bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tannic acid modulates fibroblast proliferation and differentiation in response to pro‐fibrotic stimuli
Authors: Pattarayan Dhamotharan , Sivanantham Ayyanar , Bethunaickan Ramalingam , Palanichamy Rajaguru , Rajasekaran Subbiah 
Published: April 2018

AbstractIn response to tissue injury, fibroblasts migrate into the wound, where they undergo proliferation and differentiation. The persistence of these differentiated fibroblasts (myofibroblasts) is associated with excessive scarring in various organs. We aimed to investigate the effects of Tannic acid (TA) on fibroblast proliferation and differentiation, and found that TA inhibited fibroblast differentiation as assessed by reduced expression of α‐smooth muscle actin, N‐cadherin, and type‐1‐collagen. TA also prevented the TGF‐β1‐induced alteration in the expression of two classes of genes involved in the remodeling of extracellular matrix (ECM) proteins, namely matrix metalloproteinases (Mmp‐2 and ‐9) and tissue inhibitors of metalloproteinases (Timp‐1 and ‐3). Further, TA suppressed TGF‐β1‐induced cell proliferation and induced cell cycle arrest at G0/G1 phase via targeting Cyclins expression. Finally, TA exerted its inhibitory effects by decreasing the phosphorylation of Smad and ERK signaling. In sum, our results suggesting that TA may be a potential therapeutic agent for pathological fibrosis.
The effect of plant lectins on the survival and malignant behaviors of thyroid cancer cells
Authors: Kaptan Engin , Sancar‐Bas Serap , Sancakli Aylin , Bektas Suna , Bolkent Sehnaz 
Published: April 2018

AbstractAltered or aberrant glycosylation is a common phenomenon in cancer cells and it originates from changes in the expression of the enzymes, glycosyltransferase, and glycosidase which up‐regulate in response to some oncogenes in the glycan synthesis pathway. In this present study, it has been aimed to determine the alteration of sialic acid and fucose expressions in the cell surface of human thyroid carcinoma cells and investigate the changes in tumorigenic and malignant characters after treating them with specific plant lectins. Our study showed that the cell surface glycan chains of anaplastic 8305C, follicular FTC‐133, and papillary K1 thyroid carcinoma cells were rich in α‐2,6, α‐2,3, sialic acid, and α‐1,6 fucose residues. When the cells were treated with specific doses of Maackia amurensis lectin II (MAL), Sambucus nigra agglutinin (SNA), and Aleuria aurantia lectin (AAL) which have specific binding capacity for the detected glycan residues, respectively their cancerous traits changed dramatically. Remarkable findings obtained from MAL treatment leading to necrosis in 8505C cells without any toxicity for normal thyroid epithelial cells but it had proliferative effect on K1 and FCT‐133 cells. Besides, MAL and SNA treatment decreased the mobility of 8505C and K1 cells. MAL and SNA lectins dramatically reduced the endothelial affinity of the cells and AAL significantly attenuated that of 8050C and K1 cells but not FTC‐133. These results suggest that altered cell surface glycosylation in thyroid cancer seems to be a strong candidate for developing new therapeutic strategies.
Retracted: miR‐200c, a tumor suppressor that modulate the expression of cancer stem cells markers and epithelial‐mesenchymal transition in colorectal cancer
Authors: Karimi Dermani Fateme , Amini Razieh , Saidijam Massoud , Najafi Rezvan 
Published: April 2018

