bluuebunny/crossref_metadata_2025_split huggingface dataset:
Titania nanotube morphologies for osseointegration via models of in vitro osseointegrative potential and in vivo intramedullary fixation
Authors: Baker Erin A. , Vara Alexander D. , Salisbury Meagan R. , Fleischer Mackenzie M. , Baker Kevin C. , Fortin Paul T. , Roberts Richard V. , Friedrich Craig R. 
Published: November 2019

AbstractAs total joint replacements increase annually, new strategies to attain solid bone‐implant fixation are needed to increase implant survivorship. This study evaluated two morphologies of titania nanotubes (TiNT) in in vitro experiments and an in vivo rodent model of intramedullary fixation, to simulate joint arthroplasty conditions. TiNT surfaces were prepared via an electrochemical etching process, resulting in two different TiNT morphologies, an aligned structure with nanotubes in parallel and a trabecular bone‐like structure. in vitro data showed bone marrow cell differentiation into osteoblasts as well as osteoblastic phenotypic behavior through 21 days. In vivo, both TiNT morphologies generated greater bone formation and bone‐implant contact than control at 12 weeks, as indicated by μCT analyses and histology, respectively. TiNT groups also exhibited greater strength of fixation compared to controls, when subjected to wire pull‐out testing. TiNT may be a promising surface modification for promoting osseointegration.
Smoking is an important factor that affects peripheral blood progenitor cells yield in healthy male donors
Authors: Zhen Changqing , Fang Xiaosheng , Ding Mei , Wang Xianghua , Yuan Dai , Sui Xiaohui , Liu Xin , Zhang Lingyan , Xu Hongzhi , Li Ying , Wang Xin 
Published: November 2019

AbstractBackgroundSmoking could reduce the CD34+ cells in peripheral blood of healthy individual. This study aimed to investigate the correlation between smoking load and the effect of peripheral blood hematopoietic progenitor cells (PBPCs) mobilization by granulocyte colony‐stimulating factor (G‐CSF) alone in healthy donors.MethodsRetrospective analysis was performed on 145 healthy adult PBPCs donors who underwent PBPCs mobilization and collection. Smoking factors were evaluated and correlated with mobilization responses, as indicated by the collected CD34+ cells concentration.ResultsThe collected CD34+ cells concentration was closely related to pre‐CD34 (P < .001) and CD34+ cells collected per volume blood processed (P < .001) which suggested that collected CD34+ cells concentration was a reliable indicator of PBPCs mobilization efficiency. The heavy smoking donors revealed significantly lower collected CD34+ cells concentration, compared to that of the nonsmoking (P < .001) and light smoking donors (P < .05). The levels of collected CD34+ cells in light smoking were also obviously lower than that in nonsmoking donors (P < .05).There were no obvious differences in the collected CD34+ cells concentration, overall processed blood volume and total collected CD34+ cells between nonsmoking and smoking cessation groups (P = .490; P = .464; P = .819).ConclusionCigarette smoking is an important factor that affects the yield of PBPCs in male donors, especially when the smoking load is more than five pack‐years. Mobilization of PBMCs could be restored by smoking cessation in chronic smokers.
Retracted: The circular RNA‐NRIP1 plays oncogenic roles by targeting microRNA‐505 in the renal carcinoma cell lines
Authors: Dong Zhen , Liu Yidong , Wang Qinghai , Wang Hongyang , Ji Jianlei , Huang Tao , Khanal Aashish , Niu Haitao , Cao Yanwei 
Published: November 2019

