Secukinumab plays a synergistic role with starvation therapy in promoting autophagic cell death of hepatocellular carcinoma via inhibiting IL-17A-increased BCL2 level.

It is known that IL-17A inhibits autophagy of hepatocellular carcinoma (HCC) cells, thus contributing to the carcinogenesis of HCC. Starvation therapy can promote the autophagic death of HCC cells by blocking the nutrition supply. The purpose of this study was to explore whether the pharmacological antagonist of IL-17A, secukinumab, and starvation therapy have a synergistic effect on the autophagic cell death of HCC. Here, it could be observed that compared with serum-free condition, the combination of secukinumab and serum-free status better promoted autophagy (observed by LC3 conversion rate, p62 protein expression and the formation of autophagosomes), and more significantly inhibited the survival and function (observed by Trypan blue staining, CCK-8, Transwell, and scratch assays) in HCC HepG2 cells. Moreover, secukinumab significantly decreased BCL2 protein expression under serum-normal and serum-free conditions. However, both the addition of recombinant IL-17A and overexpression of BCL2 blocked the regulation of secukinumab on the survival and autophagy in HepG2 cells. Nude mice experiments demonstrated that compared to the lenvatinib-alone group, the combination group of lenvatinib and secukinumab better inhibited the in vivo tumorigenesis of HepG2 cells and enhanced autophagy in xenotumor tissues. Furthermore, secukinumab significantly decreased BCL2 protein expression in xenotumor tissues without or with lenvatinib application. In conclusion, the antagonism of IL-17A with secukinumab, due to the upregulation on BCL2-related autophagic cell death, can cooperate with starvation therapy in inhibiting HCC carcinogenesis. Our data suggested that secukinumab can become an effective adjuvant for the treatment of HCC.

Effects of Glucose and Corn Syrup on the Physical Characteristics and Whipping Properties of Vegetable-Fat Based Whipped Creams.

The aim of this work is to evaluate the effects of glucose and corn syrup on the physical characteristics and whipping properties of whipped creams. The interfacial protein concentration and apparent viscosity of emulsions increased with an increasing sugar concentration. In whipped creams, a shorter optimum whipping time (top), higher fat coalescence degree, higher firmness and higher stability were detected as sugar concentration increased. The partial coalescence degree, overrun and firmness of whipped cream with 30 wt% glucose reached 76.49%, 306% and 3.82 N, respectively, significantly (p < 0.05) higher than those (67.15%, 235% and 3.19 N) with 30 wt% corn syrup. Compared with glucose at the same sugar concentration, higher interfacial protein concentration and less-shaped aggregates and coalescences were observed for the emulsions upon the addition of corn syrup, which caused a lower degree of fat coalescence and a lower firmness of whipped cream. The differences could be explained by the presence of maltodextrin (MDX) in corn syrup, which protects absorbed protein throughout freezing and retards the formation of a continuous network during whipping. As a result, the addition of sugars could well improve stability of emulsion, firmness and foam stability of whipped cream efficiently. With a 25−30 wt% sugar addition, even if there was a lower partial coalescence degree and firmness compared with glucose, whipped cream with corn syrup exhibited relatively good stability. These results suggest that MDX improves the stability of emulsion and, thus, has a potential use in low-sugar whipped cream.

Identification of a glycolysis-related gene signature for predicting pancreatic cancer survival.

