Acute Promyelocytic Leukemia is one of the most prevalent forms of leukemia which has been treated with arsenic trioxide (ATO) and/or all-trans retinoic acid (ATRA). Although, ATRA and ATO are broadly accessible and administrated, some adverse side effects have been reported recently. Nowadays, microvesicles (MVs) are considered as a potential therapeutic agent. Their capacity to alter the behavior of the cells is one of the most controversial issues. In this study, we investigated apoptotic effects of MVs derived from human bone marrow mesenchymal stem cells (hBM-MSCs) in combination with ATO on NB4 cell line. MVs were isolated by ultra-centrifugation. After 7 days, MTT assay, Annexin-V-fluorescein staining assay and RT-qPCR for BCL-2, KI67, BAX genes expression were performed. The results showed lower cell viability rate, higher apoptosis ratio, higher BAX gene, and lower KI67 and BCL-2 genes’ expression in cells exposed to MVs in combination with ATO compared to cells treated with each agent alone and non-treated control. We showed that MVs in combination with ATO had more apoptotic effect on NB4 cell line than each agent alone. MVs in combination with ATO in APL treatment might play an effective therapeutic role with fewer adverse side effects compared to any other agents.

The respiratory symptoms of acute respiratory distress syndrome (ARDS) in the coronavirus disease 2019 (COVID-19) patients is associated with accumulation

The CRISPR-Cas9 system has transformed biomedical research by enabling precise genetic modifications. However, efficient delivery of CRISPR components remains a major hurdle for therapeutic applications. To address this, we employed a new modified cationic hyper-branched cyclodextrin-based polymer (Ppoly) system to deliver an integrating GFP gene using the TILD-CRISPR method, which couples donor DNA linearization with RNP complexes. The physicochemical properties, loading efficiency, and cellular uptake of RNP with Ppoly were studied. After transfection, antibiotic selection and single-cell cloning were performed. Junction PCR was then performed on the isolated clones, and we compared the knock-in efficiency of Ppoly with that of the commercial CRISPRMAX™ reagent (Thermo Fisher, Invitrogen™, Waltham, MA, USA). The results demonstrate the encapsulation efficiency of over 90% for RNP and Ppoly, and cell viability remaining above 80%, reflecting the minimal toxicity of this approach. These attributes facilitated successful GFP gene integration using the TILD-CRISPR with RNP delivered via cyclodextrin-based nanosponges. The present method achieved a remarkable 50% integration efficiency in CHO-K1 cells, significantly outperforming the 14% observed with CRISPRMAX™ while maintaining lower cytotoxicity. This study highlights a promising platform for precise and efficient genome editing, with strong potential for therapeutic and regenerative medicine applications.

Aim: Human bone marrow mesenchymal stem cells (hBMSCs) may be infected by parvovirus B19 (B19V). hBMSCs support bone marrow hematopoiesis by producing stromal cells, secretion of cytokines and grow...