AbstractWe explored the roles and regulatory mechanisms of the circular RNA (circRNA) nuclear receptor‐interacting protein 1 (NRIP1; circNRIP1) in ACHN and CAKI‐1 cells. ACHN and CAKI‐1 cells were transfected with small‐interfering‐circNRIP1 (si‐circNRIP1) and microRNA‐505 (miR‐505) inhibitor or the corresponding controls. Cell viability was detected with the Cell Counting Kit‐8. The protein expression levels of Bcl‐2, Bax, cleaved‐caspase‐3, matrix metalloproteinase (MMP)‐2, MMP‐9, adenosine 5′‐monophosphate (AMP)‐activated protein kinase (AMPK), protein kinase B (AKT), phosphatidylinositol 3‐kinase (PI3K), and mammalian target of rapamycin (mTOR) were individually determined via Western blot. Quantitative reverse transcription polymerase chain reaction was used to examine the expressions of circNRIP1 and miR‐505 both in tumor cells and tissues. The apoptotic rate, the colony numbers, and the migration rate were separately determined by the Annexin V‐fluorescein isothiocyanate/propidium iodide and flow cytometer, colony formation assay, and migration assay. We found that circNRIP1 was overexpressed in tumor tissue but miR‐505 was overproduced. Silencing circZNF292 induced inhibition of cell viability, colony formation, and migration, as well as the activity of AMPK and PI3K/AKT/mTOR cascades but enhancement of apoptosis. si‐circNRIP1 stimulated the upregulation of miR‐505, whose silence abolished the effects of si‐circNRIP1 on these elements mentioned above. In conclusion, the circNRIP1 played oncogenic roles in the ACHN and the CAKI‐1 cell lines by targeting miR‐505 via stimulating AMPK and PI3K/AKT/mTOR cascades.
YY1‐mediated overexpression of long noncoding RNA MCM3AP‐AS1 accelerates angiogenesis and progression in lung cancer by targeting miR‐340‐5p/KPNA4 axis
Authors: Li Xuemei , Yu Mei , Yang Caiyong 
Published: November 2019

AbstractLung cancer is famous as an aggressive malignant tumor and is the main cause of cancer‐associated mortality globally. Tumor angiogenesis is a vital part in cancer, which influences cell proliferation and metastasis. Increasing studies have claimed that long noncoding RNAs (lncRNAs) were involved in the progression of several cancers. Based on previous studies, this study focused on the role and mechanism of lncRNA MCM3AP antisense RNA 1 (MCM3AP‐AS1) in lung cancer. At first, MCM3AP‐AS1 expression was found to be elevated in lung cancer cells. Depletion of MCM3AP‐AS1 repressed cell proliferation, migration, and angiogenesis in lung cancer cells. YY1 was confirmed to mediate MCM3AP‐AS1 transcription in lung cancer cells. Moreover, the molecular mechanism investigation revealed that MCM3AP‐AS1 could sponge miR‐340‐5p and elevate KPNA4 expression. On the basis of rescue assays, we identified that the overexpression of KPNA4 partly counteracted the suppressed effect of MCM3AP‐AS1 knockdown on angiogenesis and progression in lung cancer cells. Conclusively, the YY1‐mediated overexpression of MCM3AP‐AS1 accelerated angiogenesis and progression in lung cancer by targeting miR‐340‐5p/KPNA4 axis, which highlighted the possibility of MCM3AP‐AS1 as a promising therapeutic target for lung cancer.
M‐phase phosphoprotein 8 promotes gastric cancer growth and metastasis via p53/Bcl‐2 and EMT‐related signaling pathways
Authors: Wang Yizhuo , Xiao Huijie , Wang Chang , Wu Haitao , He Hua , Yao Cheng , Cui Jiuwei , Li Wei 
Published: November 2019

