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https://www.readbyqxmd.com/read/28913356/expression-profiling-of-cellular-microrna-in-asymptomatic-hbsag-carriers-and-chronic-hepatitis-b-patients
#1
Xianliang Hou, Yan Liang, Jianing Chen, Yingfeng Wei, Ping Zeng, Lin Wang, Chong Lu, Hongyan Diao
BACKGROUND: MicroRNAs (miRNAs) may serve as potential molecular markers to predict liver injury resulting from chronic hepatitis B (CHB). In the present study, we want to study the expression profile and clinical significance of miRNAs at different stages of CHB virus infection. METHODS: Using miRNA microarray, we investigated the global expression profiles of cellular miRNA in asymptomatic hepatitis B antigen carriers (ASCs) and CHB patients, compared with healthy controls (HCs)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28875468/multifunctional-jnk-inhibiting-nanotherapeutics-for-augmented-elastic-matrix-regenerative-repair-in-aortic-aneurysms
#2
Andrew Camardo, Dhruv Seshadri, Tom Broekelmann, Robert Mecham, Anand Ramamurthi
Growth of abdominal aortic aneurysms (AAA), localized aortal wall expansions, is driven by the disruption and subsequent loss of aortal wall elastic fibers by matrix metalloproteases (MMPs). Since elastic fibers do not naturally regenerate or repair, arresting/reversing AAA growth has not been possible. Previously, we showed utility of doxycycline (DOX), an MMP inhibitor drug, to stimulate elastic matrix neoassembly and crosslinking at low microgram per milliliter doses in addition to inhibiting MMPs. We currently show in aneurysmal smooth muscle cell (SMC) cultures that effects of exogenous DOX in this dose range are linked to its upregulation of transforming growth factor beta (TGF-β1) via its inhibition of the regulatory protein c-Jun-N-terminal kinase 2 (JNK 2)...
September 5, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28870615/luspatercept-for-the-treatment-of-anaemia-in-patients-with-lower-risk-myelodysplastic-syndromes-pace-mds-a-multicentre-open-label-phase-2-dose-finding-study-with-long-term-extension-study
#3
Uwe Platzbecker, Ulrich Germing, Katharina S Götze, Philipp Kiewe, Karin Mayer, Jörg Chromik, Markus Radsak, Thomas Wolff, Xiaosha Zhang, Abderrahmane Laadem, Matthew L Sherman, Kenneth M Attie, Aristoteles Giagounidis
BACKGROUND: Myelodysplastic syndromes are characterised by ineffective erythropoiesis. Luspatercept (ACE-536) is a novel fusion protein that blocks transforming growth factor beta (TGF β) superfamily inhibitors of erythropoiesis, giving rise to a promising new investigative therapy. We aimed to assess the safety and efficacy of luspatercept in patients with anaemia due to lower-risk myelodysplastic syndromes. METHODS: In this phase 2, multicentre, open-label, dose-finding study (PACE-MDS), with long-term extension, eligible patients were aged 18 years or older, had International Prognostic Scoring System-defined low or intermediate 1 risk myelodysplastic syndromes or non-proliferative chronic myelomonocytic leukaemia (white blood cell count <13 000/μL), and had anaemia with or without red blood cell transfusion support...
September 1, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28864263/mechanism-of-chimeric-vaccine-stimulation-of-indoleamine-2-3-dioxygenase-biosynthesis-in-human-dendritic-cells-is-independent-of-tgf-%C3%AE-signaling
#4
Grace E Esebanmen, William H R Langridge
Cholera toxin B subunit fusion to autoantigens such as proinsulin (CTB-INS) down regulate dendritic cell (DC) activation and stimulate synthesis of DC immunosuppressive cytokines. Recent studies of CTB-INS induction of immune tolerance in human DCs indicate that increased biosynthesis of indoleamine 2,3-dioxygenase (IDO1) may play an important role in CTB-INS vaccine suppression of DC activation. Studies in murine models suggest a role for transforming growth factor beta (TGF-β) in the stimulation of IDO1 biosynthesis, for the induction of tolerance in DCs...
