Current Research in Translational Medicine最新文献

{"title":"Therapeutic promise of CRISPR-Cas9 gene editing in sickle cell disease and β-thalassemia: A current review","authors":"Hassan H. Almasoudi","doi":"10.1016/j.retram.2025.103513","DOIUrl":"10.1016/j.retram.2025.103513","url":null,"abstract":"<div><div>Sickle cell disease (SCD and β-thalassemia (BT) affects millions of people worldwide. In addition, around 500,000 infants are born with SCD and 60,000 people are diagnosed with BT every year. Mutations in the <em>hemoglobin subunit beta (HBB)</em> gene are responsible for causing both BT and SCD. Indeed, the diversity of potential mutations in the <em>HBB</em> gene elucidates the diversity in clinical severity observed in individuals with BT and related morbidities. On the other hand, SCD takes place because of the alteration in a single amino acid at position 6 in the beta-globin chain, where a base substitution occurs from glutamic acid to valine, which eventually results in abnormal sickle hemoglobin. Conventional therapies for BT and SCD including pharmaceutical drugs and blood transfusion might temporarily improve the clinical severity of these diseases, however these therapies cannot cure the diseases. CRISPR-Cas9 (CC9) is revolutionizing genome engineering, offering promising therapeutic avenues for genetic diseases. Therefore, CC9-mediated gene therapy provides great hope in the treatment of both BT and SCD. CC9-mediated gene therapy has already demonstrated its effectiveness in correcting both SCD and BT-causing mutations. Moreover, CC9-mediated gene editing was found to be effective in reactivating the expression of <em>hemoglobin F (HbF)</em> and regulating <em>LRF</em> and <em>BCL11A</em>. A number of clinical trials with CC9 gene-edited therapies are being carried out to elucidate their potential in treating BT and SCD. Genetics and pathophysiological mechanisms of SCD and BT, the mechanism of CC9-mediated gene editing, and common delivery methods of the CC9 system have been discussed in this review. Moreover, an in-depth discussion on applications and the current status of CC9-mediated gene editing in SCD and BT along with current challenges and future perspectives have been provided.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 3","pages":"Article 103513"},"PeriodicalIF":3.2,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842882","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":"Perspectives on the use and availability of chimeric antigen receptor T cells (CAR-T) and cell therapies: A worldwide cross-sectional survey by the worldwide network for blood and marrow transplantation (WBMT)","authors":"Eddie HP Tan ,&nbsp;Mahmoud Aljurf ,&nbsp;Fazal Hussain ,&nbsp;Christian Chabannon ,&nbsp;Nina Worel ,&nbsp;Daniel Weisdorf ,&nbsp;Ibrahim Yakoub-Agha ,&nbsp;Sebastian Galeano ,&nbsp;Fermin Sanchez-Guijo ,&nbsp;Laurent Garderet ,&nbsp;Yoshiko Atsuta ,&nbsp;Annalisa Ruggeri ,&nbsp;Nada Hamad ,&nbsp;Sharukh Hashmi ,&nbsp;Cristobal Frutos ,&nbsp;Yoshihisa Kodera ,&nbsp;Adriana Seber ,&nbsp;Carmem Bonfim ,&nbsp;Dietger Niederwieser ,&nbsp;Damiano Rondelli ,&nbsp;Mickey BC Koh","doi":"10.1016/j.retram.2025.103515","DOIUrl":"10.1016/j.retram.2025.103515","url":null,"abstract":"<div><div>Chimeric antigen receptor T cell therapy (CAR-T) cells represent a new generation of autologous, allogeneic and personalised cell-based therapies that have revolutionised the treatment of B cell haematological malignancies. Despite their significant effectiveness in treating challenging relapsed and refractory diseases, access to this cutting-edge treatment remains a critical issue globally, even in high income countries. To gain insights into these challenges, the Worldwide Network for Blood &amp; Marrow Transplantation (WBMT) initiated a survey focused on the state of CAR-T and cellular therapy availability worldwide. The survey aimed to identify the accessibility, manufacturing capabilities, apheresis, accreditation, reimbursement, presence of regulatory frameworks and legal oversight of these cell-based therapies.