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Bone marrow dysfunction

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https://www.readbyqxmd.com/read/28224968/hematopoiesis-with-obesity-and-exercise-role-of-the-bone-marrow-niche
#1
Russell Emmons, Grace M Niemiro, Michael De Lisio
Hematopoietic stem and progenitor cells (HSPC), the most primitive cells of the hematopoietic system responsible for maintaining all mature blood cells, display the hallmark characteristics of self-renewal and multi-potent differentiation into mature cell lineages. HSPC activity is directed by the bone marrow niche, a complex environment composed of heterogeneous cell populations that regulate HSPC function through the secretion of a wide array of cytokines and growth factors. Diet induced obesity results in a dramatic remodeling of the bone marrow niche, skewing HSPC function resulting in a compromised immune system...
2017: Exercise Immunology Review
https://www.readbyqxmd.com/read/28223293/the-loss-of-macrophage-fatty-acid-oxidation-does-not-potentiate-systemic-metabolic-dysfunction
#2
Elsie Gonzalez-Hurtado, Jieun Lee, Joseph Choi, Ebru S Selen Alpergin, Samuel L Collins, Maureen R Horton, Michael J Wolfgang
Fatty acid oxidation in macrophages has been suggested to play a causative role in high-fat diet-induced metabolic dysfunction, particularly in the etiology of adipose driven insulin resistance. To understand the contribution of macrophage fatty acid oxidation directly to metabolic dysfunction in high-fat diet-induced obesity, we generated mice with a myeloid-specific knockout of carnitine palmitoyltransferase 2 (CPT2 Mϕ-KO), an obligate step in mitochondrial long-chain fatty acid oxidation. While fatty acid oxidation was clearly induced upon IL-4 stimulation, fatty acid oxidation deficient CPT2 Mϕ-KO bone marrow derived macrophages (BMDM) displayed canonical markers of M2 polarization following IL-4 stimulation in vitro...
February 21, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28219768/copper-therapy-reduces-intravascular-hemolysis-and-derepresses-ferroportin-in-mice-with-mosaic-mutation-atp7a-mo-ms-an-implication-for-copper-mediated-regulation-of-the-slc40a1-gene-expression
#3
Małgorzata Lenartowicz, Rafał R Starzyński, Aneta Jończy, Robert Staroń, Justyna Antoniuk, Wojciech Krzeptowski, Paweł Grzmil, Aleksandra Bednarz, Olga Pierzchała, Mateusz Ogórek, Zenon Rajfur, Zbigniew Baster, Paweł Lipiński
Mosaic mutant mice displaying functional dysfunction of Atp7a copper transporter (the Menkes ATPase) are an established animal model of Menkes disease and constitute a convenient tool for investigating connections between copper and iron metabolisms. This model allows to explore changes in iron metabolism in suckling mutant mice suffering from systemic copper deficiency as well as in young and adult ones undergone copper therapy, which reduces lethal effect of the Atp7a gene mutation. Our recent study demonstrated that 14-day-old mosaic mutant males display blood cell abnormalities associated with intravascular hemolysis, and show disturbances in the functioning of the hepcidin-ferroportin regulatory axis, which controls systemic iron homeostasis...
February 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28202118/-clinical-and-laboratory-features-of-macrophage-activation-syndrome
#4
Li Guo, Mei-Ping Lu, Gui-Juan Dong, Li-Ping Teng, Yi-Ping Xu, Li-Xia Zou, Qi Zheng
OBJECTIVE: To study the clinical and laboratory features of macrophage activation syndrome (MAS) at the early stage of diagnosis, and to explore a method for early identification of MAS. METHODS: A retrospective analysis was performed for the demographic data, clinical and laboratory features, and treatment outcomes of 21 MAS patients. RESULTS: Of the 21 MAS patients, 14 had systemic juvenile idiopathic arthritis, 5 had Kawasaki disease (KD), and 2 had connective tissue disease (CTD) as primary diseases...
