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Articoli di riviste sul tema "Blood play"

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Autore: Grafiati
Pubblicato: 25 luglio 2024
Ultima modifica: 31 luglio 2024

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1

Youn, Minyoung, Hee-Don Chae, Jesus Omar Gomez e Kathleen M. Sakamoto. "Pp90RSK Isoforms Play Distinct Roles during Hematopoiesis". Blood 136, Supplement 1 (5 novembre 2020): 13. http://dx.doi.org/10.1182/blood-2020-142251.

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Abstract (sommario):
Ribosomal S6 Kinases (RSKs) include a family of serine/threonine kinases that regulate cell proliferation and survival. In humans, four RSK isoforms (RSK1-4) have been identified. Although they are 73-80% conserved in sequence homology, RSK isoforms are reported to have distinct functions. RSKs phosphorylate cyclic AMP response element binding protein (CREB) which is a regulator of hematopoietic proliferation and differentiation. RSK1 is hyperactivated in AML and is therefore a potential therapeutic target for acute myeloid leukemia (AML). Therefore, inhibition of RSK requires understanding of its role during normal hematopoiesis. Furthermore, the role of RSK isoforms during hematopoiesis and leukemogenesis has not been well characterized. To study the expression of RSK isoforms in hematopoiesis, we cultured human cord blood CD34+ (CBCD34+) hematopoietic stem and progenitor cells (HSPCs) in differentiating media containing SCF, Flt3L, TOP, IL-3, IL-6, GM-CSF, and EPO and performed qPCR with mRNA of the RSK isoforms at different stages of maturation up to 14 days. RPS6KA1 (RSK1) was expressed throughout hematopoiesis, but RPS6KA3 (RSK2) and RPS6KA2 (RSK3) showed higher expression by 2-fold (p<0.05) in the earlier stages of normal hematopoiesis. Moreover, RPS6KA3 is highly expressed in CD38-CD34+ HSCs compared with other progenitor populations (LMPP, MPP, CMP, GMP, and MEP) isolated from human cord blood. RPS6KA2 expression was higher in LMPP by 7-fold (p<0.05) and CMP by 3-fold (p<0.05) compared with HSCs but was barely detectable in MEPs. RPS6KA1 was ubiquitously expressed in all progenitor populations. These results suggest that RSK2 and RSK3 have distinct functions during early myelopoiesis. To study the requirement of RSK isoforms during hematopoiesis, we knocked down RSK expression by transducing lentivirus expressing isoform-specific shRNAs or scramble controls into human CBCD34+ cells. On day 5 following transduction, cells were sorted and plated in methylcellulose media and assessed for the colony-forming activity of RSK knockdown in HSPCs. While RSK3 knockdown increased BFU-E colonies by 1.5-fold (p<0.05) compared with control cells, RSK1 knockdown decreased BFU-E and CFU-E erythroid colonies by 2-fold (p<0.05) but increased CFU-GM colonies by 2-fold (p<0.05) compared with control cells. However, RSK2 knockdown did not show any significant effects on colony-forming activity of HSPCs. We confirmed the isoform-specific effect of RSKs in normal hematopoiesis using liquid culture assays. We collected transduced cells at day 8, 11, and 14 after transduction and analyzed cell populations by flow cytometry. Similar to colony formation assay results, RSK3 knockdown increased the CD71+ erythroid population by 1.5-fold (p<0.001), but suppressed production of the CD14+ monocyte population. RSK1 knockdown enhanced production of the CD11b+/CD14+ myeloid population, but inhibited the CD71+ erythroid production by 1.5-fold (p<0.001) compared with control HSPCs. There was no significant change in blood cell differentiation in RSK2 knockdown cells. These data demonstrate that RSK1 and RSK3 exert opposite functions during erythroid and myeloid differentiation of HSPCs, suggesting a novel role for RSK isoforms as a determinant of early fate decisions of HSCs. Disclosures No relevant conflicts of interest to declare.
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2

Kipps, Thomas J. "MicroRNAs play a role in neoplasia". Blood 109, n. 12 (15 giugno 2007): 5071–72. http://dx.doi.org/10.1182/blood-2007-04-081786.

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3

Ahn, Yeon S. "Triple play of H pylori in ITP". Blood 115, n. 21 (27 maggio 2010): 4155–56. http://dx.doi.org/10.1182/blood-2010-02-269720.

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4

Au, Sam H. "Drug smuggling microparticles play dress-up". Science Translational Medicine 10, n. 452 (1 agosto 2018): eaau7382. http://dx.doi.org/10.1126/scitranslmed.aau7382.

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5

Kahn, Mark L. "Platelet collagen receptors play molecular ping-pong". Blood 103, n. 4 (15 febbraio 2004): 1180–81. http://dx.doi.org/10.1182/blood-2003-11-4080.

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6

Borges, Kelly, Alexander Rothstein, Peter Douris, Timothy Li, Olivia Ballone, Min-Kyung Jung e Joanne DiFrancisco-Donoghue. "Blood Flow In Extended ESport Play: A Pilot Study". Medicine & Science in Sports & Exercise 55, n. 9S (settembre 2023): 627. http://dx.doi.org/10.1249/01.mss.0000985676.45494.63.

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7

Walzer, Thierry. "NK-cell education: KIR-S come into play". Blood 115, n. 6 (11 febbraio 2010): 1110–11. http://dx.doi.org/10.1182/blood-2009-11-254953.

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Abstract (sommario):
Abstract In this issue of Blood, Fauriat and colleagues find that the expression of KIR2DS1 by human NK cells is associated with a decreased responsiveness to various stimuli in HLA C2/C2 but not in C1/C1 persons.
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8

Arun Kumar, Sumukh, Ankushi Sanghvi, Maya Gogtay, Harshit Khosla, Susan V. George e Ahmad Daniyal Siddiqui. "Did Physicians Have a Role to Play in National Blood Crisis?" Blood 140, Supplement 1 (15 novembre 2022): 7883–84. http://dx.doi.org/10.1182/blood-2022-160184.

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9

Fauriat, Cyril, e Daniel Olive. "AML drug resistance: c-Myc comes into play". Blood 123, n. 23 (5 giugno 2014): 3528–30. http://dx.doi.org/10.1182/blood-2014-04-566711.

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10

Hardison, Ross C. "Finding partners to play the music of regulation". Blood 127, n. 13 (31 marzo 2016): 1624–26. http://dx.doi.org/10.1182/blood-2016-02-697169.

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11

Martinez, Dolores. "From ‘Scottish’ Play to Japanese Film: Kurosawa’s Throne of Blood". Arts 7, n. 3 (10 settembre 2018): 50. http://dx.doi.org/10.3390/arts7030050.

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Shakespeare’s plays have become the subject of filmic remakes, as well as the source for others’ plot lines. This transfer of Shakespeare’s plays to film presents a challenge to filmmakers’ auterial ingenuity: Is a film director more challenged when producing a Shakespearean play than the stage director? Does having auterial ingenuity imply that the film-maker is somehow freer than the director of a play to change a Shakespearean text? Does this allow for the language of the plays to be changed—not just translated from English to Japanese, for example, but to be updated, edited, abridged, ignored for a large part? For some scholars, this last is more expropriation than pure Shakespeare on screen and under this category we might find Kurosawa’s Throne of Blood (Kumonosu-jō 1957), the subject of this essay. Here, I explore how this difficult tale was translated into a Japanese context, a society mistakenly assumed to be free of Christian notions of guilt, through the transcultural move of referring to Noh theatre, aligning the story with these Buddhist morality plays. In this manner Kurosawa found a point of commonality between Japan and the West when it came to stories of violence, guilt, and the problem of redemption.
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12

Dickson, David. "UK blood centres could play major role in gene therapy". Nature 361, n. 6412 (febbraio 1993): 486. http://dx.doi.org/10.1038/361486a0.

