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https://www.readbyqxmd.com/read/28526296/mesenchymal-stem-cells-mscs-attenuate-cutaneous-sclerodermatous-graft-versus-host-disease-scl-gvhd-through-inhibition-of-immune-cell-infiltration-in-a-mouse-model
#1
Ji-Young Lim, Da-Bin Ryu, Sung-Eun Lee, Gyeongsin Park, Chang-Ki Min
Human chronic graft-versus-host disease (CGVHD) shares clinical characteristics with a murine sclerodermatous GVHD (Scl-GVHD) model that is characterized by skin thickening and lung fibrosis. A B10.D2 → BALB/c transplant model of Scl-GVHD was used to address the therapeutic effect of mesenchymal stem cells (MSCs) on the development of CGVHD. The clinical and pathological severity of cutaneous Scl-GVHD was significantly attenuated in MSC-treated recipients relative to Scl-GVHD controls. After MSC treatment, skin collagen production was significantly reduced with consistent downregulation of TGF-β expression...
May 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28525845/novel-amidino-substituted-benzimidazole-and-benzothiazole-benzo-b-thieno-2-carboxamides-exert-strong-antiproliferative-and-dna-binding-properties
#2
Maja Cindrić, Samy Jambon, Anja Harej, Sabine Depauw, Marie-Hélène David-Cordonnier, Sandra Kraljević Pavelić, Grace Karminski-Zamola, Marijana Hranjec
Within this manuscript design, synthesis of novel 2-imidazolinyl substituted benzo[b]thieno-2-carboxamides bearing either benzimidazole or benzothiazole subunit and biological activity are presented and described. The antiproliferative activities were assessed in vitro on a panel of human cancer cell lines. Tested compounds showed moderate activity while cytotoxicity on normal fibroblasts was lower in comparison with 5-fluorouracile. The variations of 2-imidazolinyl substituent at heteroaromatic subunits in different positions led to different cytotoxic properties...
May 4, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28524742/piqueria-trinervia-as-a-source-of-metabolites-against-giardia-intestinalis
#3
Yadira Rufino-González, Martha Ponce-Macotela, Manuel Jiménez-Estrada, Candy N Jiménez-Fragoso, Guadalupe Palencia, Gabriel Sansón-Romero, Anahi Anzo-Osorio, Mario N Martínez-Gordillo
CONTEXT: Piqueria trinervia Cav. (Asteraceae) is a plant species with a long history in traditional medicine to cure diarrhoea and other digestive disorders. OBJECTIVE: The study investigates the antigiardial activity of piquerol, trinervinol, red oil and two fractions (F1 and F2) from P. trinervia. MATERIALS AND METHODS: P. trinervia was collected in the Ajusco in Mexico City. Aerial parts were ground and mixed with water to obtain the extract, which was treated with dichloromethane to isolate piquerol and trinervinol (P & T)...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28524659/synthesis-molecular-docking-molecular-dynamics-studies-and-biological-evaluation-of-4h-chromone-1-2-3-4-tetrahydropyrimidine-5-carboxylate-derivatives-as-potential-anti-leukemic-agents
#4
Zahra Dolatkhah, Shahrzad Javanshir, Ahmad Shahir Sadr, Jaber Hosseini, Soroush Sardari
Series of 4H-chromone-1,2,3,4-tetrahydropyrimidine-5-carboxylates derivatives were synthesized via a three component one-pot condensation of chromone-3-carbaldehyde, alkyl acetoacetate and urea or thiourea, using MCM-41-SO3H as an efficient Nano-catalysts, and evaluated for their anti-cancer activity using a combined in silico docking and molecular dynamics protocol to estimate the binding affinity of the title compounds with the Bcr-Abl oncogene. Two programs, AutoDock 4 and AutoDock Vina software were applied to dock the target protein with synthesized compounds and ATP...
