KDOAM-25 Overcomes Resistance to MEK Inhibitors by Targeting KDM5B in Uveal Melanoma.

Background: Uveal Melanoma (UM) is a potentially lethal cancer, and epigenetics may participate in the regulation of MEK resistance. This study is aimed at targeting the epigenetic kinase to overcome the resistance to MEK inhibitor. Method: We developed the 92.1 and OMM1 MEK-inhibitor resistant cell lines by culturing them in the trametinib (Tra) mixed medium. We utilized CCK8 analysis for detecting the viability of the cell. Western blot was used to determine the ERK1/2 and Akt phosphorylation. Small compound library screening assays were carried out by CCK8 analysis. To test the apoptosis, we employed flow cytometric analysis with Annexin-V/PI. Western blot and CCK8 were used to explore the epigenetic regulation of KDM5B in MEK-resistance cell lines. To knock out the expression level of KDM5B, we used the CRISPR/Cas9 by lentivirus delivering well-validated shRNAs in pLKO.1 vector. The directly binding affinity of KDOAM-25 to KDM5B was determined by drug affinity responsive target stability (DARTS) and microscale thermophoresis (MST). Results: The phosphorylation of ERK1/2 and Akt (T308) was inhibited in OMM1 cell lines. However, inhibition of Tra was abolished in OMM1-R cell lines. From a compound screening assay, we identified that KDOAM-25 robustly inhibited the viability and colony formation of MEK-resistance cell lines. Furthermore, KDOAM-25 significantly promoted cell death in OMM1-R cells. H3K4me3 (tri-methylation of lysine 4 on histone H3) and H3K27ac (acetyl of lysine 27 on histone H3) were both upregulated in OMM1-R cells. Tra significantly inhibited the expression of KDM5B in OMM1-P cells. However, the effect on KDM5B was abolished in OMM1-R cells. Knockdown of KDM5B robustly suppressed the cell viability in OMM1-R cells. KDOAM-25 directly interacted with KDM5B. Conclusion: KDOAM-25 inhibited the viability and colony formation and promoted cell death of MEK-resistance cell lines through H3K4me3 and H3K27ac, indicating that KDOAM-25 may be a potential therapeutic agent for MEK resistance in UM patients.

Safety Analysis of Simultaneous Cranioplasty and Ventriculoperitoneal Shunt Placement.

AIM: To investigate the safety of combined cranioplasty (CP) and ventriculoperitoneal shunt (VPS) placement. Furthermore, we investigated whether the sequence of these procedures affects the postoperative complication rates associated with staged CP and VPS placement. MATERIAL AND METHODS: We retrospectively investigated patients who developed communicating hydrocephalus after decompressive craniectomy and subsequently underwent VPS placement and CP at the hospital at which this study was performed between January 2009 and December 2019. Patients were categorized into group 1 (simultaneous CP and VPS placement) and group 2 (CP and VPS placement performed separately). Group 2 was subcategorized into subgroup 2a (CP performed before VPS placement) and subgroup 2b (VPS placement performed before CP). The Student?s t and Chi square tests were used to analyze intergroup differences. RESULTS: This study included 86 patients; 22 in group 1 and 64 in group 2 (24 patients in subgroup 2a and 40 patients in subgroup 2b). No statistically significant difference was observed in the overall complication rates between groups 1 and 2 (36.4% vs. 28.1%, P=0.591). However, the incidence of infections was significantly higher in group 1 than in group 2 (22.7% vs. 4.7%, P=0.024). Subgroup analysis showed that the overall complication rate was signi?cantly lower in subgroup 2a than in subgroup 2b (12.5% vs. 37.5%, P=0.031). CONCLUSION: Simultaneous CP and VPS placement is associated with a high incidence of infections. Moreover, compared with initial CP, initial VPS placement is associated with a significantly higher risk of overall complications in patients who undergo a staged procedure.

