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https://www.readbyqxmd.com/read/28336526/identification-of-unipotent-megakaryocyte-progenitors-in-human-hematopoiesis
#1
Kohta Miyawaki, Hiromi Iwasaki, Takashi Jiromaru, Hirotake Kusumoto, Ayano Yurino, Takeshi Sugio, Yasufumi Uehara, Jun Odawara, Shinya Daitoku, Yuya Kunisaki, Yasuo Mori, Yojiro Arinobu, Hirofumi Tsuzuki, Yoshikane Kikushige, Tadafumi Iino, Koji Kato, Katsuto Takenaka, Toshihiro Miyamoto, Takahiro Maeda, Koichi Akashi
The developmental pathway for human megakaryocytes remains unclear and the definition of pure unipotent megakaryocyte progenitor is still controversial. Using single-cell transcriptome analysis, we have identified a cluster of cells within immature hematopoietic stem and progenitor cell populations that specifically express genes related to the megakaryocyte lineage. We used CD41 as a positive marker to identify these cells within the CD34(+)CD38(+)IL-3Rα(dim)CD45RA(-) common myeloid progenitor (CMP) population...
March 23, 2017: Blood
https://www.readbyqxmd.com/read/28330619/efficient-ex%C3%A2-vivo-engineering-and-expansion-of-highly-purified-human-hematopoietic-stem-and-progenitor-cell-populations-for-gene-therapy
#2
Erika Zonari, Giacomo Desantis, Carolina Petrillo, Francesco E Boccalatte, Maria Rosa Lidonnici, Anna Kajaste-Rudnitski, Alessandro Aiuti, Giuliana Ferrari, Luigi Naldini, Bernhard Gentner
Ex vivo gene therapy based on CD34(+) hematopoietic stem cells (HSCs) has shown promising results in clinical trials, but genetic engineering to high levels and in large scale remains challenging. We devised a sorting strategy that captures more than 90% of HSC activity in less than 10% of mobilized peripheral blood (mPB) CD34(+) cells, and modeled a transplantation protocol based on highly purified, genetically engineered HSCs co-infused with uncultured progenitor cells. Prostaglandin E2 stimulation allowed near-complete transduction of HSCs with lentiviral vectors during a culture time of less than 38 hr, mitigating the negative impact of standard culture on progenitor cell function...
March 13, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28327462/neurocognitive-dysfunction-in-hiv-infected-youth-investigating-the-relationship-with-immune-activation
#3
Allison Ross Eckard, Julia C Rosebush, Mary Ann O'Riordan, Chanda C Graves, Ashley Alexander, Anita K Grover, S Thera Lee, Jakob G Habib, Joshua H Ruff, Ann Chahroudi, Grace A McComsey
BACKGROUND: HIV-infected individuals are at increased risk of neurocognitive impairment compared to the general population. Studies suggest that, despite combination antiretroviral therapy (cART), HIV infection causes immune activation which results in neural damage; however, few data exist in HIV-infected youth. METHODS: HIV-infected youth 8-26 years old on cART with virologic suppression were prospectively enrolled along with healthy controls. Neurocognitive performance was assessed by age-appropriate Wechsler Intelligence Scales...
March 22, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28326080/characterization-of-the-highly-prevalent-regulatory-cd24-hi-cd38-hi-b-cell-population-in-human-cord-blood
#4
Ana Esteve-Solé, Irene Teixidó, Angela Deyà-Martínez, Jordi Yagüe, Ana M Plaza-Martín, Manel Juan, Laia Alsina
The newborn's immune system must transition from a sterile haploidentical uterus to the world full of antigens. Regulatory B-cells (Breg; broadly defined as CD19(+)CD24(hi)CD38(hi)) are tolerance promoters in the adult immune system. They can inhibit IFN-γ and IL-17 production by T-cells and are essential in different conditions, including pregnancy. Breg have still not been well characterized in umbilical cord blood, where we hypothesize that they are pivotal in the achievement of tolerance. We studied CD19(+)CD24(hi)CD38(hi) Breg in healthy umbilical cord blood (hUCB) compared to healthy peripheral adult blood (hAPB)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28323897/hcv-coinfection-contributes-to-hiv-pathogenesis-by-increasing-immune-exhaustion-in-cd8-t-cells
#5
Norma Rallón, Marcial García, Javier García-Samaniego, Noelia Rodríguez, Alfonso Cabello, Clara Restrepo, Beatriz Álvarez, Rosa García, Miguel Górgolas, José M Benito
BACKGROUND: There are several contributors to HIV-pathogenesis or insufficient control of the infection. However, whether HIV/HCV-coinfected population exhibits worst evolution of HIV-pathogenesis remains unclear. Recently, some markers of immune exhaustion have been proposed as preferentially upregulated on T-cells during HIV-infection. Herein, we have analyzed T-cell exhaustion together with several other contributors to HIV-pathogenesis that could be affected by HCV-coinfection. PATIENTS AND METHODS: Ninety-six patients with chronic HIV-infection (60 HIV-monoinfected and 36 HIV/HCV-coinfected), and 20 healthy controls were included in the study...
