bluuebunny/crossref_metadata_2025 huggingface dataset:
Capillary electrophoresis study of systemin peptides spreading in tomato plant
Authors: Mucha Piotr , Ruczynski Jaroslaw , Dobkowski Michal , Backtrog Ewelina , Rekowski Piotr
Published: September 2018

Systemin (Sys) is an 18‐aa plant peptide hormone involved in the regulation of plant's defensive response. Sys is considered as a fast‐spreading systemic wound signal. We developed a simple and rapid CE method to monitor the spreading of Sys peptides through tomato plant. A 1,2,3‐triazole‐linked AZT‐systemin conjugate was designed as a model to study the possibility of translocating small cargo molecules 3'‐Azido‐2',3'‐dideoxythymidine by systemin. The Sys peptides (Sys, N‐propiolyl Sys, and AZT‐systemin conjugate) were injected into the stem and leaves of mature tomato plant. Its transportation throughout the plant tissue was traced by CE. The peptides were clearly visible in the crude tomato exudates and an optimum separation was achieved in 25 mM phosphate “buffer” at pH 2.5 and a voltage of 20 kV using uncoated fused silica capillary. CE analysis showed that Sys peptides are well separated from tomato plant exudates ingredients and are stable in tomato stem and leaf exudates for up to 24 h. CE study revealed that the Sys peptides are effectively spreading throughout tomato stem and leaves and the peptides could be directly detected in the crude plant matrixes. The translocation was strongly inhibited by sodium azide. The results showed that the established CE method can be used to characterize plant peptides spreading under plant physiological conditions.
Recent advances in capillary electrophoresis‐mass spectrometry: Instrumentation, methodology and applications
Authors: Stolz Alexander , Jooß Kevin , Höcker Oliver , Römer Jennifer , Schlecht Johannes , Neusüß Christian
Published: September 2018

Capillary electrophoresis (CE) offers fast and high‐resolution separation of charged analytes from small injection volumes. Coupled to mass spectrometry (MS), it represents a powerful analytical technique providing (exact) mass information and enables molecular characterization based on fragmentation. Although hyphenation of CE and MS is not straightforward, much emphasis has been placed on enabling efficient ionization and user‐friendly coupling. Though several interfaces are now commercially available, research on more efficient and robust interfacing with nano‐electrospray ionization (ESI), matrix‐assisted laser desorption/ionization (MALDI) and inductively coupled plasma mass spectrometry (ICP) continues with considerable results. At the same time, CE‐MS has been used in many fields, predominantly for the analysis of proteins, peptides and metabolites. This review belongs to a series of regularly published articles, summarizing 248 articles covering the time between June 2016 and May 2018. Latest developments on hyphenation of CE with MS as well as instrumental developments such as two‐dimensional separation systems with MS detection are mentioned. Furthermore, applications of various CE‐modes including capillary zone electrophoresis (CZE), nonaqueous capillary electrophoresis (NACE), capillary gel electrophoresis (CGE) and capillary isoelectric focusing (CIEF) coupled to MS in biological, pharmaceutical and environmental research are summarized.
Compulsive “grazing” and addictive tendencies towards food
Authors: Bonder Revi , Davis Caroline , Kuk Jennifer L. , Loxton Natalie J.
Published: September 2018

Evidence suggests that palatable foods can promote an addictive process akin to drugs of abuse. To date, research in the field of food addiction has focused largely on binge eating as a symptom of this condition. The present study investigated relationships between food addiction and other patterns of overeating, such as compulsive grazing—a behaviour with high relevance to bariatric surgery outcomes. Adults between the ages of 20 and 50 years (n = 232) were recruited for the study. Participants completed questionnaires to assess various eating behaviours and related personality measures. Regression analysis employed the Yale Food Addiction Scale (YFAS) as the dependent variable. Results indicated that addictive personality traits, reward‐driven eating, and compulsive grazing each contributed unique variance to the YFAS symptom score. These findings provide novel insight into the association between a grazing pattern of overeating and food addiction, and emphasize that similar to traditional addiction disorders such as alcoholism, binge consumption is not the only pattern of compulsive intake.
Bioenergetics-adverse outcome pathway: Linking organismal and suborganismal energetic endpoints to adverse outcomes
Authors: Goodchild Christopher G. , Simpson Adam M. , Minghetti Matteo , DuRant Sarah E.
Published: September 2018

Adverse outcome pathways (AOPs) link toxicity across levels of biological organization, and thereby facilitate the development of suborganismal responses predictive of whole-organism toxicity and provide the mechanistic information necessary for science-based extrapolation to population-level effects. Thus far AOPs have characterized various acute and chronic toxicity pathways; however, the potential for AOPs to explicitly characterize indirect, energy-mediated effects from toxicants has yet to be fully explored. Indeed, although exposure to contaminants can alter an organism's energy budget, energetic endpoints are rarely incorporated into ecological risk assessment because there is not an integrative framework for linking energetic effects to organismal endpoints relevant to risk assessment (e.g., survival, reproduction, growth). In the present analysis, we developed a generalized bioenergetics-AOP in an effort to make better use of energetic endpoints in risk assessment, specifically exposure scenarios that generate an energetic burden to organisms. To evaluate empirical support for a bioenergetics-AOP, we analyzed published data for links between energetic endpoints across levels of biological organization. We found correlations between 1) cellular energy allocation and whole-animal growth, and 2) metabolic rate and scope for growth. Moreover, we reviewed literature linking energy availability to nontraditional toxicological endpoints (e.g., locomotor performance), and found evidence that toxicants impair aerobic performance and activity. We conclude by highlighting current knowledge gaps that should be addressed to develop specific bioenergetics-AOPs. Environ Toxicol Chem 2019;38:27–45. © 2018 SETAC
Investigating the relationship between age of onset of depressive disorder and cognitive function
Authors: Eraydin Irem Ece , Mueller Christoph , Corbett Anne , Ballard Clive , Brooker Helen , Wesnes Keith , Aarsland Dag , Huntley Jonathan
Published: September 2018

Objectives

Depressive disorder is commonly associated with impaired cognitive function; however, it is unclear whether the age of onset of the first episode of depression, current depression severity, or historical severity of depressive episodes are associated with cognitive performance.

