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https://www.readbyqxmd.com/read/28211912/dna-methylation-map-in-circulating-leukocytes-mirrors-subcutaneous-adipose-tissue-methylation-pattern-a-genome-wide-analysis-from-non-obese-and-obese-patients
#1
A B Crujeiras, A Diaz-Lagares, J Sandoval, F I Milagro, S Navas-Carretero, M C Carreira, A Gomez, D Hervas, M P Monteiro, F F Casanueva, M Esteller, J A Martinez
The characterization of the epigenetic changes within the obesity-related adipose tissue will provide new insights to understand this metabolic disorder, but adipose tissue is not easy to sample in population-based studies. We aimed to evaluate the capacity of circulating leukocytes to reflect the adipose tissue-specific DNA methylation status of obesity susceptibility. DNA samples isolated from subcutaneous adipose tissue and circulating leukocytes were hybridized in the Infinium HumanMethylation 450 BeadChip...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209809/macrophage-to-myofibroblast-transition-contributes-to-interstitial-fibrosis-in-chronic-renal-allograft-injury
#2
Ying-Ying Wang, Hong Jiang, Jun Pan, Xiao-Ru Huang, Yu-Cheng Wang, Hong-Feng Huang, Ka-Fai To, David J Nikolic-Paterson, Hui-Yao Lan, Jiang-Hua Chen
Interstitial fibrosis is an important contributor to graft loss in chronic renal allograft injury. Inflammatory macrophages are associated with fibrosis in renal allografts, but how these cells contribute to this damaging response is not clearly understood. Here, we investigated the role of macrophage-to-myofibroblast transition in interstitial fibrosis in human and experimental chronic renal allograft injury. In biopsy specimens from patients with active chronic allograft rejection, we identified cells undergoing macrophage-to-myofibroblast transition by the coexpression of macrophage (CD68) and myofibroblast (α-smooth muscle actin [α-SMA]) markers...
February 16, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28208683/plasma-gelsolin-induced-glomerular-fibrosis-via-the-tgf-%C3%AE-1-smads-signal-transduction-pathway-in-iga-nephropathy
#3
Lei Zhang, Changsong Han, Fei Ye, Yan He, Yinji Jin, Tianzhen Wang, Yiqi Wu, Yang Jiang, Fengmin Zhang, Xiaoming Jin
Glomerular fibrosis has been shown to be closely related to the progression and prognosis of IgA nephropathy (IgAN). However, mechanism underlying IgAN glomerular fibrosis remains unclear. Recently, our study showed that plasma gelsolin (pGSN) was decreased in the serum of an IgAN mouse model and that pGSN deposition was found in the glomeruli. Another cytokine, TGF-β1, which is closely related to glomerular fibrosis, was also found to be highly expressed in the glomeruli. In the present study, we report that pGSN induces glomerular fibrosis through the TGF-β1/Smads signal transduction pathway...
February 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28207769/role-of-glycogen-synthase-kinase-3%C3%AE-and-ppar-%C3%AE-on-epithelial-to-mesenchymal-transition-in-dss-induced-colorectal-fibrosis
#4
Jacopo Di Gregorio, Roberta Sferra, Silvia Speca, Antonella Vetuschi, Caroline Dubuquoy, Pierre Desreumaux, Simona Pompili, Loredana Cristiano, Eugenio Gaudio, Vincenzo Flati, Giovanni Latella
BACKGROUND: Intestinal fibrosis is characterized by abnormal production and deposition of extracellular matrix (ECM) proteins by activated myofibroblasts. The main progenitor cells of activated myofibroblasts are the fibroblasts and the epithelial cells, the latter through the epithelial-mesenchymal transition (EMT). AIM: To evaluate the action of the new PPAR-γ modulator, GED-0507-34 Levo (GED) on the expression of EMT associated and regulatory proteins such as TGF-β, Smad3, E-cadherin, Snail, ZEB1, β-catenin, and GSK-3β, in a mouse model of DSS-induced intestinal fibrosis...
