bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reactive oxygen/nitrogen species (ROS/RNS) and oxidative stress in arthroplasty
Authors: Hameister Rita , Kaur Charanjit , Dheen Shaikali Thameem , Lohmann Christoph H. , Singh Gurpal 
Published: January 2020

AbstractThe interplay between implant design, biomaterial characteristics, and the local microenvironment adjacent to the implant is of utmost importance for implant performance and success of the joint replacement surgery. Reactive oxygen and nitrogen species (ROS/RNS) are among the various factors affecting the host as well as the implant components. Excessive formation of ROS and RNS can lead to oxidative stress, a condition that is known to damage cells and tissues and also to affect signaling pathways. It may further compromise implant longevity by accelerating implant degradation, primarily through activation of inflammatory cells. In addition, wear products of metallic, ceramic, polyethylene, or bone cement origin may also generate oxidative stress themselves. This review outlines the generation of free radicals and oxidative stress in arthroplasty and provides a conceptual framework on its implications for soft tissue remodeling and bone resorption (osteolysis) as well as implant longevity. Key findings derived from cell culture studies, animal models, and patients' samples are presented. Strategies to control oxidative stress by implant design and antioxidants are explored and areas of controversy and challenges are highlighted. Finally, directions for future research are identified. A better understanding of the host‐implant interplay and the role of free radicals and oxidative stress will help to evaluate therapeutic approaches and will ultimately improve implant performance in arthroplasty.
Retracted: LINC00657 activates PD‐L1 to promote osteosarcoma metastasis via miR‐106a
Authors: Zhang Jun , Chou Xubin , Zhuang Ming , Zhu Chenlei , Hu Yong , Cheng Dong , Liu Zhiwei 
Published: January 2020

AbstractOsteosarcoma (OS) cells are one of the primary cancer‐related causes of death around the world. Long noncoding RNAs are key for OS progression; however, the detailed molecular mechanism remains unknown. LINC00657, miR‐106a, and programmed death ligand‐1 (PD‐L1) genes expression were detected by reverse transcription‐quantitative PCR (RT‐qPCR) and Western blot approaches. Invasion and lymphangiogenesis were studied using transwell invasion assay and lymphatic vessel formation assay, respectively. We used bioinformatic analyses to identify putative targets of LINC00657 and miR‐106a. Luciferase activity was measured by dual‐luciferase reporter assay. PD‐L1 protein levels were examined by flow cytometry experiments. LINC00657 knockdown attenuates cell invasion and tumor growth of MG63 and lymphatic vessel formation. miR‐106a directly binds LINC00657 and they regulate each other. Furthermore, miR‐106a inhibitor strikingly enhanced lymphatic vessel formation and invasion of shLINC00657 MG63 cells. miR‐106a mimic directly targeted and downregulated PD‐L1. PD‐L1 overexpression largely rescued miR‐106a mimic‐modulated OS cell metastasis. LINC00657 and PD‐L1 were upregulated in clinical OS tumors compared to normal tissues. Lower expression levels of LINC00657 and PD‐L1 were closely associated with higher overall survival of patients with OS. Here, we suggest a novel mechanism for LINC00657‐regulated metastasis of OS cells by regulating the miR‐106a/PD‐L1 axis. Our conclusions facilitate the development of therapeutical approaches by targeting LINC00657.
Transcription factor RUNX3 promotes CD8+ T cell recruitment by CCL3 and CCL20 in lung adenocarcinoma immune microenvironment
Authors: Song Qian , Shang Jun , Zhang Chufan , Chen Jianing , Zhang Lanlin , Wu Xianghua 
Published: January 2020