2017: PloS One
https://www.readbyqxmd.com/read/28321124/combined-inhibition-of-%C3%AE-catenin-and-bcr-abl-synergistically-targets-tyrosine-kinase-inhibitor-resistant-blast-crisis-chronic-myeloid-leukemia-blasts-and-progenitors-in-vitro-and-in-vivo
#6
H Zhou, P Y Mak, H Mu, D H Mak, Z Zeng, J Cortes, Q Liu, M Andreeff, B Z Carter
Tyrosine kinase inhibitor (TKI) resistance and progression to blast crisis (BC), both related to persistent β-catenin activation remain formidable challenges for chronic myeloid leukemia (CML). We observed overexpression of β-catenin in BC-CML stem/progenitor cells, particularly in GMP progenitors, and highest among a novel CD34(+)CD38(+)CD123(hi)Tim-3(hi) subset as determined by CyTOF analysis. Co-culture with mesenchymal stromal cells (MSCs) induced the expression of β-catenin and its target CD44 in CML cells...
March 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28315874/multiple-drug-hypersensitivity
#7
Werner J Pichler, Yuttana Srinoulprasert, James Yun, Oliver Hausmann
Multiple drug hypersensitivity (MDH) is a syndrome that develops as a consequence of massive T-cell stimulations and is characterized by long-lasting drug hypersensitivity reactions (DHR) to different drugs. The initial symptoms are mostly severe exanthems or drug rash with eosinophilia and systemic symptoms (DRESS). Subsequent symptoms due to another drug often appear in the following weeks, overlapping with the first DHR, or months to years later after resolution of the initial presentation. The second DHR includes exanthema, erythroderma, DRESS, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hepatitis, and agranulocytosis...
March 18, 2017: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/28296029/cd38-promotes-angiotensin-ii-induced-cardiac-hypertrophy
#8
Xiao-Hui Guan, Xuan Hong, Ning Zhao, Xiao-Hong Liu, Yun-Fei Xiao, Ting-Tao Chen, Li-Bin Deng, Xiao-Lei Wang, Jian-Bin Wang, Guang-Ju Ji, Mingui Fu, Ke-Yu Deng, Hong-Bo Xin
Cardiac hypertrophy is an early hallmark during the clinical course of heart failure and regulated by various signalling pathways. Recently, we observed that mouse embryonic fibroblasts from CD38 knockout mice were significantly resistant to oxidative stress such as H2 O2 -induced injury and hypoxia/reoxygenation-induced injury. In addition, we also found that CD38 knockout mice protected heart from ischaemia reperfusion injury through activating SIRT1/FOXOs-mediated antioxidative stress pathway. However, the role of CD38 in cardiac hypertrophy is not explored...
March 12, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28295574/cd38-positively-regulates-postnatal-development-of-astrocytes-cell-autonomously-and-oligodendrocytes-non-cell-autonomously
#9
Tsuyoshi Hattori, Minoru Kaji, Hiroshi Ishii, Roboon Jureepon, Mika Takarada-Iemata, Hieu Minh Ta, Thuong Manh Le, Ayumu Konno, Hirokazu Hirai, Yoshitake Shiraishi, Noriyuki Ozaki, Yasuhiko Yamamoto, Hiroshi Okamoto, Shigeru Yokoyama, Haruhiro Higashida, Yasuko Kitao, Osamu Hori
Glial development is critical for the function of the central nervous system. CD38 is a multifunctional molecule with ADP-ribosyl cyclase activity. While critical roles of CD38 in the adult brain such as oxytocin release and social behavior have been reported, those in the developing brain remain largely unknown. Here we demonstrate that deletion of Cd38 leads to impaired development of astrocytes and oligodendrocytes in mice. CD38 is highly expressed in the developing brains between postnatal day 14 (P14) and day 28 (P28)...
March 13, 2017: Glia
https://www.readbyqxmd.com/read/28286236/5-hydroxytyrosol-inhibits-hiv-1-replication-in-primary-cells-of-the-lower-and-upper-female-reproductive-tract
#10
Elisa Saba, Paola Panina-Bordignon, Isabel Pagani, Massimo Origoni, Massimo Candiani, Claudio Doglioni, Gianluca Taccagni, Silvia Ghezzi, José Alcami, Elisa Vicenzi, Guido Poli
We investigated the potential anti-HIV-1 activity of the candidate microbicide 5-hydroxytyrosol (5-HT) both in primary human cervical tissue explants (CTE), established from tissues of women undergoing histerectomy, and in endometrium-associated leukocytes (EAL). CTE were exposed to either the laboratory-adapted HIV-1BaL or to primary viral isolates in the presence or absence of 5-HT or 3TC/lamivudine as control and were then monitored for 12 days in terms of HIV-1 p24 Gag antigen production in culture supernatants...
