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Activin A

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https://www.readbyqxmd.com/read/28540737/investigational-drugs-in-phase-i-and-phase-ii-clinical-trials-for-thalassemia
#1
Irene Motta, Natalia Scaramellini, Maria Domenica Cappellini
Regular transfusion and iron chelation are the current treatment of severe forms of thalassemia. As a result of this demanding supportive treatment, there are several unmet therapeutic needs. Due to a deeper understanding in the pathophysiology of thalassemia, new therapeutic strategies have been developed that are now in pre-clinical and clinical trials. Areas covered: Activin receptor ligand traps (luspatercept and sotatercept), drugs targeting ineffective erythropoiesis, showed encouraging results in Phase I and II clinical trials...
May 25, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28532044/pancreatic-differentiation-of-induced-pluripotent-stem-cells-in-activin-a-grafted-gelatin-poly-lactide-co-glycolide-nanoparticle-scaffolds-with-induction-of-ly294002-and-retinoic-acid
#2
Yung-Chih Kuo, Yu-Chuan Liu, Rajendiran Rajesh
The differentiation of induced pluripotent stem cells (iPSCs) in biomaterial scaffolds is an emerging area for biomedical applications. This study proposes, for the first time, the production of pancreatic cells from iPSCs in gelatin-poly(lactide-co-glycolide) nanoparticle (PLGA NP) scaffolds. The porosity and swelling ratio of the scaffolds decreased with increases in gelatin and PLGA NP concentrations. The adhesion efficiency of iPSCs in gelatin-PLGA NP scaffolds was found to be higher at 6.7% (w/w) PLGA NP...
August 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28527661/modulation-of-adipocyte-function-by-the-tgf-%C3%AE-family
#3
Yuhang Qiao, Shozo Tomonaga, Masashi Suenaga, Tohru Matsui, Masayuki Funaba
Members of the transforming growth factor-β (TGF-β) family are known to regulate the commitment of mesenchymal stem cells to an adipocyte lineage and the differentiation of preadipocytes to adipocytes. However, the roles of TGF-β family members in mature adipocytes are not known. The present study explored the modulation of cell function in 3T3-L1 adipocytes treated with the TGF-β family members TGF-β1, activin A, activin B, bone morphogenetic protein (BMP) 4, and BMP7. These TGF-β family members modulated the expression of some adipokines; activin A upregulated leptin expression, and activin B downregulated the expression of plasminogen activator inhibitor-1...
May 17, 2017: Cytokine
https://www.readbyqxmd.com/read/28522409/neonatal-exposure-to-17%C3%AE-ethynyl-estradiol-ee-disrupts-follicle-development-and-reproductive-hormone-profiles-in-female-rats
#4
Haolin Zhang, Kazuyoshi Taya, Kentaro Nagaoka, Midori Yoshida, Gen Watanabe
Toxic effects induced by exposure to endocrine-disrupting chemicals during fetal and neonatal periods can be irreversible and exert effects throughout an animal's entire life. Our previous study showed that neonatal exposure to 17α-ethynyl estradiol (EE) induced irregular estrous cycle in adults. To uncover the reason for the delayed effect after neonatal exposure to EE, reproductive parameters including ovarian weight, ovarian steroidogenesis, and hormonal profiles were investigated in developing female rats...
May 15, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28522401/comparison-of-the-osteogenesis-and-fusion-rates-between-activin-a-bmp-2-chimera-ab204-and-rhbmp-2-in-a-beagle-s-posterolateral-lumbar-spine-model
#5
Guang Bin Zheng, Byung-Hak Yoon, Jae Hyup Lee
BACKGROUND CONTEXT: Activin A/BMP-2 chimera (AB204) could promote bone healing more effectively than recombinant bone morphogenetic protein 2 (rhBMP-2) with much lower dose in rodent model, but there is no report about the effectiveness of AB204 in a large animal model. PURPOSE: The purpose of this study was to compare the osteogenesis and fusion rate between AB204 and rhBMP-2 using biphasic calcium phosphate (BCP) as a carrier in beagle's posterolateral lumbar fusion model...
