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John D Koerner, Dessislava Z Markova, Greg D Schroeder, Brian P Calio, Anuj Shah, Corbin W Brooks, Alexander R Vaccaro, D Greg Anderson, Chris K Kepler
BACKGROUND CONTEXT: The systemic response regarding cytokine expression after application of recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) in a rat spinal fusion model has recently been defined1 , but the local response has not. Defining the local cytokine and growth factor response at the fusion site will help explain the roles of these molecules in the fusion process, as well as that of rhBMP-2. Our hypothesis is that application of rhBMP-2 to the fusion site will alter the local levels of cytokines and growth factors throughout the fusion process, in a manner that is different than the systemic response given the tissue-specific effects of rhBMP-2...
March 14, 2018: Spine Journal: Official Journal of the North American Spine Society
Hiroaki Tanaka, Tatsuro Tamura, Yoshihiro Okita, Mami Yoshii, Mao Tokumoto, Yukie Go, Chie Sakimura, Soichiro Hiramatsu, Junya Nishimura, Yoshihito Yamagoe, Masakazu Yashiro, Yuichiro Miki, Takahiro Toyokawa, Kazuya Muguruma, Kosei Hirakawa, Masaichi Ohira
There are many reports on the association between infiltrating immune cells andcancer prognosis. It is generally thought that cancer cells escape from the immune surveillance system in vivo. Cells associatedwith tumor immunosuppressive mechanisms include macrophages, regulatory T cells, bone marrow-derived immunosuppressive cells(MDSC), andneutrophils. These immunosuppressive cells enhance the production of TGF-b andIL -10 andthe expression of PDL-1 by cytokines producedby stromal cells such as cancer cells andfibroblasts, thereby inducing cytotoxic T cells lymphocytes(CTL)...
February 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
M Ioannou, E Kouvaras, R Papamichali, M Samara, I Chiotoglou, G Koukoulis
Epithelial-mesenchymal transition (EMT) plays an important role in cancer metastasis. During EMT, tumor cells acquire the capacity to migrate and invade the stroma. Activation of the transforming growth factor-b (TGF-b) signaling pathway is of major importance for the initiation of EMT. Smad4, an essential protein of this pathway, is known to complex with multiple transcription factors (e.g. Snail-1, Slug, Twist-1), in various types of cancer, promoting the repression or activation of target genes. The role of Smad4 in colorectal cancer (CRC) is not straightforward so far...
February 21, 2018: Journal of Molecular Histology
Jones Gyamfi, Minseob Eom, Ja-Seung Koo, Junjeong Choi
Breast cancer is the most common malignancy in women worldwide, with a developmental process spanning decades. The malignant cells recruit a variety of cells including fibroblasts, endothelial cells, immune cells, and adipocytes, creating the tumor microenvironment. The tumor microenvironment has emerged as active participants in breast cancer progression and response to treatment through autocrine and paracrine interaction with the malignant cells. Adipose tissue is abundant in the breast cancer microenvironment; interactions with cancer cells create cancer-associated adipocytes which produce a variety of adipokines that influence breast cancer initiation, metastasis, angiogenesis, and cachexia...
January 30, 2018: Translational Oncology
Ayumi A Miyakawa, Thais Girao-Silva, Jose E Krieger, Elazer R Edelman
Rapamycin, the macrolide immunosuppressant and active pharmaceutic in drug-eluting stents (DES), has a well-recognized anti-proliferative action that involves inhibition of the mTOR pathway after binding to the cytosolic protein FKBP12. TGF receptor-type I (TGFRI) spontaneous activation is inhibited by the association with FKBP12. We hypothesized that rapamycin, in addition to inhibition of mTOR signaling, activates TGFRI independent of TGFb. Human umbilical vein endothelial cells (HUVEC) were treated with rapamycin (10nmoL/L) and/or TGF-b RI kinase inhibitor (TGFRIi, 100nmoL/L) for 24 hours...
January 17, 2018: Clinical Science (1979-)
Thalita Frutuoso Lobo, Camila de Moraes Borges, Rosiane Mattar, Caio Perez Gomes, Ana Geisa Santos de Angelo, Karen Priscilla Tezotto Pendeloski, Silvia Daher
PROBLEM: Maternal obesity is frequently associated with gestational diabetes mellitus (GDM), and immunological mechanisms seem to be involved in the physiopathology of these conditions. The aim of this study was to characterize the profile of immune cells in peripheral blood of overweight women with GDM. METHOD OF STUDY: This case-control study included 27 glucose-tolerant (controls) and 31 GDM overweight pregnant women. Flow cytometry was used to assess the number of regulatory T cells (Treg) and natural killer (NK) cells in the peripheral blood...
