bluuebunny/crossref_metadata_2025 huggingface dataset:
A case of coronary venous angioplasty to facilitate left ventricular lead placement
Authors: Timmer Stefan A. J. , de Swart Johannes B. R. M. , Tahapary Giovanni J. M.
Published: October 2018

Key Clinical Mesage

Coronary venous stenosis is an uncommon finding in patients referred for cardiac resynchronization therapy device implantation. Nonetheless, it may result in suboptimal lead positioning for chronic left ventricular (LV) pacing. Coronary venous angioplasty is a technique that can be performed relatively easily and safely to enable LV lead passage beyond a stenosis.
Towards the Development of Photo‐Reactive Ruthenium(II) Complexes Targeting Telomeric G‐Quadruplex DNA
Authors: Weynand Justin , Diman Aurélie , Abraham Michaël , Marcélis Lionel , Jamet Hélène , Decottignies Anabelle , Dejeu Jérôme , Defrancq Eric , Elias Benjamin
Published: October 2018

The design and characterization of new ruthenium(II) complexes aimed at targeting G‐quadruplex DNA is reported. Importantly, these complexes are based on oxidizing 1,4,5,8‐tetraazaphenanthrene (TAP) ancillary ligands known to favour photo‐induced electron transfer (PET) with DNA. The photochemistry of complexes 1–4 has been studied by classical methods, which revealed two of them to be capable of photo‐abstracting an electron from guanine. From studies of the interactions with DNA through luminescence, circular dichroism, bio‐layer interferometry, and surface plasmon resonance experiments, we have demonstrated the selectivity of these complexes for telomeric G‐quadruplex DNA over duplex DNA. Preliminary biological studies of these complexes have been performed: two of them showed remarkable photo‐cytotoxicity towards telomerase‐negative U2OS osteosarcoma cells, whereas very low mortality was observed in the dark at the same photo‐drug concentration.
Synthesis of a Series of Non‐Symmetric Bispyridinium and Related Compounds and Their Affinity Characterization at the Nicotinic Acetylcholine Receptor
Authors: Rappenglück Sebastian , Sichler Sonja , Höfner Georg , Wein Thomas , Niessen Karin V. , Seeger Thomas , Paintner Franz F. , Worek Franz , Thiermann Horst , Wanner Klaus T.
Published: October 2018

The current standard therapy to counteract organophosphate intoxication is not effective in equal measure against all types of organophosphorus compounds (OPCs), as the outcome of oxime‐induced reactivation of inactivated acetylcholinesterase (AChE) strongly depends on the particular OPC. In case the reactivation is insufficient, acetylcholine concentrations that rise to pathophysiological levels force the nicotinic acetylcholine receptor (nAChR) into a desensitized state and hence a functionally inactive state. As a consequence, neurotransmission is irreversibly disrupted at the neuromuscular junction. Previous electrophysiological studies identified the symmetric bispyridinium compound 1,1′‐(propane‐1,3‐diyl)bis[4‐(tert‐butyl)pyridin‐1‐ium] diiodide (MB327) as a re‐sensitizer of the desensitized nAChR. MB327 is thereby capable of restoring the functional activity. Very recently, in silico modeling studies suggested non‐symmetric derivatives of MB327 as potential re‐sensitizers with enhanced binding affinity and thus possible enhanced efficacy. In this study, 26 novel non‐symmetric bispyridinium compounds and related derivatives were synthesized. For the synthesis of the highly polar target compounds in sufficient quantities, newly developed and highly efficient two‐step procedures were used. Compounds were characterized in terms of their binding affinity toward the MB327 binding site at the nAChR using recently developed mass spectrometry (MS) Binding Assays. Regarding structure–affinity relationships at the MB327 binding site, the presence of two quaternary aromatic nitrogen centers as well as pyridinium systems with a tert‐butyl group at the 4‐position or a NMe2 group at the 3‐ or 4‐positions appeared to be beneficial for high binding affinities.
Hierarchical group key management for secure data sharing in a cloud‐based environment
Authors: Velumadhava Rao R. , Selvamani K. , Kanimozhi S. , Kannan A.
Published: October 2018

In cloud environment, the importance of security for the outsourced data has increased much, since the data is maintained and controlled by the semi‐trusted third‐party cloud providers. Data Security is one of the major factors to be considered in group data sharing. Using the secret key, the entire file is encrypted directly in a conventional security framework; however, in a cloud‐based environment for group mechanism, this framework cannot be applied as there is a problem of key distribution. This research paper proposes an efficient hierarchical‐based group key mechanism for a cloud‐based environment. This proposed system relies on Key Distribution Server (KDS), which performs cryptographic key operations for securing the data in the cloud. Also, this system uses logical key hierarchy (LKH) protocol to maintain hierarchical tree for scalability. The group key is generated using the group member secret values and a secret value assigned by the KDS server. Performance analysis of this system shows that the proposed key management system is more efficient and much suitable for cloud environment.
Consumer's response to CSR activities: Mediating role of brand image and brand attitude
Authors: Ramesh Kumar , Saha Raiswa , Goswami Susoban , Sekar  , Dahiya Richa
Published: October 2018

Corporate social responsibility (CSR) is a well‐touted term in management disciplines that connects the business goals and societal values. CSR is used as a strategic approach that gives competitive differentiation through coagulation of both business and overarching societal goals. Organizations believe that goodwill created by CSR activities bestows the strategic competitive advantage and sustainable development. The objective of the study is to measure the impact of CSR activities on purchase intention either directly or indirectly; for this purpose, the study has administered a structured questionnaire and collected responses from Indian citizens purchasing products from FMCG companies topping the CSR spending list and used structural equation modeling to validate the results. The findings suggest that customers process CSR details unconsciously and may not remember the explicit detail, but they are more likely to include the brand in the consideration set evokedby positive attitudes trailing behind.
SDN‐based dynamic multipath forwarding for inter–data center networking
Authors: Wang Yao‐Chun , Lin Ying‐Dar , Chang Guey‐Yun
Published: October 2018