February 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28201977/targeting-the-immune-niche-within-the-bone-marrow-microenvironment-the-rise-of-immunotherapy-in-multiple-myeloma
#5
Klaus Podar, D Jäger
Multiple Myeloma (MM) cells inhibit the development of an effective anti-MM immune response via defects in T cell function, ineffective antigen presentation; reduced phagocytic capacity; natural killer and dendritic cell dysfunction; decreased responsiveness to IL-2 and defects in B cell immunity; upregulation of inhibitory pathways; and production of excessive pro-inflammatory cytokines. Moreover, immune cells including plasmacytoid dendritic cells and macrophages trigger tumor cell proliferation, survival, and drug resistance...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28198592/bone-marrow-derived-mesenchymal-stem-cells-derived-exosomes-promote-survival-of-retinal-ganglion-cells-through-mirna-dependent-mechanisms
#6
Ben Mead, Stanislav Tomarev
The loss of retinal ganglion cells (RGC) and their axons is one of the leading causes of blindness and includes traumatic (optic neuropathy) and degenerative (glaucoma) eye diseases. Although no clinical therapies are in use, mesenchymal stem cells (MSC) have demonstrated significant neuroprotective and axogenic effects on RGC in both of the aforementioned models. Recent evidence has shown that MSC secrete exosomes, membrane enclosed vesicles (30-100 nm) containing proteins, mRNA and miRNA which can be delivered to nearby cells...
February 15, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28196338/telomerase-and-telomere-biology-in-hematological-diseases-a-new-therapeutic-target
#7
REVIEW
Alessandro Allegra, Vanessa Innao, Giuseppa Penna, Demetrio Gerace, Andrea G Allegra, Caterina Musolino
Telomeres are structures confined at the ends of eukaryotic chromosomes. With each cell division, telomeric repeats are lost because DNA polymerases are incapable to fully duplicate the very ends of linear chromosomes. Loss of repeats causes cell senescence, and apoptosis. Telomerase neutralizes loss of telomeric sequences by adding telomere repeats at the 3' telomeric overhang. Telomere biology is frequently associated with human cancer and dysfunctional telomeres have been proved to participate to genetic instability...
February 7, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28194019/il-25-stimulates-m2-macrophage-polarization-and-thereby-promotes-mitochondrial-respiratory-capacity-and-lipolysis-in-adipose-tissues-against-obesity
#8
Juan Feng, Lingyi Li, Zhiying Ou, Qiao Li, Baoyong Gong, Zhenxian Zhao, Weiwei Qi, Ti Zhou, Jun Zhong, Weibin Cai, Xia Yang, Aiping Zhao, Guoquan Gao, Zhonghan Yang
Obesity and associated metabolic diseases are characterized by a chronic low-grade inflammatory state with the infiltration of many inflammatory cells, especially macrophages. Immune molecules, including some cytokines, have a close relationship with metabolism. Interleukin (IL)-25 is a member of the IL-17 cytokine family that can regulate macrophages and alleviate some metabolic dysfunction; however, its role and mechanisms in lipid metabolism remain to be extensively clarified. Human serum and liver biopsy specimens, high-fat diet-induced obesity mice and DB/DB (Lepr-/-) animal models were used to examine IL-25 expression in obesity and nonalcoholic fatty liver diseases (NAFLD)...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28191009/defective-il-23-il-17-axis-protects-p47phox-mice-from-colon-cancer
#9
Cornelia Richter, Martina Herrero San Juan, Benno Weigmann, Dominik Bergis, Katrin Dauber, Michael H Muders, Gustavo B Baretton, Josef Martin Pfeilschifter, Halvard Bonig, Sebastian Brenner, Heinfried H Radeke
In the colon, a sophisticated balance between immune reaction and tolerance is absolutely required. Dysfunction may lead to pathologic phenotypes ranging from chronic inflammatory processes to cancer development. Two prominent modulators of colon inflammation are represented by the closely related cytokines interleukin (IL)-12 and IL-23, which initiate adaptive Th1 and Th17 immune responses, respectively. In this study, we investigated the impact of the NADPH oxidase protein p47phox, which negatively regulates IL-12 in dendritic cells, on colon cancer development in a colitis-associated colon cancer model...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28189115/n-3-polyunsaturated-fatty-acids-alleviate-high-glucose-mediated-dysfunction-of-endothelial-progenitor-cells-and-prevent-ischemic-injuries-both-in-vitro-and-in-vivo
#10
Shao-Chih Chiu, Che-Yi Chao, En-Pei Isabel Chiang, Jia-Ning Syu, Raymond L Rodriguez, Feng-Yao Tang
Hyperglycemia is associated with a reduced number of endothelial progenitor cells (EPCs) that impairs vascular function. Circulating EPCs play important roles in postnatal neovasculogenesis and the prevention of ischemic injury. Frequent consumption of fish oil (FO) that is abundant with eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) is reportedly associated with an alleviation of diabetic complications and a lowered incidence of cardiovascular disease. The aim of this study was to examine whether N-3 polyunsaturated fatty acids such as EPA and DHA would reverse the high glucose-mediated dysfunction of EPCs in vitro and thereby prevent the ischemic injury that occurs under the hyperglycemic conditions in Type 2 diabetes (T2D) db(-/-) mice...