2017: PloS One
https://www.readbyqxmd.com/read/28197539/redirecting-rna-splicing-by-smad3-turns-tgf-%C3%AE-into-a-tumor-promoter
#5
Veenu Tripathi, Ying E Zhang
Transforming growth factor β (TGF-β) is a well-known growth inhibitor of normal epithelial cells, but it is also secreted by solid tumors to promote cancer progression. Our recent discovery of SMAD3-PCBP1 complex with direct RNA-binding properties has shed light on how this conversion is implemented by controlling pre-mRNA splicing patterns.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28195240/mir302-regulates-snai1-expression-to-control-mesangial-cell-plasticity
#6
L De Chiara, D Andrews, A Watson, G Oliviero, G Cagney, J Crean
Cell fate decisions are controlled by the interplay of transcription factors and epigenetic modifiers, which together determine cellular identity. Here we elaborate on the role of miR302 in the regulation of cell plasticity. Overexpression of miR302 effected silencing of the TGFβ type II receptor and facilitated plasticity in a manner distinct from pluripotency, characterized by increased expression of Snail. miR302 overexpressing mesangial cells also exhibited enhanced expression of EZH2 coincident with Snail upregulation...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28195142/a-genome-wide-association-study-yields-five-novel-thyroid-cancer-risk-loci
#7
Julius Gudmundsson, Gudmar Thorleifsson, Jon K Sigurdsson, Lilja Stefansdottir, Jon G Jonasson, Sigurjon A Gudjonsson, Daniel F Gudbjartsson, Gisli Masson, Hrefna Johannsdottir, Gisli H Halldorsson, Simon N Stacey, Hannes Helgason, Patrick Sulem, Leigha Senter, Huiling He, Sandya Liyanarachchi, Matthew D Ringel, Esperanza Aguillo, Angeles Panadero, Enrique Prats, Almudena Garcia-Castaño, Ana De Juan, Fernando Rivera, Li Xu, Lambertus A Kiemeney, Gudmundur I Eyjolfsson, Olof Sigurdardottir, Isleifur Olafsson, Hoskuldur Kristvinsson, Romana T Netea-Maier, Thorvaldur Jonsson, Jose I Mayordomo, Theo S Plantinga, Hannes Hjartarson, Jon Hrafnkelsson, Erich M Sturgis, Unnur Thorsteinsdottir, Thorunn Rafnar, Albert de la Chapelle, Kari Stefansson
The great majority of thyroid cancers are of the non-medullary type. Here we report findings from a genome-wide association study of non-medullary thyroid cancer, including in total 3,001 patients and 287,550 controls from five study groups of European descent. Our results yield five novel loci (all with Pcombined<3 × 10(-8)): 1q42.2 (rs12129938 in PCNXL2), 3q26.2 (rs6793295 a missense mutation in LRCC34 near TERC), 5q22.1 (rs73227498 between NREP and EPB41L4A), 10q24.33 (rs7902587 near OBFC1), and two independently associated variants at 15q22...
February 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28193525/caffeic-acid-phenethyl-ester-attenuates-liver-fibrosis-via-inhibition-of-tgf-%C3%AE-1-smad3-pathway-and-induction-of-autophagy-pathway
#8
Ning Yang, Shuangsuo Dang, Juanjuan Shi, Fengping Wu, Mei Li, Xin Zhang, Yaping Li, Xiaoli Jia, Song Zhai
Caffeic acid phenethyl ester (CAPE) has been reported to possess the hepatoprotective effect. This study was to investigate the mechanism underlying CAPE against liver fibrosis in a liver fibrosis model induced by toxic carbon tetrachloride (CCl4) in male Sprague-Dawley rats and in vitro in CAPE (5 μM, 10 μM, 15 μM) treated hepatic stellate cells (HSC-T6). We found that CAPE treatment remarkably attenuated CCl4-induced liver fibrosis by blocking the activation of HSCs as determined by the expression alternation of transforming growth factor (TGF)-β1, phosphorylated Smad3 (p-Smad3), collage I, α-smooth muscle actin (α-SMA), matrix metalloproteinases (MMPs) 2, tissue inhibitor of matrix metalloproteinases (TIMPs) 1...
February 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28192879/knockdown-of-irf3-inhibits-extracellular-matrix-expression-in-keloid-fibroblasts
#9
Yi Zhang, Li Zhang, Xiao-Hua Lin, Zhi-Ming Li, Qi-Yu Zhang
Keloid is a pathologic fibro-proliferative disorder and is characterized by hyper-proliferation of fibroblasts and excess extracellular matrix (ECM) deposition. Interferon regulatory factor 3 (IRF3) is a member of the interferon-regulatory factor (IRF) family and has been shown to play a critical modulator in the progression of fibrosis. However, the function of IRF3 in dermal fibrosis remains unclear. Thus, in this study, we investigated the effects of IRF3 on keloid-derived fibroblasts (KFs) proliferation and ECM expression, and explored the underlying mechanism...
February 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28188756/therapeutic-effect-and-mechanism-of-electrical-stimulation-in-female-stress-urinary-incontinence
#10
Jie Min, Bingshu Li, Cheng Liu, Shasha Hong, Jianming Tang, Ming Hu, Yaodan Liu, Suting Li, Li Hong
OBJECTIVE: To investigate the therapeutic effect and underlying molecular mechanism of electrical stimulation (ES) in a murine SUI model. MATERIALS AND METHODS: Sixty female C57BL/6 mice were divided into four groups: CON group, no intervention; VD group, vaginal distension (VD) with an 8-mm dilator for 1 h; VD+ES 20 group, 20 Hz ES for 0.5 h for 7 days after VD; VD+ES 50 group, 50 Hz ES for 7 days after VD. For functional studies, assessments of urodynamics and sneezing test were performed; then, anterior vaginal wall specimens were collected...