AbstractColorectal cancer (CRC) is the most frequently diagnosed cancer and the most common gastrointestinal cancer worldwide. Due to the presence of populations of cancer stem cells (CSCs) that cause recurrence, the possibility of cancer treatment is very low. The aim of current study was to evaluate the inhibitory role of miR‐200c on EMT, CSCs markers and β‐catenin in HCT‐116 and SW48 cell lines. The expression of miR‐200c, EMT‐related genes, CSCs markers, and β‐catenin were quantified by qRT‐PCR. Further, expression of β‐catenin and EMT‐related proteins, and migration were analyzed by Western blot, and migration assay kit, respectively. Spheroid formation assay was used to enrich colorectal CSCs from colorectal cancer cell lines. LNA‐anti‐miR‐200c suppressed the endogenous miR‐200c in transfected cells compared with the control. qRT PCR and Western blot analysis of LNA‐anti‐miR‐200c transfected cells revealed a considerable increase in CSCs markers, vimentin, ZEB‐1, N‐cadherin, and β‐catenin expression, with a concomitant reduction in E‐cadherin expression level. Migration and sphere forming ability of HCT‐116 and SW48 cells increased in transfected cells. The results of current study revealed that downregulation of miR‐200c may be an important factor for the overexpression of CSCs markers and EMT related genes via β‐catenin upregulation in CRC.
Disulfiram/copper targets stem cell‐like ALDH+ population of multiple myeloma by inhibition of ALDH1A1 and Hedgehog pathway
Authors: Jin Na , Zhu Xiaojian , Cheng Fanjun , Zhang Liling 
Published: April 2018

AbstractMultiple myeloma stem cells (MMSCs) have been considered as the major cause resulting in relapse. Eradicating MMSCs may be an effective strategy to improve the outcome of multiple myeloma (MM). Increased activity of aldehyde dehydrogenase (ALDH) has been found in MMSCs, but whether inhibiting ALDH activity can eliminate MMSCs remains unknown. Disulfiram (DS) has been reported as an inhibitor of ALDH, and increasing studies showed it has anti‐cancer effects in a copper (Cu)‐dependent manner. In this study, we isolated ALDH+ cells of MM by Aldefluor assay and demonstrated they possessed tumorigenesis capacities in vitro and in vivo. Next, we investigated the effects of DS with or without Cu on suppressing the stemness of MM both in vitro and in vivo. We found that DS/Cu eliminated the stem cell‐like ALDH+ cells. Furthermore, we demonstrated that DS/Cu inhibited the expression of stem cell transcription factors NANOG and OCT4, and abolished the clonogenicity of MM. We also showed that DS/Cu reduced the tumor growth and inhibited stemness of MM in xenograft model. We further found the specific target of DS/Cu is ALDH1A1 and DS/Cu inhibited the Hedgehog (Hh) pathway transcription factors Gli1 and Gli2 regulated by ALDH1A1 at least in part. Our data suggest that DS/Cu can inhibit the ALDH+ stem cell‐like cells through ALDH1A1 and Hh pathway, which may be a promising therapeutic agent in eradicating stem cell‐like cells of MM.
Knockdown of LncRNA‐UCA1 suppresses chemoresistance of pediatric AML by inhibiting glycolysis through the microRNA‐125a/hexokinase 2 pathway
Authors: Zhang Yuan , Liu Yufeng , Xu Xueju 
Published: April 2018