Methods

This study examined baseline cross‐sectional data from the ongoing online PROTECT study. A total of 7344 participants, 50 years or older, with a history of depression and no diagnosis of dementia were divided into three groups according to age of onset of their first depressive episode: early‐onset, midlife‐onset, and late‐onset. Performance on measures of visuospatial episodic memory, executive function, verbal working, and visual working memory were evaluated. Demographic and clinical characteristics such as age, education, and severity of symptoms during their worst previous depressive episode and current depression severity were included in multivariate regression models.

Results

The late‐onset depression group scored significantly lower on the verbal reasoning task than the early‐onset group while there were no significant differences found on the other tasks. Midlife‐onset depression participants performed better in the visual episodic memory task, but worse on the verbal reasoning task, than early‐onset depression participants. Current depression severity was negatively correlated with all four cognitive domains, while historical severity score was found to be significantly associated with cognitive performance on the verbal reasoning and spatial working memory tasks.

Conclusions

The most important indicator of cognitive performance in depression appears to be current, rather than historic depression severity; however, late‐onset depression may be associated with more executive impairment than an early‐onset depression.
Positive and neutral effects of forest cover on dry‐season stream flow in Costa Rica identified from Bayesian regression models with informative prior distributions
Authors: Krishnaswamy Jagdish , Kelkar Nachiket , Birkel Christian
Published: September 2018

The influence of forest cover on dry‐season stream flow in the humid tropics has been of enduring interest to eco‐hydrologists and policy makers. We used data from eight nested gauging stations in the Terraba river basin (4774 km2) of Costa Rica to demonstrate how a Bayesian regression approach could be applied to test hypotheses on “infiltration‐evapotranspiration trade‐offs”, between the “sponge effect” and evapotranspiration demands of forests on dry‐season flows. We summarized three competing hypotheses as informative prior distributions for regression slopes as 1) positive, 2) zero, and 3) negative effect of forest cover, and combined them with dry‐season flow data (response), and annual rainfall and per cent forest cover (as covariates) to obtain posterior estimates. The time series (1962–2002) included a deforestation phase until the 1980s and subsequent forest recovery from the 1990s. The sign, magnitude, and uncertainty of posterior slopes showed that forest cover effects on dry‐season flow were generally positive or neutral, influenced by both forest loss and recovery. Forest cover effect on dry‐season flow for the entire basin was strongly positive. Four sub‐catchments showed weakly positive and two showed neutral effects, and only one indicated a weakly negative effect. Mean effect size of forest cover diminished with increase in basin size. Our results predict a gain of 3.3 mm in dry‐season flow for every 1% increase of forest cover, corresponding to 48 km2 of basin area. Enhanced infiltration and wet‐season groundwater recharge dominating evapotranspiration can be attributed partly to deep soils and cloud forests. We demonstrate how informative prior distributions can represent different hypotheses in Bayesian regression models offers advantages in investigating complex hydrological processes. The rigorous evidence for positive and neutral effects of forest cover on dry‐season flow, reported by our study, potentially contributes to ecohydrology‐based management of tropical landscapes undergoing rapid change.
A strong spatial association between e‐waste burn sites and childhood lymphoma in the West Bank, Palestine
Authors: Davis John‐Michael , Garb Yaakov
Published: September 2018

A paper in the International Journal of Cancer analyzed Palestinian cancer registry data in the West Bank from 1998 to 2007, showing a cluster of elevated cancer incidence in rural villages in south‐west Hebron, with a 4.10 risk ratio for childhood lymphoma (p = 0.0023). The paper called for investigation of the environmental or genetic etiologies of this cluster in an otherwise unremarkable rural area.1 Our research in these same villages shows them to be the center of an extensive informal electronic and electrical waste (e‐waste) dismantling industry in Palestine, operating for almost two decades. This entails extensive open‐burning of e‐waste components to extract valuable metals or dispose of nonvaluable waste, releasing high concentrations of hazardous contaminants, which may be an important factor in the elevated cancer incidence. We offer a first step in assessing this link. We applied a novel multitemporal object‐based method to map the prevalence and intensity of e‐waste burn sites in the entire Hebron Governorate (1,060 km2) between 1999 and 2007. A weighted standard deviation ellipse of cumulative burn activity covers a smaller area (247 km2) very closely matching the childhood lymphoma cluster: it contains 85% of the core cluster area (RR of 4.1), and falls almost entirely (95%) within the broader area of elevated risk (RR of 2.8). Extensive international evidence linking informal e‐waste processing to elevated cancer incidence and this strong spatial association of e‐waste burning activity with a distinct unexplained cancer cluster in the Palestinian context signals the urgent need for investigation and intervention.
Toward endothelialization via vascular endothelial growth factor immobilization on cell‐repelling functional polyurethanes
Authors: Liao Shurui , He Qiang , Yang Lie , Liu Shuai , Zhang Ze , Guidoin Robert , Fu Qiang , Xie Xingyi
Published: September 2018

