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Bone marrow dysfunction

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https://www.readbyqxmd.com/read/28935578/abin1-determines-severity-of-glomerulonephritis-via-activation-of-intrinsic-glomerular-inflammation
#1
Erik A Korte, Dawn J Caster, Michelle T Barati, Min Tan, Shirong Zheng, Celine C Berthier, Frank C Brosius, Mark B Vieyra, Ryan M Sheehan, Michele Kosiewicz, Marcin Wysoczynski, Patrick M Gaffney, David J Salant, Kenneth R McLeish, David W Powell
Transcription factor NF-κB regulates expression of numerous genes that control inflammation and is activated in glomerular cells in glomerulonephritis (GN). We previously identified genetic variants for a NF-κB regulatory, ubiquitin binding protein ABIN1 as risk factors for GN in systemic autoimmunity. The goal here was to define glomerular inflammatory events controlled by ABIN1 function in GN. Nephrotoxic serum nephritis was induced in wild-type (WT) and ubiquitin binding deficient ABIN1[D485N] mice; and renal pathophysiology and glomerular inflammatory phenotypes were assessed...
September 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28928910/phase-i-ii-randomized-controlled-trial-of-autologous-bone-marrow-derived-mesenchymal-stem-cell-therapy-for-chronic-stroke
#2
Kam Sze Tsang, Chi Ping Stephanie Ng, Xian Lun Zhu, George Kwok Chu Wong, Gang Lu, Anil Tejbhan Ahuja, Ka Sing Lawrence Wong, Ho Keung Ng, Wai Sang Poon
AIM: To examine the safety and efficacy of mesenchymal stem cell (MSC) therapy for intracerebral haemorrhage with neurological dysfunctions for a year. METHODS: MSC were ex vivo expanded from 29 mL (17-42 mL) autologous bone marrow. Patients were randomized to have two intravenous injections of autologous MSC or placebos in four weeks apart. Neurological functions and clinical outcomes were monitored before treatment and at 12(th), 16(th), 24(th), 36(th) and 60(th) week upon completion of the treatment...
August 26, 2017: World Journal of Stem Cells
https://www.readbyqxmd.com/read/28899386/improved-clinical-outcome-measures-of-knee-pain-and-function-with-concurrent-resolution-of-subchondral-bone-marrow-edema-lesion-and-joint-effusion-in-an-osteoarthritic-patient-following-pentosan-polysulphate-sodium-treatment-a-case-report
#3
Matthew J Sampson, Margie Kabbani, Ravi Krishnan, Michael Nganga, Annika Theodoulou, Jeganath Krishnan
BACKGROUND: At present, there are no registered products for the treatment of subchondral Bone Marrow Edema Lesion (BML) and associated knee pain. Patients who do not respond to current anti-inflammatory therapies are left with limited treatment options, and may resort to operative management with Total Knee Arthroplasty (TKA). We report the use of Pentosan Polysulphate Sodium (PPS) for the treatment of BMLs of the knee. CASE PRESENTATION: We report the case of a 70-year-old female with knee osteoarthritis presenting with a high level of knee pain, scoring 8 on the Numerical Rating Scale (NRS), and functional limitation demonstrating a poor Lysholm Knee Score of 37...
September 12, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28881756/mm-bmscs-induce-na%C3%A3-ve-cd4-t-lymphocytes-dysfunction-through-fibroblast-activation-protein-%C3%AE
#4
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...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28872489/a-case-of-pure-red-cell-aplasia-during-nivolumab-therapy-for-cardiac-metastatic-melanoma
#5
Akihiko Yuki, Tatsuya Takenouchi, Sumiko Takatsuka, Takuro Ishiguro
Nivolumab is an antibody against programmed cell death 1 and functions as an immune checkpoint inhibitor for various malignancies, including unresectable melanomas. Nivolumab causes several immune-related adverse events, which typically include skin rash, pneumonitis, thyroid dysfunction, hepatitis, and colitis; in rare cases, anemia may be present. There are several reports of autoimmune hemolytic anemia that has developed in response to nivolumab; however, there are few reports of pure red cell aplasia (PRCA)...
