Blood Cells Molecules and Diseases最新文献

{"title":"MRI-derived hepatic fat and its clinical correlates in non–transfusion-dependent thalassemia: a cross-sectional study","authors":"Antonella Meloni ,&nbsp;Laura Pistoia ,&nbsp;Paolo Ricchi ,&nbsp;Vincenzo Positano ,&nbsp;Anna Spasiano ,&nbsp;Filomena Longo ,&nbsp;Zelia Borsellino ,&nbsp;Elisabetta Corigliano ,&nbsp;Luigi Barbuto ,&nbsp;Michela Zerbini ,&nbsp;Priscilla Fina ,&nbsp;Alberto Cossu ,&nbsp;Giuseppe Peritore ,&nbsp;Andrea Barison","doi":"10.1016/j.bcmd.2026.102997","DOIUrl":"10.1016/j.bcmd.2026.102997","url":null,"abstract":"<div><div>We quantified hepatic fat fraction (FF) by magnetic resonance imaging (MRI) in non–transfusion-dependent thalassemia (NTDT) patients, and we evaluated its associations with demographic, clinical, and biochemical parameters, tissue iron overload, and alterations of glucose metabolism.</div><div>169 NTDT patients (45.75 ± 13.41 years, 56.8% females) enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network underwent standardized MRI assessments of hepatic, pancreatic, and cardiac iron and of hepatic FF. We also considered 301 transfusion-dependent thalassemia (TDT) patients and 25 healthy controls. To ensure reliable FF quantification, patients with severe hepatic iron overload (R2* &gt; 333 Hz) were excluded. Glucose metabolism was assessed using an oral glucose tolerance test (OGTT).</div><div>Both regularly transfused (RT) and never/sporadically transfused (NT) NTDT patients had hepatic FF values comparable to those of healthy controls, but significantly lower than those observed in TDT patients. RT-NTDT patients exhibited lower hepatic FF and hepatic iron levels than NT-NTDT patients. Independent of transfusional status, hepatic FF was unrelated to age, sex, splenectomy, ferritin, hepatitis C infection, or pancreatic and cardiac iron. In NT-NTDT, hepatic FF correlated positively with liver iron concentration. In RT-NTDT, hepatic FF and pancreatic iron showed similar diagnostic performance in identifying abnormal OGTT results. NT-NTDT patients exhibited higher hepatic FF than RT-NTDT patients, linked to hepatic iron levels. Hepatic fat accumulation and pancreatic iron overload may jointly contribute to altered glucose metabolism in RT-NTDT.</div></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"119 ","pages":"Article 102997"},"PeriodicalIF":1.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147388444","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":"Clinical outcomes and health-system challenges in congenital afibrinogenemia: a single-centre prospective case series","authors":"Nita Radhakrishnan ,&nbsp;Savitri Singh ,&nbsp;Archit Pandharipande ,&nbsp;Eby P. Baby ,&nbsp;Hari Gaire","doi":"10.1016/j.bcmd.2026.102986","DOIUrl":"10.1016/j.bcmd.2026.102986","url":null,"abstract":"<div><h3>Background</h3><div>Congenital afibrinogenemia is a very rare bleeding disorder which is often life threatening. Data are scarce, and only 29 Indian cases have been officially reported to World Federation of Hemophilia, mostly as isolated descriptions. This study presents a prospectively followed pediatric cohort, evaluating clinical characteristics, outcomes with human fibrinogen concentrate (HFC), and health-system challenges.</div></div><div><h3>Methods</h3><div>Children diagnosed with afibrinogenemia between 2022 and 2025 at a tertiary centre were prospectively followed. Clinical presentation, diagnostic delay, prior treatments, and outcomes with HFC were analyzed, alongside a structured review of Indian literature and comparison with international data.</div></div><div><h3>Results</h3><div>Four children (ages 0.25–13 years) constituted 0.36% of the bleeding disorder cohort in our institutional registry (<em>n</em> = 1096). Median diagnostic delay was 8.2 years (range 0.25–12.5). Three were initially misdiagnosed as hemophilia. Major bleeds included recurrent hemarthroses, menorrhagia, and subgaleal/periorbital hematoma. All had Clauss fibrinogen &lt;10 mg/dL. Two children on regular HFC prophylaxis remain bleed-free (median 39.8 months); two on on-demand therapy experience only intermittent bleeds. One developed irreversible blindness before correct diagnosis.