Inhibition of NADP(H) supply by highly active phosphatase-like ceria nanozymes to boost oxidative stress and ferroptosis

Metal complexes of malonie acid (metal = Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Ag(I)) were prepared and only the Ag(I) complex inhibited the growth of Candida albicans. Malonate complexes incorporating the chelating 1,10-phenanthroline (1,10-phen) ligand showed a range of activities: good (Mn(II), Cu(II), Ag(I)); moderate (Zn(II)); poor (Co(II), Ni(II)). Metal-free 1,10-phen and Ag(CH3CO2) were also highly active. The metal-free non-chelating ligands 1,7- phenanthroline and 4,7-phenanthroline were inactive and the Cu(II), Mn(II) and Zn(II) complexs of 1,7-phen displayed only marginal activity. Whereas the Cu(II) malonate/1,10-phen complex induces significant cellular oxidative stress the Zn(II) analogue does not.

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Catalytically active gold clusters with atomic precision for noninvasive early intervention of neurotrauma

Journal of Nanobiotechnology ◽

10.1186/s12951-021-01071-4 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Yunguang Zhang ◽

Si Sun ◽

Haile Liu ◽

Qinjuan Ren ◽

Wenting Hao ◽

...

Keyword(s):

Oxidative Stress ◽

Early Intervention ◽

Public Health Problem ◽

Gold Clusters ◽

Brain Trauma ◽

Noninvasive Treatment ◽

Highly Active ◽

Secondary Damage

Abstract Background Neurotrauma is a worldwide public health problem which can be divided into primary and secondary damge. The primary damge is caused by external forces and triggers the overproduction of peroxides and superoxides, leading to long-lasting secondary damage including oxidative stress, wound infection and immunological reactions. The emerging catalysts have shown great potential in the treatment of brain injury and neurogenic inflammation, but are limited to biosafety issues and delivery efficiency. Results Herein, we proposed the noninvasive delivery route to brain trauma by employing highly active gold clusters with enzyme-like activity to achieve the early intervention. The decomposition rate to H2O2 of the ultrasmall gold clusters is 10 times that of glassy carbon (GC) electrodes, indicating excellent catalytic activity. The gold clusters can relieve the oxidative stress and decrease the excessive O2·− and H2O2 both in vitro and in vivo. Besides, gold clusters can accelerate the wound healing of brain trauma and alleviate inflammation via inhibiting the activation of astrocytes and microglia through noninvasive adminstration. decrease the peroxide and superoxide of brain tissue. Conclusions Present work shows noninvasive treatment is a promising route for early intervention of brain trauma.

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In Vitro Molecular Biology Studies of Spirooxindole Heterocyclic Hybrids

Processes ◽

10.3390/pr8111473 ◽

2020 ◽

Vol 8 (11) ◽

pp. 1473

Author(s):

Dhaifallah M. Al-thamili ◽

Abdulrahman I. Almansour ◽

Natarajan Arumugam ◽

Faruq Mohammad ◽

Raju Suresh Kumar

Keyword(s):

Oxidative Stress ◽

Molecular Biology ◽

Cell Viability ◽

Cancer Cells ◽

Present Report ◽

Cell Loss ◽

Apoptotic Pathway ◽

Highly Active ◽

Time Periods

In the present report, we provide the results of the molecular biology studies of spiroheterocyclic hybrids, where the derivatives are found to possess potential anticancer activity towards cancer cells. A series of spiroxindole–pyrrolidine heterocyclic hybrids were evaluated for cell viability and proliferation against HepG2 cancer cells at concentrations in the range of 12.5–200 µg/mL over two different time periods of 24 and 48 h. In addition, the highly active compounds were also verified for their behavior towards noncancer cells (L929 cells), and it was found that the tested derivatives were not aggressive due to the observation of only limited cell loss, as compared to the cancer cells. Further analysis of the observed toxicity mechanism showed the apoptotic pathway was mediated by oxidative stress, with the involvement of caspases.

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Neuronal NADPH oxidase in Parkinson disease pathogenesis

10.1101/2021.05.13.443999 ◽

2021 ◽

Author(s):

Matthew T Keeney ◽

Eric K Hoffman ◽

Kyle Farmer ◽

Christopher R Bodle ◽

Marco Fazzari ◽

...

