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#32590296   2020/06/23 To Up

Quantitative and qualitative impairments in dendritic cell subsets of patients with ovarian or prostate cancer.

Dendritic cells (DCs) are the most efficient antigen-presenting cells, hence initiating a potent and cancer-specific immune response. This ability (mainly using monocyte-derived DCs) has been exploited in vaccination strategies for decades with limited clinical efficacy. Another alternative would be the use of conventional DCs (cDCs) of which at least three subsets circulate in human blood: cDC1s (CD141), cDC2s (CD1c) and plasmacytoid DCs. Despite their paucity, technical advances may allow for their selection and clinical use. However, many assumptions concerning the DC subset biology depend on observations from mouse models, hindering their translational potential. In this study, we characterise human DCs in patients with ovarian cancer (OvC) or prostate cancer (PrC).
Beatris Mastelic-Gavillet, Apostolos Sarivalasis, Leyder Elena Lozano, Tania Wyss, Susana Inoges, Ingrid Jolanda Monique de Vries, Florence Dartiguenave, Patrice Jichlinski, Laurent Derrè, George Coukos, Ignacio Melero, Alexandre Harari, Pedro Romero, Selena Viganó, Lana Elias Kandalaft

2388 related Products with: Quantitative and qualitative impairments in dendritic cell subsets of patients with ovarian or prostate cancer.

100 ml.2 ml

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#32586904   2020/06/25 To Up

In vitro and in vivo induction of fetal hemoglobin with a reversible and selective DNMT1 inhibitor.

Pharmacological induction of fetal hemoglobin (HbF) expression is an effective therapeutic strategy for the management of beta-hemoglobinopathies such as sickle cell disease. DNA methyltransferase (DNMT) inhibitors 5-azacytidine (5-aza) and 5-aza-2'-deoxycytidine (decitabine) have been shown to induce fetal hemoglobin expression in both preclinical models and clinical studies, but are not currently approved for the management of hemoglobinopathies. We report here the discovery of a novel class of orally bioavailable DNMT1-selective inhibitors as exemplified by GSK3482364. This molecule potently inhibits the methyltransferase activity of DNMT1, but not DNMT family members DNMT3A or DNMT3B. In contrast with cytidine analog DNMT inhibitors, the DNMT1 inhibitory mechanism of GSK3482364 does not require DNA incorporation and is reversible. In cultured human erythroid progenitor cells (EPCs), GSK3482364 decreased overall DNA methylation resulting in de-repression of the gamma globin genes HBG1 and HBG2 and increased HbF expression. In a transgenic mouse model of sickle cell disease, orally administered GSK3482364 caused significant increases in both HbF levels and in the percentage HbF-expressing erythrocytes, with good overall tolerability. We conclude that in these preclinical models, selective, reversible inhibition of DNMT1 is sufficient for the induction of HbF, and is well-tolerated. We anticipate that GSK3482364 will be a useful tool molecule for the further study of selective DNMT1 inhibition both in vitro and in vivo.
Aidan G Gilmartin, Arthur Groy, Elizabeth R Gore, Charity Atkins, Edward R Long, Monica N Montoute, Zining Wu, Wendy Halsey, Dean E McNulty, Daniela Ennulat, Lourdes Rueda, Melissa Pappalardi, Ryan G Kruger, Michael T McCabe, Ali Raoof, Roger Butlin, Alexandra Stowell, Mark Cockerill, Ian Waddell, Donald Ogilvie, Juan Luengo, Allan Jordan, Andrew B Benowitz

1579 related Products with: In vitro and in vivo induction of fetal hemoglobin with a reversible and selective DNMT1 inhibitor.

100 assays10 mg5mg100 ul (2 mM)100 ul100 assays100μg100 μg100 µg100.00 ug25 mg100ug Lyophilized

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#32581362   2020/06/24 To Up

Whole-genome sequencing of patients with rare diseases in a national health system.

Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. We generated WGS data for 13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to 1,138 of the 7,065 extensively phenotyped participants. We identified 95 Mendelian associations between genes and rare diseases, of which 11 have been discovered since 2015 and at least 79 are confirmed to be aetiological. By generating WGS data of UK Biobank participants, we found that rare alleles can explain the presence of some individuals in the tails of a quantitative trait for red blood cells. Finally, we identified four novel non-coding variants that cause disease through the disruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates a synergy by using WGS for diagnosis and aetiological discovery in routine healthcare.
Ernest Turro, William J Astle, Karyn Megy, Stefan Gräf, Daniel Greene, Olga Shamardina, Hana Lango Allen, Alba Sanchis-Juan, Mattia Frontini, Chantal Thys, Jonathan Stephens, Rutendo Mapeta, Oliver S Burren, Kate Downes, Matthias Haimel, Salih Tuna, Sri V V Deevi, Timothy J Aitman, David L Bennett, Paul Calleja, Keren Carss, Mark J Caulfield, Patrick F Chinnery, Peter H Dixon, Daniel P Gale, Roger James, Ania Koziell, Michael A Laffan, Adam P Levine, Eamonn R Maher, Hugh S Markus, Joannella Morales, Nicholas W Morrell, Andrew D Mumford, Elizabeth Ormondroyd, Stuart Rankin, Augusto Rendon, Sylvia Richardson, Irene Roberts, Noemi B A Roy, Moin A Saleem, Kenneth G C Smith, Hannah Stark, Rhea Y Y Tan, Andreas C Themistocleous, Adrian J Thrasher, Hugh Watkins, Andrew R Webster, Martin R Wilkins, Catherine Williamson, James Whitworth, Sean Humphray, David R Bentley, , Nathalie Kingston, Neil Walker, John R Bradley, Sofie Ashford, Christopher J Penkett, Kathleen Freson, Kathleen E Stirrups, F Lucy Raymond, Willem H Ouwehand

2334 related Products with: Whole-genome sequencing of patients with rare diseases in a national health system.

500 tests500 tests500 tests500 tests500 tests500 tests

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#32565469   2020/06/21 To Up

Effect of early cryoprecipitate transfusion versus standard care in women who develop severe postpartum haemorrhage (ACROBAT) in the UK: a protocol for a pilot cluster randomised trial.

The incidence of severe postpartum haemorrhage (PPH) that requires blood transfusion is on the increase. Fibrinogen levels have been shown to drop early and significantly during PPH, which is associated with worse outcomes. Early fibrinogen replacement could potentially improve outcomes. No studies have investigated the clinical impact of early cryoprecipitate transfusion in PPH. Prior to performing a full-scale trial, a pilot study is needed to determine feasibility of the intervention and recruitment.
Laura Green, Jahnavi Daru, Julie Dodds, Francisco Jose Gonzalez Carreras, Doris Lanz, Javier Zamora, Maria Del Carmen Pardo Llorente, Teresa Pérez Pérez, Lorna Sweeney, Shakila Thangaratinam, Amy Thomas, Khalid Saeed Khan

1149 related Products with: Effect of early cryoprecipitate transfusion versus standard care in women who develop severe postpartum haemorrhage (ACROBAT) in the UK: a protocol for a pilot cluster randomised trial.

300 units0.1ml (1mg/ml)1

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#32562599   2020/06/17 To Up

Reticular Fibroblasts Expressing the Transcription Factor WT1 Define a Stromal Niche That Maintains and Replenishes Splenic Red Pulp Macrophages.

Located within red pulp cords, splenic red pulp macrophages (RPMs) are constantly exposed to the blood flow, clearing senescent red blood cells (RBCs) and recycling iron from hemoglobin. Here, we studied the mechanisms underlying RPM homeostasis, focusing on the involvement of stromal cells as these cells perform anchoring and nurturing macrophage niche functions in lymph nodes and liver. Microscopy revealed that RPMs are embedded in a reticular meshwork of red pulp fibroblasts characterized by the expression of the transcription factor Wilms' Tumor 1 (WT1) and colony stimulating factor 1 (CSF1). Conditional deletion of Csf1 in WT1 red pulp fibroblasts, but not white pulp fibroblasts, drastically altered the RPM network without altering circulating CSF1 levels. Upon RPM depletion, red pulp fibroblasts transiently produced the monocyte chemoattractants CCL2 and CCL7, thereby contributing to the replenishment of the RPM network. Thus, red pulp fibroblasts anchor and nurture RPM, a function likely conserved in humans.
Alicia Bellomo, Isabelle Mondor, Lionel Spinelli, Marine Lagueyrie, Benjamin J Stewart, Nicolas Brouilly, Bernard Malissen, Menna R Clatworthy, Marc Bajénoff

1568 related Products with: Reticular Fibroblasts Expressing the Transcription Factor WT1 Define a Stromal Niche That Maintains and Replenishes Splenic Red Pulp Macrophages.

200ug962ug200ug200ug 100ul200ug 25UGKit62ug96

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#32549922   2020/04/28 To Up

Dual shape recovery of red blood cells flowing out of a microfluidic constriction.

