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https://www.readbyqxmd.com/read/28429185/high-content-assessment-of-cardiac-function-using-heart-on-a-chip-devices-as-drug-screening-model
#1
Genevieve Conant, Benjamin Fook Lun Lai, Rick Xing Ze Lu, Anastasia Korolj, Erika Yan Wang, Milica Radisic
Drug discovery and development continues to be a challenge to the pharmaceutical industry despite great advances in cell and molecular biology that allow for the design of better targeted therapeutics. Many potential drug compounds fail during the clinical trial due to inefficacy and toxicity that were not predicted during preclinical stages. The fundamental problem lies with the use of traditional drug screening models that still largely rely on the use of cell lines or animal cell monolayers, which leads to lack of predictive power of human tissue and organ response to the drug candidates...
April 20, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28428138/pregnane-x-receptor-regulates-the-ahr-cyp1a1-pathway-and-protects-liver-cells-from-benzo-%C3%AE-pyrene-induced-dna-damage
#2
Hongmei Cui, Xinsheng Gu, Jingshu Chen, Ying Xie, Sui Ke, Jing Wu, Andrei Golovko, Benjamin Morpurgo, Chunhong Yan, Timothy D Phillips, Wen Xie, Jianyuan Luo, Zhijun Zhou, Yanan Tian
Pregnane X receptor (PXR) plays an important role in protecting cells from mutagenic DNA damages induced by endogenous and exogenous toxicants. This protective function is often attributed to the PXR-regulated metabolic detoxification. Here we report a novel potential mechanism that PXR reduces benzo-[α]-pyrene(BaP)-induced DNA damage through inhibiting the transcriptional activity of aryl hydrocarbon receptor (AhR) which plays a pivotal role in the bioactivation of BaP. We have utilized three well-characterized cell lines, i...
April 17, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28426762/human-microrna-299-3p-decreases-invasive-behavior-of-cancer-cells-by-downregulation-of-oct4-expression-and-causes-apoptosis
#3
Axel R Göhring, Stefanie Reuter, Joachim H Clement, Xinlai Cheng, Jannick Theobald, Stefan Wölfl, Ralf Mrowka
PURPOSE: Oct4 was reported to be one of the most important pluripotency transcription factors in the biology of stem cells including cancer stem cells, and progressed malignant cells. Here we report the investigation of gene expression control of Oct4 by selected human microRNAs and the physiological effect of Oct4 silencing in invasive cancer cells. METHODS AND RESULTS: High throughput luciferase activity assay revealed the microRNA-299-3p to be the most effective in reducing gene expression of Oct4, which was confirmed by Western blot analysis and Oct4 promoter activity in a target luciferase assay...
2017: PloS One
https://www.readbyqxmd.com/read/28426707/rare-cell-isolation-and-recovery-on-open-channel-microfluidic-chip
#4
Taisuke Masuda, Woneui Song, Hayao Nakanishi, Wu Lei, Anas Mohd Noor, Fumihito Arai
The ability to accurately detect and analyze rare cells in a cell population is critical not only for the study of disease progression but also for next flow cytometry systems in clinical application. Here, we report the development of a prototype device, the 'Rare cell sorter', for isolating and recovering single rare cells from whole blood samples. On this device, we utilized an open-channel microfluidic chip for rare cell isolation. And the advantage of open-channel allows us to recover the isolated rare cell directly from the chip...
2017: PloS One
https://www.readbyqxmd.com/read/28421094/cucumber-csbpcs-regulate-the-expression-of-csabi3-during-seed-germination
#5
Ying Mu, Yumei Liu, Longqiang Bai, Shuzhen Li, Chaoxing He, Yan Yan, Xianchang Yu, Yansu Li
Cucumber seeds with shallow dormancy start to germinate in fruit that are harvested late. ABSCISIC ACID INSENSITIVE3 (ABI3), a transcription factor in the abscisic acid (ABA) signaling pathway, is one of the most important regulators in the transition from late embryogenesis to germination. Our analysis found a candidate cis-regulatory motif for cucumber BASIC PENTACYSTEINE (CsBPC) in the promoter of CsABI3. Yeast one-hybrid and chromatin immunoprecipitation (ChIP) assays showed that CsBPCs bound to the promoter of CsABI3...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28420675/integrative-analysis-unveils-new-functions-for-the-drosophila-cutoff-protein-in-non-coding-rna-biogenesis-and-gene-regulation
#6
Yuri Pritykin, Tarcisio Brito, Trudi Schupbach, Mona Singh, Attilio Pane
Piwi-Interacting RNAs (piRNAs) are central components of the piRNA pathway, which directs transposon silencing and guarantees genome integrity in the germ cells of several metazoans. In Drosophila, piRNAs are produced from discrete regions of the genome termed piRNA clusters, whose expression relies on the RDC complex comprised of the core proteins Rhino, Deadlock and Cutoff. To date, the RDC complex has been exclusively implicated in the regulation of the piRNA loci. Here we further elucidate the function of Cutoff and the RDC complex by performing genome-wide ChIP-seq and RNA-seq assays in the Drosophila germline and analyzing these data together with other publicly available data sets...
