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Bone marrow dysfunction

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https://www.readbyqxmd.com/read/29786072/mptp-driven-nlrp3-inflammasome-activation-in-microglia-plays-a-central-role-in-dopaminergic-neurodegeneration
#1
Eunju Lee, Inhwa Hwang, Sangjun Park, Sujeong Hong, Boreum Hwang, Yoeseph Cho, Junghyun Son, Je-Wook Yu
Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN) and the reduction of dopamine levels in the striatum. Although details of the molecular mechanisms underlying dopaminergic neuronal death in PD remain unclear, neuroinflammation is also considered a potent mediator in the pathogenesis and progression of PD. In the present study, we present evidences that microglial NLRP3 inflammasome activation is critical for dopaminergic neuronal loss and the subsequent motor deficits in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29784961/sarcodon-imbricatus-polysaccharides-improve-mouse-hematopoietic-function-after-cyclophosphamide-induced-damage-via-g-csf-mediated-jak2-stat3-pathway
#2
Xue Wang, Qiubo Chu, Xue Jiang, Yue Yu, Libian Wang, Yaqi Cui, Jiahui Lu, Lirong Teng, Di Wang
Sarcodon imbricatus, a rare medicinal and edible fungus, has various pharmacological bioactivities. We investigated the effects of S. imbricatus polysaccharides (SIPS) on hematopoietic function and identified the underlying mechanisms using in vitro experiments with CHRF, K562, and bone marrow mononuclear cells (BMMNCs) and in vivo experiments with a mouse model of cyclophosphamide-induced hematopoietic dysfunction. We found that SIPS induced proliferation and differentiation of CHRF and K562 cells and upregulated the expression of hematopoietic-related proteins, including p90 ribosomal S6 kinases (RSK1p90), c-Myc, and ETS transcription factor, in the two cell lines...
May 21, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29783667/bone-marrow-defects-and-platelet-function-a-focus-on-mds-and-cll
#3
REVIEW
Sarah Luu, Elizabeth E Gardiner, Robert K Andrews
The bloodstream typically contains >500 billion anucleate circulating platelets, derived from megakaryocytes in the bone marrow. This review will focus on two interesting aspects of bone marrow dysfunction and how this impacts on the quality of circulating platelets. In this regard, although megakaryocytes are from the myeloid lineage leading to granulocytes (including neutrophils), erythrocytes, and megakaryocytes/platelets, recent evidence has shown that defects in the lymphoid lineage leading to B cells, T cells, and natural killer (NK) cells also result in abnormal circulating platelets...
May 18, 2018: Cancers
https://www.readbyqxmd.com/read/29777508/endothelial-progenitor-cells-in-heart-failure-an-authentic-expectation-for-potential-future-use-and-a-lack-of-universal-definition
#4
REVIEW
Andie H Djohan, Ching-Hui Sia, Poay Sian Lee, Kian-Keong Poh
Congestive heart failure (CHF) is a prevalent disease (especially among the elderly) with high mortality and morbidity rates. The pathological hallmark of CHF is a loss of cardiomyocytes leading to cardiac fibrosis and dysfunctional cardiac remodeling, which culminates in organ failure. Endothelial progenitor cells (EPCs) are bone marrow-derived cells that contribute to maintenance of the integrity of endothelial wall and protect ischemic myocardium through forming new blood vessels (vasculogenesis) or proliferation of pre-existing vasculature (angiogenesis)...
May 17, 2018: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/29772353/cardiac-profile-of-chimeric-antigen-receptor-car-t-cell-therapy-in-children-a-single-institution-experience
#5
Danielle Burstein, Shannon Maude, Stephen Grupp, Heather Griffis, Joseph Rossano, Kimberly Lin
BACKGROUND: Immunotherapy with chimeric antigen receptor (CAR)-modified T-cells targeting CD19 for pediatric acute lymphoblastic leukemia (ALL) has demonstrated significant efficacy. The principle toxicity is cytokine release syndrome with resultant hypotension. However, the spectrum of cardiovascular effects associated with CAR T-cell therapy has not been systematically evaluated. METHODS: We reviewed all patients who received CD19-directed CAR T-cells at the Children's Hospital of Philadelphia between April 2012 and September 2016...