We screened a family of nonspecific cell‐repelling polyurethanes (PUs) whose backbones are attached with epoxy group‐terminated polyethylene glycol (PEG) side chains. Water incubation of the PU films (with 9.2–31.1 wt % PEG) caused a surface enrichment of PEG chains where vascular endothelial growth factor (VEGF) was grafted by forming secondary amine linkages between VEGF molecules and the PEG spacer. These linkages are still ionizable similar to original primary amines in VEGF, thereby retaining the original charge distribution on VEGF macromolecules. This charge conservation together with PEG steric repulsion helped to preserve VEGF conformation and bioactivity. The PU substrates with suitable hard segments contents and VEGF surface densities can selectively induce endothelial cells (ECs) adhesion and proliferation toward endothelialization. Moreover, the PU substrates, even grafted with fibrinogen (Fg), cannot trigger platelet adhesion and deformation, suggesting an inactive conformation of the grafted Fg. Thus enough antithrombogenicity of the PU substrates could be expected before full endothelialization. These PU materials might be applied onto the lumens of vascular grafts, potentially stimulating luminal endothelialization in vivo. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 965–977, 2019.
Stable composite of bacterial nanocellulose and perforated polypropylene mesh for biomedical applications
Authors: Ludwicka Karolina , Kolodziejczyk Marek , Gendaszewska‐Darmach Edyta , Chrzanowski Michal , Jedrzejczak‐Krzepkowska Marzena , Rytczak Przemyslaw , Bielecki Stanislaw
Published: September 2018

The article presents the method of preparation of new, stable bacterial cellulose composites with perforated solid materials for biomedical applications, comprising reconstructive surgery of soft and hard tissues. The composites were obtained in specially designed bioreactors equipped with a set of perforated mesh stripes threaded vertically to the culture medium, ensuring perpendicular growth of bacterial nanocellulose synthesized by Komagataeibacter xylinus E25 in stationary culture. The developed biocomposites have been tested for stability and mechanical strength, as well as for their in vitro inflammatory responses shown as mast cell degranulation with N‐acetyl‐β‐d‐hexosaminidase release and mast cell adhesion. The obtained results indicate that the composites components are well integrated after the process of cultivation and purification. Bacterial nanocellulose does not negatively influence mechanical properties of the polypropylene porous mesh, preserving its tensile strength, elasticity, and load. Moreover, application of bacterial cellulose makes the composites less immunogenic as compared to polypropylene itself. Therefore, the composites have the great potential of application in medicine, and depending on the applied porous material, might be used either in hernioplasty (if porous hernia mesh is used), cranioplasty (if perforated metal or polymeric cranial implant is applied), or as a protective barrier in any application that requires biocompatibility or antiadhesive properties improvement. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 978–987, 2019.
Collagen/β‐TCP nerve guidance conduits promote facial nerve regeneration in mini‐swine and the underlying biological mechanism: A pilot in vivo study
Authors: Zhang Zhen , Zhang Chengyao , Li Zheyi , Zhang Shijian , Liu Jiannan , Bai Yuxing , Pan Juli , Zhang Chenping
Published: September 2018

This study aimed to evaluate the efficiency of new nerve guidance conduits (NGCs) in bridging facial nerve gaps, and investigate the underlying biological mechanisms implicated in the regeneration process. A collagen/β‐TCP conduit was prepared and applied to a facial nerve gap in a mini‐swine model. Functional recovery and axonal regeneration were further evaluated by electrophysiological and histological examinations at 3 months after surgery. Furthermore, the global transcriptomic profiles of regenerated and normal tissues were analyzed by gene microarray to identify the differentially expressed genes at day three and seven, postoperatively. Subsequently, associated biological processes were analyzed by gene ontology (GO) enrichment analysis. The electrophysiological examination and morphological analysis revealed that significant nerve regeneration effects were achieved in the Col/β‐TCP group (p < 0.05). Transcriptional analysis revealed that at day three post‐surgery, the majority of overexpressed genes were associated with inflammatory, immune and stimuli response, accompanied by angiogenesis, while at day seven, the majority of overexpressed genes were associated with cell, tissue and organ regeneration and development, synaptic transmission, neurogenesis, and neuronal differentiation, as well as the WNT, MAPK/ERK, and JAK/STAT signaling pathways. In conclusion, the present results suggest that collagen/β‐TCP NGCs provide a promising tubular micro‐environment for nerve regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1122–1131, 2019.
Ideal scaffold design for total ear reconstruction using a three‐dimensional printing technique
Authors: Jung Bok Ki , Kim Jae Yoon , Kim Young Seok , Roh Tai Suk , Seo Anna , Park Keun‐Ho , Shim Jin‐Hyung , Yun In Sik
Published: September 2018

