bluuebunny/crossref_metadata_2025 huggingface dataset:
An amoeboid approach for identifying optimal citation flow in big scholarly data network
Authors: J P Nivash , L D Dhinesh Babu
Published: December 2018

Scholarly big data network is a complex network of citations from research community across the globe. An effective scholar assessment structure is essential for scholars, researchers, and universities. The research publications are an important factor in the university rankings. The fast growth of digital publishing and scholarly data is progressively challenging every day. These days, the scholarly data can be accessed effortlessly through various data analysis techniques. In this paper, a new framework is designed for big scholarly data, and an amoeboid approach article‐optimal citation flow (A‐OCF) is used to find the optimal flow of citations in the big scholarly data network. A novel modern metrics for article quality (MMAQ) metric is proposed to identify the quality of articles. The performance analysis uses different bibliometric measures, including the impact factor citations, conference proceedings citations, and other citations with the purpose of measuring the quality of cited articles. The scholar analytic results are equated with existing techniques. We have also analyzed central articles in a research area through the MMAQ metrics and tested it with benchmark data sets.
Guanidinium Perfluoridotitanate(IV) Compounds: Structural Determination of an Oligomeric [Ti6F27]3– Anion, and an Example of a Mixed‐Anion Salt Containing Two Different Fluoridotitanate(IV) Anions
Authors: Shlyapnikov Igor M. , Goreshnik Evgeny A. , Mazej Zoran
Published: December 2018

Chemical reactions between guanidinium carbonate or guanidinium chloride and titanium tetrafluoride in anhydrous hydrogen fluoride (aHF) were studied. The obtained products were recrystallized from saturated HF, SO2 and CH3CN solutions. Single‐crystal growths resulted in the detection of seven perfluoridotitanate(IV) compounds, which were structurally characterized. Three of them correspond to the phases obtained as the main products of the synthesis in aHF, i.e., [C(NH2)3]2[TiF6], [C(NH2)3]4[Ti4F20], and [C(NH2)3][Ti2F9]. When the guanidinium salt/TiF4 molar ratios were greater than 1:2, the resulting products were only sparingly soluble or completely insoluble in aHF. Therefore, single‐crystal growths were attempted from other aprotic solvents (SO2 and CH3CN). Single crystals of [C(NH2)3]3[Ti6F27]·SO2 were detected in the case of the former and [C(NH2)3]4[H3O]4[Ti4F20][TiF5]4 in the case of the latter. The presence of [H3O]+ can be explained by a contamination with traces of H2O, which is protonated in the superacid aHF. The same reason applies to the formation of the by‐products [H5O2]4[Ti8F36] and β‐[H3O][Ti2F9]. The crystal structures of the new guanidinium‐perfluoridotitanate(IV) compounds consist of oligomeric [Ti4F20]4–, [Ti6F27]3– and [Ti8F36]4–, as well as polymeric ([TiF5]–)∞ and ([Ti2F9]–)∞ perfluoridotitanate(IV) anions. The hexameric [Ti6F27]3– anion with a trigonal prismatic geometry was structurally determined for the first time. The crystal‐structure determination of the [C(NH2)3]4[H3O]4[Ti4F20][TiF5]4 revealed the first example of a mixed‐anion perfluoridotitanate(IV) compound containing two different perfluoridotitanate(IV) anions, i.e., oligomeric [Ti4F20]4– and 1‐D polymeric ([TiF5]–)∞ anions. The crystal structure of the guanidinium hydrogen difluoride salt [C(NH2)3][HF2] is also reported.
Convenient Entry to 18F‐Labeled Amines through the Staudinger Reduction
Authors: Stéen E. Johanna L. , Shalgunov Vladimir , Denk Christoph , Mikula Hannes , Kjær Andreas , Kristensen Jesper L. , Herth Matthias M.
Published: December 2018

Fluorine‐18 possesses outstanding decay characteristics for positron emission tomography (PET) imaging. Therefore, it is ideally suited for clinical applications. As such, improved strategies to incorporate fluorine‐18 into bioactive molecules are of utmost importance. Indirect 18F‐labeling with amino‐functionalized synthons is a convenient and versatile approach to synthesize a broad variety of PET tracers. Herein, we report a method to convert 18F‐labeled azides to primary amines by means of the Staudinger reduction. Aliphatic and aromatic 18F‐labeled azides were converted into the corresponding amines with high conversion yields. The method was easily automated. From a broader perspective, the applied strategy results in two useful synthons from a single precursor and thus increases the flexibility to label diverse chemical scaffolds with minimal synthetic effort.
Coping with unpleasant group memberships in Japan and Germany: Cultural differences in disidentification, confrontation and emotion regulation
Authors: Bierle Isabel , Becker Julia C. , Ikegami Tomoko
Published: December 2018

Disidentification, the psychological distancing from unpleasant group memberships, has mainly been studied in individualistic societies. We tested whether disidentification is a coping strategy to deal with conflicts in small and large groups, in Japan and Germany. Study 1 (N = 79) illustrates that Japanese recalled more unpleasant situations related to small than large groups. Study 2 (N = 198) confirms that Japanese, but not German students’ disidentification varied with group size and was stronger after small‐group conflict. Study 3 (N = 132) shows that anger was related to disidentification in Japan but to confrontation in Germany. Study 4 (N = 335) shows that, after group conflict, Japanese felt relieved when imagining to disidentify, whereas Germans felt relieved when imagining to confront the source of conflict. Combining correlational and experimental designs with culture‐sensitive situation sampling, we show that disidentification exists as a psychological construct across cultures, albeit serving different psychological functions.
Production of anti‐inflammatory compounds in Sphaeralcea angustifolia cell suspension cultivated in stirred tank bioreactor
Authors: Pérez‐Hernández Juanita , Nicasio‐Torres María del Pilar , Sarmiento‐López Luis Gerardo , Rodríguez‐Monroy Mario
Published: December 2018

