Blood Cells Molecules and Diseases最新文献

MRI-derived hepatic fat and its clinical correlates in non–transfusion-dependent thalassemia: a cross-sectional study mri衍生的肝脂肪及其在非输血依赖性地中海贫血中的临床相关性：一项横断面研究

IF 1.7 4区医学 Q3 HEMATOLOGY

Blood Cells Molecules and Diseases

Pub Date : 2026-07-01 Epub Date: 2026-03-06 DOI: 10.1016/j.bcmd.2026.102997

Antonella Meloni , Laura Pistoia , Paolo Ricchi , Vincenzo Positano , Anna Spasiano , Filomena Longo , Zelia Borsellino , Elisabetta Corigliano , Luigi Barbuto , Michela Zerbini , Priscilla Fina , Alberto Cossu , Giuseppe Peritore , Andrea Barison

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.

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* > 333 Hz) were excluded. Glucose metabolism was assessed using an oral glucose tolerance test (OGTT).

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.

我们通过磁共振成像（MRI）对非输血依赖型地中海贫血（NTDT）患者的肝脏脂肪分数（FF）进行了量化，并评估了其与人口统计学、临床和生化参数、组织铁过载和葡萄糖代谢改变的关系169NTDT患者（45.75±13.41岁，56.8%为女性）加入了地中海贫血扩展-心肌铁超载网络，对肝脏、胰腺和心脏铁以及肝脏FF进行了标准化的MRI评估。我们还考虑了301例输血依赖型地中海贫血（TDT）患者和25例健康对照。为了确保可靠的FF定量，排除了严重肝铁超载（R2* > 333 Hz）的患者。采用口服葡萄糖耐量试验（OGTT）评估葡萄糖代谢。定期输血（RT）和从未/零星输血（NT）的NTDT患者的肝脏FF值与健康对照组相当，但明显低于TDT患者。RT-NTDT患者的肝脏FF和肝铁水平低于NT-NTDT患者。与输血状态无关，肝脏FF与年龄、性别、脾切除术、铁蛋白、丙型肝炎感染或胰腺和心脏铁无关。在NT-NTDT中，肝脏FF与肝铁浓度呈正相关。在RT-NTDT中，肝脏FF和胰腺铁在识别异常OGTT结果方面表现出相似的诊断性能。NT-NTDT患者比RT-NTDT患者表现出更高的肝脏FF，这与肝铁水平有关。肝脏脂肪堆积和胰腺铁超载可能共同导致RT-NTDT中葡萄糖代谢的改变。

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引用次数: 0

Clinical outcomes and health-system challenges in congenital afibrinogenemia: a single-centre prospective case series 先天性纤原蛋白血症的临床结果和卫生系统挑战：单中心前瞻性病例系列

IF 1.7 4区医学 Q3 HEMATOLOGY

Blood Cells Molecules and Diseases

Pub Date : 2026-05-01 Epub Date: 2026-01-20 DOI: 10.1016/j.bcmd.2026.102986

Nita Radhakrishnan , Savitri Singh , Archit Pandharipande , Eby P. Baby , Hari Gaire

Background

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.

Methods

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.

Results

Four children (ages 0.25–13 years) constituted 0.36% of the bleeding disorder cohort in our institutional registry (n = 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 <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.

Conclusions

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.

背景：先天性纤原蛋白血症是一种非常罕见的出血性疾病，通常危及生命。数据很少，只有29例印度病例被正式报告给世界血友病联合会，大多是孤立的描述。本研究提出了一个前瞻性的儿科队列，评估临床特征，人类纤维蛋白原浓缩物（HFC）的结果，以及卫生系统的挑战。方法对2022年至2025年在三级中心诊断为纤维蛋白原血症的儿童进行前瞻性随访。分析了HFC的临床表现、诊断延迟、既往治疗和结果，并对印度文献进行了结构化回顾，并与国际数据进行了比较。结果4名儿童（年龄0.25-13岁）占我们机构登记的出血性疾病队列（n = 1096）的0.36%。中位诊断延迟为8.2年（范围0.25-12.5）。其中三人最初被误诊为血友病。主要出血包括复发性血肿、月经出血和galeal下/眶周血肿。所有患者均有克劳斯纤维蛋白原10 mg/dL。两名接受常规HFC预防治疗的儿童仍无出血（中位39.8个月）；两名按需治疗的患者只有间歇性出血。1例在正确诊断前发展为不可逆转的失明。结论纤维蛋白原性贫血虽然罕见，但如果不被发现，可能是灾难性的。早期诊断和预防性HFC可显著降低发病率。在资源有限的情况下，加强诊断能力、登记报告和公平获取氢氟碳化物至关重要。