Micropipette aspiration, optical tweezers, rheometry, or ecktacytometry have been used to study the shape recovery of healthy human Red Blood Cells (RBCs) and measure associated relaxation times of the order of 100-300 ms. These measurements are in good agreement with the Kelvin-Voigt model, which describes the cell as a visco-elastic material, predicting that its relaxation time only depends on cell intrinsic properties. However, such mechanical solicitation techniques are far from being relevant regarding RBC solicitation . In this paper, we report for the first time the existence of two different behaviors of the RBC shape recovery while flowing out of a microfluidic constricted channel. The calculation of the viscous stress corresponding to the frontier between the two recovery modes confirms that the RBC resistance to shear is the elastic property dominating the transition between the two recovery behaviors. We also quantified associated recovery times and report values as low as 4 ms-which is almost two decades smaller than the typical RBC relaxation time-at high viscosity and flow velocity of the carrier fluid. Although we cannot talk about relaxation time because the cell is never at rest, we believe that the measured shape recovery time arises from the coupling of the cell intrinsic deformability and the hydrodynamic stress. Depending on the flow conditions, the cell mechanics becomes dominant and drives the shape recovery process, allowing the measurement of recovery times of the same order of magnitude than relaxation times previously published. Finally, we demonstrated that the measurement of the shape recovery time can be used to distinguish (causing malaria) infected RBCs from healthy RBCs.
A Amirouche, J Esteves, A Lavoignat, S Picot, R Ferrigno, M Faivre

2975 related Products with: Dual shape recovery of red blood cells flowing out of a microfluidic constriction.

100 extractions100 extractions50 mg100ml 100ul 1 kit(s) 100ml200 assays100ug/vial96T

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#32545511   2020/06/12 To Up

The Central Role of Iron in Human Nutrition: From Folk to Contemporary Medicine.

Iron is a fundamental element in human history, from the dawn of civilization to contemporary days. The ancients used the metal to shape tools, to forge weapons, and even as a dietary supplement. This last indication has been handed down until today, when martial therapy is considered fundamental to correct deficiency states of anemia. The improvement of the martial status is mainly targeted with dietary supplements that often couple diverse co-factors, but other methods are available, such as parenteral preparations, dietary interventions, or real-world approaches. The oral absorption of this metal occurs in the duodenum and is highly dependent upon its oxidation state, with many absorption influencers possibly interfering with the intestinal uptake. Bone marrow and spleen represent the initial and ultimate step of iron metabolism, respectively, and the most part of body iron circulates bound to specific proteins and mainly serves to synthesize hemoglobin for new red blood cells. Whatever the martial status is, today's knowledge about iron biochemistry allows us to embrace exceedingly personalized interventions, which however owe their success to the mythical and historical events that always accompanied this metal.
Matteo Briguglio, Silvana Hrelia, Marco Malaguti, Giovanni Lombardi, Patrizia Riso, Marisa Porrini, Paolo Perazzo, Giuseppe Banfi

2562 related Products with: The Central Role of Iron in Human Nutrition: From Folk to Contemporary Medicine.

100 UG25 100 μg100 500 25 mg100 μg1.00 flask

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#32533699   2020/06/13 To Up

A Rare Cohort of Two Rhnull Individuals.

A 77 year old female was admitted with a subdural hematoma requiring 1 unit of apheresis platelets. She was a study subject in the 1960s and was found to be Rhnull, along with another individual who previously served as a directed donor for her.
Richard R Gammon, Alexander Delk, Patricia Houtz, Harold Alvarez, Nancy Benitez

1301 related Products with: A Rare Cohort of Two Rhnull Individuals.

100ug Lyophilized100ug100ug 5 G100ug2 mL100 100 μg100ug100ug100ug Lyophilized100μl

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#32532356   2020/06/12 To Up

Safety and efficacy assessment of allogeneic human dental pulp stem cells to treat patients with severe COVID-19: structured summary of a study protocol for a randomized controlled trial (Phase I / II).

To assess the safety and therapeutic effects of allogeneic human dental pulp stem cells (DPSCs) in treating severe pneumonia caused by COVID-19.
Qingsong Ye, Hua Wang, Xia Xia, Chenliang Zhou, Zhiming Liu, Zun-En Xia, Zhan Zhang, Yang Zhao, Jun Yehenala, Si Wang, Gangqiao Zhou, Ke Hu, Bin Wu, Chu-Tse Wu, Songling Wang, Yan He

1351 related Products with: Safety and efficacy assessment of allogeneic human dental pulp stem cells to treat patients with severe COVID-19: structured summary of a study protocol for a randomized controlled trial (Phase I / II).

1.00 flask1.00 flask25 µg0.1ml (1mg/ml)100 TESTS5 x 50 ug100 μg0.1 mg0.1 mg100 25 25 µg

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