Sphaeralcea angustifolia is a plant used for the treatment of inflammatory processes. Scopoletin, tomentin, and sphaeralcic acid were identified as the compounds with anti‐inflammatory and immunomodulatory effects. Successful establishment of the cell culture in Erlenmeyer flasks has been reported previously. The aim of this study was to evaluate the ability of cells in suspension from S. angustifolia grown in a stirred tank bioreactor and demonstrate their capacity to produce bioactive compounds. Cells in suspension grown at 200 rpm reached a maximal cell biomass in dry weight at 19.11 g/L and produced 3.47 mg/g of sphaeralcic acid. The mixture of scopoletin and tomentin was only detected at the beginning of the culture (12.13 μg/g). Considering that the profile of dissolved oxygen during the cultures was lesser than 15%, it is possible that the low growth at 100 rpm could be due to oxygen limitations or to cell sedimentation. At 400 rpm, a negative effect on cell viability could be caused by the increase in the hydrodynamic stress, including the impeller tip, average shear rate, and Reynolds number. The sphaeralcic acid content in the cell suspension of S. angustifolia obtained in the bioreactor was two orders of magnitude greater than that reported for the culture grown in Erlenmeyer flasks.
E‐Waste Based V2O5/RGO/Pt Nanocomposite for Photocatalytic Degradation of Oxytetracycline
Authors: Mohan Harshavardhan , Selvaraj Dhanakumar , Kuppusamy Shanthi , Venkatachalam Janaki , Park Yool‐Jin , Seralathan Kamala‐Kannan , Oh Byung‐Taek
Published: December 2018

The increasing prevalence of antibiotics in the environment has promoted the development of antibiotic resistant microorganisms, and novel approaches are needed to effectively remove antibiotics from water and mitigate this worldwide problem. A reduced graphene oxide‐V2O5 (RGOV) nanocomposite was synthesized and used for photocatalytic degradation of the antibiotic oxytetracycline (OTC) in aqueous solution. The Sol–Gel method was employed for V2O5 synthesis from e‐waste‐based vanadium nitrate, and a one pot solvothermal method was used to synthesize RGOV. Fourier‐transform infrared spectroscopy (FTIR), X‐ray diffraction spectroscopy (XRD), transmission electron microscopy (TEM) with energy dispersive analysis of X‐rays (EDAX) confirmed V‐O‐C bonds on the surface of the RGOV nanocomposites. A decrease in the band gap of V2O5 from 2.21 to 2.13 eV was supported by diffuse reflectance ultraviolet–visible spectrophotometry. OTC adsorption onto the nanocomposite increased with an increase in RGO concentration and saturated at 17% for RGOV with 30% graphene oxide. The composite degraded 90% of the OTC present in aqueous solution (50 mg/L). Platinum (1%) doping further increased OTC degradation by the nanocomposite to 98.7%. Optimum conditions for maximum OTC degradation are (1) an initial OTC concentration of 50 mg/L, (2) a RGOV nanocomposite dose of 0.5 g/L, and (3) a 40 min incubation time. Our results support the potential use of RGOV nanocomposite for OTC photodegradation. © 2018 American Institute of Chemical Engineers Environ Prog, 38:e13123, 2019
On the number of records for structural risk estimation in PBEE
Authors: Baltzopoulos Georgios , Baraschino Roberto , Iervolino Iunio
Published: December 2018

Response‐history nonlinear dynamic analysis is an analytical tool that often sees use in risk‐oriented earthquake engineering applications. In the context of performance‐based earthquake engineering, dynamic analysis serves to obtain a probabilistic description of seismic structural vulnerability. This typically involves subjecting a nonlinear numerical computer model to a set of ground‐motions that represent a sample of possible realizations of base acceleration at the site of interest. The analysis results are then used to calibrate a stochastic model that describes structural response as a function of shaking intensity. The sample size of the ground‐motion record set is nowadays usually governed by computation‐demand constraints, yet it directly affects the uncertainty in estimation of seismic response. The present study uses analytical and numerical means to investigate the record sample size, n, required to achieve quantifiable levels of mean relative estimation error on seismic risk metrics. Regression‐based cloud analysis in the context of Cornell's reliability method and incremental dynamic analysis using various intensity measures were employed to derive a relation of the form
, where Δ is a parameter that depends on both the dispersion of structural responses and the shape of the hazard curve at the site. For the cases examined, n can be kept in the 40 to 100 range and achieve 10% mean relative error. The study can contribute to guide engineers towards an informed a‐priori assessment of the number of records needed to achieve a desired value for the coefficient of variation of the estimator of structural seismic risk.
Behavior of I4σ(4c–6e) in tellurolane system and related species, elucidated by QTAIM dual functional analysis with QC calculations
Authors: Hayashi Satoko , Nishide Taro , Nakanishi Waro
Published: December 2018

The nature of theAI‐*‐AI andAI‐*‐BI interactions inBI‐*‐AI‐*‐AI‐*‐BI of I4σ(4c–6e) in the tellurolane system, C4H8(I)Te–I···I–I···I–Te(I)C4H8(1), and the models is elucidated with QTAIM dual functional analysis (QTAIM‐DFA). Asterisks (*) are employed to emphasize the existence of bond critical points (BCPs) on the interactions in question. Data from the fully optimized structures correspond to the static nature. Data from the perturbed structures around the fully optimized ones with the fully optimized structures represent the dynamic nature of interactions in QTAIM‐DFA. TheAI‐*‐AI andAI‐*‐BI interactions in the optimized structure of1(Ci)calcdare predicted to have the Cov‐w (weak covalent) nature appeared in the shared shell region and thet‐HBwc(typical hydrogen bonds with covalency) nature appeared in the regular closed shell (r‐CS) region, respectively. However, bothAI‐*‐AI andAI‐*‐BI interactions in the observed structure in crystals (1(Ci)obsd) appear in ther‐CS region. The isolated structure of only one molecule in vacuum for1(Ci)calcdvs that surrounded by the same molecules for1(Ci)obsdarises the different results. The nature ofAI‐*‐AI andAI‐*‐BI inBI‐*‐AI‐*‐AI‐*‐BI of I4σ(4c–6e) for the models is similarly analyzed.
Synthesis of novel fluorous pyridinium ionic liquids
Authors: Honda Mitsunori , Ashizawa Kohei , Kunimoto Ko‐Ki , Segi Masahito
Published: December 2018