AbstractDysregulation of lncRNAs is implicated in chemoresistance in varieties of tumor including acute myeloid leukemia (AML). LncRNA urothelial carcinoma‐associated 1 (UCA1) was reported to play an oncogenic role in AML. However, whether UCA1 was involved in chemoresistance in pediatric AML remains unclear. UCA1 expression in AML patients after adriamycin (ADR)‐based chemotherapy and ADR‐resistant AML cells was examined by qRT‐PCR. The effects of UCA1 on the cytotoxicity of ADR and glycolysis were evaluated by MTT assay and measuring the glucose consumption and lactate production in HL60 and HL60/ADR cells, repectively. The protein levels of hypoxia‐inducible factor 1α (HIF‐1α) and hexokinase 2 (HK2) were determined by Western blot. Luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to confirm the relationships between UCA1, HK2, and miR‐125a. We found that UCA1 expression was upregulated following ADR‐based chemotherapy. Knockdown of UCA1 increased the cytotoxic effect of ADR and inhibited HIF‐1α‐dependent glycolysis in ADR‐resistant AML cells. Additionally, UCA1 functioned as a ceRNA of miR‐125a by directly binding to miR‐125a. HK2, a target of miR‐125a, was positively regulated by UCA1 in HL60 and HL60/ADR cells. More notably, UCA1 overexpression overturned miR‐125‐mediated inhibition on HIF‐1α‐dependent glycolysis in HL60 and HL60/ADR cells. Furthermore, 2‐deoxy‐glucose (2‐DG) exposure inhibited HIF‐1α‐dependent glycolysis, and attenuated UCA1‐induced increase of chemoresistance in HL60 and HL60/ADR cells. We conclude that knockdown of UCA1 plays a positive role in overcoming the chemoresistance of pediatric AML, through suppressing glycolysis by the miR‐125a/HK2 pathway, contributing to a better understanding of the molecular mechanism of chemoresistance in AML.
A Novel GJB2 compound heterozygous mutation c.257C>G (p.T86R)/c.176del16 (p.G59A fs*18) causes sensorineural hearing loss in a Chinese family
Authors: Shi Xi , Zhang Yan , Qiu Shiwei , Zhuang Wei , Yuan Na , Sun Tiantian , Gao Jian , Qiao Yuehua , Liu Ke 
Published: April 2018

ObjectiveTo investigate whether a novel compound heterozygous mutations c.257C>G (p.T86R)/c.176del16 (p.G59A fs*18) in GJB2 result in hearing loss.MethodsAllele‐specific PCR‐based universal array (ASPUA) screening and sequence analysis were applied to identify these mutations. 3D model was built to perform molecular dynamics (MD) simulation to verify the susceptibility of the mutations. Furthermore, WT‐ and Mut‐GJB2 DNA fragments, containing the mutation of c.257C>G and c.176del16 were respectively cloned and transfected into HEK293 and spiral ganglion neuron cell (SGNs) by lenti‐virus delivery system to indicate the subcellular localization of the WT‐ and Mut‐CX26 protein.ResultsA novel compound heterozygous mutation c.257C>G (p.T86R)/c.176del16 (p.G59A fs*18) in GJB2 was identified in a Chinese family, in which 4 siblings with profound hearing loss, but the fifth child is normal. By ASPUA screening and sequencing, a compound heterozygote mutations in GJB2 c.257C>G (p.T86R)/c.176del16 (p.G59A fs*18) were identified in these four deaf children, each of the mutated GJB2 gene were inherited from their parents. There is no mutation of GJB2 gene identified in the normal child. Besides, the compound heterozygous mutation GJB2 c.257C>G (p.T86R)/c.176del16 (p.G59A fs*18) could lead to the alterations of the subcellular localization of each corresponding mutated CX26 protein and could cause the hearing loss, which has been predicted by MD simulation and verified in both 293T and SGNs cell line.ConclusionThe c.257C>G (p.T86R)/c.176del16 (p.G59A fs*18) compound mutations in GJB2 detected in this study are novel, and which may be associated with hearing loss in this Chinese family.
The characteristics of transferrin variants by carbohydrate‐deficient transferrin tests using capillary zone electrophoresis
Authors: Yoo Gilsung , Kim Juwon , Yoon Kap Joon , Lee Jong‐Han 
Published: April 2018

