bluuebunny/crossref_metadata_2025 huggingface dataset:
FXYD5/Dysadherin, a Biomarker of Endometrial Cancer Myometrial Invasion and Aggressiveness: Its Relationship With TGF-β1 and NF-κB Pathways
Authors: Besso María José , Rosso Marina , Lapyckyj Lara , Moiola Cristian Pablo , Matos María Laura , Mercogliano María Florencia , Schillaci Roxana , Reventos Jaume , Colas Eva , Gil-Moreno Antonio , Wernicke Alejandra , Orti Roberto , Vazquez-Levin Mónica Hebe
Published: December 2019

Objective: Endometrial cancer (EC) is the second most common gynecological cancer worldwide. Myometrial invasion (MI) is a key event in EC dissemination. This study aimed to evaluate FXYD5/dysadherin (FXYD5/Dys) expression in EC tissue and uterine aspirate (UA) biopsies and to assess molecular/functional changes associated with its expression in cellular models.

Methods: FXYD5/Dys messenger RNA (mRNA) levels were determined in EC tissue and UA biopsies. FXYD5/Dys expression was evaluated in EC RNAseq data from The Cancer Genome Atlas (TCGA) and GENEVESTIGATOR tools. FXYD5/Dys impact on E-cadherin expression and cell behavior was assessed in EC Hec1a cells treated with transforming growth factor (TGF)-β1, stably transfected with ETV5, and transiently transfected with FXYD5/Dys small interfering RNA (siRNA) or pcDNA3-FXYD5/Dys plasmid.

Results: FXYD5/Dys was associated with EC aggressiveness, finding high mRNA levels in tumors depicting MI > 50%, Grade 3, and intermediate/high risk of recurrence. FXYD5/Dys was highly expressed at the tumor invasive front compared to the superficial area. Most results were recapitulated in UA biopsies. FXYD5/Dys modulation in Hec1a cells altered cell migration/adhesion and E-cadherin expression. TGF-β1 treatment of Hec1a cells induced FXYD5/Dys expression. TCGA-UCEC RNAseq analysis revealed a positive correlation between FXYD5/Dys, TGF-β1, and plasminogen activator inhibitor (PAI)-1 mRNA levels. FXYD5/Dys induced nuclear factor (NF)-κB pathway activation in Hec1a cells. FXYD5/Dys mRNA levels positively correlated with transcriptional activation of NF-κB p65-regulated genes. Survival analysis revealed patient segregation into low- and high-risk groups, the latter depicting the highest FXYD5/Dys, PAI-1, tumor necrosis factor (TNF)-α, and TGF-β1 mRNA levels and shorter survival rates.

Conclusion: FXYD5/Dys is a novel biomarker of EC progression related to TGF-β1 and NF-κB pathways that collectively promote tumor dissemination and result in poor patient prognosis.
RETRACTED: RORα Suppresses Epithelial-to-Mesenchymal Transition and Invasion in Human Gastric Cancer Cells via the Wnt/β-Catenin Pathway
Authors: Su Jian , Su Bo , Xia Hong , Liu Fang , Zhao XiaoHong , Li Juan , Zhang JiZhen , Shi Ying , Zeng Ying , Zeng Xi , Ling Hui , Wu YouHua , Su Qi
Published: December 2019

Retinoid-related orphan receptor alpha (RORα) is involved in tumor development. However, the mechanisms underlying RORα inhibiting epithelial-to-mesenchymal transition (EMT) and invasion are poorly understood in gastric cancer (GC). This study revealed that the decreased expression of RORα is associated with GC development, progression, and prognosis. RORα suppressed cell proliferation, EMT, and invasion in GC cells through inhibition of the Wnt/β-catenin pathway. RORα overexpression resulted in the decreased Wnt1 expression and the increased RORα interaction with β-catenin, which could lead to the decreased intranuclear β-catenin and p-β-catenin levels, concomitant with downregulated T-cell factor-4 (TCF-4) expression and the promoter activity of c-Myc. The inhibition of Wnt/β-catenin pathway was coupled with the reduced expression of Axin, c-Myc, and c-Jun. RORα downregulated vimentin and Snail and upregulated E-cadherin protein levels in vitro and in vivo. Inversely, knockdown of RORα attenuated its inhibitory effects on Wnt/β-catenin pathway and its downstream gene expression, facilitating cell proliferation, EMT, migration, and invasion in GC cells. Therefore, RORα could play a crucial role in repressing GC cell proliferation, EMT, and invasion via downregulating Wnt/β-catenin pathway.
Prediction Models for Bioavailability of Mn, Cu, Zn, Ni and Pb in Soils of Republic of Serbia
Authors: Dinić Zoran , Maksimović Jelena , Stanojković-Sebić Aleksandra , Pivić Radmila
Published: December 2019

