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An evaluation of patient-reported outcomes in sickle cell disease within a conceptual model
CONCLUSIONS: Study results highlight the importance of the biopsychosocial model to enhance understanding of the needs of this complex population, and to design multi-dimensional approaches for providing more effective interventions to improve outcomes.PMID:35445915 | DOI:10.1007/s11136-022-03132-z
Source: Cell Research - April 21, 2022 Category: Cytology Authors: Marsha J Treadwell Swapandeep Mushiana Sherif M Badawy Liliana Preiss Allison A King Barbara Kroner Yumei Chen Jeffrey Glassberg Victor Gordeuk Nirmish Shah Angela Snyder Theodore Wun Sickle Cell Disease Implementation Consortium (SCDIC) Source Type: research

PPAR γ Regulates the ETS1/miR-27a Axis to Reduce ET-1 and Endothelial Dysfunction in the Sickle Cell Mouse Lung.
This study examines peroxisome proliferator-activated receptor gamma (PPARγ) regulation in SCD-PH and endothelial dysfunction. PH and right ventricular hypertrophy (RVH) were studied in Townes humanized sickle cell (SS) and littermate control (AA) mice. In parallel studies, SS or AA mice were gavaged with the PPARγ agonist, rosiglitazone (RSG, 10 mg/kg/d) or vehicle for 10 days. In vitro, human pulmonary artery endothelial cells (HPAECs) were treated with vehicle or hemin for 72 hours, and selected HPAECs were treated with RSG. SS mice developed PH and RVH associated with reduced lung levels of PPARγ and increased level...
Source: Am J Respir Cell Mol... - September 8, 2016 Category: Respiratory Medicine Authors: Kang BY, Park K, Kleinhenz JM, Murphy TC, Sutliff RL, Archer D, Hart CM Tags: Am J Respir Cell Mol Biol Source Type: research

Impact of the COVID-19 Pandemic on the Implementation of Mobile Health to Improve the Uptake of Hydroxyurea in Patients With Sickle Cell Disease: Mixed Methods Study
CONCLUSIONS: We found significant impacts of the early clinic lockdowns, which reduced implementation of the mHealth intervention and led to reduced patient adherence to hydroxyurea. However, disruptions were lower among participants who experienced shorter clinic lockdowns and were associated with higher hydroxyurea adherence. Investigation of added strategies to mitigate the effects of care interruptions during major emergencies (eg, patient coaching and health navigation) may "insulate" the implementation of interventions to increase medication adherence.TRIAL REGISTRATION: ClinicalTrials.gov NCT04080167; https://clinic...
Source: Cell Research - October 14, 2022 Category: Cytology Authors: Sherif M Badawy Lisa DiMartino Donald Brambilla Lisa Klesges Ana Baumann Ebony Burns Terri DeMartino Sara Jacobs Hamda Khan Chinonyelum Nwosu Nirmish Shah Jane S Hankins Sickle Cell Disease Implementation Consortium Source Type: research

Gαs proteins Activate p72(Syk) and p60-c-Src Tyrosine Kinases to Mediate Sickle Red Blood Cell Adhesion to Endothelium via LW-αvβ3 and CD44-CD44 Interactions.
Abstract G protein-coupled receptors (GPCRs) have been suggested as new drug targets to treat a variety of diseases. In sickle cell disease (SCD), the LW erythrocyte adhesion receptor can be activated by stimulation of β2 adrenergic receptors (β2ARs), to mediate sickle erythrocyte (SSRBC) adhesion to endothelium. However, the involvement of tyrosine protein kinases in β2AR signaling to activate SSRBC adhesion to endothelium has not been throughly elucidated. Either direct activation with Cholera toxin of Gαs protein, which acts downstream of β2ARs, or inhibition with Pertussis toxin of Gαi, mediating suppres...
Source: The International Journal of Biochemistry and Cell Biology - May 22, 2015 Category: Biochemistry Authors: Chiou E, Zennadi R Tags: Int J Biochem Cell Biol Source Type: research

