Current Research in Translational Medicine最新文献_第3页

Optimized GMP-grade Wharton’s jelly’s mesenchymal stromal cells manufacturing and administration protocol for Graft versus Host disease prevention 优化gmp级华氏果冻间充质间质细胞制造和给药方案，预防移植物抗宿主病

IF 3 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-09-10 DOI: 10.1016/j.retram.2025.103543

Cécile Pochon , Romain Perouf , Anne-Béatrice Notarantonio , Allan Bertrand , Naceur Charif , De Carvalho Bittencourt Marcelo , Guillemette Fouquet , Ghislaine Cauchois , Danièle Bensoussan , David Moulin , Simona Pagliuca , Natalia de Isla , Hervé Sartelet , Maud D’Aveni , Marie-Thérèse Rubio

Background

Wharton's jelly mesenchymal stromal cells (WJ-MSCs) are multipotent cells derived from the umbilical cord with immunomodulatory properties, making them a promising candidate for cell-based therapies targeting immune-related diseases. Herein, we aim to optimize the conditions of use of clinical-grade WJ-MSCs manufactured according to Good Manufacturing Practice (GMP) for the prevention of graft versus host disease (GVHD) in a preclinical xenogeneic GVHD mouse model.

Methods

GMP-compliant WJ-MSCs were primed with IFN-γ and assessed in vitro for their immunosuppressive capacity using coculture assays with activated human T cells. To evaluate in vivo efficacy, NSG mice were sub-lethally irradiated (2 Gy) and transplanted with human peripheral mononuclear cells, then treated with one or more injections of IFN-γ-primed or unprimed WJ-MSCs, to assess xeno- GVHD and its severity.

Results

GMP-produced WJ-MSCs suppressed T-cell proliferation in vitro and IFN-γ priming enhanced this effect, largely through Indoleamine 2,3-dioxygenase (IDO) activity. In vivo, three weekly injections of IFN-γ-primed WJ-MSCs significantly improved survival and reduced histological GVHD scores in the liver and skin of recipient mice.

Conclusion

These findings demonstrate that IFN-γ-primed GMP-grade WJ-MSCs effectively prevent GVHD in preclinical models, and support their use in optimized dosing regimens for future clinical testing. Given their enhanced immunosuppressive efficacy, they also hold promise as a therapeutic option for established and treatment-refractory forms of GVHD.

wharton’s jelly mesenchymal stromal cells （WJ-MSCs）是一种来自脐带的多能细胞，具有免疫调节特性，使其成为针对免疫相关疾病的细胞治疗的有希望的候选细胞。在此，我们的目标是优化临床级WJ-MSCs在临床前异种GVHD小鼠模型中用于预防移植物抗宿主病（GVHD）的使用条件。方法采用IFN-γ对符合sgmp的WJ-MSCs进行诱导，并与活化的人T细胞共培养，评估其体外免疫抑制能力。为了评估体内效果，将NSG小鼠进行亚致死照射（2 Gy）并移植人外周单核细胞，然后注射一次或多次IFN-γ引物或未引物的WJ-MSCs，以评估异种GVHD及其严重程度。结果gmp产生的WJ-MSCs体外抑制t细胞增殖，IFN-γ启动主要通过吲哚胺2,3-双加氧酶（IDO）活性增强这种作用。在体内，每周三次注射IFN-γ-引发的WJ-MSCs可显著提高受体小鼠的存活率，并降低肝脏和皮肤的GVHD组织学评分。结论IFN-γ引发的gmp级WJ-MSCs在临床前模型中可有效预防GVHD，并支持其用于未来临床试验的优化给药方案。鉴于其增强的免疫抑制功效，它们也有望成为已建立的和治疗难治性GVHD的治疗选择。

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引用次数: 0

Successful treatment of congenital sideroblastic anemia with low-dose decitabine in a patient with NDUFB11 gene mutation (c.276_278del): A case report 低剂量地西他滨治疗NDUFB11基因突变（c.276_278del）患者先天性铁母细胞性贫血1例报告

