Genetic strategies to block expression of CCR5, the major co-receptor of human immunodeficiency virus type 1 (HIV-1), are being developed as anti-HIV therapies. For example, human hematopoietic stem/precursor cells (HSPC) can be modified by the transient expression of CCR5-targeted zinc finger nucleases (ZFNs) to generate CCR5-negative cells, which could then give rise to HIV-resistant mature CD4(+) T cells following transplantation into patients. The safety and anti-HIV effects of such treatments can be evaluated by transplanting ZFN-treated HSPC into immunodeficient mice, where the extent of human cell engraftment, lineage differentiation and anti-HIV activity arising from the engineered HSPC can be examined. In this way, humanized mice are providing a powerful small animal model for pre-clinical studies of novel anti-HIV therapies.
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http://dx.doi.org/10.1093/infdis/jit382 | DOI Listing |
Ren Fail
December 2025
Department of Endocrinology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China.
Background: Monocyte to high-density lipoprotein cholesterol ratio (MHR) is considered a novel marker of inflammation. However, whether MHR can predict the risk of diabetic kidney disease (DKD) remains uncertain. Our research aimed to investigate the relationship between MHR and DKD.
View Article and Find Full Text PDFLeukemia
January 2025
The Clara D. Bloomfield Center for Leukemia Outcomes Research, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
The FLT3 gene frequently undergoes mutations in acute myeloid leukemia (AML), with internal tandem duplications (ITD) and tyrosine kinase domain (TKD) point mutations (PMs) being most common. Recently, PMs and deletions in the FLT3 juxtamembrane domain (JMD) have been identified, but their biological and clinical significance remains poorly understood. We analyzed 1660 patients with de novo AML and found FLT3-JMD mutations, mostly PMs, in 2% of the patients.
View Article and Find Full Text PDFSci Rep
January 2025
Université de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, F-67065, France.
Different approaches are being developed to efficiently produce in vitro platelets from cultured megakaryocytes to meet the constant demand of platelet transfusion and serve for research purposes. Recent works have shown that turbulence and periodic stress can significantly enhance platelet yield. Here we have developed and characterized a platelet production device that takes in account these properties.
View Article and Find Full Text PDFNat Commun
January 2025
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Acute myeloid leukemia (AML) featuring retinoic acid receptor-gamma (RARG) rearrangements exhibits morphological features resembling those of acute promyelocytic leukemia but is associated with drug resistance and poor clinical outcomes. However, the mechanisms underlying the role of RARG fusions in leukemogenesis remain elusive. Here, we show that RARG fusions disrupt myeloid differentiation and promote proliferation and self-renewal of hematopoietic stem and progenitor cells (HSPCs) by upregulating BCL2 and ATF3.
View Article and Find Full Text PDFBlood Cancer Discov
January 2025
Princess Máxima Center, Utrecht, Netherlands.
In pediatric hematopoietic cell transplantation (HCT) recipients, transplanted donor cells may need to function far beyond normal human lifespan. Here, we investigated the risk of clonal hematopoiesis (CH) in 144 pediatric long-term HCT survivors and 258 non-transplanted controls. CH was detected in 16% of HCT recipients and 8% of controls, at variant allele frequencies (VAFs) of 0.
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