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引用次数: 0

Association of metabolomics measurements with blood cell phenotypes 代谢组学测量与血细胞表型的关联

IF 1.7 4区医学 Q3 HEMATOLOGY

Blood Cells Molecules and Diseases

Pub Date : 2026-03-01 Epub Date: 2025-11-04 DOI: 10.1016/j.bcmd.2025.102966

Brian D. Chen , Amanda Tapia , Eric Boerwinkle , Clary B. Clish , Robert Gerszten , Misa Graff , Karen L. Mohlke , Alanna C. Morrison , Wimal Pathmasiri , Stephen S. Rich , Jerome I. Rotter , Blake R. Rushing , Susan Sumner , Russell P. Tracy , Kristin L. Young , Bing Yu , Bharat Thyagarajan , Alex P. Reiner , Yun Li , Laura Raffield

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.

全血细胞计数（CBCs）通常在临床实践中测量，并与不同的疾病和特征相关。在这些代谢组学流行病学研究中，对血细胞丰度或相关特征进行统计调整并不常见。然而，普通且廉价测量的血细胞能够捕捉到代谢组学测量也能捕捉到的一些变异，这似乎是合理的。在这里，我们通过对JHS、MESA、ARIC和HCHS/SOL队列中非靶向组的命名代谢物进行多种族荟萃分析，评估代谢物与血细胞特征之间的关系。在至少两个队列中测量的2859对代谢物和血细胞性状对中，734对（25.6%）显著相关。我们还在英国生物银行用靶向核磁共振代谢组学小组测试了代谢物-血细胞特征对。很大比例（92%）的测试对是显著的，并且血细胞的调整改变了代谢物与年龄和性别之间的关系。我们使用UK Biobank评估了代谢物效应大小变化，代谢物与不同事件疾病的关联调整了CBC特征。最值得注意的是，调整后代谢组学对慢性阻塞性肺病的影响减小。与调节eGFR相比，血细胞性状调整显示出相似但不重叠的效应大小变化，eGFR是代谢组学分析中用于解释肾功能的常见协变量。我们的研究结果表明，血细胞特征的统计调整可以减少混淆，并澄清代谢组学研究中现有临床生物标志物的额外预测能力。

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引用次数: 0

Oxidantscan: A novel biomarker to assess red blood cell susceptibility to oxidative stress in sickle cell disease 氧化扫描：一种新的生物标志物，用于评估镰状细胞病红细胞对氧化应激的易感性

IF 1.7 4区医学 Q3 HEMATOLOGY

Blood Cells Molecules and Diseases

Pub Date : 2026-03-01 Epub Date: 2025-11-19 DOI: 10.1016/j.bcmd.2025.102967

C.A. Hernández , M.J.M. Traets , W.W. van Solinge , A.W. Rijneveld , L. Kaestner , T. John , E. Nur , B.J. Biemond , F.A. Kuypers , E.J. van Beers , M.A.E. Rab , R. van Wijk

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 (n = 21, 729 ± 410 s) and HbSC (n = 19, 1031 ± 225 s) when compared to healthy controls (n = 20, 1739 ± 328 s, p < 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 p < 0.05). Finally, we provide preliminary evidence for the potential of this technique to evaluate antioxidant therapy with l-glutamine as SCD RBCs showed a significant improvement in T-POD (11.5 %, p = 0.01) and EI_Min (46.9 %, p = 0.03) upon ex vivo treatment with l-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.

镰状细胞病（SCD）患者的红细胞（RBC）持续暴露于高水平的氧化应激，这影响了红细胞的变形能力。在这项研究中，我们应用了一种新的技术（氧化扫描）来测量红细胞在氧化应激下剪切应力下的变形能力。使用从SCD患者和健康志愿者队列中收集的红细胞，我们测量了不同的参数，包括T-POD（开始氧化诱导的变形能力变化的时间）和EIMin（在测试中达到的最小变形能力）。HbSS患者（n = 21、729±410 s）和HbSC患者（n = 19、1031±225 s）的T-POD明显短于健康对照组（n = 20、1739±328 s, p < 0.05）。HbSS患者的EIMin（0.26±0.10）和HbSC患者的EIMin（0.30±0.10）明显低于健康对照组（0.54±0.02）。这些结果表明SCD患者的红细胞更容易受到氧化应激的影响，这可以用一种可重复和可量化的方式来测量。我们还证明了Oxidantscan结果参数与镰状行为和溶血标志物相关，表明这些关键病理生理特征与抗氧化应激能力之间可能存在联系（均p <； 0.05）。最后，我们为该技术评估l-谷氨酰胺抗氧化治疗的潜力提供了初步证据，因为SCD红细胞在体外使用l-谷氨酰胺治疗后，T-POD （11.5%, p = 0.01）和EIMin （46.9%, p = 0.03）显着改善。氧化扫描是一种很有前途的技术，用于评估SCD红细胞对氧化应激的反应，为疾病病理生理学和潜在的新治疗策略提供了新的见解。