IF 3 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-09-09 DOI: 10.1016/j.retram.2025.103542

Juan Wang , Heng Li , Nan Lv , Min Wang , Hongyu Zhao

Background

Congenital sideroblastic anemias (CSAs) are an inherited group of blood disorders due to defects of mitochondrial proteins. The NDUFB11 gene is essential for the assembly of mitochondrial complex Ⅰ protein. Mutations in the NDUFB11 gene can cause sideroblastic anemia with hyperlacticemia, microphthalmia, cardiomyopathy and encephalomyopathy with limited therapeutic options.

Case presentation

We reported a 35-year-old man with congenital sideroblastic anemia, skeletal dysplasias and hyperlacticemia. The skeletal muscle stains indicated probability of mitochondrial disorders. By whole-exome sequencing, we identified a mutation (c.276_278delCTT) in NDUFB11 gene in this patient which was inherited from his mother. He was unresponsive to the treatment of vitamin B2, vitamin B6, Coenzyme Q10, idebenone, or EPO but achieved hemoglobin concentration rise, transfusion independence and improvement of quality life after treated with low dose decitabine.

Conclusions

We proposed that epigenetic factors might play a role in pathogenesis in patients with c.276_278del (p.F93del) mutation in NDUFB11 gene and low dose decitabine may be a novel treatment in CSA patients with c.276_278del (p.F93del) mutation in NDUFB11 gene.

先天性铁母细胞性贫血（csa）是一种由线粒体蛋白缺陷引起的遗传性血液疾病。NDUFB11基因对线粒体复合体Ⅰ蛋白的组装至关重要。NDUFB11基因突变可导致铁母细胞性贫血伴高乳酸血症、小眼症、心肌病和脑肌病，治疗选择有限。我们报告了一位35岁男性先天性铁母细胞性贫血，骨骼发育不良和高乳酸血症。骨骼肌染色提示线粒体疾病的可能性。通过全外显子组测序，我们发现该患者的NDUFB11基因突变（c.276_278delCTT）遗传自其母亲。患者对维生素B2、维生素B6、辅酶Q10、依地苯酮、促红细胞生成素等治疗无反应，但经低剂量地西他滨治疗后，患者血红蛋白浓度升高，输血不依赖，生活质量改善。结论NDUFB11基因c.276_278del （p.F93del）突变可能与表观遗传因素有关，低剂量地西他滨可能是CSA NDUFB11基因c.276_278del （p.F93del）突变患者的一种新的治疗方法。

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引用次数: 0

Explainable AI for Parkinson’s disease prediction: A machine learning approach with interpretable models 帕金森病预测的可解释人工智能：具有可解释模型的机器学习方法

IF 3 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-09-05 DOI: 10.1016/j.retram.2025.103541

Adebimpe O. Esan , David B. Olawade , Afeez A. Soladoye , Bolaji A. Omodunbi , Ibrahim A. Adeyanju , Nicholas Aderinto

Background

Parkinson’s Disease (PD) is a chronic, progressive neurological disorder with significant clinical and economic impacts globally. Early and accurate prediction remains challenging with traditional diagnostic methods due to subjectivity, delayed diagnosis, and variability. Machine Learning (ML) approaches offer potential solutions, yet their clinical adoption is hindered by limited interpretability. This study aimed to develop an interpretable ML model for early and accurate PD prediction using comprehensive multimodal datasets and Explainable Artificial Intelligence (XAI) techniques.

Methods

The study applied five ML algorithms: Support Vector Machine (SVM), K-Nearest Neighbors (KNN), Logistic Regression (LR), Random Forest (RF), XGBoost, and a stacked ensemble method to a publicly available dataset (n = 2105) from Kaggle. Data encompassed demographic, medical history, lifestyle, clinical symptoms, cognitive, and functional assessments with specific inclusion/exclusion criteria applied. Preprocessing involved normalization, Synthetic Minority Oversampling Technique (SMOTE), and Sequential Backward Elimination (SBE) for feature selection. Model performance was evaluated via accuracy, precision, recall, F1-score, and Area Under Curve (AUC). The best-performing model (RF with feature selection) was interpreted using SHAP and LIME methods.

