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Cellular and Molecular Mechanisms in Oxidative Stress-Related Diseases 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (10 April 2023) | Viewed by 41420

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Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
Interests: physiology; ion trasport; band 3 protein; erythrocytes; oxidative stress; aging
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Dear Colleagues,

Oxidative stress (OS) is frequently described as the balance between production of reactive species (RS), including oxygen and nitrogen, in biological systems and the ability of the latter to defend through the sophisticated antioxidant machinery. At physiological levels, some oxidants in controlled amounts, possess an important signaling functions within the cell. Specifically, cells can generate RS with function of second messengers, use them for intracellular signaling and for stimulating redox-sensitive signaling pathways to modify the cellular content of the cytoprotective regulatory proteins. In fact, the redox state in the cell is normally regulated by a complex endogenous antioxidant system composed of proteins with enzymatic activity and non-enzymatic proteins able to quickly neutralize or ensure a low production of RS. Nevertheless, when oxidants are produced in excess, or when the antioxidant defenses that regulate them are ineffective, this balance can be perturbed, thus resulting in oxidative condition. Oxidative products are highly reactive, and can directly or indirectly modulate the functions of many enzymes and transcription factors through a complex signaling cascades. In particular, some of the pathways are preferentially linked to enhanced survival, while others are more frequently associated with cell death, and constitute important avenues for therapeutic interventions aimed at limiting oxidative damage or, alternatively, attenuating its consequences. Furthermore, the magnitude and exposure of the insult, as well as the cell type involved are key elements in defining which pathways are activated, as well as the final cell outcome.

The aim of this special issue is to collect and contribute to the dissemination of high quality research articles, as well as review articles, focusing on the relationship between oxidative stress-related diseases and cellular responses in different pathologies, including ischemic stroke, diabetes, kidney disease, cardiovascular and neurodegenerative diseases. In addition, molecular targets of cellular membrane, as well as their potential modulation under oxidative stress will be also considered, in an attempt to provide more information about cell response to oxidative stress and its possible modulation by novel pharmacological strategies.

Prof. Dr. Rossana Morabito
Dr. Alessia Remigante
Guest Editors

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Keywords

  • molecular targets of oxidative stress in oxidative stress related-diseases
  • oxidative stress and oxidative stress-related pathologies
  • cellular response to oxidative stress
  • oxidative stress and apoptosis in oxidative stress-related diseases
  • oxidative stress and related cell signaling
  • cell adaptation to oxidative stress
  • biomarkers of oxidative stress in disease
  • beneficial effects of natural or synthetic antioxidants in oxidative stress-related diseases

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Published Papers (19 papers)

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Editorial

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11 pages, 250 KiB  
Editorial
Cellular and Molecular Mechanisms in Oxidative Stress-Related Diseases 2.0/3.0
by Alessia Remigante and Rossana Morabito
Int. J. Mol. Sci. 2023, 24(21), 16018; https://doi.org/10.3390/ijms242116018 - 6 Nov 2023
Viewed by 866
Abstract
Oxidative stress is frequently described as the balance between the production of reactive species (including oxygen and nitrogen) in biological systems and the ability of the latter to defend itself through the sophisticated antioxidant machinery [...] Full article

Research

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15 pages, 1272 KiB  
Article
The Critical Assessment of Oxidative Stress Parameters as Potential Biomarkers of Carbon Monoxide Poisoning
by Piotr Hydzik, Renata Francik, Sławomir Francik, Ewa Gomółka, Ebru Derici Eker, Mirosław Krośniak, Maciej Noga and Kamil Jurowski
Int. J. Mol. Sci. 2023, 24(13), 10784; https://doi.org/10.3390/ijms241310784 - 28 Jun 2023
Cited by 2 | Viewed by 1317
Abstract
In conventional clinical toxicology practice, the blood level of carboxyhemoglobin is a biomarker of carbon monoxide (CO) poisoning but does not correspond to the complete clinical picture and the severity of the poisoning. Taking into account articles suggesting the relationship between oxidative stress [...] Read more.
