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https://www.readbyqxmd.com/read/28300161/foxo-transcription-factors-protect-against-the-diet-induced-fatty-liver-disease
#1
Xiaoyan Pan, Yang Zhang, Hyeong-Geug Kim, Suthat Liangpunsakul, X Charlie Dong
Forkhead O transcription factors (FOXOs) have been implicated in glucose and lipid homeostasis; however, the role of FOXOs in the development of nonalcoholic fatty liver disease (NAFLD) is not well understood. In this study, we designed experiments to examine the effects of two different diets-very high fat diet (HFD) and moderately high fat plus cholesterol diet (HFC)-on wildtype (WT) and liver-specific Foxo1/3/4 triple knockout mice (LTKO). Both diets induced severe hepatic steatosis in the LTKO mice as compared to WT controls...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28295446/a-recombinant-cystatin-from-ascaris-lumbricoides-attenuates-inflammation-of-dss-induced-colitis
#2
Sandra Coronado, Luis Barrios, Josefina Zakzuk, Ronald Regino, Velky Ahumada, Luis Franco, Yanet Ocampo, Luis Caraballo
Helminthiasis may ameliorate inflammatory diseases, such as inflammatory bowel disease and asthma. Information about immunomodulators from Ascaris lumbricoides is scarce, but could be important considering the co-evolutionary relationships between helminths and humans. We evaluated the immunomodulatory effects of a recombinant cystatin from A. lumbricoides on an acute model of Dextran Sodium Sulphate (DSS)-induced colitis in mice. From an A. lumbricoides cDNA library we obtained a recombinant cystatin (rAl-CPI)...
March 10, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28287848/immunomodulating-and-immunoresistance-properties-of-cancer-initiating-cells-implications-for-the-clinical-success-of-immunotherapy
#3
Cristina Maccalli, Giorgio Parmiani, Soldano Ferrone
Cancer-initiating cells (CICs) represent a relatively rare subpopulation of cells endowed with self-renewal, stemness properties, tumorigenicity in immunodeficient mice, and resistance to standard therapies as well as to immunotherapy. Here, we review the biological and immunological characteristics of CICs with special focus on the immunomodulating mechanisms they utilize to escape from immunosurveillance. The recently developed immunotherapeutic strategies have yielded remarkable clinical results in many types of tumors, indicating that indeed a patient's immune system can mount an immune response, which is effective in controlling tumor growth...
March 13, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28286209/esophageal-adenocarcinoma-cells-and-xenograft-tumors-exposed-to-erb-b2-receptor-tyrosine-kinase-2-and-3-inhibitors-activate-transforming-growth-factor-beta-signaling-which-induces-epithelial-to-mesenchymal-transition
#4
Eva A Ebbing, Anne Steins, Evelyn Fessler, Phylicia Stathi, Willem Joost Lesterhuis, Kausilia K Krishnadath, Louis Vermeulen, Jan Paul Medema, Maarten F Bijlsma, Hanneke W M van Laarhoven
BACKGROUND & AIMS: Drugs that inhibit the erb-b2 receptor tyrosine kinase 2 (ERBB2 or HER2) are the standard treatment of patients with different types of cancer, including HER2-overexpressing gastroesophageal tumors. Unfortunately, cancer cells become resistant to these drugs, so overall these drugs provide little benefit to patients with these tumors. We investigated mechanisms that mediate resistance of esophageal adenocarcinoma (EAC) cells and patient-derived xenograft (PDX) tumors to ERBB inhibitors...
March 9, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28275008/pparg-is-central-to-the-initiation-and-propagation-of-human-angiomyolipoma-suggesting-its-potential-as-a-therapeutic-target
#5
Oren Pleniceanu, Racheli Shukrun, Dorit Omer, Einav Vax, Itamar Kanter, Klaudyna Dziedzic, Naomi Pode-Shakked, Michal Mark-Daniei, Sara Pri-Chen, Yehudit Gnatek, Hadas Alfandary, Nira Varda-Bloom, Dekel D Bar-Lev, Naomi Bollag, Rachel Shtainfeld, Leah Armon, Achia Urbach, Tomer Kalisky, Arnon Nagler, Orit Harari-Steinberg, Jack L Arbiser, Benjamin Dekel
Angiomyolipoma (AML), the most common benign renal tumor, can result in severe morbidity from hemorrhage and renal failure. While mTORC1 activation is involved in its growth, mTORC1 inhibitors fail to eradicate AML, highlighting the need for new therapies. Moreover, the identity of the AML cell of origin is obscure. AML research, however, is hampered by the lack of in vivo models. Here, we establish a human AML-xenograft (Xn) model in mice, recapitulating AML at the histological and molecular levels. Microarray analysis demonstrated tumor growth in vivo to involve robust PPARG-pathway activation...
