bluuebunny/crossref_metadata_2025_split huggingface dataset:
Artemisinin inhibits angiogenesis by regulating p38 MAPK/CREB/TSP‐1 signaling pathway in osteosarcoma
Authors: Li Zhi , Ding Xiaomin , Wu Haihui , Liu Chao 
Published: February 2019

AbstractOsteosarcoma is the most common bone tumor and characterizes a high metastatic potential. In osteosarcoma, angiogenesis is reported to be closely associated with tumor metastasis. Understanding the underlying mechanisms and accordingly developing therapeutic strategies are urgently desired. Antimalarial agent, artemisinin, has been reported to inhibit tumor angiogenesis. However, we still knew little about the effects of artemisinin on angiogenesis and its potential molecular mechanisms in human osteosarcoma. In this study, we found that artemisinin could induce both the expression and secretion of thrombospondin‐1 (TSP‐1) in a dose‐dependent way in osteosarcoma cells. In addition, TSP‐1 could effectively restore the artemisinin‐induced suppression of angiogenesis in human umbilical vein endothelial cells (HUVECs). More importantly, we further found that phosphorylation of cAMP response element‐binding protein (CREB) bond specifically to the promoter of TSP‐1 and promoted its transcriptional activation. Moreover, our results showed that artemisinin could induce the phosphorylation of CREB via the activation of p38 mitogen‐activated protein kinase (MAPK) signaling pathway in osteosarcoma cells. In vivo, we also found that artemisinin could inhibit osteosarcoma proliferation and angiogenesis by regulating the p38 MAPK/CREB/TSP‐1 signaling pathway. Taken together, our findings indicated that artemisinin could inhibit angiogenesis by regulating the p38 MAPK/CREB/TSP‐1 signaling pathway in osteosarcoma.
Evaluation of prognostic usefulness of long noncoding RNA GAS5 and FAL1 in papillary thyroid carcinoma
Authors: Shams Fatemeh , Ghorbian Saeid 
Published: February 2019

AbstractGenetic studies on cancers have revealed that lncRNA‐GAS5 and lncRNA‐FAL1 are overexpressed in some cancerous cells. The aim of the present investigation was to evaluate the roles of lncRNA‐GAS5 and lncRNA‐FAL1 gene expression changes in the diagnosis and prognosis of patients with papillary thyroid carcinoma (PTC). In a case‐control investigation, we recruited a total of 140 formalin‐fixed paraffin‐embedded tissues of PTC, including 70 cancerous and noncancerous tissues. Quantitative real‐time polymerase chain reaction was used to determine the lncRNA‐GAS5 and lncRNA‐FAL1 level of gene expression in the two tissue groups. The association between the clinicopathological characteristics of patients and the expression level of lncRNA‐GAS5 and lncRNA‐FAL1 was evaluated. Our findings revealed that the level of expression in the lncRNA‐GAS5 and lncRNA‐FAL1 genes was significantly upregulated in thyroid cancerous tissues (P < 0.003 and P < 0.040, respectively). The expression of lncRNA‐GAS5 and lncRNA‐FAL1 revealed a significant association with tumor node metastasis staging (P < 0.042 and P < 0.001, respectively). It seems that the lncRNA‐GAS5 and lncRNA‐FAL1 genes play an oncogenic role in PTC. The two genes have a significant potential prognostic value and may likely be used as novel therapeutic targets for PTC patients in the future.
Interleukin‐17A‐mediated alleviation of cortical astrocyte ischemic injuries affected the neurological outcome of mice with ischemic stroke
Authors: Dai Qingqing , Li Shujuan , Liu Ting , Zheng Jiayin , Han Song , Qu Aijuan , Li Junfa 
Published: February 2019

