Blood Cells Molecules and Diseases最新文献

{"title":"Phenotypic screens reveal Plasmodium falciparum genetic factors associated with infection of sickle-trait cells.","authors":"Camilla V Pires, Jenna Oberstaller, Chengqi Wang, Justin Gibbons, Chiara Micchelli, Min Zhang, Thomas D Otto, Julian C Rayner, Steve Taylor, John H Adams","doi":"10.1016/j.bcmd.2025.102951","DOIUrl":"10.1016/j.bcmd.2025.102951","url":null,"abstract":"<p><strong>Background: </strong>Malaria causes over 200 million cases and more than half a million deaths annually. In many African regions, hemoglobinopathies, such as sickle cell trait (HbAS), confer partial protection against severe P. falciparum malaria. HbAS significantly reduces the risk of severe, life-threatening malaria by over 90 %. This study aims to describe a new analysis for the piggyBac transposon-based mutagenesis phenotypic screen to identify genes that influence the mechanisms behind this protection and tolerance of P. falciparum to the HbAS intracellular microenvironment, providing insights into potential new targets for malaria intervention and the evolutionary relationship between host and parasite.</p><p><strong>Methods: </strong>We optimized and successfully employed a phenotypic screen using a piggyBac transposon-mutant library of P. falciparum to identify genetic factors essential for parasite survival in HbAS RBCs. Parasites were cultured in vitro in HbAS and control HbAA RBCs. Parasite growth was assessed via Quantitative Insertion Site Sequencing (QIseq) to determine sensitivity of each mutant in response to the conditions of HbAS RBCs identifying sensitive and tolerant mutants. Finally, a pairwise comparison was performed between HbAS and previously published piggyBac screens to infer potential links between HbAS infection and parasite responses to heat-shock, antimalarial drugs and oxidative stress.</p><p><strong>Results: </strong>Our findings revealed that P. falciparum mutants sensitive to HbAS growth are associated with genes involved in signaling pathways, exported proteins, and host-interaction genes. These genetic factors overlap with those involved in the parasite's response to oxidative stress and antimalarial drug sensitivity, such as artemisinin derivates and proteasome inhibitor.</p><p><strong>Conclusions: </strong>Our study identifies genetic factors influencing P. falciparum infection in HbAS RBCs, shedding light on how HbAS may counteract with the parasite, suggesting a connection between sickle-trait infections and other stress responses, such as heat-shock, artemisinin and oxidative stress.</p>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"115 ","pages":"102951"},"PeriodicalIF":1.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of multi-organ complications in patients with non-transfusion and neo-transfusion dependent thalassemia: a cross-sectional survey.","authors":"Antonella Meloni, Laura Pistoia, Paolo Ricchi, Filomena Longo, Valerio Cecinati, Francesco Sorrentino, Zelia Borsellino, Elisabetta Corigliano, Vincenza Rossi, Michela Zerbini, Priscilla Fina, Luigi Barbuto, Vincenzo Positano, Alberto Clemente","doi":"10.1016/j.bcmd.2025.102953","DOIUrl":"10.1016/j.bcmd.2025.102953","url":null,"abstract":"<p><p>This cross-sectional study compared the prevalence of vascular, hepatic, cardiac, endocrine, and bone complications between adult patients with non-transfusion-dependent thalassemia (NTDT) and neo-transfusion-dependent thalassemia (neo-TDT). We evaluated 97 NTDT patients (44.73 ± 12.98 years, 48.5 % females) and 140 neo-TDT (>4 transfusions/year) patients (44.30 ± 12.13 years, 56.4 % females), enrolled in the Extension-Myocardial Iron Overload in Thalassemia project. Iron overload (IO) was assessed by magnetic resonance imaging and complications were defined by established clinical criteria. Neo-TDT patients had significantly higher hemoglobin and ferritin levels and a higher prevalence of hepatitis C virus infection. Hepatic IO was more common in NTDT patients, whereas pancreatic and cardiac IO were significantly more frequent in the neo-TDT group. No significant differences were observed in extramedullary hematopoiesis, leg ulcers, hepatic