In conventional clinical toxicology practice, the blood level of carboxyhemoglobin is a biomarker of carbon monoxide (CO) poisoning but does not correspond to the complete clinical picture and the severity of the poisoning. Taking into account articles suggesting the relationship between oxidative stress parameters and CO poisoning, it seems reasonable to consider this topic more broadly, including experimental biochemical data (oxidative stress parameters) and patients poisoned with CO. This article aimed to critically assess oxidative-stress-related parameters as potential biomarkers to evaluate the severity of CO poisoning and their possible role in the decision to treat. The critically set parameters were antioxidative, including catalase, 2,2-diphenyl-1-picryl-hydrazyl, glutathione, thiol and carbonyl groups. Our preliminary studies involved patients (n = 82) admitted to the Toxicology Clinical Department of the University Hospital of Jagiellonian University Medical College (Kraków, Poland) during 2015–2020. The poisoning was diagnosed based on medical history, clinical symptoms, and carboxyhemoglobin blood level. Blood samples for carboxyhemoglobin and antioxidative parameters were collected immediately after admission to the emergency department. To evaluate the severity of the poisoning, the Pach scale was applied. The final analysis included a significant decrease in catalase activity and a reduction in glutathione level in all poisoned patients based on the severity of the Pach scale: I°–III° compared to the control group. It follows from the experimental data that the poisoned patients had a significant increase in level due to thiol groups and the 2,2-diphenyl-1-picryl-hydrazyl radical, with no significant differences according to the severity of poisoning. The catalase-to-glutathione and thiol-to-glutathione ratios showed the most important differences between the poisoned patients and the control group, with a significant increase in the poisoned group. The ratios did not differentiate the severity of the poisoning. The carbonyl level was highest in the control group compared to the poisoned group but was not statistically significant. Our critical assessment shows that using oxidative-stress-related parameters to evaluate the severity of CO poisoning, the outcome, and treatment options is challenging. Full article
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18 pages, 2138 KiB  
Article
Toxicity of Metal Ions Released from a Fixed Orthodontic Appliance to Gastrointestinal Tract Cell Lines
by Ksenija Durgo, Sunčana Orešić, Marijana Rinčić Mlinarić, Željka Fiket and Gordana Čanadi Jurešić
Int. J. Mol. Sci. 2023, 24(12), 9940; https://doi.org/10.3390/ijms24129940 - 9 Jun 2023
Cited by 5 | Viewed by 1195
Abstract
The mechanism of toxicity and cellular response to metal ions present in the environment is still a very current area of research. In this work, which is a continuation of the study of the toxicity of metal ions released by fixed orthodontic appliances, [...] Read more.
The mechanism of toxicity and cellular response to metal ions present in the environment is still a very current area of research. In this work, which is a continuation of the study of the toxicity of metal ions released by fixed orthodontic appliances, eluates of archwires, brackets, ligatures, and bands are used to test the prooxidant effect, cytotoxicity, and genotoxicity on cell lines of the gastrointestinal tract. Eluates obtained after three immersion periods (3, 7, and 14 days) and with known amounts and types of metal ions were used. Four cell lines—CAL 27 (human tongue), Hep-G2 (liver), AGS (stomach) and CaCo-2 (colon)—were treated with each type of eluate at four concentrations (0.1×, 0.5×, 1.0×, and 2.0×) for 24 h. Most eluates had toxic effects on CAL 27 cells over the entire concentration range regardless of exposure time, while CaCo-2 proved to be the most resistant. In AGS and Hep-G2 cells, all samples tested induced free radical formation, with the highest concentration (2×) causing a decrease in free radicals formed compared to the lowest concentrations. Eluates containing Cr, Mn, and Al showed a slight pro-oxidant effect on DNA (on plasmid φX-174 RF I) and slight genotoxicity (comet assay), but these effects are not so great that the human body could not “resist” them. Statistical analysis of data on chemical composition, cytotoxicity, ROS, genotoxicity, and prooxidative DNA damage shows the influence of metal ions present in some eluates on the toxicity obtained. Fe and Ni are responsible for the production of ROS, while Mn and Cr have a great influence on hydroxyl radicals, which cause single-strand breaks in supercoiled plasmid DNA in addition to the production of ROS. On the other hand, Fe, Cr, Mn, and Al are responsible for the cytotoxic effect of the studied eluates. The obtained results confirm that this type of research is useful and brings us closer to more accurate in vivo conditions. Full article
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17 pages, 3429 KiB  
Article
Anti-Candida albicans Effects and Mechanisms of Theasaponin E1 and Assamsaponin A
by Yuhong Chen, Ying Gao, Mingan Yuan, Zhaisheng Zheng and Junfeng Yin
Int. J. Mol. Sci. 2023, 24(11), 9350; https://doi.org/10.3390/ijms24119350 - 27 May 2023
Cited by 3 | Viewed by 1750
Abstract
Candida albicans is an opportunistic human fungal pathogen, and its drug resistance is becoming a serious problem. Camellia sinensis seed saponins showed inhibitory effects on resistant Candida albicans strains, but the active components and mechanisms are unclear. In this study, the effects and [...] Read more.