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引用次数: 0

Ex vivo culture of hematopoietic stem and progenitor cells with platelet lysate: Investigating proliferation and erythroid-megakaryocytic lineage effects 用血小板裂解液体外培养造血干细胞和祖细胞：研究增殖和红细胞-巨核细胞谱系效应

IF 1.7 4区医学 Q3 HEMATOLOGY

Blood Cells Molecules and Diseases

Pub Date : 2026-03-01 Epub Date: 2025-11-19 DOI: 10.1016/j.bcmd.2025.102968

Farnaz Pirsavabi , Zahra Najafi , Mohammad Ebrahimi Siahboomi , Bewar Othman Hasan , Shaban Alizadeh , Seyyed Hadi Mousavi , Mostafa Saberian , Zahra Kashani Khatib , Saeed Mohammadi , Naser Ahmadbeigi , Azadeh Omidkhoda

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.

造血干细胞和祖细胞（HSPCs）因其自我更新和分化能力而在治疗和研究中具有重要价值。这些细胞的离体培养需要保持其独特的特性并提供类似生态位的环境。人血小板裂解液（HPL）是一种富含生长因子的物质，用于干细胞研究，影响多种生物途径。本研究探讨了HPL对HSPC增殖和红细胞巨核细胞分化的影响，探讨了改善HSPC培养条件的临床和研究应用的需要。制备HPL，对照组和添加10% HPL组培养7 d。测量细胞计数、活力和群体倍增时间（PDT）。采用qPCR和流式细胞术检测红细胞和巨核细胞的分化情况。集落形成细胞（CFC）测定证实了多系分化能力。HPL显著增加HSPCs的增殖，第7天增加1.96倍，PDT降低。CFC测定证实，这些细胞保持了分化成各种血细胞类型的能力。流式细胞术显示CD71标记物减少，但不影响红细胞总数。基因分析显示β-珠蛋白的产生增加，而其他红细胞相关基因保持稳定。与巨核细胞发育相关的标记和基因没有明显变化。HPL作为培养基的补充，在细胞培养过程中显著增强外周血源性造血干细胞的增殖，而不会诱导红细胞和巨核细胞谱系产生不必要的偏倚。

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引用次数: 0

Relationship between PCT, CRP, and IL-6 and postoperative delirium in ICU patients and its influencing factors PCT、CRP、IL-6与ICU患者术后谵妄的关系及影响因素

IF 1.7 4区医学 Q3 HEMATOLOGY

Blood Cells Molecules and Diseases

Pub Date : 2026-03-01 Epub Date: 2025-11-25 DOI: 10.1016/j.bcmd.2025.102976

Huayong Song, Lijing Shen, Wen Sun, Ludi Zhang, Lixia Xue, Qingqing Shen, Zikang Chen, Xinqing Lu

Objective

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.

Methods

Based on POD occurrence, 120 postoperative ICU patients were split into delirium (n = 72) and non-delirium (n = 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.

Results

Delirium patients were older with higher APACHE II scores, more frequent mechanical ventilation, and longer ICU stays (P < 0.05). Their serum PCT, CRP, and IL-6 levels were higher and positively correlating with POD incidence and severity (DRS-R-98 scores) (r > 0, P < 0.05). These markers were identified as independent POD predictors (OR > 1, P < 0.05), demonstrating good predictive value with AUCs of 0.936 (CRP), 0.894 (PCT), and 0.820 (IL-6).

Conclusion

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.