Equal‐cost multipath (ECMP)–based traffic engineering (TE) methods are commonly used in intra–data center (DC) networks to improve the transmission performance for east‐west traffic (ie, traffic from server to server within a DC). However, applying ECMP on inter‐DC wide area network (WAN) offers limited performance enhancement as a result of irregular network topology. Since TE can be intelligently and efficiently realized with software‐defined networking (SDN), SDN‐based multipath becomes a popular option. However, SDN suffers from scalability issue caused by limited ternary content‐addressable memory (TCAM) size. In this paper, we propose an SDN‐based TE method called dynamic flow‐entry‐saving multipath (DFSM) for inter‐DC traffic forwarding. DFSM adopts source‐destination–based multipath forwarding and latency‐aware traffic splitting to reduce the consumption of flow entries and achieve load balancing. The evaluation results indicate that DFSM saves 15% to 30% of system flow entries in practical topologies and reduces the standard deviation of path latencies from 10% to 7% than do label‐switched tunneling, and also reduces average latency by 10% to 48% by consuming 6% to 20% more flow entries than do ECMP in less‐interconnected topologies. Note that the performance gain may not always be proportional to flow entry investment, with the interconnectivity between nodes being an important factor. The evaluation also indicates that per‐flow provision consumes several times the flow entries consumed by DFSM but reduces latency by 10% at most. Besides, DFSM reduces the standard deviation of path latencies from 14% to 7% than do even traffic splitting.
The effect of plant identity and mixed feeding on the detection of seed DNA in regurgitates of carabid beetles
Authors: Sint Daniela , Guenay Yasemin , Mayer Rebecca , Traugott Michael , Wallinger Corinna
Published: October 2018

Carabids are abundant in temperate agroecosystems and play a pivotal role as biocontrol agents for weed seed and pest regulation. While there is good knowledge regarding their effects on invertebrate pests, direct evidence for seed predation in the field is missing. Molecular approaches are ideally suited to investigate these feeding interactions; however, the effects of an omnivorous diet, which is characteristic for many carabid species, and seed identity on the detection success of seed DNA has not yet been investigated. In a series of feeding experiments, seeds of six different Central European weed species were fed to beetles of the speciesPseudoophonus rufipes, to determine post‐feeding seed DNA detection rates and how these are affected by plant identity, meal size, and chemical seed composition. Moreover, we investigated the effect of a mixed diet of seeds and mealworm on prey DNA detection. Four out of six seed species were detectable for up to five days after consumption, and seed species identity significantly affected post‐feeding detection rates. Detectability was negatively influenced by protein content and seed mass, whereas oil content and meal size had a positive effect. The mixed diet led to both increased detection rates and post‐feeding detection intervals of seed DNA. This suggests that mixed feeding leads to an enhancement of food detection intervals in carabid beetles and that seed identity, their chemical composition, and meal size can affect DNA detection of consumed seeds. These aspects and potential implications of this non‐invasive approach are discussed as they can become highly relevant for interpreting field‐derived data.
Leaf phenology of thirteen African origins of baobab (Adansonia digitata (L.)) as influenced by daylength and water availability
Authors: Di Lucchio Luisa Maddalena , Fensholt Rasmus , Markussen Bo , Ræbild Anders
Published: October 2018

Water availability is often described as one of the main drivers of phenology of tropical dry forests but experimental studies to identify the cues triggering phenological changes are few. In a greenhouse trial, we exposed seedlings of thirteen origins, seven from West and six from East Africa, respectively, of Adansonia digitata L.(baobab) to a well‐watered control treatment and a water withholding treatment in combination with exposure to three different daylengths (11.5, 12.0, and 12.5 hr). Responses were measured in terms of meristematic activity, number of leaves, and height growth followed over 6.5 months. Multi‐level mixed‐effects statistical models were used to analyze how environmental and inter‐population variables affected phenological behavior. Flushing was influenced by the daylength with the lowest degree of meristematic activity observed in the short daylength treatment. Daylength also influenced the number of leaves through an interaction with the water regime. The water regime influenced all variables through interactions with the origins. Seedlings subjected to water stress had higher meristematic activity, but initially lower numbers of leaves than continuously watered plants. Height growth in continuously watered plants was fastest or at par with water‐stressed plants, depending on the origin. Origins from West Africa tended to have higher meristematic activity and their phenology was found to be less influenced by water withholding than East African origins. There were no signs of significant differences between origins in their response to photoperiod. In conclusion, baobab seedlings show opportunistic behavior, setting leaves when water is available, but larger activity is found when days are long. We discuss the results in terms of triggering factors for baobab phenology and adaptation to specific environmental conditions at the site of origins.
Synthesis and Physicochemical Properties of Ruthenium(II) Complexes Having Pentadentate Scaffolds: Water Oxidation Activity and Deactivation Pathway
Authors: Kundu Animesh , Khan Srimoyee , Dey Subhasis , Dutta Chiranjit , Anoop Anakuthil , Mandal Sukanta
Published: October 2018