May 19, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28514770/mm-bmscs-induce-na%C3%A3-ve-cd4-t-lymphocytes-dysfunction-through-fibroblast-activation-protein-%C3%AE
#5
Xiaofei Wu, Yadan Wang, Jian Xu, Ting Luo, Jun Deng, Yu Hu
BACKGROUND: The tumor microenvironment plays a major role in multiple myelomas (MM). MM-BMSCs (bone marrow mesenchymal stromal cells) can support tumor growth and immune surveillance escape. On the other hand, fibroblast activation protein α, expressed by cancer stroma cells including BMSCs, has been shown to potentiate epithelial cancers growth and immune suppression. RESULTS: MM-BMSC inhibited proliferation of T cells (P = 0.0138), promoted senescence of T cells (P < 0...
April 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28510629/fibroblast-growth-factor-receptor-2-fgfr2-is-required-for-meibomian-gland-homeostasis-in-the-adult-mouse
#6
Lixing W Reneker, Lanlan Wang, Rebecca T Irlmeier, Andrew J W Huang
Purpose: Little is known about the signaling mechanisms controlling meibomian gland (MG) homeostasis and the pathogenic processes leading to MG atrophy and dysfunction in dry eye disease (DED). We investigated the role of fibroblast growth factor receptor 2 (FGFR2) in the MG homeostasis of adult mice. Methods: A triple transgenic mouse strain (Krt14-rtTA; tetO-Cre; Fgfr2flox/flox), referred to as Fgfr2CKO mice, was generated in which the Fgfr2 gene is ablated by Cre recombinase in keratin 14 (Krt14)-expressing epithelial cells on doxycycline (Dox) induction...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28510269/kallikrein-related-peptidase-4-induces-cancer-associated-fibroblast-features-in-prostate-derived-stromal-cells
#7
T Kryza, L M Silva, N Bock, R A Fuhrman-Luck, C R Stephens, J Gao, H Samaratunga, M G Lawrence, J D Hooper, Y Dong, G P Risbridger, J A Clements
The reciprocal communication between cancer cells and their microenvironment is critical in cancer progression. Although involvement of cancer-associated fibroblasts (CAF) in cancer progression is long established, the molecular mechanisms leading to differentiation of CAFs from normal fibroblasts are poorly understood. Here, we report that kallikrein-related peptidase-4 (KLK4) promotes CAF differentiation. KLK4 is highly expressed in prostate epithelial cells of premalignant (prostatic intra-epithelial neoplasia) and malignant lesions compared to normal prostate epithelia, especially at the peri-stromal interface...
May 16, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28507545/clinical-and-molecular-heterogeneity-of-rtel1-deficiency
#8
Carsten Speckmann, Sushree Sangita Sahoo, Marta Rizzi, Shinsuke Hirabayashi, Axel Karow, Nina Kathrin Serwas, Marc Hoemberg, Natalja Damatova, Detlev Schindler, Jean-Baptiste Vannier, Simon J Boulton, Ulrich Pannicke, Gudrun Göhring, Kathrin Thomay, J J Verdu-Amoros, Holger Hauch, Wilhelm Woessmann, Gabriele Escherich, Eckart Laack, Liliana Rindle, Maximilian Seidl, Anne Rensing-Ehl, Ekkehart Lausch, Christine Jandrasits, Brigitte Strahm, Klaus Schwarz, Stephan R Ehl, Charlotte Niemeyer, Kaan Boztug, Marcin W Wlodarski
Typical features of dyskeratosis congenita (DC) resulting from excessive telomere shortening include bone marrow failure (BMF), mucosal fragility, and pulmonary or liver fibrosis. In more severe cases, immune deficiency and recurring infections can add to disease severity. RTEL1 deficiency has recently been described as a major genetic etiology, but the molecular basis and clinical consequences of RTEL1-associated DC are incompletely characterized. We report our observations in a cohort of six patients: five with novel biallelic RTEL1 mutations p...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28506283/prolactin-blocks-the-expression-of-receptor-activator-of-nuclear-factor-%C3%AE%C2%BAb-ligand-and-reduces-osteoclastogenesis-and-bone-loss-in-murine-inflammatory-arthritis
#9
Maria G Ledesma-Colunga, Norma Adán, Georgina Ortiz, Mariana Solís-Gutiérrez, Fernando López-Barrera, Gonzalo Martínez de la Escalera, Carmen Clapp
BACKGROUND: Prolactin (PRL) reduces joint inflammation, pannus formation, and bone destruction in rats with polyarticular adjuvant-induced arthritis (AIA). Here, we investigate the mechanism of PRL protection against bone loss in AIA and in monoarticular AIA (MAIA). METHODS: Joint inflammation, trabecular bone loss, and osteoclastogenesis were evaluated in rats with AIA treated with PRL (via osmotic minipumps) and in mice with MAIA that were null (Prlr-/-) or not (Prlr+/+) for the PRL receptor...
