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Molecular Research on Oxidative Stress and Health

A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 9251

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Guest Editor
Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK
Interests: oxidative stress; reactive oxygen species (ROS); free radicals; inflammation; microcirculation; blood–brain barrier
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Oxidative stress is defined as an imbalance between the production of reactive oxygen species (ROS) and antioxidant defenses, ultimately leading to excessive accumulation of ROS. Radiation exposure, obesity, smoking, pollution, alcohol consumption, and high-fat diets are all factors that contribute to oxidative stress, mainly altering the physiological antioxidant defense system. This excessive accumulation of ROS has been identified as a causative factor in different pathological conditions, such as neurodegenerative diseases, cancer, atherosclerosis, diabetes, infertility and fibrosis. At the molecular level, potential mechanisms leading to oxidative-induced cellular dysfunction include mitochondrial damage, autophagy, mitophagy, endoplasmic reticulum stress, and apoptosis, but there is little information about their interactions and what they experience in metabolic diseases. There is still a lot to learn about the changes. Given the relevance of this topic, we welcome several research articles or reviews on the role of oxidative stress and the underlying molecular mechanisms.

Dr. Mosharraf Sarker
Guest Editor

Manuscript Submission Information

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Keywords

  • oxidative stress
  • gene regulation
  • antioxidants
  • mitochondrial dysfunction
  • insulin resistance
  • inflammation
  • autophagy

Published Papers (6 papers)

