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Borzo Gharibi, Mandeep S Ghuman, Giuseppe Cama, Simon C F Rawlinson, Agamemnon E Grigoriadis, Francis J Hughes
The osteoporosis-resistant nature of skull bones implies inherent differences exist between their cellular responses and those of other osteoporosis-susceptible skeletal sites. Phenotypic differences in calvarial and femoral osteoblastic responses to induction of osteogenesis, mechanical loading, estrogen, growth factor and cytokine stimulation were investigated. Primary rat calvarial and femoral adult male osteoblasts were cultured and osteoblastic mineralisation and maturation determined using Alizarin Red staining and expression of osteogenic marker genes assessed...
June 18, 2018: Molecular and Cellular Endocrinology
Mohamad Al-Dujaili, Trudy J Milne, Richard D Cannon, Mauro Farella
OBJECTIVES: The condylar cartilage is a key site of growth and development of the mandible. The aim of this research was to determine the mRNA expression levels of a number of chondrogenic and osteogenic regulatory factors in the condylar cartilage of the postnatal rat. MATERIALS AND METHODS: Condyles were extracted from 40 rats aged 4, 10, 21 or 90 days with 10 rats assigned to each age group. The condyles from one rat from each age group was fixed and decalcified in 10% EDTA for histology...
June 1, 2018: Archives of Oral Biology
Fang Li, Tengjiao Zhu, Yao Yue, Xiang Zhu, Jiadong Wang, Li Liang
Non‑small cell lung cancer (NSCLC) is one of the most severe malignant tumor types worldwide. Recent studies have reported an important role of PD‑L1 in mediating immune evasion in the tumor microenvironment. In addition, increasing research has indicated that the expression of PD‑L1 is related to the epithelial‑mesenchymal transition (EMT) process, but the related mechanisms remain to be explored. In the present study, we explored the molecular mechanisms underlying the regulation of PD‑L1 expression during the EMT process in NSCLC cells treated with transforming growth factor‑β1 (TGF‑β1) and fibroblast growth factor 2 (FGF2)...
June 5, 2018: Oncology Reports
Sheng Wang, Yiyang Qin, Zhongmin Wang, Junjian Xiang, Yu Zhang, Meng Xu, Baiyong Li, Yu Xia, Peng Zhang, Hong Wang
Compelling evidence implicates that overexpression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor 1 (FGFR1) in non-small cell lung cancer (NSCLC) drives tumor progression, can serve as prognostic biomarkers or therapeutic targets for NSCLC patients. But at present, we still lack of effective drugs for bFGF. The preparation of monoclonal antibodies against bFGF or to understand its mechanism of action is urgently need. Previously, we used hybridoma technology to produce a murine anti-bFGF monoclonal antibody (E12)...
2018: Journal of Cancer
Hyun Young Koo, Lamis M F El-Baz, Stacey L House, Sarah N Cilvik, Samuel J Dorry, Nahla M Shoukry, Mohamed L Salem, Hani S Hafez, Nickolai O Dulin, David M Ornitz, Robert D Guzy
Fibroblast growth factor (FGF) signaling has been implicated in the pathogenesis of pulmonary fibrosis. Mice lacking FGF2 have increased mortality and impaired epithelial recovery after bleomycin exposure, supporting a protective or reparative function following lung injury. To determine whether FGF2 overexpression reduces bleomycin-induced injury, we developed an inducible genetic system to express FGF2 in type II pneumocytes. Double-transgenic (DTG) mice with doxycycline-inducible overexpression of human FGF2 (SPC-rtTA; TRE-hFGF2) or single-transgenic controls were administered intratracheal bleomycin and fed doxycycline chow, starting at either day 0 or 7...
June 6, 2018: Journal of Pathology
Yan Su, Janet M Denbeigh, Emily T Camilleri, Scott M Riester, Joshua A Parry, Eric R Wagner, Michael J Yaszemski, Allan B Dietz, Simon M Cool, Andre J van Wijnen, Sanjeev Kakar
Purpose: The poor healing potential of intra-articular ligament injuries drives a need for the development of novel, viable 'neo-ligament' alternatives. Ex vivo approaches combining stem cell engineering, 3-dimensional biocompatible scaffold design and enhancement of biological and biomechanical functionality via the introduction of key growth factors and morphogens, represent a promising solution to ligament regeneration. Methods: We investigated growth, differentiation and extracellular matrix (ECM) protein production of human adipose-derived mesenchymal stem/stromal cells (MSCs), cultured in 5% human platelet lysate (PL) and seeded on three-dimensional polycaprolactone (PCL) scaffolds, in response to the connective-tissue related ligands fibroblast growth factor 2 (basic) (FGF2) and growth and differentiation factor-5 (GDF5)...
March 2018: Gene Reports
Jiahui Ding, Xiujuan Tan, Kunkun Song, Wenwen Ma, Jing Xiao, Yufan Song, Mingmin Zhang
Bushen Huoxue recipe (BSHXR) is a classic Chinese herbal prescription for nourishing the kidney and activating blood circulation. It consists of six herbs: Astragali radix , Angelicae sinensis radix , Ligustici Chuanxiong Rhizoma , Cuscutae semen , Taxilli Herba , and Dipsaci Radix , and the main active constituents of BSHXR are ferulic acid, calycosin-7-glucopyranoside, hyperoside, quercitrin, and asperosaponin VI. In clinical practice, BSHXR is traditionally used to treat failed pregnancy and its complications...