August 21, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28806736/unravelling-the-interplay-of-sphingolipids-and-tgf-%C3%AE-signaling-in-the-human-corneal-stroma
#5
Sarah E Nicholas, Tyler G Rowsey, Shrestha Priyadarsini, Nawajes A Mandal, Dimitrios Karamichos
PURPOSE: To delineate the role of Sphingolipids (SPLs) in the human cornea and their cross-talks with transforming growth factor beta (TGF-β) in order to develop novel, non-invasive therapies. METHODS: Human corneal fibroblasts (HCFs) were harvested from healthy donors, stimulated with Vitamin C to promote extracellular matrix assembly, treated with exogenous sphingosine-1-phosphate (S1P) or sphingosine kinase inhibitor 2 (SPHK I2) and isolated after 4 weeks for further analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28801914/blockade-of-transforming-growth-factor-%C3%AE-signaling-enhances-oncolytic-herpes-simplex-virus-efficacy-in-patient-derived-recurrent-glioblastoma-models
#6
Shinichi Esaki, Fares Nigim, Esther Moon, Samantha Luk, Juri Kiyokawa, William Curry, Daniel P Cahill, Andrew S Chi, A John Iafrate, Robert L Martuza, Samuel D Rabkin, Hiroaki Wakimoto
Despite the current standard of multimodal management, glioblastoma (GBM) inevitably recurs and effective therapy is not available for recurrent disease. A subset of tumor cells with stem-like properties, termed GBM stem-like cells (GSCs), are considered to play a role in tumor relapse. Although oncolytic herpes simplex virus (oHSV) is a promising therapeutic for GBM, its efficacy against recurrent GBM is incompletely characterized. Transforming growth factor beta (TGF-β) plays vital roles in maintaining GSC stemness and GBM pathogenesis...
August 12, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28789942/statins-reduce-tgf-beta2-modulation-of-the-extracellular-matrix-in-cultured-astrocytes-of-the-human-optic-nerve-head
#7
Mi-Lyang Kim, Kyung Rim Sung, Jin A Shin, Joo Young Yoon, Joonhee Jang
Statins are cholesterol lowering drugs and have shown beneficial effects on glaucoma. With regard to the mechanism of statin action on glaucoma, we investigated the effects of statins on transforming growth factor-beta 2 (TGF-β2)-induced expression of extracellular matrix (ECM) proteins in human astrocytes of the optic nerve head (ONH) lamina cribrosa (LC). By using primary human ONH astrocytes, we found that both simvastatin and lovastatin inhibited TGF-β2-mediated expression of ECM proteins such as connective tissue growth factor, collagen I, fibronectin, and plasminogen activator inhibitor-1...
August 5, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28696894/preference-of-aerosolized-pirfenidone-to-oral-intake-an-experimental-model-of-pulmonary-fibrosis-by-paraquat
#8
Rokhsana Rasooli, Hamid Rajaian, Abbas Pardakhty, Ali Mandegary
BACKGROUND: Inhalation drug delivery is a fast, effective, and safe route of delivering medication directly to the lungs. Thanks to the large surface area and highly vascularized epithelium in lung, pulmonary drug delivery has been considered as an effective route to deliver drugs to the systemic circulation. Pirfenidone (PF), an oral antifibrotic agent, has been shown to slow down the progression of the lung fibrosis. Inhalation or intrapulmonary delivery of PF appears to be a good alternative to optimize drug delivery and minimize the dosage, adverse and nonspecific effects...
July 11, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/28663339/the-influence-of-connective-tissue-growth-factor-on-rabbit-ligament-injury-repair
#9
X Sun, W Liu, G Cheng, X Qu, H Bi, Z Cao, Q Yu
OBJECTIVES: The injured anterior cruciate ligament (ACL) is thought to exhibit an impaired healing response, and attempts at surgical repair have not been successful. Connective tissue growth factor (CTGF) is reported to be associated with wound healing, probably through transforming growth factor beta 1 (TGF-β1). METHODS: A rabbit ACL injury model was used to study the effect of CTGF on ligament recovery. Quantitative real-time PCR (qRT-PCR) was performed for detection of changes in RNA levels of TGF-β1, type 1 collagen (COL1), type 2 collagen (COL2), SRY-related high mobility group-box gene9 (SOX9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metallopeptidase 13 (MMP-13)...
July 2017: Bone & Joint Research
https://www.readbyqxmd.com/read/28649665/tgf-%C3%AE-target-genes-are-differentially-regulated-in-corneal-epithelial-cells-and-fibroblasts
#10
Xiaoqing Guo, Audrey E K Hutcheon, Jennifer A Tran, James D Zieske
PURPOSE: Transforming growth factor-beta (TGF-β) activates the canonical Smad pathway, which includes the Smad family of proteins and SARA (Smad Anchor for Receptor Activation) and other less understood pathways, including one involving p38(MAPK). The goal of the current research was to determine if corneal epithelial cells and fibroblasts used the classical or alternative TGF-β-signaling pathways. To examine this question, we made use of Trx-SARA, which inhibits native SARA, thus blocking the Smad pathway...