</div></div><div><h3>Conclusions</h3><div>Afibrinogenemia, though rare, can be catastrophic if unrecognized. Early diagnosis and prophylactic HFC markedly reduce morbidity. Strengthening diagnostic capacity, registry reporting, and equitable HFC access are critical in resource-limited settings.</div></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"118 ","pages":"Article 102986"},"PeriodicalIF":1.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037292","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":"Association of metabolomics measurements with blood cell phenotypes","authors":"Brian D. Chen ,&nbsp;Amanda Tapia ,&nbsp;Eric Boerwinkle ,&nbsp;Clary B. Clish ,&nbsp;Robert Gerszten ,&nbsp;Misa Graff ,&nbsp;Karen L. Mohlke ,&nbsp;Alanna C. Morrison ,&nbsp;Wimal Pathmasiri ,&nbsp;Stephen S. Rich ,&nbsp;Jerome I. Rotter ,&nbsp;Blake R. Rushing ,&nbsp;Susan Sumner ,&nbsp;Russell P. Tracy ,&nbsp;Kristin L. Young ,&nbsp;Bing Yu ,&nbsp;Bharat Thyagarajan ,&nbsp;Alex P. Reiner ,&nbsp;Yun Li ,&nbsp;Laura Raffield","doi":"10.1016/j.bcmd.2025.102966","DOIUrl":"10.1016/j.bcmd.2025.102966","url":null,"abstract":"<div><div>Complete blood counts (CBCs) are commonly measured in clinical practice and are associated with different diseases and traits. Statistical adjustment for blood cell abundance or related traits in these metabolomic epidemiology studies is not a common practice. However, it is plausible that common and cheaply measured blood cells would capture some of the variation also captured by metabolomic measures. Here, we assessed the association between metabolites and blood cell traits with a multi-ethnic meta-analysis of named metabolites from untargeted panels in the JHS, MESA, ARIC, and the HCHS/SOL cohorts. Among 2859 metabolite and blood cell trait pairs measured in at least two cohorts, 734 (25.6 %) were significantly associated. We also tested metabolite-blood cell trait pairs in the UK Biobank with a targeted NMR-based metabolomics panel. A large percentage (92 %) of the tested pairs was significant, and adjustment for blood cells altered relationships between metabolites and age and sex. We evaluated metabolite effect size changes for metabolite association with different incident diseases adjusting for CBC traits using the UK Biobank. Most notably, the metabolomic effect sizes on COPD were downweighted after adjustment. Blood cell trait adjustment showed similar but not overlapping effect size changes when compared to adjusting for eGFR, which is a common covariate in metabolomics analyses to account for kidney function. Our results show that statistical adjustment for blood cell traits may reduce confounding and clarify additional predictive power above existing clinical biomarkers in metabolomic studies.</div></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"117 ","pages":"Article 102966"},"PeriodicalIF":1.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145578888","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":"Oxidantscan: A novel biomarker to assess red blood cell susceptibility to oxidative stress in sickle cell disease","authors":"C.A. Hernández ,&nbsp;M.J.M. Traets ,&nbsp;W.W. van Solinge ,&nbsp;A.W. Rijneveld ,&nbsp;L. Kaestner ,&nbsp;T. John ,&nbsp;E. Nur ,&nbsp;B.J. Biemond ,&nbsp;F.A. Kuypers ,&nbsp;E.J. van Beers ,&nbsp;M.A.E. Rab ,&nbsp;R. van Wijk","doi":"10.1016/j.bcmd.2025.102967","DOIUrl":"10.1016/j.bcmd.2025.102967","url":null,"abstract":"<div><div>Red blood cells (RBC) from patients with sickle cell disease (SCD) are continuously exposed to high levels of oxidative stress, which impacts RBC deformability. In this study, we applied a novel technique (oxidantscan) to measure deformability of RBCs under shear stress while exposed to oxidative stress. Using RBCs collected from a cohort of patients with SCD and healthy volunteers, we measured different parameters including T-POD (Time to initiate Oxidant-induced change in Deformability) and EI_Min (the minimum deformability reached during the test). T-POD was significantly shorter in patients with HbSS (<em>n</em> = 21, 729 ± 410 s) and HbSC (<em>n</em> = 19, 1031 ± 225 s) when compared to healthy controls (<em>n</em> = 20, 1739 ± 328 s, <em>p</em> &lt; 0.05). Also EI_Min was significantly lower in patients with HbSS (0.26 ± 0.10) and HbSC (0.30 ± 0.10) compared to healthy controls (0.54 ± 0.02). These results indicate that RBCs from patients with