AbstractBackgroundThe main issue of this study is to demonstrate whether M‐phase phosphoprotein 8 (MPP8) affect gastric tumor growth and metastasis.MethodsRetrospective study was proceeded in 280 patients' surgical specimens with different disease stages. Loss‐of‐function assays, including 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide, flow cytometry, and transwell assays were performed to evaluate the biological function of MPP8 in gastric cancer cells. Apoptosis and metastasis relative biomarkers were measured by quantitative real‐time polymerase chain reaction and Western blot analysis.ResultsCompared with normal adjacent tissues, obviously elevated MPP8 expression was found in gastric cancer tissues. Elevated MPP8 expression was associated with male sex (vs female sex), intermediate differentiation (vs poorly differentiated cancer), and later stage (vs earlier stage). Furthermore, MPP8 overexpression in tumor tissues was marginally associated with a poor prognosis, with a significant relationship between MPP8 overexpression and prognosis among patients with poorly differentiated gastric cancer. Inhibition of MPP8 in these cells significantly suppressed proliferation and colony formation, promoted apoptosis, and repressed invasion. Furthermore, silencing of MPP8 remarkably increased apoptosis‐related proteins (p53, Bax, and PARP) expression, but downregulated Bcl‐2 expression. Silencing of MPP8 also decreased the expression of metastasis pathway‐related proteins (N‐cadherin and vimentin), and as well as the levels of anti‐oncogene ZEB1, MET, and KRAS mRNA.ConclusionOur findings demonstrated that MPP8 might be an oncogene by positively regulating gastric cancer cell function through the p53/Bcl‐2 and epithelial to mesenchymal transition‐related signaling pathways.
Identifying prognostic biomarkers in endometrial carcinoma based on ceRNA network
Authors: Zhao Dongli , Ren Chune , Yao Yan , Wang Qinjian , Li Fei , Li Yang , Jiang Aifang , Wang Guili 
Published: November 2019

AbstractPurposeEndometrial carcinoma (EC), a common gynecological malignancy with high incidence, affects the mental and physical health of women. Mounting evidence shows that long noncoding RNAs (lncRNAs), messenger RNAs (mRNAs), and microRNAs (miRNAs) have instrumental roles in various biological processes associated with the pathogenesis of EC. In this research, we intend to further study the mechanism of EC and the potential predictive markers of EC.MethodsFirst, we obtained original data of EC RNA transcripts from The Cancer Genome Atlas database and performed differential analysis. Subsequently, according to the miRcode online software, relationship pairs of lncRNA‐miRNA were constructed, and miRNA‐mRNA pairs were established based on miRDB, TargetScan, and miRTarBase. Then, we constructed the competing endogenous RNA (ceRNA) network based on lncRNA‐miRNA and miRNA‐mRNA pairs. To further explain the function of the ceRNA network and explore the potential prognostic markers, functional enrichment analysis, and survival analysis were carried out.ResultsThe research showed that there were 744 differential expression lncRNAs (DElncRNAs), 164 differential expression miRNAs (DEmiRNAs), and 2447 differential expression mRNAs (DEmRNAs) between EC tissues and normal tissues. Subsequently, we built 103 DEmiRNA‐DEmRNA interaction pairs and 369 DElncRNA‐DEmiRNA pairs. Then, we established the ceRNA network of EC, including 62 DElncRNAs, 26 DEmiRNAs, and 70 DEmRNAs. Moreover, 10 of 62 lncRNAs, 19 of 70 mRNAs, and 4 of 26 miRNAs that closely related to the survival of EC with P < .05 were obtained. Notably, based on this network, it was found that LINC00261‐hsa‐mir‐31 pair and LINC00261‐hsa‐mir‐211 target pairs could be used as the potential prognostic markers of EC.ConclusionThis research recommended an available basis for the molecular mechanism of EC and prognosis prediction, which could help guide the subsequent treatments and predict the prognosis for patients with EC.
Identification of key microRNAs and hub genes in non‐small‐cell lung cancer using integrative bioinformatics and functional analyses
Authors: Song Feifeng , Xuan Zixue , Yang Xiuli , Ye Xiaolan , Pan Zongfu , Fang Qingxia 
Published: November 2019