May 14, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29768025/the-post-injury-inflammatory-state-and-the-bone-marrow-response-to-anemia
#6
Tyler J Loftus, Juan C Mira, Elizabeth S Miller, Kolenkode B Kannan, Jessica M Plazas, Daniel Delitto, Julie A Stortz, Jennifer E Hagen, Hari K Parvataneni, Kalia K Sadasivan, Scott C Brakenridge, Frederick A Moore, Lyle L Moldawer, Philip A Efron, Alicia M Mohr
RATIONALE: The pathophysiology of persistent injury-associated anemia is incompletely understood, and human data are sparse. OBJECTIVE: To translate pre-clinical findings by characterizing injury-associated anemia among critically ill trauma patients. This study compared elective hip repair patients with an acute stress response to severely injured trauma patients with a prolonged stress response and evaluated the bone marrow response to anemia. METHODS: A translational prospective observational cohort study comparing severely injured, blunt trauma patients who had operative fixation of a hip or femur fracture (n=17) with elective hip repair patients (n=22) and healthy donors (n=8)...
May 16, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29767474/mesenchymal-stromal-cells-from-shwachman-diamond-syndrome-patients-fail-to-recreate-a-bone-marrow-niche-in-vivo-and-exhibit-impaired-angiogenesis
#7
Donatella Bardelli, Erica Dander, Cristina Bugarin, Claudia Cappuzzello, Alice Pievani, Grazia Fazio, Paolo Pierani, Paola Corti, Piero Farruggia, Carlo Dufour, Simone Cesaro, Marco Cipolli, Andrea Biondi, Giovanna D'Amico
Shwachman-Diamond syndrome (SDS) is a rare multi-organ recessive disease mainly characterised by pancreatic insufficiency, skeletal defects, short stature and bone marrow failure (BMF). As in many other BMF syndromes, SDS patients are predisposed to develop a number of haematopoietic malignancies, particularly myelodysplastic syndrome and acute myeloid leukaemia. However, the mechanism of cancer predisposition in SDS patients is only partially understood. In light of the emerging role of mesenchymal stromal cells (MSCs) in the regulation of bone marrow homeostasis, we assessed the ability of MSCs derived from SDS patients (SDS-MSCs) to recreate a functional bone marrow niche, taking advantage of a murine heterotopic MSC transplant model...
May 16, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29765083/adeno-associated-virus-vector-mediated-interleukin-10-induction-prevents-vascular-inflammation-in-a-murine-model-of-kawasaki-disease
#8
Jun Nakamura, Sachiko Watanabe, Hiroaki Kimura, Motoi Kobayashi, Tadayoshi Karasawa, Ryo Kamata, Fumitake Usui-Kawanishi, Ai Sadatomo, Hiroaki Mizukami, Noriko Nagi-Miura, Naohito Ohno, Tadashi Kasahara, Seiji Minota, Masafumi Takahashi
Kawasaki disease (KD), which is the leading cause of pediatric heart disease, is characterized by coronary vasculitis and subsequent aneurysm formation. Although intravenous immunoglobulin therapy is effective for reducing aneurysm formation, a certain number of patients are resistant to this therapy. Because interleukin-10 (IL-10) was identified as a negative regulator of cardiac inflammation in a murine model of KD induced by Candida albicans water-soluble fraction (CAWS), we investigated the effect of IL-10 supplementation in CAWS-induced vasculitis...
May 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29761600/loss-of-angiotensin-converting-enzyme-2-exacerbates-diabetic-retinopathy-by-promoting-bone-marrow-dysfunction
#9
Yaqian Duan, Eleni Beli, Sergio Li Calzi, Judith L Quigley, Rehae C Miller, Leni Moldovan, Dongni Feng, Tatiana E Salazar, Sugata Hazra, Jude Al-Sabah, Kakarla V Chalam, Thao Le Phuong Trinh, Marya Meroueh, Troy A Markel, Matthew C Murray, Ruchi J Vyas, Michael E Boulton, Patricia Parsons-Wingerter, Gavin Y Oudit, Alexander G Obukhov, Maria B Grant
Angiotensin-converting enzyme 2 (ACE2) is the primary enzyme of the vasoprotective axis of the renin angiotensin system (RAS). We tested the hypothesis that loss of ACE2 would exacerbate diabetic retinopathy by promoting bone marrow dysfunction. ACE2-/y were crossed with Akita mice, a model of type 1 diabetes. When comparing the bone marrow of the ACE2-/y -Akita mice to that of Akita mice, we observed a reduction of both short-term and long-term repopulating hematopoietic stem cells, a shift of hematopoiesis towards myelopoiesis, and an impairment of lineage- c-kit+ hematopoietic stem/progenitor cell (HS/PC) migration and proliferation...