September 1, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28864889/methylglyoxal-derived-advanced-glycation-end-products-contribute-to-negative-cardiac-remodeling-and-dysfunction-post-myocardial-infarction
#6
Nick J R Blackburn, Branka Vulesevic, Brian McNeill, Cagla Eren Cimenci, Ali Ahmadi, Mayte Gonzalez-Gomez, Aleksandra Ostojic, Zhiyuan Zhong, Michael Brownlee, Paul J Beisswenger, Ross W Milne, Erik J Suuronen
Advanced glycation end-products (AGEs) have been associated with poorer outcomes after myocardial infarction (MI), and linked with heart failure. Methylglyoxal (MG) is considered the most important AGE precursor, but its role in MI is unknown. In this study, we investigated the involvement of MG-derived AGEs (MG-AGEs) in MI using transgenic mice that over-express the MG-metabolizing enzyme glyoxalase-1 (GLO1). MI was induced in GLO1 mice and wild-type (WT) littermates. At 6 h post-MI, mass spectrometry revealed that MG-H1 (a principal MG-AGE) was increased in the hearts of WT mice, and immunohistochemistry demonstrated that this persisted for 4 weeks...
September 1, 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28864152/deformation-analysis-of-myocardial-layers-detects-early-cardiac-dysfunction-after-chemotherapy-in-bone-marrow-transplantation-patients-a-continuous-and-additive-cardiotoxicity-process
#7
Ioannis A Paraskevaidis, George Makavos, Panagiotis Tsirigotis, Panagiotis Psarogiannakopoulos, John Parissis, Konstantinos Gkirkas, Ilias Pessach, Ignatios Ikonomidis
BACKGROUND: Chemotherapy-induced cardiotoxicity has not been extensively validated in bone marrow transplantation (BMT) patients. Speckle-tracking echocardiography is a sensitive method for the detection of subclinical cardiac dysfunction. METHODS: Cardiac function was prospectively assessed in 80 patients (44 men; mean age, 45 ± 11 years) after BMT for non-Hodgkin's lymphoma and acute or chronic myeloid leukemia by means of various echocardiographic techniques...
August 29, 2017: Journal of the American Society of Echocardiography
https://www.readbyqxmd.com/read/28835616/leukocytic-toll-like-receptor-2-deficiency-preserves-cardiac-function-and-reduces-fibrosis-in-sustained-pressure-overload
#8
Jiong-Wei Wang, Magda S C Fontes, Xiaoyuan Wang, Suet Yen Chong, Elise L Kessler, Ya-Nan Zhang, Judith J de Haan, Fatih Arslan, Saskia C A de Jager, Leo Timmers, Toon A B van Veen, Carolyn S P Lam, Dominique P V de Kleijn
An involement of Toll-like receptor 2 (TLR2) has been established in cardiac dysfunction after acute myocardial infarction; however, its role in chronic pressure overload is unclear. We sought to evaluate the role of TLR2 in cardiac hypertrophy, fibrosis and dysfunction in sustained pressure overload. We induced pressure overload via transverse aortic constriction (TAC) in TLR2(-/-) and wild type (WT) mice, and followed temporal changes over 8 weeks. Despite similar increases in heart weight, left ventricular (LV) ejection fraction (EF) and diastolic function (mitral E/A ratio) were preserved in TLR2(-/-) mice but impaired in WT mice following TAC...
August 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28827474/p2y12-receptor-promotes-pressure-overload-induced-cardiac-remodeling-via-platelet-driven-inflammation-in-mice
#9
Lujin Wu, Fujie Zhao, Meiyan Dai, Huaping Li, Chen Chen, Jiali Nie, Peihua Wang, Dao Wen Wang
Inflammation plays a critical role in adverse cardiac remodeling and heart failure. The P2y12 receptor is one of the predominant activating receptors for platelets, thus initiating inflammatory responses under various diseases. In this study, we investigated the functional significance of P2y12-mediated platelet activation in pressure overload-induced cardiac remodeling. Notably, P2y12 knockout (P2y12(-)(/-)) mice exhibited suppressed transverse aortic constriction-induced changes in cardiac hypertrophy, collagen synthesis, inflammatory cell recruitment, and cardiac dysfunction...
August 21, 2017: Hypertension
https://www.readbyqxmd.com/read/28827409/genomic-and-functional-integrity-of-the-hematopoietic-system-requires-tolerance-of-oxidative-dna-lesions
#10
Ana Martín-Pardillos, Anastasia Tsaalbi-Shtylik, Si Chen, Seka Lazare, Ronald P van Os, Albertina Dethmers-Ausema, Nima Borhan Fakouri, Matthias Bosshard, Rossana Aprigliano, Barbara van Loon, Daniela C F Salvatori, Keiji Hashimoto, Celia Dingemanse-van der Spek, Masaaki Moriya, Lene Juel Rasmussen, Gerald de Haan, Marc H G P Raaijmakers, Niels de Wind
Endogenous DNA damage is causally associated with the functional decline and transformation of stem cells that characterize ageing. DNA lesions that have escaped DNA repair can induce replication stress and genomic breaks that induce senescence and apoptosis. It is not clear how stem and proliferating cells cope with accumulating endogenous DNA lesions, and how these ultimately affect the physiology of cells and tissues. Here we have addressed these questions by investigating the hematopoietic system of mice deficient for Rev1, a core factor in DNA translesion synthesis (TLS), the post-replicative bypass of damaged nucleotides...