AbstractNon‐small‐cell lung cancer (NSCLC) is an extremely debilitating respiratory malignancy. However, the pathogenesis of NSCLC has not been fully clarified. The main objective of our study was to identify potential microRNAs (miRNAs) and their regulatory mechanism in NSCLC. Using a systematic review, two NSCLC‐associated miRNA data sets (GSE102286 and GSE56036) were obtained from Gene Expression Omnibus, and the differentially expressed miRNAs (DE‐miRNAs) were accessed by GEO2R. Survival analysis of candidate DE‐miRNAs was conducted using the Kaplan‐Meier plotter database. To further illustrate the roles of DE‐miRNAs in NSCLC, their potential target genes were predicted by miRNet and were annotated by the Database for Annotation, Visualization and Integrated Discovery (DAVID) program. Moreover, the protein‐protein interaction (PPI) and miRNA‐hub gene regulatory network were established using the STRING database and Cytoscape software. The function of DE‐miRNAs in NSCLC cells was evaluated by transwell assay. Compared with normal tissues, a total of eight DE‐miRNAs was commonly changed in two data sets. The survival analysis showed that six miRNAs (miR‐21‐5p, miR‐31‐5p, miR‐708‐5p, miR‐30a‐5p, miR‐451a, and miR‐126‐3p) were significantly correlated with overall survival. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that target genes of upregulated miRNAs were enriched in pathways in cancer, microRNAs in cancer and proteoglycans in cancer, while the target genes of downregulated miRNAs were mainly associated with pathways in cancer, the PI3K‐Akt signaling pathway and HTLV‐I infection. Based on the miRNA‐hub gene network and expression analysis, PTEN, EGFR, STAT3, RHOA, VEGFA, TP53, CTNNB1, and KRAS were identified as potential target genes. Furthermore, all six miRNAs exhibited significant effects on NSCLC cell invasion. These findings indicate that six DE‐miRNAs and their target genes may play important roles in the pathogenesis of NSCLC, which will provide novel information for NSCLC treatments.
Compromising the constitutive p16INK4a expression sensitizes human neuroblastoma cells to Hsp90 inhibition and promotes premature senescence
Authors: Kanugovi Abhijnya Vijayavittal , Joseph Chitra , Siripini Satish , Paithankar Khanderao , Amere Sreedhar Subbarao 
Published: November 2019

AbstractThe Hsp90 chaperone has become the attractive pharmacological target to inhibit tumor cell proliferation. However, tumor cells can evolve with mechanisms to overcome Hsp90 inhibition. Using human neuroblastoma, we have investigated one such limitation. Here, we demonstrate that neuroblastoma cells overcome the interference of tumor suppressor p16INK4a in cell proliferation, which is due to its latent interaction with CDK4 and CDK6. Cells also displayed impedance to the pharmacological inhibition of cancer chaperone Hsp90 inhibition with respect to induced cytotoxicity. However, the p16INK4a knockdown has triggered the activation of cyclin‐CDK6 axis and enhanced the cell proliferation. These cells are eventually sensitized to Hsp90 inhibition by activating the DNA damage response mediated through p53‐p21WAF‐1 axis and G1 cell cycle exit. While both CDK4 and CDK6 have exhibited low affinity to p16INK4a, CDK6 has exhibited high affinity to Hsp90. Destabilizing the CDK6 interaction with Hsp90 has prolonged G2/M cell cycle arrest fostering to premature cellular senescence. The senescence driven cells exhibited compromised metastatic potential both in vitro as well as in mice xenografts. Our study unravels that cancer cells can be adapted to the constitutive expression of tumor suppressors to overcome therapeutic interventions. Our findings display potential implication of Hsp90 inhibitors to overcome such adaptations.
M2‐polarized tumor‐associated macrophages promote epithelial‐mesenchymal transition via activation of the AKT3/PRAS40 signaling pathway in intrahepatic cholangiocarcinoma
Authors: Sun Dalong , Luo Tiancheng , Dong Pingping , Zhang Ningping , Chen Jing , Zhang Shuncai , Dong Ling , Janssen Harry L. A. , Zhang Si 
Published: November 2019

