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.
{"title":"Anti-sickling efficacy and safety of Sailin-HbS, an indigenous Ayurvedic formulation","authors":"Shruti Bhatt , Anil Bhansali , Apratim Sai Rajesh , Satyabrata Meher , Rabindra Kumar Jena , Bishnu Prasad Dash , Pradip Kumar Panda , Kalpna Gupta , 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":"2026-02-01","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}
Pub Date : 2026-02-01Epub Date: 2025-10-25DOI: 10.1016/j.bcmd.2025.102965
Wenjue Xu , Huiyan Han , Binbin Li , Rui Huang , Qing Lin , Guowei Zhang
Platelet-targeted gene therapy for hemophilia entails modifying a patient's hematopoietic stem cells (HSCs) ex vivo to produce platelets containing coagulation factors, offering a potential cure by localized factor release at injury sites. However, the associated bone marrow transplantation carries significant risks, underscoring the critical need for low-toxicity conditioning regimens to enable clinical translation. This study evaluated G-CSF and 5-FU as conditioning regimens to facilitate the engraftment of HSCs expressing platelet-targeted FIX Padua. Hemophilia B (HB) mice were conditioned with G-CSF, 5-FU alone, or a combination of G-CSF, plerixafor, and 5-FU. Bone marrow mononuclear cells (BM-MNCs) from transgenic donors (2bF9-R338L) expressing platelet-stored FIX Padua were transplanted. G-CSF conditioning enabled long-term engraftment with 1 × 108 BM-MNCs; however, the efficacy declined significantly with lower cell doses. A single-dose of 5-FU (150 mg/kg) administered one day pre-transplant achieved optimal FIX expression and minimal toxicity. Critically, a combined regimen of G-CSF/plerixafor plus timed 5-FU (day -1) yielded stable, long-term platelet FIX expression and phenotypic rescue. The success of 5-FU underscores the importance of creating a transient niche vacancy for donor HSC engraftment. These results demonstrate that this mobilization-based, non-myeloablative conditioning strategy is a promising approach for platelet-targeted gene therapy for hemophilia.
{"title":"Effects of G-CSF and 5-FU as conditioning regimens in platelet-targeted gene therapy for hemophilia B","authors":"Wenjue Xu , Huiyan Han , Binbin Li , Rui Huang , Qing Lin , Guowei Zhang","doi":"10.1016/j.bcmd.2025.102965","DOIUrl":"10.1016/j.bcmd.2025.102965","url":null,"abstract":"<div><div>Platelet-targeted gene therapy for hemophilia entails modifying a patient's hematopoietic stem cells (HSCs) ex vivo to produce platelets containing coagulation factors, offering a potential cure by localized factor release at injury sites. However, the associated bone marrow transplantation carries significant risks, underscoring the critical need for low-toxicity conditioning regimens to enable clinical translation. This study evaluated G-CSF and 5-FU as conditioning regimens to facilitate the engraftment of HSCs expressing platelet-targeted FIX Padua. Hemophilia B (HB) mice were conditioned with G-CSF, 5-FU alone, or a combination of G-CSF, plerixafor, and 5-FU. Bone marrow mononuclear cells (BM-MNCs) from transgenic donors (2bF9-R338L) expressing platelet-stored FIX Padua were transplanted. G-CSF conditioning enabled long-term engraftment with 1 × 10<sup>8</sup> BM-MNCs; however, the efficacy declined significantly with lower cell doses. A single-dose of 5-FU (150 mg/kg) administered one day pre-transplant achieved optimal FIX expression and minimal toxicity. Critically, a combined regimen of G-CSF/plerixafor plus timed 5-FU (day -1) yielded stable, long-term platelet FIX expression and phenotypic rescue. The success of 5-FU underscores the importance of creating a transient niche vacancy for donor HSC engraftment. These results demonstrate that this mobilization-based, non-myeloablative conditioning strategy is a promising approach for platelet-targeted gene therapy for hemophilia.</div></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"116 ","pages":"Article 102965"},"PeriodicalIF":1.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145408265","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}
Pub Date : 2025-11-01Epub Date: 2025-07-04DOI: 10.1016/j.bcmd.2025.102941
Yonatan Diamond , Alexandra Satty , Lenat Joffe , Jonathan D. Fish
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.
{"title":"Burden beyond the cure: Iron overload following pediatric stem cell transplantation","authors":"Yonatan Diamond , Alexandra Satty , Lenat Joffe , 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":"2025-11-01","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}
Pub Date : 2025-11-01Epub Date: 2025-07-25DOI: 10.1016/j.bcmd.2025.102951
Camilla V Pires, Jenna Oberstaller, Chengqi Wang, Justin Gibbons, Chiara Micchelli, Min Zhang, Thomas D Otto, Julian C Rayner, Steve Taylor, John H Adams
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
{"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}
Pub Date : 2025-11-01Epub Date: 2025-08-14DOI: 10.1016/j.bcmd.2025.102955
Liana Hatoum , Hannah Song Lee , John N. Oshinski , Edward A. Botchwey , Manu O. Platt
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.
{"title":"A case series of cerebrovascular abnormalities in Townes sickle cell mice visualized with magnetic resonance imaging and angiography","authors":"Liana Hatoum , Hannah Song Lee , John N. Oshinski , Edward A. Botchwey , 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":"2025-11-01","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}
Pub Date : 2025-11-01Epub Date: 2025-08-05DOI: 10.1016/j.bcmd.2025.102953
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
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.