</div><div>The survey included questions on demographics, the respondent's centre, CAR-T availability, details about haematopoietic stem cell transplant programs, supply and indications for CAR-T, quality assurance, and information about other cell and gene therapy products beside CAR-T. Conducted online over three months in 2023, the survey garnered 181 complete responses from various geographical regions, from North America, Asia, Europe, South and Central America, Australia and New Zealand, and Africa.</div><div>Our findings suggested a promising level of awareness and interest in CAR-T therapy globally, even in lower-income regions. However, survey respondents cited cost as the primary barrier to access, alongside infrastructure and governmental support issues. The survey also highlighted the varying reimbursement strategies across regions, with costs in Europe and North America being relatively similar while Asia showed more variability. There was also variability in the regulatory and accreditation frameworks associated with delivery of these novel therapies</div><div>As CAR-T therapy continues to grow, innovative solutions such as global partnerships, in-house production, and the establishment of cellular therapy centres in developing countries are essential. Addressing the challenges of access requires a comprehensive approach that combines efforts to lower costs, enhance healthcare infrastructure, and foster international collaborations, ensuring that CAR-T therapy becomes available to all who need it.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 2","pages":"Article 103515"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850346","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":"Acute-onset chronic inflammatory demyelinating polyneuropathy in a 23-year-old male exacerbated by an asymptomatic COVID-19 infection","authors":"Sawsan Ismail ,&nbsp;Aiman Abo Al shamat ,&nbsp;Ali Ghalion ,&nbsp;Hanafi Alyman Hannouf ,&nbsp;Tamim Alsuliman ,&nbsp;Kanaan Al-Tameemi","doi":"10.1016/j.retram.2025.103511","DOIUrl":"10.1016/j.retram.2025.103511","url":null,"abstract":"","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 3","pages":"Article 103511"},"PeriodicalIF":3.2,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785894","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":"Immune cell dysfunction: A critical player in development of diabetes complications","authors":"Mohamed J. Saadh ,&nbsp;Omer Qutaiba B. Allela ,&nbsp;Radhwan Abdul Kareem ,&nbsp;Ashishkumar Kyada ,&nbsp;H. Malathi ,&nbsp;Deepak Nathiya ,&nbsp;Deepak Bhanot ,&nbsp;Hayder Naji Sameer ,&nbsp;Atheer Khdyair Hamad ,&nbsp;Zainab H. Athab ,&nbsp;Mohaned Adil","doi":"10.1016/j.retram.2025.103510","DOIUrl":"10.1016/j.retram.2025.103510","url":null,"abstract":"<div><div>Diabetes mellitus, a global health challenge, influences millions worldwide by leading to severe complications and premature death. A key factor in its pathogenesis is immune cell dysfunction, which aggravates both type 1 and type 2 diabetes. The important role that immune cell dysregulation plays in the emergence of diabetes complications is investigated in this research. It highlights the manner in which diabetes compromises the immune system's adaptive as well as innate responses. Key defects in innate immunity include impaired pathogen recognition, and dysfunctional behavior of macrophages, neutrophils, and natural killer (NK) cells. Additionally, the complement system is dysregulated, and cytokine production is altered, affecting overall immune signaling. The study investigates the dysfunction of several T and B cell subsets, such as CD4+ T cells, CD8+ T cells, regulatory T cells, and B cells, in relation to adaptive immunity. These dysfunctions collectively contribute to chronic inflammation, reduced pathogen clearance, and increased susceptibility to infections, ultimately exacerbating diabetes complications. Developing targeted therapies to reduce diabetes complications and enhance patient outcomes requires an understanding of these mechanisms.