Results

Random Forest combined with Backward Elimination Feature Selection achieved the highest predictive accuracy (93 %), precision (93 %), recall (93 %), F1-score (93 %), and AUC (0.97). SHAP and LIME analyses indicated UPDRS scores, cognitive impairment, functional assessment, and motor symptoms as primary predictors, enhancing clinical interpretability.

Conclusion

The study demonstrated the effectiveness of an interpretable RF model for accurate PD prediction. Integration of ML and XAI significantly improves clinical decision-making, diagnosis timing, and personalized patient care.

帕金森病（PD）是一种慢性进行性神经系统疾病，在全球范围内具有重要的临床和经济影响。由于主观性、延迟诊断和可变性，传统诊断方法的早期和准确预测仍然具有挑战性。机器学习（ML）方法提供了潜在的解决方案，但其临床应用受到有限的可解释性的阻碍。本研究旨在利用综合多模态数据集和可解释人工智能（XAI）技术，开发一个可解释的ML模型，用于PD的早期和准确预测。方法采用支持向量机（SVM）、k近邻（KNN）、逻辑回归（LR）、随机森林（RF）、XGBoost和堆叠集成方法等5种机器学习算法对Kaggle公开数据集（n = 2105）进行分析。数据包括人口统计学、病史、生活方式、临床症状、认知和功能评估，并采用了特定的纳入/排除标准。预处理包括归一化、合成少数过采样技术（SMOTE）和序列反向消除（SBE）进行特征选择。通过准确性、精密度、召回率、f1评分和曲线下面积（AUC）来评估模型的性能。使用SHAP和LIME方法解释表现最佳的模型（带特征选择的RF）。结果随机森林结合后向消除特征选择的预测准确率最高（93%），准确率最高（93%），召回率最高（93%），f1得分最高（93%），AUC最高（0.97）。SHAP和LIME分析表明，UPDRS评分、认知障碍、功能评估和运动症状是主要预测因素，增强了临床可解释性。结论该研究证明了可解释的射频模型对PD的准确预测的有效性。ML和XAI的集成显著改善了临床决策、诊断时机和个性化患者护理。

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引用次数: 0

Could adherence to SAMPL Guidelines improve statistical reporting in clinical manuscripts? Insights from 150 editorial reviews for specialty journals 遵守SAMPL指南能改善临床手稿的统计报告吗？来自专业期刊150篇社论评论的见解

IF 3 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-08-18 DOI: 10.1016/j.retram.2025.103536

Michal Ordak

Background

Although statistical reporting guidelines such as SAMPL (Statistical Analyses and Methods in the Published Literature) exist, statistical errors remain common in biomedical manuscripts. This study investigates whether early author adherence to SAMPL can reduce the need for statistical revision and offers recommendations for broader editorial implementation.

Methods

A retrospective analysis was conducted on 150 statistical reviews performed by the author between 2020 and 2025 for clinical medicine journals. Each manuscript was assessed for adherence to key SAMPL principles, including clarity of statistical methods, reporting of assumptions, and presentation of descriptive data. Outcomes were categorized as acceptance, revision (major/minor), or rejection.

Results

Of the 150 manuscripts, 99 (66 %) were accepted following SAMPL-based revisions: 87 after one round and 12 after two rounds (p < 0.001). The remaining 51 (34 %) were rejected, primarily due to issues such as inappropriate test use or lack of methodological justification. Among 39 manuscripts with conflicting reviewer opinions, SAMPL-based review helped resolve ambiguity, resulting in 25 rejections and 14 acceptances (p = 0.02). Of the accepted manuscripts, 65 % required major revisions and 35 % minor revisions (p = 0.004).