February 7, 2017: Urology
https://www.readbyqxmd.com/read/28185953/a-novel-smad3-mutation-caused-multiple-aneurysms-in-a-patient-without-osteoarthritis-symptoms
#11
Audrey Courtois, Wouter Coppieters, Vincent Bours, Jean-Olivier Defraigne, Alain Colige, Natzi Sakalihasan
Heterozygous mutations in the SMAD3 gene were recently described as the cause of a form of non-syndromic familial aortic thoracic aneurysm and dissection (FTAAD) transmitted as an autosomal dominant disorder and often associated with early-onset osteoarthritis. This new clinical entity, called aneurysms-osteoarthritis syndrome (AOS) or Loeys-Dietz syndrome 3 (LDS3), is characterized by aggressive arterial damages such as aneurysms, dissections and tortuosity throughout the arterial tree. We report, here, the case of a 45 year-old man presenting multiple visceral arteries and abdominal aortic aneurysms but without dissection of the thoracic aorta and without any sign of osteoarthritis...
February 6, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/28182006/coordinate-activities-of-brd4-and-cdk9-in-the-transcriptional-elongation-complex-are-required-for-tgf%C3%AE-induced-nox4-expression-and-myofibroblast-transdifferentiation
#12
Talha Ijaz, Mohammad Jamaluddin, Yingxin Zhao, Yueqing Zhang, Jayson Jay, Celeste C Finnerty, David N Herndon, Ronald G Tilton, Allan R Brasier
Transdifferentiation of quiescent dermal fibroblasts to secretory myofibroblasts has a central role in wound healing and pathological scar formation. This myofibroblast transdifferentiation process involves TGFβ-induced de novo synthesis of alpha smooth muscle cell actin (αSMA)+ fibers that enhance contractility as well as increased expression of extracellular matrix (ECM) proteins, including collagen and fibronectin. These processes are mediated upstream by the reactive oxygen species (ROS)-producing enzyme Nox4, whose induction by TGFβ is incompletely understood...
February 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28168411/potential-therapeutic-role-of-punicalagin-against-mechanical-trauma-induced-stress-urinary-incontinence-via-upregulation-of-nrf2-and-tgf-%C3%AE-1-signaling-effect-of-punicalagin-on-mechanical-trauma-induced-sui
#13
Jianming Tang, Cheng Liu, Jie Min, Ming Hu, Yang Li, Li Hong
INTRODUCTION AND HYPOTHESIS: We investigated the effect of punicalagin (PUN; 2,3-hexahydroxydiphenoyl-gallagyl-D-glucose), on mechanical-trauma-induced stress urinary incontinence (SUI) in mouse and the mechanisms underlying any effects. METHODS: Ninety virgin female C57BL/6 mice were randomized into six groups: five groups underwent vaginal distention (VD) for 1 h and leak-point pressure (LPP) was measured on the 1st, 3rd, 7th, 14th, and 28th day following (VD groups 1 d, 3 d, 7 d, 14 d, and 28 d)...
February 6, 2017: International Urogynecology Journal
https://www.readbyqxmd.com/read/28167353/genetic-risk-analysis-of-coronary-artery-disease-in-pakistani-subjects-using-a-genetic-risk-score-of-21-variants
#14
Saleem Ullah Shahid, Shabana, Jackie A Cooper, Katherine E Beaney, Kawah Li, Abdul Rehman, Steve E Humphries
BACKGROUND AND AIMS: Conventional coronary artery disease (CAD) risk factors like age, gender, blood lipids, hypertension and smoking have been the basis of CAD risk prediction algorithms, but provide only modest discrimination. Genetic risk score (GRS) may provide improved discrimination over and above conventional risk factors. Here we analyzed the genetic risk of CAD in subjects from Pakistan, using a GRS of 21 variants in 18 genes and examined whether the GRS is associated with blood lipid levels...
January 22, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28165563/hoxa13-upregulation-in-gastric-cancer-is-associated-with-enhanced-cancer-cell-invasion-and-epithelial-to-mesenchymal-transition
#15
Y-X He, X-H Song, Z-Y Zhao, H Zhao
OBJECTIVE: In this study, we investigated the association between HOXA13 dysregulation and gastric cancer progression. We also explored the functional role of HOXA13 in invasion and epithelial-to-mesenchymal transition (EMT) of gastric cancer cells and the possible signaling pathway it might involve in. MATERIALS AND METHODS: The microarray (E-GEOD-19826) examined the transcription profiles of 12 adjacent normal/tumor-matched gastric tissues was downloaded from the ArrayExpress and reanalyzed...
