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Christelle Sanchez, Gabriel Mazzucchelli, Cécile Lambert, Fanny Comblain, Edwin DePauw, Yves Henrotin
OBJECTIVE: Osteoarthritis (OA) is characterized by cartilage degradation but also by other joint tissues modifications like subchondral bone sclerosis. In this study, we used a proteomic approach to compare secretome of osteoblast isolated from sclerotic (SC) or non sclerotic (NSC) area of OA subchondral bone. DESIGN: Secretome was analyzed using differential quantitative and relative label free analysis on nanoUPLC G2 HDMS system. mRNA of the more differentially secreted proteins were quantified by RT-PCR in cell culture from 5 other patients...
2018: PloS One
Guang Shi, Jun-Wei Zhao, Xiao-Xu Sun, Jun-Fen Ma, Pan Wang, Fu-Cheng He, Liang Ming
The interaction between inflammatory processes and a hypercoagulant state may aggravate the severity of asthma and stimulate the airway remodeling of asthma. The aim of the current study was to evaluate the association between the negative inflammatory regulator tumor necrosis factor α induced protein-8 like-2 (TIPE2) and the coagulating substances tissue factor (TF) and thrombospondin-1 (TSP-1) in patients with bronchial asthma. Compared with healthy controls, TIPE2 expression was significantly downregulated, whereas TF expression was upregulated in the peripheral blood mononuclear cells (PBMCs) of patients with bronchial asthma...
April 2018: Experimental and Therapeutic Medicine
Sanjay Tewari, George Renney, John Brewin, Kate Gardner, Fenella Kirkham, Baba Inusa, James E Barrett, Stephan Menzel, Swee Lay Thein, Malcolm Ward, David C Rees
Silent cerebral infarction is the commonest neurological abnormality in children with sickle cell anemia, affecting 30-40% 14 year olds. There are no known biomarkers to identify children with silent cerebral infarcts and the pathological basis is also unknown. We used an unbiased proteomic discovery approach to identify plasma proteins differing in concentration between children with and without silent cerebral infarcts. Clinical parameters and plasma samples were analysed from 51 children (mean age 11.8 years, range 6-18) with sickle cell anemia (HbSS)...
March 15, 2018: Haematologica
Yue Kui Jian, Huan Ye Zhu, Xing Lin Wu, Bo Li
Osteosarcomas, especially those with metastatic or unresectable disease, have limited treatment options. The antitumoreffects of pharmacologic inhibitors of angiogenesis in osteosarcomas are hampered in patients by the rapid development of tumor resistance, notably through increased invasiveness and accelerated metastasis. Here, we demonstrated that thrombospondin 1 (TSP1) is a potent inhibitor of osteosarcoma cells MG-63 growth and metastasis. Moreover, we demonstrate up-regulation of TSP-1 facilitated expression of vasculostatin in MG-63 cells...
March 14, 2018: Oncology Research
George Inana, Christopher Murat, Weijun An, Xiang Yao, Ian R Harris, Jing Cao
BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly characterized by retinal pigment epithelium (RPE) degeneration with accumulation of abnormal intracellular deposits (lipofuscin) and photoreceptor death. RPE is vital for the retina and integrity of photoreceptors through its phagocytic function which is closely linked to formation of lipofuscin through daily phagocytosis of discarded photoreceptor outer segments (POS). Although phagocytosis has been implicated in AMD, it has not been directly shown to be altered in AMD...
March 13, 2018: Journal of Translational Medicine
Chantal C Clark, Mirjam M Mebius, Steven de Maat, Aloysius G M Tielens, Philip G de Groot, Rolf T Urbanus, Rob Fijnheer, Bouke P C Hazenberg, Jaap J van Hellemond, Coen Maas
ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) cleaves von Willebrand Factor (VWF) multimers to control their thrombogenicity. The fibrinolytic enzyme plasmin can cleave VWF in a similar manner. However, plasmin can also cleave ADAMTS13, which ultimately inactivates it. This leaves the overall role of plasmin in primary haemostasis uncertain.We investigated the combined molecular effects of plasmin on VWF and ADAMTS13. We first identified that plasmin destroys FRETS-VWF73 substrate by cleaving the ADAMTS13 binding region in a buffered system...
March 2018: Thrombosis and Haemostasis
Vojtech Franc, Jing Zhu, Albert J R Heck
The human complement hetero-trimeric C8αβγ (C8) protein assembly (~ 150 kDa) is an important component of the membrane attack complex (MAC). C8 initiates membrane penetration and coordinates MAC pore formation. Here, we charted in detail the structural micro-heterogeneity within C8, purified from human plasma, combining high-resolution native mass spectrometry and (glyco)peptide-centric proteomics. The intact C8 proteoform profile revealed at least ~ 20 co-occurring MS signals. Additionally, we employed ion exchange chromatography to separate purified C8 into four distinct fractions...