May 15, 2017: Spine Journal: Official Journal of the North American Spine Society
https://www.readbyqxmd.com/read/28515224/activin-a-regulates-activation-of-mouse-neutrophils-by-smad3-signalling
#6
Yan Qi, Jingyan Ge, Chunhui Ma, Na Wu, Xueling Cui, Zhonghui Liu
Activin A, a member of the transforming growth factor beta superfamily, acts as a pro-inflammatory factor in acute phase response, and influences the pathological progress of neutrophil-mediated disease. However, whether activin A can exert an effect on the activities of neutrophils remains unclear. In this study, we found that the release of activin A was enhanced from neutrophils of mouse when stimulated with lipopolysaccharide. Furthermore, neutrophils were not only the source of activin A but also the target cells in response to activin A, in which canonical activin signalling components existed, and levels of ACTRIIA, SMAD3 and p-SMAD3 proteins were elevated in activin A-treated neutrophils...
May 2017: Open Biology
https://www.readbyqxmd.com/read/28500669/anti-m%C3%A3-llerian-hormone-signaling-is-influenced-by-follistatin-288-but-not-14-other-transforming-growth-factor-beta-superfamily-regulators
#7
Yui Kawagishi, Michael W Pankhurst, Yoshio Nakatani, Ian S McLennan
The hypothesis that, in contrast to other transforming growth factor-beta (TGFβ) superfamily ligands, the dose-response curve of Anti-Müllerian hormone (AMH) is unmodulated was tested by examining whether known TGFB superfamily modulators affect AMH signaling, using a P19/BRE luciferase reporter assay. AMHC and AMHN,C activated the reporter with an EC50 of approximately 0.5 nM. Follistatins (FS) produced concentration-dependent increases in AMHC - and AMHN,C -initiated reporter activity, with FS288 being more potent than FS315; however, the maximum bioactivity of AMH was not altered by either follistatin...
May 13, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28489857/vitamin-d-supplementation-lowers-thrombospondin-1-levels-and-blood-pressure-in-healthy-adults
#8
Anjalee T Amarasekera, Bahador Assadi-Khansari, Saifei Liu, Marilyn Black, Greer Dymmott, Natasha M Rogers, Aaron L Sverdlov, John D Horowitz, Doan T M Ngo
INTRODUCTION: Vitamin D insufficiency, defined as 25-hydroxyvitamin D (25(OH)D) levels < 75nmol/L is associated with cardio-metabolic dysfunction. Vitamin D insufficiency is associated with inflammation and fibrosis, but it remains uncertain whether these anomalies are readily reversible. Therefore, we aimed to determine the effects of vitamin D supplementation on markers of: 1) nitric oxide (NO) signaling, 2) inflammation, and 3) fibrosis, in healthy volunteers with mild hypovitaminosis...
2017: PloS One
https://www.readbyqxmd.com/read/28489849/utilizing-bmp-2-muteins-for-treatment-of-multiple-myeloma
#9
Axel Seher, Charlotte Lagler, Thorsten Stühmer, Urs Dietmar Achim Müller-Richter, Alexander Christian Kübler, Walter Sebald, Thomas Dieter Müller, Joachim Nickel
Multiple myeloma (MM) represents a haematological cancer characterized by the pathological hyper proliferation of antibody-producing B-lymphocytes. Patients typically suffer from kidney malfunction and skeletal disorders. In the context of MM, the transforming growth factor β (TGFβ) member Activin A was recently identified as a promoter of both accompanying symptoms. Because studies have shown that bone morphogenetic protein (BMP)-2-mediated activities are counteracted by Activin A, we analysed whether BMP2, which also binds to the Activin A receptors ActRII and ActRIIB but activates the alternative SMAD-1/5/8 pathway, can be used to antagonize Activin A activities, such as in the context of MM...
2017: PloS One
https://www.readbyqxmd.com/read/28486664/microrna-21-plays-a-pivotal-role-in-the-oocyte-secreted-factor-induced-suppression-of-cumulus-cell-apoptosis%C3%A2
#10
Xiao Han, Rui Xue, Hong-Jie Yuan, Tian-Yang Wang, Juan Lin, Jie Zhang, Bo Liang, Jing-He Tan
It is known that oocytes and cumulus cells (CCs) are more resistant to apoptosis than other compartments of the antral follicle. However, although oocyte-secreted factors (OSFs) have been found to be involved in suppressing bovine CC apoptosis, little is known about the intra-cellular mechanisms by which OSFs render CCs resistant to apoptosis. Here we show that coculture with mouse or pig cumulus-denuded oocytes, culture with recombinant mouse growth differentiation factor-9 (GDF-9) or culture in pig oocyte-conditioned medium (POCM) significantly inhibited CC apoptosis of mouse oocytectomized cumulus oophorus complexes (OOXs)...