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13

Snyder, Edward L., e N. Rebecca Haley. "Cord blood units for adult transplantation: child's play no longer". Transfusion 45, n. 6 (giugno 2005): 829–31. http://dx.doi.org/10.1111/j.1537-2995.2005.05103.x.

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14

Hung, Kimberly T., Stela Z. Berisha, Brian M. Ritchey, Jennifer Santore e Jonathan D. Smith. "Red Blood Cells Play a Role in Reverse Cholesterol Transport". Arteriosclerosis, Thrombosis, and Vascular Biology 32, n. 6 (giugno 2012): 1460–65. http://dx.doi.org/10.1161/atvbaha.112.248971.

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15

Grieshaber, Matthias C., e Josef Flammer. "Does the Blood-brain Barrier Play a Role in Glaucoma?" Survey of Ophthalmology 52, n. 6 (novembre 2007): S115—S121. http://dx.doi.org/10.1016/j.survophthal.2007.08.005.

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16

Jill Shepherd, Ashley, Ann Glenesk e Catherine Niven. "What influence does experience play in heel prick blood sampling?" Journal of Neonatal Nursing 12, n. 3 (giugno 2006): 97–102. http://dx.doi.org/10.1016/j.jnn.2006.03.012.

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17

Scuteri, Angelo. "Depression and cardiovascular risk: does blood pressure play a role?" Journal of Hypertension 26, n. 9 (settembre 2008): 1738–39. http://dx.doi.org/10.1097/hjh.0b013e32830dfff7.

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18

Ozturk, Murat, e Isa An. "Do blood groups play a role in etiology of rosacea?" Journal of Cosmetic Dermatology 19, n. 2 (5 settembre 2019): 400–403. http://dx.doi.org/10.1111/jocd.13143.

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19

Cermenati, Solei, Silvia Moleri, Simona Cimbro, Paola Corti, Luca Del Giacco, Roberta Amodeo, Elisabetta Dejana, Peter Koopman, Franco Cotelli e Monica Beltrame. "Sox18 and Sox7 play redundant roles in vascular development". Blood 111, n. 5 (1 marzo 2008): 2657–66. http://dx.doi.org/10.1182/blood-2007-07-100412.

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Mutations in SOX18 cause the human hypotrichosis-lymphedema-telangiectasia (HLT) syndrome. Their murine counterparts are the spontaneous ragged mutants, showing combined defects in hair follicle, blood vessel, and lymphatic vessel development. Mice null for Sox18 display only mild coat defects, suggesting a dominant-negative effect of Sox18/ragged mutations and functional redundancy between Sox18 and other Sox-F proteins. We addressed this point in zebrafish. The zebrafish homologs of Sox18 and of Sox7 are expressed in angioblasts and in the endothelial component of nascent blood vessels in embryos. Knockdown of either gene, using moderate doses of specific morpholinos, had minimal effects on vessels. In contrast, simultaneous knockdown of both genes resulted in multiple fusions between the major axial vessels. With combined use of transgenic lines and molecular markers, we could show that endothelial cells are specified, but fail to acquire a correct arteriovenous identity. Venous endothelial cell differentiation was more severely affected than arterial. Thus, sox7 and sox18 play redundant but collectively essential roles in the establishment of proper arteriovenous identity in zebrafish. Our data suggest that a defect in arteriovenous identity could be responsible for the formation of telangiectases in patients with HLT.
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20

Labrinidis, Agatha, Vasilios Liapis, Le M. Thai, Gerald J. Atkins, Cristina Vincent, Shelley Hay, Natalie A. Sims, Andrew C. W. Zannettino, David M. Findlay e Andreas Evdokiou. "Does Apo2L/TRAIL play any physiologic role in osteoclastogenesis?" Blood 111, n. 11 (1 giugno 2008): 5411–12. http://dx.doi.org/10.1182/blood-2008-03-144261.

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21

Huang, Junwei, Qifa Liu e Hua Jin. "Tim-3 Mutation Might Play in the Pathophysiology of Acute Myeloid Leukemia". Blood 138, Supplement 1 (5 novembre 2021): 2379. http://dx.doi.org/10.1182/blood-2021-146704.

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Abstract Genetic polymorphisms and expression of T-cell immunoglobulin mucin-3 (Tim-3) were associated with susceptibility and prognosis in some tumors, but the relationship between Tim-3 mutation and acute myeloid leukemia (AML) was rarely reported. This study explored the effects of Tim-3 mutations on AML. Four hundred and ninety-one de novo newly diagnosed AML patients were enrolled in this exploratory study. A genomic panel of 167 gene targets were detected by next-generation sequencing (NGS). A matched-pair analysis was designed for prognosis based on 1:2 ratio. 26 patients carried Tim-3 mutations, including 20 Tim-3 p.Y82C and other 6 mutations of p.E273K, p.E182N190del, p.Ter302E, p.A28V, p.R184W, p.G54fs. The median number of somatic mutations apart from Tim-3 was 6 and 7 in Tim-3 + and Tim-3 - groups (P=0.543), respectively. Tim-3 expression was lower, and white blood cell (WBC) at diagnose was higher (P=0.045) in Tim-3 + than Tim-3 - groups. The 2-year cumulative incidence of relapse was 50.8% and 28.7% (P=0.043), overall survival (OS) was 42.6% and 68.5% (P=0.048), and event-free survival (EFS) was 26.8% and 49.6% (P=0.028) in both groups, respectively. Multivariate analysis showed that WBC at diagnose was the risk factor (P=0.004, 0.011 and 0.000, respectively) while transplantation was the protective factor (P=0.015，0.000 and 0.000) for relapse, OS and EFS, and Tim-3 mutation was the risk factor for relapse (P=0.006) in the normal karyotype patients. In vitro, AML cell lines with Tim-3 p.Y82C overexpression revealed lower Tim-3 expression and apoptotic rate as well as lower sensitivity to cytarabine. The bioinformatic analysis also indicated Tim-3 low expression was associated with lower survival in AML patients (P=0.0009). Our findings provide new viewpoint that Tim-3 mutation results in Tim-3 lower expression and is a poor prognostic factor in AML. Disclosures No relevant conflicts of interest to declare.
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22

Hole, Paul Spencer, Richard Lawrence Darley e Alex Tonks. "Do reactive oxygen species play a role in myeloid leukemias?" Blood 117, n. 22 (2 giugno 2011): 5816–26. http://dx.doi.org/10.1182/blood-2011-01-326025.