Conclusion

Proactive adherence to the SAMPL Guidelines may reduce editorial workload, improve clarity, and lower preventable rejections. Integrating structured reporting standards into submission processes could enhance transparency and consistency in statistical reporting. These findings support the use of SAMPL-based checklists to improve manuscript quality and streamline peer review.

尽管存在诸如SAMPL（已发表文献中的统计分析和方法）之类的统计报告指南，但生物医学论文中的统计错误仍然很常见。本研究调查了早期作者遵守SAMPL是否可以减少统计修订的需要，并为更广泛的编辑实施提供了建议。方法回顾性分析作者在2020 ~ 2025年间发表在临床医学期刊上的150篇统计综述。评估每份稿件是否符合SAMPL的关键原则，包括统计方法的清晰度、假设的报告和描述性数据的呈现。结果分为接受、修改（主要/次要）或拒绝。结果在150篇论文中，99篇（66%）在基于sampl的修订后被接受：87篇在一轮后被接受，12篇在两轮后被接受（p < 0.001）。其余51例（34%）被拒绝，主要是由于不适当的测试使用或缺乏方法学证明等问题。在39篇审稿人意见有冲突的稿件中，基于sampl的审稿有助于消除歧义，结果有25篇被拒，14篇被接受（p = 0.02）。在接受的手稿中，65%需要主要修改，35%需要次要修改（p = 0.004）。结论积极遵守SAMPL指南可以减少编辑工作量，提高清晰度，降低可预防的退稿率。将结构化报告标准纳入提交过程可以提高统计报告的透明度和一致性。这些发现支持使用基于sampl的检查表来提高稿件质量和简化同行评审。

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引用次数: 0

Expert consensus on the management of cytomegalovirus infection in pediatric allogeneic hematopoietic stem cell transplantation 专家对小儿异基因造血干细胞移植中巨细胞病毒感染处理的共识

IF 3 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-08-15 DOI: 10.1016/j.retram.2025.103535

Simone Cesaro , Manuela Spadea , Franca Fagioli , Fulvio Porta , Marco Rabusin , Giulia Ferrando , Adriana Balduzzi , Arcangelo Prete , Marco Zecca , Maura Faraci

Cytomegalovirus (CMV) infection is the most frequent viral complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the pediatric setting, several issues on its management are still debated due to the limited evidence compared to adults. The aim of this consensus was to promote harmonization of practices to improve prevention, control and treatment of CMV infection in children and adolescents.

Consensus was generated through voting by a panel of experts from 8 Italian pediatric transplant units who selected 11 topics on prevention of CMV infection and disease, risk factors, diagnosis, prophylaxis, pre-emptive, and therapeutic approaches and formulated 11 statements.

Statements were generated on impact of CMV infection on allo-HSCT outcome; risk factors for infection; monitoring of patients at risk; duration of infection risk; CMV prophylaxis and CMV pre-emptive strategies; choice of the antiviral therapy; use of CMV-IgG; antiviral combination therapy; role of adoptive cell therapy; therapeutic drug monitoring. All statements reached a mean score of ≥7 (agreement) at the first voting round and reached an even higher level of consensus at the second voting round after discussion and possible modification of some statements.

In conclusion, CMV infection is a risk factor for lower survival and higher non-relapse mortality. We propose a set of expert consensus-generated recommendations aimed at harmonizing the management of CMV infection in pediatric allo-HSCT. We recognize that this field has several unmet needs and emphasize the need for further specific clinical investigations.