Candida albicans is an opportunistic human fungal pathogen, and its drug resistance is becoming a serious problem. Camellia sinensis seed saponins showed inhibitory effects on resistant Candida albicans strains, but the active components and mechanisms are unclear. In this study, the effects and mechanisms of two Camellia sinensis seed saponin monomers, theasaponin E1 (TE1) and assamsaponin A (ASA), on a resistant Candida albicans strain (ATCC 10231) were explored. The minimum inhibitory concentration and minimum fungicidal concentration of TE1 and ASA were equivalent. The time–kill curves showed that the fungicidal efficiency of ASA was higher than that of TE1. TE1 and ASA significantly increased the cell membrane permeability and disrupted the cell membrane integrity of C. albicans cells, probably by interacting with membrane-bound sterols. Moreover, TE1 and ASA induced the accumulation of intracellular ROS and decreased the mitochondrial membrane potential. Transcriptome and qRT-PCR analyses revealed that the differentially expressed genes were concentrated in the cell wall, plasma membrane, glycolysis, and ergosterol synthesis pathways. In conclusion, the antifungal mechanisms of TE1 and ASA included the interference with the biosynthesis of ergosterol in fungal cell membranes, damage to the mitochondria, and the regulation of energy metabolism and lipid metabolism. Tea seed saponins have the potential to be novel anti-Candida albicans agents. Full article
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22 pages, 6065 KiB  
Article
Molecular Mechanisms of Oxidative Stress Relief by CAPE in ARPE−19 Cells
by Changjie Ren, Peiran Zhou, Mingliang Zhang, Zihao Yu, Xiaomin Zhang, Joyce Tombran-Tink, Colin J. Barnstable and Xiaorong Li
Int. J. Mol. Sci. 2023, 24(4), 3565; https://doi.org/10.3390/ijms24043565 - 10 Feb 2023
Cited by 2 | Viewed by 1721
Abstract
Caffeic acid phenylethyl ester (CAPE) is an antioxidative agent originally derived from propolis. Oxidative stress is a significant pathogenic factor in most retinal diseases. Our previous study revealed that CAPE suppresses mitochondrial ROS production in ARPE−19 cells by regulating UCP2. The present study [...] Read more.
Caffeic acid phenylethyl ester (CAPE) is an antioxidative agent originally derived from propolis. Oxidative stress is a significant pathogenic factor in most retinal diseases. Our previous study revealed that CAPE suppresses mitochondrial ROS production in ARPE−19 cells by regulating UCP2. The present study explores the ability of CAPE to provide longer-term protection to RPE cells and the underlying signal pathways involved. ARPE−19 cells were given CAPE pretreatment followed by t-BHP stimulation. We used in situ live cell staining with CellROX and MitoSOX to measure ROS accumulation; Annexin V-FITC/PI assay to evaluate cell apoptosis; ZO−1 immunostaining to observe tight junction integrity in the cells; RNA-seq to analyze changes in gene expression; q-PCR to validate the RNA-seq data; and Western Blot to examine MAPK signal pathway activation. CAPE significantly reduced both cellular and mitochondria ROS overproduction, restored the loss of ZO−1 expression, and inhibited apoptosis induced by t-BHP stimulation. We also demonstrated that CAPE reverses the overexpression of immediate early genes (IEGs) and activation of the p38-MAPK/CREB signal pathway. Either genetic or chemical deletion of UCP2 largely abolished the protective effects of CAPE. CAPE restrained ROS generation and preserved the tight junction structure of ARPE−19 cells against oxidative stress-induced apoptosis. These effects were mediated via UCP2 regulation of p38/MAPK-CREB-IEGs pathway. Full article
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21 pages, 2423 KiB  
Article
Polymorphisms in Genes Encoding VDR, CALCR and Antioxidant Enzymes as Predictors of Bone Tissue Condition in Young, Healthy Men
by Ewa Jówko, Barbara Długołęcka, Igor Cieśliński and Jadwiga Kotowska
Int. J. Mol. Sci. 2023, 24(4), 3373; https://doi.org/10.3390/ijms24043373 - 8 Feb 2023
Cited by 2 | Viewed by 1110
Abstract
The aim of the study was to assess significant predictors of bone mineral content (BMC) and bone mineral density (BMD) in a group of young, healthy men at the time of reaching peak bone mass. Regression analyses showed that age, BMI and practicing [...] Read more.
