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https://www.readbyqxmd.com/read/28346399/endothelial-cell-specific-activation-of-transforming-growth-factor-%C3%AE-signaling-in-mice-induces-cutaneous-visceral-and-microvascular-fibrosis
#1
Peter J Wermuth, Kellan R Carney, Fabian A Mendoza, Sonsoles Piera-Velazquez, Sergio A Jimenez
In this study, we tested the hypothesis that constitutive endothelial cell-specific activation of TGF-β signaling induces tissue fibrosis and vasculopathy resembling the characteristic fibrotic and vascular alterations of systemic sclerosis. Transgenic mice with inducible expression of a constitutively active TGF-β receptor I specifically in endothelial cells were generated by intercrossing mice harboring a constitutively active TGF-β receptor I with a mouse strain containing the endothelial cell-specific Cdh5 gene promoter directing the tamoxifen-inducible expression of the Cre-ER(T2) cassette...
March 27, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28345812/reduced-expression-of-let-7f-activates-tgf-%C3%AE-alk5-pathway-and-leads-to-impaired-ischaemia-induced-neovascularization-after-cigarette-smoke-exposure
#2
Wahiba Dhahri, Sylvie Dussault, Paola Haddad, Julie Turgeon, Sophie Tremblay, Kevin Rolland, Michel Desjarlais, Katia Y Cáceres-Gorriti, Raphael Mathieu, Alain Rivard
This study sought to determine the potential role of microRNAs (miRNAs) in the detrimental effects of cigarette smoke on angiogenesis and neovascularization. Using large-scale miRNA profiling and qRT-PCR analyses, we identified let-7f as a pro-angiogenic miRNA which expression is significantly reduced in HUVECs treated with cigarette smoke extracts (CSE), and in the ischemic muscles of mice that are exposed to cigarette smoke (MES). In a mouse model of hindlimb ischaemia, intramuscular injection of let-7f mimic restored ischaemia-induced neovascularization in MES...
March 27, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28345488/deep-infiltrating-endometriosis-and-endometrial-adenocarcinoma-express-high-levels-of-myostatin-and-its-receptors-messenger-rnas
#3
Patrizia Carrarelli, Lucia Funghi, Pasquapina Ciarmela, Gabriele Centini, Fernando M Reis, Cynthia Dela Cruz, Alberto Mattei, Silvia Vannuccini, Felice Petraglia
Myostatin is a growth factor member of the transforming growth factor β superfamily, which is known to play major roles in cell proliferation and differentiation. The present study investigated the messenger RNA (mRNA) expression of myostatin and myostatin receptors (activin receptor-like kinase 4 [ALK4], transforming growth factor (TGF)-β type I receptor kinase [ALK5] and activin receptor type IIB [ActRIIB]) in endometrium of healthy women during menstrual cycle as well as in benign (endometriosis, polyps) and malignant (endometrial adenocarcinoma) conditions...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28344891/tumor-infiltrating-cd39-%C3%AE-%C3%AE-tregs-are-novel-immunosuppressive-t-cells-in-human-colorectal-cancer
#4
Guoming Hu, Pin Wu, Pu Cheng, Zhigang Zhang, Zhen Wang, Xiuyan Yu, Xuan Shao, Dang Wu, Jun Ye, Tao Zhang, Xiaochen Wang, Fuming Qiu, Jun Yan, Jian Huang
Tumor microenvironment (TME) promotes immune suppression through recruiting and expanding suppressive immune cells such as regulatory T cells (Tregs) to facilitate cancer progression. In this study, we identify a novel CD39(+) γδTreg in human colorectal cancer (CRC). CD39(+) γδTregs are the predominant regulatory T cells and have more potent immunosuppressive activity than CD4(+) or CD8(+) Tregs via the adenosine-mediated pathway but independent of TGF-β or IL-10. They also secrete cytokines including IL-17A and GM-CSF, which may chemoattract myeloid-derived suppressive cells (MDSCs), thus establishing an immunosuppressive network...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344883/acquisition-of-tumor-cell-phenotypic-diversity-along-the-emt-spectrum-under-hypoxic-pressure-consequences-on-susceptibility-to-cell-mediated-cytotoxicity
