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https://www.readbyqxmd.com/read/29148543/endothelial-specific-m-6-a-modulates-mouse-hematopoietic-stem-and-progenitor-cell-development-via-notch-signaling
#1
Junhua Lv, Yifan Zhang, Suwei Gao, Chunxia Zhang, Yusheng Chen, Wei Li, Yun-Gui Yang, Qi Zhou, Feng Liu
No abstract text is available yet for this article.
November 17, 2017: Cell Research
https://www.readbyqxmd.com/read/29147753/defective-wnt-signaling-associates-with-bone-marrow-fibrosis-a-cross-sectional-cohort-study-in-a-family-with-wnt1-osteoporosis
#2
R E Mäkitie, R Niinimäki, S Kakko, T Honkanen, P E Kovanen, O Mäkitie
This study explores bone marrow function in patients with defective WNT1 signaling. Bone marrow samples showed increased reticulin and altered granulopoiesis while overall hematopoiesis was normal. Findings did not associate with severity of osteoporosis. These observations provide new insight into the role of WNT signaling in bone marrow homeostasis. INTRODUCTION: WNT signaling regulates bone homeostasis and survival and self-renewal of hematopoietic stem cells. Aberrant activation may lead to osteoporosis and bone marrow pathology...
November 16, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/29146882/physiological-srsf2-p95h-expression-causes-impaired-hematopoietic-stem-cell-functions-and-aberrant-rna-splicing-in-mice
#3
Ayana Kon, Satoshi Yamazaki, Yasuhito Nannya, Keisuke Kataoka, Yasunori Ota, Masahiro Marshall Nakagawa, Kenichi Yoshida, Yusuke Shiozawa, Maiko Morita, Tetsuichi Yoshizato, Masashi Sanada, Manabu Nakayama, Haruhiko Koseki, Hiromitsu Nakauchi, Seishi Ogawa
Splicing factor (SF) mutations are characteristic of myelodysplastic syndromes (MDS) and related myeloid neoplasms and implicated in their pathogenesis, but their roles in the development of MDS have not fully been elucidated. Here, we investigated the consequence of mutant Srsf2 expression using newly generated Vav1-Cre-mediated conditional knock-in mice. Mice carrying a heterozygous Srsf2 P95H mutation showed significantly reduced numbers of hematopoietic stem and progenitor cells (HSPCs) and differentiation defects both in the steady-state condition and transplant settings...
November 16, 2017: Blood
https://www.readbyqxmd.com/read/29146734/humanized-mice-in-studying-efficacy-and-mechanisms-of-pd-1-targeted-cancer-immunotherapy
#4
Minan Wang, Li-Chin Yao, Mingshan Cheng, Danying Cai, Jan Martinek, Chong-Xian Pan, Wei Shi, Ai-Hong Ma, Ralph W De Vere White, Susan Airhart, Edison T Liu, Jacques Banchereau, Michael A Brehm, Dale L Greiner, Leonard D Shultz, Karolina Palucka, James G Keck
Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into the mechanisms underlying cancer immunotherapy. To this end, non-obese diabetic (NOD).Cg-Prkdc(scid)IL2rg(tm1Wjl) /Sz (null; NSG) mice were transplanted with human (h)CD34(+) hematopoietic progenitor and stem cells, which leads to the development of human hematopoietic and immune systems [humanized NSG (HuNSG)]. HuNSG mice received human leukocyte antigen partially matched tumor implants from patient-derived xenografts [PDX; nonsmall cell lung cancer (NSCLC), sarcoma, bladder cancer, and triple-negative breast cancer (TNBC)] or from a TNBC cell line-derived xenograft (CDX)...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29146707/outcomes-after-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-acute-myeloid-leukemia-harboring-t-7-11-p15-p15
#5
Kaito Harada, Noriko Doki, Jun Aoki, Jinichi Mori, Shinichiro Machida, Masayoshi Masuko, Naoyuki Uchida, Yuho Najima, Takahiro Fukuda, Heiwa Kanamori, Hiroyasu Ogawa, Shuichi Ota, Kazuei Ogawa, Satoshi Takahashi, Masanobu Kasai, Akio Maeda, Koji Nagafuji, Toshiro Kawakita, Tatsuo Ichinohe, Yoshiko Atsuta
No abstract text is available yet for this article.