May 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28504692/mint3-mediated-l1cam-expression-in-fibroblasts-promotes-cancer-cell-proliferation-via-integrin-%C3%AE-5%C3%AE-1-and-tumour-growth
#10
H J Nakaoka, Z Tanei, T Hara, J S Weng, A Kanamori, T Hayashi, H Sato, A Orimo, K Otsuji, K Tada, T Morikawa, T Sasaki, M Fukayama, M Seiki, Y Murakami, T Sakamoto
Fibroblasts are some of the major cells in tumour tissues that influence tumour progression and drug resistance. However, our understanding on fibroblast-mediated tumour malignancy remains incomplete. Munc18-1-interacting protein 3 (Mint3) is known as an activator of hypoxia-inducible factor-1 (HIF-1) even during normoxia in cancer cells, macrophages and fibroblasts. Although Mint3 promotes ATP production via glycolysis by activating HIF-1 in cancer cells and macrophages, the biological role of Mint3-mediated HIF-1 activation in fibroblasts remains unclear...
May 15, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28501760/stromal-pdgfr-%C3%AE-activation-enhances-matrix-stiffness-impedes-mammary-ductal-development-and-accelerates-tumor-growth
#11
Anisha M Hammer, Gina M Sizemore, Vasudha C Shukla, Alex Avendano, Steven T Sizemore, Jonathan J Chang, Raleigh D Kladney, Maria C Cuitiño, Katie A Thies, Quinn Verfurth, Arnab Chakravarti, Lisa D Yee, Gustavo Leone, Jonathan W Song, Samir N Ghadiali, Michael C Ostrowski
The extracellular matrix (ECM) is critical for mammary ductal development and differentiation, but how mammary fibroblasts regulate ECM remodeling remains to be elucidated. Herein, we used a mouse genetic model to activate platelet derived growth factor receptor-alpha (PDGFRα) specifically in the stroma. Hyperactivation of PDGFRα in the mammary stroma severely hindered pubertal mammary ductal morphogenesis, but did not interrupt the lobuloalveolar differentiation program. Increased stromal PDGFRα signaling induced mammary fat pad fibrosis with a corresponding increase in interstitial hyaluronic acid (HA) and collagen deposition...
May 11, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28501567/depletion-of-jmjd1c-impairs-adipogenesis-in-murine-3t3-l1-cells
#12
Florian Buerger, Silvana Müller, Nadja Ney, Juliane Weiner, John T Heiker, Sonja Kallendrusch, Peter Kovacs, Dorit Schleinitz, Joachim Thiery, Sonja C Stadler, Ralph Burkhardt
Differentiation of adipocytes is a highly regulated process modulated by multiple transcriptional co-activators and co-repressors. JMJD1C belongs to the family of jumonji C (jmjC) domain-containing histone demethylases and was originally described as a ligand-dependent co-activator of thyroid hormone and androgen receptors. Here, we explored the potential role of Jmjd1c in white adipocyte differentiation. To investigate the relevance of Jmjd1c in adipogenesis, murine 3T3-L1 preadipocyte cells with transient knock-down of Jmjd1c (3T3_Jmjd1c) were generated...