#5
Stéphane Terry, Stéphanie Buart, Tuan Zea Tan, Gwendoline Gros, Muhammad Zaeem Noman, James B Lorens, Fathia Mami-Chouaib, Jean Paul Thiery, Salem Chouaib
Tumor escape to immunosurveillance and resistance to immune attacks present a major hurdle in cancer therapy, especially in the current era of new cancer immunotherapies. We report here that hypoxia, a hallmark of most solid tumors, orchestrates carcinoma cell heterogeneity through the induction of phenotypic diversity and the acquisition of distinct epithelial-mesenchymal transition (EMT) states. Using lung adenocarcinoma cells derived from a non-metastatic patient, we demonstrated that hypoxic stress induced phenotypic diversity along the EMT spectrum, with induction of EMT transcription factors (EMT-TFs) SNAI1, SNAI2, TWIST1, and ZEB2 in a hypoxia-inducible factor-1α (HIF1A)-dependent or -independent manner...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28344757/leveraging-blood-serotonin-as-an-endophenotype-to-identify-de-novo-and-rare-variants-involved-in-autism
#6
Rui Chen, Lea K Davis, Stephen Guter, Qiang Wei, Suma Jacob, Melissa H Potter, Nancy J Cox, Edwin H Cook, James S Sutcliffe, Bingshan Li
BACKGROUND: Autism spectrum disorder (ASD) is one of the most highly heritable neuropsychiatric disorders, but underlying molecular mechanisms are still unresolved due to extreme locus heterogeneity. Leveraging meaningful endophenotypes or biomarkers may be an effective strategy to reduce heterogeneity to identify novel ASD genes. Numerous lines of evidence suggest a link between hyperserotonemia, i.e., elevated serotonin (5-hydroxytryptamine or 5-HT) in whole blood, and ASD. However, the genetic determinants of blood 5-HT level and their relationship to ASD are largely unknown...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28344175/transforming-growth-factor-%C3%AE-family-in-the-pathogenesis-of-meningiomas
#7
REVIEW
Mahlon D Johnson
OBJECTIVES: Meningiomas represent thirty-six percent of primary brain tumors. The pathogenesis of these tumors is not completely established hindering development of effective chemotherapy. Recently, numerous studies have identified alterations in several growth factors/receptor kinases that regulate meningioma growth. These may be targets for new therapies. . Of these and, sometimes overlooked, is the TGF-β family, its receptors and signaling pathways plays a critical role in the development or progression of many forms of neoplasia...
March 23, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28343781/sublingual-targeting-of-sting-with-3-3-cgamp-promotes-systemic-and-mucosal-immunity-against-anthrax-toxins
#8
Tara L Martin, Junbae Jee, Eunsoo Kim, Haley E Steiner, Estelle Cormet-Boyaka, Prosper N Boyaka
Anthrax is caused by Bacillus anthracis, a zoonotic bacterial pathogen affecting humans and livestock worldwide. The current human anthrax vaccine, anthrax vaccine adsorbed (AVA), is an injected vaccine with a cumbersome administration schedule and fails to promote mucosal immunity. Bacterial enterotoxins, which stimulate production of the cyclic nucleotide cAMP are effective experimental mucosal vaccine adjuvants, but their inherent toxicity has precluded their use in humans. We investigated whether cyclic dinucleotides that target Stimulator of Interferon Gamma Genes (STING) in mammalian cells could represent an alternative to bacterial enterotoxins as adjuvant for sublingual immunization and promotion of mucosal immunity and secretory IgA responses in addition to systemic immunity...