BackgroundTransferrin is the major plasma transport protein for iron. We aimed to investigate the characteristics of transferrin variant by carbohydrate‐deficient transferrin (CDT) test using capillary zone electrophoresis.MethodsWe retrospectively analyzed the CDT tests of 2449 patients from March 2009 to May 2017 at a tertiary hospital in Korea. CDT was quantified using a Capillarys 2 system (Sebia, Lisses, France) by capillary zone electrophoresis. The characteristics of variant transferrin patterns using electropherogram of CDT tests were analyzed.ResultsSeventy‐seven (3.1%) patients were classified as variant transferrin. Mean age of these patients was 51.8 years, and the male‐to‐female ratio was 3.5:1. The most common variants were the BC variants (n = 37), followed by the CD variants (n = 27), unclear patterns (n = 7), BD variants (n = 3), CC variants (n = 2), misclassification (n = 1). In the variant Tf group, the most common disease was alcoholic liver cirrhosis (n = 22, 28.6%), followed by the toxic effects of substances (n = 17, 22.1%), and mental and behavioral disorders attributable to alcohol (n = 11, 14.3%). Nonvariant group showed a predominance of the toxic substance effects (n = 880, 37.1%), a personal history of suicide attempts (n = 634, 26.7%), and mental and behavioral disorders due to alcohol (n = 336, 14.2%).ConclusionWe analyzed the basic characteristics of variant transferrin by CDT tests using capillary zone electrophoresis. The prevalence of variant transferrin was 3.1% of the study subjects. Male patients, alcohol abusers, and liver cirrhosis patients predominated in the variant transferrin population. Further prospective studies are warranted to elucidate variant transferrin in clinical practice.
Primary Endpoints in Pediatric Efficacy Trials Submitted to the US FDA
Authors: Green Dionna J. , Burnham Janelle M. , Schuette Paul , Liu Xiaomei I. , Maas Brian M. , Yao Lynne , McCune Susan K. , Chen Joseph , van den Anker John N. , Burckart Gilbert J. 
Published: April 2018

AbstractThe selection of appropriate endpoints in pediatric drug development trials is a critical aspect of trial design. Given the high pediatric trial failure rate, selecting optimal trial design elements, such as the primary efficacy endpoint, is essential to ensuring increased potential for trial success. The objectives of this study were to identify the primary efficacy endpoints measured in pediatric drug development trials submitted to the US Food and Drug Administration and to relate endpoint attributes to trial and label outcome. The analysis included pediatric pivotal efficacy studies submitted from September 2007 to July 2016 for which there was a corresponding adult trial for the same indication. Two hundred and thirty‐four efficacy trials on 138 unique products studied in pediatric patients were assessed. The adult and pediatric endpoints were the same in 141 of the 234 trials (60.3%), and these trials succeeded in meeting their primary endpoint more often (122 of 141 [86.5%]) than when the adult and pediatric endpoints differed (57 of 93 [61.3%]; odds ratio, 4.03; 95%CI, 2.10–7.80). Trials that included both pediatric and adult patients succeeded more frequently than those trials that did not combine pediatric and adult patients (85 of 95 versus 94 of 139, respectively; odds ratio, 4.05; 95%CI, 1.94–9.31). No differences were observed in pediatric trial success between those using subjective and objective endpoints. Using the same endpoint in the pediatric trial as was measured in the corresponding adult trial and enrolling pediatric and adult patients in the same trial were attributes associated with trial success.
Impact of electrocoagulation on membrane filtration resistance under different proportions of industrial wastewater
Authors: Qian Guangsheng , Ye Linlin , Li Liang , Hu Xiaomin 
Published: April 2018

AbstractBACKGROUNDThe principal purpose of the present work was to explore the mechanism of mitigation of membrane fouling in a periodic reversal submerged electro‐coagulation membrane bioreactor (SECMBR) with Fe–C electrodes. In this study, membrane resistance and activated sludge performance were compared in a SECMBR and a conventional submerged membrane bioreactor (SMBR).RESULTSAdsorption fouling had a strong direct correlation with the soluble microbial products (SMP) and carbohydrates in SMP and had a moderate correlation with the mixed liquor volatile suspended solids, viscosity and average particle size. SECMBR enhanced the flocculation of suspended sludge, decreased the absolute value of the ζ potential, and maintained microbial activities. With increasing proportion of oil shale wastewater, more soluble microbial products were secreted by microorganisms in the SECMBR than in the SMBR.CONCLUSIONElectrocoagulation technology has the capacity to increase the sludge particle size and decrease the absolute value of the ζ potential to alleviate cake layer fouling and total resistance. As the proportion of oil shale wastewater was increased, microbial activity in the conventional MBR was inhibited, leading to less secreted SMP and a lower adsorption fouling rate. The results provide insight into understanding the mechanism of mitigation of membrane resistance in an SECMBR. © 2018 Society of Chemical Industry
pDNA capture using grafted adsorbents
Authors: Singh Naveen K , Dsouza Roy N , Yelemane Vikas , Nentwig Nina , Grasselli Mariano , Fernández‐Lahore Marcelo 
Published: April 2018