August 21, 2017: Blood
https://www.readbyqxmd.com/read/28826860/the-microenvironment-in-myelodysplastic-syndromes-niche-mediated-disease-initiation-and-progression
#11
REVIEW
Allison J Li, Laura M Calvi
Myelodysplastic syndromes (MDSs) are clonal disorders of hematopoietic stem and progenitor cells and represent the most common cause of acquired marrow failure. Hallmarked by ineffective hematopoiesis, dysplastic marrow, and risk of transformation to acute leukemia, MDS remains a poorly treated disease. Although identification of hematopoietic aberrations in human MDS has contributed significantly to our understanding of MDS pathogenesis, evidence now identify the bone marrow microenvironment (BMME) as another key contributor to disease initiation and progression...
August 18, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28822917/coexistence-of-aberrant-hematopoietic-and-stromal-elements-in-myelodysplastic-syndromes
#12
Salar Abbas, Archana Kini, Vivi M Srivastava, Marie Therese M, Sukesh C Nair, Aby Abraham, Vikram Mathews, Biju George, Sanjay Kumar, Aparna Venkatraman, Alok Srivastava
Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic disorders related to hematopoietic stem and progenitor cell dysfunction. Several studies have shown the role of the bone marrow microenvironment in regulating hematopoietic stem, and progenitor function and their individual abnormalities have been associated with disease pathogenesis. In this study, we simultaneously evaluated hematopoietic stem cells (HSC), hematopoietic stem progenitor cells (HSPCs) and different stromal elements in a cohort of patients with MDS-refractory cytopenia with multilineage dysplasia (RCMD)...
August 9, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28821815/epac1-deficient-mice-have-bleeding-phenotype-and-thrombocytes-with-decreased-gpib%C3%AE-expression
#13
Gyrid Nygaard, Lars Herfindal, Kathrine S Asrud, Ronja Bjørnstad, Reidun K Kopperud, Eystein Oveland, Frode S Berven, Lene Myhren, Erling A Hoivik, Turid Helen Felli Lunde, Marit Bakke, Stein O Døskeland, Frode Selheim
Epac1 (Exchange protein directly activated by cAMP 1) limits fluid loss from the circulation by tightening the endothelial barrier. We show here that Epac1(-/-) mice, but not Epac2(-/-) mice, have prolonged bleeding time, suggesting that Epac1 may limit fluid loss also by restraining bleeding. The Epac1(-/-) mice had deficient in vitro secondary hemostasis. Quantitative comprehensive proteomics analysis revealed that Epac1(-/-) mouse platelets (thrombocytes) had unbalanced expression of key components of the glycoprotein Ib-IX-V (GPIb-IX-V) complex, with decrease of GP1bβ and no change of GP1bα...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819363/combined-analysis-of-endothelial-hematopoietic-and-mesenchymal-stem-cell-compartments-shows-simultaneous-but-independent-effects-of-age-and-heart-disease
#14
Carine Ghem, Lucinara Dadda Dias, Roberto Tofani Sant'Anna, Renato A K Kalil, Melissa Markoski, Nance Beyer Nardi
Clinical trials using stem cell therapy for heart diseases have not reproduced the initial positive results obtained with animal models. This might be explained by a decreased regenerative capacity of stem cells collected from the patients. This work aimed at the simultaneous investigation of endothelial stem/progenitor cells (EPCs), mesenchymal stem/progenitor cells (MSCs), and hematopoietic stem/progenitor cells (HSCs) in sternal bone marrow samples of patients with ischemic or valvular heart disease, using flow cytometry and colony assays...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28809938/perinatal-testosterone-exposure-potentiates-vascular-dysfunction-by-er%C3%AE-suppression-in-endothelial-progenitor-cells
#15
Weiguo Xie, Mingming Ren, Ling Li, Yin Zhu, Zhigang Chu, Zhigang Zhu, Qiongfang Ruan, Wenting Lou, Haimou Zhang, Zhen Han, Xiaodong Huang, Wei Xiang, Tao Wang, Paul Yao
Recent clinical cohort study shows that testosterone therapy increases cardiovascular diseases in men with low testosterone levels, excessive circulating androgen levels may play a detrimental role in the vascular system, while the potential mechanism and effect of testosterone exposure on the vascular function in offspring is still unknown. Our preliminary results showed that perinatal testosterone exposure in mice induces estrogen receptor β (ERβ) suppression in endothelial progenitor cells (EPCs) in offspring but not mothers, while estradiol (E2) had no effect...