March 23, 2017: Vaccine
https://www.readbyqxmd.com/read/28342452/contribution-of-genetic-factors-to-platinum-based-chemotherapy-sensitivity-and-prognosis-of-non-small-cell-lung-cancer
#9
REVIEW
Cristina Pérez-Ramírez, Marisa Cañadas-Garre, Miguel Ángel Molina, Ana I Robles, María José Faus-Dáder, Miguel Ángel Calleja-Hernández
Although platinum-based chemotherapy remains the standard treatment for advanced NSCLC patients, clinical outcomes are poor and most patients develop high-grade toxicities. Genetic factors, such as single nucleotide polymorphisms (SNPs) involved in platinum pharmacodynamics, metabolism and mechanism of action, may account for inter-individual differences shown in effectiveness and toxicity. Polymorphisms in genes involved in DNA repair and others such as PI3K/PTEN/AKT and TGF-β pathways have been demonstrated to be associated with response, survival and toxicity in advanced NSCLC patients treated with platinum-based chemotherapy...
January 2017: Mutation Research
https://www.readbyqxmd.com/read/28340570/the-therapeutic-hiv-env-c5-gp41-vaccine-candidate-vacc-c5-induces-specific-t-cell-regulation-in-a-phase-i-ii-clinical-study
#10
Kristin Brekke, Maja Sommerfelt, Mats Ökvist, Anne Margarita Dyrhol-Riise, Dag Kvale
BACKGROUND: Levels of non-neutralising antibodies (AB) to the C5 domain of HIV Env gp120 are inversely related to progression of HIV infection. In this phase I/II clinical study we investigated safety of Vacc-C5, a peptide-based therapeutic vaccine candidate corresponding to C5/gp41(732-744) as well as the effects on pre-existing AB levels to C5/gp41(732-744), immune activation and T cell responses including exploratory assessments of Vacc-C5-induced T cell regulation. Our hypothesis was that exposure of the C5 peptide motif may have detrimental effects due to several of its HLA-like features and that enhancement of non-neutralising anti-C5 AB by vaccination could reduce C5 exposure and thereby chronic immune activation...
March 24, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28340277/immunomodulatory-and-neuroprotective-effect-of-cryopreserved-allogeneic-mesenchymal-stem-cells-on-spinal-cord-injury-in-rats
#11
I R Rosado, P H Carvalho, E G L Alves, T M Tagushi, J L Carvalho, J F Silva, M S L Lavor, K M Oliveira, R Serakides, A M Goes, E G Melo
This study aimed to evaluate the immunomodulatory and neuroprotective effects of allogeneic and cryopreserved mesenchymal stem cells (MSCs) on spinal cord injury. A total of 120 rats were distributed into the following groups: negative control (NC) - without injury, positive control (PC) - with injury without treatment, and group treated with MSC (GMSC) - with injury and treated. Motor function was evaluated by the BBB test at 24, 48, and 72 h and at 8 and 21 postoperative days. Spinal cords were evaluated by histopathology and immunohistochemistry to determine the expression of CD68, NeuN, and GFAP...
March 22, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28339646/tgf-%C3%AE-receptor-inhibition-prevents-ventricular-fibrosis-in-a-mouse-model-of-progressive-cardiac-conduction-disease
#12
Mickael Derangeon, Jérôme Montnach, Cynthia Ore Cerpa, Benoit Jagu, Justine Patin, Gilles Toumaniantz, Aurore Girardeau, Christopher Lh Huang, William H Colledge, Andrew A Grace, Isabelle Baró, Flavien Charpentier
Loss-of-function mutations in SCN5A, the gene encoding Nav1.5 channel, have been associated with inherited progressive cardiac conduction disease (PCCD). We have proposed that Scn5a heterozygous knock-out (Scn5a+/-) mice, which are characterized by ventricular fibrotic remodeling with ageing, represent a model for PCCD. Our objectives were to identify the molecular pathway involved in fibrosis development and prevent its activation. Methods and results: Our study shows that myocardial interstitial fibrosis occurred in Scn5a+/- mice only after 45 weeks of age...