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Abstract Reactive oxygen species (ROS) are a heterogeneous group of molecules that are generated by mature myeloid cells during innate immune responses, and are also implicated in normal intracellular signaling. Excessive production of ROS (and/or a deficiency in antioxidant pathways) can lead to oxidative stress, a state that has been observed in several hematopoietic malignancies including acute and chronic myeloid leukemias (AML and CML). Currently it is unclear what the cause of oxidative stress might be and whether oxidative stress contributes to the development, progression, or maintenance of these diseases. This article reviews the current evidence suggesting a role for ROS both in normal hematopoiesis and in myeloid leukemogenesis, and discusses the usefulness of therapeutically targeting oxidative stress in myeloid malignancy.
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23

Dumont, Celine, Agnieszka Corsoni-Tadrzak, Sandra Ruf, Jasper de Boer, Adam Williams, Martin Turner, Dimitris Kioussis e Victor L. J. Tybulewicz. "Rac GTPases play critical roles in early T-cell development". Blood 113, n. 17 (23 aprile 2009): 3990–98. http://dx.doi.org/10.1182/blood-2008-09-181180.

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Abstract The Rac1 and Rac2 GTPases play important roles in many processes including cytoskeletal reorganization, proliferation, and survival, and are required for B-cell development. Previous studies had shown that deficiency in Rac2 did not affect T-cell development, whereas the function of Rac1 in this process has not been investigated. We now show that simultaneous absence of both GTPases resulted in a very strong developmental block at the pre-TCR checkpoint and in defective positive selection. Unexpectedly, deficiency of Rac1 and Rac2 also resulted in the aberrant survival of thymocytes lacking expression of TCRβ, showing hallmarks of hyperactive Notch signaling. Furthermore, we found a similar novel phenotype in the absence of Vav1, Vav2, and Vav3, which function as guanine nucleotide exchange factors for Rac1 and Rac2. These results show that a pathway containing Vav and Rac proteins may negatively regulate Notch signaling during early thymic development.
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24

Rabenhorst, Anja, Max Schlaak, Lukas C. Heukamp, Anja Förster, Sebastian Theurich, Michael von Bergwelt-Baildon, Reinhard Büttner et al. "Mast cells play a protumorigenic role in primary cutaneous lymphoma". Blood 120, n. 10 (6 settembre 2012): 2042–54. http://dx.doi.org/10.1182/blood-2012-03-415638.

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AbstractPrimary cutaneous lymphomas (PCLs) are clonal T- or B-cell neoplasms, which originate in the skin. In recent years, mast cells were described as regulators of the tumor microenvironment in different human malignancies. Here, we investigated the role of mast cells in the tumor microenvironment of PCL. We found significantly increased numbers of mast cells in skin biopsies from patients with cutaneous T-cell lymphoma (CTCL) and cutaneous B-cell lymphoma (CBCL). Mast cell infiltration was particularly prominent in the periphery, at lymphoma rims. Interestingly, CTCL and CBCL patients with a progressive course showed higher mast cell counts than stable patients, and mast cell numbers in different stages of CTCL correlated positively with disease progression. In addition, mast cell numbers positively correlated with microvessel density. Incubating primary CTCL cells with mast cell supernatant, we observed enhanced proliferation and production of cytokines. In line with our in vitro experiments, in a mouse model of cutaneous lymphoma, tumor growth in mast cell–deficient transgenic mice was significantly decreased. Taken together, these experiments show that mast cells play a protumorigenic role in CTCL and CBCL. Our data provide a rationale for exploiting tumor-associated mast cells as a prognostic marker and therapeutic target in PCL.
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25

González Bermúdez, Patricia. "Blood Wedding in (re)translation". International Journal of Iberian Studies 32, n. 3 (1 settembre 2019): 195–207. http://dx.doi.org/10.1386/ijis_00005_1.

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Abstract This article is a comparative study of four different translations into English of Federico García Lorca's play Bodas de sangre (1933) carried out in the United Kingdom and Ireland throughout the 1990s. Since the publication of Antoine Berman's seminal article on 'retranslation', this theoretical concept has provided a fecund framework for descriptive translation studies, illuminating the variety of solutions translators provide when confronted with the same original text. This article furthers that body of scholarship while simultaneously providing new angles on Lorca's dramatic work. The comparative approach to several English translations of this classic work concentrates on two key scenes of the play and discusses the linguistic, pragmatic and theatrical adequacy of each translation.
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26

Mars, Tanya. "Personal Reflections on Blood Bath". Canadian Theatre Review 86 (marzo 1996): 5–8. http://dx.doi.org/10.3138/ctr.86.001.

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Level I. Press play. Click. Play. Click click. Load. Soundtrack: a heartbeat rhythm./boom boom. boom boom. boom boom./I am armed with a .38. An abandoned van sits in a desolate landscape. The back door is open. (Boom boom. Boom boom. Boom boom.) I don’t know what I’m waiting for. (Boom boom. Boom boom.) Whatever is out there, it isn’t friendly. (Boom boom. Boom boom.) I think I see something. (Boom boom.) Where? (Boom. boom.) My finger caresses the trigger. (Boom. boom.) There! Bang! Bang! Bang! Bang! Bang! (Boom. boom. Argh!!!) And there! (Boom. boom. Argh!!!) Bang! Bang! (Boom. boom. Argh!!!) And there … click click. Bang! splat. got me! Red blood fills the screen. Empty. Fade to red.
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Irvan, Arimbi, Arifuddin Usman e Anto Sukamto. "Speed play training toward changes hematocrit value and cardiorespiration basket athlete". Jurnal SPORTIF : Jurnal Penelitian Pembelajaran 7, n. 4 (19 febbraio 2022): 38–51. http://dx.doi.org/10.29407/js_unpgri.v7i4.16955.

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The purpose of this study was to determine the effect of regular exercise with the speed play method in increasing cardiorespiratory capacity and blood hematocrit levels in Pinisi basketball athletes. The research method used was the one-group pre-post test design experiment. The instruments used in this study were the Multistage Test (MFT) for cardiorespiratory and hct meter to measure blood hematocrit levels. This study found that the percentage of blood hematocrit after the intervention of the speed play training method for the Pinisi basketball athletes was 44.94% higher than the average hematocrit level before being given the speed play training method for the Pinisi basketball athletes, which was 41.64%. There was a change with an average value of 3.3% per 100 mg of blood, meanwhile the average cardiorespiratory capacity after the implementation of the speed play training program in Pinisi basketball athletes was 43.49 ml/kg/minute, which means an increase from the average capacity cardiorespiratory training before being given speed play training in phinisi basketball athletes of 40.95 ml/kg/minute experienced an average change of 2.54 ml/kg/minute.
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Lesiak, Atom J., e Joan C. Griswold. "Blood Sugar Balance". American Biology Teacher 85, n. 5 (1 maggio 2023): 270–77. http://dx.doi.org/10.1525/abt.2023.85.5.270.

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Blood Sugar Balance (BSB) is an accessible web-based game, created as an extension of our federally funded type 2 diabetes curriculum for high school biology classrooms. Modeling of complex systems and diseases, like metabolism and type 2 diabetes (T2D), is especially difficult and deeply impactful when executed in an engaging way. Blood Sugar Balance integrates environmental factors, biological factors, and personal choices to model glucose metabolism and understand the impact and risk factors for type 2 diabetes. Players earn points during gameplay by ensuring their game character maintains healthy blood glucose levels throughout the play period by regulating them. Players must make choices about food, exercise, and the release of hormones from the pancreas to manage blood glucose levels. Game settings can model the stages of type 2 diabetes as well as environmental factors that limit access to food, exercise, and health care options. Gameplay is fast and engaging, allowing exploration of factors that impact the final score. For example, how might accessibility to insulin impact the final score while playing at the type 2 diabetes setting? Here we describe the development of Blood Sugar Balance and the integration of data analysis into the accompanying NGSS-aligned lesson plan.
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Mohamad, Safa F., Meaghan McGuinness, Chad Everett Harris e David A. Williams. "Septin11 and Septin 8 Play Critical and Overlapping Roles Murine Stem Cell Function". Blood 142, Supplement 1 (28 novembre 2023): 5583. http://dx.doi.org/10.1182/blood-2023-181991.