AbstractConsidering the existence of immune‐desert in tumor microenvironment, the clinical efficacy of immunotherapy for lung adenocarcinoma is limited. This study aims to investigate the ability of transcription factors in regulating tumor immune microenvironment in lung adenocarcinoma. RNA‐seq data were collected from the The Cancer Genome Atlas database. The relationships between transcription factors and immune infiltrates were assessed. Runt‐related transcription factor 3 (RUNX3)‐associated immune pathways were investigated by the Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and Gene set enrichment analysis. Upregulated chemokines in the RUNX3‐overexpressed cell line were determined by quantitative real‐time polymerase chain reaction, western blot, and enzyme‐linked immunosorbent assay. These chemokines were further confirmed in RUNX3‐downregulated cell lines. Immunochemistry was conducted to determine the expression of RUNX3, CCL3, CCL20, and the numbers of CD8+ T lymphocytes in human lung cancer tissues. Chemokine receptors in CD8+ T cells were explored by flow cytometry and immunofluorescence. T cell recruitment was investigated by transwell assay. After screening 406 transcription factors, RUNX3 was found strongly correlated T cells, cytotoxic lymphocytes, and CD8+ T cells. RUNX3 was associated with a variety of immunomodulators, including LAG3, CTLA‐4, PD‐1, and TIGIT. More importantly, RUNX3 was involved in immune‐related pathways, especially immune cell migration‐related pathways. Further investigation exhibited RUNX3 could upregulate CCL3 and CCL20 whose receptors CCR5 and CCR6 were upregulated in CD8+ effector T cells, while downregulation of RUNX3 decreased the expression of CCL3 and CCL20 and the infiltration of CD8+ T cells in RUNX3‐downregulated lung cancer cell lines. Immunochemistry exhibited positive correlations of RUNX3 with CCL3 and CD8+ T cells in clinical lung adenocarcinoma samples. The chemotaxis assay proved RUNX3 could promote CD8+ T cell recruitment by upregulating CCL3 and CCL20. This study unearths RUNX3 related molecular mechanisms of tumor immune microenvironment and may reverse the immune‐desert condition in lung adenocarcinoma and be combined with immune checkpoint blockade and adoptive cell therapy.
Comprehensive analysis of biological networks and the eukaryotic initiation factor 4A‐3 gene as pivotal in hepatocellular carcinoma
Authors: Lin Yan , Liang Rong , Mao Yingwei , Ye Jiazhou , Mai Rongyun , Gao Xing , Liu Ziyu , Wainwright Taylor , Li Qian , Luo Min , Ge Lianying , Li Yongqiang , Zou Donghua 
Published: January 2020

AbstractEukaryotic initiation factor 4A‐3 (EIF4A3) is a core component of the exon junction complex (EJC). Abnormalities in EIF4A3 are associated with carcinogenesis. The present study aimed to determine the biological role of EIF4A3 in hepatocellular carcinoma (HCC). Our study is based on the analysis of HCC sequencing data from public databases. We first used the Gene Expression Profiling Interactive Analysis tool and ONCOMINE to analyze the EIF4A3 expression, and the results were validated in human clinical tissues by a quantitative real‐time polymerase chain reaction, Western blot, and immunohistochemical. Then, we used cBioPortal to identify EIF4A3 alterations and function networks. Finally, we created a network of genes that were positively correlated with EIF4A3 using LinkedOmics, and analyzed this network using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. For the genes identified, we also analyzed the relevant kinase and transcription factor target networks as well as the protein‐protein interaction networks. Our results show that EIF4A3 was overexpressed in HCC tissues in comparison with normal tissues, and high EIF4A3 expression was significantly associated with poor prognosis. Analysis of the functional networks of genes that were co‐occurring with EIF4A3 amplification revealed connections with several chemokine signaling pathways. Furthermore, genes that positively correlated with EIF4A3 were mainly related to cell cycle and spliceosome pathways, several cell cycle regulatory kinases, and tumor‐associated transcription factors. Finally, crosslinking‐immunoprecipitation and high‐throughput sequencing (CLIP‐seq) data showed that EIF4A3 protein binds to multiple exon regions of the cell cycle regulatory genes cyclin‐dependent kinases 1 and 2 and transcription factor E2F1. Our study unveils potential biological networks in HCC and the pivotal role of EIF4A3 as a bridging protein, highlighting the need for an in‐depth study of EIF4A3 in carcinogenesis.
LncRNA CRNDE is activated by SP1 and promotes osteosarcoma proliferation, invasion, and epithelial‐mesenchymal transition via Wnt/β‐catenin signaling pathway
Authors: Ding Qiuyue , Mo Fengbo , Cai Xianyi , Zhang Wenda , Wang Jinglong , Yang Shuhua , Liu Xianzhe 
Published: January 2020