AbstractBACKGROUND‘Expanded’ composite materials are of interest as an alternative, or as a supplement, to packed‐bed chromatography during bioproduct recovery and purification. Functionalized non‐woven fabrics and mega‐porous bodies are examples of systems that showed promise. However, there is scarce information on their suitability to capture and release plasmid DNA (pDNA), an important type of product employed in gene therapy.RESULTSComposite adsorbents were prepared using either chemical (CG‐DEAE‐NW) or gamma‐irradiated graft‐polymerization (GIR‐DEAE‐MP), and subsequently modified to have diethylamino ethanol (DEAE) functionality. Capture experiments showed that pDNA can actually reversibly bind to the two mentioned adsorbents, with capacity values of 2.4 and 1.3 mg per mL, respectively. These values are in the range of what can be expected from commercial beaded adsorbents but lower that the values expected from monoliths.CONCLUSIONSExpanded materials, due to their high voidage, may present limited capacity for pDNA. However, such materials are able to bind proteins and other contaminants from bacterial lysate, opening the way for their utilization in the ‘negative’ mode. © 2018 Society of Chemical Industry
Synthesis of Ethylene Tethered Isatin‐Coumarin Hybrids and Evaluation of Their in vitro Antimycobacterial Activities
Authors: Gao Tao , Zeng Zhigang , Wang Gangqiang , Sun Shaofa , Liu Yi 
Published: April 2018

A series of novel isatin‐coumarin derivatives tethered through ethylene were designed, synthesized, and evaluated for their in vitro antimycobacterial activities against Mycobacterium tuberculosis (MTB) H37Rv and multidrug‐resistant tuberculosis (MDR‐TB). All hybrids exhibited potential antimycobacterial activities against MTB H37Rv and MDR‐TB with minimum inhibitory concentration (MIC) ranging from 32 to 256 μg/mL. In particular, the hybrid 4h (MIC: 50 and 32 μg/mL) was most active against MTB H37Rv and MDR‐TB strains, which was 2 and >4 folds more potent than the first‐line antitubercular agents rifampicin (MIC: 64 μg/mL) and isoniazid (MIC: >128 μg/mL) against MDR‐TB, warrant further optimization.
The anticoagulant properties of cadmium telluride quantum dots
Authors: Maguire Ciarán M. , Lavin Michelle , Doyle Mairead , Byrne Mary , Prina‐Mello Adriele , O'Donnell James S. , Volkov Yuri 
Published: April 2018

AbstractThe size‐dependent optical properties of quantum dots (QDs) are frequently exploited for use in medical imaging and labelling applications. Similarly, presented here, they also elicit profound size‐dependent anticoagulant properties. Cadmium telluride quantum dot (QDs) (3.2 nm) were shown to have a dramatic anticoagulant effect centred on around the intrinsic coagulation pathway, compared to their 3.6 nm counterparts. Several clinically relevant diagnostic tests were carried out over a concentration range of the QDs and demonstrated that the 3.2 nm QDs elicited their response on the intrinsic pathway as a whole, yet the activity of the individual intrinsic coagulation factors was not affected. The mechanism appears also to be strongly influenced by the concentration of calcium ions and not cadmium ions leached from the QDs. Static and shear‐based primary haemostasis assays were also carried out, demonstrating a profound anticoagulant effect which was independent of platelets and phospholipids. The data presented here suggest that the physical–chemical properties of the QDs may have a role in the modulation of haemostasis and the coagulation cascade, in a yet not fully understood mechanism. This study has implications for the use of similar QDs as diagnostic or therapeutic tools in vivo, and for the occupational health and safety of those working with such materials.
The role of the oath in credibility assessment
Authors: Wu Song , Cai Wei 
Published: April 2018

