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Qingqing Wei, Ruiqi Li, Liang Zhong, Haiyuan Mu, Shaopeng Zhang, Liang Yue, Jinzhu Xiang, Enhong Li, Minglei Zhi, Suying Cao, Jianyong Han
After zygotic genome activation and lineage specification, zygotes develop into late blastocysts comprising three distinct cell types. The molecular mechanisms underlying this progress are largely unknown in pigs. Here, we intended to analyze an extensive set of regulators at the single-cell level to define the events involved in the development of the porcine blastocysts. Using a quantitative microfluidics approach in single cells, we detected mRNA levels of 96 genes known to function in early embryonic development and maintenance of stem cell pluripotency simultaneously in 480 individual cells derived from porcine preimplantation embryos...
March 13, 2018: Biology of Reproduction
Yu Wu, Ze-Yang Ding, Guan-Nan Jin, Yi-Xiao Xiong, Bin Yu, Yi-Min Sun, Wei Wang, Hui-Fang Liang, Bixiang Zhang, Xiao-Ping Chen
Hepatic progenitor cells (HPCs) are a subpopulation of cells which was usually expanded in chronic liver injury and are contributed to liver regeneration through differentiating into hepatocytes and cholangiocytes. Epithelial-mesenchymal transition is a dynamic process which is important for the progression of liver fibrosis and cancer initiation. This study demonstrated that LE/6 and WB-F344 cells, both of which were HPC derived cell lines, were undergoing partial epithelial-mesenchymal transition states, which was indicated by the co-expression of epithelial markers (E-cadherin and zona occludin 1), and mesenchymal markers (vimentin, fibronectin, collagen 1and α-SMA)...
March 12, 2018: Biochimie
Vu Huy Luong, Takenao Chino, Noritaka Oyama, Takashi Matsushita, Yoko Sasaki, Dai Ogura, Shin-Ichiro Niwa, Tanima Biswas, Akiyuki Hamasaki, Mikako Fujita, Yoshinari Okamoto, Masami Otsuka, Hironobu Ihn, Minoru Hasegawa
BACKGROUND: Transforming growth factor-β (TGF-β)/Smad signaling is well known to play a critical role in the pathogenesis of systemic sclerosis (SSc). We previously developed an artificial molecule, the histidine-pyridine-histidine ligand derivative HPH-15, which may have an antifibrotic effect. The purpose of the present study was to clarify the effects of this drug in human skin fibroblasts and in a preclinical model of SSc. METHODS: The effects of HPH-15 on expression of extracellular matrix components and TGF-β signaling in human dermal fibroblasts were analyzed...
March 15, 2018: Arthritis Research & Therapy
Liang Liang, Ming Zeng, Haixia Pan, Hao Liu, Yangke He
Previous studies have demonstrated that nicotinamide N-methyltransferase (NNMT) is aberrantly expressed in a number of tumors. In the present study, it was demonstrated that the gene and protein levels of NNMT were significantly increased in gastric cancer cells. Furthermore, upregulation of NNMT significantly increased the expression of mesenchymal markers, including α-smooth muscle actin (SMA), vimentin and fibronectin, but decreased the levels of epithelial cadherin. Since transforming growth factor (TGF)-β1 may serve a key function in epithelial-mesenchymal transition (EMT), the effects of NNMT on the expression of TGF-β1 were investigated in BGC-823 cells...
April 2018: Oncology Letters
Verity A Jackson, Dimphna H Meijer, Maria Carrasquero, Laura S van Bezouwen, Edward D Lowe, Colin Kleanthous, Bert J C Janssen, Elena Seiradake
Teneurins are ancient cell-cell adhesion receptors that are vital for brain development and synapse organisation. They originated in early metazoan evolution through a horizontal gene transfer event when a bacterial YD-repeat toxin fused to a eukaryotic receptor. We present X-ray crystallography and cryo-EM structures of two Teneurins, revealing a ~200 kDa extracellular super-fold in which eight sub-domains form an intricate structure centred on a spiralling YD-repeat shell. An alternatively spliced loop, which is implicated in homophilic Teneurin interaction and specificity, is exposed and thus poised for interaction...