May 8, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28479070/the-effects-of-activin-a-on-the-migration-of-human-breast-cancer-cells-and-neutrophils-and-their-migratory-interaction
#11
Dongxue Xie, Zhonghui Liu, Jiandong Wu, Wenfang Feng, Ke Yang, Jixian Deng, Ganghong Tian, Susy Santos, Xueling Cui, Francis Lin
Activin A belongs to the superfamily of transforming growth factor beta (TGFβ) and is a critical regulatory cytokine in breast cancer and inflammation. However, the role of activin A in migration of breast cancer cells and immune cells was not well characterized. Here, a microfluidic device was used to examine the effect of activin A on the migration of human breast cancer cell line MDA-MB-231 cells and human blood neutrophils as well as their migratory interaction. We found that activin A promoted the basal migration but impaired epidermal growth factor (EGF)-induced migration of breast cancer cells...
May 4, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28473268/the-congenital-great-toe-malformation-of-fibrodysplasia-ossificans-progressiva-a-close-call
#12
O Will Towler, Eileen M Shore, Meiqi Xu, Abbey Bamford, Ilse Anderson, Robert J Pignolo, Frederick S Kaplan
BACKGROUND: Congenital bilateral hallux valgus with associated absence or fusion of the interphalangeal joint is a classic diagnostic feature of fibrodysplasia ossificans progressiva (FOP), a human genetic disease of extra-skeletal bone formation caused in nearly all cases by a gain-of-function mutation in Activin A Receptor I/Activin-like Kinase 2 (ACVR1/ALK2), which encodes a bone morphogenetic protein (BMP) Type 1 receptor. This toe malformation prompts the suspicion of FOP even before the appearance of extra-skeletal bone...
May 1, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/28471505/role-of-follistatin-in-muscle-and-bone-alterations-induced-by-gravity-change-in-mice
#13
Naoyuki Kawao, Hironobu Morita, Koji Obata, Kohei Tatsumi, Hiroshi Kaji
Interactions between muscle and bone have been recently noted. We reported that the vestibular system plays crucial roles in the changes in muscle and bone induced by hypergravity in mice. However, the details of the mechanisms by which gravity change affects muscle and bone through the vestibular system still remain unknown. Here, we investigated the roles of humoral factors linking muscle to bone and myostatin-related factors in the hypergravity-induced changes in muscle and bone in mice with vestibular lesions (VL)...
May 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28468752/usp4-inhibits-smad4-monoubiquitination-and-promotes-activin-and-bmp-signaling
#14
Fangfang Zhou, Feng Xie, Ke Jin, Zhengkui Zhang, Marcello Clerici, Rui Gao, Maarten van Dinther, Titia K Sixma, Huizhe Huang, Long Zhang, Peter Ten Dijke
SMAD4 is a common intracellular effector for TGF-β family cytokines, but the mechanism by which its activity is dynamically regulated is unclear. We demonstrated that ubiquitin-specific protease (USP) 4 strongly induces activin/BMP signaling by removing the inhibitory monoubiquitination from SMAD4. This modification was triggered by the recruitment of the E3 ligase, SMURF2, to SMAD4 following ligand-induced regulatory (R)-SMAD-SMAD4 complex formation. Whereas the interaction of the negative regulator c-SKI inhibits SMAD4 monoubiquitination, the ligand stimulates the recruitment of SMURF2 to the c-SKI-SMAD2 complex and triggers c-SKI ubiquitination and degradation...
May 3, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28466868/a-sequential-emt-met-mechanism-drives-the-differentiation-of-human-embryonic-stem-cells-towards-hepatocytes
#15
Qiuhong Li, Andrew P Hutchins, Yong Chen, Shengbiao Li, Yongli Shan, Baojian Liao, Dejin Zheng, Xi Shi, Yinxiong Li, Wai-Yee Chan, Guangjin Pan, Shicheng Wei, Xiaodong Shu, Duanqing Pei
Reprogramming has been shown to involve EMT-MET; however, its role in cell differentiation is unclear. We report here that in vitro differentiation of hESCs to hepatic lineage undergoes a sequential EMT-MET with an obligatory intermediate mesenchymal phase. Gene expression analysis reveals that Activin A-induced formation of definitive endoderm (DE) accompanies a synchronous EMT mediated by autocrine TGFβ signalling followed by a MET process. Pharmacological inhibition of TGFβ signalling blocks the EMT as well as DE formation...