November 16, 2017: Haematologica
https://www.readbyqxmd.com/read/29146706/the-clinical-and-laboratory-evaluation-of-familial-hemophagocytic-lymphohistiocytosis-and-the-importance-of-hepatic-and-spinal-cord-involvement-a-single-center-experience
#6
Burcin Beken, Selin Aytac, Gunay Balta, Baris Kuskonmaz, Duygu Uckan, Sule Unal, Mualla Cetin, Fatma Gumruk
Familial hemophagocytic lymphohistiocytosis is an autosomal recessive, life-threatening condition characterized by defective immune response. A retrospective analysis was performed on 57 patients diagnosed with familial hemophagocytic lymphohistiocytosis at Hacettepe University Pediatric Hematology Department. Mutation analysis was performed on 37 patients and of these; 11 had UNC13D, 10 had PRF1 and 3 had STX11 gene mutation. Of these patients 44% were found to have central nervous system involvement on admission and spinal cord involvement was also seen in 5 patients...
November 16, 2017: Haematologica
https://www.readbyqxmd.com/read/29146005/bone-marrow-adipocytes-in-haematological-malignancies
#7
Ewa Frączak, Mateusz Olbromski, Aleksandra Piotrowska, Natalia Glatzel-Plucińska, Piotr Dzięgiel, Jarosław Dybko, Kazimierz Kuliczkowski, Tomasz Wróbel
Bone marrow adipocytes (BMAs) derived from mesenchymal stem cells (MSC) are an active and significant element of the bone marrow microenvironment. They are involved in metabolic functions, complex interactions with other stromal cells, and in the development and progression of tumours. Currently, there is little data regarding the role of BMAs in haematological malignancies. Due to this, we have attempted to characterise the BMAs in these malignancies in terms of quantity and morphology. Our study included 30 patients aged 22-76 with myelo- (n=17) and lymphoproliferative malignancies (n=13), both with and without bone marrow infiltration...
November 13, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/29145145/alleviation-of-ginsenoside-rg1-on-hematopoietic-homeostasis-defects-caused-by-lead-acetate
#8
Shi-Zhong Cai, Yue Zhou, Jun Liu, Cheng-Peng Li, Dao-Yong Jia, Meng-Si Zhang, Ya-Ping Wang
The hematopoietic system is one of the potential targets of lead intoxication. Recognition of the lead-related deleterious outcomes promotes us to explore the potential therapeutic intervention. Here, we show that ginsenoside Rg1 (Rg1), extracted from the Chinese herb Panax ginseng, remarkably ameliorates the lead acetate-caused hematological index distortion as well as advanced hematopoietic stem cells (HSCs) aging and aging associated inflammation response. Specifically, Rg1 administration alleviated the increment of aging associated p53-p21-Rb signaling in aged HSCs induced by lead acetate...
November 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29144272/body-composition-in-children-with-chronic-illness-accuracy-of-bedside-assessment-techniques
#9
Enid E Martinez, Craig D Smallwood, Nicolle L Quinn, Katelyn Ariagno, Lori J Bechard, Christopher P Duggan, Nilesh M Mehta
OBJECTIVE: To evaluate the accuracy of estimated fat mass and fat-free mass from bedside methods compared with reference methods in children with chronic illnesses. STUDY DESIGN: Fat mass and fat-free mass values were obtained by skinfold, bioelectrical impedance analysis (BIA), dual-energy x-ray absorptiometry (DXA), and deuterium dilution method in children with spinal muscular atrophy, intestinal failure, and post hematopoietic stem cell transplantation (HSCT)...
November 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/29143804/telomeres-and-telomerase-in-hematopoietic-dysfunction-prognostic-implications-and-pharmacological-interventions
#10
REVIEW
Theresa Vasko, Andrea Kaifie, Matthias B Stope, Thomas Kraus, Patrick Ziegler
Leukocyte telomere length (TL) has been suggested as a marker of biological age in healthy individuals, but can also reflect inherited and acquired hematopoietic dysfunctions or indicate an increased turnover of the hematopoietic stem and progenitor cell compartment. In addition, TL is able to predict the response rate of tyrosine kinase inhibitor therapy in chronic myeloid leukemia (CML), indicates clinical outcomes in chronic lymphocytic leukemia (CLL), and can be used as screening tool for genetic sequencing of selected genes in patients with inherited bone marrow failure syndromes (BMFS)...