AbstractWe previously reported that astrocytes are the main sources of interleukin (IL)‐17A production that could aggravate neuronal injuries in ischemic stroke. However, the effects of IL‐17A on ischemic astrocytes themselves and the underlying molecular mechanism are still unclear. In this study, we found that recombinant mouse (rm) IL‐17A could significantly (P < 0.05 or <0.001) alleviate 1‐hour oxygen‐glucose deprivation (OGD)/reoxygenation (R) 24‐hour–induced ischemic injuries in cortical astrocytes with a dose‐dependent manner (n = 6 per group). The Western blot and cell cycle analysis results revealed that rmIL‐17A significantly (
P < 0.05) inhibited procaspase‐3 cleavage without affecting cell proliferation in 1‐hour OGD/R 24‐hour–treated cortical astrocytes (n = 6 per group). Among the five IL‐17 receptor subunits (IL‐RA, ‐RB, ‐RC, ‐RD, and ‐RE), only IL‐17RA (
P < 0.01) and ‐17RC (
P < 0.05) membrane translocation (not messenger RNA and protein) levels were downregulated in cortical astrocytes following 1‐hour OGD/reperfusion 24 hours, and rmIL‐17A could significantly (
P < 0.05 or <0.001) inhibit this downregulation (n = 6 per group). To further verify the impact of IL‐17A on the neurological outcome of ischemic stroke, we found that the intracerebroventricular injection of IL‐17A neutralizing monoclonal antibody remarkably (
P < 0.001) reduced the astrocyte activation and improve neurological function (
P < 0.05 or <0.01) of mice following 1‐hour middle cerebral artery occlusion/reperfusion (R) 3 to 7 days (n = 6 or 8 per group). These results suggested that IL‐17A‐mediated alleviation of cortical astrocyte ischemic injuries could affect the neurological outcome of mice with ischemic stroke, which might be mainly dependent on the cell apoptosis pathway through inhibiting the downregulation of IL‐17RA and ‐17RC membrane translocations.
The effects of adipose‐derived stem cells on CD133‐expressing bladder cancer cells
Authors: Maj Malgorzata , Kokocha Anna , Bajek Anna , Drewa Tomasz 
Published: February 2019

AbstractMesenchymal stem cells (MSCs) hold great promise as therapeutic agents in regenerative medicine. They are also considered as a preferred cell source for urinary tract reconstruction. However, as MSCs exhibit affinity to tumor microenvironment, possible activation of tumor‐initiating cells remains a major concern in the application of stem cell‐based therapies for patients with a bladder cancer history. To analyze the influence of adipose‐derived stem cells (ASCs) on bladder cancer cells with stem cell‐like properties, we isolated CD133‐positive bladder cancer cells and cultured them in conditioned medium from ASCs (ASC‐CM). Our results showed that parental 5637 and HB‐CLS‐1 cells showed induced clonogenic potential when cultured in ASC‐CM. Soluble mediators secreted by ASCs increased proliferation and viability of unsorted cells as well as CD133+ and CD133− subpopulations. Furthermore, incubation with ASC‐CM modulated activation of intracellular signaling pathways. Soluble mediators secreted by ASCs increased phosphorylation of AKT1/2/3 (1.4‐fold, P < 0.05), ERK1/2 (1.6‐fold, P < 0.02), and p70 S6K (1.4‐fold) in CD133+ cells isolated from 5637 cell line. In turn, decreased phosphorylation of those three proteins involved in PI3K/Akt and MAPK signaling was observed in CD133+ cells isolated from HB‐CLS‐1 cell line. Our results revealed that bladder cancer stem‐like cells are responsive to signals from ASCs. Paracrine factors secreted by locally‐delivered ASCs may, therefore, contribute to the modulation of signaling pathways involved in cancer progression, metastasis, and drug resistance.
Cell‐specific elevation of Runx2 promotes hepatic infiltration of macrophages by upregulating MCP‐1 in high‐fat diet‐induced mice NAFLD
Authors: Zhong Li , Huang Lu , Xue Qian , Liu Chang , Xu Keshu , Shen Wei , Deng Liang 
Published: February 2019

AbstractObjectiveWe have demonstrated runt‐related transcription factor 2 (Runx2) plays important role in atherosclerosis. It has been indicated that atherosclerosis shares the similar histopathology with nonalcoholic steatohepatitis (NASH), a progressive stage of nonalcoholic fatty liver disease (NAFLD), on macrophages infiltration. However, the function of Runx2 in NAFLD is completely unknown. Here, we investigated the underlying mechanism of Runx2 triggering macrophages infiltration in the development of NAFLD.MethodsMice were fed with high‐fat diet (HFD) for a long time. Histopathologic features, macrophages infiltration, expression of monocyte chemotactic protein 1 (MCP‐1), and Runx2 were, respectively, analyzed in vivo. Lentivirus or short interfering RNA were transfected in murine hepatic stellate cells (HSCs) and the transwell assay was performed to verify the contribution of Runx2 for macrophages migration in vitro.ResultsLong‐term treatment with HFD induced the progression of NAFLD, and NASH was initiated from 8 months on diet. HFD increased the expression of F4/80 upon HFD feeding, indicated HFD promotes hepatic infiltration of macrophages in NAFLD. In addition, HFD upregulated the expression of MCP‐1 and Runx2 during NAFLD development. Unexpectedly, Runx2 upregulation is cell‐type depended in NAFLD, and only abundantly elevated in activated HSCs. Furthermore, we found that Runx2 could increase or decrease the expression of MCP‐1 in HSCs, and regulate macrophages migration by influencing MCP‐1 production in vitro.ConclusionsOur results give evidence that the upregulation of Runx2 specific in activated HSCs promotes hepatic infiltration of macrophages by increasing MCP‐1 expression in NAFLD, which reveals a novel mechanism and provides a cell‐specific therapeutic target for NAFLD.
Profiles analysis reveals circular RNAs involving zebrafish physiological development
Authors: Liu Heng , Hu Yin , Yin Jing , Yan Xiang‐Yun , Chen Wen‐Juan , Jiang Cheng‐Yao , Hu Xiao‐Shan , Wang Xing‐Yun , Zhu Jin‐Gai , Yu Zhang‐Bin , Han Shu‐Ping 
Published: February 2019