Five mononuclear RuII complexes supported by two pentadentate polypyridyl ligands, N,N‐bis(2‐pyridylmethyl)‐N‐(bis‐2‐pyridylmethyl)amine (N4Py) {[Ru(N4Py)(Cl)](PF6), 1Cl; [Ru(N4Py)(OH2)](PF6)2, 1Aq} and newly designed N‐benzyl‐N‐((6‐(6‐methylpyridin‐2‐yl)pyridin‐2‐yl)methyl)dipyridin‐2‐yl‐methanamine (N2Py‐MeBpy‐Bz) {[Ru(N2Py‐MeBpy‐Bz)(Cl)](PF6)·MeCN, 2Cl·MeCN; [Ru(N2Py‐MeBpy‐Bz)(OH2)](PF6)2·3H2O·MeOH, 2Aq·3H2O·MeOH and [Ru(N2Py‐MeBpy‐Bz)(MeCN)](PF6)2·0.5MeCN·H2O, 2ACN·0.5MeCN·H2O} were synthesized and characterized using different spectroscopic techniques such as UV/Vis, IR, 1D and 2D NMR spectroscopy, and mass spectrometry. The physicochemical properties of complexes 1Cl and 1Aq, and structural analysis of 1Aq were reported by Kojima and co‐workers (Chem. Sci. 2012, 3, 3421–3431). Structural characterizations of 1Cl, 2Cl·MeCN, and 2ACN·0.5MeCN·H2O were done by using single‐crystal X‐ray diffraction analyses. Catalytic water oxidation activities of aqua‐ligated RuII complexes, using CeIV as sacrificial electron acceptor at pH 1, were examined. Complex 2Aq shows higher activity as compared to 1Aq. Electrochemical study suggests that a formal [RuVI=O]4+ species is the active species which triggers the oxidation of water. Mechanistic investigation reveals that O–O bond formation takes place via water nucleophilic attack (WNA) pathway. The deactivation pathway of catalyst 2Aq has also been investigated. It was observed that complex 2Aq lost its water oxidation activity primarily due to ligand degradation via oxidative N‐debenzylation pathway.
Silver‐Catalyzed Chemo‐ and Regioselective Nitration of Anilides
Authors: Kianmehr Ebrahim , Nasab Sepideh Bahrami
Published: October 2018

A new and efficient Ag‐catalyzed method for the nitration of anilides by using sodium nitrite as a cheap and available NO2 source has been developed. This C–H functionalization reaction is ortho‐selective, achieves moderate to high yields and shows excellent functional group tolerance. Furthermore, it provides a novel approach to ortho‐nitrated anilides, which are very tricky to access with traditional methods.
Enzymatic acylation of flavone isolated from extractive of bamboo leaves with oleic acid and antioxidant activity of acylated product
Authors: Qian Junqing , Gou Lihong , Chen Yan , Ding Jing , Xu Jiang , Guo Hui
Published: October 2018

This present study aims to establish a relatively cheap and effective method for preparation of ester of flavone isolated from bamboo‐leaf extracts. According to this method, the solubility of bamboo leaf extract in a lipid medium could be improved, which would expand the utilization of bamboo leaf extract. Acylation of flavone with oleic acid was efficient in a system containing dried tert‐amyl‐alcohol and molecular sieves. The bioconversion yield ranged from 24 to 63% in different conditions. the type of fatty acids, the amount of the lipase, water content and temperature of the system were investigated in detail to influence on the performance of the acylation reaction. High purity of ester (>95%) was obtained by a two‐step solvent purification procedure and chromatographic separation. Followed by the 1H and 13C nuclear magnetic resonance spectroscopy analysis, single product of 6′′‐O‐oleate isoorientin ester was detected. Introducing an acyl group into isoorientin significantly improved its lipophilicity yet slightly reduced their antioxidant activity, while its antioxidant activity still significantly better than VE.
Magnetic Resonance Imaging Is Cost‐Effective for Hepatocellular Carcinoma Surveillance in High‐Risk Patients With Cirrhosis
Authors: Kim Hye‐Lin , An Jihyun , Park Jae‐A , Park Seung‐Hoo , Lim Young‐Suk , Lee Eui‐Kyung
Published: October 2018

Ultrasonography (US) is generally recommended for the surveillance of hepatocellular carcinoma (HCC) in patients at risk. However, in patients with cirrhosis who have sufficiently high HCC incidence, surveillance using magnetic resonance imaging (MRI) with liver‐specific contrast showed markedly higher sensitivity in detecting early‐stage HCC than US. This study aimed to compare the cost‐effectiveness of semiannual surveillance using MRI versus US in patients with compensated cirrhosis and to identify the population that would gain optimal cost‐effectiveness through MRI surveillance. We designed a Markov model to compare the expected costs and quality‐adjusted life‐years (QALYs), between MRI and US, with a 20‐year time horizon, from the health care system perspective. The starting age of the cohort was 50 years, and 71% had hepatitis B virus–associated cirrhosis. The cycle length was 6 months. Transition probabilities and costs were obtained mainly from a prospective cohort study (the PRIUS study, NCT01446666). Cost and effectiveness were discounted at 5%. An incremental cost‐effectiveness ratio (ICER) was calculated and tested using sensitivity analyses. The cost‐effectiveness analysis indicated that the use of MRI incurred $5,562 incremental costs, 0.384 incremental life‐years (LYs), and 0.221 incremental QALYs compared to US. The annual HCC incidence was the most influential factor on the ICER. The ICERs were $14,474/LY and $25,202/QALY at an annual HCC incidence of 3%. When the HCC incidence rate was >1.81%, the ICER was below $50,000/QALY. With increased HCC incidence, MRI surveillance was acceptable as a cost‐effective option, even with an increased MRI/US cost ratio. Conclusion: Semiannual surveillance using MRI with liver‐specific contrast may be more cost‐effective than US in patients with virus‐associated compensated cirrhosis at sufficiently high HCC risk despite the higher test cost of MRI.
Prospective study of oral microbiome and colorectal cancer risk in low‐income and African American populations
Authors: Yang Yaohua , Cai Qiuyin , Shu Xiao‐Ou , Steinwandel Mark D. , Blot William J. , Zheng Wei , Long Jirong
Published: October 2018