March 12, 2018: Journal of the American Society for Mass Spectrometry
Seokjo Kang, Jayoung Byun, Sung Min Son, Inhee Mook-Jung
Alzheimer's disease (AD) is often characterized by the impairment of mitochondrial function caused by excessive mitochondrial fragmentation. Thrombospondin-1 (TSP-1), which is primarily secreted from astrocytes in the central nervous system (CNS), has been suggested to play a role in synaptogenesis, spine morphology, and synaptic density of neurons. In this study, we investigate the protective role of TSP-1 in the recovery of mitochondrial morphology and function in amyloid β (Aβ)-treated mouse hippocampal neuroblastoma cells (HT22)...
December 2018: Cell Death Discovery
Luciana Teixeira de Siqueira, Marcela Silvestre Outtes Wanderley, Roberto Afonso da Silva, Adriana da Silva Andrade Pereira, José Luiz de Lima Filho, Álvaro Antônio Bandeira Ferraz
BACKGROUND: Obesity has been associated with the development of various types of cancer. Biomarker studies may provide molecular level knowledge of the factors involved in this association, improving clinical practice through new methods of prevention and treatment. PURPOSE: The present study aimed to analyze proteins found in the plasma of obese patients prior to and 6 months after bariatric surgery, using body mass index (BMI) and percentage total weight loss (%TWL) to evaluate, in a prospective manner, the effects of weight loss on the regulation of proteins related to the appearance of tumors...
March 10, 2018: Obesity Surgery
Yuka Matsunaga, Masataka Ishimura, Hazumu Nagata, Kiyoshi Uike, Tadamune Kinjo, Masayuki Ochiai, Kenichiro Yamamura, Hidetoshi Takada, Yoshihisa Tanoue, Masaki Hayakawa, Masanori Matsumoto, Toshiro Hara, Shouichi Ohga
BACKGROUND: Thrombotic microangiopathies (TMA) are microvascular occlusive disorders characterized by systemic or intrarenal platelet aggregation, thrombocytopenia, and red cell fragmentation. Post-operative TMA mostly occurs in adult patients with cardiovascular surgery, with the distinct pathophysiology from classical thrombotic thrombocytopenic purpura (TTP) although the exact pathophysiology remains unclear. CASE PRESENTATION: A one-month-old infant developed TMA after the initial surgery of double outlet right ventricle...
February 7, 2018: Pediatrics and Neonatology
A Tuğşen Aydemir, Meltem Alper, Feray Köçkar
ADAMTS3 is a member of procollagen N-proteinase subfamily of ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) gene family. It has an important function in the procollagen maturation process. The removal of N-peptidases is required for the accurate processing of fibrillar collagens. Otherwise, several disorders can occur that is related with the collagenous tissues. ADAMTS3 mainly maturates type II collagen molecule which is the main component of the bone and cartilage. There are several expression studies about ADAMTS3 gene however its transcriptional regulation has not been lightened up, yet...
March 5, 2018: Gene
Nataliya Rohr-Udilova, Eva Bauer, Gerald Timelthaler, Robert Eferl, Klaus Stolze, Matthias Pinter, Martha Seif, Hubert Hayden, Thomas Reiberger, Rolf Schulte-Hermann, Markus Peck-Radosavljevic, Dagmar Stoiber, Michael Trauner
Insufficient supplementation with the micronutrient selenium and persistent hepatic inflammation predispose to hepatocellular carcinoma (HCC). Inflammation-associated reactive oxygen species attack membrane lipids and form lipid hydroperoxides able to propagate oxidative hepatic damage. Selenium-containing enzyme glutathione peroxidase 4 (GPx4) antagonizes this damage by reducing lipid hydroperoxides to respective hydroxides. However, the role of GPx4 in HCC remains elusive. We generated two human HCC cell lines with stable overexpression of GPx4, performed xenotransplantation into NOD...
February 9, 2018: Oncotarget
J Zhang, K X Liu, W Gao, X S Xie
Objective: To establish a rat model of paraquat (PQ) -induced pulmonary fibrosis and observe the changes in thrombospondin-1 (TSP-1) and its receptor CD47 in lung tissue, and to investigate their roles in the pathogenesis of PQ-induced pulmonary fibrosis. Methods: Fifty-four clean adult male Sprague-Dawley rats were randomly divided into normal control group ( n =6) and 2 h, 12 h, 1 d, 3 d, 7 d, and 14 d PQ poisoning groups ( n =8 per group). A rat model of PQ poisoning was established by a single gavage of 20 wt...
December 20, 2017: Chinese Journal of Industrial Hygiene and Occupational Diseases
Shuang Deng, Jian-Lin Zhou, Hao Peng, Hong-Song Fang, Feng Liu, Jin-Qing Weng
In the pathophysiology of osteoarthritis (OA), articular cartilage degeneration exhibits a significant role. Vascular endothelial growth factor (VEGF) is considered to be an effective angiogenic factor and a crucial regulator of articular cartilage degeneration in the development of OA. Therefore, the present study aimed to investigate the underlying influences of exogenous VEGF on articular cartilage degeneration in OA model rat. A total of 24 male Sprague‑Dawley rats were randomly allocated into 3 groups...