Regulating the Interlayer Spacings of Hard Carbon Nanofibers Enables Enhanced Pore Filling Sodium Storage.

Hard carbon (HC) represents an attractive anode material for sodium-ion batteries. However, most HC materials deliver limited capacity and the sodium storage mechanisms in the slope and plateau regions are controversial. Herein, a series of hard carbon nanofibers (HCNFs) with tunable interlayer spacings are designed to understand the sodium storage manners in HC. The optimized HCNFs featuring short-range graphitic layers with sufficient interlayer spacings (0.37-0.40 nm) for Na+ intercalation deliver a high reversible capacity (388 mAh g-1 at 30 mA g-1 ) and good rate capability. In-situ X-ray diffraction and Raman characterizations reveal a revised adsorption/insertion-filling sodium storage mechanism. Combined with the density functional theory (DFT) calculation, the detailed relationship between pore-filling plateau capacity and interlayer spacing is disclosed. It is found that sufficient interlayer spacings (>0.37 nm) provide diffusion channels for Na+ to reach the pores for further filling. Additionally, the reason for plateau-region capacity degradation of the HCNFs is completely demonstrated. This contribution provides insights into the sodium storage mechanism and rational construction of high-performance HC anode materials.

Qingjie Fuzheng Granule Inhibits EMT and Induces Autophagy in Colorectal Cancer via mTOR Signaling Pathways.

Qingjie Fuzheng granule (QFG) is a traditional Chinese medicinal formula used extensively as an alternative medicine for cancer treatment, including colorectal cancer (CRC). But its pathological mechanism in CRC is unclear. To study antitumor treatment effects and mechanisms of QFG, we established a CRC HCT-116 xenograft mouse model and assessed QFG on EMT and autophagy progression in vivo. The mice were randomly divided into 2 groups (n = 10 each group) and treated with intragastric administration of 1 g/kg of QFG or saline 6 days a week for 28 days (4 weeks). Body weight was measured every other day with electronic balance. At the end of the treatment, the tumor weight was measured. Immunohistochemical (IHC) and western blot (WB) assay were used to detect the expression level of E-cadherin, N-cadherin, vimentin, and TWIST1 to evaluate the effect of QFG on tumor cell EMT progression. IHC and WB assay were also used to detect the expression level of beclin-1, LC3-II, and p62 to evaluate the effect of QFG on tumor cell autophagy progression. Furthermore, the expression level of relative proteins in mTOR pathway was detected by WB assay to investigate the mechanism of QFG effect on CRC. We discovered that QFG inhibited the rise of tumor weight while it had no effect on mice body weight, which proved that QFG could inhibit CRC growth progression without significant side effects in vivo. In addition, QFG treatment inhibited EMT and induced autophagy progression in CRC tumor cells, including that QFG upregulated the expression of E-cadherin, beclin-1, and LC3-II, but downregulated the expression of N-cadherin, vimentin, TWIST1, and p62. And, QFG decreased the ratio of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR, but increased the ratio of p-AMPK/AMPK. All findings from this research proved that QFG can induce autophagy and inhibit EMT progression in CRC via regulating the mTOR signaling pathway.

[Development and evaluation of a novel method for rapid screening of Pichia pastoris strains capable of efficiently expressing recombinant proteins].