SCD are more susceptible to oxidative stress, which can be measured in a reproducible and quantifiable way. We also demonstrate that Oxidantscan outcome parameters correlated with sickling behavior and markers of hemolysis, indicating a possible link between these key pathophysiological features and the ability to withstand oxidative stress (all <em>p</em> &lt; 0.05). Finally, we provide preliminary evidence for the potential of this technique to evaluate antioxidant therapy with <span>l</span>-glutamine as SCD RBCs showed a significant improvement in T-POD (11.5 %, <em>p</em> = 0.01) and EI_Min (46.9 %, <em>p</em> = 0.03) upon ex vivo treatment with <span>l</span>-glutamine. The Oxidantscan is a promising technique for evaluating the response of SCD RBCs to oxidative stress, providing new insights in disease pathophysiology and potential novel treatment strategies.</div></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"117 ","pages":"Article 102967"},"PeriodicalIF":1.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145578796","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":"Ex vivo culture of hematopoietic stem and progenitor cells with platelet lysate: Investigating proliferation and erythroid-megakaryocytic lineage effects","authors":"Farnaz Pirsavabi ,&nbsp;Zahra Najafi ,&nbsp;Mohammad Ebrahimi Siahboomi ,&nbsp;Bewar Othman Hasan ,&nbsp;Shaban Alizadeh ,&nbsp;Seyyed Hadi Mousavi ,&nbsp;Mostafa Saberian ,&nbsp;Zahra Kashani Khatib ,&nbsp;Saeed Mohammadi ,&nbsp;Naser Ahmadbeigi ,&nbsp;Azadeh Omidkhoda","doi":"10.1016/j.bcmd.2025.102968","DOIUrl":"10.1016/j.bcmd.2025.102968","url":null,"abstract":"<div><div>Hematopoietic stem and progenitor cells (HSPCs) are valuable for therapies and research due to their self-renewal and differentiation abilities. The ex vivo culture of these cells necessitates conditions that maintain their unique properties and provide a niche-like environment. Human platelet lysate (HPL), a growth factor-rich substance used in stem cell studies, influences various biological pathways. This study investigates HPL's effects on HSPCs' proliferation and erythroid-megakaryocytic differentiation, addressing the need to improve HSPC culture conditions for clinical and research applications. HPL was prepared, and isolated peripheral blood-derived HSPCs were cultured for 7 days in control and 10 % HPL-supplemented groups. Cell counts, viability, and population doubling time (PDT) were measured. Erythroid and megakaryocytic differentiation was assessed using qPCR and flow cytometry. Colony-forming cell (CFC) assays confirmed multilineage differentiation capacity. HPL significantly increased HSPCs proliferation, resulting in a 1.96-fold increase by day 7 and a reduced PDT. CFC assays confirmed that the cells maintained their ability to differentiate into various blood cell types. Flow cytometry showed a decrease in the CD71 marker without affecting the overall red blood cell population. Gene analysis revealed increased β-globin production while other red blood cell-related genes remained stable. Markers and genes associated with megakaryocyte development showed no significant changes. HPL as a culture medium supplement markedly enhances the proliferation of peripheral blood-derived hematopoietic stem cells during cell culture without inducing unwanted bias into the erythroid and megakaryocytic lineages.</div></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"117 ","pages":"Article 102968"},"PeriodicalIF":1.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617000","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":"Relationship between PCT, CRP, and IL-6 and postoperative delirium in ICU patients and its influencing factors","authors":"Huayong Song,&nbsp;Lijing Shen,&nbsp;Wen Sun,&nbsp;Ludi Zhang,&nbsp;Lixia Xue,&nbsp;Qingqing Shen,&nbsp;Zikang Chen,&nbsp;Xinqing Lu","doi":"10.1016/j.bcmd.2025.102976","DOIUrl":"10.1016/j.bcmd.2025.102976","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the relationship of procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6) with postoperative delirium (POD) in intensive care unit (ICU) patients, and to identify influencing factors.