March 14, 2018: Nature Communications
Gwen K Healey, William Alexander Macdonald, Stefan Grzybowski, Robert Nevin, Jude Kornelsen, William E Hogg
OBJECTIVE: To investigate whether the fetal fibronectin assay would be useful for determining if a woman was close to a term delivery. If effective, this test would allow parturient women to stay in their communities longer. DESIGN: This feasibility study used a prospective cohort design to examine the negative predictive value of the fetal fibronectin test at term. SETTING: Iqaluit, NU. PARTICIPANTS: A total of 30 parturient women from rural and isolated communities in Nunavut...
March 2018: Canadian Family Physician Médecin de Famille Canadien
Marianna Caterino, Miriam Zacchia, Michele Costanzo, Giuliana Bruno, Davide Arcaniolo, Francesco Trepiccione, Rosa Anna Siciliano, Maria Fiorella Mazzeo, Margherita Ruoppolo, Giovambattista Capasso
BACKGROUND: /Aims: Renal disease is a common cause of morbidity in patients with Bardet-Biedl syndrome (BBS), however the severity of kidney dysfunction is highly variable. To date, there is little information on the pathogenesis, the risk and predictor factors for poor renal outcome in this setting. The present study aims to analyze the spectrum of urinary proteins in BBS patients, in order to potentially identify 1) disease-specific proteomic profiles that may differentiate the patients from normal subjects; 2) urinary markers of renal dysfunction...
March 8, 2018: Kidney & Blood Pressure Research
Clifford M Csizmar, Jacob Petersburg, Alexander Hendricks, Lawrence A Stern, Benjamin J Hackel, Carston R Wagner
Membrane-engineered cells displaying antigen-targeting ligands are useful as both scientific tools and clinical therapeutics. While genetically-encoded artificial receptors have proven efficacious, their scope remains limited as this approach is not amenable to all cell types and the modification is often permanent. Our group has developed a non-genetic method to rapidly, stably, and reversibly modify any cell membrane with a chemically self-assembled nanoring (CSAN) that can function as a prosthetic receptor...
March 14, 2018: Bioconjugate Chemistry
Małgorzata Pupek, Dorota Krzyżanowska-Gołąb, Daniel Kotschy, Wojciech Witkiewicz, Wiesława Kwiatkowska, Maria Kotschy, Iwona Kątnik-Prastowska
Fibronectin (FN) may be involved in time- and stage-dependent and inter-related controlled processes of inflammation, coagulation, and wound healing accompanying peripheral arterial disease (PAD). In the present study, FN and FN-containing extra-domain A (EDA-FN), macromolecular FN-fibrin complexes, and FN monomer were analysed in the plasma of 142 PAD patients, including 37 patients with restenosis, for 37 months after revascularisation. FN concentration increased significantly in the plasma of PAD patients within 7 to 12 months after revascularisation, whereas the high concentration of EDA-FN was maintained up to 24 months, significantly higher in the group 7 to 12 months after revascularisation with recurrence of stenosis and lower in the PAD groups 1 to 3 months and 4 to 6 months after revascularisation with comorbid diabetes and ulceration, respectively...
March 13, 2018: International Wound Journal
Sunil S Adav, Jin Wei, Jingru Qian, Nicola Yi'An Gan, Leonard W L Yip, Siu Kwan Sze
PURPOSE: Primary angle-closure glaucoma (PACG) is associated with increased intraocular pressure, optic nerve damage, and progressive vision loss, but the molecular mechanism that underpins retinal ganglion neuropathy in PACG remains poorly understood. To better understand the pathogenesis of human PACG, we performed the first comprehensive proteomic analysis of aqueous humor (AH) samples from PACG patients and matched control donors to study pathogenic alteration in AH composition in disease...