cirrhosis, thrombosis, or pulmonary hypertension. Cardiac arrhythmias and impaired glucose metabolism were significantly more prevalent among neo-TDT patients. Hypogonadism, hypothyroidism, and hypoparathyroidism were more frequent in neo-TDT patients, though not statistically significant. Bone disorders were the most common in both groups, with a significantly higher prevalence in neo-TDT. In conclusion, neo-TDT patients exhibited a greater burden of cardiac arrhythmias, glucose metabolism disturbances, and bone metabolism disorders, highlighting the need for comprehensive and early multi-organ monitoring and timely intervention strategies.</p>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"115 ","pages":"102953"},"PeriodicalIF":1.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-sickling efficacy and safety of Sailin-HbS, an indigenous Ayurvedic formulation","authors":"Shruti Bhatt ,&nbsp;Anil Bhansali ,&nbsp;Apratim Sai Rajesh ,&nbsp;Satyabrata Meher ,&nbsp;Rabindra Kumar Jena ,&nbsp;Bishnu Prasad Dash ,&nbsp;Pradip Kumar Panda ,&nbsp;Kalpna Gupta ,&nbsp;Suman Kundu","doi":"10.1016/j.bcmd.2025.102956","DOIUrl":"10.1016/j.bcmd.2025.102956","url":null,"abstract":"<div><div>Sickle Cell Disease (SCD) is a hereditary condition characterized by a mutation in globin chains of hemoglobin. Polymerization of deoxygenated sickle hemoglobin (HbS) leads to rigid sickle shaped red blood cells (RBC), the primary cause of SCD pathobiology and multiple comorbidities including organ damage and pain. Gene therapy is the only treatment to reduce sickling, but its limitations including high cost, advanced technical resources and age limit pose a major challenge in its application. We examined the potential of a nutraceutical Sailin-HbS, formulated from the extract of 5 different plant sources with anti-oxidant and anti-inflammatory property, to ameliorate RBC sickling. Using sickle RBCs from individuals with SCD (SS-RBCs), Sailin-HbS demonstrated ∼74 % inhibition of sickling under low oxygen conditions; and significantly inhibited hypoxia-induced HbS polymerization by reducing polymerization kinetics at 700 nm. Osmotic fragility tests demonstrated enhanced resistance of SS-RBCs to osmotic stress in the presence of Sailin-HbS. We compared the anti-sickling effect of Sailin-HbS with known anti-sickling agents, Niprisan, SCD 101, AES-103/5-HMF and GBT440/Voxelotor, and found it to be equally and/or more effective. We tested the safety/toxicity of Sailin-HbS in 2 rodent models which showed a high safety threshold, with an oral LD50 exceeding 2000 mg/kg, placing it within the OECD-GHS category class 5. Sub-acute and chronic toxicity assessments in rats reveal no adverse effects on organ function or body weight, biochemical parameters, or complete blood counts, demonstrating its safety profile with established threshold levels. Thus, Sailin-HbS exhibits considerable anti-sickling efficacy without inducing toxicity, suggesting its translational potential in SCD.</div></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"116 ","pages":"Article 102956"},"PeriodicalIF":1.7,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145027161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WGCNA and LASSO regression-based selection and validation of microRNA biomarkers of β-thalassemia","authors":"Fang Yang ,&nbsp;Ling Shi ,&nbsp;Sha Su ,&nbsp;Yin Li ,&nbsp;Hui Chen ,&nbsp;Zhongping Liang ,&nbsp;Lihong Pang ,&nbsp;Ketong Lai","doi":"10.1016/j.bcmd.2025.102957","DOIUrl":"10.1016/j.bcmd.2025.102957","url":null,"abstract":"<div><h3>Objective</h3><div>In patients with severe β-thalassemia, fetal hemoglobin (HbF) upregulation may provide an avenue to better therapeutic outcomes. The mechanisms that regulate the expression of HbF, however, are currently unclear. This study was developed with the goal of exploring biomarkers and molecular mechanisms associated with HbF expression to help inform the development of novel therapeutic strategies.</div></div><div><h3>Methods</h3><div>The GSE93973 dataset from the GEO database was used. These miRNA expression data were subjected to WGCNA, differential expression, and LASSO regression analyses to identify hub miRNAs. The knockdown and overexpression of selected hub miRNAs were performed in K-562 cells to clarify how they affect HbF expression.