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Research

14 pages, 4506 KiB  
Article
Plastoquinone-Derivative SkQ1 Improved the Biliary Intraepithelial Neoplasia during Liver Fluke Infection
by Oxana Zaparina, Anna Kovner, Viktoria Petrova, Nataliya Kolosova, Viatcheslav Mordvinov and Maria Pakharukova
Curr. Issues Mol. Biol. 2024, 46(2), 1593-1606; https://doi.org/10.3390/cimb46020103 - 17 Feb 2024
Viewed by 563
Abstract
Carcinogenic food-borne liver fluke infections are a serious epidemiological threat worldwide. The major complications of Opisthorchis felineus infection are chronic inflammation and biliary intraepithelial neoplasia. Although evidence has accumulated that increased reactive oxygen species production is observed in liver fluke infection, a direct [...] Read more.
Carcinogenic food-borne liver fluke infections are a serious epidemiological threat worldwide. The major complications of Opisthorchis felineus infection are chronic inflammation and biliary intraepithelial neoplasia. Although evidence has accumulated that increased reactive oxygen species production is observed in liver fluke infection, a direct relationship between the oxidative stress and biliary intraepithelial neoplasia has not been shown. Quinones and SkQ1, a derivative of plastoquinone, have been demonstrated to be cytoprotective in numerous liver injuries due to their potent antioxidant properties. This study is aimed to assess the level of biliary intraepithelial neoplasia in O. felineus-infected hamsters after treatment with mitochondria-targeted SkQ1. SkQ1 significantly reduced the biliary intraepithelial neoplasia, which was accompanied by a decrease in lipid and DNA oxidation byproducts, mRNA expression and level of proteins associated with inflammation (TNF-α, CD68) and fibrogenesis (CK7, αSMA), and was also associated with an activation of the Keap1-Nrf2 pathway. Thus, a direct relationship was found between oxidative stress and the severity of biliary intraepithelial neoplasia in O. felineus-infected hamsters. The hepatoprotective effect of plastoquinone-derivative SkQ1 was established; therefore, this compound is a promising agent in complex therapy in the treatment of opisthorchiasis. Full article
(This article belongs to the Special Issue Molecular Research on Oxidative Stress and Health)
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21 pages, 3918 KiB  
Article
Beeswax Alcohol Prevents Low-Density Lipoprotein Oxidation and Demonstrates Antioxidant Activities in Zebrafish Embryos and Human Subjects: A Clinical Study
by Kyung-Hyun Cho, Seung-Hee Baek, Hyo-Seon Nam, Ashutosh Bahuguna, Luis Ernesto López-González, Iván Rodríguez-Cortina, José Illnait-Ferrer, Julio César Fernández-Travieso, Vivian Molina-Cuevas, Yohani Pérez-Guerra, Ambar Oyarzabal Yera and Sarahi Mendoza-Castaño
Curr. Issues Mol. Biol. 2024, 46(1), 409-429; https://doi.org/10.3390/cimb46010026 - 02 Jan 2024
Viewed by 2294
Abstract
Oxidative stress is one of the primary instigators of the onset of various human ailments, including cancers, cardiovascular diseases, and dementia. Particularly, oxidative stress severely affects low-density lipid & protein (LDL) oxidation, leading to several detrimental health effects. Therefore, in this study, the [...] Read more.
Oxidative stress is one of the primary instigators of the onset of various human ailments, including cancers, cardiovascular diseases, and dementia. Particularly, oxidative stress severely affects low-density lipid & protein (LDL) oxidation, leading to several detrimental health effects. Therefore, in this study, the effect of beeswax alcohol (BWA) was evaluated in the prevention of LDL oxidation, enhancement of paraoxonase 1 (PON-1) activity of high-density lipid & protein (HDL), and zebrafish embryo survivability. Furthermore, the implication of BWA consumption on the oxidative plasma variables was assessed by a preliminary clinical study on middle-aged and older human subjects (n = 50). Results support BWA augmentation of PON-1 activity in a dose-dependent manner (10–30 μM), which was significantly better than the effect exerted by coenzyme Q10 (CoQ10). Moreover, BWA significantly curtails LDL/apo-B oxidation evoked by CuSO4 (final 0.5 μM) and a causes a marked reduction in lipid peroxidation in LDL. The transmission electron microscopy (TEM) analysis revealed a healing effect of BWA towards the restoration of LDL morphology and size impaired by the exposure of Cu2+ ions (final 0.5 μM). Additionally, BWA counters the toxicity induced by carboxymethyllysine (CML, 500 ng) and rescues zebrafish embryos from development deformities and apoptotic cell death. A completely randomized, double-blinded, placebo-controlled preliminary clinical study on middle- and older-aged human subjects (n = 50) showed that 12 weeks of BWA (100 mg/day) supplementation efficiently diminished serum malondialdehyde (MDA) and total hydroperoxides and enhanced total antioxidant status by 25%, 27%, and 22%, respectively, compared to the placebo-control and baseline values. Furthermore, the consumption of BWA did not exhibit any noteworthy changes in physical variables, lipid profile, glucose levels, and biomarkers pertinent to kidney and liver function, thus confirming the safety of BWA for consumption. Conclusively, in vitro, BWA prevents LDL oxidation, enhances PON-1 activity in HDL, and positively influences oxidative variables in human subjects. Full article