Oral microbiome may play an important role in cancer pathogenesis. However, no study has prospectively investigated the association of the oral microbiome with subsequent risk of developing colorectal cancer (CRC). We conducted a nested case–control study including 231 incident CRC cases and 462 controls within the Southern Community Cohort Study with 75% of the subjects being African‐Americans. The controls were individually matched to cases based on age, ethnic group, smoking, season‐of‐study enrollment and recruitment method. Oral microbiota were assessed using 16S rRNA gene sequencing in pre‐diagnostic mouth rinse samples. Multiple bacterial taxa showed an association with CRC risk at p <0.05. Oral pathogens Treponema denticola and Prevotella intermedia were associated with an increased risk of CRC, with odds ratios (ORs) and 95% confidence intervals (CIs) of 1.76(1.19–2.60) and 1.55(1.08–2.22), respectively, for the individuals carrying these bacteria compared to non‐carriers. In the phylum Actinobacteria, Bifidobacteriaceae was more abundant among CRC patients than among controls. In the phylum Bacteroidetes, Prevotella denticola and Prevotella sp. oral taxon 300 were associated with an increased CRC risk, while Prevotella melaninogenica was associated with a decreased risk of CRC. In the phylum Firmicutes, Carnobacteriaceae, Streptococcaceae, Erysipelotrichaceae, Streptococcus, Solobacterium, Streptococcus sp. oral taxon 058 and Solobacterium moorei showed associations with a decreased risk of CRC. Most of these associations were observed among both African‐ and European‐Americans. Most of the associations were not significant after Bonferroni correction for multiple testing, which may be conservative. Our study suggests that the oral microbiome may play a significant role in CRC etiology.
Banking efficiency in emerging economies: Does foreign banks entry matter in the Ghanaian context?
Authors: Ofori‐Sasu Daniel , Mensah Lord , Akuma John Kwame , Doku Isaac
Published: October 2018

This study empirically examines the effect of foreign banks entry on banking efficiency scores, using the truncated regression data envelopment analysis model for 25s banks in Ghana, over a 6‐year period (2010–2015). We decompose the efficiency scores into three (technical, cost, and allocative efficiency), and the results indicate that banks in Ghana are marginally inefficient in operating closer to their optimal capacity. The findings show that the input‐oriented model slacks are needed to push an inefficient bank closer to where an efficient bank is positioned. From the results, an immediate and a short‐term entry of foreign banks have a consistent negative relationship with both technical‐ and cost‐efficiency scores whereas long‐term entry of foreign banks shows an inconsistent relationship with the three banking efficiency scores. Thus, the drive towards a positive impact of foreign banks entry on the three efficiency scores is dependent on the form of banking efficiency considered and the interaction term between competitive banking environment (competition) and foreign banks' entry. The study suggests that policymakers and managers in emerging markets should improve on their bank efficiencies in both a competitive banking environment and during periods of foreign bank entry. Moreover, managers of banks should make adjustment to their input resources in order to cope with new banking technologies from foreign bank entry—thereby improving banking efficiencies.
Effect of early “quilting” sutures on morbidity in postpartum hemorrhage
Authors: Stein Werner , Spätling Ludwig
Published: October 2018

Objective

To examine whether “quilting” sutures are safe and effective in preventing hysterectomy among women with postpartum hemorrhage (PPH) and whether early application might reduce the incidence of transfusion.

Methods

Data were reviewed from women treated via quilting sutures after cesarean delivery at a university hospital between 2007 and 2016. Objective and subjective data were collected by analyzing medical records and performing telephone interviews. To observe trends during the study period, data from the first 50% of women treated were compared with those from the second 50%.

Results

Overall, 26 cesareans with quilting sutures were performed. Two hysterectomies could not be avoided. During 2012–2106, 18 quilting sutures were performed as compared with 8 in 2007–2011, pointing to a more liberal indication. Intensive care was required twice as frequently among the first 13 procedures than among the second 13 procedures (10 vs 5, respectively). A similar observation was made for the use of blood transfusions or clotting activation (9 vs 4, respectively). Three women who desired to have a child subsequently delivered a newborn.

Conclusion

Quilting sutures were found to be a safe and simple technique to prevent hysterectomies in PPH. Morbidity was reduced when the decision to perform sutures was taken early.
The promotional role of meaning in life in future‐oriented coping: Positive affect as a mediator
Authors: Miao Miao , Gan Yiqun
Published: October 2018

The present study examined the role of meaning in life (MIL) in predicting positive affect and future‐oriented coping, and whether positive affect mediated the relationship between MIL and future‐oriented coping. The participants were 68 Chinese university students who were randomly assigned to two conditions: a MIL priming condition and a control condition. Positive affect was measured before and after the manipulation. MIL, positive affect and future‐oriented coping were assessed at 1‐week follow‐up. The results showed that the level of positive affect increased after the manipulation in the MIL priming condition. Fifty‐five of the participants completed the follow‐up survey, and results showed that the MIL priming condition exhibited higher levels of future‐oriented coping at follow‐up compared to the control condition. Mediation analyses confirmed that MIL promoted proactive coping via positive affect. This study provides empirical support for the promotional role of MIL in future‐oriented coping and clarifies the mechanism via the mediating effect of positive affect.
Identification of six miRNAs serving as predictive biomarkers in coronary artery disease
Authors: Ren Fei , Gao Wen‐Chuang , Ke Zun‐Ping , Xu Yong , Liu Yu
Published: October 2018