Pichia pastoris is one of the most widely used recombinant protein expression systems. In this study, a novel method for rapid screening of P. pastoris strains capable of efficiently expressing recombinant proteins was developed. Firstly, the ability to express recombinant proteins of the modified strain GS115-E in which a functional Sec63-EGFP (Enhanced green fluorescent protein) fusion protein replaced the endogenous endoplasmic reticulum transmembrane protein Sec63 was tested. Next, the plasmids carrying different copy numbers of phytase (phy) gene or xylanase (xyn) gene were transformed into GS115-E to obtain recombinant strains with different expression levels of phytase or xylanase, and the expression levels of EGFP and recombinant proteins in different strains were tested. Finally, a flow cytometer sorter was used to separate a mixture of cells with different phytase expression levels into sub-populations according to green fluorescence intensity. A good linear correlation was found between the fluorescence intensities of EGFP and the expression levels of the recombinant proteins in the recombinant strains (0.8<|R|<1). By using the flow cytometer, high-yielding P. pastoris cells were efficiently screened from a mixture of cells. The expression level of phytase of the selected high-fluorescence strains was 4.09 times higher than that of the low-fluorescence strains after 120 h of methanol induction. By detecting the EGFP fluorescence intensity instead of detecting the expression level and activity of the recombinant proteins in the recombinant strains, the method developed by the present study possesses the greatly improved performance of convenience and versatility in screening high-yielding P. pastoris strains. Combining the method with high-throughput screening instruments and technologies, such as flow cytometer and droplet microfluidics, the speed and throughput of this method will be further increased. This method will provide a simple and rapid approach for screening and obtaining P. pastoris with high abilities to express recombinant proteins.

Preparation of Epidermal Growth Factor-Modified Targeted Doxorubicin Nanoliposomes and Therapy of Liver Cancer.

The objective of this study was to prepare doxorubicin-loaded EGF modified PEG-nanoparticles and evaluate its targeting capability and therapeutic effects with EGFR-expressing hepatocellular carcinoma cells. The morphology, particle size distribution, and doxorubicin content of the nanoparticles were measured, and the drug loading and encapsulation efficiency were calculated. The doxorubicin nanoparticles prepared were regular circular, with good dispersibility, no adhesion, and the average particle size was (136.7±9.3) nm. The average encapsulation efficiency was (76.67±8.63)%, the average drug loading was (3.86±0.55)%; the drug release rate of doxorubicin was 100% for 12 h, and the doxorubicin nanometer was loaded. The drug release rate of the granules was 52.9% at 24 h and 81.2% at 144 h. The inhibition rate of the proliferation of hepatocarcinoma cells by the doxorubicin-containing nanoparticles was slower than that of doxorubicin, and the IC50 of the two cells was 1.844 and 0.345 µg/mL, respectively. At the same time, apoptosis and cycle analysis showed that the doxorubicin nanoparticles could significantly inhibit the cell cycle of hepatoma cells and promote the apoptosis of hepatoma cells. This study successfully produced nanoparticles loaded with doxorubicin targeting EGFR, which has a good sustained release effect, and its antitumor effect is stronger than free doxorubicin.

Babao Dan inhibits the migration and invasion of gastric cancer cells by suppressing epithelial-mesenchymal transition through the TGF-ß/Smad pathway.

OBJECTIVE: To investigate the anti-metastatic effects of Babao Dan (BBD) on gastric cancer (GC) cells (AGS and MGC80-3) and explore the underlying molecular mechanisms by which it inhibits epithelial-mesenchymal transition (EMT). METHODS: AGS and MGC80-3 cells were treated with BBD. In addition, cells were treated with the EMT inducer transforming growth factor-ß1 (TGF-ß1). Cell viability was determined using the MTT assay, and the live cell ratio was calculated via cell counting. Cell invasion and migration were evaluated using the Transwell assay. Western blotting was performed to measure the protein expression of EMT biomarkers and related genes. RESULTS: BBD inhibited the viability, migration, and invasion of AGS and MGC80-3 cells, but it did not reduce the live cell ratio. Furthermore, BBD inhibited the expression of N-cadherin, vimentin, zinc finger E-box binding homeobox (ZEB)1, ZEB2, Twist1, matrix metalloproteinase (MMP)2, MMP9, TGF-ß1, and p-Smad2/3, whereas E-cadherin expression was increased in AGS and MGC80-3 cells to different degrees. Using a GC cell model of EMT induced by TGF-ß1, we proved that BBD inhibited p-Smad2/3 and N-cadherin expression, cell migration, and cell invasion. CONCLUSION: BBD suppressed cell migration and invasion by inhibiting TGF-ß-induced EMT and inactivating TGF-ß/Smad signaling in GC cells.