AbstractTumor‐associated macrophages (TAMs) have been considered as a major component of the tumor microenvironment. However, the crosstalk between M2‐polarized tumor‐associated macrophages (M2‐TAMs) and intrahepatic cholangiocarcinoma (ICC) remains undetermined. In the present study, we aimed to clarify the role of M2‐TAMs in ICC and the underlying mechanism. The in vitro assay demonstrated M2‐TAMs promoted epithelial‐mesenchymal transition (EMT) of ICC cells, resulting in enhanced cell invasion and metastasis ability. Moreover, M2‐TAMs modulated the microenvironment of ICC by increasing the secretion of cytokines (GM‐CSF, tumor necrosis factor‐α [TNF‐α], ICAM‐1, interleukin‐6 [IL‐6], etc) and chemokines (CCL1, CCL3, etc). In addition, p‐AKT (Ser473) and p‐PRAS40 (Thr246) were upregulated in ICC cells when cocultured with M2‐TAMs or treated with M2‐TAMs secreted core cytokines (GM‐CSF, TNF‐α, ICAM‐1, and IL‐6). Consistently, AKT3 silencing (but not AKT1 silencing and AKT2 silencing) markedly inhibited phosphorylation of AKT and PRAS40 of ICC cells and inhibited the EMT process when cocultured with M2‐TAMs. Taken together, the current data indicated that M2‐TAMs promoted ICC cells EMT, partially through increasing secretion of cytokines and chemokines, thus modulating the microenvironment and activating the AKT3/PRAS40 signaling pathway.
Comparison of the roles of estrogens and androgens in breast cancer and prostate cancer
Authors: Liu Wen‐Jing , Zhao Gang , Zhang Chen‐Yan , Yang Chang‐Qing , Zeng Xiang‐Bin , Li Jin , Zhu Kun , Zhao Shi‐Qi , Lu Hui‐Meng , Yin Da‐Chuan , Lin Sheng‐Xiang 
Published: November 2019

AbstractBreast cancer (BC) and prostate cancer (PC) are the second most common malignant tumors in women and men in western countries, respectively. The risks of death are 14% for BC and 9% for PC. Abnormal estrogen and androgen levels are related to carcinogenesis of the breast and prostate. Estradiol stimulates cancer development in BC. The effect of estrogen on PC is concentration‐dependent, and estrogen can regulate androgen production, further affecting PC. Estrogen can also increase the risk of androgen‐induced PC. Androgen has dual effects on BC via different metabolic pathways, and the role of the androgen receptor (AR) in BC also depends on cell subtype and downstream target genes. Androgen and AR can stimulate both primary PC and castration‐resistant PC. Understanding the mechanisms of the effects of estrogen and androgen on BC and PC may help us to improve curative BC and PC treatment strategies.
Extracellular vesicles from oviductal isthmus and ampulla stimulate the induced acrosome reaction and signaling events associated with capacitation in bovine spermatozoa
Authors: Franchi A. , Moreno‐Irusta A. , Domínguez E. M. , Adre A. J. , Giojalas L. C. 
Published: November 2019

AbstractCells can communicate with other neighboring or distant cells through the secretion of extracellular vesicles (EV), composed of a lipid bilayer and bearing surface molecules that allow them to recognize target cells. In this way, EV induce signaling via different mechanisms, modulating the physiological state of the recipient cell. EV have been identified in both male and female reproductive fluids, however, the possible role of EV isolated from female reproductive fluids has become an emerging field only recently. It is known that ejaculated mammalian spermatozoa need to undergo physiological preparation in the female reproductive tract to fertilize the egg. EV secreted by different regions of the female tract constitute signals that may have a key role in regulating sperm functions. The aims of the present study were isolating EV from different regions of the bovine oviduct and analyzing their interaction and physiological effects on spermatozoa. Here, we report the characterization of bovine oviductal fluid EV from the isthmus and ampulla region and their effect on the induced acrosome reaction and signaling events associated with sperm capacitation. EV induced an increase in sperm protein tyrosine phosphorylation, while cell survival of cryopreserved bovine spermatozoa was maintained. We also show that EV uptake regulates the sperm calcium levels by inducing an immediate increase in the intracellular calcium concentration and sperm priming, after a pre‐incubation period, of the progesterone‐induced intracellular calcium rise. Our data contribute to understand the role of EV in the communication between the female reproductive tract and the sperm physiology, information that may be used to improve the efficiency of reproductive assisted technologies.
Molecular characterization of lung cancer: A two‐miRNA prognostic signature based on cancer stem‐like cells related genes
Authors: Cheng Yanping , Yang Sheng , Shen Bo , Zhang Yan , Zhang Xiaomei , Liu Tong , Xu Siyi , Sui Jing , Yin Lihong , Pu Yuepu , Liang Geyu 
Published: November 2019