The synthesis of a novel class of fluorous ionic liquids was investigated. The 2,6‐diperfluoroalkyl‐substituted pyridinium salts 2b‐f were solids at ambient temperature and insoluble in perfluoromethylcyclohexane. The addition of much further fluorous alkyl group to nitrogen atom of 2,6‐disubstituted pyridines 1 did not proceed to afford the pyridinium salts 3 having two or three perfluoroalkyl groups. On the other hand, the reaction of 3,5‐diperfluoroalkyl‐substituted pyridine 4 with perfluoroalkyl iodide proceeded to give N‐perfluoroalkylpyridinium salts 6a and 7a in good yields. Furthermore, the addition of tris(perfluoroalkyl)silylpropyl iodide afforded the corresponding pyridinium salt 8a excellently. The anion exchange of the resulting iodides gave the ionic liquids with high fluorophilicity.
Vitamin E: Regulatory Role on Signal Transduction
Authors: Zingg Jean‐Marc
Published: December 2018

Vitamin E modulates signal transduction pathways by several molecular mechanisms. As a hydrophobic molecule located mainly in membranes it contributes together with other lipids to the physical and structural characteristics such as membrane stability, curvature, fluidity, and the organization into microdomains (lipid rafts). By acting as the main lipid‐soluble antioxidant, it protects other lipids such as mono‐ and poly‐unsaturated fatty acids (MUFA and PUFA, respectively) against chemical reactions with reactive oxygen and nitrogen species (ROS and RNS, respectively) and prevents membrane destabilization and cellular dysfunction. In cells, vitamin E affects signaling in redox‐dependent and redox‐independent molecular mechanisms by influencing the activity of enzymes and receptors involved in modulating specific signal transduction and gene expression pathways. By protecting and preventing depletion of MUFA and PUFA it indirectly enables regulatory effects that are mediated by the numerous lipid mediators derived from these lipids. In recent years, some vitamin E metabolites have been observed to affect signal transduction and gene expression and their relevance for the regulatory function of vitamin E is beginning to be elucidated. In particular, the modulation of the CD36/FAT scavenger receptor/fatty acids transporter by vitamin E may influence many cellular signaling pathways relevant for lipid homeostasis, inflammation, survival/apoptosis, angiogenesis, tumorigenesis, neurodegeneration, and senescence. Thus, vitamin E has an important role in modulating signal transduction and gene expression pathways relevant for its uptake, distribution, metabolism, and molecular action that when impaired affect physiological and patho‐physiological cellular functions relevant for the prevention of a number of diseases. © 2018 IUBMB Life, 71(4):456–478, 2019
Rapid endothelialization and controlled smooth muscle regeneration by electrospun heparin‐loaded polycaprolactone/gelatin hybrid vascular grafts
Authors: Shi Jie , Chen Siyuan , Wang Lina , Zhang Xiangyun , Gao Jingchen , Jiang Li , Tang Di , Zhang Lin , Midgley Adam , Kong Deling , Wang Shufang
Published: December 2018

The bioinert characteristic of polycaprolactone (PCL) remains a major defect when using PCL‐based materials as small‐diameter vascular grafts for implantation in vivo. To improve the hydrophilicity, cytocompatibility, and biodegradation of PCL vascular grafts, we constructed hybrid vascular grafts from electrospun PCL/gelatin. The PCL/gelatin hybrid vascular graft was further functionalized with the addition of heparin, to improve hemocompatibility. This study investigated the performance of heparin‐loaded PCL/gelatin hybrid vascular grafts in vivo. Our results showed that the combination of gelatin and PCL was an effective approach to overcome each individual component's shortcomings, in the context of vascular graft generation. Furthermore, by loading heparin onto the grafts, thrombosis, which could be otherwise induced by gelatin, was prevented. Overall, our electrospun heparin‐loaded PCL/gelatin vascular grafts promoted endothelialization and regulated smooth muscle regeneration. The data presented here show PCL/gelatin and heparin‐loaded vascular grafts as an effective biomaterial candidate for the generation of artificial small‐diameter vascular grafts. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2040–2049, 2019.
Long noncoding RNA MEG3 inhibits breast cancer growth via upregulating endoplasmic reticulum stress and activating NF‐κB and p53
Authors: Zhang Yan , Wu Jiang , Jing Hong , Huang Gui , Sun Zhulei , Xu Shouming
Published: December 2018