巨细胞病毒（CMV）感染是同种异体造血干细胞移植后最常见的病毒并发症。在儿科环境中，由于与成人相比证据有限，有关其管理的几个问题仍存在争议。达成这一共识的目的是促进统一做法，以改善儿童和青少年巨细胞病毒感染的预防、控制和治疗。来自意大利8个儿科移植单位的专家小组通过投票达成共识，他们选择了11个主题，包括巨细胞病毒感染和疾病的预防、危险因素、诊断、预防、预防和治疗方法，并制定了11项声明。生成了关于巨细胞病毒感染对同种异体造血干细胞移植结果影响的声明；感染的危险因素；监测高危患者；感染风险持续时间；巨细胞病毒预防和巨细胞病毒预防策略；抗病毒治疗的选择；CMV-IgG的使用；抗病毒联合治疗；过继细胞治疗的作用；治疗药物监测。在第一轮投票中，所有陈述的平均得分均达到≥7分（一致），在第二轮投票中，经过讨论和可能修改的部分陈述，达成了更高的共识。总之，巨细胞病毒感染是低生存率和高非复发死亡率的危险因素。我们提出了一套专家共识生成的建议，旨在协调儿童同种异体造血干细胞移植中巨细胞病毒感染的管理。我们认识到这一领域有几个未满足的需求，并强调需要进一步的具体临床研究。

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引用次数: 0

Immunotherapy with ex vivo–expanded donor-derived NK cells after haploidentical HSCT in pediatric patients with AML: a phase I pilot study 儿童AML患者单倍体造血干细胞移植后体外扩增供体来源NK细胞的免疫治疗：一项I期试点研究

IF 3 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-08-06 DOI: 10.1016/j.retram.2025.103534

Tahereh Rostami , Mohammad Ahmadvand , Bahram Chahardoli , Mohammad Reza Rostami , Mojtaba Azari , Morteza Azari , Azadeh Kiumarsi , Ghasem Janbabaei

Background

Post-transplant relapse remains a considerable challenge for achieving successful outcomes in pediatric patients with acute myeloid leukemia (AML) receiving haploidentical hematopoietic stem cell transplantation (HSCT). Adoptive immune cell therapy strategies utilizing highly purified donor-derived natural killer (NK) cells have been extensively explored in various transplantation settings, demonstrating promise in preventing disease recurrence, especially in pediatric AML patients.

Methods

Five pediatric and adolescent patients with high-risk AML were included in this pilot study and received haploidentical HSCT. On day 7 post-HSCT, all the patients received a single infusion of interleukin (IL)-2 stimulated ex vivo-expanded haploidentical NK cells (1 × 10⁶/kg CD56+ cells of patient body weight).

Results

All the patients tolerated the administration of NK cells without any adverse events during or after the infusion. Relapse occurred in two patients, both within the first 100 days post-transplantation, while three patients remained alive and disease-free one year post-transplantation.

Conclusion

This pilot study demonstrated that the activation, expansion, and infusion of NK cells from readily available haploidentical donors in pediatric and adolescent patients with high-risk AML after HSCT is safe and feasible.

对于接受单倍同型造血干细胞移植（HSCT）的急性髓系白血病（AML）患儿，移植后复发仍然是一个相当大的挑战。利用高度纯化的供体来源的自然杀伤（NK）细胞的过继免疫细胞治疗策略已经在各种移植环境中进行了广泛的探索，显示出预防疾病复发的希望，特别是在儿科AML患者中。方法5例儿童和青少年高危AML患者接受单倍同型造血干细胞移植。在hsct后第7天，所有患者接受单次输注白细胞介素(IL)-2刺激的体外扩增单倍体NK细胞（1 × 106/kg患者体重CD56+细胞）。结果所有患者在输注NK细胞期间及输注后均能耐受，无不良反应发生。2例患者复发，均在移植后的前100天内，而3例患者在移植后一年内存活且无疾病。本初步研究表明，在儿童和青少年高危AML患者HSCT后，激活、扩增和输注来自单倍体相同供体的NK细胞是安全可行的。

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引用次数: 0

Effect of adipose-derived mesenchymal stromal/stem cells on mouse mammary tumour growth and formation of lung metastases 脂肪源性间充质干细胞对小鼠乳腺肿瘤生长和肺转移形成的影响

IF 3 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-07-28 DOI: 10.1016/j.retram.2025.103532

Kimberly T. Peta , Chrisna Durandt , Marlene B. van Heerden , Michael S. Pepper , Melvin A. Ambele