January 28, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28186707/mesenchymal-stromal-cell-therapy-for-chronic-lung-allograft-dysfunction-results-of-a-first-in-man-study
#11
Daniel C Chambers, Debra Enever, Sharon Lawrence, Marian J Sturm, Richard Herrmann, Stephanie Yerkovich, Michael Musk, Peter M A Hopkins
Chronic lung transplant rejection (termed chronic lung allograft dysfunction [CLAD]) is the main impediment to long-term survival after lung transplantation. Bone marrow-derived mesenchymal stromal cells (MSCs) represent an attractive cell therapy in inflammatory diseases, including organ rejection, given their relative immune privilege and immunosuppressive and tolerogenic properties. Preclinical studies in models of obliterative bronchiolitis and human trials in graft versus host disease and renal transplantation suggest potential efficacy in CLAD...
February 1, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28186701/bone-marrow-derived-mesenchymal-stem-cells-derived-exosomes-promote-survival-of-retinal-ganglion-cells-through-mirna-dependent-mechanisms
#12
Ben Mead, Stanislav Tomarev
The loss of retinal ganglion cells (RGC) and their axons is one of the leading causes of blindness and includes traumatic (optic neuropathy) and degenerative (glaucoma) eye diseases. Although no clinical therapies are in use, mesenchymal stem cells (MSC) have demonstrated significant neuroprotective and axogenic effects on RGC in both of the aforementioned models. Recent evidence has shown that MSC secrete exosomes, membrane enclosed vesicles (30-100 nm) containing proteins, mRNA and miRNA which can be delivered to nearby cells...
January 26, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28186348/transplantation-with-hypoxia-preconditioned-mesenchymal-stem-cells-suppresses-brain-injury-caused-by-cardiac-arrest-induced-global-cerebral-ischemia-in-rats
#13
Ji-Wen Wang, Yu-Ru Qiu, Yue Fu, Jun Liu, Zhi-Jie He, Zi-Tong Huang
Cardiac arrest-induced global cerebral ischemia is a main cause of neurological dysfunction in emergency medicine. Transplantation with bone marrow mesenchymal stem cells (MSCs) has been used in stroke models to repair the ischemic brain injury, but it is little studied in models with global cerebral ischemia. In the present study, a hypoxia precondition was used to improve the efficacy of MSC transplantation, given the low survival and migration rates and limited differentiation capacities of MSCs. We found that hypoxia can increase the expansion and migration of MSCs by activating the PI3K/AKT and hypoxia-inducible factor-1α/CXC chemokine receptor-4 pathways...
February 10, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28159473/nicotinamide-phosphoribosyltransferase-nampt-may-serve-as-the-marker-for-osteoblast-differentiation-of-bone-marrow-derived-mesenchymal-stem-cells
#14
Xu He, Jiaxue He, Yingai Shi, Chenchen Pi, Yue Yang, Yanan Sun, Cao Ma, Lin Lin, Lihong Zhang, Yulin Li, Yan Li
Decreased bone volume and strength with aging and enhanced risk of fractures are in part due to reduced number of bone-forming mesenchymal stem cells (MSCs) and cellular dysfunction. In a previous study, we found that osteogenic differentiation of the multipotent and omnipotent preosteoblasts are accompanied by the alterations of intracellular NAD metabolism in which nicotinamide phosphoribosyltransferase (Nampt) plays a regulatory role. The increased Nampt during osteoblast differentiation, the enzyme catalyzing NAD resynthesis from nicotinamide was noted...
January 31, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28146004/epithelial-specific-toll-like-receptor-tlr-5-activation-mediates-barrier-dysfunction-in-experimental-ileitis
#15
Loris R Lopetuso, Ruo Jia, Xiao-Ming Wang, Li-Guo Jia, Valentina Petito, Wendy A Goodman, Jon B Meddings, Fabio Cominelli, Brian K Reuter, Theresa T Pizarro
BACKGROUND: A large body of evidence supports a central role of TLR5 and its natural ligand, flagellin, in Crohn's disease (CD), with the precise mechanism(s) still unresolved. METHODS: We investigated the role of flagellin/TLR5 in SAMP1/YitFc (SAMP) mice, a spontaneous model of Crohn's disease-like ileitis. RESULTS: Ileal Tlr5 and serum antiflagellin IgG antibodies were increased in SAMP before the onset of inflammation and during established disease; these trends were abrogated in the absence of colonizing commensal bacteria...