May 15, 2018: Stem Cells
https://www.readbyqxmd.com/read/29760547/comparison-of-the-effects-of-deferasirox-deferoxamine-and-combination-of-deferasirox-and-deferoxamine-on-an-aplastic-anemia-mouse-model-complicated-with-iron-overload
#10
Dijiong Wu, Xiaowen Wen, Wenbin Liu, Huijin Hu, Baodong Ye, Yuhong Zhou
Background and aim: Iron overload is commonly observed during the course of aplastic anemia (AA), which is believed to aggravate hematopoiesis, cause multiple organ dysfunction, lead to disease progression, and impair quality of life. Deferasirox (DFX) and deferoxamine (DFO) are among the most common iron chelation agents available in the clinical setting. The aim of this study was to investigate if the combination therapy with DFX and DFO is superior in hematopoietic recovery and iron chelation...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29754885/langerhans-cell-histiocytosis-in-children-history-classification-pathobiology-clinical-manifestations-and-prognosis
#11
REVIEW
Jolie Krooks, Milen Minkov, Angela G Weatherall
Langerhans cell histiocytosis (LCH) is an inflammatory neoplasia of myeloid precursor cells driven by mutations in the mitogen-activated protein kinase pathway. When disease involves the skin, LCH most commonly presents as a seborrheic dermatitis or eczematous eruption on the scalp and trunk. Evaluation for involvement of other organ systems is essential, because 9 of 10 patients presenting with cutaneous disease also have multisystem involvement. Clinical manifestations range from isolated disease with spontaneous resolution to life-threatening multisystem disease...
June 2018: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29748965/subchondroplasty-for-the-treatment-of-post-traumatic-bone-marrow-lesions-of-the-medial-femoral-condyle-in-a-pre-clinical-canine-model
#12
Olubusola A Brimmo, Chantelle C Bozynski, Cristi R Cook, Keiichi Kuroki, Seth L Sherman, Ferris M Pfeiffer, Aaron M Stoker, James L Cook
This study characterizes long-term outcomes associated with subchondroplasty (SCP) treatment for impact-induced subchondral bone marrow lesions (BML) using a validated pre-clinical canine model. With IACUC approval, purpose-bred research hounds (n = 16) underwent arthroscopic impact injury (40N) to both medial femoral condyles. At 3 months, functional assessments, arthroscopy and MRI were performed and knees (n = 32) were randomly assigned to SCP (3 mL fluoroscopically guided percutaneous injection of AccuFill BSM into BML bone defects) or sham injection (Control)...
May 10, 2018: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/29745272/extracellular-vesicles-in-hematological-malignancies
#13
Zofia Litwińska, Karolina Łuczkowska, Bogusław Machaliński
Extracellular vesicles (EVs) act as transporters that carry regulatory molecules between cells in physiologic and pathologic states; therefore, they play a crucial role in thrombosis, inflammation, angiogenesis, vascular dysfunction and other processes that affect the course of hematologic diseases. Within the tumor microenvironment, for example the leukemic bone marrow, EVs-mediated signaling may direct the activities of surrounding cells and act as a positive feedback loop that contributes to cancer progression...
May 10, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29743399/-successful-treatment-of-x-linked-sideroblastic-anemia-with-alas2-r452h-mutation-using-vitamin-b-6
#14
Toru Kawakami, Hideyuki Nakazawa, Fumihiro Kawakami, Shuji Matsuzawa, Yuriko Sudo, Hitoshi Sakai, Sayaka Nishina, Noriko Senoo, Yasushi Senoo, Michiharu Komatsu, Takeji Umemura, Tomomi Yamaguchi, Tomoki Kosho, Tohru Fujiwara, Hideo Harigae, Fumihiro Ishida
A 45-year-old man presented with fatigue and pain in the finger joints. Despite having a history of suspected sideroblastic anemia since the age of 18 years, he had not been followed up for years. Upon presentation, laboratory data revealed microcytic anemia and elevated serum ferritin levels. In addition, ringed sideroblasts were increased in the bone marrow. A liver biopsy revealed hemochromatosis and cirrhosis. Furthermore, genetic analysis revealed that he harbored the ALAS2 R452H mutation, leading to the diagnosis of X-linked sideroblastic anemia (XLSA)...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29740436/understanding-the-cellular-origin-of-the-mononuclear-phagocyte-system-sheds-light-on-the-myeloid-postulate-of-immune-paralysis-in-sepsis
#15
REVIEW
Lionel Franz Poulin, Corentin Lasseaux, Mathias Chamaillard
Sepsis, in essence, is a serious clinical condition that can subsequently result in death as a consequence of a systemic inflammatory response syndrome including febrile leukopenia, hypotension, and multiple organ failures. To date, such life-threatening organ dysfunction remains one of the leading causes of death in intensive care units, with an increasing incidence rate worldwide and particularly within the rapidly growing senior population. While most of the clinical trials are aimed at dampening the overwhelming immune response to infection that spreads through the bloodstream, based on several human immunological investigations, it is now widely accepted that susceptibility to nosocomial infections and long-term sepsis mortality involves an immunosuppressive phase that is characterized by a decrease in some subsets of dendritic cells (DCs)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29739800/loss-of-the-liver-x-receptors-disrupts-the-balance-of-hematopoietic-populations-with-detrimental-effects-on-endothelial-progenitor-cells
#16
Adil Rasheed, Ricky Tsai, Carolyn L Cummins
BACKGROUND: The liver X receptors (LXRs; α/β) are nuclear receptors known to regulate cholesterol homeostasis and the production of select hematopoietic populations. The objective of this study was to determine the importance of LXRs and a high-fat high-cholesterol diet on global hematopoiesis, with special emphasis on endothelial progenitor cells (EPCs), a vasoreparative cell type that is derived from bone marrow hematopoietic stem cells. METHODS AND RESULTS: Wild-type and LXR double-knockout ( Lxr αβ -/- ) mice were fed a Western diet (WD) to increase plasma cholesterol levels...