Coronary artery disease (CAD) is quite a common disease with high risk. It was reported that microRNAs (miRNAs) had significant effect on the occurrence of CAD. The previously published results are inconsistent due to the parameters, such as sequencing platform, samples selection, and the filter conditions. Here we aimed to explore the critical miRNAs in the occurrence of CAD, which may function as the potential biomarkers. A total of 12 representative datasets of miRNAs related to the occurrence of miRNAs were finally selected, and the critical miRNAs were determined by the comparison of the overlap relations. TargetScan software was used to predict the target genes of these critical miRNAs. Besides, DAVID and Tfacts dataset were used to analyze the functional enrichment and the transcriptional factors analysis. At last, a total of six signature miRNAs were identified, among which five were significantly upregulated and one was downregulated. The target gene of upregulated miRNAs was mostly enriched in the process of RNA Polymerase II promoter and the transcription of DNA template, whereas the target genes of downregulated miRNAs were mostly enriched in the regulation of transcription, DNA‐templated. Besides, the result of the transcriptional factor analysis showed that there were 43 factors coexisting in two kinds of target genes. In summary, six critical miRNAs, as well as the corresponding target genes and transcriptional factors, were identified in the occurrence of CAD by bioinformatics analysis. These identified miRNAs may function as potential biomarkers in the clinical management of CAD.
Knockdown of PSMC3IP suppresses the proliferation and xenografted tumorigenesis of hepatocellular carcinoma cell
Authors: Ding Jingli , Li Yang , Fan Huxiong , Xu Weichang , Gao Rifeng , Bai Shuheng , Zhu Zhigang , Yang Wei , Gong Yi , Yang Juesheng , Zhou Jianliang
Published: October 2018

Hepatocellular carcinoma (HCC) is the fifth most frequent malignancy and the second leading cause of cancer‐related death worldwide. Proteasome 26S subunit ATPase 3 interacting protein (PSMC3IP) is an oncogene in breast cancer, while its role in HCC remains unclear. Here, we found that PSMC3IP was critical for the cell proliferation and tumorigenic capacity of HCC cells. Upregulation of PSMC3IP was observed in HCC specimens, and high PSMC3IP expression predicted poor overall survival of HCC patients. In vitro, knockdown of PSMC3IP blunted the proliferation and colony formation of BEL‐7404 and SMMC‐7721 cells. Likewise, PSMC3IP silencing suppressed the xenografted tumor development of BEL‐7404 cells. Mechanistically, apoptosis was enhanced after PSMC3IP knockdown in both BEL‐7404 and SMMC‐7721 cells. At the molecular level, TP53 and GNG4 were upregulated and eukaryotic translation initiation factor 4E (EIF4E) and insulin like growth factor 1 receptor (IGF1R) were downregulated in shPSMC3IP compared with shCtrl BEL‐7404 cells. Therefore, targeting PSMC3IP maybe a promising strategy for HCC.
RSPO2 enhances cell invasion and migration via the WNT/β‐catenin pathway in human gastric cancer
Authors: Zhang Haibo , Han Xiaoyan , Wei Bo , Fang Jiafeng , Hou Xuerui , Lan Tianyun , Wei Hongbo
Published: October 2018

R‐spondins comprise a group of secreted WNT agonists. R‐spondin2 (RSPO2) plays a crucial role in the activation of the WNT/β‐catenin pathway and oncogenesis, though its specific role in human gastric cancer (GC) remains unclear. In the current study, RSPO2 expression levels were upregulated in cancer specimens and cell lines (AGS and BGC‐823). Inhibition of RSPO2 expression levels had distinct effects on cell invasion, migration, and epithelial‐mesenchymal transition (EMT) in AGS and BGC‐823 cells in vitro. Furthermore, RSPO2 positively correlated with leucine‐rich repeat‐containing G‐protein‐coupled receptor 5 (LGR5), the receptor of RSPO2. Silencing RSPO2 reduced the expression of LGR5 and WNT/β‐catenin effector molecule β‐catenin together with downstream targets TCF‐4 and Cyclin‐D1. These observations demonstrate that upregulation of RSPO2 in GC specimens and cell lines is closely related to tumor invasion and migration and that RSPO2 promotes EMT in gastric cancer cells by activating WNT/β‐catenin signaling.
Loss of miR‐146b‐5p promotes T cell acute lymphoblastic leukemia migration and invasion via the IL‐17A pathway
Authors: Tu Zhenbo , Xiong Jie , Xiao Ruijing , Shao Liang , Yang Xiangyong , Zhou Lu , Yuan Wen , Wang Meng , Yin Qian , Wu Yingjie , Pan Shan , Leng Jun , Jiang Daozi , He Chunjiang , Zhang Qiuping
Published: October 2018

