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Maria Myzithras, Tammy Bigwarfe, Erica Waltz, Hua Li, Jennifer Ahlberg, Irina Rybina, Sarah Low, Cynthia Hess Kenny, John Miglietta, Rachel Kroe-Barrett
AIM: The fully automated microfluidics-based Gyrolab is a popular instrument for the bioanalysis of protein therapeutics; requiring minimal sample and reagent volumes. Gyros offers affinity software for determining binding affinity in solution using a high-throughput method and miniaturized reactions. RESULTS: Using this affinity software, multiple CTGF-targeting reagents were characterized on the Gyrolab after <100% target coverage was seen in a cynomolgus pharmacokinetic/PD study dosed with anti-CTGF antibodies...
February 16, 2018: Bioanalysis
Yun Zeng, Zhengjie Shen, Wenzhe Gu, Mianhua Wu
This study aimed to explore crucial genes, transcription factors (TFs), and microRNAs (miRNAs) associated with the effects of curcumin against hepatocellular carcinoma (HCC). We downloaded data (GSE59713) from Gene Expression Omnibus to analyze differentially expressed genes (DEGs) between curcumin-treated and untreated HCC cell lines. Then, we identified the disease ontology (DO) and functional enrichment analysis of these DEGs and analyzed their protein-protein interactions (PPIs). Additionally, we constructed TF-target gene and miRNA-target gene regulatory networks and explored the potential functions of these DEGs...
February 2, 2018: Gene
L X Zhang, W Jin, J Zheng, Y X Dai, Y Song, H B Ni, J Jiang, W B Liang
AIM: To evaluate the correlation between miRNA-375 and cell proliferation and apoptosis in glioma cancer cell. METHODS: Collecting 30 cases of glioma cancer patients and 30 cases of cerebral infarction patients. The miRNA-375 and CTGF protein expressions were evaluated by ISH and IHC methods. In the cell experiment, the U87 cells were divided into 3 groups: NC group (the cells were treated with normal method); BL group (the cells were transfected with empty vector) and miRNA group (the cells were transfected with miRNA-375)...
2018: Bratislavské Lekárske Listy
Beijia Chen, Guinan Liu
The Hippo signaling pathway is involved in the formation and development of the cardiovascular system. In the present study, the effects of WWC family member 3 (WWC3) on vascular smooth muscle cells (VSMCs) following injury were investigated, in addition to the associated mechanisms underlying this process. Platelet‑derived growth factor BB (PDGF‑BB) was used as a cell injury factor, and rats with balloon injuries were used as a model of carotid intimal injury. Furthermore, the expression levels of WWC3 in VSMCs and arteries post‑injury were investigated, in addition to the effect of WWC3 on the proliferation and migration of VSMCs...
January 25, 2018: Molecular Medicine Reports
Bisher Abuyassin, Mohammad Badran, Najib T Ayas, Ismail Laher
Epidemiological studies demonstrate an association between obstructive sleep apnea (OSA) and accelerated loss of kidney function. It is unclear whether the decline in function is due to OSA per se or to other confounding factors such as obesity. In addition, the structural kidney abnormalities associated with OSA are unclear. The objective of this study was to determine whether intermittent hypoxia (IH), a key pathological feature of OSA, induces renal histopathological damage using a mouse model. Ten 8-week old wild-type male CB57BL/6 mice were randomly assigned to receive either IH or intermittent air (IA) for 60 days...
2018: PloS One
J Emanuel Ramos de Carvalho, Milan T Verwoert, Ilse M C Vogels, Eric A Reits, Cornelis J F Van Noorden, Ingeborg Klaassen, Reinier O Schlingemann
Emerging evidence suggests that dysfunction of the ubiquitin-proteasome system is involved in the pathogenesis of numerous senile degenerative diseases including retinal disorders. The aim of this study was to assess whether there is a link between proteasome regulation and retinal pigment epithelium (RPE)-mediated expression of extracellular matrix genes. For this purpose, human retinal pigment epithelial cells (ARPE-19) were treated with different concentrations of transforming growth factor-β (TGFβ), connective tissue growth factor (CTGF), interferon-γ (IFNγ) and the irreversible proteasome inhibitor epoxomicin...
March 2018: Biochemistry and Biophysics Reports
Kunihiro Hayakawa, Keigo Ikeda, Maki Fujishiro, Yuko Yoshida, Takuya Hirai, Hiroshi Tsushima, Tomoko Miyashita, Shinji Morimoto, Yasushi Suga, Kenji Takamori, Hideoki Ogawa, Iwao Sekigawa
Background: Connective tissue growth factor (CTGF) is a multifunctional cellular protein and playing a role as a central mediator in tissue remodeling and fibrosis. The physiological function of CTGF in psoriasis is unknown. Objective: The purpose of this study was to investigate the function of CTGF in psoriasis using the established imiquimod (IMQ)-induced psoriasis murine model and psoriasis patients. Methods: Anti-CTGF monoclonal antibody was applied to IMQ induced psoriasis mice and those skin were clinically, pathologically and immunologically analyzed...
