Review
Immunology
Vasilios A. Morikis, Alfredo A. Hernandez, John L. Magnani, Markus Sperandio, Scott I. Simon
Summary: This article discusses the dual role of neutrophils in SCD and the mechanism of vascular occlusion associated with sickle cell disease. Regulation of neutrophil impact on patients through selectin-mediated integrin adhesive bond formation is highlighted.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Hematology
Jennell White, Michael U. Callaghan, Xiufeng Gao, Ke Liu, Ahmar Zaidi, Michael Tarasev, Patrick C. Hines
Summary: This study evaluated the relationship between FA-WB-VCAM and SCD severity, finding a strong correlation. SCD patients with high frequency of self-reported VOCs exhibited a pro-adhesive phenotype at steady state, potentially impacting the frequency of VOC occurrences.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Cell Biology
Lidiane S. Torres, Hanan Chweih, Fernanda C. Z. Fabris, Erica M. F. Gotardo, Flavia C. Leonardo, Sara T. Olalla Saad, Fernando F. Costa, Nicola Conran
Summary: This study investigates the role of transforming growth factor beta-1 (TGF-beta 1) in vascular inflammation and vaso-occlusion in a sickle cell disease (SCD) animal model. The results suggest that TGF-beta 1 may have a significant ameliorative effect on SCD pathophysiology by modulating inflammation and vaso-occlusion.
Article
Hematology
Patrick C. Hines, Michael U. Callaghan, Ahmar U. Zaidi, Xiufeng Gao, Ke Liu, Jennell White, Michael Tarasev
Summary: The study found that adhesion of blood cells to P-selectin and VCAM1 is significantly increased on VOC days in patients with SCD. By establishing optimal cutoff values and a multimarker risk score, a better ability to identify VOC risk was demonstrated.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Medicine, General & Internal
John D. Belcher, Selvaraj Nataraja, Fuad Abdulla, Ping Zhang, Chunsheng Chen, Julia Nguyen, Conglin Ruan, Maneet Singh, Shilpa Demes, Lyndsay Olson, Domi Stickens, Jeff Stanwix, Emer Clarke, Yongzhao Huang, Margaret Biddle, Gregory M. Vercellotti
Summary: In sickle cell disease, heme released during hemolysis can cause oxidative stress, inflammation, and blockage of blood vessels. However, free heme can also activate the expression of antioxidant and globin genes. ASP8731 is a small molecule inhibitor of a transcription factor called BACH1, and it has been found to modulate pathways involved in sickle cell disease pathophysiology.
FRONTIERS IN MEDICINE
(2023)
Article
Medicine, General & Internal
Joanna Gemel, Jared Zhang, Yifan Mao, Gabrielle Lapping-Carr, Eric C. Beyer
Summary: The study found that extracellular vesicles (EVs) in the plasma of patients with sickle cell disease (SCD) disrupt the integrity of endothelial cell monolayers, especially during episodes of acute chest syndrome (ACS). The findings suggest that circulating EVs may be involved in modulating endothelial integrity and contributing to the pathogenesis of different complications of SCD.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Boris Tchernychev, Huihui Li, Sung-Kyun Lee, Xin Gao, Raghunath Ramanarasimhaiah, Guang Liu, Katherine C. Hall, Sylvie G. Bernier, Juli E. Jones, Susanne Feil, Robert Feil, Emmanuel S. Buys, Regina M. Graul, Paul S. Frenette, Jaime L. Masferrer
Summary: The sGC stimulator olinciguat attenuates inflammation, vaso-occlusion, and kidney injury in mouse models of SCD and systemic inflammation. Co-treatment with hydroxyurea enhances the anti-inflammatory effect of olinciguat, showing a potential beneficial impact on disease progression.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Immunology
Joan D. Beckman, Fuad Abdullah, Chunsheng Chen, Rachel Kirchner, Dormarie Rivera-Rodriguez, Zachary M. Kiser, Aithanh Nguyen, Ping Zhang, Julia Nguyen, Robert P. Hebbel, John D. Belcher, Gregory M. Vercellotti
Summary: This study found that in sickle cell disease, endothelial cell TLR4 expression, rather than hematopoietic cell TLR4, is crucial for initiating vaso-occlusive physiology.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Engineering, Biomedical
Yuhao Qiang, Darryl Dieujuste, Jia Liu, Ofelia Alvarez, E. Du
Summary: Sickle cell disease is characterized by painful vaso-occlusive crises, in which poorly deformable sickle cells play an important role. This study presents a microfluidic chip that integrates electrical impedance sensing and microvascular mimics for rapid quantification of vaso-occlusion by rigid, sickled cells. The chip demonstrated real-time detection of different sickle cell flow behaviors and proved to be sensitive in detecting vaso-occlusion under deoxygenation.