The bioavailability of trace elements (TEs) is one of the major factors for successful plant production and environmental protection. The aim of this study was to determine the extent to which TEs are bioavailable and which of the basic soil parameters affect bioavailability. The survey included agricultural soil samples taken from 240 locations on the territory of the Republic of Serbia, where the soil analytics were carried out. On the basis of the analyzed data the prediction models were derived based on the Freundlich model, showing the dependence between trace elements (TEs) extracted using the DTPA buffer solution in relation to the trace elements extracted using an aqua regia, the organic matter content (SOM), the clay fractions content, and soil pH. On one part of the samples, the prediction models were separated on the basis of a suspension for determining the pH in H2O and 1M KCl. The model was applied for the following TEs: Mn, Ni, Pb, Zn, and Cu. The content of the pseudo total forms of TEs statistically significantly influenced the bioavailability of TEs in all prediction models for all studied elements. The pH value statistically significantly affected the bioavailability of Ni, Mn, Pb, and Cu also in all prediction models. The impact of SOM and clay varied depending on the model and TEs. Multiple linear regression showed that the prediction models for TE Cu (R2 = 0.763–0.848) were the most reliable and that the bioavailability of Cu was significantly influenced by all the studied soil parameters except clay. Reliable results were also shown by the prediction models for TE Pb, but the values of the determination coefficient and investigated parameters that influenced the bioavailability varied depending on the model. The derived models for TE Mn, Zn, and Ni were less reliable (R2 is approximately 50% or less), and the effect of the tested parameters on bioavailability varied depending on the model and TEs.
Application of Plackett–Burman Design in Screening of Natural Antioxidants Suitable for Anchovy Oil
Authors: Wen Yun-Qi , Xue Chang-Hu , Xu Li-Li , Wang Xiao-Han , Bi Shi-Jie , Xue Qian-Qian , Zhang Tao , Xue Yong , Li Zhao-Jie , Chen Gui-Dong , Jiang Xiao-Ming
Published: December 2019

Considering the safety of synthetic antioxidants, more and more natural antioxidants have been developed and utilized in foods. This study aimed to screen out a natural antioxidant combination from many antioxidants, which could significantly affect the oxidation stability of anchovy oil, while Plackett–Burman design (PBD) methodology was employed in this screening. According to the statistical results of this design, sesamol, dihydromyricetin, teapolyphenol, and rosemary acid were four significant parameters on the oxidation stability of anchovy oil. Moreover, dihydromyricetin presented the best antioxidant effect among nine kinds of selected antioxidants when they were used alone in anchovy oil. Meanwhile, a combination including sesamol (0.02%), teapolyphenol (0.02%). and rosemary acid (0.02%) was adopted, and its antioxidant ability was similar to that of tert-butylhydroquinone (TBHQ). Additionally, phytic acid as a synergist was used and combined with sesamol, and the antioxidant ability of this combination was better than that of TBHQ. This study presented a reference for the industrial applications of natural antioxidants and synergists in anchovy oil.
Magnetic Fields Trump Oxygen in Controlling the Death of Erythro-Leukemia Cells
Authors: Li Ying , Héroux Paul
Published: December 2019

Expansions in power and telecommunications systems have created a new electromagnetic environment. Here, we compare the death rate of human cancer cells in vitro in the pre-industrial electromagnetic environment of the past (“Zero Field”) with that of an electromagnetic environment typical of contemporary human exposures (“Incubator Field”). A cell incubator provides magnetic fields comparable to those in the current human environment. Steel shields divert those same fields away from cell preparations in the “pre-industrial” assays. Large changes in oxygen levels are provided by nitrogen or atmospheric gas over the cell cultures. Human cancer cells are then separated according to three categories: necrotic, early apoptotic, or late apoptotic. The results are compiled for two variables, magnetic field and oxygen, in 16 different situations (“Transitions”) likely to occur in the human body under present living conditions. We find that magnetic fields are a more powerful determinant of cell death than oxygen, and induce death by different mechanisms. This has important implications for the reproducibility of in vitro biological experiments focusing on cell survival or metabolism, and for public health. The rate and mechanisms of cell death are critical to many chronic human ailments such as cancer, neurological diseases, and diabetes.
Microchannel Fabrication in Fused Quartz by Backside Laser-Induced Plasma Ablation Using 248 nm KrF Excimer Laser
Authors: Zhao Yu , Li Qian , Wang Zhengfei , Dai Ziruo , Chen Tao
Published: December 2019

Laser-induced plasma ablation (LIPA) using a 248 nm KrF excimer laser was investigated for microchannel fabrication. Examination of the morphology in relation to ablation performance was emphasized, and a synthetic LIPA mechanism model was proposed based on the results. Backside LIPA with a metal target on the bottom can be attributed to a combination of two phenomena: laser-induced plasma vaporization thermal ablation from the metal target below and enhanced laser–glass direct interaction from the plasma residuum. The laser absorption enhancement of quartz substrate resulting from the metal residuum was validated clearly using absorption spectrum measurements. The influence of laser parameters on the etching quality during LIPA was also analyzed for processing optimization. Finally, fused quartz glass microchannels of outstanding surface quality and dimension uniformity were implemented. The channel depth was 28 μm, and the bottom surface roughness was better than several hundred nanometers.
Lightweight Research in Engineering: A Review
Authors: Wang Jiao , Li Yan , Hu Gang , Yang Mingshun
Published: December 2019

In the field of mechanical equipment manufacturing, the focus of research and development is not on weight reduction, but on how to choose between the rigidity and performance of components (such as strength or flexibility). For this contradiction, lightweight is one of the best solutions. The problems associated with lightweight were initially considered and systematically studied in aircraft manufacturing in engineering. Therefore, lightweight has been greatly developed in aviation research and has played an increasingly important role in construction machinery. This paper presents a brief description of the current status of lightweight in machinery by reviewing some significant progress made in the last decades. Potential research topics are also discussed from the four aspects of material, structure, bionics, and manufacturing, and they forecast the development trend of lightweight in the future construction machinery. The entire body of literature about the field is not covered due to the limitation of the length of paper. The scope of this review is limited and closely related to the development of lightweight technology in engineering applications.
Tire Model with Temperature Effects for Formula SAE Vehicle
Authors: Harsh Diwakar , Shyrokau Barys
Published: December 2019