Metastatic disease remains the primary cause of death for individuals with T cell acute lymphoblastic leukemia (T‐ALL). microRNAs (miRNAs) play important roles in the pathogenesis of T‐ALL by inhibiting gene expression at posttranscriptional levels. The goal of the current project is to identify any significant miRNAs in T‐ALL metastasis. We observed miR‐146b‐5p to be downregulated in T‐ALL patients and cell lines, and bioinformatics analysis implicated miR‐146b‐5p in the hematopoietic system. miR‐146b‐5p inhibited the migration and invasion in T‐ALL cells. Interleukin‐17A (IL‐17A) was predicted to be a target of miR‐146b‐5p; this was confirmed by luciferase assays. Interestingly, T‐ALL patients and cell lines secreted IL‐17A and expressed the IL‐17A receptor (IL‐17RA). IL‐17A/IL‐17RA interactions promoted strong T‐ALL cell migration and invasion responses. Gene set enrichment analysis (GSEA) and quantitative polymerase chain reaction (qPCR) analysis indicated that matrix metallopeptidase‐9 (MMP9), was a potential downstream effector of IL‐17A activation, and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) signaling was also implicated in this process. Moreover, IL‐17A activation promoted T‐ALL cell metastasis to the liver in IL17A
−/− mouse models. These results indicate that reduced miR‐146b‐5p expression in T‐ALL may lead to the upregulation of IL‐17A, which then promotes T‐ALL cell migration and invasion by upregulating MMP9 via NF‐κB signaling.
P2X4R silence suppresses glioma cell growth through BDNF/TrkB/ATF4 signaling pathway
Authors: Huo Jun‐Feng , Chen Xiao‐Bing
Published: October 2018

Purinergic receptor P2X 4 (P2X4R), a member of purinergic channels family and a subtype of ionotropic adenosine triphosphate receptors, plays a critical role in tumorigenesis. Evidence suggested that P2X4R is expressed in rat C6 glioma model, however, its role and the underlying mechanism of action are still unclear in human glioblastoma multiforme (GBM). In the current study, our aim is to examine the function and the molecular basis of P2X4R in GBM. We first observed that GBM cells, U251, T98, U87, U373, and A172 were all high expressed P2X4R, when compared with the normal human astrocytes (NHA) cells. To gain the function of P2X4R, P2X4R silence cells were constructed by transfection with P2X4R small interfering RNA (siRNA). We found that P2X4R deletion impeded T98 and U87 cell viability and proliferation, and further studies indicated that cell apoptosis and caspase‐3 activity was increased in T98 and U87 cell transfected with P2X4R siRNA. Subsequently, we confirmed that P2X4R silence suppressed brain‐derived neurotrophic factor (BDNF), Trk receptor tyrosine kinases (TrkB), and activating transcription factor 4 (ATF4) expression in T98 and U87 cells. And P2X4R siRNA–induced ATF4‐expression inhibition dependent on BDNF/TrkB signaling pathway. The impact of P2X4R silence on T98 and U87 cell growth and apoptosis was reversed by ATF4 overexpression. In summary, this study provides the first evidence that P2X4R plays important roles in GBM cell growth and apoptosis.
TANGO: A high through‐put conformation generation and semiempirical method‐based optimization tool for ligand molecules
Authors: Gavane Vivek , Koulgi Shruti , Jani Vinod , Uppuladinne Mallikarjunachari V. N. , Sonavane Uddhavesh , Joshi Rajendra
Published: October 2018

Lead optimization is one of the crucial steps in the drug discovery pipeline. After identifying the lead molecule and obtaining its 2D geometry, understanding the best conformation it would attain in 3D still remains one of the most challenging steps in drug discovery. There have been multiple methods and algorithms that are directed toward achieving best conformation for the lead molecules. TANGO focuses on conformation generation and its optimization using semiempirical energy calculations. The conformation generation is based on torsion angle rotation of the exocyclic bonds. The energy calculations are performed using MOPAC. The unique feature of this tool lies in the implementation of Message Passing Interface (MPI) for conformation generation and semiempirical‐based optimization. A well‐defined architecture handling the input and output generation has been used. The master and slave approach to handle operations involved in torsion angle rotation and energy calculations has helped in load balancing the process of conformation generation. The benchmarking results suggest that TANGO scales significantly well across eight nodes with each node utilizing 16 cores. This tool may prove to very useful in high throughput generation of semiempirically optimized small molecule conformations. The use of semiempirical methods for optimization generates a conformational ensemble thereby helping to obtain stable and alternate stable conformers for a given ligand molecule. © 2018 Wiley Periodicals, Inc.
Fully optimized implementation of the cluster‐in‐molecule local correlation approach for electron correlation calculations of large systems
Authors: Ni Zhigang , Li Wei , Li Shuhua
Published: October 2018

A fully optimized implementation of the cluster‐in‐molecule (CIM) local correlation method for faster and more accurate electron correlation calculations of large systems is reported. The speedup comes from the new procedure of constructing virtual localized molecular orbitals of clusters. In the new procedure, Boughton–Pulay projection method is employed instead of a much more expensive Boys localization procedure. In addition, basis set superposition error correction for binding energy calculations and parallelized electron correlation calculations of clusters are now implemented. Benchmark calculations and illustrative applications at the Møller–Plesset perturbation theory, coupled cluster singles and doubles (CCSD), and CCSD with perturbative triples correction levels show that this newly optimized CIM approach is a reliable theoretical tool for electron correlation calculations of various large chemical systems. © 2018 Wiley Periodicals, Inc.
The roles of FOX proteins in virus‐associated cancers
Authors: Ramezani Ali , Nikravesh Hojatolla , Faghihloo Ebrahim
Published: October 2018