Long noncoding RNA (lncRNA) maternally expressed 3 (MEG3) has been implicated as a tumor suppressor gene in several human cancer types. However, little is known regarding its involvement and potential mechanism in human breast cancer. In this study, we explored the effect of MEG3 on the growth of human breast cancer cell line MDA‐MB‐231 in vitro and in vivo, and sought to elucidate the potential signaling mechanisms. Ectopic overexpression of MEG3 using a lentiviral vector Lv‐MEG3 significantly inhibited breast cancer cell growth in vitro and a cancer xenograft growth in vivo. MEG3 overexpression led to marked increase of apoptosis in breast cancer cells as determined using flow cytometry and fragmented DNA labeling. Moreover, ectopic expression of MEG3 increased the expression of endoplasmic reticulum (ER) stress–related proteins required for unfolded protein response, including glucose‐regulated protein 78 (GRP78), inositol‐requiring enzyme 1 (IRE1), protein kinase RNA (PKR)‐like ER kinase (PERK), and activated transcription factor 6 (ATF6), as well as proapoptotic proteins CCAAT/enhancer binding protein homologous protein (CHOP) and caspase‐3. Finally, MEG3 overexpression markedly increased nuclear factor κB (NF‐κB) expression, NF‐κB translocation to the nucleus, and p53 expression, whereas pharmacological inhibition of NF‐κB completely abolished MEG3‐induced activation of p53. Together, these results suggest that MEG3 inhibits breast cancer growth and induces breast cancer apoptosis, partially via the activation of the ER stress, NF‐κB and p53 pathways, and that NF‐κB signaling is required for MEG3‐induced p53 activation in breast cancer cells. Our results indicate targeting lncRNA MEG3 may represent a novel strategy for breast cancer therapy.
HSP90 inhibitor 17‐AAG prevents apoptosis of cardiomyocytes via miR‐93–dependent mitigation of endoplasmic reticulum stress
Authors: Guo Jingjing , Li Shengnan , Li Yanming , Yan Chenyun , Wan Qilin , Wang Zhizhong
Published: December 2018

Heart failure accounts for substantial morbidity and mortality worldwide. Accumulating evidence suggests that aberrant cardiac cell death caused by endoplasmic reticulum stress (ERS) is often associated with structural or functional cardiac abnormalities that lead to insufficient cardiac output. The detailed molecular mechanism underlying the pathological death of cardiomyocytes still remains poorly understood. We found that 17‐AAG (tanespimycin), an HSP90 (heat shock protein 90) inhibitor often used to kill cancer cells, could potently inhibit tunicamycin‐induced ERS and the downstream nuclear factor kappa B activity in neonatal rat cardiomyocytes, leading to diminished apoptotic signaling and thus enhanced cell survival. Interestingly, the antiapoptotic effect of 17‐AAG on cardiomyocytes required normal expression of miR‐93, an oncogenic microRNA known to promote cell survival and growth. Our study implicated a new pharmacological role of 17‐AAG in supporting the miR‐93–associated oncogenic signaling to prevent the pathological death of cardiomyocytes. The results opened opportunities for exploring new strategies in the development of therapeutic agents.
MEG3 affects the progression and chemoresistance of T‐cell lymphoblastic lymphoma by suppressing epithelial‐mesenchymal transition via the PI3K/mTOR pathway
Authors: Deng Rui , Fan Fang‐Yi , Yi Hai , Liu Fang , He Guang‐Cui , Sun Hao‐Ping , Su Yi
Published: December 2018

Long noncoding RNAs (lncRNA) are emerging as integral functional and regulatory components in the development of different diseases including cancer. Maternally expressed gene 3 (MEG3), is a lncRNA, that has a depressed expression in multiple tumor types, including T‐cell lymphoblastic lymphoma (T‐LBL). However, the molecular mechanisms that regulate the tumorigenic functions of MEG3 in T‐LBL remain largely unknown. In this study, we aimed to discover and identify the function of MEG3 in T‐LBL tumorigenesis, epithelial‐mesenchymal transition (EMT) and drug resistance, and explore their mechanisms of action. Knockdown MEG3 promoted the proliferation, migration, invasion, and drug resistance of T‐LBL cells while overexpression of MEG3 gets the opposite results. The mechanism study showed that decreased MEG3 expression in T‐LBL cells could activate PI3K/mTOR signaling pathways, increase the expression of p‐glycoprotein and affect the expression of EMT markers for transforming to mesenchymal cells in vitro and in vivo. Together, these results indicate that MEG3 could inhibit the migration, invasion, and drug resistance in T‐LBL cells by suppression of the PI3K/mTOR pathway. MEG3 might be a potential target, through which poor prognosis with high recurrence and drug resistance of T‐LBL in a clinical setting could be reversed.
Clinical observation of the reduced glutathione in the treatment of diabetic chronic kidney disease
Authors: Zuo Man‐hua , Tang Jun , Xiang Miao‐miao , Long Qing , Dai Jian‐ping , Yu Guo‐dan , Zhang Hua‐guo , Hu Hui
Published: December 2018

Background

Diabetic chronic kidney disease (CKD) has become the main cause of death in diabetic patients, but its pathogenesis has not yet been clear.

Objective

To investigate the effects of reduced glutathione (GSH) on oxidative stress (OS), angiogenesis factors and lymphocyte subsets in diabetic CKD patients.

Methods

A total of 130 subjects were retrospectively studied. The subjects were divided into the control group (45 cases), treatment group (45 cases, treated with reduced GSH), and a healthy control group (40 cases). The levels of superoxide dismutase (SOD), advanced oxidation protein products (AOPP), malondialdehyde (MDA), endostatin (ES), and vascular endothelial growth factor (VEGF), and the percentages of lymphocyte subsets were detected.

Results

After treatment, the indexes of OS and angiogenesis and the percentage of CD3−CD19+B cells were obviously decreased, and the percentages of T cell subsets and natural killer (NK) cell subsets were markedly increased in the treatment group compared with the control group. AOPP was positively correlated with angiogenesis indexes, MDA and CD3−CD19+B cells, and negatively correlated with SOD and other lymphocyte subsets. SOD was inversely associated with angiogenesis indexes and MDA, and positively associated with lymphocyte subsets. Moreover, MDA had a positive correlation with angiogenesis indexes, B and T cell subsets, and a negative correlation with NK cell subsets. AOPP, MDA, SOD, VEGF, CD3+T cells, CD3+CD8+T cells, CD3−CDl6+CD56+NK cells, and CD3−CDl6+CD56+NK T cells were the risk factors of diabetic CKD.