March 8, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28260098/identification-of-crucial-genes-associated-with-rat-traumatic-spinal-cord-injury
#6
Zibin Yang, Qiao Lv, Zhengxiang Wang, Xiliang Dong, Rongxin Yang, Wei Zhao
The aim of the present study was to investigate the key genes associated with traumatic spinal cord injuries (TSCI). The dataset GSE52763 was downloaded from the Gene Expression Omnibus, for which lumbar spinal cord samples were obtained from rats at 1 and 3 weeks following contusive spinal cord injury and 1 week subsequent to a sham laminectomy, and used to identify differentially expressed genes (DEGs). Functional enrichment analysis, co‑expression analysis and transcription factor (TF) identification were performed for DEGs common to the 1 and 3 week injury samples...
March 1, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28250236/tgfb1-represses-the-expression-of-sf1-and-lrh1-to-inhibit-e2-production-in-rat-lcs
#7
Qianqian Yang, Binfang Ma, Huilian Qiao, He Ma, Yuhang Dong, Liang Cao, Jing Ma, Zhen Li
Leydig cells (LCs) in the adult testis have been identified as the major sites of oestrogen production, which is crucial for mammalian germ cell differentiation. Our previous work showed that transforming growth factor beta 1 (TGFB1) inhibits estradiol (E2) secretion via down-regulating Cyp19 gene expression in mature rat (LCs). However, the mechanism remains unclear. In the present study, the effects of TGFB1 on the expression levels of steroidogenic factor 1 (SF1), liver receptor homolog 1 (LRH1), cAMP response element-binding protein (CREB) and cAMP responsive element modulator (CREM) were evaluated by Western blotting and immunofluorescence staining both in primary cultured LCs and in rat testis...
March 1, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28215431/global-decrease-in-the-expression-of-signalling-pathways-genes-in-murine-uterus-during-preimplantation-pregnancy
#8
Katarzyna Buska, Anna Ewa Kedzierska, Anna Slawek, Anna Chelmonska-Soyta
Early preimplantation embryo-maternal communication is crucial for the establishment and development of pregnancy. Though the involvement of several candidate genes and proteins in this complex event has been described, the hierarchy of molecular networks governing this communication remains unknown. The primary objective of this study was to determine whether the presence of embryos in the uterine lumen stimulated or inhibited gene expression in the uterine tissue on day 3.5 post coitum. To answer this question, we investigated the gene expression of dedicated signal transduction pathways in the uterus of CD-1 mice during the preimplantation stage of pregnancy and compared this expression to mice with induced pseudopregnancy...
February 15, 2017: Reproductive Biology
https://www.readbyqxmd.com/read/28174730/inhibitors-of-arg-gly-asp-binding-integrins-reduce-development-of-pancreatic-fibrosis-in-mice
#9
Barbara Ulmasov, Brent A Neuschwander-Tetri, Jinping Lai, Vladimir Monastyrskiy, Trisha Bhat, Matthew P Yates, Jonathan Oliva, Michael J Prinsen, Peter G Ruminski, David W Griggs
BACKGROUND & AIMS: Pancreatic stellate cells (PSCs) regulate the development of chronic pancreatitis (CP) and are activated by the cytokine transforming growth factor β (TGFB). Integrins of the αv family promote TGFB signaling in mice, probably by interacting with the Arg-Gly-Asp (RGD) sequence of the TGFB latency-associated peptide, which frees TGFB to bind its cellular receptors. However, little is known about the role of integrins in the development of CP. We investigated the effects of small-molecule integrin inhibitors in a mouse model of CP...
July 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28161077/m1-macrophages-are-predominantly-recruited-to-the-major-pelvic-ganglion-of-the-rat-following-cavernous-nerve-injury
#10
Hotaka Matsui, Nikolai A Sopko, Johanna L Hannan, Allison A Reinhardt, Max Kates, Takahiro Yoshida, Xiaopu Liu, Fabio Castiglione, Petter Hedlund, Emmanuel Weyne, Maarten Albersen, Trinity J Bivalacqua
INTRODUCTION: Neurogenic erectile dysfunction is a common sequela of radical prostatectomy. The etiology involves injury to the autonomic cavernous nerves, which arise from the major pelvic ganglion (MPG), and subsequent neuroinflammation, which leads to recruitment of macrophages to the injury site. Currently, two macrophage phenotypes are known: neurotoxic M1 macrophages and neuroprotective M2 macrophages. AIM: To examine whether bilateral cavernous nerve injury (BCNI) in a rat model of erectile dysfunction would increase recruitment of neurotoxic M1 macrophages to the MPG...