May 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28466843/the-careg-element-reveals-a-common-regulation-of-regeneration-in-the-zebrafish-myocardium-and-fin
#16
Catherine Pfefferli, Anna Jaźwińska
The existence of common mechanisms regulating organ regeneration is an intriguing concept. Here we report on a regulatory element that is transiently activated during heart and fin regeneration in zebrafish. This element contains a ctgfa upstream sequence, called careg, which is induced by TGFβ/Activin-β signalling in the peri-injury zone of the myocardium and the fin mesenchyme. In addition, this reporter demarcates a primordial cardiac layer and intraray osteoblasts. Using genetic fate mapping, we show the regenerative competence of careg-expressing cells...
May 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28466233/age-related-expression-of-tgf-beta-family-receptors-in-human-cumulus-oophorus-cells
#17
A Ribeiro, C Freitas, L Matos, A Gouveia, F Gomes, J L Silva Carvalho, H Almeida
PURPOSE: During ovarian follicle growth, local cellular interactions are essential for oocyte quality acquisition and successful fertilization. While cumulus cells (CCs) nurture oocytes, they also deliver oocyte-secreted factors (OSFs) that activate receptors on CCs. We hypothesized that disturbance of those interactions contributes to age-related lower reproductive success in women submitted to assisted reproductive technology treatments. METHODS: Women aged 27-48, without recognized personal reproductive disorder, were enrolled in the study and divided in <35- and ≥35-year-old groups...
May 2, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28464076/impact-of-a-timed-release-follicle-stimulating-hormone-treatment-from-one-to-three-months-of-age-on-endocrine-and-testicular-development-of-prepubertal-bulls
#18
B R Harstine, L H Cruppe, F M Abreu, M D Utt, R S Cipriano, A Lemes, C Premanandan, J M DeJarnette, M L Day
In prepubertal bulls, FSH facilitates testis maturation and a transient proliferation of Sertoli cells. Two experiments examined the effects of exogenous FSH on hormone secretion and testis development in Angus bulls. Exogenous FSH treatment consisted of an intramuscular injection (i.m.) of 30 mg FSH (Folltropin-V) in a 2% hyaluronic acid solution (FSH-HA). In Exp. 1, bulls (50 ± 6.5 d of age) received either FSH-HA ( = 5) or saline (control; = 5) on d 50 and 53.5. Blood samples were collected via jugular venipuncture to assess FSH concentrations every 6 h for 24 h after treatment and every 12 h until 84 h...
April 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28452368/activin-a-more-prominently-regulates-muscle-mass-in-primates-than-does-gdf8
#19
Esther Latres, Jason Mastaitis, Wen Fury, Lawrence Miloscio, Jesus Trejos, Jeffrey Pangilinan, Haruka Okamoto, Katie Cavino, Erqian Na, Angelos Papatheodorou, Tobias Willer, Yu Bai, Jee Hae Kim, Ashique Rafique, Stephen Jaspers, Trevor Stitt, Andrew J Murphy, George D Yancopoulos, Jesper Gromada
Growth and differentiation factor 8 (GDF8) is a TGF-β superfamily member, and negative regulator of skeletal muscle mass. GDF8 inhibition results in prominent muscle growth in mice, but less impressive hypertrophy in primates, including man. Broad TGF-β inhibition suggests another family member negatively regulates muscle mass, and its blockade enhances muscle growth seen with GDF8-specific inhibition. Here we show that activin A is the long-sought second negative muscle regulator. Activin A specific inhibition, on top of GDF8 inhibition, leads to pronounced muscle hypertrophy and force production in mice and monkeys...
April 28, 2017: Nature Communications
https://www.readbyqxmd.com/read/28443351/current-and-future-chemical-therapies-for-treating-anaemia-in-chronic-kidney-disease
#20
Francesco Locatelli, Lucia Del Vecchio, Maria Carmen Luise
Erythropoiesis-stimulating agents (ESAs) are not perfect, since they have potential side effects. Iron therapy is also receiving growing attention in recent years. Areas covered: We performed a literature search on PubMed using the following key words: anemia, chronic kidney disease, HIF stabilisers, sotatercept, actin traps, iron, iron-containing phosphate binders, iron dialysate. We reviewed new drugs that are under clinical development to obtain better safety and activity and/or easier and cheaper manufacturing processes in comparison to available ESAs...
June 2017: Expert Opinion on Pharmacotherapy
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