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https://www.readbyqxmd.com/read/29239282/generation-of-human-induced-pluripotent-stem-cells-from-wolfram-syndrome-type-2-patients-bearing-the-c-103-1g-a-cisd2-mutation-for-disease-modeling
#1
Alberto La Spada, Aikaterini Ntai, Stefano Genovese, Maurizio Rondinelli, Pasquale De Blasio, Ida Biunno
Wolfram syndrome (WFS) is a rare autosomal premature aging syndrome that shows signs of diabetes mellitus (DM), optic atrophy (OA) and deafness in addition to central nervous system and endocrine complications. The frequent form of WFS, type 1 (WFS1), harbours causative mutations in the WFS1 gene, while the rare form or type 2 (WFS2), involves CISD2. Mutations in these two genes are recognized by a subset of variable clinical symptoms and a set of overlapping features. Here we report on the generation of stable human induced pluripotent stem cells (hiPSCs) derived from primary fibroblasts of a previously reported Italian family with CISD2 mutation (c...
December 14, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/29238989/nanoparticle-delivery-of-rna-based-therapeutics-to-alter-the-vocal-fold-tissue-response-to-injury
#2
Nao Hiwatashi, Iv Kraja, Peter A Benedict, Gregory R Dion, Renjie Bing, Bernard Rousseau, Milan R Amin, Danielle M Nalband, Kent Kirshenbaum, Ryan C Branski
OBJECTIVES/HYPOTHESIS: Our laboratory and others hypothesized that Smad3 is a principle mediator of the fibrotic phenotype in the vocal folds (VFs), and we further posited that alteration of Smad3 expression through short interfering (si)RNA holds therapeutic promise, yet delivery remains challenging. To address this issue, we employed a novel synthetic oligomer, lipitoid, complexed with siRNA to improve stability and cellular uptake with the goal of increased efficiency of RNA-based therapeutics...
December 14, 2017: Laryngoscope
https://www.readbyqxmd.com/read/29237438/effects-of-sesamin-on-primary-human-synovial-fibroblasts-and-sw982-cell-line-induced-by-tumor-necrosis-factor-alpha-as-a-synovitis-like-model
#3
Manatsanan Khansai, Thanyaluck Phitak, Jeerawan Klangjorhor, Sasimol Udomrak, Kanda Fanhchaksai, Peraphan Pothacharoen, Prachya Kongtawelert
BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic synovitis, cartilage degradation and bone deformities. Synovitis is the term for inflammation of the synovial membrane, an early stage of RA. The pathogenesis of the disease occurs through cytokine induction. The major cytokine that increases the severity of RA is TNF-α. Thus, inhibition of the TNF-α cascade is an effective way to diminish the progression of the disease. We are interested in investigating the difference between primary human synovial fibroblast (hSF) cells and SW982 as synovitis models induced by TNF-α and in monitoring their responses to sesamin as an anti-inflammatory phytochemical...
December 13, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29237381/targeting-fgfr-with-bgj398-in-breast-cancer-effect-on-tumor-growth-and-metastasis
#4
Ana Sahores, Maria May, Gonzalo Sequeira, Cynthia Fuentes, Britta Jacobsen, Claudia Lanari, Caroline Ana Lamb
BACKGROUND: Endocrine resistance and metastatic dissemination comprise major clinical challenges for breast cancer treatment. The fibroblast growth factor receptor family (FGFR) consists of four tyrosine kinase transmembrane receptors, involved in key biological processes. Genomic alterations in FGFR have been identified in advanced breast cancer and thus, FGFR are an attractive therapeutic target. However, the efficacy of FGFR inhibitors on in vivo tumor growth is still controversial...
December 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29237089/title-toll-like-receptor-3-l412f-polymorphism-promotes-a-persistent-clinical-phenotype-in-pulmonary-sarcoidosis
#5
Gordon Cooke, Ijaz Kamal, Monika Strengert, Emily Hams, Leona Mawhinney, Aisling Tynan, Ciaran O' Reilly, David N O' Dwyer, Steven L Kunkel, Ulla G Knaus, Denis C Shields, David R Moller, Andrew G Bowie, Padraic G Fallon, Cory M Hogaboam, Michelle E Armstrong, Seamas C Donnelly
Background: Sarcoidosis is a multisystemic disorder of unknown etiology, characterised by the presence of non-caseating granulomas in target organs. In ninety percent of cases, there is thoracic involvement. Fifty to seventy percent of pulmonary sarcoidosis patients will experience acute, self-limiting disease. For the subgroup of patients who develop persistent disease, no targeted therapy is currently available. Aim: To investigate the potential of the single nucleotide polymorphism (SNP), Toll-like receptor 3 Leu412Phe (TLR3 L412F; rs3775291), as a causative factor in the development of, and in disease persistence in pulmonary sarcoidosis...