April 18, 2017: RNA
https://www.readbyqxmd.com/read/28420331/arsenic-treatment-increase-aurora-a-overexpression-through-e2f1-activation-in-bladder-cells
#7
Yu-Ting Kao, Chin-Han Wu, Shan-Ying Wu, Sheng-Hui Lan, Hsiao-Sheng Liu, Ya-Shih Tseng
BACKGROUND: Arsenic is a widely distributed metalloid compound that has biphasic effects on cultured cells. In large doses, arsenic can be toxic enough to trigger cell death. In smaller amounts, non-toxic doses may promote cell proliferation and induces carcinogenesis. Aberration of chromosome is frequently detected in epithelial cells and lymphocytes of individuals from arsenic contaminated areas. Overexpression of Aurora-A, a mitotic kinase, results in chromosomal instability and cell transformation...
April 18, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28418430/wat-on-a-chip-a-physiologically-relevant-microfluidic-system-incorporating-white-adipose-tissue
#8
Peter Loskill, Thiagarajan Sezhian, Kevin M Tharp, Felipe T Lee-Montiel, Shaheen Jeeawoody, Willie Mae Reese, Peter-James H Zushin, Andreas Stahl, Kevin E Healy
Organ-on-a-chip systems possess a promising future as drug screening assays and as testbeds for disease modeling in the context of both single-organ systems and multi-organ-chips. Although it comprises approximately one fourth of the body weight of a healthy human, an organ frequently overlooked in this context is white adipose tissue (WAT). WAT-on-a-chip systems are required to create safety profiles of a large number of drugs due to their interactions with adipose tissue and other organs via paracrine signals, fatty acid release, and drug levels through sequestration...
April 18, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28415608/collagen-type-iv-alpha-1-col4a1-and-collagen-type-xiii-alpha-1-col13a1-produced-in-cancer-cells-promote-tumor-budding-at-the-invasion-front-in-human-urothelial-carcinoma-of-the-bladder
#9
Makito Miyake, Shunta Hori, Yosuke Morizawa, Yoshihiro Tatsumi, Michihiro Toritsuka, Sayuri Ohnishi, Keiji Shimada, Hideki Furuya, Vedbar S Khadka, Youping Deng, Kenta Ohnishi, Kota Iida, Daisuke Gotoh, Yasushi Nakai, Takeshi Inoue, Satoshi Anai, Kazumasa Torimoto, Katsuya Aoki, Nobumichi Tanaka, Noboru Konishi, Kiyohide Fujimoto
Current knowledge of the molecular mechanism driving tumor budding is limited. Here, we focused on elucidating the detailed mechanism underlying tumor budding in urothelial cancer of the bladder. Invasive urothelial cancer was pathologically classified into three groups as follows: nodular, trabecular, and infiltrative (tumor budding). Pathohistological analysis of the orthotopic tumor model revealed that human urothelial cancer cell lines MGH-U3, UM-UC-14, and UM-UC-3 displayed typical nodular, trabecular, and infiltrative patterns, respectively...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414324/correlation-between-histone-acetylation-and-expression-of-notch1-in-human-lung-carcinoma-and-its-possible-role-in-combined-small-cell-lung-carcinoma
#10
Wael Abdo Hassan, Shin-Ichiro Takebayashi, Mohamed Osama Ali Abdalla, Kosuke Fujino, Shinji Kudoh, Yamoto Motooka, Yonosuke Sato, Yoshiki Naito, Koichi Higaki, Joeji Wakimoto, Seiji Okada, Mituyoshi Nakao, Yuichi Ishikawa, Takaaki Ito
Combined small-cell lung carcinoma (cSCLC) is composed of small-cell lung carcinoma (SCLC) admixed with non-small-cell lung carcinoma (NSCLC). Evaluating the molecular differences between SCLC and NSCLC could lead to a better understanding of the pathogenesis of such neoplasms. Therefore, in this study, we investigated the correlation between histone acetylation and Notch1 expression in lung carcinoma. Using chromatin immunoprecipitation (ChIP) assay, we measured the level of acetylated histone H3 around the promoter region of Notch1 in SCLC and NSCLC cells...