February 28, 2018: Molecular Medicine Reports
Shangkun Tang, Qian Tang, Jialei Jin, Gang Zheng, Jianchen Xu, Wu Huang, Xiaobin Li, Ping Shang, Haixiao Liu
Osteoarthritis (OA), which is characterized by progressive degradation of the articular cartilage, is the most prevalent form of human arthritis. Accumulating evidence has shown that polydatin (PD) exerts special biological functions in a variety of diseases. However, whether it protects against OA development has remained unknown. Here, we investigated the anti-inflammatory and chondroprotective effects of PD on interleukin (IL)-1β-induced human osteoarthritic chondrocytes and in the surgical destabilization of medial meniscus mouse (DMM) OA models...
February 27, 2018: Food & Function
Lubna Kouser, Basudev Paudyal, Anuvinder Kaur, Gudrun Stenbeck, Lucy A Jones, Suhair M Abozaid, Cordula M Stover, Emmanuel Flahaut, Robert B Sim, Uday Kishore
Development of nanoparticles as tissue-specific drug delivery platforms can be considerably influenced by the complement system because of their inherent pro-inflammatory and tumorigenic consequences. The complement activation pathways, and its recognition subcomponents, can modulate clearance of the nanoparticles and subsequent inflammatory response and thus alter the intended translational applications. Here, we report, for the first time, that human properdin, an upregulator of the complement alternative pathway, can opsonize functionalized carbon nanotubes (CNTs) via its thrombospondin type I repeat (TSR) 4 and 5...
2018: Frontiers in Immunology
Baisheng Yuan, Wei Ji, Bing Fan, Binglei Zhang, Yulin Zhao, Jianmin Li
The aim of this study is to determine the contribution of 2 single nucleotide polymorphisms (SNPs) in thrombospondin 2 (THBS2) gene to the development of intervertebral disc degeneration (IDD) in a Chinese Han population.We studied 138 patients with radiographically proven IDD and 136 healthy volunteers with no history of back problems. Magnetic resonance images (MRIs) were obtained for all the patients and controls. Image evaluation for IDD was performed to evaluate the severity of IDD. All patients and controls were genotyped for rs6422747 and rs6422748...
January 2018: Medicine (Baltimore)
Nozomi Aibara, Kaname Ohyama, Masaaki Hidaka, Naoya Kishikawa, Yasuyoshi Miyata, Mitsuhisa Takatsuki, Susumu Eguchi, Naotaka Kuroda
Liver transplantation is a life-saving procedure for many end-stage liver diseases; however, rejection after transplantation is still occurs in some recipients. The most common form of rejection is T cell-related acute cellular rejection (ACR). To understand the mechanism of rejection, it is necessary to identify immune targets. Since the development of B cell immunity depends upon concordant T cell immunity, we hypothesized that rejection-specific antigens in circulating immune complexes (CICs) may be present in the sera of recipients experiencing rejection, and as such, may be useful as diagnostic biomarkers for ACR...
February 22, 2018: Transplant Immunology
Lan Liu, Zhaoting Yang, Weidong Ni, Yanhua Xuan
BACKGROUND: A disintegrin and metalloprotease with thrombospondin motif (ADAMTS) enzymes play important roles in cell functions including adhesion, invasion, migration, and proliferation. ADAMTS-6 is a member of the ADAMTS family; reports of its relationship with esophageal squamous cell carcinoma (ESCC) progression are rare. It is unclear whether ADAMTS-6 could be an independent ESCC biomarker. METHODS: ADAMTS-6 expression was detected by immunohistochemistry (IHC) in 171 paraffin-embedded ESCC specimens; relationships with patients' clinicopathological features and Twist-1 expression were analyzed by the Pearson Chi-square method, respectively...
February 20, 2018: Experimental and Molecular Pathology
Gang Zheng, Yu Zhan, Qian Tang, Tianhe Chen, Fanghong Zheng, Haoli Wang, Jianle Wang, Dengying Wu, Xiaobing Li, Ying Zhou, Xiaobin Wang, Yaosen Wu, Yifei Zhou, Huazi Xu, Naifeng Tian, Xiaolei Zhang
Osteoarthritis (OA) is an age-related degenerative disease and is the fourth major cause of disability, but there are no effective therapies because of its complex pathology and the side effects of the drugs. Previous research demonstrated that inflammation and ECM degradation play major roles in OA development. Monascin is an azaphilonoid pigment extracted from Monascus-fermented rice with a potential anti-inflammatory effect reported in various preclinical studies. In the present study, we investigated the protectiveness of monascin on interleukin (IL)-1β-induced mouse chondrocytes and surgical destabilization of the medial meniscus mouse (DMM) OA models...
February 23, 2018: Food & Function
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