Dimethyl sulfoxide (DMSO) is widely used in biological studies as a cryoprotective agent for cells and tissues, and also for cryopreserved platelets (PLTs). However, few data on the toxic effects of DMSO following intravenous infusion of cryopreserved PLTs are available. The aim of this study was to explore dose‐related effects of DMSO on red blood cells (RBCs), PLTs and vascular endothelial cells in vitro. The results showed that DMSO treatments had significant effects on RBCs, affecting osmotic fragility and increasing hemolysis. Free hemoglobin (FHb) level of RBCs was 0.64 ± 0.19 g L−1 after incubation for 6 h with 0.6% DMSO, and these levels were elevated compared with controls (0.09 ± 0.05 g L−1). Aggregation of PLTs induced by adenosine diphosphate, thrombin (THR), and thrombin receptor activator peptide (TRAP) were inhibited by DMSO treatment because the THR generation capacity was reduced. The intensity of the cytosolic esterase‐induced fluorescence response from carboxy dimethyl fluorescein diacetate (CMFDA) in PLTs was decreased about 29% ± 0.04% after treatment with DMSO. DMSO also inhibited the proliferation of the vascular endothelial cell line EAhy926 cells by blocking the G1 phase. Apoptosis of EAhy926 cells with 0.6% DMSO stimulation was increased threefold compared to controls. On the basis of these findings, it was concluded that DMSO was toxic to the hematologic system. This should be taken into account when assessing the infusion effects of cryopreserved PLTs or other blood products requiring DMSO as a vehicle, such as cryopreserved stem cells, in order to avoid adverse therapeutic effects.
Resveratrol (Res) is a multi-functional polyphenol compound that has protective functions in cardiovascular and neurodegenerative diseases. This study aimed to determine the effect of Res on osteogenic differentiation and bone mineralization in zebrafish (
Danio rerio
) with dexamethasone (Dex)-induced bone damage. Our results showed that Dex exposure (15 μmol/l) decreased the green fluorescence areas and the integrated optic density (IOD) values in the skull bones of zebrafish larvae of the TG(SP7:EGFP) strain in a dose-dependent manner (
p
< 0.01). Furthermore, Dex exposure decreased the alizarin red S-stained areas (bone mineralization area) in the skeleton and spinal bones of zebrafish larvae of the AB strain in a dose-dependent manner (
p
< 0.01). By contrast, Res treatment (150 μmol/l) significantly increased both the green fluorescence and bone mineralization area in Dex-exposed zebrafish larvae. Thus, our data show that Res improves bone mineralization after glucocorticoid-induced bone damage in a zebrafish model. Res may be a candidate drug for the prevention of osteoporosis.
Aim: To investigate the antitumor activities of an anti-ErbB2 scFv-Fc-interleukin 2 (IL-2) fusion protein (HFI) in vitro and in vivo. Methods: Fusion protein HFI was constructed. The efficacy of HFI in mediating tumor cell lysis was determined by colorimetric lactate dehydrogenase release assays. The antitumor activity of HFI was evaluated in tumor xenograft models. Results: The fusion protein was folded as a homodimer formed by covalently linking Fc portions and it retained ErbB2 specificity and IL-2 biological activity. HFI mediated antibody-dependent cellmediated cytotoxicity (ADCC) at low effector-to-target ratios in vitro and improved the therapeutic efficacy of IL-2 in experiments in vivo. Conclusion: The genetically-engineered anti-ErbB2 scFv-Fc-IL-2 fusion protein exhibited high efficiency both in mediating ADCC in vitro and significant antitumor activity in tumor xenograft models.
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