Background: Pancreatic cancer (PC) is one of the most common malignant tumors of the digestive tract. Its clinical symptoms are obscure and atypical. It is difficult to diagnose and treat. Tumor cells mainly obtain energy through glycolysis to promote their growth. Inhibiting glycolysis can inhibit proliferation and kill tumor cells. Methods: Using bioinformatics method, we investigate the relationships between glycolysis-related genes and PC tumor samples' epidemiologic information comprehensively. Results: Different expression levels of 27 genes were identified. Using bioinformatics methods, we plotted two subgroup curves based on glycolysis-related gene expression level. Potential predictive genes were screened and their prognostic values were analyzed. Survival among high-risk group and low risk group had significant difference. Receiver operating characteristic (ROC) curve analysis indicated that area under curve (AUC) of 10 genes was greater than 0.8. These genes could be used for clinical diagnosis and prediction for PC. Two potential predictors [Kinesin Family Member 20A (KIF20A) and MET Proto-Oncogene, Receptor Tyrosine Kinase (MET)] that met the independent predictive value were selected. In univariate analysis, we screened out 3 regulators MET, protein kinase CAMP-activated catalytic subunit alpha (PRKACA) and KIF20A. According to the 3 regulatory factors, the prognostic signals of PC were constructed, by which the samples with good prognosis and poor prognosis can be clearly distinguished independently of potential confounding factors. Conclusions: Our results indicate that for PC, glycolysis -related genes could be promising therapeutic targets or prognostic indicators.

Long noncoding RNA PVT1 inhibits interferon-α mediated therapy for hepatocellular carcinoma cells by interacting with signal transducer and activator of transcription 1.

Long noncoding RNA (LncRNA) PVT1 has recently been reported to be involved in the development of hepatocellular carcinoma (HCC) and hsigh expression of oncogenic PVT1 is associated with poor prognosis of HCC. Interferon-α (IFN-α) has been used in clinic for HCC therapy. However, whether PVT1 is involved in the IFN-α therapy for HCC is completely unknown. Our study found that high PVT1 expression in HCC cells is associated with high unmethylation in PVT1 promoter region. IFN-α treatment further increases PVT1 expression in HCC cells by enhancing H3K4me3 modification on the promoter. Furthermore, PVT1 knockdown enhances IFN-α-induced HCC cell apoptosis by promoting phosphorylation of signal transducer and activator of transcription 1 (STAT1) and upregulating IFN-stimulated genes expression. Moreover, PVT1 specifically interacts with STAT1 in HCC cells. Taken together, these results for the first time indicate that IFN-α treatment promotes oncogenic PVT1 expression in HCC cells, which interacts with STAT1 to inhibit IFN-α signaling, ultimately blocking IFN-α-induced cells apoptosis, suggesting that lncRNA PVT1 may be a potential target to improve IFN-α-mediated HCC immunotherapies.

Microfluidic Devices for Characterizing Pore-scale Event Processes in Porous Media for Oil Recovery Applications.

Microfluidic devices are versatile tools for studying transport processes at a microscopic scale. A demand exists for microfluidic devices that are resistant to low molecular-weight oil components, unlike traditional polydimethylsiloxane (PDMS) devices. Here, we demonstrate a facile method for making a device with this property, and we use the product of this protocol for examining the pore-scale mechanisms by which foam recovers crude oil. A pattern is first designed using computer-aided design (CAD) software and printed on a transparency with a high-resolution printer. This pattern is then transferred to a photoresist via a lithography procedure. PDMS is cast on the pattern, cured in an oven, and removed to obtain a mold. A thiol-ene crosslinking polymer, commonly used as an optical adhesive (OA), is then poured onto the mold and cured under UV light. The PDMS mold is peeled away from the optical adhesive cast. A glass substrate is then prepared, and the two halves of the device are bonded together. Optical adhesive-based devices are more robust than traditional PDMS microfluidic devices. The epoxy structure is resistant to swelling by many organic solvents, which opens new possibilities for experiments involving light organic liquids. Additionally, the surface wettability behavior of these devices is more stable than that of PDMS. The construction of optical adhesive microfluidic devices is simple, yet requires incrementally more effort than the making of PDMS-based devices. Also, though optical adhesive devices are stable in organic liquids, they may exhibit reduced bond-strength after a long time. Optical adhesive microfluidic devices can be made in geometries that act as 2-D micromodels for porous media. These devices are applied in the study of oil displacement to improve our understanding of the pore-scale mechanisms involved in enhanced oil recovery and aquifer remediation.