Ear reconstruction using three‐dimensional (3D) printing technique has been considered as a good substitute for conventional surgery, because it can provide custom‐made 3D framework. However, there are difficulties with its application in clinical use. Researchers have reported 3D scaffolds for ear cartilage regeneration, but the designs of the 3D scaffolds were not appropriate to be used in surgery. Hence, we propose the design of an ideal 3D ear scaffold for use in ear reconstruction surgery. Facial computed tomography (CT) images of the unaffected ear were extracted using a “segmentation” procedure. The selected data were converted to a 3D model and mirrored to create a model of the affected side. The design of 3D model was modified to apply to Nagata's two‐stage surgery. Based on the 3D reconstructed model, a 3D scaffold was 3D printed using polycaprolactone. The 3D scaffold closely resembled the real cartilage framework used in current operations in terms of ear anatomy. To account for skin thickness, the 3D scaffold was made 4 mm smaller than the real ear. Furthermore, 2 mm pores were included to allow the implantation of diced cartilage to promote regeneration of the cartilage. 3D printing technology can overcome the limitations of previous auricular reconstruction methods. Further studies are required to achieve a functional and stable substitute for auricular cartilage and to extend the clinical use of the 3D‐printed construct. Additionally, the ethical and legal issues regarding the transplantation of 3D‐printed constructs and cell culture technologies using human stem cells remain to be solved. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1295–1303, 2019.
Inhibition of protein kinase R protects against palmitic acid–induced inflammation, oxidative stress, and apoptosis through the JNK/NF‐kB/NLRP3 pathway in cultured H9C2 cardiomyocytes
Authors: Mangali Sureshbabu , Bhat Audesh , Udumula Mary Priyanka , Dhar Indu , Sriram Dharmarajan , Dhar Arti
Published: September 2018

Background and Purpose

Double‐stranded RNA‐dependent protein kinase (PKR) is a critical regulator of apoptosis, oxidative stress, and inflammation under hyperlipidemic and insulin resistance conditions. Saturated free fatty acids, such as palmitic acid (PA), are known inducers of apoptosis in numerous cell types. However, the underlying molecular mechanism is not fully understood. The aim of the present study was to examine the effect of PA on cultured rat H9C2 cardiac myocytes cells and to investigate the PKR mediated harmful effects of PA in vitro in cultured cardiomyocytes.

Experimental Approach

PKR expression was determined by immunofluorescence and immunoblotting. Oxidative stress and apoptosis were determined by flow cytometry and assay kits. The expression of different gene markers of apoptosis, oxidative stress, and inflammation were measured by Western blot analysis and reverse transcription polymerase chain reaction.

Key Results

PKR expression, reactive oxygen species levels as well as apoptosis were increased in PA‐treated cultured H9C2 cardiomyocytes. The harmful effects of PA were attenuated by a selective PKR inhibitor, C16. Moreover, we observed that upregulation of c‐Jun N‐terminal kinase (JNK), nuclear factor‐kB (NF‐kB) and NACHT, LRR and PYD domains‐containing protein 3 (NLRP3) pathways is associated with increased expression of interleukin 6 and tumor necrosis factor‐α in PA‐treated cardiomyocytes and attenuation by a selective PKR inhibitor.

Conclusion and Implications

Our study reports, for the first time, that PKR‐mediated harmful effects of PA in cultured cardiomyocytes via activation of JNK, NF‐kB, and NLRP3 pathways. Inhibition of PKR is one of the possible mechanistic approaches to inhibit inflammation, oxidative stress, and apoptosis in lipotoxicity‐induced cardiomyocyte damage.
Pingchuanning decoction attenuates airway inflammation by suppressing autophagy via phosphatidylinositol 3‐kinase/protein kinase B/mammalian target of rapamycin signaling pathway in rat models of asthma
Authors: Wang Xinheng , Gao Yating , Yang Qinjun , Fang Xiangming , Li Zegeng
Published: September 2018

Background

Pingchuanning decoction is a well‐known traditional Chinese medicine for the treatment of airway inflammatory diseases, including asthma. However, the potential mechanism by which Pingchuanning decoction contributes to the amelioration of airway inflammation remains unknown.

Methods

A rat model of asthma was well established by inducing ovalbumin. Lipopolysaccharide‐stimulated rat tracheal epithelial (RTE) cells were used as cellular model. Lung histopathology and goblet cell hyperplasia were assessed by hematoxylin‐eosin (HE) and periodic acid Schiff staining, respectively. Total inflammatory cells count and RTE cell apoptosis were analyzed by flow cytometry. The autophagic activities were evaluated by immunohistochemical and immunofluorescence analysis and Western blot analysis of autophagy‐related proteins. We also detected the effects of Pingchuanning decoction on phosphatidylinositol 3‐kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) and high‐mobility group box 1 (HMGB1)‐mediated toll‐like receptor 4 (TLR4)/NF‐κB pathways‐related proteins and inflammatory cytokines using the Western blot analysis and enzyme‐linked immunosorbent assay.

Results

Pingchuanning decoction effectively attenuated pulmonary pathology and autophagy. Treatment with Pingchuanning decoction activated PI3K/Akt/mTOR pathway and inhibited HMGB1/TLR4/NF‐κB pathway, which could be overturned by LY294002, a PI3K antagonist, or rapamycin (Rapa), an autophagy inducer.

Conclusion

Pingchuanning decoction exerted a therapeutic effect on asthma by inhibiting autophagy via PI3K/Akt /mTOR signaling pathway.
Study on the mechanism of excessive apoptosis of nucleus pulposus cells induced by shRNA‐Piezo1 under abnormal mechanical stretch stress
Authors: Yang Qining , Zhou Yongwei , Wang Jinhua , Fu Weicong , Li Xiaofei
Published: September 2018

Objective

The aim of the study was to explore the mechanism of excessive apoptosis of nucleus pulposus cells induced by short hairpin RNA (shRNA) Piezo type mechanosensitive ion channel component 1 (Piezo1) under abnormal mechanical stretch stress.