April 17, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28413484/inhibitor-%C3%AE%C2%BAb%C3%AE-protein-therapy-alleviates-severe-pneumonia-through-inhibition-of-nuclear-factor-%C3%AE%C2%BAb
#11
Haizhou Xu, Bing Mei, Meitang Wang, Shuogui Xu
To investigate the effect of inhibitor κBα (IκBα) on severe pneumonia and explain the mechanisms of nuclear factor κB (NF-κB), the activation of NF-κB was induced in Sprague-Dawley (SD) rats infected with Klebsiella pneumoniae (K. pneumoniae). The rats were then treated with differing concentrations of IκBα protein. A histological analysis was performed to compare the lung structure prior to and following treatment, and an immunohistochemistry assay was used to detect NF-κB activity. In addition, the expression of certain inflammatory factors was detected using a protein chip assay...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28412955/long-non-coding-rna-nkila-inhibits-migration-and-invasion-of-non-small-cell-lung-cancer-via-nf-%C3%AE%C2%BAb-snail-pathway
#12
Zhiliang Lu, Yuan Li, Jingnan Wang, Yun Che, Shouguo Sun, Jianbing Huang, Zhaoli Chen, Jie He
BACKGROUND: Numerous studies have shown that long non-coding RNAs (lncRNAs) play key roles during multiple cancer processes, such as cell proliferation, apoptosis, migration and invasion. The previous studies found that NKILA interacted with and suppressed the nuclear translocation of NF-KappaB, which influenced metastasis and prognosis in breast cancer. However the clinical significance and biological role of NKILA in non-small cell lung cancer (NSCLC) remains unknown. METHODS: We examined expression levels of NKILA in 106 pairs of NSCLC tissues and cell lines...
April 17, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28412351/effect-of-apoa4-on-serpina3-mediated-by-nuclear-receptors-nr4a1-and-nr1d1-in-hepatocytes
#13
Yupeng Zhang, Jing He, Jing Zhao, Min Xu, Danwen Lou, Patrick Tso, Zongfang Li, Xiaoming Li
ApoA4 exerts anti-inflammatory effects, but the mechanism remains unclear. SERPINA3 is a member of the serine proteinase inhibitor gene family, and has been shown to be involved in anti-inflammation and associated with a number of human diseases. In this study, we revealed that ApoA4 stimulates the gene expression of SERPINA3 in mouse hepatocytes both in vivo and in vitro, in a dose- and time-dependent manner. The transcriptional response of SERPINA3 to ApoA4 is regulated through the binding of ApoA4 with nuclear receptors NR4A1 and NR1D1 on the SERPINA3 promoter, which was verified with ChIP, Luciferase activity assay and RNA interference-mediated NR4A1 or NR1D1 gene knockdown...
April 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28412217/dalbergia-odorifera-extract-promotes-angiogenesis-through-upregulation-of-vegfrs-and-pi3k-mapk-signaling-pathways
#14
Zhu-Ming Fan, Da-Ying Wang, Jian-Mei Yang, Zhi-Xiu Lin, Ai-Lin Yang, Hua Fan, Min Cao, Su-Yun Yuan, Zong-Jun Liu, Xin Zhou, You-Hua Wang
ETHNOPHARMACOLOGICAL RELEVANCE: The heart wood of Dalbergia odorifera is a Chinese herbal medicine commonly used for the treatment of various ischemic diseases in Chinese medicine practice. AIM OF THE STUDY: In this study, therapeutic angiogenesis effects of the Dalbergia odorifera extract (DOE) were investigated on transgenic zebrafish in vivo and human umbilical vein endothelial cells (HUVECs) in vitro. MATERIALS AND METHODS: The pro-angiogenic effects of DOE on zebrafish were examined by subintestinal vessels (SIVs) sprouting assay and intersegmental vessels (ISVs) injury assay...
April 12, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28407300/thrombin-induces-ccl2-expression-in-human-lung-fibroblasts-via-p300-mediated-histone-acetylation-and-nf-kappab-activation
#15
Xiaoling Deng, Xiaoqiong Zhou, Yan Deng, Fan Liu, Xiaofan Feng, Qi Yin, Yinzhen Gu, Songlin Shi, Mingyan Xu
BACKGROUND AND OBJECTIVE: Thrombin has been shown to play a key role in lung diseases such as pulmonary fibrosis via the induction of fibrotic cytokine- chemokine (CC motif) ligand-2 (CCL2) expression. We previously reported that transcription factor nuclear factor-κB (NF-κB) is responsible for thrombin-induced CCL2 expression in human lung fibroblasts (HLFs). Here we extended our study to investigate the epigenetic regulation mechanism for thrombin-induced CCL2 expression in HLF. METHODS: HLFs were cultured in F-12 medium...
