AimAmong therapeutic proposals for amyloid-associated disorders, special attention has been given to the exploitation of nanoparticles (NPs) as promising agents against aggregation.MethodsIn this paper, the inhibitory effect of cerium oxide (CeO2) NPs against α-synuclein (α-syn) amyloid formation was explored by different methods such as Thioflavin T (ThT) and 8-anilinonaphthalene-1-sulfonic acid (ANS) fluorescence spectroscopy, Congo red adsorption assay, circular dichroism (CD) spectroscopy, transmission electron microscopy (TEM), and bioinformatical approaches. Also, the cytotoxicity of α-syn amyloid either alone or with CeO2 NPs against neuron-like cells (SH-SY5Y) was examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and quantitative real-time polymerase chain reaction (Bax and Bcl-2 gene expression) assays.ResultsThT and ANS fluorescence assays indicated that CeO2 NPs inhibit the formation of aggregated species and hydrophobic patches of α-syn in amyloidogenic conditions, respectively. Congo red and CD assays demonstrated that CeO2 NPs reduce the formation of amyloid species and β-sheets structures of α-syn molecules, respectively. TEM investigation also confirmed that CeO2 NPs limited the formation of well-defined fibrillary structures of α-syn molecules. Molecular docking and dynamic studies revealed that CeO2 NPs could bind with different affinities to α-syn monomer and amyloid species and fibrillar structure of α-syn is disaggregated in the presence of CeO2 NPs. Moreover, cellular assays depicted that CeO2 NPs mitigate the cell mortality, apoptosis, and the ratio of Bax/Bcl-2 gene expression associated with α-syn amyloids.ConclusionIt may be concluded that CeO2 NPs can be used as therapeutic agents to reduce the aggregation of proteins and mitigate the occurrence of neurodegenerative diseases.
Background and Purpose: The pandemic of COVID-19 has caused a worldwide health crisis. Candidemia is a potentially lethal condition that has not yet been enough discussed in patients with COVID‐ 19. The current study aimed to investigate the prevalence of candidemia among Iranian COVID‐ 19 patients and characterize its causative agents and the antifungal susceptibility pattern.
Materials and Methods: The present cross-sectional survey was carried out from March 2020 to March 2021 at Imam Khomeini Hospital, Tehran, Iran. Blood specimens were obtained from patients with confirmed coronavirus infection who also had criteria for candidemia and were examined for any Candida species by conventional and molecular techniques. Susceptibility of isolates to amphotericin B, voriconazole, itraconazole, fluconazole, caspofungin, and 5-flucytosine was tested using the CLSI broth dilution technique.
Results: In total, 153 patients with COVID-19 were included and candidemia was confirmed in 12 (7.8 %) of them. The majority of patients were ≥ 50 years of age (n=9) and female (n=8). Moreover, 6 out of the 12 patients were diabetic. The presence of central venous catheters, broad-spectrum antibiotic therapy, ICU admission, andmechanical ventilation was observed in all patients. The C. albicans (n=7, 58.3 %) and C. dubliniensis (n=2, 16.7%) were the most common isolated species. Amphotericin B and 5-flucytosine were the most active drugs. Despite antifungal treatment, 4 out of 12 patients (33.3 %) died.
Conclusion: Due to the high mortality, the early diagnosis and proper treatment of candidemia are essential requirements for optimal clinical outcomes in COVID-19 patients.
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