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Marco Tucci, Stefania Stucci, Anna Passarelli, Stella D'Oronzo, Franco Silvestris
Interleukin-17A (IL-17A) promotes the osteoclast (OC)-like differentiation of dendritic cells (DCs) in multiple myeloma (MM), and contributes to the pathogenesis of myeloma bone disease (MBD). In our study, EVR significantly abrogated the in vitro OC-like activity of DCs from 12 MM patients. Exploring the EVR effects, we found that the inhibition of the osteo-erosive activity of OC-DCs was mostly due to the blockade of signals driven by the IL-17A receptor toward CEBPbeta/MAFB axis Therefore, MM patients with MBD would probably benefit from mTOR inhibition...
October 17, 2016: Experimental Hematology
Cheng-Chao Ruan, Yan Li, Yu Ma, Ding-Liang Zhu, Ping-Jin Gao
OBJECTIVE: Previous studies have indicated that adiponectin (APN) protects against hypertension-related cardiovascular disease. However, whether APN is involved in the regulation of hypertensive renal damage remains unclear. The present study aimed to elucidate how APN regulates renal epithelial to mesenchymal transdifferentiation (EMT) in desoxycorticosterone (DOCA)-salt hypertensive mice. DESIGN AND METHOD: Male APN knockout (APNKO) mice and wild-type (WT) C57BL/6 littermates were sc infused with DOCA pellet (50 mg for 21 day release)...
September 2016: Journal of Hypertension
Alberto Avolio
Blood vessels function as conduits for distribution of blood throughout the circulatory system. Large arteries, in addition to the essential conduit function, also serve to dampen the effect of pulsatile ventricular ejection that generates pulsatile pressure with each cardiac cycle; that is, they exhibit a 'cushion' function. The conduit function can be compromised by intimal effects that cause obstruction to flow, generally attributed to plaque formation due to intimal changes affected by atherosclerotic processes...
September 2016: Journal of Hypertension
Renjing Liu, Kun-Yong Kim, Yong-Wook Jung, In-Hyun Park
DNA methylation is an important epigenetic mark that regulates gene expression. Dnmt1 plays an important role in maintaining DNA methylation patterns on daughter DNA strands. Studies have shed light into the functional role of Dnmt1 regulation in the hematopoietic and epidermal systems. Here we show that Dnmt1 is required for myogenesis. Loss of Dnmt1 results in reduced expression of myogenic genes and defects in myogenic differentiation. We have utilized a conditional knockout mouse approach to examine the functional consequences of Dnmt1 depletion specifically in the developing muscle...
October 18, 2016: Scientific Reports
Maggie L Diller, Ragini R Kudchadkar, Keith A Delman, David H Lawson, Mandy L Ford
Th17 cells represent a distinct subset of CD4 effector T cells with potent pathogenic qualities, capable of directly mediating tumor cell destruction. IL-2 has frequently been shown to have a negative effect on Th17 differentiation while supporting regulatory T-cell (FoxP3CD4, TREG) growth and development in both in vitro models and in vivo animal models. We investigated the effect of in vivo IL-2 on both the Th17 and FoxP3CD4 T-cell compartments in a human model of cancer. High-dose IL-2 (HDIL-2) was administered at a dose of 720,000 IU/kg to patients with melanoma (n=7) and peripheral blood was collected at baseline and at 24, 48, 72, and 96 hours posttreatment...
November 2016: Journal of Immunotherapy
Sophie Guelfi, Hugues Duffau, Luc Bauchet, Bernard Rothhut, Jean-Philippe Hugnot
Glioblastomas are devastating and extensively vascularized brain tumors from which glioblastoma stem-like cells (GSCs) have been isolated by many groups. These cells have a high tumorigenic potential and the capacity to generate heterogeneous phenotypes. There is growing evidence to support the possibility that these cells are derived from the accumulation of mutations in adult neural stem cells (NSCs) as well as in oligodendrocyte progenitors. It was recently reported that GSCs could transdifferentiate into endothelial-like and pericyte-like cells both in vitro and in vivo, notably under the influence of Notch and TGFβ signaling pathways...
2016: Stem Cells International
Uma S Kamaraj, Julian Gough, Jose M Polo, Enrico Petretto, Owen J L Rackham
Directed cell conversion (or transdifferentiation) of one somatic cell-type to another can be achieved by ectopic expression of a set of transcription factors. Since the experimental identification of transcription factors for transdifferentiation is extremely time-consuming and expensive, there are still relatively few transdifferentiations achieved in comparison to the number of human cell-types. However, the growing volume of transcriptional data available and the recent introduction of data-driven algorithmic approaches that predict factors for transdifferentiation holds great promise for accelerating this field...