Background

The role of mesenchymal stromal/stem cells (MSCs) in tumour development and progression remains a subject of debate. Previous studies have reported contradictory outcomes, possibly due to variations in experimental design and the use of xenograft models. Xenograft models limit interpretation and translation due to cross-species variability. To address these limitations, we employed an isogenic mouse model of spontaneous breast cancer (BC) to investigate the impact of murine MSCs on BC development and progression. Methods: MSCs isolated from FVB/N mouse adipose tissue (mASCs) were administered to female mice with palpable mammary tumours. Tumour volume and mass were assessed, and analysis of histopathological necrosis and gene expression was conducted on mammary (MT) and lung metastatic tumours (LT). Results: No change in MT mass and volume was observed between mASC-treated and control mice. However, mASC treatment led to increased necrosis in LT but not in MT. Immunohistochemistry revealed that mASC-treated mice had fewer CD163+ anti-inflammatory macrophages in the LT but not in the MT. Tgf-β3, vegfr1, and cd105 were observed and downregulated in both MT and LT in mASC-treated mice. The downregulation of cd36 and tgf-β3 contributes to pro-tumourigenic activities, whereas the downregulation of vegfr1 and cd105 is associated with an anti-tumour effect. In the mASC treatment group, all cytokines tested for, except IL-27, were elevated. Conclusion: This study suggests that mASCs are anti-tumourigenic in pulmonary metastatic BC. Our findings emphasize the importance of considering the tumour microenvironment and employing relevant animal models when investigating the impact of MSCs on tumour progression.

背景间充质基质/干细胞（MSCs）在肿瘤发生和发展中的作用仍然是一个有争议的话题。先前的研究报告了相互矛盾的结果，可能是由于实验设计和异种移植模型的使用不同。由于物种间的差异，异种移植模型限制了解释和翻译。为了解决这些局限性，我们采用了一个等基因小鼠自发性乳腺癌（BC）模型来研究小鼠间充质干细胞对BC发展和进展的影响。方法：从FVB/N小鼠脂肪组织（mASCs）中分离的MSCs给予可触及乳腺肿瘤的雌性小鼠。对乳腺（MT）和肺转移瘤（LT）进行肿瘤体积和质量评估，并进行组织病理学坏死和基因表达分析。结果：经masc处理的小鼠与对照组相比，MT的质量和体积没有变化。然而，mASC治疗导致LT中坏死增加，而MT中没有。免疫组织化学显示，mASC治疗小鼠LT中CD163+抗炎巨噬细胞减少，而MT中没有。Tgf-β3、vegfr1和cd105在mASC治疗小鼠MT和LT中均观察到下调。cd36和tgf-β3的下调有助于促肿瘤活性，而vegfr1和cd105的下调与抗肿瘤作用有关。在mASC治疗组中，除IL-27外，所有细胞因子检测均升高。结论：本研究提示mASCs在肺转移性BC中具有抗肿瘤作用。我们的研究结果强调了在研究MSCs对肿瘤进展的影响时考虑肿瘤微环境和使用相关动物模型的重要性。

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引用次数: 0

CRISPR-Cas9: a prominent genome editing tool in the management of inherited blood disorders and hematological malignancies CRISPR-Cas9：在遗传性血液疾病和血液系统恶性肿瘤的管理突出的基因组编辑工具

IF 3 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-07-27 DOI: 10.1016/j.retram.2025.103531

Ghazaleh Behrouzian Fard, Mohammad Hossein Ahmadi, Mehran Gholamin, Mahdi Hosseini Bafghi

