bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of telomerase inhibitor on epigenetic chromatin modification enzymes in malignancies
Authors: Biray Avci Cigir , Dogan Fatma , Ozates Ay Neslihan Pinar , Goker Bagca Bakiye , Abbaszadeh Zeka , Gunduz Cumhur 
Published: August 2018

AbstractTelomerase has a critical role in cell proliferation, tumor maintaining, and therapy resistance, which act by modifying many signaling pathways. 2‐[(E)‐3‐Naphtalen‐2‐yl‐but‐2‐enoylamino]‐benzoic acid (BIBR1532) is one of the most studied telomerase inhibitors, and it targets telomerase components TERC and TERT. In this novel study, we aimed to investigate the epigenetic effects of BIBR1532 on both hematologic malignancies and solid tumors. K‐562 human chronic myeloid leukemia cell line and U87MG glioblastoma cell line were compared with control groups without BIBR1532 treatment. Cytotoxic effects of BIBR1532 were determined by using WST‐1 assay. Apoptotic effects of BIBR1532 were detected by using annexin V method. To assess expression changes in the human epigenetic chromatin modification enzyme genes, total RNA was isolated from K‐562 and U87MG cells treated with BIBR1532 and untreated control cells. BIBR1532 induced 2.41‐fold apoptotic cell death in U87MG cell lines compared with control groups. Apoptosis was slightly induced in K‐562 cells with BIBR1532 treatment compared with control cells. We observed that BIBR1532 also regulates similar genes in both cell lines, and it is useful on epigenetic mechanisms. As a result, telomerase inhibitor BIBR1532 has a significant effect on both hematological malignancies and solid tumors.
RNA sequencing and bioinformatics analysis of the long noncoding RNA–mRNA network in colorectal cancer
Authors: Zhang Zheying , Jia Huijie , Gu Tengteng , Hu Qing , Yu Jian , Zang Dan , Song Na , Wang Haijun 
Published: August 2018

AbstractLong noncoding RNA (lncRNA) plays an important regulatory role in tumorigenesis. This study aims to analyze the lncRNA–messenger RNA (mRNA) expression network and potential roles in colorectal cancer (CRC). The LncRNA expression profile was analyzed in CRC tissue by RNA sequencing and the functions of differentially expressed genes were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The lncRNA‐mRNA network was predicted with bioinformatics. From the result, we identified 485 differential expression lncRNAs and 2383 mRNAs in CRC, GO, and KEGG analyses showed that the changes in lncRNAs were mainly associated with metabolism and transcription regulation that were different from mRNA function. Additionally, based on the predicted coexpression network, we identified that NONHSAT074176.2, downregulated in CRC tissue and cell lines, was a hub lncRNA in the development of CRC. Our results describe the lncRNA‐mRNA network in detail and indicate that lncRNA NONHSAT074176.2 may be useful as a candidate diagnostic biomarker and may be a promising therapeutic target for CRC.
LPS promotes the expression of PD‐L1 in gastric cancer cells through NF‐κB activation
Authors: Li Hui , Xia Jun‐Quan , Zhu Fang‐Shi , Xi Zhao‐Hong , Pan Cheng‐Yu , Gu Li‐Mei , Tian Yao‐Zhou 
Published: August 2018

