Survivin Inhibition Is Critical for Bcl-2 Inhibitor-Induced Apoptosis in Hepatocellular Carcinoma Cells

Our study aims to study the therapeutic effects of a novel Bcl-2 inhibitor, ABT-263, on hepatocellular carcinoma (HCC) and to provide primary preclinical data for future clinical trial with ABT-263. In this study we showed that Bcl-xL and survivin were up-regulated in HCC cell lines and human liver cancer tissues. Clinic used ABT-263 single treatment had no apoptotic effects on HCC cells whereas higher doses of ABT-263 did. Interestingly, the combination treatment of ABT-263 with survivin inhibitor YM-155 could result in significant apoptosis in HCC cells. Survivin inhibition through gene silencing significantly enhanced ABT-263 to induce apoptosis in HCC cells. We found that low dose of ABT-263 single treatment resulted in ERK activation and survivin up-regulation, which might be involved in the resistance of HCC cells to ABT-263 since blockade of ERK activation sensitized ABT-263-induced apoptosis. Importantly, ABT-263 and YM-155 combination treatment had no apoptotic effects on normal human hepatocytes. Taken together, these data suggest the combination treatment of Bcl-2 inhibitor and survivin inhibition may have a great potential for liver cancer therapy

Iatrogenic hemobilia: imaging features and management with transcatheter arterial embolization in 30 patients

PURPOSE:We aimed to evaluate the imaging features of computed tomography (CT) and angiography and the efficacy of transcatheter arterial embolization (TAE) in patients with hemobilia of different iatrogenic causes.METHODS:Thirty patients with hemobilia were divided into two groups according to their iatrogenic causes, i.e., group 1, 11 patients (36.7%) with transhepatic intervention and group 2, 19 patients (63.3%) with surgical procedures in the hilar area. Seventeen patients (56.7%) underwent abdominal contrast-enhanced CT before selective angiography. Polyvinyl alcohol particles, gelatin sponges, and coils were used for TAE. Data from the two groups were compared using Fisher’s exact test and the Mann-Whitney U test.RESULTS:Contrast-enhanced CT showed a hematoma, extravasation of contrast material, and pseudoaneurysm. The bleeding source was determined by angiographic features in all patients, which were not significantly different between the two groups (P = 0.127), and pseudoaneurysm was the most common. The embolic material and number of coils used for TAE were significantly different between the two groups (P < 0.001), but the embolization was technically successful in all patients. The clinical success rate of the first embolization was 100% in group 1 vs. 84.2% in group 2. The overall clinical success rate of TAE was 100% in all patients. The complication rate was 63.6% in group 1 vs. 68.4% in group 2 (P = 1.000).CONCLUSION:CT was useful in diagnosing hemobilia, and angiograms enabled determination of the bleeding source. Pseudoaneurysm was one of the most common angiographic features. TAE was successfully performed with different embolic materials on the basis of the iatrogenic cause and bleeding location

Recognition of dipole-induced electric field in 2D materials for surface-enhanced Raman scattering

The application of two-dimensional (2D) materials, including metallic graphene, semiconducting transition metal dichalcogenides, and insulating hexagonal boron nitride (h-BN) for surface-enhancement Raman spectroscopy has attracted extensive research interest. This article provides a critical overview of the recent developments in surface-enhanced Raman spectroscopy using 2D materials. By re-examining the relationship between the lattice structure and Raman enhancement characteristics, including vibration selectivity and thickness dependence, we highlight the important role of dipoles in the chemical enhancement of 2D materials

The Output Cost of Gender Discrimination: A Model-based Macroeconomics Estimate

We use a growth model in which saving, fertility and labour market participation are endogenous, to quantify the cost that barriers to female labour force participation impose in terms of an economy’s output. The model is calibrated to mimic the U.S. economy’s behavior in the long-run. We find that a 50 percent increase in the gender wage gap leads to a 35 percent decrease in income per capita in steady-state. Using independent estimates of the female to male earnings ratio for a wide cross-section of countries, we construct an economy with parameters similar to those calibrated for the U.S. economy, except for the degree of gender barriers. Higher discrimination decreases steady-state output per capita for two distinct reasons: a direct effect due to the decrease in female labour market participation, and an indirect effect working through an increase in fertility. For several countries, a large fraction of the difference between the country’s output and U.S. output can be ascribed to differences in gender discrimination. In addition, we find that close to half of the overall decrease in output per capita is due to the effect of gender discrimination in fertility.This paper has benefited from the financial support from Egide and Nova Forum at Universidade Nova de Lisboa, from the Funda¸cao para Ciencia e Tecnologia (FCT) and POCTI through FEDER, and from the Conselho Nacional de Desenvolvimento Cientıfico e Tecnologico (CNPq-Brazil)