(This article belongs to the Special Issue Molecular Research on Oxidative Stress and Health)
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20 pages, 3781 KiB  
Article
Lactic Acid Bacteria-Derived Exopolysaccharides Mitigate the Oxidative Response via the NRF2-KEAP1 Pathway in PC12 Cells
by Seda Şirin
Curr. Issues Mol. Biol. 2023, 45(10), 8071-8090; https://doi.org/10.3390/cimb45100510 - 02 Oct 2023
Viewed by 1025
Abstract
Parabiotics, including L-EPSs, have been administered to patients with neurodegenerative disorders. However, the antioxidant properties of L-EPSs against H2O2-induced oxidative stress in PC12 cells have not been studied. Herein, we aimed to investigate the antioxidant properties of the L-EPSs, [...] Read more.
Parabiotics, including L-EPSs, have been administered to patients with neurodegenerative disorders. However, the antioxidant properties of L-EPSs against H2O2-induced oxidative stress in PC12 cells have not been studied. Herein, we aimed to investigate the antioxidant properties of the L-EPSs, their plausible targets, and their mechanism of action. We first determined the amount of L-EPSs in Lactobacillus delbrueckii ssp. bulgaricus B3 and Lactiplantibacillus plantarum GD2 using spectrophotometry. Afterwards, we studied their effects on TDH, TOS/TAS, antioxidant enzyme activities, and intracellular ROS level. Finally, we used qRT-PCR and ELISA to determine the effects of L-EPSs on the NRF2-KEAP1 pathway. According to our results, the L-EPS groups exhibited significantly higher total thiol activity, native thiol activity, disulfide activity, TAS levels, antioxidant enzyme levels, and gene expression levels (GCLC, HO-1, NRF2, and NQO1) than did the H2O2 group. Additionally, the L-EPS groups caused significant reductions in TOS levels and KEAP1 gene expression levels compared with those in the H2O2 group. Our results indicate that H2O2-induced oxidative stress was modified by L-EPSs. Thus, we revealed that L-EPSs, which regulate H2O2-induced oxidative stress, could have applications in the field of neurochemistry. Full article
(This article belongs to the Special Issue Molecular Research on Oxidative Stress and Health)
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26 pages, 5532 KiB  
Article
Molecular Aspects of Hypoxic Stress Effects in Chronic Ethanol Exposure of Neuronal Cells
by Simona Isabelle Stoica, Gelu Onose, Ioana Madalina Pitica, Ana Iulia Neagu, Gabriela Ion, Lilia Matei, Laura Denisa Dragu, Lacramioara-Elena Radu, Mihaela Chivu-Economescu, Laura Georgiana Necula, Aurelian Anghelescu, Carmen Cristina Diaconu, Constantin Munteanu and Coralia Bleotu
Curr. Issues Mol. Biol. 2023, 45(2), 1655-1680; https://doi.org/10.3390/cimb45020107 - 16 Feb 2023
Cited by 5 | Viewed by 1548
Abstract
Experimental models of a clinical, pathophysiological context are used to understand molecular mechanisms and develop novel therapies. Previous studies revealed better outcomes for spinal cord injury chronic ethanol-consuming patients. This study evaluated cellular and molecular changes in a model mimicking spinal cord injury [...] Read more.
Experimental models of a clinical, pathophysiological context are used to understand molecular mechanisms and develop novel therapies. Previous studies revealed better outcomes for spinal cord injury chronic ethanol-consuming patients. This study evaluated cellular and molecular changes in a model mimicking spinal cord injury (hypoxic stress induced by treatment with deferoxamine or cobalt chloride) in chronic ethanol-consuming patients (ethanol-exposed neural cultures (SK-N-SH)) in order to explain the clinical paradigm of better outcomes for spinal cord injury chronic ethanol-consuming patients. The results show that long-term ethanol exposure has a cytotoxic effect, inducing apoptosis. At 24 h after the induction of hypoxic stress (by deferoxamine or cobalt chloride treatments), reduced ROS in long-term ethanol-exposed SK-N-SH cells was observed, which might be due to an adaptation to stressful conditions. In addition, the HIF-1α protein level was increased after hypoxic treatment of long-term ethanol-exposed cells, inducing fluctuations in its target metabolic enzymes proportionally with treatment intensity. The wound healing assay demonstrated that the cells recovered after stress conditions, showing that the ethanol-exposed cells that passed the acute step had the same proliferation profile as the cells unexposed to ethanol. Deferoxamine-treated cells displayed higher proliferative activity than the control cells in the proliferation–migration assay, emphasizing the neuroprotective effect. Cells have overcome the critical point of the alcohol-induced traumatic impact and adapted to ethanol (a chronic phenomenon), sustaining the regeneration process. However, further experiments are needed to ensure recovery efficiency is more effective in chronic ethanol exposure. Full article
(This article belongs to the Special Issue Molecular Research on Oxidative Stress and Health)