AbstractGastric cancers are a group of highly aggressive malignancies with a huge disease burden worldwide. Gastric infections, such as helicobacter pylori, can induce the occurrence of gastric cancers. However, the role of gastric infection in gastric cancer development is unclear. Programmed death‐ligand 1 (PD‐L1, B7‐H1) is a member of the B7 family of cell surface ligands, which binds the PD‐1 transmembrane receptor and inhibits T‐cell activation within cancer tissues. It has been reported that the expression of PD‐L1 is inversely related to the prognosis of patients with gastric cancers. Therefore, the regulation of PD‐L1 expression in gastric cancers needs to be studied. In the current study, we explored the possible effects of lipopolysaccharide (LPS) on PD‐L1 expression in gastric cancer cells. We observed that LPS stimulation could markedly increase PD‐L1 expression in gastric cancer cells. Furthermore, we found that nuclear factor‐κB (NF‐κB) activation was involved in PD‐L1 expression in gastric cancer cells exposed to LPS stimulation through p65‐binding to the PD‐L1 promoter. Taken together, these data indicate that gastric infection might promote the development of gastric cancers thought the LPS‐NF‐κB‐PD‐L1 axis.
Imaging the interaction of αv integrin‐GFP in osteosarcoma cells with RFP‐expressing host stromal cells and tumor‐scaffold collagen in the primary and metastatic tumor microenvironment
Authors: Tome Yasunori , Kiyuna Tasuku , Uehara Fuminari , Bouvet Michael , Tsuchiya Hiroyuki , Kanaya Fuminori , Hoffman Robert M. 
Published: August 2018

AbstractHuman osteosarcoma 143B cells were previously stably transfected with an αv integrin green flourescent protein (GFP) vector. 143B cells expressing αv integrin‐GFP were transplanted orthotopically in the tibia of transgenic nude mice ubiquitously expressing red fluorescent protein (RFP). The primary tumors acquired RFP‐expressing stroma and were passaged orthotopically in the tibia in noncolored nude mice, which maintained the RFP stroma. The interaction of αv integrin‐GFP expression in 143B cells with RFP‐expressing host stromal cells was observed by confocal microscopy using the Olympus FV1000. Collagen fibers were imaged simultaneously in reflectance mode. The RFP‐expressing stroma included cancer‐associated fibroblasts (CAFs) and tumor‐associated macrophages (TAMs) which persisted even 3 weeks after passage to nontransgenic nude mice. CAFs expressing RFP were aligned between collagen fibers and cancer cells expressing αv integrin‐GFP. Six weeks after transplantation, pulmonary metastases expressing αv integrin‐GFP could be identified. TAMs expressing RFP accompanied metastasized osteosarcoma cells expressing αv integrin‐GFP in the lung. The current study demonstrates the importance of αv integrin interaction with stromal elements in osteosarcoma.
Long noncoding RNA MALAT1 downregulates cardiac transient outward potassium current by regulating miR‐200c/HMGB1 pathway
Authors: Zhu Peng , Yang Manli , Ren Hui , Shen Guidong , Chen Jinye , Zhang Junkang , Liu Jun , Sun Chaofeng 
Published: August 2018

AbstractThe dysregulation of long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) participates in the remodeling of electrophysiological/ion channel in cardiomyocytes during arrhythmia. The lncRNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) is reported to be highly expressed in myocardial ischemia‐reperfusion injury and offsets cardioprotective effects of fentanyl. However, the roles of MALAT1 and its related miRNAs during arrhythmia are poorly understood. In this study, the overexpression of MALAT1 was firstly indicated in cardiomyocytes from arrhythmic model rats. After downregulation of MALAT1 by RNA interference, transient outward potassium current (Ito), peak current density, and the levels of Kv4.2 and Kv4.3 channel proteins were increased in rat cardiomyocytes. Then, miR‐200c was predicted and convinced to be a direct target of MALAT1, and high‐mobility group box 1 (HMGB1) was verified to be a target of miR‐200c during arrhythmia. HMGB1 expression reduced by the knockdown of MALAT1 was further decreased by miR‐200c overexpression. In addition, cardiac Ito, peak current density, and the levels of Kv4.2 and Kv4.3 in arrhythmic model rats were detected to be negatively correlated with the expression of HMGB1, and to be positively with miR‐200c expression. Taken together, these results suggested that MALAT1 may act as a competing endogenous RNA for miR‐200c to upregulate the expression of HMGB1 and downregulate cardiac Ito.
Preconditioned neurons with NaB and nicorandil, a favorable source for stroke cell therapy
Authors: Hosseini Seyed Mojtaba , Ziaee Seyyed Mohyeddin , Haider Khawaja Husnanin , Karimi Aliashghar , Tabeshmehr Parisa , Abbasi Zahra 
Published: August 2018