Targeted Delivery of Chemotherapy Agents Using a Liver Cancer-Specific Aptamer

Using antibody/aptamer-drug conjugates can be a promising method for decreasing toxicity, while increasing the efficiency of chemotherapy.In this study, the antitumor agent Doxorubicin (Dox) was incorporated into the modified DNA aptamer TLS11a-GC, which specifically targets LH86, a human hepatocellular carcinoma cell line. Cell viability tests demonstrated that the TLS11a-GC-Dox conjugates exhibited both potency and target specificity. Importantly, intercalating Dox into the modified aptamer inhibited nonspecific uptake of membrane-permeable Dox to the non-target cell line. Since the conjugates are selective for cells that express higher amounts of target proteins, both criteria noted above are met, making TLS11a-GC-Dox conjugates potential candidates for targeted delivery to liver cancer cells.Considering the large number of available aptamers that have specific targets for a wide variety of cancer cells, this novel aptamer-drug intercalation method will have promising implications for chemotherapeutics in general

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Mass Balance Studies of Chlorpheniramine Hydrochloride in the Body of Channel Catfish (<i>Ictalurus punctatus</i>)

This study aims to determine the mass balance of chlorpheniramine hydrochloride (ROBH) in the body of Channel catfish (Ictalurus punctatus). ROBH was administered orally at a dose of 20 mg/kg; following drug administration, the water samples were collected at predetermined time points (12, 24, 48, 72, 96, 120, 144, and 168 h), the experimental fish were executed after the water samples were obtained at 168 h, and the tissue samples were collected separately from the bones. The water and tissue samples were analyzed by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC–MS/MS) for concentrations of ROBH and its potential major metabolites, 4-chlorohippuric acid (PCHA) and 4-chlorobenzoic acid (PCBA). The tissue samples were prepared using a modified QuEChERS procedure; the water samples were prepared using a liquid–liquid extraction (LLE) procedure. The results show that the recovery rate of ROBH in fish is very low, less than 2% of the total amount of the drug, and the recovery in water can reach 80.7% of the total amount of the drug. The content of PCBA accounted for 42.4% of the total amount of the drug; the content of ROBH accounted for 38.3% of the total amount of the drug. The content of PCHA accounted for less than 1% of the total amount of the drug. The results show that, after a single administration, ROBH is rapidly metabolized in vivo and excreted in the form of ROBH as well as metabolite PCBA. ROBH and PCBA can be used as the main targets for the metabolism detection of ROBH in Channel catfish

Tuning the optical bandgap of TiO2-TiN composite films as photocatalyst in the visible light

TiO2-TiN composite catalysts were prepared by oxidizing the TiN films in air at 350 °C. By adjusting the oxidation time to control the oxidation stage of TiN films, the optical band gap of the TiO2-TiN composites can be varied in a wide range from 1.68 eV to 3.23 eV. These composite films all showed red shift in photo-response towards the visible region, and depending on the optical band gap, some composite films exhibited good catalytic activity in the visible light region. This study provides a simple but effective method to prepare film photocatalyst working in visible light

Simultaneous Quantification of Avermectins in Six Aquatic Foods by UHPLC/FLD with Precolumn Derivatization

In this study, a fast, concise and reliable ultra-high performance liquid chromatography-fluorescence (UHPLC/FLD) detection method for simultaneous quantification of avermectins (AVMs), including avermectin (AVM), ivermectin (IVM), emamectin (EMM), moxidectin (MOX) and doramectin (DOR) in six aquatic foods was established. Based on the QuEChERS pretreatment method, the samples were extracted with 0.2% (v/v) ammonia acetonitrile. N-methyl imidazole mixed with acetonitrile (1:1, v/v) and trifluoroacetic anhydride with acetonitrile (1:2, v/v) were used as derivatization reagents. The mobile phase consists of acetonitrile and water with a flow rate of 1.0 mL/min. An Infinity Lab Poroshell 120 EC-C18 column was used for optimum chromatographic separation of target analytes at 40 &deg;C; the excitation and emission wavelengths were set at 365 nm and 465 nm, respectively. In six kinds of aquatic foods, the limits of detection (LODs) of AVM, IVM, EMM, MOX, and DOR were 2.7 &mu;g/kg, 1.8 &mu;g/kg, 2.1 &mu;g/kg, 1.2 &mu;g/kg, and 2.7 &mu;g/kg, respectively, and the limits of quantification (LOQs) of AVM, IVM, EMM, MOX, and DOR were 5 &mu;g/kg, 4.5 &mu;g/kg, 4.5 &mu;g/kg, 3.5 &mu;g/kg and 5.0 &mu;g/kg, respectively. The recoveries were all above 85.38% when the samples were spiked with the target compounds at the concentration level of 5, 10, 50, and 100 &mu;g/kg. The intra-day and inter-day relative standard deviations (RSDs) were all less than 15%. This method considers the requirements of sensitivity, accuracy, and economics of the instrument

Bcl-xL is up-regulated in liver tumor tissues and HCC cells.

<p><b>A</b>. Lysates from normal liver tissues and liver tumor tissues of different patients were prepared and subjected to Western blotting. Bcl-xL, Mcl-1, and survivin expressions were detected with specific antibodies. β-actin protein levels were assessed as an equal protein loading control (P1, P2, and P3: patient number). <b>B</b>. Cell lysates from human normal primary hepatocytes and HCC cells LH86 and Huh7 were prepared and Western blotting was performed to detect Bcl-xL, Mcl-1, and survivin expression with specific antibodies. β-actin protein levels were assessed as an equal protein loading control.</p