December 11, 2017: QJM: Monthly Journal of the Association of Physicians
https://www.readbyqxmd.com/read/29235573/constitutively-elevated-levels-of-socs1-suppress-innate-responses-in-df-1-immortalised-chicken-fibroblast-cells
#6
E S Giotis, C S Ross, R C Robey, A Nohturfft, S Goodbourn, M A Skinner
The spontaneously immortalised DF-1 cell line is rapidly replacing its progenitor primary chicken embryo fibroblasts (CEFs) for studies on avian viruses such as avian influenza but no comprehensive study has as yet been reported comparing their innate immunity phenotypes. We conducted microarray analyses of DF-1 and CEFs, under both normal and stimulated conditions using chicken interferon-α (chIFN-α) and the attenuated infectious bursal disease virus vaccine strain PBG98. We found that DF-1 have an attenuated innate response compared to CEFs...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29235191/the-effect-of-cyanidin-3-o-glucoside-on-uva-induced-damage-in-human-dermal-fibroblasts
#7
Shi Wu, Yunfeng Hu, Zhen Li, Weibin Bai, Jiayi Zhao, Cuiqin Huang, Qin Li, Chongzhu Fan, Liehua Deng, Daxiang Lu
BACKGROUND/PURPOSE: Ultraviolet-A (UVA) radiation can induce photoaging and skin cancer, but means to prevent or treat UVA-induced skin damage require further study. We investigated the effects of cyanidin-3-o-glucoside (C3G), a monomer of anthocyanin, on UVA-induced damage in primary human dermal fibroblasts (HDFs), and we identify possible mechanisms underlying the protective effects of this compound. METHODS: Primary HDFs were pretreated with 80 μM C3G for 2 h and UVA irradiated at 12 J/cm2 ...
December 13, 2017: Photodermatology, Photoimmunology & Photomedicine
https://www.readbyqxmd.com/read/29234096/transit-and-integration-of-extracellular-mitochondria-in-human-heart-cells
#8
Douglas B Cowan, Rouan Yao, Jerusha K Thedsanamoorthy, David Zurakowski, Pedro J Del Nido, James D McCully
Tissue ischemia adversely affects the function of mitochondria, which results in impairment of oxidative phosphorylation and compromised recovery of the affected organ. The impact of ischemia on mitochondrial function has been extensively studied in the heart because of the morbidity and mortality associated with injury to this organ. As conventional methods to preserve cardiac cell viability and contractile function following ischemia are limited in their efficacy, we developed a unique approach to protect the heart by transplanting respiration-competent mitochondria to the injured region...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29231289/a-cell-friendly-window-for-the-interaction-of-cells-with-hyaluronic-acid-poly-l-lysine-multilayers
#9
Narayanan Madaboosi, Katja Uhlig, Stephan Schmidt, Anna S Vikulina, Helmuth Möhwald, Claus Duschl, Dmitry Volodkin
Polyelectrolyte multilayers assembled from hyaluronic acid (HA) and poly-l-lysine (PLL) are most widely studied showing excellent reservoir characteristics to host molecules of diverse nature; however, thick (HA/PLL)n films are often found cell repellent. By a systematic study of the adhesion and proliferation of various cells as a function of bilayer number "n" a correlation with the mechanical and chemical properties of films is developed. The following cell lines have been studied: mouse 3T3 and L929 fibroblasts, human foreskin primary fibroblasts VH-Fib, human embryonic kidney HEK-293, human bone cell line U-2-OS, Chinese hamster ovary CHO-K and mouse embryonic stem cells...