目的：探讨降钙素原（PCT）、c反应蛋白（CRP）、白细胞介素-6 （IL-6）与重症监护病房（ICU）患者术后谵妄（POD）的关系，并探讨影响因素。方法：将120例术后ICU患者根据POD的发生情况分为谵妄组（72例）和非谵妄组（48例）。收集临床资料及术后24小时血清PCT、CRP、IL-6水平。Pearson相关性评估了这些炎症标志物、谵妄发生率和DRS-R-98评分之间的关系。多因素logistic回归确定预测因子，ROC曲线评估炎症标志物的预测价值。结果：谵妄患者年龄越大，APACHEⅱ评分越高，机械通气次数越多，ICU住院时间越长（P < 0, P < 1, P >）。结论：术后炎症是ICU患者发生POD的独立危险因素。血清PCT、CRP和IL-6水平有助于早期发现和风险评估，支持预防策略和减轻pod相关并发症。

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引用次数: 0

Transfusion-related iron overload in survivors of childhood cancer 儿童癌症幸存者输血相关铁超载

IF 1.7 4区医学 Q3 HEMATOLOGY

Blood Cells Molecules and Diseases

Pub Date : 2026-03-01 Epub Date: 2025-12-23 DOI: 10.1016/j.bcmd.2025.102977

Kiranmye Reddy , Jonathan D. Fish , Jennifer Eng , Claire A. Carlson , Jill P. Ginsberg

Purpose

To assess the prevalence and severity of transfusion-associated iron overload (IO) in childhood cancer survivors (CCS).

Patients and methods

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.

Results

Forty-nine patients qualified for second level studies. Of these, 35 completed the MRI scans. Fifteen patients had a liver iron concentration (LIC) >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.

Conclusion

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.

目的评估儿童癌症幸存者（CCS）输血相关铁超载（IO）的患病率和严重程度。患者和方法测定了75例儿童癌症幸存者的血清铁、总铁结合能力、铁饱和度百分比和铁蛋白。此外，血库记录被审查，以确定在癌症治疗期间给药的红细胞（红细胞）的总量。接受红细胞≥120 mL/kg或铁蛋白≥1000μg/L的患者行肝脏R2和心脏T2* MRI进行铁定量、超声心动图、肝脏和内分泌功能评估以及遗传性血色素沉着症的遗传分析。结果49例患者符合二级研究条件。其中35人完成了核磁共振扫描。15例患者肝铁浓度（LIC）为3 mg铁/g（中度肝铁超载），其中8例患者LIC大于7 mg铁/g（严重肝铁超载），平均LIC为4.3 mg铁/g （0-15.6 mg铁/g）。LIC与红细胞总体积和铁蛋白相关。无患者MRI显示心脏铁负荷。与遗传性血色素沉着症相关的突变11例为杂合子，1例为纯合子。铁超载与遗传性血色素沉着症基因状态无相关性。结论儿童癌症幸存者中存在较高的输血相关性铁超载发生率。考虑到与癌症治疗相关的器官毒性与已知与铁超载相关的器官毒性之间的重叠，这一点令人担忧。LIC与铁蛋白之间的密切相关性表明铁蛋白可能是该患者人群铁负荷的可靠指标。

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引用次数: 0

WGCNA and LASSO regression-based selection and validation of microRNA biomarkers of β-thalassemia 基于WGCNA和LASSO回归的β-地中海贫血microRNA生物标志物的选择和验证

IF 1.7 4区医学 Q3 HEMATOLOGY

Blood Cells Molecules and Diseases

Pub Date : 2026-02-01 Epub Date: 2025-09-01 DOI: 10.1016/j.bcmd.2025.102957

Fang Yang , Ling Shi , Sha Su , Yin Li , Hui Chen , Zhongping Liang , Lihong Pang , Ketong Lai

Objective

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.

Methods

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.

Results

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.

Conclusion

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.

目的探讨胎儿血红蛋白（HbF）上调对重度β-地中海贫血患者治疗效果的影响。然而，调控HbF表达的机制目前尚不清楚。本研究的目的是探索与HbF表达相关的生物标志物和分子机制，以帮助开发新的治疗策略。方法使用GEO数据库的GSE93973数据集。对这些miRNA表达数据进行WGCNA、差异表达和LASSO回归分析，以鉴定中心miRNA。在K-562细胞中进行了选定的枢纽mirna的敲低和过表达，以阐明它们如何影响HbF的表达。结果在WGCNA分析中，与HbF水平关系最密切的模块是粉色模块。生物信息学分析确定miR-19b-3p为枢纽miRNA。当miR-19b-3p在K-562细胞中过表达时，这导致HbF上调，而当它被敲低时，则相反。双荧光素酶报告基因检测证实了miR-19b-3p直接调控SOX6的能力。miR-19b-3p过表达时，SOX6下调，miR-19b-3p敲低后，SOX6上调。在抢救实验中，SOX6的敲低足以部分消除miR-19b-3p敲低对HbF表达的影响。结论这些结果表明miR-19b-3p是通过调节SOX6而与β-地中海贫血中HbF表达相关的核心miRNA，暗示了一种新的HbF诱导机制，可能为β-地中海贫血患者增加HbF提供新的靶点。