Forkhead box (FOX) proteins play a crucial role in regulating the expression of genes involved in multiple biological processes, such as metabolism, development, differentiation, proliferation, apoptosis, migration, invasion, and longevity. Deregulation of FOX proteins is commonly associated with cancer initiation, progression, and chemotherapeutic drug resistance in many human tumors. FOX proteins deregulate through genetic events and the perturbation of posttranslational modification. The purpose of the present review is to describe the deregulation of FOX proteins by oncoviruses. Oncoviruses utilize various mechanisms to deregulate FOX proteins, including alterations in posttranslational modifications, cellular localization independently of posttranslational modifications, virus‐encoded miRNAs, activation or suppression of a series of cell signaling pathways. This deregulation can affect proliferation, metastasis, chemotherapy resistance, and immunosuppression in virus‐induced cancers and help to chronic viral infection, development of gluconeogenic responses, and inflammation. Since the PI3K/Akt/mTOR signaling pathway is the upstream FOXO, suppressing it can cause FOXO function to return, and this can be one of the reasons for patients to recover from the infection of the viruses used to treat these inhibitors. Hence, FOX proteins could serve as prognosis markers and target therapy specifically in cancers caused by oncoviruses.
Involvement of H19/miR‐326 axis in hepatocellular carcinoma development through modulating TWIST1
Authors: Wei Li‐Qing , Li Li , Lu Chi , Liu Juan , Chen Yanhao , Wu Hongbin
Published: October 2018

Overexpression of long noncoding RNA (lncRNA) H19 has been observed in various cancers, which indicates that H19 exert important roles in the progression of carcinogenesis. MiR‐326 has been reported to play tumor suppressive roles in multiple tumors. Recently, the competing endogenous RNA (ceRNA) hypothesis has implied that lncRNAs might function as molecular sponges for microRNAs in various cancers. However, the roles of H19/miR‐326 in human hepatocellular carcinoma (HCC) still remain unclear. The aim of our study was to determine H19/miR‐326 expression in HCC cells and investigate their roles in HCC development. We found that H19 was significantly elevated and miR‐326 was decreased in HCC cells including Hep3B, HepG2, MHCC‐97L, SK‐hep1, Hun7, SMCC‐7721 compared with LO2 cells, respectively. In the subsequent experiments, we observed that inhibition of H19 can repress HCC cell growth, migration, and invasion in vitro. H19 downregulation can increase miR‐326 expression in HCC cells. Meanwhile, miR‐326 mimics can also inhibit HCC progression, whereas miR‐326 inhibitors exhibited a reverse phenomenon by modulating H19 expression. In addition, a negative association between H19 and miR‐326 was predicted and confirmed. Furthermore, the transcription factor TWIST1 has been recognized as a significant regulator in tumor progression. Here, by performing bioinformatics analysis, TWIST1 was identified as a downstream target of miR‐326. The findings of our study implied that lncRNA H19 can serve as a ceRNA to sponge miR‐326 and modulate TWIST1 levels in HCC pathogenesis. Taken these together, these findings indicated that H19/miR‐326/TWIST1 axis was involved in HCC development and can indicate a novel HCC target.
Contriving multiepitope subunit vaccine by exploiting structural and nonstructural viral proteins to prevent Epstein–Barr virus‐associated malignancy
Authors: Ojha Rupal , Nandani Raj , Prajapati Vijay Kumar
Published: October 2018

Cancer is one of the common lifestyle diseases and is considered to be the leading cause of death worldwide. Epstein–Barr virus (EBV)‐infected individuals remain asymptomatic; but under certain stress conditions, EBV may lead to the development of cancers such as Burkitt’s and Hodgkin’s lymphoma and nasopharyngeal carcinoma. EBV‐associated cancers result in a large number of deaths in Asian and African population, and no effective cure has still been developed. We, therefore, tried to devise a subunit vaccine with the help of immunoinformatic approaches that can be used for the prevention of EBV‐associated malignancies. The epitopes were predicted through B‐cell, cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL) from the different oncogenic proteins of EBV. A vaccine was designed by combining the B‐cell and T‐cell (HTL and CTL) epitopes through linkers, and for the enhancement of immunogenicity, an adjuvant was added at the N‐terminal. Further, homology modeling was performed to generate the 3D structure of the designed vaccine. Moreover, molecular docking was performed between the designed vaccine and immune receptor (TLR‐3) to determine the interaction between the final vaccine construct and the immune receptor complex. In addition, molecular dynamics was performed to analyze the stable interactions between the ligand final vaccine model and receptor TLR‐3 molecule. Lastly, to check the expression of our vaccine construct, we performed in silico cloning. This study needed experimental validation to ensure its effectiveness and potency to control malignancy.
The role of SDF1 in prostate epithelial morphogenesis
Authors: Barbosa Guilherme Oliveira , Augusto Taize Machado , Bruni‐Cardoso Alexandre , Carvalho Hernandes F.
Published: October 2018

Androgens induce rat prostate induction from the urogenital sinus epithelium at embryonic day 17.5. Subsequent morphogenesis, including epithelial cord growth, branching, and canalization, results from concerted paracrine interactions with the stroma. A significant number of paracrine factors bind heparan sulfate (HS). We hypothesized that interfering with overall sulfation could disrupt the signaling mediated by HS‐binding factors and that the undersulfated environment would allow investigation of individual exogenous morphogens. First, we investigated whether acinar morphogenesis involved HS‐proteoglycan expression and found that syndecans 1 and 3 were upregulated in RWPE1 cells in the transition from two‐ to three‐dimensional (3D) Matrigel, capable of promoting spheroid formation. We then investigated whether sodium chlorate, a general sulfation inhibitor, interfered with spheroid formation by RWPE1 cells and acinar morphogenesis in ex vivo ventral prostate (VP) organ culture. As expected, treatment with sodium chlorate inhibited spheroid formation by RWPE1 cells in 3D culture. Chlorate also inhibited ex vivo VP epithelial branching and canalization, resulting in long branchless epithelial structures. We then investigated whether the HS‐binding factors, FGF10, TGFβ1, and SDF1, could reverse the effect of sodium chlorate. Although no effect was seen in the FGF10‐ and TGFβ1‐treated samples, SDF1 promoted epithelial canalization in the low sulfated environment, highlighting its specific role in lumen formation. Altogether, the results show that sodium chlorate perturbed prostate morphogenesis and allowed investigation of factors involved in branching and/or canalization, implicating SDF1 signaling in epithelial canalization.
Immunological biomarkers of tolerance in human kidney transplantation: An updated literature review
Authors: Mirzakhani Mohammad , Shahbazi Mehdi , Oliaei Farshid , Mohammadnia‐Afrouzi Mousa
Published: October 2018