December 12, 2017: Macromolecular Bioscience
https://www.readbyqxmd.com/read/29230065/the-toll-like-receptor-2-6-agonist-fsl-1-lipopeptide-therapeutically-mitigates-acute-radiation-syndrome
#10
Cathryn J Kurkjian, Hao Guo, Nathan D Montgomery, Ning Cheng, Hong Yuan, Joseph R Merrill, Gregory D Sempowski, W June Brickey, Jenny P-Y Ting
Risks of radiation exposure from nuclear incidents and cancer radiotherapy are undeniable realities. These dangers urgently compel the development of agents for ameliorating radiation-induced injuries. Biologic pathways mediated by myeloid differentiation primary response gene 88 (MyD88), the common adaptor for toll-like receptor (TLR) and Interleukin-1 receptor signaling, are critical for radioprotection. Treating with agonists prior to radiation enhances survival by activating TLR signaling, whereas radiomitigating TLR-activating therapeutics given after exposure are less defined...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29229270/intratracheal-instillation-of-alveolar-type-ii-cells-enhances-recovery-from-acute-lung-injury-in-rats
#11
Raquel Guillamat-Prats, Ferranda Puig, Marta Camprubí-Rimblas, Raquel Herrero, Anna Serrano-Mollar, Maria Nieves Gómez, Jessica Tijero, Michael A Matthay, Lluís Blanch, Antonio Artigas
BACKGROUND: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by excess production of inflammatory factors. Alveolar type II (ATII) cells help repair damaged lung tissue, rapidly proliferating and differentiating into alveolar type I cells after epithelial cell injury. In ALI, the lack of viable ATII favors progression to more severe lung injury. ATII cells regulate the immune response by synthesizing surfactant and other anti-inflammatory proteins and lipids...
November 8, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/29228832/nadph-oxidase-4-mediates-ros-production-in-radiation-induced-senescent-cells-and-promotes-migration-of-inflammatory-cells
#12
Yuri Sakai, Tohru Yamamori, Yoji Yoshikawa, Tomoki Bo, Motofumi Suzuki, Kumiko Yamamoto, Tetsuro Ago, Osamu Inanami
Excessive DNA damage induced by ionizing radiation (IR) to normal tissue cells is known to trigger cellular senescence, a process termed stress-induced premature senescence (SIPS). SIPS is often accompanied by the production of reactive oxygen species (ROS), and this is reported to be important for the initiation and maintenance of SIPS. However, the source of ROS during SIPS after IR and their significance in radiation-induced normal tissue damage remain elusive. In the present study, we tested the hypothesis that the NADPH oxidase (NOX) family of proteins mediates ROS production in SIPS-induced cells after IR and plays a role in SIPS-associated biological events...
December 12, 2017: Free Radical Research
https://www.readbyqxmd.com/read/29226265/st2-gene-products-critically-contribute-to-cellular-transformation-caused-by-an-oncogenic-ras-mutant
#13
Kenji Tago, Satoshi Ohta, Masaki Kashiwada, Megumi Funakoshi-Tago, Jitsuhiro Matsugi, Shin-Ichi Tominaga, Ken Yanagisawa
The ST2 gene was originally identified as a primary responsive gene, and the expressions of its gene products are induced by stimulation with growth factors and by oncogenic stresses. In this study, we observed that oncogenic Ras mutant induced the expression of ST2 and ST2L proteins. Interestingly, the enforced expression of ST2 gene products in NIH-3T3 murine fibroblasts remarkably enhanced Ras (G12V)-induced cellular transformation. Furthermore, when the expression of ST2 gene products was silenced by RNA-interference technique, Ras (G12V)-induced cellular transformation was drastically suppressed...
October 2017: Heliyon
https://www.readbyqxmd.com/read/29223023/live-cell-imaging-reveals-different-modes-of-cytotoxic-action-of-extracts-derived-from-commonly-used-luting-cements
#14
Rita Trumpaitė-Vanagienė, Alina Čebatariūnienė, Virginijus Tunaitis, Alina Pūrienė, Augustas Pivoriūnas
OBJECTIVE: To compare cytotoxicity of extracts derived from commonly used luting cements: Hoffmann's Zinc Phosphate (ZPC), GC Fuji Plus Resin Modified Glass Ionomer (RMGIC) and 3M ESPE RelyX Unicem Resin Cement (RC) on primary human gingival fibroblasts (HGFs). DESIGN: HGFs were exposed to different concentrations of the ZPC, RMGIC and RC extracts. The cytotoxicity was assessed with the PrestoBlue Cell Viability Reagent and viable cells were counted by a haemocytometer using the trypan blue exclusion test...