2017: New Front Ophthalmol
https://www.readbyqxmd.com/read/28647356/optimizing-bone-morphogenic-protein-4-mediated-human-embryonic-stem-cell-differentiation-into-trophoblast-like-cells-using-fibroblast-growth-factor-2-and-transforming-growth-factor-%C3%AE-activin-nodal-signalling-inhibition
#11
Mariann Koel, Urmo Võsa, Kaarel Krjutškov, Elisabet Einarsdottir, Juha Kere, Juha Tapanainen, Shintaro Katayama, Sulev Ingerpuu, Viljar Jaks, Ulf-Hakan Stenman, Karolina Lundin, Timo Tuuri, Andres Salumets
Several studies have demonstrated that human embryonic stem cells (hESC) can be differentiated into trophoblast-like cells if exposed to bone morphogenic protein 4 (BMP4) and/or inhibitors of fibroblast growth factor 2 (FGF2) and the transforming growth factor beta (TGF-β)/activin/nodal signalling pathways. The goal of this study was to investigate how the inhibitors of these pathways improve the efficiency of hESC differentiation when compared with basic BMP4 treatment. RNA sequencing was used to analyse the effects of all possible inhibitor combinations on the differentiation of hESC into trophoblast-like cells over 12 days...
September 2017: Reproductive Biomedicine Online
https://www.readbyqxmd.com/read/28642549/focal-adhesion-kinase-regulates-hepatic-stellate-cell-activation-and-liver-fibrosis
#12
Xue-Ke Zhao, Lei Yu, Ming-Liang Cheng, Pulin Che, Yin-Ying Lu, Quan Zhang, Mao Mu, Hong Li, Li-Li Zhu, Juan-Juan Zhu, Meng Hu, Po Li, Yue-Dong Liang, Xin-Hua Luo, Yi-Ju Cheng, Zhi-Xiang Xu, Qiang Ding
Understanding the underlying molecular mechanisms of liver fibrosis is important to develop effective therapy. Herein, we show that focal-adhesion-kinse (FAK) plays a key role in promoting hepatic stellate cells (HSCs) activation in vitro and liver fibrosis progression in vivo. FAK activation is associated with increased expression of α-smooth muscle actin (α-SMA) and collagen in fibrotic live tissues. Transforming growth factor beta-1 (TGF-β1) induces FAK activation in a time and dose dependent manner. FAK activation precedes the α-SMA expression in HSCs...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28632033/overexpression-of-alk5-induces-human-tenon-s-capsule-fibroblasts-transdifferentiation-and-fibrosis-in-vitro
#13
Shu-Hao Fu, Hui-Ying Wang, Jia-Ying Zhang, Hui-Min Shi, Nan Zhang, Wen Ye, Yi-Qin Xiao
PURPOSE: To investigate the involvement of activin receptor-like kinase 5 (ALK5) in human Tenon's capsule fibroblasts (HTFs) transdifferentiation and fibrosis. METHODS: (1) Cultured HTFs were treated with transforming growth factor beta 1 (TGF-β1) at different concentrations for different durations, mRNA expression of ALK5 and plasminogen activator inhibitor-1 (PAI-1) was measured by quantitative polymerase chain reaction (PCR) while protein expression of ALK5, α-smooth muscle actin (α-SMA), and extracellular matrix deposition including fibronectin (FN) and collagen I (Col1) was assessed by western blot...
February 28, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28625142/proteotoxic-stress-desensitizes-tgf-beta-signaling-through-receptor-downregulation-in-retinal-pigment-epithelial-cells
#14
X Tan, C Chen, Y Zhu, J Deng, X Qiu, S Huang, F Shang, B Cheng, Y Liu
BACKGROUND: Transforming growth factor (TGFβ)-induced epithelial-mesenchymal transition (EMT) and proteotoxic stress are two main contributors of intraocular fibrotic disorders, including proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). However, how these two factors communicate with each other is not well-characterized. OBJECTIVE: The aim was to investigate the regulatory role of proteotoxic stress on TGFβ signaling in retinal pigment epithelium...
June 19, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28610976/dioscin-suppresses-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-and-suppresses-a549-lung-cancer-migration-and-invasion
#15
Won-Chul Lim, Hyunhee Kim, Young-Joo Kim, Kyung-Chul Choi, In Ho Lee, Ki Heon Lee, Mi Kyung Kim, Hyeonseok Ko
Epithelial-to-mesenchymal transition (EMT), an important cellular process, occurs during cancer development and progression, has a crucial role in metastasis by enhancing the motility of tumor cells. Dioscin is a polyphenolic component isolated from Phyllanthus amarus, which exhibits a wide range of pharmacological and physiological activities, such as anti-tumor, anti-inflammatory, anti-obesity, anti-fungal, and anti-viral activities. However, the possible role of dioscin in the EMT is unclear. We investigated the suppressive effect of dioscin on the EMT...