January 5, 2018: American Journal of Reproductive Immunology: AJRI
Xiao-Bing Wang, Hong Zhu, Wei Song, Jian-Hua Su
BACKGROUND Gremlin has been reported to be up-regulated in glomerular mesangial cells in diabetic nephropathy (DN). However, the regulation of gremlin in podocytes is still rarely reported. This study aimed to investigate the underlying mechanisms by which gremlin mediates the pathogenesis of DN via transforming growth factor-β (TGF-β) signaling pathways. MATERIAL AND METHODS Lentiviral and RNAi transfection were performed to increase and decrease gremlin expression in high-glucose conditions. Expression at the mRNA and protein level was detected by RT-qPCR and Western blotting...
January 9, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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, which cause tissue fibrosis in response to TGFB1, leading to renal failure. Here, we define a novel interaction between the SET9 lysine methyltransferase (also known as SETD7) and SMAD3, the principal mediator of TGFB1 signalling in myofibroblasts. We show that SET9-deficient fibroblasts exhibit globally altered gene expression profiles in response to TGFB1, whilst overexpression of SET9 enhances SMAD3 transcriptional activity...
January 8, 2018: Journal of Cell Science
Sebastian Gatica, Claudio Cabello-Verrugio, Felipe Simon
This review includes a comprehensive, but succinct, summary on the essentials of TGF-b structure, family members, receptors, and intracellular mediators. Also provided is a select list of original publications that report novel roles and facets of TGF-b in vascular function and signaling in the contexts of health and disease.
November 27, 2017: Current Protein & Peptide Science
Ye Tian, Li-Huang Cui, Shou-Yang Xiang, Wen-Xiao Xu, De-Chun Chen, Rui Fu, Chang-Long Zhou, Xiao-Qi Liu, Yu-Fu Wang, Xin-Tao Wang
Autogenous bone graft is the best for spinal fusion in clinics, however, lacking sources, bleeding and infection are limited its practice. Seeking alternative materials are urgent for orthopaedic surgeon. Here, we evaluated osteoblast-oriented differentiation of rabbit BMSCs by co-culturing with composite scaffolds constructed using silicon-substituted-CaP-fine particulate bone powder-alginate. Using CCk8-kit, biocompatibility was evaluated by testing BMSCs proliferation; morphology and survival of osteoblasts within scaffolds were observed using EM and HE staining; growth factors and related genes were detected using RT-PCR...
October 24, 2017: Oncotarget
Dallas Jones, C Preston Neff, Brent E Palmer, Kurt Stenmark, Maria A Nagel
Objective: To test whether varicella zoster virus (VZV) infection of human brain vascular cells and of lung fibroblasts directly increases proinflammatory cytokine levels, consistent with VZV as a causative agent in intracerebral VZV vasculopathy and giant-cell arteritis (GCA). Methods: Conditioned supernatant from mock- and VZV-infected human brain vascular adventitial fibroblasts (HBVAFs), human perineurial cells (HPNCs), human brain vascular smooth muscle cells (HBVSMCs), and human fetal lung fibroblasts (HFLs) were collected at 72 hours postinfection and analyzed for levels of 30 proinflammatory cytokines using the Meso Scale Discovery Multiplex ELISA platform...
September 2017: Neurology® Neuroimmunology & Neuroinflammation
Johanna Abrigo, Felipe Simon, Daniel Cabrera, Gonzalo Cordova, Capucine Trollet, Claudio Cabello-Verrugio
Among the soluble factors that regulate skeletal muscle function, Transforming Growth Factor type Beta 1 (TGF-b1) is one of the most studied. This factor inhibits myogenesis and regeneration by regulating the activity and function of satellite cells (SCs). Indeed, TGF-b has a central role in muscle pathologies in which there is development of fibrosis and/or atrophy of skeletal muscle. Thus, in this review we present the critical and recent antecedents regarding the mechanisms and cellular targets involved in the effects of TGF-b1 in the muscle, in pathological processes such as the inhibition of regeneration, fibrosis and atrophy...
November 16, 2017: Current Protein & Peptide Science
Drirh Khare, Neta Goldschmidt, Aya Bardugo, Devorah Gur-Wahnon, Iddo Z Ben-Dov, Batia Avni
Early detection of relapsed lymphoma improves response and survival. Current tools lack power for detection of early relapse, while being cumbersome and expensive. We searched for sensitive biomarkers that precede clinical relapse, and serve for further studies on therapy response and relapse. We recruited 20 healthy adults, 14 diffuse large B-cell lymphoma (DLBCL) patients and 11 Hodgkin lymphoma (HL) patients at diagnosis. Using small-RNA sequencing we identified in DLBCL patients increased plasma levels of miR-124 and miR-532-5p, and decreased levels of miR-425, miR-141, miR-145, miR-197, miR-345, miR-424, miR-128 and miR-122...
2017: PloS One
Nolan B Ayers, Chenming Sun, Shi-You Chen
Systemic sclerosis (SSc) is a complex, multiorgan autoimmune disease of unknown etiology. Manifestation of the disease results from an interaction of three key pathologic features including irregularities of the antigen-specific immune system and the non-specific immune system, resulting in autoantibody production; vascular endothelial activation of small blood vessels; and tissue fibrosis as a result of fibroblast dysfunction. Given the heterogeneity of clinical presentation of the disease, a lack of universal models has impeded adequate testing of potential therapies for SSc...