Methods

In vitro mechanical stretch stress model of nucleus pulposus cells in vitro was established, in which the expression of Piezo1 was interfered by transfection of shRNA‐Piezo1 interfering vector. Both messenger RNA and protein level of Piezo1 were measured by reverse‐transcription polymerase chain reaction and Western blot analysis, respectively. Cytoplasmic Ca2+ was detected by Fluo3‐AM kit, and changes of mitochondrial membrane potential in cells were detected using Cell Meter Assay kit. Finally, the apoptosis was evaluated with annexin V‐fluorescein isothiocyanate kit.

Results

The highest transfection efficiency of lentivirus titer was 1 × 10 TU/mL and the nucleus pulposus cells were transfected with plural multiplicity of infection = 50. Homo‐3201 sequence exhibited the most effective silencing effect and was used in subsequent experiments as the default sequence of shRNA‐Piezo1. The calcium content in the cytoplasm of the tension stress group increased significantly compared with that in the blank control group (
q = 3.773;
P < 0.05). The level of cytosolic calcium in shRNA‐interference group was significantly lower than that in stretch stress group (
q = 5.159;
P < 0.05). Stretch stress treatment resulted in an elevated ratio of mitochondrial membrane potential turnover as opposed to blank control group (
q = 4.332;
P < 0.05), while shRNA‐interference group showed smaller ratio of mitochondrial membrane potential turnover than that in stretch stress group (
q = 4.974;
P < 0.05). Similar results were also observed in apoptosis rate analysis (
q = 3.175;
P < 0.05).

Conclusion

ShRNA‐Piezo1 can protect cells by reducing the level of intracellular Ca2+ and the change of mitochondrial membrane potential.
Ouabain attenuates oxidative stress and modulates lipid composition in hippocampus of rats in lipopolysaccharide‐induced hypocampal neuroinflammation in rats
Authors: Garcia Israel José Pereira , Kinoshita Paula Fernanda , Silva Lílian Nara David e , De Souza Busch Mileane , Atella Georgia Correa , Scavone Cristoforo , Cortes Vanessa Faria , Barbosa Leandro Augusto , De Lima Santos Hérica
Published: September 2018

Our study aimed to analyze the effect of ouabain (OUA) administration on lipopolysaccharide (LPS)‐induced changes in hippocampus of rats. Oxidative parameters were analyzed in Wistar rats after intraperitoneal injection of OUA (1.8 µg/kg), LPS (200 µg/kg), or OUA plus LPS or saline. To reach our goal, activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), in addition to levels of reduced glutathione (GSH), protein carbonyl (PCO) and lipid peroxidation (LPO) were evaluated. We also analyzed the membrane lipid profile and some important lipids for the nervous system, such as phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidic acid and sphingomyelin. The group that received only LPS showed increased oxidative stress, as evidenced by an increase in LPO (about twice), PCO (about three times) levels, and CAT activity (80%). Conversely, administration of LPS decreased GSH levels (55%), and GPx activity (30%), besides a reduction in the amount of PI (60%) and PC (45%). By other side, OUA alone increased the amount of PI (45%), PE (85%), and PC (70%). All harmful effects recorded were attenuated by OUA, suggesting a protective effect against LPS‐induced oxidative stress. The relevance of our results extends beyond changes in oxidative parameters induced by LPS, because nanomolar doses of OUA may be useful in neurodegenerative models. Other studies on other cardenolides and substances related issues, as well as the development of new molecules derived from OUA, could also be useful in general oxidative and/or cellular stress, a condition favoring the appearance of neuronal pathologies.
The AP2M1 gene expression is a promising biomarker for predicting survival of patients with hepatocellular carcinoma
Authors: Cho Sung Hwan , Pak Kyoungjune , Jeong Dae Cheon , Han Myoung‐Eun , Oh Sae‐Ock , Kim Yun Hak
Published: September 2018

There is a growing need for the discovery of new prognostic factors for cases where the scoring and staging system of hepatocellular carcinoma (HCC) does not result in a clear definition. We analyzed whether AP‐2 complex subunit mu (AP2M1) expression could be a new prognostic marker for HCC based on the roles of AP2M1 in influencing hepatocyte growth factor (HGF) promoter regulation and hepatitis C virus (HCV) assembly. Patient data were extracted from cohorts of the Gene Expression Omnibus (GSE10186), International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). Differential expression value between matched cancer and normal liver was identified using ICGC cohort. Subsequently, we compared AP2M1 expression as a prognostic gene with other well‐known prognostic genes for HCC, using the time‐dependent area under the curve (AUC) of the Uno's C‐index, the AUC value of the receiver operating characteristics at 5 years, Kaplan‐Meier survival curve, and multivariate analysis. Particularly, TCGA and GSE10186 patients were divided into subgroups based on alcohol intake, hepatitis B, and C viral infections, and analyzed in the same methods. The AP2M1 expression values in patients with cancer were much higher than matched normal liver. The AP2M1 level showed excellent prognosis predictions in comparison with existing markers in the three independent cohorts (n = 647). In particular, it was more predictive of prognosis than other markers in alcohol intake and HCV infections. In conclusion, we were confident that AP2M1 provides sufficient value as a new prognostic marker for HCC especially patients with HCV infection and/or alcohol intake.
Itraconazole inhibits proliferation of pancreatic cancer cells through activation of Bak‐1
Authors: Jiang Fan , Xing Hong‐S. , Chen Wei‐Y. , Du Jie , Ruan Yue‐l. , Lin An‐Y. , Zhou Chi‐Z.
Published: September 2018