Conclusion

GSH could inhibit OS and abnormal angiogenesis, and improve cellular immune response in CKD patients.
An 11‐gene‐based prognostic signature for uveal melanoma metastasis based on gene expression and DNA methylation profile
Authors: Li Yang , Yang Xuan , Yang Jingyan , Wang Heng , Wei Wenbin
Published: December 2018

Uveal melanoma (UM) is the most common intraocular tumor worldwide. We proposed to identify a vital gene signature that has prognostic value for UM metastasis. For this purpose, we obtained a published DNA methylation and gene expression data set associated with UM from the Gene Expression Omnibus. The genes whose aberrant expression significantly associated with UM patients’ metastasis‐free survival (MFS) were identified by applying a univariate Cox proportional hazards model to the gene expression data set followed by a robust likelihood‐based survival analysis to screen the optimal prognostic gene signatures (PGS). A formula for calculating the risk score that represents UM metastasis risk was constructed by including the PGSs’ expression values weighted by their regression coefficients, which were obtained by a multivariate Cox regression analysis. As a result, aberrant expression of 2884 genes were found to be significantly associated with UM patients’ MFS, which were referred to as MFSGs, and 11 out of those MFSGs, GJC1, TCEA1, MFSD3, FAF2, TLCD1, GPAA1, CYC1, ASAP1, JPH1, LDB3, and KDELR3, were identified as PGSs through which we could accurately separate UM samples with shorter MFS from those with longer MFS. By combining the DNA methylation data set and MFSGs, we further identified 265 MFSGs, which contained CpG sites that significantly hyper‐ or hypo‐methylated in UM samples compared with control samples. Functional enrichment analysis and pathway crosstalk analysis of those genes indicated significant enrichment of cancer‐related pathways. In conclusion, we identified an 11‐gene‐based prognostic signature and several gene biomarkers for UM metastasis, which should be helpful for selecting an appropriate treatment method for specific patients with UM.
Downregulation of lnRNA‐NEF is involved in the postoperative cancer distant recurrence in prostate carcinoma patients
Authors: Wan Xiaodong , Xiang Jun , Zhang Qimin , Bian Cuidong
Published: December 2018

LnRNA‐NEF has characterized functionality only in liver cancer. In the present study, we observed that plasma lnRNA‐NEF was downregulated, while plasma transforming growth factor‐β1 (TGF‐β1) was upregulated in patients with early‐stage prostate carcinoma (PC) than in healthy controls. The levels of plasma lnRNA‐NEF and plasma TGF‐β1 were inversely correlated in patients with PC but not in healthy controls. After surgical resection, the follow‐up was performed for 5 years. It was observed that lnRNA‐NEF was further decreased in patients with distant recurrence (DR), but not in patients with local recurrence and nonrecurrence. lnRNA‐NEF overexpression caused inhibited TGF‐β1 expression in cells of PC cell lines, while TGF‐β1 overexpression failed to affect lnRNA‐NEF expression. LnRNA‐NEF overexpression inhibited, while the TGF‐β1 overexpression promoted the migration and invasion of cells of PC cell lines. TGF‐β1 overexpression partially rescued the inhibited migration and invasion of cells of PC cell lines caused by the lnRNA‐NEF overexpression. Therefore, the downregulation of lnRNA‐NEF may contribute to the postoperative DR in patients with PC through the interactions with TGF‐β1.
Promising immunotherapy: Highlighting cytokine‐induced killer cells
Authors: Shirjang Solmaz , Alizadeh Nazila , Mansoori Behzad , Mahmoodpoor Ata , Kafil Hossein Samadi , Hojjat‐Farsangi Mohammad , Yousefi Mehdi
Published: December 2018

For many years, cancer therapy has appeared to be a challenging issue for researchers and physicians. By the introduction of novel methods in immunotherapy, the prospect of cancer therapy even more explained than before. Cytokine‐induced killer (CIK) cell‐based immunotherapy demonstrated to have potentiality in improving clinical outcomes and relieving major side effects of standard treatment options. In addition, given the distinctive features such as high safety, low toxicity effects on healthy cells, numerous clinical trials conducted on CIK cells. Due to the shortcomings that observed in CIK cell immunotherapy alone, arising a tendency to make modifications (combined modality therapy or combination therapy) including the addition of various types of cytokines, genetic engineering, combination with immune checkpoints, and so on. In this review, we have tried to bring forth the latest immunotherapy methods and their overview. We have discussed the combination therapies with CIK cells and the conducted clinical trials. This helps the future studies to use integrated therapies with CIK cells as a promising treatment of many types of cancers.
Prognostic factors of budesonide therapy for the management of Crohn’s disease: A meta‐analysis
Authors: Li Yajun , Meng Xiangwei , Duan Xiumei , Tang Tongyu , He Chuan , Li Yuqin
Published: December 2018

Background

This study aimed to identify factors that affect the prognosis of budesonide therapy for Crohn’s disease patients.

Method

Change in Crohn’s disease activity index (CDAI) scores at latest follow‐up after budesonide therapy reported by individual studies were pooled to gain overall effect size under random effects model and then metaregression analyses were performed to identify factors affecting the change in CDAI scores after budesonide treatment.