The aim of the study was to assess significant predictors of bone mineral content (BMC) and bone mineral density (BMD) in a group of young, healthy men at the time of reaching peak bone mass. Regression analyses showed that age, BMI and practicing combat sports and team sports at a competitive level (trained vs. untrained group; TR vs. CON, respectively) were positive predictors of BMD/BMC values at various skeletal sites. In addition, genetic polymorphisms were among the predictors. In the whole population studied, at almost all measured skeletal sites, the SOD2 AG genotype proved to be a negative predictor of BMC, while the VDR FokI GG genotype was a negative predictor of BMD. In contrast, the CALCR AG genotype was a positive predictor of arm BMD. ANOVA analyses showed that, regarding SOD2 polymorphism, the TR group was responsible for the significant intergenotypic differences in BMC that were observed in the whole study population (i.e., lower BMC values of leg, trunk and whole body were observed in AG TR compared to AA TR). On the other hand, higher BMC at L1–L4 was observed in the SOD2 GG genotype of the TR group compared to in the same genotype of the CON group. For the FokI polymorphism, BMD at L1–L4 was higher in AG TR than in AG CON. In turn, the CALCR AA genotype in the TR group had higher arm BMD compared to the same genotype in the CON group. In conclusion, SOD2, VDR FokI and CALCR polymorphisms seem to affect the association of BMC/BMD values with training status. In general, at least within the VDR FokI and CALCR polymorphisms, less favorable genotypes in terms of BMD (i.e., FokI AG and CALCR AA) appear to be associated with a greater BMD response to sports training. This suggests that, in healthy men during the period of bone mass formation, sports training (combat and team sports) may attenuate the negative impact of genetic factors on bone tissue condition, possibly reducing the risk of osteoporosis in later age. Full article
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22 pages, 3108 KiB  
Article
Evaluation of Oxidative Stress and Metabolic Profile in a Preclinical Kidney Transplantation Model According to Different Preservation Modalities
by Simona Mrakic-Sposta, Alessandra Vezzoli, Emanuela Cova, Elena Ticcozzelli, Michela Montorsi, Fulvia Greco, Vincenzo Sepe, Ilaria Benzoni, Federica Meloni, Eloisa Arbustini, Massimo Abelli and Maristella Gussoni
Int. J. Mol. Sci. 2023, 24(2), 1029; https://doi.org/10.3390/ijms24021029 - 5 Jan 2023
Cited by 3 | Viewed by 1715
Abstract
This study addresses a joint nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopy approach to provide a platform for dynamic assessment of kidney viability and metabolism. On porcine kidney models, ROS production, oxidative damage kinetics, and metabolic changes occurring both during [...] Read more.
This study addresses a joint nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopy approach to provide a platform for dynamic assessment of kidney viability and metabolism. On porcine kidney models, ROS production, oxidative damage kinetics, and metabolic changes occurring both during the period between organ retrieval and implantation and after kidney graft were examined. The 1H-NMR metabolic profile—valine, alanine, acetate, trimetylamine-N-oxide, glutathione, lactate, and the EPR oxidative stress—resulting from ischemia/reperfusion injury after preservation (8 h) by static cold storage (SCS) and ex vivo machine perfusion (HMP) methods were monitored. The functional recovery after transplantation (14 days) was evaluated by serum creatinine (SCr), oxidative stress (ROS), and damage (thiobarbituric-acid-reactive substances and protein carbonyl enzymatic) assessments. At 8 h of preservation storage, a significantly (p < 0.0001) higher ROS production was measured in the SCS vs. HMP group. Significantly higher concentration data (p < 0.05–0.0001) in HMP vs. SCS for all the monitored metabolites were found as well. The HMP group showed a better function recovery. The comparison of the areas under the SCr curves (AUC) returned a significantly smaller (−12.5 %) AUC in the HMP vs. SCS. EPR-ROS concentration (μmol·g−1) from bioptic kidney tissue samples were significantly lower in HMP vs. SCS. The same result was found for the NMR monitored metabolites: lactate: −59.76%, alanine: −43.17%; valine: −58.56%; and TMAO: −77.96%. No changes were observed in either group under light microscopy. In conclusion, a better and more rapid normalization of oxidative stress and functional recovery after transplantation were observed by HMP utilization. Full article
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14 pages, 3200 KiB  
Article
Microplastics Exacerbate Cadmium-Induced Kidney Injury by Enhancing Oxidative Stress, Autophagy, Apoptosis, and Fibrosis
by Hui Zou, Yan Chen, Huayi Qu, Jian Sun, Tao Wang, Yonggang Ma, Yan Yuan, Jianchun Bian and Zongping Liu
Int. J. Mol. Sci. 2022, 23(22), 14411; https://doi.org/10.3390/ijms232214411 - 19 Nov 2022
Cited by 15 | Viewed by 2480
Abstract
Cadmium (Cd) is a potential pathogenic factor in the urinary system that is associated with various kidney diseases. Microplastics (MPs), comprising of plastic particles less than 5 mm in diameter, are a major carrier of contaminants. We applied 10 mg/L particle 5 μm [...] Read more.
Cadmium (Cd) is a potential pathogenic factor in the urinary system that is associated with various kidney diseases. Microplastics (MPs), comprising of plastic particles less than 5 mm in diameter, are a major carrier of contaminants. We applied 10 mg/L particle 5 μm MPs and 50 mg/L CdCl2 in water for three months in vivo assay to assess the damaging effects of MPs and Cd exposure on the kidney. In vivo tests showed that MPs exacerbated Cd-induced kidney injury. In addition, the involvement of oxidative stress, autophagy, apoptosis, and fibrosis in the damaging effects of MPs and Cd on mouse kidneys were investigated. The results showed that MPs aggravated Cd-induced kidney injury by enhancing oxidative stress, autophagy, apoptosis, and fibrosis. These findings provide new insights into the toxic effects of MPs on the mouse kidney. Full article
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12 pages, 3420 KiB  
Article
Protective Effect of Resveratrol in an Experimental Model of Salicylate-Induced Tinnitus
by Anji Song, Gwang-Won Cho, Changjong Moon, Ilyong Park and Chul Ho Jang
Int. J. Mol. Sci. 2022, 23(22), 14183; https://doi.org/10.3390/ijms232214183 - 16 Nov 2022
Cited by 3 | Viewed by 1758 | Correction
Abstract
To date, the effect of resveratrol on tinnitus has not been reported. The attenuative effects of resveratrol (RSV) on a salicylate-induced tinnitus model were evaluated by in vitro and in vivo experiments. The gene expression of the activity-regulated cytoskeleton-associated protein (ARC), [...] Read more.