January 31, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28143656/bone-marrow-transplantation-improves-proximal-tubule-dysfunction-in-a-mouse-model-of-dent-disease
#16
Sarah S Gabriel, Hendrica Belge, Alkaly Gassama, Huguette Debaix, Alessandro Luciani, Thomas Fehr, Olivier Devuyst
Dent disease is a rare X-linked tubulopathy caused by mutations in the endosomal chloride-proton exchanger (ClC-5) resulting in defective receptor-mediated endocytosis and severe proximal tubule dysfunction. Bone marrow transplantation has recently been shown to preserve kidney function in cystinosis, a lysosomal storage disease causing proximal tubule dysfunction. Here we test the effects of bone marrow transplantation in Clcn5(Y/-) mice, a faithful model for Dent disease. Transplantation of wild-type bone marrow in Clcn5(Y/-) mice significantly improved proximal tubule dysfunction, with decreased low-molecular-weight proteinuria, glycosuria, calciuria, and polyuria four months after transplantation, compared to Clcn5(Y/-) mice transplanted with ClC-5 knockout bone marrow...
January 28, 2017: Kidney International
https://www.readbyqxmd.com/read/28138553/influenza-a-induces-dysfunctional-immunity-and-death-in-mecp2-overexpressing-mice
#17
James C Cronk, Jasmin Herz, Taeg S Kim, Antoine Louveau, Emily K Moser, Ashish K Sharma, Igor Smirnov, Kenneth S Tung, Thomas J Braciale, Jonathan Kipnis
Loss of function or overexpression of methyl-CpG-binding protein 2 (MeCP2) results in the severe neurodevelopmental disorders Rett syndrome and MeCP2 duplication syndrome, respectively. MeCP2 plays a critical role in neuronal function and the function of cells throughout the body. It has been previously demonstrated that MeCP2 regulates T cell function and macrophage response to multiple stimuli, and that immune-mediated rescue imparts significant benefit in Mecp2-null mice. Unlike Rett syndrome, MeCP2 duplication syndrome results in chronic, severe respiratory infections, which represent a significant cause of patient morbidity and mortality...
January 26, 2017: JCI Insight
https://www.readbyqxmd.com/read/28127506/chemotherapy-induced-neuropathies-a-growing-problem-for-patients-and-health-care-providers
#18
Marta Banach, Judyta K Juranek, Aneta L Zygulska
INTRODUCTION: Chemotherapy-induced neuropathies are one of the most common side effects of cancer treatment, surpassing bone marrow suppression and kidney dysfunction. Chemotherapy effects on the nervous system vary between different classes of drugs and depend on specific chemical and physical properties of the drug used. The three most neurotoxic classes of anti-cancer drugs are: platinum-based drugs, taxanes, and thalidomide and its analogs; other, less neurotoxic but also commonly used drugs are: bortezomib, ixabepilone, and vinca alkaloids...
January 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28120605/hemophagocytic-lymphohistiocytosis-mimics-many-common-conditions-case-series-and-review-of-literature
#19
A T Akenroye, N Madan, F Mohammadi, J Leider
Introduction. Hemophagocytic lymphohistiocytosis (HLH), a rare but potentially fatal disease, is characterized by excessive immune activation and cytokine release which stimulates bone marrow macrophages to engulf hematopoietic cells. HLH could be secondary to infections: viral, fungal, and bacterial; malignancies and autoimmune diseases. The diagnosis of HLH is usually delayed due to the presence of non-specific symptoms at presentation. This delay contributes to increased mortality. Cases and review. We present the case of 4 patients who presented with subjective fevers and extreme fatigue...
January 2017: European Annals of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28118112/development-of-a-novel-murine-model-of-combined-radiation-and-peripheral-tissue-trauma-injuries
#20
Vlado Antonic, Isabel L Jackson, Gurung Ganga, Terez Shea-Donohue, Zeljko Vujaskovic
Detonation of a 10-kiloton nuclear bomb in an urban setting would result in >1 million casualties, the majority of which would present with combined injuries. Combined injuries, such as peripheral tissue trauma and radiation exposure, trigger inflammatory events that lead to multiple organ dysfunction (MOD) and death, with gastrointestinal (GI) and pulmonary involvement playing crucial roles. The objective of this study was to develop an animal model of combined injuries, peripheral tissue trauma (TBX animal model) combined with total body irradiation with 5% bone marrow shielding (TBI/BM5) to investigate if peripheral tissue trauma contributes to reduced survival...
January 24, 2017: Radiation Research
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