Evaluation of hepatic fibrosis by ultrasonic acoustic structure quantification.

To evaluate the diagnostic accuracy of ultrasonic acoustic structure quantification (ASQ) for grading hepatic fibrosis/cirrhosis by comparing ultrasonographic features of regions of interest on ASQ images with the pathological characteristics of stage F0-F4 hepatic fibrosis cases.We retrospectively analyzed the medical records of 97 patients with chronic hepatitis who underwent ASQ evaluation at the Ultrasound Room of Dongfang Hepatobiliary Surgery Hospital (Shanghai, China) between July 2012 and October 2013. Regions of interest on stored ASQ images were analyzed to obtain cm values on modes, averages, and standard deviations. Correlation analysis, principal component analysis (PCA), and multivariate analysis of variance (MANOVA) of the mean cm values with hepatic fibrosis staging were performed. A receiver operating characteristic (ROC) curve was used to assess the diagnostic accuracy of ASQ.The mean cm of ASQ correlated with the pathological stage of hepatic fibrosis, with the best correlation coefficient (r = 0.81) in the right lobe below rib 2. The best cm average 1 and 2 values, which differed significantly among different hepatic fibrosis/cirrhosis stages, were also found in this area. The maximal area under the ROC curve (0.969) was for cmaverage 1 for the F0 versus F1 to F4 group, with a low criterion (110), while the maximal criterion (145) was for cm average 2 for the F0-F3 versus F4 group, with a relatively small AUC (0.882).With objective and accurate results, ASQ analysis is a promising non-invasive method for grading hepatic fibrosis, although this should be verified in further studies.

Bufalin Suppresses Migration and Invasion of Hepatocellular Carcinoma Cells Elicited by Poly (I:C) Therapy.

The Toll-like receptor 3 (TLR3) agonists as polyriboinosinic-polyribocytidylic acid (poly (I:C)) have been implicated as potential immunotherapy adjuvant for cancer whereas the exact roles of TLR3 agonists in hepatocellular carcinoma (HCC) treatment have not been clearly evaluated. In consistent with previous reports, we found that poly (I:C) triggering of TLR3 inhibited cell proliferation and induced apoptosis in HCC cells. However, poly (I:C), when used at lower concentration that cannot remarkably inhibit proliferation and induce apoptosis in HCC cells, enhanced the migration and invasion in vitro and the metastasis in vivo. More importantly, we found that bufalin, a prominent component of toad venom, could suppress poly (I:C)-inspired migration, invasion and metastasis of HCC cells despite that bufalin could not potentiate poly (I:C)-induced inhibition of proliferation and induction of apoptosis. In MHCC97 H cells, bufalin impaired poly (I:C)-induced activation of Tank-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) pathway and NF-κB pathway. Inhibitor for TBK1 but not NF-κB suppressed poly (I:C)-inspired migration and invasion, which was further supported by using TBK1 deficient (Tbk1-/- ) cells. In another model using poly (I:C) transfection, bufalin could also suppress the migration and invasion of HCC cells, which was not observed in Tbk1-/- MHCC97 H cells. Our data suggest that bufalin can suppress the metastasis of HCC cells in poly (I:C) therapy by impairing TBK1 activation, indicating that bufalin may be used in combination with poly (I:C) therapy in HCC treatment for the sake of reversing poly (I:C)-triggered metastasis of HCC cells.

SQLE induces epithelial-to-mesenchymal transition by regulating of miR-133b in esophageal squamous cell carcinoma.