AbstractLong noncoding RNAs (lncRNAs) were identified as a vital part in the development and progression of cancer in recent years. Colorectal neoplasia differentially expressed (CRNDE), a lncRNA, functions as an oncogene in some malignant neoplasias, but its role in the progression of osteosarcoma (OS) is still poorly understood. To dissect the difference in the expression of CRNDE, quantitative real‐time polymerase chain reaction was utilized to evaluate it in OS tissues and cell lines (U2OS, MG63, and MNNG/HOS) compared with that in the adjacent normal tissues/osteoblast cells (hFOB1.19). The role of CRNDE in OS lines was assessed using Cell Counting Kit‐8, colony formation, 5‐ethynyl‐2′‐deoxyuridine staining, terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick‐end labeling staining, flow cytometry, Transwell assays, and Western blot, respectively. The results demonstrated that the expression of CRNDE was high in OS tissues and cell lines, and partly induced by SP1. CRNDE knockdown attenuated OS cell proliferation and invasion and induced apoptosis and G0/G1 arrest. Moreover, the expression of mesenchymal markers N‐cadherin, Vimentin and Snail were downregulated, while the expression of epithelial markers E‐cadherin and ZO‐1 were conversely upregulated due to CRNDE knockdown. The mechanistic investigations showed that CRNDE promoted glycogen synthase kinase‐3β phosphorylation to activate the Wnt/β‐catenin pathway. The results suggested that lncRNA CRNDE indeed contributed to OS proliferation, invasion, and epithelial‐mesenchymal transition, working as an oncogene, demonstrating that lncRNA CRNDE may be a valid therapeutic target for the OS.
A novel miRNA located in the GATA4 gene regulates the expression of IGF‐1R and AKT1/2 genes and controls cell proliferation
Authors: Medlej Abdallah , Mohammad Soltani Bahram , Javad Mowla Seyed , Hosseini Saeid , Baharvand Hossein 
Published: January 2020

AbstractGATA4 gene is a zinc‐finger transcription factor known to be involved in cardiogenesis and the progression of different cancer types. Its diverse functions might be attributed to noncoding RNAs that could be embedded within its sequence. Here, we predicted a stable RNA stem‐loop structure that is located in the second intron of the GATA4 gene. Available microRNA (miRNA) sequencing data and molecular genetics tools confirmed the identity of a mature miRNA (named GATA4‐miR1) originating from the predicted stem‐loop. In silico analysis predicted IGF‐1R and AKT1/2 genes as potential targets for GATA4‐miR1. Indeed, direct interactions between GATA4‐miR1 and 3′ untranslated regions sequences of IGF‐1R and AKT1/2 genes were documented by dual luciferase assay. In addition, overexpression of GATA4‐miR1 in SW480 cells resulted in the reduction of IGF‐1R and AKT1/2 genes’ expression, detected by reverse transcription quantitative (RT‐q) polymerase chain reaction and Western blot analysis. This observation was consistent with a deduced negative correlation between the expression patterns of GATA4‐miR1 and IGF‐1R genes during cardiomyocyte differentiation. Moreover, overexpressing GATA4‐miR1 in SW480 and PC3 cells resulted in a significant increase of the sub‐G1 population in both cell lines, as detected by propidium iodide flow cytometry. Further analysis by 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide assay indicated a reduction in the survival and proliferation rates of SW480 cells overexpressing GATA4‐miR1, but no impact was observed on apoptosis progression, as indicated by Annexin‐V flow cytometry. Overall, GATA4‐miR1 represents a promising candidate for further research in the fields of cancer and cardiovascular therapeutics.
A switch in bidirectional histone mark leads to differential modulation of lincRNAs involved in neuronal and hematopoietic cell differentiation from their progenitors
Authors: Murad Md. Wahid , Khan Md. Abdullah‐Al‐Kamran , Islam Md. Sajedul , Islam Abul Bashar Mir Md. Khademul 
Published: January 2020

AbstractLong intergenic noncoding RNAs (lincRNAs) are more than 200 bases long, transcribed from intergenic genomic regions and do not undergo translation. They have regulatory roles in differentiation and development. However, how their transcription is activated and how their expression is differentially modulated in differentiation is quite unclear. In this study, we explored and analyzed data at the transcriptomic and epigenetic level to address these questions. Here, we identified novel lincRNAs that are differentially expressed in neuronal and hematopoietic differentiation and showed that such differential modulations are achieved under epigenetic regulations. lincRNAs that are upregulated in mature cells than in progenitor are activated from a bivalent poised state where activating H3K4me3/H3K9ac/H3K27ac and suppressive H3K9me3/H3K27me3 marks are colocalized. And, lincRNAs that are downregulated in mature cells after differentiation are suppressed by the addition of H3K9me3/H3K27me3 marks. Moreover, here we show a tissue‐specific expression pattern of lincRNAs in various cell lines and normal tissues. The study reveals bidirectional histone marks as an epigenetic means of directing the differential expression of lincRNAs which are found to be involved in the process of cellular differentiation.
Long‐term cultivation of human amniotic fluid stem cells: The impact on proliferative capacity and differentiation potential
Authors: Gasiūnienė Monika , Valatkaitė Elvina , Navakauskienė Rūta 
Published: January 2020

