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Weifeng Yuan, Shaohua Hou, Hong Jia, Zhizhao Qiu, Tao Liu, Xinsheng Chen, Hongjun Li, Yanchen Sun, Lin Liang, Xiukun Sui, Xinghui Zhao, Zhanzhong Zhao
Gingivitis is evidenced by inflammation of the free gingiva, and still reversible. If left untreated, it may then progress to periodontitis. In the present study, the therapeutical effect of ketotifen fumarate on gingivitis was explored. Domestic cats with varying degrees of gingivitis naturally were enrolled in this study. Subgroups of animals were treated twice daily for one week with or without ketotifen fumarate (5 mg/kg). Effects of ketotifen fumarate were measured on gingival index, cells accumulation, mediators release, receptor-ligand interaction, oxidative stress, MAPK and NF-κB pathways, epithelial barrier and apoptosis...
October 10, 2018: International Immunopharmacology
Jingting Zhang, Tao Ruan, Tianyu Sheng, Jiongjiong Wang, Jing Sun, Jin Wang, Richard A Prinz, Daxin Peng, Xiufan Liu, Xiulong Xu
The non-structural protein 1 (NS1) of different influenza A virus (IAV) strains can differentially regulate the activity of c-Jun terminal kinase (JNK) and PI-3 kinase (PI3K). Whether varying JNK and PI3K activation impacts autophagy and IAV replication differently remains uncertain. Here we report that H5N1 (A/mallard/Huadong/S/2005) influenza A virus induced functional autophagy, as evidenced by increased LC3 lipidation and decreased p62 levels, and the presence of autolysosomes in chicken fibroblast cells...
October 10, 2018: Virology
Hauke Baumann, Magdalena Jahn, Alexander Muenchau, Michaela Trilck-Winkler, Katja Lohmann, Philip Seibler
Mutations in THAP1 (THAP domain-containing apoptosis-associated protein 1) cause a form of early-onset, isolated dystonia (DYT-THAP1, aka DYT6). Here, we describe the generation of eight human induced pluripotent stem cell (iPSC) lines of manifesting and non-manifesting carriers of the THAP1 mutations p.Lys158Asnfs*23 or p.Arg13His (each 4 lines). Dermal fibroblasts were reprogrammed using non-integrating Sendai virus. The iPSC lines were comprehensively characterized including expression analyses of pluripotency markers, the potential to differentiate into cells of all three germ layers, and stable karyotypes...
October 1, 2018: Stem Cell Research
Quentin Muller, Marie-Josée Beaudet, Thiéry De Serres-Bérard, Sabrina Bellenfant, Vincent Flacher, François Berthod
Cutaneous innervation is increasingly recognized as a major element of skin physiopathology through the neurogenic inflammation driven by neuropeptides that are sensed by endothelial cells and the immune system. To investigate this process in vitro, models of innervated tissue-engineered skin (TES) were developed, yet exclusively with murine sensory neurons extracted from dorsal root ganglions. In order to build a fully human model of innervated TES, we used induced pluripotent stem cells (iPSC) generated from human skin fibroblasts...
October 10, 2018: Acta Biomaterialia
Bruna Donida, Bárbara Tauffner, Marco Raabe, Maira F Immich, Marcelo A de Farias, Diego de Sá Coutinho, Andryele Zaffari Machado, Rejane Gus Kessler, Rodrigo V Portugal, Andressa Bernardi, Rudimar Frozza, Dinara J Moura, Fernanda Poletto, Carmen Regla Vargas
Lysosomal Storage Disorders (LSDs) are characterized by an abnormal accumulation of substrates within the lysosome and comprise more than 50 genetic disorders with a frequency of 1:5000 live births. Nanotechnology may be a promising way to circumvent the drawbacks of the current therapies for lysosomal diseases. The blood circulation time and bioavailability of the enzymes or drugs could be improved by inserting them in nanocarriers, which could decrease and/or avoid the need of frequent intravenous infusions along with the minimization or elimination of associated immunogenic responses...