Keyword(s):

Oxidative Stress ◽

Nadph Oxidase ◽

Parkinson Disease ◽

Alpha Synuclein ◽

Dopamine Neurons ◽

Proximity Ligation Assay ◽

Post Translational Modification ◽

Highly Active ◽

Downstream Effects

Mitochondrial dysfunction and oxidative stress are strongly implicated in the pathogenesis of Parkinson disease (PD) and there is evidence that mitochondrially-generated superoxide can activate NADPH oxidase 2 (NOX2), which is a major enzymatic generator of superoxide. Although NOX2 has been examined in the context of PD, previous studies have focused on microglial function; the role of neuronal NOX2 in PD pathogenesis remains to be defined. Here we devised and validated a proximity ligation assay for NOX2 activity and demonstrated that in human PD and 2 models thereof, neuronal NOX2 is highly active in substantia nigra dopamine neurons. Further, NOX2 activity is responsible for accumulation, post-translational modification and oligomerization of alpha-synuclein as well as activation of leucine-rich repeat kinase 2 (LRRK2). Administration of a brain-penetrant, specific NOX2 inhibitor prevented NOX2 activation and its downstream effects in vivo in a rat model of PD. We conclude that neuronal NOX2 is a major contributor to oxidative stress in PD, to alpha-synuclein pathology and to LRRK2 activation in idiopathic PD. In this context, NOX2 inhibitors hold potential as a disease-modifying therapy in PD.

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Investigation of the levels of oxidative stress parameters in HIV and HIV-TB co-infected patients

The Journal of Infection in Developing Countries ◽

10.3855/jidc.1906 ◽

2011 ◽

Vol 6 (01) ◽

pp. 79-85 ◽

Cited By ~ 17

Author(s):

Olufunsho Awodele ◽

Sunday O Olayemi ◽

Joseph A Nwite ◽

Titilope A Adeyemo

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

University Teaching ◽

Haematological Parameters ◽

Normal Male ◽

Hiv Patients ◽

Staff Members ◽

Highly Active ◽

High Level ◽

Immunodeficiency Syndrome

Introduction: Among opportunistic pathogens associated with acquired immunodeficiency syndrome (AIDS), Mycobacterium tuberculosis is distinguished by its relative virulence and potential for person-to-person transmission. Oxidative stress is associated with TB infection with a high level in patients with HIV-TB co-infection. However, the comparative level of oxidative stress in HIV patients on highly active anti-retroviral therapy (HAART) and naïve (untreated) HIV patients is not clear.Methodology: This study is aimed to determine the level of oxidative stress and haematological parameters in HIV patients (naïve), HIV patients undergoing HAART, and HIV-TB co-infected patients. In total, 100 consenting subjects were recruited from the AIDS Prevention Iniative in Nigeria (APIN) Clinic. For controls, normal male healthy volunteers were recruited from the blood donor clinic and females from the APIN clinic staff members, both of the Lagos University Teaching Hospital. Measurements of antioxidant enzyme activity and lipid peroxidation were performed according to standard procedures. Haematological parameters were determined using a fully automated hematology analyzer.Results: Red blood cells significantly decreased (P ≤ 0.001) in all patients when compared with control subjects. The lipid peroxidation (MDA) was significantly high (P ≤ 0.05) in naive patients when compared to HIV patients on HAART. The decrease in the levels of GSH in both naive and HIV-TB co-infected patients (P≤0.001) and HIV patients on HAART (P < 0.05) were significant when compared to control patients.Conclusion: There is lower antioxidant level and higher MDA in naive and HIV-TB co-infected patients as compared to HIV patients on HAART and the seronegative patients.

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Ginsenoside Rb1 Blocks Ritonavir-Induced Oxidative Stress and eNOS Downregulation through Activation of Estrogen Receptor-Beta and Upregulation of SOD in Human Endothelial Cells

International Journal of Molecular Sciences ◽

10.3390/ijms20020294 ◽

2019 ◽

Vol 20 (2) ◽

pp. 294 ◽

Cited By ~ 6

Author(s):

Jian-Ming Lü ◽

Jun Jiang ◽

Md Jamaluddin ◽

Zhengdong Liang ◽

Qizhi Yao ◽

...

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Estrogen Receptor Beta ◽

Luciferase Reporter ◽

Oxygen Species ◽

Ginsenoside Rb1 ◽

Human Endothelial Cells ◽

Highly Active ◽

Low Levels ◽

Receptor Beta

We have previously shown that ritonavir (RTV), a highly active anti-retroviral therapy (HAART) drug, can cause endothelial dysfunction through oxidative stress. Several antioxidants including ginsenoside Rb1, a compound with antioxidant effect, can effectively block this side effect of RTV in endothelial cells. In the current study, we explored a mechanism by which ginsenoside Rb1 could protect these cells via binding of estrogen receptors (ERs). We found that several human endothelial cell lines differentially expressed ER-β and had very low levels of ER-α. RTV treatment significantly increased the production of reactive oxygen species (ROS) and decreased the expression of endothelial nitric oxidase synthase (eNOS) and superoxide dismutase (SOD) in HUVECs, while Rb1 effectively blocked these effects of RTV. These effects of Rb1 were effectively inhibited by silencing ER-β, indicating that ginsenoside Rb1 requires ER-β for its antioxidant activity in inhibiting the deleterious effect of RTV in human endothelial cells. Furthermore, Rb1 specifically activated ER-β transactivation activity by ER-β luciferase reporter assay. Rb1 competitively bound to ER-β, which was determined by the high sensitive fluorescent polarization assay.