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 3","pages":"Article 103510"},"PeriodicalIF":3.2,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918500","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":"The vaso-occlusive pain crisis in sickle cell patients: A focus on pathogenesis","authors":"Fatemeh Javaherforoosh Zadeh ,&nbsp;Azadeh Fateh ,&nbsp;Hamed Saffari ,&nbsp;Mohammadtaghi Khodadadi ,&nbsp;Mohammadamin Eslami Samarian ,&nbsp;Nasim Nikoubakht ,&nbsp;Fatemeh Dadgar ,&nbsp;Vahid Goodarzi","doi":"10.1016/j.retram.2025.103512","DOIUrl":"10.1016/j.retram.2025.103512","url":null,"abstract":"<div><div>Vaso-occlusive pain crisis (VOC) is recognized as a prominent complication of sickle cell disease, accompanied by debilitating pain and serious consequences for patients, making it the primary cause of visits to hospital emergency departments. In the etiology of VOC, the intricate interaction of endothelial cells, hypoxia, inflammation, and the coagulation system is pivotal. Hemoglobin S polymerization under hypoxic conditions leads to the formation of rigid and adhesive red blood cells that interact with vascular endothelial cells and other blood cells, causing occlusion and subsequent inflammation. Hemolysis of red blood cells results in anemia and heightened inflammation, whereas oxidative stress and involvement of the coagulation system further complicate matters. In this review, we strive to examine the pathophysiology of VOC from these mentioned aspects by consolidating findings from various studies, as a comprehensive understanding of the causes of VOC is essential for the development of targeted therapeutic interventions and the prevention and management of pain, ultimately improving the quality of life for patients.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 3","pages":"Article 103512"},"PeriodicalIF":3.2,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815694","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":"Pneumonia definition in allogeneic hematopoietic cell transplant recipients: Update and challenges in 2024. Recommendations from the EBMT Infectious Diseases Working Party and Practice Harmonization and Guidelines committee","authors":"Dionysios Neofytos ,&nbsp;Paul E. Verweij ,&nbsp;Dina Averbuch ,&nbsp;Malgorzata Mikulska ,&nbsp;Jan Styczynski ,&nbsp;José Luis Piñana ,&nbsp;Simone Cesaro ,&nbsp;Isabel Sanchez-Ortega ,&nbsp;Raffaella Greco ,&nbsp;Francesco Onida ,&nbsp;Ibrahim Yakoub-Agha ,&nbsp;Per Ljungman ,&nbsp;Camara Rafael de la ,&nbsp;Anne Bergeron","doi":"10.1016/j.retram.2025.103509","DOIUrl":"10.1016/j.retram.2025.103509","url":null,"abstract":"<div><div>To optimize and homogenize data on infectious diseases complications, the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation (IDWP EBMT) participated in the 2023 EBMT international workshop focusing on the standardization of the definition of specific infections, including respiratory infections [1]. This is pertinent considering that a new software for data collection, including data on post-transplant infectious disease complications, was launched in 2023 and which will remain the main tool for future epidemiological studies. In this report, we briefly discuss our proposals for pneumonia definition, predominately focusing on bacterial and fungal pneumonias. We specifically address definitions of pneumonia diagnosis, infection onset date, resolution, recurrence, and breakthrough infection, and the challenges we encountered as a group to accurately define pneumonia in hematopoietic cell transplant (HCT) recipients (Table 1). Infections with community acquired respiratory viruses and adenovirus are discussed in a separate report [1]. Definitions on CMV pneumonia have been previously described and recently updated and hence not discussed in this paper [2,3].</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 3","pages":"Article 103509"},"PeriodicalIF":3.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A complex clinical presentation of ultra-high risk acute promyelocytic leukemia: A case report and insights on management","authors":"Lucrezia De Marchi ,&nbsp;Giovangiacinto Paterno ,&nbsp;Kristian Taka ,&nbsp;Laura Giannì ,&nbsp;Giulia Colafranceschi ,&nbsp;Tiziana Ottone ,&nbsp;Manuela Rizzo ,&nbsp;Mariadomenica Divona ,&nbsp;Raffaele Palmieri ,&nbsp;Francesco Buccisano ,&nbsp;Luca Maurillo ,&nbsp;Maria Ilaria Del Principe ,&nbsp;Maria Teresa Voso ,&nbsp;Carmelo Gurnari ,&nbsp;Adriano Venditti","doi":"10.1016/j.retram.2025.103506","DOIUrl":"10.1016/j.retram.2025.103506","url":null,"abstract":"","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 