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Septins are highly conserved GTP binding proteins which regulate a variety of cellular functions including cytokinesis, polarity, cell cycle, vesicle trafficking, and exocytosis and are now considered the fourth component of the cytoskeleton. Septins are implicated in T and B cell lymphomas; and acute myeloid leukemias, where they frequently act as fusion partners with the Mixed-Lineage Leukemia (MLL) gene. Previous data in our laboratory led to the discovery of a small molecular inhibitor, DW0254, which inhibits RAS function and its downstream target RhoGTPase, Rac, including the hematopoietic-specific Rac2 GTPase, also implicated in MLL leukemias. The inhibitor leads to apoptosis of leukemia cell lines. Using biophysical methods, we discovered that DW0254 binds both the RAS chaperone, PDE6D, and Septin11, which is a member of the Septin6 family (Sara CN, et al., Blood Cancer 2022). Although Septins have been reported to be involved in function of the RhoGTPase Cdc42 and hematopoietic stem progenitor cell (HSPC) polarity, the role of Septin11 in hematopoiesis has not been reported. Septin11 is a member of the Septin6 family of proteins which consists of Septin6, 8, 10, 11 and 14 with significant homology between family members. Previous data in yeast has hypothesized functional overlap within each family of Septin proteins. To better understand the functional role of Septin11, we created lentivirus vectors tagged with a GFP reporter that contained shmiRs against Septin11. Culture of Septin11 knockdown (Septin11 KD) murine HSPC in IMDM (10ng/ml IL-3, 25ng/ml of SCF, TPO, Flt-3 and IL-6) resulted in an average of 13-fold decrease in cell counts compared to controls (p=0.02) and a decrease in total clonogenic activity (Figure 1) with defects seen in both myeloid (GM) and erythroid (BFU-E) colonies. Reduced clonogenic numbers were accompanied by a significant increase in early apoptotic cells suggesting that Septin11 is important in regulating apoptosis in HSPC. To determine the potential role of Septin11 in more primitive hematopoietic cells, we utilized competitive repopulation assays. Transduced BoyJ HSPC (GFP+ Septin11 KD and BFP+ control, mixed 1:1) were injected into lethally irradiated C57Bl/6 mice. We observed a reduction in multilineage chimerism in the peripheral blood, bone marrow, spleen and thymus in primary transplant recipients after knockdown of Septin11 (Table 1). To better define function in specific hematopoietic populations of HSPC, we performed knockdown in FACS-sorted purified cells. Engraftment studies demonstrated a significant reduction in bone marrow chimerism in primary transplant recipients after knockdown of Septin11 most clearly in LT-HSC and ST-HSC (Table 1) with no statistically significant change in MPP. Therefore, to better study the hematopoietic stem cell compartment, we performed secondary transplants utilizing the cells obtained from primary competitive repopulation assays. We observed an unexpected recovery in engraftment in secondary transplant recipients that was accompanied by an increase in the mRNA expression of Septin8. Since Septin8 and Septin11 are closely related we hypothesized that induction of Septin8 was subserving key functions of Septin11. To test this hypothesis, we created a lentivirus vector that expressed both a shmiR against Septin11 and the Septin8 cDNA. Concurrent overexpression of Septin8 with Septin11 knockdown HSPC caused a significant increase in the total number of colonies compared to controls (Figure 1). These data indicate an important role of Septin11 in murine hematopoiesis and a potential redundant role for Septin8.
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Ottens, Jane, Sigrid C. Tuble, Andrew J. Sanderson, John L. Knight e Robert A. Baker. "Improving Cardiopulmonary Bypass: Does Continuous Blood Gas Monitoring Have a Role to Play?" Journal of ExtraCorporeal Technology 42, n. 3 (settembre 2010): 191–98. http://dx.doi.org/10.1051/ject/201042191.

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Abstract (sommario):
The CDI™500 (Terumo Cardiovascular Systems, Ann Arbor, MI) is an in-line blood gas monitoring device that has been used in clinical practice for over a decade. Few randomized studies have evaluated the value of this device with respect to improved perfusion management. We routinely use automated continuous quality indicator programs to assess perfusion management. The aim of this study is to investigate in a prospective randomized trial the role of in-line blood gas monitoring in the improvement of blood gas management during cardiopulmonary bypass (CPB) utilizing continuous quality indicators. Patients were randomized into two groups (Control, CDI). Patients in the Control group received our standard CPB blood gas management, with intermittent blood gas results. Continuous blood gas measurements from the CDI™500 were recorded at 20-second intervals, with the perfusionist blinded to these measurements. Patients in the CDI group received standard CPB blood gas management, in addition to continuous blood gas measurements visible on the CDI™500, the alarm system activated, and the data recorded. Perfusion management for all cases was guided by institutional protocols. One hundred patients (50 in each group) were included in the study. No significant difference existed between the groups on demographic, surgical, or clinical outcomes. Blood gas levels of patients in the CDI group were able to be maintained in accordance to protocol a greater percentage of the time, e.g., pCO2 management was 2% versus 20% (p = .008); this was most notable for differences between the Control and the CDI group for pCO2 > 45 mmHg (p = .003). Practice variation determined via statistical control charts improved for both pH and pCO2, represented by a decrease in the variation associated with practice. Continuous blood gas monitoring with the CDI™500 results in significantly improved blood gas management as determined by adherence to institutional protocols.
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31

Arimbi, Arimbi, Arifuddin Usman, Poppy Elisano Arfanda, Sarifin Sarifin e Wahyana Mujari Wahid. "Pengaruh Latihan Speed Play Terhadap Nilai Hematokrit Dan Kardiorespirasi Atlet Basket". Journal on Education 6, n. 4 (4 giugno 2024): 19768–77. http://dx.doi.org/10.31004/joe.v6i4.5933.

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Abstract (sommario):
The purpose of this study was to determine the effect of regular exercise with the speed play method in increasing cardiorespiratory capacity and blood hematocrit levels in Pinisi basketball athletes. The research method used was the one-group pre-posttest design experiment. The instruments used in this study were the Multistage Test (MFT) for cardiorespiratory and hct meter to measure blood hematocrit levels. The results of this study found that the percentage of blood hematocrit after the intervention of the speed play training method for the Pinisi basketball athletes was 44.94% higher than the average hematocrit level before being given the speed play training method for the Pinisi basketball athletes, which was 41.64%. There was a change with an average value of 3.3% in per 100 mg of blood, meanwhile the average cardiorespiratory capacity after the implementation of the speed play training program in Pinisi basketball athletes was 43.49 ml/kg/minute, which means an increase from the average capacity cardiorespiratory training before being given speed play training in phinisi basketball athletes of 40.95 ml/kg/minute experienced an average change of 2.54 ml/kg/minute.
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32

Da Ros, Martina, Veronica De Gregorio, Anna Iorio, Laura Giunti, Milena Guidi, Maurizio de Martino, Lorenzo Genitori e Iacopo Sardi. "Glioblastoma Chemoresistance: The Double Play by Microenvironment and Blood-Brain Barrier". International Journal of Molecular Sciences 19, n. 10 (22 settembre 2018): 2879. http://dx.doi.org/10.3390/ijms19102879.