Itraconazole is an FDA‐approved antifungal agent, which has been reported to possess promising anticancer activities in recent years. This study investigates the antiproliferative effects of itraconazole on pancreatic cancer cells and the molecular mechanism of its apoptosis‐inducing effects. In this study, our results showed that itraconazole inhibited the growth of pancreatic cancer cells in vitro, and it also significantly inhibited the tumor growth of CFPAC‐1 xenografts in vivo. Itraconazole induced apoptosis through ROS generation and mitochondrial membrane depolarization. A Bak‐1 activation dependent apoptosis was identified in CFPAC‐1 cells. These data suggested that itraconazole exhibited antiproliferative effects in pancreatic cancer cells by inducing apoptosis through Bak‐1 activation.
From an increase in the number of tandem repeats through the decrease of sialylation to the downregulation of MUC1 expression level
Authors: Syrkina Marina , Viushkov Vladimir , Potashnikova Daria , Veiko Vladimir , Vassetzky Yegor , Rubtsov Mikhail
Published: September 2018

Enhanced glucose uptake by cancer cells was demonstrated in many studies in vitro and in vivo. Glycolysis is one of the main ways of obtaining energy in hypoxia conditions. However, in addition to energy exchange, carbohydrates are also necessary for the posttranslational modification of the protein molecules. Cancer cells are often characterized by an enhanced expression of different glycoproteides. Correct glycosylation defines the structure and activity of such molecules. We demonstrated that under the same cultivation conditions, the intensity of glycosylation does not depend on the total number of potential O‐glycosylation sites in one molecule. As a model for the investigation, the tandem repeat region (region with variable number of tandem repeats) of the human mucin MUC1, in which each of the repeats carries four potential
O‐glycosylation sites, was used. An increase of the tandem repeat number in the recombinant protein did not lead to a proportional increase in the level of sLea glycosides. A consequence of this was a reduction in the number of recombinant proteins associated with the cytoplasmic membrane at an overall high expression level. Prolongation of the cultivation duration led to a reduction in the expression level of the recombinant proteins by up to 30% of the initial level, and the intensity of this reduction was in a direct ratio to the number of tandem repeats in the protein molecule.
microRNA‐211 promotes proliferation, migration, and invasion ability of oral squamous cell carcinoma cells via targeting the bridging integrator 1 protein
Authors: Zheng Jiabao , Wang Jiali , Jia Yunlong , Liu Tianxu , Duan Yuqing , Liang Xing , Liu Lihua
Published: September 2018

Oral squamous cell carcinoma (OSCC), the most common pathological type of oral cancer, is still a frequent malignancy with unsatisfactory prognosis. Accumulating studies have proven some microRNAs (miRNAs) can function as oncogenes in OSCC by targeting tumor suppressors. In this study, we first investigated the expression and role of tumor suppressor bridging integrator‐1 (BIN1) in OSCC tissues and cells. Our results indicated that BIN1 was low expressed in the OSCC tissues and cell lines (SCC6, SCC9, SCC25, HN4, and HN6) along with miR‐211 was highly expressed in OSCC tissues and cell lines, and BIN1 overexpression could evidently inhibit their proliferation, migration, and invasion abilities. Next, we used bioinformation algorithms to predict the potential miRNA targeting BIN1 and chose miR‐211 for further study. miR‐211, a highly expressed miRNA in OSCC cells, could specifically bind with the 3′‐untranslated region (3′‐UTR) of BIN1 to trigger its degradation. Addition of miR‐211 inhibitor could evidently suppress the malignant behaviors of OSCC cells by upregulating BIN1 expression and inhibit the activation of the EGFR/MAPK pathway. Taken together the findings of the study indicated that miR‐211 mediated BIN1 downregulation had crucial significances in OSCC, suggesting the miR‐211 might be a novel potential therapeutic target for the OSCC treatment.
MSLN (Mesothelin), ANTXR1 (TEM8), and MUC3A are the potent antigenic targets for CAR T cell therapy of gastric adenocarcinoma
Authors: Sotoudeh Masoud , Shirvani Seyed Iman , Merat Shahin , Ahmadbeigi Naser , Naderi Mahmood
Published: September 2018

Gastric adenocarcinoma is usually diagnosed in late stages, necessitating the use of different therapeutic modalities. Currently, antibody‐based therapies have also been approved through with limited clinical efficacy. Reinforcing antibody‐based immunotherapy by using chimeric antigen receptor (CAR) T cells may enhance the approach. However, the cells can cause severe on‐target and off‐tumor toxicities owing to their higher sensitivity to low‐level antigen expressions. To address the need for safe and reliable targets, we made a bioinformatics pipeline by which we screened overexpressed genes in the disease for off‐tumor sites in many normal tissues. Our inspection showed that MSLN (Mesothelin), ANTXR1 (TEM8), and MUC3A are the probable targets of CAR T cell therapy in gastric adenocarcinoma. The proposed antigenic targets might respond to the need to simultaneously target multiple antigens in a tumor matrix to prevent resistance.
20(S)‐protopanaxadiol induces apoptosis in human umbilical vein endothelial cells by activating the PERK‐eIF2alpha‐ATF4 signaling pathway
Authors: Wang Xue , Xia Hua‐Ying , Qin Hong‐You , Kang Xiang‐Ping , Hu Hai‐Yan , Zheng Jing , Jiang Jia‐Ye , Yao Ling‐Ai , Xu Yan‐Wu , Zhang Tong , Zhang Xue‐Li
Published: September 2018