AbstractPoor survival of stem cells in the harsh microenvironment at the site of stroke, especially during acute phase of injury, remains a serious obstacle to achieve the desired prognosis. We hypothesized that combined treatment of neural stem cells (NSCs) with small molecules would precondition them to become robust and survive better as compared with the native nonpreconditioned cells. Mouse ganglionic NSCs were isolated, cultured, and characterized. The cells were preconditioned by treatment with sodium butyrate (NaB) and nicorandil (Nico) and transplanted in an experimentally induced stroke model. Sham‐operated animals without treatment or animals with experimental stroke treated with basal medium, native NSCs, NSCs preconditioned with NaB or Nico alone were used as controls. The tissue samples and cells with different treatments were used to measure brain‐tissue–derived neurotrophic factor (BDNF) level and the activity of phosphatidylinositol‐3 kinase (PI3K), apurinic/apyrimidinic endonuclease 1 (APE1), and nuclear factor‐κB (NF‐κB) p50 both in vitro and in vivo, respectively. Additionally, survival of the cells and recovery indices for stroke were studied. The combined treatment with NaB + Nico resulted in increased BDNF level and higher PI3K, APE1, and the downstream NF‐κB activation, which were blocked by pretreatment with their respective inhibitors. Donor cell survival increased postengraftment as assessed by 5‐bromo‐2′‐deoxyuridine immunostaining and reduced Terminal deoxynucleotide transferase dUTP Nick End Labeling positivity at the site of engraftment. There was reduction in proinflammatory cytokines and infiltration of both GFAP
+ and CD68
+ at the injury site. There was reduction in the infarct size and neurological function was preserved in the preconditioned cell treatment group. Our preconditioning approach with small molecules effectively improved the survival as well as functionality of NSCs.
Comparative mechanism based study on disinfectants against multidrug‐resistant Acinetobacter baumannii
Authors: Biswas Deepika , Tiwari Monalisa , Tiwari Vishvanath 
Published: August 2018

AbstractAcinetobacter baumannii has emerged as a hospital‐acquired pathogen and has spread in the hospital settings, leading to enhanced nosocomial outbreaks associated with high death rates. Therefore, the aim of the current study is to determine the effective concentration of disinfectants like sodium hypochlorite, hydrogen peroxide, and chlorine dioxide, against multidrug‐resistant (MDR) strains of A. baumannii. In this study, we have investigated the effect of disinfectants on different MDR strains i.e. RS307, RS6694, RS7434, RS10953, RS122, and sensitive strain ATCC‐19606 of A. baumannii, via differential growth curves analysis, disc diffusion assay, estimation of reactive oxygen species (ROS), lipid peroxidation, and protein carbonylation. All the results collectively showed that 1% sodium hypochlorite (P value < 0.0027), 2.5% hydrogen peroxide (P value = 0.0032), and 10 mM (P value = 0.017) chlorine dioxide significantly inhibit the growth of MDR strains of A. baumannii. A significant increase in the ROS generations, altered lipid peroxidation, and a decrease in protein carbonylation was also observed after treatment with disinfectants, which confirmed its ROS‐dependent damage mechanism. These disinfectants also enhance the membrane leakage of reducing sugar, protein, and DNA. The current study highlights and recommends the use of 2.5% hydrogen peroxide to control the MDR strains of A. baumannii in the hospital setup. Therefore, the present results will help in selecting concentrations of different disinfectants for regular use in hospital setups to eradicate the multidrug‐resistant A. baumannii from the hospital setup.
Upregulation of LINC00319 indicates a poor prognosis and promotes cell proliferation and invasion in cutaneous squamous cell carcinoma
Authors: Li Fumin , Liao Jinfeng , Duan Xiling , He Yuanmin , Liao Yongmei 
Published: August 2018