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Abstract (sommario):
For glioblastoma, the tumor microenvironment (TME) is pivotal to support tumor progression and therapeutic resistance. TME consists of several types of stromal, endothelial and immune cells, which are recruited by cancer stem cells (CSCs) to influence CSC phenotype and behavior. TME also promotes the establishment of specific conditions such as hypoxia and acidosis, which play a critical role in glioblastoma chemoresistance, interfering with angiogenesis, apoptosis, DNA repair, oxidative stress, immune escape, expression and activity of multi-drug resistance (MDR)-related genes. Finally, the blood brain barrier (BBB), which insulates the brain microenvironment from the blood, is strongly linked to the drug-resistant phenotype of glioblastoma, being a major physical and physiological hurdle for the delivery of chemotherapy agents into the brain. Here, we review the features of the glioblastoma microenvironment, focusing on their involvement in the phenomenon of chemoresistance; we also summarize recent advances in generating systems to modulate or bypass the BBB for drug delivery into the brain. Genetic aspects associated with glioblastoma chemoresistance and current immune-based strategies, such as checkpoint inhibitor therapy, are described too.
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33

Cherpokova, Deya, Charlotte C. Jouvene, Stephania Libreros, Elise P. DeRoo, Long Chu, Xavier de la Rosa, Paul C. Norris, Denisa D. Wagner e Charles N. Serhan. "Resolvin D4 attenuates the severity of pathological thrombosis in mice". Blood 134, n. 17 (12 luglio 2019): 1458–68. http://dx.doi.org/10.1182/blood.2018886317.

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34

Kachuri, Linda, Soyoung Jeon, Andrew T. DeWan, Catherine Metayer, John S. Witte, Xiaomei Ma, Charleston W. K. Chiang, Joseph L. Wiemels e Adam J. de Smith. "Genetic Determinants of Blood Cell Traits Play a Role in Susceptibility to Acute Lymphoblastic Leukemia". Blood 136, Supplement 1 (5 novembre 2020): 10–11. http://dx.doi.org/10.1182/blood-2020-141443.

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Abstract (sommario):
Background: Genome-wide association studies (GWAS) have identified several genes associated with childhood acute lymphoblastic leukemia (ALL) that are also implicated in variation in hematological traits. We performed a comprehensive study of the shared heritability of blood cell traits and ALL, and investigated whether genetic variation in blood cell traits may underlie ALL risk. Methods: We leveraged genome-wide single nucleotide polymorphism (SNP) data from: 1) 335,332 European ancestry, cancer-free subjects without immune deficiencies or hematopoietic disorders in the UK Biobank (UKB); and 2) a childhood ALL GWAS meta-analysis including 2,121 cases and 59,965 controls of European ancestry, to investigate the shared genetic basis of blood cell trait variation and ALL susceptibility. Co-heritability between blood cell profiles and ALL susceptibility was evaluated by LD score regression. To formally test variation in blood cell traits as potential causal pathways in ALL development, we conducted Mendelian randomization (MR) analyses, which use genetic predictors of blood cell phenotypes to overcome potential confounding and reverse causation in directly measured blood counts. Genetic instruments for MR were developed using a two-stage GWAS of 6 cell types (lymphocytes, monocytes, neutrophils, eosinophils, basophils, platelets), and their ratios (lymphocyte/monocyte - LMR; neutrophil/monocyte - NLR; platelet/lymphocyte - PLR) in the UKB. Next we applied multi-trait analysis of GWAS (MTAG) to improve power for identifying trait-specific loci by exploiting the correlated nature of blood cell traits. Causal odds ratios (OR) for ALL were estimated per 1 standard deviation increase in normalized cell counts (109cells/L) or 1-unit increase in cell type ratios. Results: Using genome-wide SNP data, we found that ALL has a heritability of hg=0.235 (95% confidence intervals, CI:0.203-0.268) in European ancestry individuals. In LD score regression, ALL susceptibility was correlated at the genetic level with overall blood cell counts (rg=0.070, P=0.003), lymphocyte counts (rg=0.088, P=0.004), LMR (rg=0.065, P=0.012), and PLR (rg= -0.072, P=0.001). Genetic instruments for MR were selected from independent (LD r2<0.05) variants with P<5×10-8 in the discovery blood cell trait GWAS/MTAG (N=234,778) and P<0.05 in the replication analysis (N=100,554). The resulting genetic predictors explained between 4.0% (basophils, NSNP=144) and 23.9% (platelets, NSNP=661) of trait variation. Our findings lend support to a modest but significant causal effect of variation in lymphocyte counts (OR=1.16, 95% CI:1.01-1.33), LMR (OR=1.23, 95% CI:1.07-1.41), NLR (OR=0.67, 95% CI:0.54-0.83), and PLR (OR=0.80, 95% CI:0.70-0.92) on ALL risk. There was no evidence of directional pleiotropy based on the MR Egger intercept test (P>0.05). However, significant heterogeneity among SNP-specific causal effects (Cochran's Q P<0.05) indicated potential for confounding due to balanced pleiotropy. In sensitivity analyses using MR-PRESSO framework, which corrects for distortion in causal effects due to pleiotropy, the associations with ALL risk became attenuated for lymphocytes (OR=1.14, 95% CI:0.98-1.32), but persisted for LMR (OR=1.18, 95% CI:1.01-1.38), NLR (OR=0.76, 95% CI:0.60-0.97), and PLR (OR=0.82, 95% CI:0.70-0.95). Next, we searched for individual variants that may underlie the effects on ALL risk using heterogeneity-based clustering of genetic instruments. This analysis confirmed that regulation of blood cell traits partially mediates the effects of known ALL risk variants: rs4948492, rs4245597 (ARID5B), rs2239630 (CEBPE), and rs78697948 (IKZF1). We also identified putative novel ALL risk loci at chromosome 2q22 (OR=1.28, P=2.5×10-6), chr6q23 (OR=1.21, P=9.3×10-6), and chr13q12 (OR=1.79, P=3.2×10-5), though further analyses are required to confirm these associations and identify likely causal variants and genes at these loci. Conclusions: Our findings suggest that dysregulation of blood cell profiles characterized by a genetic predisposition to increased lymphocyte counts, particularly in relation to neutrophils, monocytes, and platelets, confers a modest but significant increase in ALL risk. Additional research is required to determine whether a genetic propensity to higher lymphocyte levels is associated with ALL subtypes or clinical outcomes in ALL patients. Disclosures Ma: Celgene/BMS: Research Funding; BMS: Consultancy.
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35

Munawaroh, Alviatul. "Pengembangan Media Game Adventure of Blood Berbasis Role Play Peredaran Darah Manusia". Journal of Education Research 5, n. 2 (30 giugno 2024): 2431–41. http://dx.doi.org/10.37985/jer.v5i2.1179.