To date, the effect of resveratrol on tinnitus has not been reported. The attenuative effects of resveratrol (RSV) on a salicylate-induced tinnitus model were evaluated by in vitro and in vivo experiments. The gene expression of the activity-regulated cytoskeleton-associated protein (ARC), tumor necrosis factor-alpha (TNFα), and NMDA receptor subunit 2B (NR2B) in SH-SY5Y cells was examined using qPCR. Phosphorylated cAMP response element-binding protein (p-CREB), apoptosis markers, and reactive oxygen species (ROS) were evaluated by in vitro experiments. The in vivo experiment evaluated the gap-prepulse inhibition of the acoustic startle reflex (GPIAS) and auditory brainstem response (ABR) level. The NR2B expression in the auditory cortex (AC) was determined by immunohistochemistry. RSV significantly reduced the salicylate-induced expression of NR2B, ARC, and TNFα in neuronal cells; the GPIAS and ABR thresholds altered by salicylate in rats were recovered close to their normal range. RSV also reduced the salicylate-induced NR2B overexpression of the AC. These results confirmed that resveratrol exerted an attenuative effect on salicylate-induced tinnitus and may have a therapeutic potential. Full article
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13 pages, 603 KiB  
Article
Usefulness of Urinary Biomarkers for Assessing Bladder Condition and Histopathology in Patients with Interstitial Cystitis/Bladder Pain Syndrome
by Yuan-Hong Jiang, Jia-Fong Jhang, Yuan-Hsiang Hsu and Hann-Chorng Kuo
Int. J. Mol. Sci. 2022, 23(19), 12044; https://doi.org/10.3390/ijms231912044 - 10 Oct 2022
Cited by 17 | Viewed by 2392
Abstract
This study investigated the usefulness of urinary biomarkers for assessing bladder condition and histopathology in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). We retrospectively enrolled 315 patients (267 women and 48 men) diagnosed with IC/BPS and 30 controls. Data on clinical and urodynamic [...] Read more.
This study investigated the usefulness of urinary biomarkers for assessing bladder condition and histopathology in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). We retrospectively enrolled 315 patients (267 women and 48 men) diagnosed with IC/BPS and 30 controls. Data on clinical and urodynamic characteristics (visual analog scale (VAS) score and bladder capacity) and cystoscopic hydrodistention findings (Hunner’s lesion, glomerulation grade, and maximal bladder capacity (MBC)) were recorded. Urine samples were utilized to assay inflammatory, neurogenic, and oxidative stress biomarkers, including interleukin (IL)-8, C-X-C motif chemokine ligand 10 (CXCL10), monocyte chemoattractant protein-1 (MCP-1), brain-derived neurotrophic factor (BDNF), eotaxin, IL-6, macrophage inflammatory protein 1 beta (MIP-1β), regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and 8-isoproatane, and total antioxidant capacity. Further, specific histopathological findings were identified via bladder biopsy. The associations between urinary biomarker levels and bladder conditions and histopathological findings were evaluated. The results reveal that patients with IC/BPS had significantly higher urinary MCP-1, eotaxin, TNF-α, PGE2, 8-OHdG, and 8-isoprostane levels than controls. Patients with Hunner’s IC (HIC) had significantly higher IL-8, CXCL10, BDNF, eotaxin, IL-6, MIP-1β, and RANTES levels than those with non-Hunner’s IC (NHIC). Patients with NHIC who had an MBC of ≤760 mL had significantly high urinary CXCL10, MCP-1, eotaxin, IL-6, MIP-1β, RANTES, PGE2, and 8-isoprostane levels and total antioxidant capacity. Patients with NHIC who had a higher glomerulation grade had significantly high urinary MCP-1, IL-6, RANTES, 8-OHdG, and 8-isoprostane levels. A significant association was observed between urinary biomarkers and glomerulation grade, MBC, VAS score, and bladder sensation. However, bladder-specific histopathological findings were not well correlated with urinary biomarker levels. The urinary biomarker levels can be useful for identifying HIC and different NHIC subtypes. Higher urinary inflammatory and oxidative stress biomarker levels are associated with IC/BPS. Most urinary biomarkers are not correlated with specific bladder histopathological findings; nevertheless, they are more important in the assessment of bladder condition than bladder histopathology. Full article
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9 pages, 1636 KiB  
Article
Lead Exposure Causes Spinal Curvature during Embryonic Development in Zebrafish
by Xueting Li, Ce Chen, Mingyue He, Lidong Yu, Renhao Liu, Chunmeng Ma, Yu Zhang, Jianbo Jia, Bingsheng Li and Li Li
Int. J. Mol. Sci. 2022, 23(17), 9571; https://doi.org/10.3390/ijms23179571 - 24 Aug 2022
Cited by 4 | Viewed by 1983
Abstract
Lead (Pb) is an important raw material for modern industrial production, they enter the aquatic environment in several ways and cause serious harm to aquatic ecosystems. Lead ions (Pb2+) are highly toxic and can accumulate continuously in organisms. In addition to [...] Read more.