Several hematologic diseases with genetic defects, like sickle cell disease and β-thalassemia can be treated with allogeneic hematopoietic stem cell transplantation (HSCT) from healthy donors. However, suitable tissue-matched donors are often unavailable, and HSCT involves risks such as graft-versus-host disease and potential disease relapse. Due to the genetic heterogeneity of blood disorders and the complexity of the hematopoietic system, identifying effective genes for managing and treating both benign and malignant conditions remains a significant challenge. The genome editing field is rapidly expanding and is essential for identifying genetic factors in pathological processes. These developments highlight the importance of using ex vivo gene therapy approaches for autologous hematopoietic stem cells. Also, gene editing technologies are gaining significant interest in engineered cell therapies for hematological malignancies . Today, various programmable nucleases are available for genome editing, with the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system standing out due to its high efficiency, low cytotoxicity, cost-effectiveness, and precision. This system can serve as a genomic modification tool for treating blood disorders, including hereditary diseases and immunotherapy for cancer using chimeric antigen receptor T cells (CAR-T cells). Advancements in CRISPR-Cas9 are expected to significantly impact medical research and clinical applications. However, challenges such as off-target effects and immunogenicity must be addressed. This review summarizes the mechanism and delivery strategies of CRISPR-Cas9, discusses its applications in treating inherited blood disorders such as sickle cell disease, β-thalassemia, and fanconi anemia, as well as hematological malignancies, and highlights the associated challenges.

一些具有遗传缺陷的血液病，如镰状细胞病和β-地中海贫血，可以通过健康供体的同种异体造血干细胞移植（HSCT）治疗。然而，合适的组织匹配供体往往是不可用的，并且移植涉及移植物抗宿主病和潜在的疾病复发等风险。由于血液疾病的遗传异质性和造血系统的复杂性，确定有效的基因来管理和治疗良性和恶性疾病仍然是一个重大的挑战。基因组编辑领域正在迅速扩大，对于识别病理过程中的遗传因素至关重要。这些进展突出了使用体外基因治疗方法治疗自体造血干细胞的重要性。此外，基因编辑技术在血液恶性肿瘤的工程细胞疗法中也引起了极大的兴趣。如今，各种可编程核酸酶可用于基因组编辑，聚集规律间隔短回文重复序列(CRISPR)-CRISPR相关蛋白9 （Cas9）系统因其高效率、低细胞毒性、成本效益和准确性而脱颖而出。该系统可以作为治疗血液疾病的基因组修饰工具，包括遗传性疾病和使用嵌合抗原受体T细胞（CAR-T细胞）进行癌症免疫治疗。CRISPR-Cas9的进展有望对医学研究和临床应用产生重大影响。然而，必须解决脱靶效应和免疫原性等挑战。本文综述了CRISPR-Cas9的机制和传递策略，讨论了其在镰状细胞病、β-地中海贫血、范可尼贫血等遗传性血液疾病以及血液系统恶性肿瘤治疗中的应用，并指出了相关挑战。

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引用次数: 0

Adolescent and young adult patients with ‘Philadelphia negative’ myeloproliferative neoplasms: a real world, UK tertiary-centre study 青少年和年轻成人患者的“费城阴性”骨髓增生性肿瘤：一个真实的世界，英国三级中心的研究

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-07-22 DOI: 10.1016/j.retram.2025.103530

Dipal Mehta, Holly Theaker, Hugo Ferreira, Syeda Ahmed, Aisha Roble, Emma Shambrook, Jonathan Lambert, Andrew Wilson, Donal P McLornan, Samah Alimam

Increasing numbers of adolescent and young adult (AYA) patients are diagnosed with myeloproliferative neoplasms (MPNs). Management strategies are often extrapolated from older MPN cohorts and frequently fail to address specific needs. Through retrospective description of 107 AYA patients registered at a UK specialist centre, we identify unique clinicopathological features compared with older patients, including lower incidence of JAK2 V617F and additional non-driver mutations, and a reduced rate of transformation. Despite these favourable disease characteristics, we demonstrate significant rates of venous thrombosis (>14 %). This data highlights areas of unmet clinical need and calls for tailored management approaches for AYA MPN patients.