</div></div><div><h3>Results</h3><div>In the WGCNA analysis, the module most closely associated with HbF levels was the pink module. Bioinformatics analyses identified miR-19b-3p as the hub miRNA. When miR-19b-3p was overexpressed in K-562 cells, this resulted in HbF upregulation, whereas the opposite was evident when it was knocked down. Dual-luciferase reporter assays confirmed the ability of miR-19b-3p to directly regulate SOX6. SOX6 downregulation was observed when miR-19b-3p was overexpressed, while SOX6 was upregulated following miR-19b-3p knockdown. In rescue experiments, the knockdown of SOX6 was sufficient to partially abrogate the impact of miR-19b-3p knockdown on the expression of HbF.</div></div><div><h3>Conclusion</h3><div>These results highlight miR-19b-3p as a core miRNA associated with the expression of HbF in β-thalassemia through its ability to regulate SOX6, which allude to a novel mechanism of HbF induction and could provide new targets for increasing HbF in patients with β-thalssemia major.</div></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"116 ","pages":"Article 102957"},"PeriodicalIF":1.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145021038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A case series of cerebrovascular abnormalities in Townes sickle cell mice visualized with magnetic resonance imaging and angiography","authors":"Liana Hatoum ,&nbsp;Hannah Song Lee ,&nbsp;John N. Oshinski ,&nbsp;Edward A. Botchwey ,&nbsp;Manu O. Platt","doi":"10.1016/j.bcmd.2025.102955","DOIUrl":"10.1016/j.bcmd.2025.102955","url":null,"abstract":"<div><div>Arterial complications in sickle cell disease (SCD), including stenoses and occlusions, are critical contributors to stroke. Townes SCD mice exhibit neurocognitive deficits and micro-vasculopathy, however stenoses and occlusions that could be causal to ischemic strokes have not yet been confirmed, which has led to challenges whether murine pathology reflects human pathology for strokes due to SCD. In our longitudinal study using label-free magnetic resonance angiography (MRA) to image carotid arteries in Townes SCD mice as they aged from 1 to 7 months, we identified multiple stenoses and occlusions consistent with abnormalities seen in individuals with SCD and stroke complications. We report three cases showing abnormalities: Case 1, middle cerebral artery occlusion associated with seizures and a T1-weighted hyperintense lesion in the brain; Case 2, persistent internal carotid artery occlusion and side-specific artery size differences; and Case 3, persistent stenosis in the common carotid artery with aging. This study highlights the utility of MRA in tracking arterial changes in SCD mice where assessing symptomatic damage due to stroke is challenging. This study provides evidence of mouse-to-mouse variability in initiation and persistence of stenoses and occlusions resembling the variability of SCD complications in humans.</div></div><div><h3>Headline</h3><div>MRA identifies arterial lesions in mice with SCD.</div></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"115 ","pages":"Article 102955"},"PeriodicalIF":1.7,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI for patient education: Insights from DeepSeek's responses on megaloblastic anemia","authors":"Nidhi Chandrashekar Patil","doi":"10.1016/j.bcmd.2025.102954","DOIUrl":"10.1016/j.bcmd.2025.102954","url":null,"abstract":"","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"115 ","pages":"Article 102954"},"PeriodicalIF":1.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144841503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Refractory immune thrombocytopenia with Trex1 mutation positive probable monogenic lupus","authors":"Bhuvnesh Narain Purohit ,&nbsp;Vivek Mohan ,&nbsp;Varun Capoor ,&nbsp;Sachin Jain ,&nbsp;Anu Dabar ,&nbsp;Rahul Naithani","doi":"10.1016/j.bcmd.2025.102952","DOIUrl":"10.1016/j.bcmd.2025.102952","url":null,"abstract":"","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"115 ","pages":"Article 102952"},"PeriodicalIF":2.