scholarly journals Cytotoxic Action of Artemisinin and Scopoletin on Planktonic Forms and on Biofilms of Candida Species

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 476 ◽  
Author(s):  
Sourav Das ◽  
Lilla Czuni ◽  
Viktória Báló ◽  
Gábor Papp ◽  
Zoltán Gazdag ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Candida Species ◽  
Underlying Mechanism ◽  
Candida Guilliermondii ◽  
Cytotoxic Action ◽  
Plant Metabolites ◽  
Minimum Effective Concentration ◽  
Drug Concentrations ◽  
Antifungal Action ◽  
Metabolic Activities

We investigated the antifungal activities of purified plant metabolites artemisinin (Ar) and scopoletin (Sc) including inhibition, effects on metabolic activities, viability, and oxidative stress on planktonic forms and on preformed biofilms of seven Candida species. The characteristic minimum inhibitory concentration (MIC90) of Ar and Sc against Candida species ranged from 21.83–142.1 µg/mL and 67.22–119.4 µg/mL, respectively. Drug concentrations causing ≈10% CFU decrease within 60 min of treatments were also determined (minimum effective concentration, MEC10) using 100-fold higher CFUs than in the case of MIC90 studies. Cytotoxic effects on planktonic and on mature biofilms of Candida species at MEC10 concentrations were further evaluated with fluorescent live/dead discrimination techniques. Candida glabrata, Candida guilliermondii, and Candida parapsilosis were the species most sensitive to Ar and Sc. Ar and Sc were also found to promote the accumulation of intracellular reactive oxygen species (ROS) by increasing oxidative stress at their respective MEC10 concentrations against the tested planktonic Candida species. Ar and Sc possess dose-dependent antifungal action but the underlying mechanism type (fungistatic and fungicidal) is not clear yet. Our data suggest that Ar and Sc found in herbal plants might have potential usage in the fight against Candida biofilms.

scholarly journals Glyoxalase I disruption and external carbonyl stress impair mitochondrial function in human induced pluripotent stem cells and derived neurons

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tomonori Hara ◽  
Manabu Toyoshima ◽  
Yasuko Hisano ◽  
Shabeesh Balan ◽  
Yoshimi Iwayama ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Caspase 3 ◽  
Intervention Strategy ◽  
Underlying Mechanism ◽  
Carbonyl Stress ◽  
Gene Encoding ◽  
Induced Pluripotent

AbstractCarbonyl stress, a specific form of oxidative stress, is reported to be involved in the pathophysiology of schizophrenia; however, little is known regarding the underlying mechanism. Here, we found that disruption of GLO1, the gene encoding a major catabolic enzyme scavenging the carbonyl group, increases vulnerability to external carbonyl stress, leading to abnormal phenotypes in human induced pluripotent stem cells (hiPSCs). The viability of GLO1 knockout (KO)-hiPSCs decreased and activity of caspase-3 was increased upon addition of methylglyoxal (MGO), a reactive carbonyl compound. In the GLO1 KO-hiPSC-derived neurons, MGO administration impaired neurite extension and cell migration. Further, accumulation of methylglyoxal-derived hydroimidazolone (MG-H1; a derivative of MGO)-modified proteins was detected in isolated mitochondria. Mitochondrial dysfunction, including diminished membrane potential and dampened respiratory function, was observed in the GLO1 KO-hiPSCs and derived neurons after addition of MGO and hence might be the mechanism underlying the effects of carbonyl stress. The susceptibility to MGO was partially rescued by the administration of pyridoxamine, a carbonyl scavenger. Our observations can be used for designing an intervention strategy for diseases, particularly those induced by enhanced carbonyl stress or oxidative stress.

scholarly journals NAC and Vitamin D Restore CNS Glutathione in Endotoxin-Sensitized Neonatal Hypoxic-Ischemic Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 489
Author(s):  
Lauren E. Adams ◽  
Hunter G. Moss ◽  
Danielle W. Lowe ◽  
Truman Brown ◽  
Donald B. Wiest ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Redox Status ◽  
Therapeutic Window ◽  
Post Injury ◽  
Artery Ligation ◽  
Cellular Redox ◽  
Carotid Artery Ligation ◽  
Drug Concentrations