2018: Frontiers in Pharmacology
Lucia Saucedo, Cristian Sobarzo, Nicolás Brukman, Hector Alejandro Guidobaldi, Livia Lustig, Laura Cecilia Giojalas, Mariano Gabriel Buffone, Monica Hebe Vazquez-Levin, Clara Marín-Briggiler
Fibroblast Growth Factor 2 (FGF2) and its receptors (FGFRs) have been described in several tissues, where they regulate cellular proliferation, differentiation, motility and apoptosis. Although FGF2/FGFRs expression in the male reproductive tract has been reported, there is scarce evidence on their presence in the female reproductive tract and their involvement in the modulation of sperm function. Therefore, the objective of this study was to determine the expression of FGF2 in the female reproductive tract and to assess the role of the FGF2/FGFRs system in the regulation of sperm physiology using the murine model...
June 4, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
Sarah C McDermott, Christie Rodriguez-Ramirez, Sean P McDermott, Max S Wicha, Jacques E Nör
Patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) have poor prognosis with less than 1-year median survival. Platinum-based chemotherapy remains the first-line treatment for HNSCC. The cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self-renewing CSC population that is also capable of differentiating into non-self renewing cell populations that constitute the bulk of the tumor. A small population of CSC exists within HNSCC that are relatively resistant to chemotherapy and clinically predicted to contribute to tumor recurrence...
May 18, 2018: Oncotarget
Thierry Menguy, Anne Briaux, Elisabeth Jeunesse, Jérôme Giustiniani, Alexandre Calcei, Thierry Guyon, Jacques Mizrahi, Hélène Haegel, Vanessa Duong, Vincent Soler, Pierre Brousset, Armand Bensussan, Isabelle Raymond Letron, Philippe Le Bouteiller
Purpose: To assess the efficacy of the murine first-in-class CL1-R2 monoclonal antibody (mAb) targeting human CD160 (alone or in combination with bevacizumab) by using the rabbit corneal neovascularization (CNV) model, and determine the safety and efficacy of ELB01101, a novel CL1-R2-derived humanized IgG4 mAb, in a monkey model of choroidal neovascularization (ChNV). Methods: Comparison of effect of CL1-R2, bevacizumab, or aflibercept or IgG1 (control) injections in early and late treatment schemes on evolution of VEGF- or FGF2-induced rabbit CNV was performed...
June 1, 2018: Investigative Ophthalmology & Visual Science
Kaixuan Wang, Wenxiang Ji, Yongfeng Yu, Ziming Li, Xiaomin Niu, Weiliang Xia, Shun Lu
Epithelial-mesenchymal transition (EMT) is an important process for cancer metastasis, drug resistance, and cancer stem cells. Activation of fibroblast growth factor receptor 1 (FGFR1) was found to promote EMT and metastasis in prostate and breast cancers, but the effects and mechanisms in lung cancer was unclear. In this study, we aimed to explore whether and how activation of FGFR1 promotes EMT and metastasis in FGFR1-amplified lung cancer. We show that activation of FGFR1 by its ligand fibroblast growth factor 2 (FGF2) promoted proliferation, EMT, migration, and invasion in FGFR1-amplified lung cancer cell lines H1581 and DMS114, whereas inhibition of FGFR1 suppressed these processes...
June 1, 2018: Oncogene
G Gibor, N Ilan, S Journo, A Sharabi, J Dreyer, S Gertel, P Singh, A Menachem, N Snir, O Elkayam, I Vlodavsky, U Arad
OBJECTIVES: The chondrocytes' pericellular matrix acts as a mechanosensor by sequestering growth factors that are bound to heparan sulfate (HS) proteoglycans. Heparanase is the sole mammalian enzyme with HS degrading endoglycosidase activity. Here, we aimed to ascertain whether heparanase plays a role in modulating the anabolic or catabolic responses of human articular chondrocytes. METHODS: Primary chondrocytes were incubated with pro-heparanase and catabolic and anabolic gene expression was analyzed by quantitative PCR...
May 24, 2018: Osteoarthritis and Cartilage
Erlend C S Landsend, Øygunn A Utheim, Hilde R Pedersen, Hans Christian D Aass, Neil Lagali, Darlene A Dartt, Rigmor C Baraas, Tor P Utheim
Purpose: To investigate the tear cytokine profile in congenital aniridia, and correlate cytokine levels with ophthalmologic findings. Methods: We examined 35 patients with aniridia and 21 healthy controls. Tear fluid was collected with Schirmer I test and capillary tubes from each eye, and the concentration of 27 inflammatory cytokines determined using multiplex bead assay. Eyes of all participants were examined with tests for dry eye disease, including evaluation of meibomian glands (meibography)...