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144702315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Burden beyond the cure: Iron overload following pediatric stem cell transplantation","authors":"Yonatan Diamond ,&nbsp;Alexandra Satty ,&nbsp;Lenat Joffe ,&nbsp;Jonathan D. Fish","doi":"10.1016/j.bcmd.2025.102941","DOIUrl":"10.1016/j.bcmd.2025.102941","url":null,"abstract":"<div><div>Iron overload (IOL) is an increasingly recognized complication among pediatric and young adult survivors of hematopoietic stem cell transplantation (HSCT) contributing to significant morbidity and mortality. The pathogenesis of IOL post-HSCT is multifactorial, driven by transfusion burden, impaired erythropoiesis, and increased gastrointestinal iron absorption, leading to toxic non-transferrin bound iron accumulation and oxidative tissue injury. Despite its clinical significance, consensus guidelines for the diagnosis, monitoring, and management of IOL in this population remain limited. This review examines the physiology and pathophysiology of iron metabolism, the clinical impact of post-HSCT IOL, whilst discussing evidence-based strategies for prevention and treatment. Particular attention is given to the unique challenges of managing iron overload in children, adolescents, and young adults, where individualized treatment and careful surveillance are critical.</div></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"115 ","pages":"Article 102941"},"PeriodicalIF":2.1,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel ELANE variant causing severe congenital neutropenia diagnosed in adulthood","authors":"Renato Cerqueira ,&nbsp;Josefina A.P. Braga ,&nbsp;Elyse Moritz ,&nbsp;João B. Pesquero ,&nbsp;José O. Bordin","doi":"10.1016/j.bcmd.2025.102940","DOIUrl":"10.1016/j.bcmd.2025.102940","url":null,"abstract":"","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"113 ","pages":"Article 102940"},"PeriodicalIF":2.1,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of elevated red blood cell membrane cholesterol in sickle cell anemia patients: Effects of BRN-002, a 2-hydroxypropyl-β-cyclodextrin derivate, on red blood cell lipids, deformability, sickling and hemolysis","authors":"Claire Bordat ,&nbsp;Philippe Connes ,&nbsp;Philippe Joly ,&nbsp;Solene Poutrel ,&nbsp;Carine Halfon-Domenech ,&nbsp;Anne Perez ,&nbsp;Eric Niesor ,&nbsp;Elie Nader","doi":"10.1016/j.bcmd.2025.102939","DOIUrl":"10.1016/j.bcmd.2025.102939","url":null,"abstract":"<div><div>Sickle cell anemia (SCA) patients are characterized by poorly deformable and fragile red blood cells (RBCs). Few studies reported an increased cholesterol content in SCA RBC membrane. However, the consequences of this elevated cholesterol level in the above-mentioned RBC alterations are currently unknown. The aim of this study was to assess, in vitro, the effects of BRN-002 (2-Hydroxypropyl-β-cyclodextrin derivate (HPBCD)), a cholesterol-depleting molecule, on RBC membrane cholesterol, hemolysis and RBC sickling and deformability in SCA patients.</div><div>Forty patients with SCA and 10 healthy individuals (AA) were included in the different experiments of the study. SCA RBCs were incubated with BRN-002 and the following parameters were assessed: i) RBC and supernatant cholesterol content; ii) RBC deformability by oxygen-gradient ektacytometry; iii) hemolysis by measuring free hemoglobin concentration.</div><div>Results confirmed that SCA patients have increased RBC membrane cholesterol compared to AA. BRN-002 effectively removed cholesterol in SCA RBC membrane and reduced free hemoglobin release during incubation. BRN-002 also increased RBC deformability in hypoxia and decreased the pO₂ at which sickling occurs.</div><div>These findings suggest that excess of RBC membrane cholesterol may participate in the typical RBC alterations found in SCA patients. Therefore, interventions focusing on RBC-cholesterol removal may be beneficial for SCA patients.</div></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"113 ","pages":"Article 102939"},"PeriodicalIF":2.1,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144262638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}