BIOMEDICAL MICRODEVICES
(2023)
Article
Biochemistry & Molecular Biology
Omika Katoch, Ramakrishna Ungalara, Tomasz Kaminski, Ziming Li, Rikesh K. Dubey, Isabella Burholt, Shweta Gudapati, Tirthadipa Pradhan-Sundd
Summary: The long-term effect of L-glutamine administration in the liver was investigated in humanized SCD mice. Chronic L-glutamine administration reduced hepatic hemoglobin-heme-iron levels but failed to ameliorate ischemic liver injury. This failure was found to be associated with reduced expression of hepatic Kupffer cells post-L-glutamine treatment.
Review
Medicine, Research & Experimental
Tim Jang, Maria Poplawska, Emanuela Cimpeanu, George Mo, Dibyendu Dutta, Seah H. Lim
Summary: VOC remains the most common reason for presentation in SCD patients, but current treatments to shorten VOC have had disappointing results. Exploration of the reasons for ineffective monotherapy and consideration of combination approaches with multiple agents may be necessary to target complex downstream pathways of VOC.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Review
Hematology
Connor Stewart, Tim Jang, George Mo, Nader Mohamed, Maria Poplawska, Ogechukwu Egini, Dibyendu Dutta, Seah H. Lim
Summary: The clinical use of hydroxyurea remains low among SCD patients in the US. Recent studies suggest a link between bacterial overgrowth, dysbiosis, and intestinal pathophysiological changes in SCD, affecting neutrophil aging and potentially contributing to vaso-occlusive crises. Understanding this relationship may lead to new antibiotic-based therapeutic approaches for modifying the clinical course of VOC in SCD.
Review
Medicine, Research & Experimental
Nicola Conran, Stephen H. Embury
Summary: Sickle cell anemia is a hereditary hemoglobinopathy characterized by abnormal hemoglobin polymerization that triggers pathological mechanisms leading to various severe complications. Recent research has focused on the role of leukocytes in vaso-occlusive processes and the importance of adhesion by different cell types, including endothelial cells, platelets, leukocytes, and red blood cells.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2021)
Article
Plant Sciences
Denise Rubinho dos Santos Martins, Caroline Honaiser Lescano, Alberto Fernando Oliveira Justo, Julia Modesto Vicente, Sergio Henrique Sousa Santos, Charles Martins Aguilar, Alexandre Borges, Ivan Pires de Oliveira, Eliana Janet Sanjinez-Argandona
Summary: The study found that applying ultrasonic turbolization combined with acidified water significantly increased the levels of anthocyanins and antioxidant activity in the Hibiscus sabdariffa L. calyx extract. The extract showed effects such as antiplatelet aggregation, reduction in calcium mobilization, and promotion of cyclic nucleotide levels and vasodilation.
PLANT FOODS FOR HUMAN NUTRITION
(2023)
Article
Hematology
Carlton D. Dampier, Marilyn Jo Telen, Ted Wun, R. Clark Brown, Payal Desai, Fuad El Rassi, Beng Fuh, Julie Kanter, Yves Pastore, Jennifer Rothman, James G. Taylor, David Readett, Krupa M. Sivamurthy, Brinda Tammara, Li-Jung Tseng, Jay Nelson Lozier, Helen Thackray, John L. Magnani, Kathryn L. Hassell
Summary: This study evaluated the efficacy and safety of rivipansel in vaso-occlusive crisis (VOC) requiring hospitalization. The results showed that rivipansel did not significantly impact the primary end point, but early treatment with rivipansel after pain onset can accelerate the resolution of acute VOC.
Article
Oncology
Antonio Bruno Alves-Silva, Bruna Alves Fenerich, Natasha Peixoto Fonseca, Jaqueline Cristina Fernandes, Juan Luiz Coelho-Silva, Diego Antonio Pereira-Martins, Thiago Mantello Bianco, Priscila Santos Scheucher, Eduardo Magalhaes Rego, Fernando Chahud, Joao Agostinho Machado-Neto, Lorena Lobo Figueiredo-Pontes, Fabiola Traina
Summary: This study investigated the effects of phenformin on Jak2(V617F)-knockin MPN mice. The results showed that phenformin increased the percentages of LSK, MP, and MPP populations in the bone marrow, but did not reduce the disease burden. Further studies are needed to understand the effects of phenformin on early hematopoietic progenitors.