October 10, 2018: European Journal of Pharmaceutics and Biopharmaceutics
Yilang Tang, Sonja Reissig, Elke Glasmacher, Tommy Regen, Florian Wanke, Alexei Nikolaev, Katharina Gerlach, Vanessa Popp, Khalad Karram, Massimo C Fantini, Jörn M Schattenberg, Peter R Galle, Markus F Neurath, Benno Weigmann, Florian C Kurschus, Nadine Hövelmeyer, Ari Waisman
BACKGROUND & AIMS: The CYLD lysine 63 deubiquitinase gene (CYLD) encodes tumor suppressor protein that is mutated in familial cylindromatosis, and variants have been associated with Crohn's disease (CD). Splice forms of CYLD that lack exons 7 and 8 regulate transcription factors and functions of immune cells. We examined expression of splice forms of CYLD in colon tissues from patients with CD and their effects in mice. METHODS: We performed immunohistochemical analyses of colon tissues from untreated patients with CD and patients without inflammatory bowel diseases (controls)...
October 10, 2018: Gastroenterology
Rachel J Jerrell, Mitchell J Leih, Aron Parekh
During the dermal wound healing process, the mechanical rigidity of the newly deposited extracellular matrix and transforming growth factor-β1 promote the transition of fibroblasts into myofibroblasts. Myofibroblasts generate large cellular forces that contract and remodel the extracellular matrix leading to scar formation. In contrast, myofibroblasts are not detected in fetal dermal wounds which are more compliant and contain less transforming growth factor-β1 than adult wounds. Instead, fetal fibroblasts orchestrate scarless healing of dermal wounds resulting in healed tissues that resemble uninjured dermis...
October 13, 2018: Wound Repair and Regeneration
Rogger P Carmen-Orozco, Danitza G Dávila-Villacorta, Yudith Cauna, Edson G Bernal-Teran, Leandra Bitterfeld, Graham L Sutherland, Nancy Chile, Rensson H Céliz, María C Ferrufino-Schmidt, Cesar M Gavídia, Charles R Sterling, Héctor H García, Robert H Gilman, Manuela Renee Verástegui
Neurocysticercosis (NCC) is a helminth infection affecting the central nervous system caused by the larval stage (cysticercus) of Taenia solium. Since vascular alteration and blood-brain barrier (BBB) disruption contribute to NCC pathology, it is postulated that angiogenesis could contribute to the pathology of this disease. This study used a rat model for NCC and evaluated the expression of two angiogenic factors called vascular endothelial growth factor (VEGF-A) and fibroblast growth factor (FGF2). Also, two markers for BBB disruption, the endothelial barrier antigen and immunoglobulin G, were evaluated using immunohistochemical and immunofluorescence techniques...
October 13, 2018: Journal of Neuroscience Research
Harikrishnareddy Paluvai, Eros Di Giorgio, Claudio Brancolini
Expression of the class IIa HDACs is frequently altered in different human cancers. In mouse models these transcriptional repressors can trigger transformation, acting as bona fide oncogenes. Whether class IIa HDACs also exhibit transforming activities in human cells is currently unknown. We infected primary human fibroblasts with retroviruses to investigate the transforming activity of HDAC4 in cooperation with well-known oncogenes. We have discovered that HDAC4-TM, a nuclear resident version of the deacetylase, triggers TP53 stabilization and OIS (Oncogene-induced senescence)...
October 13, 2018: Molecular Oncology
Ting Gong, Chi Zhang, Jing Kang, J J Lamb, Jack J Jiang
OBJECTIVES/HYPOTHESIS: Vocal fold scarring remains a major treatment challenge, and scar prevention without residual lesions remains a dilemma. Cryotherapy has shown cosmetic outcomes on skin lesions with minimal scarring. The aim of this study was to clarify the beneficial effects of cryotherapy for the prevention and the treatment of vocal fold scarring. STUDY DESIGN: In vitro. METHODS: Primary cultures of human vocal fold fibroblasts (VFFs) were used in this study...