Destabilization, Propagation, and Generation of Surfactant-Stabilized Foam during Crude Oil Displacement in Heterogeneous Model Porous Media.

Foam flooding in porous media is of increasing interest due to its numerous applications such as enhanced oil recovery, aquifer remediation, and hydraulic fracturing. However, the mechanisms of oil-foam interactions have yet to be fully understood at the pore level. Here, we present three characteristic zones identified in experiments involving the displacement of crude oil from model porous media via surfactant-stabilized foam, and we describe a series of pore-level dynamics in these zones which were not observed in experiments involving paraffin oil. In the displacement front zone, foam coalesces upon initial contact with crude oil, which is known to destabilize the liquid lamellae of the foam. Directly upstream, a transition zone occurs where surface wettability is altered from oil-wet to water-wet. After this transition takes place, a strong foam bank zone exists where foam is generated within the porous media. We visualized each zone using a microfluidic platform, and we discuss the unique physicochemical phenomena that define each zone. In our analysis, we also provide an updated mechanistic understanding of the "smart rheology" of foam which builds upon simple "phase separation" observations in the literature.

1H-NMR metabolomics analysis of nutritional components from two kinds of freshwater fish brain extracts.

There are a number of bioactive compounds in freshwater fish brains, and their functional roles have not been clearly elucidated. NMR-based metabolic profiling could enable rapid characterization of the nutritional composition a fish's brain. Here, two kinds of freshwater fish brains were investigated, crucian carp and yellow catfish. A 1H-NMR based metabolomic approach was used to illustrate the nutritional components of these two kinds of brain. At first, the microwave method was utilized to cease the activity of the enzymes in the brain, and the chemicals were extracted for NMR analysis. These two kinds of brain had significant differences in metabolic patterns, and the chemical compositions of the yellow catfish brain were similar to those of rodent and human brains. Furthermore, most of the different metabolites were significantly higher in the yellow catfish, except for acetamide. This study could provide comprehensive information regarding the utilization of fish heads during processing of fish and dietary nutrition guidance.

Surface complexation modeling of calcite zeta potential measurements in brines with mixed potential determining ions (Ca2+, CO32-, Mg2+, SO42-) for characterizing carbonate wettability.

This study presents experiment and surface complexation modeling (SCM) of synthetic calcite zeta potential in brine with mixed potential determining ions (PDI) under various CO2 partial pressures. Such SCM, based on systematic zeta potential measurement in mixed brines (Mg2+, SO42-, Ca2+ and CO32-), is currently not available in the literature and is expected to facilitate understanding of the role of electrostatic forces in calcite wettability alteration. We first use a double layer SCM to model experimental zeta potential measurements and then systematically analyze the contribution of charged surface species. Calcite surface charge is investigated as a function of four PDIs and CO2 partial pressure. We show that our model can accurately predict calcite zeta potential in brine containing a combination of four PDIs and apply it to predict zeta potential in ultra-low and pressurized CO2 environments for potential application in enhanced oil recovery in carbonate reservoirs. Model prediction reveals that calcite surface will be positively charged in all considered brines in pressurized CO2 environment (>1atm). The calcite zeta potential is sensitive to CO2 partial pressure in the various brine in the order of Na2CO3>Na2SO4>NaCl>MgCl2>CaCl2 (Ionic strength=0.1M).

Role of Gas Type on Foam Transport in Porous Media.

We present the results of an experimental investigation of the effect of gas type and composition on foam transport in porous media. Steady-state foam strengths with respect to three cases of distinct gases and two cases containing binary mixtures of these gases were compared. The effects of gas solubility, the stability of lamellae, and the gas diffusion rate across the lamellae were examined. Our experimental results showed that the steady-state foam strength is inversely correlated with the gas permeability across a liquid lamella, a parameter that characterizes the rate of mass transport. The results are also in good agreement with existing observations that the foam strength for a mixture of gases is correlated with the less soluble component. Three hypotheses with different predictions of the underlying mechanism that explain the role of gas type and composition in foam strength are discussed in detail.