March 13, 2018: International Ophthalmology
Fawaz Abomaray, Sebastian Gidlöf, Bartosz Bezubik, Mikael Engman, Cecilia Götherström
Endometriosis is an inflammatory disease marked by ectopic growth of endometrial cells. Mesenchymal stromal cells (MSC) have immunosuppressive properties that have been suggested as a treatment for inflammatory diseases. Therefore, the aim herein was to examine effects of allogeneic MSC on endometriosis-derived cells in vitro as a potential therapy for endometriosis. MSC from allogeneic adipose tissue (Ad-MSC) and stromal cells from endometrium (ESCendo ) and endometriotic ovarian cysts (ESCcyst ) from women with endometriosis were isolated...
2018: Stem Cells International
V Z Nezametdinova, D A Mavletova, M G Alekseeva, M S Chekalina, N V Zakharevich, V N Danilenko
The objective of this study was to determine for phosphorylated substrates of the species-specific serine-threonine protein kinase (STPK) Pkb2 from Bifidobacterium longum subsp. longum GT15. Two approaches were employed: analyses of phosphorylated membrane vesicles protein spectra following kinase reactions and analyses of the genes surrounding pkb2. A bioinformatics analysis of the genes surrounding pkb2 found a species-specific gene cluster PFNA in the genomes of 34 different bifidobacterial species. The identified cluster consisted of 5-8 genes depending on the species...
March 10, 2018: Anaerobe
T Tian, Z Hua, L Z Wang, X Y Wang, H Y Chen, Z H Liu, Z M Cui
Objective: To elucidate the impact of over-expression of S100A7 on migration, invasion, proliferation, cell cycle, and epithelial-mesenchymal transition (EMT) in human cervical cancer HeLa and CaSki cells. Methods: (1) Immunohistochemistry of SP was used to examine the expression of S100A7 in 40 cases of squamous cervical cancer tissues and 20 cases of normal cervical tissues. (2) The vectors of pLVX-IRES-Neo-S100A7 and pLVX-IRES-Neo were used to transfect human cervical cancer HeLa and CaSki cells, and the positive clones were screened and identified...
February 25, 2018: Zhonghua Fu Chan Ke za Zhi
Yan-Hua Xiao, Xiao-Yun He, Qing Han, Fan Yang, Su-Xian Zhou
Platelet-activating factor (PAF) promotes glomerular extracellular matrix (ECM) deposition, primarily through activation of the protein kinase C (PKC) pathway. The present study was designed to investigate whether atorvastatin, which mediates a protective effect against glomerular ECM deposition and diabetic neuropathy, may interfere with the PKC‑transforming growth factor‑β1 (TGF‑β1) pathway in a model of human mesangial cells (HMCs) exposed to a high glucose (HG) and lysophosphatidylcholine (LPC) environment...
March 9, 2018: Molecular Medicine Reports
Paola Occhetta, Giuseppe Isu, Marta Lemme, Chiara Conficconi, Philipp Oertle, Christian Räz, Roberta Visone, Giulia Cerino, Marija Plodinec, Marco Rasponi, Anna Marsano
In vitro cardiac models able to mimic the fibrotic process are paramount to develop an effective anti-fibrosis therapy that can regulate fibroblast behaviour upon myocardial injury. In previously developed in vitro models, typical fibrosis features were induced by using scar-like stiffness substrates and/or potent morphogen supplementation in monolayer cultures. In our model, we aimed to mimic in vitro a fibrosis-like environment by applying cyclic stretching of cardiac fibroblasts embedded in three-dimensional fibrin-hydrogels alone...