March 7, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28283809/genes-related-to-oxytocin-and-arginine-vasopressin-pathways-associations-with-autism-spectrum-disorders
#11
REVIEW
Rong Zhang, Hong-Feng Zhang, Ji-Sheng Han, Song-Ping Han
Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorders characterized by impaired social interactions, communication deficits, and repetitive behavior. Although the mechanisms underlying its etiology and manifestations are poorly understood, several lines of evidence from rodent and human studies suggest involvement of the evolutionarily highly-conserved oxytocin (OXT) and arginine-vasopressin (AVP), as these neuropeptides modulate various aspects of mammalian social behavior. As far as we know, there is no comprehensive review of the roles of the OXT and AVP systems in the development of ASD from the genetic aspect...
April 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28281454/immune-stimulatory-effects-of-neutrophil-extracellular-traps-in-granulomatosis-with-polyangiitis
#12
Christina Lange, Elena Csernok, Frank Moosig, Julia U Holle
OBJECTIVES: The aim of this study was to analyse the role of netting neutrophils in the pathogenesis of granulomatosis with polyangiitis (GPA), especially their interplay with peripheral blood mononuclear cells (PBMCs). METHODS: The amount of cell-free DNA (cfDNA) was determined in sera from GPA patients (pairs active/inactive state of disease, n=18) and from healthy controls (HCs, n=10). Furthermore, we performed in vitro incubation experiments using PBMCs and NETs from patients and HCs for accessing the effect of NETs on PBMC behaviour...
March 8, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28280640/hhv8-ebv-coinfection-lymphoproliferative-disorder-rare-entity-with-a-favorable-outcome
#13
Dhouha Bacha, Beya Chelly, Houda Kilani, Lamia Charfi, Amel Douggaz, Samia Chatti, Emna Chelbi
HHV8/EBV-associated germinotropic lymphoproliferative disorder (GLD) is a challenging diagnosis given its rarity, the particular clinical presentation, and the lack of expression of markers usually used in establishing hematopoietic lineage. We report a new case of HHV8/EBV GLD in an immunocompetent 78-year-old woman. The diagnosis was made in an incidentally discovered lymphadenopathy. Histological examination showed a nodular lymphoid proliferation centered by aggregates of atypical plasmablastic cells admixed with small lymphoid cells...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28279038/-expression-of-septin2-in-hodgkin-lymphoma-cell-line-l428-and-its-role-in-promoting-h-rs-cells-redifferentiation-to-b-lymphocytes
#14
Q C Sun, L Zhong, B Qiu, T Zhao, X H Zhou
Objective: To explore the role of GTP binding protein 2 (Septin2) in the differentiation of Hodgkin's Lymphoma H/RS cells (Hodgkin/Reed-Sternberg) to B lymphocytes. Methods: The expressions of Septin2 mRNA and protein in Hodgkin's Lymphoma cell line L428 which CD99 was overexpressed were detected by RT-qPCR and Western blot,confocal laser microscopy and immunocytochemistry (ICC) . RT-qPCR and Western blot were used to assay the expression of Septin2 after Septin2-siRNA transfected into L428 cells, and confocal laser microscopy, CCK8 assay and flow cytometry were used to analyze the changes of F-actin cytoskeleton,cell proliferation ability and immunophenotype...
February 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28278296/robust-growth-of-avirulent-phase-ii-coxiella-burnetii-in-bone-marrow-derived-murine-macrophages
#15
Diane C Cockrell, Carrie M Long, Shelly J Robertson, Jeffrey G Shannon, Heather E Miller, Lara Myers, Charles L Larson, Tregei Starr, Paul A Beare, Robert A Heinzen
Published data show that murine bone marrow-derived macrophages (BMDM) restrict growth of avirulent phase II, but not virulent phase I, Coxiella burnetii. Growth restriction of phase II bacteria is thought to result from potentiated recognition of pathogen-associated molecular patterns, which leads to production of inhibitory effector molecules. Past studies have used conditioned medium from L-929 murine fibroblasts as a source of macrophage-colony stimulating factor (M-CSF) to promote differentiation of bone marrow-derived myeloid precursors into macrophages...