2017: PloS One
https://www.readbyqxmd.com/read/28807051/mesenchymal-stromal-cells-ameliorate-oxidative-stress-induced-islet-endothelium-apoptosis-and-functional-impairment-via-wnt4-%C3%AE-catenin-signaling
#16
Lingshu Wang, Li Qing, He Liu, Na Liu, Jingting Qiao, Chen Cui, Tianyi He, Ruxing Zhao, Fuqiang Liu, Fei Yan, Chuan Wang, Kai Liang, Xinghong Guo, Ying H Shen, Xinguo Hou, Li Chen
BACKGROUND: Islet dysfunction and destruction are the common cause for both type 1 and type 2 diabetes mellitus (T2DM). The islets of Langerhans are highly vascularized miniorgans, and preserving the structural integrity and full function of the microvascular endothelium is vital for protecting the islets from the infiltration of immune cells and secondary inflammatory attack. Mesenchymal stromal cell (MSC)-based therapies have been proven to promote angiogenesis of the islets; however, the underlying mechanism for the protective role of MSCs in the islet endothelium is still vague...
August 14, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28804562/premature-exhaustion-of-mesenchymal-stromal-cells-from-myelodysplastic-syndrome-patients
#17
Yanbin Pang, Chengxin Deng, Suxia Geng, Jianyu Weng, Peilong Lai, Pengjun Liao, Lingji Zeng, Zesheng Lu, Jing Zhang, Xin Du
Myelodysplastic syndrome (MDS) predominantly occurs in aging people. Over the past decades, the cellular and molecular pathologies of MDS cells have been intensively investigated. However, how the bone marrow stromal niches are altered during MDS development remains elusive. In this study, we attempted to isolate and characterize mesenchymal stromal cells (MSCs) from 30 MDS patients. We observed that only 9/30 bone marrow aspirations from MDS patients successfully formed a monolayer in vitro, while 17/17 bone marrow aspirations from normal donors (median age 45 years, range: 22-73 years) succeeded in this process...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28804458/induced-pluripotent-stem-cells-derived-mesenchymal-stem-cells-attenuate-cigarette-smoke-induced-cardiac-remodeling-and-dysfunction
#18
Yingmin Liang, Xiang Li, Yuelin Zhang, Sze Chun Yeung, Zhe Zhen, Mary S M Ip, Hung Fat Tse, Qizhou Lian, Judith C W Mak
The strong relationship between cigarette smoking and cardiovascular disease (CVD) has been well-documented, but the mechanisms by which smoking increases CVD risk appear to be multifactorial and incompletely understood. Mesenchymal stem cells (MSCs) are regarded as an important candidate for cell-based therapy in CVD. We hypothesized that MSCs derived from induced pluripotent stem cell (iPSC-MSCs) or bone marrow (BM-MSCs) might alleviate cigarette smoke (CS)-induced cardiac injury. This study aimed to investigate the effects of BM-MSCs or iPSC-MSCs on CS-induced changes in serum and cardiac lipid profiles, oxidative stress and inflammation as well as cardiac function in a rat model of passive smoking...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28804041/cell-therapy-as-a-new-approach-to-the-treatment-of-posttraumatic-syringomyelia
#19
Jesús Vaquero, Rasha Hassan, Cecilia Fernández, Gregorio Rodríguez-Boto, Mercedes Zurita
BACKGROUND: Cell transplantation with autologous bone marrow-derived mesenchymal stromal cells (MSCs) seems to be a therapeutic promise for patients with established spinal cord injury (SCI), achieving improvement in their quality of life, but there is no experience about the application of this type of cell therapy in patients suffering posttraumatic syringomyelia. OBJECTIVE: To study the possible utility of cell therapy with autologous MSCs in posttraumatic syringomyelia...
August 10, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28797104/increased-microrna-93-5p-inhibits-osteogenic-differentiation-by-targeting-bone-morphogenetic-protein-2
#20
Ying Zhang, Qiu-Shi Wei, Wei-Bin Ding, Lei-Lei Zhang, Hui-Chao Wang, Ying-Jie Zhu, Wei He, Yu-Na Chai, You-Wen Liu
BACKGROUND AND PURPOSE: Trauma-induced osteonecrosis of the femoral head (TIONFH) is a major complication of femoral neck fractures. Degeneration and necrosis of subchondral bone can cause collapse, which results in hip joint dysfunction in patients. The destruction of bone metabolism homeostasis is an important factor for osteonecrosis. MicroRNAs (miRNAs) have an important role in regulating osteogenic differentiation, but the mechanisms underlying abnormal bone metabolism of TIONFH are poorly understood...
2017: PloS One
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