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11 pages, 3050 KiB  
Article
Repurposing HIV Protease Inhibitors Atazanavir and Darunavir as Antifungal Treatments against Candida albicans Infections: An In Vitro and In Vivo Study
by Juliana de C. Fenley, Patrícia P. de Barros, Paulo H. F. do Carmo, Maíra T. Garcia, Rodnei D. Rossoni and Juliana C. Junqueira
Curr. Issues Mol. Biol. 2022, 44(11), 5379-5389; https://doi.org/10.3390/cimb44110364 - 01 Nov 2022
Cited by 3 | Viewed by 1321
Abstract
Candida albicans is the chief etiological agent of candidiasis, a mycosis prevalent in individuals with acquired immunodeficiency syndrome (AIDS). In recent years, the introduction of human immunodeficiency virus (HIV) protease inhibitors (HIV-PI) has reduced the prevalence of candidiasis in these patients. Seeking new [...] Read more.
Candida albicans is the chief etiological agent of candidiasis, a mycosis prevalent in individuals with acquired immunodeficiency syndrome (AIDS). In recent years, the introduction of human immunodeficiency virus (HIV) protease inhibitors (HIV-PI) has reduced the prevalence of candidiasis in these patients. Seeking new therapeutic strategies based on the perspective of drug repositioning, we evaluated the effects of two second-generation HIV-PIs, atazanavir (ATV) and darunavir (DRV), on virulence factors of C. albicans and experimental candidiasis. For this, clinical strains of C. albicans were subjected to in vitro and in vivo treatments with ATV or DRV. As a result, ATV and DRV exhibited antifungal activity against fungal cells at 512 μg/mL, reduced the viability and biomass of biofilms, and inhibited filamentation of C. albicans. In addition, these HIV-PIs downregulated the expression of SAP2 and BRC1 genes of C. albicans. In an in vivo study, prophylactic use of ATV and DRV prolonged the survival rate of Galleria mellonella larvae infected with C. albicans. Therefore, ATV and DRV showed activity against C. albicans by reducing cell growth, biofilm formation, filamentation, and expression of virulence genes. Furthermore, ATV and DRV decreased experimental candidiasis, suggesting the repurposing of HIV-PIs as antifungal treatments for C. albicans infections. Full article
(This article belongs to the Special Issue Molecular Research on Oxidative Stress and Health)
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18 pages, 6263 KiB  
Article
Status of Fungicide Resistance and Physiological Characterization of Tebuconazole Resistance in Rhizocotonia solani in Sichuan Province, China
by Changwei Gong, Min Liu, Dan Liu, Qiulin Wang, Ali Hasnain, Xiaoxu Zhan, Jian Pu, Yueyang Liang, Xuemei Liu and Xuegui Wang
Curr. Issues Mol. Biol. 2022, 44(10), 4859-4876; https://doi.org/10.3390/cimb44100330 - 13 Oct 2022
Cited by 4 | Viewed by 1587
Abstract
The resistance prevalence of chemical fungicides has caused increasingly serious agro-ecological environmental problems. However, there are few previous reports about resistance to succinate dehydrogenase (SDHI) or sterol demethylation inhibitor (DMI) in Rhizoctonia solani, one of the main agro-diseases. In this study, the [...] Read more.
The resistance prevalence of chemical fungicides has caused increasingly serious agro-ecological environmental problems. However, there are few previous reports about resistance to succinate dehydrogenase (SDHI) or sterol demethylation inhibitor (DMI) in Rhizoctonia solani, one of the main agro-diseases. In this study, the fungicide resistance of 122 R. solani isolates in Sichuan Province was monitored by the mycelial growth rate method. Results showed that all isolates were susceptible to hexaconazole and most isolates were susceptible to thifluzamide, except for the field isolate MSRS-2-7 due to a moderate resistance to thifluzamide (16.43-fold resistance ratio, RR), compared to the sensitivity baseline of thifluzamide (0.042 μg/mL EC50 values). On the contrary, many isolates showed moderate or high resistance to tebuconazole (10.59- to 60.78-fold RR), reaching EC50 values of 0.54~3.10 μg/mL, especially for a highly resistant isolate LZHJ-1-8 displaying moderate resistance to epoxiconazole (35.40-fold RR due to a 3.54 μg/mL EC50 value). The fitness determination found that the tebuconazole-resistant isolates showed higher fitness cost with these characteristics, including a lower growth rate, higher relative electric conductivity, an increased ability to tolerate tebuconazole, and high osmotic pressure. Four new mutations of cytochrome P450 sterol 14α-demethylase (CYP51), namely, S94A, N406S, H793R, and L750P, which is the target for DMI fungicides, was found in the tebuconazole-resistant isolates. Furthermore, the lowest binding energy with tebuconazole was also found in the LZHJ-1-8 isolate possessing all the mutations through analyses with Discovery Studio software. Therefore, these new mutation sites of CYP51 may be linked to the resistance against tebuconazole, and its application for controlling R. solani should be restricted in some areas. Full article
(This article belongs to the Special Issue Molecular Research on Oxidative Stress and Health)
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