INVESTIGATIONAL NEW DRUGS
(2022)
Article
Genetics & Heredity
Pedro Rodrigues Sousa da Cruz, Galina Ananina, Rodrigo Secolin, Vera Lucia Gil-da-Silva-Lopes, Carmen Silvia Passos Lima, Paulo Henrique Condeixa de Franca, Amanda Donatti, Gustavo Jacob Lourenco, Tania Kawasaki de Araujo, Milena Simioni, Iscia Lopes-Cendes, Fernando Ferreira Costa, Monica Barbosa de Melo
Summary: The genetic structure of Latino populations is affected by their complex demographic history, including multiple admixing events, bottlenecks and/or expansions, and unique adaptive events. The study found that the amount of American and African ancestry is related to the decay of linkage disequilibrium, and the extent of identity by descent sharing is correlated with historical effective population sizes. Long runs of homozygosity were only enriched in Peruvians and Native Americans. Positive selection signals were observed in certain markers, indicating human adaptation to the American continent.
G3-GENES GENOMES GENETICS
(2022)
Article
Cell Biology
Lidiane S. Torres, Hanan Chweih, Fernanda C. Z. Fabris, Erica M. F. Gotardo, Flavia C. Leonardo, Sara T. Olalla Saad, Fernando F. Costa, Nicola Conran
Summary: This study investigates the role of transforming growth factor beta-1 (TGF-beta 1) in vascular inflammation and vaso-occlusion in a sickle cell disease (SCD) animal model. The results suggest that TGF-beta 1 may have a significant ameliorative effect on SCD pathophysiology by modulating inflammation and vaso-occlusion.
Letter
Hematology
Nicola Conran, Claudia de Alvarenga Maximo, Thais Oliveira, Kleber Y. Fertrin, Clarisse Lobo, Fernando F. Costa
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Medicine, Research & Experimental
Bidossessi Wilfried Hounkpe, Carla Roberta Peachazepi Moraes, Carolina Lanaro, Magnun Nueldo Nunes Santos, Fernando Ferreira Costa, Erich Vinicius De Paula
Summary: Hemoglobin can induce the expression and activation of tissue factor, contributing to the pathogenesis of hypercoagulability in hemolytic diseases.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2022)
Letter
Hematology
Keith W. Pratz, Courtney D. DiNardo, Dominik Selleslag, Junmin Li, Kazuhito Yamamoto, Marina Konopleva, Don Stevens, Hagop Kantarjian, Fabiola Traina, Adriano Venditti, Jiri Mayer, Melissa Montez, Huan Jin, Yinghui Duan, Deanna Brackman, Jiuhong Zha, Jalaja Potluri, Michael Werner, Brian A. Jonas
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Hematology
Diego A. Pereira-Martins, Juan L. Coelho-Silva, Isabel Weinhauser, Pedro L. Franca-Neto, Douglas R. Silveira, Cesar Ortiz, Amanda Moreira-Aguiar, Marinus M. Lima, Luisa C. Koury, Raul A. de Melo, Ana B. Gloria, Evandro M. Fagundes, Bruno K. Lino, Katia Pagnano, Rosane Bittencourt, Elenaide Nunes, Fabiola Traina, Lorena Figueiredo-Pontes, Armand Keating, Martin S. Tallman, Raul C. Ribeiro, Richard Dilon, Arnold Ganser, Miguel A. Sanz, Nancy Berliner, Peter Valk, Bob Lowenberg, Tiziana Ottone, Nelida Noguera, Maria T. Voso, Francesca Paoloni, Paola Fazi, Emanuele Ammatuna, Gerwin Huls, Jan Jacob Schuringa, Eduardo M. Rego, Antonio R. Lucena-Araujo
Summary: A growing body of evidence indicates that higher-than-normal mitochondrial DNA content (mtDNAc) is associated with better prognosis in acute promyelocytic leukemia (APL) patients, regardless of tumor burden. This effect is more pronounced in low-risk patients. The multivariate Cox proportional hazard model reveals that high mtDNAc is independently associated with a decreased cumulative incidence of relapse. These findings highlight the potential role of mitochondrial metabolism in APL patients treated with ATRA.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Toxicology
Jaqueline Cristina Fernandes, Bruna Alves Fenerich, Antonio Bruno Alves-Silva, Natasha Peixoto Fonseca, Juan Luiz Coelho-Silva, Priscila Santos Scheucher, Eduardo Magalhaes Rego, Lorena Lobo Figueiredo-Pontes, Joao Agostinho Machado-Neto, Fabiola Traina
Summary: This study compared the potency and efficacy of three inhibitors of IGF1R-related pathways in a JAK2(V617F)-driven cellular model, finding that these inhibitors all have antineoplastic activity with NT157 being the most potent. The downregulation of the JAK2/STAT signaling pathway was a beneficial off-target effect of all three inhibitors.