March 13, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
Dong Weng, Jian-Xia Chen, Hao-Hao Li, Feng Liu, Li-Dan Zhou, Hai-Peng Liu, Rui-Juan Zheng, Yan Jiang, Zhong-Hua Liu, Baoxue Ge
The epithelial-mesenchymal transition (EMT) is a multifunctional cell process involved in the pathogenesis of numerous conditions, including fibrosis and cancer. Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by fibroblast accumulation and collagen deposition in the lungs. The fibroblasts involved in this process partially originate from lung epithelial cells via the EMT. Evidence suggests that the EMT contributes to progression, invasion, and metastasis of various types of cancer...
December 2018: Cell Death Discovery
Francis D Gratte, Sara Pasic, John K Olynyk, George C T Yeoh, David Tosh, Deirdre R Coombe, Janina E E Tirnitz-Parker
The rising prevalence of chronic liver disease, coupled with a permanent shortage of organs for liver transplantation, has sparked enormous interest in alternative treatment strategies. Previous protocols to generate hepatocyte-like cells (HLCs) via pancreas-to-liver transdifferentiation have utilised fetal bovine serum, introducing unknown variables and severely limiting study reproducibility. Therefore, the main goal of this study was to develop a protocol for transdifferentiation of pancreatic progenitor cells to HLCs in a chemically defined, serum-free culture medium...
March 12, 2018: Scientific Reports
Ya-Kun Li, Dong-Xia Ma, Zhi-Min Wang, Xiao-Fan Hu, Shang-Lin Li, Hong-Zhe Tian, Meng-Jun Wang, Yan-Wen Shu, Jun Yang
Renal fibrosis is recognized as the common route of all chronic kidney disease (CKD) progressing to end-stage renal disease (ESRD). Additionally, accumulating evidence suggests that epithelial-mesenchymal transition (EMT) plays a significant role in the process of renal fibrogenesis. Liraglutide is a long-acting glucagon-like peptide-1 (GLP-1) analog that has been widely used to treat type 2 diabetes. Recent studies have demonstrated that the GLP-1 analogs could also exert protective effects in cardiac fibrosis models...
March 9, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Letícia Sayuri Murase, João Vítor Perez de Souza, Quirino Alves de Lima Neto, Tatiane França Perles de Mello, Bruna Muller Cardoso, Daniele Stéfanie Sara Lopes Lera-Nonose, Jorge Juarez Vieira Teixeira, Maria Valdrinez Campana Lonardoni, Izabel Galhardo Demarchi
This is a systematic review on the role of metalloproteases in the pathogenicity of the American tegumentary leishmaniasis (ATL) caused by New World Leishmania species. The review followed the PRISMA method, searching for articles in PubMed, EMBASE, LILACS and ISI Web of Science, by employing the following terms: 'leishmaniasis', 'cutaneous leishmaniasis', 'mucocutaneous leishmaniasis', 'diffuse cutaneous leishmaniasis', 'Leishmania' and 'metalloproteases'. GP63 of New World Leishmania species is a parasite metalloproteases involved in the degradation and cleavage of many biological molecules as kappa-B nuclear factor, fibronectin, tyrosine phosphatases...
March 13, 2018: Parasitology
Brij Bhushan Mehta, Anil Tiwari, Saniya Sharma, Ashu Shukla, Maryada Sharma, Rakesh K Vasishta, Ramesh K Sen, Aman Sharma, Manni Luthra-Guptasarma
Tenascin-C (TN-C) levels are elevated in the synovial tissue and fluid, as well as cartilage of rheumatoid arthritis (RA) patients. In addition, the presence of TN-C fragments has also been documented in arthritic cartilage. We have previously shown that a single chain variable fragment antibody (TN64), directed against the fibronectin type III repeats 1-5 (TNfnIII 1-5) of TN-C, effectively inhibits fibrotic pathology. Given that fibrosis results from chronic inflammation, and the fact that increased levels of TN-C in the synovial fluid of patients with RA contributes to synovial inflammation and joint destruction, we aimed to investigate the role of TNfnIII 1-5 region of TN-C in RA pathogenesis...
March 9, 2018: International Immunopharmacology
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