February 2018: Annals of Dermatology
Christin Fischer, Natalie Deininger, Gunter Wolf, Ivonne Loeffler
Tubulointerstitial fibrosis (TIF) is a pivotal pathophysiological process in patients with diabetic nephropathy (DN). Multiple profibrotic factors and cell types, including transforming growth factor beta 1 (TGF-β1) and interstitial myofibroblasts, respectively, are responsible for the accumulation of extracellular matrix in the kidney. Matrix-producing myofibroblasts can originate from different sources and different mechanisms are involved in the activation process of the myofibroblasts in the fibrotic kidney...
January 30, 2018: Journal of Clinical Medicine
Kelly J Hunt, Miran A Jaffa, Sara M Garrett, Deirdre K Luttrell, Kenneth E Lipson, Maria F Lopes-Virella, Louis M Luttrell, Ayad A Jaffa
OBJECTIVE: Connective tissue growth factor (CTGF), also known as CCN2, is a potent chemotactic and extracellular matrix-inducing matricellular protein that has been implicated in progression of inflammatory and fibroproliferative disorders. An emerging role of CTGF/CCN2 is that of a prosclerotic factor implicated in the development of cardiac disease. Our objective was to determine the role of CTGF/CCN2 as a predictor of cardiovascular events in type 2 diabetes in the Veterans Affairs Diabetes Trial (VADT) cohort...
January 30, 2018: Diabetes Care
Yan-Wu Sun, Yi-Yi Zhang, Xin-Jie Ke, Xue-Jing Wu, Zhi-Fen Chen, Pan Chi
Radiation-induced intestinal fibrosis (RIF) is a chronic toxicity following radiation, and can be very difficult to treat. Pirfenidone is a promising anti-fibrotic agent that inhibits fibrosis progression in various clinical and experimental studies. This study was aimed to explore whether pirfenidone could protect against RIF, and to evaluate the underlying mechanism. An animal model of RIF was induced by exposure of a single dose of 20Gy to the pelvis. Rats were orally administered with pirfenidone (200, 400 md/kg/d) for 12 weeks...
January 25, 2018: European Journal of Pharmacology
Madhuram Khandelwal, Vivek Anand, Sandeep Appunni, Amlesh Seth, Prabhjot Singh, Sandeep Mathur, Alpana Sharma
Genetic abnormalities and epigenetic alterations both play vital role in initiation as well as progression of cancer. Whereas genetic mutations cannot be reversed, epigenetic alterations such as DNA methylation can be reversed by the application of DNA methyltransferase inhibitor decitabine. Epigenetic silencing of RASSF1A and involvement of hippo pathway both have been shown to involve in chemo-resistance. Purpose of this study was to observe the effect of combination treatment of decitabine with cisplatin or doxorubicin on bladder cancer cells involving hippo pathway through RASSF1A...
January 24, 2018: Molecular and Cellular Biochemistry
Wei Kang, Tingting Huang, Yuhang Zhou, Jinglin Zhang, Raymond W M Lung, Joanna H M Tong, Anthony W H Chan, Bin Zhang, Chi Chun Wong, Feng Wu, Yujuan Dong, Shiyan Wang, Weiqin Yang, Yi Pan, Wing Po Chak, Alvin H K Cheung, Jesse C S Pang, Jun Yu, Alfred S L Cheng, Ka Fai To
miR-375 is a tumor-suppressive microRNA (miRNA) in gastric cancer (GC). However, its molecular mechanism remains unclear. The aim of this study is to comprehensively investigate how miR-375 is involved in Hippo pathway by targeting multiple oncogenes. miR-375 expression in gastric cancer cell lines and primary GC was investigated by qRT-PCR. The regulation of YAP1, TEAD4, and CTGF expression by miR-375 was evaluated by qRT-PCR, western blot, and luciferase reporter assays, respectively. The functional roles of the related genes were examined by siRNA-mediated knockdown or ectopic expression assays...
January 24, 2018: Cell Death & Disease
Aadil A Khan, James T Paget, Martin McLaughlin, Joan N Kyula, Michelle J Wilkinson, Timothy Pencavel, David Mansfield, Victoria Roulstone, Rohit Seth, Martin Halle, Navita Somaiah, Jessica K R Boult, Simon P Robinson, Hardev S Pandha, Richard G Vile, Alan A Melcher, Paul A Harris, Kevin J Harrington
Improvements in cancer survival mean that long-term toxicities, which contribute to the morbidity of cancer survivorship, are being increasingly recognized. Late adverse effects (LAEs) in normal tissues after radiotherapy (RT) are characterized by vascular dysfunction and fibrosis causing volume loss and tissue contracture, for example, in the free flaps used for immediate breast reconstruction after mastectomy. We evaluated the efficacy of lentivirally delivered superoxide dismutase 2 (SOD2) overexpression and connective tissue growth factor (CTGF) knockdown by short hairpin RNA in reducing the severity of LAEs in an animal model of free flap LAEs...
