Isoflurophate

Parkinson’s disease (PD), the second most common neurodegenerative illness, is thought to have impacted 9.4 million people globally in 2020. The causation framework for Parkinson’s disease is a combination of genetics, age, and environment. Iron chelators have been studied as potential treatment agents for Parkinson’s disease (PD) because they can reduce oxidative stress and iron accumulation. Deferiprone (DFP) is one such drug.

To systematically review and analyze available clinical studies assessing the efficacy and safety of deferiprone in patients with Parkinson’s disease, with particular focus on motor outcomes, iron accumulation, and adverse effects.

A comprehensive search was conducted in PubMed, Scopus, clinicaltrials.gov.in, and Web of Science databases, and a total of 3 studies were included and reviewed. The studies’ baseline data included the first author’s name, the year of the study, the place of the study, the number of subjects and controls, the mean age, gender, dosage, and route of DFP, the Estimated years of Disease (EYO), the MDS-UPDRS score, the PDQ-39 score, the MOCA score, the MMSE score, MRI T2 changes, and serum ferritin levels. Data regarding adverse effects and deaths were also extracted. A pooled analysis of the collected data was performed using R Studio.

The MDS-UPDRS score increased less in the test group’s patients than in the placebo group (SMD=−0.69, 95% CI=−5.64 to 4.25, P =<0.00001, I 2 =98%). However, there was no significant difference between the 2 groups in the serum ferritin levels and the MRI T2 changes in caudate, nigra, pallidum, and putamen.

Deferiprone shows potential in slowing motor symptom progression in Parkinson’s disease, although its impact on brain iron levels remains inconclusive. Further large-scale, long-term studies are warranted to establish its clinical efficacy and safety.

This article investigated the effect and mechanism of artesunate(ART) on ferroptosis in triple-negative breast cancer. Triple-negative breast cancer MDA-MB-231 cells and MDA-MB-468 cells were cultured in vitro. The effect of ART at different concentrations on the viability of MDA-MB-231 cells and MDA-MB-468 cells was detected by cell counting kit-8(CCK-8), and the appropriate treatment concentration of ART was screened out. The cells were randomly separated into a control group and groups of ART, ART + ferroptosis inhibitor Ferrostatin-1(Fer-1), ART + ferroptosis inhibitor deferiprone(DFP), and ART + Wnt/β-catenin agonist(SKL2001). The CCK-8 method was used to detect cell viability. Commercial kits were used to detect the release of lactate dehydrogenase(LDH) and the level of glutathione(GSH), superoxide dismutase(SOD), and malondialdehyde(MDA). Immunofluorescence was used to measure the level of reactive oxygen species(ROS) and intracellular Fe~(2+) and the protein expression level of glutathione peroxidase 4(GPX4) and β-catenin. Western blot was used to detect the protein expression of transferrin receptor 1(TFR1), divalent metal transporter 1(DMT1), light polypeptide(FTL), acyl-CoA synthetase long-chain family member 4(ACSL4), solute carrier family 7 member 11(SLC7A11), GPX4, β-catenin, and phosphorylated glycogen synthase kinase 3β(p-GSK-3β). The results showed that the survival rate of MDA-MB-231 cells and MDA-MB-468 cells decreased with increasing ART concentration. Compared with those of the control group, the LDH release rate and the levels of ROS, intracellular Fe~(2+), and MDA were significantly elevated(P<0.01), and the TFR1, DMT1, and ACSL4 protein expressions were significantly increased(P<0.01) in the ART group. The GSH and SOD levels were significantly reduced(P<0.01), and the FTL, SLC7A11, GPX4, β-catenin, and p-GSK-3β protein expressions were significantly decreased(P<0.05 or P<0.01) in the ART group. Compared with those of the ART group, the LDH release rate and the levels of ROS, intracellular Fe~(2+), and MDA were significantly decreased(P<0.05 or P<0.01), and the TFR1, DMT1, and ACSL4 protein expressions were significantly reduced(P<0.01) in the ART + Fer-1 group and the ART + DFP group. The GSH and SOD levels were significantly increased(P<0.05 or P<0.01), and the FTL, SLC7A11, and GPX4 protein expressions were significantly elevated(P<0.05 or P<0.01) in the ART + Fer-1 group and the ART + DFP group. After using SKL2001, the inhibitory effect of ART on the Wnt/β-catenin pathway was weakened. To sum up, ART inhibits the proliferation of triple-negative breast cancer cells by inducing ferroptosis, and its mechanism may be related to the regulation of the Wnt/β-catenin signaling pathway.