Formula Society of Automotive Engineers (SAE) (FSAE) is a student design competition organized by SAE International (previously known as the Society of Automotive Engineers, SAE). Commonly, the student team performs a lap simulation as a point mass, bicycle or planar model of vehicle dynamics allow for the design of a top-level concept of the FSAE vehicle. However, to design different FSAE components, a full vehicle simulation is required including a comprehensive tire model. In the proposed study, the different tires of a FSAE vehicle were tested at a track to parametrize the tire based on the empirical approach commonly known as the magic formula. A thermal tire model was proposed to describe the tread, carcass, and inflation gas temperatures. The magic formula was modified to incorporate the temperature effect on the force capability of a FSAE tire to achieve higher accuracy in the simulation environment. Considering the model validation, the several maneuvers, typical for FSAE competitions, were performed. A skidpad and full lap maneuvers were chosen to simulate steady-state and transient behavior of the FSAE vehicle. The full vehicle simulation results demonstrated a high correlation to the measurement data for steady-state maneuvers and limited accuracy in highly dynamic driving. In addition, the results show that neglecting temperature in the tire model results in higher root mean square error (RMSE) of lateral acceleration and yaw rate.
Analysis of Elastic Nonlinearity Using Continuous Waves: Validation and Applications
Authors: Di Bella Angelo , Gliozzi Antonio S. , Scalerandi Marco , Tortello Mauro
Published: December 2019

The nonlinear elastic response of consolidated granular or damaged materials is the result of the combination of nonlinear attenuation and velocity, coupled with hysteresis, which is linked to non equilibrium effects (often termed conditioning). Thus, a preliminary step towards the comprehension of the physical mechanisms responsible of the nonlinear elastic behaviours consists in quantifying and separating the various contributions. To this purpose, an approach based on a semi-analytical treatment of signals resulting from a monochromatic continuous wave excitation can be successfully implemented. Its validation is discussed here, applying the proposed approach to the analysis of numerical data obtained by using a finite difference spring model code. The accuracy, sensibility and robustness of the protocol are verified in different nonlinear conditions.
Advanced Constraints Management Strategy for Real-Time Optimization of Gas Turbine Engine Transient Performance
Authors: Nikolaidis Theoklis , Li Zhuo , Jafari Soheil
Published: December 2019

Motivated by the growing technology of control and data processing as well as the increasingly complex designs of the new generation of gas turbine engines, a fully automatic control strategy that is capable of dealing with different aspects of operational and safety considerations is required to be implemented on gas turbine engines. An advanced practical control mode satisfaction method for the entire operating envelope of gas turbine engines is proposed in this paper to achieve the optimal transient performance for the engine. A constraint management strategy is developed to generate different controller settings for short-range fighters as well as long-range intercontinental aircraft engines at different operating conditions by utilizing a model predictive control approach. Then, the designed controller is tuned and modified with respect to different realistic considerations including the practicality, physical limitations, system dynamics, and computational efforts. The simulation results from a verified two-spool turbofan engine model and controller show that the proposed method is capable of maneuverability and/or fuel economy optimization indices while satisfying all the predefined constraints successfully. Based on the parameters, natural frequencies, and dynamic behavior of the system, a set of optimized weighting factors for different engine parameters is also proposed to achieve the optimal and safe operation for the engine at different flight conditions. The paper demonstrates the effects of the prediction length and control horizon; adding new constraints on the computational effort and the controller performance are also discussed in detail to confirm the effectiveness and practicality of the proposed approach in developing a fully automatic optimized real-time controller for gas turbine engines.
An Improved Probabilistic Neural Network Model for Directional Prediction of a Stock Market Index
Authors: Chandrasekara Vasana , Tilakaratne Chandima , Mammadov Musa
Published: December 2019

Financial market prediction attracts immense interest among researchers nowadays due to rapid increase in the investments of financial markets in the last few decades. The stock market is one of the leading financial markets due to importance and interest of many stakeholders. With the development of machine learning techniques, the financial industry thrived with the enhancement of the forecasting ability. Probabilistic neural network (PNN) is a promising machine learning technique which can be used to forecast financial markets with a higher accuracy. A major limitation of PNN is the assumption of Gaussian distribution as the distribution of input variables which is violated with respect to financial data. The main objective of this study is to improve the standard PNN by incorporating a proper multivariate distribution as the joint distribution of input variables and addressing the multi-class imbalanced problem persisting in the directional prediction of the stock market. This model building process is illustrated and tested with daily close prices of three stock market indices: AORD, GSPC and ASPI and related financial market indices. Results proved that scaled t distribution with location, scale and shape parameters can be used as more suitable distribution for financial return series. Global optimization methods are more appropriate to estimate better parameters of multivariate distributions. The global optimization technique used in this study is capable of estimating parameters with considerably high dimensional multivariate distributions. The proposed PNN model, which considers multivariate scaled t distribution as the joint distribution of input variables, exhibits better performance than the standard PNN model. The ensemble technique: multi-class undersampling based bagging (MCUB) was introduced to handle class imbalanced problem in PNNs is capable enough to resolve multi-class imbalanced problem persisting in both standard and proposed PNNs. Final model proposed in the study with proposed PNN and proposed MCUB technique is competent in forecasting the direction of a given stock market index with higher accuracy, which helps stakeholders of stock markets make accurate decisions.
A Novel Magnetic Equivalent Circuit Model for the Corner of Inductor Core
Authors: Wang Xiaodong , Chen Hui , Shi Mingquan , Douadji Lyes
Published: December 2019