February 17, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28339124/gliadin-reactive-t-cells-in-italian-children-from-preventcd-cohort-at-high-risk-for-celiac-disease
#13
Alessandra Camarca, Renata Auricchio, Stefania Picascia, Olga Fierro, Mariantonia Maglio, Erasmo Miele, Basilio Malamisura, Luigi Greco, Riccardo Troncone, Carmen Gianfrani
BACKGROUND: Newborns at high risk for celiac disease (CD) were recruited in Italy in the context of the PreventCD Study and closely monitored for CD, from 4 months up to a mean age of 8 years at follow-up. The aim of our study was to investigate intestinal T cell reactivity to gliadin at the first clinical and/or serological signs of CD. METHODS: Gliadin-reactive T cell lines were generated from intestinal biopsies of 19 HLA-DQ2 or HLA-DQ8 positive children. At biopsy, 11 children had a diagnosis of acute CD, two of potential CD, and six were non-celiac controls...
March 24, 2017: Pediatric Allergy and Immunology
https://www.readbyqxmd.com/read/28339095/expression-of-yes-associated-protein%C3%A2-1-and-its-clinical-significance-in-ovarian-serous-cystadenocarcinoma
#14
Sang Yeon Cho, Kwanghun Kim, Min Soo Park, Mi Young Jang, Young Hwan Choi, Suyeon Han, Hyun Mo Shin, Chaeuk Chung, Hye Young Han, Jung Bo Yang, Young Bok Ko, Heon Jong Yoo
Yes-associated protein 1 (YAP1) is a key transcriptional regulator in the Hippo signaling pathway that plays a critical role in the development and progression of several types of malignancies, including ovarian cancer. Herein, we investigated the expression of YAP1 and its clinical significance in a large population of patients with ovarian serous cystadenocarcinoma (OSC), which is the most common form of epithelial ovarian neoplasm, using the TCGA database. Surprisingly, cross-cancer mRNA expression and alterations in YAP1 were higher in OSC than in those of other types of cancers in the TCGA database...
March 21, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28339056/nobiletin-inhibits-invasion-via-inhibiting-akt-gsk3%C3%AE-%C3%AE-catenin-signaling-pathway-in-slug-expressing-glioma-cells
#15
Xiang Zhang, Kebin Zheng, Chunhui Li, Yonghui Zhao, Heyang Li, Xuguang Liu, Yinbo Long, Junchao Yao
Epithelial-mesenchymal transition (EMT) is a pivotal event in tumor progression during which cancer cells undergo dramatic changes acquiring highly invasive properties. In this study, we found that nobiletin, a polymethoxylated flavone, suppressed migration and invasion in both U87 and U251 glioma cells. Expression of epithelial markers (E-cadherin and occludin) was upregulated; mesenchymal markers (N-cadherin, fibronectin) and the transcriptional factor Slug were downregulated after nobiletin treatment. Transforming growth factor β (TGF-β) was applied to stimulate EMT and the results showed that nobiletin not only influenced basal level cell migration but also prevented TGF-β-triggered migration and EMT, with the AKT/GSK3β/β-catenin signaling pathway greatly involved...
March 23, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28338957/regulation-of-tgf-%C3%AE-mediated-endothelial-mesenchymal-transition-by-microrna-27
#16
Hiroshi I Suzuki, Akihiro Katsura, Hajime Mihira, Masafumi Horie, Akira Saito, Kohei Miyazono
Multiple microRNAs (miRNAs) regulate epithelial-mesenchymal transition and endothelial-mesenchymal transition (EndMT). Here we report that microRNA-27b (miR-27b) positively regulates transforming growth factor-β (TGF-β)-induced EndMT of MS-1 mouse pancreatic microvascular endothelial cells. TGF-β induced miR-23b/24-1/27b expression, and inhibition of miR-27 suppressed TGF-β-mediated induction of mesenchymal genes. Genome-wide miRNA target analysis revealed that miR-27 targets Elk1, which acts as a competitive inhibitor of myocardin-related transcription factor-serum response factor signalling and as a myogenic repressor...