The half‐life of transplanted kidneys is <10 years. Acute or chronic rejections have a negative impact on transplant outcome. Therefore, achieving to allograft tolerance for improving long‐term transplant outcome is a desirable goal of transplantation field. In contrast, there are evidence that distinct immunological characteristics lead to tolerance in some transplant recipients. In contrast, the main reason for allograft loss is immunological responses. Various immune cells including T cells, B cells, dendritic cells, macrophages, natural killer, and myeloid‐derived suppressor cells damage graft tissue and, thereby, graft loss happens. Therefore, being armed with the comprehensive knowledge about either preimmunological or postimmunological characteristics of renal transplant patients may help us to achieve an operational tolerance. In the present study, we are going to review and discuss immunological characteristics of renal transplant recipients with rejection and compare them with tolerant subjects.
CXCL8 gene silencing promotes neuroglial cells activation while inhibiting neuroinflammation through the PI3K/Akt/NF‐κB‐signaling pathway in mice with ischemic stroke
Authors: Lv Hui , Li Jie , Che Yu‐Qin
Published: October 2018

Objective

Ischemic stroke is known as a neurodegenerative disorder, which induces long‐period tissue damage. Chemokine (C–X–C motif) ligand 8 (CXCL8) is involved in acute inflammation and tumor progression through the phosphoinositide‐3‐kinase/protein kinase B/nuclear factor‐κB (PI3K/Akt/NF‐κB)‐signaling pathway. In this study, we aimed to explore the mechanism of CXCL8 in ischemic stroke in relation to the PI3K/Akt/NF‐κB‐signaling pathway.

Methods

Microarray‐based gene expression profiling of peripheral blood mononuclear cells was used to identify ischemic stroke‐related differentially expressed genes and explore role of CXCL8 in ischemic stroke. Next, the ischemic mice model was successfully established, with transfection efficiency detected. After that, deflection index, recovery of nervous system, infarct sizes, ischemia‐induced apoptosis, and neuroinflammatory response in ischemic stroke were measured. At last, the content of inflammatory factors as well as the expression of CXCL8, caspase‐3, caspase‐9, Bad, interleukin‐6 (IL‐6), IL‐1β, tumor necrosis factor‐α (TNF‐α), Akt, PI3K, and NF‐κB were determined.

Results

Comprehensive gene expression profiling analysis identified that CXCL8 might affect the development of ischemic stroke through regulating the PI3K/Akt/NF‐κB‐signaling pathway. CXCL8 silencing significantly reduced deflection index and infarct size, improved neurological function, and suppressed neuroglial cell loss and apoptosis index. In addition, glial fibrillary acidic portein (GFAP) and ionized calcium‐binding adapter molecule 1 (IBA‐1) expressions were decreased following CXCL8 suppression, suggesting CXCL8 affected neuroglial activation. Importantly, we also found that CXCL8 silencing activated neuroglial cell and suppressed inflammatory cytokine production in ischemic stroke mice.

Conclusion

Taken together, these findings highlight that functional suppression of CXCL8 promotes neuroglial activation and inhibits neuroinflammation by regulating the PI3K/Akt/NF‐κB‐signaling pathway in mice with ischemic stroke, which might provide new insight for ischemic stroke treatment.
Meldonium improves Huntington’s disease mitochondrial dysfunction by restoring peroxisome proliferator‐activated receptor γ coactivator 1α expression
Authors: Di Cristo Francesca , Finicelli Mauro , Digilio Filomena Anna , Paladino Simona , Valentino Anna , Scialò Filippo , D’Apolito Maria , Saturnino Carmela , Galderisi Umberto , Giordano Antonio , Melone Mariarosa Anna Beatrice , Peluso Gianfranco
Published: October 2018

Mitochondrial dysfunction seems to play a fundamental role in the pathogenesis of neurodegeneration in Huntington’s disease (HD). We assessed possible neuroprotective actions of meldonium, a small molecule affecting mitochondrial fuel metabolism, in in vitro and in vivo HD models. We found that meldonium was able to prevent cytotoxicity induced by serum deprivation, to reduce the accumulation of mutated huntingtin (mHtt) aggregates, and to upregulate the expression of peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α) in mHTT‐expressing cells. The PGC‐1α increase was accompanied by the increment of mitochondrial mass and by the rebalancing of mitochondrial dynamics with a promotion of the mitochondrial fusion. Meldonium‐induced PGC‐1α significantly alleviated motor dysfunction and prolonged the survival of a transgenic HD Drosophila model in which mHtt expression in the nervous system led to progressive motor performance deficits. Our study strongly suggests that PGC‐1α, as a master coregulator of mitochondrial biogenesis, energy homeostasis, and antioxidant defense, is a potential therapeutic target in HD.