The accurate calculation of inductance is the most basic problem of inductor design. Based on finite element method (FEM) analysis of the flux density distribution in the corner of the core, a local corner magnetic equivalent circuit (MEC) model is proposed for a core-type inductor. In this model, the corner is divided into three parallel branches, and the joint part of the corner and the core limb are divided into two branches, one of which is continuously divided into three branches. In addition, a flux leakage branch of the core window inner corner is modeled. These branches form a local corner MEC by series and parallel to describe the flux distribution of the corner. The calculation results show that, in the local corner MEC model, the core flux density distribution is consistent with the FEM simulation. The maximum relative error of the inductance is less than 6% and the average relative error is less than 4% compared to the physical prototype measured data with the range of current from 20 A to 1000 A, which shows that the local corner MEC model has a high accuracy inductance calculation.
Exploration of Feature Extraction Methods and Dimension for sEMG Signal Classification
Authors: Wu Yutong , Hu Xinhui , Wang Ziwei , Wen Jian , Kan Jiangming , Li Wenbin
Published: December 2019

It is necessary to complete the two parts of gesture recognition and wireless remote control to realize the gesture control of the automatic pruning machine. To realize gesture recognition, in this paper, we have carried out the research of gesture recognition technology based on surface electromyography signal, and discussed the influence of different numbers and different gesture combinations on the optimal size. We have calculated the 630-dimensional eigenvector from the benchmark scientific database of sEMG signals and extracted the features using principal component analysis (PCA). Discriminant analysis (DA) has been used to compare the processing effects of each feature extraction method. The experimental results have shown that the recognition rate of four gestures can reach 100.0%, the recognition rate of six gestures can reach 98.29%, and the optimal size is 516~523 dimensions. This study lays a foundation for the follow-up work of the pruning machine gesture control, and p rovides a compelling new way to promote the creative and human computer interaction process of forestry machinery.
TIPE2 Induced the Proliferation, Survival, and Migration of Lung Cancer Cells Through Modulation of Akt/mTOR/NF-κB Signaling Cascade
Authors: Bordoloi Devivasha , Banik Kishore , Padmavathi Ganesan , Vikkurthi Rajesh , Harsha Choudhary , Roy Nand Kishor , Singh Anuj Kumar , Monisha Javadi , Wang Hong , Kumar Alan Prem , Kunnumakkara Ajaikumar B
Published: December 2019

Lung cancer represents the most common cause of cancer deaths in the world, constituting around 11.6% of all new cancer cases and 18.4% of cancer-related deaths. The propensity for early spread, lack of suitable biomarkers for early diagnosis, as well as prognosis and ineffective existing therapies, contribute to the poor survival rate of lung cancer. Therefore, there is an urgent need to develop novel biomarkers for early diagnosis and prognosis which in turn can facilitate newer therapeutic avenues for the management of this aggressive neoplasm. TIPE2 (tumor necrosis factor-α-induced protein 8-like 2), a recently identified cytoplasmic protein, possesses enormous potential in this regard. Immunohistochemical analysis showed that TIPE2 was significantly upregulated in different stages and grades of lung cancer tissues compared to normal lung tissues, implying its involvement in the positive regulation of lung cancer. Further, knockout of TIPE2 resulted in significantly reduced proliferation, survival, and migration of human lung cancer cells through modulation of the Akt/mTOR/NF-κB signaling axis. In addition, knockout of TIPE2 also caused arrest in the S phase of the cell cycle of lung cancer cells. As tobacco is the most predominant risk factor for lung cancer, we therefore evaluated the effect of TIPE2 in tobacco-mediated lung carcinogenesis as well. Our results showed that TIPE2 was involved in nicotine-, nicotine-derived nitrosamine ketone (NNK)-, N-nitrosonornicotine (NNN)-, and benzo[a]pyrene (BaP)-mediated lung cancer through inhibited proliferation, survival, and migration via modulation of nuclear factor kappa B (NF-κB)- and NF-κB-regulated gene products, which are involved in the regulation of diverse processes in lung cancer cells. Taken together, TIPE2 possesses an important role in the development and progression of lung cancer, particularly in tobacco-promoted lung cancer, and hence, specific targeting of it holds an enormous prospect in newer therapeutic interventions in lung cancer. However, these findings need to be validated in the in vivo and clinical settings to fully establish the diagnostic and prognostic importance of TIPE2 against lung cancer.
Participation of the miR-22-HDAC4-DLCO Axis in Patients with COPD by Tobacco and Biomass
Authors: Velasco-Torres Yadira , Ruiz Víctor , Montaño Martha , Pérez-Padilla Rogelio , Falfán-Valencia Ramcés , Pérez-Ramos Julia , Pérez-Bautista Oliver , Ramos Carlos
Published: December 2019

Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation and systemic inflammation. The main causes of COPD include interaction between genetic and environmental factors associated with tobacco smoking (COPD-TS) and/or exposure to biomass smoke (COPD-BS). Several microRNAs (miRNAs) control posttranscriptional regulation of COPD-TS associated gene expression. The miR-22-HDAC4-IL-17 axis was recently characterized. It is still unknown, however, whether this axis, participates in COPD-BS. To investigate, 50 patients diagnosed with severe-to-very severe COPD GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages III/IV, were recruited, 25 women had COPD-BS (never smokers, exposed heavily to BS) and 25 had COPD-TS. Serum levels of miRNA-22-3p were measured by RT (Reverse Transcription)-qPCR, while the concentration of HDAC4 (Histone deacetylase 4) was detected by ELISA. Additionally, we looked for association between serum HDAC4 and DLCOsb (Single-breath diffusing capacity of the lung for carbon monoxide), as % of predicted by age, height, and gender, one of the main differences described between COPD-BS and COPD-TS. Women with COPD-BS were older and shorter and had a higher DLCOsb %P (percent predicted) compared to COPD-TS. Serum miR-22-3p was downregulated in COPD-BS relative to COPD-TS. In contrast, the concentration of HDAC4 was higher in COPD-BS compared to COPD-TS. Furthermore, a positive correlation between serum HDAC4 levels and DLCOsb %P was observed. We concluded that the miR-22-HDAC4-DLCO axis behaves differently in patients with COPD-BS and COPD-TS.
Honokiol Enhances TRAIL-Mediated Apoptosis through STAMBPL1-Induced Survivin and c-FLIP Degradation
Authors: Woo Seon Min , Seo Seung Un , Kubatka Peter , Min Kyoung-jin , Kwon Taeg Kyu
Published: December 2019

Honokiol is a natural biphenolic compound extracted from traditional Chinese medicine Magnolia species, which have been known to display various biological effects including anti-cancer, anti-proliferative, anti-angiogenic, and anti-metastatic activities in cancer cells. Here, we found that honokiol sensitizes cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through downregulation of anti-apoptotic proteins survivin and c-FLIP. Ectopic expression of survivin and c-FLIP markedly abolished honokiol and TRAIL-induced apoptosis. Mechanistically, honokiol induced protein degradation of c-FLIP and survivin through STAMBPL1, a deubiquitinase. STAMBPL1 interacted with survivin and c-FLIP, resulted in reduction of ubiquitination. Knockdown of STAMBPL1 reduced survivin and c-FLIP protein levels, while overexpression of STAMBPL1 inhibited honokinol-induced survivin and c-FLIP degradation. Our findings provided that honokiol could overcome TRAIL resistance through survivin and c-FLIP degradation induced by inhibition of STAMBPL1 expression.
Ovarian Cancer Dissemination—A Cell Biologist’s Perspective
Authors: Farsinejad Sadaf , Cattabiani Thomas , Muranen Taru , Iwanicki Marcin
Published: December 2019

Epithelial ovarian cancer (EOC) comprises multiple disease states representing a variety of distinct tumors that, irrespective of tissue of origin, genetic aberrations and pathological features, share common patterns of dissemination to the peritoneal cavity. EOC peritoneal dissemination is a stepwise process that includes the formation of malignant outgrowths that detach and establish widespread peritoneal metastases through adhesion to serosal membranes. The cell biology associated with outgrowth formation, detachment, and de novo adhesion is at the nexus of diverse genetic backgrounds that characterize the disease. Development of treatment for metastatic disease will require detailed characterization of cellular processes involved in each step of EOC peritoneal dissemination. This article offers a review of the literature that relates to the current stage of knowledge about distinct steps of EOC peritoneal dissemination, with emphasis on the cell biology aspects of the process.
Hispidulin Enhances TRAIL-Mediated Apoptosis via CaMKKβ/AMPK/USP51 Axis-Mediated Bim Stabilization
Authors: Woo Seon Min , Seo Seung Un , Kim Sang Hyun , Nam Ju-Ock , Kim Shin , Park Jong-Wook , Min Kyoung-jin , Kwon Taeg Kyu
Published: December 2019

Hispidulin, a natural compound present in herbs, has anti-cancer effects. Here, we investigated whether hispidulin sensitizes human carcinoma cells to apoptosis induced by TRAIL. Sub-lethal dosages of TRAIL alone and hispidulin alone does not increase apoptosis, but hispidulin increases sensitivity to TRAIL, resulting in induction of apoptosis in hispidulin plus TRAIL-treated cancer cells. In addition, combined treatment with hispidulin and TRAIL also reduced tumor growth and increased apoptosis in xenograft models. However, hispidulin did not alter cell viability in human renal normal mesangial cells and human skin fibroblast. Hispidulin markedly increased the BH3-only proteins Bim at the post-translational levels. Depletion of Bim with siRNA significantly blocked hispidulin plus TRAIL-induced apoptosis. Furthermore, we found that activation of AMPK by hispidulin has a crucial role in Bim proteins stability through up-regulation of USP51 expression. Our findings suggest that USP51-dependent stabilization of Bim by AMPK activation plays a critical role in hispidulin-mediated sensitization of cancer cells to apoptosis induced by TRAIL.
NF-kappa B Signaling-Related Signatures Are Connected with the Mesenchymal Phenotype of Circulating Tumor Cells in Non-Metastatic Breast Cancer
Authors: Popeda Marta , Stokowy Tomasz , Bednarz-Knoll Natalia , Jurek Anna , Niemira Magdalena , Bielska Agnieszka , Kretowski Adam , Kalinowski Leszek , Szade Jolanta , Markiewicz Aleksandra , Zaczek Anna J.
Published: December 2019