Lead (Pb) is an important raw material for modern industrial production, they enter the aquatic environment in several ways and cause serious harm to aquatic ecosystems. Lead ions (Pb2+) are highly toxic and can accumulate continuously in organisms. In addition to causing biological deaths, it can also cause neurological damage in vertebrates. Our experiment found that Pb2+ caused decreased survival, delayed hatching, decreased frequency of voluntary movements at 24 hpf, increased heart rate at 48 hpf and increased malformation rate in zebrafish embryos. Among them, the morphology of spinal malformations varied, with 0.4 mg/L Pb2+ causing a dorsal bending of the spine of 72 hpf zebrafish and a ventral bending in 120 hpf zebrafish. It was detected that spinal malformations were mainly caused by Pb2+-induced endoplasmic reticulum stress and apoptosis. The genetic changes in somatic segment development which disrupted developmental polarity as well as osteogenesis, resulting in uneven myotomal development. In contrast, calcium ions can rescue the series of responses induced by lead exposure and reduce the occurrence of spinal curvature. This article proposes new findings of lead pollution toxicity in zebrafish. Full article
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Review

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17 pages, 1361 KiB  
Review
The Potential of Cylindromatosis (CYLD) as a Therapeutic Target in Oxidative Stress-Associated Pathologies: A Comprehensive Evaluation
by Zhenzhou Huang and Yanjie Tan
Int. J. Mol. Sci. 2023, 24(9), 8368; https://doi.org/10.3390/ijms24098368 - 6 May 2023
Cited by 2 | Viewed by 1967
Abstract
Oxidative stress (OS) arises as a consequence of an imbalance between the formation of reactive oxygen species (ROS) and the capacity of antioxidant defense mechanisms to neutralize them. Excessive ROS production can lead to the damage of critical biomolecules, such as lipids, proteins, [...] Read more.
Oxidative stress (OS) arises as a consequence of an imbalance between the formation of reactive oxygen species (ROS) and the capacity of antioxidant defense mechanisms to neutralize them. Excessive ROS production can lead to the damage of critical biomolecules, such as lipids, proteins, and DNA, ultimately contributing to the onset and progression of a multitude of diseases, including atherosclerosis, chronic obstructive pulmonary disease, Alzheimer’s disease, and cancer. Cylindromatosis (CYLD), initially identified as a gene linked to familial cylindromatosis, has a well-established and increasingly well-characterized function in tumor inhibition and anti-inflammatory processes. Nevertheless, burgeoning evidence suggests that CYLD, as a conserved deubiquitination enzyme, also plays a pivotal role in various key signaling pathways and is implicated in the pathogenesis of numerous diseases driven by oxidative stress. In this review, we systematically examine the current research on the function and pathogenesis of CYLD in diseases instigated by oxidative stress. Therapeutic interventions targeting CYLD may hold significant promise for the treatment and management of oxidative stress-induced human diseases. Full article
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16 pages, 899 KiB  
Review
Molecular Pathology, Oxidative Stress, and Biomarkers in Obstructive Sleep Apnea
by Piero Giuseppe Meliante, Federica Zoccali, Francesca Cascone, Vanessa Di Stefano, Antonio Greco, Marco de Vincentiis, Carla Petrella, Marco Fiore, Antonio Minni and Christian Barbato
Int. J. Mol. Sci. 2023, 24(6), 5478; https://doi.org/10.3390/ijms24065478 - 13 Mar 2023
Cited by 13 | Viewed by 2866
Abstract
Obstructive sleep apnea syndrome (OSAS) is characterized by intermittent hypoxia (IH) during sleep due to recurrent upper airway obstruction. The derived oxidative stress (OS) leads to complications that do not only concern the sleep-wake rhythm but also systemic dysfunctions. The aim of this [...] Read more.