AbstractRecent studies have found that known functions of circular RNAs (circRNAs) include sequestration of microRNAs (miRNAs) or proteins, modulation of transcription and interference with splicing, and even translation to produce polypeptides. The zebrafish model is also demonstrably similar to humans in many studies. To explore the changes in circRNAs during embryonic development and to further research the mechanism of action of circRNAs in development‐related diseases, Zebrafish embryos at the blastula period, gastrula period, segmentation period, throat stage, and incubation period were collected. Illumina deep‐sequencing technology and CircRNA Identifier (CIRI) algorithm were used to detect circRNAs. In total, we identified 1,028 circRNAs (junction reads ≥5 and p < 0.05). Considering that the function of circRNAs is related to host genes, a bioinformatics analysis revealed these differentially expressed host genes are involved in NOTCH signaling pathways, cardiovascular system development, retinal ganglion cell axon guidance, and so on. Moreover, circRNAs can participate in biological regulation through the function of miRNA sponges. TargetScan and miRanda were used to predict 73 miRNAs binding to circRNAs such as miR‐19b, miR‐124, and so on. Some miRNAs play important roles in embryogenesis. The peak expression of circRNAs is distributed at different time points, suggesting that it may be involved in embryogenesis at different stages. Our study provides a foundation for understanding the dynamic regulation of circRNA transcriptomes during embryogenesis and identifies novel key circRNAs that might control embryonic development in a zebrafish model.
Endoplasmic reticulum stress and NLRP3 inflammasome: Crosstalk in cardiovascular and metabolic disorders
Authors: Ji Ting , Han Yuehu , Yang Wenwen , Xu Baoping , Sun Meng , Jiang Shuai , Yu Yuan , Jin Zhenxiao , Ma Zhiqiang , Yang Yang , Hu Wei 
Published: February 2019

AbstractWhen endoplasmic reticulum (ER) homeostasis is disrupted, known as ER stress (ERS), the ER generates an adaptive signaling pathway called the unfolded protein response to maintain the homeostasis of this organelle. However, if homeostasis is not restored, the ER initiates death signaling pathways, which contribute to the pathogenesis of various disorders. The activation of inflammatory mechanisms is also emerging as a crucial component of cardiovascular and metabolic disorders. Furthermore, the nucleotide‐binding oligomerization domain‐like receptor family, pyrin domain containing 3 (NLRP3) inflammasome has attracted more attention than others and is the best‐characterized member of the NLR family of inflammasomes to date. ERS intersects with many different inflammatory pathways, particularly the NLRP3 inflammasome. In this review, we focus on the interactions between ERS and the NLRP3 inflammasome. The pharmacologic and nonpharmaceutical manipulation of these two processes may offer novel opportunities for the treatment of cardiovascular and metabolic disorders.
Long noncoding RNA nuclear enriched abundant transcript 1 promotes the proliferation and migration of Schwann cells by regulating the miR‐34a/Satb1 axis
Authors: Liu Xiangyu , Yu Xueyuan , He Youcheng , Wang Lu 
Published: February 2019