</div></div><div><h3>Methods</h3><div>Based on POD occurrence, 120 postoperative ICU patients were split into delirium (<em>n</em> = 72) and non-delirium (<em>n</em> = 48) groups. Clinical data and post-operative 24-h serum PCT, CRP, and IL-6 levels were gathered. Pearson correlation assessed relationships between these inflammatory markers, delirium incidence, and DRS-R-98 scores. Multivariate logistic regression identified predictors, and ROC curves evaluated the predictive value of the inflammatory markers.</div></div><div><h3>Results</h3><div>Delirium patients were older with higher APACHE II scores, more frequent mechanical ventilation, and longer ICU stays (<em>P</em> &lt; 0.05). Their serum PCT, CRP, and IL-6 levels were higher and positively correlating with POD incidence and severity (DRS-R-98 scores) (<em>r</em> &gt; 0, <em>P</em> &lt; 0.05). These markers were identified as independent POD predictors (OR &gt; 1, <em>P</em> &lt; 0.05), demonstrating good predictive value with AUCs of 0.936 (CRP), 0.894 (PCT), and 0.820 (IL-6).</div></div><div><h3>Conclusion</h3><div>Postoperative inflammation serves as an independent risk factor for POD in ICU patients. Serum PCT, CRP, and IL-6 levels facilitate early detection and risk assessment, supporting preventive strategies and mitigating POD-related complications.</div></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"117 ","pages":"Article 102976"},"PeriodicalIF":1.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145660348","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":"Transfusion-related iron overload in survivors of childhood cancer","authors":"Kiranmye Reddy ,&nbsp;Jonathan D. Fish ,&nbsp;Jennifer Eng ,&nbsp;Claire A. Carlson ,&nbsp;Jill P. Ginsberg","doi":"10.1016/j.bcmd.2025.102977","DOIUrl":"10.1016/j.bcmd.2025.102977","url":null,"abstract":"<div><h3>Purpose</h3><div>To assess the prevalence and severity of transfusion-associated iron overload (IO) in childhood cancer survivors (CCS).</div></div><div><h3>Patients and methods</h3><div>Serum iron, total iron binding capacity, percent iron saturation and ferritin were measured in 75 survivors of childhood cancer. In addition, blood bank records were reviewed to determine the total volume of packed red blood cells (pRBCs) administered during cancer therapy. Patients who received ≥120 mL/kg of pRBCs or had a ferritin ≥1000μg/L underwent hepatic R2 and cardiac T2* MRI for iron quantification, echocardiogram, assessment of liver and endocrine function, and genetic analysis for hereditary hemochromatosis.</div></div><div><h3>Results</h3><div>Forty-nine patients qualified for second level studies. Of these, 35 completed the MRI scans. Fifteen patients had a liver iron concentration (LIC) &gt;3 mg iron/g (moderate hepatic iron overload), including eight patients who had an LIC greater than 7 mg iron/g (severe hepatic iron overload), with a mean LIC of 4.3 mg iron/g (0–15.6 mg iron/g). LIC correlated with total volume of pRBCs and ferritin. No patient had cardiac iron loading by MRI. Eleven patients were heterozygous and one was homozygous for mutations associated with hereditary hemochromatosis. There was no correlation between iron overload and hereditary hemochromatosis gene status.</div></div><div><h3>Conclusion</h3><div>There is a high prevalence of transfusion-associated iron overload among survivors of childhood cancer. This is concerning given the overlap between organ toxicities associated with cancer treatment and those known to be associated with iron overload. The tight correlation between LIC and ferritin suggests ferritin may be a reliable indicator of iron load in this patient population.</div></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"117 ","pages":"Article 102977"},"PeriodicalIF":1.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145836449","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":"2026-02-01","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":"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":"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}

{"title":"Effects of G-CSF and 5-FU as conditioning regimens in platelet-targeted gene therapy for hemophilia B","authors":"Wenjue Xu ,&nbsp;Huiyan Han ,&nbsp;Binbin Li ,&nbsp;Rui Huang ,&nbsp;Qing Lin ,&nbsp;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 × 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.</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}