Results

Fifteen studies (1875 patients; age, 35.6 years [95% confidence interval (CI): 34.1, 37.0]; 41.66% [95% CI: 37.44, 45.88] males; 33.3% [95% CI: 24.3, 42.3] smokers; weight, 64.7 kg [95% CI: 62.71 66.6] and height, 168 cm [95% CI: 165, 171]) were included. Disease duration was 7.0 years [95% CI: 5.7, 8.2] and duration of the current episode was 3.1 months [95% CI: 1.7, 4.4]. Proportion of patients with prior resection was 42% [95% CI: 34%, 50%]. The disease was 21% in the ileum, 61% in ileocecum, and 18% in the colon. Budesonide dose was 8.83 mg/d [95% CI: 7.52, 10.14]. In a follow‐up duration of 21.0 weeks [95% CI: 15.2, 26.8], budesonide treatment was associated with improvement in CDAI score of −117.8 [95% CI: −134.0, −102.0]. The magnitude of the change in CDAI score at the latest follow‐up was significantly inversely associated with the percentage of smokers, but positively associated with the baseline CDAI score and duration of the current episode.

Conclusion

Budesonide therapy to Crohn’s disease patients appears to be more effective in patients with the more serious condition. Smoking may also affect the prognosis.
Molecular mechanisms, prevalence, and molecular methods for familial combined hyperlipidemia disease: A review
Authors: Taghizadeh Eskandar , Mardani Rajab , Rostami Daryoush , Taghizadeh Hassan , Bazireh Homa , Hayat Seyed Mohammad Gheibi
Published: December 2018

Familial combined hyperlipidemia (FCHL) is the most common genetic dyslipidemia disorder which is accompanied by increasing of triglyceride and cholesterol. This disorder is a complex genetic disease although it also has monogenic forms. The familial form has several criteria for diagnosis that can be distinguished of nonfamilial position. It has been shown that a variety of internal and external risk factors are involved in the pathogenesis of FCHL. Environmental factors and the genetic background also play an important role in the FCHL pathogenesis. Many mechanisms and pathways are involved in lipid metabolism (ie, dysfunctional adipose tissue, hepatic fat and very low‐density lipoprotein overproduction, triglyceride‐rich lipoproteins, and clearance of low‐density lipoprotein particles) that could lead to FCHL. Individuals with a positive family history like those who have a positive family history of cardiovascular diseases are more predispositions for this disorder. To date several methods have been used to identify the genetic background of the FCHL. In the current review, we summarized the prevalence and the molecular mechanisms involved in the FCHL disease. Moreover, we highlighted the used molecular methods for determining the genes involved in the FCHL.
lncRNA A1BG‐AS1 suppresses proliferation and invasion of hepatocellular carcinoma cells by targeting miR‐216a‐5p
Authors: Bai Jigang , Yao Bowen , Wang Liang , Sun Liankang , Chen Tianxiang , Liu Runkun , Yin Guozhi , Xu Qiuran , Yang Wei
Published: December 2018

Extensive evidence indicate that long noncoding RNAs (lncRNAs) regulates the tumorigenesis and progression of hepatocellular carcinoma (HCC). However, the expression and biological function of lncRNA A1BG antisense RNA 1 (A1BG‐AS1) were poorly known in HCC. Here, we found the underexpression of A1BG‐AS1 in HCC via analysis of The Cancer Genome Atlas database. Further analyses confirmed that A1BG‐AS1 expression in HCC was markedly lower than that in noncancerous tissues based on our HCC cohort. Clinical association analysis revealed that low A1BG‐AS1 expression correlated with poor prognostic features, such as microvascular invasion, high tumor grade, and advanced tumor stage. Follow‐up data indicated that low A1BG‐AS1 level evidently correlated with poor clinical outcomes of HCC patients. Moreover, forced expression of A1BG‐AS1 repressed proliferation, migration, and invasion of HCC cells in vitro. Conversely, A1BG‐AS1 knockdown promoted these malignant behaviors in HepG2 cells. Mechanistically, A1BG‐AS1 functioned as a competing endogenous RNA by directly sponging miR‐216a‐5p in HCC cells. Notably, miR‐216a‐5p restoration rescued A1BG‐AS1 attenuated proliferation, migration and invasion of HCCLM3 cells. A1BG‐AS1 positively regulated the levels of phosphatase and tensin homolog and SMAD family member 7, which were reduced by miR‐216a‐5p in HCC cells. Altogether, we conclude that A1BG‐AS1 exerts a tumor suppressive role in HCC progression.
WISP1 silencing confers protection against epithelial–mesenchymal transition of renal tubular epithelial cells in rats via inactivation of the wnt/β‐catenin signaling pathway in uremia
Authors: Chen Yuan‐Zhen , Sun Dan‐Qin , Zheng Yi , Zheng Guang‐Kuai , Chen Rong‐Quan , Lin Mei , Huang Lian‐Fang , Huang Cong , Song Dan , Wu Ben‐Qing
Published: December 2018

Uremia can affect hepatic metabolism of drugs by regulating the clearance of drugs, but it has not been clarified whether gene silencing could modulate the epithelial–mesenchymal transition (EMT) process in uremia. Hence, we investigated the effect of WISP1 gene silencing on the renal tubular EMT in uremia through the wnt/β‐catenin signaling pathway. Initially, microarray‐based gene expression profiling of uremia was used to identify differentially expressed genes. Following the establishment of uremia rat model, serum creatinine, and urea nitrogen of rats were detected. Renal tubular epithelial cells (TECs) were transfected with shRNA‐WISP1 lentivirus interference vectors and LiCI (the wnt/β‐catenin signaling pathway activator) to explore the regulatory mechanism of WISP1 in uremia in relation to the wnt/β‐catenin signaling pathway. Then, expression of WISP1, wnt2b, E‐cadherin, α‐SMA, c‐myc, Cyclin D1, MMP‐2, and MMP‐9 was determined. Furthermore, TEC migration and invasion were evaluated. Results suggested that WISP1 and the wnt/β‐catenin signaling pathway were associated with uremia. Uremic rats exhibited increased serum creatinine and urea nitrogen levels, upregulated WISPl, and activated wnt/β‐catenin signaling pathway. Subsequently, WISP1 silencing decreased wnt2b, c‐myc, Cyclin D1, α‐SMA, MMP‐2, and MMP‐9 expression but increased E‐cadherin expression, whereas LiCI treatment exhibited the opposite trends. In addition, WISP1 silencing suppressed TEC migration and invasion, whereas LiCI treatment promoted TEC migration and invasion. The findings indicate that
WISP1 gene silencing suppresses the activation of the wnt/β‐catenin signaling pathway, thus reducing EMT of renal TECs in uremic rats.
microRNA‐338‐3p promotes ox‐LDL‐induced endothelial cell injury through targeting BAMBI and activating TGF‐β/Smad pathway
Authors: Yin Jian , Hou Xuhui , Yang Songbai
Published: December 2018