AbstractThe proliferation and migration of Schwann cells contribute to axonal outgrowth and functional recovery after peripheral nerve injury. Studies have found that long noncoding RNAs (lncRNAs) were abnormally expressed after peripheral nerve injury and they played vital roles in peripheral nerve regeneration. LncRNA nuclear enriched abundant transcript 1 (NEAT1) was increased in the cerebral cortex surrounding the injury site of mice after traumatic brain injury, and it promoted the functional recovery in mice. However, its role and mechanism in peripheral nerve injury remain unknown. The expression of NEAT1, miR‐34a, and Special AT‐rich sequence‐binding protein‐1 (Satb1) was detected in the sciatic nerve of mice after sciatic nerve crush at 0, 1, 4 and 7 days. The effects of NEAT1 on the proliferation and migration of Schwann cells were detected by 5‐Ethynyl‐20‐deoxyuridine (Edu) and transwell by gain‐ and loss‐of‐functions. The mechanism was focused on the miR‐34a/Satb1 pathway. In addition, the effect of NEAT1 in Schwann cells on axon outgrowth of dorsal root ganglion neurons was further investigated. We found that the NEAT1 and Satb1 expression was increased, whereas miR‐34a was reduced, in injured sciatic nerve at different time points. Overexpression of NEAT1 promoted, whereas knockdown of NEAT1 suppressed the proliferation and migration of Schwann cells. NEAT1 functioned as a competing endogenous RNA to regulate the Satb1 expression via sponging miR‐34a. NEAT1 enhanced the axon outgrowth of dorsal root ganglion neurons via regulating the miR‐34a and Satb1 expression. In conclusion, NEAT1 promotes the proliferation and migration of Schwann cell via miR‐34a/Satb1, which may provide a new approach to peripheral nerve regeneration.
Utilization of Adult Data in Designing Pediatric Pharmacokinetic Studies: How Much Are Historical Adult Data Worth?
Authors: Hsu Chyi‐Hung , Steven Xu Xu , Wang Jian , Zhang Liping , Liu Chao , Wang Yaning 
Published: February 2019

AbstractIn pediatric drug development, large amounts of adult data are often available before the start of a pediatric study. It is believed that borrowing this information will improve the efficiency. However, when adult information is not sufficiently similar to that of pediatrics, incorporating adult data will introduce bias and consequently result in efficiency loss. A Bayesian alternative—namely, commensurate prior approach where the level of information borrowing is based on the concordance of adult and pediatric data—was investigated. Simulation results indicate that the commensurate prior approach, in general, provides a balanced and robust trade‐off between bias and efficiency gain. The benefit of this approach was quantified in terms of sample size savings, and recommended sample sizes are provided.
Long‐term evaluation of urinary copper excretion and non‐caeruloplasmin associated copper in Wilson disease patients under medical treatment
Authors: Pfeiffenberger Jan , Lohse Christine Marie , Gotthardt Daniel , Rupp Christian , Weiler Markus , Teufel Ulrike , Weiss Karl Heinz , Gauss Annika 
Published: February 2019

AbstractObjectiveUrinary copper excretion rates and non‐caeruloplasmin associated copper concentrations are increased in patients with Wilson disease. However, there is little literature describing the monitoring of these parameters over the long term.MethodsThis is a monocentric retrospective study including data collected between 2003 and 2015 from 321 patients with Wilson disease by chart review. The patients were under therapy with D‐penicillamine, trientine, or zinc. 24‐h urinary copper excretion rates, non‐caeruloplasmin associated copper, and total serum copper concentrations were determined at the start of therapy, as well as 6, 12, 18, 24, 36, and ≥ 60 months after the start of therapy. For patients taking chelating agents, all parameters were measured while under continued therapy, as well as after a 48‐h dose interruption. A mathematical formula to predict 24‐h urinary copper excretion rates under different therapies was established.ResultsIn all treatment groups, urinary copper excretion rates decreased over time, but the inter‐individual variation of the results was high. Non‐caeruloplasmin associated copper concentrations tended to decline over time, but with a higher variation of results than that observed for urinary copper excretion rates.ConclusionDue to their variability, urinary copper excretion rates and serum copper concentrations are less than ideal parameters by which to monitor the benefit of a copper‐reducing therapy. Urinary copper excretion rates seem to be more suitable than non‐caeruloplasmin associated copper concentrations for this purpose.
Dynamic functional nucleus is a potential biomarker for structural degeneration in cervical spine discs
Authors: LeVasseur Clarissa M. , Wawrose Richard , Pitcairn Samuel , Donaldson William F. , Lee Joon Y. , Anderst William J. 
Published: February 2019