Genomic analyses of pneumococci from children with sickle cell disease expose host-specific bacterial adaptations and deficits in current interventions.
Abstract Sickle cell disease (SCD) patients are at high risk of contracting pneumococcal infection. To address this risk, they receive pneumococcal vaccines, and antibiotic prophylaxis and treatment. To assess the impact of SCD and these interventions on pneumococcal genetic architecture, we examined the genomes of more than 300 pneumococcal isolates from SCD patients over 20 years. Modern SCD strains retained invasive capacity but shifted away from the serotypes used in vaccines. These strains had specific genetic changes related to antibiotic resistance, capsule biosynthesis, metabolism, and metal transport. A m...
Source: Cell Host and Microbe - May 14, 2014 Category: Microbiology Authors: Carter R, Wolf J, van Opijnen T, Muller M, Obert C, Burnham C, Mann B, Li Y, Hayden RT, Pestina T, Persons D, Camilli A, Flynn PM, Tuomanen EI, Rosch JW Tags: Cell Host Microbe Source Type: research

Pneumococcus adapts to the sickle cell host.
Abstract Children with sickle cell disease (SCD) have significantly increased risk of invasive pneumococcal disease. In this issue of Cell Host & Microbe, Carter et al. (2014) report that pneumococcal strains from SCD children have genetic mutations associated with the unique SCD environment, which need to be considered in developing new vaccines. PMID: 24832446 [PubMed - in process]
Source: Cell Host and Microbe - May 14, 2014 Category: Microbiology Authors: Mitchell TJ, Mitchell AM Tags: Cell Host Microbe Source Type: research

Hemoglobin inhibits albumin uptake by proximal tubule cells: implications for sickle cell disease.
Abstract Proximal tubule (PT) dysfunction, including tubular proteinuria, is a significant complication in young sickle cell disease (SCD) that can eventually lead to chronic kidney disease. Hemoglobin (Hb) dimers released from red blood cells upon hemolysis are filtered into the kidney and internalized by megalin/cubilin receptors into PT cells. The PT is especially sensitive to heme toxicity, and tubular dysfunction in SCD is thought to result from prolonged exposure to filtered Hb. Here we show that concentrations of Hb predicted to enter the tubule lumen during hemolytic crisis competitively inhibit the uptake...
Source: Am J Physiol Cell Ph... - March 29, 2017 Category: Cytology Authors: Eshbach ML, Kaur A, Rbaibi Y, Tejero J, Weisz OA Tags: Am J Physiol Cell Physiol Source Type: research

NO-independent sGC Activation Improves Vascular Function and Cardiac Remodeling in Sickle Cell Disease.
Abstract Sickle cell disease (SCD) is associated with intravascular hemolysis and oxidative inhibition of nitric oxide (NO) signaling. BAY 54-6544 is a small molecule activator of oxidized sGC; which unlike endogenous NO and the sGC stimulator BAY 41-8543; preferentially binds and activates heme-free, NO-insensitive sGC to restore enzymatic cGMP production. We tested orally delivered sGC activator BAY 54-6544, sGC stimulator BAY 41-8543, sildenafil, or placebo for 4-12 weeks in a transgenic mouse model of SCD (BERK-SCD) and their hemizygous littermate controls (BERK-Hemi). Right ventricular maximum systolic pressu...
Source: Am J Respir Cell Mol... - December 21, 2017 Category: Respiratory Medicine Authors: Potoka KP, Wood KC, Baust JJ, Bueno M, Hahn SA, Vanderpool RR, Bachman T, Mallampalli GM, Osei-Hwedieh DO, Schrott V, Sun B, Bullock GC, Becker-Pelster EM, Wittwer M, Stampfuss J, Mathar I, Stasch JP, Truebel H, Sandner P, Mora AL, Straub AC, Gladwin MT Tags: Am J Respir Cell Mol Biol Source Type: research