microRNAs (miRNAs) have been revealed to participate in the pathological process of atherosclerosis (AS). However, the exact role of miR‐338‐3p, a target miRNA of BMP and activin membrane‐bound inhibitor (BAMBI), and its possible molecular mechanism in AS remain unidentified. In this study, we found that BAMBI was significantly decreased, whereas miR‐338‐3p increased in patients with AS and oxidized low‐density lipoprotein (ox‐LDL)‐induced HUVEC cells. Furthermore, overexpression of miR‐338‐3p significantly decreased cell viability and elevated cell apoptosis, whereas its inhibition significantly promoted cell viability and inhibited cell apoptosis in ox‐LDL‐induced HUVEC cells. Moreover, miR‐338‐3p overexpression increased TGF‐β/Smad pathway activation in ox‐LDL‐induced HUVEC cells. A dual‐luciferase reporter assay confirmed the direct interaction between miR‐338‐3p and the 3′‐untranslated region of BAMBI messenger RNA. Furthermore, the suppression of BAMBI ameliorated the effect of miR‐338‐3p inhibition against ox‐LDL‐induced HUVEC cell injury. In conclusion, our study thus suggests that miR‐338‐3p promoted ox‐LDL‐induced HUVEC cell injury by targeting BAMBI and activating the TGF‐β/Smad pathway, which may provide a novel and promising therapeutic target for AS.
Identification of LINC01615 as potential metastasis‐related long noncoding RNA in hepatocellular carcinoma
Authors: Ji Dong , Chen Guo‐Feng , Liu Xiaoliu , Zhu Jing , Sun Jin‐Yu , Zhang Xiao‐Yu , Lu Xiao‐Jie
Published: December 2018

Hepatocellular carcinoma is one of the most prevalent and fatal cancers. Studying the long noncoding RNA (lncRNA) alterations in hepatocellular carcinoma may lead to new therapeutic strategies. We checked whether there were correlations between The Cancer Genome Atlas expression profiles of the differentially expressed lncRNAs and their DNA methylation status or the copy number variations for hepatocellular carcinoma. We obtained 41 lncRNAs that were differentially expressed between tumor and normal samples, and their DNA methylation status was negatively correlated with the expression levels. We identified five lncRNAs that were recurrently amplified or deleted in tumor samples, but none of them were associated with the messenger RNA (mRNA) expression levels. To obtain the biological function of these lncRNAs, the coexpressed mRNAs in the hepatocellular carcinoma were figured out. A total of 10 lncRNAs were highly correlated with at least one gene. Six out of the ten lncRNAs were already known to be related with cancer previously. LINC01615 had 72 coexpressed genes, and we carried out the gene ontology (GO) term enrichment for these protein‐coding genes. The results suggested that these lncRNAs were associated with extracellular matrix organization. To summarize, we identified 41 potentially cancer‐related lncRNAs. In particular, we proposed that LINC01615 potentially affected the extracellular matrix and had further impacts on the metastasis of hepatocellular carcinoma.
Integration of metabolomic and transcriptomic data reveals metabolic pathway alteration in breast cancer and impact of related signature on survival
Authors: Luo Xiao , Yu Hong , Song Yan , Sun Tong
Published: December 2018

Objective

Breast cancer (BC) is a malignant tumor which threat to women's physical and mental health. However, the mechanism of metabolism alteration in BC remains unclear. This study is intended to figure out the relationship between the alternation of metabolism and the progression of BC.

Methods

In this study, metabolites of plasma in 60 BC patients and 40 healthy volunteers were detected using liquid chromatography mass spectrometer (LC‐MS). Transcriptomic data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Kyoto Encyclopedia of Genes and Genomes (KEGG) database was performed to enrich the pathways.

Results

A total of 97 metabolites have been identified and measured, of which 17 compounds exhibited the differential expression between tumor group and control group (p < 0.05; FDR < 0.05). Metabolites set enrichment analysis (MSEA) displayed that there were 12 significantly enriched pathways in all. Through the KEGG database, 382 genes were found closely correlated with the altered metabolic pathways. TCGA and GEO transcriptomic profiling revealed that 5,018 genes significantly changed between tumor group and control group. Integrating these genes with the transcriptomic data from the corresponding KEGG data set, we identified most of the differential expressed genes were related to purine metabolism. A total of 28 different expression genes were hub genes, wherein AMPD1 and RRM2 were significantly effective in the prediction of survival of BC patients, with 0.04 and 0.02, respectively.