Therapeutic hypothermia does not improve outcomes in neonatal hypoxia ischemia (HI) complicated by perinatal infection, due to well-described, pre-existing oxidative stress and neuroinflammation that shorten the therapeutic window. For effective neuroprotection post-injury, we must first define and then target CNS metabolomic changes immediately after endotoxin-sensitized HI (LPS-HI). We hypothesized that LPS-HI would acutely deplete reduced glutathione (GSH), indicating overwhelming oxidative stress in spite of hypothermia treatment in neonatal rats. Post-natal day 7 rats were randomized to sham ligation, or severe LPS-HI (0.5 mg/kg 4 h before right carotid artery ligation, 90 min 8% O2), followed by hypothermia alone or with N-acetylcysteine (25 mg/kg) and vitamin D (1,25(OH)2D3, 0.05 μg/kg) (NVD). We quantified in vivo CNS metabolites by serial 7T MR Spectroscopy before, immediately after LPS-HI, and after treatment, along with terminal plasma drug concentrations. GSH was significantly decreased in all LPS-HI rats compared with baseline and sham controls. Two hours of hypothermia alone did not improve GSH and allowed glutamate + glutamine (GLX) to increase. Within 1 h of administration, NVD increased GSH close to baseline and suppressed GLX. The combination of NVD with hypothermia rapidly improved cellular redox status after LPS-HI, potentially inhibiting important secondary injury cascades and allowing more time for hypothermic neuroprotection.

MiR-22-3p Suppresses Vascular Remodeling and Oxidative Stress by Targeting CHD9 during the Development of Hypertension

2021 ◽  
pp. 1-11
Author(s):  
Hanqing Chen ◽  
Xiru Xu ◽  
Zhengqing Liu ◽  
Yong Wu
Keyword(s):  
Oxidative Stress ◽  
Vascular Remodeling ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Spontaneously Hypertensive ◽  
Aortic Smooth Muscle ◽  
Phenotype Switch ◽  
And Oxidative Stress

Hypertension is considered a risk factor for a series of systematic diseases. Known factors including genetic predisposition, age, and diet habits are strongly associated with the initiation of hypertension. The current study aimed to investigate the role of miR-22-3p in hypertension. In this study, we discovered that the miR-22-3p level was significantly decreased in the thoracic aortic vascular tissues and aortic smooth muscle cells (ASMCs) of spontaneously hypertensive rats. Functionally, the overexpression of miR-22-3p facilitated the switch of ASMCs from the synthetic to contractile phenotype. To investigate the underlying mechanism, we predicted 11 potential target mRNAs for miR-22-3p. After screening, chromodomain helicase DNA-binding 9 (CHD9) was validated to bind with miR-22-3p. Rescue assays showed that the co-overexpression of miR-22-3p and CHD9 reversed the inhibitory effect of miR-22-3p mimics on cell proliferation, migration, and oxidative stress in ASMCs. Finally, miR-22-3p suppressed vascular remodeling and oxidative stress in vivo. Overall, miR-22-3p regulated ASMC phenotype switch by targeting CHD9. This new discovery provides a potential insight into hypertension treatment.

scholarly journals Protective role of ABCG2 against oxidative stress in colorectal cancer and its potential underlying mechanism

2018 ◽  
Author(s):  
Shuang Nie ◽  
Yaqing Huang ◽  
Mengyue Shi ◽  
Xuetian Qian ◽  
Hongzhen Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Underlying Mechanism ◽  
Protective Role

scholarly journals Neuronal-specific function of hTim8a in Complex IV assembly provides insight into the molecular mechanism underlying Mohr-Tranebjærg syndrome

2019 ◽  
Author(s):  
Yilin Kang ◽  
Alexander J. Anderson ◽  
David P. De Souza ◽  
Catherine S. Palmer ◽  
Kenji M. Fujihara ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disease ◽  
Neuronal Cells ◽  
Underlying Mechanism ◽  
Copper Chaperone ◽  
Intermembrane Space ◽  
Specific Function ◽  
Hydrophobic Membrane ◽  
Complex Iv ◽  
Enhanced Sensitivity

AbstractHuman Tim8a is a member of an intermembrane space chaperone network, known as the small TIM family, which transport hydrophobic membrane proteins through this compartment. Mutations in TIMM8A cause a neurodegenerative disease, Mohr-Tranebjærg syndrome (MTS), which is characterised by sensorineural hearing loss, dystonia and blindness. Nothing is known about the function of hTim8a in neuronal cells and consequently how lack of hTim8a leads to a neurodegenerative disease. We identified a novel cell-specific function of hTim8a in the assembly of Complex IV, which is mediated through a transient interaction with the copper chaperone COX17. Complex IV assembly defects in cells lacking hTim8a leads to oxidative stress and changes to key apoptotic regulators, including cytochrome c and Bax, which primes cells for cell death. Alleviation of oxidative stress using Vitamin E rescues cells from apoptotic vulnerability. We hypothesis that enhanced sensitivity of neuronal cells to apoptosis is the underlying mechanism of MTS.

scholarly journals Visualizing Cancer Cell Metabolic Dynamics Regulated With Aromatic Amino Acids Using DO-SRS and 2PEF Microscopy