November 27, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/29222466/deciphering-transcriptional-regulation-in-human-embryonic-stem-cells-specified-towards-a-trophoblast-fate
#15
Ashish Jain, Toshihiko Ezashi, R Michael Roberts, Geetu Tuteja
Differentiated human embryonic stem cells (hESC) continue to provide a model for studying early trophoblast cells (TB), but many questions have been raised regarding their true identity. Therefore, we carried out a global and unbiased analysis on previously published transcriptomic profiles for hESC differentiated to TB by means of bone morphogenetic protein-4 and inhibitors of activin A and fibroblast growth factor-2 signaling (BAP treatment). Our results confirm that BAP treated hESC (ESCd) lack a mesoderm signature and are a subtype of placental cells unlike those present at term...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29222115/the-methyltransferase-set9-regulates-tgf-b-1-activation-of-renal-fibroblasts-via-interaction-with-smad3
#16
Victoria G Shuttleworth, Luke Gaughan, Lotfia Nawafa, Caitlin A Mooney, Steven L Cobb, Neil S Sheerin, Ian R Logan
Chronic kidney disease (CKD) is a global socioeconomic problem. It is characterised by the presence of differentiated myofibroblasts that, in response to TGF B-1, produce tissue fibrosis, leading to renal failure. Here we define a novel interaction between the SET9 lysine methyltransferase and SMAD3, the principle mediator of TGF B-1 signalling in myofibroblasts. We show that SET9 deficient fibroblasts exhibit globally altered gene expression profiles in response to TGF B-1, whilst overexpression of SET9 enhances SMAD3 transcriptional activity...
December 8, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29221952/danshensu-prevents-hypoxic-pulmonary-hypertension-in-rats-by-inhibiting-the-proliferation-of-pulmonary-artery-smooth-muscle-cells-via-tgf-%C3%AE-smad3-associated-pathway
#17
Ning Zhang, Mingqing Dong, Ying Luo, Feng Zhao, Yongjun Li
Hypoxic pulmonary hypertension is characterized by the remodeling of pulmonary artery. Previously we showed that tanshinone IIA, one lipid-soluble component from the Chinese herb Danshen, ameliorated hypoxic pulmonary hypertension by inhibiting pulmonary artery remodeling. Here we explored the effects of danshensu, one water-soluble component of Danshen, on hypoxic pulmonary hypertension and its mechanism. Rats were exposed to hypobaric hypoxia for 4 weeks to develop hypoxic pulmonary hypertension along with administration of danshensu...
December 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29221185/tgf%C3%AE-1-in-fibroblasts-derived-exosomes-promotes-epithelial-mesenchymal-transition-of-ovarian-cancer-cells
#18
Wenqian Li, Xiaoxue Zhang, Ji Wang, Mengchen Li, Canhui Cao, Jiahong Tan, Ding Ma, Qinglei Gao
Cancer-associated fibroblasts (CAF), a major component of the tumor microenvironment, play an important role in interacting with neoplastic cells to promote ovarian cancer progression. Exosomes are nano-sized vesicles that mediate the cross-talk between different cell types. An increasing number of studies have focused on the fact that tumor cell-derived exosomes influence stromal cells. However, the mechanism by which CAF-derived exosomes modulate cancer cells in ovarian cancer remains obscure. To investigate the role of CAF exosomes in ovarian cancer, we examined the exosomal content of paired primary, metastatic and normal fibroblasts from seven stage IIIC ovarian cancer patients by ELISA...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29221122/checkpoint-kinase-1-inhibition-sensitises-transformed-cells-to-dihydroorotate-dehydrogenase-inhibition
#19
Stéphanie Arnould, Geneviève Rodier, Gisèle Matar, Charles Vincent, Nelly Pirot, Yoann Delorme, Charlène Berthet, Yoan Buscail, Jean Yohan Noël, Simon Lachambre, Marta Jarlier, Florence Bernex, Hélène Delpech, Pierre Olivier Vidalain, Yves L Janin, Charles Theillet, Claude Sardet
Reduction in nucleotide pools through the inhibition of mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) has been demonstrated to effectively reduce cancer cell proliferation and tumour growth. The current study sought to investigate whether this antiproliferative effect could be enhanced by combining Chk1 kinase inhibition. The pharmacological activity of DHODH inhibitor teriflunomide was more selective towards transformed mouse embryonic fibroblasts than their primary or immortalised counterparts, and this effect was amplified when cells were subsequently exposed to PF477736 Chk1 inhibitor...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29218493/direct-biological-effects-of-fractional-ultrapulsed-co2-laser-irradiation-on-keratinocytes-and-fibroblasts-in-human-organotypic-full-thickness-3d-skin-models
#20
L Schmitt, S Huth, P M Amann, Y Marquardt, R Heise, K Fietkau, L Huth, T Steiner, F Hölzle, J M Baron
Molecular effects of various ablative and non-ablative laser treatments on human skin cells-especially primary effects on epidermal keratinocytes and dermal fibroblasts-are not yet fully understood. We present the first study addressing molecular effects of fractional non-sequential ultrapulsed CO2 laser treatment using a 3D skin model that allows standardized investigations of time-dependent molecular changes ex vivo. While histological examination was performed to assess morphological changes, we utilized gene expression profiling using microarray and qRT-PCR analyses to identify molecular effects of laser treatment...
December 7, 2017: Lasers in Medical Science
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