20(S)‐protopanaxadiol (PPD)‐type ginsenosides are generally believed to be the most pharmacologically active components of Panax ginseng. These compounds induce apoptotic cell death in various cancer cells, which suggests that they have anti‐cancer activity. Anti‐angiogenesis is a promising therapeutic approach for controlling angiogenesis‐related diseases such as malignant tumors, age‐related macular degeneration, and atherosclerosis. Studies showed that 20(S)‐PPD at low concentrations induces endothelial cell growth, but in our present study, we found 20(S)‐PPD at high concentrations inhibited cell growth and mediated apoptosis in human umbilical vein endothelial cells (HUVECs). The mechanism by which high concentrations of 20(S)‐PPD mediate endothelial cell apoptosis remains elusive. The present current study investigated how 20(S)‐PPD induces apoptosis in HUVECs for the first time. We found that caspase‐9 and its downstream caspase, caspase‐3, were cleaved into their active forms after 20(S)‐PPD treatment. Treatment with 20(S)‐PPD decreased the level of Bcl‐2 expression but did not change the level of Bax expression. 20(S)‐PPD induced endoplasmic reticulum stress in HUVECs and stimulated UPR signaling, initiated by protein kinase R‐like endoplasmic reticulum kinase (PERK) activation. Total protein expression and ATF4 nuclear import were increased, and CEBP‐homologous protein (CHOP) expression increased after treatment with 20(S)‐PPD. Furthermore, siRNA‐mediated knockdown of PERK or ATF4 inhibited the induction of CHOP expression and 20(s)‐PPD‐induced apoptosis. Collectively, our findings show that 20(S)‐PPD inhibits HUVEC growth by inducing apoptosis and that ATF4 expression activated by the PERK‐eIF2α signaling pathway is essential for this process. These findings suggest that high concentrations of 20(S)‐PPD could be used to treat angiogenesis‐related diseases.
Uniform decompositions of complete multigraphs into cycles
Authors: Berry Duncan , Bryant Darryn , Dean Matthew , Maenhaut Barbara
Published: September 2018

The notion of uniformity, as in uniform ‐factorisations, extends naturally to graph decompositions generally. The existence of uniform decompositions of complete multigraphs into cycles is investigated and some connections with families of classical designs are established. We show that if there exists a uniform decomposition of into ‐cycles then (A) and , or (B) and , or (C) , and or (D) and . For case A, there are only a few small values of and to consider, and we exhibit all uniform decompositions up to isomorphism for each such and . In each of cases B and C, we construct examples of uniform decompositions for infinitely many values of , and we investigate the isomorphism classes of our examples for each such . We have no examples of uniform decompositions in case D, but we rule out the smallest example, namely and , and we prove that if such decompositions exist, then so do large quasiresidual designs that are not residual.
Mosaic trisomy 22 in a 4‐year‐old boy with congenital heart disease and general hypotrophy: A case report
Authors: Kalayinia Samira , Shahani Tina , Biglari Alireza , Maleki Majid , Rokni‐Zadeh Hassan , Razavi Zahra , Mahdieh Nejat
Published: September 2018

Background

Trisomy 22 mosaicism is a rare autosomal anomaly with survival compatibility. Recognition of the complete trisomy 22 which is incompatible with life from the mosaic form is critical for genetic counseling. Affected mosaic cases have prevalent clinical presentations such as webbed neck, developmental delay, abnormal ears, cardiac disorders, and microcephaly. Phenotype of these patients is milder than full chromosomal aneuploidy, and the severity of the phenotype depends on the count of trisomic cells. We describe a 4‐year‐old boy with mosaic trisomy 22 from healthy parents and no family history of any genetic disorders in the pedigree.

Method and Results

The patient had determined dysmorphic clinical features including facial asymmetry, cleft palate, gastroenteritis, hydronephrosis, developmental delay, genital anomalies, dysplastic toenails, flattened nasal bridge, congenital heart defect, hearing loss, cryptorchidism, and hypotonic muscle. He is the first reported with hypothyroidism and larynx wall thickness in worldwide and the first with atrial septal defect (ASD) from Iran. Chromosomal analyses using G‐banding indicated a de novo Mos 47,XY,+22(6)/46,XY(44) karyotype with no other chromosomal structural changes.

Conclusions

Our observations confirm the importance of cytogenetic analyses for determining the cause of congenital anomalies and provide a useful genetic counseling. In addition, due to the fact that some of mosaic trisomy 22 features are unavoidable such asCHDand general hypotrophy, we suggest including echocardiography test for early diagnosis during the clinical assessment.
Elevation of serum oxLDL/β2‐GPI complexes was correlated with diabetic microvascular complications in Type 2 diabetes mellitus patients
Authors: Xie Lianzhi , Lin Hui , Wang Caihong
Published: September 2018

Background

High levels of oxLDL/β2‐GPI complexes might be a consequence of LDL atherogenic modification mediated by oxidative stress. We aimed to determine whether the levels of serum oxLDL/β2‐GPI complexes were correlated with diabetic microvascular complications in type 2 diabetes mellitus (T2DM) patients.

Methods

Levels of oxLDL/β2‐GPI complexes, oxLDL, routine lipid/lipoprotein parameters were measured in 100 healthy controls, 128 T2DM patients without any microvascular complications, and 172 T2DM patients with microvascular complications. Spearman's correlation, multivariable linear regression logistic regression analysis, and receiver operating characteristic (ROC) curve were performed.