2017: PloS One
https://www.readbyqxmd.com/read/28275109/intermittent-and-graded-exercise-effects-on-nk-cell-degranulation-markers-lamp-1-lamp-2-and-cd8-cd38-in-chronic-fatigue-syndrome-myalgic-encephalomyelitis
#16
Suzanne Broadbent, Rosanne Coutts
There is substantial evidence of immune system dysfunction in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) but little is understood of exercise training effects on lymphocyte function in this illness. This study investigated whether graded and intermittent exercise improved CD8(+) lymphocyte activation and natural killer cell degranulation markers compared to no exercise. Twenty-four chronic fatigue syndrome (CFS) patients (50.2 ± 10 year) were randomized to graded exercise (GE), intermittent exercise (IE) or usual care (UC) groups; a control group (CTL) of 18 matched sedentary non-CFS/ME participants were included for immunological variable comparisons...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28273784/thymosin-%C3%AE-1-expands-deficient-il-10-producing-regulatory-b-cell-subsets-in-relapsing-remitting-multiple-sclerosis-patients
#17
Elena Giacomini, Fabiana Rizzo, Marilena P Etna, Melania Cruciani, Rosella Mechelli, Maria Chiara Buscarinu, Francesca Pica, Cartesio D'Agostini, Marco Salvetti, Eliana M Coccia, Martina Severa
BACKGROUND: B cells are key pathogenic effectors in multiple sclerosis (MS) and several therapies have been designed to restrain B cell abnormalities by directly targeting this lymphocyte population. OBJECTIVES: Moving from our data showing a Toll-like receptor (TLR)7-driven dysregulation of B cell response in relapsing-remitting multiple sclerosis (RRMS) and having found a low serum level of Thymosin-α1 (Tα1) in patients, we investigated whether the addition of this molecule to peripheral blood mononuclear cells (PBMCs) would influence the expansion of regulatory B cell subsets, known to dampen autoimmune inflammation...
February 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28270436/focal-adhesion-kinase-as-a-potential-target-in-aml-and-mds
#18
Bing Z Carter, Po Yee Mak, Xiangmeng Wang, Hui Yang, Guillermo Garcia-Manero, Duncan Mak, Hong Mu, Vivian Ruvolo, Yihua Qiu, Kevin Coombes, Nianxiang Zhang, Brittany Ragon, David T Weaver, Jonathan A Pachter, Steven Kornblau, Michael Andreeff
Although overexpression/activation of focal adhesion kinase (FAK) is widely known in solid tumors to control cell growth, survival, invasion, metastasis, gene expression, and stem cell self-renewal, its expression and function in myeloid leukemia are not well investigated. Using reverse-phase protein arrays in large cohorts of newly diagnosed acute myeloid leukemia (AML) and myeloid dysplastic syndrome (MDS) samples, we found that high FAK expression was associated with unfavorable cytogenetics (P = 2 x 10-4) and relapse (P = 0...
March 7, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28266575/cordycepin-disrupts-leukemia-association-with-mesenchymal-stromal-cells-and-eliminates-leukemia-stem-cell-activity
#19
Shu-Man Liang, Yi-Jhu Lu, Bor-Sheng Ko, Yee-Jee Jan, Song-Kun Shyue, Shaw-Fang Yet, Jun-Yang Liou
Maintaining stemness of leukemic stem cells (LSCs) and reciprocal interactions between leukemia and stromal cells support leukemic progression and resistance to chemotherapy. Targeting the niche-based microenvironment is thus a new approach for leukemia therapy. Cordycepin is an analogue of adenosine and has been suggested to possess anti-leukemia properties. However, whether cordycepin influences association of leukemia and mesenchymal stromal cells has never been investigated. Here we show that cordycepin reduces CD34(+)CD38(-) cells in U937 and K562 cells and induces Dkk1 expression via autocrine and paracrine regulation in leukemia and mesenchymal stromal/stem cells (MSCs)...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28259300/immunotherapy-for-the-treatment-of-multiple-myeloma
#20
REVIEW
Sung-Hoon Jung, Hyun-Ju Lee, Manh-Cuong Vo, Hyeoung-Joon Kim, Je-Jung Lee
Immunotherapy has recently emerged as a promising treatment for multiple myeloma (MM). There are now several monoclonal antibodies that target specific surface antigens on myeloma cells or the checkpoints of immune and myeloma cells. Elotuzumab (targeting SLAMF7), daratumumab (targeting CD38), and pembrolizumab (targeting PD-1) have shown clinical activity in clinical studies with relapsed/refractory MM. Dendritic cell vaccination is a safe strategy that has shown some efficacy in a subset of myeloma patients and may become a crucial part of MM treatment when combined with immunomodulatory drugs or immune check-point blockade...
March 2017: Critical Reviews in Oncology/hematology
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