Increasing evidence suggests that microRNAs, which control gene expression at the post-transcriptional level, are aberrantly expressed in cancers and play significant roles in carcinogenesis and cancer progression. In this study, we show differential miR-133b down-expression in human esophageal squamous cell carcinoma (ESCC) cells and tissues. In addition, squalene epoxidase (SQLE), a key enzyme of cholesterol synthesis, is identified as the direct downstream target gene of miR-133b by luciferase gene reporter assay. Furthermore, ectogenic miR-133b expression and SQLE knockdown can inhibit proliferation, invasion, and metastasis, and diminish epithelial-to-mesenchymal transition (EMT) traits of ESCC in vitro, implying that miR-133b-dependent SQLE can induce tumorigenicity and that SQLE is an EMT inducer. Xenograft experiment results also proved the biological function of SQLE in vivo. Therefore, we conclude that miR-133b-dependent SQLE plays a critical role in the potential metastasis mechanisms in ESCC.

Emodin inhibits migration and invasion of MHCC-97H human hepatocellular carcinoma cells.

Emodin, an anthraquinone derivative from the root and rhizome of Rheum palmatum L., was found to have antitumor effects in different types of cancer by regulating multi-molecular targets. The aim of the present study was to explore the effect of emodin on the migration and invasion of MHCC-97H human hepatocellular carcinoma cells and the underlying molecular mechanisms. Firstly, it was demonstrated that emodin can inhibit cell proliferation and induce apoptosis of cells in a time- and dose-dependent manner, using a MTT assay and flow cytometry, respectively. However, when emodin concentration was <50 µmol/l, it had little effect on the inhibition of proliferation or the induction of apoptosis. Then, it was observed that emodin can significantly suppress cell migration and invasion with a treatment dose <50 µmol/l compared with the control (P<0.05), which was not attributed to a decrease in cell number. Further study demonstrated that emodin significantly suppressed the expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 compared with the control, which may be mediated by the activation of the p38 mitogen-activated protein kinases (MAPK) signaling pathway and suppression of extracellular signal regulated kinase (ERK)/MAPK and phosphatidylinositol 3-kinase/Akt signaling pathways. Therefore, the present study, for the first time, used MHCC-97H cells, which have the high potential of malignant invasion, to demonstrate that emodin may inhibit cell migration and invasion.

Emodin induces hepatocellular carcinoma cell apoptosis through MAPK and PI3K/AKT signaling pathways in vitro and in vivo.

Emodin is an active ingredient derived from root and rhizome of Rheum palmatum L and many studies have reported that it exhibits anticancer effects in a number of human tumors. However, there is little information demonstrating the possible effects of emodin on the proliferation and apoptosis of hepatocellular carcinoma (HCC). In the present study, we show that emodin may inhibit the proliferation of SMMC-7721 cells in a dose- and time-dependent manner and induced apoptosis of cells in a concentration-dependent manner after treatment for 24 h. Moreover, we further discovered that the possible molecular mechanisms involved may relate to the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Emodin may induce the phosphorylation of extracellular-signal-regulated kinase (ERK) and p38 while mildly suppressed the expression of p-c-Jun-N-terminal kinase (p-JNK). However, emodin did not affect the expression of the total (t)-ERK, t-p38 or t-JNK. Furthermore, emodin also suppressed the activation of p-AKT, but not the t-AKT. In vivo, we found that emodin suppressed tumor growth in experimental mice without an obvious change in body weight, which may work through the antiproliferation and apoptosis inducing effects. Moreover, emodin improves the liver and kidney function in mice, revealing that emodin may improve the life quality of the mice with implanted tumors. In conclusion, the above findings indicate that emodin may be a potentially effective and safe drug to induce apoptosis of HCC.

Decreased TUSC3 Promotes Pancreatic Cancer Proliferation, Invasion and Metastasis.