October 12, 2018: Laryngoscope
Wei Tang, Ren Guo, Shi-Jun Shen, Yang Zheng, Yu-Ting Lu, Meng-Meng Jiang, Xue Cui, Ci-Zhong Jiang, Xin Xie
Human liver or hepatocyte transplantation is limited by a severe shortage of donor organs. Direct reprogramming of other adult cells into hepatic cells may offer a solution to this problem. In a previous study, we have generated hepatocyte-like cells from mouse fibroblasts using only one transcription factor (TF) plus a chemical cocktail. Here, we show that human urine-derived epithelial-like cells (hUCs) can also be transdifferentiated into human hepatocyte-like cells (hiHeps) using one TF (Foxa3, Hnf1α, or Hnf4α) plus the same chemical cocktail CRVPTD (C, CHIR99021; R, RepSox; V, VPA; P, Parnate; T, TTNPB; and D, Dznep)...
October 12, 2018: Acta Pharmacologica Sinica
Sharissa L Latham, Nadja Ehmke, Patrick Y A Reinke, Manuel H Taft, Dorothee Eicke, Theresia Reindl, Werner Stenzel, Michael J Lyons, Michael J Friez, Jennifer A Lee, Ramona Hecker, Michael C Frühwald, Kerstin Becker, Teresa M Neuhann, Denise Horn, Evelin Schrock, Indra Niehaus, Katharina Sarnow, Konrad Grützmann, Luzie Gawehn, Barbara Klink, Andreas Rump, Christine Chaponnier, Constanca Figueiredo, Ralf Knöfler, Dietmar J Manstein, Nataliya Di Donato
Germline mutations in the ubiquitously expressed ACTB, which encodes β-cytoplasmic actin (CYA), are almost exclusively associated with Baraitser-Winter Cerebrofrontofacial syndrome (BWCFF). Here, we report six patients with previously undescribed heterozygous variants clustered in the 3'-coding region of ACTB. Patients present with clinical features distinct from BWCFF, including mild developmental disability, microcephaly, and thrombocytopenia with platelet anisotropy. Using patient-derived fibroblasts, we demonstrate cohort specific changes to β-CYA filament populations, which include the enhanced recruitment of thrombocytopenia-associated actin binding proteins (ABPs)...
October 12, 2018: Nature Communications
Jie Duan, Xishi Liu, Honglin Wang, Sun-Wei Guo
RESEARCH QUESTION: Recent research has shown that endometriotic lesions are essentially wounds that undergo repeated tissue injury and repair, which results in epithelial-mesenchymal transition, fibroblast-to-myofibroblast transdifferentiation, smooth muscle metaplasia and ultimately fibrosis. Macrophages are a key regulator of tissue repair and fibrogenesis. But do macrophages also play a role in fibrogenesis of endometriosis, and, if yes, which subset of macrophages? DESIGN: To elucidate the role of macrophages in fibrogenesis of endometriosis, we conducted three experiments in mice...
September 2018: Reproductive Biomedicine Online
Jeannie Devereaux, Kulmira Nurgali, Dimitrios Kiatos, Samy Sakkal, Vasso Apostolopoulos
Platelet-rich plasma is an autologous and safe blood product containing a high concentration of platelets and leucocytes. Platelets, growth factors, leucocytes and plasma are fundamental fibroblast proliferation agents. Leucocytes' plasticity, reparative qualities, cross-talk between cells and capacity to orchestrate diverse outcomes are receiving considerable research attention. Fibroblasts are able to migrate and proliferate into the tissue surrounding a wound and subsequently deposit granulation tissue, which minimises scarring...
November 2018: Maturitas
Xionglin Chen, Xiaoming Cao, He Jiang, Xiangxin Che, Xiaoyuan Xu, Baicheng Ma, Jie Zhang, Tao Huang
: Skin wound healing is a complex and dynamic process that involves angiogenesis and growth factor secretion. Newly formed vessels can provide nutrition and oxygen for skin wound healing. Growth factors in skin wounds are important for keratinocytes and fibroblasts proliferation, epithelialization, extracellular matrix remodeling, and angiogenesis, which accelerate skin wound healing. Therefore, treatment strategies that enhance angiogenesis and growth factors secretion in skin wounds can accelerate skin wound healing...