August 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28608941/tgf-%C3%AE-stimulates-expression-of-chondroitin-polymerizing-factor-in-nucleus-pulposus-cells-through-the-smad3-rhoa-rock1-and-mapk-signaling-pathways
#16
Bo Hu, Chen Xu, Peng Cao, Ye Tian, Ying Zhang, Changgui Shi, Jun Xu, Wen Yuan, Huajiang Chen
The enzyme chondroitin polymerizing factor (ChPF) is primarily involved in extension of the chondroitin sulfate backbone required for the synthesis of sulfated glycosaminoglycan (sGAG). Transforming growth factor beta (TGF-β) upregulates sGAG synthesis in nucleus pulposus cells; however, the mechanisms mediating this induction are incompletely understood. Our study demonstrated that ChPF expression was negatively correlated with the grade of degenerative intervertebral disc disease. Treatment of nucleus pulposus cells with TGF-β induced ChPF expression and enhanced Smad2/3, RhoA/ ROCK activation, and the JNK, p38 and ERK1/2 MAPK signaling pathways...
June 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28545810/thymic-stromal-lymphopoietin-and-apocynin-alter-the-expression-of-airway-remodeling-factors-in-human-rhinovirus-infected-cells
#17
Joanna Wieczfinska, Rafal Pawliczak
Airway remodeling is a characteristic of bronchial asthma. The process involves the expression of many genes, such as transforming growth factor-beta (TGF-β), tissue inhibitors of metalloproteinases (TIMP-1), MMP and arginase. Human rhinovirus (HRV) is known to cause asthma exacerbations, and viral infections might be involved in the development of airway remodeling. Therefore, the aim of this study was to determine the influence of HRV on the genes involved in airway remodeling and to examine the impact of thymic stromal lymphopoietin (TSLP) and contribution of oxidative stress on airway remodeling in the context of HRV infection...
August 2017: Immunobiology
https://www.readbyqxmd.com/read/28529481/topical-ophthalmic-formulation-of-trichostatin-a-and-surr9-c84a-for-quick-recovery-post-alkali-burn-of-corneal-haze
#18
Kislay Roy, Chun Hei Antonio Cheung, Rupinder K Kanwar, Rajat Sandhir, Jagat R Kanwar
Alkali burn injury is a true ocular emergency of the conjunctiva and cornea that requires immediate precision. Lack of an immediate therapy can lead to a substantial damage in the ocular surface and anterior segment further causing visual impairment and disfigurement. We explored the regenerative capability of dominant negative survivin protein (SurR9-C84A) and histone deacetylase inhibitor trichostatin-A (TSA) in vivo, in a rat alkali burn model. A topical insult in rat eyes with NaOH led to degradation of the conjunctival and corneal epithelium...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28512472/pulsed-electromagnetic-field-regulates-microrna-21-expression-to-activate-tgf-%C3%AE-signaling-in-human-bone-marrow-stromal-cells-to-enhance-osteoblast-differentiation
#19
Nagarajan Selvamurugan, Zhiming He, Daniel Rifkin, Branka Dabovic, Nicola C Partridge
Pulsed electromagnetic fields (PEMFs) have been documented to promote bone fracture healing in nonunions and increase lumbar spinal fusion rates. However, the molecular mechanisms by which PEMF stimulates differentiation of human bone marrow stromal cells (hBMSCs) into osteoblasts are not well understood. In this study the PEMF effects on hBMSCs were studied by microarray analysis. PEMF stimulation of hBMSCs' cell numbers mainly affected genes of cell cycle regulation, cell structure, and growth receptors or kinase pathways...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28507001/p38-mapk-as-an-essential-regulator-of-dorsal-ventral-axis-specification-and-skeletogenesis-during-sea-urchin-development-a-re-evaluation
#20
Maria Dolores Molina, Magali Quirin, Emmanuel Haillot, Felipe Jimenez, Aline Chessel, Thierry Lepage
Dorsal-ventral axis formation in the sea urchin embryo relies on the asymmetrical expression of the TGFβ Nodal. The p38-MAPK pathway has been proposed to be essential for dorsal-ventral axis formation by acting upstream of nodal expression. Here, we report that, in contrast to previous studies that used pharmacological inhibitors of p38, manipulating the activity of p38 by genetic means has no obvious impact on morphogenesis. Instead, we discovered that p38 inhibitors strongly disrupt specification of all germ layers by blocking signalling from the Nodal receptor and by interfering with the ERK pathway...
June 15, 2017: Development
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