January 24, 2018: Science Translational Medicine
Jordan L Williams, Omer Cavus, Emefah C Loccoh, Sara Adelman, John C Daugherty, Sakima A Smith, Benjamin Canan, Paul M L Janssen, Sara Koenig, Crystal F Kline, Peter J Mohler, Elisa A Bradley
AIMS: Right ventricular failure (RVF) varies significantly from the more common left ventricular failure (LVF). This study was undertaken to determine potential molecular pathways that are important in human right ventricular (RV) function and may mediate RVF. MATERIALS AND METHODS: We analyzed mRNA of human non-failing LV and RV samples and RVF samples from patients with pulmonary arterial hypertension (PAH), and post-LVAD implantation. We then performed transcript analysis to determine differential expression of genes in the human heart samples...
January 20, 2018: Life Sciences
Yang Yi, Jun Ma, Lu Jianrao, Hangqing Wang, Yingdan Zhao
CCN family, a group of six extracellular matrix-associated proteins, plays an important role in fibrosis. WISP3 has addressed as a pro-fibrotic molecule in the development of human lung fibrosis. However, whether WISP3 involved in the activation and proliferation of renal fibroblast, and ultimately inhibited fibroblast-myofibroblast transdifferentiation remained unknown. Herein, we found that down-regulated WISP3 was involved in the fibrogenesis of rat renal NRK-49F cells induced by transforming growth (TGF-β1), which was further confirmed in a rat renal fibrosis induced by unilateral ureteral obstruction (UUO)...
January 17, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Camilo Riquelme-Guzman, Osvaldo Contreras, Enrique Brandan
Fibrosis is a common feature of several chronic diseases, and is characterized by exacerbated accumulation of extracellular matrix (ECM). Understanding the cellular and molecular mechanisms involved in the development of this condition is crucial for designing efficient treatments for those pathologies. Connective tissue growth factor (CTGF/CCN2) is a pleiotropic protein with strong pro-fibrotic activity. In this report, we present experimental evidence showing that ECM stimulates the synthesis of CTGF in response to lysophosphatidic acid (LPA)...
December 27, 2017: American Journal of Physiology. Cell Physiology
Takanori Konishi, Rebecca M Schuster, Alex B Lentsch
Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are key regulators of cell proliferation and organ size, however, their physiological contribution after liver injury has not been fully understood. In this study, we sought to determine the role of YAP and TAZ during liver recovery after ischemia-reperfusion (I/R). A murine model of partial (70%) I/R was used to induce liver injury and study the reparative and regenerative response. After liver injury, there was marked activation and proliferation of hepatic stellate cells...
January 11, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Mark D Sternlicht, Ute Wirkner, Sebastian Bickelhaupt, Ramon Lopez Perez, Alexandra Tietz, Kenneth E Lipson, Todd W Seeley, Peter E Huber
BACKGROUND: Fibrosis is a delayed side effect of radiation therapy (RT). Connective tissue growth factor (CTGF) promotes the development of fibrosis in multiple settings, including pulmonary radiation injury. METHODS: To better understand the cellular interactions involved in RT-induced lung injury and the role of CTGF in these responses, microarray expression profiling was performed on lungs of irradiated and non-irradiated mice, including mice treated with the anti-CTGF antibody pamrevlumab (FG-3019)...
January 18, 2018: Respiratory Research
Quanyou Gong, Zhaoxia Qin, Fangli Hou
Small hepatocellular carcinoma is an important leading cause of death amongst cancer patients, our study was designed in order to test the hypothesis that radiofrequency ablation (RFA) combined with a chemotherapeutic drug would improve the outcome for patients. Two groups of patients presenting early small hepatocellular carcinoma were treated with either conventional RFA alone (50 individuals in the control group), or with a combination of RFA and oral sorafenib (40 individuals in an observation group). Individual clinical and laboratory evaluations were done during an average follow-up time of 35 months, and all the data recorded was used to compare results of both treatment approaches...
December 2017: Oncology Letters
Sascha Kopp, Jayashree Sahana, Tawhidul Islam, Asbjørn Graver Petersen, Johann Bauer, Thomas J Corydon, Herbert Schulz, Kathrin Saar, Norbert Huebner, Lasse Slumstrup, Stefan Riwaldt, Markus Wehland, Manfred Infanger, Ronald Luetzenberg, Daniela Grimm
Human MCF-7 breast cancer cells were exposed to a Random Positioning Machine (RPM). After 24 hours (h) the cells grew either adherently within a monolayer (AD) or within multicellular spheroids (MCS). AD and MCS populations were separately harvested, their cellular differences were determined performing qPCR on genes, which were differently expressed in AD and MCS cells. Gene array technology was applied to detect RPM-sensitive genes in MCF-7 cells after 24 h. Furthermore, the capability to form multicellular spheroids in vitro was compared with the intracellular distribution of NF-kappaB (NFκB) p65...
January 17, 2018: Scientific Reports
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