May 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28499587/the-phosphodiesterase-4-inhibitor-apremilast-inhibits-th1-but-promotes-th17-responses-induced-by-6-sulfo-lacnac-slan-dendritic-cells
#13
Stephanie Oehrl, Hridayesh Prakash, Annette Ebling, Nina Trenkler, Priscila Wölbing, Anja Kunze, Thomas Döbel, Marc Schmitz, Alexander Enk, Knut Schäkel
BACKGROUND: The phosphodiesterase 4 (PDE4) inhibitor apremilast increases cellular cAMP levels and has proven effective in the treatment of psoriasis and psoriasis arthritis. We recently described 6-sulfo LacNAc dendritic cells (slanDCs) as immature DCs in blood and as a subset of inflammatory dermal DCs in psoriasis with a pronounced capacity to produce proinflammatory cytokines and to program Th17/Th1 T cell responses. OBJECTIVE: The aim of this study was to investigate possible immune regulatory effects of the PDE4 inhibitor apremilast on slanDCs...
April 20, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28498357/adiponectin-is-involved-in-connective-tissue-growth-factor-induced-proliferation-migration-and-overproduction-of-the-extracellular-matrix-in-keloid-fibroblasts
#14
Limin Luo, Jun Li, Han Liu, Xiaoqing Jian, Qianlei Zou, Qing Zhao, Qu Le, Hongdou Chen, Xinghua Gao, Chundi He
Adiponectin, an adipocyte-derived hormone, exerts pleiotropic biological effects on metabolism, inflammation, vascular homeostasis, apoptosis and immunity. Recently, adiponectin has been suggested to attenuate the progression of human dermal fibrosis. Connective tissue growth factor (CTGF) is induced in keloids and is thought to be participated in the formation of keloid fibrosis. However, the roles played by adiponectin in keloids remain unclear. In this study, we explored the effects of adiponectin on CTGF-induced cell proliferation, migration and the deposition of extracellular matrix (ECM) and their associated intracellular signalling pathways in keloid fibroblasts (KFs)...
May 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28490746/pathogenic-p62-sqstm1-mutations-impair-energy-metabolism-through-limitation-of-mitochondrial-substrates
#15
Fernando Bartolome, Noemi Esteras, Angeles Martin-Requero, Claire Boutoleau-Bretonniere, Martine Vercelletto, Audrey Gabelle, Isabelle Le Ber, Tadashi Honda, Albena T Dinkova-Kostova, John Hardy, Eva Carro, Andrey Y Abramov
Abnormal mitochondrial function has been found in patients with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Mutations in the p62 gene (also known as SQSTM1) which encodes the p62 protein have been reported in both disorders supporting the idea of an ALS/FTD continuum. In this work the role of p62 in energy metabolism was studied in fibroblasts from FTD patients carrying two independent pathogenic mutations in the p62 gene, and in a p62-knock-down (p62 KD) human dopaminergic neuroblastoma cell line (SH-SY5Y)...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28490361/adducin-family-proteins-possess-different-nuclear-export-potentials
#16
Chia-Mei Liu, Wen-Hsin Hsu, Wan-Yi Lin, Hong-Chen Chen
BACKGROUND: The adducin (ADD) family proteins, namely ADD1, ADD2, and ADD3, are actin-binding proteins that play important roles in the stabilization of membrane cytoskeleton and cell-cell junctions. All the ADD proteins contain a highly conserved bipartite nuclear localization signal (NLS) at the carboxyl termini, but only ADD1 can localize to the nucleus. The reason for this discrepancy is not clear. METHODS: To avoid the potential effect of cell-cell junctions on the distribution of ADD proteins, HA epitope-tagged ADD proteins and mutants were transiently expressed in NIH3T3 fibroblasts and their distribution in the cytoplasm and nucleus was examined by immunofluorescence staining...