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Abstract (sommario):
Pelaksanaan metode role play pada materi sistem peredaran darah menggunakan media kertas memiliki kekurangan yaitu efisiensi waktu, kondusifitas, dan tidak sesuai dengan perkembangan teknologi. Maka dari itu peneliti mencoba mengembangkan permainan role play tradisional menjadi media game adventure of blood berbasis role play modern dengan gadget dan komputer. Tujuan penelitian yaitu mengukur validitas dan efektifitas media game adventure of blood berbasis role play. Jenis penelitian pengembangan model ADDIE. Subjek penelitian 23 siswa kelas 5 SDN Barurambat Kota 5 Pamekasan. Pengumpulan data menggunakan observasi, wawancara, angket, Pretest Posttest, dan dokumentasi. Uji coba desain One Group kepada 23 siswa. Hasil penelitian menunjukkan skor persentase ahli materi 91%, ahli media 89%, praktisi pembelajaran 86%, dan ahli Bahasa 85% kategori sangat layak. Nilai kepraktisan media 95% sangat praktis. Rerata penilaian pakar 88% kategori sangat layak. Hasil belajar meningkat rerata pre-test post-test yaitu 66,96 < 82,83 selisih 15,87. Hasil uji-t SPSS paired sample t-test tingkat signifikan <.001 hasil kurang dari 0,05 berarti efektif meningkatkan hasil belajar. Hasil uji-t manual nilai thitung 97,3 > ttabel 1,717 sehingga H0 ditolak dan Ha diterima. Media pembelajaran interaktif valid, praktis, dan efektif meningkatkan hasil belajar siswa kelas 5 SDN Barurambat Kota 5 Pamekasan.
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36

Russell, Mark, David Benton e Michael Kingsley. "Carbohydrate Ingestion Before and During Soccer Match Play and Blood Glucose and Lactate Concentrations". Journal of Athletic Training 49, n. 4 (1 agosto 2014): 447–53. http://dx.doi.org/10.4085/1062-6050-49.3.12.

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Abstract (sommario):
Context: The ingestion of carbohydrate (CHO) before and during exercise and at halftime is commonly recommended to soccer players for maintaining blood glucose concentrations throughout match play. However, an exercise-induced rebound glycemic response has been observed in the early stages of the second half of simulated soccer-specific exercise when CHO-electrolyte beverages were consumed regularly. Therefore, the metabolic effects of CHO beverage consumption throughout soccer match play remain unclear. Objective: To investigate the blood glucose and blood lactate responses to CHOs ingested before and during soccer match play. Design: Crossover study. Setting: Applied research study. Patients or Other Participants: Ten male outfield academy soccer players (age = 15.6 ± 0.2 years, height = 1.74 ± 0.02 m, mass = 65.3 ± 1.9 kg, estimated maximal oxygen consumption = 58.4 ± 0.8 mL·kg−1·min−1). Intervention(s): Players received a 6% CHO-electrolyte solution or an electrolyte (placebo) solution 2 hours before kickoff, before each half (within 10 minutes), and every 15 minutes throughout exercise. Blood samples were obtained at rest, every 15 minutes during the match (first half: 0–15, 15–30, and 30–45 minutes; second half: 45–60, 60–75, and 75–90 minutes) and 10 minutes into the halftime break. Main Outcome Measure(s): Metabolic responses (blood glucose and blood lactate concentrations) and markers of exercise intensity (heart rate) were recorded. Results: Supplementation influenced the blood glucose response to exercise (time × treatment interaction effect: P ≤ .05), such that glucose concentrations were higher at 30 to 45 minutes in the CHO than in the placebo condition. However, in the second half, blood glucose concentrations were similar between conditions because of transient reductions from peak values occurring in both trials at halftime. Blood lactate concentrations were elevated above those at rest in the first 15 minutes of exercise (time-of-sample effect: P &lt; .001) and remained elevated throughout exercise. Supplementation did not influence the pattern of response (time × treatment interaction effect: P = .49). Conclusions: Ingestion of a 6% CHO-electrolyte beverage before and during soccer match play did not benefit blood glucose concentrations throughout the second half of exercise.
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Ansari, Junaid, Elena Y. Senchenkova, Shantel A. Vital, Zaki Al-Yafeai, Gaganpreet Kaur, Erica M. Sparkenbaugh, A. Wayne Orr et al. "Targeting the AnxA1/Fpr2/ALX pathway regulates neutrophil function, promoting thromboinflammation resolution in sickle cell disease". Blood 137, n. 11 (18 marzo 2021): 1538–49. http://dx.doi.org/10.1182/blood.2020009166.

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Abstract (sommario):
Abstract Neutrophils play a crucial role in the intertwined processes of thrombosis and inflammation. An altered neutrophil phenotype may contribute to inadequate resolution, which is known to be a major pathophysiological contributor of thromboinflammatory conditions such as sickle cell disease (SCD). The endogenous protein annexin A1 (AnxA1) facilitates inflammation resolution via formyl peptide receptors (FPRs). We sought to comprehensively elucidate the functional significance of targeting the neutrophil-dependent AnxA1/FPR2/ALX pathway in SCD. Administration of AnxA1 mimetic peptide AnxA1Ac2-26 ameliorated cerebral thrombotic responses in Sickle transgenic mice via regulation of the FPR2/ALX (a fundamental receptor involved in resolution) pathway. We found direct evidence that neutrophils with SCD phenotype play a key role in contributing to thromboinflammation. In addition, AnxA1Ac2-26 regulated activated SCD neutrophils through protein kinase B (Akt) and extracellular signal–regulated kinases (ERK1/2) to enable resolution. We present compelling conceptual evidence that targeting the AnxA1/FPR2/ALX pathway may provide new therapeutic possibilities against thromboinflammatory conditions such as SCD.
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38

Álvarez Nadal, Marta, Irene Martín Capón, Elizabeth Romelia Viera Ramírez e Milagros Fernández Lucas. "Absolute blood volume variations during hemodialysis: Does dialysate temperature play a role?" Seminars in Dialysis 34, n. 4 (13 febbraio 2021): 309–14. http://dx.doi.org/10.1111/sdi.12958.

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39

Baneke, Alex. "What role does the blood brain barrier play in acute mountain sickness?" Travel Medicine and Infectious Disease 8, n. 4 (luglio 2010): 257–62. http://dx.doi.org/10.1016/j.tmaid.2010.04.006.

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40

Ballard, Mary E., Robert H. Hamby, Cameron D. Panee e Erica E. Nivens. "Repeated Exposure to Video Game Play Results in Decreased Blood Pressure Responding". Media Psychology 8, n. 4 (novembre 2006): 323–41. http://dx.doi.org/10.1207/s1532785xmep0804_1.

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41

Behal, R., R. Jain, K. K. Behal e T. N. Dhole. "600 DO BLOOD GROUP PLAY A ROLE IN HEPATITIS C VIRUS INFECTION?" Journal of Hepatology 48 (gennaio 2008): S224. http://dx.doi.org/10.1016/s0168-8278(08)60602-9.

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42

Zhao, Tongtong, Kai Zhang, Yelei Zhang, Yating Yang, Xiaoshuai Ning, Yu Hu, Xiaoyue Li et al. "Do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders?" Psychopharmacology 238, n. 7 (27 marzo 2021): 1979–90. http://dx.doi.org/10.1007/s00213-021-05824-9.