AbstractHuman amniotic fluid mesenchymal stem cells (AF‐MSCs) are a valuable, easily obtainable alternative source of SCs for regenerative medicine. Usually, amounts of cells required for the translational purposes are large thus the goal of this study was to assess the potency of AF‐MSCs to proliferate and differentiate during long‐term cultivation in vitro. AF‐MSCs were isolated from amniotic fluid of healthy women in the second trimester of pregnancy and cultivated in vitro. AF‐MSCs were cultivated up to 42 passages and they still maintained pluripotency genes, such as OCT4, SOX2, and NANOG, expression at a similar level as in the initial passages as determined by reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR). Fluorescence‐activated cell sorting analysis demonstrated that the cell surface markers CD34 (negative), CD44, and CD105 (positive) expression was also stable, only the expression of SCs marker CD90 decreased during the cultivation. The morphology of AF‐MSCs changed over passage, acridine orange/ethidium bromide staining revealed that more cells entered into apoptosis and the first signs of aging were detected only at late passages (later than p33) using SA‐β‐gal assay. Concomitantly, the differentiation potential towards cardiomyogenic lineage, induced with DNA methyltransferases inhibitors decitabine, zebularine, and RG108, was impaired when comparing AF‐MSCs at p31/33 with p6. The expression of cardiomyocytes genes MYH6, TNNT2, DES together with ion channels genes of the heart (sodium, calcium, and potassium) decreased in p31/33 induced AF‐MSCs. AF‐MSCs have a great proliferative capacity and maintain most of the characteristics up to 33 passages; however, the cardiomyogenic differentiation capacity decreases to a certain extent during the long‐term cultivation. These results provide useful insights for the potential use of AF‐MSCs for biobanking and broad applications requiring high yield of cells or repeated infusions. Hence, it is vital to take into account the passage number of AF‐MSCs, cultivated in culture, when utilizing them in vivo or in clinical experiments.
Lnc‐MUC20‐9 binds to ROCK1 and functions as a tumor suppressor in bladder cancer
Authors: Dai Ranran , Zhou You , Chen Zhishan , Zou Zihao , Pan Zhaojun , Liu Ping , Gao Xingcheng 
Published: January 2020

AbstractThe study aimed to investigate the expression and function of bladder cancer (BC) long noncoding RNAs (lncRNAs) using a high‐throughput platform. High‐throughput sequencing was used to compare the expression profiles of lncRNA in BC and adjacent normal tissues. Quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR), in situ hybridization, gene ontology, and Kyoto Encyclopedia of Genes and Genomes analysis were performed to verify differential expression of lncRNA. The effect of lncRNA overexpression on cellular proliferation, apoptosis, migration, and invasion was analyzed following the transfection of lncRNA overexpressing lentivirus into 5637 and T24 cell lines. The overexpressing cells were subcutaneously injected into nude mice to evaluate their effects on tumor growth. Tumor‐associated RNA‐binding proteins of lncRNA were analyzed by RNA pull‐down combined with mass spectrometry. A total of 93 lncRNA genes were upregulated and 352 lncRNA genes were downregulated in the tissues of patients with BC. Of which, we investigated the function of downregulated lnc‐MUC20‐9. Overexpression of lnc‐MUC20‐9 in 5637 and T24 cells resulted in decreased tumor cell viability and cell clones, decreased migration and invasion, and increased apoptosis. Similarly, nude mice bearing lnc‐MUC20‐9 overexpressing tumor cells exhibited smaller tumor size and volume than that of mice bearing control cells. Mass spectrometry analysis showed that lnc‐MUC20‐9 binds to ROCK1, an oncogene whose expression was decreased in lnc‐MUC20‐9 overexpressing cells. The study revealed that lnc‐MUC20‐9 has the function of inhibiting tumor growth, migration, and invasion. In BC cells, lnc‐MUC20‐9 binds to ROCK1 and may be involved in lnc‐MUC20‐9‐mediated tumor suppressor function, which might be potential therapeutic targets for BC.
Bio‐based benzoxazines synthesized in a deep eutectic solvent: A greener approach toward vesicular nanosystems
Authors: Behalo Mohamed S. , Bloise Ermelinda , Mele Giuseppe , Salomone Antonio , Messa Francesco , Carbone Luigi , Mazzetto Selma Elaine , Lomonaco Diego 
Published: January 2020

AbstractA green synthesis of benzoxazines, based upon reaction of cardanol with formaldehyde and primary amines, is achieved in high yields using choline chloride‐urea mixture as deep eutectic solvent. Then, it is demonstrated how the cardanol‐based benxoxazines can be employed as only component for the preparation of a nanovesicular systems.
Administration of gamma‐hydroxybutyrate instead of beta‐hydroxybutyrate to a liver transplant recipient suffering from propionic acidemia and cardiomyopathy: A case report on a medication prescribing error
Authors: Tuchmann‐Durand Caroline , Thevenet Eloise , Moulin Florence , Lesage Fabrice , Bouchereau Juliette , Oualha Mehdi , Khraiche Diala , Brassier Anaïs , Wicker Camille , Gobin‐Limballe Stéphanie , Arnoux Jean‐Baptiste , Lacaille Florence , Wicart Clotilde , Coat Bruno , Schlattler Joel , Cisternino Salvatore , Renolleau Sylvain , Secretan Philippe‐Henri , De Lonlay Pascale 
Published: January 2020