AbstractBased on the adaptive lie detector theory, this study is an examination of whether taking an oath, as context‐general information, increases the credibility of a suspect. The consistency of the testimonies of 6 eyewitnesses was manipulated so that it could be used as individuating information. There were 2 sets of testimonies: one that was consistent and one that was inconsistent. The results supported the adaptive lie detector theory. The participants judged those persons who took an oath to be more credible than those who did not, but this only happened in situations where the testimonies of the eyewitnesses were inconsistent. The theoretical and practical implications of the findings and future directions are then discussed.
Comparative anatomy and development of pectoral and pelvic girdles in hylid anurans
Authors: Soliz Mónica C. , Ponssa María Laura , Abdala Virginia 
Published: April 2018

AbstractThe development of the tetrapod pectoral and pelvic girdles is intimately linked to the proximal segments of the fore‐ and hindlimbs. Most studies on girdles are osteological and provide little information about soft elements such as muscles and tendons. Moreover, there are few comparative developmental studies. Comparative data gleaned from cleared‐and‐stained whole mounts and serial histological sections of 10 species of hylid frogs are presented here. Adult skeletal morphology, along with bones, muscles, and connective tissue of both girdles and their association with the proximal portions of the anuran fore‐ and hindlimbs are described. The data suggest that any similarity could be attributable to the constraints of their ball‐and‐socket joints, including incorporation of the girdle and stylopodium into a single developmental module. An ancestral state reconstruction of key structures and developmental episodes reveals that several development events occur at similar stages in different species, thereby preventing heterochronic changes. The medial contact of the halves of the pectoral girdle coincides with the emergence of the forelimbs from the branchial chamber and with the total differentiation of the linkage between the axial skeleton and the girdles. The data suggest that morphogenic activity in the anterior dorsal body region is greater than in the posterior one, reflecting the evolutionary sequence of the development of the two girdles in ancient tetrapods. The data also document the profound differences in the anatomy and development of the pectoral and pelvic girdles, supporting the proposal that the pectoral and pelvic girdles are not serially homologous, as was long presumed.
Semianalytical modeling of the depletion layers and their effects on the threshold voltage of a junctionless double‐gate MOSFET including trapped charges
Authors: Beigi Kobra , Hashemi Seyed Amir 
Published: April 2018

AbstractThis paper considers the depletion regions at the source and drain sides in a symmetric junctionless double‐gate metal‐oxide‐semiconductor field‐effect transistor with trapped charges working in subthreshold condition. The effects of depletion layers on the potential, threshold voltage, drain‐induced barrier lowering (DIBL), and the current of the device have been investigated. The channel of the transistor is divided into 4 regions: 2 regions without and with trapped charges and 2 depletion regions on either side of the channel. Solving the 2‐dimensional Poisson's equation, a semianalytical model for the potential is achieved in these regions and the threshold voltage, the DIBL, and the current are calculated. Also, the depletion widths are calculated during the modeling and their variation against the positive and negative trapped charges is investigated. To show the importance of the depletion layers, another junctionless double‐gate metal‐oxide‐semiconductor field‐effect transistor without depletion layers is considered and the mentioned electrical properties of the 2 devices are compared with each other. Smaller central potential, threshold voltage, and current and higher DIBL are achieved when the depletion layers are considered. Good agreement between the results of the proposed model and the simulated results by TCAD software shows the physical validity of the proposed model.