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Abstract (sommario):
Abstract Rationale and objective Clozapine (CLZ) is the most effective drug for treatment-resistant schizophrenia but is associated with many side effects, including glycometabolism disorders. Immunological mechanisms may be involved in the development of clozapine side effects. Research relating the immunomodulatory effects of clozapine and its early markers to clinically relevant adverse events is needed to reduce the harmful side effects of clozapine. This study aimed to investigate the role of proinflammatory cytokines in clozapine-associated glycometabolism disorders. Methods We measured the effect of a range of doses of clozapine on glycometabolism-related parameters and proinflammatory cytokines levels in mice peripheral blood. We also examined the differences between these indicators in the peripheral blood of clozapine-treated schizophrenia patients and healthy controls. Furthermore, we detected proinflammatory cytokines expression in mice pancreatic tissue. Results Following clozapine administration, glucagon significantly decreased in mouse serum, and proinflammatory cytokine IL-β levels markedly increased. Clozapine reliably increased proinflammatory cytokines (IL-1β, IL-6, and TNF-α) expression in murine pancreatic tissue. Compared with healthy controls, clozapine-treated patients’ BMI, blood glucose, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) increased significantly. In clozapine-treated patients, a higher clozapine daily dosage was associated with higher levels of the proinflammatory cytokines IL-1β and IL-6, and a significant positive correlation was observed between blood glucose levels and the proinflammatory cytokines IL-6 and TNF-α. Conclusion Findings from animal experiments and clinical trials have shown clear evidence that clozapine has a regulatory effect on immune-related proinflammatory cytokines and influences glycometabolism indicators.
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43

Brown, Clive M., Luc Barberini, Abdul G. Dulloo e Jean-Pierre Montani. "Cardiovascular responses to water drinking: does osmolality play a role?" American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 289, n. 6 (dicembre 2005): R1687—R1692. http://dx.doi.org/10.1152/ajpregu.00205.2005.

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Abstract (sommario):
Water drinking activates the autonomic nervous system and induces acute hemodynamic changes. The actual stimulus for these effects is undetermined but might be related to either gastric distension or to osmotic factors. In the present study, we tested whether the cardiovascular responses to water drinking are related to water's relative hypoosmolality. Therefore, we compared the cardiovascular effects of a water drink (7.5 ml/kg body wt) with an identical volume of a physiological (0.9%) saline solution in nine healthy subjects (6 male, 3 female, aged 26 ± 2 years), while continuously monitoring beat-to-beat blood pressure (finger plethysmography), cardiac intervals (electrocardiography), and cardiac output (thoracic impedance). Total peripheral resistance was calculated as mean blood pressure/cardiac output. Cardiac interval variability (high-frequency power) was assessed by spectral analysis as an index of cardiac vagal tone. Baroreceptor sensitivity was evaluated using the sequence technique. Drinking water, but not saline, decreased heart rate ( P = 0.01) and increased total peripheral resistance ( P < 0.01), high-frequency cardiac interval variability ( P = 0.03), and baroreceptor sensitivity ( P = 0.01). Neither water nor saline substantially increased blood pressure. These responses suggest that water drinking simultaneously increases sympathetic vasoconstrictor activity and cardiac vagal tone. That these effects were absent after drinking physiological saline indicate that the cardiovascular responses to water drinking are influenced by its hypoosmotic properties.
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44

Pluznick, Jennifer L. "Renal and cardiovascular sensory receptors and blood pressure regulation". American Journal of Physiology-Renal Physiology 305, n. 4 (15 agosto 2013): F439—F444. http://dx.doi.org/10.1152/ajprenal.00252.2013.

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Abstract (sommario):
Studies over the past decade have highlighted important roles played by sensory receptors outside of traditionally sensory tissues; for example, taste receptors participate in pH sensing in the cerebrospinal fluid, bitter taste receptors mediate bronchodilation and ciliary beating in the lung (Deshpande DA, Wang WC, McIlmoyle EL, Robinett KS, Schillinger RM, An SS, Sham JS, Liggett SB. Nat Med 16: 1299–1304, 2010; Shah AS, Ben-Shahar Y, Moninger TO, Kline JN, Welsh MJ. Science 325: 1131–1134, 2009), and olfactory receptors play roles in both sperm chemotaxis and muscle cell migration (Griffin CA, Kafadar KA, Pavlath GK. Cell 17: 649–661, 2009). More recently, several studies have shown that sensory receptors also play important roles in the regulation of blood pressure. This review will focus on several recent studies examining the roles that sensory receptors play in blood pressure regulation, with an emphasis on three pathways: the adenylate cyclase 3 (AC3) pathway, the Gpr91-succinate signaling pathway, and the Olfr78/Gpr41 short-chain fatty acid signaling pathway. Together, these pathways demonstrate that sensory receptors play important roles in mediating blood pressure control and that blood pressure regulation is coupled to the metabolism of the host as well as the metabolism of the gut microbiota.
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45

Faict, Sylvia, Josephine Muller, Kim De Veirman, Ken Maes, Elke De Bruyne, Rik Schots, Jo Caers, Karin Vanderkerken e Eline Menu. "Exosomes Play a Key Role in Multiple Myeloma Bone Disease and Tumor Development". Blood 132, Supplement 1 (29 novembre 2018): 4484. http://dx.doi.org/10.1182/blood-2018-99-112428.

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Abstract (sommario):
Abstract Multiple Myeloma (MM) is an often incurable plasma cell proliferative disorder, representing about 10% of all hematologic malignancies. Osteolysis is one of the hallmarks of this malignancy, meaning that almost every patient will manifest with an osteolytic lesion during their disease course, resulting in increased morbidity and pain with ultimately a severe impact on the quality of life. The development and progression of MM is largely dependent on the bone marrow (BM) microenvironment wherein communication through different factors including extracellular vesicles (EVs) takes place. This crosstalk not only leads to drug resistance but also to the development of osteolysis. Targeting vesicle secretion could therefore simultaneously ameliorate drug response and bone disease. Here we examined the effects of MM exosomes on different aspects of osteolysis using the 5TGM1 murine model. This syngeneic murine model highly mimics human MM disease and presents with typical MM characteristics such as osteolysis, angiogenesis and a serum M-spike. We first investigated the effects of 5TGM1 small EVs or exosomes, sized 50-120nm in diameter, on osteoclasts and osteoblasts in vitro. 5TGM1 exosomes were able to enhance the resorptive active of osteoclasts. In contrast, these exosomes induced apoptosis in pre-osteoblasts while also blocking their differentiation to mature osteoblasts. RT-PCR showed a downregulation of Runx2, Osterix and Collagen 1A1 expression, while DKK-1 expression was upregulated. Mechanistically, we confirmed the presence of DKK-1 on the 5TGM1 exosomes, which led to a downregulation of the Wnt pathway in osteoblasts. In vivo, we uncovered that 5TGM1 exosomes could induce osteolysis in a similar pattern as the MM cells themselves. We injected C57BL/KalwRij intravenously during three weeks with 5TGM1 exosomes, and analyzed the femurs by micro-computed tomography. These mice had a significantly lower trabecular bone volume, as the result of a lower trabecular number combined with a higher trabecular separation. Next, we inhibited exosome secretion in 5TGM1-inoculated mice to prevent bone loss and increase sensitivity to bortezomib. For blocking exosome secretion we used the neutral sphingomyelinase inhibitor GW4869. This increased cortical bone volume and decreased bone resorption markers (C-terminal telopeptide of collagen type I) without significantly affecting tumor load. This indicates that inhibiting exosome secretion in the MM microenvironment has a protective effect on myeloma bone disease, not associated with effects on tumor load. Furthermore, blocking exosome secretion by GW4869 also sensitized the myeloma cells to bortezomib, leading to a strong anti-tumor response in vivo when GW4869 and bortezomib were combined. Altogether, our results indicate a key role for exosomes in the myeloma BM microenvironment and suggest a novel therapeutic target for anti-myeloma therapy. Disclosures No relevant conflicts of interest to declare.
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46

Gambaryan, Stepan, Andreas Friebe e Ulrich Walter. "Does the NO/sGC/cGMP/PKG pathway play a stimulatory role in platelets?" Blood 119, n. 22 (31 maggio 2012): 5335–36. http://dx.doi.org/10.1182/blood-2011-12-396374.