3","pages":"Article 103506"},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642346","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":"Using machine learning to predict Hemophilia A severity","authors":"Daniel de Almeida Duque ,&nbsp;Débora Dummer Meira ,&nbsp;Lorena Souza Castro Altoé ,&nbsp;Matheus Correia Casotti ,&nbsp;Tiago José da Silva Lopes ,&nbsp;Iuri Drumond Louro ,&nbsp;Flávio Miguel Varejão","doi":"10.1016/j.retram.2025.103508","DOIUrl":"10.1016/j.retram.2025.103508","url":null,"abstract":"<div><div>Hemophilia A is a rare genetic condition that predominantly affects men and is characterized by a deficiency in Factor VIII clotting (FVIII). This research focuses on the development of a classification model to predict the severity of Hemophilia A, using data from point mutations in the FVIII protein. The study employs a variety of classification models, including RandomForest, XGBoost, and LightGBM, and performs a robust analysis of the data to select the most relevant features. The final model achieved an accuracy of 65.5 %, demonstrating significant performance against a simple gaussian naive bayes model that achieves 51.1 % of accuracy. Although the model cannot yet replace the FVIII measurement test in the blood for diagnostic purposes, the results represent a significant advance in Hemophilia A research. This work provides data analysis that deepens the understanding of the characteristics of the FVIII protein and contributes to the development of models capable of classifying the severity of this condition into its three possible classes: mild, moderate, or severe.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 3","pages":"Article 103508"},"PeriodicalIF":3.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143681477","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":"VEXAS associated acute disseminated Encephalo-Myelitis (ADEM)-like syndrome: A case report and review of the literature","authors":"Gregorio Maria Bergonzi ,&nbsp;Corrado Campochiaro ,&nbsp;Alessandro Tomelleri ,&nbsp;Anna Del Poggio ,&nbsp;Raffaello Bonacchi ,&nbsp;Laura Ferré ,&nbsp;Giulia Furnari ,&nbsp;Costanza Piccolo ,&nbsp;Gianluca Scorpio ,&nbsp;Fabio Ciceri ,&nbsp;Lorenzo Dagna ,&nbsp;Massimo Filippi ,&nbsp;Elisa Diral","doi":"10.1016/j.retram.2025.103505","DOIUrl":"10.1016/j.retram.2025.103505","url":null,"abstract":"","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 3","pages":"Article 103505"},"PeriodicalIF":3.2,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619118","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":"Variability in expression of homeobox genes (HOXA9) and (HOXA7) in acute myeloid leukemia patients","authors":"Zainab Tallima ,&nbsp;Dalia Ibraheem ,&nbsp;Manal Wilson ,&nbsp;Sally Elfishawi","doi":"10.1016/j.retram.2025.103503","DOIUrl":"10.1016/j.retram.2025.103503","url":null,"abstract":"<div><div>The strong association between NPM1 mutation and increased expression levels of HOXA7 and HOXA9 implies that HOXA genes may be utilized as targeted treatment markers in NPM1-mutated patients. We examined HOXA7 and HOXA9 gene expression in acute myeloid leukemia (AML) patients with nucleophosmin1 (NPM1) mutation. This study included 91 cases of AML and 23 samples of matched healthy controls. HOXA7 and HOXA9 gene expression was analyzed using real-time PCR with SYBR Green dye. All cases were subjected to NPM1 mutation detection. Both HOXA7 and HOXA9 gene expressions were significantly correlated with age, with adult patients exhibiting substantially higher gene expression than pediatric patients (<em>p</em> &lt; 0.01). Both HOXA7 and HOXA9 high gene expressions were significantly associated with NPM1 mutation (<em>p</em> = 0.032 and <em>p</em> = 0.001, respectively). Adult patients with AML demonstrated a higher level of HOXA9 expression, which has a negative impact on the disease-free survival of NPM1-mutated patients (<em>p</em> = 0.055). Therefore, targeting the HOXA9 pathway presents a highly plausible treatment option for NPM1-mutated adult AML patients.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 2","pages":"Article 103503"},"PeriodicalIF":3.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579114","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}