2021 ◽  
Vol 8 ◽  
Author(s):  
Pegah Bagheri ◽  
Khang Hoang ◽  
Anthony A. Fung ◽  
Sahran Hussain ◽  
Lingyan Shi
Keyword(s):  
Oxidative Stress ◽  
Amino Acids ◽  
Protein Synthesis ◽  
Spatial Distribution ◽  
Lipid Droplets ◽  
De Novo ◽  
Culture Media ◽  
Aromatic Amino Acids ◽  
Unsaturated Lipids ◽  
Metabolic Activities

Oxidative imbalance plays an essential role in the progression of many diseases that include cancer and neurodegenerative diseases. Aromatic amino acids (AAA) such as phenylalanine and tryptophan have the capability of escalating oxidative stress because of their involvement in the production of Reactive Oxygen Species (ROS). Here, we use D2O (heavy water) probed stimulated Raman scattering microscopy (DO-SRS) and two Photon Excitation Fluorescence (2PEF) microscopy as a multimodal imaging approach to visualize metabolic changes in HeLa cells under excess AAA such as phenylalanine or trytophan in culture media. The cellular spatial distribution of de novo lipogenesis, new protein synthesis, NADH, Flavin, unsaturated lipids, and saturated lipids were all imaged and quantified in this experiment. Our studies reveal ∼10% increase in de novo lipogenesis and the ratio of NADH to flavin, and ∼50% increase of the ratio of unsaturated lipids to saturated lipid in cells treated with excess phenylalanine or trytophan. In contrast, these cells exhibited a decrease in the protein synthesis rate by ∼10% under these AAA treatments. The cellular metabolic activities of these biomolecules are indicators of elevated oxidative stress and mitochondrial dysfunction. Furthermore, 3D reconstruction images of lipid droplets were acquired and quantified to observe their spatial distribution around cells’ nuceli under different AAA culture media. We observed a higher number of lipid droplets in excess AAA conditions. Our study showcases that DO-SRS imaging can be used to quantitatively study how excess AAA regulates metabolic activities of cells with subcellular resolution in situ.

scholarly journals Antifungal susceptibility profiles of otomycosis etiological agents in Ahvaz, Iran

2020 ◽  
Author(s):  
Maral Gharaghani ◽  
Marzieh Halvaeezadeh ◽  
Gholam Ali Jalaee ◽  
Simin Taghipour ◽  
Neda Kiasat ◽  
...  
Keyword(s):  
Aspergillus Niger ◽  
Candida Species ◽  
Geometric Mean ◽  
Antifungal Susceptibility ◽  
Morphological Characteristics ◽  
Aspergillus Species ◽  
Great Activity ◽  
Minimum Effective Concentration ◽  
Microdilution Method ◽  
Physiological Tests

Background and Purpose: Otomycosis is a secondary ear fungal infection among predisposed individuals in humid conditions. Aspergillus species are the most common etiologic agents of this infection. Several ototopical antifungals are currently used for the treatment of this disease; however, recurrence and treatment failure are usually observed in some cases. Regarding this, the present study was conducted to investigate the antifungal activity of caspofungin, azoles, and terbinafine against the isolated agents of otomycosis. Materials and Methods: This study was conducted on the specimens collected from 90 patients with otomycosis. The samples were cultured on Sabouraud dextrose agar and identified based on morphological characteristics, physiological tests, and microscopic features. Furthermore, the microdilution method was used for antifungal susceptibility testing according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Finally, the minimum inhibitory concentration (MIC) and minimum effective concentration (MEC) ranges, MIC/MEC50, MIC/MEC90, and geometric mean (GM) MIC/MEC were calculated for the isolates. Results: According to the results, 77 patients with otomycosis were positive for different Aspergillus (88.3%) and Candida (11.7%) species. Aspergillus niger complex (n=36) was found to be the most common agent, followed by A. flavus, A. terreus, and A. nidulans complexes. Furthermore, epidemiological cutoff values (ECVs) were lower than those presented by the CLSI for itraconazole and caspofungin in 98.5% and 42.6% of Aspergillus species, respectively. Terbinafine exhibited a great activity against Aspergillus species, while fluconazole revealed a low activity against both Aspergillus species. Based on the results, 77.8% of Candida species were resistant to caspofungin; however, miconazole and econazole had low MIC ranges. Conclusion: Aspergillus niger and A. flavus complexes were identified as the most common agents accounting for 85.7% of the isolates. In addition, terbinafine was identified as the best antifungal for both Aspergillus and Candida species. Moreover, tested azoles had relatively low MICs, whereas most of the isolates had the MIC values beyond the caspofungin ECVs.