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47

Huang, Jianping, Caroline Jochems, Tara Talaie, Austin Anderson, Alessandra Jales, Kwong Y. Tsang, Ravi A. Madan, James L. Gulley e Jeffrey Schlom. "Elevated serum soluble CD40 ligand in cancer patients may play an immunosuppressive role". Blood 120, n. 15 (11 ottobre 2012): 3030–38. http://dx.doi.org/10.1182/blood-2012-05-427799.

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Abstract (sommario):
Abstract Tumor cells can induce certain cytokines and soluble receptors that have a suppressive effect on the immune system. In this study, we showed that an extracellular portion of a membrane-bound ligand of CD40 (soluble CD40 ligand; sCD40L) was significantly elevated in the serum of cancer patients compared with healthy donors. In addition, PBMCs from cancer patients had a relatively larger population of myeloid-derived suppressor cells (MDSCs), defined as CD33+HLA-DR− cells, and these cells expressed higher levels of CD40. T-cell proliferation and IFN-γ production decreased when stimulated T cells were cocultured with an increased amount of autologous MDSCs. The addition of recombinant monomeric sCD40L enriched MDSCs and had an additive inhibitory effect on T-cell proliferation. PBMCs cultured in vitro with sCD40L also showed an expansion of regulatory T cells (CD4+CD25highFoxp3+), as well as induction of cytokines, such as IL-10 and IL-6. Moreover, sCD40L-induced enrichment of programmed death-1–expressing T cells was greater in cancer patients than in healthy donors. Preexisting sCD40L also inhibited IL-12 production from monocytes on activation. These data suggest that the higher levels of sCD40L seen in cancer patients may have an immunosuppressive effect. These studies were registered at www.clinicaltrials.gov as NCT00060528, NCT00019695, NCT00179309, NCT00514072, NCT00081848, and NCT00436956.
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48

Radosinska, Jana, Tomas Jasenovec, Angelika Puzserova, Juraj Krajcir, Jana Lacekova, Katarina Kucerova, Terezia Kalnovicova, Lubomira Tothova, Ivona Kovacicova e Norbert Vrbjar. "Promotion of whole blood rheology after vitamin C supplementation: focus on red blood cells". Canadian Journal of Physiology and Pharmacology 97, n. 9 (settembre 2019): 837–43. http://dx.doi.org/10.1139/cjpp-2018-0735.

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Abstract (sommario):
Hemorheological properties represent significant contributors in the pathogenesis of cardiovascular diseases. As plasma vitamin C is inversely associated with blood viscosity in humans, we aimed to characterize the effect of vitamin C supplementation on hemorheology with an emphasis on erythrocyte functions. Twenty young healthy volunteers were asked to take vitamin C (1000 mg per day) for 3 weeks. We observed beneficial effect of intervention on multiple hemorheological parameters: whole blood viscosity in the range of medium to high shear rates, Casson yield stress, complex viscosity, and storage and loss moduli. As erythrocyte properties play a significant role in hemorheology, we characterized their deformability, nitric oxide production, and sodium pump activity in erythrocyte membranes. We can conclude that observed promotion in whole blood rheology may be consequence of improved erythrocyte functionality as concerns their ability to pass through narrow capillaries of the microcirculation, nitric oxide production, and sodium pump activity. Parameters reflecting oxidative stress and antioxidant status in plasma were not affected by our intervention. As improvement in hemorheology may play an important role in cardioprotection, it would be challenging to investigate the vitamin C supplementation to patients suffering from microcirculatory disturbances and worsened organ perfusion in the case of cardiovascular diseases.
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49

Takizawa, Daisuke, Haruhiko Hiraoka, Fumio Goto, Koujirou Yamamoto e Ryuya Horiuchi. "Human Kidneys Play an Important Role in the Elimination of Propofol". Anesthesiology 102, n. 2 (1 febbraio 2005): 327–30. http://dx.doi.org/10.1097/00000542-200502000-00014.

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Abstract (sommario):
Background Extrahepatic clearance of propofol has been suggested because its total body clearance exceeds hepatic blood flow. However, it remains uncertain which organs are involved in the extrahepatic clearance of propofol. In vitro studies suggest that the kidneys contribute to the clearance of this drug. The purpose of this study was to confirm whether human kidneys participate in propofol disposition in vivo. Methods Ten patients scheduled to undergo nephrectomy were enrolled in this study. Renal blood flow was measured using para-aminohippurate. Anesthesia was induced with vecuronium (0.1 mg/kg) and propofol (2 mg/kg) and then maintained with nitrous oxide (60%), sevoflurane (1 approximately 2%) in oxygen, and an infusion of propofol (2 mg . kg . h). Radial arterial blood for propofol and para-aminohippurate analysis was collected from a cannula inserted in the radial artery. The renal venous sample and the radial arterial sample were obtained at the same time after the steady state of propofol was established. Results The renal extraction ratio of propofol was 0.58 +/- 0.15 (mean +/- SD). The renal clearance of propofol was 0.41 +/- 0.15 l/min (mean +/- SD), or 27 +/- 9.9% (mean +/- SD) of total body clearance. Conclusion Human kidneys play an important role in the elimination of propofol.
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Demirhan, Osman, Deniz Taştemir Korkmaz e Nesrin Çetinel. "Cytogenetic differences in blood and cancer tissue samples of the same patient group". Cancer Research and Cellular Therapeutics 4, n. 1 (7 agosto 2020): 01–03. http://dx.doi.org/10.31579/2640-1053/070.

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Abstract (sommario):
Breast cancer (BC) is the most prevalent malignant disease in females worldwide. Genomic instability in tumor tissue has been associated with tumor progression. These genetic changes may take a variety of forms, including numerical and structural chromosomal abnormalities (CAs), epigenetic changes, and gene expression alterations. Many tumor tissues are made up of genetically different cell populations, and the study of the causes and consequences of this heterogeneity play a central role in cancer research. In this study, CAs in blood and cancer tissues of patients with sporadic BC were examined. Our findings shows that the increase in numerical sex aneuploidy in BC tissues is significantly higher than in blood tissue. These aneuploidy increases in cancer tissues seem to be compatible with the development and increase of cancer, and can play a role in the pathogenesis of cancers. These changes are consistent with early and long-standing exposure to carcinogens, especially estrogens. These findings should clarify our understanding of breast carcinogenesis in breast tissues and promote development of improved methods for risk assessment and BC prevention in women.
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