Obstructive sleep apnea syndrome (OSAS) is characterized by intermittent hypoxia (IH) during sleep due to recurrent upper airway obstruction. The derived oxidative stress (OS) leads to complications that do not only concern the sleep-wake rhythm but also systemic dysfunctions. The aim of this narrative literature review is to investigate molecular alterations, diagnostic markers, and potential medical therapies for OSAS. We analyzed the literature and synthesized the evidence collected. IH increases oxygen free radicals (ROS) and reduces antioxidant capacities. OS and metabolic alterations lead OSAS patients to undergo endothelial dysfunction, osteoporosis, systemic inflammation, increased cardiovascular risk, pulmonary remodeling, and neurological alterations. We treated molecular alterations known to date as useful for understanding the pathogenetic mechanisms and for their potential application as diagnostic markers. The most promising pharmacological therapies are those based on N-acetylcysteine (NAC), Vitamin C, Leptin, Dronabinol, or Atomoxetine + Oxybutynin, but all require further experimentation. CPAP remains the approved therapy capable of reversing most of the known molecular alterations; future drugs may be useful in treating the remaining dysfunctions. Full article
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22 pages, 1127 KiB  
Review
The Yin and Yang Effect of the Apelinergic System in Oxidative Stress
by Benedetta Fibbi, Giada Marroncini, Laura Naldi and Alessandro Peri
Int. J. Mol. Sci. 2023, 24(5), 4745; https://doi.org/10.3390/ijms24054745 - 1 Mar 2023
Cited by 3 | Viewed by 2057
Abstract
Apelin is an endogenous ligand for the G protein-coupled receptor APJ and has multiple biological activities in human tissues and organs, including the heart, blood vessels, adipose tissue, central nervous system, lungs, kidneys, and liver. This article reviews the crucial role of apelin [...] Read more.
Apelin is an endogenous ligand for the G protein-coupled receptor APJ and has multiple biological activities in human tissues and organs, including the heart, blood vessels, adipose tissue, central nervous system, lungs, kidneys, and liver. This article reviews the crucial role of apelin in regulating oxidative stress-related processes by promoting prooxidant or antioxidant mechanisms. Following the binding of APJ to different active apelin isoforms and the interaction with several G proteins according to cell types, the apelin/APJ system is able to modulate different intracellular signaling pathways and biological functions, such as vascular tone, platelet aggregation and leukocytes adhesion, myocardial activity, ischemia/reperfusion injury, insulin resistance, inflammation, and cell proliferation and invasion. As a consequence of these multifaceted properties, the role of the apelinergic axis in the pathogenesis of degenerative and proliferative conditions (e.g., Alzheimer’s and Parkinson’s diseases, osteoporosis, and cancer) is currently investigated. In this view, the dual effect of the apelin/APJ system in the regulation of oxidative stress needs to be more extensively clarified, in order to identify new potential strategies and tools able to selectively modulate this axis according to the tissue-specific profile. Full article
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36 pages, 1963 KiB  
Review
Molecular Genetics of Abnormal Redox Homeostasis in Type 2 Diabetes Mellitus
by Iuliia Azarova, Alexey Polonikov and Elena Klyosova
Int. J. Mol. Sci. 2023, 24(5), 4738; https://doi.org/10.3390/ijms24054738 - 1 Mar 2023
Cited by 10 | Viewed by 3207
Abstract
Numerous studies have shown that oxidative stress resulting from an imbalance between the production of free radicals and their neutralization by antioxidant enzymes is one of the major pathological disorders underlying the development and progression of type 2 diabetes (T2D). The present review [...] Read more.
Numerous studies have shown that oxidative stress resulting from an imbalance between the production of free radicals and their neutralization by antioxidant enzymes is one of the major pathological disorders underlying the development and progression of type 2 diabetes (T2D). The present review summarizes the current state of the art advances in understanding the role of abnormal redox homeostasis in the molecular mechanisms of T2D and provides comprehensive information on the characteristics and biological functions of antioxidant and oxidative enzymes, as well as discusses genetic studies conducted so far in order to investigate the contribution of polymorphisms in genes encoding redox state-regulating enzymes to the disease pathogenesis. Full article
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30 pages, 6695 KiB  
Review
Manipulation of Oxidative Stress Responses by Non-Thermal Plasma to Treat Herpes Simplex Virus Type 1 Infection and Disease
by Julia Sutter, Peter J. Bruggeman, Brian Wigdahl, Fred C. Krebs and Vandana Miller
Int. J. Mol. Sci. 2023, 24(5), 4673; https://doi.org/10.3390/ijms24054673 - 28 Feb 2023
Cited by 6 | Viewed by 3969
Abstract
Herpes simplex virus type 1 (HSV-1) is a contagious pathogen with a large global footprint, due to its ability to cause lifelong infection in patients. Current antiviral therapies are effective in limiting viral replication in the epithelial cells to alleviate clinical symptoms, but [...] Read more.