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引用次数: 0

Anti-sickling efficacy and safety of Sailin-HbS, an indigenous Ayurvedic formulation 本土阿育吠陀配方Sailin-HbS的抗镰状病功效和安全性

IF 1.7 4区医学 Q3 HEMATOLOGY

Blood Cells Molecules and Diseases

Pub Date : 2026-02-01 Epub Date: 2025-09-03 DOI: 10.1016/j.bcmd.2025.102956

Shruti Bhatt , Anil Bhansali , Apratim Sai Rajesh , Satyabrata Meher , Rabindra Kumar Jena , Bishnu Prasad Dash , Pradip Kumar Panda , Kalpna Gupta , Suman Kundu

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.

镰状细胞病（SCD）是一种以血红蛋白珠蛋白链突变为特征的遗传性疾病。脱氧镰状血红蛋白（HbS）聚合导致坚硬的镰状红细胞（RBC），这是SCD病理生物学和包括器官损伤和疼痛在内的多种合并症的主要原因。基因治疗是减少镰状病的唯一治疗方法，但其成本高、技术资源落后、年龄限制等局限性给其应用带来了重大挑战。我们研究了一种营养保健品Sailin-HbS的潜力，该营养品由5种不同植物来源的提取物配制而成，具有抗氧化和抗炎特性，可以改善红细胞镰状细胞。使用来自SCD患者的镰状红细胞（ss - rbc）， Sailin-HbS在低氧条件下显示出~ 74%的镰状红细胞抑制作用；并通过降低700 nm聚合动力学显著抑制缺氧诱导的HbS聚合。渗透脆弱性测试表明，在Sailin-HbS的存在下，ss -红细胞对渗透胁迫的抵抗力增强。我们将Sailin-HbS的抗镰状细胞效应与已知的抗镰状细胞效应药物Niprisan、SCD 101、es -103/5- hmf和GBT440/Voxelotor进行了比较，发现它们的抗镰状细胞效应相同，甚至更有效。我们在2种啮齿动物模型中测试了Sailin-HbS的安全性/毒性，结果显示出较高的安全阈值，口服LD50超过2000 mg/kg，将其列入OECD-GHS类别5类。大鼠的亚急性和慢性毒性评估显示，对器官功能或体重、生化参数或全血细胞计数没有不良影响，表明其在既定阈值水平下的安全性。因此，Sailin-HbS在不诱导毒性的情况下表现出相当大的抗镰状细胞损伤作用，提示其在SCD中的翻译潜力。

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引用次数: 0

Effects of G-CSF and 5-FU as conditioning regimens in platelet-targeted gene therapy for hemophilia B G-CSF和5-FU作为调节方案在血友病B血小板靶向基因治疗中的作用。

IF 1.7 4区医学 Q3 HEMATOLOGY

Blood Cells Molecules and Diseases

Pub Date : 2026-02-01 Epub Date: 2025-10-25 DOI: 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.

针对血友病的血小板靶向基因治疗需要在体外修饰患者的造血干细胞（hsc），以产生含有凝血因子的血小板，通过在损伤部位局部释放因子提供潜在的治疗。然而，相关的骨髓移植具有显著的风险，强调了低毒调理方案的迫切需要，以实现临床转化。本研究评估了G-CSF和5-FU作为促进表达血小板靶向FIX Padua的造血干细胞移植的调节方案。血友病B （HB）小鼠分别用G-CSF、5-FU单独或G-CSF、plerixafor和5-FU联合治疗。移植来自表达血小板储存FIX Padua的转基因供体（2bF9-R338L）的骨髓单核细胞（BM-MNCs）。G-CSF调节使1 × 108 BM-MNCs长期植入；然而，随着细胞剂量的降低，疗效显著下降。移植前1天给予单剂量5-FU （150 mg/kg）可获得最佳的FIX表达和最小的毒性。关键的是，G-CSF/plerixafor联合治疗方案加上定时5-FU（第1天）可产生稳定、长期的血小板FIX表达和表型拯救。5-FU的成功强调了为供体HSC移植创造一个短暂的生态位空缺的重要性。这些结果表明，这种以动员为基础的非清髓调节策略是一种有前途的血小板靶向血友病基因治疗方法。

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引用次数: 0