The role of circulating tumor cells (CTCs), tumor microenvironment (TME), and the immune system in the formation of metastasis is evident, yet the details of their interactions remain unknown. This study aimed at exploring the immunotranscriptome of primary tumors associated with the status of CTCs in breast cancer (BCa) patients. The expression of 730 immune-related genes in formalin-fixed paraffin-embedded samples was analyzed using the multigenomic NanoString technology and correlated with the presence and the phenotype of CTCs. Upregulation of 37 genes and downregulation of 1 gene were observed in patients characterized by a mesenchymal phenotype of CTCs when compared to patients with epithelial CTCs. The upregulated genes were involved in NF-kappa B signaling and in the production of type I interferons. The clinical significance of the differentially expressed genes was evaluated using The Cancer Genome Atlas (TCGA) data of a breast invasive carcinoma (BRCA) cohort. Five of the upregulated genes—PSMD7, C2, IFNAR1, CD84, and CYLD—were independent prognostic factors in terms of overall and disease-free survival. To conclude, our data identify a group of genes that are upregulated in BCa patients with mesenchymal CTCs and reveal their prognostic potential, thus indicating that they merit further investigation.
Titanate Nanotubes Engineered with Gold Nanoparticles and Docetaxel to Enhance Radiotherapy on Xenografted Prostate Tumors
Authors: Loiseau Alexis , Boudon Julien , Oudot Alexandra , Moreau Mathieu , Boidot Romain , Chassagnon Rémi , Mohamed Saïd Nasser , Roux Stéphane , Mirjolet Céline , Millot Nadine
Published: December 2019

Nanohybrids based on titanate nanotubes (TiONts) were developed to fight prostate cancer by intratumoral (IT) injection, and particular attention was paid to their step-by-step synthesis. TiONts were synthesized by a hydrothermal process. To develop the custom-engineered nanohybrids, the surface of TiONts was coated beforehand with a siloxane (APTES), and coupled with both dithiolated diethylenetriaminepentaacetic acid-modified gold nanoparticles (Au@DTDTPA NPs) and a heterobifunctional polymer (PEG3000) to significantly improve suspension stability and biocompatibility of TiONts for targeted biomedical applications. The pre-functionalized surface of this scaffold had reactive sites to graft therapeutic agents, such as docetaxel (DTX). This novel combination, aimed at retaining the AuNPs inside the tumor via TiONts, was able to enhance the radiation effect. Nanohybrids have been extensively characterized and were detectable by SPECT/CT imaging through grafted Au@DTDTPA NPs, radiolabeled with 111In. In vitro results showed that TiONts-AuNPs-PEG3000-DTX had a substantial cytotoxic activity on human PC-3 prostate adenocarcinoma cells, unlike initial nanohybrids without DTX (Au@DTDTPA NPs and TiONts-AuNPs-PEG3000). Biodistribution studies demonstrated that these novel nanocarriers, consisting of AuNP- and DTX-grafted TiONts, were retained within the tumor for at least 20 days on mice PC-3 xenografted tumors after IT injection, delaying tumor growth upon irradiation.
Mangiferin-Loaded Polymeric Nanoparticles: Optical Characterization, Effect of Anti-topoisomerase I, and Cytotoxicity
Authors: Razura-Carmona Francisco Fabian , Pérez-Larios Alejandro , González-Silva Napoleón , Herrera-Martínez Mayra , Medina-Torres Luis , Sáyago-Ayerdi Sonia Guadalupe , Sánchez-Burgos Jorge Alberto
Published: December 2019

Mangiferin is an important xanthone compound presenting various biological activities. The objective of this study was to develop, characterize physicochemical properties, and evaluate the anti-topoisomerase activity of poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing mangiferin. The nanoparticles were developed by the emulsion solvent evaporation method and the optimal formulation was obtained with a response surface methodology (RSM); this formulation showed a mean size of 176.7 ± 1.021 nm with a 0.153 polydispersibility index (PDI) value, and mangiferin encapsulation efficiency was about 55%. The optimal conditions (6000 rpm, 10 min, and 300 μg of mangiferin) obtained 77% and the highest entrapment efficiency (97%). The in vitro release profile demonstrated a gradual release of mangiferin from 15 to 180 min in acidic conditions (pH 1.5). The fingerprint showed a modification in the maximum absorption wavelength of both the polymer and the mangiferin. Results of anti-toposiomerase assay showed that the optimal formulation (MG4, 25 µg/mL) had antiproliferative activity. High concentrations (2500 µg/mL) of MG4 showed non-in vitro cytotoxic effect on BEAS 2B and HEPG2. Finally, this study showed an encapsulation process with in vitro gastric digestion resistance (1.5 h) and without interfering with the metabolism of healthy cells and their biological activity.
Induction of NK Cell Reactivity against B-Cell Acute Lymphoblastic Leukemia by an Fc-Optimized FLT3 Antibody
Authors: Schmied Bastian J. , Lutz Martina S. , Riegg Fabian , Zekri Latifa , Heitmann Jonas S. , Bühring Hans-Jörg , Jung Gundram , Salih Helmut R.
Published: December 2019

Antibody-dependent cellular cytotoxicity (ADCC) is a major mechanism by which antitumor antibodies mediate therapeutic efficacy. At present, we evaluate an Fc-optimized (amino acid substitutions S239D/I332E) FLT3 antibody termed 4G8-SDIEM (FLYSYN) in patients with acute myeloid leukemia (NCT02789254). Here we studied the possibility to induce NK cell ADCC against B-cell acute lymphoblastic leukemia (B-ALL) by Fc-optimized FLT3 antibody treatment. Flow cytometric analysis confirmed that FLT3 is widely expressed on B-ALL cell lines and leukemic cells of B-ALL patients. FLT3 expression did not correlate with that of CD20, which is targeted by Rituximab, a therapeutic monoclonal antibody (mAb) employed in B-ALL treatment regimens. Our FLT3 mAb with enhanced affinity to the Fc receptor CD16a termed 4G8-SDIE potently induced NK cell reactivity against FLT3-transfectants, the B-ALL cell line SEM and primary leukemic cells of adult B-ALL patients in a target-antigen dependent manner as revealed by analyses of NK cell activation and degranulation. This was mirrored by potent 4G8-SDIE mediated NK cell ADCC in experiments with FLT3-transfectants, the cell line SEM and primary cells as target cells. Taken together, the findings presented in this study provide evidence that 4G8-SDIE may be a promising agent for the treatment of B-ALL, particularly in CD20-negative cases.
Recent Organic Transformations with Silver Carbonate as a Key External Base and Oxidant
Authors: Yoo Kwangho , Jwa Dong Gyun , Lee Ha-Eun , Kim Hyun Jin , Kim Cheoljae , Kim Min
Published: December 2019