May 10, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28489314/unclassifiable-pattern-of-hypopigmentation-in-a-patient-with-mosaic-partial-12p-tetrasomy-without-pallister-killian-syndrome
#17
Viola Alesi, Maria L Dentici, Fabrizia Restaldi, Valeria Orlando, Maria T Liambo, Chiara Calacci, Rossella Capolino, Maria C Digilio, May El Hachem, Antonio Novelli, Andrea Diociaiuti, Bruno Dallapiccola
Pallister-Killian syndrome (PKS-#OMIM601803) is a multisystem developmental disorder typically due to the presence of an aneuploidy cell line, consisting of a supernumerary tetrasomic chromosomal marker (SCM) arisen from the short arm of chromosome 12 (12p isochromosome). The clinical phenotype, which is strictly related to the percentage and tissue distribution of aneuploid cells, is characterized by craniofacial dysmorphisms, pigmentary skin anomalies, limb shortening, congenital heart defects, diaphragmatic hernia, hypotonia, intellectual disability, and epilepsy...
May 10, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28487847/recombinant-tghsp70-immunization-protects-against-toxoplasma-gondii-brain-cyst-formation-by-enhancing-inducible-nitric-oxide-expression
#18
Paulo Czarnewski, Ester C B Araújo, Mário C Oliveira, Tiago W P Mineo, Neide M Silva
Toxoplasma gondii is known to cause congenital infection in humans and animals and severe disease in immunocompromised individuals; consequently development of vaccines against the parasite is highly necessary. Under stress conditions, T. gondii expresses the highly immunogenic heat shock protein 70 (TgHSP70). Here, we assessed the protective efficacy of rTgHSP70 immunization combined with Alum in oral ME-49 T. gondii infection and the mechanisms involved on it. It was observed that immunized mice with rTgHSP70 or rTgHSP70 adsorbed in Alum presented a significantly reduced number of cysts in the brain that was associated with increased iNOS+ cell numbers in the organ, irrespective the use of the adjuvant...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28486777/double-hydrophobic-elastin-like-polypeptides-with-added-functional-motifs-self-assembly-and-cytocompatibility
#19
Duc H T Le, Yoko Tsutsui, Ayae Sugawara-Narutaki, Hiroshi Yukawa, Yoshinobu Baba, Chikara Ohtsuki
We have recently developed a novel double-hydrophobic elastin-like triblock polypeptide called GPG, designed after the uneven distribution of two different hydrophobic domains found in elastin, an extracellular matrix protein providing elasticity and resilience to tissues. Upon temperature trigger, GPG undergoes a sequential self-assembling process to form flexible beaded nanofibers with high homogeneity and excellent dispersibility in water. Given that GPG might be a potential elastin-mimetic material, we sought to explore the biological activities of this block polypeptide...
May 9, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28485781/effects-of-htert-antisense-oligodeoxynucleotide-on-cell-apoptosis-and-expression-of-htert-and-bcl-2-mrna-in-keloid-fibroblasts
#20
Y Huang, L-X Lin, Q-X Bi, P Wang, X-M Wang, J Liu, Y-T Wang
OBJECTIVE: This study was purposed to investigate the effects of hTERT antisense oligodeoxynucleotide (ASODN) on cell apoptosis and expression of hTERT and bcl-2 mRNA in keloid fibroblasts and to explore its anti-keloid effect. MATERIALS AND METHODS: Primary cultures of dermal fibroblasts derived from 12 keloid samples were established, strains of fibroblasts at passages 3 to 4 were used in this study. After treated by hTERT ASODN the proliferation of the fibroblasts was measured by cell count and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay method, the apoptosis was analyzed by flow cytometry (FCM), and the expression of hTERT and bcl-2 mRNA were observed by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR)...
April 2017: European Review for Medical and Pharmacological Sciences
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