October 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29143796/angelica-sinensis-polysaccharides-ameliorate-stress-induced-premature-senescence-of-hematopoietic-cell-via-protecting-bone-marrow-stromal-cells-from-oxidative-injuries-caused-by-5-fluorouracil
#11
Hanxianzhi Xiao, Lirong Xiong, Xiaoying Song, Pengwei Jin, Linbo Chen, Xiongbin Chen, Hui Yao, Yaping Wang, Lu Wang
Myelosuppression is the most common complication of chemotherapy. Decline of self-renewal capacity and stress-induced premature senescence (SIPS) of hematopoietic stem cells (HSCs) induced by chemotherapeutic agents may be the cause of long-term myelosuppression after chemotherapy. Whether the mechanism of SIPS of hematopoietic cells relates to chemotherapeutic injury occurred in hematopoietic microenvironment (HM) is still not well elucidated. This study explored the protective effect of Angelica sinensis polysaccharide (ASP), an acetone extract polysaccharide found as the major effective ingredients of a traditional Chinese medicinal herb named Chinese Angelica (Dong Quai), on oxidative damage of homo sapiens bone marrow/stroma cell line (HS-5) caused by 5-fluorouracil (5-FU), and the effect of ASP relieving oxidative stress in HM on SIPS of hematopoietic cells...
October 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29142307/genetic-polymorphism-related-to-monocyte-macrophage-function-is-associated-with-graft-versus-host-disease
#12
Kati Hyvärinen, Jarmo Ritari, Satu Koskela, Riitta Niittyvuopio, Anne Nihtinen, Liisa Volin, David Gallardo, Jukka Partanen
Despite detailed human leukocyte antigen (HLA) matching and modern immunosuppressive therapy, severe graft-versus-host disease (GvHD) remains a major hurdle for successful allogeneic hematopoietic stem cell transplantation (HSCT). As the genetic diversity in GvHD complicates the systematic discovery of associated variants across populations, we studied 122 GvHD-associated single nucleotide polymorphisms (SNPs) in 492 HLA-matched sibling HSCT donor-recipient pairs from Finland and Spain. The association between these candidate SNPs and grade III-IV acute GvHD and extensive chronic GvHD was assessed...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29142066/characterization-of-sgn-cd123a-a-potent-cd123-directed-antibody-drug-conjugate-for-acute-myeloid-leukemia
#13
Fu Li, May Kung Sutherland, Changpu Yu, Roland B Walter, Lori Westendorf, John Valliere-Douglass, Lucy Pan, Ashley Cronkite, Django Sussman, Kerry Klussman, Michelle Ulrich, Martha E Anderson, Ivan J Stone, Weiping Zeng, Mechthild Jonas, Timothy S Lewis, Maitrayee Goswami, Sa A Wang, Peter D Senter, Che-Leung Law, Eric J Feldman, Dennis R Benjamin
Treatment choices for acute myeloid leukemia (AML) patients resistant to conventional chemotherapies are limited and novel therapeutic agents are needed. Interleukin-3 receptor alpha (IL-3Rα, or CD123) is expressed on the majority of AML blasts and there is evidence that its expression is increased on leukemic relative to normal hematopoietic stem cells, which makes it an attractive target for antibody-based therapy. Here we report the generation and preclinical characterization of SGN-CD123A, an antibody-drug conjugate utilizing the pyrrolobenzodiazepine dimer (PBD) linker and a humanized CD123 antibody with engineered cysteines for site-specific conjugation...
November 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29141947/aging-of-hematopoietic-stem-cells
#14
Gerald de Haan, Seka Lazare
Hematopoietic stem cells (HSCs) ensure a balanced production of all blood cells throughout life. As they age, HSCs gradually lose their self-renewal and regenerative potential, while the occurrence of cellular derailment strongly increases. Here we review our current understanding of the molecular mechanisms that contribute to HSC aging. We argue that most of the causes that underlie HSC aging result from cell-intrinsic pathways, and reflect on which aspects of the aging process may be reversible. As many hematological pathologies are strongly age-associated, strategies to intervene in aspects of the stem cell aging process may have significant clinical relevance...
November 15, 2017: Blood
https://www.readbyqxmd.com/read/29141946/age-related-clonal-hematopoiesis-arch
#15
Liran I Shlush
Age related alterations in the human blood system occur in B cells, T cells, cells of the innate system, as well as in hematopoietic stem and progenitor cells (HSPCs). Interestingly, age related, reduced genetic diversity can be identified both at the stem cell level, but also independently in B cells and T cells. This reduced diversity is most probably related to somatic mutations, or to changes in the micro-environmental niche. Either process can select for specific clones, or cause repeated evolutionary bottlenecks...