April 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28406939/role-of-neurod1-on-the-negative-regulation-of-pomc-expression-by-glucocorticoid
#16
Rehana Parvin, Akiko Saito-Hakoda, Hiroki Shimada, Kyoko Shimizu, Erika Noro, Yasumasa Iwasaki, Ken Fujiwara, Atsushi Yokoyama, Akira Sugawara
The mechanism of the negative regulation of proopiomelanocortin gene (Pomc) by glucocorticoids (Gcs) is still unclear in many points. Here, we demonstrated the involvement of neurogenic differentiation factor 1 (NeuroD1) in the Gc-mediated negative regulation of Pomc. Murine pituitary adrenocorticotropic hormone (ACTH) producing corticotroph tumor-derived AtT20 cells were treated with dexamethasone (DEX) (1-100 nM) and cultured for 24 hrs. Thereafter, Pomc mRNA expression was studied by quantitative real-time PCR and rat Pomc promoter (-703/+58) activity was examined by luciferase assay...
2017: PloS One
https://www.readbyqxmd.com/read/28405676/ulinastatin-protects-against-lipopolysaccharide-induced-cardiac-microvascular-endothelial-cell-dysfunction-via-downregulation-of-lncrna-malat1-and-ezh2-in-sepsis
#17
Zhaoxia Yu, Aisa Rayile, Xiangyang Zhang, Ying Li, Qiang Zhao
The present study aimed to evaluate the effects of ulinastatin on the permeability and apoptosis of lipopolysaccharide (LPS)-induced cardiac microvascular endothelial cells (CMVECs), and investigate its molecular mechanisms in sepsis. The sepsis rat model was induced by cecal ligation and puncture (CLP), and rat CMVECs were isolated and treated with LPS or/and ulinastatin. Then, cell permeability was evaluated by transendothelial electrical resistance, reactive oxygen species (ROS) levels were assessed by 2,7-dichlorofluorescein diacetate, cell apoptosis was detected using Annexin V-FITC apoptosis detection kit, and the expression levels of Bcl-2, Bax, caspase-3, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and EZH2 were detected by RT-qPCR and/or western blotting...
May 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28405258/rapid-isolation-of-blood-plasma-using-a-cascaded-inertial-microfluidic-device
#18
M Robinson, H Marks, T Hinsdale, K Maitland, G Coté
Blood, saliva, mucus, sweat, sputum, and other biological fluids are often hindered in their ability to be used in point-of-care (POC) diagnostics because their assays require some form of off-site sample pre-preparation to effectively separate biomarkers from larger components such as cells. The rapid isolation, identification, and quantification of proteins and other small molecules circulating in the blood plasma from larger interfering molecules are therefore particularly important factors for optical blood diagnostic tests, in particular, when using optical approaches that incur spectroscopic interference from hemoglobin-rich red blood cells (RBCs)...
March 2017: Biomicrofluidics
https://www.readbyqxmd.com/read/28397458/mapping-of-dna-hypermethylation-and-hypomethylation-induced-by-folate-deficiency-in-sporadic-colorectal-cancer-and-clinical-implication-analysis-of-hypermethylation-pattern-in-cbs-promoter
#19
Zaizhong Zhang, Yang He, Xiaohuang Tu, Sheng Huang, Zhuo Chen, Lie Wang, Jingxiang Song
BACKGROUND: Aberrant DNA methylation patterns play a major role in tumorigenesis and the effects of nutrients, especially folate in the diet, on methylation changes is of great importance in colorectal cancer (CRC). Folate deficiency would disrupt methylation patterns; however, its exact effects on DNA methylation patterns in CRC are unclear. This study was performed to gain insight into the methylation changes induced by folate deficiency and the putative role of methylation pattern diversities of related genes in the clinical outcome of CRC...
April 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28394504/systematic-identification-of-the-protein-substrates-of-udp-galnac-polypeptide-n-acetylgalactosaminyltransferase-t1-t2-t3-using-a-human-proteome-microarray
#20
Zhijue Xu, Xing Li, Shumin Zhou, Wenxian Xie, Jing Wang, Li Cheng, Sheng Wang, Shujuan Guo, Zhaowei Xu, Xin Cao, Menghui Zhang, Biao Yu, Hisashi Narimatsu, Sheng-Ce Tao, Yan Zhang
O-GalNAc glycosylation is the initial step of the mucin-type O-glycosylation. In humans, it is catalyzed by a family of 20 homologous UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts). So far, there is very limited information on their protein substrate specificities. In this study, we developed an on-chip ppGalNAc-Ts assay which could rapidly and systematically identify the protein substrates of each ppGalNAc-T. In detail, we utilized a human proteome microarray as the protein substrates and UDP-GalNAz as the nucleotide sugar donor for click chemistry detection...
April 10, 2017: Proteomics
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