AbstractBeta‐hydroxybutyrate (BHB) is a synthetic ketone body used as an adjuvant energy substrate in the treatment of patients with metabolic cardiomyopathy. A medication prescribing error led to the administration of the general anesthetic sodium gamma‐hydroxybutyrate (GHB) instead of sodium BHB in a liver transplant recipient with propionic acidemia and cardiomyopathy, causing acute coma. A 15‐year‐old boy suffering from neonatal propionic acidemia underwent liver transplantation (LT) for metabolic decompensation and cardiomyopathy (treated with cardiotropic drugs and BHB) diagnosed a year previously. The patient had been rapidly extubated after LT, and was recovering well. Eight days after LT, the patient suddenly became comatose. No metabolic, immunological, hypertensive, or infectious complications were apparent. The brain magnetic resonance imaging and electroencephalography results were normal. The coma was soon attributed to a medication prescribing error: administration of GHB instead of BHB on day 8 post‐LT. The patient recovered fully within a few hours of GHB withdrawal. The computerized prescription system had automatically suggested the referenced anesthetic GHB (administered intravenously) instead of the non‐referenced ketone body BHB, triggering coma in our patient. A computerized prescription system generated a medication prescribing error for a rare disease, in which the general anesthetic GHB was mistaken for the nonreferenced energy substrate BHB.
The multi‐component Hekla Ö Tephra, Iceland: a complex widespread mid‐Holocene tephra layer
Authors: Jónsson Daníel Freyr , Gudmundsdóttir Esther Ruth , Larsen Gudrún , Óladóttir Bergrún Arna , Erlendsson Egill , Eddudóttir Sigrún Dögg , Sigmarsson Olgeir 
Published: January 2020

ABSTRACTLarge Plinian eruptions from Hekla volcano, Iceland, produce compositionally zoned tephra used as key markers in tephrochronology. However, spatial variations in chemical composition of a tephra layer may complicate its identification. An example is the 5950–6180 cal a bp Hekla Ö tephra layer, which shows compositional spread from rhyolite, dacite and andesite to basalt. In soil sections north of Hekla, the SiO2 content of the tephra glass reaches 76 wt% in the lowest unit of the Hekla Ö deposit and decreases to 62–63 wt% in the uppermost unit. Intermingled within the whole deposit are basalt tephra grains having 46–47 wt% SiO2. The composition of the basalt glass includes primitive basalt and a more evolved basalt (MgO >6 and <6 wt%, respectively). Together with literature data, the Hekla Ö tephra and the so‐called T‐Tephra/Hekla‐T are most likely from contemporaneous eruptions of different vents on the Hekla volcanic system, forming a single important marker tephra (Hekla ÖT) deposited over 80% of Iceland. Identification is complicated by its spatial compositional heterogeneity, such as systematic decrease in SiO2 content from the east to the west of Hekla volcano. Consequently, an individual tephra layer from a large explosive eruption can have different composition at different locations. © 2020 John Wiley & Sons, Ltd.
Head‐attached live sperm cell for label‐free micro‐Raman evaluation of sperm DNA integrity: A preliminary study
Authors: Huang Zufang , Du ShengRong , Liang Xiaozhou , Sun Yan , Chen Xiwen , Lin Juqiang , Li Yongzeng , Chen Guannan , Feng Shangyuan 
Published: January 2020

AbstractHigh‐quality spermatozoa are essential for intracytoplasmic sperm injection. However, there is still a lack of noninvasive, objective tools that provide biochemical characteristics to select high‐quality spermatozoa in clinical settings. In this work, a facile yet efficient approach was proposed, rendering the live sperm cell with its head being attached on the surface of a substrate, which allows the subsequent micro‐Raman‐based biochemical analysis and evaluation of sperm DNA integrity noninvasively and nondestructively. Moreover, our preliminary results show that Raman peaks at 1,050 and 1,095 cm−1, which are assigned to DNA backbone mode and whose spectral intensity ratio are suggested as a potential spectral biomarker for evaluation of sperm DNA integrity, can be clearly observed, thus implying our facile yet efficient technique for further potential DNA integrity assessment of live sperm cell.