AbstractCutaneous squamous cell carcinoma (CSCC), an epidermal keratinocyte‐derived skin tumor, is one of the most leading causes of cancer‐associated morbidity and mortality worldwide. Long noncoding RNAs have emerged as key regulators of tumor development and progression. Recent studies have identified LINC00319, a long intergenic noncoding RNA, as an oncogene in lung cancer. However, the biological role of LINC00319 in CSCC remains largely unknown. The current study aimed to explore the role of LINC00319 in CSCC and uncover the molecular mechanisms. In current study, we found that LINC00319 was significantly upregulated in both CSCC tissues and cell lines. Besides, the χ2 test showed that increased expression of LINC00319 was associated with larger tumor size, advanced TNM stage, and lymphovascular invasion. Gain‐of‐function and loss‐of‐function approaches were applied to investigate the effects of LINC00319 on CSCC cells. Functional studies demonstrated that LINC00319 promoted CSCC cell proliferation, accelerated cell cycle progression, facilitated cell migration and invasion, and inhibited cell apoptosis. Mechanistic studies revealed that LINC00319 exerts its oncogenic functions in CSCC via miR‐1207‐5p‐mediated regulation of cyclin‐dependent kinase 3. Taken together, upregulation of LINC00319 implies a potential link with poor prognosis and reflects CSCC progression. Collectively, this study may provide some evidence for LINC00319 as a candidate target in CSCC treatment.
Eu3+/Sm3+ dual‐label time‐resolved fluoroimmunoassay for measurement of hepatitis C virus antibodies
Authors: Yang Xue , Ye Yan , Wang Tingting , Li Mei , Yu Lei , Xia Min , Qian Jun , Hu Zhigang 
Published: August 2018

AimTo develop a new immunoassay based on the time‐resolved fluorescence immunoassay (TRFIA) system for the simultaneous measurement of IgM and IgG antibodies to HCV.MethodsCoated recombinant HCV antigens and Eu3+‐labeled IgM and Sm3+‐labeled IgG antibodies were prepared. HCV‐IgM/IgG TRFIA was established and optimized, followed by a methodological assessment. Data were expressed as +SD and analyzed using the SPSS 13.0 software. The percentile method was used to calculate cutoff values.ResultsThe detection sensitivities of HCV‐IgM and HCV‐IgG were 0.06 S/CO and 0.15 S/CO, respectively. There was a good linear response from 1:40 to 1:40 960 for HCV‐IgM and 1:20 to 1:40 960 for HCV‐IgG, when samples strongly positive for HCV‐IgM and HCV‐IgG were serially diluted from 1:10 to 1:81 920. The average intra‐assay coefficients of variation (CV) for HCV‐IgM and ‐IgG were 3.45% and 3.71% and the inter‐assay coefficients of variation (CV) were 6.49% and 6.79%, respectively. When HCV‐negative/positive sera were tested by ELISA and using established kits, the negative, positive, and total conformity rates for HCV‐IgM were 93.3% (28/30), 100% (25/25), and 96.4% (53/55), and those for HCV‐IgG were 93.3% (28/30), 100% (35/35), and 96.9% (63/65), respectively. Additionally, the established kit exhibited good stability, with declines in fluorescence values to 11.1% and 9.5%, respectively, after storage at 37°C for 7 days.ConclusionWe established a dual‐label HCV‐IgM/IgG TRFIA assay with a wide detection range, high specificity, high sensitivity, good stability, and good clinical value for the simultaneous measurement of HCV‐IgM and HCV‐IgG titers in a single test.
Differences in erythrocyte sedimentation rates using a modified Westergren method and an alternate method
Authors: Schapkaitz Elise , RabuRabu Shilla , Engelbrecht Marcel 
Published: August 2018