May 8, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29733407/bone-inflammation-and-the-bone-marrow-niche-in-chronic-kidney-disease-what-do-we-know
#17
Sandro Mazzaferro, Giuseppe Cianciolo, Antonio De Pascalis, Chiara Guglielmo, Pablo A Urena Torres, Jordi Bover, Lida Tartaglione, Marzia Pasquali, Gaetano La Manna
Recent improvements in our understanding of physiology have altered the way in which bone is perceived: no longer is it considered as simply the repository of divalent ions, but rather as a sophisticated endocrine organ with potential extraskeletal effects. Indeed, a number of pathologic conditions involving bone in different ways can now be reconsidered from a bone-centred perspective. For example, in metabolic bone diseases like osteoporosis (OP) and renal osteodystrophy (ROD), the association with a worse cardiovascular outcome can be tentatively explained by the possible derangements of three recently discovered bone hormones (osteocalcin, fibroblast growth factor 23 and sclerostin) and a bone-specific enzyme (alkaline phosphatase)...
May 4, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29731841/the-potential-function-of-micrornas-as-biomarkers-and-therapeutic-targets-in-multiple-myeloma
#18
REVIEW
Bingying Zhu, Shaoqing Ju, Haidan Chu, Xianjuan Shen, Yan Zhang, Xi Luo, Hui Cong
Multiple myeloma (MM), accounting for ~1% of all types of human cancer and 13% of all hematological malignancies, is characterized by the malignant proliferation of monoclonal plasma cells (PCs) in the bone marrow. MM leads to end stage organ impairment, including bone lesions, renal dysfunction, hypercalcemia and anemia. So far, the specific pathogenesis of MM remains unclear and no early-stage sensitive biomarker of MM has been well characterized. Furthermore, treating MM is difficult, as the majority of patients eventually relapse or become refractory following treatment using presently available methods...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29728415/crispr-mediated-gene-editing-to-assess-the-roles-of-tet2-and-dnmt3a-in-clonal-hematopoiesis-and-cardiovascular-disease
#19
Soichi Sano, Kousei Ohshima, Ying Wang, Yasufumi Katanasaka, Miho Sano, Kenneth Walsh
<u>Rationale:</u> Clonal hematopoiesis has been associated with increased mortality and cardiovascular disease (CVD). This condition can arise from somatic mutations in pre-leukemic driver genes within hematopoietic stem/progenitor cells (HSPC). Approximately 40 candidate driver genes have been identified, but mutations in only one of these genes, Ten-Eleven Translocation-2 (TET2), has been shown to casually contribute to CVD in murine models. <u>Objective:</u> To develop a facile system to evaluate the disease characteristics of different clonal hematopoiesis driver genes using lentivirus vector and CRISPR/Cas9 methodology...
May 4, 2018: Circulation Research
https://www.readbyqxmd.com/read/29717657/bone-marrow-cd133-stem-cells-ameliorate-visual-dysfunction-in-streptozotocin-induced-diabetic-mice-with-early-diabetic-retinopathy
#20
Liyuan Rong, Xianliang Gu, Jing Xie, Yuxiao Zeng, Qiyou Li, Siyu Chen, Ting Zou, Langyue Xue, Haiwei Xu, Zheng Qin Yin
Diabetic retinopathy (DR), one of the leading causes of vision loss worldwide, is characterized by neurovascular disorders. Emerging evidence has demonstrated retinal neurodegeneration in the early pathogenesis of DR, and no treatment has been developed to prevent the early neurodegenerative changes that precede detectable microvascular disorders. Bone marrow CD133+ stem cells with revascularization properties exhibit neuroregenerative potential. However, whether CD133+ cells can ameliorate the neurodegeneration at the early stage of DR remains unclear...
January 1, 2018: Cell Transplantation
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