February 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/28160548/regulation-of-mirna-29c-and-its-downstream-pathways-in-preneoplastic-progression-of-triple-negative-breast-cancer
#11
Anjana Bhardwaj, Harpreet Singh, Kimal Rajapakshe, Kazunoshin Tachibana, Nivetha Ganesan, Yinghong Pan, Preethi H Gunaratne, Cristian Coarfa, Isabelle Bedrosian
Little is understood about the early molecular drivers of triple-negative breast cancer (TNBC), making the identification of women at risk and development of targeted therapy for prevention significant challenges. By sequencing a TNBC cell line-based breast cancer progression model we have found that miRNA-29c is progressively lost during TNBC tumorigenesis. In support of the tumor suppressive role of miRNA 29c, we found that low levels predict poor overall patient survival and, conversely, that ectopic expression of miRNA-29c in preneoplastic cell models inhibits growth...
January 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28120021/matrix-metalloproteinase-14-triggers-an-anti-inflammatory-proteolytic-cascade-in-endotoxemia
#12
Alina Aguirre, Jorge Blázquez-Prieto, Laura Amado-Rodriguez, Inés López-Alonso, Estefanía Batalla-Solís, Adrián González-López, Moisés Sánchez-Pérez, Carlos Mayoral-Garcia, Ana Gutiérrez-Fernández, Guillermo M Albaiceta
ᅟ: Matrix metalloproteinases can modulate the inflammatory response through processing of cyto- and chemokines. Among them, MMP-14 is a non-dispensable collagenase responsible for the activation of other enzymes, triggering a proteolytic cascade. To identify the role of MMP-14 during the pro-inflammatory response, wildtype and Mmp14 (-/-) mice were challenged with lipopolysaccharide. MMP-14 levels decreased after endotoxemia. Mutant animals showed 100% mortality, compared to 50% in wildtype mice. The increased mortality was related to a more severe lung injury, an impaired lung MMP-2 activation, and increased levels of the alarmin S100A9...
January 24, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28053020/blocking-tumor-educated-msc-paracrine-activity-halts-osteosarcoma-progression
#13
Serena Rubina Baglio, Tonny Lagerweij, Maria Pérez Lanzón, Dung Xuan Ho, Nicolas Léveillé, Sonia A Melo, Anne-Marie Cleton-Jansen, Ekaterina S Jordanova, Laura Roncuzzi, Michelina Greco, Monique A J van Eijndhoven, Giulia Grisendi, Massimo Dominici, Roberta Bonafede, Sinead Lougheed, Tanja D de Gruijl, Nicoletta Zini, Silvia Cervo, Agostino Steffan, Vincenzo Canzonieri, Aare Martson, Katre Maasalu, Sulev Koks, Thomas Wurdinger, Nicola Baldini, Dirk M Pegtel
PURPOSE: Human osteosarcoma is a genetically heterogeneous bone malignancy with poor prognosis despite the employment of aggressive chemotherapy regimens. Because druggable driver mutations have not been established, dissecting the interactions between osteosarcoma cells and supporting stroma may provide insights into novel therapeutic targets. EXPERIMENTAL DESIGN: By using a bioluminescent orthotopic xenograft mouse model of osteosarcoma we evaluated the effect of tumor extracellular vesicle (EV)-educated mesenchymal stem cells (TEMSCs) on osteosarcoma progression...
January 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28030800/the-role-of-mir-17-92-in-the-miregulatory-landscape-of-ewing-sarcoma
#14
Raphaela Schwentner, David Herrero-Martin, Maximilian O Kauer, Cornelia N Mutz, Anna M Katschnig, Grzegorz Sienski, Javier Alonso, Dave Nt Aryee, Heinrich Kovar
MicroRNAs serve to fine-tune gene expression and play an important regulatory role in tissue specific gene networks. The identification and validation of miRNA target genes in a tissue still poses a significant problem since the presence of a seed sequence in the 3'UTR of an mRNA and its expression modulation upon ectopic expression of the miRNA do not reliably predict regulation under physiological conditions. The chimeric oncoprotein EWS-FLI1 is the driving pathogenic force in Ewing sarcoma. MiR-17-92, one of the most potent oncogenic miRNAs, was recently reported to be among the top EWS-FLI1 activated miRNAs...