ABSTRACTIf intervertebral disc degeneration can be identified early, preventative treatments may be initiated before symptoms become disabling and costly. Changes in disc mechanics, such as the decrease in the compressive modulus of the nucleus, are some of the earliest signs of degeneration. Therefore, in vivo changes in the disc response to compressive load may serve as a biomarker for pending or early disc degeneration. The aim of this study was to assess the potential for using in vivo dynamic disc deformation to identify pathologic structural degeneration of the intervertebral disc. A validated model‐based tracking technique determined vertebral motion from biplane radiographs collected during dynamic flexion/extension and axial rotation of the cervical spine. A computational model of the subaxial intervertebral discs was developed to identify the dynamic functional nucleus of each disc, that is, the disc region that underwent little to no additional compression during dynamic movements. The size and location of the dynamic functional nucleus was determined for 10 C5/C6 spondylosis patients, 10 C5/C6/C7 spondylosis patients, and 10 asymptomatic controls. The dynamic functional nucleus size was sensitive (significantly smaller than controls in 5 of 6 measurements at the diseased disc) and specific (no difference from controls in 9 of 10 measurements at non‐diseased discs) to pathologic disc degeneration. These results provide evidence to suggest that structural disc degeneration, manifested by changes in the disc response to functional loading, may be identified in vivo from dynamic imaging collected during functional movements. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1–7, 2019.
Integrated bioinformatics analysis of key genes involved in progress of colon cancer
Authors: Yang Haojie , Wu Jiong , Zhang Jingjing , Yang Zhigang , Jin Wei , Li Ying , Jin Lei , Yin Lu , Liu Hua , Wang Zhenyi 
Published: February 2019

AbstractBackgroundColon cancer is one of most malignant cancers around worldwide. Nearly 20% patients were diagnosed at colon cancer with metastasis. However, the lack of understanding regarding its pathogenesis brings difficulties to study it.MethodsIn this study, we acquired high‐sequence data from GEO dataset, and performed integrated bioinformatic analysis including differently expressed genes, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways analysis, protein–protein analysis, survival analysis to analyze the development of colon cancer.ResultsBy comparing the colon cancer tissues with normal colon tissues, 109 genes were dysregulated; among them, 83 genes were downregulated and 26 genes were upregulated. Two clusters were founded based on the STRING database and MCODE plugin of cytoscape software. Then, six genes with prognostic value were filtered out in UALCAN website.ConclusionWe found that SPP1, VIP, COL11A1, CA2, ADAM12, INHBA could provide great significant prognostic value for colon cancer.
A linear programming approach to inverse planning in Gamma Knife radiosurgery
Authors: Sjölund J. , Riad S. , Hennix M. , Nordström H. 
Published: February 2019

PurposeLeksell Gamma Knife® is a stereotactic radiosurgery system that allows fine‐grained control of the delivered dose distribution. We describe a new inverse planning approach that both resolves shortcomings of earlier approaches and unlocks new capabilities.MethodsWe fix the isocenter positions and perform sector‐duration optimization using linear programming, and study the effect of beam‐on time penalization on the trade‐off between beam‐on time and plan quality. We also describe two techniques that reduce the problem size and thus further reduce the solution time: dualization and representative subsampling.ResultsThe beam‐on time penalization reduces the beam‐on time by a factor 2–3 compared with the naïve alternative. Dualization and representative subsampling each leads to optimization time‐savings by a factor 5–20. Overall, we find in a comparison with 75 clinical plans that we can always find plans with similar coverage and better selectivity and beam‐on time. In 44 of these, we can even find a plan that also has better gradient index. On a standard GammaPlan workstation, the optimization times ranged from 2.3 to 26 s with a median time of 5.7 s.ConclusionWe present a combination of techniques that enables sector‐duration optimization in a clinically feasible time frame.
Technical Note: A comparison of point set registration methods for electromagnetic tracking
Authors: Götz TI. , Wankerl H. , Tomé A. M. , Meyer‐Baese A. , Bert Ch. , Hensel B. , Lang E. W. 
Published: February 2019

PurposeHigh dose rate brachytherapy applies intense and destructive radiation. A treatment plan defines radiation source dwell positions to avoid irradiating healthy tissue. The study discusses methods to quantify any positional changes of source locations along the various treatment sessions.MethodsElectromagnetic tracking (EMT) localizes the radiation source during the treatment sessions. But in each session the relative position of the patient relative to the filed generator is changed. Hence, the measured dwell point sets need to be registered onto each other to render them comparable. Two point set registration techniques are compared: a probabilistic method called coherent point drift (CPD) and a multidimensional scaling (MDS) technique.ResultsBoth enable using EMT without external registration and achieve very similar results with respect to dwell position determination of the radiation source. Still MDS achieves smaller grand average deviations (CPD‐rPSR: MD = 2.55 mm, MDS‐PSR: MD = 2.15 mm) between subsequent dwell position determinations, which also show less variance (CPD‐rPSR: IQR = 4 mm, MDS‐PSR: IQR = 3 mm). Furthermore, MDS is not based on approximations and does not need an iterative procedure to track sensor positions inside the implanted catheters.ConclusionAlthough both methods achieve similar results, MDS is to be preferred over rigid CPD while nonrigid CPD is unsuitable as it does not preserve topology.