October 13, 2016: Cell Cycle
Julian Pulecio, Oriol Alejo-Valle, Sandra Capellera-Garcia, Marianna Vitaloni, Paula Rio, Eva Mejía-Ramírez, Ilaria Caserta, Juan A Bueren, Johan Flygare, Angel Raya
Current sources of platelets for transfusion are insufficient and associated with risk of alloimmunization and blood-borne infection. These limitations could be addressed by the generation of autologous megakaryocytes (MKs) derived in vitro from somatic cells with the ability to engraft and differentiate in vivo. Here, we show that overexpression of a defined set of six transcription factors efficiently converts mouse and human fibroblasts into MK-like progenitors. The transdifferentiated cells are CD41(+), display polylobulated nuclei, have ploidies higher than 4N, form MK colonies, and give rise to platelets in vitro...
October 11, 2016: Cell Reports
Michael Ibrahim, Pavan Atluri
No abstract text is available yet for this article.
September 16, 2016: Journal of Thoracic and Cardiovascular Surgery
Jens Geginat, Moira Paroni, Ilko Kastirr, Paola Larghi, Massimiliano Pagani, Sergio Abrignani
Th17 cells are a heterogeneous population of pro-inflammatory T cells that have been shown to mediate immune responses against intestinal bacteria. Th17 cells are highly plastic and can transdifferentiate to Th1/17 cells or unconventional Th1 cells, which are highly pathogenic in animal models of immune-mediated diseases such as inflammatory bowel diseases. A recent European Journal of Immunology article by Liu et al. (Eur. J. Immunol. 2015. 45:1010-1018) showed, surprisingly, that Th1 cells have a similar plasticity, and could transdifferentiate to Th17 cells...
October 2016: European Journal of Immunology
Bo Zhu, Yumei Chen, Xiaolu Shen, Xishi Liu, Sun-Wei Guo
BACKGROUND: Recently emerging evidence indicates that endometriotic lesions are wounds undergoing repeated tissue injury and repair (ReTIAR), and platelets induce epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT), leading ultimately to fibrosis. Due to the commonality of cyclic bleeding as in endometriosis, adenomyotic lesions are also wounds that undergo ReTIAR, and we have recently provided evidence corroborating platelet-induced EMT, FMT and fibrogenesis in adenomyosis...
October 10, 2016: Reproductive Biology and Endocrinology: RB&E
Hang Zhao, Zhiying He, Dandan Huang, Jun Gao, Yanfang Gong, Hongyu Wu, Aifang Xu, Xiangjun Meng, Zhaoshen Li
Background & Aims. Severe acute pancreatitis (SAP) remains a high-mortality disease. Bone marrow (BM) mesenchymal stem cells (MSCs) have been demonstrated to have plasticity of transdifferentiation and to have immunomodulatory functions. In the present study, we assessed the roles of MSCs in SAP and the therapeutic effects of MSC on SAP after transplantation. Methods. A pancreatitis rat model was induced by the injection of taurocholic acid (TCA) into the pancreatic duct. After isolation and characterization of MSC from BM, MSC transplantation was conducted 24 hrs after SAP induction by tail vein injection...
2016: Stem Cells International
Misty R Riddle, Erik A Spickard, Angela Jevince, Ken C Q Nguyen, David H Hall, Pradeep M Joshi, Joel H Rothman
The differentiated cell identities and structure of fully formed organs are generally stable after their development. In contrast, we report here that development of the C. elegans proximal somatic gonad (hermaphrodite uterus and spermathecae, and male vas deferens) can be redirected into intestine-like organs by brief expression of the ELT-7 GATA transcription factor. This process converts one developing organ into another and can hence be considered "transorganogenesis." We show that, following pulsed ELT-7 expression, cells of the uterus activate and maintain intestine-specific gene expression and are transformed at the ultrastructural level to form an epithelial tube resembling the normal intestine formed during embryogenesis...
October 4, 2016: Developmental Biology
Krishna C Vadodaria, Maria C Marchetto, Jerome Mertens, Fred H Gage
Technologies for deriving human neurons in vitro have transformed our ability to study cellular and molecular components of human neurotransmission. Three groups, including our own, have recently published methods for efficiently generating human serotonergic neurons in vitro. Remarkably, serotonergic neurons derived from each method robustly produce serotonin, express raphe genes, are electrically active, and respond to selective serotonin reuptake inhibitors in vitro. Two of the methods utilize transdifferentiation technology by overexpressing key serotonergic transcription factors...