Pancreatic cancer is an aggressive disease with dismal prognosis. It is of paramount importance to understand the underlying etiological mechanisms and identify novel, consistent, and easy-to-apply prognostic factors for precision therapy. TUSC3 (tumor suppressor candidate 3) was identified as a potential tumor suppressor gene and previous study showed TUSC3 is decreased in pancreatic cancer at mRNA level, but its putative tumor suppressor function remains to be verified. In this study, TUSC3 expression was found to be suppressed both at mRNA and protein levels in cell line models as well as in clinical samples; decreased TUSC3 expression was associated with higher pathological TNM staging and poorer outcome. In three pairs of cell lines with different NF-κB activity, TUSC3 expression was found to be reversely correlated with NF-κB activity. TUSC3-silenced pancreatic cancer cell line exhibited enhanced potential of proliferation, migration and invasion. In an orthotopic implanted mice model, TUSC3 silenced cells exhibited more aggressive phenotype with more liver metastasis. In conclusion, the current study shows that decreased immunological TUSC3 staining is a factor prognostic of poor survival in pancreatic cancer patients and decreased TUSC3 promotes pancreatic cancer cell proliferation, invasion and metastasis. The reverse correlation between NF-κB activity and TUSC3 expression may suggest a novel regulation pattern for this molecule.

Suppression of PDCD4 mediated by the long non-coding RNA HOTAIR inhibits the proliferation and invasion of glioma cells.

Programmed cell death protein 4 (PDCD4) has recently been demonstrated to be implicated in translation and transcription, and the regulation of cell growth. However, the mechanisms underlying PDCD4 function in glioma cells remain to be elucidated. The current study investigated the function and regulation of PDCD4 and the results demonstrated that the expression of PDCD4 was significantly reduced in glioma cells compared with normal cells. When PDCD4 was overexpressed in glioma cells, the proliferation rate and invasive capability of the cells greatly decreased, suggesting that PDCD4 functions as a tumor suppressor in this cell type. In addition, the histone modification status of the PDCD4 gene was analyzed, and chromatin immunoprecipitation assay identified a high density of histone 3 lysine 27 trimethylation on the promoter of PDCD4, which was associated with the long non-coding RNA, homeobox transcript antisense RNA (HOTAIR). The expression of HOTAIR was significantly increased in glioma cells compared with normal cells, and it exerted its function in a polycomb repressive complex 2-dependent manner. These results may provide novel approaches to therapeutically target PDCD4 and HOTAIR in patients with gliomas.

A combined bilateral approach to anterior communicating artery aneurysm.

AIM: To discuss the features, feasibility, and safety of a combined bilateral approach in the endovascular treatment of intracranial anterior communicating artery (ACoA) aneurysm. MATERIAL AND METHODS: We performed a retrospective analysis of the clinical data of patients with ACoA aneurysm treated with a combined bilateral approach. RESULTS: We successfully embolized aneurysms in nine patients with intracranial ACoA aneurysm using a combined bilateral approach. All treated patients had an open ACoA connecting with the bilateral anterior cerebral arteries. CONCLUSION: Because the ACoA connects the intracranial arteries in both hemispheres, patients with ACoA aneurysm can be endovascularly treated with a combined bilateral approach. Notably, surgeon experience and dexterity play important roles in the success of this procedure.

[Spatial variability and management zone of soil major nutrients in tobacco fields in Qiannan mountainous region].

Spatial variability and management zone of soil major nutrients in tobacco fields in Qian-nan mountainous region were analyzed using geostatistics and fuzzy c-mean algorithm. Results indicated that the level of soil organic matter (OM) was moderate, and alkalytic nitrogen (AN), available phosphorus (AP) and available potassium (AK) were rich according to tobacco soil nutrient classification standards. Coefficients of variation (CV) of OM, AN, AP and AK were moderate. Contents of OM, AN, AP and AK fitted log-normal distributions. Correlation analysis showed moderate correlations between OM and AN, AP and AK. OM and AN were best described by Gaussian semivariogram models, while AP and AK were described by exponential models. The four nutrients displayed moderate spatial autocorrelation. There were significant differences among lag distances of four soil nutrients. OM, AN, AP and AK in the majority of studied regions varied at moderate to very rich levels, and deficiencies of OM, AN, AP and AK only accounted for 0.93%, 0.53%, 0.24% and 7.91% of the total studied region, respectively. Based on the results, the studied region was divided into two management zones (MZ), namely MZ1 and MZ2, accounting for 69. 8% and 30. 2% of the studied region respectively. The soil levels of OM, AN, AP and AK in MZ1 were significantly lower than those in MZ2 (P < 0.01).