November 15, 2017: Blood
https://www.readbyqxmd.com/read/29141886/pd-l1-genetic-overexpression-or-pharmacological-restoration-in-hematopoietic-stem-and-progenitor-cells-reverses-autoimmune-diabetes
#16
Moufida Ben Nasr, Sara Tezza, Francesca D'Addio, Chiara Mameli, Vera Usuelli, Anna Maestroni, Domenico Corradi, Silvana Belletti, Luca Albarello, Gabriella Becchi, Gian Paolo Fadini, Christian Schuetz, James Markmann, Clive Wasserfall, Leonard Zon, Gian Vincenzo Zuccotti, Paolo Fiorina
Immunologically based clinical trials performed thus far have failed to cure type 1 diabetes (T1D), in part because these approaches were nonspecific. Because the disease is driven by autoreactive CD4 T cells, which destroy β cells, transplantation of hematopoietic stem and progenitor cells (HSPCs) has been recently offered as a therapy for T1D. Our transcriptomic profiling of HSPCs revealed that these cells are deficient in programmed death ligand 1 (PD-L1), an important immune checkpoint, in the T1D nonobese diabetic (NOD) mouse model...
November 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29141868/geographic-clonal-tracking-in-macaques-provides-insights-into-hspc-migration-and-differentiation
#17
Chuanfeng Wu, Diego A Espinoza, Samson J Koelle, E Lake Potter, Rong Lu, Brian Li, Di Yang, Xing Fan, Robert E Donahue, Mario Roederer, Cynthia E Dunbar
The geographic distribution of hematopoiesis at a clonal level is of interest in understanding how hematopoietic stem and progenitor cells (HSPCs) and their progeny interact with bone marrow (BM) niches during regeneration. We tagged rhesus macaque autologous HSPCs with genetic barcodes, allowing clonal tracking over time and space after transplantation. We found marked geographic segregation of CD34(+) HSPCs for at least 6 mo posttransplantation, followed by very gradual clonal mixing at different BM sites over subsequent months to years...
November 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29141658/thioredoxin-mitigates-radiation-induced-hematopoietic-stem-cell-injury-in-mice
#18
Pasupathi Sundaramoorthy, Qinhong Wang, Zhihong Zheng, Yiqun Jiao, Benny J Chen, Phuong L Doan, Nelson J Chao, Yubin Kang
BACKGROUND: Radiation exposure poses a significant threat to public health. Hematopoietic injury is one of the major manifestations of acute radiation sickness. Protection and/or mitigation of hematopoietic stem cells (HSCs) from radiation injury is an important goal in the development of medical countermeasure agents (MCM). We recently identified thioredoxin (TXN) as a novel molecule that has marked protective and proliferative effects on HSCs. In the current study, we investigated the effectiveness of TXN in rescuing mice from a lethal dose of total body radiation (TBI) and in enhancing hematopoietic reconstitution following a lethal dose of irradiation...
November 15, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29141316/-a-clinical-analysis-of-micafungin-treatment-of-pulmonary-invasive-fungal-infection-in-pediatric-patients-with-acute-leukemia-or-post-hematopoietic-stem-cells-transplantation
#19
K Huang, K Y Qiu, L L Deng, J P Fang, Y Li, H X Guo, D H Zhou
Objective: To investigate the efficacy and safety of micafungin (MCF) for pulmonary invasive fungal disease (PIFD) in pediatric patients with acute leukemia or post hematopoietic stem cells transplantation. Method: Twenty-five neutropenic PIFD children with acute leukemia or post hematopoietic stem cells transplantation in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were selected from January 2012 to June 2015, including 12 males and 13 females, age range 2-15 (average 6.2±2.0) years. There were 12 cases of acute leukemia (AL) after chemotherapy, 4 cases of acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 9 cases of β-thalassemia major after allo-HSCT...
November 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/29140941/phenotype-and-management-of-infantile-onset-inflammatory-bowel-disease-experience-from-a-tertiary-care-center-in-china
#20
Ziqing Ye, Ying Zhou, Ying Huang, Yuhuan Wang, Junping Lu, Zifei Tang, Shijian Miao, Kuiran Dong, Zhinong Jiang
BACKGROUND: Infantile-onset inflammatory bowel disease (IBD) comprises rare and clinically severe disorders. We examined the phenotypes and genetic causes of patients with infantile-onset IBD from a tertiary medical center. METHODS: We enrolled 38 patients with infantile-onset IBD and applied standardized treatment with medical, surgical, and supportive care. Targeted sequencing and whole-exome sequencing were performed. Clinical data were retrieved from medical records...
December 2017: Inflammatory Bowel Diseases
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