Silver carbonate (Ag2CO3), a common transition metal-based inorganic carbonate, is widely utilized in palladium-catalyzed C–H activations as an oxidant in the redox cycle. Silver carbonate can also act as an external base in the reaction medium, especially in organic solvents with acidic protons. Its superior alkynophilicity and basicity make silver carbonate an ideal catalyst for organic reactions with alkynes, carboxylic acids, and related compounds. This review describes recent reports of silver carbonate-catalyzed and silver carbonate-mediated organic transformations, including cyclizations, cross-couplings, and decarboxylations.
Synthesis, Modification, and Characterization of CuO/ZnO/ZrO2 Mixed Metal Oxide Catalysts for CO2/H2 Conversion
Authors: Borovinskaya Ekaterina S. , Trebbin Sebastian , Alscher Felix , Breitkopf Cornelia
Published: December 2019

CuO/ZnO/ZrO2 catalyst systems were synthesized in different ways and comprehensively characterized in order to study synthesis-to-property relations. A series of catalyst samples was prepared by coprecipitation, one-pot synthesis, and wet impregnation. The coprecipitation of multicomponent precipitates is usually a preliminary stage for preparation of mixed oxide catalysts. Cetyltrimethylammonium bromide (CTAB) was used in the surfactant-supported coprecipitation to improve the structural or textural characteristics of the catalytic samples. In the one-pot synthesis, all necessary components are simultaneously converted by evaporation from solutions into solids. During the wet impregnation, zirconium hydroxide is loaded with metal salts. After thermal treatment, all samples formed pure metal oxide forms, which was confirmed by XRD. The specific surface area of the investigated samples and their porous texture were determined by nitrogen adsorption. The reducibility of metal oxides and the kind of CuO phase was characterized by temperature-programmed reduction (TPR), and the surface acid properties by temperature-programmed ammonia desorption (TPAD). The CuO/ZnO/ZrO2 sample with the highest amount of strong acid sites is characterized by the formation of large CuO particles combined with the worst reducibility so that potentially catalytic active Cu/CuO pairs can be formed. One catalyst system was further characterized by in situ diffuse reflection Fourier transform infrared spectroscopy (DRIFTS) to identify surface intermediate species, which may occur during the conversion of CO2/H2 to methanol.
Targeting mTOR and Metabolism in Cancer: Lessons and Innovations
Authors: Magaway Cedric , Kim Eugene , Jacinto Estela
Published: December 2019

Cancer cells support their growth and proliferation by reprogramming their metabolism in order to gain access to nutrients. Despite the heterogeneity in genetic mutations that lead to tumorigenesis, a common alteration in tumors occurs in pathways that upregulate nutrient acquisition. A central signaling pathway that controls metabolic processes is the mTOR pathway. The elucidation of the regulation and functions of mTOR can be traced to the discovery of the natural compound, rapamycin. Studies using rapamycin have unraveled the role of mTOR in the control of cell growth and metabolism. By sensing the intracellular nutrient status, mTOR orchestrates metabolic reprogramming by controlling nutrient uptake and flux through various metabolic pathways. The central role of mTOR in metabolic rewiring makes it a promising target for cancer therapy. Numerous clinical trials are ongoing to evaluate the efficacy of mTOR inhibition for cancer treatment. Rapamycin analogs have been approved to treat specific types of cancer. Since rapamycin does not fully inhibit mTOR activity, new compounds have been engineered to inhibit the catalytic activity of mTOR to more potently block its functions. Despite highly promising pre-clinical studies, early clinical trial results of these second generation mTOR inhibitors revealed increased toxicity and modest antitumor activity. The plasticity of metabolic processes and seemingly enormous capacity of malignant cells to salvage nutrients through various mechanisms make cancer therapy extremely challenging. Therefore, identifying metabolic vulnerabilities in different types of tumors would present opportunities for rational therapeutic strategies. Understanding how the different sources of nutrients are metabolized not just by the growing tumor but also by other cells from the microenvironment, in particular, immune cells, will also facilitate the design of more sophisticated and effective therapeutic regimen. In this review, we discuss the functions of mTOR in cancer metabolism that have been illuminated from pre-clinical studies. We then review key findings from clinical trials that target mTOR and the lessons we have learned from both pre-clinical and clinical studies that could provide insights on innovative therapeutic strategies, including immunotherapy to target mTOR signaling and the metabolic network in cancer.
Adenine Nucleotide Translocase 1 Expression Is Coupled to the HSP27-Mediated TLR4 Signaling in Cardiomyocytes
Authors: Winter Julia , Hammer Elke , Heger Jacqueline , Schultheiss Heinz-Peter , Rauch Ursula , Landmesser Ulf , Dörner Andrea
Published: December 2019