IntroductionWorldwide laboratories have adopted the use of modified or alternate methods for measurement of the erythrocyte sedimentation rate (ESR). The iSED from Alcor Scientific is a novel, alternate ESR method based on photometric aggregometry which offers improved operator safety and reduced analysis time. This study evaluated the diagnostic utility of the iSED in a South African patient population with a range of inflammatory disorders.MethodsWe compared the iSED with the predicate modified Westergren method (StaRRsed, Mechatronics, Zwaag, the Netherlands) measured at 60 minutes. Analysis was performed on K2EDTA samples at three ESR measurement ranges (<20, 20‐80 and >80 mm/h) in 120 pediatric and adult inpatients and outpatients over a 2‐week period. Precision, stability, and carryover were performed in accordance with the revised International Council for Standardisation in Haematology guidelines.ResultsThe iSED demonstrated acceptable imprecision with minimal carryover (2.86%). The correlation coefficients at the 3 ESR measurement ranges were r = 0.58, r = 0.71, and r = 0.56, respectively. The y‐intercepts were −10.74 (CI −29.17 to 7.69), −5.95 (CI −18.60 to 6.69) and 246.05 (CI 591.42‐99.31). This indicated a difference of a constant nature with an overall mean difference of 7.99 mm/h (CI 5.87‐10.13) (P < 0.001). iSED ESR measurements were stable up to 24 hours when stored at room temperature or at 4‐8°C.ConclusionThis study demonstrated differences in ESR results, predominantly at extremes of the analytical range, using an alternate method. Careful consideration and performance monitoring of these novel methods are advised.
Ketamine induces reactive oxygen species and enhances autophagy in SV‐HUC‐1 human uroepithelial cells
Authors: Shan Zhengfei , Wei Liqin , Yu Shengqiang , Jiang Shanling , Ma Yue , Zhang Chengjun , Wang Jiantao , Gao Zhenli , Wan Fengchun , Zhuang Guimin , Wu Jitao , Liu Dongfu 
Published: August 2018

AbstractThis study was aimed at exploring the underlying mechanisms of ketamine in the SV‐40 immortalized human ureteral epithelial (SV‐HUC‐1) cells. The viability and apoptosis of SV‐HUC‐1 cells treated with 0.01, 0.1, and 1 mM ketamine were respectively detected via cell counting kit‐8 (CCK‐8) assay and terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining. Reactive oxygen species (ROS) level was measured through ROS probe staining. Apoptosis‐related proteins (B‐cell lymphoma 2 [Bcl‐2] and Bax) and autophagy‐associated proteins (light chain 3‐I [LC3‐I] and LC3‐II) were determined by western blot or immunofluorescent assay. Additionally, transmission electron microscopy (TEM) was used to evaluate the formation of autophagosomes. After cotreatment of 3‐methyladenine (3‐MA) or N‐acetyl‐l‐cysteine (NAC), the biological functions of SV‐HUC‐1 cells were analyzed to determine the association of ROS with cell viability and autophagy. CCK‐8 assay and TUNEL staining indicated that ketamine effectively decreased the viability of SV‐HUC‐1 cells and accelerated apoptosis of SV‐HUC‐1 cells through regulating the expression level of IKBα (phospho), nuclear factor кB (P65), Bcl‐2, and Bax proteins. Enhanced ROS production was also confirmed in ketamine‐treated SV‐HUC‐1 cells treated with ketamine. Ketamine‐induced autophagosomes in SV‐HUC‐1 cells were observed by means of TEM, and increased levels of LC3 II/I ratio and Beclin 1 were examined through western blot and immunofluorescent assay. Furthermore, ketamine exerted effects on SV‐HUC‐1 cells in a dose‐dependent and time‐dependent manner. Additionally, cotreatment of NAC with 3‐MA significantly attenuated the ROS level and suppressed the cell autophagy. Ketamine promoted SV‐HUC‐1 cell autophagy and impaired the cell viability of SV‐HUC‐1 cells by inducing ROS.
Inactivated Sendai virus strain Tianjin induces apoptosis and autophagy through reactive oxygen species production in osteosarcoma MG‐63 cells
Authors: Han Zhe , Li Qing , Sun Shuya , Zhao Wei , Shi Liying 
Published: August 2018