Stent-assisted coiling of cerebral aneurysms using the Enterprise and the Solitaire devices.

OBJECTIVE: To evaluate the technical feasibility, peri- and post-procedural morbidity and mortality as well as clinical and angiographic follow-up using the Enterprise and the Solitaire stent currently available to be used for stent-assisted coiling of broad-based cerebral aneurysms. MATERIAL AND METHODS: We conducted a retrospective study to investigate differences in aneurysms stented with the Enterprise (n  =  58) and Solitaire stents (n  =  19). Angiographic follow-up (mean: 8.25 onths) was available in 82.6% of patients treated with stent-assisted coiling. RESULTS: All stents were successfully deployed. There is a higher acute in-stent thrombosis complication in Solitaire stent placement (P  =  0.012). However, we observed no significant differences in peri-procedural morbidity and mortality rate (P  =  0.253), angiographic results (P  =  0.411), recurrence rate (P  =  1.000), or long-term neurological deficit (P  =  0.435). CONCLUSION: Both stents exhibited similar immediate and mid-term results with major neurological morbidities and mortality rate being low. More thrombogenic complications overall were found in Solitaire group.

Stent placement to treat ruptured vertebral dissecting aneurysms.

Conventional endovascular treatment may have limitations for vertebral dissecting aneurysm involving the origin of the posterior inferior cerebellar artery (PICA). We report our experiences of treating vertebral dissecting aneurysm with PICA origin involvement by placing a stent from the distal vertebral artery (VA) to the PICA to save the patency of the PICA. Stenting from the distal VA to the PICA was attempted to treat ruptured VA dissecting aneurysm involving the PICA origin with sufficient contralateral VA in eight patients. The procedure was successfully performed in seven patients with one failure because of PICA origin stenosis, which was treated with two overlapping stents. In the seven patients, PICAs had good patency on postoperative angiography and transient lateral brainstem ischemia represents a procedure-related complication. Follow-up angiographies were performed in seven patients and showed recanalization of the distal VA in three patients without evidence of aneurysmal filling. There was no evidence of aneurysm rupture during the follow-up period, and eight patients had favorable outcomes (mRS, 0 - 1). Placing a stent from the distal VA to the PICA with VA occlusion may present an alternative to conventional endovascular treatment for vertebral dissecting aneurysm with PICA origin involvement with sufficient contralateral VA.

A computation to integrate the analysis of genetic variations occurring within regulatory elements and their possible effects.

Single nucleotide polymorphisms (SNPs) and short tandem repeats (STRs) are the most common genetic variations, are widespread within genomes, and form the diversity within species. These genetic variations affect many regulatory elements such as transcription factor binding sites (TFBSs), DNA methylation sites on CpG islands, and microRNA target sites; these elements have been found to play major as well as indirect roles in regulating gene expression. Currently, systems are available to display such genetic variation occurring within regulatory elements. To understand and display all the potential variation described above, we have developed a web-based system tool, the Regulatory Element and Genetic Variation Viewer (REGV Viewer [REGV]), which provides a friendly web interface for users and shows genetic variation information within regulatory elements by either inputting a gene list or selecting a chromosome by name. Moreover, our tool not only supports logic operation queries, but after a query is submitted, it also shows a high-throughput simulation, including combined data, statistical graphs, and graphical views of the genetic variants and regulatory elements. Additionally, when the SNP variation occurs within TFBSs and if the SNP allele frequency and TFBS position weight matrices (PWMs) are available, our system will show the new putative TFBSs resulting from the SNP variation.