December 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27956229/milk-fat-globule-egf-factor-8-secreted-by-mesenchymal-stem-cells-protects-against-liver-fibrosis-in-mice
#15
Su Yeon An, Yu Jin Jang, Hee-Joung Lim, Jiyou Han, Jaehun Lee, Gyunggyu Lee, Ji Young Park, Seo-Young Park, Ji Hyang Kim, Byung-Rok Do, Chugseong Han, Hee-Kyung Park, Ok-Hee Kim, Myeong Jun Song, Say-June Kim, Jong-Hoon Kim
BACKGROUND & AIMS: Mesenchymal stem cells (MSCs) mediate tissue repair and might be used to prevent or reduce liver fibrosis. However, little is known about the anti-fibrotic factors secreted from MSCs or their mechanisms. METHODS: Umbilical cord-derived MSCs (UCMSCs) were differentiated into hepatocyte-like cells (hpUCMSCs), medium was collected, and secretome proteins were identified and quantified using nanochip-liquid chromatography/quadruple time-of-flight mass spectrometry...
December 9, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27879343/serine-threonine-kinase-receptor-associated-protein-regulates-early-follicle-development-in-the-mouse-ovary
#16
Isam B Sharum, Sofia Granados-Aparici, Fiona C Warrander, Felicity P Tournant, Mark A Fenwick
The molecular mechanisms involved in regulating the development of small, gonadotrophin-independent follicles are poorly understood; however, many studies have highlighted an essential role for TGFB ligands. Canonical TGFB signalling is dependent upon intracellular SMAD proteins that regulate transcription. STRAP has been identified in other tissues as an inhibitor of the TGFB-SMAD signalling pathway. Therefore, in this study we aimed to determine the expression and role of STRAP in the context of early follicle development...
February 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/27859672/immune-activation-and-regulation-related-patterns-in-stable-hand-transplant-recipients
#17
Dorota Kamińska, Katarzyna Kościelska-Kasprzak, Magdalena Krajewska, Adam Chełmoński, Jerzy Jabłecki, Marcelina Żabińska, Marta Myszka, Mirosław Banasik, Maria Boratyńska, Agnieszka Gomółkiewicz, Piotr Dzięgiel, Marian Klinger
We assessed cell subsets and expression of a set of genes related to the T-cell populations in peripheral blood mononuclear cells to elucidate whether immune status of stable hand transplant recipients (HTx) differs from stable kidney transplant recipients (KTx). The study was conducted on five HTx 4.8 ± 1.7 years after transplantation and 30 stable KTx 7.9 ± 2.4 years after transplantation as well as 18 healthy volunteers. The research involved PBMC gene expression analysis of CD4, CD8, CTLA4, GZMB, FOXP3, IL10, IL4, ILR2A, NOTCH, PDCD1, PRF1, TGF-B, and TNF-A genes on a custom-designed low-density array (TaqMan) as well as flow cytometry assessment of lymphocyte subpopulations...
November 9, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/27827279/plasma-rich-in-growth-factors-promotes-dermal-fibroblast-proliferation-migration-and-biosynthetic-activity
#18
COMPARATIVE STUDY
E Anitua, A Pino, G Orive
OBJECTIVE: The use of plasma rich in growth factors (PRGF) has gained importance in many medical fields due to its regenerative potential. The aim of this study is to evaluate the effects of PRGF on primary skin fibroblasts assessing cell proliferation, migration and secretion of growth factors. The age of the patients from who PRGF was prepared was also studied to determine whether it influenced the outcomes. METHOD: Human dermal fibroblasts were isolated from three healthy volunteers...
November 2, 2016: Journal of Wound Care
https://www.readbyqxmd.com/read/27815749/co-expression-modules-identified-from-published-immune-signatures-reveal-five-distinct-immune-subtypes-in-breast-cancer
#19
Dominic Amara, Denise M Wolf, Laura van 't Veer, Laura Esserman, Michael Campbell, Christina Yau
PURPOSE: There is a growing body of literature demonstrating that immune-related expression signatures predict breast cancer prognosis and chemo-/targeted-therapy responsiveness. However, it is unclear whether these signatures correlate with each other or represent distinct immune-related signals. METHODS: We evaluated 57 published immune-related expression signatures in four public breast cancer datasets totaling 3295 samples. For each dataset, we used consensus clustering to group signatures together based on their co-expression pattern...
November 4, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27808102/bioinspired-seeding-of-biomaterials-using-three-dimensional-microtissues-induces-chondrogenic-stem-cell-differentiation-and-cartilage-formation-under-growth-factor-free-conditions
#20
J Leijten, L S Moreira Teixeira, J Bolander, W Ji, B Vanspauwen, J Lammertyn, J Schrooten, F P Luyten
Cell laden biomaterials are archetypically seeded with individual cells and steered into the desired behavior using exogenous stimuli to control growth and differentiation. In contrast, direct cell-cell contact is instructive and even essential for natural tissue formation. Namely, microaggregation and condensation of mesenchymal progenitor cells triggers chondrogenesis and thereby drives limb formation. Yet a biomimetic strategy translating this approach into a cell laden biomaterial-based therapy has remained largely unexplored...
November 3, 2016: Scientific Reports
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