September 22, 2016: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
Harun Najib Noristani, Jean Charles Sabourin, Hassan Boukhaddaoui, Emilie Chan-Seng, Yannick Nicolas Gerber, Florence Evelyne Perrin
BACKGROUND: Neurons have intrinsic capability to regenerate after lesion, though not spontaneously. Spinal cord injury (SCI) causes permanent neurological impairments partly due to formation of a glial scar that is composed of astrocytes and microglia. Astrocytes play both beneficial and detrimental roles on axonal re-growth, however, their precise role after SCI is currently under debate. METHODS: We analyzed molecular changes in astrocytes at multiple stages after two SCI severities using cell-specific transcriptomic analyses...
October 6, 2016: Molecular Neurodegeneration
Christian Freise, Nadja Kretzschmar, Uwe Querfeld
BACKGROUND: Vascular calcifications such as arteriosclerosis, which is characterized by a calcificiation of the tunica media, represent major comorbidities e.g. in patients with chronic kidney disease (CKD). An essential step during the development of arteriosclerosis is the transdifferentiation/calcification of vascular smooth muscle cells (VSMC) resembling osteogenesis. The matrix metalloproteinases (MMP)-2 and -9 were shown to promote these VSMC calcifications and their inhibition is of therapeutic value to prevent arteriosclerosis in preclinical studies...
September 30, 2016: BMC Cardiovascular Disorders
Katharina Koch, Rudolf Hartmann, Friederike Schröter, Abigail Kora Suwala, Donata Maciaczyk, Andrea Caroline Krüger, Dieter Willbold, Ulf Dietrich Kahlert, Jaroslaw Maciaczyk
Glioblastoma (GBM) is the most malignant brain tumor with very limited therapeutic options. Standard multimodal treatments, including surgical resection and combined radio-chemotherapy do not target the most aggressive subtype of glioma cells, brain tumor stem cells (BTSCs). BTSCs are thought to be responsible for tumor initiation, progression, and relapse. Furthermore, they have been associated with the expression of mesenchymal features as a result of epithelial-mesenchymal transition (EMT) thereby inducing tumor dissemination and chemo resistance...
September 29, 2016: Oncotarget
Pablo H Cutini, María B Rauschemberger, Marisa J Sandoval, Virginia L Massheimer
In this work we investigate whether, despite the procalcific action of alendronate on bone, the drug would be able to regulate in vitro the main cellular events that take part in atherosclerotic lesion generation. Using endothelial cell cultures we showed that Alendronate (1-50μM) acutely enhances nitric oxide production (10-30min). This stimulatory action of the bisphosphonate involves the participation of MAPK signaling transduction pathway. Under inflammatory stress, the drug reduces monocytes and platelets interactions with endothelial cells induced by lipopolysaccharide...
October 2, 2016: Journal of Molecular and Cellular Cardiology
Atsuko Tanaka, Yoichiro Hoshino, Chikako Nagasato, Taizo Motomura
Tissue wounds are mainly caused by herbivory, which is a serious threat for macro-algae, and brown algae are known to regenerate branches or buds in response to wounding. In the present paper, we describe a branch regeneration system, induced by sever damage, in the brown alga Dictyota dichotoma. Segmentations of juvenile thalli induced branch regenerations unless explants possessed apical cells. Apical excisions in distinct positions elucidated that disruption of an apical cell or disconnection of tissue with an apical cell triggered the branch regeneration...
October 4, 2016: Protoplasma
Evgeny Kushnerev, Susan G Shawcross, Shankari Sothirachagan, Fiona Carley, Arun Brahma, Julian M Yates, M Chantal Hillarby
Purpose: The corneal epithelium is sloughed off surface of the eye by the action of blinking and is continually replaced by division and maturation of the limbal stem cells (LSCs). In the case of injury or disease, LSCs can be lost or damaged to a point at which the corneal epithelial layer is no longer maintained. leading to LSC deficiencies (LSCDs). When this occurs, the opaque conjunctiva overgrows the anterior surface of the eye, leading to vision impairment or loss. Dental pulp stem cells (DPSCs) are promising candidates as autologous LSC substitutes...
October 1, 2016: Investigative Ophthalmology & Visual Science
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