{"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}
Pub Date : 2025-11-01Epub Date: 2025-08-12DOI: 10.1016/j.bcmd.2025.102954
Nidhi Chandrashekar Patil
{"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":"2025-11-01","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}
Pub Date : 2025-07-01Epub Date: 2025-05-23DOI: 10.1016/j.bcmd.2025.102936
Inayat Ur Rahman , Muhammad Tariq Masood Khan , Zahid Ali , Shafiq Ahmad , Muhammad Shahid , Shafaq Zafar , Faheela Faizi Aamir , Imran Khan , Muhammad Ali , Musharraf Jelani , Khalid Khan , Nafees Ahmad , Yasar Yousafzai , Afsar Ali Mian , Sami Siraj
Bacground
Transfusion-dependent β-thalassemia (TDT) requires regular transfusions, often causing iron overload and organ damage. Thalidomide, a fetal hemoglobin (HbF) inducer, may reduce transfusion needs, but scientific data are limited.
Methods
This two-arm, non-randomized clinical trial followed a total of 164 TDT patients over 30 months: 72 received thalidomide and 92 underwent standard transfusions. Complete blood count was assessed at baseline and 6, 12, 18, 24, and 30 months. SNP genotyping and β-globin mutation analysis were performed using sanger sequencing. GATA-1 and KLF gene expression were assessed at baseline and after 30 months via qRT-PCR
Results
Hemoglobin level in the thalidomide group significantly increased from 6.12 ± 0.65 g/dL to 8.36 ± 2.04 g/dL (p < 0.001). Among thalidomide-treated patients, 34.7 % were excellent responders (ER), 25 % good responders (GR), 13.9 % partial responders (PR), and 26.4 % non-responders (NR). ERs showed the highest GATA-1 [3.09 (IQR 2.0–3.38)] and KLF [3.24 (IQR 3.01–5.42)] expression levels (p < 0.001). Better response was observed in patients with AFT >12 months and those carrying the minor allele C at HBS1L-MYB rs9399137 (p < 0.05)
Conclusion
Thalidomide effectively increases hemoglobin levels and reduces transfusion needs in TDT patients, particularly through upregulation of GATA-1 and KLF. AFT and SNP genotype at HBS1L-MYB rs9399137 may help predict response
{"title":"Thalidomide confers therapeutic benefit in beta thalassemia patients by enhancing hemoglobin and hematopoietic gene expression: A non-randomized clinical trial","authors":"Inayat Ur Rahman , Muhammad Tariq Masood Khan , Zahid Ali , Shafiq Ahmad , Muhammad Shahid , Shafaq Zafar , Faheela Faizi Aamir , Imran Khan , Muhammad Ali , Musharraf Jelani , Khalid Khan , Nafees Ahmad , Yasar Yousafzai , Afsar Ali Mian , Sami Siraj","doi":"10.1016/j.bcmd.2025.102936","DOIUrl":"10.1016/j.bcmd.2025.102936","url":null,"abstract":"<div><h3>Bacground</h3><div>Transfusion-dependent β-thalassemia (TDT) requires regular transfusions, often causing iron overload and organ damage. Thalidomide, a fetal hemoglobin (HbF) inducer, may reduce transfusion needs, but scientific data are limited.</div></div><div><h3>Methods</h3><div>This two-arm, non-randomized clinical trial followed a total of 164 TDT patients over 30 months: 72 received thalidomide and 92 underwent standard transfusions. Complete blood count was assessed at baseline and 6, 12, 18, 24, and 30 months. SNP genotyping and β-globin mutation analysis were performed using sanger sequencing. <em>GATA-1</em> and <em>KLF</em> gene expression were assessed at baseline and after 30 months via qRT-PCR</div></div><div><h3>Results</h3><div>Hemoglobin level in the thalidomide group significantly increased from 6.12 ± 0.65 g/dL to 8.36 ± 2.04 g/dL (<em>p</em> < 0.001). Among thalidomide-treated patients, 34.7 % were excellent responders (ER), 25 % good responders (GR), 13.9 % partial responders (PR), and 26.4 % non-responders (NR). ERs showed the highest <em>GATA-1</em> [3.09 (IQR 2.0–3.38)] and <em>KLF</em> [3.24 (IQR 3.01–5.42)] expression levels (p < 0.001). Better response was observed in patients with AFT >12 months and those carrying the minor allele C at <em>HBS1L-MYB</em> rs9399137 (<em>p</em> < 0.05)</div></div><div><h3>Conclusion</h3><div>Thalidomide effectively increases hemoglobin levels and reduces transfusion needs in TDT patients, particularly through upregulation of <em>GATA-1</em> and <em>KLF</em>. AFT and SNP genotype at <em>HBS1L-MYB</em> rs9399137 may help predict response</div></div><div><h3>Trial registration</h3><div><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> ID: <span><span>NCT06146478</span><svg><path></path></svg></span></div></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"113 ","pages":"Article 102936"},"PeriodicalIF":2.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144170590","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}
Pub Date : 2025-07-01Epub Date: 2025-06-09DOI: 10.1016/j.bcmd.2025.102939
Claire Bordat , Philippe Connes , Philippe Joly , Solene Poutrel , Carine Halfon-Domenech , Anne Perez , Eric Niesor , Elie Nader
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.
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.
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.
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.
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