgical resection, and at the 5-month follow-up there was no evidence of recurrence.

[Effect of beta-catenin on the activation of hepatic stellate cells induced by transforming growth factor-beta1].

OBJECTIVE: To investigate the effect of beta-catenin on the activation of hepatic fibrosis by transforming growth factor-beta 1 (TGFbeta1). METHODS: The recombinant expression plasmids pcDNA3.1(+)-beta-catenin and pEGFP-N1 were cotransfected into cultured HSC-T6 cells. The expression of smad3, beta-catenin and alpha-SMA, beta-catenin protein in TGFbeta1 treated HSC-T6 cells were detected by RT-PCR and Western-blot. RESULTS: The expression of smad3 and beta-catenin in the co-transfected cells was higher than that in the untransfected cells (smad3 mRNA were 0.642 +/- 0.011, 0.501 +/- 0.021, 0.511 +/- 0.019, 0.356 +/- 0.017, respectively, F = 135.304, P < than 0.05. beta-catenin mRNA were 0.783 +/- 0.021, 0.543 +/- 0.033, 0.538 +/- 0.024, 0.212 +/- 0.019, respectively, F = 267.340, P < than 0.05. smad3 protein were 0.892 +/- 0.012, 0.124 +/- 0.011, 0.130 +/- 0.021, 0.003 +/- 0.001, F = 2823.813, P < l than 0.05. beta-catenin protein were 0.921 +/- 0.020, 0.210 +/- 0.010, 0.208 +/- 0.008, 0.002 +/- 0.001, respectively, F = 3440.982, P < than 0.05). The expression of beta-catenin and smad3 protein had a positive correlation with the level of alpha-SMA protein in cells (r = 0.901, P < than 0.01; r = 0.939, P < than 0.01). CONCLUSIONS: Expression of smad3/alpha-SMA/beta-catenin is increased in the cultured HSC-T6 cells transfected by beta-catenin gene, especially when the transfected cells are stimulated by TGFbeta1. Our data suggest that beta-catenin could aggravate hepatic fibrosis induced by TGFbeta1.