Results

Levels of serum oxLDL/β2‐GPI complexes and oxLDL were significantly higher in T2DM patients with microvascular complications (oxLDL/β2‐GPI complexes: 1.10 ± 0.18 U/mL; oxLDL: 48.12 ± 7.24 mmol/L) than those in T2DM patients without microvascular complications (oxLDL/β2‐GPI complexes: 0.98 ± 0.16 U/mL; oxLDL: 41.45 ± 6.81 mmol/L) and controls (oxLDL/β2‐GPI complexes: 0.79 ± 0.15 U/mL; oxLDL: 27.85 ± 5.32 mmol/L). Variables that remained significantly associated with oxLDL/β2‐GPI complexes were oxLDL (β = 0.568, P < 0.001), TC (β = 0.312, P = 0.013) and microvascular complications (β = 0.205, P = 0.027), which accounted for 58.3% of the variation of the level of oxLDL/β2‐GPI complexes in T2DM patients (R2 = 0.583). Logistic regression analysis demonstrated that elevation of oxLDL/β2‐GPI complexes (OR = 3.14, 95% CI: 1.04‐9.46, P = 0.042) and oxLDL levels (OR = 3.02, 95% CI: 1.16‐7.83, P = 0.023) were independently associated with occurrence of microvascular complications. Cutoff value of oxLDL/β2‐GPI for the presence of microvascular complications was 1.05 U/mL, and AUC area of ROC curve was 0.783 (95%CI: 0.713‐0.853), yielding a sensitivity of 86.8% and specificity of 64.9%.

Conclusions

Elevation of serum oxLDL/β2‐GPI complexes was associated with microvascular complications in T2DM patients.
Utility of cell population data (VCS parameters) as a rapid screening tool for Acute Myeloid Leukemia (AML) in resource‐constrained laboratories
Authors: Virk Harpreet , Varma Neelam , Naseem Shano , Bihana Ishwar , Sukhachev Dmitry
Published: September 2018

Introduction

Despite advances in diagnostic techniques, many cases of acute myeloid leukemia (AML) remain underdiagnosed in remote centers unequipped with these technologies. We hypothesized that the automated cellular indices with scatter plots and flags may aid in rapid and cost‐effective screening of AML.

Methods

Cell population data (CPD) parameters from 100 de novo AML samples were analyzed by Coulter LH 780 automated analyzer and were compared with 100 age‐matched controls. Similar parameters were also compared with 100 and 50 reactive cases of neutrophilia and monocytosis, respectively. System‐generated flags and scatter plot patterns were also analyzed.

Results

Results were compared between AML cases and normal controls; AML FAB M2, M3, M4 vs reactive neutrophilia; AML FAB M4, M5 vs reactive monocytosis. Significant parameters were selected from all comparison groups. Using appropriate statistical tools, we calculated the cutoff values of these parameters and were able to screen out AML cases with 94% sensitivity and 95% specificity. Three statistical equations were generated using two of the most significant parameters which improved the sensitivity to 98% and specificity to 99%. Five hypothetical scatter plot patterns were devised and were classified according to FAB categories of AML. Most common pattern was selected in AML which was seen in 56% of the cases. Output was analyzed combining these patterns and flags with CPD parameters.

Conclusion

CPD either alone or in the form of statistical equations along with scatter plots and flags can provide rapid and economic tool in preliminary diagnosis of AML in cost‐constrained settings.
Blockade of NEAT1 represses inflammation response and lipid uptake via modulating miR‐342‐3p in human macrophages THP‐1 cells
Authors: Wang Lei , Xia Jing‐Wen , Ke Zun‐Ping , Zhang Bing‐Hong
Published: September 2018

Atherosclerosis has been recognized as a chronic inflammation process induced by lipid of the vessel wall. Oxidized low‐density lipoprotein (ox‐LDL) can drive atherosclerosis progression involving macrophages. Recently, long noncoding RNAs (lncRNAs) have been reported to play critical roles in atherosclerosis development. In our current study, we focused on the biological roles of lncRNA NEAT1 in atherosclerosis progress. Here, we found that ox‐LDL was able to trigger human macrophages THP‐1 cells, a human monocytic cell line, apoptosis in a dose‐dependent and time‐dependent course. In addition, we observed that NEAT1 was significantly increased in THP‐1 cells incubated with ox‐LDL and meanwhile miR‐342‐3p was greatly decreased. Then, NEAT1 was silenced by transfection of small interfering RNA (siRNA) of NEAT1 into THP‐1 cells. As exhibited, CD36, oil‐red staining levels, total cholesterol (TC), total cholesterol (TG) levels and THP‐1 cell apoptosis were obviously repressed by knockdown of NEAT1. Furthermore, inhibition of NEAT1 contributed to the repression of inflammation in vitro. Interleukin 6 (IL‐6), IL‐1β, cyclooxygenase‐2 (COX‐2) and tumour necrosis factor‐alpha (TNF‐α) protein levels were remarkably depressed by NEAT1 siRNA in THP‐1 cells. By using bioinformatics analysis, miR‐342‐3p was predicted as a downstream target of NEAT1 and the correlation between them was confirmed in our study. Moreover, overexpression of miR‐342‐3p could also greatly suppress inflammation response and lipid uptake in THP‐1 cells. Knockdown of NEAT1 and miR‐342‐3p mimics inhibited lipid uptake in THP‐1 cells. In conclusion, we implied that blockade of NEAT1 repressed inflammation response through modulating miR‐342‐3p in human macrophages THP‐1 cells and NEAT1 may offer a promising strategy to treat atherosclerotic cardiovascular diseases.