TOXICOLOGY IN VITRO
(2022)
Article
Multidisciplinary Sciences
Livia Bassani Lins de Miranda, Keli Lima, Juan Luiz Coelho-Silva, Fabiola Traina, Susumu S. Kobayashi, Joao Agostinho Machado-Neto
Summary: The compound NT157 has been found to inhibit the growth and migration of lung cancer cells, induce apoptosis, and suppress signaling pathways. At the molecular level, NT157 reduces the expression of oncogenes and increases the expression of genes related to cellular stress and apoptosis. It was also discovered that JNK plays a key role in NT157-induced phosphorylation of IRS1 and IRS2. Additionally, NT157 has synergistic effects with EGFR inhibitors.
SCIENTIFIC REPORTS
(2022)
Meeting Abstract
Hematology
Amanda F. O. Costa, Valeriya Kuznetsova, Leticia O. Marani, Izabela A. Lopes, Larissa S. Binelli, Priscila S. Scheucher, Josiane L. Schiavinato, Joana T. B. Faria, Maria Isabel A. Madeira, Katia B. Pagnano, Bruno K. Duarte, Ana Beatriz F. Gloria, Eduardo M. Rego, Fabiola Traina, Robert Welner, Lorena L. Figueiredo-Pontes
Meeting Abstract
Hematology
Diego Pereira-Martins, Noortje van Dijk, Isabel Weinhaeuser, Douglas Ra Silveira, Juan Coelho Da Silva, Thiago M. Bianco, Cesar Alexander Ortiz, Fabiola Traina, Lorena L. Figueiredo-Pontes, Emanuele Ammatuna, Lynn Quek, Gerwin A. Huls, Antonio R. Lucena-Araujo, Eduardo M. Rego, Jan Jacob Schuringa
Meeting Abstract
Hematology
Natasha Peixoto Fonseca, Bruna Alves Fenerich, Diego A. Pereira-Martins, Pedro Manoel Marques Garibaldi, Juan L. Coelho-Silva, Antonio Bruno Alves Silva, Jaqueline Cristina Fernandes, Cleide Lucia Silva, Eduardo M. Rego, Joao Agostinho Machado-Neto, Fabiola Traina
Editorial Material
Medicine, Research & Experimental
Nicola Conran, Muriel Lambert, Nancy D. Turner
Summary: This issue of Experimental Biology and Medicine commemorates the significant impact made by women leaders in biomedical sciences in recent history. Scientists from diverse fields have contributed original research and state-of-the-art reviews to showcase the daily work of women leaders dedicated to advancing scientific knowledge in their respective fields. This introduction provides a brief overview of the information included in the invited papers.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2022)
Article
Hematology
Elie Nader, Nicola Conran, Flavia C. Leonardo, Aline Hatem, Camille Boisson, Romain Carin, Celine Renoux, Fernando F. Costa, Philippe Joly, Pamela L. Brito, Sofia Esperti, Joelle Bernard, Alexandra Gauthier, Solene Poutrel, Yves Bertrand, Caroline Garcia, Sara T. O. Saad, Stephane Egee, Philippe Connes
Summary: Haemoglobin S polymerization in the red blood cells of individuals with sickle cell anaemia can cause cellular alterations. Piezo1 protein activation and Gardos channel activity decrease sickle red blood cell deformability and increase their propensity to sickle and adhere to laminin. These results suggest that Piezo1 may represent a potential therapeutic target for sickle cell anaemia.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Renata Sesti-Costa, Fernando F. F. Costa, Nicola Conran
Summary: Sickle cell disease (SCD) is a genetic blood disorder characterized by the production of sickle-shaped red blood cells due to a gene mutation. The disease leads to various complications such as anemia, inflammation, and tissue damage. Macrophages play a role in removing damaged red blood cells and recycling iron for the generation of new red blood cells. In SCD, anemia and inflammation may induce stress erythropoiesis, expanding the number of erythroblastic islands in the bone marrow. Understanding the mechanisms of stress erythropoiesis could potentially contribute to controlling the pathophysiology of SCD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)