Herpes simplex virus type 1 (HSV-1) is a contagious pathogen with a large global footprint, due to its ability to cause lifelong infection in patients. Current antiviral therapies are effective in limiting viral replication in the epithelial cells to alleviate clinical symptoms, but ineffective in eliminating latent viral reservoirs in neurons. Much of HSV-1 pathogenesis is dependent on its ability to manipulate oxidative stress responses to craft a cellular environment that favors HSV-1 replication. However, to maintain redox homeostasis and to promote antiviral immune responses, the infected cell can upregulate reactive oxygen and nitrogen species (RONS) while having a tight control on antioxidant concentrations to prevent cellular damage. Non-thermal plasma (NTP), which we propose as a potential therapy alternative directed against HSV-1 infection, is a means to deliver RONS that affect redox homeostasis in the infected cell. This review emphasizes how NTP can be an effective therapy for HSV-1 infections through the direct antiviral activity of RONS and via immunomodulatory changes in the infected cells that will stimulate anti-HSV-1 adaptive immune responses. Overall, NTP application can control HSV-1 replication and address the challenges of latency by decreasing the size of the viral reservoir in the nervous system. Full article
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39 pages, 4644 KiB  
Review
Significance of Singlet Oxygen Molecule in Pathologies
by Kazutoshi Murotomi, Aya Umeno, Mototada Shichiri, Masaki Tanito and Yasukazu Yoshida
Int. J. Mol. Sci. 2023, 24(3), 2739; https://doi.org/10.3390/ijms24032739 - 1 Feb 2023
Cited by 23 | Viewed by 4422
Abstract
Reactive oxygen species, including singlet oxygen, play an important role in the onset and progression of disease, as well as in aging. Singlet oxygen can be formed non-enzymatically by chemical, photochemical, and electron transfer reactions, or as a byproduct of endogenous enzymatic reactions [...] Read more.
Reactive oxygen species, including singlet oxygen, play an important role in the onset and progression of disease, as well as in aging. Singlet oxygen can be formed non-enzymatically by chemical, photochemical, and electron transfer reactions, or as a byproduct of endogenous enzymatic reactions in phagocytosis during inflammation. The imbalance of antioxidant enzymes and antioxidant networks with the generation of singlet oxygen increases oxidative stress, resulting in the undesirable oxidation and modification of biomolecules, such as proteins, DNA, and lipids. This review describes the molecular mechanisms of singlet oxygen production in vivo and methods for the evaluation of damage induced by singlet oxygen. The involvement of singlet oxygen in the pathogenesis of skin and eye diseases is also discussed from the biomolecular perspective. We also present our findings on lipid oxidation products derived from singlet oxygen-mediated oxidation in glaucoma, early diabetes patients, and a mouse model of bronchial asthma. Even in these diseases, oxidation products due to singlet oxygen have not been measured clinically. This review discusses their potential as biomarkers for diagnosis. Recent developments in singlet oxygen scavengers such as carotenoids, which can be utilized to prevent the onset and progression of disease, are also described. Full article
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21 pages, 1112 KiB  
Review
Recent Developments in the Understanding of Immunity, Pathogenesis and Management of COVID-19
by Aram Yegiazaryan, Arbi Abnousian, Logan J. Alexander, Ali Badaoui, Brandon Flaig, Nisar Sheren, Armin Aghazarian, Dijla Alsaigh, Arman Amin, Akaash Mundra, Anthony Nazaryan, Frederick T. Guilford and Vishwanath Venketaraman
Int. J. Mol. Sci. 2022, 23(16), 9297; https://doi.org/10.3390/ijms23169297 - 18 Aug 2022
Cited by 5 | Viewed by 2392
Abstract
Coronaviruses represent a diverse family of enveloped positive-sense single stranded RNA viruses. COVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus-2, is a highly contagious respiratory disease transmissible mainly via close contact and respiratory droplets which can result in severe, life-threatening respiratory pathologies. It [...] Read more.
Coronaviruses represent a diverse family of enveloped positive-sense single stranded RNA viruses. COVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus-2, is a highly contagious respiratory disease transmissible mainly via close contact and respiratory droplets which can result in severe, life-threatening respiratory pathologies. It is understood that glutathione, a naturally occurring antioxidant known for its role in immune response and cellular detoxification, is the target of various proinflammatory cytokines and transcription factors resulting in the infection, replication, and production of reactive oxygen species. This leads to more severe symptoms of COVID-19 and increased susceptibility to other illnesses such as tuberculosis. The emergence of vaccines against COVID-19, usage of monoclonal antibodies as treatments for infection, and implementation of pharmaceutical drugs have been effective methods for preventing and treating symptoms. However, with the mutating nature of the virus, other treatment modalities have been in research. With its role in antiviral defense and immune response, glutathione has been heavily explored in regard to COVID-19. Glutathione has demonstrated protective effects on inflammation and downregulation of reactive oxygen species, thereby resulting in less severe symptoms of COVID-19 infection and warranting the discussion of glutathione as a treatment mechanism. Full article
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1 pages, 542 KiB  
Correction
Correction: Song et al. Protective Effect of Resveratrol in an Experimental Model of Salicylate-Induced Tinnitus. Int. J. Mol. Sci. 2022, 23, 14183
by Anji Song, Gwang-Won Cho, Changjong Moon, Ilyong Park and Chul Ho Jang
Int. J. Mol. Sci. 2023, 24(11), 9460; https://doi.org/10.3390/ijms24119460 - 30 May 2023
Viewed by 777
Abstract
In the original publication [...] Full article
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