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1.
Biochem Biophys Res Commun ; 626: 192-199, 2022 10 20.
Article in English | MEDLINE | ID: mdl-35994829

ABSTRACT

Extra Low-frequency Magnetic Fields (ELF-MFs) significantly enhance cellular uptake of methotrexate by inducing transient plasma membrane pores/damage. This enhanced 'dose loading' of methotrexate via the electromagnetically induced membrane pores leads to similar outcomes as the normal control while using significantly smaller therapeutic doses in vitro when compared to non-ELF-MF treated control. Approximately 10% of the typical therapeutic dose yielded similar results when used with ELF-MF. ELF-MFs increase PC12, THP-1 and HeLa proliferation in vitro (120% of the control). Analysis of adherent cells demonstrate significantly less migration towards an induced scratch injury (20 µm in 24 h when compared to a control). Our results suggest an important role for the use of ELF-MFs in the treatment of tumours that opens some new and exciting possibilities including using smaller therapeutic doses of chemotherapeutic agents and disrupting tumour metastasis.


Subject(s)
Methotrexate , Neoplasms , Cell Line , Cell Membrane , Electromagnetic Fields , Humans , Magnetic Fields , Methotrexate/pharmacology , Neoplasms/drug therapy
2.
J Extracell Vesicles ; 9(1): 1697124, 2020.
Article in English | MEDLINE | ID: mdl-32002165

ABSTRACT

This study sought to measure medium-sized extracellular vesicles (mEVs) in plasma, when patients have low Plasmodium falciparum early in infection. We aimed to define the relationship between plasma mEVs and: (i) parasitaemia, (ii) period from onset of malaria symptoms until seeking medical care (patient delay, PD), (iii) age and (iv) gender. In this cross-sectional study, n = 434 patients were analysed and Nanosight Tracking Analysis (NTA) used to quantify mEVs (vesicles of 150-500 nm diameter, isolated at 15,000 × g, ß-tubulin-positive and staining for annexin V, but weak or negative for CD81). Overall plasma mEV levels (1.69 × 1010 mEVs mL-1) were 2.3-fold higher than for uninfected controls (0.51 × 1010 mEVs mL-1). Divided into four age groups, we found a bimodal distribution with 2.5- and 2.1-fold higher mEVs in infected children (<11 years old [yo]) (median:2.11 × 1010 mEVs mL-1) and the elderly (>45 yo) (median:1.92 × 1010 mEVs mL-1), respectively, compared to uninfected controls; parasite density varied similarly with age groups. There was a positive association between mEVs and parasite density (r = 0.587, p < 0.0001) and mEVs were strongly associated with PD (r = 0.919, p < 0.0001), but gender had no effect on plasma mEV levels (p = 0.667). Parasite density was also exponentially related to patient delay. Gender (p = 0.667) had no effect on plasma mEV levels. During periods of low parasitaemia (PD = 72h), mEVs were 0.93-fold greater than in uninfected controls. As 75% (49/65) of patients had low parasitaemia levels (20-500 parasites µL-1), close to the detection limits of microscopy of Giemsa-stained thick blood films (5-150 parasites µL-1), mEV quantification by NTA could potentially have early diagnostic value, and raises the potential of Pf markers in mEVs as early diagnostic targets.

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