Conclusions

Combining with the transcriptomic and metabolomics data, we found that the dysregulation of purine metabolism pathway might affect the progression of BC.
Fabrication of plumbagin on silver nanoframework for tunable redox modulation: Implications for therapeutic angiogenesis
Authors: Duraipandy Natarajan , Dharunya Govindarajan , Lakra Rachita , Korapatti Purna Sai , Syamala Kiran Manikantan
Published: December 2018

The redox state of the endothelial cells plays a key role in the regulation of the angiogenic process. The modulation of the redox state of endothelial cells (ECs) could be a viable target to alter angiogenic response. In the present work, we synthesized a redox modulator by caging 5‐hydroxy 2‐methyl 1, 4‐napthoquinone (Plumbagin) on silver nano framework (PCSN) for tunable reactive oxygen species (ROS) inductive property and tested its role in ECs during angiogenic response in physiological and stimulated conditions. In physiological conditions, the redox modulators induced the angiogenic response by establishing ECs cell–cell contact in tube formation model, chorio allontoic membrane, and aortic ring model. The molecular mechanism of angiogenic response was induced by vascular endothelial growth factor receptor 2 (VEGFR2)/p42‐mitogen‐activated protein kinase signaling pathway. Under stimulation, by mimicking tumor angiogenic conditions it induced cytotoxicity by generation of excessive ROS and inhibited the angiogenic response by the loss of spatiotemporal regulation of matrix metalloproteases, which prevents the tubular network formation in ECs and poly‐ADP ribose modification of VEGF. The mechanism of opposing effects of PCSN was due to modulation of PKM2 enzyme activity, which increased the EC sensitivity to ROS and inhibited EC survival in stimulated condition. In normal conditions, the endogenous reactive states of NOX4 enzyme helped the EC survival. The results indicated that a threshold ROS level exists in ECs that promote angiogenesis and any significant enhancement in its level by redox modulator inhibits angiogenesis. The study provides the cues for the development of redox‐based therapeutic molecules to cure the disease‐associated aberrant angiogenesis.
Chrysanthemulide A induces apoptosis through DR5 upregulation via JNK‐mediated autophagosome accumulation in human osteosarcoma cells
Authors: Zhuo Fang‐Fang , Zhang Chao , Zhang Hao , Xia Yuanzheng , Xue Gui‐Min , Yang Lei , Kong Ling‐Yi
Published: December 2018

Osteosarcoma is the most frequent malignant primary bone tumor, and it generally develops a multidrug resistance. Chrysanthemulide A (CA) is a sesquiterpenoid from the herb Chrysanthemum indicum that has demonstrated a great anti‐osteosarcoma potential. In this study, CA‐induced apoptotic cell death resulted in the activation of the caspase‐8‐mediated caspase cascade, as evidenced by the cleavage of the substrate protein Bid and the caspase‐8 inhibitor Z‐VAD‐FMK. The CA treatment upregulated the expression of death receptor 5 (DR5) in both whole cells and the cell membrane. Blocking DR5 expression by the small interfering RNA (siRNA) treatment decreased the caspase‐8‐mediated caspase cascade and efficiently attenuated CA‐induced apoptosis, suggesting the critical role of DR5 in CA‐induced apoptotic cell death. CA‐induced upregulation of the DR5 protein was accompanied by the accumulation of LC3B‐II, indicating the formation of autophagosomes. Importantly, DR5 upregulation was mediated by transcriptionally controlled autophagosome accumulation, as blockade of autophagosomes by LC3B or ATG‐5 siRNA substantially decreased DR5 upregulation. Furthermore, CA activated the c‐Jun N‐terminal kinase (JNK) signaling pathway, and treatment with JNK siRNAs or inhibitor SP600125 significantly attenuated CA‐mediated autophagosome accumulation and DR5‐mediated cell apoptosis. Finally, CA sensitized the osteosarcoma cells to the DR5 ligand tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)‐induced apoptotic cell death. Above all, these results suggest that CA induces apoptosis through upregulating DR5 via JNK‐mediated autophagosome accumulation and that combined treatment with CA and TRAIL might be a promising therapy for osteosarcoma.
Extending partial representations of circle graphs
Authors: Chaplick Steven , Fulek Radoslav , Klavík Pavel
Published: December 2018

The partial representation extension problem is a recently introduced generalization of the recognition problem. A circle graph is an intersection graph of chords of a circle. We study the partial representation extension problem for circle graphs, where the input consists of a graph and a partial representation giving some predrawn chords that represent an induced subgraph of . The question is whether one can extend to a representation of the entire graph , that is, whether one can draw the remaining chords into a partially predrawn representation to obtain a representation of . Our main result is an time algorithm for partial representation extension of circle graphs, where is the number of vertices. To show this, we describe the structure of all representations of a circle graph using split decomposition. This can be of independent interest.
Loss of NFAT2 expression results in the acceleration of clonal evolution in chronic lymphocytic leukemia
Authors: Müller David J , Wirths Stefan , Fuchs Alexander R , Märklin Melanie , Heitmann Jonas S , Sturm Marc , Haap Michael , Kirschniak Andreas , Sasaki Yoshiteru , Kanz Lothar , Kopp Hans-Georg , Müller Martin R
Published: December 2018

Chronic lymphocytic leukemia (CLL) can be defined as a clonal expansion of B cells with stereotypic BCRs. Somatic hypermutation of the BCR heavy chains (IGVH) defines a subgroup of patients with a better prognosis. In up to 10% of CLL cases, a transformation to an aggressive B cell lymphoma (Richter’s syndrome) with a dismal prognosis can be observed over time. NFAT proteins are transcription factors originally identified in T cells, which also play an important role in B cells. The TCL1 transgenic mouse is a well-accepted model of CLL. Upon B cell-specific deletion of NFAT2, TCL1 transgenic mice develop a disease resembling human Richter’s syndrome. Whereas TCL1 B cells exhibit tonic anergic BCR signaling characteristic of human CLL, loss of NFAT2 expression leads to readily activated BCRs indicating different BCR usage with altered downstream signaling. Here, we analyzed BCR usage in wild-type and TCL1 transgenic mice with and without NFAT2 deletion employing conventional molecular biology techniques and next-generation sequencing (NGS). We demonstrate that the loss of NFAT2 in CLL precipitates the selection of unmutated BCRs and the preferential usage of certain VDJ recombinations, which subsequently results in the accelerated development of oligoclonal disease.