January 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28165488/restenosis-inhibition-and-re-differentiation-of-tgf%C3%AE-smad3-activated-smooth-muscle-cells-by-resveratrol
#16
Yichen Zhu, Toshio Takayama, Bowen Wang, Alycia Kent, Mengxue Zhang, Bernard Y K Binder, Go Urabe, Yatao Shi, Daniel DiRenzo, Shakti A Goel, Yifan Zhou, Christopher Little, Drew A Roenneburg, Xu Dong Shi, Lingjun Li, William L Murphy, K Craig Kent, Jianjuan Ke, Lian-Wang Guo
To date, there is no periadventitial drug delivery method available in the clinic to prevent restenotic failure of open vascular reconstructions. Resveratrol is a promising anti-restenotic natural drug but subject to low bioavailability when systemically administered. In order to reconcile these two prominent issues, we tested effects of periadventitial delivery of resveratrol on all three major pro-restenotic pathologies including intimal hyperplasia (IH), endothelium impairment, and vessel shrinkage. In a rat carotid injury model, periadventitial delivery of resveratrol either via Pluronic gel (2-week), or polymer sheath (3-month), effectively reduced IH without causing endothelium impairment and vessel shrinkage...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28161409/gain-of-function-stat1-mutations-are-associated-with-intracranial-aneurysms
#17
Mete Dadak, Roland Jacobs, Jelena Skuljec, Adan Chari Jirmo, Özlem Yildiz, Frank Donnerstag, Niklas Thomas Baerlecken, Reinhold Ernst Schmidt, Heinrich Lanfermann, Thomas Skripuletz, Philipp Schwenkenbecher, Christoph Kleinschnitz, Hayrettin Tumani, Martin Stangel, Refik Pul
Chronic mucocutaneous candidiasis, characterized by persistent or recurrent fungal infections, represents the clinical hallmark in gain-of-function (GOF) signal transducer and activator of transcription 1 (STAT1) mutation carriers. Several cases of intracranial aneurysms have been reported in patients with GOF STAT1 mutation but the paucity of reported cases likely suggested this association still as serendipity. In order to endorse this association, we link the development of intracranial aneurysms with STAT1 GOF mutation by presenting the two different cases of a patient and her mother, and demonstrate upregulated phosphorylated STAT4 and IL-12 receptor β1 upon stimulation in patient's blood cells...
February 1, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28149008/transforming-growth-factor-%C3%AE-1-smad3-signaling-and-redox-status-in-experimentally-induced-nephrotoxicity-impact-of-carnosine
#18
Walaa Arafa Keshk, Mohamed Alaa Katary
: Exposure to various organic compounds including drugs and environmental toxins causes cellular damage through generation of free radicals. Carnosine a dipeptide was used in this study to evaluate its effect against CCl4-induced nephrotoxicity. Sixty male albino rats were involved in this study and were equally divided into four groups. CCl4 (3 ml/kg body weight; biweekly for 4 weeks) was given to group II and III. Carnosine (10 mg/kg body weight; once daily for 4 weeks) was given to group III and VI...
March 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28143872/musashi-rna-binding-proteins-as-cancer-drivers-and-novel-therapeutic-targets
#19
Alexander E Kudinov, John Karanicolas, Erica A Golemis, Yanis Boumber
Aberrant gene expression that drives human cancer can arise from epigenetic dysregulation. While much attention has focused on altered activity of transcription factors and chromatin-modulating proteins, proteins that act post-transcriptionally can potently affect expression of oncogenic signaling proteins. The RNA-binding proteins (RBPs) Musashi-1 (MSI1) and Musashi-2 (MSI2) are emerging as regulators of multiple critical biological processes relevant to cancer initiation, progression, and drug resistance...
January 31, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28138219/resveratrol-inhibits-transforming-growth-factor-%C3%AE-2-induced-epithelial-to-mesenchymal-transition-in-human-retinal-pigment-epithelial-cells-by-suppressing-the-smad-pathway
#20
Ching-Long Chen, Yi-Hao Chen, Ming-Cheng Tai, Chang-Min Liang, Da-Wen Lu, Jiann-Torng Chen
Proliferative vitreoretinopathy (PVR) is the main cause of failure following retinal detachment surgery. Transforming growth factor (TGF)-β2-induced epithelial-to-mesenchymal transition (EMT) plays an important role in the development of PVR, and EMT inhibition decreases collagen gel contraction and fibrotic membrane formation, resulting in prevention of PVR. Resveratrol is naturally found in red wine and has inhibitory effects on EMT. Resveratrol is widely used in cardioprotection, neuroprotection, chemotherapy, and antiaging therapy...
2017: Drug Design, Development and Therapy
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