The Oxidative Stress Pathway May be an Important Pathway Leading to The Recurrence of Ewing Sarcoma —— Based On Weighted Gene Co-Expression Network Analysis

2020 ◽  
Author(s):  
Jianfeng Li ◽  
Shaoyu Hu ◽  
Song Hao ◽  
Shengjia Huang ◽  
Yi Qin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Network Analysis ◽  
Ewing Sarcoma ◽  
Underlying Mechanism ◽  
Data Sets ◽  
Oxidative Stress Pathway ◽  
Important Pathway ◽  
First Time ◽  
Stress Pathway

Abstract Background The role of gene and pathway in recurrence of Ewing sarcoma (ES) was not clear. Thus, we investigated the biological role and underlying mechanism of gene and pathway in recurrence of ES. Methods Data sets of patients with ES were collected from the GEO database. We used dataset GSE63155 and GSE63156 to construct co-expression networks by weighted gene co-expression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by Database for Annotation, Visualization and Integrated Discovery (DAVID). Results We can find that genes with significant interactions in the genes of the recurrence group include SRSF11, TRIM39, SOCS3,NUPL2,COPS5. They work primarily through the oxidative stress pathway. Conclusion Through our research, for the first time found that ES by SRSF11 TRIM39, SOCS3, NUPL2, COPS5 interaction, activation of phosphorylation of bone and oxidative stress is affecting tumor recurrence.

scholarly journals Circulating uromodulin inhibits systemic oxidative stress by inactivating the TRPM2 channel

2019 ◽  
Vol 11 (512) ◽  
pp. eaaw3639 ◽  
Author(s):  
Kaice A. LaFavers ◽  
Etienne Macedo ◽  
Pranav S. Garimella ◽  
Camila Lima ◽  
Shehnaz Khan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transient Receptor Potential ◽  
Kidney Injury ◽  
Receptor Potential ◽  
Underlying Mechanism ◽  
High Serum ◽  
Systemic Oxidative Stress ◽  
Trpm2 Channel ◽  
Poor Outcomes

High serum concentrations of kidney-derived protein uromodulin [Tamm-Horsfall protein (THP)] have recently been shown to be independently associated with low mortality in both older adults and cardiac patients, but the underlying mechanism remains unclear. Here, we show that THP inhibits the generation of reactive oxygen species (ROS) both in the kidney and systemically. Consistent with this experimental data, the concentration of circulating THP in patients with surgery-induced acute kidney injury (AKI) correlated with systemic oxidative damage. THP in the serum dropped after AKI and was associated with an increase in systemic ROS. The increase in oxidant injury correlated with postsurgical mortality and need for dialysis. Mechanistically, THP inhibited the activation of the transient receptor potential cation channel, subfamily M, member 2 (TRPM2) channel. Furthermore, inhibition of TRPM2 in vivo in a mouse model mitigated the systemic increase in ROS during AKI and THP deficiency. Our results suggest that THP is a key regulator of systemic oxidative stress by suppressing TRPM2 activity, and our findings might help explain how circulating THP deficiency is linked with poor outcomes and increased mortality.

scholarly journals Plant-Derived Substances in the Fight Against Infections Caused by Candida Species

2020 ◽  
Vol 21 (17) ◽  
pp. 6131
Author(s):  
Ibeth Guevara-Lora ◽  
Grazyna Bras ◽  
Justyna Karkowska-Kuleta ◽  
Miriam González-González ◽  
Kinga Ceballos ◽  
...  
Keyword(s):  
Candida Species ◽  
Biofilm Formation ◽  
Defense Mechanisms ◽  
Antifungal Agents ◽  
Standard Treatment ◽  
Antifungal Drugs ◽  
Host Immune System ◽  
Plant Metabolites ◽  
Fungal Cell ◽  
Mucosal Surfaces

Yeast-like fungi from the Candida genus are predominantly harmless commensals that colonize human skin and mucosal surfaces, but under conditions of impaired host immune system change into dangerous pathogens. The pathogenicity of these fungi is typically accompanied by increased adhesion and formation of complex biofilms, making candidal infections challenging to treat. Although a variety of antifungal drugs have been developed that preferably attack the fungal cell wall and plasma membrane, these pathogens have acquired novel defense mechanisms that make them resistant to standard treatment. This causes an increase in the incidence of candidiasis and enforces the urgent need for an intensified search for new specifics that could be helpful, alone or synergistically with traditional drugs, for controlling Candida pathogenicity. Currently, numerous reports have indicated the effectiveness of plant metabolites as potent antifungal agents. These substances have been shown to inhibit growth and to alter the virulence of different Candida species in both the planktonic and hyphal form and during the biofilm formation. This review focuses on the most recent findings that provide evidence of decreasing candidal pathogenicity by different substances of plant origin, with a special emphasis on the mechanisms of their action. This is a particularly important issue in the light of the currently increasing frequency of emerging Candida strains and species resistant to standard antifungal treatment.

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