April 1, 2018: Investigative Ophthalmology & Visual Science
I C Tobias, R R Isaac, J G Dierolf, R Khazaee, R C Cumming, D H Betts
Pluripotent stem cells (PSCs) have been described in naïve or primed pluripotent states. Domestic dogs are useful translational models in regenerative medicine, but their embryonic stem cells (cESCs) remain narrowly investigated. Primed-like cESCs expanded in the presence of leukemia inhibitory factor and fibroblast growth factor 2 (LIF-FGF2) acquire features of naïve pluripotency when exposed to chemical inhibitors and LIF (2iL). However, proliferation of cESCs is influenced by the pluripotent state and is comparatively slower than human or mouse PSCs...
May 16, 2018: Stem Cell Research
Akira Kasuya, Taisuke Ito, Yoshiki Tokura
BACKGROUND: De novo hair regeneration occurs in scars of normal adult mice. This interesting phenomenon is termed as wound-induced hair neogenesis (WIHN). We hypothesized that M2 macrophages are crucially involved in WIHN. OBJECTIVE: To clarify the contribution of M2 macrophages to WIHN. METHOD: We established a mouse model of WIHN. A full thickness skin excision was implemented on the back of C57BL/6 (B6) mice. Newly developing hair follicles were detected by a whole-mount assay...
May 12, 2018: Journal of Dermatological Science
Sousuke Kanaya, Binlu Xiao, Yukihiko Sakisaka, Mizuki Suto, Kentaro Maruyama, Masahiro Saito, Eiji Nemoto
We previously reported that elevated extracellular calcium (Ca2+) levels increase bone morphogenetic protein 2 expression in human dental pulp (hDP) cells. However, it is unknown whether extracellular Ca2+ affects the expression of other growth factors such as fibroblast growth factor 2 (FGF2). The present study aimed to examine the effect of extracellular Ca2+ on FGF2 gene expression in hDP and immortalized mouse dental papilla (mDP) cells. Cells were stimulated with 10 mM CaCl2 in the presence or absence of cell signaling inhibitors...
May 14, 2018: Journal of Applied Oral Science: Revista FOB
Z-F Tang, H-Y Li
OBJECTIVE: To investigate the effect of low intensity ultrasound irradiation combine with fibroblast growth factors (FGF2) on the repair of the knee articular cartilage and to explore its mechanism in rabbit. MATERIALS AND METHODS: The model of the rabbit knee joint injury was established. 40 rabbits were divided into four groups, including control group, model group, FGF2 group and FGF2 + low intensity pulsed ultrasound group (FGF2 + LIPU). The knee joints of rabbits were taken at 4 and 8 weeks, respectively...
April 2018: European Review for Medical and Pharmacological Sciences
Juan Pena, Nihan Dulger, Tanya Singh, Jing Zhou, Robert Majeska, Stephen Redenti, Maribel Vazquez
Emerging therapies have begun to evaluate the abilities of Müller glial cells (MGCs) to protect and/or regenerate neurons following retina injury. The migration of donor cells is central to many reparative strategies, where cells must achieve appropriate positioning to facilitate localized repair. Although chemical cues have been implicated in the MGC migratory responses of numerous retinopathies, MGC-based therapies have yet to explore the extent to which external biochemical stimuli can direct MGC behavior...
May 10, 2018: Experimental Eye Research
Elizabeth Ann L Enninga, Kyriakos Chatzopoulos, John T Butterfield, Shari L Sutor, Alexey A Leontovich, Wendy K Nevala, Thomas J Flotte, Svetomir N Markovic
In patients with metastatic melanoma, high blood levels of galectin-9 are correlated with worse overall survival and a bias towards a Th2 inflammatory state supportive of tumor growth. Although galectin-9 signaling through TIM3 on T cells has been described, less is known about the interaction of galectin-9 with macrophages. We aimed to determine whether galectin-9 is a binding partner of CD206 on macrophages and whether the result of this interaction is tumor-supportive. It was determined that incubation of CD68+ macrophages with galectin-9 or anti-CD206 blocked target binding and that both CD206 and galectin-9 were detected by immunoprecipitation of cell lysates...
May 7, 2018: Journal of Pathology
Rui-Lan Huang, Hsiang-Ju Chen, Lin-Yu Chen, Tai-Kuang Chao, Wei-Yu Lin, Phui-Ly Liew, Po-Hsuan Su, Yu-Chun Weng, Yu-Chi Wang, Chi-Chun Liao, Yaw-Wen Hsu, Hui- Chen Wang, Hung-Cheng Lai
Precision medicine requires markers for therapeutic guidance. The purpose of this study was to determine whether epithelial ovarian cancer (EOC) epigenetics can lead to the identification of biomarkers for precision medicine. Through integrative methylomics, we discovered and validated the epigenetic signature of NEFH and HS3ST2 as an independent prognostic factor for type II EOC in our dataset (n = 84), two independent methylomics datasets (total n = 467). Integrated transcriptomics dataset (n = 1147) and tissue microarrays (n = 54) of HS3ST2 also related to high-methylation statuses and the EOC prognosis...
May 7, 2018: International Journal of Cancer. Journal International du Cancer
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