The cardiac-specific overexpression of the adenine nucleotide translocase 1 (ANT1) has cardioprotective effects in various experimental heart disease models. Here, we analyzed the link between ANT1 expression and heat shock protein 27 (HSP27)-mediated toll-like receptor 4 (TLR4) signaling, which represents a novel communication pathway between mitochondria and the extracellular environment. The interaction between ANT1 and HSP27 was identified by co-immunoprecipitation from neonatal rat cardiomyocytes. ANT1 transgenic (ANT1-TG) cardiomyocytes demonstrated elevated HSP27 expression levels. Increased levels of HSP27 were released from the ANT1-TG cardiomyocytes under both normoxic and hypoxic conditions. Extracellular HSP27 stimulated TLR4 signaling via protein kinase B (AKT). The HSP27-mediated activation of the TLR4 pathway was more pronounced in ANT1-TG cardiomyocytes than in wild-type (WT) cardiomyocytes. HSP27-specific antibodies inhibited TLR4 activation and the expression of HSP27. Inhibition of the HSP27-mediated TLR4 signaling pathway with the TLR4 inhibitor oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) reduced the mitochondrial membrane potential (∆ψm) and increased caspase 3/7 activity, which are both markers for cell stress. Conversely, treating cardiomyocytes with recombinant HSP27 protein stimulated TLR4 signaling, induced HSP27 and ANT1 expression, and stabilized the mitochondrial membrane potential. The activation of HSP27 signaling was verified in ischemic ANT1-TG heart tissue, where it correlated with ANT1 expression and the tightness of the inner mitochondrial membrane. Our study shows a new mechanism by which ANT1 is part of the cardioprotective HSP27-mediated TLR4 signaling.
Thermomechanical Characterisation of Mullite Zirconia Composites Sintered from Andalusite for High Temperature Applications
Authors: Chotard Thierry , Arbelaez Morales Lizeth , Bouchetou Marie-Laure , Poirier Jacques
Published: December 2019

Mullite-Zirconia refractories are well known for their good resistance to corrosion and thermal shock. In this study, several mullite-zirconia composites were developed from andalusite, alumina and zircon sintered at 1600 °C for 10 hours. The samples were subjected to thermal shock carried out after heating at 1200 °C, in order to study the mechanical and thermomechanical behaviour as a function of the amount of zirconia dispersed in the mullite matrix. It appears that that the amorphous phase (SiO2), determined by X-ray diffraction, produced by the decomposition of andalusite, increases considerably with the amount of final zirconia in the composite and has a very important influence on the porosity. This amorphous phase seems also to have an important influence on the mechanical properties of the material. The characterisation of the thermomechanical behaviour (elastic properties and damage monitoring) was carried out thanks to ultrasonic techniques (US echography and Acoustic Emission). The “surprising” evolution (increase) of the Young’s modulus E of the material after being submitted to repeated thermal shocks is highlighted and explained. The acoustic emission technique carried out at high temperature and also coupled to 4-points bending tests (at room temperature) demonstrates its effectiveness for providing a better understanding of the chronology of the involved mechanisms involved at microstructural scale.
Acne Severity and Sleep Quality in Adults
Authors: Schrom Kory P. , Ahsanuddin Sayeeda , Baechtold Michelle , Tripathi Raghav , Ramser Amy , Baron Elma
Published: December 2019

Poor sleep quality is extremely prevalent, with about one third of adults in the USA obtaining less than the recommended amount of sleep. In addition, poor sleep quality has been linked to an increased risk of many conditions, including diabetes, hypertension, psychiatric conditions, and overall all-cause mortality. Research has shown that sleep disturbance does impact skin disease, although many details of this relationship are still unclear. The goal of this study is to determine if there is a relationship between acne severity and sleep quality in adults. Forty subjects with acne were recruited from dermatology clinics in Cleveland, OH, to participate in this study. Acne severity was assessed using the Global Acne Grading Scale (GAGS). To assess sleep quality, subjects completed the Pittsburgh Sleep Quality Index (PSQI) and completed a seven-day sleep journal. Subjects also completed the Dermatology Life Quality Index (DLQI), the Patient Health Questionnaire-2 (PHQ-2), and provided information about current and past acne treatments as well as their opinion regarding their own acne severity and exacerbating factors. Our findings support the hypothesis that there is a potential relationship between sleep quality and acne.
Effect of Ag/rGO on the Optical Properties of Plasmon-Modified SnO2 Composite and Its Application in Self-Powered UV Photodetector
Authors: Abdalla James Taban , Wang Jinzhong , Wang Dongbo
Published: December 2019

A facile hydrothermal method was employed to synthesize silver–reduced graphene oxide (Ag/rGO) plasmon-modified SnO2 composite, by incorporating Ag–reduced graphene oxide (Ag/rGO) into SnO2 nanorods as a photoanode for assembling a self-powered ultraviolet photodetector (UVPD). The as-synthesized samples were investigated in detail by X-ray diffraction (XRD), scanning electron microscopy (SEM), Raman spectroscopy, and UV visible spectrophotometer. The as-prepared Ag/rGO films show enhanced light absorption attributed to the localized surface plasmon resonance (LSPR). The optimized 1.0 wt.% Ag/rGO incorporated into SnO2-based UVPD exhibits a significant photocurrent response due to the enhanced absorption light and effective suppression of charge recombination. This UVPD demonstrates a high performance, with photocurrent density reaching 0.29 mAcm−2 compared to the SnO2-based device with 0.16 mAcm−2. This device also exhibits a high on:off ratio of 195 and fast response time, which are superior to that of the free-modified one. In addition, the UVPD based on plasmon-modified SnO2 photoanode treated with TiCl4-aqueous solution has attained a higher photocurrent with a maximum value reaching 5.4 mAcm−2, making this device favorable in ultraviolet detection.