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Transcriptional profile of postmortem skeletal muscle

Physiological Genomics ◽

10.1152/physiolgenomics.00137.2003 ◽

2004 ◽

Vol 16 (2) ◽

pp. 222-228 ◽

Cited By ~ 31

Author(s):

Despina Sanoudou ◽

Peter B. Kang ◽

Judith N. Haslett ◽

Mei Han ◽

Louis M. Kunkel ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Skeletal Muscle ◽

Protein Biosynthesis ◽

Major Gene ◽

Postmortem Changes ◽

Highly Active ◽

Biological Studies ◽

Autopsy Specimens ◽

Almost All

Autopsy specimens are often used in molecular biological studies of disease pathophysiology. However, few analyses have focused specifically on postmortem changes in skeletal muscles, and almost all of those investigate protein or metabolic changes. Although some structural and enzymatic changes have been described, the sequence of transcriptional events associated with these remains unclear. We analyzed a series of new and preexisting human skeletal muscle data sets on ≃12,500 genes and expressed sequence tags (ESTs) generated by the Affymetrix U95Av2 GeneChips from seven autopsy and seven surgical specimens. Remarkably, postmortem specimens (up to 46 h) revealed a significant and prominent upregulation of transcripts involved with protein biosynthesis. Additional upregulated transcripts are associated with cellular responses to oxidative stress, hypoxia, and ischemia; however, only a subset of genes in these pathways was affected. Overexpression was also seen for apoptosis-related, cell cycle regulation/arrest-related, and signal transduction-related genes. No major gene expression differences were seen between autopsy specimens with <20-h and 34- to 46-h postmortem intervals or between pediatric and adult cases. These data demonstrate that, likely in response to hypoxia and oxidative stress, skeletal muscle undergoes a highly active transcriptional, and possibly, translational phase during the initial 46-h postmortem interval. Knowledge of these changes is important for proper interpretation of gene expression studies utilizing autopsy specimens.

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Cardioprotective Effects of Nanoemulsions Loaded with Anti-Inflammatory Nutraceuticals against Doxorubicin-Induced Cardiotoxicity

Nutrients ◽

10.3390/nu10091304 ◽

2018 ◽

Vol 10 (9) ◽

pp. 1304 ◽

Cited By ~ 21

Author(s):

Vincenzo Quagliariello ◽

Raffaele Vecchione ◽

Carmela Coppola ◽

Chiara Di Cicco ◽

Alberta De Capua ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Cell Viability ◽

Antineoplastic Agent ◽

H9c2 Cells ◽

Necrosis Factor Alpha ◽

Highly Active ◽

Tnf Α ◽

Anti Inflammatory ◽

High Pressure Homogenizer

Doxorubicin is a highly active antineoplastic agent, but its clinical use is limited because of its cardiotoxicity. Although nutraceuticals endowed with anti-inflammatory properties exert cardioprotective activity, their bioavailability and stability are inconsistent. In an attempt to address this issue, we evaluated whether bioavailable nanoemulsions loaded with nutraceuticals (curcumin and fresh and dry tomato extracts rich in lycopene) protect cardiomyoblasts (H9C2 cells) from doxorubicin-induced toxicity. Nanoemulsions were produced with a high-pressure homogenizer. H9C2 cells were incubated with nanoemulsions loaded with different nutraceuticals alone or in combination with doxorubicin. Cell viability was evaluated with a modified MTT method. The levels of the lipid peroxidation products malondialdehyde (MDA) and 4-hydroxy-2-butanone (4-HNA), and of the cardiotoxic-related interleukins IL-6, IL-8, IL-1β and IL-10, tumor necrosis factor-alpha (TNF-α), and nitric oxide were analyzed in cardiomyoblasts. The hydrodynamic size of nanoemulsions was around 100 nm. Cell viability enhancement was 35–40% higher in cardiomyoblasts treated with nanoemulsion + doxorubicin than in cardiomyoblasts treated with doxorubicin alone. Nanoemulsions also protected against oxidative stress as witnessed by a reduction of MDA and 4-HNA. Notably, nanoemulsions inhibited the release of IL-6, IL-8, IL-1β, TNF-α and nitric oxide by around 35–40% and increased IL-10 production by 25–27% versus cells not treated with emulsions. Of the nutraceuticals evaluated, lycopene-rich nanoemulsions had the best cardioprotective profile. In conclusion, nanoemulsions loaded with the nutraceuticals described herein protect against cardiotoxicity, by reducing inflammation and lipid oxidative stress. These results set the stage for studies in preclinical models.

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