Hemoglobin Alters Vitamin Carrier Uptake and Vitamin D Metabolism in Proximal Tubule Cells: Implications for Sickle Cell Disease.
Abstract Kidney disease, including proximal tubule (PT) dysfunction, and vitamin D deficiency are among the most prevalent complications in sickle cell disease (SCD) patients. Although these two comorbidities have never been linked in SCD, the PT is the primary site for activation of vitamin D. Precursor 25(OH)D bound to vitamin D binding protein (DBP) is taken up by PT cells via megalin/cubilin receptors, hydroxylated to the active 1,25(OH)2D form, and released into the bloodstream. We tested the hypothesis that cell-free hemoglobin (Hb) filtered into the PT lumen impairs vitamin D uptake and metabolism. Hb at co...
Source: Am J Physiol Cell Ph... - September 10, 2019 Category: Cytology Authors: Gliozzi ML, Rbaibi Y, Long KR, Vitturi DA, Weisz OA Tags: Am J Physiol Cell Physiol Source Type: research

Sickle Cell Anemia: time for personalized prescription of hydroxyurea? Focus on "OATP1B transporters modulate hydroxyurea pharmacokinetics."
Abstract N/A. PMID: 24005044 [PubMed - as supplied by publisher]
Source: Am J Physiol Cell Ph... - September 4, 2013 Category: Cytology Authors: Thornburg CD Tags: Am J Physiol Cell Physiol Source Type: research

Rescuing Decrepit Soluble Guanylate Cyclase: A Therapy for Sickle Cell Disease?
PMID: 29714629 [PubMed - in process]
Source: American Journal of Respiratory Cell and Molecular Biology - May 1, 2018 Category: Molecular Biology Authors: Schumacker PT Tags: Am J Respir Cell Mol Biol Source Type: research

Hemin Causes Lung Microvascular Endothelial Barrier Dysfunction by Necroptotic Cell Death.
In this study, we examined whether hemin can cause lung microvascular endothelial barrier dysfunction. By assessing transendothelial resistance using electrical cell impedance sensing, and by directly measuring trans-monolayer FITC-dextran flux, we found that hemin does cause endothelial barrier dysfunction in a concentration-dependent manner. Pre-treatment with either a TLR4 inhibitor, TAK-242, or an antioxidant, N-acetylcysteine, abrogated this effect. Increased monolayer permeability was found to be associated with programmed cell death by necroptosis as evidenced by Trypan blue staining, TUNEL assay, Western blotting f...
Source: American Journal of Respiratory Cell and Molecular Biology - April 19, 2017 Category: Molecular Biology Authors: Singla S, Sysol JR, Dille B, Jones N, Chen J, Machado RF Tags: Am J Respir Cell Mol Biol Source Type: research

Hematopoietic-Stem-Cell-Targeted Gene-Addition and Gene-Editing Strategies for β-hemoglobinopathies.
Abstract Sickle cell disease (SCD) is caused by a well-defined point mutation in the β-globin gene and therefore is an optimal target for hematopoietic stem cell (HSC) gene-addition/editing therapy. In HSC gene-addition therapy, a therapeutic β-globin gene is integrated into patient HSCs via lentiviral transduction, resulting in long-term phenotypic correction. State-of-the-art gene-editing technology has made it possible to repair the β-globin mutation in patient HSCs or target genetic loci associated with reactivation of endogenous γ-globin expression. With both approaches showing signs of therapeutic effica...
Source: Cell Stem Cell - February 4, 2021 Category: Stem Cells Authors: Drysdale CM, Nassehi T, Gamer J, Yapundich M, Tisdale JF, Uchida N Tags: Cell Stem Cell Source Type: research

An open data ecosystem for cell migration research.
Abstract Cell migration research has recently become both a high content and a high throughput field thanks to technological, computational, and methodological advances. Simultaneously, however, urgent bioinformatics needs regarding data management, standardization, and dissemination have emerged. To address these concerns, we propose to establish an open data ecosystem for cell migration research. PMID: 25484346 [PubMed - as supplied by publisher]
Source: Trends in Cell Biology - December 4, 2014 Category: Cytology Authors: Masuzzo P, Martens L, The 2014 Cell Migration Workshop Participants Tags: Trends Cell Biol Source Type: research

A Cell-ebration of Induced Pluripotency.
Abstract PAPERCLIP. PMID: 26849296 [PubMed - as supplied by publisher]
Source: Cell Stem Cell - February 4, 2016 Category: Stem Cells Authors: editorial teams of Cell and Cell Stem Cell Tags: Cell Stem Cell Source Type: research