October 11, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Soo Kim, Seul Ki Lee, Hyunjung Kim, Tae Min Kim
Induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) serve as a unique source for cell therapy. We investigated whether exosomes from iMSCs promote the proliferation of human keratinocytes (HaCaT) and human dermal fibroblasts (HDFs). iPSCs were established from human Wharton's jelly MSCs and were allowed to differentiate into iMSCs. Exosomes were collected from the culture supernatant of MSCs (MSC-exo) and iMSCs (iMSC-exo), and their characteristics were investigated. Both exosome types possessed basic characteristics of exosomes and were taken up by skin cells in vitro and in vivo...
October 11, 2018: International Journal of Molecular Sciences
Bullo Saifullah, Kalaivani Buskaran, Rabia Baby Shaikh, Farahnaz Barahuie, Sharida Fakurazi, Mohd Aris Mohd Moklas, Mohd Zobir Hussein
The treatment of cancer through chemotherapy is limited by its toxicity to healthy tissues and organs, and its inability to target the cancer site. In this study, we have designed an anticancer nanocomposite delivery system for protocatechuic acid (PCA) using graphene oxide⁻polyethylene glycol as the nanocarrier, and coated with folic acid (GO⁻PEG⁻PCA⁻FA) for targeting the cancer cells. The designed anticancer delivery system was found to show much better anticancer activity than the free drug PCA against liver cancer HEP-G2 cells and human colon cancer HT-29 cells; at same time, it was found to be less toxic to normal fibroblast 3T3 cells...
October 11, 2018: Nanomaterials
Dawei Lian, Linfeng Dai, Zhaoyu Xie, Xing Zhou, Xiaohong Liu, Yang Zhang, Yi Huang, Yang Chen
Inflammasomes serve as an intracellular machinery to initiate inflammatory response to various danger signals. However, the chronic periodontitis pathological relevance of this inflammasome activation, particularly in periodontal ligament fibroblasts, remains largely unknown. The present study demonstrated that Nlrp3 inflammasome components abundantly expressed in cultured mouse periodontal ligament fibroblasts (mPDLFs). In addition, our data demonstrated that P.g-LPS (Porphyromonas gingivalis Lipopolysaccharide), a major injurious factor during chronic periodontitis, could induce the mPDLFs migration dysfunction and the inhibition of Nlrp3 inflammasome by Isoliquiritigenin (ISO) markedly recovered the migration dysfunction in mPDLFs...
October 9, 2018: Molecular Immunology
Brittany E Jewell, Mo Liu, Linchao Lu, Ruoji Zhou, Jian Tu, Dandan Zhu, Zijun Huo, An Xu, Donghui Wang, Helen Mata, Weidong Jin, Weiya Xia, Pulivarthi H Rao, Ruiying Zhao, Mien-Chie Hung, Lisa L Wang, Dung-Fang Lee
The DNA helicase RECQL4 is known for its roles in DNA replication and repair. RECQL4 mutations cause several genetic disorders including Rothmund-Thomson syndrome (RTS), characterized by developmental defects and predisposition to osteosarcoma. Here we reprogrammed fibroblasts with a heterozygous RECQL4 mutation (c.1878 + 32_1878 + 55del24) to induced pluripotent stem cells (iPSCs). These iPSCs are pluripotent and are able to be differentiated into all three germ layers, providing a novel tool to further interrogate the role of RECQL4 DNA helicase in vitro...
October 2, 2018: Stem Cell Research
Zora Rukavina, Maja Šegvić Klarić, Jelena Filipović-Grčić, Jasmina Lovrić, Željka Vanić
Antibiotic delivery via liposomal encapsulation represents a promising approach for the efficient topical treatment of skin infections. The present study aimed to investigate the potential of using different types of azithromycin (AZT)-loaded liposomes to locally treat skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) strains. Conventional liposomes (CLs), deformable liposomes (DLs), propylene glycol-containing liposomes (PGLs) and cationic liposomes (CATLs) encapsulating AZT were prepared, and their physical characteristics, drug release profiles, ex vivo skin penetration/deposition abilities, in vitro anti-MRSA activities (planktonic bacteria and biofilm) and cell biocompatibilities were assessed...
October 9, 2018: International Journal of Pharmaceutics
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