AbstractSendai virus strain Tianjin, a novel genotype of Sendai virus, has been proven to possess potent antitumor effect on certain cancer cell types although inactivated by ultraviolet (UV). This study was carried out to investigate the in vitro anticancer properties of UV‐inactivated Sendai virus strain Tianjin (UV‐Tianjin) on human osteosarcoma cells and the underlying molecular mechanism. Our studies demonstrated UV‐Tianjin significantly inhibited the viability of human osteosarcoma cell lines and triggered apoptosis through activation of both extrinsic and intrinsic pathways in MG‐63 cells. Meanwhile, autophagy occurred in UV‐Tianjin‐treated cells. Blockade of autophagy with 3‐methyladenine remarkably attenuated the inhibition of cell proliferation by UV‐Tianjin, suggesting that UV‐Tianjin‐induced autophagy may be contributing to cell death. Furthermore, UV‐Tianjin induced reactive oxygen species (ROS) production, which was involved in the execution of MG‐63 cell apoptosis and autophagy, as evidenced by the result that treatment of N‐acetyl‐L‐cysteine, a ROS scavenger, attenuated both apoptosis and autophagy. In addition, inhibition of apoptosis promoted autophagy, whereas suppression of autophagy attenuated apoptosis. Our results suggest that UV‐Tianjin triggers apoptosis and autophagic cell death via generation of the ROS in MG‐63 cells, which might provide important insights into the effectiveness of novel strategies for osteosarcoma therapy.
Astragaloside IV enhances taxol chemosensitivity of breast cancer via caveolin‐1‐targeting oxidant damage
Authors: Zheng Yifeng , Dai Yan , Liu Weiping , Wang Neng , Cai Youli , Wang Shengqi , Zhang Fengxue , Liu Pengxi , Chen Qianjun , Wang Zhiyu 
Published: August 2018

AbstractAccumulating evidence suggests that caveolin‐1 (CAV‐1) is a stress‐related oncotarget and closely correlated to chemoresistance. Targeting CAV‐1 might be a promising strategy to improve chemosensitivity for breast cancer treatment. Astragaloside IV (AS‐IV), a bioactive compound purified from Astragalus membranaceus, has been shown to exhibit multiple bioactivities, including anticancer. However, the involved molecular targets are still ambiguous. In this study, we investigated the critical role of CAV‐1 in mediating the chemosensitizing effects of AS‐IV to Taxol on breast cancer. We found that AS‐IV could enhance the chemosensitivity of Taxol with minimal direct cytotoxicity on breast cancer cell lines MCF‐7 and MDA‐MB‐231, as well as the nontumor mammary epithelial cell line MCF‐10A. AS‐IV was further demonstrated to aggravate Taxol‐induced apoptosis and G2/M checkpoint arrest. The phosphorylation of mitogen‐activated protein kinase (MAPK) signaling extracellular signal‐regulated kinase (ERK) and c‐Jun N‐terminal Kinase (JNK), except p38, was also abrogated by a synergistic interaction between AS‐IV and Taxol. Moreover, AS‐IV inhibited CAV‐1 expression in a dose‐dependent manner and reversed CAV‐1 upregulation induced by Taxol administration. Mechanism study further demonstrated that AS‐IV treatment triggered the eNOS/NO/ONOO− pathway via inhibiting CAV‐1, which led to intense oxidant damage. CAV‐1 overexpression abolished the chemosensitizing effects of AS‐IV to Taxol by inhibiting oxidative stress. In vivo experiments further validated that AS‐IV increased Taxol chemosensitivity on breast cancer via inhibiting CAV‐1 expression, followed by activation of the eNOS/NO/ONOO− pathway. Taken together, our findings not only suggested the potential of AS‐IV as a promising candidate to enhance chemosensitivity, but also highlighted the significance of CAV‐1 as the target to reverse cancer drug resistance.