March 13, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28337819/pai-1-in-granulosa-cells-is-suppressed-directly-by-statin-and-indirectly-by-suppressing-tgf-%C3%AE-and-tnf-%C3%AE-in-mononuclear-cells-by-insulin-sensitizing-drugs
#17
Kaori Yamada-Nomoto, Osamu Yoshino, Ikumi Akiyama, Akira Iwase, Yosuke Ono, Tomoko Nakamura, Miyuki Harada, Akitoshi Nakashima, Tomoko Shima, Akemi Ushijima, Yutaka Osuga, Russell Jeffrey Chang, Shunichi Shimasaki, Shigeru Saito
PROBLEM: Plasminogen activator inhibitor-1 (PAI-1) is elevated in women with polycystic ovary syndrome (PCOS), but the regulation in granulosa cells (GCs) is unclear. METHOD OF STUDY: PAI-1 expression in PCOS ovaries was investigated immunohistologically. PAI-1 expressions in HGrC1, a human GC cell line, were investigated at mRNA and activity levels. The expressions of TGF-β and TNF-α in peritoneal fluid mononuclear cells (PFMCs) were measured with quantitative PCR...
March 24, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28337662/a83-01-inhibits-tgf-%C3%AE-induced-upregulation-of-wnt3-and-epithelial-to-mesenchymal-transition-in-her2-overexpressing-breast-cancer-cells
#18
Yanyuan Wu, Trinh Tran, Sami Dwabe, Marianna Sarkissyan, Juri Kim, Miguel Nava, Sheilah Clayton, Richard Pietras, Robin Farias-Eisner, Jaydutt V Vadgama
PURPOSE: The aim of this study is to investigate the mechanisms of interactions between TGF-β and Wnt/β-catenin pathways that induce and regulate EMT and promote breast cancer cells to become resistant to treatment. METHODS: The effect of TGF-β on Wnt/β-catenin signaling pathway was examined by using a human Wnt/β-catenin-regulated cDNA plate array and western blot analysis. The interaction of Twist at promoter of Wnt3 was examined by chromatin immunoprecipitation (ChIP) assay...
March 23, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28337441/pentoxifylline-regulates-plasminogen-activator-inhibitor-1-expression-and-protein-kinase-a-phosphorylation-in-radiation-induced-lung-fibrosis
#19
Jong-Geol Lee, Sehwan Shim, Min-Jung Kim, Jae Kyung Myung, Won-Suk Jang, Chang-Hwan Bae, Sun-Joo Lee, Kyeong Min Kim, Young-Woo Jin, Seung-Sook Lee, Sunhoo Park
Purpose. Radiation-induced lung fibrosis (RILF) is a serious late complication of radiotherapy. In vitro studies have demonstrated that pentoxifylline (PTX) has suppressing effects in extracellular matrix production in fibroblasts, while the antifibrotic action of PTX alone using clinical dose is yet unexplored. Materials and Methods. We used micro-computed tomography (micro-CT) and histopathological analysis to evaluate the antifibrotic effects of PTX in a rat model of RILF. Results. Micro-CT findings showed that lung density, volume loss, and mediastinal shift are significantly increased at 16 weeks after irradiation...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28337306/thymoquinone-potentiates-chemoprotective-effect-of-vitamin-d3-against-colon-cancer-a-pre-clinical-finding
#20
Amr M Mohamed, Bassem A Refaat, Adel G El-Shemi, Osama A Kensara, Jawwad Ahmad, Shakir Idris
Prevention of colon cancer among high-risk group has been long lasting research goal. Emerging data have evidenced the anticancer activities of Vitamin D3 (Vit.D) and Thymoquinone (TQ). The aim of the current study was to evaluate the synergistic potential of Thymoquinone and Vitamin D3 in the control of colon cancer progression using azoxymethane-induced rat model. Vit.D and TQ were given individually or in combination 4 week prior to induction and continued for a total of 20 week. At the end of the study, all animals were euthanized and their resected colons were examined macroscopically and microscopically for tumor growth...
2017: American Journal of Translational Research
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