越来越多的青少年和年轻成人（AYA）患者被诊断为骨髓增生性肿瘤（mpn）。管理策略通常是从较老的MPN队列中推断出来的，经常不能解决具体的需要。通过对在英国专科中心登记的107例AYA患者的回顾性描述，我们确定了与老年患者相比的独特临床病理特征，包括JAK2 V617F和其他非驱动突变的发生率较低，以及转化率较低。尽管这些有利的疾病特征，我们证明静脉血栓形成的显著率（> 14%）。这些数据突出了未满足临床需求的领域，并呼吁为AYA MPN患者量身定制管理方法。

引用次数: 0

Green solvent-based synthesis of diclofenac diethylamine-loaded PCL nanoparticles for sustained drug delivery 绿色溶剂基合成双氯芬酸二乙胺负载PCL纳米颗粒的持续给药

IF 3.2 4区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Current Research in Translational Medicine

Pub Date : 2025-07-17 DOI: 10.1016/j.retram.2025.103529

Soolafa Al Soliman , Zaki Ali Ajji , Antoun Al-Laham

Background

Diclofenac, a non-steroidal anti-inflammatory drug (NSAID), has demonstrated promising antitumor properties; however, its clinical application is limited by systemic toxicity. Encapsulation in biodegradable polymeric nanoparticles offers a strategy to enhance therapeutic efficacy while minimizing adverse effects. Nevertheless, the use of toxic organic solvents in nanoparticle fabrication remains a significant challenge.

Objective

This study aimed to develop and characterize diclofenac diethylamine-loaded polycaprolactone (PCL) nanoparticles using green solvents and to compare two preparation methods-emulsification solvent evaporation/extraction and spontaneous emulsification solvent diffusion-for producing diclofenac-loaded nanoparticles with potential applications in tumor therapy.

Methods

Diclofenac diethylamine-loaded PCL nanoparticles were prepared using both methods, employing a novel green solvent system. The nanoparticles were characterized in terms of size, polydispersity index (PDI), zeta potential, morphology, and encapsulation efficiency. In vitro drug release profiles were evaluated and fitted to kinetic models.

Results

The developed diclofenac diethylamine-loaded PCL nanoparticles exhibited a mean diameter below 200 nm, a monodisperse population, and a negative surface charge. Both preparation methods achieved high encapsulation efficiency and prolonged, diffusion-controlled drug release. The spontaneous solvent diffusion method provided slightly better control over particle size.

Conclusion

These nanoparticles are well-suited for cancer therapy, offering sustained drug release, enhanced safety due to the use of green solvents, and robust physicochemical stability. The findings support their potential as an innovative, effective, and safe delivery system for antitumoral applications.

双氯芬酸是一种非甾体抗炎药（NSAID），具有良好的抗肿瘤特性；然而，其临床应用受到全身毒性的限制。包封在可生物降解的聚合物纳米颗粒提供了一种策略，以提高治疗效果，同时尽量减少不良反应。然而，在纳米颗粒制造中使用有毒有机溶剂仍然是一个重大挑战。目的利用绿色溶剂制备双氯芬酸二乙胺负载的聚己内酯（PCL）纳米颗粒，并对其进行表征，比较乳化溶剂蒸发/萃取和自发乳化溶剂扩散两种制备双氯芬酸负载纳米颗粒的方法。方法采用新型绿色溶剂体系，采用两种方法制备双氯芬酸二乙胺负载PCL纳米颗粒。从尺寸、多分散性指数（PDI）、zeta电位、形貌和包封效率等方面对纳米颗粒进行了表征。体外药物释放曲线进行评估，并拟合动力学模型。结果制备的双氯芬酸二乙胺负载PCL纳米粒子平均直径小于200 nm，粒子群单分散，表面带负电荷。两种制备方法均具有较高的包封效率和较长的扩散控制药物释放时间。自发溶剂扩散法对粒径的控制稍好一些。结论这些纳米颗粒具有药物缓释、使用绿色溶剂增强安全性和良好的物理化学稳定性等优点，非常适合用于癌症治疗。这些发现支持了它们作为一种创新、有效和安全的抗肿瘤给药系统的潜力。

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