AbstractLung cancer is one of the deadliest cancers worldwide. To increase the survival rate of lung cancer, it is necessary to explore specific prognosis markers. More and more evidence finds that noncoding RNA is closely associated with the survival of lung cancer, and cancer stem cells (CSCs) also play a significant role in the progress of lung cancer. The objective of this study is to find CSLCs genes that affect the prognosis of lung cancer. The differential expression of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), messenger RNAs (mRNAs) in the Cancer Genome Atlas (TCGA) database and differential expression data from microarray of CD326+ and CD326− A549 cell are intersected to identify stable and consistent expression genes (2 lncRNAs, 15 miRNAs, and 134 mRNAs). The intersection of lncRNAs and miRNAs is analyzed by univariate and multivariate Cox regression to obtained prognostic genes. Two miRNAs (miR‐30b‐5p and miR‐29c‐3p) are significantly correlated with the overall survival rate. Then using these two miRNAs to construct a risk score model as a prognosis signature of lung cancer. Subsequently, we analyzed the association between two miRNAs and clinical information of lung cancer patients, of which T stage, Neoplasm cancer and risk score (P < .05) can be used as independent prognostic indicators of lung cancer. Finally, target genes of 2 miRNAs and 134 mRNAs were annotated with Gene Ontology and analyzed with Kyoto Encyclopedia of Genes and Genomes pathway, and verified with the GEO database. In summary, this study illustrates the role of miRNAs in the promotion of lung cancer by CSCs, which is important to find molecular biomarkers of lung cancer.
Genetic diversity of Paramecium species on the basis of multiple loci analysis and ITS secondary structure models
Authors: Tasneem Fareeda , Shakoori Farah R. , Ilyas Muhammad , Shahzad Naveed , Potekhin Alexey , Shakoori Abdul R. 
Published: November 2019

AbstractAmong ciliates, Paramecium has become a privileged model for the study of “species problem” particularly in the case of the “Paramecium aurelia complex” that has been intensely investigated. Despite extensive studies, the taxonomy of Paramecium is still challenging. The major problem is an uneven sampling of Paramecium with relatively few representatives of each species. To investigate species from the less discovered region (Pakistan), 10 isolates of Paramecium species including a standing‐alone FT8 strain previously isolated by some of us were subjected to molecular characterization. Fragments of 18S recombinant DNA (rDNA), ITS1‐5.8S‐ITS2‐5′LSU rDNA, cytochrome c oxidase subunit II, and hsp70 genes were used as molecular markers for phylogenetic analysis of particular isolates. The nucleotide sequences of polymerase chain reaction products of all markers were compared with the available sequences of relevant markers of other Paramecium species from GenBank. Phylogenetic trees based on all molecular markers showed that all the nine strains had a very close relationship with Paramecium primaurelia except for the FT8 strain. FT8 consistently showed its unique position in comparison to all other species in the phylogenetic trees. Available sequences of internal transcribed spacer 1 (ITS1) and ITS2 and some other ciliate sequences from GenBank were used for the construction of secondary models. Two highly conserved helices supported by compensatory base changes among all ciliates of ITS2 secondary structures were found similar to other eukaryotes. Therefore, the most conserved 120 to 180 base pairs regions were identified for their comparative studies. We found that out of the three helices in ITS1 structure, helix B was more conserved in Paramecium species. Despite various substitutions in the primary sequence, it was observed that secondary structures of ITS1 and ITS2 could be helpful in interpreting the phylogenetic relationships both at species as well as at generic level.