November 1, 2017: Journal of Biomedical Research
Yang Yang, Changwei Ji, Suhan Guo, Xin Su, Xiaozhi Zhao, Shiwei Zhang, Guangxiang Liu, Xuefeng Qiu, Qing Zhang, Hongqian Guo, Huimei Chen
MicroRNAs have been broadly implicated in cancer, but their exact function and mechanism in carcinogenesis remain poorly understood. Aberrant miR-486-5p expression is frequently found in human cancers. Here we showed a significant overexpression of miR-486-5p in prostate cancer compared with that in normal tissue and cells, and we proposed that altered expression of miR-486-5p in the prostate contributed to prostate cancer. Firstly, miR-486-5p inhibition expression reduced prostate cancercell proliferation, migration, and colonization in vitro and prostate tumor development in vivo...
September 22, 2017: Oncotarget
V W Tsai, H P Zhang, R Manandhar, K K M Lee-Ng, H Lebhar, C P Marquis, Y Husaini, A Sainsbury, D A Brown, S N Breit
OBJECTIVES: To test the potential efficacy of recombinant macrophage inhibitory cytokine-1 (MIC-1/GDF15) as an obesity therapeutic. METHODS: Male C57BL/6 J mice, either fed on normal chow or high-fat diet for 16 weeks to induce diet-induced obesity, were infused with either recombinant MIC-1/GDF15 or vehicle for 34 days by osmotic minipump. During the experimental period metabolic parameters were measured. Blood and tissue were collected for analysis of inflammatory markers...
December 5, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Koichiro Kajiwara, Shunsuke Takata, Thao T To, Kenyo Takara, Yuji Hatakeyama, Sachio Tamaoki, Richard Peters Darveau, Hiroyuki Ishikawa, Yoshihiko Sawa
BACKGROUND: Recently, we reported that toll-like receptor (TLR)2 and TLR4 localized on the glomerular endothelium in the glomeruli of streptozotocin (STZ)-induced type 1 diabetic mice and high fat diet feed-induced type 2 diabetic mice, and that periodontal pathogen Porphyromonas gingivalis LPS (Pg-LPS) administration lowered the survival rate of diabetic mice. The present study aims to examine the effect of TLR4 blocking on the suppression of Pg-LPS-induced diabetic nephropathy. METHODS: The survival rate and morphological/biochemical features for streptozotocin-induced diabetic mice with Pg-LPS and TLR4 blocker eritoran administration were investigated by reporter gene assay, urine and blood analysis, immunohistochemistry, and real time-PCR...
2017: Diabetology & Metabolic Syndrome
Nesrine S El-Mezayen, Wessam F El-Hadidy, Wessam M El-Refaie, Th I Shalaby, Mahmoud M Khattab, Aiman S El-Khatib
Liver fibrosis is a global health problem without approved treatment. Imatinib inhibits two key profibrotic pathways; platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-β) and thus can be used to treat liver fibrosis. However, conventional imatinib therapy is hampered by low concentration at target tissue and increased toxicity to other tissues especially heart, lung and liver. Since hepatic stellate cells (HSCs) are the main contributors to liver fibrosis pathogenesis and sole hepatic vitamin A (VA ) storage cells, they can be actively targeted by coupling liposomes to VA ...
November 28, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
Kuan-Meng Soo, Bahariah Khalid, Siew-Mooi Ching, Chau Ling Tham, Rusliza Basir, Hui-Yee Chee
BACKGROUND: Dengue viral infection is an acute infection that has the potential to have severe complications as its major sequela. Currently, there is no routine laboratory biomarker with which to predict the severity of dengue infection or monitor the effectiveness of standard management. Hence, this meta-analysis compared biomarker levels between dengue fever (DF) and severe dengue infections (SDI) to identify potential biomarkers for SDI. METHODS: Data concerning levels of cytokines, chemokines, and other potential biomarkers of DF, dengue hemorrhagic fever, dengue shock syndrome, and severe dengue were obtained for patients of all ages and populations using the Scopus, PubMed, and Ovid search engines...
2017: PeerJ
Patricia G Wilson, Joel C Thompson, Meghan H Yoder, Richard Charnigo, Lisa R Tannock
Animal studies demonstrate that hyperlipidemia and renal lipid accumulation contribute to the pathogenesis of diabetic nephropathy (DN). We previously demonstrated that renal lipoproteins colocalize with biglycan, a renal proteoglycan. The purpose of this study was to determine whether prevention of renal lipid (apoB) accumulation attenuates DN. Biglycan-deficient and biglycan wild-type Ldlr -/- mice were made diabetic via streptozotocin and fed a high cholesterol diet. As biglycan deficiency is associated with elevated transforming growth factor-β (TGF-β), in some experiments mice were injected with either the TGF-β-neutralizing antibody, 1D11, or with 13C4, an irrelevant control antibody...
December 2017: Journal of Lipid Research
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