Polymyxin B accelerates the α-synuclein aggregation

Mohapatra, Anshuman; Bohara, Vijay Singh; Kumar, Sachin; Chaudhary, Nitin

doi:10.1016/j.bpc.2021.106628

Cited by 6 publications

(2 citation statements)

References 39 publications

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“…During the treatment period, the number of nephrotoxicity cases in the observation group was 3 cases (6.82%), which was not significantly different from 4 cases (10.00%) in the control group. Many previous studies have reported [ 16 , 17 ] that nephrotoxicity is the most common adverse reaction in the clinical application of polymyxin B. Combined with the conclusions of this study, some differences may be related to the relatively small number of samples included in this study.…”

Section: Discussionmentioning

confidence: 68%

Effects of Aerosol Inhalation Combined with Intravenous Drip of Polymyxin B on Bacterial Clearance, Symptoms Improvement, and Serum Infection Indexes in Patients with Pneumonia Induced by Multidrug-Resistant Gram-Negative Bacteria

Lin

Liu

Sun

2022

Emergency Medicine International

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In recent years, the incidence of pneumonia caused by multidrug-resistant (MDR) Gram-negative bacteria (G−) has increased year by year. Polymyxin B has a good clinical effect in the treatment of MDR, but there is controversy about the administration route of this drug. In this study, we retrospectively analyzed the clinical data of 84 cases of MDR Gram-negative bacterial pneumonia, and aimed to explore the effects of aerosol inhalation combined with intravenous polymyxin B infusion on the bacterial clearance, symptom improvement, and serum infection indexes of MDR patients on the patients with Gram-negative (G−) bacterial pneumonia. The results show that aerosol inhalation combined with intravenous drip of polymyxin B can improve bacterial clearance rate, reduce levels of serum inflammatory factors, and improve clinical symptoms in patients with pneumonia induced by MDR G-bacteria.

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Section: Discussionmentioning

confidence: 68%

Effects of Aerosol Inhalation Combined with Intravenous Drip of Polymyxin B on Bacterial Clearance, Symptoms Improvement, and Serum Infection Indexes in Patients with Pneumonia Induced by Multidrug-Resistant Gram-Negative Bacteria

Lin

Liu

Sun

2022

Emergency Medicine International

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“…The sonicated sample was boiled at 95 °C. The insoluble white precipitate was then pelleted at 20,000 g for 1 h. The clear supernatant was passed through a 0.45 μm filter before further purifying using chromatographic methods as described elsewhere (33).…”

Section: Methodsmentioning

confidence: 99%

Alpha-synuclein expression in neuron modulates the Japanese encephalitis virus infection

Gupta,

Mohapatra,

Kaur

et al. 2023

Preprint

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Japanese encephalitis virus (JEV) stands as a prominent vector-borne zoonotic pathogen, displaying neurotropism and eliciting Parkinson’s disease (PD)-like symptoms among most symptomatic survivors. A characteristic feature of PD is aggregation of mutated α-synuclein (α-syn) that damages the dopaminergic neurons. Considering this link between JEV-induced PD-like symptoms and α-syn pathogenesis, we explored the role of α-syn in JEV infectivity in neuronal cells. Our investigation revealed significant increase in endogenous α-syn expression in JEV-infected cells. Additionally, treatment with exogenous α-syn (Exoα-syn) led to a substantial reduction in JEV replication, suggesting its anti-JEV effect. Furthermore, Exoα-syn treatment led to the upregulation of superoxide dismutase 1 (SOD1) and reduction in reactive oxygen species (ROS). The results were validated by endogenous α-syn-silencing, that decreased SOD1 level and raised ROS level in neuronal cells. Similarly, the SOD1 inhibition via LCS-1 also intensified ROS and JEV infection. Overall, our results suggest that α-syn exerts an anti-JEV effect by regulating protein involved in oxidative stress inside neuronal cells. This study contributes valuable insights into the interplay between α-syn expression and JEV infectivity, shedding light on avenues to further investigate the potential role of α-syn in JEV pathogenesis.ImportanceJapanese encephalitis virus (JEV) poses significant threat particularly to children. Despite extensive research efforts, the development of effective treatments against JEV has been impeded. One of the major setbacks is a lack of comprehensive understanding of neurotropism. The study focuses on alpha synuclein (α-syn), a neuronal protein, and aims to determine its role in JEV pathogenesis. Present study reveals that host cell upregulates α-syn in response of JEV infection. α-syn restrains JEV propagation by modulating superoxide dismutase 1 (SOD1) expression which further blocks JEV-induced ROS generation. Endogenous α-syn silencing led to decrease in SOD1 expression and increased viral titer. α-syn plays crucial role in counteracting oxidative stress through SOD1, which is essential for limiting JEV replication. This study provides broader implications for antiviral strategies and its possible role in neurodegenerative diseases; however, there is still much to explore, particularly regarding its aggregation kinetics in JEV infection.

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